Surrogate endpoints play an important role in drug development when they can
be used to measure treatment effect early compared to the final clinical
outcome and to predict clinical benefit or harm. Such endpoints are assessed
for their predictive value of clinical benefit by investigating the surrogate
relationship between treatment effects on the surrogate and final outcomes
using meta-analytic methods. When surrogate relationships vary across treatment
classes, such validation may fail due to limited data within each treatment
class. In this paper, two alternative Bayesian meta-analytic methods are
introduced which allow for borrowing of information from other treatment
classes when exploring the surrogacy in a particular class. The first approach
extends a standard model for the evaluation of surrogate endpoints to a
hierarchical meta-analysis model assuming full exchangeability of surrogate
relationships across all the treatment classes, thus facilitating borrowing of
information across the classes. The second method is able to relax this
assumption by allowing for partial exchangeability of surrogate relationships
across treatment classes to avoid excessive borrowing of information from
distinctly different classes. We carried out a simulation study to assess the
proposed methods in nine data scenarios and compared them with subgroup
analysis using the standard model within each treatment class. We also applied
the methods to an illustrative example in colorectal cancer which led to
obtaining the parameters describing the surrogate relationships with higher
precision.

Progression free survival (PFS) and tumour response (TR) have been
investigated as surrogate endpoints for overall survival (OS) in advanced
colorectal cancer (aCRC), however their validity has been shown to be
suboptimal. In recent years, meta-analytic methods allowing for use of multiple
surrogate endpoints jointly have been proposed. The aim of this research was to
assess if PFS and TR used jointly as surrogate endpoints to OS improve their
predictive value. Data were obtained from a systematic review of randomised
controlled trials investigating effectiveness of different pharmacological
therapies in aCRC: systemic chemotherapies, anti-epidermal growth factor
receptor therapies, anti-angiogenic agents, other multi-targeted antifolate
treatments and intra-hepatic arterial chemotherapy. Multivariate meta-analysis
was used to model the association patterns between treatment effects on the
surrogate endpoints (PFS, TR) and the final outcome (OS). Analysis of 33 trials
which reported treatment effects on all three outcomes showed reasonably strong
association between treatment effects on PFS and OS. A weak surrogate
relationship was noted between the treatment effects on TR and OS. Modelling
the two surrogate endpoints, TR and PFS, jointly as predictors of OS gave no
marked improvement in neither surrogacy patterns nor the precision of predicted
treatment effect in the cross-validation procedure. When investigating
subgroups of therapy, only small improvement in precision of predicted
treatment effects on the final outcome in studies investigating anti-angiogenic
therapy was noted. Overall, the simultaneous modelling of two surrogate
endpoints did not lead to improvement in association between treatment effects
on surrogate and final endpoints in aCRC.

Background. Despite the high prevalence of postnatal depression (PND), few women seek help. Internet interventions may overcome many of the barriers to PND treatment use. We report a phase II evaluation of a 12-session, modular,
guided Internet behavioural activation (BA) treatment modified to address postnatal-specific concerns [Netmums Helping with Depression (NetmumsHWD)].

Method. To assess feasibility, we measured recruitment and attrition to the trial and examined telephone session support
and treatment adherence. We investigated sociodemographic and psychological predictors of treatment adherence. Effectiveness outcomes were estimated with the Edinburgh Postnatal Depression Scale (EPDS), Generalized Anxiety
Disorder-7, Work and Social Adjustment Scale, Postnatal Bonding Questionnaire, and Social Provisions Scale.

Results. A total of 249 women were recruited via a UK parenting site, Netmums.com. A total of 83 women meeting DSM-IV criteria for major depressive disorder were randomized to NetmumsHWD (n=41) or treatment-as-usual
(TAU; n=42). of the 83 women, 71 (86%) completed the EPDS at post-treatment, and 71% (59/83) at the 6-month follow-up. Women completed an average of eight out of 12 telephone support sessions and five out of 12 modules. Working women and those with less support completed fewer modules. There was a large effect size favouring women who received NetmumsHWD on depression, work and social impairment, and anxiety scores at post-treatment
compared with women in the TAU group, and a large effect size on depression at 6 months post-treatment. There were small effect sizes for postnatal bonding and perceived social support.

Conclusions. A supported, modular, Internet BA programme can be feasibly delivered to postpartum women, offering promise to improve depression, anxiety and functioning.

BACKGROUND & AIMS: Biopsy-confirmed liver fibrosis is a prognostic factor for patients with nonalcoholic fatty liver disease (NAFLD). We performed a systematic review to quantify the prognostic value of fibrosis stage in patients with NAFLD and the subgroup of patients with nonalcoholic steatohepatitis (NASH) and to assess the evidence that change in fibrosis stage is a surrogate endpoint. METHODS: We searched the MEDLINE, Embase, Cochrane Library, and trial registry databases through August 2018 for prospective or retrospective cohort studies of liver-related clinical events and outcomes in adults with NAFLD or NASH. We collected data on mortality (all cause and liver related) and morbidity (cirrhosis, liver cancer, and all liver-related events) by stage of fibrosis, determined by biopsy, for patients with NAFLD or NASH. Using fibrosis stage 0 as a reference population, we calculated fibrosis stage-specific relative risk (RR) and 95% confidence interval (CI) values for mortality and morbidities. We performed fixed-effect and random-effect model meta-analyses. Metaregression was used to examine associations among study design (prospective vs retrospective cohort), overall risk of bias (medium or high), and mean duration of follow-up (in years). RESULTS: Our meta-analysis included 13 studies, comprising 4428 patients with NAFLD; 2875 of these were reported to have NASH. Compared with no fibrosis (stage 0), unadjusted risk increased with increasing stage of fibrosis (stage 0 vs 4): all-cause mortality RR, 3.42 (95% CI, 2.63-4.46); liver-related mortality RR, 11.13 (95% CI, 4.15-29.84); liver transplant RR, 5.42 (95% CI, 1.05-27.89); and liver-related events RR, 12.78 (95% CI, 6.85-23.85). The magnitude of RR did not differ significantly after adjustment for confounders, including age or sex in the subgroup of NAFLD patients with NASH. Three studies examined the effects of increasing fibrosis on quality of life had inconsistent findings. CONCLUSIONS: in a systematic review and meta-analysis, we found biopsy-confirmed fibrosis to be associated with risk of mortality and liver-related morbidity in patients with NAFLD, with and without adjustment for confounding factors and in patients with reported NASH. Further studies are needed to assess the association between fibrosis stage and patient quality of life and establish that change in liver fibrosis stage is a valid endpoint for use in clinical trials.

© the Author(s) 2019. Objective: to assess the clinical and cost-effectiveness of cognitive rehabilitation for attention and memory problems in people with multiple sclerosis. Design: Multicentre, pragmatic, randomized controlled trial. Setting: Community Participants: People with multiple sclerosis aged 18–69 years, who reported cognitive problems in daily life and had cognitive problems on standardized assessment. Interventions: a group cognitive rehabilitation programme delivered in 10 weekly sessions in comparison with usual care. Main measures: the primary outcome was the Multiple Sclerosis Impact Scale Psychological subscale at 12 months after randomization. Secondary outcomes included measures of everyday memory problems, mood, fatigue, cognitive abilities and employment at 6 and 12 months after randomization. Results: in all, 245 participants were allocated to cognitive rehabilitation and 204 to usual care. Mean Multiple Sclerosis Impact Scale Psychological at 12 months was 22.2 (SD = 6.1) for cognitive rehabilitation and 23.4 (SD = 6.0) for usual care group; adjusted difference −0.6, 95% confidence interval (CI) = −1.5 to 0.3, P = 0.20. No differences were observed in cognitive abilities, fatigue or employment. There were small differences in favour of cognitive rehabilitation for the Multiple Sclerosis Impact Scale Psychological at 6 months and everyday memory and mood at 6 and 12 months. There was no evidence of an effect on costs (−£808; 95% CI = −£2248 to £632) or on quality-adjusted life year gain (0.00; 95% CI = −0.01 to 0.02). Conclusion: This rehabilitation programme had no long-term benefits on the impact of multiple sclerosis on quality of life, but there was some evidence of an effect on everyday memory problems and mood.

PURPOSE: Cardiovascular disease is the leading cause of mortality and morbidity in lower-middle income countries (LMICs), including Bangladesh. Cardiac rehabilitation (CR) as part of secondary prevention of cardiovascular disease has been shown to reduce mortality and morbidity and improve quality of life and exercise capacity. However, to date, very few controlled trials of CR have been conducted in LMICs. METHODS: a quasi-randomized controlled trial comparing home-based CR plus usual care with usual care alone was undertaken with patients following coronary artery bypass graft surgery. Participants in the CR group received an in-hospital CR class and were introduced to a locally developed educational booklet with details of a home-based exercise program and then received monthly telephone calls for 12 mo. Primary outcomes were coronary heart disease (CHD) risk factors, health-related quality of life (HRQOL), and mental well-being. Maximal oxygen uptake as a measure of exercise capacity was a secondary outcome. RESULTS: in total, 142 of 148 eligible participants took part in the trial (96%); 71 in each group. At 12-mo follow-up, 61 patients (86%) in the CR group and 40 (56%) in the usual care group provided complete outcome data. Greater reductions in CHD risk factors and improvements in HRQOL, mental well-being, and exercise capacity were seen for the CR group compared with the usual care group. CONCLUSIONS: in the context of a single-center LMIC setting, this study demonstrated the feasibility of home-based CR programs and offers a model of service delivery that could be replicated on a larger scale.

We assessed the effects of the patient education strategy 'Learning and Coping' (LC) in cardiac rehabilitation (CR) on mortality and readmissions by exploring results from the LC-REHAB trial. In all, 825 patients with ischaemic heart disease or heart failure were randomized to the intervention arm (LC-CR) or the control arm (standard CR) at three hospitals in Denmark. LC-CR was situational and inductive, with experienced patients as co-educators supplemented with two individual interviews. Group-based training and education hours were the same in both arms. Outcomes were time to death or readmission, length of stay and absolute number of deaths or readmissions. No between-arm differences were found in time to death, first readmission, or length of stay. Within 30 days after completion of CR, the absolute number of all-cause readmissions was 117 in the LC arm and 146 in the control arm, adjusted odds ratio 78 (95% CI: 0.61-1.01), P = 0.06. This trend diminished over time. Adding LC strategies to standard CR showed a short term but no significant long-term effect on mortality or readmissions. However, the study was not powered to detect differences in mortality and morbidity. Thus, a risk of overseeing a true effect was present.

BACKGROUND: Painful diabetic neuropathy (PDN), a debilitating and progressive chronic pain condition that significantly impacts quality of life, is one of the common complications seen with long-standing diabetes mellitus. Neither pharmacological treatments nor low-frequency spinal cord stimulation (SCS) has provided significant and long-term pain relief for patients with PDN. This study aims to document the value of 10-kHz SCS in addition to conventional medical management (CMM) compared with CMM alone in patients with refractory PDN. METHODS: in a prospective, multicenter, randomized controlled trial (SENZA-PDN), 216 subjects with PDN will be assigned 1:1 to receive 10-kHz SCS combined with CMM or CMM alone after appropriate institutional review board approvals and followed for 24 months. Key inclusion criteria include (1) symptoms of PDN for at least 12 months, (2) average pain intensity of at least 5 cm-on a 0- to 10-cm visual analog scale (VAS)-in the lower limbs, and (3) an appropriate candidate for SCS. Key exclusion criteria include (1) large or gangrenous ulcers or (2) average pain intensity of at least 3 cm on VAS in the upper limbs or both. Along with pain VAS, neurological assessments, health-related quality of life, sleep quality, and patient satisfaction will be captured. The primary endpoint comparing responder rates (≥50% pain relief) and safety rates between the treatment groups will be assessed at 3 months. Several secondary endpoints will also be reported on. DISCUSSION: Enrollment commenced in 2017 and was completed in 2019. This study will help to determine whether 10-kHz SCS improves clinical outcomes and health-related quality of life and is a cost-effective treatment for PDN that is refractory to CMM. TRIAL REGISTRATION: ClincalTrials.gov identifier: NCT03228420 (registered 24 July 2017).

INTRODUCTION: Chronic neuropathic low back pain (CNLBP) is a debilitating condition in which established medical treatments seldom alleviate symptoms. Evidence demonstrates that high-frequency 10 kHz spinal cord stimulation (SCS) reduces pain and improves health-related quality of life in patients with failed back surgery syndrome (FBSS), but evidence of this effect is limited in individuals with CNLBP who have not had surgery. The aim of this multicentre randomised trial is to assess the clinical and cost-effectiveness of 10 kHz SCS for this population. METHODS: This is a multicentre, double-blind, randomised, sham-controlled trial with a parallel economic evaluation. A total of 96 patients with CNLBP who have not had spinal surgery will be implanted with an epidural lead and a sham lead outside the epidural space without a screening trial. Patients will be randomised 1:1 to 10 kHz SCS plus usual care (intervention group) or to sham 10 kHz SCS plus usual care (control group) after receiving the full implant. The SCS devices will be programmed identically using a cathodal cascade. Participants will use their handheld programmer to alter the intensity of the stimulation as per routine practice. The primary outcome will be a 7-day daily pain diary. Secondary outcomes include the Oswestry Disability Index, complications, EQ-5D-5 L, and health and social care costs. Outcomes will be assessed at baseline (pre-randomisation) and at 1 month, 3 months and 6 months after device activation. The primary analyses will compare primary and secondary outcomes between groups at 6 months, while adjusting for baseline outcome scores. Incremental cost per quality-adjusted life year (QALY) will be calculated at 6 months and over the lifetime of the patient. DISCUSSION: the outcomes of this trial will inform clinical practice and healthcare policy on the role of high-frequency 10 kHz SCS for use in patients with CNLBP who have not had surgery. TRIAL REGISTRATION: Clinicaltrials.gov, NCT03470766. Registered on 20 March 2018. DISCLAIMER: the views expressed here are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. The NIHR had no role in the study design, writing of the manuscript or the decision to submit for publication. ROLES AND RESPONSIBILITIES: AK, SP, DP, SW, RST, AC, SE, LM, RD and JF all contributed to the trial design and to securing trial funding. AK, JR, SP, DP, and SE are involved in the recruitment, the intervention and the follow-up. SW will perform data collection and analysis. RST will be responsible for the statistical analysis, and RD will be responsible for the health economic analysis. All authors read and approved the final manuscript.

OBJECTIVES: the recent availability of paraesthesia/sensation free spinal cord stimulation (SCS) modalities allow the design of clinical trials of SCS using placebo/sham controls and blinding of patients, clinicians, and researchers. The aims of this study were to: 1) systematically review the current evidence base of randomized controlled trials (RCTs) of SCS placebo/sham trials and 2) to undertake a methodological critique of their methods. Based on this critique, we developed a checklist for the design and reporting of future RCTs of SCS. MATERIALS AND METHODS: Electronic data bases were searched from inception until January 2019 for RCTs of SCS using a placebo/sham control. RCTs with only an active comparator arm were excluded. The results are presented as a narrative synthesis. RESULTS: Searches identified 12 eligible RCTs. SCS modalities included paraesthesia stimulation, subthreshold, burst, and high-frequency SCS and were mainly conducted in patients with failed back surgery syndrome, complex regional pain syndrome, and refractory angina. The quality and transparency of reporting of the methods of placebo stimulation, blinding of patients, clinicians, and researchers varied markedly across studies. CONCLUSIONS: to date the methods of placebo/sham control and blinding in RCTs have been poorly reported, leading to concerns about the validity and replicability of the findings. Important aspects that need to be clearly reported in the design of placebo-/sham-controlled RCTs of SCS include the transparent reporting of stimulation programming parameters, patient position during perception threshold measurement, management of the patient handheld programmer, frequency of recharging, and assessment of the fidelity of blinding.

The aims of this review were to systematically identify the current evidence base of placebo (or "sham") randomised controlled trials (RCTs) of spinal cord stimulation (SCS) for neuropathic pain and to undertake a meta-analysis to investigate the effectiveness of SCS when compared with a placebo comparator arm. Electronic databases were searched from inception until January 2019 for RCTs of SCS using a placebo/sham control. Searches identified 8 eligible placebo-controlled randomised trials of SCS for neuropathic pain. Meta-analysis shows a statistically significant reduction in pain intensity during the active stimulation treatment periods compared with the control treatment periods, pooled mean difference -1.15 (95% confidence interval -1.75 to -0.55, P = 0.001) on a 10-point scale. Exploratory study-level subgroup analysis suggests a larger treatment effect in RCTs using a placebo control (defined as studies where the device was inactive and at least one of the study procedures was different between the arms) than a sham control (defined as all study procedures being equal between arms including SCS device behaviour). Our findings demonstrate limited evidence that SCS is effective in reducing pain intensity when compared with a placebo intervention. Our analyses suggest that the magnitude of treatment effect varies across trials and, in part, depends on the quality of patient blinding and minimisation of carryover effects. Improved reporting and further methodological research is needed into placebo and blinding approaches in SCS trials. Furthermore, we introduce a differentiation between placebo and sham concepts that may be generalisable to trials evaluating surgical or medical procedures.

OBJECTIVES: to compare the effectiveness of peripheral nerve stimulation utilizing a subcutaneous lead implant technique-subcutaneous nerve stimulation (SQS) plus optimized medical management (SQS + OMM arm) vs. optimized medical management alone (OMM arm) in patients with back pain due to failed back surgery syndrome. PATIENTS AND METHODS: Patients were recruited from 21 centers, in Europe, Israel, and Australia. Eligible patients were randomized (1:1) to SQS + OMM or OMM arms. Those in the SQS arm were implanted with a neurostimulator and up to two subcutaneous percutaneous cylindrical leads in the area of pain. Patients were evaluated pre-randomization and at one, three, six, and nine months post-randomization. The primary endpoint was the proportion of subjects with a ≥50% reduction in back pain intensity ("responder") from baseline to nine months. Secondary outcomes included proportion of responders with a ≥50% reduction in back pain intensity at six months and ≥30% reduction at nine months, and the mean change from baseline in back pain intensity at six and nine months between the two arms. RESULTS: Due to the slow rate of recruitment, the study was terminated early with 116 subjects randomized. A total of 33.9% (19/56, missing: n = 20 [36%]) of subjects in the SQS + OMM arm and 1.7% (1/60, missing: n = 24 [40%]) in the OMM arm were responders at Month 9 (p 

OBJECTIVE: to undertake a methodological review of statistical methods used in randomized controlled trials (RCTs) for handling intervention nonadherence. STUDY DESIGN AND SETTING: Bibliographic databases were searched using predefined search terms. RESULTS: a substantive number of identified studies (56%) were excluded as they only used naive per protocol analysis for handling nonadherence. Our review included 58 articles published between 1991 and 2015. A total of 88 methodological applications were made by these studies. The two most used methods were complier average causal effect (56%) and instrumental variable (23%) predominantly with the use of maximum likelihood (ML) estimators. These alternative applications typically produced treatment effects greater than the intention-to-treat effect but as their standard errors were larger there was no statistical difference between the methods. CONCLUSION: a substantive proportion of RCTs rely on naive per protocol for handling nonadherence. Recent years have seen an increasing number of applications of more appropriate statistical methods, in particular complier average causal effect and instrumental variable methods. However, these later methods rely on strong underlying assumptions that may be vulnerable to violation. More empirical studies are needed that directly compare the usability and performance of different statistical methods for nonadherence in RCTs.

OBJECTIVES: Currently little objective evidence exists regarding the phenotype or somato-sensory profile of patients with Failed Back Surgery Syndrome (FBSS). The aim of this study is to characterize the somato-sensory profile of the patients with FBSS undergoing spinal cord stimulation (SCS). METHODS: a combined quantitative sensory test and questionnaire approach was used to characterize the somatosensory profiles of patients undergoing SCS. RESULTS: Baseline somatosensory profiles were obtained from 23 patients and full three-month data was obtained from 19 patients. At baseline, there was a high prevalence (>50% prevalence of moderate to severe sensation) of burning, tingling, electric shock, numbness, and pressure pain sensitivity. None of the sensory symptoms were present at significant levels at three months following SCS. At baseline, 65% of patients had an inefficient conditioned pain modulation (CPM). Three months post-SCS, 95% of patients had an efficient CPM. All the patients who had an inefficient CPM at baseline had a successful implant at three months and their CPM became efficient in all but one patient. Only 50% of the patients with an efficient CPM at baseline, had a successful implant at three months post-SCS. CONCLUSION: Although very low numbers, we could demonstrate the somatosensory profiles of patients with FBSS undergoing SCS. Early indication may associate an efficient CPM profile having a higher chance of an unsuccessful implant at three months.

BACKGROUND: for patients with painful knee osteoarthritis, long-term symptomatic relief may improve quality of life. Cooled radiofrequency ablation (CRFA) has demonstrated significant improvements in pain, physical function and health-related quality of life compared with conservative therapy with intra-articular steroid (IAS) injections. This study aimed to establish the cost-effectiveness of CRFA compared with IAS for managing moderate to severe osteoarthritis-related knee pain, from the US Medicare system perspective. METHODS: We conducted a cost-effectiveness analysis utilizing efficacy data (Oxford Knee Scores) from a randomized, crossover trial on CRFA (NCT02343003), which compared CRFA with IAS out to 6 and 12 months, and with IAS patients who subsequently crossed over to receive CRFA after 6 months. Outcomes included health benefits (quality-adjusted life-years [QALYs]), costs and cost-effectiveness (expressed as cost per QALY gained). QALYs were estimated by mapping Oxford Knee Scores to the EQ-5D generic utility measure using a validated algorithm. Secondary analyses explored differences in the settings of care and procedures used in-trial versus real-world clinical practice. RESULTS: CRFA resulted in an incremental QALY gain of 0.091 at an incremental cost of $1711, equating to a cost of US$18,773 per QALY gained over a 6-month time horizon versus IAS. Over a 12-month time horizon, the incremental QALY gain was 0.229 at the same incremental cost, equating to a cost of US$7462 per QALY gained versus IAS. Real-world cost assumptions resulted in modest increases in the cost per QALY gained to a maximum of US$21,166 and US$8296 at 6 and 12 months, respectively. Sensitivity analyses demonstrated that findings were robust to variations in efficacy and cost parameters. CONCLUSIONS: CRFA is a highly cost-effective treatment option for patients with osteoarthritis-related knee pain, compared with the US$100,000/QALY threshold typically used in the US.

Following publication of the original article [1], we have been notified that the final specification of randomisation implemented in the study is slightly different to that stated in the protocol and needs to be corrected as follows.

AIMS: Prescribed exercise is effective in adults with coronary heart disease (CHD), chronic heart failure (CHF), intermittent claudication, body mass index (BMI) ≥25 kg/m2, hypertension or type 2 diabetes mellitus (T2DM), but the evidence for its cost-effectiveness is limited, shows large variations and is partly contradictory. Using World Health Organization and American Heart Association/American College of Cardiology value for money thresholds, we report the cost-effectiveness of exercise therapy, exercise training and exercise-based cardiac rehabilitation. METHODS: Electronic databases were searched for incremental cost-effectiveness and incremental cost-utility ratios and/or the probability of cost-effectiveness of exercise prescribed as therapy in economic evaluations conducted alongside randomized controlled trials (RCTs) published between 1 July 2008 and 28 October 2018. RESULTS: of 19 incremental cost-utility ratios reported in 15 RCTs in patients with CHD, CHF, intermittent claudication or BMI ≥25 kg/m2, 63% met both value for money thresholds as 'highly cost-effective' or 'high value', with 26% 'not cost-effective' or of 'low value'. The probability of intervention cost-effectiveness ranged from 23 to 100%, probably due to the different populations, interventions and comparators reported in the individual RCTs. Confirmation with the Consolidated Health Economic Evaluation Reporting checklist varied widely across the included studies. CONCLUSIONS: the findings of this review support the cost-effectiveness of exercise therapy in patients with CHD, CHF, BMI ≥25 kg/m2 or intermittent claudication, but, with concerns about reporting standards, need further confirmation. No eligible economic evaluation based on RCTs was identified in patients with hypertension or T2DM.

© 2019 the Cochrane Collaboration. Background: Despite advances in treatment, the increasing and ageing population makes heart failure an important cause of morbidity and death worldwide. It is associated with high healthcare costs, partly driven by frequent hospital readmissions. Disease management interventions may help to manage people with heart failure in a more proactive, preventative way than drug therapy alone. This is the second update of a review published in 2005 and updated in 2012. Objectives: to compare the effects of different disease management interventions for heart failure (which are not purely educational in focus), with usual care, in terms of death, hospital readmissions, quality of life and cost-related outcomes. Search methods: We searched CENTRAL, MEDLINE, Embase and CINAHL for this review update on 9 January 2018 and two clinical trials registries on 4 July 2018. We applied no language restrictions. Selection criteria: We included randomised controlled trials (RCTs) with at least six months' follow-up, comparing disease management interventions to usual care for adults who had been admitted to hospital at least once with a diagnosis of heart failure. There were three main types of intervention: case management; clinic-based interventions; multidisciplinary interventions. Data collection and analysis: We used standard methodological procedures expected by Cochrane. Outcomes of interest were mortality due to heart failure, mortality due to any cause, hospital readmission for heart failure, hospital readmission for any cause, adverse effects, quality of life, costs and cost-effectiveness. Main results: We found 22 new RCTs, so now include 47 RCTs (10,869 participants). Twenty-eight were case management interventions, seven were clinic-based models, nine were multidisciplinary interventions, and three could not be categorised as any of these. The included studies were predominantly in an older population, with most studies reporting a mean age of between 67 and 80 years. Seven RCTs were in upper-middle-income countries, the rest were in high-income countries. Only two multidisciplinary-intervention RCTs reported mortality due to heart failure. Pooled analysis gave a risk ratio (RR) of 0.46 (95% confidence interval (CI) 0.23 to 0.95), but the very low-quality evidence means we are uncertain of the effect on mortality due to heart failure. Based on this limited evidence, the number needed to treat for an additional beneficial outcome (NNTB) is 12 (95% CI 9 to 126). Twenty-six case management RCTs reported all-cause mortality, with low-quality evidence indicating that these may reduce all-cause mortality (RR 0.78, 95% CI 0.68 to 0.90; NNTB 25, 95% CI 17 to 54). We pooled all seven clinic-based studies, with low-quality evidence suggesting they may make little to no difference to all-cause mortality. Pooled analysis of eight multidisciplinary studies gave moderate-quality evidence that these probably reduce all-cause mortality (RR 0.67, 95% CI 0.54 to 0.83; NNTB 17, 95% CI 12 to 32). We pooled data on heart failure readmissions from 12 case management studies. Moderate-quality evidence suggests that they probably reduce heart failure readmissions (RR 0.64, 95% CI 0.53 to 0.78; NNTB 8, 95% CI 6 to 13). We were able to pool only two clinic-based studies, and the moderate-quality evidence suggested that there is probably little or no difference in heart failure readmissions between clinic-based interventions and usual care (RR 1.01, 95% CI 0.87 to 1.18). Pooled analysis of five multidisciplinary interventions gave low-quality evidence that these may reduce the risk of heart failure readmissions (RR 0.68, 95% CI 0.50 to 0.92; NNTB 11, 95% CI 7 to 44). Meta-analysis of 14 RCTs gave moderate-quality evidence that case management probably slightly reduces all-cause readmissions (RR 0.92, 95% CI 0.83 to 1.01); a decrease from 491 to 451 in 1000 people (95% CI 407 to 495). Pooling four clinic-based RCTs gave low-quality and somewhat heterogeneous evidence that these may result in little or no difference in all-cause readmissions (RR 0.90, 95% CI 0.72 to 1.12). Low-quality evidence from five RCTs indicated that multidisciplinary interventions may slightly reduce all-cause readmissions (RR 0.85, 95% CI 0.71 to 1.01); a decrease from 450 to 383 in 1000 people (95% CI 320 to 455). Neither case management nor clinic-based intervention RCTs reported adverse effects. Two multidisciplinary interventions reported that no adverse events occurred. GRADE assessment of moderate quality suggested that there may be little or no difference in adverse effects between multidisciplinary interventions and usual care. Quality of life was generally poorly reported, with high attrition. Low-quality evidence means we are uncertain about the effect of case management and multidisciplinary interventions on quality of life. Four clinic-based studies reported quality of life but we could not pool them due to differences in reporting. Low-quality evidence indicates that clinic-based interventions may result in little or no difference in quality of life. Four case management programmes had cost-effectiveness analyses, and seven reported cost data. Low-quality evidence indicates that these may reduce costs and may be cost-effective. Two clinic-based studies reported cost savings. Low-quality evidence indicates that clinic-based interventions may reduce costs slightly. Low-quality data from one multidisciplinary intervention suggested this may be cost-effective from a societal perspective but less so from a health-services perspective. Authors' conclusions: We found limited evidence for the effect of disease management programmes on mortality due to heart failure, with few studies reporting this outcome. Case management may reduce all-cause mortality, and multidisciplinary interventions probably also reduce all-cause mortality, but clinic-based interventions had little or no effect on all-cause mortality. Readmissions due to heart failure or any cause were probably reduced by case-management interventions. Clinic-based interventions probably make little or no difference to heart failure readmissions and may result in little or no difference in readmissions for any cause. Multidisciplinary interventions may reduce the risk of readmission for heart failure or for any cause. There was a lack of evidence for adverse effects, and conclusions on quality of life remain uncertain due to poor-quality data. Variations in study location and time of occurrence hamper attempts to review costs and cost-effectiveness. The potential to improve quality of life is an important consideration but remains poorly reported. Improved reporting in future trials would strengthen the evidence for this patient-relevant outcome.

BACKGROUND: the projected reduced mortality effect of reduced sodium intake in model-based studies conflicts with the observed increased mortality associated with low sodium intake in population studies. This may reflect an overestimation of the dose-response relation between sodium reduction (SR) and blood pressure (BP) used in mortality modeling studies. OBJECTIVES: the present meta-regression analysis sought to estimate the dose-response relations between SR and BP in study groups with mean BP above or below the 75th percentile of the general population. METHODS: Based on a literature search from 1 January 1946 to 11 April 2018, we identified 133 randomized controlled trials allocating healthy or hypertensive individuals to SR or usual sodium intake. Multivariable regression analyses of the mean SR versus the mean blood pressure effect adjusted for effect modifiers were performed. RESULTS: in study groups with mean BP above the 75th percentile [131/78 mm Hg systolic BP (SBP)/diastolic BP (DBP)], there was strong evidence of a linear dose-response relation between SR and BP. For SBP, the dose-response relation was -7.7 mm Hg/100 mmol SR (95% CI: -10.4, -5.0), and for DBP it was -3.0 mm Hg/100 mmol SR (95% CI: -4.6, -1.4). In study groups with mean BP ≤ 131/78 mm Hg, the relation between SR and BP was weak. For SBP it was -1.46 mm Hg/100 mmol SR (95% CI: -2.7, -0.20) and for DBP it was: -0.07 mm Hg/100 mmol SR (95% CI: -1.5, 1.4). CONCLUSIONS: Only study groups with a BP in the highest 25th percentile of the population showed a clinically significant drop in BP with SR. The policy of lowering dietary sodium intake in the general population may need to be reframed to target patients with hypertension. This study was registered at PROSPERO 2015 as CRD42015017773.

BACKGROUND: Previous meta-analyses based on aggregate group-level data report antihypertensive effects of isometric resistance training (IRT). However, individual participant data meta-analyses provide more robust effect size estimates and permit examination of demographic and clinical variables on IRT effectiveness. METHODS: We conducted a systematic search and individual participant data (IPD) analysis, using both a one-step and two-step approach, of controlled trials investigating at least 3 weeks of IRT on resting systolic, diastolic and mean arterial blood pressure. RESULTS: Anonymized individual participant data were provided from 12 studies (14 intervention group comparisons) involving 326 participants (52.7% medicated for hypertension); 191 assigned to IRT and 135 controls, 25.2% of participants had diagnosed coronary artery disease. IRT intensity varied (8-30% MVC) and training duration ranged from 3 to 12 weeks. The IPD (one-step) meta-analysis showed a significant treatment effect for the exercise group participants experiencing a reduction in resting SBP of -6.22 mmHg (95% CI -7.75 to -4.68; P 

OBJECTIVES: This study performed a contemporary systematic review and meta-analysis of exercise-based cardiac rehabilitation (ExCR) for heart failure (HF). BACKGROUND: There is an increasing call for trials of models of ExCR for patients with HF that provide alternatives to conventional center-based provision and recruitment of patients that reflect a broader HF population. METHODS: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, and PsycINFO databases were searched between January 2013 and January 2018. Randomized trials comparing patients undergoing ExCR to control patients not undergoing exercise were included. Study outcomes were pooled using meta-analysis. Metaregression examined potential effect modification according to ExCR program characteristics, and risk of bias, trial sequential analysis (TSA), and Grading of Recommendations Assessment Development and Evaluation (GRADE) were applied. RESULTS: Across 44 trials (n = 5,783; median follow-up of 6 months), compared with control subjects, ExCR did not reduce the risk of all-cause mortality (relative risk [RR]: 0.89; 95% confidence interval [CI]: 0.66 to 1.21; TSA-adjusted CI: 0.26 to 3.10) but did reduce all-cause hospitalization (RR: 0.70; 95% CI: 0.60 to 0.83; TSA-adjusted CI: 0.54 to 0.92) and HF-specific hospitalization (RR: 0.59; 95% CI: 0.42 to 0.84; TSA-adjusted CI: 0.14 for 2.46), and patients reported improved Minnesota Living with Heart Failure questionnaire overall scores (mean difference: -7.1; 95% CI: -10.5 to -3.7; TSA-adjusted CI: -13.2 to -1.0). No evidence of differential effects across different models of delivery, including center- versus home-based programs, were found. CONCLUSIONS: This review supports the beneficial effects of ExCR on patient outcomes. These benefits appear to be consistent across ExCR program characteristics. GRADE and TSA assessments indicated that further high-quality randomized trials are needed.

© 2019 the Cochrane Collaboration. Published by JohnWiley. &. Sons, Ltd. An effective way of preventing sudden cardiac death is the use of an implantable cardioverter defibrillator (ICD). In spite of the potential mortality benefits of receiving an ICD device, psychological problems experienced by patients after receiving an ICD may negatively impact their health-related quality of life, and lead to increased readmission to hospital and healthcare needs, loss of productivity and employment earnings, and increased morbidity and mortality. Evidence from other heart conditions suggests that cardiac rehabilitation should consist of both exercise training and psychoeducational interventions; such rehabilitation may benefit patients with an ICD. Prior systematic reviews of cardiac rehabilitation have excluded participants with an ICD. A systematic review was therefore conducted to assess the evidence for the use of exercise-based intervention programmes following implantation of an ICD. Objectives to assess the benefits and harms of exercise-based cardiac rehabilitation programmes (exercise-based interventions alone or in combination with psychoeducational components) compared with control (group of no intervention, treatment as usual or another rehabilitation programme with no physical exercise element) in adults with an ICD. Search methods We searched CENTRAL, MEDLINE, Embase and four other databases on 30 August 2018 and three trials registers on 14 November 2017. We also undertook reference checking, citation searching and contacted study authors for missing data. Selection criteria We included randomised controlled trials (RCTs) if they investigated exercise-based cardiac rehabilitation interventions compared with no intervention, treatment as usual or another rehabilitation programme. The trial participants were adults (aged 18 years or older), who had been treated with an ICD regardless of type or indication.

BACKGROUND: Chronic heart failure (HF) is a growing global health challenge. People with HF experience substantial burden that includes low exercise tolerance, poor health-related quality of life (HRQoL), increased risk of mortality and hospital admission, and high healthcare costs. The previous (2014) Cochrane systematic review reported that exercise-based cardiac rehabilitation (CR) compared to no exercise control shows improvement in HRQoL and hospital admission among people with HF, as well as possible reduction in mortality over the longer term, and that these reductions appear to be consistent across patient and programme characteristics. Limitations noted by the authors of this previous Cochrane Review include the following: (1) most trials were undertaken in patients with HF with reduced (< 45%) ejection fraction (HFrEF), and women, older people, and those with preserved (≥ 45%) ejection fraction HF (HFpEF) were under-represented; and (2) most trials were undertaken in the hospital/centre-based setting. OBJECTIVES: to determine the effects of exercise-based cardiac rehabilitation on mortality, hospital admission, and health-related quality of life of people with heart failure. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and three other databases on 29 January 2018. We also checked the bibliographies of systematic reviews and two trial registers. SELECTION CRITERIA: We included randomised controlled trials that compared exercise-based CR interventions with six months' or longer follow-up versus a no exercise control that could include usual medical care. The study population comprised adults (> 18 years) with evidence of HF - either HFrEF or HFpEF. DATA COLLECTION AND ANALYSIS: Two review authors independently screened all identified references and rejected those that were clearly ineligible for inclusion in the review. We obtained full papers of potentially relevant trials. Two review authors independently extracted data from the included trials, assessed their risk of bias, and performed GRADE analyses. MAIN RESULTS: We included 44 trials (5783 participants with HF) with a median of six months' follow-up. For this latest update, we identified 11 new trials (N = 1040), in addition to the previously identified 33 trials. Although the evidence base includes predominantly patients with HFrEF with New York Heart Association classes II and III receiving centre-based exercise-based CR programmes, a growing body of studies include patients with HFpEF and are undertaken in a home-based setting. All included studies included a no formal exercise training intervention comparator. However, a wide range of comparators were seen across studies that included active intervention (i.e. education, psychological intervention) or usual medical care alone. The overall risk of bias of included trials was low or unclear, and we downgraded results using the GRADE tool for all but one outcome.Cardiac rehabilitation may make little or no difference in all-cause mortality over the short term (≤ one year of follow-up) (27 trials, 28 comparisons (2596 participants): intervention 67/1302 (5.1%) vs control 75/1294 (5.8%); risk ratio (RR) 0.89, 95% confidence interval (CI) 0.66 to 1.21; low-quality GRADE evidence) but may improve all-cause mortality in the long term (> 12 months follow up) (6 trials/comparisons (2845 participants): intervention 244/1418 (17.2%) vs control 280/1427 (19.6%) events): RR 0.88, 95% CI 0.75 to 1.02; high-quality evidence). Researchers provided no data on deaths due to HF. CR probably reduces overall hospital admissions in the short term (up to one year of follow-up) (21 trials, 21 comparisons (2182 participants): (intervention 180/1093 (16.5%) vs control 258/1089 (23.7%); RR 0.70, 95% CI 0.60 to 0.83; moderate-quality evidence, number needed to treat: 14) and may reduce HF-specific hospitalisation (14 trials, 15 comparisons (1114 participants): (intervention 40/562 (7.1%) vs control 61/552 (11.1%) RR 0.59, 95% CI 0.42 to 0.84; low-quality evidence, number needed to treat: 25). After CR, a clinically important improvement in short-term disease-specific health-related quality of life may be evident (Minnesota Living with Heart Failure questionnaire - 17 trials, 18 comparisons (1995 participants): mean difference (MD) -7.11 points, 95% CI -10.49 to -3.73; low-quality evidence). Pooling across all studies, regardless of the HRQoL measure used, shows there may be clinically important improvement with exercise (26 trials, 29 comparisons (3833 participants); standardised mean difference (SMD) -0.60, 95% CI -0.82 to -0.39; I² = 87%; Chi² = 215.03; low-quality evidence). ExCR effects appeared to be consistent different models of ExCR delivery: centre vs. home-based, exercise dose, exercise only vs. comprehensive programmes, and aerobic training alone vs aerobic plus resistance programmes. AUTHORS' CONCLUSIONS: This updated Cochrane Review provides additional randomised evidence (11 trials) to support the conclusions of the previous version (2014) of this Cochane Review. Compared to no exercise control, CR appears to have no impact on mortality in the short term (< 12 months' follow-up). Low- to moderate-quality evidence shows that CR probably reduces the risk of all-cause hospital admissions and may reduce HF-specific hospital admissions in the short term (up to 12 months). CR may confer a clinically important improvement in health-related quality of life, although we remain uncertain about this because the evidence is of low quality. Future ExCR trials need to continue to consider the recruitment of traditionally less represented HF patient groups including older, female, and HFpEF patients, and alternative CR delivery settings including home- and using technology-based programmes.

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. Objectives Exercise-based cardiac rehabilitation (CR) may be beneficial to patients following transcatheter aortic valve implantation (TAVI) and open surgical aortic valve replacement (SAVR). We aimed to undertake a systematic review and meta-analysis to evaluate the efficacy, safety and costs of exercise-based CR post-TAVI and post-SAVR. Methods We searched numerous databases, including Embase, CENTRAL and MEDLINE, up to October 2017. We included randomised controlled trials (RCTs) and non-randomised controlled trials (non-RCTs) of exercise-based CR compared with no exercise control in TAVI or SAVR patients ≥18 years. Data extraction and risk of bias assessments were performed independently by two reviewers. Narrative synthesis and meta-analysis (where appropriate) were carried out for all relevant outcomes, and a Grading of Recommendations Assessment, Development and Evaluation (GRADE) analysis was also performed. Results Six studies, all at low risk of bias, were included: three RCTs and three non-RCTs (total of 27 TAVI, 99 SAVR and 129 mixed patients), with follow-up of 2-12 months. There was an increase in pooled exercise capacity (standardised mean difference: 0.41, 95% CI 0.11 to 0.70; moderate certainty evidence as assessed by GRADE), with exercise-based rehabilitation compared with control. Data on other outcomes including quality of life and clinical events were limited. Conclusions Exercise-based CR probably improves exercise capacity of post-TAVI and post-SAVR patients in the short term. Well conducted multicentre fully powered RCTs of ≥12 months follow-up are needed to fully assess the clinical and cost-effectiveness of exercise-based CR in this patient population. PROSPERO Protocol Registration Number CRD42017084716.

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ. A systematic review was undertaken to assess the effects of exercise-based cardiac rehabilitation (CR) for patients with stable angina. Methods Databases (Cochrane Central Register of Controlled Trials, MEDLINE, Embase and CINAHL) were searched up to October 2017, without language restriction. Randomised trials comparing CR programmes with no exercise control in adults with stable angina were included. Where possible, study outcomes were pooled using meta-analysis. Grading of Recommendations Assessment, Development and Evaluation was used to assess the quality of evidence. The protocol was published on the Cochrane Database of Systematic Reviews. Results Seven studies (581 patients), with a median of 12-month follow-up, were included. The effect of exercise-based CR on all-cause mortality (risk ratio (RR) 1.01, 95 % CI: 0.18 to 5.67), acute myocardial infarction (RR 0.33, 95% CI: 0.07 to 1.63) and cardiovascular-related hospital admissions (RR 0.14, 95% CI: 0.02 to 1.1) relative to control were uncertain. We found low-quality evidence that exercise-based CR results in a moderate improvement in exercise capacity (standard mean difference 0.45, 95% CI: 0.20 to 0.70). There was limited and very low-quality evidence for the effect of exercise-based CR on health-related quality of life (HRQoL), adverse events and costs. No data were identified on cost-effectiveness or return to work. Conclusions Exercise-based CR may improve the short-term exercise capacity of patients with stable angina pectoris. Well-designed randomised controlled trials are needed to definitely determine the impact of CR on outcomes including mortality, morbidity, HRQoL, and costs in the population of patients with stable angina receiving contemporary medical therapy.

© 2019 Background: Previous systematic reviews have indicated that exercise-based cardiac rehabilitation (ExCR) for patients with heart failure (HF) has a beneficial effect on health-related quality-of-life (HRQoL) and exercise capacity. However, there is uncertainty regarding potential differential effects of ExCR across HF patient subgroups. Objectives: the authors sought to undertake an individual participant data (IPD) meta-analysis to: 1) assess the impact of ExCR on HRQoL and exercise capacity in patients with HF; and 2) investigate differential effects of ExCR according to a range of patient characteristics: age, sex, ethnicity, New York Heart Association functional class, ischemic etiology, ejection fraction, and exercise capacity. Methods: a single dataset was produced, comprising randomized trials where ExCR (delivered for 3 weeks or more) was compared with a no exercise control group. Each trial provided IPD on HRQoL or exercise capacity (or both), with follow-up of 6 months or more. One- and 2-stage meta-analysis models were used to investigate the effect of ExCR overall and the interactions between ExCR and participant characteristics. Results: IPD was obtained from 13 trials for 3,990 patients, predominantly (97%) with reduced ejection fraction HF. Compared with the control group, there was a statistically significant difference in favor of ExCR for HRQoL and exercise capacity. At 12-month follow-up, improvements were seen in 6-min walk test (mean 21.0 m; 95% confidence interval: 1.57 to 40.4 m; p = 0.034) and Minnesota Living with HF score (mean improvement 5.9; 95% confidence interval: 1.0 to 10.9; p = 0.018). No consistent evidence was found of differential intervention effects across patient subgroups. Conclusions: These results, based on an IPD meta-analysis of randomized trials, confirm the benefit of ExCR on HRQoL and exercise capacity and support the Class I recommendation of current international clinical guidelines that ExCR should be offered to all HF patients. (Exercise Training for Chronic Heart Failure [ExTraMATCH II]: protocol for an individual participant data meta-analysis; PROSPERO: international database of systematic reviews CRD42014007170)

© 2019 the Cochrane Collaboration. Background: International clinical practice guidelines routinely recommend that cardiac patients participate in rehabilitation programmes for comprehensive secondary prevention. However, data show that only a small proportion of these patients utilise rehabilitation. Objectives: First, to assess interventions provided to increase patient enrolment in, adherence to, and completion of cardiac rehabilitation. Second, to assess intervention costs and associated harms, as well as interventions intended to promote equitable CR utilisation in vulnerable patient subpopulations. Search methods: Review authors performed a search on 10 July 2018, to identify studies published since publication of the previous systematic review. We searched the Cochrane Central Register of Controlled Trials (CENTRAL); the National Health Service (NHS) Centre for Reviews and Dissemination (CRD) databases (Health Technology Assessment (HTA) and Database of Abstracts of Reviews of Effects (DARE)), in the Cochrane Library (Wiley); MEDLINE (Ovid); Embase (Elsevier); the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (EBSCOhost); and Conference Proceedings Citation Index - Science (CPCI-S) on Web of Science (Clarivate Analytics). We checked the reference lists of relevant systematic reviews for additional studies and also searched two clinical trial registers. We applied no language restrictions. Selection criteria: We included randomised controlled trials (RCTs) in adults with myocardial infarction, with angina, undergoing coronary artery bypass graft surgery or percutaneous coronary intervention, or with heart failure who were eligible for cardiac rehabilitation. Interventions had to aim to increase utilisation of comprehensive phase II cardiac rehabilitation. We included only studies that measured one or more of our primary outcomes. Secondary outcomes were harms and costs, and we focused on equity. Data collection and analysis: Two review authors independently screened the titles and abstracts of all identified references for eligibility, and we obtained full papers of potentially relevant trials. Two review authors independently considered these trials for inclusion, assessed included studies for risk of bias, and extracted trial data independently. We resolved disagreements through consultation with a third review author. We performed random-effects meta-regression for each outcome and explored prespecified study characteristics. Main results: Overall, we included 26 studies with 5299 participants (29 comparisons). Participants were primarily male (64.2%). Ten (38.5%) studies included patients with heart failure. We assessed most studies as having low or unclear risk of bias. Sixteen studies (3164 participants) reported interventions to improve enrolment in cardiac rehabilitation, 11 studies (2319 participants) reported interventions to improve adherence to cardiac rehabilitation, and seven studies (1567 participants) reported interventions to increase programme completion. Researchers tested a variety of interventions to increase utilisation of cardiac rehabilitation. In many studies, this consisted of contacts made by a healthcare provider during or shortly after an acute care hospitalisation. Low-quality evidence shows an effect of interventions on increasing programme enrolment (19 comparisons; risk ratio (RR) 1.27, 95% confidence interval (CI) 1.13 to 1.42). Meta-regression revealed that the intervention deliverer (nurse or allied healthcare provider; P = 0.02) and the delivery format (face-to-face; P = 0.01) were influential in increasing enrolment. Low-quality evidence shows interventions to increase adherence were effective (nine comparisons; standardised mean difference (SMD) 0.38, 95% CI 0.20 to 0.55), particularly when they were delivered remotely, such as in home-based programs (SMD 0.56, 95% CI 0.37 to 0.76). Moderate-quality evidence shows interventions to increase programme completion were also effective (eight comparisons; RR 1.13, 95% CI 1.02 to 1.25), but those applied in multi-centre studies were less effective than those given in single-centre studies, leading to questions regarding generalisability. A moderate level of statistical heterogeneity across intervention studies reflects heterogeneity in intervention approaches. There was no evidence of small-study bias for enrolment (insufficient studies to test for this in the other outcomes). With regard to secondary outcomes, no studies reported on harms associated with the interventions. Only two studies reported costs. In terms of equity, trialists tested interventions designed to improve utilisation among women and older patients. Evidence is insufficient for quantitative assessment of whether women-tailored programmes were associated with increased utilisation, and studies that assess motivating women are needed. For older participants, again while quantitative assessment could not be undertaken, peer navigation may improve enrolment. Authors' conclusions: Interventions may increase cardiac rehabilitation enrolment, adherence and completion; however the quality of evidence was low to moderate due to heterogeneity of the interventions used, among other factors. Effects on enrolment were larger in studies targeting healthcare providers, training nurses, or allied healthcare providers to intervene face-to-face; effects on adherence were larger in studies that tested remote interventions. More research is needed, particularly to discover the best ways to increase programme completion.

AIM: to quantify the impact of involving caregivers in self-management interventions on health-related quality of life of patients with heart failure or chronic obstructive pulmonary disease. DESIGN: Systematic review, meta-analysis. DATA SOURCES: Searched: Medline Ebsco, PsycINFO, CINAHL, Embase, Web of Science, the British Library and ProQuest. Search time frame; January 1990-March 2018. REVIEW METHODS: Randomized controlled trials involving caregivers in self-management interventions (≥2 components) compared with usual care for patients with heart failure or chronic obstructive pulmonary disease. A matched sample based on publication year, geographic location and inclusion of an exercise intervention of studies not involving caregivers were identified. Primary outcome of analysis was patient health-related quality of life. RESULTS: Thirteen randomized controlled trials (1,701 participants: 1,439 heart failure; 262 chronic obstructive pulmonary disease) involving caregivers (mean age 59; 58% female) were identified. Reported patient health-related quality of life measures included; Minnesota Living with Heart Failure questionnaire, St. George's respiratory questionnaire and Short-Form-36. Compared with usual care, there was similar magnitude in mean improvement in patient health-related quality of life with self-management interventions in trials involving caregivers (SMD: 0.23, 95% confidence interval: -0.15-0.61) compared with trials without caregivers (SMD: 0.27, 0.08-0.46). CONCLUSION: Within the methodological constraints of this study, our results indicate that involving caregivers in self-management interventions does not result in additional improvement in patient health-related quality of life in heart failure or chronic obstructive pulmonary disease. However, involvement of caregivers in intervention delivery remains an important consideration and key area of research. IMPACT: Greater understanding and awareness is needed of the methodology of caregiver engagement in intervention development and delivery and its impact on patient outcomes.

Despite optimal medical management (OMM), low back pain (LBP) can be disabling, particularly after spinal surgery. Spinal cord stimulation (SCS) is effective in reducing neuropathic leg pain; however, evidence is limited for LBP. This prospective, open-label, parallel-group trial randomized (1:1) failed back surgery syndrome (FBSS) patients with predominant LBP to SCS plus OMM (SCS group) or OMM alone (OMM group) at 28 sites in Europe and the Americas. If trial stimulation was successful, a multicolumn SCS system was implanted. Outcomes were assessed at baseline (before randomization) and at 1, 3, 6, and 12 months after randomization. Patients could change treatment groups at 6 months. The primary outcome was the proportion of patients with ≥50% reduction in LBP (responder) at 6 months. Secondary outcomes included change in pain intensity, functional disability, and health-related quality of life (HRQoL). The results are posted at ClinicalTrials.gov under registration number NCT01697358. In the intent-to-treat analysis, there were more responders in the SCS group than in the OMM group (13.6%, 15/110 vs 4.6%, 5/108, difference 9% with 95% confidence interval 0.6%-17.5%, P = 0.036) at 6 months. The SCS group improved in all secondary outcomes compared with the OMM group. The OMM group only improved in HRQoL. In the SCS group, 17.6% (18/102) experienced SCS-related adverse events through 6 months, with 11.8% (12/102) requiring surgical reintervention. Adding multicolumn SCS to OMM improved pain relief, HRQoL, and function in a traditionally difficult-to-treat population of failed back surgery syndrome patients with predominant LBP. Improvements were sustained at 12 and 24 months.

Combined exercise rehabilitation for chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF) is potentially attractive. Uncertainty remains as to the baseline profiling assessments and outcome measures that should be collected within a programme. Current evidence surrounding outcome measures in cardiac and pulmonary rehabilitation were presented by experts at a stakeholder consensus event and all stakeholders (n = 18) were asked to (1) rank in order of importance a list of categories, (2) prioritise outcome measures and (3) prioritise baseline patient evaluation measures that should be assessed in a combined COPD and CHF rehabilitation programme. The tasks were completed anonymously and related to clinical rehabilitation programmes and associated research. Health-related quality of life, exercise capacity and symptom evaluation were voted as the most important categories to assess for clinical purposes (median rank: 1, 2 and 3 accordingly) and research purposes (median rank; 1, 3 and 4.5 accordingly) within combined exercise rehabilitation. All stakeholders agreed that profiling symptoms at baseline were 'moderately', 'very' or 'extremely' important to assess for clinical and research purposes in combined rehabilitation. Profiling of frailty was ranked of the same importance for clinical purposes in combined rehabilitation. Stakeholders identified a suite of multidisciplinary measures that may be important to assess in a combined COPD and CHF exercise rehabilitation programme.

© 2019 the Cochrane Collaboration. Published by John Wiley. &. Sons, Ltd. This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: to assess the effectiveness and safety of physical activity promotion and exercise training interventions in individuals with congenital heart disease.

Copyright © 2019 the Cochrane Collaboration. Published by John Wiley. &. Sons, Ltd. This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:. To assess the efficacy and costs of psychological interventions (alone, or with CR or pharmacotherapy, or both) in adults who have a diagnosis of CHD, HF or AF compared to no intervention, or treatment as usual, on psychological and clinical outcomes.

BACKGROUND AND AIMS: Patients with moderate-to-severe chronic kidney disease (CKD) are underrepresented in clinical trials of cardiac resynchronization therapy (CRT)-defibrillation (CRT-D) or CRT-pacing (CRT-P). We sought to determine whether outcomes after CRT-D are better than after CRT-P over a wide spectrum of CKD. METHODS AND RESULTS: Clinical events were quantified in relation to preimplant estimated glomerular filtration rate (eGFR) after CRT-D (n = 410 [39.2%]) or CRT-P (n = 636 [60.8%]) implantation. Over a follow-up period of 3.7 years (median, interquartile range: 2.1-5.7), the eGFR 

PURPOSE: to assess the likelihood of persistent postoperative pain (PPP) following reoperation after lumbar surgery and to estimate associated healthcare costs. METHODS: This is a retrospective cohort study using two linked UK databases: Hospital Episode Statistics and UK Clinical Practice Research Datalink. Costs and outcomes associated with reoperation were evaluated over a 2-year postoperative period using multivariate logistic regression for cases who underwent reoperation and controls who did not, based on demographics, index surgery type, smoking status, and pre-index comorbidities using propensity score matching. RESULTS: Risk factors associated with reoperation included younger age and the presence of diabetes with complications or rheumatic disease. The rate of PPP after reoperation was much higher than after index surgery, with 79 of 200 (39.5%; 95% CI 32.5%, 46.5%) participants experiencing ongoing pain compared with 983 of 5022 (19.5%; 95% CI 18.5%, 20.7%) after index surgery. Mean costs in the 2 years following reoperation were £1889 higher (95% CI £2, £3809) than for patients with PPP who did not undergo repeat surgery over an equivalent follow-up period. With the cost of reoperation itself included, the mean cost difference for patients who underwent reoperation compared with matched controls rose to £7221 (95% CI £5273, £9206). CONCLUSIONS: High rates of PPP and associated healthcare costs suggest that returning to the operating room is a complex and challenging decision. Spinal surgeons should review whether the potential benefits of additional surgery are justified when other approaches to managing and relieving chronic pain have demonstrated superior outcomes. These slides can be retrieved under Electronic Supplementary Material.

BACKGROUND: Low back pain (LBP) is a ubiquitous, heterogeneous disorder that affects most people at some point in their lives. The efficient management of LBP remains elusive, with direct and indirect costs attributed to LBP surpassing many other common conditions. An emphasis on a structural basis of LBP often fails to recognize movement, specifically patterns of movement that may provide biomechanical signatures of painful conditions. The primary objective of this registry is to understand the differences in movement patterns among those with LBP and those without pain in a U.S. population sample. METHODS: This ongoing, non-randomized, prospective post-market registry will consist of two groups: patients with LBP, and age and sex-matched controls without LBP. We will seek to recruit 132 subjects in each group. Data collection will take place in two phases: (1) baseline assessment of LBP patients and matched controls; (2) assessment of LBP patients at 6 and 12-months follow up. The primary outcome measure will be differences in movement patterns between those with LBP and those without LBP. Secondary outcomes will include differences in patient reported outcomes including pain, disability and quality of life. DISCUSSION: the findings will help determine if there are meaningful differences in movement patterns between those with and those without LBP. Further, an initial understanding of movement signatures specific to certain subtypes of patients with LBP may be achieved. TRIAL REGISTRATION: the study was registered on the clinicaltrials.gov portal: NCT03001037. Trial retrospectively registered 12/22/2016.

BACKGROUND: the Medtronic Registry for Epilepsy (MORE; Medtronic Inc, Dublin, Ireland) is an open label observational study evaluating the long-term effectiveness, safety, and performance of deep brain stimulation (DBS) of the anterior nucleus of thalamus (ANT) for the treatment of refractory epilepsy. OBJECTIVE: to compare the difference in success rate of placing contacts at ANT-target region (ANT-TR) between transventricular (TV) and extraventricular (EV) lead trajectories in 73 ANT-DBS implants in 17 European centers participating in the MORE registry. METHODS: the success rate of placing contacts at ANT-TR was evaluated using a screening method combining both individual patient imaging information and stereotactic atlas information to identify contacts at ANT-TR. RESULTS: EV lead trajectory was used in 53% of the trajectories. Approximately, 90% of the TV lead trajectories had at least 1 contact at ANT-TR, vs only 71% of the EV lead trajectories. The success rate for placing at least 1 contact at ANT-TR bilaterally was 84% for TV implants and 58% for EV implants (P <. 05; Fisher's exact). No intracranial bleedings were observed, but 1 cortical infarct was reported following EV lead trajectory. CONCLUSION: the results of this registry support the use of TV lead trajectories for ANT-DBS as they have a higher probability in placing contacts at ANT-TR, without appearing to compromise procedural safety. Follow-up data collection is continuing in the MORE registry. These data will provide outcomes associated with TV and EV trajectories.

OBJECTIVE: to assess the experiences of unpaid caregivers providing care to people with heart failure (HF) or chronic obstructive pulmonary disease (COPD) or coronary artery disease (CAD). Design Mixed methods systematic review including qualitative and quantitative studies. Data sources Databases searched: Medline Ebsco, PsycInfo, CINAHL Plus with Full Text, Embase, Web of Science, Ethos: the British Library and ProQuest. Grey literature identified using: Global Dissertations and Theses and Applied Sciences Index and hand searches and citation checking of included references. Search time frame: 1 January 1990 to 30 August 2017. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Inclusion was limited to English language studies in unpaid adult caregivers (>18 years), providing care for patients with HF, COPD or CAD. Studies that considered caregivers for any other diagnoses and studies undertaken in low-income and middle-income countries were excluded. Quality assessment of included studies was conducted by two authors. DATA ANALYSIS/SYNTHESIS: a results-based convergent synthesis was conducted. RESULTS: Searches returned 8026 titles and abstracts. 54 studies-21 qualitative, 32 quantitative and 1 mixed method were included. This totalled 26 453 caregivers who were primarily female (63%), with median age of 62 years. Narrative synthesis yielded six concepts related to caregiver experience: (1) mental health, (2) caregiver role, (3) lifestyle change, (4) support for caregivers, (5) knowledge and (6) relationships. There was a discordance between paradigms regarding emerging concepts. Four concepts emerged from qualitative papers which were not present in quantitative papers: (1) expert by experience, (2) vigilance, (3) shared care and (4) time. CONCLUSION: Caregiving is life altering and complex with significant health implications. Health professionals should support caregivers who in turn can facilitate the recipient to manage their long-term condition. Further longitudinal research exploring the evolution of caregiver experiences over time of patients with chronic cardiopulmonary conditions is required. TRIAL REGISTRATION NUMBER: CRD42016053412.

BACKGROUND: Around 17% of people attending UK cardiac rehabilitation programmes have depression. Optimising psychological wellbeing is a rehabilitation goal, but provision of psychological care is limited. We developed and piloted an Enhanced Psychological Care (EPC) intervention embedded within cardiac rehabilitation, aiming to test key areas of uncertainty to inform the design of a definitive randomised controlled trial (RCT) and economic evaluation. METHODS: an external pilot randomised controlled trial (RCT) randomised eight cardiac rehabilitation teams (clusters) to either usual care of cardiac rehabilitation provision (UC), or EPC in addition to UC. EPC comprised mental health care coordination and patient-led behavioural activation with nurse support. Adults eligible for cardiac rehabilitation following an acute coronary syndrome and identified with new-onset depressive symptoms during an initial nurse assessment were eligible. Measures were performed at baseline and 5- and 8-month follow-ups and compared between EPC and UC. Team and participant recruitment and retention rates, and participant outcomes (clinical events, depression, anxiety, health-related quality of life, patient experiences, and resource use) were assessed. RESULTS: Eight out of twenty teams were recruited and randomised. of 614 patients screened, 55 were eligible and 29 took part (5%, 95% CI 3 to 7% of those screened), with 15 patient participants cluster randomised to EPC and 14 to UC. Nurse records revealed that 8/15 participants received the maximum number of EPC sessions offered; and 4/15 received no sessions. Seven out of fifteen EPC participants were referred to another NHS psychological service compared to none in UC. We followed up 27/29 participants at 5 months and 17/21 at 8 months. The mean difference (EPC minus UC) in depressive symptoms (Beck Depression Inventory) at follow-up (adjusting for baseline score) was 1.7 (95% CI - 3.8 to 7.3; N = 26) at 5 months and 4.4 (95% CI - 1.4 to 10.2; N = 17) at 8 months. DISCUSSION: While valued by patients and nurses, organisational and workload constraints are significant barriers to EPC implementation. There remains a need to develop and test new models of psychological care within cardiac rehabilitation. Our study offers important data to inform the design of future trials of similar interventions. TRIAL REGISTRATION: ISRCTN34701576. Registered on 29 May 2014. Funding details: UK NIHR HTA Programme (project 12/189/09).

OBJECTIVE: to undertake a systematic review and meta-analysis to assess the impact of cardiac rehabilitation (CR) on physical activity (PA) levels of patients with heart disease and the methodological quality of these studies. METHODS: Databases (MEDLINE, EMBASE, CENTRAL, CINAHL, PsychINFO and SportDiscus) were searched without language restriction from inception to January 2017 for randomised controlled trials (RCTs) comparing CR to usual care control in adults with heart failure (HF) or coronary heart disease (CHD) and measuring PA subjectively or objectively. The direction of PA difference between CR and control was summarised using vote counting (ie, counting the positive, negative and non-significant results) and meta-analysis. RESULTS: Forty RCTs, (6480 patients: 5825 CHD, 655 HF) were included with 26% (38/145) PA results showing a statistically significant improvement in PA levels with CR compared with control. This pattern of results appeared consistent regardless of type of CR intervention (comprehensive vs exercise-only) or PA measurement (objective vs subjective). Meta-analysis showed PA increases in the metrics of steps/day (1423, 95% CI 757.07 to 2089.43, p

Objectives: Transcatheter aortic valve implantation (TAVI) is often undertaken in the oldest frailest cohort of patients undergoing cardiac interventions. We plan to investigate the potential benefit of cardiac rehabilitation (CR) in this vulnerable population. Design: We undertook a pilot randomised trial of CR following TAVI to inform the feasibility and design of a future randomised clinical trial (RCT). Participants: We screened patients undergoing TAVI at a single institution between June 2016 and February 2017. Interventions: Participants were randomised post-TAVI to standard of care (control group) or standard of care plus exercise-based CR (intervention group). Outcomes: We assessed recruitment and attrition rates, uptake of CR, and explored changes in 6-min walk test, Nottingham Activities of Daily Living, Fried and Edmonton Frailty scores and Hospital Anxiety and Depression Score, from baseline (30 days post TAVI) to 3 and 6 months post randomisation. We also undertook a parallel study to assess the use of the Kansas City Cardiomyopathy Questionnaire (KCCQ) in the post-TAVI population. Results: of 82 patients screened, 52 met the inclusion criteria and 27 were recruited (3 patients/month). In the intervention group, 10/13 (77%) completed the prescribed course of 6 sessions of CR (mean number of sessions attended 7.5, SD 4.25) over 6 weeks. At 6 months, all participants were retained for follow-up. There was apparent improvement in outcome scores at 3 and 6 months in control and CR groups. There were no recorded adverse events associated with the intervention of CR. The KCCQ was well accepted in 38 post-TAVI patients: mean summary score 72.6 (SD 22.6). Conclusions: We have demonstrated the feasibility of recruiting post-TAVI patients into a randomised trial of CR. We will use the findings of this pilot trial to design a fully powered multicentre RCT to inform the provision of CR and support guideline development to optimise health-related quality of life outcomes in this vulnerable population. Retrospectively registered 3rd October 2016 clinicaltrials.gov NCT02921880. Trial registration: Clinicaltrials.Gov identifier NCT02921880.

BACKGROUND: Standardised home-based pulmonary rehabilitation (PR) programmes offer an alternative model to centre-based supervised PR for which uptake is currently poor. We determined if a structured home-based unsupervised PR programme was non-inferior to supervised centre-based PR for participants with COPD. METHODS: a total of 287 participants with COPD who were referred to PR (187 male, mean (SD) age 68 (8.86) years, FEV1% predicted 48.34 (17.92)) were recruited. They were randomised to either centre-based PR or a structured unsupervised home-based PR programme including a hospital visit with a healthcare professional trained in motivational interviewing, a self-management manual and two telephone calls. Fifty-eight (20%) withdrew from the centre-based group and 51 (18%) from the home group. The primary outcome was dyspnoea domain in the chronic respiratory disease questionnaire (Chronic Respiratory Questionnaire Self-Report; CRQ-SR) at 7 weeks. Measures were taken blinded. We undertook a modified intention-to-treat (mITT) complete case analysis, comparing groups according to original random allocation and with complete data at follow-up. The non-inferiority margin was 0.5 units. RESULTS: There was evidence of significant gains in CRQ-dyspnoea at 7 weeks in both home and centre-based groups. There was inconclusive evidence that home-based PR was non-inferior to PR in dyspnoea (mean group difference, mITT: -0.24, 95% CI -0.61 to 0.12, p=0.18), favouring the centre group at 7 weeks. CONCLUSIONS: the standardised home-based programme provides benefits in dyspnoea. Further evidence is needed to definitively determine if the health benefits of the standardised home-based programme are non-inferior or equivalent to supervised centre-based rehabilitation. TRIAL REGISTRATION NUMBER: ISRCTN81189044.

BACKGROUND: the U.S. Food and Drug Administration (FDA) often approves new drugs based on trials that use surrogate markers for endpoints, which involve certain trade-offs and may risk making erroneous inferences about the medical product's actual clinical effect. This study aims to compare the treatment effects among pivotal trials supporting FDA approval of novel therapeutics based on surrogate markers of disease with those observed among postapproval trials for the same indication. METHODS: We searched Drugs@FDA and PubMed to identify published randomized superiority design pivotal trials for all novel drugs initially approved by the FDA between 2005 and 2012 based on surrogate markers as primary endpoints and published postapproval trials using the same surrogate markers or patient-relevant outcomes as endpoints. Summary ratio of odds ratios (RORs) and difference between standardized mean differences (dSMDs) were used to quantify the average difference in treatment effects between pivotal and matched postapproval trials. RESULTS: Between 2005 and 2012, the FDA approved 88 novel drugs for 90 indications based on one or multiple pivotal trials using surrogate markers of disease. of these, 27 novel drugs for 27 indications were approved based on pivotal trials using surrogate markers as primary endpoints that could be matched to at least one postapproval trial, for a total of 43 matches. For nine (75.0%) of the 12 matches using the same non-continuous surrogate markers as trial endpoints, pivotal trials had larger treatment effects than postapproval trials. On average, treatment effects were 50% higher (more beneficial) in the pivotal than the postapproval trials (ROR 1.5; 95% confidence interval CI 1.01-2.23). For 17 (54.8%) of the 31 matches using the same continuous surrogate markers as trial endpoints, pivotal trials had larger treatment effects than the postapproval trials. On average, there was no difference in treatment effects between pivotal and postapproval trials (dSMDs 0.01; 95% CI -0.15-0.16). CONCLUSIONS: Many postapproval drug trials are not directly comparable to previously published pivotal trials, particularly with respect to endpoint selection. Although treatment effects from pivotal trials supporting FDA approval of novel therapeutics based on non-continuous surrogate markers of disease are often larger than those observed among postapproval trials using surrogate markers as trial endpoints, there is no evidence of difference between pivotal and postapproval trials using continuous surrogate markers.

BACKGROUND: the TRIAL-STIM Study aims to assess the diagnostic performance, clinical outcomes and cost-effectiveness of a screening trial prior to full implantation of a spinal cord stimulation (SCS) device. METHODS/DESIGN: the TRIAL-STIM Study is a superiority, parallel-group, three-centre, randomised controlled trial in patients with chronic neuropathic pain with a nested qualitative study and economic evaluation. The study will take place in three UK centres: South Tees Hospitals NHS Foundation Trust (The James Cook University Hospital); Basildon and Thurrock University Hospitals NHS Foundation Trust; and Leeds Teaching Hospitals NHS Trust. A total of 100 adults undergoing SCS implantation for the treatment of neuropathy will be included. Subjects will be recruited from the outpatient clinics of the three participating sites and randomised to undergo a screening trial prior to SCS implant or an implantation-only strategy in a 1:1 ratio. Allocation will be stratified by centre and minimised on patient age (≥ 65 or 

© 2018 the Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license Background Although childhood overweight and obesity prevalence has increased substantially worldwide in the past three decades, scarce evidence exists for effective preventive strategies. We aimed to establish whether a school-based intervention for children aged 9–10 years would prevent excessive weight gain after 24 months. Methods This pragmatic cluster randomised controlled trial of the Healthy Lifestyles Programme (HeLP), a school-based obesity prevention intervention, was done in 32 schools in southwest England. All state-run primary and junior schools in Devon and Plymouth (UK) with enough pupils for at least one year-5 class were eligible. Schools were assigned (1:1) using a computer-generated sequence to either intervention or control, stratified by the number of year-5 classes (one vs more than one) and the proportion of children eligible for free school meals (

BACKGROUND: Around 19% of people screened by UK cardiac rehabilitation programmes report having moderate or severe symptoms of depression. These individuals are at an increased risk of cardiac mortality and morbidity, reduced quality of life and increased use of health resources compared with their non-depressed counterparts. Maximising psychological health is a goal of cardiac rehabilitation, but psychological care is patchy. OBJECTIVE(S): to examine the feasibility and acceptability of embedding enhanced psychological care (EPC) within cardiac rehabilitation, we tested the feasibility of developing/implementing EPC and documented the key uncertainties associated with undertaking a definitive evaluation. DESIGN: a two-stage multimethods study; a feasibility study and a qualitative evaluation, followed by an external pilot cluster randomised controlled trial (RCT) with a nested qualitative study. SETTING: UK comprehensive cardiac rehabilitation teams. PARTICIPANTS: Adults eligible for cardiac rehabilitation following an acute coronary syndrome with new-onset depressive symptoms on initial nurse assessment. Patients who had received treatment for depression in the preceding 6 months were excluded. INTERVENTIONS: the EPC intervention comprised nurse-led mental health-care co-ordination and behavioural activation within cardiac rehabilitation. The comparator was usual cardiac rehabilitation care. MAIN OUTCOME MEASURES: Measures at baseline, and at the 5- (feasibility and pilot) and 8-month follow-ups (pilot only). Process measures related to cardiac team and patient recruitment, and participant retention. Outcomes included depressive symptoms, cardiac mortality and morbidity, anxiety, health-related quality of life and service resource use. Interviews explored participant and nurses' views and experiences. RESULTS: Between September 2014 and May 2015, five nurses from four teams recruited participants into the feasibility study. of the 203 patients screened, 30 were eligible and nine took part (the target was 20 participants). At interview, participants and nurses gave valuable insights into the EPC intervention design and delivery. Although acceptable, the EPC delivery was challenging for nurses (e.g. the ability to allocate sufficient time within existing workloads) and the intervention was modified accordingly. Between December 2014 and February 2015, 8 out of 20 teams approached agreed to participate in the pilot RCT [five were randomised to the EPC arm and three were randomised to the usual-care (UC) arm]. of the 614 patients screened, 55 were eligible and 29 took part (the target was 43 participants). At baseline, the trial arms were well matched for sex and ethnicity, although the EPC arm participants were younger, from more deprived areas and had higher depression scores than the UC participants. A total of 27 out of 29 participants were followed up at 5 months. Interviews with 18 participants (12 in the EPC arm and six in the UC arm) and seven nurses who delivered EPC identified that both groups acknowledged the importance of receiving psychological support embedded within routine cardiac rehabilitation. For those experiencing/delivering EPC, the intervention was broadly acceptable, albeit challenging to deliver within existing care. LIMITATIONS: Both the feasibility and the pilot studies encountered significant challenges in recruiting patients, which limited the power of the pilot study analyses. CONCLUSIONS: Cardiac rehabilitation nurses can be trained to deliver EPC. Although valued by both patients and nurses, organisational and workload constraints were significant barriers to implementation in participating teams, suggesting that future research may require a modified approach to intervention delivery within current service arrangements. We obtained important data informing definitive research regarding participant recruitment and retention, and optimal methods of data collection. FUTURE RESEARCH: Consideration should be given to the delivery of EPC by dedicated mental health practitioners, working closely with cardiac rehabilitation services. TRIAL REGISTRATION: Current Controlled Trials ISRCTN34701576. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 30. See the NIHR Journals Library website for further project information.

INTRODUCTION: the 'Engager' programme is a 'through-the-gate' intervention designed to support prisoners with common mental health problems as they transition from prison back into the community. The trial will evaluate the clinical and cost-effectiveness of the Engager intervention. METHODS AND ANALYSIS: the study is a parallel two-group randomised controlled trial with 1:1 individual allocation to either: (a) the Engager intervention plus standard care (intervention group) or (b) standard care alone (control group) across two investigation centres (South West and North West of England). Two hundred and eighty prisoners meeting eligibility criteria will take part. Engager is a person-centred complex intervention delivered by practitioners and aimed at addressing offenders' mental health and social care needs. It comprises one-to-one support for participants prior to release from prison and for up to 20 weeks postrelease. The primary outcome is change in psychological distress measured by the Clinical Outcomes in Routine Evaluation-Outcome Measure at 6 months postrelease. Secondary outcomes include: assessment of subjective met/unmet need, drug and alcohol use, health-related quality of life and well-being-related quality of life measured at 3, 6 and 12 months postrelease; change in objective social domains, drug and alcohol dependence, service utilisation and perceived helpfulness of services and change in psychological constructs related to desistence at 6 and 12 months postrelease; and recidivism at 12 months postrelease. A process evaluation will assess fidelity of intervention delivery, test hypothesised mechanisms of action and look for unintended consequences. An economic evaluation will estimate the cost-effectiveness. ETHICS AND DISSEMINATION: This study has been approved by the Wales Research Ethics Committee 3 (ref: 15/WA/0314) and the National Offender Management Service (ref: 2015-283). Findings will be disseminated to commissioners, clinicians and service users via papers and presentations. TRIAL REGISTRATION NUMBER: ISRCTN11707331; Pre-results.

BACKGROUND: a previous Cochrane review has shown that exercise-based cardiac rehabilitation (CR) can benefit myocardial infarction and post-revascularisation patients. However, the impact on stable angina remains unclear and guidance is inconsistent. Whilst recommended in the guidelines of American College of Cardiology/American Heart Association and the European Society of Cardiology, in the UK the National Institute for Health and Care Excellence (NICE) states that there is "no evidence to suggest that CR is clinically or cost-effective for managing stable angina". OBJECTIVES: to assess the effects of exercise-based CR compared to usual care for adults with stable angina. SEARCH METHODS: We updated searches from the previous Cochrane review 'Exercise-based cardiac rehabilitation for patients with coronary heart disease' by searching the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, DARE, CINAHL and Web of Science on 2 October 2017. We searched two trials registers, and performed reference checking and forward-citation searching of all primary studies and review articles, to identify additional studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) with a follow-up period of at least six months, which compared structured exercise-based CR with usual care for people with stable angina. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the risk of bias and extracted data according to the Cochrane Handbook for Systematic Reviews of Interventions. Two review authors also independently assessed the quality of the evidence using GRADE principles and we presented this information in a 'Summary of findings' table. MAIN RESULTS: Seven studies (581 participants) met our inclusion criteria. Trials had an intervention length of 6 weeks to 12 months and follow-up length of 6 to 12 months. The comparison group in all trials was usual care (without any form of structured exercise training or advice) or a no-exercise comparator. The mean age of participants within the trials ranged from 50 to 66 years, the majority of participants being male (range: 74% to 100%). In terms of risk of bias, the majority of studies were unclear about their generation of the randomisation sequence and concealment processes. One study was at high risk of detection bias as it did not blind its participants or outcome assessors, and two studies had a high risk of attrition bias due to the numbers of participants lost to follow-up. Two trials were at high risk of outcome reporting bias. Given the high risk of bias, small number of trials and participants, and concerns about applicability, we downgraded our assessments of the quality of the evidence using the GRADE tool.Due to the very low-quality of the evidence base, we are uncertain about the effect of exercise-based CR on all-cause mortality (risk ratio (RR) 1.01, 95% confidence interval (CI) 0.18 to 5.67; 195 participants; 3 studies; very low-quality evidence), acute myocardial infarction (RR 0.33, 95% CI 0.07 to 1.63; 254 participants; 3 studies; very low-quality evidence) and cardiovascular-related hospital admissions (RR 0.14, 95% CI 0.02 to 1.1; 101 participants; 1 study; very low-quality evidence). We found low-quality evidence that exercise-based CR may result in a small improvement in exercise capacity compared to control (standardised mean difference (SMD) 0.45, 95% CI 0.20 to 0.70; 267 participants; 5 studies, low-quality evidence). We were unable to draw conclusions about the impact of exercise-based CR on quality of life (angina frequency and emotional health-related quality-of-life score) and CR-related adverse events (e.g. skeletomuscular injury, cardiac arrhythmia), due to the very low quality of evidence. No data were reported on return to work. AUTHORS' CONCLUSIONS: Due to the small number of trials and their small size, potential risk of bias and concerns about imprecision and lack of applicability, we are uncertain of the effects of exercise-based CR compared to control on mortality, morbidity, cardiovascular hospital admissions, adverse events, return to work and health-related quality of life in people with stable angina. Low-quality evidence indicates that exercise-based CR may result in a small increase in exercise capacity compared to usual care. High-quality, well-reported randomised trials are needed to assess the benefits and harms of exercise-based CR for adults with stable angina. Such trials need to collect patient-relevant outcomes, including clinical events and health-related quality of life. They should also assess cost-effectiveness, and recruit participants that are reflective of the real-world population of people with angina.

© Author(s) (or their employer(s)) 2018. Objective the aim of this study was to undertake a contemporary review of the impact of exercise-based cardiac rehabilitation (CR) targeted at patients with atrial fibrillation (AF). Methods We conducted searches of PubMED, EMBASE and the Cochrane Library of Controlled Trials (up until 30 November 2017) using key terms related to exercise-based CR and AF. Randomised and non-randomised controlled trials were included if they compared the effects of an exercise-based CR intervention to a no exercise or usual care control group. Meta-analyses of outcomes were conducted where appropriate. Results the nine randomised trials included 959 (483 exercise-based CR vs 476 controls) patients with various types of AF. Compared with control, pooled analysis showed no difference in all-cause mortality (risk ratio (RR) 1.08, 95% CI 0.77 to 1.53, p=0.64) following exercise-based CR. However, there were improvements in health-related quality of life (mean SF-36 mental component score (MCS): 4.00, 95% CI 0.26 to 7.74; p=0.04 and mean SF-36 physical component score: 1.82, 95% CI 0.06 to 3.59; p=0.04) and exercise capacity (mean peak VO 2 : 1.59 ml/kg/min, 95% CI 0.11 to 3.08; p=0.04; mean 6 min walk test: 46.9 m, 95% CI 26.4 to 67.4; p

OBJECTIVES: to assess the feasibility of delivering and evaluating a weight management (WM) programme for overweight patients with a family history (FH) of breast cancer (BC) or colorectal cancer (CRC). STUDY DESIGN: a two-arm (intervention vs usual care) randomised controlled trial. SETTING: National Health Service (NHS) Tayside and NHS Grampian. PARTICIPANTS: People with a FH of BC or CRC aged≥18 years and body mass index of ≥25 kg/m2 referred to NHS genetic services. INTERVENTION: Participants were randomised to a control (lifestyle booklet) or 12-week intervention arm where they were given one face-to-face counselling session, four telephone consultations and web-based support. A goal of 5% reduction in body weight was set, and a personalised diet and physical activity (PA) programme was provided. Behavioural change techniques (motivational interviewing, action and coping plans and implementation intentions) were used. PRIMARY OUTCOME: Feasibility measures: recruitment, programme implementation, fidelity measures, achieved measurements and retention, participant satisfaction assessed by questionnaire and qualitative interviews. SECONDARY OUTCOMES: Measured changes in weight and PA and reported diet and psychosocial measures between baseline and 12-week follow-up. RESULTS: of 480 patients approached, 196 (41%) expressed interest in the study, and of those, 78 (40%) patients were randomised. Implementation of the programme was challenging within the time allotted and fidelity to the intervention modest (62%). Qualitative findings indicated the programme was well received. Questionnaires and anthropometric data were completed by >98%. Accelerometer data were attained by 84% and 54% at baseline and follow-up, respectively. Retention at 12 weeks was 76%. Overall, 36% of the intervention group (vs 0% in control) achieved 5% weight loss. Favourable increases in PA and reduction in dietary fat were also reported. CONCLUSIONS: a lifestyle programme for people with a family history of cancer is feasible to conduct and acceptable to participants, and indicative results suggest favourable outcomes. TRIAL REGISTRATION NUMBER: ISRCTN13123470; Pre-results.

Aims: Common methodologies for analysis of analogous data sets are needed for international comparisons of treatment and outcomes. This study tests using administrative hospital discharge (HD) databases in five European countries to investigate variation/trends in pacemaker (PM) and implantable cardioverter defibrillator (ICD) implant rates in terms of patient characteristics/management, device subtype, and initial implantation vs. replacement, and compares findings with existing literature and European Heart Rhythm Association (EHRA) reports. Methods and results: HD databases from 2008 to 2012 in Austria, England, Germany, Italy and Slovenia were interrogated to extract admissions (without patient identification) associated with PM and ICD implants and replacements, using direct cross-referencing of procedure codes and common methodology to compare aggregate data. 1 338 199 records revealed 212 952 PM and 62 567 ICD procedures/year on average for a 204.4 million combined population, a crude implant rate of about 104/100 000 inhabitants for PMs and 30.6 for ICDs. The first implant/replacement rate ratios were 81/24 (PMs) and 25/7 (ICDs). Rates have increased, with cardiac resynchronization therapy (CRT) subtypes for both devices rising dramatically. Significant between- and within-country variation persists in lengths of stay and rates (Germany highest, Slovenia lowest). Adjusting for age lessened differences for PM rates, scarcely affected ICDs. Male/female ratios remained stable at 56/44% (PMs) and 79/21% (ICDs). About 90% of patients were discharged to home; 85-100% were inpatient admissions. Conclusion: to aid in policymaking and track outcomes, HD administrative data provides a reliable, relatively cheap, methodology for tracking implant rates for PMs and ICDs across countries, as comparisons to EHRA data and the literature indicated.

AIMS: to undertake an individual patient data (IPD) meta-analysis to assess the impact of exercise-based cardiac rehabilitation (ExCR) in patients with heart failure (HF) on mortality and hospitalisation, and differential effects of ExCR according to patient characteristics: age, sex, ethnicity, New York Heart Association functional class, ischaemic aetiology, ejection fraction, and exercise capacity. METHODS AND RESULTS: Randomised trials of exercise training for at least 3 weeks compared with no exercise control with 6-month follow-up or longer, providing IPD time to event on mortality or hospitalisation (all-cause or HF-specific). IPD were combined into a single dataset. We used Cox proportional hazards models to investigate the effect of ExCR and the interactions between ExCR and participant characteristics. We used both two-stage random effects and one-stage fixed effect models. IPD were obtained from 18 trials including 3912 patients with HF with reduced ejection fraction. Compared to control, there was no statistically significant difference in pooled time to event estimates in favour of ExCR although confidence intervals (CIs) were wide [all-cause mortality: hazard ratio (HR) 0.83, 95% CI 0.67-1.04; HF-specific mortality: HR 0.84, 95% CI 0.49-1.46; all-cause hospitalisation: HR 0.90, 95% CI 0.76-1.06; and HF-specific hospitalisation: HR 0.98, 95% CI 0.72-1.35]. No strong evidence was found of differential intervention effects across patient characteristics. CONCLUSION: Exercise-based cardiac rehabilitation did not have a significant effect on the risk of mortality and hospitalisation in HF with reduced ejection fraction. However, uncertainty around effect estimates precludes drawing definitive conclusions.

INTRODUCTION: Physical activity is recommended for improving health among people with common chronic conditions such as obesity, diabetes, hypertension, osteoarthritis and low mood. One approach to promote physical activity is via primary care exercise referral schemes (ERS). However, there is limited support for the effectiveness of ERS for increasing long-term physical activity and additional interventions are needed to help patients overcome barriers to ERS uptake and adherence.This study aims to determine whether augmenting usual ERS with web-based behavioural support, based on the LifeGuide platform, will increase long-term physical activity for patients with chronic physical and mental health conditions, and is cost-effective. METHODS AND ANALYSIS: a multicentre parallel two-group randomised controlled trial with 1:1 individual allocation to usual ERS alone (control) or usual ERS plus web-based behavioural support (intervention) with parallel economic and mixed methods process evaluations. Participants are low active adults with obesity, diabetes, hypertension, osteoarthritis or a history of depression, referred to an ERS from primary care in the UK.The primary outcome measure is the number of minutes of moderate-to-vigorous physical activity (MVPA) in ≥10 min bouts measured by accelerometer over 1 week at 12 months.We plan to recruit 413 participants, with 88% power at a two-sided alpha of 5%, assuming 20% attrition, to demonstrate a between-group difference of 36-39 min of MVPA per week at 12 months. An improvement of this magnitude represents an important change in physical activity, particularly for inactive participants with chronic conditions. ETHICS AND DISSEMINATION: Approved by North West Preston NHS Research Ethics Committee (15/NW/0347). Dissemination will include publication of findings for the stated outcomes, parallel process evaluation and economic evaluation in peer-reviewed journals.Results will be disseminated to ERS services, primary healthcare providers and trial participants. TRIAL REGISTRATION NUMBER: ISRCTN15644451; Pre-results.

BACKGROUND: Rates of common mental health problems are much higher in prison populations, but access to primary care mental health support falls short of community equivalence. Discontinuity of care on release is the norm and is further complicated by substance use and a range of social problems, e.g. homelessness. To address these problems, we worked with criminal justice, third sector social inclusion services, health services and people with lived experiences (peer researchers), to develop a complex collaborative care intervention aimed at supporting men with common mental health problems near to and following release from prison. This paper describes an external pilot trial to test the feasibility of a full randomised controlled trial. METHODS: Eligible individuals with 4 to 16 weeks left to serve were screened to assess for common mental health problems. Participants were then randomised at a ratio of 2:1 allocation to ENGAGER plus standard care (intervention) or standard care alone (treatment as usual). Participants were followed up at 1 and 3 months' post release. Success criteria for this pilot trial were to meet the recruitment target sample size of 60 participants, to follow up at least 50% of participants at 3 months' post release from prison, and to deliver the ENGAGER intervention. Estimates of recruitment and retention rates and 95% confidence intervals (CIs) are reported. Descriptive analyses included summaries (percentages or means) for participant demographics, and baseline characteristics are reported. RESULTS: Recruitment target was met with 60 participants randomised in 9 months. The average retention rates were 73% at 1 month [95% CI 61 to 83] and 47% at 3 months follow-up [95% CI 35 to 59]. Ninety percent of participants allocated to the intervention successfully engaged with a practitioner before release and 70% engaged following release. CONCLUSIONS: This pilot confirms the feasibility of conducting a randomised trial for prison leavers with common mental health problems. Based on this pilot study and some minor changes to the trial design and intervention, a full two-centre randomised trial assessing the clinical and cost-effectiveness of the ENGAGER intervention is currently underway.

Background Although psychological interventions are recommended for the management of coronary heart disease (CHD), there remains considerable uncertainty regarding their effectiveness. Design Systematic review and meta-analysis of randomised controlled trials (RCTs) of psychological interventions for CHD. Methods the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL and PsycINFO were searched to April 2016. Retrieved papers, systematic reviews and trial registries were hand-searched. We included RCTs with at least 6 months of follow-up, comparing the direct effects of psychological interventions to usual care for patients following myocardial infarction or revascularisation or with a diagnosis of angina pectoris or CHD defined by angiography. Two authors screened titles for inclusion, extracted data and assessed risk of bias. Studies were pooled using random effects meta-analysis and meta-regression was used to explore study-level predictors. Results Thirty-five studies with 10,703 participants (median follow-up 12 months) were included. Psychological interventions led to a reduction in cardiovascular mortality (rfcelative risk 0.79, 95% confidence interval [CI] 0.63 to 0.98), although no effects were observed for total mortality, myocardial infarction or revascularisation. Psychological interventions improved depressive symptoms (standardised mean difference [SMD] -0.27, 95% CI -0.39 to -0.15), anxiety (SMD -0.24, 95% CI -0.38 to -0.09) and stress (SMD -0.56, 95% CI -0.88 to -0.24) compared with controls. Conclusions We found that psychological intervention improved psychological symptoms and reduced cardiac mortality for people with CHD. However, there remains considerable uncertainty regarding the magnitude of these effects and the specific techniques most likely to benefit people with different presentations of CHD.

BACKGROUND: There is currently no robust long-term data on costs of treating patients with Parkinson's disease. The objective of this study was to report levels of health care utilization and associated costs in the 10 years after diagnosis among PD patients in the United Kingdom. METHODS: We undertook a retrospective population-based cohort study using linked data from the UK Clinical Practice Research Datalink and Hospital Episode Statistics databases. Total health care costs of PD patients were compared with those of a control group of patients without PD selected using 1:1 propensity score matching based on age, sex, and comorbidity. RESULTS: Between 1994 and 2013, 7271 PD patients who met study inclusion criteria were identified in linked Clinical Practice Research Datalink-Hospital Episode Statistics; 7060 were matched with controls. The mean annual health care cost difference (at 2013 costs) between PD patients and controls was £2471 (US$3716) per patient in the first year postdiagnosis (P 

BACKGROUND: in bipolar spectrum disorder, some individuals experience ongoing, frequent fluctuations in mood outside of affective episodes. There are currently no evidence-based psychological interventions designed to address this. This feasibility study is a phase II evaluation of a dialectical behavioural therapy-informed approach (Therapy for Inter-episode mood Variability in Bipolar [ThrIVe-B]). It seeks to examine the feasibility and acceptability of a future definitive trial evaluating the clinical and cost effectiveness of the ThrIVe-B programme. METHODS/DESIGN: Patients will be randomised 1:1 to either treatment as usual only (control arm) or the ThrIVe-B intervention plus treatment as usual (intervention arm). Follow-up points will be at 3, 6, 9 and 15 months after baseline, with 9 months as the primary end point for the candidate primary outcome measures. We aim to recruit 48 individuals meeting diagnostic criteria for a bipolar spectrum disorder and reporting frequent mood swings outside of acute episodes, through primary and secondary care services and self-referral. To evaluate feasibility and acceptability, we will examine recruitment and retention rates, completion rates for study measures and feedback from participants on their experience of study participation and therapy. DISCUSSION: Proceeding to a definitive trial will be indicated if the following criteria are met: (1) trial participation does not lead to serious negative consequences for our participants; (2) any serious concerns about the acceptability and feasibility of the trial procedures can be rectified prior to a definitive trial; (3) follow-up data at 9 months are available for at least 60% of participants; (4) at least 60% of patients in the ThrIVe-B arm complete treatment. TRIAL REGISTRATION: ISRCTN, ISRCTN54234300. Registered on 20 July 2017.

BACKGROUND: Following up released prisoners is demanding, particularly for those prisoners with mental health problems, for whom stigma and chaotic lifestyles are problematic. Measurement of mental health outcomes after release is challenging. To evaluate mental healthcare for offender populations, using high-quality randomised controlled trials, evidenced-based methods must be developed to engage them while in custody, to locate and re-interview them after release, and to collect potentially stigmatising mental health outcomes data. METHODS: We developed an initial theoretical model and operational procedures for collecting baseline and follow-up data informed by a literature search, focus groups, and case studies. Male prisoners from five prisons in two sites were invited to participate. The inclusion criteria included individuals who were above threshold on nine-item Patient Health Questionnaire, seven-item Generalized Anxiety Disorder, or post-traumatic stress disorder scales, or who had reported mental health problems in the past 2 years or had been assessed with a likely personality disorder. Potential participants were interviewed to generate baseline data and were re-contacted before their release. We then contacted them for a follow-up interview, which included repeating the earlier data collection measures 2-8 weeks after release. A qualitative formative process evaluation produced and refined a model procedure for the recruitment and retention of male prison leavers in trials, identified the mechanisms which promoted engagement and retention, and mapped these against a theoretical behaviour change model. RESULTS: We developed a flexible procedure which was successful in recruiting male prison leavers to a pilot trial: 185/243 (76%, 95% confidence interval (CI) 70-81%) of those approached agreed to participate. We also retained 63% (95% CI 54-71%) of those eligible to participate in a follow-up interview 2-8 weeks after release. Mental health outcomes data was collected at both these time points. CONCLUSIONS: it is possible to design acceptable procedures to achieve sustained engagement critical for delivering and evaluating interventions in prison and in the community and to collect mental health outcomes data. These procedures may reduce attrition bias in future randomised controlled trials of mental health interventions for prison leavers. This procedure has been replicated and successfully delivered in a subsequent pilot trial and a definitive randomised controlled trial.

© 2018 Objectives: This study sought to validate exercise capacity (EC) as a surrogate for mortality, hospitalization, and health-related quality of life (HRQOL). Background: EC is often used as a primary outcome in exercise-based cardiac rehabilitation (CR) trials of heart failure (HF) via direct cardiorespiratory assessment of maximum oxygen uptake (VO2peak) or through submaximal tests, such as the 6-min walk test (6MWT). Methods: After a systematic review, 31 randomized trials of exercise-based CR compared with no exercise control (4,784 HF patients) were included. Outcomes were pooled using random effects meta-analyses, and inverse variance weighted linear regression equations were fitted to estimate the relationship between the CR on EC and all-cause mortality, hospitalization, and HRQOL. Spearman correlation coefficient (ρ), R2 at trial level, and surrogate threshold effect (STE) were calculated. STE represents the intercept of the prediction band of the regression line with null effect on the final outcome. Results: Exercise-based CR is associated with positive effects on EC measured through VO2peak (+3.10 ml/kg/min; 95% confidence interval [CI]: 2.01 to 4.20) or 6MWT (+41.15 m; 95% CI: 16.68 to 65.63) compared to control. The analyses showed a low level of association between improvements in EC (VO2peak or 6MWT) and mortality and hospitalization. Moderate levels of correlation between EC with HRQOL were seen (e.g. R2

Evaluation of clinical effectiveness of medical devices differs in some aspects from the evaluation of pharmaceuticals. One of the main challenges identified is lack of robust evidence and a will to make use of experimental and observational studies (OSs) in quantitative evidence synthesis accounting for internal and external biases. Using a case study of total hip replacement to compare the risk of revision of cemented and uncemented implant fixation modalities, we pooled treatment effect estimates from OS and RCTs, and simplified existing methods for bias-adjusted evidence synthesis to enhance practical application. We performed an elicitation exercise using methodological and clinical experts to determine the strength of beliefs about the magnitude of internal and external bias affecting estimates of treatment effect. We incorporated the bias-adjusted treatment effects into a generalized evidence synthesis, calculating both frequentist and Bayesian statistical models. We estimated relative risks as summary effect estimates with 95% confidence/credibility intervals to capture uncertainty. When we compared alternative approaches to synthesizing evidence, we found that the pooled effect size strongly depended on the inclusion of observational data as well as on the use bias-adjusted estimates. We demonstrated the feasibility of using observational studies in meta-analyses to complement RCTs and incorporate evidence from a wider spectrum of clinically relevant studies and healthcare settings. To ensure internal validity, OS data require sufficient correction for confounding and selection bias, either through study design and primary analysis, or by applying post-hoc bias adjustments to the results. © 2017 the Authors. Health Economics published by John Wiley & Sons, Ltd.

INTRODUCTION: Individual cohort studies in various populations and study-level meta-analyses have shown interarm differences (IAD) in blood pressure to be associated with increased cardiovascular and all-cause mortality. However, key questions remain, such as follows: (1) What is the additional contribution of IAD to prognostic risk estimation for cardiovascular and all-cause mortality? (2) What is the minimum cut-off value for IAD that defines elevated risk? (3) is there a prognostic value of IAD and do different methods of IAD measurement impact on the prognostic value of IAD? We aim to address these questions by conducting an individual patient data (IPD) meta-analysis. METHODS AND ANALYSIS: This study will identify prospective cohort studies that measured blood pressure in both arms during recruitment, and invite authors to contribute IPD datasets to this collaboration. All patient data received will be combined into a single dataset. Using one-stage meta-analysis, we will undertake multivariable time-to-event regression modelling, with the aim of developing a new prognostic model for cardiovascular risk estimation that includes IAD. We will explore variations in risk contribution of IAD across predefined population subgroups (eg, hypertensives, diabetics), establish the lower limit of IAD that is associated with additional cardiovascular risk and assess the impact of different methods of IAD measurement on risk prediction. ETHICS AND DISSEMINATION: This study will not include any patient identifiable data. Included datasets will already have ethical approval and consent from their sponsors. Findings will be presented to international conferences and published in peer reviewed journals, and we have a comprehensive dissemination strategy in place with integrated patient and public involvement. PROSPERO REGISTRATION NUMBER: CRD42015031227.

BACKGROUND: Depression is a common, debilitating and costly disorder. The best-evidenced psychological therapy - cognitive-behavioural therapy (CBT) - is complex and costly. A simpler therapy, behavioural activation (BA), may be an effective alternative. OBJECTIVES: to determine the clinical effectiveness and cost-effectiveness of BA compared with CBT for depressed adults at 12 and 18 months' follow-up, and to investigate the processes of treatments. DESIGN: Randomised controlled, non-inferiority trial stratified by depression severity, antidepressant use and recruitment site, with embedded process evaluation; and randomisation by remote computer-generated allocation. SETTING: Three community mental health services in England. PARTICIPANTS: Adults aged ≥ 18 years with major depressive disorder (MDD) recruited from primary care and psychological therapy services. INTERVENTIONS: BA delivered by NHS junior mental health workers (MHWs); CBT by NHS psychological therapists. OUTCOMES: Primary: depression severity (as measured via the Patient Health Questionnaire-9; PHQ-9) at 12 months. Secondary: MDD status; number of depression-free days; anxiety (as measured via the Generalised Anxiety Disorder-7); health-related quality of life (as measured via the Short Form questionnaire-36 items) at 6, 12 and 18 months; and PHQ-9 at 6 and 18 months, all collected by assessors blinded to treatment allocation. Non-inferiority margin was 1.9 PHQ-9 points. We undertook intention-to-treat (ITT) and per protocol (PP) analyses. We explored cost-effectiveness by collecting direct treatment and other health- and social-care costs and calculating quality-adjusted life-years (QALYs) using the EuroQol-5 Dimensions, three-level version, at 18 months. RESULTS: We recruited 440 participants (BA, n = 221; CBT, n = 219); 175 (79%) BA and 189 (86%) CBT participants provided ITT data and 135 (61%) BA and 151 (69%) CBT participants provided PP data. At 12 months we found that BA was non-inferior to CBT {ITT: CBT 8.4 PHQ-9 points [standard deviation (SD) 7.5 PHQ-9 points], BA 8.4 PHQ-9 points (SD 7.0 PHQ-9 points), mean difference 0.1 PHQ-9 points, 95% confidence interval (CI) -1.3 to 1.5 PHQ-9 points, p = 0.89; PP: CBT 7.9 PHQ-9 points (SD 7.3 PHQ-9 points), BA 7.8 PHQ-9 points (SD 6.5 PHQ-9 points), mean difference 0.0 PHQ-9 points, 95% CI -1.5 to 1.6 PHQ-9 points, p = 0.99}. We found no differences in secondary outcomes. We found a significant difference in mean intervention costs (BA, £975; CBT, £1235; p 

BACKGROUND: Depression and debt are common in the UK. Debt Counselling for Depression in Primary Care: an adaptive randomised controlled pilot trial (DeCoDer) aimed to assess the clinical effectiveness and cost-effectiveness of the addition of a primary care debt counselling advice service to usual care for patients with depression and debt. However, the study was terminated early during the internal pilot trial phase because of recruitment delays. This report describes the rationale, methods and findings of the pilot study, and implications for future research. OBJECTIVES: the overarching aim of the internal pilot was to identify and resolve problems, thereby assessing the feasibility of the main trial. The specific objectives were to confirm methods for practice recruitment and the ability to recruit patients via the proposed approaches; to determine the acceptability of the study interventions and outcome measures; to assess contamination; to confirm the randomisation method for main trial and the level of participant attrition; and to check the robustness of data collection systems. DESIGN: an adaptive, parallel, two-group multicentre randomised controlled pilot trial with a nested mixed-methods process and economic evaluation. Both individual- and cluster (general practice)-level were was used in the pilot phase to assign participants to intervention or control groups. SETTING: General practices in England and Wales. PARTICIPANTS: Individuals were included who were aged ≥ 18 years, scored ≥ 14 on the Beck Depression Inventory II and self-identified as having debt worries. The main exclusion criteria were being actively suicidal or psychotic and/or severely depressed and unresponsive to treatment; having a severe addiction to alcohol/illicit drugs; being unable/unwilling to give written informed consent; currently participating in other research including follow-up phases; having received Citizens Advice Bureau (CAB) debt advice in the past year; and not wanting debt advice via a general practice. INTERVENTIONS: the participants in the intervention group were given debt advice provided by the CAB and shared biopsychosocial assessment, in addition to treatment as usual (TAU) and two debt advice leaflets. The participants in the control group were given advice leaflets provided by the general practitioner and TAU only. MAIN OUTCOME MEASURES: (1) Outcomes of the pilot trial - the proportion of eligible patients who consented, the number of participants recruited compared with target, assessment of contamination, and assessment of patient satisfaction with intervention and outcome measures. (2) Participant outcomes - primary - Beck Depression Inventory II; secondary - psychological well-being, health and social care utilisation, service satisfaction, substance misuse, record of priority/non-priority debts, life events and difficulties, and explanatory measures. Outcomes were assessed at baseline (pre-randomisation) and at 4 months post randomisation. Other data sources - qualitative interviews were conducted with participants, clinicians and CAB advisors. RESULTS: of the 238 expressions of interest screened, 61 participants (26%) were recruited and randomised (32 in the intervention group and 29 in the control group). All participants provided baseline outcomes and 52 provided the primary outcome at 4 months' follow-up (14.7% dropout). Seventeen participants allocated to the intervention saw a CAB advisor. Descriptive statistics are reported for participants with complete outcomes at baseline and 4 months' follow-up. Our qualitative findings suggest that the relationship between debt and depression is complex, and the impact of each on the other is compounded by other psychological, social and contextual influences. CONCLUSIONS: As a result of low recruitment, this trial was terminated at the internal pilot phase and was too small for inferential statistical analysis. We recommend ways to reduce this risk when conducting complex trials among vulnerable populations recruited in community settings. These cover trial design, the design and delivery of interventions, recruitment strategies and support for sites. TRIAL REGISTRATION: Current Controlled Trials ISRCTN79705874. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 21, No. 35. See the NIHR Journals Library website for further project information. Mark Gabbay and Adele Ring are part-funded by NIHR Collaborations for Leadership in Applied Health Research and Care (CLAHRC) North West Coast and Richard Byng and Rod S Taylor, Vashti Berry and Elizabeth Shaw part-funded by NIHR CLAHRC South West Peninsula.

AIM: Residual β-cell function is present at the time of diagnosis with Type 1 diabetes. Preserving this β-cell function reduces complications. We hypothesized that exercise preserves β-cell function in Type 1 diabetes and undertook a pilot trial to address the key uncertainties in designing a definitive trial to test this hypothesis. METHODS: a randomized controlled pilot trial in adults aged 16-60 years diagnosed with Type 1 diabetes within the previous 3 months was undertaken. Participants were assigned to control (usual care) or intervention (exercise consultation every month), in a 1 : 1 ratio for 12 months. The primary outcomes were recruitment rate, drop out, exercise adherence [weeks with ≥ 150 min of self-reported moderate to vigorous physical activity (MVPA)], and exercise uptake in the control group. The secondary outcomes were differences in insulin sensitivity and rate of loss of β-cell function between intervention and control at 6 and 12 months. RESULTS: of 507 individuals who were approached, 58 (28 control, 30 intervention) entered the study and 41 completed it. Participants were largely white European males, BMI 24.8 ± 3.8 kg/m2 , HbA1c 75 ± 25 mmol/mol (9 ± 2%). Mean level of objectively measured MVPA increased in the intervention group (mean 243 to 273 min/week) and 61% of intervention participants reached the target of ≥ 150 min/week of self-reported MVPA on at least 42 weeks of the year. Physical activity levels fell slightly in the control group (mean 277 to 235 min of MVPA/week). There was exploratory evidence that intervention group became more insulin sensitive and required less insulin. However, the rate of loss of β-cell function appeared similar between the groups, although the change in insulin sensitivity may have affected this. CONCLUSION: We show that it is possible to recruit and randomize people with newly diagnosed Type 1 diabetes to a trial of an exercise intervention, and increase and maintain their exercise levels for 12 months. Future trials need to incorporate measures of greater adherence to exercise training targets, and include more appropriate measures of β-cell function. (Clinical Trials Registry No; ISRCTN91388505).

BACKGROUND: Exercise-based cardiac rehabilitation may benefit adults with atrial fibrillation or those who had been treated for atrial fibrillation. Atrial fibrillation is caused by multiple micro re-entry circuits within the atrial tissue, which result in chaotic rapid activity in the atria. OBJECTIVES: to assess the benefits and harms of exercise-based rehabilitation programmes, alone or with another intervention, compared with no-exercise training controls in adults who currently have AF, or have been treated for AF. SEARCH METHODS: We searched the following electronic databases; CENTRAL and the Database of Abstracts of Reviews of Effectiveness (DARE) in the Cochrane Library, MEDLINE Ovid, Embase Ovid, PsycINFO Ovid, Web of Science Core Collection Thomson Reuters, CINAHL EBSCO, LILACS Bireme, and three clinical trial registers on 14 July 2016. We also checked the bibliographies of relevant systematic reviews identified by the searches. We imposed no language restrictions. SELECTION CRITERIA: We included randomised controlled trials (RCT) that investigated exercise-based interventions compared with any type of no-exercise control. We included trials that included adults aged 18 years or older with atrial fibrillation, or post-treatment for atrial fibrillation. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data. We assessed the risk of bias using the domains outlined in the Cochrane Handbook for Systematic Reviews of Interventions. We assessed clinical and statistical heterogeneity by visual inspection of the forest plots, and by using standard Chi² and I² statistics. We performed meta-analyses using fixed-effect and random-effects models; we used standardised mean differences where different scales were used for the same outcome. We assessed the risk of random errors with trial sequential analysis (TSA) and used the GRADE methodology to rate the quality of evidence, reporting it in the 'Summary of findings' table. MAIN RESULTS: We included six RCTs with a total of 421 patients with various types of atrial fibrillation. All trials were conducted between 2006 and 2016, and had short follow-up (eight weeks to six months). Risks of bias ranged from high risk to low risk.The exercise-based programmes in four trials consisted of both aerobic exercise and resistance training, in one trial consisted of Qi-gong (slow and graceful movements), and in another trial, consisted of inspiratory muscle training.For mortality, very low-quality evidence from six trials suggested no clear difference in deaths between the exercise and no-exercise groups (relative risk (RR) 1.00, 95% confidence interval (CI) 0.06 to 15.78; participants = 421; I² = 0%; deaths = 2). Very low-quality evidence from five trials suggested no clear difference between groups for serious adverse events (RR 1.01, 95% CI 0.98 to 1.05; participants = 381; I² = 0%; events = 8). Low-quality evidence from two trials suggested no clear difference in health-related quality of life for the Short Form-36 (SF-36) physical component summary measure (mean difference (MD) 1.96, 95% CI -2.50 to 6.42; participants = 224; I² = 69%), or the SF-36 mental component summary measure (MD 1.99, 95% CI -0.48 to 4.46; participants = 224; I² = 0%). Exercise capacity was assessed by cumulated work, or maximal power (Watt), obtained by cycle ergometer, or by six minute walking test, or ergospirometry testing measuring VO2 peak. We found moderate-quality evidence from two studies that exercise-based rehabilitation increased exercise capacity, measured by VO2 peak, more than no exercise (MD 3.76, 95% CI 1.37 to 6.15; participants = 208; I² = 0%); and very low-quality evidence from four studies that exercise-based rehabilitation increased exercise capacity more than no exercise, measured by the six-minute walking test (MD 75.76, 95% CI 14.00 to 137.53; participants = 272; I² = 85%). When we combined the different assessment tools for exercise capacity, we found very low-quality evidence from six trials that exercise-based rehabilitation increased exercise capacity more than no exercise (standardised mean difference (SMD) 0.86, 95% CI 0.46 to 1.26; participants = 359; I² = 65%). Overall, the quality of the evidence for the outcomes ranged from moderate to very-low. AUTHORS' CONCLUSIONS: Due to few randomised patients and outcomes, we could not evaluate the real impact of exercise-based cardiac rehabilitation on mortality or serious adverse events. The evidence showed no clinically relevant effect on health-related quality of life. Pooled data showed a positive effect on the surrogate outcome of physical exercise capacity, but due to the low number of patients and the moderate to very low-quality of the underpinning evidence, we could not be certain of the magnitude of the effect. Future high-quality randomised trials are needed to assess the benefits and harms of exercise-based cardiac rehabilitation for adults with atrial fibrillation on patient-relevant outcomes.

© 2017 the Cochrane Collaboration. Published by John Wiley. &. Sons, Ltd. This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: to assess the effects of exercise-based CR for patients with stable angina compared to usual care.

BACKGROUND: Heart transplantation is considered to be the gold standard treatment for selected patients with end-stage heart disease when medical therapy has been unable to halt progression of the underlying pathology. Evidence suggests that aerobic exercise training may be effective in reversing the pathophysiological consequences associated with cardiac denervation and prevent immunosuppression-induced adverse effects in heart transplant recipients. OBJECTIVES: to determine the effectiveness and safety of exercise-based rehabilitation on the mortality, hospital admissions, adverse events, exercise capacity, health-related quality of life, return to work and costs for people after heart transplantation. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE (Ovid), Embase (Ovid), CINAHL (EBSCO) and Web of Science Core Collection (Thomson Reuters) to June 2016. We also searched two clinical trials registers and handsearched the reference lists of included studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of parallel group, cross-over or cluster design, which compared exercise-based interventions with (i) no exercise control (ii) a different dose of exercise training (e.g. low- versus high-intensity exercise training); or (iii) an active intervention (i.e. education, psychological intervention). The study population comprised adults aged 18 years or over who had received a heart transplant. DATA COLLECTION AND ANALYSIS: Two review authors independently screened all identified references for inclusion based on pre-specified inclusion criteria. Disagreements were resolved by consensus or by involving a third person. Two review authors extracted outcome data from the included trials and assessed their risk of bias. One review author extracted study characteristics from included studies and a second author checked them against the trial report for accuracy. MAIN RESULTS: We included 10 RCTs that involved a total of 300 participants whose mean age was 54.4 years. Women accounted for fewer than 25% of all study participants. Nine trials which randomised 284 participants to receive exercise-based rehabilitation (151 participants) or no exercise (133 participants) were included in the main analysis. One cross-over RCT compared high-intensity interval training with continued moderate-intensity training in 16 participants. We reported findings for all trials at their longest follow-up (median 12 weeks).Exercise-based cardiac rehabilitation increased exercise capacity (VO2peak) compared with no exercise control (MD 2.49 mL/kg/min, 95% CI 1.63 to 3.36; N = 284; studies = 9; moderate quality evidence). There was evidence from one trial that high-intensity interval exercise training was more effective in improving exercise capacity than continuous moderate-intensity exercise (MD 2.30 mL/kg/min, 95% CI 0.59 to 4.01; N = 16; 1 study). Four studies reported health-related quality of life (HRQoL) measured using SF-36, Profile of Quality of Life in the Chronically Ill (PLC) and the World Health Organization Quality of Life (WHOQoL) - BREF. Due to the variation in HRQoL outcomes and methods of reporting we were unable to meta-analyse results across studies, but there was no evidence of a difference between exercise-based cardiac rehabilitation and control in 18 of 21 HRQoL domains reported, or between high and moderate intensity exercise in any of the 10 HRQoL domains reported. One adverse event was reported by one study.Exercise-based cardiac rehabilitation improves exercise capacity, but exercise was found to have no impact on health-related quality of life in the short-term (median 12 weeks follow-up), in heart transplant recipients whose health is stable.There was no evidence of statistical heterogeneity across trials for exercise capacity and no evidence of small study bias. The overall risk of bias in included studies was judged as low or unclear; more than 50% of included studies were assessed at unclear risk of bias with respect to allocation concealment, blinding of outcome assessors and declaration of conflicts of interest. Evidence quality was assessed as moderate according to GRADE criteria. AUTHORS' CONCLUSIONS: We found moderate quality evidence suggesting that exercise-based cardiac rehabilitation improves exercise capacity, and that exercise has no impact on health-related quality of life in the short-term (median 12 weeks follow-up), in heart transplant recipients. Cardiac rehabilitation appears to be safe in this population, but long-term follow-up data are incomplete and further good quality and adequately-powered trials are needed to demonstrate the longer-term benefits of exercise on safety and impact on both clinical and patient-related outcomes, such as health-related quality of life, and healthcare costs.

BACKGROUND: Pain of lumbar facet-joint origin is a common cause of low back pain in adults and may lead to chronic pain and disability, with associated health and socioeconomic implications. The socioeconomic burden includes an inability to return to work resulting in loss of productivity in addition to direct and indirect health-care utilisation costs. Lumbar facet-joints are paired synovial joints between the superior and inferior articular processes of consecutive lumbar vertebrae and between the fifth lumbar vertebra and the sacrum. Facet-joint pain is defined as pain that arises from any structure that is part of the facet-joints, including the fibrous capsule, synovial membrane, hyaline cartilage and bone. This pain may be treated by intra-articular injections with local anaesthetic and steroid, although this treatment is not standardised. At present, there is no definitive research to support the use of targeted lumbar facet-joint injections to manage this pain. Because of the lack of high-quality, robust clinical evidence, the National Institute for Health and Care Excellence (NICE) guidelines on the management of chronic low back pain [NICE. Low Back Pain in Adults: Early Management. Clinical guideline (CG88). London: NICE; 2009] did not recommend the use of spinal injections despite their perceived potential to reduce pain intensity and improve rehabilitation, with NICE calling for further research to be undertaken. The updated guidelines [NICE. Low Back Pain and Sciatica in over 16s: Assessment and Management. NICE guideline (NG59). London: NICE; 2016] again do not recommend the use of spinal injections. OBJECTIVES: to assess the feasibility of carrying out a definitive study to evaluate the clinical effectiveness and cost-effectiveness of lumbar facet-joint injections compared with a sham procedure in patients with non-specific low back pain of > 3 months' duration. DESIGN: Blinded parallel two-arm pilot randomised controlled trial. SETTING: Initially planned as a multicentre study involving three NHS trusts in the UK, recruitment took place in the pain and spinal orthopaedic clinics at Barts Health NHS Trust only. PARTICIPANTS: Adult patients referred by their GP to the specialist clinics with non-specific low back pain of at least 3 months' duration despite NICE-recommended best non-invasive care (education and one of a physical exercise programme, acupuncture or manual therapy). Patients who had already received lumbar facet-joint injections or who had had previous back surgery were excluded. INTERVENTIONS: Participants who had a positive result following a diagnostic test (single medial branch nerve blocks) were randomised and blinded to receive either intra-articular lumbar facet-joint injections with steroids (intervention group) or a sham procedure (control group). All participants were invited to attend a group-based combined physical and psychological (CPP) programme. MAIN OUTCOME MEASURES: in addition to the primary outcome of feasibility, questionnaires were used to assess a range of pain-related (including the Brief Pain Inventory and Short-Form McGill Pain Questionnaire version 2) and disability-related (including the EuroQol-5 Dimensions five-level version and Oswestry Low Back Pain Questionnaire) issues. Health-care utilisation and cost data were also assessed. The questionnaire visits took place at baseline and at 6 weeks, 3 months and 6 months post randomisation. The outcome assessors were blinded to the allocation groups. RESULTS: of 628 participants screened for eligibility, nine were randomised to receive the study intervention (intervention group, n = 5; sham group, n = 4), six completed the CPP programme and eight completed the study. LIMITATIONS: Failure to achieve our expected recruitment targets led to early closure of the study by the funder. CONCLUSIONS: Because of the small number of participants recruited to the study, we were unable to draw any conclusions about the clinical effectiveness or cost-effectiveness of intra-articular lumbar facet-joint injections in the management of non-specific low back pain. Although we did not achieve the target recruitment rate from the pain clinics, we demonstrated our ability to develop a robust study protocol and deliver the intended interventions safely to all nine randomised participants, thus addressing many of the feasibility objectives. FUTURE WORK: Stronger collaborations with primary care may improve the recruitment of patients earlier in their pain trajectory who are suitable for inclusion in a future trial. TRIAL REGISTRATION: EudraCT 2014-003187-20 and Current Controlled Trials ISRCTN12191542. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 21, No. 74. See the NIHR Journals Library website for further project information.

BACKGROUND: Cardiovascular disease is the most common cause of death globally. Traditionally, centre-based cardiac rehabilitation programmes are offered to individuals after cardiac events to aid recovery and prevent further cardiac illness. Home-based cardiac rehabilitation programmes have been introduced in an attempt to widen access and participation. This is an update of a review previously published in 2009 and 2015. OBJECTIVES: to compare the effect of home-based and supervised centre-based cardiac rehabilitation on mortality and morbidity, exercise-capacity, health-related quality of life, and modifiable cardiac risk factors in patients with heart disease. SEARCH METHODS: We updated searches from the previous Cochrane Review by searching the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid), Embase (Ovid), PsycINFO (Ovid) and CINAHL (EBSCO) on 21 September 2016. We also searched two clinical trials registers as well as previous systematic reviews and reference lists of included studies. No language restrictions were applied. SELECTION CRITERIA: We included randomised controlled trials, including parallel group, cross-over or quasi-randomised designs) that compared centre-based cardiac rehabilitation (e.g. hospital, gymnasium, sports centre) with home-based programmes in adults with myocardial infarction, angina, heart failure or who had undergone revascularisation. DATA COLLECTION AND ANALYSIS: Two review authors independently screened all identified references for inclusion based on pre-defined inclusion criteria. Disagreements were resolved through discussion or by involving a third review author. Two authors independently extracted outcome data and study characteristics and assessed risk of bias. Quality of evidence was assessed using GRADE principles and a Summary of findings table was created. MAIN RESULTS: We included six new studies (624 participants) for this update, which now includes a total of 23 trials that randomised a total of 2890 participants undergoing cardiac rehabilitation. Participants had an acute myocardial infarction, revascularisation or heart failure. A number of studies provided insufficient detail to enable assessment of potential risk of bias, in particular, details of generation and concealment of random allocation sequencing and blinding of outcome assessment were poorly reported.No evidence of a difference was seen between home- and centre-based cardiac rehabilitation in clinical primary outcomes up to 12 months of follow up: total mortality (relative risk (RR) = 1.19, 95% CI 0.65 to 2.16; participants = 1505; studies = 11/comparisons = 13; very low quality evidence), exercise capacity (standardised mean difference (SMD) = -0.13, 95% CI -0.28 to 0.02; participants = 2255; studies = 22/comparisons = 26; low quality evidence), or health-related quality of life up to 24 months (not estimable). Trials were generally of short duration, with only three studies reporting outcomes beyond 12 months (exercise capacity: SMD 0.11, 95% CI -0.01 to 0.23; participants = 1074; studies = 3; moderate quality evidence). However, there was evidence of marginally higher levels of programme completion (RR 1.04, 95% CI 1.00 to 1.08; participants = 2615; studies = 22/comparisons = 26; low quality evidence) by home-based participants. AUTHORS' CONCLUSIONS: This update supports previous conclusions that home- and centre-based forms of cardiac rehabilitation seem to be similarly effective in improving clinical and health-related quality of life outcomes in patients after myocardial infarction or revascularisation, or with heart failure. This finding supports the continued expansion of evidence-based, home-based cardiac rehabilitation programmes. The choice of participating in a more traditional and supervised centre-based programme or a home-based programme may reflect local availability and consider the preference of the individual patient. Further data are needed to determine whether the effects of home- and centre-based cardiac rehabilitation reported in the included short-term trials can be confirmed in the longer term and need to consider adequately powered non-inferiority or equivalence study designs.

OBJECTIVES: the aim of this study was to investigate if exercise intensity guided by rating of perceived exertion (RPE) results in an equivalent cardiovascular response when applied in either a center-based or a home-based setting. DESIGN: Data from patients with heart disease (post-valve surgery and atrial fibrillation post-radiofrequency ablation) participating in exercise-based rehabilitation were included. Patients performed a 12-week program in either a center- or a home-based setting. Using RPE, patients recorded their exercise intensity 3 times during an aerobic training phase. Exercise intensity was objectively measured using heart rate (HR) monitors. RESULTS: a total of 2622 RPE values with corresponding HR data were available. There was no difference in the level of association (interaction P = 0.51) between HR and RPE seen in the center-based setting (mean of 6.1 beats/min per 1.0 difference in RPE; 95% confidence interval, 4.8-7.5 beats/min) compared with the home-based setting (mean of 5.3 beats/min per 1.0 difference in RPE; 95% confidence interval, 4.0-6.5 beats/min). The level of patient familiarization, exercise intensity, and patient characteristics did not affect the level of association between RPE and HR. CONCLUSIONS: Independent of exercise setting, RPE appears to be equally effective in guiding exercise intensity of patients participating in cardiac rehabilitation.

Much criticism has been directed at the licencing requirements for medical devices (MDs) as they often result in a lack of robust evidence to inform health technology assessment (HTA) decisions. To better understand the current international decisional framework on MD technologies, we undertook three linked research studies: a review of the device regulatory procedures, a survey of current HTA practices and an empirical comparison of HTA reports of drugs versus MDs. Our review confirms that current device regulatory processes across the globe are substantially less stringent than drugs. As a result, international HTA agencies report that they face a number of challenges when assessing MDs, including reliance on suboptimal data to make clinical and cost-effectiveness decisions. Whilst many HTA agencies have adapted their processes and procedures to handle MD technology submissions, in our comparison of HTA reports we found little evidence of the application of methodologies that take account of device-specific issues, such as incremental development. Overall, our research reinforces the need for better linkage between licencing and HTA and the development and application of innovative HTA methodologies with the objective of securing faster patient access for those technologies that can be shown to represent good value for money. © 2017 the Authors. Health Economics Published by John Wiley & Sons, Ltd.

BACKGROUND: Coronary heart disease (CHD) is the single most common cause of death globally. However, with falling CHD mortality rates, an increasing number of people live with CHD and may need support to manage their symptoms and improve prognosis. Cardiac rehabilitation is a complex multifaceted intervention which aims to improve the health outcomes of people with CHD. Cardiac rehabilitation consists of three core modalities: education, exercise training and psychological support. This is an update of a Cochrane systematic review previously published in 2011, which aims to investigate the specific impact of the educational component of cardiac rehabilitation. OBJECTIVES: 1. To assess the effects of patient education delivered as part of cardiac rehabilitation, compared with usual care on mortality, morbidity, health-related quality of life (HRQoL) and healthcare costs in patients with CHD.2. To explore the potential study level predictors of the effects of patient education in patients with CHD (e.g. individual versus group intervention, timing with respect to index cardiac event). SEARCH METHODS: We updated searches from the previous Cochrane review, by searching the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library, Issue 6, 2016), MEDLINE (Ovid), Embase (Ovid), PsycINFO (Ovid) and CINAHL (EBSCO) in June 2016. Three trials registries, previous systematic reviews and reference lists of included studies were also searched. No language restrictions were applied. SELECTION CRITERIA: 1. Randomised controlled trials (RCTs) where the primary interventional intent was education delivered as part of cardiac rehabilitation.2. Studies with a minimum of six-months follow-up and published in 1990 or later.3. Adults with a diagnosis of CHD. DATA COLLECTION AND ANALYSIS: Two review authors independently screened all identified references for inclusion based on the above inclusion criteria. One author extracted study characteristics from the included trials and assessed their risk of bias; a second review author checked data. Two independent reviewers extracted outcome data onto a standardised collection form. For dichotomous variables, risk ratios and 95% confidence intervals (CI) were derived for each outcome. Heterogeneity amongst included studies was explored qualitatively and quantitatively. Where appropriate and possible, results from included studies were combined for each outcome to give an overall estimate of treatment effect. Given the degree of clinical heterogeneity seen in participant selection, interventions and comparators across studies, we decided it was appropriate to pool studies using random-effects modelling. We planned to undertake subgroup analysis and stratified meta-analysis, sensitivity analysis and meta-regression to examine potential treatment effect modifiers. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to evaluate the quality of the evidence and the GRADE profiler (GRADEpro GDT) to create summary of findings tables. MAIN RESULTS: This updated review included a total of 22 trials which randomised 76,864 people with CHD to an education intervention or a 'no education' comparator. Nine new trials (8215 people) were included for this update. We judged most included studies as low risk of bias across most domains. Educational 'dose' ranged from one 40 minute face-to-face session plus a 15 minute follow-up call, to a four-week residential stay with 11 months of follow-up sessions. Control groups received usual medical care, typically consisting of referral to an outpatient cardiologist, primary care physician, or both.We found evidence of no difference in effect of education-based interventions on total mortality (13 studies, 10,075 participants; 189/5187 (3.6%) versus 222/4888 (4.6%); random effects risk ratio (RR) 0.80, 95% CI 0.60 to 1.05; moderate quality evidence). Individual causes of mortality were reported rarely, and we were unable to report separate results for cardiovascular mortality or non-cardiovascular mortality. There was evidence of no difference in effect of education-based interventions on fatal and/or non fatal myocardial infarction (MI) (2 studies, 209 participants; 7/107 (6.5%) versus 12/102 (11.8%); random effects RR 0.63, 95% CI 0.26 to 1.48; very low quality of evidence). However, there was some evidence of a reduction with education in fatal and/or non-fatal cardiovascular events (2 studies, 310 studies; 21/152 (13.8%) versus 61/158 (38.6%); random effects RR 0.36, 95% CI 0.23 to 0.56; low quality evidence). There was evidence of no difference in effect of education on the rate of total revascularisations (3 studies, 456 participants; 5/228 (2.2%) versus 8/228 (3.5%); random effects RR 0.58, 95% CI 0.19 to 1.71; very low quality evidence) or hospitalisations (5 studies, 14,849 participants; 656/10048 (6.5%) versus 381/4801 (7.9%); random effects RR 0.93, 95% CI 0.71 to 1.21; very low quality evidence). There was evidence of no difference between groups for all cause withdrawal (17 studies, 10,972 participants; 525/5632 (9.3%) versus 493/5340 (9.2%); random effects RR 1.04, 95% CI 0.88 to 1.22; low quality evidence). Although some health-related quality of life (HRQoL) domain scores were higher with education, there was no consistent evidence of superiority across all domains. AUTHORS' CONCLUSIONS: We found no reduction in total mortality, in people who received education delivered as part of cardiac rehabilitation, compared to people in control groups (moderate quality evidence). There were no improvements in fatal or non fatal MI, total revascularisations or hospitalisations, with education. There was some evidence of a reduction in fatal and/or non-fatal cardiovascular events with education, but this was based on only two studies. There was also some evidence to suggest that education-based interventions may improve HRQoL. Our findings are supportive of current national and international clinical guidelines that cardiac rehabilitation for people with CHD should be comprehensive and include educational interventions together with exercise and psychological therapy. Further definitive research into education interventions for people with CHD is needed.

© 2017 Objective to assess patient preference for exercise setting and examine if choice of setting influences the long-term health benefit of exercise-based cardiac rehabilitation. Methods Patients participating in a randomised controlled trial following either heart valve surgery, or radiofrequency ablation for atrial fibrillation were given the choice to perform a 12-week exercise programme in either a supervised centre-based, or a self-management home-based setting. Exercise capacity and physical and mental health outcomes were assessed for up to 24 months after hospital discharge. Outcomes between settings were compared using a time × setting interaction using a mixed effects regression model. Results Across the 158 included patients, an equivalent proportion preferred to undertake exercise rehabilitation in a centre-based setting (55%, 95% CI: 45% to 63%) compared to a home-based setting (45%, 95% CI: 37% to 53%, p = 0.233). At baseline, those who preferred a home-based setting reported better physical health (mean difference in physical component score: 5.0, 95% CI 2.3 to 7.4; p = 0.001) and higher exercise capacity (mean between group difference 15.9 watts, 95% CI 3.7 to 28.1; p = 0.011). With the exception of the depression score in the Hospital Anxiety and Depression Score (F(3.65), p = 0.004), there was no evidence of a significant difference in outcomes between settings. Conclusion the preference of patients to participate in home-based and centre-based exercise programmes appears to be equivalent and provides similar health benefits. Whilst these findings support that patients should be given the choice between exercise-settings when initiating cardiac rehabilitation, further confirmatory evidence is needed.

BACKGROUND: Coronary heart disease (CHD) is the most common cause of death globally, although mortality rates are falling. Psychological symptoms are prevalent for people with CHD, and many psychological treatments are offered following cardiac events or procedures with the aim of improving health and outcomes. This is an update of a Cochrane systematic review previously published in 2011. OBJECTIVES: to assess the effectiveness of psychological interventions (alone or with cardiac rehabilitation) compared with usual care (including cardiac rehabilitation where available) for people with CHD on total mortality and cardiac mortality; cardiac morbidity; and participant-reported psychological outcomes of levels of depression, anxiety, and stress; and to explore potential study-level predictors of the effectiveness of psychological interventions in this population. SEARCH METHODS: We updated the previous Cochrane Review searches by searching the following databases on 27 April 2016: CENTRAL in the Cochrane Library, MEDLINE (Ovid), Embase (Ovid), PsycINFO (Ovid), and CINAHL (EBSCO). SELECTION CRITERIA: We included randomised controlled trials (RCTs) of psychological interventions compared to usual care, administered by trained staff, and delivered to adults with a specific diagnosis of CHD. We selected only studies estimating the independent effect of the psychological component, and with a minimum follow-up of six months. The study population comprised of adults after: a myocardial infarction (MI), a revascularisation procedure (coronary artery bypass graft (CABG) or percutaneous coronary intervention (PCI)), and adults with angina or angiographically defined coronary artery disease (CAD). RCTs had to report at least one of the following outcomes: mortality (total- or cardiac-related); cardiac morbidity (MI, revascularisation procedures); or participant-reported levels of depression, anxiety, or stress. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles and abstracts of all references for eligibility. A lead review author extracted study data, which a second review author checked. We contacted study authors to obtain missing information. MAIN RESULTS: This review included 35 studies which randomised 10,703 people with CHD (14 trials and 2577 participants added to this update). The population included mainly men (median 77.0%) and people post-MI (mean 65.7%) or after undergoing a revascularisation procedure (mean 27.4%). The mean age of participants within trials ranged from 53 to 67 years. Overall trial reporting was poor, with around a half omitting descriptions of randomisation sequence generation, allocation concealment procedures, or the blinding of outcome assessments. The length of follow-up ranged from six months to 10.7 years (median 12 months). Most studies (23/35) evaluated multifactorial interventions, which included therapies with multiple therapeutic components. Ten studies examined psychological interventions targeted at people with a confirmed psychopathology at baseline and two trials recruited people with a psychopathology or another selecting criterion (or both). of the remaining 23 trials, nine studies recruited unselected participants from cardiac populations reporting some level of psychopathology (3.8% to 53% with depressive symptoms, 32% to 53% with anxiety), 10 studies did not report these characteristics, and only three studies excluded people with psychopathology.Moderate quality evidence showed no risk reduction for total mortality (risk ratio (RR) 0.90, 95% confidence interval (CI) 0.77 to 1.05; participants = 7776; studies = 23) or revascularisation procedures (RR 0.94, 95% CI 0.81 to 1.11) with psychological therapies compared to usual care. Low quality evidence found no risk reduction for non-fatal MI (RR 0.82, 95% CI 0.64 to 1.05), although there was a 21% reduction in cardiac mortality (RR 0.79, 95% CI 0.63 to 0.98). There was also low or very low quality evidence that psychological interventions improved participant-reported levels of depressive symptoms (standardised mean difference (SMD) -0.27, 95% CI -0.39 to -0.15; GRADE = low), anxiety (SMD -0.24, 95% CI -0.38 to -0.09; GRADE = low), and stress (SMD -0.56, 95% CI -0.88 to -0.24; GRADE = very low).There was substantial statistical heterogeneity for all psychological outcomes but not clinical outcomes, and there was evidence of small-study bias for one clinical outcome (cardiac mortality: Egger test P = 0.04) and one psychological outcome (anxiety: Egger test P = 0.012). Meta-regression exploring a limited number of intervention characteristics found no significant predictors of intervention effects for total mortality and cardiac mortality. For depression, psychological interventions combined with adjunct pharmacology (where deemed appropriate) for an underlying psychological disorder appeared to be more effective than interventions that did not (β = -0.51, P = 0.003). For anxiety, interventions recruiting participants with an underlying psychological disorder appeared more effective than those delivered to unselected populations (β = -0.28, P = 0.03). AUTHORS' CONCLUSIONS: This updated Cochrane Review found that for people with CHD, there was no evidence that psychological treatments had an effect on total mortality, the risk of revascularisation procedures, or on the rate of non-fatal MI, although the rate of cardiac mortality was reduced and psychological symptoms (depression, anxiety, or stress) were alleviated; however, the GRADE assessments suggest considerable uncertainty surrounding these effects. Considerable uncertainty also remains regarding the people who would benefit most from treatment (i.e. people with or without psychological disorders at baseline) and the specific components of successful interventions. Future large-scale trials testing the effectiveness of psychological therapies are required due to the uncertainty within the evidence. Future trials would benefit from testing the impact of specific (rather than multifactorial) psychological interventions for participants with CHD, and testing the targeting of interventions on different populations (i.e. people with CHD, with or without psychopathologies).

OBJECTIVE: to characterise incidence and healthcare costs associated with persistent postoperative pain (PPP) following lumbar surgery. DESIGN: Retrospective, population-based cohort study. SETTING: Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES) databases. PARTICIPANTS: Population-based cohort of 10 216 adults who underwent lumbar surgery in England from 1997/1998 through 2011/2012 and had at least 1 year of presurgery data and 2 years of postoperative follow-up data in the linked CPRD-HES. PRIMARY AND SECONDARY OUTCOMES MEASURES: Incidence and total healthcare costs over 2, 5 and 10 years attributable to persistent PPP following initial lumbar surgery. RESULTS: the rate of individuals undergoing lumbar surgery in the CPRD-HES linked data doubled over the 15-year study period, fiscal years 1997/1998 to 2011/2012, from 2.5 to 4.9 per 10 000 adults. Over the most recent 5-year period (2007/2008 to 2011/2012), on average 20.8% (95% CI 19.7% to 21.9%) of lumbar surgery patients met criteria for PPP. Rates of healthcare usage were significantly higher for patients with PPP across all types of care. Over 2 years following initial spine surgery, the mean cost difference between patients with and without PPP was £5383 (95% CI £4872 to £5916). Over 5 and 10 years following initial spine surgery, the mean cost difference between patients with and without PPP increased to £10 195 (95% CI £8726 to £11 669) and £14 318 (95% CI £8386 to £19 771), respectively. Extrapolated to the UK population, we estimate that nearly 5000 adults experience PPP after spine surgery annually, with each new cohort costing the UK National Health Service in excess of £70 million over the first 10 years alone. CONCLUSIONS: Persistent pain affects more than one-in-five lumbar surgery patients and accounts for substantial long-term healthcare costs. There is a need for formal, evidence-based guidelines for a coherent, coordinated management strategy for patients with continuing pain after lumbar surgery.

© 2017 Elsevier B.V. Background Despite proven benefits of cardiac rehabilitation (CR), adherence to CR remains suboptimal. This trial aimed to assess the impact of the patient education ‘Learning and Coping Strategies’ (LC) on patient adherence to an eight-week CR program. Methods 825 patients with ischaemic heart disease or heart failure were open label randomised to either the LC arm (LC plus CR) or the control arm (CR alone) across three hospital units in Denmark. Both arms received same amount of training and education hours. LC consisted of individual clarifying interviews, participation of experienced patients as co-educators, situational, reflective and inductive teaching. The control arm received structured deductive teaching. The primary outcomes were patient adherence to at least 75% of the exercise training or education sessions. We tested for subgroup effects on the primary outcomes using interaction terms. The primary outcomes were compared across arms using logistic regression. Results More patients in the LC arm adhered to at least 75% of the exercise training sessions than control (80% versus 73%, adjusted odds ratio (OR):1.48; 95% CI:1.07 to 2.05, P = 0.018) and 75% of education sessions (79% versus 70%, adjusted OR:1.61, 1.17 to 2.22, P = 0.003). Some evidence of larger effects of LC on adherence was seen for patients with heart failure, low education and household income. Conclusions Addition of LC strategies improved adherence in rehabilitation both in terms of exercise training and education. Patients with heart failure, low levels of education and household income appear to benefit most from this adherence promoting intervention. Trial registration www.clinicaltrials.gov identifier NCT01668394

© 2017 International Society for Pharmacoeconomics and Outcomes Research (ISPOR) the efficacy of medicines, medical devices, and other health technologies should be proved in trials that assess final patient-relevant outcomes such as survival or morbidity. Market access and coverage decisions are, however, often based on surrogate end points, biomarkers, or intermediate end points, which aim to substitute and predict patient-relevant outcomes that are unavailable because of methodological, financial, or practical constraints. We provide a summary of the present use of surrogate end points in health care policy, discussing the case for and against their adoption and reviewing validation methods. We introduce a three-step framework for policymakers to handle surrogates, which involves establishing the level of evidence, assessing the strength of the association, and quantifying relations between surrogates and final outcomes. Although the use of surrogates can be problematic, they can, when selected and validated appropriately, offer important opportunities for more efficient clinical trials and faster access to new health technologies that benefit patients and health care systems.

INTRODUCTION: the cardiopulmonary exercise test (CPET) assesses maximal oxygen uptake (VO2max) and is commonly performed on a leg cycle ergometer (LC). However, some individuals would rather perform the CPET on an arm cycle ergometer (AC). OBJECTIVE: the objectives of this study were to undertake a systematic review and meta-analysis of the difference in VO2max achieved by AC compared to LC in healthy adults and to explore factors that may be predictive of this difference. METHODS: MEDLINE, EMBASE, CINAHL, and PEDro were searched in April 2015. The differences in VO2max (ACLCdiff) were pooled across studies using random effects meta-analysis and three different methods were used to estimate the ratio between the values obtained from the tests (ACLCratio). RESULTS: This paper included 41 studies with a total of 581 participants. The mean ACLCdiff across studies was 12.5 ml/kg/min and 0.89 l/min with a mean ACLCratio of 0.70. The ACLCdiff was lower in studies with higher mean age and lower aerobic capacity. CONCLUSION: There is linear association between the AC and LC values in healthy adults. The AC values were on average 70% of the LC values. The magnitude of this difference appeared to be reduced in studies on older and less active populations. LEVEL OF EVIDENCE: 3a.

BACKGROUND: Identification of permanent hearing impairment at the earliest possible age is crucial to maximise the development of speech and language. Universal newborn hearing screening identifies the majority of the 1 in 1000 children born with a hearing impairment, but later onset can occur at any time and there is no optimum time for further screening. A universal but non-standardised school entry screening (SES) programme is in place in many parts of the UK but its value is questioned. OBJECTIVES: to evaluate the diagnostic accuracy of hearing screening tests and the cost-effectiveness of the SES programme in the UK. DESIGN: Systematic review, case-control diagnostic accuracy study, comparison of routinely collected data for services with and without a SES programme, parental questionnaires, observation of practical implementation and cost-effectiveness modelling. SETTING: Second- and third-tier audiology services; community. PARTICIPANTS: Children aged 4-6 years and their parents. MAIN OUTCOME MEASURES: Diagnostic accuracy of two hearing screening devices, referral rate and source, yield, age at referral and cost per quality-adjusted life-year. RESULTS: the review of diagnostic accuracy studies concluded that research to date demonstrates marked variability in the design, methodological quality and results. The pure-tone screen (PTS) (Amplivox, Eynsham, UK) and HearCheck (HC) screener (Siemens, Frimley, UK) devices had high sensitivity (PTS ≥ 89%, HC ≥ 83%) and specificity (PTS ≥ 78%, HC ≥ 83%) for identifying hearing impairment. The rate of referral for hearing problems was 36% lower with SES (Nottingham) relative to no SES (Cambridge) [rate ratio 0.64, 95% confidence interval (CI) 0.59 to 0.69; p 

INTRODUCTION: Economically disadvantaged smokers not intending to stop may benefit from interventions aimed at reducing their smoking. This study assessed the effects of a behavioral intervention promoting an increase in physical activity versus usual care in a pilot randomized controlled trial. METHODS: Disadvantaged smokers who wanted to reduce but not quit were randomized to either a counseling intervention of up to 12 weeks to support smoking reduction and increased physical activity (n = 49) or usual care (n = 50). Data at 16 weeks were collected for various smoking and physical activity outcomes. Primary analyses consisted of an intention to treat analysis based on complete case data. Secondary analyses explored the impact of handling missing data. RESULTS: Compared with controls, intervention smokers were more likely to initiate a quit attempt (36 vs. 10%; odds ratio 5.05, [95% CI: 1.10; 23.15]), and a greater proportion achieved at least 50% reduction in cigarettes smoked (63 vs. 32%; 4.21 [1.32; 13.39]). Postquit abstinence measured by exhaled carbon monoxide at 4-week follow-up showed promising differences between groups (23% vs. 6%; 4.91 [0.80; 30.24]). No benefit of intervention on physical activity was found. Secondary analyses suggested that the standard missing data assumption of "missing" being equivalent to "smoking" may be conservative resulting in a reduced intervention effect. CONCLUSIONS: a smoking reduction intervention for economically disadvantaged smokers which involved personal support to increase physical activity appears to be more effective than usual care in achieving reduction and may promote cessation. The effect does not appear to be influenced by an increase in physical activity.

BACKGROUND: Around 17% of people eligible for UK cardiac rehabilitation programmes following an acute coronary syndrome report moderate or severe depressive symptoms. While maximising psychological health is a core goal of cardiac rehabilitation, psychological care can be fragmented and patchy. This study tests the feasibility and acceptability of embedding enhanced psychological care, composed of two management strategies of proven effectiveness in other settings (nurse-led mental health care coordination and behavioural activation), within the cardiac rehabilitation care pathway. METHODS/DESIGN: This study tests the uncertainties associated with a large-scale evaluation by conducting an external pilot trial with a nested qualitative study. We aim to recruit and randomise eight comprehensive cardiac rehabilitation teams (clusters) to intervention (embedding enhanced psychological care into routine cardiac rehabilitation programmes) or control (routine cardiac rehabilitation programmes alone) arms. Up to 64 patients (eight per team) identified with depressive symptoms upon initial assessment by the cardiac rehabilitation team will be recruited, and study measures will be administered at baseline (before starting rehabilitation) and at 5 months and 8 months post baseline. Outcomes include depressive symptoms, cardiac mortality and morbidity, anxiety, health-related quality of life and service resource use. Trial data on cardiac team and patient recruitment, and the retention and flow of patients through treatment will be used to assess intervention feasibility and acceptability. Qualitative interviews will be undertaken to explore trial participants' and cardiac rehabilitation nurses' views and experiences of the trial methods and intervention, and to identify reasons why patients declined to take part in the trial. Outcome data will inform a sample size calculation for a definitive trial. DISCUSSION: the pilot trial and qualitative study will inform the design of a fully powered cluster randomised controlled trial to evaluate the effectiveness and cost-effectiveness of the provision of enhanced psychological care within cardiac rehabilitation programmes. TRIAL REGISTRATION: ISRCTN34701576 (Registered 29 May 2014).

© 2016 the Cochrane Collaboration. This is the protocol for a review and there is no abstract. The objectives are as follows: Our objective is to appraise the effectiveness of beta blockers in patients with heart failure. Our protocol defined main outcome is all cause mortality. The specific a priori defined aims are to examine: the effectiveness of beta blockers in all trials of patients with heart failure, and examine the importance of the presence or absence of ischaemic cardiomyopathy in patients included in trials and vasodilator properties of beta blocking agents used. We will also examine the predictive value of left ventricular function, age, use of angiotensin converting enzyme inhibitors and New York Heart Association Class (NYHA), and the rate of discontinuation of therapy due to treatment. There are a number of important ongoing trials for which data will become available in the next few years. Thus a systematic review which may be updated regularly is required to provide an up to date synthesis of the available data in this increasingly important area.

The study aimed to gain consensus on key priorities for developing breathlessness rehabilitation services for patients with chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF). Seventy-four invited stakeholders attended a 1-day conference to review the evidence base for exercise-based rehabilitation in COPD and CHF. In addition, 47 recorded their views on a series of statements regarding breathlessness rehabilitation tailored to the needs of both patient groups. A total of 75% of stakeholders supported symptom-based rather than disease-based rehabilitation for breathlessness with 89% believing that such services would be attractive for healthcare commissioners. A total of 87% thought patients with CHF could be exercised using COPD training principles and vice versa. A total of 81% felt community-based exercise training was safe for patients with severe CHF or COPD, but only 23% viewed manual-delivered rehabilitation an effective alternative to supervised exercise training. Although there was strong consensus that exercise training was a core component of rehabilitation in CHF and COPD populations, only 36% thought that this was the 'most important' component, highlighting the need for psychological and other non-exercise interventions for breathlessness. Patients with COPD and CHF face similar problems of breathlessness and disability on a background of multi-morbidity. Existing pulmonary and cardiac rehabilitation services should seek synergies to provide sufficient flexibility to accommodate all patients with COPD and CHF. Development of new services could consider adopting a patient-focused rather than disease-based approach. Exercise training is a core component, but rehabilitation should include other interventions to address dyspnoea, psychological and education needs of patients and needs of carers.

OBJECTIVE: the evidence for cardiac rehabilitation after valve surgery remains sparse. Current recommendations are therefore based on patients with ischaemic heart disease. The aim of this randomised clinical trial was to assess the effects of cardiac rehabilitation versus usual care after heart valve surgery. METHODS: the trial was an investigator-initiated, randomised superiority trial (The CopenHeartVR trial, VR; valve replacement or repair). We randomised 147 patients after heart valve surgery 1:1 to 12â€
weeks of cardiac rehabilitation consisting of physical exercise and monthly psycho-educational consultations (intervention) versus usual care without structured physical exercise or psycho-educational consultations (control). Primary outcome was physical capacity measured by VO2 peak and secondary outcome was self-reported mental health measured by Short Form-36. RESULTS: 76% were men, mean age 62â€
years, with aortic (62%), mitral (36%) or tricuspid/pulmonary valve surgery (2%). Cardiac rehabilitation compared with control had a beneficial effect on VO2 peak at 4â€
months (24.8â€
mL/kg/min vs 22.5â€
mL/kg/min, p=0.045) but did not affect Short Form-36 Mental Component Scale at 6â€
months (53.7 vs 55.2 points, p=0.40) or the exploratory physical and mental outcomes. Cardiac rehabilitation increased the occurrence of self-reported non-serious adverse events (11/72 vs 3/75, p=0.02). CONCLUSIONS: Cardiac rehabilitation after heart valve surgery significantly improves VO2 peak at 4â€
months but has no effect on mental health and other measures of exercise capacity and self-reported outcomes. Further research is needed to justify cardiac rehabilitation in this patient group. TRIAL REGISTRATION NUMBER: NCT01558765, Results.

BACKGROUND: Parkinson's disease (PD) is a debilitating illness associated with considerable impairment of quality of life and substantial costs to health care systems. Deep brain stimulation (DBS) is an established surgical treatment option for some patients with advanced PD. The EARLYSTIM trial has recently demonstrated its clinical benefit also in patients with early motor complications. We sought to evaluate the cost-effectiveness of DBS, compared to best medical therapy (BMT), among PD patients with early onset of motor complications, from a United Kingdom (UK) payer perspective. METHODS: We developed a Markov model to represent the progression of PD as rated using the Unified Parkinson's Disease Rating Scale (UPDRS) over time in patients with early PD. Evidence sources were a systematic review of clinical evidence; data from the EARLYSTIM study; and a UK Clinical Practice Research Datalink (CPRD) dataset including DBS patients. A mapping algorithm was developed to generate utility values based on UPDRS data for each intervention. The cost-effectiveness was expressed as the incremental cost per quality-adjusted life-year (QALY). One-way and probabilistic sensitivity analyses were undertaken to explore the effect of parameter uncertainty. RESULTS: over a 15-year time horizon, DBS was predicted to lead to additional mean cost per patient of £26,799 compared with BMT (£73,077/patient versus £46,278/patient) and an additional mean 1.35 QALYs (6.69 QALYs versus 5.35 QALYs), resulting in an incremental cost-effectiveness ratio of £19,887 per QALY gained with a 99% probability of DBS being cost-effective at a threshold of £30,000/QALY. One-way sensitivity analyses suggested that the results were not significantly impacted by plausible changes in the input parameter values. CONCLUSION: These results indicate that DBS is a cost-effective intervention in PD patients with early motor complications when compared with existing interventions, offering additional health benefits at acceptable incremental cost. This supports the extended use of DBS among patients with early onset of motor complications.

BACKGROUND: the Healthy Lifestyles Programme (HeLP) trial is being conducted to determine whether a novel school-based intervention is effective and cost-effective in preventing obesity in 9-10 year-old children. This article describes the detailed statistical analysis plan for the HeLP trial, including an amendment (and rationale for amendment) made to originally planned sensitivity analyses. METHODS AND DESIGN: the HeLP trial is a definitive, pragmatic, superiority, cluster randomised controlled trial with two parallel groups and blinded outcome assessment. This update article describes in detail (1) the primary and secondary outcomes, (2) the statistical analysis principles (including which children will be included in each analysis, how the clustered nature of the study design will be accounted for, which covariates will be included in each analysis, how the results will be presented), (3) planned sensitivity analyses, planned subgroup analyses and planned adherence-adjusted analyses for the primary outcome, (4) planned analyses for the secondary outcomes and (e) planned longitudinal analyses. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number (ISRCTN) register: ISRCTN15811706. Registered on 1 May 2012.

BACKGROUND AND PURPOSE: Our aim was to update previous European Federation of Neurological Societies guidelines on neurostimulation for neuropathic pain, expanding the search to new techniques and to chronic pain conditions other than neuropathic pain, and assessing the evidence with the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. METHODS: a systematic review and meta-analysis of trials published between 2006 and December 2014 was conducted. Pain conditions included neuropathic pain, fibromyalgia, complex regional pain syndrome (CRPS) type I and post-surgical chronic back and leg pain (CBLP). Spinal cord stimulation (SCS), deep brain stimulation (DBS), epidural motor cortex stimulation (MCS), repetitive transcranial magnetic stimulation (rTMS) and transcranial direct electrical stimulation (tDCS) of the primary motor cortex (M1) or dorsolateral prefrontal cortex (DLPFC) were assessed. The GRADE system was used to assess quality of evidence and propose recommendations. RESULTS: the following recommendations were reached: 'weak' for SCS added to conventional medical management in diabetic painful neuropathy, CBLP and CRPS, for SCS versus reoperation in CBLP, for MCS in neuropathic pain, for rTMS of M1 in neuropathic pain and fibromyalgia and for tDCS of M1 in neuropathic pain; 'inconclusive' for DBS in neuropathic pain, rTMS and tDCS of the DLPFC, and for motor cortex tDCS in fibromyalgia and spinal cord injury pain. CONCLUSIONS: Given the poor to moderate quality of evidence identified by this review, future large-scale multicentre studies of non-invasive and invasive neurostimulation are encouraged. The collection of higher quality evidence of the predictive factors for the efficacy of these techniques, such as the duration, quality and severity of pain, is also recommended.

© 2016 American College of Cardiology Foundation. Background Although recommended in guidelines for the management of coronary heart disease (CHD), concerns have been raised about the applicability of evidence from existing meta-analyses of exercise-based cardiac rehabilitation (CR). Objectives the goal of this study is to update the Cochrane systematic review and meta-analysis of exercise-based CR for CHD. Methods the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, and Science Citation Index Expanded were searched to July 2014. Retrieved papers, systematic reviews, and trial registries were hand-searched. We included randomized controlled trials with at least 6 months of follow-up, comparing CR to no-exercise controls following myocardial infarction or revascularization, or with a diagnosis of angina pectoris or CHD defined by angiography. Two authors screened titles for inclusion, extracted data, and assessed risk of bias. Studies were pooled using random effects meta-analysis, and stratified analyses were undertaken to examine potential treatment effect modifiers. Results a total of 63 studies with 14,486 participants with median follow-up of 12 months were included. Overall, CR led to a reduction in cardiovascular mortality (relative risk: 0.74; 95% confidence interval: 0.64 to 0.86) and the risk of hospital admissions (relative risk: 0.82; 95% confidence interval: 0.70 to 0.96). There was no significant effect on total mortality, myocardial infarction, or revascularization. The majority of studies (14 of 20) showed higher levels of health-related quality of life in 1 or more domains following exercise-based CR compared with control subjects. Conclusions This study confirms that exercise-based CR reduces cardiovascular mortality and provides important data showing reductions in hospital admissions and improvements in quality of life. These benefits appear to be consistent across patients and intervention types and were independent of study quality, setting, and publication date.

BACKGROUND Although recommended in guidelines for the management of coronary heart disease (CHD),
concerns have been raised about the applicability of evidence from existing meta-analyses of exercise-based cardiac
rehabilitation (CR).
OBJECTIVES the goal of this study is to update the Cochrane systematic review and meta-analysis of exercise-based
CR for CHD.
METHODS the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, and Science Citation Index
Expanded were searched to July 2014. Retrieved papers, systematic reviews, and trial registries were hand-searched.
We included randomized controlled trials with at least 6 months of follow-up, comparing CR to no-exercise controls
following myocardial infarction or revascularization, or with a diagnosis of angina pectoris or CHD defined by angiography.
Two authors screened titles for inclusion, extracted data, and assessed risk of bias. Studies were pooled using
random effects meta-analysis, and stratified analyses were undertaken to examine potential treatment effect modifiers.
RESULTS a total of 63 studies with 14,486 participants with median follow-up of 12 months were included. Overall, CR
led to a reduction in cardiovascular mortality (relative risk: 0.74; 95% confidence interval: 0.64 to 0.86) and the risk of
hospital admissions (relative risk: 0.82; 95% confidence interval: 0.70 to 0.96). There was no significant effect on total
mortality, myocardial infarction, or revascularization. The majority of studies (14 of 20) showed higher levels of healthrelated
quality of life in 1 or more domains following exercise-based CR compared with control subjects.
CONCLUSIONS This study confirms that exercise-based CR reduces cardiovascular mortality and provides important
data showing reductions in hospital admissions and improvements in quality of life. These benefits appear to be
consistent across patients and intervention types and were independent of study quality, setting, and publication date.

© 2016 the Cochrane Collaboration. Background: Exercise-based cardiac rehabilitation may benefit heart valve surgery patients. We conducted a systematic review to assess the evidence for the use of exercise-based intervention programmes following heart valve surgery. Objectives: to assess the benefits and harms of exercise-based cardiac rehabilitation compared with no exercise training intervention, or treatment as usual, in adults following heart valve surgery. We considered programmes including exercise training with or without another intervention (such as a psycho-educational component). Search methods: We searched: the Cochrane Central Register of Controlled Trials (CENTRAL); the Database of Abstracts of Reviews of Effects (DARE); MEDLINE (Ovid); EMBASE (Ovid); CINAHL (EBSCO); PsycINFO (Ovid); LILACS (Bireme); and Conference Proceedings Citation Index-S (CPCI-S) on Web of Science (Thomson Reuters) on 23 March 2015. We handsearched Web of Science, bibliographies of systematic reviews and trial registers (ClinicalTrials.gov, Controlled-trials.com, and the World Health Organization International Clinical Trials Registry Platform). Selection criteria: We included randomised clinical trials that investigated exercise-based interventions compared with no exercise intervention control. The trial participants comprised adults aged 18 years or older who had undergone heart valve surgery for heart valve disease (from any cause) and received either heart valve replacement, or heart valve repair. Data collection and analysis: Two authors independently extracted data. We assessed the risk of systematic errors ('bias') by evaluation of bias risk domains. Clinical and statistical heterogeneity were assessed. Meta-analyses were undertaken using both fixed-effect and random-effects models. We used the GRADE approach to assess the quality of evidence. We sought to assess the risk of random errors with trial sequential analysis. Main results: We included two trials from 1987 and 2004 with a total 148 participants who have had heart valve surgery. Both trials had a high risk of bias. There was insufficient evidence at 3 to 6 months follow-up to judge the effect of exercise-based cardiac rehabilitation compared to no exercise on mortality (RR 4.46 (95% confidence interval (CI) 0.22 to 90.78); participants = 104; studies = 1; quality of evidence: very low) and on serious adverse events (RR 1.15 (95% CI 0.37 to 3.62); participants = 148; studies = 2; quality of evidence: very low). Included trials did not report on health-related quality of life (HRQoL), and the secondary outcomes of New York Heart Association class, left ventricular ejection fraction and cost. We did find that, compared with control (no exercise), exercise-based rehabilitation may increase exercise capacity (SMD -0.47, 95% CI -0.81 to -0.13; participants = 140; studies = 2, quality of evidence: moderate). There was insufficient evidence at 12 months follow-up for the return to work outcome (RR 0.55 (95% CI 0.19 to 1.56); participants = 44; studies = 1; quality of evidence: low). Due to limited information, trial sequential analysis could not be performed as planned. Authors' conclusions: Our findings suggest that exercise-based rehabilitation for adults after heart valve surgery, compared with no exercise, may improve exercise capacity. Due to a lack of evidence, we cannot evaluate the impact on other outcomes. Further high-quality randomised clinical trials are needed in order to assess the impact of exercise-based rehabilitation on patient-relevant outcomes, including mortality and quality of life.

Background
Coronary heart disease (CHD) is the single most common cause of death globally. However, with falling CHD mortality rates, an
increasing number of people live with CHD and may need support to manage their symptoms and prognosis. Exercise-based cardiac
rehabilitation (CR) aims to improve the health and outcomes of people with CHD. This is an update of a Cochrane systematic review
previously published in 2011.
Objectives
To assess the effectiveness and cost-effectiveness of exercise-based CR (exercise training alone or in combination with psychosocial or
educational interventions) compared with usual care on mortality, morbidity and HRQL in patients with CHD.
To explore the potential study level predictors of the effectiveness of exercise-based CR in patients with CHD.
Search methods
We updated searches from the previous Cochrane review, by searching Cochrane Central Register of Controlled Trials (CENTRAL)
(The Cochrane Library, Issue 6, 2014) from December 2009 to July 2014. We also searched MEDLINE (Ovid), EMBASE (Ovid),
CINAHL (EBSCO) and Science Citation Index Expanded (December 2009 to July 2014).
Selection criteria
We included randomised controlled trials (RCTs) of exercise-based interventions with at least six months’ follow-up, compared with a
no exercise control. The study population comprised men and women of all ages who have had a myocardial infarction (MI), coronary
artery bypass graft (CABG) or percutaneous coronary intervention (PCI), or who have angina pectoris, or coronary artery disease. We
included RCTs that reported at least one of the following outcomes: mortality, MI, revascularisations, hospitalisations, health-related
quality of life (HRQL), or costs. Data collection and analysis
Two review authors independently screened all identified references for inclusion based on the above inclusion and exclusion criteria.
One author extracted data from the included trials and assessed their risk of bias; a second review author checked data. We stratified
meta-analysis by the duration of follow up of trials, i.e. short-term: 6 to 12 months, medium-term: 13 to 36 months, and long-term:
> 3 years.
Main results
This review included 63 trials which randomised 14,486 people with CHD. This latest update identified 16 new trials (3872 participants).
The population included predominantly post-MI and post-revascularisation patients and the mean age of patients within the
trials ranged from 47.5 to 71.0 years.Women accounted for fewer than 15% of the patients recruited. Overall trial reporting was poor,
although there was evidence of an improvement in quality of reporting in more recent trials.
As we found no significant difference in the impact of exercise-based CR on clinical outcomes across follow-up, we focused on reporting
findings pooled across all trials at their longest follow-up (median 12 months). Exercise-based CR reduced cardiovascular mortality
compared with no exercise control (27 trials; risk ratio (RR) 0.74, 95% CI 0.64 to 0.86). There was no reduction in total mortality
with CR (47 trials, RR 0.96, 95% CI 0.88 to 1.04). The overall risk of hospital admissions was reduced with CR (15 trials; RR 0.82,
95% CI 0.70 to 0.96) but there was no significant impact on the risk of MI (36 trials; RR 0.90, 95% CI 0.79 to 1.04), CABG (29
trials; RR 0.96, 95% CI 0.80 to 1.16) or PCI (18 trials; RR 0.85, 95% CI 0.70 to 1.04).
There was little evidence of statistical heterogeneity across trials for all event outcomes, and there was evidence of small study bias for
MI and hospitalisation, but no other outcome. Predictors of clinical outcomes were examined across the longest follow-up of studies
using univariate meta-regression. Results show that benefits in outcomes were independent of participants’ CHD case mix (proportion
of patients with MI), type of CR (exercise only vs comprehensive rehabilitation) dose of exercise, length of follow-up, trial publication
date, setting (centre vs home-based), study location (continent), sample size or risk of bias.
Given the heterogeneity in outcome measures and reporting methods, meta-analysis was not undertaken for HRQL. In five out of 20
trials reporting HRQL using validated measures, there was evidence of significant improvement in most or all of the sub-scales with
exercise-based CR compared to control at follow-up. Four trial-based economic evaluation studies indicated exercise-based CR to be a
potentially cost-effective use of resources in terms of gain in quality-adjusted life years.
The quality of the evidence for outcomes reported in the review was rated using the GRADE method. The quality of the evidence
varied widely by outcome and ranged from low to moderate.
Authors’ conclusions
This updated Cochrane review supports the conclusions of the previous version of this review that, compared with no exercise control,
exercise-based CR reduces the risk of cardiovascular mortality but not total mortality. We saw a significant reduction in the risk of
hospitalisation with CR but not in the risk of MI or revascularisation. We identified further evidence supporting improved HRQL
with exercise-based CR. More recent trials were more likely to be well reported and include older and female patients. However, the
population studied in this review still consists predominantly of lower risk individuals following MI or revascularisation. Further well
conducted RCTs are needed to assess the impact of exercise-based CR in higher risk CHD groups and also those presenting with stable
angina. These trials should include validated HRQL outcome measures, explicitly report clinical event outcomes including mortality
and hospital admissions, and assess costs and cost-effectiveness.

© 2016 the Cochrane Collaboration. This is the protocol for a review and there is no abstract. The objectives are as follows: to determine the effectiveness and safety of exercise-based rehabilitation on the mortality, hospital admissions, morbidity, exercise capacity, health-related quality of life, and return to work of people after heart transplantation.

BACKGROUND: Study attrition has the potential to compromise a trial's internal and external validity. The aim of the present study was to identify factors associated with participant attrition in a pilot trial of the effectiveness of a novel behavioural support intervention focused on increasing physical activity to reduce smoking, to inform the methods to reduce attrition in a definitive trial. METHODS: Disadvantaged smokers who wanted to reduce but not quit were randomised (N = 99), of whom 61 (62 %) completed follow-up assessments at 16 weeks. Univariable logistic regression was conducted to determine the effects of intervention arm, method of recruitment, and participant characteristics (sociodemographic factors, and lifestyle, behavioural and attitudinal characteristics) on attrition, followed by multivariable logistic regression on those factors found to be related to attrition. RESULTS: Participants with low confidence to quit, and who were undertaking less than 150 mins of moderate and vigorous physical activity per week at baseline were less likely to complete the 16-week follow-up assessment. Exploratory analysis revealed that those who were lost to follow-up early in the trial (i.e. by 4 weeks), compared with those completing the study, were younger, had smoked for fewer years and had lower confidence to quit in the next 6 months. Participants who recorded a higher expired air carbon monoxide reading at baseline were more likely to drop out late in the study, as were those recruited via follow-up telephone calls. Multivariable analyses showed that only completing less than 150 mins of physical activity retained any confidence in predicting attrition in the presence of other variables. CONCLUSIONS: the findings indicate that those who take more effort to be recruited, are younger, are heavier smokers, have less confidence to quit, and are less physically active are more likely to withdraw or be lost to follow-up.

© 2015 Published on behalf of the European Society of Cardiology. All rights reserved. Aims the clinical response to cardiac resynchronization therapy (CRT) is variable. Multipoint left ventricular (LV) pacing could achieve more effective haemodynamic response than single-point LV pacing. Deployment of an LV lead over myocardial scar is associated with a poor haemodynamic response to and clinical outcome of CRT. We sought to determine whether the acute haemodynamic response to CRT using three-pole LV multipoint pacing (CRT3P-MPP) is superior to that to conventional CRT using single-site LV pacing (CRTSP) in patients with ischaemic cardiomyopathy and an LV free wall scar. Methods and results Sixteen patients with ischaemic cardiomyopathy [aged 72.6 ± 7.7 years (mean ± SD), 81.3% male, QRS: 146.0 ± 14.2 ms, LBBB in 14 (87.5%)] in whom the LV lead was intentionally deployed straddling an LV free wall scar (assessed using cardiac magnetic resonance), underwent assessment of LV + dP/dtmax during CRT3P-MPP and CRTSP. Interindividually, the ΔLV + dP/dtmax in relation to AAI pacing with CRT3P-MPP (6.2 ± 13.3%) was higher than with basal and mid CRTSP (both P < 0.001), but similar to apical CRTSP. Intraindividually, significant differences in the ΔLV + dP/dtmax to optimal and worst pacing configurations were observed in 10 (62.5%) patients. of the 8 patients who responded to at least one configuration, CRT3P-MPP was optimal in 5 (62.5%) and apical CRTSP was optimal in 3 (37.5%) (P = 0.0047). Conclusions in terms of acute haemodynamic response, CRT3P-MPP was comparable an apical CRTSP and superior to basal and distal CRTSP. In the absence of within-device haemodynamic optimization, CRT3P-MPP may offer a haemodynamic advantage over a fixed CRTSP configuration.

© 2016 Elsevier Ireland Ltd Aims to assess the effectiveness of home-based cardiac rehabilitation (CR) for heart failure compared to either usual medical care (i.e. no CR) or centre-based CR on mortality, morbidity, exercise capacity, health-related quality of life, drop out, adherence rates, and costs. Methods Randomised controlled trials were initially identified from previous systematic reviews of CR. We undertook updated literature searches of MEDLINE, EMBASE, CINAHL, PsycINFO and Cochrane Library to December 2015. A total of 19 trials with median follow up of 3 months were included — 17 comparisons of home-based CR to usual care (995 patients) and four comparing home and centre-based CR (295 patients). Results Compared to usual care, home-based CR improved VO2max (mean difference: 1.6 ml/kg/min, 0.8 to 2.4) and total Minnesota Living with Quality of Life score (− 3.3, − 7.5 to 1.0), with no difference in mortality, hospitalisation or study drop out. Outcomes and costs were similar between home-based and centre-based CR with the exception of higher levels of trial completion in the home-based group (relative risk: 1.2, 1.0 to 1.3). Conclusions Home-based CR results in short-term improvements in exercise capacity and health-related quality of life of heart failure patients compared to usual care. The magnitude of outcome improvement is similar to centre-based CR. Home-based CR appears to be safe with no evidence of increased risk of hospitalisation or death. These findings support the provision of home-based CR for heart failure as an evidence-based alternative to the traditional centre-based model of provision.

BACKGROUND: Differences in blood pressure between arms are associated with increased cardiovascular mortality in cohorts with established vascular disease or substantially elevated cardiovascular risk. AIM: to explore the association of inter-arm difference (IAD) with mortality in a community-dwelling cohort that is free of cardiovascular disease. DESIGN AND SETTING: Cohort analysis of a randomised controlled trial in central Scotland, from April 1998 to October 2008. METHOD: Volunteers from Lanarkshire, Glasgow, and Edinburgh, free of pre-existing vascular disease and with an ankle-brachial index ≤0.95, had systolic blood pressure measured in both arms at recruitment. Inter-arm blood pressure differences were calculated and examined for cross-sectional associations and differences in prospective survival. Outcome measures were cardiovascular events and all-cause mortality during mean follow-up of 8.2 years. RESULTS: Based on a single pair of measurements, 60% of 3350 participants had a systolic IAD ≥5 mmHg and 38% ≥10 mmHg. An IAD ≥5 mmHg was associated with increased cardiovascular mortality (adjusted hazard ratio [HR] 1.91, 95% confidence interval [CI] = 1.19 to 3.07) and all-cause mortality (adjusted HR 1.44, 95% CI = 1.15 to 1.79). Within the subgroup of 764 participants who had hypertension, IADs of ≥5 mmHg or ≥10 mmHg were associated with both cardiovascular mortality (adjusted HR 2.63, 95% CI = 0.97 to 7.02, and adjusted HR 2.96, 95% CI = 1.27 to 6.88, respectively) and all-cause mortality (adjusted HR 1.67, 95% CI = 1.05 to 2.66, and adjusted HR 1.63, 95% CI = 1.06 to 2.50, respectively). IADs ≥15 mmHg were not associated with survival differences in this population. CONCLUSION: Systolic IADs in blood pressure are associated with increased risk of cardiovascular events, including mortality, in a large cohort of people free of pre-existing vascular disease.

© 2016 Taylor et al. Background: Left ventricular (LV) mid-wall fibrosis (MWF), which occurs in about a quarter of patients with non-ischemic cardiomyopathy (NICM), is associated with high risk of pump failure. The mid LV wall is the site of circumferential myocardial fibers. We sought to determine the effect of MWF on LV myocardial mechanics. Methods: Patients with NICM (n = 116; age: 62.8 ± 13.2 years; 67 % male) underwent late gadolinium enhancement cardiovascular magnetic resonance (CMR) and were categorized according to the presence (+) or absence (-) of MWF. Feature tracking (FT) CMR was used to assess myocardial deformation. Results: Despite a similar LVEF (24.3 vs 27.5 %, p = 0.20), patients with MWF (32 [24 %]) had lower global circumferential strain (εcc: -6.6 % vs -9.4 %, P = 0.004), but similar longitudinal (εll: -7.6 % vs. -9.4 %, p = 0.053) and radial (εrr: 14.6 % vs. 17.8 % p = 0.18) strain. Compared with - MWF, + MWF was associated with reduced LV systolic, circumferential strain rate (-0.38 ± 0.1 vs -0.56 ± 0.3 s-1, p = 0.005) and peak LV twist (4.65 vs. 6.31°, p = 0.004), as well as rigid LV body rotation (64 % vs 28 %, P

OBJECTIVES: Increased physical activity predicts survival and reduces risk of readmission in patients with coronary heart disease. However, few data show how physical activity is associated with survival and readmission after heart valve surgery. Objective were to assess the association between physical activity levels 6-12â€
months after heart valve surgery and (1) survival, (2) hospital readmission 18-24â€
months after surgery and (3) participation in exercise-based cardiac rehabilitation. METHODS: Prospective cohort study with registry data from the CopenHeart survey, the Danish National Patient Register and the Danish Civil Registration System of 742 eligible patients. Physical activity was quantified with the International Physical Activity Questionnaire and analysed using Kaplan-Meier analysis and Cox regression and logistic regression methods. RESULTS: Patients with a moderate to high physical activity level had a reduced risk of mortality (3 deaths in 289 patients, 1%) compared with those with a low physical activity level (13 deaths in 235 patients, 5.5%) with a fully adjusted HR of 0.19 (95% CI 0.05 to 0.70). In contrast, physical activity level was not associated with the risk of hospital readmission. Patients who participated in exercise-based cardiac rehabilitation (n=297) were more likely than the non-participants (n=200) to have a moderate or high physical activity level than a low physical activity level (fully adjusted OR: 1.52, 95% CI 1.03 to 2.24). CONCLUSIONS: Moderate to high levels of physical activity after heart valve surgery are positively associated with higher survival rates and participation in cardiac rehabilitation.

BACKGROUND: the aim of this study was to undertake a comprehensive assessment of the patient, intervention and trial-level factors that may predict exercise capacity following exercise-based rehabilitation in patients with coronary heart disease and heart failure. DESIGN: Meta-analysis and meta-regression analysis. METHODS: Randomized controlled trials of exercise-based rehabilitation were identified from three published systematic reviews. Exercise capacity was pooled across trials using random effects meta-analysis, and meta-regression used to examine the association between exercise capacity and a range of patient (e.g. age), intervention (e.g. exercise frequency) and trial (e.g. risk of bias) factors. RESULTS: 55 trials (61 exercise-control comparisons, 7553 patients) were included. Following exercise-based rehabilitation compared to control, overall exercise capacity was on average 0.95 (95% CI: 0.76-1.41) standard deviation units higher, and in trials reporting maximum oxygen uptake (VO2max) was 3.3 ml/kg.min(-1) (95% CI: 2.6-4.0) higher. There was evidence of a high level of statistical heterogeneity across trials (I(2) statistic > 50%). In multivariable meta-regression analysis, only exercise intervention intensity was found to be significantly associated with VO2max (P = 0.04); those trials with the highest average exercise intensity had the largest mean post-rehabilitation VO2max compared to control. CONCLUSIONS: We found considerable heterogeneity across randomized controlled trials in the magnitude of improvement in exercise capacity following exercise-based rehabilitation compared to control among patients with coronary heart disease or heart failure. Whilst higher exercise intensities were associated with a greater level of post-rehabilitation exercise capacity, there was no strong evidence to support other intervention, patient or trial factors to be predictive.

BACKGROUND: Various prevalence figures have been reported for inter-arm differences in blood pressure (IAD); variation may be explained by differing population vascular risk and by measurement method. AIM: to review the literature to derive robust estimates of IAD prevalence relevant to community populations. DESIGN AND SETTING: Systematic review and meta-analysis. METHOD: MEDLINE, Embase, and CINAHL were searched for cross-sectional studies likely to represent general or primary care populations, reporting prevalence of IAD and employing a simultaneous method of measurement. Using study-level data, pooled estimates of mean prevalence of systolic IADs were calculated and compared using a random effects model. RESULTS: Eighty IAD studies were identified. Sixteen met inclusion criteria: pooled estimates of prevalence for systolic IAD ≥10 mmHg were 11.2% (95% confidence interval [CI] = 9.1 to 13.6) in hypertension, 7.4% (95% CI = 5.8 to 9.2) in diabetes, and 3.6% (95% CI = 2.3 to 5.0) for a general adult population (P

© 2015, SSIEM. Background: Acute liver failure (ALF) in infancy and childhood is a life-threatening emergency and in about 50 % the etiology remains unknown. Recently biallelic mutations in NBAS were identified as a new molecular cause of ALF with onset in infancy, leading to recurrent acute liver failure (RALF). Methods: the phenotype and medical history of 14 individuals with NBAS deficiency was studied in detail and functional studies were performed on patients’ fibroblasts. Results: the phenotypic spectrum of NBAS deficiency ranges from isolated RALF to a multisystemic disease with short stature, skeletal dysplasia, immunological abnormalities, optic atrophy, and normal motor and cognitive development resembling SOPH syndrome. Liver crises are triggered by febrile infections; they become less frequent with age but are not restricted to childhood. Complete recovery is typical, but ALF crises can be fatal. Antipyretic therapy and induction of anabolism including glucose and parenteral lipids effectively ameliorates the course of liver crises. Patients’ fibroblasts showed an increased sensitivity to high temperature at protein and functional level and a disturbed tethering of vesicles, pointing at a defect of intracellular transport between the endoplasmic reticulum and Golgi. Conclusions: Mutations in NBAS cause a complex disease with a wide clinical spectrum ranging from isolated RALF to a multisystemic phenotype. Thermal susceptibility of the syntaxin 18 complex is the basis of fever dependency of ALF episodes. NBAS deficiency is the first disease related to a primary defect of retrograde transport. Identification of NBAS deficiency allows optimized therapy of liver crises and even prevention of further episodes.

OBJECTIVES: to investigate whether self-rating level of perceived exertion can adequately guide exercise intensity during a 12-week cardiac rehabilitation programme. DESIGN: Linear regression analysis using rehabilitation data from two randomised controlled trials. METHODS: Patients undergoing radiofrequency ablation for atrial fibrillation or following heart valve surgery and participating in exercise-based rehabilitation were included. The 12-week rehabilitation outpatient programme comprised three weekly training sessions, each consisting of 20min aerobic exercise divided into three steps. Patients were asked to base their exercise intensity for each step on a predefined rating of perceived exertion specified in a training diary. Exercise intensity was objectively measured by heart rate during the last 2min for each exercise step. Comparative analysis and linear regression of the rating of perceived exertion and heart rate were performed. RESULTS: a total of 2622 ratings of perceived exertion were collected from 874 training sessions in 97 patients. Heart rate and rating of perceived exertion were associated both across all three exercise steps and individually for each step, with a mean of 6 to7bpm per 1-point difference in the rating of perceived exertion (p

BACKGROUND: Patients with "refractory angina" (RA) unsuitable for coronary revascularization experience high levels of hospitalization and poor health-related quality of life. Randomized trials have shown spinal cord stimulation (SCS) to be a promising treatment for chronic stable angina and RA; however, none has compared SCS with usual care (UC). The aim of this pilot study was to address the key uncertainties of conducting a definitive multicenter trial to assess the clinical and cost-effectiveness of SCS in RA patients, i.e. recruitment and retention of patients, burden of outcome measures, our ability to standardize UC in a UK NHS setting. METHODS: RA patients deemed suitable were randomized in a 1:1 ratio to SCS plus UC (SCS group) or UC alone (UC group). We sought to assess: recruitment, uptake, and retention of patients; feasibility and acceptability of SCS treatment; the feasibility and acceptability of standardizing UC; and the feasibility and acceptability of the proposed trial outcome measures. Patient outcomes were assessed at baseline (prerandomization) and three and six months postrandomization. RESULTS: We failed to meet our planned recruitment target (45 patients) and randomized 29 patients (15 SCS group, 14 UC group) over a 42-month period across four sites. None of the study participants chose to withdraw following consent and randomization. With exception of two deaths, all completed evaluation at baseline and follow-up. Although the study was not formally powered to compare outcomes between groups, we saw a trend toward larger improvements in both primary and secondary outcomes in the SCS group. CONCLUSIONS: While patient recruitment was found to be challenging, levels of participant retention, outcome completion, and acceptability of SCS therapy were high. A number of lessons are presented in order to take forward a future definitive pragmatic randomized trial.

BACKGROUND: Evidence suggests acupuncture may be effective for treating the symptoms of knee osteoarthritis. Offering this in a group setting may offer cost savings. The aim of this study was to establish the feasibility of a definitive trial to assess the clinical and cost-effectiveness of Western medical acupuncture given in groups, or given individually, for adults with severe knee pain attributable to osteoarthritis. METHODS: a pilot randomised controlled trial (RCT) was conducted. Participants were recruited from seven general practices in Plymouth, Devon. Acupuncture was provided, at a dosage that increased up to and including electroacupuncture if no pain relief was reported, by one experienced acupuncturist in a community clinic. Potentially eligible adults aged at least 45 years with knee osteoarthritis were identified from practice registers, screened and randomised to either: (1) standardised advice and exercise booklet alone ('standard'); (2) booklet plus group acupuncture ('group'); and (3) booklet plus individual acupuncture ('individual'). Both acupuncture arms received up to ten treatments over 12 weeks. Recruitment, retention and data completion rates were recorded, and participants completed questionnaires on acceptability. We collected pain, stiffness and function data (using the Western Ontario McMaster Universities Osteoarthritis Index; WOMAC) and general health (EQ-5D) and economic measures at baseline and 14 weeks post-randomisation. RESULTS: We screened 149 people and randomised 60 (40 %), 20 per arm. The overall 14 week follow-up rate was 77 %, but only 70 % in the 'standard' group; 4.1 % of data points were missing. The study was acceptable to participants. Changes in WOMAC pain score (intention to treat complete case analysis) from baseline to 14 week follow-up were: 'standard', 0.4 (95 % confidence interval (CI) -1.4, 2.2, n = 14); 'group' -3.2 (95 % CI -5.1, -1.4, n = 17); 'individual' -2.4 (95 % CI -4.1, -0.7, n = 15). CONCLUSIONS: a definitive three-arm trial is feasible. Further follow-up reminders, minimum data collection and incentives should be considered to improve participant retention in the follow-up processes in the standardised advice and exercise booklet arm. TRIAL REGISTRATION: ISRCTN05305406.

OBJECTIVE: We previously reported the association of inter-arm differences in blood pressure measurements (IAD) with increased cardiovascular and all-cause mortality. Several new large cohorts have been reported since our 2012 meta-analysis. We have therefore updated our meta-analyses to take account of these new data. DESIGN AND METHOD: Systematic review and meta-analysis: Medline, Embase and CINAHL were searched for studies reporting survival data in association with IAD. Study level hazard ratios (HR) were extracted for systolic IADs >=10mmHg and >=15mmHg, and pooled using generic inverse variance in a random effects model. Statistical heterogeneity was assessed using the I statistic. RESULTS: Searches to 12th November 2014 identified 3514 unique citations. Eighty full texts were assessed, and 13 studies (reporting data for 14 unique cohorts) contributed to the analyses, Median follow up ranged from 3 to 13 years. Five cohorts employed a simultaneous method of IAD measurement; the remainder used sequential measurements. Ten cohorts were recruited from community populations, including one hypertensive and one diabetic cohort. Four were selected hospital cohorts at increased vascular risk.Cardiovascular mortality was greater with an IAD >=10mmHg (HR 1.9 (95%CI 1.3 to 2.6; 7 cohorts, 13815 participants; I = 45%) and an IAD >=15mmHg (HR 1.7 (1.2 to 2.4; 9 cohorts; 18241 participants; I = 30%). For all-cause mortality HRs were 1.4 (1.2 to 1.8; 10 cohorts, 17709 participants; I = 62%) for IAD >=10mmHg and 1.4 (1.1 to 1.7; 12 cohorts, 18714 participants; I = 46%) for IAD >=15mmHg. Heterogeneity between studies could be accounted for by stratification according to underlying population cardiovascular risk, with higher HRs seen in populations at elevated risk; cardiovascular mortality with an IAD >=10mmHg: HR 1.4 (1.1 to 1.8; I = 0%) for community based cohorts compared to 3.8 (2.2 to 6.6; I = 0%) for those at elevated cardiovascular risk (p = 0.001; Figure).(Figure is included in full-text article.) CONCLUSIONS: : New studies confirming the association of an IAD with increased cardiovascular and all-cause mortality are consistent with previously published findings. Risks associated with an IAD rise in association with the underlying vascular risk of the population studied.

© 2015 the Author(s). Objective. To evaluate how municipality-based post-discharge follow-up visits including a general practitioner and municipal nurse affect early readmission among high-risk older people discharged from a hospital department of internal medicine. Design and setting. Centrally randomized single-centre pragmatic controlled trial comparing intervention and usual care with investigator-blinded outcome assessment. Intervention. The intervention was home visits with a general practitioner and municipal nurse within seven days of discharge focusing on medication, rehabilitation plan, functional level, and need for further health care initiatives. The visit was concluded by planning one or two further visits. Controls received standard health care services. Patients. People aged 65 + years discharged from Holbæk University Hospital, Denmark, in 2012 considered at high risk of readmission. Main outcome measures. The primary outcome was readmission within 30 days. Secondary outcomes at 30 and 180 days included readmission, primary health care, and municipal services. Outcomes were register-based and analysis used the intention-to-treat principle. Results. A total of 270 and 261 patients were randomized to intervention and control groups, respectively. The groups were similar in baseline characteristics. In all 149 planned discharge follow-up visits were carried out (55%). Within 30 days, 24% of the intervention group and 23% of the control group were readmitted (p = 0.93). No significant differences were found for any other secondary outcomes except that the intervention group received more municipal nursing services. Conclusion. This municipality-based follow-up intervention was only feasible in half the planned visits. The intervention as delivered had no effect on readmission or subsequent use of primary or secondary health care services.

INTRODUCTION: the Rehabilitation EnAblement in CHronic Heart Failure (REACH-HF) trial is part of a research programme designed to develop and evaluate a health professional facilitated, home-based, self-help rehabilitation intervention to improve self-care and health-related quality of life in people with heart failure and their caregivers. The trial will assess the clinical effectiveness and cost-effectiveness of the REACH-HF intervention in patients with systolic heart failure and impact on the outcomes of their caregivers. METHODS AND ANALYSIS: a parallel two group randomised controlled trial with 1:1 individual allocation to the REACH-HF intervention plus usual care (intervention group) or usual care alone (control group) in 216 patients with systolic heart failure (ejection fraction

Background
Depression is associated with physical inactivity, which may mediate the relationship between depression and a range of chronic physical health conditions. However, few interventions have combined a psychological intervention for depression with behaviour change techniques, such as behavioural activation (BA), to promote increased physical activity.

Methods
To determine procedural and clinical uncertainties to inform a definitive randomised controlled trial (RCT), a pilot parallel-group RCT was undertaken within two Improving Access to Psychological Therapies (IAPT) services in South West England. We aimed to recruit 80 adults with depression and randomise them to a supported, written self-help programme based on either BA or BA plus physical activity promotion (BAcPAc). Data were collected at baseline and 4 months post-randomisation to evaluate trial retention, intervention uptake and variance in outcomes to inform a sample size calculation. Qualitative data were collected from participants and psychological wellbeing practitioners (PWPs) to assess the acceptability and feasibility of the trial methods and the intervention. Routine data were collected to evaluate resource use and cost.

Results
Sixty people with depression were recruited, and a 73 % follow-up rate was achieved. Accelerometer physical activity data were collected for 64 % of those followed. Twenty participants (33 %) attended at least one treatment appointment. Interview data were analysed for 15 participants and 9 study PWPs. The study highlighted the challenges of conducting an RCT within existing IAPT services with high staff turnover and absences, participant scheduling issues, PWP and participant preferences for cognitive focussed treatment, and deviations from BA delivery protocols. The BAcPAc intervention was generally acceptable to patients and PWPs.

Conclusions
Although recruitment procedures and data collection were challenging, participants generally engaged with the BAcPAc self-help booklets and reported willingness to increase their physical activity. A number of feasibility issues were identified, in particular the under-use of BA as a treatment for depression, the difficulty that PWPs had in adapting their existing procedures for study purposes and the instability of the IAPT PWP workforce. These problems would need to be better understood and resolved before proceeding to a full-scale RCT.

The ESTEEM trial was a randomised-controlled trial of telephone triage consultations in general practice. We conducted exploratory analyses on data from 9154 patients from 42 UK general practices who returned a questionnaire containing self-reported ratings of satisfaction with care following a request for a same-day consultation. Mode of care was identified through case notes review. There were seven main types: a GP face-to-face consultation, GP or nurse telephone triage consultation with no subsequent same day care, or a GP or nurse telephone triage consultation with a subsequent face-to-face consultation with a GP or a nurse. We investigated the contribution of mode of care to patient satisfaction and distance between the patient’s home and the practice as a potential moderating factor. There was no overall association between patient satisfaction and distance from practice. However, patients managed by a nurse telephone consultation showed lowest levels of satisfaction, and satisfaction for this group of patients increased the further they lived from the practice. There was no association between any of the other modes of management and distance from practice.

BACKGROUND: Individuals with a history of recurrent depression have a high risk of repeated depressive relapse or recurrence. Maintenance antidepressants for at least 2 years is the current recommended treatment, but many individuals are interested in alternatives to medication. Mindfulness-based cognitive therapy (MBCT) has been shown to reduce risk of relapse or recurrence compared with usual care, but has not yet been compared with maintenance antidepressant treatment in a definitive trial. We aimed to see whether MBCT with support to taper or discontinue antidepressant treatment (MBCT-TS) was superior to maintenance antidepressants for prevention of depressive relapse or recurrence over 24 months. METHODS: in this single-blind, parallel, group randomised controlled trial (PREVENT), we recruited adult patients with three or more previous major depressive episodes and on a therapeutic dose of maintenance antidepressants, from primary care general practices in urban and rural settings in the UK. Participants were randomly assigned to either MBCT-TS or maintenance antidepressants (in a 1:1 ratio) with a computer-generated random number sequence with stratification by centre and symptomatic status. Participants were aware of treatment allocation and research assessors were masked to treatment allocation. The primary outcome was time to relapse or recurrence of depression, with patients followed up at five separate intervals during the 24-month study period. The primary analysis was based on the principle of intention to treat. The trial is registered with Current Controlled Trials, ISRCTN26666654. FINDINGS: Between March 23, 2010, and Oct 21, 2011, we assessed 2188 participants for eligibility and recruited 424 patients from 95 general practices. 212 patients were randomly assigned to MBCT-TS and 212 to maintenance antidepressants. The time to relapse or recurrence of depression did not differ between MBCT-TS and maintenance antidepressants over 24 months (hazard ratio 0·89, 95% CI 0·67-1·18; p=0·43), nor did the number of serious adverse events. Five adverse events were reported, including two deaths, in each of the MBCT-TS and maintenance antidepressants groups. No adverse events were attributable to the interventions or the trial. INTERPRETATION: We found no evidence that MBCT-TS is superior to maintenance antidepressant treatment for the prevention of depressive relapse in individuals at risk for depressive relapse or recurrence. Both treatments were associated with enduring positive outcomes in terms of relapse or recurrence, residual depressive symptoms, and quality of life. FUNDING: National Institute for Health Research (NIHR) Health Technology Assessment (HTA) programme, and NIHR Collaboration for Leadership in Applied Health Research and Care South West Peninsula.

© 2015 the Cochrane Collaboration. This is the protocol for a review and there is no abstract. The objectives are as follows: to assess the benefits and harms of exercise-based cardiac rehabilitation programmes (exercise-based interventions alone or in combination with psycho-educational components) compared with control (no intervention, treatment as usual or another rehabilitation programme) in adults who have received an ICD.

OBJECTIVE: to update the Cochrane systematic review of exercise-based cardiac rehabilitation (CR) for heart failure. METHODS: a systematic review and meta-analysis of randomised controlled trials was undertaken. MEDLINE, EMBASE and the Cochrane Library were searched up to January 2013. Trials with 6 or more months of follow-up were included if they assessed the effects of exercise interventions alone or as a component of comprehensive CR programme compared with no exercise control. RESULTS: 33 trials were included with 4740 participants predominantly with a reduced ejection fraction (

STUDY QUESTION: Which variables at 15 and 20 weeks' gestation, particularly those amenable to modification before pregnancy, are associated with a subsequent uncomplicated pregnancy? SUMMARY ANSWER: Normalising body mass index, increasing fruit intake before pregnancy, reducing blood pressure, stopping misuse of drugs, and being in paid employment are all associated with subsequent uncomplicated pregnancy outcomes.

BACKGROUND: the ESTEEM trial was a cluster randomised controlled trial that compared two telephone triage management systems (general practitioner (GP) or a nurse supported by computer decision support software) with usual care, in response to a request for same-day consultation in general practice. AIM: to investigate associations between trial patients' demographic, health, and lifestyle characteristics, and their reported experiences of care. SETTING: Recruitment of 20â€
990 patients occurred between May 2011 and December 2012 in 42 GP practices in England (13 GP triage, 15 nurse triage, 14 usual care). METHOD: Patients reported their experiences via a postal questionnaire issued 4â€
weeks after their initial request for a same-day consultation. Overall satisfaction, ease of accessing medical help/advice, and convenience of care were analysed using linear hierarchical modelling. RESULTS: Questionnaires were returned by 12â€
132 patients (58%). Older patients reported increased overall satisfaction compared with patients aged 25-59â€
years, but patients aged 16-24â€
years reported lower satisfaction. Compared with white patients, patients from ethnic minorities reported lower satisfaction in all three arms, although to a lesser degree in the GP triage arm. Patients from ethnic minorities reported higher satisfaction in the GP triage than in usual care, whereas white patients reported higher satisfaction with usual care. Patients unable to take time away from work or who could only do so with difficulty reported lower satisfaction across all three trial arms. CONCLUSIONS: Patient characteristics, such as age, ethnicity and ability to attend their practice during work hours, were associated with their experiences of care following a same-day consultation request in general practice. Telephone triage did not increase satisfaction among patients who were unable to attend their practice during working hours. TRIAL REGISTRATION NUMBER: ISCRTN20687662.

© 2015 Elsevier Masson SAS. Background: the current definition of Failed Back Surgery Syndrome (FBSS) has a pejorative and restrictive connotation of blame and failure. Optimally, the evaluation of FBSS patients might be based on a multidimensional approach, involving an array of practitioners including spine surgeons, pain physicians, physiotherapists and behavioural specialists. Even though these clinical interactions should lead to a unique approach, one main problem comes from the fact that FBSS definition has varied over time and remains extremely controversial. There is now a need for global consensus about what we call FBSS, why, when and how. Discussing the name of this syndrome appears to be a logical starting point. Discussion: "PostOperative Persistent Syndrome", summarised by the acronym "POPS", could be an appropriate term to not only encapsulate failure but pain, function and psychosocial dysfunction following unsuccessful spine surgery whether from a technical or expectation standpoint. A return to the source might help to identify the real clinical problem, i.e. the pain mechanism: nociceptive, neuropathic pain or mixed. A clinical and radiological spine assessment is key to ensure that no further surgery is required, by distinguishing within the so-called FBSS population, "true" FBSS patients and "potential" FBSS patients, who are actually not FBSS patients, as an aetiological treatment of potential pain generators still remains possible. Conclusion: We propose to replace the FBSS acronym by POPS. The ultimate goal of this redefinition would be to guide the patient towards the future rather than the past and to reach a consensus, based on network discussions, concerning the following items: integrate pain mechanisms into the diagnostic process; implement the notion of a predominant ratio between mechanical/neuropathic pain mechanisms, which defines the potential target for treatment options; create a network supported by a database, to prospectively pool and analyse data, using homogeneous evaluation tools and ultimately define outcome predictors in this population.

© 2014 Elsevier Masson SAS. Introduction: Failed back surgery syndrome (FBSS) results from a cascade of medical and surgical events that lead to or leave the patient with chronic back and radicular pain. This concept is extremely difficult to understand, both for the patient and for the therapist. The difficulty is related to the connotations of failure and blame directly associated with this term. The perception of the medical situation varies enormously according to the background and medical education of the clinician who manages this type of patient. Eight health system experts (2 pain physicians, 1 orthopaedic spine surgeon, 1 neuro spine surgeon, 1 functional neurosurgeon, 1 physiatrist, 1 psychologist and one health-economic expert) were asked to define and share their specialist point of view concerning the management of postoperative back and radicular pain. Ideally, it could be proposed that the patient would derive optimal benefit from systematic confrontation of these various points of view in order to propose the best treatment option at a given point in time to achieve the best possible care pathway. Conclusion: the initial pejorative connotation of FBSS suggesting failure or blame must now be replaced to direct the patient and therapists towards a temporal concept focusing on the future rather than the past. In addition to the redefinition of an optimised care pathway, a consensus based on consultation would allow redefinition and renaming of this syndrome in order to ensure a more positive approach centered on the patient.

BACKGROUND: the current definition of Failed Back Surgery Syndrome (FBSS) has a pejorative and restrictive connotation of blame and failure. Optimally, the evaluation of FBSS patients might be based on a multidimensional approach, involving an array of practitioners including spine surgeons, pain physicians, physiotherapists and behavioural specialists. Even though these clinical interactions should lead to a unique approach, one main problem comes from the fact that FBSS definition has varied over time and remains extremely controversial. There is now a need for global consensus about what we call FBSS, why, when and how. Discussing the name of this syndrome appears to be a logical starting point. DISCUSSION: "PostOperative Persistent Syndrome", summarised by the acronym "POPS", could be an appropriate term to not only encapsulate failure but pain, function and psychosocial dysfunction following unsuccessful spine surgery whether from a technical or expectation standpoint. A return to the source might help to identify the real clinical problem, i.e. the pain mechanism: nociceptive, neuropathic pain or mixed. A clinical and radiological spine assessment is key to ensure that no further surgery is required, by distinguishing within the so-called FBSS population, "true" FBSS patients and "potential" FBSS patients, who are actually not FBSS patients, as an aetiological treatment of potential pain generators still remains possible. CONCLUSION: We propose to replace the FBSS acronym by POPS. The ultimate goal of this redefinition would be to guide the patient towards the future rather than the past and to reach a consensus, based on network discussions, concerning the following items: integrate pain mechanisms into the diagnostic process; implement the notion of a predominant ratio between mechanical/neuropathic pain mechanisms, which defines the potential target for treatment options; create a network supported by a database, to prospectively pool and analyse data, using homogeneous evaluation tools and ultimately define outcome predictors in this population.

INTRODUCTION: Failed back surgery syndrome (FBSS) results from a cascade of medical and surgical events that lead to or leave the patient with chronic back and radicular pain. This concept is extremely difficult to understand, both for the patient and for the therapist. The difficulty is related to the connotations of failure and blame directly associated with this term. The perception of the medical situation varies enormously according to the background and medical education of the clinician who manages this type of patient. Eight health system experts (2 pain physicians, 1 orthopaedic spine surgeon, 1 neuro spine surgeon, 1 functional neurosurgeon, 1 physiatrist, 1 psychologist and one health-economic expert) were asked to define and share their specialist point of view concerning the management of postoperative back and radicular pain. Ideally, it could be proposed that the patient would derive optimal benefit from systematic confrontation of these various points of view in order to propose the best treatment option at a given point in time to achieve the best possible care pathway. CONCLUSION: the initial pejorative connotation of FBSS suggesting failure or blame must now be replaced to direct the patient and therapists towards a temporal concept focusing on the future rather than the past. In addition to the redefinition of an optimised care pathway, a consensus based on consultation would allow redefinition and renaming of this syndrome in order to ensure a more positive approach centered on the patient.

Copyright © Cambridge University Press 2015. Objectives: the aim of this study was to review and compare current health technology assessment (HTA) activities for medical devices across non-European Union HTA agencies. Methods: HTA activities for medical devices were evaluated from three perspectives: organizational structure, processes, and methods. Agencies were primarily selected upon membership of existing HTA networks. The data collection was performed in two stages: stage 1-agency Web-site assessment using a standardized questionnaire, followed by review and validation of the collected data by a representative of the agency; and stage 2-semi-structured telephone interviews with key informants of a sub-sample of agencies. Results: in total, thirty-six HTA agencies across twenty non-EU countries assessing medical devices were included. Twenty-seven of thirty-six (75 percent) agencies were judged at stage 1 to have adopted HTA-specific approaches for medical devices (MD-specific agencies) that were largely organizational or procedural. There appeared to be few differences in the organization, process and methods between MD-specific and non-MD-specific agencies. Although the majority (69 percent) of both categories of agency had specific methods guidance or policy for evidence submission, only one MD-specific agency had developed methodological guidelines specific to medical devices. In stage 2, many MD-specific agencies cited insufficient resources (budget, skilled employees), lack of coordination (between regulator and reimbursement bodies), and the inability to generalize findings from evidence synthesis to be key challenges in the HTA of medical devices. Conclusions: the lack of evidence for differentiation in scientific methods for HTA of devices raises the question of whether HTA needs to develop new methods for medical devices but rather adapt existing methodological approaches. In contrast, organizational and/or procedural adaptation of existing HTA agency frameworks to accommodate medical devices appear relatively commonplace.

OBJECTIVES: the aim of this study was to review and compare current health technology assessment (HTA) activities for medical devices across non-European Union HTA agencies. METHODS: HTA activities for medical devices were evaluated from three perspectives: organizational structure, processes, and methods. Agencies were primarily selected upon membership of existing HTA networks. The data collection was performed in two stages: stage 1-agency Web-site assessment using a standardized questionnaire, followed by review and validation of the collected data by a representative of the agency; and stage 2-semi-structured telephone interviews with key informants of a sub-sample of agencies. RESULTS: in total, thirty-six HTA agencies across twenty non-EU countries assessing medical devices were included. Twenty-seven of thirty-six (75 percent) agencies were judged at stage 1 to have adopted HTA-specific approaches for medical devices (MD-specific agencies) that were largely organizational or procedural. There appeared to be few differences in the organization, process and methods between MD-specific and non-MD-specific agencies. Although the majority (69 percent) of both categories of agency had specific methods guidance or policy for evidence submission, only one MD-specific agency had developed methodological guidelines specific to medical devices. In stage 2, many MD-specific agencies cited insufficient resources (budget, skilled employees), lack of coordination (between regulator and reimbursement bodies), and the inability to generalize findings from evidence synthesis to be key challenges in the HTA of medical devices. CONCLUSIONS: the lack of evidence for differentiation in scientific methods for HTA of devices raises the question of whether HTA needs to develop new methods for medical devices but rather adapt existing methodological approaches. In contrast, organizational and/or procedural adaptation of existing HTA agency frameworks to accommodate medical devices appear relatively commonplace.

BACKGROUND: Cardiovascular disease is the most common cause of death globally. Traditionally, centre-based cardiac rehabilitation programmes are offered to individuals after cardiac events to aid recovery and prevent further cardiac illness. Home-based cardiac rehabilitation programmes have been introduced in an attempt to widen access and participation. This is an update of a review originally published in 2009. OBJECTIVES: to compare the effect of home-based and supervised centre-based cardiac rehabilitation on mortality and morbidity, health-related quality of life, and modifiable cardiac risk factors in patients with heart disease. SEARCH METHODS: to update searches from the previous Cochrane review, we searched the Cochrane Central Register of Controlled Trials (CENTRAL, the Cochrane Library, Issue 9, 2014), MEDLINE (Ovid, 1946 to October week 1 2014), EMBASE (Ovid, 1980 to 2014 week 41), PsycINFO (Ovid, 1806 to October week 2 2014), and CINAHL (EBSCO, to October 2014). We checked reference lists of included trials and recent systematic reviews. No language restrictions were applied. SELECTION CRITERIA: Randomised controlled trials (RCTs) that compared centre-based cardiac rehabilitation (e.g. hospital, gymnasium, sports centre) with home-based programmes in adults with myocardial infarction (MI), angina, heart failure or who had undergone revascularisation. DATA COLLECTION AND ANALYSIS: Two authors independently assessed the eligibility of the identified trials and data were extracted by a single author and checked by a second. Authors were contacted where possible to obtain missing information. MAIN RESULTS: Seventeen trials included a total of 2172 participants undergoing cardiac rehabilitation following an acute MI or revascularisation, or with heart failure. This update included an additional five trials on 345 patients with heart failure. Authors of a number of included trials failed to give sufficient detail to assess their potential risk of bias, and details of generation and concealment of random allocation sequence were particularly poorly reported. In the main, no difference was seen between home- and centre-based cardiac rehabilitation in outcomes up to 12 months of follow up: mortality (relative risk (RR) = 0.79, 95% confidence interval (CI) 0.43 to 1.47, P = 0.46, fixed-effect), cardiac events (data not poolable), exercise capacity (standardised mean difference (SMD) = -0.10, 95% CI -0.29 to 0.08, P = 0.29, random-effects), modifiable risk factors (total cholesterol: mean difference (MD) = 0.07 mmol/L, 95% CI -0.24 to 0.11, P = 0.47, random-effects; low density lipoprotein cholesterol: MD = -0.06 mmol/L, 95% CI -0.27 to 0.15, P = 0.55, random-effects; systolic blood pressure: mean difference (MD) = 0.19 mmHg, 95% CI -3.37 to 3.75, P = 0.92, random-effects; proportion of smokers at follow up (RR = 0.98, 95% CI 0.79 to 1.21, P = 0.83, fixed-effect), or health-related quality of life (not poolable). Small outcome differences in favour of centre-based participants were seen in high density lipoprotein cholesterol (MD = -0.07 mmol/L, 95% CI -0.11 to -0.03, P = 0.001, fixed-effect), and triglycerides (MD = -0.18 mmol/L, 95% CI -0.34 to -0.02, P = 0.03, fixed-effect, diastolic blood pressure (MD = -1.86 mmHg; 95% CI -0.76 to -2.95, P = 0.0009, fixed-effect). In contrast, in home-based participants, there was evidence of a marginally higher levels of programme completion (RR = 1.04, 95% CI 1.01 to 1.07, P = 0.009, fixed-effect) and adherence to the programme (not poolable). No consistent difference was seen in healthcare costs between the two forms of cardiac rehabilitation. AUTHORS' CONCLUSIONS: This updated review supports the conclusions of the previous version of this review that home- and centre-based forms of cardiac rehabilitation seem to be equally effective for improving the clinical and health-related quality of life outcomes in low risk patients after MI or revascularisation, or with heart failure. This finding, together with the absence of evidence of important differences in healthcare costs between the two approaches, supports the continued expansion of evidence-based, home-based cardiac rehabilitation programmes. The choice of participating in a more traditional and supervised centre-based programme or a home-based programme should reflect the preference of the individual patient. Further data are needed to determine whether the effects of home- and centre-based cardiac rehabilitation reported in these short-term trials can be confirmed in the longer term. A number of studies failed to give sufficient detail to assess their risk of bias.

BACKGROUND: Telephone triage represents one strategy to manage demand for face-to-face GP appointments in primary care. However, limited evidence exists of the challenges GP practices face in implementing telephone triage. We conducted a qualitative process evaluation alongside a UK-based cluster randomised trial (ESTEEM) which compared the impact of GP-led and nurse-led telephone triage with usual care on primary care workload, cost, patient experience, and safety for patients requesting a same-day GP consultation. The aim of the process study was to provide insights into the observed effects of the ESTEEM trial from the perspectives of staff and patients, and to specify the circumstances under which triage is likely to be successfully implemented. Here we report perspectives of staff. METHODS: the intervention comprised implementation of either GP-led or nurse-led telephone triage for a period of 2-3 months. A qualitative evaluation was conducted using staff interviews recruited from eight general practices (4 GP triage, 4 Nurse triage) in the UK, implementing triage as part of the ESTEEM trial. Qualitative interviews were undertaken with 44 staff members in GP triage and nurse triage practices (16 GPs, 8 nurses, 7 practice managers, 13 administrative staff). RESULTS: Staff reported diverse experiences and perceptions regarding the implementation of telephone triage, its effects on workload, and on the benefits of triage. Such diversity were explained by the different ways triage was organised, the staffing models used to support triage, how the introduction of triage was communicated across practice staff, and by how staff roles were reconfigured as a result of implementing triage. CONCLUSION: the findings from the process evaluation offer insight into the range of ways GP practices participating in ESTEEM implemented telephone triage, and the circumstances under which telephone triage can be successfully implemented beyond the context of a clinical trial. Staff experiences and perceptions of telephone triage are shaped by the way practices communicate with staff, prepare for and sustain the changes required to implement triage effectively, as well as by existing practice culture, and staff and patient behaviour arising in response to the changes made. TRIAL REGISTRATION: Current Controlled Trials ISRCTN20687662. Registered 28 May 2009.

OBJECTIVE: Nurse or pharmacist-led care may improve control of hypertension. We have undertaken a new Cochrane review of evidence for allied health professional led interventions in the management of hypertension. DESIGN AND METHOD: We searched multiple bibliographic databases to October 2013 for randomised controlled trials. We included any nursing, pharmacist, or allied health professional-led intervention designed to improve control of blood pressure (BP), compared to usual management of hypertension.Primary outcome measures were change in systolic BP, achievement of study target BP and use of antihypertensive medication. Two authors independently assessed studies for inclusion, extracted data, and assessed risk of bias using Cochrane criteria. Intervention effects were pooled using odds ratios (OR) or mean differences (MD). RESULTS: We identified 579 potential unique citations; 234 full-texts were assessed, and 98 papers met the inclusion criteria. Overall, half the risk of bias judgments across studies were rated as low risk.Compared to usual care, greater falls in systolic BP were seen for both nurse-led interventions (MD -3.8mmHg (95% CI: -5.6 to -2.0); 28 studies, 10573 participants) and pharmacist-led interventions (MD -7.6mmHg (-9.7 to -5.4); 30 studies, 6504 participants, p 

OBJECTIVE: on reviewing the evidence for allied health professional led interventions in the management of hypertension, we observed that blood pressure (BP) also falls within the usual care arms of included studies. Therefore we have undertaken further analysis to quantify the change in blood pressure in control arms of BP intervention studies included in the review. DESIGN AND METHOD: We used data from our Cochrane review (A115) that included 58 randomised controlled trials in 6897 patients identified in searches up to October 2013. This review included any nurse, pharmacist, or allied health professional-led intervention designed to improve control of BP, compared to usual management of hypertension.We used the primary outcome of change in systolic and diastolic BP from baseline to final follow up reported in usual care control arms of included trials. Changes in BP were expressed as weighted mean differences pooled using generic inverse variance taking account of within patient correlation. RESULTS: Mean systolic BP fell by -3.9mmHg (95% CI: -5.5 to -2.4) and diastolic BP fell by -2.7mmHg (-3.4 to -1.9) during usual care. Heterogeneity between studies was marked (systolic I2 = 97% and diastolic I2 = 94%). Usual care consisted of routine care only (45 trials) or enhancement with educational support for health professionals or patients (13 trials). Type of usual care did not account for observed heterogeneity, however restricting analyses to 24 high quality studies indicated a trend towards greater BP reductions with enhanced usual care compared to routine care only: diastolic -4.6mmHg (-6.5 to -2.7) for enhanced vs. -1.9mmHg (-3.1 to -0.7; p = 0.02) for routine care and systolic -6.9mmHg (-11.5 to -2.2) for enhanced vs. -4.2mmHg (-6.9 to -1.6; p = 0.33) for routine care. CONCLUSIONS: Statistically and clinically significant reductions in BP were seen in the control arms of BP intervention studies in this review, with greater reductions when usual care is enhanced within studies. Further work to establish whether this finding can be generalised to other BP intervention studies is required. This trend should be considered when interpreting BP intervention studies and in designing future interventions.

OBJECTIVES: to quantify and compare the treatment effects on three surrogate end points, progression-free survival (PFS), time to progression (TTP), and tumor response rate (TR) vs. overall survival (OS) based on a meta-analysis of randomized controlled trials (RCTs) of drug interventions in advanced colorectal cancer (aCRC). STUDY DESIGN AND SETTING: We systematically searched for RCTs of pharmacologic therapies in aCRC between 2003 and 2013. Trial characteristics, risk of bias, and outcomes were recorded based on a predefined form. Univariate and multivariate random-effects meta-analyses were used to estimate pooled summary treatment effects. The ratio of hazard ratios (HRs)/odds ratios (ORs) and difference in medians were used to quantify the degree of difference in treatment effects on the surrogate end points and OS. Spearman ρ, surrogate threshold effect (STE), and R(2) were also estimated across predefined trial-level covariates. RESULTS: We included 101 RCTs. In univariate and multivariate meta-analyses, we found larger treatment effects for the surrogates than for OS. Compared with OS, treatment effects were on average 13% higher when HRs were measured and 3% to 45% higher when ORs were considered; differences in median PFS/TTP were higher than on OS by an average of 0.5 month. Spearman ρ ranged from 0.39 to 0.80, mean R(2) from 0.06 to 0.65, and STE was 0.8 for HRPFS, 0.64 for HRTTP, or 0.28 for ORTR. The stratified analyses revealed high variability across all strata. CONCLUSION: None of the end points in this study were found to achieve the level of evidence (ie, mean R(2)trial > 0.60) that has been set to select high or excellent correlation levels by common surrogate evaluation tools. Previous surrogacy relationships observed between PFS and TTP vs. OS in selected settings may not apply across other classes or lines of therapy.

INTRODUCTION: Failed back surgery syndrome (FBSS) constitutes a constellation of symptoms grouped together and attributed to prior surgical intervention. Clinicians often poorly understand the heterogeneity of this condition combined with the etiological factors responsible for its development. Therefore, it would follow that an algorithmic treatment approach to patients diagnosed with this syndrome might pose challenges. The clinical work-up of the patient involves history, examination and appropriate diagnostic imaging as well as behavioral assessment. MATERIALS AND METHODS: We sought to conduct a narrative review of the available literature focused on the medical, rehabilitative and behavioral treatment of FBSS. To that end, we conducted a literature search using PubMed (through March 2013). We focused on studies published over the last 20years. Only English language articles were included. Search terms included "failed back surgery syndrome", "FBSS", "failed back syndrome", and "post-laminectomy syndrome". Studies included in our review focused on randomized controlled trials (RCTs), prospective cohort studies, and case series (retrospective and prospective). Studies were organized by intervention (e.g. medical management, physical therapy and rehabilitation, and psychosocial) and presented to emphasize the quality of evidence (e.g. RCTs, prospective studies, etc.). CONCLUSION: Overall, the literature provides very limited guidance on the comprehensive management of patients suffering from FBSS. There are rehabilitative interventions and behavioral protocols that demonstrate promise. Pathways based on medication management remain difficult to clearly define.

Patients with heart failure (HF) were once discouraged from participating in exercise programs because of concerns regarding safety and the potential for harm to an already damaged myocardium. However, studies over the last 3 decades have provided extensive insights into both the health outcome benefits of exercise and the mechanisms underlying these benefits. Studies on the outcome benefits of exercise training, including mortality and hospitalization, have been convincing. This article reviews the physiologic benefits of exercise training in HF, studies on exercise training in women, results and implications of the HF-ACTION trial, and recent meta-analyses using the Cochrane data base.

© 2015 the Cochrane Collaboration. This is the protocol for a review and there is no abstract. The objectives are as follows: to assess the impact of the routine use of patient-reported outcomes (PROs) in clinical practice on the process of care (including patient-physician communication, professionals awareness of patients' quality of life, diagnosis and recognition rates, treatment rates, health services and resource use, as well as patient behaviour); patients' and professionals' experiences of care; and health outcomes (both generic and disease-specific, using both routinely-used clinical measures and PROs).

BACKGROUND: Telephone triage is proposed as a method of managing increasing demand for primary care. Previous studies have involved small samples in limited settings, and focused on nurse roles. Evidence is limited regarding the impact on primary care workload, costs, and patient safety and experience when triage is used to manage patients requesting same-day consultations in general practice. OBJECTIVES: in comparison with usual care (UC), to assess the impact of GP-led telephone triage (GPT) and nurse-led computer-supported telephone triage (NT) on primary care workload and cost, patient experience of care, and patient safety and health status for patients requesting same-day consultations in general practice. DESIGN: Pragmatic cluster randomised controlled trial, incorporating economic evaluation and qualitative process evaluation. SETTING: General practices (n = 42) in four regions of England, UK (Devon, Bristol/Somerset, Warwickshire/Coventry, Norfolk/Suffolk). PARTICIPANTS: Patients requesting same-day consultations. INTERVENTIONS: Practices were randomised to GPT, NT or UC. Data collection was not blinded; however, analysis was conducted by a statistician blinded to practice allocation. MAIN OUTCOME MEASURES: Primary - primary care contacts [general practice, out-of-hours primary care, accident and emergency (A&E) and walk-in centre attendances] in the 28 days following the index consultation request. Secondary - resource use and costs, patient safety (deaths and emergency hospital admissions within 7 days of index request, and A&E attendance within 28 days), health status and experience of care. RESULTS: of 20,990 eligible randomised patients (UC n = 7283; GPT n = 6695; NT n = 7012), primary outcome data were analysed for 16,211 patients (UC n = 5572; GPT n = 5171; NT n = 5468). Compared with UC, GPT and NT increased primary outcome contacts (over 28-day follow-up) by 33% [rate ratio (RR) 1.33, 95% confidence interval (CI) 1.30 to 1.36] and 48% (RR 1.48, 95% CI 1.44 to 1.52), respectively. Compared with GPT, NT was associated with a marginal increase in primary outcome contacts by 4% (RR 1.04, 95% CI 1.01 to 1.08). Triage was associated with a redistribution of primary care contacts. Although GPT, compared with UC, increased the rate of overall GP contacts (face to face and telephone) over the 28 days by 38% (RR 1.38, 95% CI 1.28 to 1.50), GP face-to-face contacts were reduced by 39% (RR 0.61, 95% CI 0.54 to 0.69). NT reduced the rate of overall GP contacts by 16% (RR 0.84, 95% CI 0.78 to 0.91) and GP face-to-face contacts by 20% (RR 0.80, 95% CI 0.71 to 0.90), whereas nurse contacts increased. The increased rate of primary care contacts in triage arms is largely attributable to increased telephone contacts. Estimated overall patient-clinician contact time on the index day increased in triage (GPT = 10.3 minutes; NT = 14.8 minutes; UC = 9.6 minutes), although patterns of clinician use varied between arms. Taking account of both the pattern and duration of primary outcome contacts, overall costs over the 28-day follow-up were similar in all three arms (approximately £75 per patient). Triage appeared safe, and no differences in patient health status were observed. NT was somewhat less acceptable to patients than GPT or UC. The process evaluation identified the complexity associated with introducing triage but found no consistency across practices about what works and what does not work when implementing it. CONCLUSIONS: Introducing GPT or NT was associated with a redistribution of primary care workload for patients requesting same-day consultations, and at similar cost to UC. Although triage seemed to be safe, investigation of the circumstances of a larger number of deaths or admissions after triage might be warranted, and monitoring of these events is necessary as triage is implemented. TRIAL REGISTRATION: Current Controlled Trials ISRCTN20687662. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 19, No. 13. See the NIHR Journals Library website for further project information.

BACKGROUND: Individuals with a history of recurrent depression have a high risk of repeated depressive relapse/recurrence. Maintenance antidepressant medication (m-ADM) for at least 2 years is the current recommended treatment, but many individuals are interested in alternatives to m-ADM. Mindfulness-based cognitive therapy (MBCT) has been shown to reduce the risk of relapse/recurrence compared with usual care but has not yet been compared with m-ADM in a definitive trial. OBJECTIVES: to establish whether MBCT with support to taper and/or discontinue antidepressant medication (MBCT-TS) is superior to and more cost-effective than an approach of m-ADM in a primary care setting for patients with a history of recurrent depression followed up over a 2-year period in terms of preventing depressive relapse/recurrence. Secondary aims examined MBCT's acceptability and mechanism of action. DESIGN: Single-blind, parallel, individual randomised controlled trial. SETTING: UK general practices. PARTICIPANTS: Adult patients with a diagnosis of recurrent depression and who were taking m-ADM. INTERVENTIONS: Participants were randomised to MBCT-TS or m-ADM with stratification by centre and symptomatic status. Outcome data were collected blind to treatment allocation and the primary analysis was based on the principle of intention to treat. Process studies using quantitative and qualitative methods examined MBCT's acceptability and mechanism of action. MAIN OUTCOMES MEASURES: the primary outcome measure was time to relapse/recurrence of depression. At each follow-up the following secondary outcomes were recorded: number of depression-free days, residual depressive symptoms, quality of life, health-related quality of life and psychiatric and medical comorbidities. RESULTS: in total, 212 patients were randomised to MBCT-TS and 212 to m-ADM. The primary analysis did not find any evidence that MBCT-TS was superior to m-ADM in terms of the primary outcome of time to depressive relapse/recurrence over 24 months [hazard ratio (HR) 0.89, 95% confidence interval (CI) 0.67 to 1.18] or for any of the secondary outcomes. Cost-effectiveness analysis did not support the hypothesis that MBCT-TS is more cost-effective than m-ADM in terms of either relapse/recurrence or quality-adjusted life-years. In planned subgroup analyses, a significant interaction was found between treatment group and reported childhood abuse (HR 1.89, 95% CI 1.06 to 3.38), with delayed time to relapse/recurrence for MBCT-TS participants with a more abusive childhood compared with those with a less abusive history. Although changes in mindfulness were specific to MBCT (and not m-ADM), they did not predict outcome in terms of relapse/recurrence at 24 months. In terms of acceptability, the qualitative analyses suggest that many people have views about (dis)/continuing their ADM, which can serve as a facilitator or a barrier to taking part in a trial that requires either continuation for 2 years or discontinuation. CONCLUSIONS: There is no support for the hypothesis that MBCT-TS is superior to m-ADM in preventing depressive relapse/recurrence among individuals at risk for depressive relapse/recurrence. Both treatments appear to confer protection against relapse/recurrence. There is an indication that MBCT may be most indicated for individuals at greatest risk of relapse/recurrence. It is important to characterise those most at risk and carefully establish if and why MBCT may be most indicated for this group. TRIAL REGISTRATION: Current Controlled Trials ISRCTN26666654. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and the National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care South West Peninsula and will be published in full in Health Technology Assessment; Vol. 19, No. 73. See the NIHR Journals Library website for further project information.

© 2015 Sibilitz et al. Background: Heart valve diseases are common with an estimated prevalence of 2.5% in the Western world. The number is rising because of an ageing population. Once symptomatic, heart valve diseases are potentially lethal, and heavily influence daily living and quality of life. Surgical treatment, either valve replacement or repair, remains the treatment of choice. However, post-surgery, the transition to daily living may become a physical, mental and social challenge. We hypothesize that a comprehensive cardiac rehabilitation program can improve physical capacity and self-assessed mental health and reduce hospitalization and healthcare costs after heart valve surgery. Methods: This randomized clinical trial, CopenHeartVR, aims to investigate whether cardiac rehabilitation in addition to usual care is superior to treatment as usual after heart valve surgery. The trial will randomly allocate 210 patients 1:1 to an intervention or a control group, using central randomization, and blinded outcome assessment and statistical analyses. The intervention consists of 12 weeks of physical exercise and a psycho-educational intervention comprising five consultations. The primary outcome is peak oxygen uptake (VO2 peak) measured by cardiopulmonary exercise testing with ventilatory gas analysis. The secondary outcome is self-assessed mental health measured by the standardized questionnaire Short Form-36. Long-term healthcare utilization and mortality as well as biochemistry, echocardiography and cost-benefit will be assessed. A mixed-method design will be used to evaluate qualitative and quantitative findings, encompassing a survey-based study before the trial and a qualitative pre-and post-intervention study. Conclusion: This randomized clinical trial will contribute with evidence of whether cardiac rehabilitation should be provided after heart valve surgery. The study is approved by the local regional Research Ethics Committee (H-1-2011-157), and the Danish Data Protection Agency (j.nr. 2007-58-0015).

BACKGROUND: There have been few rigorous studies on the effects of behavioural support for helping smokers to reduce who do not immediately wish to quit. While reduction may not have the health benefits of quitting, it may lead smokers to want to quit. Physical activity (PA) helps to reduce cravings and withdrawal symptoms, and also reduces weight gain after quitting, but smokers may be less inclined to exercise. There is scope to develop and determine the effectiveness of interventions to support smoking reduction and increase physical activity, for those not ready to quit. OBJECTIVE: to conduct a pilot randomised controlled trial (RCT) [Exercise Assisted Reduction then Stop (EARS) smoking study] to (1) design and evaluate the feasibility and acceptability of a PA and smoking-reduction counselling intervention [for disadvantaged smokers who do not wish to quit but do want to reduce their smoking (to increase the likelihood of quitting)], and (2) to inform the design of a large RCT to determine the clinical effectiveness and cost-effectiveness of the intervention. DESIGN: a single-centre, pragmatic, pilot trial with follow-up up to 16 weeks. A mixed methods approach assessed the acceptability and feasibility of the intervention and trial methods. Smokers were individually randomised to intervention or control arms. SETTING: General practices, NHS buildings, community venues, and the Stop Smoking Service (SSS) within Plymouth, UK. PARTICIPANTS: Aged > 18 years, smoking ≥ 10 cigarettes per day (for ≥ 2 years) who wished to cut down. We excluded individuals who were contraindicated for moderate PA, posed a safety risk to the research team, wished to quit immediately or use Nicotine Replacement Therapy, not registered with a general practitioner, or did not converse in English. INTERVENTION: We designed a client-centred, counselling-based intervention designed to support smoking reduction and increases in PA. Support sessions were delivered by trained counsellors either face to face or by telephone. Both intervention and control arms were given information at baseline on specialist SSS support available should they have wished to quit. MAIN OUTCOME MEASURES: the primary outcome was 4-week post-quit expired air carbon monoxide (CO)-confirmed abstinence from smoking. Secondary outcomes included validated behavioural, cognitive and emotional/affective and health-related quality of life measures and treatment costs. RESULTS: the study randomised 99 participants, 49 to the intervention arm and 50 to the control arm, with a 62% follow-up rate at 16 weeks. In the intervention and control arms, 14% versus 4%, respectively [relative risk = 3.57; 95% confidence interval (CI) 0.78 to 16.35], had expired CO-confirmed abstinence at least 4 and up to 8 weeks after quit day; 22% versus 6% (relative risk = 3.74; 95% CI 1.11 to 12.60) made a quit attempt; 10% versus 4% (relative risk = 92.55; 95% CI 0.52 to 12.53) achieved point-prevalent abstinence at 16 weeks; and 39% versus 20% (relative risk = 1.94; 95% CI 1.01 to 3.74) achieved at least a 50% reduction in the number of cigarettes smoked daily. The percentage reporting using PA for controlling smoking in the intervention versus control arms was 55% versus 22%, respectively at 8 weeks and 37% versus 16%, respectively, at 16 weeks. The counsellors generally delivered the intervention as planned and participants responded with a variety of smoking reduction strategies, sometimes supported by changes in PA. The intervention costs were approximately £192 per participant. Exploratory cost-effectiveness modelling indicates that the intervention may be cost-effective. CONCLUSIONS: the study provided valuable information on the resources needed to improve study recruitment and retention. Offering support for smoking reduction and PA appears to have value in promoting reduction and cessation in disadvantaged smokers not currently motivated to quit. A large RCT is needed to assess the clinical effectiveness and cost-effectiveness of the intervention in this population. TRIAL REGISTRATION: ISRCTN 13837944. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment, Vol. 18, No. 4. See the NIHR Journals Library website for further project information.

Background: Challenges remain to find ways to support patients with depression who have low levels of physical activity (PA) to overcome perceived barriers and enhance the perceived value of PA for preventing future relapse. There is an evidence-base for behavioural activation (BA) for depression, which focuses on supporting patients to restore activities that have been avoided, but practitioners have no specific training in promoting PA. We aimed to design and evaluate an integrated BA and PA (BAcPAc) practitioner-led, written, self-help intervention to enhance both physical and mental health.Methods/design: This study is informed by the Medical Research Council Complex Intervention Framework and describes a protocol for a pilot phase II randomised controlled trial (RCT) to test the feasibility and acceptability of the trial methods to inform a definitive phase III RCT. Following development of the augmented written self-help intervention (BAcPAc) incorporating behavioural activation with physical activity promotion, depressed adults are randomised to receive up to 12 sessions over a maximum of 4 months of either BAcPAc or behavioural activation alone within a written self-help format, which represents treatment as usual. The study is located within two 'Improving Access to Psychological Therapies' services in South West England, with both written self-help interventions supported by mental health paraprofessionals. Measures assessed at 4, 9, and 12 month follow-up include the following: CIS-R, PHQ-9, accelerometer recorded (4 months only) and self-reported PA, body mass index, blood pressure, Insomnia Severity Index, quality of life, and health and social care service use. Process evaluation will include analysis of recorded support sessions and patient and practitioner interviews. At the time of writing the study has recruited 60 patients.Discussion: the feasibility outcomes will inform a definitive RCT to assess the clinical and cost-effectiveness of the augmented BAcPAc written self-help intervention to reduce depression and depressive relapse, and bring about improvements across a range of physical health outcomes.Trial registration: Current Controlled Trials ISRCTN74390532, 26.03.2013. © 2014 Farrand et al.; licensee BioMed Central Ltd.

BACKGROUND: Challenges remain to find ways to support patients with depression who have low levels of physical activity (PA) to overcome perceived barriers and enhance the perceived value of PA for preventing future relapse. There is an evidence-base for behavioural activation (BA) for depression, which focuses on supporting patients to restore activities that have been avoided, but practitioners have no specific training in promoting PA. We aimed to design and evaluate an integrated BA and PA (BAcPAc) practitioner-led, written, self-help intervention to enhance both physical and mental health. METHODS/DESIGN: This study is informed by the Medical Research Council Complex Intervention Framework and describes a protocol for a pilot phase II randomised controlled trial (RCT) to test the feasibility and acceptability of the trial methods to inform a definitive phase III RCT. Following development of the augmented written self-help intervention (BAcPAc) incorporating behavioural activation with physical activity promotion, depressed adults are randomised to receive up to 12 sessions over a maximum of 4 months of either BAcPAc or behavioural activation alone within a written self-help format, which represents treatment as usual. The study is located within two 'Improving Access to Psychological Therapies' services in South West England, with both written self-help interventions supported by mental health paraprofessionals. Measures assessed at 4, 9, and 12 month follow-up include the following: CIS-R, PHQ-9, accelerometer recorded (4 months only) and self-reported PA, body mass index, blood pressure, Insomnia Severity Index, quality of life, and health and social care service use. Process evaluation will include analysis of recorded support sessions and patient and practitioner interviews. At the time of writing the study has recruited 60 patients. DISCUSSION: the feasibility outcomes will inform a definitive RCT to assess the clinical and cost-effectiveness of the augmented BAcPAc written self-help intervention to reduce depression and depressive relapse, and bring about improvements across a range of physical health outcomes. TRIAL REGISTRATION: Current Controlled Trials ISRCTN74390532, 26.03.2013.

Objectives to define the key terms and concepts relating physical activity to chronic pain; to provide a brief overview of the various methods of assessment of physical activity; to review the current literature about physical activity and chronic pain; and to identify needs for future research. Materials and Methods a narrative review based on results of a PubMed search (to May 2011) and the references of recent systematic reviews. Results Many methods exist for measuring physical activity. Movement sensors, such as accelerometers, offer objective assessment of physical activity of patients with chronic pain. It is often assumed that patients who feel disabled and report daily life restrictions due to chronic pain also will be less physically active. Studies that have compared the activity of patients with chronic back pain with that of healthy individuals consistently showed that the relationship of physical activity and severity of pain, as well as the change in activity following interventions, was variable and complex. Conclusions it is important to understand the relationship between physical activity and chronic pain. Future studies should objectively assess not only the pattern and complexity of that relationship but also the interaction with the patient's mood and ability to cope with the pain. © 2014 International Neuromodulation Society.

© 2014 the Cochrane Collaboration. This is the protocol for a review and there is no abstract. The objectives are as follows: the primary aim of this overview is to summarise the research question, methods and findings of the Cochrane reviews on cardiac rehabilitation (CR) and to provide a 'friendly front end' to this portfolio of reviews. In addition, we will aim to: Identify the opportunities for merging and splitting across the reviews to inform the direction of future Cochrane CR review updates; Identify key evidence gaps across the reviews to inform de novo Cochrane CR reviews; and Identify disparities in current reporting outputs and provide recommendations to encourage uniformity of reporting of future trials and systematic reviews.

BACKGROUND: Overviews are a new approach to summarising evidence and synthesising results from related systematic reviews. OBJECTIVES: to conduct an overview of Cochrane systematic reviews to provide a contemporary review of the evidence for delivery of cardiac rehabilitation, to identify opportunities for merging or splitting existing Cochrane reviews, and to identify current evidence gaps to inform new cardiac rehabilitation systematic review titles. METHODS: We searched the Cochrane Database of Systematic Reviews (2014, Issue 10) to identify systematic reviews that addressed the objectives of this overview. We assessed the quality of included reviews using the Revised Assessment of Multiple Systematic Reviews (R-AMSTAR) measurement tool and the quality of the evidence for reported outcomes using the GRADE framework. The focus of the data presentation was descriptive with detailed tabular presentations of review level and trial level characteristics and results. MAIN RESULTS: We found six Cochrane systematic reviews and judged them to be of high methodological quality. They included 148 randomised controlled trials (RCTs) in 98,093 participants. Compared with usual care alone, the addition of exercise-based cardiac rehabilitation in low-risk people after myocardial infarction or percutaneous coronary intervention or with heart failure appeared to have no impact on mortality, but did reduce hospital admissions and improved health-related quality of life. Psychological- and education-based interventions alone appeared to have little or no impact on mortality or morbidity but may have improved health-related quality of life. Home- and centre-based programmes were equally effective in improving quality of life outcomes at similar healthcare costs. Selected interventions can increase the uptake of cardiac rehabilitation programmes whilst there is currently only weak evidence to support interventions that improve adherence to cardiac rehabilitation programmes. The quality of the primary RCTs in the included systematic reviews was variable, and limitations in the methodological quality of the RCTs led to downgrading of the quality of the evidence, which varied widely by review and by outcome. AUTHORS' CONCLUSIONS: Exercise-based cardiac rehabilitation is an effective and safe therapy to be used in the management of clinically stable people following myocardial infarction or percutaneous coronary intervention or who have heart failure. Future RCTs of cardiac rehabilitation need to improve their reporting methods and reflect the real world practice better including the recruitment of higher risk people and consideration of contemporary models of cardiac rehabilitation delivery, and identify effective interventions for enhancing adherence to rehabilitation.

INTRODUCTION: Overviews are a new approach to summarising evidence and synthesising results from related systematic reviews. OBJECTIVES: to conduct an overview of Cochrane systematic reviews to provide a contemporary review of the evidence for cardiac rehabilitation (CR), identify opportunities for merging or splitting existing Cochrane reviews, and identify current evidence gaps to inform new review titles. METHODS: the Cochrane Database of Systematic Reviews was searched to identify reviews that address the objectives of this overview. Data presentation is descriptive with tabular presentations of review- and trial-level characteristics and results. RESULTS: the six included Cochrane systematic reviews were of high methodological quality and included 148 randomised controlled trials in 97,486 participants. Compared to usual care alone, exercise-based CR reduces hospital admissions and improves patient health related quality of life (HRQL) in low to moderate risk heart failure and coronary heart disease (CHD) patients. At 12 months or more follow-up, there was evidence of some reduction in mortality in patients with CHD. Psychological- and education-based interventions appear to have little impact on mortality or morbidity but may improve HRQL. Home- and centre-based programmes are equally effective in improving HRQL at similar costs. Selected interventions can increase the uptake of CR programmes but evidence to support interventions that improve adherence is weak. CONCLUSIONS: This overview confirms that exercise-based CR is effective and safe in the management of clinically stable heart failure and post-MI and PCI patients. We discuss the implications of this overview on the future direction of the Cochrane CR reviews portfolio.

Patient ratings of satisfaction with their postoperative pain treatment tend to be high even in those with substantial pain. Determinants are poorly understood and have not previously been studied in large-scale, international datasets. PAIN OUT, a European Union-funded acute pain registry and research project, collects patient-reported outcome data on postoperative day 1 using the self-reported International Pain Outcome Questionnaire (IPO), and patient, clinical, and treatment characteristics. We investigated correlates of satisfaction and consistency of effects across centres and countries using multilevel regression modelling. Our sample comprised 16,868 patients (median age 55 years; 55% female) from 42 centres in 11 European countries plus Israel, USA, and Malaysia, who underwent a wide range of surgical procedures, for example, joint, limb, and digestive tract surgeries. Median satisfaction was 9 (interquartile range 7-10) on a 0-10 scale. Three IPO items showed strong associations and explained 35% of the variability present in the satisfaction variable: more pain relief received, higher allowed participation in pain treatment decisions, and no desire to have received more pain treatment. Patient factors and additional IPO items reflecting pain experience (eg, worst pain intensity), pain-related impairment, and information on pain treatment added little explanatory value, partially due to covariate correlations. Effects were highly consistent across centres and countries. We conclude that satisfaction with postoperative pain treatment is associated with the patients' actual pain experience, but more strongly with impressions of improvement and appropriateness of care. To the degree they desire, patients should be provided with information and involved in pain treatment decisions. ©2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Patient ratings of satisfaction with their postoperative pain treatment tend to be high even in those with substantial pain. Determinants are poorly understood and have not previously been studied in large-scale, international datasets. PAIN OUT, a European Union-funded acute pain registry and research project, collects patient-reported outcome data on postoperative day 1 using the self-reported International Pain Outcome Questionnaire (IPO), and patient, clinical, and treatment characteristics. We investigated correlates of satisfaction and consistency of effects across centres and countries using multilevel regression modelling. Our sample comprised 16,868 patients (median age 55 years; 55% female) from 42 centres in 11 European countries plus Israel, USA, and Malaysia, who underwent a wide range of surgical procedures, for example, joint, limb, and digestive tract surgeries. Median satisfaction was 9 (interquartile range 7-10) on a 0-10 scale. Three IPO items showed strong associations and explained 35% of the variability present in the satisfaction variable: more pain relief received, higher allowed participation in pain treatment decisions, and no desire to have received more pain treatment. Patient factors and additional IPO items reflecting pain experience (eg, worst pain intensity), pain-related impairment, and information on pain treatment added little explanatory value, partially due to covariate correlations. Effects were highly consistent across centres and countries. We conclude that satisfaction with postoperative pain treatment is associated with the patients' actual pain experience, but more strongly with impressions of improvement and appropriateness of care. To the degree they desire, patients should be provided with information and involved in pain treatment decisions.

BACKGROUND: Cognitive behaviour therapy (CBT) is an effective treatment for depression. However, CBT is a complex therapy that requires highly trained and qualified practitioners, and its scalability is therefore limited by the costs of training and employing sufficient therapists to meet demand. Behavioural activation (BA) is a psychological treatment for depression that may be an effective alternative to CBT and, because it is simpler, might also be delivered by less highly trained and specialised mental health workers. METHODS/DESIGN: COBRA is a two-arm, non-inferiority, patient-level randomised controlled trial, including clinical, economic, and process evaluations comparing CBT delivered by highly trained professional therapists to BA delivered by junior professional or para-professional mental health workers to establish whether the clinical effectiveness of BA is non-inferior to CBT and if BA is cost effective compared to CBT. Four hundred and forty patients with major depressive disorder will be recruited through screening in primary care. We will analyse for non-inferiority in per-protocol and intention-to-treat populations. Our primary outcome will be severity of depression symptoms (Patient Health Questionnaire-9) at 12 months follow-up. Secondary outcomes will be clinically significant change and severity of depression at 18 months, and anxiety (General Anxiety Disorder-7 questionnaire) and health-related quality of life (Short-Form Health Survey-36) at 12 and 18 months. Our economic evaluation will take the United Kingdom National Health Service/Personal Social Services perspective to include costs of the interventions, health and social care services used, plus productivity losses. Cost-effectiveness will explored in terms of quality-adjusted life years using the EuroQol-5D measure of health-related quality of life. DISCUSSION: the clinical and economic outcomes of this trial will provide the evidence to help policy makers, clinicians and guideline developers decide on the merits of including BA as a first-line treatment of depression. TRIAL REGISTRATION: Current Controlled Trials ISRCTN27473954.

BACKGROUND: the magnitude of the 'white coat effect', the alerting rise in blood pressure, is greater for doctors than nurses. This could bias interpretation of studies on nurse-led care in hypertension, and risks overestimating or overtreating high blood pressure by doctors in clinical practice. AIM: to quantify differences between blood pressure measurements made by doctors and nurses. DESIGN AND SETTING: Systematic review and meta-analysis using searches of MEDLINE, CENTRAL, CINAHL, Embase, journal collections, and conference abstracts. METHOD: Studies in adults reporting mean blood pressures measured by doctors and nurses at the same visit were selected, and mean blood pressures extracted, by two reviewers. Study risk of bias was assessed using modified Cochrane criteria. Outcomes were pooled across studies using random effects meta-analysis. RESULTS: in total, 15 studies (11 hypertensive; four mixed hypertensive and normotensive populations) were included from 1899 unique citations. Compared with doctors' measurements, nurse-measured blood pressures were lower (weighted mean differences: systolic -7.0 [95% confidence interval {CI} = -4.7 to -9.2] mmHg, diastolic -3.8 [95% CI = -2.2 to -5.4] mmHg). For studies at low risk of bias, differences were lower: systolic -4.6 (95% CI = -1.9 to -7.3) mmHg; diastolic -1.7 (95% CI = -0.1 to -3.2) mmHg. White coat hypertension was diagnosed more frequently based on doctors' than on nurses' readings: relative risk 1.6 (95% CI =1.2 to 2.1). CONCLUSIONS: the white coat effect is smaller for blood pressure measurements made by nurses than by doctors. This systematic difference has implications for hypertension diagnosis and management. Caution is required in pooling data from studies using both nurse- and doctor-measured blood pressures.

Background: Interventions promoting physical activity by General Practitioners (GPs) lack a strong evidence base. Recruiting participants to trials in primary care is challenging. We investigated the feasibility of (i) delivering three interventions to promote physical activity in inactive participants and (ii) different methods of participant recruitment and randomised allocation.Methods: We recruited general practices from Devon, Bristol and Coventry. We used a 2-by-2 factorial design for participant recruitment and randomisation. Recruitment strategies were either opportunistic (approaching patients attending their GP surgery) or systematic (selecting patients from practice lists and approaching them by letter). Randomisation strategies were either individual or by practice cluster. Feasibility outcomes included time taken to recruit the target number of participants within each practice. Participants were randomly allocated to one of three interventions: (i) written advice (control); (ii) brief GP advice (written advice plus GP advice on physical activity), and (iii) brief GP advice plus a pedometer to self-monitor physical activity during the trial. Participants allocated to written advice or brief advice each received a sealed pedometer to record their physical activity, and were instructed not to unseal the pedometer before the scheduled day of data collection. Participant level outcomes were reported descriptively and included the mean number of pedometer steps over a 7-day period, and European Quality of Life (EuroQoL)-5 dimensions (EQ-5D) scores, recorded at 12 weeks' follow-up.Results: We recruited 24 practices (12 using each recruitment method; 18 randomising by cluster, 6 randomising by individual participant), encompassing 131 participants. Opportunistic recruitment was associated with less time to target recruitment compared with systematic (mean difference (days) -54.9, 95% confidence interval (CI) -103.6; -6.2) but with greater loss to follow up (28.8% versus. 6.9%; mean difference 21.9% (95% CI 9.6%; 34.1%)). There were differences in the socio-demographic characteristics of participants according to recruitment method. There was no clear pattern of change in participant level outcomes from baseline to 12 weeks across the three arms.Conclusions: Delivering and trialling GP-led interventions to promote physical activity is feasible, but trial design influences time to participant recruitment, participant withdrawal, and possibly, the socio-demographic characteristics of participants.Trial registration number: ISRCTN73725618. © 2014 Warren et al.; licensee BioMed Central Ltd.

Background Patients with chronic heart failure (HF) experience a marked reduction in their exercise capacity, health-related quality of life, and life expectancy. Despite substantive evidence supporting exercise training in HF, uncertainties remain in the interpretation and understanding of this evidence base. Clinicians and healthcare providers seek definitive estimates of impact on mortality, hospitalisation and health-related quality of life, and which HF patient subgroups are likely to most benefit. The original Exercise Training Meta-Analysis for Chronic Heart Failure (ExTraMATCH) individual participant data (IPD) meta-analysis conducted in 2004 will be updated by the current collaboration (ExTraMATCH II), to investigate the effects of exercise training in HF. Methods Randomised controlled trials have been identified from the updated 2014 Cochrane systematic review and the original ExTraMATCH IPD meta-analysis with exercise training of 3 weeks' duration or more compared with a non-exercise control and a minimum follow-up of 6 months. Particular outcomes of interest are mortality, hospitalisation and health-related quality of life plus key baseline patient demographic and clinical data. Original IPD will be requested from the authors of all eligible trials; we will check original data and compile a master dataset. IPD meta-analyses will be conducted using a one-step approach where the IPD from all studies are modelled simultaneously whilst accounting for the clustering of participants with studies. Discussion the information from ExTraMATCH II will help inform future national and international clinical and policy decision-making on the use of exercise-based interventions in HF and improve the quality, design and reporting of future trials in this field. © 2014 Elsevier Ireland Ltd.

BACKGROUND: Patients with chronic heart failure (HF) experience a marked reduction in their exercise capacity, health-related quality of life, and life expectancy. Despite substantive evidence supporting exercise training in HF, uncertainties remain in the interpretation and understanding of this evidence base. Clinicians and healthcare providers seek definitive estimates of impact on mortality, hospitalisation and health-related quality of life, and which HF patient subgroups are likely to most benefit. The original Exercise Training Meta-Analysis for Chronic Heart Failure (ExTraMATCH) individual participant data (IPD) meta-analysis conducted in 2004 will be updated by the current collaboration (ExTraMATCH II), to investigate the effects of exercise training in HF. METHODS: Randomised controlled trials have been identified from the updated 2014 Cochrane systematic review and the original ExTraMATCH IPD meta-analysis with exercise training of 3 weeks' duration or more compared with a non-exercise control and a minimum follow-up of 6 months. Particular outcomes of interest are mortality, hospitalisation and health-related quality of life plus key baseline patient demographic and clinical data. Original IPD will be requested from the authors of all eligible trials; we will check original data and compile a master dataset. IPD meta-analyses will be conducted using a one-step approach where the IPD from all studies are modelled simultaneously whilst accounting for the clustering of participants with studies. DISCUSSION: the information from ExTraMATCH II will help inform future national and international clinical and policy decision-making on the use of exercise-based interventions in HF and improve the quality, design and reporting of future trials in this field.

© 2014 the Cochrane Collaboration. This is the protocol for a review and there is no abstract. The objectives are as follows: the aim of this review is to assess the benefits and harms of rehabilitation programmes consisting of a physical exercise component that focuses on increasing exercise capacity, and may include a psychoeducational intervention that focuses on improving mental health and the patient's self management skills, compared with no intervention or treatment as usual in adults who currently have AF or have been treated for AF.

BACKGROUND: Previous systematic reviews and meta-analyses consistently show the positive effect of exercise-based rehabilitation for heart failure (HF) on exercise capacity; however, the direction and magnitude of effects on health-related quality of life, mortality and hospital admissions in HF remain less certain. This is an update of a Cochrane systematic review previously published in 2010. OBJECTIVES: to determine the effectiveness of exercise-based rehabilitation on the mortality, hospitalisation admissions, morbidity and health-related quality of life for people with HF. Review inclusion criteria were extended to consider not only HF due to reduced ejection fraction (HFREF or 'systolic HF') but also HF due to preserved ejection fraction (HFPEF or 'diastolic HF'). SEARCH METHODS: We updated searches from the previous Cochrane review. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue1, 2013) from January 2008 to January 2013. We also searched MEDLINE (Ovid), EMBASE (Ovid), CINAHL (EBSCO) and PsycINFO (Ovid) (January 2008 to January 2013). We handsearched Web of Science, bibliographies of systematic reviews and trial registers (Controlled-trials.com and Clinicaltrials.gov). SELECTION CRITERIA: Randomised controlled trials of exercise-based interventions with six months' follow-up or longer compared with a no exercise control that could include usual medical care. The study population comprised adults over 18 years and were broadened to include individuals with HFPEF in addition to HFREF. DATA COLLECTION AND ANALYSIS: Two review authors independently screened all identified references and rejected those that were clearly ineligible. We obtained full-text papers of potentially relevant trials. One review author independently extracted data from the included trials and assessed their risk of bias; a second review author checked data. MAIN RESULTS: We included 33 trials with 4740 people with HF predominantly with HFREF and New York Heart Association classes II and III. This latest update identified a further 14 trials. The overall risk of bias of included trials was moderate. There was no difference in pooled mortality between exercise-based rehabilitation versus no exercise control in trials with up to one-year follow-up (25 trials, 1871 participants: risk ratio (RR) 0.93; 95% confidence interval (CI) 0.69 to 1.27, fixed-effect analysis). However, there was trend towards a reduction in mortality with exercise in trials with more than one year of follow-up (6 trials, 2845 participants: RR 0.88; 95% CI 0.75 to 1.02, fixed-effect analysis). Compared with control, exercise training reduced the rate of overall (15 trials, 1328 participants: RR 0.75; 95% CI 0.62 to 0.92, fixed-effect analysis) and HF specific hospitalisation (12 trials, 1036 participants: RR 0.61; 95% CI 0.46 to 0.80, fixed-effect analysis). Exercise also resulted in a clinically important improvement superior in the Minnesota Living with Heart Failure questionnaire (13 trials, 1270 participants: mean difference: -5.8 points; 95% CI -9.2 to -2.4, random-effects analysis) - a disease specific health-related quality of life measure. However, levels of statistical heterogeneity across studies in this outcome were substantial. Univariate meta-regression analysis showed that these benefits were independent of the participant's age, gender, degree of left ventricular dysfunction, type of cardiac rehabilitation (exercise only vs. comprehensive rehabilitation), mean dose of exercise intervention, length of follow-up, overall risk of bias and trial publication date. Within these included studies, a small body of evidence supported exercise-based rehabilitation for HFPEF (three trials, undefined participant number) and when exclusively delivered in a home-based setting (5 trials, 521 participants). One study reported an additional mean healthcare cost in the training group compared with control of USD3227/person. Two studies indicated exercise-based rehabilitation to be a potentially cost-effective use of resources in terms of gain in quality-adjusted life years (QALYs) and life-years saved. AUTHORS' CONCLUSIONS: This updated Cochrane review supports the conclusions of the previous version of this review that, compared with no exercise control, exercise-based rehabilitation does not increase or decrease the risk of all-cause mortality in the short term (up to 12-months' follow-up) but reduces the risk of hospital admissions and confers important improvements in health-related quality of life. This update provides further evidence that exercise training may reduce mortality in the longer term and that the benefits of exercise training on appear to be consistent across participant characteristics including age, gender and HF severity. Further randomised controlled trials are needed to confirm the small body of evidence seen in this review for the benefit of exercise in HFPEF and when exercise rehabilitation is exclusively delivered in a home-based setting.

Background: the National Institute for Health and Care Excellence (NICE) Technology Appraisal Guidance on spinal cord stimulation (SCS) was published in 2008 and updated in 2012 with no change. This guidance recommends SCS as a cost-effective treatment for patients with neuropathic pain. Objective: to assess the impact of NICE guidance by comparing SCS uptake in England pre-NICE (2008-2009) and post-NICE (2009-2012) guidance. We also compared the English SCS uptake rate with that of Belgium, the Netherlands, France and Germany. Design: SCS implant data for England was obtained from the Hospital Episode Statistics (HES) database and compared with other European countries where comparable data were available. Results: the HES data showed small increases in SCS implantation and replacement/revision procedures, and a large increase in SCS trials between 2008 and 2012. The increase in the total number of SCS procedures per million of population in England is driven primarily by revision/replacements and increased trial activity. Marked variability in SCS uptake at both health regions and primary care trust level was observed. Conclusions: Despite the positive NICE recommendation for the routine use of SCS, we found no evidence of a significant impact on SCS uptake in England. Rates of SCS implantation in England are lower than many other European countries.

Background. Despite the high prevalence of postnatal depression (PND), few women seek help. Internet interventions
may overcome many of the barriers to PND treatment use. We report a phase II evaluation of a 12-session, modular,
guided Internet behavioural activation (BA) treatment modified to address postnatal-specific concerns [Netmums
Helping with Depression (NetmumsHWD)].
Method. To assess feasibility, we measured recruitment and attrition to the trial and examined telephone session support
and treatment adherence. We investigated sociodemographic and psychological predictors of treatment adherence.
Effectiveness outcomes were estimated with the Edinburgh Postnatal Depression Scale (EPDS), Generalized Anxiety
Disorder-7, Work and Social Adjustment Scale, Postnatal Bonding Questionnaire, and Social Provisions Scale.
Results. A total of 249 women were recruited via a UK parenting site, Netmums.com. A total of 83 women meeting
DSM-IV criteria for major depressive disorder were randomized to NetmumsHWD (n=41) or treatment-as-usual
(TAU; n=42). of the 83 women, 71 (86%) completed the EPDS at post-treatment, and 71% (59/83) at the 6-month
follow-up. Women completed an average of eight out of 12 telephone support sessions and five out of 12 modules.
Working women and those with less support completed fewer modules. There was a large effect size favouring
women who received NetmumsHWD on depression, work and social impairment, and anxiety scores at post-treatment
compared with women in the TAU group, and a large effect size on depression at 6 months post-treatment. There were
small effect sizes for postnatal bonding and perceived social support.
Conclusions. A supported, modular, Internet BA programme can be feasibly delivered to postpartum women, offering
promise to improve depression, anxiety and functioning.

© 2014 John Wiley. &. Sons, Ltd. Rationale, aims and objectives Management of post-operative pain is unsatisfactory worldwide. An estimated 240 million patients undergo surgery each year. Forty to 60% of these patients report clinically significant pain. Discrepancy exists between availability of evidence-based medicine (EBM)-derived knowledge about management of perioperative pain and increased implementation of related practices versus lack of improvement in patient-reported outcomes (PROs). We aimed to assist health care providers to optimize perioperative pain management by developing and validating a medical registry that measures variability in care, identifies best pain management practices and assists clinicians in decision making. Methods PAIN OUT was established from 2009 to 2012 with funding from the European Commission. It now continues as a self-sustaining, not-for-profit project, targeting health care professionals caring for patients undergoing surgery. Results the growing registry includes data from 40 898 patients, 60 hospitals and 17 countries. Collaborators upload data (demographics, clinical, PROs) from patients undergoing surgery in their hospital/ward into an Internet-based portal. Two modules make use of the data: (1) online, immediate feedback and benchmarking compares PROs across sites while offline analysis permits in-depth analysis; and (2) the case-based clinical decision support system offers practice-based treatment recommendations for individual patients; it is available now as a prototype. The Electronic Knowledge Library provides succinct summaries on perioperative pain management, supporting knowledge transfer and application of EBM. Conclusion PAIN OUT, a large, growing international registry, allows use of 'real-life' data related to management of perioperative pain. Ultimately, comparative analysis through audit, feedback and benchmarking will improve quality of care.

We sought to assess the extent to which pain relief in chronic back and leg pain (CBLP) following spinal cord stimulation (SCS) is influenced by patient-related factors, including pain location, and technology factors. A number of electronic databases were searched with citation searching of included papers and recent systematic reviews. All study designs were included. The primary outcome was pain relief following SCS, we also sought pain score (pre- and post-SCS). Multiple predictive factors were examined: location of pain, history of back surgery, initial level of pain, litigation/worker's compensation, age, gender, duration of pain, duration of follow-up, publication year, continent of data collection, study design, quality score, method of SCS lead implant, and type of SCS lead. Between-study association in predictive factors and pain relief were assessed by meta-regression. Seventy-four studies (N = 3,025 patients with CBLP) met the inclusion criteria; 63 reported data to allow inclusion in a quantitative analysis. Evidence of substantial statistical heterogeneity (P 

We sought to assess the extent to which pain relief in chronic back and leg pain (CBLP) following spinal cord stimulation (SCS) is influenced by patient-related factors, including pain location, and technology factors. A number of electronic databases were searched with citation searching of included papers and recent systematic reviews. All study designs were included. The primary outcome was pain relief following SCS, we also sought pain score (pre- and post-SCS). Multiple predictive factors were examined: location of pain, history of back surgery, initial level of pain, litigation/worker's compensation, age, gender, duration of pain, duration of follow-up, publication year, continent of data collection, study design, quality score, method of SCS lead implant, and type of SCS lead. Between-study association in predictive factors and pain relief were assessed by meta-regression. Seventy-four studies (N = 3,025 patients with CBLP) met the inclusion criteria; 63 reported data to allow inclusion in a quantitative analysis. Evidence of substantial statistical heterogeneity (P 

Objectives Systemic lupus erythematosus (SLE; OMIM 152700) is characterised by the production of antibodies to nuclear antigens. We previously identified variants in complement receptor 2 (CR2/CD21) that were associated with decreased risk of SLE. This study aimed to identify the causal variant for this association. Methods Genotyped and imputed genetic variants spanning CR2 were assessed for association with SLE in 15 750 case-control subjects from four ancestral groups. Allele-specific functional effects of associated variants were determined using quantitative real-time PCR, quantitative flow cytometry, electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP)-PCR. Results the strongest association signal was detected at rs1876453 in intron 1 of CR2 (pmeta=4.2×10-4, OR 0.85), specifically when subjects were stratified based on the presence of dsDNA autoantibodies (case-control pmeta=7.6×10-7, OR 0.71; case-only pmeta=1.9×10-4, OR 0.75). Although allele-specific effects on B cell CR2 mRNA or protein levels were not identified, levels of complement receptor 1 (CR1/CD35) mRNA and protein were significantly higher on B cells of subjects harbouring the minor allele (p=0.0248 and p=0.0006, respectively). The minor allele altered the formation of several DNA protein complexes by EMSA, including one containing CCCTC-binding factor (CTCF), an effect that was confirmed by ChIP-PCR. Conclusions These data suggest that rs1876453 in CR2 has long-range effects on gene regulation that decrease susceptibility to lupus. Since the minor allele at rs1876453 is preferentially associated with reduced risk of the highly specific dsDNA autoantibodies that are present in preclinical, active and severe lupus, understanding its mechanisms will have important therapeutic implications. © 2014 BMJ Publishing Group Ltd & European League Against Rheumatism.

Objective: an international panel of pain specialists (anesthesiology, neurology, neurosurgery, and psychology) and research methodologists developed a screening tool to identify patients who may be suitable for spinal cord stimulation (SCS)-the Refractory Chronic Pain Screening Tool (RCPST) prototype. We describe a feasibility study to explore practicality and validity of this prototype. Design: Consecutive outpatients were screened in two centers (United Kingdom and United States). Sixty chronic pain adults without satisfactory pain relief despite treatment were assessed using RCPST (by pain specialist without expertise in neurostimulation) and then evaluated by two pain specialists experienced in SCS implantation and management to determine whether the patient should be referred for SCS. To maintain blinding, the participating physicians did not inform each other or the patient of assessment outcome. Sensitivity and specificity of the RCPST prototype were calculated using implanters' judgment as "gold standard." Results: the average age of patients was 47.7 years; 53% were female. Fifty-seven patients completed the study (one withdrew consent, two lost to follow-up). The pain specialists agreed the prototype was easy to use and took

Background: Retinitis Pigmentosa (RP) is a hereditary genetic disease causing bilateral retinal degeneration. RP is a leading cause of blindness resulting in incurable visual impairment and drastic reduction in the Quality of life of the patients. Second Sight Medical Products Inc. developed Argus II, a retinal prosthesis system for treating RP. Argus II is the world's first ever-commercial implant intended to restore some vision in the blind patients. The objective of this study was to assess the cost-effectiveness of the Argus® II Retinal Prosthesis System (Argus II) in Retinitis Pigmentosa (RP) patients. Method. A multi -state transition Markov model was developed to determine the cost-effectiveness of Argus II versus usual care in RP from the perspective of healthcare payer. A hypothetical cohort of 1000 RP patients aged 46 years followed up over a (lifetime) 25-year time horizon. Health outcomes were expressed as quality adjusted life years (QALYs) and direct healthcare costs expressed in 2012. Results are reported as incremental cost per ratios (ICERs) with outcomes and costs discounted at an annual rate of 3.5%. Results: the ICER for Argus II was 14,603/QALY. Taking into account the uncertainty in model inputs the ICER was 14,482/QALY in the probabilistic analysis. In the scenarios of an assumption of no reduction on cost across model visual acuity states or a model time horizon as short as 10 years the ICER increased to 31,890/QALY and 49,769/QALY respectively. Conclusion: This economic evaluation shows that Argus II is a cost-effective intervention compared to usual care of the RP patients. The lifetime analysis ICER for Argus II falls below the published societal willingness to pay of EuroZone countries. © 2014 Vaidya et al.; licensee BioMed Central Ltd.

Background: Chronic pain is distressing for patients and a burden on healthcare systems and society. Recent research demonstrates different aspects of the negative impact of chronic pain and the positive impact of successful treatment, making an overview of the costs and consequences of chronic pain appropriate. Objective: to examine recent literature on chronic noncancer and neuropathic pain prevalence, impact on quality and quantity of life, societal and healthcare costs, and impact of successful therapy. Methods: Systematic reviews (1999 to February 2012) following PRISMA guidelines were conducted to identify studies reporting appropriate outcomes. Results: Chronic pain has a weighted average prevalence in adults of 20%; 7% have neuropathic pain, and 7% have severe pain. Chronic pain impeded activities of daily living, work and work efficiency, and reduced quality and quantity of life. Effective pain therapy (pain intensity reduction of at least 50%) resulted in consistent improvements in fatigue, sleep, depression, quality of life, and work. Conclusion: Strenuous efforts should be put into obtaining good levels of pain relief for people in chronic pain, including the opportunity for multiple drug switching, using reliable, validated, and relatively easily applied patient-centered outcomes. Detailed, thoughtful and informed decision analytic policy modeling would help understand the key elements in organizational change or service reengineering to plan the optimum pain management strategy to maximize pain relief and its stream of benefits against budgetary and other constraints. This paper contains the information on which such models can be based. © 2013 World Institute of Pain.

OBJECTIVE: to investigate the psychometric properties of the Work and Social Adjustment Scale (WSAS) as an outcome measure for the Improving Access to Psychological Therapy programme, assessing its value as an addition to the Patient Health (PHQ-9) and Generalised Anxiety Disorder questionnaires (GAD-7). Little research has investigated these properties to date. METHODS: Reliability and responsiveness to change were assessed using data from 4,835 patients. Principal components analysis was used to determine whether the WSAS measures a factor distinct from the PHQ-9 and GAD-7. RESULTS: the WSAS measures a distinct social functioning factor, has high internal reliability, and is sensitive to treatment effects. CONCLUSIONS: the WSAS, PHQ-9 and GAD-7 perform comparably on measures of reliability and sensitivity. The WSAS also measures a distinct social functioning component suggesting it has potential as an additional outcome measure.

BACKGROUND: Depression is a common and distressing mental health problem that is responsible for significant individual disability and cost to society. Medication and psychological therapies are effective for treating depression and maintenance anti-depressants (m-ADM) can prevent relapse. However, individuals with depression often express a wish for psychological help that can help them recover from depression in the long-term. A recently developed treatment, mindfulness-based cognitive therapy (MBCT), shows potential as a brief group program for people with recurring depression.This trial asks the policy research question; is MBCT with support to taper/discontinue antidepressant medication (MBCT-TS) superior to m-ADM in terms of: a primary outcome of preventing depressive relapse/recurrence over 24 months; and secondary outcomes of (a) depression free days, (b) residual depressive symptoms, (c) antidepressant medication (ADM) usage, (d) psychiatric and medical co-morbidity, (e) quality of life, and (f) cost effectiveness? an explanatory research question also asks whether an increase in mindfulness skills is the key mechanism of change.The design is a single-blind, parallel randomized controlled trial examining MBCT-TS versus m-ADM with an embedded process study. To answer the main policy research question the proposed trial compares MBCT-TS with m-ADM for patients with recurrent depression. Four hundred and twenty patients with recurrent major depressive disorder in full or partial remission will be recruited through primary care. RESULTS: Depressive relapse/recurrence over two years is the primary outcome variable. Analyses will be conducted following CONSORT standards and overseen by the trial's Data Monitoring and Safety Committee. Initial analyses will be conducted on an intention-to-treat basis, with subsequent analyses being per protocol. The explanatory question will be addressed in two mutually informative ways: quantitative measurement of potential mediating variables pre- and post-treatment and a qualitative study of service users' views and experiences. CONCLUSIONS: If the results of our exploratory trial are extended to this definitive trial, MBCT-TS will be established as an alternative approach to maintenance antidepressants for people with a history of recurrent depression. The process studies will provide evidence about the effective components which can be used to improve MBCT and inform theory as well as other therapeutic approaches. TRIAL REGISTRATION: Trial registered 7 May 2009; ISRCTN26666654.

OBJECTIVES: Licensing of, and coverage decisions on, new therapies should rely on evidence from patient-relevant endpoints such as overall survival (OS). Nevertheless, evidence from surrogate endpoints may also be useful, as it may not only expedite the regulatory approval of new therapies but also inform coverage decisions. It is, therefore, essential that candidate surrogate endpoints be properly validated. However, there is no consensus on statistical methods for such validation and on how the evidence thus derived should be applied by policy makers. METHODS: We review current statistical approaches to surrogate-endpoint validation based on meta-analysis in various advanced-tumor settings. We assessed the suitability of two surrogates (progression-free survival [PFS] and time-to-progression [TTP]) using three current validation frameworks: Elston and Taylor's framework, the German Institute of Quality and Efficiency in Health Care's (IQWiG) framework and the Biomarker-Surrogacy Evaluation Schema (BSES3). RESULTS: a wide variety of statistical methods have been used to assess surrogacy. The strength of the association between the two surrogates and OS was generally low. The level of evidence (observation-level versus treatment-level) available varied considerably by cancer type, by evaluation tools and was not always consistent even within one specific cancer type. CONCLUSIONS: Not in all solid tumors the treatment-level association between PFS or TTP and OS has been investigated. According to IQWiG's framework, only PFS achieved acceptable evidence of surrogacy in metastatic colorectal and ovarian cancer treated with cytotoxic agents. Our study emphasizes the challenges of surrogate-endpoint validation and the importance of building consensus on the development of evaluation frameworks.

BACKGROUND: Chronic radicular pain can be effectively treated with spinal cord stimulation, but this therapy is not always sufficient for chronic back pain. Subcutaneous nerve stimulation (SQS) refers to the placement of percutaneous leads in the subcutaneous tissue within the area of pain. Case series data show that failed back surgery syndrome (FBSS) patients experience clinically important levels of pain relief following SQS and may also reduce their levels of analgesic therapy and experience functional well-being. However, to date, there is no randomized controlled trial evidence to support the use of SQS in FBSS. METHODS/DESIGN: the SubQStim study is a multicenter randomized controlled trial comparing SQS plus optimized medical management ('SQS arm') versus optimized medical management alone ('OMM arm') in patients with predominant back pain due to FBSS. Up to 400 patients will be recruited from approximately 33 centers in Europe and Australia and will be randomized 1:1 to the SQS or OMM arms. After 9 months, patients who fail to reach the primary outcome will be allowed to switch treatments. Patients will be evaluated at baseline (prior to randomization) and at 1, 3, 6, 9, 12, 18, 24, and 36 months after randomization. The primary outcome is the proportion of patients at 9 months with a ≥50% reduction in back pain intensity compared to baseline. The secondary outcomes are: back and leg pain intensity score, functional disability, health-related quality of life, patient satisfaction, patient global impression of change, healthcare resource utilization/costs, cost-effectiveness analysis and adverse events. Outcomes arms will be compared between SQS and OMM arms at all evaluation points up to and including 9 months. After the 9-month assessment visit, the main analytic focus will be to compare within patient changes in outcomes relative to baseline. DISCUSSION: the SubQStim trial began patient recruitment in November 2012. Recruitment is expected to close in late 2014. TRIAL REGISTRATION: ClinicalTrials.gov NCT01711619.

OBJECTIVE: to quantify and compare the treatment effect and risk of bias of trials reporting biomarkers or intermediate outcomes (surrogate outcomes) versus trials using final patient relevant primary outcomes. DESIGN: Meta-epidemiological study. DATA SOURCES: all randomised clinical trials published in 2005 and 2006 in six high impact medical journals: Annals of Internal Medicine, BMJ, Journal of the American Medical Association, Lancet, New England Journal of Medicine, and PLoS Medicine. STUDY SELECTION: Two independent reviewers selected trials. DATA EXTRACTION: Trial characteristics, risk of bias, and outcomes were recorded according to a predefined form. Two reviewers independently checked data extraction. The ratio of odds ratios was used to quantify the degree of difference in treatment effects between the trials using surrogate outcomes and those using patient relevant outcomes, also adjusted for trial characteristics. A ratio of odds ratios >1.0 implies that trials with surrogate outcomes report larger intervention effects than trials with patient relevant outcomes. RESULTS: 84 trials using surrogate outcomes and 101 using patient relevant outcomes were considered for analyses. Study characteristics of trials using surrogate outcomes and those using patient relevant outcomes were well balanced, except for median sample size (371 v 741) and single centre status (23% v 9%). Their risk of bias did not differ. Primary analysis showed trials reporting surrogate endpoints to have larger treatment effects (odds ratio 0.51, 95% confidence interval 0.42 to 0.60) than trials reporting patient relevant outcomes (0.76, 0.70 to 0.82), with an unadjusted ratio of odds ratios of 1.47 (1.07 to 2.01) and adjusted ratio of odds ratios of 1.46 (1.05 to 2.04). This result was consistent across sensitivity and secondary analyses. CONCLUSIONS: Trials reporting surrogate primary outcomes are more likely to report larger treatment effects than trials reporting final patient relevant primary outcomes. This finding was not explained by differences in the risk of bias or characteristics of the two groups of trials.

Background: to assess the effects of patient education on mortality, morbidity, health-related quality of life (HRQoL), and healthcare costs in people with coronary heart disease (CHD). Design: Systematic review and meta-analysis. Methods: Data sources were Cochrane Library, Medline, Embase, PsycINFO, CINAHL, and ongoing trial registries until August 2010. We also checked study references. The study selection was based on design (randomized controlled trials with follow up of at least 6 months, published from 1990 onwards), population (adults with CHD), intervention (patient education stated to be the primary intervention), and comparators (usual care or no educational intervention). Results: Thirteen studies (68,556 people with CHD) were included. Educational interventions ranged from two visits to a 4-week residential stay with 11 months of reinforcement sessions. Compared to no educational intervention, there was weak evidence that education reduced all-cause mortality (pooled relative risk (RR) 0.79, 95% CI 0.55 to 1.13) and cardiac morbidity outcomes: myocardial infarction (pooled RR 0.63, 95% CI 0.26 to 1.48), revascularization (pooled RR 0.58, 95% CI 0.19 to 1.71), and hospitalization (pooled RR 0.83, 95% CI 0.65 to 1.07) at median 18-months follow up. There was evidence to suggest that education can improve HRQoL and decrease healthcare costs by reductions in downstream healthcare utilization. Conclusions: Our review had insufficient power to exclude clinically important effects of education on mortality and morbidity. Nevertheless it supports the practice of CHD secondary prevention and rehabilitation programmes including education as an intervention. Further research is needed to determine the most effective and cost-effective format, duration, timing, and methods of education delivery. © 2012 the European Society of Cardiology.

Objectives: to update previous systematic reviews of interventions targeting asthma self-care in adults with asthma. To use meta-regression to examine the association between the use of specific behavior change techniques and intervention effectiveness.
Methods: Electronic bibliographies were searched systematically to identify randomized controlled trials of interventions targeting asthma self-care. Intervention content was coded using a published taxonomy of behavior change techniques. For trials with a low-to-moderate risk of bias, study outcomes were pooled using random effects meta-analysis. Associations between intervention content and effect size were explored using meta-regression.
Results: Meta-analysis of 38 trials (7883 patients) showed that interventions targeting asthma self-care reduced symptoms (Standardized mean difference (SMD))=-0.38;(-0.52,-0.24)) and unscheduled health care use (Odds ratio (OR))=0.71;(0.56 to 0.90)) and increased adherence to preventive medication (OR=2.55;(2.11 to 3.10)). Meta-regression analyses found that ‘active involvement of participants’ was associated with a reduction in unscheduled health care use (OR=0.50 vs. 0.79). Inclusion of ‘stress management’ techniques was associated with an increase in asthma symptoms (SMD= 0.01vs. -0.44). Existing recommendations about the ‘optimal’ content of asthma self-care interventions were tested, but were not supported by the data.
Conclusions: Interventions targeting asthma self-care are effective. Active involvement of participants is associated with increased intervention effectiveness, but the use of stress management techniques may be counter-productive. Taxonomy based systematic reviews using meta-regression have potential for identifying techniques associated with increased effectiveness in behavioral interventions.

© 2013 the Cochrane Collaboration. This is the protocol for a review and there is no abstract. The objectives are as follows: to assess the benefits and harms of exercise-based intervention programmes (exercise-based interventions alone or in combination with psycho-educational components), compared to no intervention, or treatment as usual, in adults who have had heart valve surgery. In this review we will focus on programmes that include an exercise-based intervention with, or without, another rehabilitation component (such as a psycho-educational component).

Objectives: Applications to run clinical trials in Europe fell 25% between 2007 and 2011. Costs, speed of approvals and shortcomings of European Clinical Trial Directive are commonly invoked to explain this unsatisfactory performance. However, no hard evidence is available on the actual weight of these factors or has it been previously investigated whether other criteria may also impact clinical trial site selection. Design: the Survey of Attitudes towards Trial sites in Europe (SAT-EU Study) was an anonymous, crosssectional web-based survey that systematically assessed factors impacting European clinical trial site selection. It explored 19 factors across investigatordriven, hospital-driven and environment-driven criteria, and costs. It also surveyed perceptions of the European trial environment. Setting and participants: Clinical research organisations (CROs), academic clinical trial units (CTUs) and industry invited to respond. Outcome measures: Primary outcome: weight assigned to each factor hypothesised to impact trial site selection and trial incidence. Secondary outcome: desirability of European countries to run clinical trials. Results: Responses were obtained from 485 professionals in 34 countries: 49% from BioPharma, 40% from CTUs or CROs. Investigator-dependent, environment-dependent and hospital-dependent factors were rated highly important, costs being less important (p

BACKGROUND: to inform the design of a randomised controlled trial (RCT) of an exercise-based programme for long term stroke survivors, we conducted a mixed methods before-and-after case series with assessment at three time points. We evaluated Action for Rehabilitation from Neurological Injury (ARNI), a personalised, functionally-focussed programme. It was delivered through 24 hours of one-to-one training by an Exercise Professional (EP), plus at least 2 hours weekly unsupervised exercise, over 12- 14 weeks. Assessment was by patient-rated questionnaires addressing function, physical activity, confidence, fatigue and health-related quality of life; objective assessment of gait quality and speed; qualitative individual interviews conducted with participants. Data were collected at baseline, 3 months and 6 months. Fidelity and acceptability was assessed by participant interviews, audit of participant and EP records, and observation of training. FINDINGS: Four of six enrolled participants completed the exercise programme. Quantitative data demonstrated little change across the sample, but marked changes on some measures for some individuals. Qualitative interviews suggested that small benefits in physical outcomes could be of great psychological significance to participants. Participant-reported fatigue levels commonly increased, and non-completers said they found the programme too demanding. Most key components of the intervention were delivered, but there were several potentially important departures from intervention fidelity. DISCUSSION: the study provided data and experience that are helping to inform the design of an RCT of this intervention. It suggested the need for a broader recruitment strategy; indicated areas that could be explored in more depth in the qualitative component of the trial; and highlighted issues that should be addressed to enhance and evaluate fidelity, particularly in the preparation and monitoring of intervention providers. The experience illustrates the value of even small sample before-and-after studies in the development of trials of complex interventions.

Background: Despite the high prevalence of postnatal depression (PND), few women seek help. The internet may increase timely access to treatment. We report a randomized controlled trial of a minimal intervention internet Behavioral Activation (iBA) treatment modified to address postnatal specific concerns (Postnatal-iBA).
Methods: Women (n=910) recruited via a popular UK parenting site, Netmums.com, scoring above 12 on the Edinburgh Postnatal Depression Scale (EPDS) were randomly assigned to receive either Postnatal-iBA delivered or treatment-as-usual (TAU). We investigated the feasibility (recruitment, trial and treatment adherence) and effectiveness (depression status EPDS >12) of the intervention.
Results:. Recruitment was excellent; 1261 women, 961 of whom met inclusion criteria, signed up to the trial within two 2- week recruitment periods. Thirty-eight percent (343/910) of women completed the 15-week outcome assessment. of those who completed 15-week assessment, fewer exceeded the depression cutoff in the Postnatal-iBA group (n = 66/181) compared to TAU (n=91/162). Assuming all non-respondents remained depressed, the Postnatal-iBA effect was reduced.
Limitations: the study suffered from high attrition and future trials need to consider strategies for improving outcome completion. Some women reported struggles “keeping up” with the treatment.
Conclusions:. A minimal support, widely accessible internet Behavioral Activation program for PND is feasible to deliver to community populations when embedded within popular parenting sites. For women who provide outcome data, postnatal-iBA offers promise as an effective treatment for PND. The addition of support may reduce women’s struggles to keep pace with the treatment.

Background: Despite the high prevalence of postnatal depression (PND), few women seek help. The internet may increase timely access to treatment. We report a randomized controlled trial of a minimal intervention internet Behavioral Activation (iBA) treatment modified to address postnatal specific concerns (Postnatal-iBA). Methods: Women (n=910) recruited via a popular UK parenting site, Netmums.com, scoring above 12 on the Edinburgh Postnatal Depression Scale (EPDS) were randomly assigned to receive either Postnatal-iBA delivered or treatment-as-usual (TAU). We investigated the feasibility (recruitment, trial and treatment adherence) and effectiveness (depression status EPDS > 12) of the intervention. Results: Recruitment was excellent; 1261 women, 961 of whom met inclusion criteria, signed up to the trial within two 2-week recruitment periods. Thirty-eight percent (343/910) of women completed the 15-week outcome assessment. of those who completed 15-week assessment, fewer exceeded the depression cutoff in the Postnatal-iBA group (n = 66/181) compared to TAU (n=91/162). Assuming all non-respondents remained depressed, the Postnatal-iBA effect was reduced. Limitations: the study suffered from high attrition and future trials need to consider strategies for improving outcome completion. Some women reported struggles "keeping up" with the treatment. Conclusions: a minimal support, widely accessible internet Behavioral Activation program for PND is feasible to deliver to community populations when embedded within popular parenting sites. For women who provide outcome data, postnatal-iBA offers promise as an effective treatment for PND. The addition of support may reduce women's struggles to keep pace with the treatment. © 2013 Elsevier B.V. All rights reserved.

Background
Volunteering has been advocated by the United Nations, and American and European governments as a way to engage people in their local communities and improve social capital, with the potential for public health benefits such as improving wellbeing and decreasing health inequalities. Furthermore, the US Corporation for National and Community Service Strategic Plan for 2011–2015 focused on increasing the impact of national service on community needs, supporting volunteers’ wellbeing, and prioritising recruitment and engagement of underrepresented populations. The aims of this review were to examine the effect of formal volunteering on volunteers’ physical and mental health and survival, and to explore the influence of volunteering type and intensity on health outcomes.

Methods
Experimental and cohort studies comparing the physical and mental health outcomes and mortality of a volunteering group to a non-volunteering group were identified from twelve electronic databases (Cochrane Library, Medline, Embase, PsychINFO, CINAHL, ERIC, HMIC, SSCI, ASSIA, Social Care Online, Social Policy and Practice) and citation tracking in January 2013. No language, country or date restrictions were applied. Data synthesis was based on vote counting and random effects meta-analysis of mortality risk ratios.

Results
Forty papers were selected: five randomised controlled trials (RCTs, seven papers); four non-RCTs; and 17 cohort studies (29 papers). Cohort studies showed volunteering had favourable effects on depression, life satisfaction, wellbeing but not on physical health. These findings were not confirmed by experimental studies. Meta-analysis of five cohort studies found volunteers to be at lower risk of mortality (risk ratio: 0.78; 95% CI: 0.66, 0.90). There was insufficient evidence to demonstrate a consistent influence of volunteering type or intensity on outcomes.

Conclusion
Observational evidence suggested that volunteering may benefit mental health and survival although the causal mechanisms remain unclear. Consequently, there was limited robustly designed research to guide the development of volunteering as a public health promotion intervention. Future studies should explicitly map intervention design to clear health outcomes as well as use pragmatic RCT methodology to test effects.

PAIN OUT is a European Commission-funded project aiming at improving postoperative pain management. It combines a registry that can be useful for quality improvement and research using treatment and patient-reported outcome measures. The core of the project is a patient questionnaire - the International Pain Outcomes questionnaire - that comprises key patient-level outcomes of postoperative pain management, including pain intensity, physical and emotional functional interference, side effects, and perceptions of care. Its psychometric quality after translation and adaptation to European patients is the subject of this validation study. The questionnaire was administered to 9,727 patients in 10 languages in 8 European countries and Israel. Construct validity was assessed using factor analysis. Discriminant validity assessment used Mann-Whitney U tests to detect mean group differences between 2 surgical disciplines. Internal consistency reliability was calculated as Cronbach's alpha. Factor analysis resulted in a 3-factor structure explaining 53.6% of variance. Cronbach's alpha at overall scale level was high (.86), and for the 3 subscales was low, moderate, or high (range.53-.89). Significant mean group differences between general and orthopedic surgery patients confirmed discriminant validity. The psychometric quality of the International Pain Outcomes questionnaire can be regarded as satisfactory. Perspective the International Pain Outcomes questionnaire provides an instrument for postoperative pain assessment and improvement of quality of care, which demonstrated good psychometric quality when translated into a variety of languages in a large European and Israeli patient population. This measure provides the basis for the first comprehensive postoperative pain registry in Europe and other countries. © 2013 by the American Pain Society.

Background: Although results of case series support the use of spinal cord stimulation in failed back surgery syndrome patients with predominant low back pain, no confirmatory randomized controlled trial has been undertaken in this patient group to date. PROMISE is a multicenter, prospective, randomized, open-label, parallel-group study designed to compare the clinical effectiveness of spinal cord stimulation plus optimal medical management with optimal medical management alone in patients with failed back surgery syndrome and predominant low back pain.Method/Design: Patients will be recruited in approximately 30 centers across Canada, Europe, and the United States. Eligible patients with low back pain exceeding leg pain and an average Numeric Pain Rating Scale score ≥5 for low back pain will be randomized 1:1 to spinal cord stimulation plus optimal medical management or to optimal medical management alone. The investigators will tailor individual optimal medical management treatment plans to their patients. Excluded from study treatments are intrathecal drug delivery, peripheral nerve stimulation, back surgery related to the original back pain complaint, and experimental therapies. Patients randomized to the spinal cord stimulation group will undergo trial stimulation, and if they achieve adequate low back pain relief a neurostimulation system using the Specify® 5-6-5 multi-column lead (Medtronic Inc. Minneapolis, MN, USA) will be implanted to capture low back pain preferentially in these patients. Outcome assessment will occur at baseline (pre-randomization) and at 1, 3, 6, 9, 12, 18, and 24 months post randomization. After the 6-month visit, patients can change treatment to that received by the other randomized group. The primary outcome is the proportion of patients with ≥50% reduction in low back pain at the 6-month visit. Additional outcomes include changes in low back and leg pain, functional disability, health-related quality of life, return to work, healthcare utilization including medication usage, and patient satisfaction. Data on adverse events will be collected. The primary analysis will follow the intention-to-treat principle. Healthcare use data will be used to assess costs and long-term cost-effectiveness.Discussion: Recruitment began in January 2013 and will continue until 2016. Trial registration: Clinicaltrials.gov: NCT01697358 (http://www.clinicaltrials.gov). © 2013 Rigoard et al.; licensee BioMed Central Ltd.

We comment on a recent article by Hawkins et al. presenting different analytic approaches for the inclusion of surrogate and final outcomes in cost-effectiveness analyses. This methodological case study provides a timely and valuable contribution to build on the debate about the use of evidence based on surrogate outcomes in health technology assessment.

We comment on a recent article by Hawkins et al. presenting different analytic approaches for the inclusion of surrogate and final outcomes in cost-effectiveness analyses. This methodological case study provides a timely and valuable contribution to build on the debate about the use of evidence based on surrogate outcomes in health technology assessment. Copyright © 2012 John Wiley & Sons, Ltd.

BACKGROUND: Multiple guidelines are often available to inform practice in complex interventions. Guidance implementation may be facilitated if it is tailored to particular clinical issues and contexts. It should also aim to specify all elements of interventions that may mediate and modify effectiveness, including both their content and delivery. We conducted a focused synthesis of recommendations from stroke practice guidelines to produce a structured and comprehensive account to facilitate the development of community-based exercise programmes after stroke. METHODS: Published stroke clinical practice guidelines were searched for recommendations relevant to the content and delivery of community-based exercise interventions after stroke. These were synthesised using a framework based on target intervention outcomes, personal and programme proximal objectives, and recommended strategies. RESULTS: Nineteen guidelines were included in the synthesis (STRIDES; STroke Rehabilitation Intervention-Development Evidence Synthesis). Eight target outcomes, 14 proximal objectives, and 94 recommended strategies were identified. The synthesis was structured to present best practice recommendations in a format that could be used by intervention programme developers. It addresses both programme content and context, including personal factors, service standards and delivery issues. Some recommendations relating to content, and many relating to delivery and other contextual issues, were based on low level evidence or expert opinion. Where opinion varied, the synthesis indicates the range of best practice options suggested in guidelines. CONCLUSIONS: the synthesis may assist implementation of best practice by providing a structured intervention description that focuses on a particular clinical application, addresses practical issues involved in programme development and provision, and illustrates the range of best-practice options available to users where robust evidence is lacking. The synthesis approach could be applied to other areas of stroke rehabilitation or to other complex interventions.

BACKGROUND: over the last three decades there has been a substantial increase in the proportion of children who are overweight or obese. The Healthy Lifestyles Programme (HeLP) is a novel school-based intervention, using highly interactive and creative delivery methods to prevent obesity in children. METHODS/DESIGN: We describe a cluster randomised controlled trial to evaluate the effectiveness and cost effectiveness of HeLP. The intervention has been developed using intervention mapping (involving extensive stakeholder involvement) and has been guided by the Information, Motivation, Behavioural Skills model. HeLP includes creating a receptive environment, drama activities, goal setting and reinforcement activities and runs over three school terms. Piloting showed that 9 to 10 year olds were the most receptive and participative. This study aims to recruit 1,300 children from 32 schools (over half of which will have ≥19% of pupils eligible for free school meals) from the southwest of England. Participating schools will be randomised to intervention or control groups with baseline measures taken prior to randomisation. The primary outcome is change in body mass index standard deviation score (BMI SDS) at 24 months post baseline. Secondary outcomes include, waist circumference and percent body fat SDS and proportion of children classified as overweight or obese at 18 and 24 months and objectively measured physical activity and food intake at 18 months. Between-group comparisons will be made using random effects regression analysis taking into account the hierarchical nature of the study design. An economic evaluation will estimate the incremental cost-effectiveness of HeLP, compared to control, from the perspective of the National Health Service (NHS)/third party payer. An in-depth process evaluation will provide insight into how HeLP works, and whether there is any differential uptake or engagement with the programme. DISCUSSION: the results of the trial will provide evidence on the effectiveness and cost effectiveness of the Healthy Lifestyles Programme in affecting the weight status of children. TRIAL REGISTRATION: ISRCTN15811706.

Purpose: Corneal neovascularization (CNV) is thought to negatively influence visual acuity. New therapeutic options that offer a differentiated influence on the ingrowths or regression of either corneal blood or lymphatic vessels force us to re-evaluate the association between CNV and visual acuity. Methods: a systematic review was conducted. Electronic databases were searched up to August 2009. Given the heterogeneity in study populations, interventions and measures of association, we were unable to undertake meta-analysis. The association between CNV and visual acuity was reported descriptively for each study. Results: Eleven studies using either vascular endothelial growth factor inhibitor treatments (i.e. bevacizumab, Avastin®; Hoffmann-La Roche AG, Basel, Switzerland) or an antiangiogenic treatment based on IRS-1 modulation [Gene-Signal (GS) 101, Aganirsen®; GeneSignal, Evry (Paris), France] in a total of 131 patients (142 eyes) with corneal neovascularization were included. Ten of the eleven studies reported evidence of a statistically significant reduction in neovascularization following treatment. However, only four studies reported a statistically significant improvement in visual acuity following therapy. We found no studies that assessed the patient-level association between the change in neovascularization and visual acuity. Conclusion: This systematic review found that there is currently weak evidence to support the hypothesis that in patients with pathological neovascularization, a treatment-related reduction in neovascularization is associated with an increase in visual acuity. There is a need for future appropriately designed studies. © 2011 the Authors. Acta Ophthalmologica © 2011 Acta Ophthalmologica Scandinavica Foundation.

PURPOSE: Corneal neovascularization (CNV) is thought to negatively influence visual acuity. New therapeutic options that offer a differentiated influence on the ingrowths or regression of either corneal blood or lymphatic vessels force us to re-evaluate the association between CNV and visual acuity. METHODS: a systematic review was conducted. Electronic databases were searched up to August 2009. Given the heterogeneity in study populations, interventions and measures of association, we were unable to undertake meta-analysis. The association between CNV and visual acuity was reported descriptively for each study. RESULTS: Eleven studies using either vascular endothelial growth factor inhibitor treatments (i.e. bevacizumab, Avastin(®) ; Hoffmann-La Roche AG, Basel, Switzerland) or an antiangiogenic treatment based on IRS-1 modulation [Gene-Signal (GS) 101, Aganirsen(®) ; GeneSignal, Evry (Paris), France] in a total of 131 patients (142 eyes) with corneal neovascularization were included. Ten of the eleven studies reported evidence of a statistically significant reduction in neovascularization following treatment. However, only four studies reported a statistically significant improvement in visual acuity following therapy. We found no studies that assessed the patient-level association between the change in neovascularization and visual acuity. CONCLUSION: This systematic review found that there is currently weak evidence to support the hypothesis that in patients with pathological neovascularization, a treatment-related reduction in neovascularization is associated with an increase in visual acuity. There is a need for future appropriately designed studies.

BACKGROUND: the RASCAL (Refractory Angina Spinal Cord stimulation and usuAL care) pilot study seeks to assess the feasibility of a definitive trial to assess if addition of spinal cord stimulation (SCS) to usual care is clinically superior and more cost-effective than usual care alone in patients with refractory angina. METHODS/DESIGN: This is an external pilot, patient-randomized controlled trial.The study will take place at three centers in the United Kingdom - South Tees Hospitals NHS Foundation Trust (The James Cook University Hospital), Dudley Group of Hospitals NHS Foundation Trust, and Basildon and Thurrock University Hospitals NHS Foundation Trust.The subjects will be 45 adults with refractory angina, that is, limiting angina despite optimal anti-angina therapy, Canadian Cardiovascular Society Functional Classification Class III and IV, angiographically documented coronary artery disease not suitable for revascularization, satisfactory multidisciplinary assessment and demonstrable ischemia on functional testing.The study will be stratified by center, age and Canadian Cardiovascular Society Functional Classification.Interventions will involve spinal cord stimulation plus usual care ('SCS group') or usual care alone ('UC group'). Usual care received by both groups will include consideration of an education session with a pain consultant, trial of a transcutaneous electrical neurostimulation, serial thoracic sympathectomy and oral/systemic analgesics.Expected outcomes will be recruitment and retention rates; reasons for agreeing/declining participation; variability in primary and secondary outcomes (to inform power calculations for a definitive trial); and completion rates of outcome measures. Trial patient-related outcomes include disease-specific and generic health-related quality of life, angina exercise capacity, intake of angina medications, frequency of angina attacks, complications and adverse events, and satisfaction. DISCUSSION: the RASCAL pilot trial seeks to determine the feasibility and design of a definitive randomized controlled trial comparing the addition of spinal cord stimulation to usual care versus usual care alone for patients with refractory angina.Fifteen patients have been recruited since recruitment opened in October 2011. The trial was originally scheduled to end in April 2013 but due to slow recruitment may have to be extended to late 2013. TRIAL REGISTRATION: ISRCTN65254102.

BACKGROUND: Recent years have seen an increase in primary care workload, especially following the introduction of a new General Medical Services contract in 2004. Telephone triage and telephone consultation with patients seeking health care represent initiatives aimed at improving access to care. Some evidence suggests that such approaches may be feasible but conclusions regarding GP workload, cost, and patients' experience of care, safety, and health status are equivocal. The ESTEEM trial aims to assess the clinical- and cost-effectiveness of nurse-led computer-supported telephone triage and GP-led telephone triage, compared to usual care, for patients requesting same-day consultations in general practice. METHODS/DESIGN: ESTEEM is a pragmatic, multi-centre cluster randomised clinical trial with patients randomised at practice level to usual care, computer decision-supported nurse triage, or GP-led triage. Following triage of 350-550 patients per practice we anticipate estimating and comparing total primary care workload (volume and time), the economic cost to the NHS, and patient experience of care, safety, and health status in the 4-week period following the index same-day consultation request across the three trial conditions.We will recruit all patients seeking a non-emergency same-day appointment in primary care. Patients aged 12.0-15.9 years and temporary residents will be excluded from the study.The primary outcome is the number of healthcare contacts taking place in the 4-week period following (and including) the index same-day consultation request. A range of secondary outcomes will be examined including patient flow, primary care NHS resource use, patients' experience of care, safety, and health status.The estimated sample size required is 3,751 patients (11,253 total) in each of the three trial conditions, to detect a mean difference of 0.36 consultations per patient in the four week follow-up period between either intervention group and usual care 90% power, 5% alpha, and an estimated intracluster correlation coefficient ICC of 0.05. The primary analysis will be based on the intention-to-treat principle and take the form of a random effects regression analysis taking account of the hierarchical nature of the study design. Statistical models will allow for adjustment for practice level minimisation variables and patient-level baseline covariates shown to differ at baseline. TRIAL REGISTRATION: Current Controlled Trials ISCRTN20687662.

Objectives: to examine how the severity of postoperative pain affects patient's health-related quality of life (HRQoL) at 1 week following surgery and to compare two generic validated HRQoL instruments. Methods: Patients undergoing general or orthopaedic surgery at the Royal London Hospital were randomly sampled. The following patient outcome data were collected EQ-5D (EuroQoL) pre-operatively and the Revised American Pain Society Patient Outcome Questionnaire (APS-POQ-R) at 24 hours postoperation; and EQ-5D, Short-Form-12 (SF-12) and APS-POQ-R at 7 days postoperation. The degree of association between pain and HRQoL was assessed using Pearson's correlation coefficient and multivariate generalized linear regression models. Results: of the 228 patients included, 166 patients provided data at 7 days. Sixteen percent reported severe pain ≥ 50% of the day at 7 days. The severity of pain on both the APS-POQ-R pain severity and interference and affective impairment domains at 7 days was highly correlated with a decrease in HRQoL as assessed by the SF-12 Physical Component Score (PCS), SF-12 Mental Component Score (MCS), and EQ-5D scores (r = -0.34 to -0.61, P 

OBJECTIVES: to examine how the severity of postoperative pain affects patient's health-related quality of life (HRQoL) at 1 week following surgery and to compare two generic validated HRQoL instruments. METHODS: Patients undergoing general or orthopaedic surgery at the Royal London Hospital were randomly sampled. The following patient outcome data were collected EQ-5D (EuroQoL) pre-operatively and the Revised American Pain Society Patient Outcome Questionnaire (APS-POQ-R) at 24 hours postoperation; and EQ-5D, Short-Form-12 (SF-12) and APS-POQ-R at 7 days postoperation. The degree of association between pain and HRQoL was assessed using Pearson's correlation coefficient and multivariate generalized linear regression models. RESULTS: of the 228 patients included, 166 patients provided data at 7 days. Sixteen percent reported severe pain ≥ 50% of the day at 7 days. The severity of pain on both the APS-POQ-R pain severity and interference and affective impairment domains at 7 days was highly correlated with a decrease in HRQoL as assessed by the SF-12 Physical Component Score (PCS), SF-12 Mental Component Score (MCS), and EQ-5D scores (r = -0.34 to -0.61, P 

BACKGROUND: in the UK, approximately 10 000 people have cochlear implants, more than 99% with a unilateral implant. Evidence shows that adults implanted bilaterally may benefit from binaural advantages; however, systematic review evidence is limited. OBJECTIVES OF THE REVIEW: to conduct a systematic review to discover the evidence for effectiveness and cost-effectiveness of using bilateral cochlear implants in adults with severe-to-profound hearing loss by comparing their effectiveness with unilateral cochlear implantation or unilateral cochlear implantation and acoustic hearing aid in the contralateral ear. TYPE OF REVIEW: Systematic review. SEARCH STRATEGY: This examined 16 electronic databases, plus bibliographies and references for published and unpublished studies. EVALUATION METHOD: Abstracts were independently assessed against inclusion criteria by two researchers, and disagreements were resolved. Selected papers were then retrieved and further independently assessed in a similar way. Included studies had their data extracted by one reviewer and checked by another. RESULTS: Searches yielded 2892 abstracts producing 19 includable studies. Heterogeneity between studies precluded meta-analysis. However, all studies reported that bilateral cochlear implants improved hearing and speech perception: one randomised controlled trial found a significant binaural benefit over the first ear alone for speech and noise from the front (12.6 ± 5.4%, P < 0.001) and when noise was ipsilateral to the first ear (21 ± 6%, P < 0.001); and another found a significant benefit for spatial hearing at 3 and 9 months post-implantation compared with pre-implantation [mean difference (sd) scores: 3 months = 1.46 (0.83-2.09), P < 0.01].Quality of life results varied, showing bilateral implantation may improve quality of life in the absence of worsening tinnitus. Limited cost-effectiveness evidence showed that bilateral implantation is probably only cost-effective at a willingness-to-pay threshold above £62 000 per quality adjusted life year. CONCLUSIONS: Despite inconsistency in the quality of available evidence, the robustness of systematic review methods gives weight to the positive findings of included studies demonstrating that bilateral implantation is clinically effective in adults but unlikely to be cost-effective.

BACKGROUND: People with Parkinson's (PwP) experience frequent and recurrent falls. As these falls may have devastating consequences, there is an urgent need to identify cost-effective interventions with the potential to reduce falls in PwP. The purpose of this economic evaluation is to compare the costs and cost-effectiveness of a targeted exercise programme versus usual care for PwP who were at risk of falling. METHODS: One hundred and thirty participants were recruited through specialist clinics, primary care and Parkinson's support groups and randomised to either an exercise intervention or usual care. Health and social care utilisation and health-related quality of life (EQ-5D) were assessed over the 20 weeks of the study (ten-week intervention period and ten-week follow up period), and these data were complete for 93 participants. Incremental cost per quality adjusted life year (QALY) was estimated. The uncertainty around costs and QALYs was represented using cost-effectiveness acceptability curves. RESULTS: the mean cost of the intervention was £76 per participant. Although in direction of favour of exercise intervention, there was no statistically significant differences between groups in total healthcare (-£128, 95% CI: -734 to 478), combined health and social care costs (£-35, 95% CI: -817 to 746) or QALYs (0.03, 95% CI: -0.02 to 0.03) at 20 weeks. Nevertheless, exploration of the uncertainty surrounding these estimates suggests there is more than 80% probability that the exercise intervention is a cost-effective strategy relative to usual care. CONCLUSION: Whilst we found no difference between groups in total healthcare, total social care cost and QALYs, analyses indicate that there is high probability that the exercise intervention is cost-effective compared with usual care. These results require confirmation by larger trial-based economic evaluations and over the longer term.

Introduction: We conducted a systematic review to assess the effect of exercise training in patients with heart failure with preserved ejection fraction (HFPEF). Methods: a number of electronic databases were searched up to November 2011 to identify comparative studies of exercise training in HFPEF. Where possible, outcome data from included studies were pooled using meta-analysis. Results: Three randomised controlled trials, one non-randomised controlled trial and one pre-post study were included, for a total of 228 individuals. The combined duration of exercise programmes and follow-up ranged from 12 to 24 weeks. No deaths, hospital admissions or serious adverse events were observed during or immediately following exercise training. Compared to control, the change in exercise capacity at follow-up was higher with exercise training (between group mean difference: 3.0 ml/kg/min, 95% CI: 2.4 to 2.6). In the four studies, that reported the Minnesota Living with Heart Failure questionnaire, there was evidence of a larger gain in health-related quality of life with exercise training (7.3 units, 3.3 to 11.4). The largest study showed some evidence of improvement in the E/E′ ratio with exercise training, but this was not confirmed in the other studies (overall - 0.9, - 3.8 to 2.0); E/A ratios were not changed. Conclusions: Exercise training for patients with HFPEF confers benefit in terms of enhancements in exercise capacity and health-related quality of life and appears to be safe. The impact on diastolic function remains unclear. Further trials should provide data on long term effects, prognostic relevance and cost-effectiveness. © 2012 Elsevier Ireland Ltd.

INTRODUCTION: We conducted a systematic review to assess the effect of exercise training in patients with heart failure with preserved ejection fraction (HFPEF). METHODS: a number of electronic databases were searched up to November 2011 to identify comparative studies of exercise training in HFPEF. Where possible, outcome data from included studies were pooled using meta-analysis. RESULTS: Three randomised controlled trials, one non-randomised controlled trial and one pre-post study were included, for a total of 228 individuals. The combined duration of exercise programmes and follow-up ranged from 12 to 24 weeks. No deaths, hospital admissions or serious adverse events were observed during or immediately following exercise training. Compared to control, the change in exercise capacity at follow-up was higher with exercise training (between group mean difference: 3.0 ml/kg/min, 95% CI: 2.4 to 2.6). In the four studies, that reported the Minnesota Living with Heart Failure questionnaire, there was evidence of a larger gain in health-related quality of life with exercise training (7.3 units, 3.3 to 11.4). The largest study showed some evidence of improvement in the E/E' ratio with exercise training, but this was not confirmed in the other studies (overall -0.9, -3.8 to 2.0); E/A ratios were not changed. CONCLUSIONS: Exercise training for patients with HFPEF confers benefit in terms of enhancements in exercise capacity and health-related quality of life and appears to be safe. The impact on diastolic function remains unclear. Further trials should provide data on long term effects, prognostic relevance and cost-effectiveness.

Background the development of widely accessible, effective psychological interventions for depression is a priority. This randomized trial provides the first controlled data on an innovative cognitive bias modification (CBM) training guided self-help intervention for depression.Method One hundred and twenty-one consecutively recruited participants meeting criteria for current major depression were randomly allocated to treatment as usual (TAU) or to TAU plus concreteness training (CNT) guided self-help or to TAU plus relaxation training (RT) guided self-help. CNT involved repeated practice at mental exercises designed to switch patients from an unhelpful abstract thinking habit to a helpful concrete thinking habit, thereby targeting depressogenic cognitive processes (rumination, overgeneralization).Results the addition of CNT to TAU significantly improved depressive symptoms at post-treatment [mean difference on the Hamilton Rating Scale for Depression (HAMD) 4.28, 95% confidence interval (CI) 1.29-7.26], 3-and 6-month follow-ups, and for rumination and overgeneralization post-treatment. There was no difference in the reduction of symptoms between CNT and RT (mean difference on the HAMD 1.98, 95% CI âÌ‚'1.14 to 5.11), although CNT significantly reduced rumination and overgeneralization relative to RT post-treatment, suggesting a specific benefit on these cognitive processes.Conclusions This study provides preliminary evidence that CNT guided self-help may be a useful addition to TAU in treating major depression in primary care, although the effect was not significantly different from an existing active treatment (RT) matched for structural and common factors. Because of its relative brevity and distinct format, it may have value as an additional innovative approach to increase the accessibility of treatment choices for depression. © 2011 Cambridge University Press.

BACKGROUND: the development of widely accessible, effective psychological interventions for depression is a priority. This randomized trial provides the first controlled data on an innovative cognitive bias modification (CBM) training guided self-help intervention for depression. METHOD: One hundred and twenty-one consecutively recruited participants meeting criteria for current major depression were randomly allocated to treatment as usual (TAU) or to TAU plus concreteness training (CNT) guided self-help or to TAU plus relaxation training (RT) guided self-help. CNT involved repeated practice at mental exercises designed to switch patients from an unhelpful abstract thinking habit to a helpful concrete thinking habit, thereby targeting depressogenic cognitive processes (rumination, overgeneralization). RESULTS: the addition of CNT to TAU significantly improved depressive symptoms at post-treatment [mean difference on the Hamilton Rating Scale for Depression (HAMD) 4.28, 95% confidence interval (CI) 1.29-7.26], 3- and 6-month follow-ups, and for rumination and overgeneralization post-treatment. There was no difference in the reduction of symptoms between CNT and RT (mean difference on the HAMD 1.98, 95% CI -1.14 to 5.11), although CNT significantly reduced rumination and overgeneralization relative to RT post-treatment, suggesting a specific benefit on these cognitive processes. CONCLUSIONS: This study provides preliminary evidence that CNT guided self-help may be a useful addition to TAU in treating major depression in primary care, although the effect was not significantly different from an existing active treatment (RT) matched for structural and common factors. Because of its relative brevity and distinct format, it may have value as an additional innovative approach to increase the accessibility of treatment choices for depression.

Background: the effectiveness of exercise referral schemes (ERS) is influenced by uptake and adherence to the scheme. The identification of factors influencing low uptake and adherence could lead to the refinement of schemes to optimise investment. Objectives: to quantify the levels of ERS uptake and adherence and to identify factors predictive of uptake and adherence. Methods: a systematic review and meta-analysis was undertaken. MEDLINE, EMBASE, PsycINFO, Cochrane Library, ISI WOS, SPORTDiscus and ongoing trial registries were searched (to October 2009) and included study references were checked. Included studies were required to report at least one of the following: (1) a numerical measure of ERS uptake or adherence and (2) an estimate of the statistical association between participant demographic or psychosocial factors (eg, level of motivation, self-efficacy) or programme factors and uptake or adherence to ERS. Results: Twenty studies met the inclusion criteria, six randomised controlled trials (RCTs) and 14 observational studies. The pooled level of uptake in ERS was 66% (95% CI 57% to 75%) across the observational studies and 81% (95% CI 68% to 94%) across the RCTs. The pooled level of ERS adherence was 49% (95% CI 40% to 59%) across the observational studies and 43% (95% CI 32% to 54%) across the RCTs. Few studies considered anything other than gender and age. Women were more likely to begin an ERS but were less likely to adhere to it than men. Older people were more likely to begin and adhere to an ERS. Limitations: Substantial heterogeneity was evident across the ERS studies. Without standardised definitions, the heterogeneity may have been reflective of differences in methods of defining uptake and adherence across studies. Conclusions: to enhance our understanding of the variation in uptake and adherence across ERS and how these variations might affect physical activity outcomes, future trials need to use quantitative and qualitative methods.

BACKGROUND: the effectiveness of exercise referral schemes (ERS) is influenced by uptake and adherence to the scheme. The identification of factors influencing low uptake and adherence could lead to the refinement of schemes to optimise investment. OBJECTIVES: to quantify the levels of ERS uptake and adherence and to identify factors predictive of uptake and adherence. METHODS: a systematic review and meta-analysis was undertaken. MEDLINE, EMBASE, PsycINFO, Cochrane Library, ISI WOS, SPORTDiscus and ongoing trial registries were searched (to October 2009) and included study references were checked. Included studies were required to report at least one of the following: (1) a numerical measure of ERS uptake or adherence and (2) an estimate of the statistical association between participant demographic or psychosocial factors (eg, level of motivation, self-efficacy) or programme factors and uptake or adherence to ERS. RESULTS: Twenty studies met the inclusion criteria, six randomised controlled trials (RCTs) and 14 observational studies. The pooled level of uptake in ERS was 66% (95% CI 57% to 75%) across the observational studies and 81% (95% CI 68% to 94%) across the RCTs. The pooled level of ERS adherence was 49% (95% CI 40% to 59%) across the observational studies and 43% (95% CI 32% to 54%) across the RCTs. Few studies considered anything other than gender and age. Women were more likely to begin an ERS but were less likely to adhere to it than men. Older people were more likely to begin and adhere to an ERS. LIMITATIONS: Substantial heterogeneity was evident across the ERS studies. Without standardised definitions, the heterogeneity may have been reflective of differences in methods of defining uptake and adherence across studies. CONCLUSIONS: to enhance our understanding of the variation in uptake and adherence across ERS and how these variations might affect physical activity outcomes, future trials need to use quantitative and qualitative methods.

Context: a low sodium diet has been proposed to reduce the risk of heart failure (HF) hospitalisations and is currently advocated in consensus guidelines, yet some evidence suggests adverse neurohumoral activation for sodium restriction in the HF setting. Objectives: to evaluate the effects of a restricted sodium diet in patients with systolic HF. Data sources: a systematic review and meta-analysis of randomised trials OVID MEDLINE, PubMed, Excerpta Medica (Embase), the Cochrane Controlled Trials Register, Scopus, Web of Science and Google Scholar were searched up to April 2012. Study selection: Two independent reviewers selected studies for inclusion on the basis of a randomised controlled trial design that included adults with systolic HF receiving a restricted salt diet or control diet and reporting mortality (all-cause, sudden death or HF-related) and HF-related hospitalisations. Data extraction and analysis: Descriptive and quantitative information was extracted from included studies. A random-effects model was used to compute pooled risk ratios (RR) for mortality and morbidity outcomes. Results: Six randomised trials comparing low sodium diets (1.8 g/day) with normal sodium diets (2.8 g/d) in 2747 patients with systolic HF were identified. Compared with a normal sodium diet, a low sodium diet significantly increased all cause mortality (RR 1.95, 95% CI 1.66 to 2.29), sudden death (RR 1.72, 95% CI 1.21 to 2.44), death due to HF (RR 2.23, 95% CI 1.77 to 2.81) and HF readmissions (RR 2.10, 95% CI 1.67 to 2.64). Conclusion: Compared with a normal sodium diet, a low sodium diet significantly increases morbidity and mortality in systolic HF.Copyright Article author (or their employer) 2012.

Background: Research on the relationship between Health Related Quality of Life (HRQoL) and physical activity (PA), to date, have rarely investigated how this relationship differ across objective and subjective measures of PA. The aim of this paper is to explore the relationship between HRQoL and PA, and examine how this relationship differs across objective and subjective measures of PA, within the context of a large representative national survey from England. Methods. Using a sample of 5,537 adults (40-60years) from a representative national survey in England (Health Survey for England 2008), Tobit regressions with upper censoring was employed to model the association between HRQoL and objective, and subjective measures of PA controlling for potential confounders. We tested the robustness of this relationship across specific types of PA. HRQoL was assessed using the summary measure of health state utility value derived from the EuroQol-5 Dimensions (EQ-5D) whilst PA was assessed via subjective measure (questionnaire) and objective measure (accelerometer- actigraph model GT1M). The actigraph was worn (at the waist) for 7days (during waking hours) by a randomly selected sub-sample of the HSE 2008 respondents (4,507 adults - 16 plus years), with a valid day constituting 10 hours. Analysis was conducted in 2010. Results: Findings suggest that higher levels of PA are associated with better HRQoL (regression coefficient: 0.026 to 0.072). This relationship is consistent across different measures and types of PA although differences in the magnitude of HRQoL benefit associated with objective and subjective (regression coefficient: 0.047) measures of PA are noticeable, with the former measure being associated with a relatively better HRQoL (regression coefficient: 0.072). Conclusion: Higher levels of PA are associated with better HRQoL. Using an objective measure of PA compared with subjective shows a relatively better HRQoL. © 2012 Anokye et al.; licensee BioMed Central Ltd.

Background: Chronic pain (CP) poses a diverse and substantial burden for employees, employers, and society. The deleterious consequences of CP in the workplace are frequently underestimated. Objective: to estimate the burden of CP in the European workplace. Methods: a systematic review following PRISMA statement guidelines was conducted to identify studies reporting work-related outcomes for people with CP. EMBASE, MEDLINE, EconLit, and Cochrane Library databases were searched up to 18th August 2010. Results: We identified 91 observational studies. Few were specifically designed to investigate the association between CP, productivity, and employment. The focus for this review was studies clearly reporting outcomes relating to the burden of CP on employment status (n=37), sickness absence (absenteeism, n=47), and loss of productivity because of reduced ability at work (presenteeism, n=8). Conclusion: the body of evidence identified from the systematic review indicates that CP has a substantial negative impact on work-related outcomes, supporting the importance of interventions to reduce the burden of CP. Well-designed prospective studies specifically assessing the direct consequences of CP on employment are needed to confirm these findings. © 2012 Abacus Internation Pain Practice © 2012 World Institute of Pain.

OBJECTIVE: to determine whether a difference in systolic blood pressure readings between arms can predict a reduced event free survival after 10 years. DESIGN: Cohort study. SETTING: Rural general practice in Devon, United Kingdom. PARTICIPANTS: 230 people receiving treatment for hypertension in primary care. INTERVENTION: Bilateral blood pressure measurements recorded at three successive surgery attendances. MAIN OUTCOME MEASURES: Cardiovascular events and deaths from all causes during a median follow-up of 9.8 years. RESULTS: at recruitment 24% (55/230) of participants had a mean interarm difference in systolic blood pressure of 10 mm Hg or more and 9% (21/230) of 15 mm Hg or more; these differences were associated with an increased risk of all cause mortality (adjusted hazard ratio 3.6, 95% confidence interval 2.0 to 6.5 and 3.1, 1.6 to 6.0, respectively). The risk of death was also increased in 183 participants without pre-existing cardiovascular disease with an interarm difference in systolic blood pressure of 10 mm Hg or more or 15 mm Hg or more (2.6, 1.4 to 4.8 and 2.7, 1.3 to 5.4). An interarm difference in diastolic blood pressure of 10 mm Hg or more was weakly associated with an increased risk of cardiovascular events or death. CONCLUSIONS: Differences in systolic blood pressure between arms can predict an increased risk of cardiovascular events and all cause mortality over 10 years in people with hypertension. This difference could be a valuable indicator of increased cardiovascular risk. Bilateral blood pressure measurements should become a routine part of cardiovascular assessment in primary care.

Failed back surgery syndrome (FBSS) is a generalised disorder that is characterised by chronic pain in the lower back and/or legs that persists or recurs following anatomically successful spinal surgery. This paper aims to (1) assess the burden of failed back surgery in terms of its epidemiology, impact on health outcomes and costs and (2) summarise the evidence base for the cost-effectiveness of interventions for the management of FBSS. A narrative review based on a search of MEDLINE (PubMed) up to August 2012 was undertaken. Despite advances in technology and surgical techniques and increasing rates of spine surgery, a proportion of individuals continue to suffer from FBSS. Estimates from randomised controlled trials indicate that 5-50% of patients may have an unsuccessful outcome following lumbar spinal surgery. The understanding of the epidemiology and burden of FBSS remains poor and further research is needed in this area. The impact of FBSS on an individual's health-related quality of life and its economic cost to society are considerable and more disabling than other common chronic pain and chronic medical conditions, such as heart failure and motor neuron disease. There is a substantive body of evidence in FBSS patients showing spinal cord stimulation (SCS) to be cost-effective (

BACKGROUND: Chronic pain (CP) poses a diverse and substantial burden for employees, employers, and society. The deleterious consequences of CP in the workplace are frequently underestimated. OBJECTIVE: to estimate the burden of CP in the European workplace. METHODS: a systematic review following PRISMA statement guidelines was conducted to identify studies reporting work-related outcomes for people with CP. EMBASE, MEDLINE, EconLit, and Cochrane Library databases were searched up to 18th August 2010. RESULTS: We identified 91 observational studies. Few were specifically designed to investigate the association between CP, productivity, and employment. The focus for this review was studies clearly reporting outcomes relating to the burden of CP on employment status (n = 37), sickness absence (absenteeism, n = 47), and loss of productivity because of reduced ability at work (presenteeism, n = 8). CONCLUSION: the body of evidence identified from the systematic review indicates that CP has a substantial negative impact on work-related outcomes, supporting the importance of interventions to reduce the burden of CP. Well-designed prospective studies specifically assessing the direct consequences of CP on employment are needed to confirm these findings.

OBJECTIVES: to determine why so few patients with chronic heart failure in England, Wales and Northern Ireland take part in cardiac rehabilitation. DESIGN: Two-stage, postal questionnaire-based national survey. PARTICIPANTS AND SETTING: Stage 1: 277 cardiac rehabilitation centres that provided phase 3 cardiac rehabilitation in England, Wales and Northern Ireland registered on the National Audit of Cardiac Rehabilitation register. Stage 2: 35 centres that indicated in stage 1 that they provide a separate cardiac rehabilitation programme for patients with heart failure. RESULTS: Full data were available for 224/277 (81%) cardiac rehabilitation centres. Only 90/224 (40%) routinely offered phase 3 cardiac rehabilitation to patients with heart failure. of these 90 centres that offered rehabilitation, 43% did so only when heart failure was secondary to myocardial infarction or revascularisation. Less than half (39%) had a specific rehabilitation programme for heart failure. of those 134 centres not providing for patients with heart failure, 84% considered a lack of resources and 55% exclusion from commissioning contracts as the reason for not recruiting patients with heart failure. Overall, only 35/224 (16%) centres provided a separate rehabilitation programme for people with heart failure. CONCLUSIONS: Patients with heart failure as a primary diagnosis are excluded from most cardiac rehabilitation programmes in England, Wales and Northern Ireland. A lack of resources and direct exclusion from local commissioning agreements are the main barriers for not offering rehabilitation to patients with heart failure.

Background: Most systematic reviews conclude that another clinical trial is needed. Measures of sufficiency and stability may indicate whether this is true.Objectives: to show how evidence accumulated on centre-based versus home-based cardiac rehabilitation, including estimates of sufficiency and stability. Methods: Systematic reviews of clinical trials of home versus centre-based cardiac rehabilitation were used to develop a cumulative meta-analysis over time. We calculated the standardised mean difference (SMD) in effect, confidence intervals and indicators of sufficiency and stability. Sufficiency refers to whether the meta-analytic database adequately demonstrates that an intervention works - is statistically superior to another. It does this by assessing the number of studies with null results that would be required to make the meta-analytic effect non-statistically significant. Stability refers to whether the direction and size of the effect is stable as new studies are added to the meta-analysis.Results: the standardised mean effect difference reduced over fourteen comparisons from a non-significant difference favouring home-based cardiac rehabilitation to a very small difference favouring hospital (SMD -0.10, 95% CI -0.32 to 0.13). This difference did not reach the sufficiency threshold (failsafe ratio 0.039 < 1) but did achieve the criteria for stability (cumulative slope 0.003 < 0.005).Conclusions: the evidence points to a relatively small effect difference which was stable but not sufficient in terms of the suggested thresholds. Sufficiency should arguably be based on substantive significance and decided by patients. Research on patient preferences should be the priority. Sufficiency and stability measures are useful tools that need to be tested in further case studies. © 2011 Dent et al; licensee BioMed Central Ltd.

BACKGROUND: Social isolation affects a significant proportion of older people and is associated with poor health outcomes. The current evidence base regarding the effectiveness of interventions targeting social isolation is poor, and the potential utility of mentoring for this purpose has not previously been rigorously evaluated. The purpose of this study was to examine the effectiveness of a community-based mentoring service for improving mental health, social engagement and physical health for socially isolated older people. METHODS: This prospective controlled trial compared a sample of mentoring service clients (intervention group) with a matched control group recruited through general practice. One hundred and ninety five participants from each group were matched on mental wellbeing and social activity scores. Assessments were conducted at baseline and at six month follow-up. The primary outcome was the Short Form Health Survey v2 (SF-12) mental health component score (MCS). Secondary outcomes included the SF-12 physical health component score (PCS), EuroQol EQ-5D, Geriatric Depression Score (GDS-10), social activity, social support and morbidities. RESULTS: We found no evidence that mentoring was beneficial across a wide range of participant outcomes measuring health status, social activity and depression. No statistically significant between-group differences were observed at follow-up in the primary outcome (p = 0.48) and in most secondary outcomes. Identifying suitable matched pairs of intervention and control group participants proved challenging. CONCLUSIONS: the results of this trial provide no substantial evidence supporting the use of community mentoring as an effective means of alleviating social isolation in older people. Further evidence is needed on the effectiveness of community-based interventions targeting social isolation. When using non-randomised designs, there are considerable challenges in the recruitment of suitable matches from a community sample. TRIAL REGISTRATION: SCIE Research Register for Social Care 105923.

Objective: to assess the impact of exercise referral schemes on physical activity and health outcomes. Design: Systematic review and meta-analysis. Data sources: Medline, Embase, PsycINFO, Cochrane Library, ISI Web of Science, SPORTDiscus, and ongoing trial registries up to October 2009. We also checked study references. Study selection: Design: randomised controlled trials or non-randomised controlled (cluster or individual) studies published in peer review journals. Population: sedentary individuals with or without medical diagnosis. Exercise referral schemes defined as: clear referrals by primary care professionals to third party service providers to increase physical activity or exercise, physical activity or exercise programmes tailored to individuals, and initial assessment and monitoring throughout programmes. Comparators: usual care, no intervention, or alternative exercise referral schemes. Results: Eight randomised controlled trials met the inclusion criteria, comparing exercise referral schemes with usual care (six trials), alternative physical activity intervention (two), and an exercise referral scheme plus a self determination theory intervention (one). Compared with usual care, follow-up data for exercise referral schemes showed an increased number of participants who achieved 90-150 minutes of physical activity of at least moderate intensity per week (pooled relative risk 1.16, 95% confidence intervals 1.03 to 1.30) and a reduced level of depression (pooled standardised mean difference -0.82, -1.28 to -0.35). Evidence of a between group difference in physical activity of moderate or vigorous intensity or in other health outcomes was inconsistent at follow-up. We did not find any difference in outcomes between exercise referral schemes and the other two comparator groups. None of the included trials separately reported outcomes in individuals with specific medical diagnoses. Substantial heterogeneity in the quality and nature of the exercise referral schemes across studies might have contributed to the inconsistency in outcome findings. Conclusions: Considerable uncertainty remains as to the effectiveness of exercise referral schemes for increasing physical activity, fitness, or health indicators, or whether they are an efficient use of resources for sedentary people with or without a medical diagnosis.

OBJECTIVE: to assess the impact of exercise referral schemes on physical activity and health outcomes. Design Systematic review and meta-analysis. DATA SOURCES: Medline, Embase, PsycINFO, Cochrane Library, ISI Web of Science, SPORTDiscus, and ongoing trial registries up to October 2009. We also checked study references. Study selection Design: randomised controlled trials or non-randomised controlled (cluster or individual) studies published in peer review journals. POPULATION: sedentary individuals with or without medical diagnosis. Exercise referral schemes defined as: clear referrals by primary care professionals to third party service providers to increase physical activity or exercise, physical activity or exercise programmes tailored to individuals, and initial assessment and monitoring throughout programmes. Comparators: usual care, no intervention, or alternative exercise referral schemes. RESULTS: Eight randomised controlled trials met the inclusion criteria, comparing exercise referral schemes with usual care (six trials), alternative physical activity intervention (two), and an exercise referral scheme plus a self determination theory intervention (one). Compared with usual care, follow-up data for exercise referral schemes showed an increased number of participants who achieved 90-150 minutes of physical activity of at least moderate intensity per week (pooled relative risk 1.16, 95% confidence intervals 1.03 to 1.30) and a reduced level of depression (pooled standardised mean difference -0.82, -1.28 to -0.35). Evidence of a between group difference in physical activity of moderate or vigorous intensity or in other health outcomes was inconsistent at follow-up. We did not find any difference in outcomes between exercise referral schemes and the other two comparator groups. None of the included trials separately reported outcomes in individuals with specific medical diagnoses. Substantial heterogeneity in the quality and nature of the exercise referral schemes across studies might have contributed to the inconsistency in outcome findings. Conclusions Considerable uncertainty remains as to the effectiveness of exercise referral schemes for increasing physical activity, fitness, or health indicators, or whether they are an efficient use of resources for sedentary people with or without a medical diagnosis.

BACKGROUND: Previous reviews demonstrate uncertainty about the effectiveness of nurse-led interventions in the management of hypertension. No specific reviews in diabetes have been identified. We have systematically reviewed the evidence for effectiveness of nurse-led interventions for people with diabetes mellitus. METHODS: in this systematic review and meta-analysis, searches of Medline, Embase, CINAHL and the Cochrane Central Trials register were undertaken to identify studies comparing any intervention conducted by nurses in managing hypertension in diabetes with usual doctor-led care. Additional citations were identified from papers retrieved and correspondence with authors. Outcome measures were absolute systolic and diastolic blood pressure, change in blood pressure, proportions achieving study target blood pressure and proportions prescribed anti-hypertensive medication. RESULTS:   Eleven studies were identified. Interventions included adoption of treatment algorithms, nurse-led clinics and nurse prescribing. Meta-analysis showed greater reductions in blood pressure in favour of any nurse-led interventions (systolic weighted mean difference -5.8 mmHg, 95% CI -9.6 to -2.0; diastolic weighted mean difference -4.2 mmHg, 95% CI -7.6 to -0.7) compared with usual doctor-led care. No overall superiority in achievement of study targets or in the use of medication was evident for any nurse-based interventions over doctor-led care. CONCLUSIONS: There is some evidence for improved blood pressure outcomes with nurse-led interventions for hypertension in people with diabetes compared with doctor-led care. Nurse-based interventions require an algorithm to structure care and there is some preliminary evidence for better outcomes with nurse prescribing. Further work is needed to elucidate which nurse-led interventions are most effective.

BACKGROUND: Cardiac rehabilitation (CR) is a complex multifaceted intervention consisting of three core modalities: education, exercise training and psychological support. Whilst exercise and psychological interventions for patients with coronary heart disease (CHD) have been the subject of Cochrane systematic reviews, the specific impact of the educational component of CR has not previously been investigated. OBJECTIVES: 1. Assess effects of patient education on mortality, morbidity, health-related quality of life (HRQofL) and healthcare costs in patients with CHD.2. Explore study level predictors of the effects of patient education (e.g. individual versus group intervention, timing with respect to index cardiac event). SEARCH METHODS: the following databases were searched: the Cochrane Library, (CENTRAL, CDSR, DARE, HTA, NHSEED), MEDLINE (OVID), EMBASE (OVID), PsycINFO (EBSCOhost) and CINAHL (EBSCOhost). Previous systematic reviews and reference lists of included studies were also searched. No language restrictions were applied. SELECTION CRITERIA: 1. Randomised controlled trials (RCTs) where the primary interventional intent was education.2. Studies with a minimum of six-months follow-up and published in 1990 or later.3. Adults with diagnosis of CHD. DATA COLLECTION AND ANALYSIS: Two review authors selected studies and extracted data. Attempts were made to contact all study authors to obtain relevant information not available in the published manuscript. For dichotomous variables, risk ratios and 95% confidence intervals (CI) were derived for each outcome. For continuous variables, mean differences and 95% CI were calculated for each outcome. MAIN RESULTS: Thirteen RCTs involving 68,556 subjects with CHD and follow-up from six to 60 months were found. Overall, methodological quality of included studies was moderate to good. Educational 'dose' ranged from a total of two clinic visits to a four-week residential stay with 11 months of follow-up sessions. Control groups typically received usual medical care. There was no strong evidence of an effect of education on all-cause mortality (Relative Risk (RR): 0.79, 95% CI 0.55 to 1.13), cardiac morbidity (subsequent myocardial infarction RR: 0.63, 95% CI 0.26 to 1.48, revascularisation RR: 0.58, 95% CI 0.19 to 1.71) or hospitalisation (RR: 0.83, 95% CI:0.65 to 1.07). Whilst some HRQofL domain scores were higher with education, there was no consistent evidence of superiority across all domains. Different currencies and years studies were performed making direct comparison of healthcare costs challenging, although there is evidence to suggest education may be cost-saving by reducing subsequent healthcare utilisation.This review had insufficient power to exclude clinically important effects of education on mortality and morbidity of patients with CHD. AUTHORS' CONCLUSIONS: We did not find strong evidence that education reduced all cause mortality, cardiac morbidity, revascularisation or hospitalisation compared to control. There was some evidence to suggest that education may improve HRQofL and reduce overall healthcare costs. Whilst our findings are generally supportive of current guidelines that CR should include not only exercise and psychological interventions, further research into education is needed.

PURPOSE: Given the high burden of epilepsy on both health-related quality of life (HRQoL) and costs, identification of factors that are predictive of either reduced HRQoL or increased expenditure is central to the better future targeting and optimization of existing and emerging interventions and management strategies for epilepsy. METHODS: Searches of Medline, Embase, and Cochrane Library (up to July 2010) to identify studies examining the association between demographic, psychosocial, and condition-related factors and HRQoL, resource utilization or costs in adults with epilepsy. For each study, predictor factor associations were summarized on the basis of statistical significance and direction; the results were then combined across studies. KEY FINDINGS: Ninety-three HRQoL and 16 resource utilization/cost studies were included. Increases in seizure frequency, seizure severity, level of depression, and level of anxiety and presence of comorbidity were strongly associated with reduced HRQoL. The majority of studies were cross-sectional in design and had an overall methodologic quality that was judged to be "moderate" for HRQoL studies and "poor" for health care resource or costs studies. In the 53 multivariate studies, age, gender, marital status, type of seizure, age at diagnosis, and duration of epilepsy did not appear to be associated with HRQoL, whereas the predictive influence of educational and employment status, number of antiepileptic drugs (AEDs) and AED side effects was unclear. The association between predictive factors and HRQoL appeared to be consistent across individuals whether refractory or seizures controlled or managed by AEDs. There were insufficient multivariate studies (five) to reliably comment on the predictors of resource utilization or cost in epilepsy. SIGNIFICANCE: in addition to seizure control, effective epilepsy management requires the early detection of those most at risk of psychological dysfunction and comorbidity, and the targeting of appropriate interventions. There is need for more rigorous studies with appropriate multivariate statistical methods that prospectively investigate the predictors of HRQoL, resource utilization, and costs in epilepsy.

BACKGROUND: an earlier Cochrane review of dietary advice identified insufficient evidence to assess effects of reduced salt intake on mortality or cardiovascular events. OBJECTIVES: 1. To assess the long term effects of interventions aimed at reducing dietary salt on mortality and cardiovascular morbidity.2. To investigate whether blood pressure reduction is an explanatory factor in any effect of such dietary interventions on mortality and cardiovascular outcomes. SEARCH STRATEGY: the Cochrane Library (CENTRAL, Health Technology Assessment (HTA) and Database of Abstracts of Reviews of Effect (DARE)), MEDLINE, EMBASE, CINAHL and PsycInfo were searched through to October 2008. References of included studies and reviews were also checked. No language restrictions were applied. SELECTION CRITERIA: Trials fulfilled the following criteria: (1) randomised with follow up of at least six-months, (2) intervention was reduced dietary salt (restricted salt dietary intervention or advice to reduce salt intake), (3) adults, (4) mortality or cardiovascular morbidity data was available. Two reviewers independently assessed whether studies met these criteria. DATA COLLECTION AND ANALYSIS: Data extraction and study validity were compiled by a single reviewer, and checked by a second. Authors were contacted where possible to obtain missing information. Events were extracted and relative risks (RRs) and 95% CIs calculated. MAIN RESULTS: Seven studies (including 6,489 participants) met the inclusion criteria - three in normotensives (n=3518), two in hypertensives (n=758), one in a mixed population of normo- and hypertensives (n=1981) and one in heart failure (n=232) with end of trial follow-up of seven to 36 months and longest observational follow up (after trial end) to 12.7 yrs. Relative risks for all cause mortality in normotensives (end of trial RR 0.67, 95% CI: 0.40 to 1.12, 60 deaths; longest follow up RR 0.90, 95% CI: 0.58 to 1.40, 79 deaths) and hypertensives (end of trial RR 0.97, 95% CI: 0.83 to 1.13, 513 deaths; longest follow up RR 0.96, 95% CI; 0.83 to 1.11, 565 deaths) showed no strong evidence of any effect of salt reduction. Cardiovascular morbidity in people with normal blood pressure (longest follow-up RR 0.71, 95% CI: 0.42 to 1.20, 200 events) or raised blood pressure at baseline (end of trial RR 0.84, 95% CI: 0.57 to 1.23, 93 events) also showed no strong evidence of benefit. Salt restriction increased the risk of all-cause death in those with congestive heart failure (end of trial relative risk: 2.59, 95% 1.04 to 6.44, 21 deaths). We found no information on participants health-related quality of life. AUTHORS' CONCLUSIONS: Despite collating more event data than previous systematic reviews of randomised controlled trials (665 deaths in some 6,250 participants), there is still insufficient power to exclude clinically important effects of reduced dietary salt on mortality or cardiovascular morbidity in normotensive or hypertensive populations. Further RCT evidence is needed to confirm whether restriction of sodium is harmful for people with heart failure. Our estimates of benefits from dietary salt restriction are consistent with the predicted small effects on clinical events attributable to the small blood pressure reduction achieved.

BACKGROUND: Although meta-analyses of randomized controlled trials (RCTs) of salt reduction report a reduction in the level of blood pressure (BP), the effect of reduced dietary salt on cardiovascular disease (CVD) events remains unclear. METHODS: We searched for RCTs with follow-up of at least 6 months that compared dietary salt reduction (restricted salt dietary intervention or advice to reduce salt intake) to control/no intervention in adults, and reported mortality or CVD morbidity data. Outcomes were pooled at end of trial or longest follow-up point. RESULTS: Seven studies were identified: three in normotensives, two in hypertensives, one in a mixed population of normo- and hypertensives and one in heart failure. Salt reduction was associated with reductions in urinary salt excretion of between 27 and 39 mmol/24 h and reductions in systolic BP between 1 and 4 mm Hg. Relative risks (RRs) for all-cause mortality in normotensives (longest follow-up-RR: 0.90, 95% confidence interval (CI): 0.58-1.40, 79 deaths) and hypertensives (longest follow-up RR 0.96, 0.83-1.11, 565 deaths) showed no strong evidence of any effect of salt reduction CVD morbidity in people with normal BP (longest follow-up: RR 0.71, 0.42-1.20, 200 events) and raised BP at baseline (end of trial: RR 0.84, 0.57-1.23, 93 events) also showed no strong evidence of benefit. Salt restriction increased the risk of all-cause mortality in those with heart failure (end of trial RR 2.59, 1.04-6.44, 21 deaths).We found no information on participant's health-related quality of life. CONCLUSIONS: Despite collating more event data than previous systematic reviews of RCTs (665 deaths in some 6,250 participants) there is still insufficient power to exclude clinically important effects of reduced dietary salt on mortality or CVD morbidity. Our estimates of benefits from dietary salt restriction are consistent with the predicted small effects on clinical events attributable to the small BP reduction achieved.

BACKGROUND: Topical non-steroidal anti-inflammatory drugs (NSAIDs) are clinically proven for the management of musculoskeletal conditions. It is important that prescribers and patients are aware of the safety profile of topical NSAIDs. OBJECTIVES: to evaluate the risk of adverse events (AEs) associated with topical diclofenac for the treatment of acute and chronic musculoskeletal conditions. DESIGN: Systematic review and meta-analysis of blinded, randomized, placebo-, vehicle- or active-controlled trials. RESULTS: the risk of any type of AE experienced with topical diclofenac was slightly higher compared with placebo/vehicle (RR 1.11), but was more than 50% lower than the risk observed with active topical comparators (RR 0.53). Absolute risk values indicated differences in the risk of AEs depending on the diclofenac formulation used; in particular, lower rates of local skin reactions were observed with diclofenac patches (e.g. 2.5% in placebo/vehicle-controlled studies) and gels (4.2%) compared with diclofenac solutions containing dimethylsulfoxide (34.2%). Dry skin/crusting and rash were the most common local skin reactions reported (9.0% and 3.0% of patients, respectively, in placebo/vehicle-controlled studies), which were usually mild-to-moderate and self-resolving. The discontinuation rate due to local skin reactions with topical diclofenac (1.9%) was low and comparable with non-active comparators (0.7%), and the tolerability of topical diclofenac treatment was rated as 'good' to 'excellent' by >90% physicians and patients. CONCLUSIONS: Topical diclofenac appears to be generally well tolerated for cutaneous use in acute and chronic musculoskeletal conditions.

Overweight and obesity in pre-school children are an increasing problem, with poor diet and exercise habits laying the foundation for serious health risks in later life. Yet most research into childhood obesity has focused on school-age children. Two previous systematic reviews of pre-school children have included uncontrolled designs and self-report outcomes potentially biasing the results in favour of the interventions. We have conducted a systematic review of the effectiveness and cost-effectiveness of weight management schemes for the under fives restricting the inclusion criteria to controlled trials with objective measures. We found four effectiveness randomized controlled trials of prevention. No treatment or cost-effectiveness studies were found. Only one study in a Latino community showed a statistically significant advantage from the intervention in a slower rate of increase in body mass index. However, trends in decrease in body mass index and weight loss favoured the intervention groups in other studies. From the studies characteristics we hypothesize that important features to include in future interventions may be; cultural sensitivity, sustained moderate to vigorous exercise, active engagement of the parents in the programme and as role models of healthy living and active engagement of the children in nutrition education. Further randomized controlled trials are needed in this population.

BACKGROUND: Exercise referral schemes (ERS) aim to identify inactive adults in the primary-care setting. The GP or health-care professional then refers the patient to a third-party service, with this service taking responsibility for prescribing and monitoring an exercise programme tailored to the needs of the individual. OBJECTIVE: to assess the clinical effectiveness and cost-effectiveness of ERS for people with a diagnosed medical condition known to benefit from physical activity (PA). The scope of this report was broadened to consider individuals without a diagnosed condition who are sedentary. DATA SOURCES: MEDLINE; EMBASE; PsycINFO; the Cochrane Library, ISI Web of Science; SPORTDiscus and ongoing trial registries were searched (from 1990 to October 2009) and included study references were checked. METHODS: Systematic reviews: the effectiveness of ERS, predictors of ERS uptake and adherence, and the cost-effectiveness of ERS; and the development of a decision-analytic economic model to assess cost-effectiveness of ERS. RESULTS: Seven randomised controlled trials (UK, n = 5; non-UK, n = 2) met the effectiveness inclusion criteria, five comparing ERS with usual care, two compared ERS with an alternative PA intervention, and one to an ERS plus a self-determination theory (SDT) intervention. In intention-to-treat analysis, compared with usual care, there was weak evidence of an increase in the number of ERS participants who achieved a self-reported 90-150 minutes of at least moderate-intensity PA per week at 6-12 months' follow-up [pooled relative risk (RR) 1.11, 95% confidence interval 0.99 to 1.25]. There was no consistent evidence of a difference between ERS and usual care in the duration of moderate/vigorous intensity and total PA or other outcomes, for example physical fitness, serum lipids, health-related quality of life (HRQoL). There was no between-group difference in outcomes between ERS and alternative PA interventions or ERS plus a SDT intervention. None of the included trials separately reported outcomes in individuals with medical diagnoses. Fourteen observational studies and five randomised controlled trials provided a numerical assessment of ERS uptake and adherence (UK, n = 16; non-UK, n = 3). Women and older people were more likely to take up ERS but women, when compared with men, were less likely to adhere. The four previous economic evaluations identified suggest ERS to be a cost-effective intervention. Indicative incremental cost per quality-adjusted life-year (QALY) estimates for ERS for various scenarios were based on a de novo model-based economic evaluation. Compared with usual care, the mean incremental cost for ERS was £169 and the mean incremental QALY was 0.008, with the base-case incremental cost-effectiveness ratio at £20,876 per QALY in sedentary people without a medical condition and a cost per QALY of £14,618 in sedentary obese individuals, £12,834 in sedentary hypertensive patients, and £8414 for sedentary individuals with depression. Estimates of cost-effectiveness were highly sensitive to plausible variations in the RR for change in PA and cost of ERS. LIMITATIONS: We found very limited evidence of the effectiveness of ERS. The estimates of the cost-effectiveness of ERS are based on a simple analytical framework. The economic evaluation reports small differences in costs and effects, and findings highlight the wide range of uncertainty associated with the estimates of effectiveness and the impact of effectiveness on HRQoL. No data were identified as part of the effectiveness review to allow for adjustment of the effect of ERS in different populations. CONCLUSIONS: There remains considerable uncertainty as to the effectiveness of ERS for increasing activity, fitness or health indicators or whether they are an efficient use of resources in sedentary people without a medical diagnosis. We failed to identify any trial-based evidence of the effectiveness of ERS in those with a medical diagnosis. Future work should include randomised controlled trials assessing the cinical effectiveness and cost-effectivenesss of ERS in disease groups that may benefit from PA. FUNDING: the National Institute for Health Research Health Technology Assessment programme.

BACKGROUND: Exercise referral schemes (ERS) aim to identify inactive adults in the primary care setting. The primary care professional refers the patient to a third party service, with this service taking responsibility for prescribing and monitoring an exercise programme tailored to the needs of the patient. This paper examines the cost-effectiveness of ERS in promoting physical activity compared with usual care in primary care setting. METHODS: a decision analytic model was developed to estimate the cost-effectiveness of ERS from a UK NHS perspective. The costs and outcomes of ERS were modelled over the patient's lifetime. Data were derived from a systematic review of the literature on the clinical and cost-effectiveness of ERS, and on parameter inputs in the modelling framework. Outcomes were expressed as incremental cost per quality-adjusted life-year (QALY). Deterministic and probabilistic sensitivity analyses investigated the impact of varying ERS cost and effectiveness assumptions. Sub-group analyses explored the cost-effectiveness of ERS in sedentary people with an underlying condition. RESULTS: Compared with usual care, the mean incremental lifetime cost per patient for ERS was £169 and the mean incremental QALY was 0.008, generating a base-case incremental cost-effectiveness ratio (ICER) for ERS at £20,876 per QALY in sedentary individuals without a diagnosed medical condition. There was a 51% probability that ERS was cost-effective at £20,000 per QALY and 88% probability that ERS was cost-effective at £30,000 per QALY. In sub-group analyses, cost per QALY for ERS in sedentary obese individuals was £14,618, and in sedentary hypertensives and sedentary individuals with depression the estimated cost per QALY was £12,834 and £8,414 respectively. Incremental lifetime costs and benefits associated with ERS were small, reflecting the preventative public health context of the intervention, with this resulting in estimates of cost-effectiveness that are sensitive to variations in the relative risk of becoming physically active and cost of ERS. CONCLUSIONS: ERS is associated with modest increase in lifetime costs and benefits. The cost-effectiveness of ERS is highly sensitive to small changes in the effectiveness and cost of ERS and is subject to some significant uncertainty mainly due to limitations in the clinical effectiveness evidence base.

Objectives: to evaluate the two-compound formulation (TCF) calcipotriol and betamethasone dipropionate (BDP) gel versus other topical therapies for scalp psoriasis in adults using direct and indirect comparisons. Methods: a systematic review identified 10 randomised controlled trials (RCTs) of topical treatments used in clinical practice for moderately severe scalp psoriasis. A meta-analysis was undertaken to obtain estimates of clinical effectiveness using recommended efficacy and safety outcome measures. We determined the proportion of responding patients using two definitions: i) 'controlled disease' using the Investigator Global Assessment (IGA) rating scale and ii) a score of 0 or 1 on the Total Sign Score (TSS). Tolerability was extracted in terms of percentages of patients experiencing all adverse events (AEs), skin AEs and withdrawals due to AEs. Direct comparisons were performed where head-to-head data were available. For other comparators where TCF gel was compared indirectly, 'pairs' of trials were compared on the basis of a common comparator using meta-regression in order to derive an indirect comparison estimate, while preserving randomisation within trials. Assumptions of comparability were considered regarding study homogeneity (data can be pooled in a meta-analysis), similarity of trials (clinical and methodological) and consistency of findings from direct and indirect evidence. Results: the meta-analysis showed that TCF gel was statistically significantly more effective than other topical treatments in terms of achieving a response defined according to both IGA and TSS criteria. TCF gel was generally associated with a statistically significant lower risk of AEs, skin AEs or patients withdrawing from RCTs due to AEs. Conclusions: Although direct and indirect evidence in this analysis is sparse, this indirect comparison suggests that the TCF gel has significant benefits over other topical therapies considered in the routine management of patients with moderately severe scalp psoriasis. Despite other analysis limitations in terms of study heterogeneity inevitable across an evidence base spanning decades, these results were consistent, using a number of efficacy and tolerability outcome measures. © 2011 Informa UK Ltd.

PURPOSE: to investigate for socially isolated older people, and older people at risk of social isolation: (1) health status and health-related quality of life (HRQL); (2) the relationship between social isolation and health status/HRQL; (3) the relationship between two alternative measures of health status/HRQL. METHODS: Older people at risk of social isolation (n = 393) completed the EQ-5D and the SF-12. Multiple regression analyses were performed to examine the relationship between levels of social isolation and health status/HRQL, controlling for demographic/clinical characteristics. The agreement between EQ-5D and SF-6D (SF-12) scores was explored using descriptive psychometric techniques. RESULTS: Health status and health state values were much lower than UK general population age-matched norms. After controlling for depression, physical co-morbidities, age, gender, living alone status, employment and accommodation, social isolation was significantly associated, to a degree that was clinically relevant, with EQ-5D DSI, SF-6D (SF-12) and SF-12 MCS scores. The potential for ceiling effects on the EQ-5D with this population was identified. CONCLUSION: This work highlights the burden that social isolation may have on the health and well-being of older people. The potential HRQL gains from addressing social isolation may be considerable, with those at risk of social isolation also a key target group.

OBJECTIVES:   Failed back surgery syndrome (FBSS) patients experience pain, functional disability, and reduced health-related quality of life (HRQoL) despite anatomically successful surgery. Examining sub-dimensions of health outcomes measures provides insight into patient well-being. MATERIALS AND METHODS:   the international multicenter PROCESS trial collected detailed HRQoL (EuroQol-5D; Short-Form 36) and function (Oswestry Disability Index) information on 100 FBSS patients. RESULTS:   at baseline, patients reported moderate-to-severe leg and back pain adversely affecting all dimensions of function and HRQoL. Compared with conventional medical management alone, patients also receiving spinal cord stimulation (SCS) reported superior pain relief, function, and HRQoL at six months on overall and most sub-component scores. The majority of these improvements with SCS were sustained at 24 months. Nonetheless, 36-40% of patients experienced ongoing marked disability (standing, lifting) and HRQoL problems (pain/discomfort). CONCLUSIONS:   Longer-term patient management and research must focus on these refractory FBSS patients with persisting poor function and HRQoL outcomes.

To determine the preferred means by which participants in a study of cardiac rehabilitation wish to be informed of the study's results. Postal questionnaire survey of participants in a randomized controlled trial. Cornwall, southwest England. Patients recruited to the Cornwall Heart Attack Rehabilitation Management Study (CHARMS). Participants recruited to CHARMS who were alive 3 years and 9 months after the trial was completed were contacted by letter and invited to return a reply slip with four short questions indicating how they would prefer to be informed about the published results of the study. In March 2008, 191/230 participants originally recruited to CHARMS were still alive. General practitioners deemed 166/191 (88%) survivors medically appropriate to be contacted through a postal survey, and 154/166 (93%) participants responded to the invitation to participate in the follow-up survey. 86% (143/166) of participants indicated that they wished to be informed about the results: 115 (80%) of these elected to receive information by letter and 25 (18%) of these preferred to attend a meeting. Men older than 65 years predominated in this latter group. Women respondents preferred to receive the study results by letter; none preferred communication by email or the web. Survivors of acute myocardial infarction who participated in a RCT of cardiac rehabilitation wanted to receive a summary of the aggregate study results. Participants had preferences regarding how they would wish to be informed about the results of the study. Most participants preferred to be informed by letter or email, but some preferred the interaction of a group or a meeting.

Topic: Preoperative corneal neovascularization (CNV) is thought to be associated with an increased rate of corneal graft failure and potentially also graft rejection. Clinical Relevance: New therapeutic options that offer differential influence on the ingrowths or regression of either corneal blood or lymphatic vessels force us to re-evaluate the known data about the role of CNV in keratoplasty. Methods: Electronic databases and corneal registries were searched (up through September 2008). Results were reported both descriptively for each study and using random effects meta-analysis. Potential moderating factors for the association between vascularization and graft failure and rejection were examined using metaregression analysis. Results: Nineteen studies reporting on a total of 24 944 grafts undergoing keratoplasty were included. An increase in the risk of graft failure and rejection in the presence of pathologic CNV was seen in studies with a pooled risk ratio of 1.32 (95% confidence interval [CI], 1.151.49) for graft failure and 2.07 (95% CI, 0.983.15) for graft rejection. There was evidence of incremental increase of risk for graft failure and rejection as more corneal quadrants were affected by neovascularization. The 2 factors predictive of increased risk of neovascularization and graft failure were increased recipient age (P =0.003) and male gender (P = 0.046). Conclusions: Graft failure and rejection risk increase with an increasing number of corneal quadrants affected by neovascularization before keratoplasty. These data support the study of novel topical antiangiogenic therapies at the cornea to precondition such a cornea for future corneal grafting. © 2010 by the American Academy of Ophthalmology.

BACKGROUND: from previous systematic reviews and meta-analyses there is consensus about the positive effect of exercise training on exercise capacity; however, the effects on health-related quality of life, mortality and hospital admissions in heart failure remain uncertain. OBJECTIVES: to update the previous systematic review which determined the effectiveness of exercise-based interventions on the mortality, hospitalisation admissions, morbidity and health-related quality of life for patients with systolic heart failure. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2007, Issue 4). To update searches from the previous review, MEDLINE, EMBASE, CINAHL, and PsycINFO were searched (2001 to January 2008). ISI Proceedings and bibliographies of identified reviews were checked. SELECTION CRITERIA: Randomised controlled trials of exercise-based interventions with six months follow up or longer compared to usual medical care or placebo. The study population comprised adults of all ages (> 18 years) with evidence of chronic systolic heart failure. DATA COLLECTION AND ANALYSIS: all identified references were independently screened by two review authors and those that were clearly ineligible were rejected. Full papers of potentially relevant trials were obtained. Data were independantly extracted from the included trials and their risk of bias assessed by a single review author and checked by a second. MAIN RESULTS: Nineteen trials (3647 participants) met the inclusion criteria. One large trial recuited 2331 of the participants. There was no significant difference in pooled mortality between groups in the 13 trials with < 1 year follow up. There was evidence of a non-significant trend toward a reduction in pooled mortality with exercise in the four trials with > 1 year follow up. A reduction in the hospitalisation rate was demonstrated with exercise training programmes. Hospitalisations due to systolic heart failure were reduced with exercise and there was a significant improvement in health-related quality of life (HRQoL). The effect of cardiac exercise training on total mortality and HRQoL were independent of the degree of left ventricular dysfunction, type of cardiac rehabilitation, dose of exercise intervention, length of follow up, trial quality, and trial publication date. AUTHORS' CONCLUSIONS: the previous version of this review showed that exercise training improved exercise capacity in the short term in patients with mild to moderate heart failure when compared to usual care. This updated review provides evidence that in a similar population of patients, exercise does not increase the risk of all-cause mortality and may reduce heart failure-related hospital admissions. Exercise training may offer important improvements in patients' health-related quality of life.

To determine the effect of exercise training on clinical events and health-related quality of life (HRQoL) of patients with systolic heart failure. Methods and results: We searched electronic databases including Medline, EMBASE, and Cochrane Library up to January 2008 to identify randomized controlled trials (RCTs) comparing exercise training and usual care with a minimum follow-up of 6 months. Nineteen RCTs were included with a total of 3647 patients, the majority of whom were male, low-to-medium risk, and New York Heart Association class II-III with a left ventricular ejection fraction of

BACKGROUND: the burden of cardiovascular disease world-wide is one of great concern to patients and health care agencies alike. Traditionally centre-based cardiac rehabilitation (CR) programmes are offered to individuals after cardiac events to aid recovery and prevent further cardiac illness. Home-based cardiac rehabilitation programmes have been introduced in an attempt to widen access and participation. OBJECTIVES: to determine the effectiveness of home-based cardiac rehabilitation programmes compared with supervised centre-based cardiac rehabilitation on mortality and morbidity, health-related quality of life and modifiable cardiac risk factors in patients with coronary heart disease. SEARCH STRATEGY: We updated the search of a previous review by searching the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library (2007, Issue 4), MEDLINE, EMBASE and CINAHL from 2001 to January 2008. We checked reference lists and sought advice from experts. No language restrictions were applied. SELECTION CRITERIA: Randomised controlled trials (RCTs) that compared centre-based cardiac rehabilitation (e.g. hospital, gymnasium, sports centre) with home-based programmes, in adults with myocardial infarction, angina, heart failure or who had undergone revascularisation. DATA COLLECTION AND ANALYSIS: Studies were selected independently by two reviewers, and data extracted by a single reviewer and checked by a second one. Authors were contacted where possible to obtain missing information. MAIN RESULTS: Twelve studies (1,938 participants) met the inclusion criteria. The majority of studies recruited a lower risk patient following an acute myocardial infarction (MI) and revascularisation. There was no difference in outcomes of home- versus centre-based cardiac rehabilitation in mortality risk ratio (RR) was1.31 (95% confidence interval (C) 0.65 to 2.66), cardiac events, exercise capacity standardised mean difference (SMD) -0.11 (95% CI -0.35 to 0.13), as well as in modifiable risk factors (systolic blood pressure; diastolic blood pressure; total cholesterol; HDL-cholesterol; LDL-cholesterol) or proportion of smokers at follow up or health-related quality of life. There was no consistent difference in the healthcare costs of the two forms of cardiac rehabilitation. AUTHORS' CONCLUSIONS: Home- and centre-based cardiac rehabilitation appear to be equally effective in improving the clinical and health-related quality of life outcomes in acute MI and revascularisation patients. This finding, together with an absence of evidence of difference in healthcare costs between the two approaches, would support the extension of home-based cardiac rehabilitation programmes such as the Heart Manual to give patients a choice in line with their preferences, which may have an impact on uptake of cardiac rehabilitation in the individual case.

Mindfulness-based cognitive therapy (MBCT) is an efficacious psychosocial intervention for recurrent depression (Kuyken et al. 2008; Ma & Teasdale, 2004; Teasdale et al. 2000). To date, no compelling research addresses MBCT's mechanisms of change. This study determines whether MBCT's treatment effects are mediated by enhancement of mindfulness and self-compassion across treatment, and/or by alterations in post-treatment cognitive reactivity. The study was embedded in a randomized controlled trial comparing MBCT with maintenance antidepressants (mADM) with 15-month follow-up (Kuyken et al. 2008). Mindfulness and self-compassion were assessed before and after MBCT treatment (or at equivalent time points in the mADM group). Post-treatment reactivity was assessed one month after the MBCT group sessions or at the equivalent time point in the mADM group. One hundred and twenty-three patients with ≥3 prior depressive episodes, and successfully treated with antidepressants, were randomized either to mADM or MBCT. The MBCT arm involved participation in MBCT, a group-based psychosocial intervention that teaches mindfulness skills, and discontinuation of ADM. The mADM arm involved maintenance on a therapeutic ADM dose for the duration of follow-up. Interviewer-administered outcome measures assessed depressive symptoms and relapse/recurrence across 15-month follow-up. Mindfulness and self-compassion were measured using self-report questionnaire. Cognitive reactivity was operationalized as change in depressive thinking during a laboratory mood induction. MBCT's effects were mediated by enhancement of mindfulness and self-compassion across treatment. MBCT also changed the nature of the relationship between post-treatment cognitive reactivity and outcome. Greater reactivity predicted worse outcome for mADM participants but this relationship was not evident in the MBCT group. MBCT's treatment effects are mediated by augmented self-compassion and mindfulness, along with a decoupling of the relationship between reactivity of depressive thinking and poor outcome. This decoupling is associated with the cultivation of self-compassion across treatment.

Objective: to review trials of nurse led interventions for hypertension in primary care to clarify the evidence base, establish whether nurse prescribing is an important intervention, and identify areas requiring further study. Design: Systematic review and meta-analysis. Data sources: Ovid Medline, Cochrane Central Register of Controlled Trials, British Nursing Index, Cinahl, Embase, Database of Abstracts of Reviews of Effects, and the NHS Economic Evaluation Database. Study selection: Randomised controlled trials of nursing interventions for hypertension compared with usual care in adults. Data extraction: Systolic and diastolic blood pressure, percentages reaching target blood pressure, and percentages taking antihypertensive drugs. Intervention effects were calculated as relative risks or weighted mean differences, as appropriate, and sensitivity analysis by study quality was undertaken. Data synthesis: Compared with usual care, interventions that included a stepped treatment algorithm showed greater reductions in systolic blood pressure (weighted mean difference -8.2 mm Hg, 95% confidence interval -11.5 to -4.9), nurse prescribing showed greater reductions in blood pressure (systolic -8.9 mm Hg, -12.5 to -5.3 and diastolic -4.0 mm Hg, -5.3 to -2.7), telephone monitoring showed higher achievement of blood pressure targets (relative risk 1.24, 95% confidence interval 1.08 to 1.43), and community monitoring showed greater reductions in blood pressure (weighted mean difference, systolic -4.8 mm Hg, 95% confidence interval -7.0 to -2.7 and diastolic -3.5 mm Hg, -4.5 to -2.5). Conclusions: Nurse led interventions for hypertension require an algorithm to structure care. Evidence was found of improved outcomes with nurse prescribers from non-UK healthcare settings. Good quality evidence from UK primary health care is insufficient to support widespread employment of nurses in the management of hypertension within such healthcare systems.

OBJECTIVE: to review trials of nurse led interventions for hypertension in primary care to clarify the evidence base, establish whether nurse prescribing is an important intervention, and identify areas requiring further study. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Ovid Medline, Cochrane Central Register of Controlled Trials, British Nursing Index, Cinahl, Embase, Database of Abstracts of Reviews of Effects, and the NHS Economic Evaluation Database. STUDY SELECTION: Randomised controlled trials of nursing interventions for hypertension compared with usual care in adults. DATA EXTRACTION: Systolic and diastolic blood pressure, percentages reaching target blood pressure, and percentages taking antihypertensive drugs. Intervention effects were calculated as relative risks or weighted mean differences, as appropriate, and sensitivity analysis by study quality was undertaken. DATA SYNTHESIS: Compared with usual care, interventions that included a stepped treatment algorithm showed greater reductions in systolic blood pressure (weighted mean difference -8.2 mm Hg, 95% confidence interval -11.5 to -4.9), nurse prescribing showed greater reductions in blood pressure (systolic -8.9 mm Hg, -12.5 to -5.3 and diastolic -4.0 mm Hg, -5.3 to -2.7), telephone monitoring showed higher achievement of blood pressure targets (relative risk 1.24, 95% confidence interval 1.08 to 1.43), and community monitoring showed greater reductions in blood pressure (weighted mean difference, systolic -4.8 mm Hg, 95% confidence interval -7.0 to -2.7 and diastolic -3.5 mm Hg, -4.5 to -2.5). CONCLUSIONS: Nurse led interventions for hypertension require an algorithm to structure care. Evidence was found of improved outcomes with nurse prescribers from non-UK healthcare settings. Good quality evidence from UK primary health care is insufficient to support widespread employment of nurses in the management of hypertension within such healthcare systems.

This is the protocol for a review and there is no abstract. The objectives are as follows: to assess the effects of patient education compared with usual care on mortality and morbidity in patients with CHD.To explore the potential study level predictors of the effects of patient education in patients with CHD.

Objectives: Patients with failed back surgery syndrome (FBSS) and chronic neuropathic pain experience levels of health-related quality of life (HRQoL) that are considerably lower than those reported in other areas of chronic pain. The aim of this article was to quantify the extent to which reductions in (leg and back) pain and disability over time translate into improvements in generic HRQoL as measured by the EuroQoL-5D and SF-36 instruments. Methods: Using data from the multinational Prospective, Randomized, Controlled, Multicenter Study of Patients with Failed Back Surgery Syndrome trial, we explore the relationship between generic HRQoL - assessed using two instruments often used in clinical trials (i.e. the SF-36 and EuroQol-5D) - and disease-specific outcome measures (i.e. Oswestry disability index [ODI], leg and back pain visual analog scale [VAS]) in neuropathic patients with FBSS. Results: in our sample of 100 FBSS patients, generic HRQoL was moderately associated with ODI (correlation coefficient: -0.462 to -0.638) and mildly associated with leg pain VAS (correlation coefficient: -0.165 to -0.436). The multilevel regression analysis results indicate that functional ability (as measured by the ODI) is significantly associated with HRQoL, regardless of the generic HRQoL instrument used. On the other hand, changes over time in leg pain were significantly associated with changes in the EuroQoL-5D and physical component summary scores, but not with the mental component summary score. Conclusions: Reduction in leg pain and functional disability is statistically significantly associated with improvements in generic HRQoL. This is the first study to investigate the longitudinal relationship between generic and disease-specific HRQoL of neuropathic pain patients with FBSS, using multinational data. © 2009, International Society for Pharmacoeconomics and Outcomes Research (ISPOR).

BACKGROUND: Depression is a common and distressing mental health problem that is responsible for significant individual disability and cost to society. Medication and psychological therapies are effective for treating depression and maintenance anti-depressants (m-ADM) can prevent relapse. However, individuals with depression often express a wish for psychological help that can help them recover from depression in the long-term. We need to develop psychological therapies that prevent depressive relapse/recurrence. A recently developed treatment, Mindfulness-based Cognitive Therapy (MBCT, see http://www.mbct.co.uk) shows potential as a brief group programme for people with recurring depression. In two studies it has been shown to halve the rates of depression recurring compared to usual care.This trial asks the policy research question, is MBCT superior to m-ADM in terms of: a primary outcome of preventing depressive relapse/recurrence over 24 months; and, secondary outcomes of (a) depression free days, (b) residual depressive symptoms, (c) antidepressant (ADM) usage, (d) psychiatric and medical co-morbidity, (e) quality of life, and (f) cost effectiveness? an explanatory research question asks is an increase in mindfulness skills the key mechanism of change? METHODS/DESIGN: the design is a single blind, parallel RCT examining MBCT vs. m-ADM with an embedded process study. To answer the main policy research question the proposed trial compares MBCT plus ADM-tapering with m-ADM for patients with recurrent depression. Four hundred and twenty patients with recurrent major depressive disorder in full or partial remission will be recruited through primary care. Depressive relapse/recurrence over two years is the primary outcome variable. The explanatory question will be addressed in two mutually informative ways: quantitative measurement of potential mediating variables pre/post-treatment and a qualitative study of service users' views and experiences. DISCUSSION: If the results of our exploratory trial are extended to this definitive trial, MBCT will be established as an alternative approach to maintenance anti-depressants for people with a history of recurrent depression. The process studies will provide evidence about the effective components which can be used to improve MBCT and inform theory as well as other therapeutic approaches. TRIAL REGISTRATION NUMBER: ISRCTN26666654.

OBJECTIVE: in the UK approximately 3% of over 50 years olds and 8% of over 70 year olds have severe (794-94 dBHL) to deafness. As deafness increased, hearing aids become increasingly ineffective. Cochelear implants can provide an alternative treatment. OBJECTIVE OF REVIEW: to bring together the research evidence through the robustness of a systematic review of the effectiveness of unilateral cochlear implants for adults. We also sought to systematically review the published literature on cost-effectiveness. TYPES OF REVIEW: Systematic review. SEARCH STRATEGY: This examined 16 electronic databases, plus bibliographies and references for published and unpublished studies from inception to june 2009. EVALUATION METHOD: Abstracts were independently assessed against inclusion criteria by two researchers were compared and disagreements resolved. Included papers were then retrieved and further independently assessed in a similar way. Remaining studies had their data independently extracted by one of five reviewers and checked by another reviewer. RESULTS: from 1,580 titles and abstracts nine studies were included. These were of variable quality; some study's results should be viewed with caution. The studies were too hetrogeneous to pool the data. However, overall the results firmly supported the use of unilateral cochler implants for severe to profoundly deaf adults. Additionally, four UK based economic evaluations found unilateral cochlear implants to be cost-effectivene in adults at UK implants centres. CONCLUSION: the methodologically weak but universally positive body of effectiveness evidence supports the use of unilateral cochlear implants in adults. Previous economic evaluations indicate that such implants are likely to be cost-effective.

Patients with neuropathic pain (NeuP) experience substantially lower health-related quality of life (HRQoL) than the general population. The aim of this systematic review and meta-analysis is to test the hypothesis that NeuP is associated with low levels of health utility. A structured search of electronic databases (MEDLINE, EMBASE, Cochrane Library and CINAHL) was undertaken. Reference lists of retrieved reports were also reviewed. Studies reporting utility single-index measures (preference based) in NeuP were included. Random effects meta-analysis was used to pool EQ-5D index utility estimates across NeuP conditions. The association of utilities and pre-defined factors (NeuP condition, patient age, sex, duration and severity of pain and method of utility scoring) was examined using meta-regression. Twenty-four studies reporting health utility values in patients with NeuP were included in the review. Weighted pooled utility score across the studies varied from a mean of 0.15 for failed back surgery syndrome to 0.61 for post-herpetic neuralgia and diabetic neuropathy. Although there was substantial heterogeneity (P < 0.0001) across studies, we found little variation in utility as a function of patient and study characteristics. The single exception was a significant relationship (P < 0.0001) between increasing neuropathic pain severity and a reduction in utility. This study confirms the hypothesis that patients with NeuP experience low utilities and therefore low HRQoL. However, the contribution of non-NeuP co-morbidity remains unclear. Neuropathic pain severity emerged as a primary predictor of the negative health impact of NeuP. © 2010 International Association for the Study of Pain.

OBJECTIVES: Health-care policymakers and payers require cost-effectiveness evidence to inform their treatment funding decisions. The aims of this study were to assess the cost-effectiveness of the addition of spinal cord stimulation (SCS) compared with conventional management alone (CMM) in patients with complex regional pain syndrome (CRPS), and to determine the cost-effectiveness of nonrechargeable versus rechargeable SCS implanted pulse generators (IPGs). METHODS: a decision analytic model was used to synthesize data on CRPS patient outcomes and health-care costs over a 15-year time horizon from the perspective of the UK National Health Services. Data were sourced from two SCS randomized controlled trials. Results are expressed as an incremental cost per quality-adjusted life-year (QALY) in 2008 GBP. RESULTS: the incremental cost-effectiveness of SCS compared with CMM was £3562 per QALY, a finding that was robust across sensitivity analyses with an 87% probability that SCS is cost-effective at a willingness to pay threshold of £30,000. When the longevity of an IPG is 4 years or less, a rechargeable (and initially more expensive) IPG is more cost-effective than a nonrechargeable IPG. CONCLUSIONS: in selected patients with CRPS, SCS is cost-effective as an adjunct to CMM. Despite their initial increased expense, rechargeable IPGs should be considered when IPG longevity is likely to be short. These findings support policymakers to extend the use of SCS as a good value for money treatment for CRPS.

OBJECTIVES: Healthcare policy makers and payers require cost-effectiveness evidence to inform their treatment funding decisions. Thus, in 2008, the United Kingdom's National Institute of Health and Clinical Excellence analyzed the cost effectiveness of spinal cord stimulation (SCS) compared with conventional medical management (CMM) and with reoperation and recommended approval of SCS in selected patients with failed back surgery syndrome (FBSS). We present previously unavailable details of the National Institute of Health and Clinical Excellence analysis and an analysis of the impact on SCS cost effectiveness of rechargeable implanted pulse generators (IPGs). METHODS: We used a decision analytic model to examine the cost effectiveness of SCS versus CMM and versus reoperation in patients with FBSS. We also modeled the impact of nonrechargeable versus rechargeable IPGs. RESULTS: the incremental cost-effectiveness of SCS compared with CMM was pound5624 per quality-adjusted life year, with 89% probability that SCS is cost effective at a willingness to pay threshold of pound20,000. Compared with reoperation, the incremental cost-effectiveness of SCS was pound6392 per quality-adjusted life year, with 82% probability of cost-effectiveness at the pound20,000 threshold. When the longevity of an IPG is 4 years or less, a rechargeable (and initially more expensive) IPG is more cost-effective than a nonrechargeable IPG. DISCUSSION: in selected patients with FBSS, SCS is cost effective both as an adjunct to CMM and as an alternative to reoperation. Despite their initial increased expense, rechargeable IPGs should be considered when IPG longevity is likely to be short.

AIM: to determine the feasibility of recruiting patients with early chronic obstructive pulmonary disease (COPD) to the Health Enhancing Activity in Lung THerapy (HEALTH) exercise and education programme. METHODS: Patients with early COPD were identified from general practices. Those meeting the study inclusion criteria were administered tiotropium throughout the study period. Participants were randomised to either an eight-week health enhancing and physical activity (HEPA) programme, or to a control group (usual care). Behavioural, physiological and psychosocial outcome measures were reported preand post-intervention. RESULTS: Out of 27 practices approached, 16 (59.3%) agreed to participate. of 215 potentially eligible patients contacted, 60 (27.9%) replied. Twenty (33.3%) were randomised to either HEPA intervention (n=10) or usual care (n=10). Fourteen patients attended a postintervention assessment. CONCLUSION: This study provides valuable information on the feasibility of conducting such a trial involving a physical activity intervention.

AIMS: Supervised exercise can benefit selected patients with heart failure, however the effectiveness of home-based exercise remains uncertain. We aimed to assess the effectiveness of a home-based exercise programme in addition to specialist heart failure nurse care. METHODS AND RESULTS: This was a randomized controlled trial of a home-based walking and resistance exercise programme plus specialist nurse care (n=84) compared with specialist nurse care alone (n=85) in a heart failure population in the West Midlands, UK. PRIMARY OUTCOME: Minnesota Living with Heart Failure Questionnaire (MLwHFQ) at 6 and 12 months. SECONDARY OUTCOMES: composite of death, hospital admission with heart failure or myocardial infarction; psychological well-being; generic quality of life (EQ-5D); exercise capacity. There was no statistically significant difference between groups in the MLwHFQ at 6 month (mean, 95% CI) (-2.53, -7.87 to 2.80) and 12 month (-0.55, -5.87 to 4.76) follow-up or secondary outcomes with the exception of a higher EQ-5D score (0.11, 0.04 to 0.18) at 6 months and lower Hospital Anxiety and Depression Scale score (-1.07, -2.00 to -0.14) at 12 months, in favour of the exercise group. At 6 months, the control group showed deterioration in physical activity, exercise capacity, and generic quality of life. CONCLUSION: Home-based exercise training programmes may not be appropriate for community-based heart failure patients.

BACKGROUND: Annually an estimated 223 children in the UK are born with or acquire permanent profound bilateral deafness (PBHL >or= 95 dB). These children may gain little or no benefit from acoustic hearing aids. However, cochlear implants might enable them to hear. OBJECTIVES OF THE REVIEW: to bring together the diverse research in this area under the rigor of a systematic review to discover the strength of evidence when comparing the effectiveness of unilateral cochlear implants with non-technological support or acoustic hearing aids in children with PBHL. TYPE OF REVIEW: Systematic review. SEARCH STRATEGY: This examined 16 electronic data bases, plus bibliographies and references for published and unpublished studies. EVALUATION METHOD: Abstracts were independently assessed against inclusion criteria by two researchers, results were compared and disagreements resolved. Included papers were then retrieved and further independently assessed in a similar way. Remaining studies had their data independently extracted by one of five reviewers and checked by another reviewer. RESULTS: from 1,580 abstracts and titles 15 studies were included. These were of moderate to poor quality. The large amount of heterogeneity in design and outcomes precluded meta-analysis. However, all studies reported that unilateral cochlear implants improved scores on all outcome measures. Additionally five economic evaluations found unilateral cochlear implants to be cost-effective for profoundly deaf children at UK implant centres. CONCLUSIONS: the robustness of systematic review methods gives weight to the positive findings of 15 papers reporting on this subject that they individually lack; while an RCT to show this would be unethical.

A diferencia de las terapias farmacológicas, las terapias intervencionales contra el dolor comprenden la compleja interacción entre el técnico clínico ("el operador"), el procedimiento clínico, y el equipo/aparato médico. Es fundamental entender dicha interacción para apreciar los desafíos que presenta el diseño de ensayos clínicos para procedimientos Intervencionales contra el dolor crónico. El presente artículo resume la evolución de la evidencia que requieren quines toman las decisiones y quienes pagan los servicios de salud para definir sus políticas, examina los retos específicos que se presentan en el diseño de ensayos clínicos de procedimientos intervencionales, y perfila posibles soluciones de diseño que respondan a estos retos.

OBJECTIVE: to evaluate the cost-effectiveness of combined resynchronisation and implantable defibrillator therapy for left ventricular dysfunction and explore subgroups in which such devices might be most cost-effective. DESIGN: Markov model-based economic evaluation. SETTING: UK NHS. PARTICIPANTS: a simulated mixed age cohort of NYHA class III and IV patients with left ventricular systolic dysfunction and prolonged QRS interval. MAIN OUTCOME MEASURES: Cost per quality adjusted life year gained over the patient lifetime. RESULTS: the incremental cost-effectiveness of resynchronisation therapy alone compared with optimal medical therapy was pound16,735 (95% CI: pound14,630 to pound20,333) with a 91% probability of being cost-effective at a willingness to pay threshold of pound30,000. Compared with resynchronisation alone, the incremental cost-effectiveness of combined implantable defibrillator was pound40,160 (95% CI: pound26,645 to pound59,391) with only a 26% probability of cost-effectiveness at the pound30,000 threshold. In a direct comparison across three treatments (medical treatment, resynchronisation alone and combined resynchronisation with implantable defibrillator therapy) resynchronisation alone was found to be the most cost-effective option. CONCLUSION: Combined resynchronisation and implantable defibrillator therapy is not cost-effective for left ventricular dysfunction. Instead resynchronisation alone remains the most cost-effective policy option in this population. Combined devices are more likely to be cost-effective in the subgroups of younger patients or those with high risk of sudden cardiac death who would qualify for resynchronisation therapy.

BACKGROUND: the aim of this paper was undertake a systematic review and meta-analysis of the use of spinal cord stimulation (SCS) in the management of refractory angina. METHODS: We searched a number of electronic databases including Medline, Embase and Cochrane Library up to February 2008 to identify randomised controlled trials (RCTs) reporting exercise capacity, ischemic burden, functional class, quality of life, usage of anti-anginal medication, costs and adverse events including mortality. Results were reported both descriptively for each study and using random effects meta-analysis. Given the variety in outcomes reported, some outcome results were pooled as standardised mean differences (SMD) and reported in standard deviation units. RESULTS: Seven RCTs were identified in a total of 270 refractory angina patients. The outcomes of SCS were found to be similar when directly compared to coronary artery bypass grafting (CABG) and percutaneous myocardial laser revascularisation (PMR). Compared to a 'no stimulation' control, there was some evidence of improvement in all outcomes following SCS implantation with significant gains observed in pooled exercise capacity (SMD: 0.76, 0.07 to 1.46, p = 0.03) and health-related quality of life (SMD: 0.83, 95% CI: 0.32 to 1.34, p = 0.001). Trials were small and were judged to range considerably in their quality. The healthcare costs of SCS appeared to be lower than CABG at 2-years follow up. CONCLUSION: SCS appears to be an effective and safe treatment option in the management of refractory angina patients and of similar efficacy and safety to PMR, a potential alternative treatment. Further high quality RCT and cost effectiveness evidence is needed before SCS can be accepted as a routine treatment for refractory angina.

OBJECTIVE: to search for, review and synthesise studies of the effectiveness and cost-effectiveness of weight management schemes for the under fives. DATA SOURCES: MEDLINE [Ovid], MEDLINE In-Process [Ovid], EMBASE [Ovid], CAB [Ovid], Health Management Information Consortium [Ovid], the Cochrane Database of Systematic Reviews, Cochrane Register of Controlled Trials, Science Citation Index Expanded [Web of Science], Conference Proceedings Citation Index [The Web of Science], Database of Abstract Reviews [CRD; Centre for Reviews and Dissemination], HTA [CRD], PsycINFO [Ebsco], NHS CRD. These databases were searched from 1990 to February 2009. Supplementary internet searches were additionally conducted. REVIEW METHODS: Relevant clinical effectiveness studies were identified in two stages. Titles and abstracts returned by the search strategy were examined independently by three researchers and screened for possible inclusion. Disagreements were resolved by discussion. Full texts of the identified studies were obtained. Three researchers examined these independently for inclusion or exclusion, and disagreements were again resolved by discussion. RESULTS: One of the randomised controlled trials (RCTs) was from the UK. It measured the effects of a physical activity intervention for children in nurseries combined with home-based health education for their parents; this was compared to usual care. The main outcome measure was body mass index (BMI); secondary measures were weight and physical activity. At the 12-month follow-up, no statistically significant differences were found between the groups on any measure. However, a trend, favouring the intervention, was found for BMI and weight. The other two RCTs were from the USA. The larger trial investigated the effects of a combined preschool and home intervention in African American and Latino communities. Nutrition education and physical activity programmes were aimed at under fives in preschool. The home component consisted of related health education and homework for the parents, who received a small financial reward on completion. The 1- and 2-year results for the African American sites showed a significantly slower rate of increase in BMI than for results at baseline, for the intervention group than for the control group. However, in the Latino communities no such differences were found. The second US trial was a much smaller home-based parental education programme in Native American communities in the USA and Canada. The intervention consisted of a parental skills course for parents to improve their children's diet and physical activity. This was compared with a course providing skills to improve child behaviour. Follow-up was at 16 weeks and showed no significant differences between groups in BMI. CONCLUSIONS: No controlled trials addressing the issue of treating obesity or evidence of cost-effectiveness studies in the under fives' population were found. From the three prevention studies, apart from the larger US trial, the interventions showed no statistically significant differences in BMI and weight between the intervention and control groups (although there was some evidence of positive trends for BMI and weight). It should also be noted that these conclusions are based on only three dissimilar studies, thereby making the drawing of firm conclusions difficult. Research is urgently needed in further well-designed UK-based RCTs of weight management schemes aimed at the prevention of obesity, that combine with cost-effectiveness studies targeted at preschool children with long-term follow-up.

OBJECTIVE: to compare the outcomes of home-based (using the Heart Manual) and centre-based cardiac rehabilitation programmes. DESIGN: Randomised controlled trial and parallel economic evaluation. SETTING: Predominantly inner-city, multi-ethnic population in the West Midlands, England. PATIENTS: 525 patients referred to four hospitals for cardiac rehabilitation following myocardial infarction or coronary revascularisation. INTERVENTIONS: a home-based cardiac rehabilitation programme compared with centre-based programmes. MAIN OUTCOME MEASURES: Smoking cessation, blood pressure (systolic blood pressure (SBP), diastolic blood pressure (DBP)), total cholesterol (TC) and high-density lipoprotein (HDL)-cholesterol, psychological status (HADS anxiety and depression) and exercise capacity (incremental shuttle walking test, ISWT) measured at 12 months. Health service resource use, quality of life utility and costs were quantified. RESULTS: There were no significant differences in the main outcomes when the home-based was compared with the centre-based programme at 12 months. Adjusted mean difference (95% CI) for SBP was 1.94 mm Hg (-1.1 to 5.0); DBP 0.42 mm Hg (-1.25 to 2.1); TC 0.1 mmol/l (-0.05 to 0.24); HADS anxiety -0.02 (-0.69 to 0.65); HADS depression -0.35 (-0.95 to 0.25); distance on ISWT -21.5 m (-48.3 to 5.2). The relative risk of being a smoker in the home arm was 0.90. The cost per patient to the NHS was significantly higher in the home arm at 198 pounds, (95% CI 189 to 208) compared to 157 pounds (95% CI 139 to 175) in the centre-based arm. However when the patients' cost of travel was included, these differences were no longer significant. Conclusions a home-based cardiac rehabilitation programme does not produce inferior outcomes when compared to traditional centre-based programmes as provided in the United Kingdom.

For chronic pain syndromes, the least expensive therapy is the one that offers sufficient clinical benefit to reduce the patient's consumption of health care resources by a sufficient degree for a sufficient amount of time to recapture the cost of the therapy. An additional bonus accrues if the pain therapy provides more than symptomatic relief and improves the underlying condition that is causing the pain. Like most medical devices, SCS incurs high upfront costs and thus it must substantially improve the health of patients and/or produce later savings to be cost-effective. This chapter shows how SCS can improve a patient's state of health, which has a direct impact on the patient's quality of life, and lead to savings associated with a reduced consumption of healthcare resources. Among the benefits that have been documented in patients with SCS therapies are improved quality of life/ability to engage in the activities of daily living, reduction in the symptoms of depression, improved neurologic function, and ability to return to work. The types of cost studies that have been conducted vary from simple cost descriptions to full economic evaluations, although no cost evaluation has been performed from a societal perspective. Which costs are identified, how they are measured and valued, and how the data are collected are all important factors of cost studies. SCS also poses special challenges for healthcare economists who are developing models and analytical techniques for conducting economic evaluations. Improving equipment can also result in cost savings if the improvement increases the number of successful patient outcomes. The timing of SCS treatment is also of the utmost importance in patients with critical lower-limb ischemia, since SCS can promote healing only if trophic ischemic lesions have not progressed to 3 cm2. © 2009 Elsevier Ltd all rights reserved.

BACKGROUND: Conduct problems are common, disabling and costly. The prognosis for children with conduct problems is poor, with outcomes in adulthood including criminal behaviour, alcoholism, drug abuse, domestic violence, child abuse and a range of psychiatric disorders. There has been a rapid expansion of group based parent-training programmes for the treatment of children with conduct problems in a number of countries over the past 10 years. Existing reviews of parent training have methodological limitations such as inclusion of non-randomised studies, the absence of investigation for heterogeneity prior to meta-analysis or failure to report confidence intervals. The objective of the current study was to systematically review randomised controlled trials of parenting programmes for the treatment of children with conduct problems. METHODS: Standard systematic review methods were followed including duplicate inclusion decisions, data extraction and quality assessment. Twenty electronic databases from the fields of medicine, psychology, social science and education were comprehensively searched for RCTs and systematic reviews to February 2006. Inclusion criteria were: randomised controlled trial; of structured, repeatable parenting programmes; for parents/carers of children up to the age of 18 with a conduct problem; and at least one measure of child behaviour. Meta-analysis and qualitative synthesis were used to summarise included studies. RESULTS: 57 RCTs were included. Studies were small with an average group size of 21. Meta-analyses using both parent (SMD -0.67; 95% CI: -0.91, -0.42) and independent (SMD -0.44; 95% CI: -0.66, -0.23) reports of outcome showed significant differences favouring the intervention group. There was insufficient evidence to determine the relative effectiveness of different approaches to delivering parenting programmes. CONCLUSION: Parenting programmes are an effective treatment for children with conduct problems. The relative effectiveness of different parenting programmes requires further research.

Objectives: to investigate whether it is clinically effective and cost-effective to provide (i) a unilateral cochlear implant for severely to profoundly deaf people (using or not using hearing aids), and (ii) a bilateral cochlear implant for severely to profoundly deaf people with a single cochlear implant (unilateral or unilateral plus hearing aid). Data sources: Main electronic databases [MEDLINE; EMBASE; Cochrane Database of Systematic Reviews; CENTRAL; NHS EED; DARE; HTA (NHS-CRD); EconLit; National Research Register; and ClinicalTrials. gov] searched in October 2006, updated July 2007. Review methods: a systematic review of the literature was undertaken according to standard methods. A state-transition (Markov) model of the main care pathways deaf people might follow and the main complications and device failures was developed. Results: the clinical effectiveness review included 33 papers, of which only two were RCTs. They used 62 different outcome measures and overall were of moderate to poor quality. All studies in children comparing one cochlear implant with non-technological support or an acoustic hearing aid reported gains on all outcome measures, some demonstrating greater gain from earlier implantation. The strongest evidence for an advantage from bilateral over unilateral implantation was for understanding speech in noisy conditions (mean improvement 13.2%, p < 0.0001); those receiving their second implant earlier made greater gains. Comparison of bilateral with unilateral cochlear implants plus an acoustic hearing aid was compromised by small sample sizes and poor reporting, but benefits were seen with bilateral implants. Cochlear implants improved children's quality of life, and those who were implanted before attending school were more likely to do well academically and attend mainstream education than those implanted later. In adults, there was a greater benefit from cochlear implants than from nontechnological support in terms of speech perception. Increased age at implantation may reduce effectiveness and there is a negative correlation between duration of deafness and effectiveness. Speech perception measures all showed benefits for cochlear implants over acoustic hearing aids [e.g. mean increase in score of 37 points in noisy conditions (p < 0.001) with BKB sentences]; however, prelingually deafened adults benefited less than those postlingually deafened (mean change scores 20% versus 62%). For unilateral versus bilateral implantation, benefits in speech perception were significant in noisy conditions on all measures [e.g. 76% for HINT sentences (p < 0.0001)]. Quality of life measured with generic and disease-specific instruments or by interview mostly showed significant gains or positive trends from using cochlear implants. The Markov model base-case analysis estimated that, for prelingually profoundly deaf children, the incremental cost-effectiveness ratio (ICER) for unilateral implantation compared with no implantation was £13,413 per quality-adjusted life-year (QALY). Assuming the utility gain for bilateral implantation is the same for adults and children, the ICERs for simultaneous and sequential bilateral implantation versus unilateral implantation were £40,410 and £54,098 per QALY respectively. For postlingually sensorineurally profoundly deaf adults, the corresponding ICERs were £14,163, £49,559 and £60,301 per QALY respectively. Probabilistic threshold analyses suggest that unilateral implants are highly likely to be cost-effective for adults and children at willingness to pay thresholds of £20,000 or £30,000 per QALY. There are likely to be overall additional benefits from bilateral implantation, enabling children and adults to hold conversations more easily in social situations. Conclusions: Unilateral cochlear implantation is safe and effective for adults and children and likely to be cost-effective in profoundly deaf adults and profoundly and prelingually deaf children. However, decisions on the cost-effectiveness of bilateral cochlear implants should take into account the high degree of uncertainty within the model regarding the probable utility gain. © 2009 Queen's Printer and Controller of HMSO. All rights reserved.

OBJECTIVES: to investigate whether it is clinically effective and cost-effective to provide (i) a unilateral cochlear implant for severely to profoundly deaf people (using or not using hearing aids), and (ii) a bilateral cochlear implant for severely to profoundly deaf people with a single cochlear implant (unilateral or unilateral plus hearing aid). DATA SOURCES: Main electronic databases [MEDLINE; EMBASE; Cochrane Database of Systematic Reviews; CENTRAL; NHS EED; DARE; HTA (NHS-CRD); EconLit; National Research Register; and ClinicalTrials.gov] searched in October 2006, updated July 2007. REVIEW METHODS: a systematic review of the literature was undertaken according to standard methods. A state-transition (Markov) model of the main care pathways deaf people might follow and the main complications and device failures was developed. RESULTS: the clinical effectiveness review included 33 papers, of which only two were RCTs. They used 62 different outcome measures and overall were of moderate to poor quality. All studies in children comparing one cochlear implant with non-technological support or an acoustic hearing aid reported gains on all outcome measures, some demonstrating greater gain from earlier implantation. The strongest evidence for an advantage from bilateral over unilateral implantation was for understanding speech in noisy conditions (mean improvement 13.2%, p < 0.0001); those receiving their second implant earlier made greater gains. Comparison of bilateral with unilateral cochlear implants plus an acoustic hearing aid was compromised by small sample sizes and poor reporting, but benefits were seen with bilateral implants. Cochlear implants improved children's quality of life, and those who were implanted before attending school were more likely to do well academically and attend mainstream education than those implanted later. In adults, there was a greater benefit from cochlear implants than from non-technological support in terms of speech perception. Increased age at implantation may reduce effectiveness and there is a negative correlation between duration of deafness and effectiveness. Speech perception measures all showed benefits for cochlear implants over acoustic hearing aids [e.g. mean increase in score of 37 points in noisy conditions (p < 0.001) with BKB sentences]; however, prelingually deafened adults benefited less than those postlingually deafened (mean change scores 20% versus 62%). For unilateral versus bilateral implantation, benefits in speech perception were significant in noisy conditions on all measures [e.g. 76% for HINT sentences (p < 0.0001)]. Quality of life measured with generic and disease-specific instruments or by interview mostly showed significant gains or positive trends from using cochlear implants. The Markov model base-case analysis estimated that, for prelingually profoundly deaf children, the incremental cost-effectiveness ratio (ICER) for unilateral implantation compared with no implantation was 13,413 pounds per quality-adjusted life-year (QALY). Assuming the utility gain for bilateral implantation is the same for adults and children, the ICERs for simultaneous and sequential bilateral implantation versus unilateral implantation were 40,410 pounds and 54,098 pounds per QALY respectively. For postlingually sensorineurally profoundly deaf adults, the corresponding ICERs were 14,163 pounds, 49,559 pounds and 60,301 pounds per QALY respectively. Probabilistic threshold analyses suggest that unilateral implants are highly likely to be cost-effective for adults and children at willingness to pay thresholds of 20,000 pounds or 30,000 pounds per QALY. There are likely to be overall additional benefits from bilateral implantation, enabling children and adults to hold conversations more easily in social situations. CONCLUSIONS: Unilateral cochlear implantation is safe and effective for adults and children and likely to be cost-effective in profoundly deaf adults and profoundly and prelingually deaf children. However, decisions on the cost-effectiveness of bilateral cochlear implants should take into account the high degree of uncertainty within the model regarding the probable utility gain.

Objectives: to investigate the harmful health effects of taking ecstasy (3,4-methylenedioxymethamphetamine, MDMA) for recreational purposes. Data sources: MEDLINE, EMBASE, PsycINFO and Web of Knowledge were searched. Additional information on deaths was collected from the General Mortality Register (GMR) and the Special Mortality Register collated by the National Programme on Substance Abuse Deaths (np-SAD). Review methods: Studies were categorised according to design, with systematic research syntheses (Level I evidence) the most valid and least open to bias. Where Level I evidence was not available, controlled observational studies (Level II evidence) were systematically reviewed. If neither Level I nor Level II evidence was available, uncontrolled case series and case reports (Level III evidence) were systematically surveyed. Data were extracted by one reviewer and a sample checked by a second. The heterogeneity of Level II evidence was addressed by undertaking stratified analyses for current and former ecstasy users and comparing them either with control groups using other illegal drugs but not ecstasy (polydrug controls) or with controls naïve to illegal drugs (drug-naïve controls). Statistical heterogeneity was minimised by using a random-effects model throughout and investigated using study-level regression analysis (metaregression). Results: Five Level I syntheses were identified; for each it was difficult to ascertain the exact methods adopted and evidence included. Small but significant deficits for ecstasy users compared to controls were reported in areas relating to attention, memory, psychomotor speed, executive systems functioning, and self-reported depressive symptoms. Data from Level II studies were directly pooled for seven individual outcomes, suggesting that ecstasy users performed worse than controls on common measures of immediate and delayed verbal recall (RAVLT, RBMT, digit span). No difference was seen in IQ (NART). The 915 outcome measures identified in Level II studies were analysed in broad domains: immediate and delayed verbal and visual memory, working memory, two measures of attention, three measures of executive function, perceptual organisation, self-rated depression, memory and anxiety, and impulsivity measured objectively and subjectively. Ecstasy users performed significantly worse than polydrug controls in 13/16 domains and significantly worse than drug-naïve controls in 7/12 domains for which sufficient data were available. The largest, most consistent exposure effects were seen in meta-analyses of memory (especially verbal and working memory, with less marked effects seen in visual memory). Former ecstasy users frequently showed deficits that matched or exceeded those seen amongst current users. At aggregate level, the effects do not appear to be dose-related, but are variably confounded by other drug use, particularly alcohol. of Level III evidence, in the 10 years to 2006, the np-SAD and the GMR recorded an average of around 50 drug-related deaths per year involving ecstasy; it was the sole drug implicated in around 10 cases per year. Retrospective case series, based on hospital emergency department records, reported a death rate of 0-2% from emergency admissions related to ecstasy. Two major syndromes are most commonly reported as the immediate cause of death in fatal cases: hyperthermia and hyponatraemia. Conclusions: a broad range of relatively low-quality literature suggests that recreational use of ecstasy is associated with significant deficits in neurocognitive function (particularly immediate and delayed verbal memory) and increased psychopathological symptoms. The clinical significance of the exposure effect in individual cases will be variable but, on average, deficits are likely to be relatively small. Ecstasy is associated with a range of acute harms but appears to be a rare cause of death in isolation. © 2009 Queen's Printer and Controller of HMSO. All rights reserved.

To investigate the harmful health effects of taking ecstasy (3,4-methylenedioxymethamphetamine, MDMA) for recreational purposes. MEDLINE, EMBASE, PsycINFO and Web of Knowledge were searched. Additional information on deaths was collected from the General Mortality Register (GMR) and the Special Mortality Register collated by the National Programme on Substance Abuse Deaths (np-SAD). Studies were categorised according to design, with systematic research syntheses (Level I evidence) the most valid and least open to bias. Where Level I evidence was not available, controlled observational studies (Level II evidence) were systematically reviewed. If neither Level I nor Level II evidence was available, uncontrolled case series and case reports (Level III evidence) were systematically surveyed. Data were extracted by one reviewer and a sample checked by a second. The heterogeneity of Level II evidence was addressed by undertaking stratified analyses for current and former ecstasy users and comparing them either with control groups using other illegal drugs but not ecstasy (polydrug controls) or with controls naïve to illegal drugs (drug-naïve controls). Statistical heterogeneity was minimised by using a random-effects model throughout and investigated using study-level regression analysis (metaregression). Five Level I syntheses were identified; for each it was difficult to ascertain the exact methods adopted and evidence included. Small but significant deficits for ecstasy users compared to controls were reported in areas relating to attention, memory, psychomotor speed, executive systems functioning, and self-reported depressive symptoms. Data from Level II studies were directly pooled for seven individual outcomes, suggesting that ecstasy users performed worse than controls on common measures of immediate and delayed verbal recall (RAVLT, RBMT, digit span). No difference was seen in IQ (NART). The 915 outcome measures identified in Level II studies were analysed in broad domains: immediate and delayed verbal and visual memory, working memory, two measures of attention, three measures of executive function, perceptual organisation, self-rated depression, memory and anxiety, and impulsivity measured objectively and subjectively. Ecstasy users performed significantly worse than polydrug controls in 13/16 domains and significantly worse than drug-naïve controls in 7/12 domains for which sufficient data were available. The largest, most consistent exposure effects were seen in meta-analyses of memory (especially verbal and working memory, with less marked effects seen in visual memory). Former ecstasy users frequently showed deficits that matched or exceeded those seen amongst current users. At aggregate level, the effects do not appear to be dose-related, but are variably confounded by other drug use, particularly alcohol. of Level III evidence, in the 10 years to 2006, the np-SAD and the GMR recorded an average of around 50 drug-related deaths per year involving ecstasy; it was the sole drug implicated in around 10 cases per year. Retrospective case series, based on hospital emergency department records, reported a death rate of 0-2% from emergency admissions related to ecstasy. Two major syndromes are most commonly reported as the immediate cause of death in fatal cases: hyperthermia and hyponatraemia. A broad range of relatively low-quality literature suggests that recreational use of ecstasy is associated with significant deficits in neurocognitive function (particularly immediate and delayed verbal memory) and increased psychopathological symptoms. The clinical significance of the exposure effect in individual cases will be variable but, on average, deficits are likely to be relatively small. Ecstasy is associated with a range of acute harms but appears to be a rare cause of death in isolation.

Objective(s): to evaluate the clinical effectiveness and cost-effectiveness of a range of diagnostic strategies for investigating patients with-unilateral hearing loss and/or tinnitus, with a view to confirming or eliminating a diagnosis of acoustic neuroma, and to describe the natural history of acoustic neuroma. Data sources: Major electronic databases were searched from January 1980 to August 2008. Review methods: Selected studies were assessed and subjected to data extraction and quality assessment using standard methods. Results: Studies comparing auditory brainstem response (ABR) with magnetic resonance (MR) imaging were highly heterogeneous. ABR has high sensitivity compared with MR imaging for acoustic neuromas greater than 1 cm in size but not for smaller neuromas. The sensitivities of T2-weighted (T2W) and T2-star-weighted (T2*W) imaging strategies compared with gadolinium-enhanced T1-weighted (GdTIW) MR imaging (gold standard) were high and relatively homogeneous. The specificity of T2W and T2*W studies ranged from 90% to 100% and from 86% to 99% respectively. The review of cost-effectiveness showed that GdTIW MR imaging immediately or in conjunction with ABR appears to be more cost-effective than 'traditional' protocols; ABR/GdTIW MR imaging protocols were more cost-effective than going directly to GdTIW MR imaging. Non-contrast-enhanced MR imaging was found to be a more cost-effective test for acoustic neuroma than GdTIW MR imaging. The incidence of acoustic neuroma has increased over the last 30 years, with the median age at diagnosis remaining at 55 years. Most patients present with insidious symptoms of unilateral hearing impairment, tinnitus and/ or vertigo. The pattern and rate of growth of acoustic neuroma are highly variable and currently unpredictable. At least 50% of tumours do not grow, at least for some years after diagnosis. Some studies have found large initial size to be a determinant of later growth, with the opposite also being reported. The mean growth rate for all tumours varies between 1 and 2 mm/year, with a rate of 2-4 mm/year for only those that grow; however, there are cases with significant regression (5%) or exceptional growth (which may exceed 18 mm/year). Conclusions: the majority of the evidence reviewed was poorly reported and there is therefore an inherent risk of bias. Given the recent improvement in resolution and reduction in cost of MR imaging, ABR can no longer be considered appropriate as the primary test used to screen for acoustic neuroma. T2W or T2*W sequences enable accurate evaluation of the VIIIth and VIIth cranial nerves within the cerebellopontine angle and internal auditory canal as well as evaluation of the cochlea and labyrinth, and inclusion of GdTIW sequences is unlikely to contribute information that would alter patient management in the screening population. The quality of the imaging chain and experience of the reporting radiologist are key factors determining the efficacy of a non-contrast screening strategy. Based on a cost-effectiveness model developed to reflect UK practice it was concluded that a diagnostic algorithm that deploys non-contrast MR imaging as an initial imaging screen in the investigation of acoustic neuroma is less costly than and likely to be as effective as available contrast MR imaging. © 2009 Queen's Printer and Controller of HMSO. All rights reserved.

To evaluate the clinical effectiveness and cost-effectiveness of a range of diagnostic strategies for investigating patients with unilateral hearing loss and/or tinnitus, with a view to confirming or eliminating a diagnosis of acoustic neuroma, and to describe the natural history of acoustic neuroma. Major electronic databases were searched from January 1980 to August 2008. Selected studies were assessed and subjected to data extraction and quality assessment using standard methods. Studies comparing auditory brainstem response (ABR) with magnetic resonance (MR) imaging were highly heterogeneous. ABR has high sensitivity compared with MR imaging for acoustic neuromas greater than 1 cm in size but not for smaller neuromas. The sensitivities of T2-weighted (T2W) and T2-star-weighted (T2*W) imaging strategies compared with gadolinium-enhanced T1-weighted (GdT1W) MR imaging (gold standard) were high and relatively homogeneous. The specificity of T2W and T2*W studies ranged from 90% to 100% and from 86% to 99% respectively. The review of cost-effectiveness showed that GdT1W MR imaging immediately or in conjunction with ABR appears to be more cost-effective than 'traditional' protocols; ABR/GdT1W MR imaging protocols were more cost-effective than going directly to GdT1W MR imaging. Non-contrast-enhanced MR imaging was found to be a more cost-effective test for acoustic neuroma than GdT1W MR imaging. The incidence of acoustic neuroma has increased over the last 30 years, with the median age at diagnosis remaining at 55 years. Most patients present with insidious symptoms of unilateral hearing impairment, tinnitus and/or vertigo. The pattern and rate of growth of acoustic neuroma are highly variable and currently unpredictable. At least 50% of tumours do not grow, at least for some years after diagnosis. Some studies have found large initial size to be a determinant of later growth, with the opposite also being reported. The mean growth rate for all tumours varies between 1 and 2 mm/year, with a rate of 2-4 mm/year for only those that grow; however, there are cases with significant regression (5%) or exceptional growth (which may exceed 18 mm/year). The majority of the evidence reviewed was poorly reported and there is therefore an inherent risk of bias. Given the recent improvement in resolution and reduction in cost of MR imaging, ABR can no longer be considered appropriate as the primary test used to screen for acoustic neuroma. T2W or T2*W sequences enable accurate evaluation of the VIIIth and VIIth cranial nerves within the cerebellopontine angle and internal auditory canal as well as evaluation of the cochlea and labyrinth, and inclusion of GdT1W sequences is unlikely to contribute information that would alter patient management in the screening population. The quality of the imaging chain and experience of the reporting radiologist are key factors determining the efficacy of a non-contrast screening strategy. Based on a cost-effectiveness model developed to reflect UK practice it was concluded that a diagnostic algorithm that deploys non-contrast MR imaging as an initial imaging screen in the investigation of acoustic neuroma is less costly than and likely to be as effective as available contrast MR imaging.

To explore the use of surrogate outcomes in Health Technology Assessment (HTA) and provide a basis for guidance for their future use, validation and reporting. This report focuses on the role of surrogate outcomes in cost-effectiveness models (CEMs) within UK HTA Programme reports. Reports published in the UK HTA Programme monograph series in 2005 and 2006 formed the sampling frame for this study. Reports were selected on the basis that they addressed a treatment effectiveness/efficacy question, that they included a CEM and that the CEM was primarily based on a surrogate outcome. Reports addressing diagnostic, screening, aetiology, prognostic and methodological questions were excluded. Information was extracted from included reports by two reviewers using a standardised proforma. Surrogate outcomes were assessed according to two published validation frameworks [Journal of the American Medical Association (JAMA) criteria and Outcomes Measures in Rheumatology Clinical Trials (OMERACT) scoring schema]. A narrative synthesis of findings is presented in the form of tabular summaries and illustrative qualitative quotations. A total of 35 UK HTA reports published in 2005 and 2006 addressed an effectiveness/efficacy question and contained a CEM. of these, four were found to have based their CEM on a surrogate outcome. All four reports sourced treatment-related changes in surrogate outcomes through a systematic review of the literature; however, there was some variability in the consistency and transparency by which these reports provided evidence of the validation for the surrogate-final outcome relationship. Only one of the reports undertook a systematic review to specifically seek the evidence base for the association between surrogate and final outcomes. Furthermore, this was the only report to provide level 1 surrogate-final outcome validation evidence, i.e. RCT data showing a strong association between the change in surrogate outcome (BPAR) and the change in final outcome (graft survival) at an individual patient level. This report met the JAMA criteria for acceptable evidence of a surrogate. Two reports provided level 2 evidence, i.e. observational study data showing the relationship between the surrogate and final outcome, and one report provided level 3 evidence, i.e. a review of disease natural history. None of the four reports achieved a sufficient score on the OMERACT schema to be judged to have acceptable evidence of a surrogate outcome by its authors. In this survey of UK HTA reports about 10% of the CEMs therein were explicitly based on surrogate outcomes. The strength of evidence for the surrogate-final outcome relationship, transparency of quantification a nd exploration of uncertainty of this relationship were found to vary considerably. Recommendations are made for the use of surrogate outcomes in future HTA reports.

OBJECTIVES: to explore the use of surrogate outcomes in Health Technology Assessment (HTA) and provide a basis for guidance for their future use, validation and reporting. This report focuses on the role of surrogate outcomes in cost-effectiveness models (CEMs) within UK HTA Programme reports. DATA SOURCES: Reports published in the UK HTA Programme monograph series in 2005 and 2006 formed the sampling frame for this study. REVIEW METHODS: Reports were selected on the basis that they addressed a treatment effectiveness/efficacy question, that they included a CEM and that the CEM was primarily based on a surrogate outcome. Reports addressing diagnostic, screening, aetiology, prognostic and methodological questions were excluded. Information was extracted from included reports by two reviewers using a standardised proforma. Surrogate outcomes were assessed according to two published validation frameworks [Journal of the American Medical Association (JAMA) criteria and Outcomes Measures in Rheumatology Clinical Trials (OMERACT) scoring schema]. A narrative synthesis of findings is presented in the form of tabular summaries and illustrative qualitative quotations. RESULTS: a total of 35 UK HTA reports published in 2005 and 2006 addressed an effectiveness/efficacy question and contained a CEM. of these, four were found to have based their CEM on a surrogate outcome. All four reports sourced treatment-related changes in surrogate outcomes through a systematic review of the literature; however, there was some variability in the consistency and transparency by which these reports provided evidence of the validation for the surrogate-final outcome relationship. Only one of the reports undertook a systematic review to specifically seek the evidence base for the association between surrogate and final outcomes. Furthermore, this was the only report to provide level 1 surrogate-final outcome validation evidence, i.e. RCT data showing a strong association between the change in surrogate outcome (BPAR) and the change in final outcome (graft survival) at an individual patient level. This report met the JAMA criteria for acceptable evidence of a surrogate. Two reports provided level 2 evidence, i.e. observational study data showing the relationship between the surrogate and final outcome, and one report provided level 3 evidence, i.e. a review of disease natural history. None of the four reports achieved a sufficient score on the OMERACT schema to be judged to have acceptable evidence of a surrogate outcome by its authors. CONCLUSIONS: in this survey of UK HTA reports about 10% of the CEMs therein were explicitly based on surrogate outcomes. The strength of evidence for the surrogate-final outcome relationship, transparency of quantification and exploration of uncertainty of this relationship were found to vary considerably. Recommendations are made for the use of surrogate outcomes in future HTA reports.

OBJECTIVES: the aim of this study was to explore the use of surrogate outcomes--a substitute outcome that predicts final patient-related outcomes--in cost-effectiveness models (CEM) within health technology assessment (HTA) reports and provide guidance for their future use. METHODS: Our sampling frame was all UK HTA Program monograph series reports published in 2005 and 2006. Reports were included if they addressed a treatment effectiveness/efficacy question and included a CEM based on a surrogate outcome. The two authors independently applied inclusion and exclusion criteria, and the following data was extracted from included reports: source of surrogate outcome, level of evidence for validation of the surrogate outcomes, methods used in report to quantify link between surrogate outcome and final outcome, and consideration of the uncertainty associated with using surrogate outcomes in the results or conclusions of report. RESULTS: of 100 HTA reports, 35 complied with the inclusion criteria. of these, four (11 percent) reports included a CEM based on a surrogate outcome. All four reports sourced treatment-related changes in surrogate outcome through a systematic review of the literature. One provided Level 1 surrogate evidence (randomized controlled trial data showing a strong association between the change in surrogate outcome and change final outcome); two reported Level 2 evidence (observational study data); and one provided Level 3 evidence (disease natural/ history data). The transparency of quantification and exploration of uncertainty of the surrogate and final outcome relationship varied considerably across all four reports. CONCLUSIONS: Recommendations are made for the use of surrogate outcomes in future HTA reports.

Objective.  in a randomized controlled trial comparing manual with automated computerized adjustment of spinal cord stimulators in patients with implanted power generators, automated adjustment conferred the following advantages: 1) more settings tested in a given time, 2) significantly greater pain/paresthesia overlap, 3) increased battery life, and 4) a $303,756 (95% confidence intervals = $116,503-491,009) reduction in lifetime per patient cost. The current study analyzes the sensitivity of this cost-savings to usage time/day, inflation, discount rate, and years of use. Methods.  We analyzed cost-sensitivity with a standard spreadsheet method and suitably adjusted standard equation. Results.  Regardless of hours of use/day, inflation, discount rate, or years of use, spinal cord stimulation remains significantly less expensive with automated rather than manual adjustment. This savings is attributable to increased battery life. Conclusion.  Sensitivity analyzes reveal that the significant cost-savings achieved with computerized, patient-directed adjustment of spinal cord stimulation in selected patients with chronic pain is robust across a representative range of parameters.

There is currently little data on the longer term efficacy and safety of balloon kyphoplasty (BKP) in patients with metastatic vertebral compression fractures (VCFs). To prospectively assess the long-term efficacy and safety of BKP in treating thoracic and lumbar spinal metastatic fractures that result in pain or instability. Sixty-five patients (37 men, mean age: 66 years) underwent 99 BKP procedures. Patient-related outcomes of pain visual analogue scale (VAS) and Oswestry Disability Index were assessed pre- and post-operatively and after 3, 6, 12 and 24 months. Correction of vertebral height and kyphotic deformity were assessed by radiographic measurements. Mean pain VAS and Oswestry Disability Index significantly improved from pre- to post-treatment (P < 0.0001), this improvement being sustained up to 24-month follow up. A gain in height restoration and a reduction of the post-operative kyphotic angle were seen post-operatively and at 3 months although these radiographic outcomes returned to pre-operative levels at 12 months. BKP was associated with a rate of cement leakage and incidence vertebral fracture of 12 and 8%, respectively. No symptomatic cement leaks or serious adverse events were seen during the 24 months of follow up. BKP is a minimally invasive procedure that provides immediate and long-term pain relief and improvement in functional ability in selected patients with metastatic VCFs. The procedure appears to have good long-term safety. © 2008 the Author(s).

BACKGROUND: Angiotensin receptor blockers (ARBs) are widely prescribed for hypertension so it is essential to determine and compare their effects on blood pressure (BP), heart rate and withdrawals due to adverse effects (WDAE). OBJECTIVES: to quantify the dose-related systolic and/or diastolic BP lowering efficacy of ARBs versus placebo in the treatment of primary hypertension. SEARCH STRATEGY: We searched CENTRAL (The Cochrane Library 2007, Issue 1), MEDLINE (1966 to February 2007), EMBASE (1988 to February 2007) and reference lists of articles. SELECTION CRITERIA: Double-blind, randomized, controlled trials evaluating the BP lowering efficacy of fixed-dose monotherapy with an ARB compared with placebo for a duration of 3 to 12 weeks in patients with primary hypertension. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. We contacted study authors for additional information. WDAE information was collected from the trials. MAIN RESULTS: Forty six RCTs evaluated the dose-related trough BP lowering efficacy of 9 ARBs in 13 451 participants with a baseline BP of 156/101 mm Hg. The data do not suggest that any one ARB is better or worse at lowering BP. A dose of 1/8 or 1/4 of the manufacturers' maximum recommended daily dose (Max) achieved a BP lowering effect that was 60 to 70% of the BP lowering effect of Max. A dose of 1/2 Max achieved a BP lowering effect that was 80% of Max. ARB doses above Max did not significantly lower BP more than Max. Due to evidence of publication bias, the largest trials provide the best estimate of the trough BP lowering efficacy for ARBs as a class of drugs: -8 mm Hg for SBP and -5 mm Hg for DBP. ARBs reduced BP measured 1 to 12 hours after the dose by about 12/7 mm Hg. AUTHORS' CONCLUSIONS: the evidence from this review suggests that there are no clinically meaningful BP lowering differences between available ARBs. The BP lowering effect of ARBs is modest and similar to ACE inhibitors as a class; the magnitude of average trough BP lowering for ARBs at maximum recommended doses and above is -8/-5 mmHg. Furthermore, 60 to 70% of this trough BP lowering effect occurs with recommended starting doses. The review did not provide a good estimate of the incidence of harms associated with ARBs because of the short duration of the trials and the lack of reporting of adverse effects in many of the trials.

In contrast to drug therapy, interventional pain therapies involve a complex "interaction" between the clinician ("the operator"), the clinical procedure and medical device/equipment. An appreciation of this interaction is fundamental to the understanding of the challenges of designing clinical trials for interventional procedures in chronic pain. This article overviews the evolving evidence requirements of healthcare policy makers and payers, discusses the specific challenges of designing clinical trials of interventional procedures, and outlines some potential clinical trial design solutions to these challenges.

Objectives: to review the clinical effectiveness and cost-effectiveness of cyclooxygenase-2 (COX-2) selective non-steroidal anti-inflammatory drugs (NSAIDs) (etodolac, meloxicam, celecoxib, rofecoxib, etoricoxib, valdecoxib and lumiracoxib) for osteoarthritis (OA) and rheumatoid arthritis (RA). Data sources: Electronic databases were searched up to November 2003. Industry submissions to the National Institute for Health and Clinical Excellence (NICE) in 2003 were also reviewed. Review methods: Systematic reviews of randomised controlled trials (RCTs) and a model-based economic evaluation were undertaken. Meta-analyses were undertaken for each COX-2 selective NSAID compared with placebo and non-selective NSAIDs. The model was designed to run in two forms: the 'full Assessment Group Model (AGM)', which includes an initial drug switching cycle, and the 'simpler AGM', where there is no initial cycle and no opportunity for the patient to switch NSAID. Results: Compared with non-selective NSAIDs, the COX-2 selective NSAIDs were found to be equally as efficacious as the non-selective NSAIDs (although meloxicam was found to be of inferior or equivalent efficacy) and also to be associated with significantly fewer clinical upper gastrointestinal (UGI) events (although relatively small numbers of clinical gastrointestinal (GI) and myocardial infarction (MI) events were reported across trials). Subgroup analyses of clinical and complicated UGI events and MI events in relation to aspirin use, steroid use, prior GI history and Helicobacter pylori status were based on relatively small numbers and were inconclusive. In the RCTs that included direct COX-2 comparisons, the drugs were equally tolerated and of equal efficacy. Trials were of insufficient size and duration to allow comparison of risk of clinical UGI events, complicated UGI events and MIs. One RCT compared COX-2 (celecoxib) with a non-selective NSAID combined with a gastroprotective agent (diclofenac combined with omeprazole); this included arthritis patients who had recently suffered a GI haemorrhage. Although no significant difference in clinical GI events was reported, the number of events was small and more such studies, where patients genuinely need NSAIDs, are required to confirm these data. A second trial showed that rofecoxib was associated with fewer diarrhoea events than a combination of diclofenac and misoprostol (Arthrotec). Previously published cost-effectiveness analyses indicated a wide of range of possible incremental cost per quality-adjusted life-year (QALY) gained estimates. Using the simpler AGM, with ibuprofen or diclofenac alone as the comparator, all of the COX-2 products are associated with higher costs (i.e. positive incremental costs) and small increases in effectiveness (i.e. positive incremental effectiveness), measured in terms of QALYs. The magnitude of the incremental costs and the incremental effects, and therefore the incremental cost-effectiveness ratios, vary considerably across all COX-2 selective NSAIDs. The base-case incremental cost per QALY results for COX-2 selective NSAIDs compared with diclofenac for the simpler model are: celecoxib (low dose) £68,400; celecoxib (high dose) £151,000; etodolac (branded) £42,400; etodolac (generic) £17,700; etoricoxib £31,300; lumiracoxib £70,400; meloxicam (low dose) £10,300; meloxicam (high dose) £17,800; rofecoxib £97,400; and valdecoxib £35,500. When the simpler AGM was run using ibuprofen or diclofenac combined with proton pump inhibitor (PPI) as the comparator, the results change substantially, with the COX-2 selective NSAIDs looking generally unattractive from a cost-effectiveness point of view (COX-2 selective NSAIDs were dominated by ibuprofen or diclofenac combined with PPI in most cases). This applies both to 'standard' and 'high-risk' arthritis patients defined in terms of previous GI ulcers. The full AGM produced results broadly in line with the simpler model. Conclusions: the COX-2 selective NSAIDs examined were found to be similar to non-selective NSAIDs for the symptomatic relief of RA and OA and to provide superior GI tolerability (the majority of evidence is in patients with OA). Although COX-2 selective NSAIDs offer protection against serious GI events, the amount of evidence for this protective effect varied considerably across individual drugs. The volume of trial evidence with regard to cardiovascular safety also varied substantially between COX-2 selective NSAIDs. Increased risk of MI compared to non-selective NSAIDs was observed among those drugs with greater volume of evidence in terms of exposure in patient-years. Economic modelling shows a wide range of possible costs per QALY gained in patients with OA and RA. Costs per QALY also varied if individual drugs were used in 'standard' or 'high'-risk patients, the choice of non-selective NSAID comparator and whether that NSAID was combined with a PPI. With reduced costs of PPIs, future primary research needs to compare the effectiveness and costeffectiveness of COX-2 selective NSAIDs relative to non-selective NSAIDs with a PPI. Direct comparisons of different COX-2 selective NSAIDs, using equivalent doses, that compare GI and MI risk are needed. Pragmatic studies that include a wider range of people, including the older age groups with a greater burden of arthritis, are also necessary to inform clinical practice. © Queen's Printer and Controller of HMSO 2008. All rights reserved.

For people at risk of depressive relapse, mindfulness-based cognitive therapy (MBCT) has an additive benefit to usual care (H. F. Coelho, P. H. Canter, & E. Ernst, 2007). This study asked if, among patients with recurrent depression who are treated with antidepressant medication (ADM), MBCT is comparable to treatment with maintenance ADM (m-ADM) in (a) depressive relapse prevention, (b) key secondary outcomes, and (c) cost effectiveness. The study design was a parallel 2-group randomized controlled trial comparing those on m-ADM (N = 62) with those receiving MBCT plus support to taper/discontinue antidepressants (N = 61). Relapse/recurrence rates over 15-month follow-ups in MBCT were 47%, compared with 60% in the m-ADM group (hazard ratio = 0.63; 95% confidence interval: 0.39 to 1.04). MBCT was more effective than m-ADM in reducing residual depressive symptoms and psychiatric comorbidity and in improving quality of life in the physical and psychological domains. There was no difference in average annual cost between the 2 groups. Rates of ADM usage in the MBCT group was significantly reduced, and 46 patients (75%) completely discontinued their ADM. For patients treated with ADM, MBCT may provide an alternative approach for relapse prevention.

BACKGROUND: Chronic back and leg pain conditions result in patients' loss of function, reduced quality of life and increased costs to the society. AIMS: to assess health-related quality of life (HRQoL) and cost implications of spinal cord stimulation plus non-surgical conventional medical management (SCS group) versus non-surgical conventional medical management alone (CMM group) in the management of neuropathic pain in patients with failed back surgery syndrome. METHODS: a total of 100 patients were randomised to either the SCS or CMM group. Healthcare resource consumption data relating to screening, the use of the implantable generator in SCS patients, hospital stay, and drug and non-drug pain-related treatment were collected prospectively. Resource consumption was costed using UK and Canadian 2005-2006 national figures. HRQoL was assessed using the EuroQol-5D (EQ-5D) questionnaire. Costs and outcomes were assessed for each patient over their first 6-months of the trial. RESULTS: the 6-month mean total healthcare cost in the SCS group (CAN$19,486; 12,653 euros) was significantly higher than in the CMM group (CAN$3994; 2594 euros), with a mean adjusted difference of CAN$15,395 (9997 euros) (p

The incremental shuttle walking test (ISWT) is recommended to assess the exercise capacity of patients attending cardiac rehabilitation (CR) as a cost-effective alternative to the treadmill test. We used the Bland Altman limits of agreement method on 353 paired ISWTs to explore whether the recommended practice test is necessary. The mean increase in distance from the practice to the second walk was 29.5 m (95% CI 23.0, 36.0) p

Parkinson's disease (PD) is a neurodegenerative disorder affecting the physical, psychological, social, and functional status of individuals. Exercise programs may be an effective strategy to delay or reverse functional decline for people with PD and a large body of empirical evidence has emerged in recent years. The objective is to systematically review randomized controlled trials (RCTs) reporting on the effectiveness of exercise interventions on outcomes (physical, psychological or social functioning, or quality of life) for people with PD. RCTs meeting the inclusion criteria were identified by systematic searching of electronic databases. Key data were extracted by two independent researchers. A mixed methods approach was undertaken using narrative, vote counting, and random effects meta-analysis methods. Fourteen RCTs were included and the methodological quality of most studies was moderate. Evidence supported exercise as being beneficial with regards to physical functioning, health-related quality of life, strength, balance and gait speed for people with PD. There was insufficient evidence support or refute the value of exercise in reducing falls or depression. This review found evidence of the potential benefits of exercise for people with PD, although further good quality research is needed. Questions remain around the optimal content of exercise interventions (dosing, component exercises) at different stages of the disease.

OBJECTIVE: After randomizing 100 failed back surgery syndrome patients to receive spinal cord stimulation (SCS) plus conventional medical management (CMM) or CMM alone, the results of the 6-month Prospective Randomized Controlled Multicenter Trial of the Effectiveness of Spinal Cord Stimulation (i.e. PROCESS) showed that SCS offered superior pain relief, health-related quality of life, and functional capacity. Because the rate of crossover favoring SCS beyond 6 months would bias a long-term randomized group comparison, we present all outcomes in patients who continued SCS from randomization to 24 months and, for illustrative purposes, the primary outcome (>50% leg pain relief) per randomization and final treatment. METHODS: Patients provided data on pain, quality of life, function, pain medication use, treatment satisfaction, and employment status. Investigators documented adverse events. Data analysis included inferential comparisons and multivariate regression analyses. RESULTS: the 42 patients continuing SCS (of 52 randomized to SCS) reported significantly improved leg pain relief (P < 0.0001), quality of life (P

This systematic review updates the understanding of the evidence base for balloon kyphoplasty (BKP) in the management of vertebral compression fractures. Detailed searches of a number of electronic databases were performed from March to April 2006. Citation searches of included studies were undertaken and no language restrictions were applied. All controlled and uncontrolled studies were included with the exception of case reports. Prognostic factors responsible for pain relief and cement leakage were examined using meta-regression. Combined with previous evidence, a total of eight comparative studies (three against conventional medical therapy and five against vertebroplasty) and 35 case series were identified. The majority of studies were undertaken in older women with osteoporotic vertebral compression fractures with long-term pain that was refractory to medical treatment. In direct comparison to conventional medical management, patients undergoing BKP experienced superior improvements in pain, functionality, vertebral height and kyphotic angle at least up to 3-years postprocedure. Reductions in pain with BKP appeared to be greatest in patients with newer fractures. Uncontrolled studies suggest gains in health-related quality of life at 6 and 12-months following BKP. Although associated with a finite level of cement leakage, serious adverse events appear to be rare. Osteoporotic vertebral compression fractures appear to be associated with a higher level of cement leakage following BKP than non-osteoporotic vertebral compression fractures. In conclusion, there are now prospective studies of low bias, with follow-up of 12 months or more, which demonstrate balloon kyphoplasty to be more effective than medical management of osteoporotic vertebral compression fractures and as least as effective as vertebroplasty. Results from ongoing RCTs will provide further information in the near future.

Clinical practice should follow evidence-based medicine, which is derived from clinical trials. The outcomes of clinical practice, however, may not equal that of trials if there are differences in the patients or the quality of treatment they receive. We report the example of cardiac rehabilitation to illustrate this point, comparing the characteristics of patients and treatments offered in randomised controlled trials (RCTs) in this area with those included in two large surveys of cardiac rehabilitation in the UK. We found that cardiac rehabilitation as currently practised in the UK is unlikely to be as effective as clinical trials may suggest.

BACKGROUND: We wanted to use a Punjabi version of the Hospital Anxiety and Depression Scale (HADS) to enable non-English speaking patients to participate in a clinical trial. The aim of the study was to translate and validate the Hospital Anxiety and Depression Scale into Punjabi. METHODS: the HADS was translated into Punjabi by a multidisciplinary team, verified against the original version, and administered to 73 bilingual patients attending an outpatient clinic. RESULTS: One sample t-tests and the Bland-Altman plots demonstrated acceptable linguistic agreement between the two versions of the HADS. Spearman's rank-order correlation coefficients (p < 0.0001) demonstrate excellent conceptual agreement between each item and its corresponding subscale score, for both versions. Concordance rates revealed that the Punjabi HADS adequately identified borderline cases of anxiety (80.8%), definite cases of anxiety (91.8%) and depression (91.8%), but was less reliable in identifying borderline cases of depression (65.8%). Cronbach alpha coefficients revealed high levels of internal consistency for both the Punjabi and English versions (0.81 and 0.86 for anxiety and 0.71 and 0.85 for depression, respectively). CONCLUSION: the Punjabi HADS is an acceptable, reliable and valid measure of anxiety and depression among physically ill Punjabi speaking people in the United Kingdom.

Objectives: to describe and analyse in detail current practice of school entry hearing screening (SES) in the UK. Data sources: Main electronic databases were searched up to May 2005. Review methods: a national postal questionnaire survey was addressed to all leads for SES in the UK, considering current practice in terms of implementation, protocols, target population and performance data. Primary data from cohort studies in one area of London were examined. A systematic review of alternative SES tests, test performance and impact on outcomes was carried out. Finally, a review of published studies on costs, plus economic modelling of current and alternative programmes was prepared. Results: the survey suggested that SES is used in most of England, Wales and Scotland; just over 10% of respondents have abandoned the screen; others are awaiting national guidance. Coverage of SES is variable, but is often over 90% for children in state schools. Referral rates are variable, with a median of about 8%. The test used for the screen is the pure tone sweep test but with wide variation in implementation, with differing frequencies, pass criteria and retest protocols; written examples of protocols were often poor and ambiguous. There is no national approach to data collection, audit and quality assurance, and there are variable approaches at local level. The screen is performed in less than ideal test conditions and resources are often limited, which has an impact on the quality of the screen. The primary cohort studies show that the prevalence of permanent childhood hearing loss continues to increase through infancy. of the 3.47 in 1000 children with a permanent hearing loss at school screen age, 1.89 in 1000 required identification after the newborn screen. Newborn hearing screening is likely to reduce significantly the yield of SES for permanent bilateral and unilateral hearing impairments; yield had fallen from about 1.11 in 1000 before newborn screening to about 0.34 in 1000 for cohorts that had had newborn screening, of which only 0.07 in 1000 were unilateral impairments. just under 20% of permanent moderate or greater bilateral, mild bilateral and unilateral impairments, known to services as 6-year-olds or older, remained to be identified around the time of school entry. No good-quality published comparative trials of alternative screens or tests for SES were identified and studies concerned with the relative accuracy of alternative tests are difficult to compare and often flawed by differing referral criteria and case definitions; with full pure tone audiometry as the reference test, the pure tone sweep test appears to have high sensitivity and high specificity for minimal, mild and greater hearing impairments, better than alternative tests for which evidence was identified. There is insufficient evidence regarding possible harm of the screen. There were no published studies identified that examined the possible effects of SES on longer term outcomes. No good-quality published economic evaluations of SES were identified and a universal SES based on pure tone sweep tests was associated with higher costs and slightly higher quality-adjusted life-years (QALYs) compared with no screen and other screen alternatives; the incremental cost-effectiveness ratio for such a screen is around £2500 per QALY gained; the range of expected costs, QALYs and net benefits was broad, indicating a considerable degree of uncertainty. Targeted screening could be more cost-effective than universal school entry screening; however, the lack of primary data and the wide limits for variables in the modelling mean that any conclusions must be considered indicative and exploratory only. A national screening programme for permanent hearing impairment at school entry meets all but three of the criteria for a screening programme, but at least six criteria are not met for screening for temporary hearing impairment. Conclusions: the lack of good-quality evidence in this area remains a serious problem. Services should improve quality and audit screen performance for identification of previously unknown permanent hearing impairment, pending evidence-based policy decisions based on the research recommendations. Further research is needed into a number of important areas including the evaluation of an agreed national protocol for services delivering SES to make future studies and audits of screen performance more directly comparable. © Queen's Printer and Controller of HMSO 2007. All rights reserved.

Objectives: to describe and analyse in detail current practice of school entry hearing screening (SES) in the UK. Data sources: Main electronic databases were searched up to May 2005. Review methods: a national postal questionnaire survey was addressed to all leads for SES in the UK, considering current practice in terms of implementation, protocols, target population and performance data. Primary data from cohort studies in one area of London were examined. A systematic review of alternative SES tests, test performance and impact on outcomes was carried out. Finally, a review of published studies on costs, plus economic modelling of current and alternative programmes was prepared. Results: the survey suggested that SES is used in most of England, Wales and Scotland; just over 10% of respondents have abandoned the screen; others are awaiting national guidance. Coverage of SES is variable, but is often over 90% for children in state schools. Referral rates are variable, with a median of about 8%. The test used for the screen is the pure tone sweep test but with wide variation in implementation, with differing frequencies, pass criteria and retest protocols; written examples of protocols were often poor and ambiguous. There is no national approach to data collection, audit and quality assurance, and there are variable approaches at local level. The screen is performed in less than ideal test conditions and resources are often limited, which has an impact on the quality of the screen. The primary cohort studies show that the prevalence of permanent childhood hearing loss continues to increase through infancy. of the 3.47 in 1000 children with a permanent hearing loss at school screen age, 1.89 in 1000 required identification after the newborn screen. Newborn hearing screening is likely to reduce significantly the yield of SES for permanent bilateral and unilateral hearing impairments; yield had fallen from about 1.11 in 1000 before newborn screening to about 0.34 in 1000 for cohorts that had had newborn screening, of which only 0.07 in 1000 were unilateral impairments. just under 20% of permanent moderate or greater bilateral, mild bilateral and unilateral impairments, known to services as 6-year-olds or older, remained to be identified around the time of school entry. No good-quality published comparative trials of alternative screens or tests for SES were identified and studies concerned with the relative accuracy of alternative tests are difficult to compare and often flawed by differing referral criteria and case definitions; with full pure tone audiometry as the reference test, the pure tone sweep test appears to have high sensitivity and high specificity for minimal, mild and greater hearing impairments, better than alternative tests for which evidence was identified. There is insufficient evidence regarding possible harm of the screen. There were no published studies identified that examined the possible effects of SES on longer term outcomes. No good-quality published economic evaluations of SES were identified and a universal SES based on pure tone sweep tests was associated with higher costs and slightly higher quality-adjusted life-years (QALYs) compared with no screen and other screen alternatives; the incremental cost-effectiveness ratio for such a screen is around £2500 per QALY gained; the range of expected costs, QALYs and net benefits was broad, indicating a considerable degree of uncertainty. Targeted screening could be more cost-effective than universal school entry screening; however, the lack of primary data and the wide limits for variables in the modelling mean that any conclusions must be considered indicative and exploratory only. A national screening programme for permanent hearing impairment at school entry meets all but three of the criteria for a screening programme, but at least six criteria are not met for screening for temporary hearing impairment. Conclusions: the lack of good-quality evidence in this area remains a serious problem. Services should improve quality and audit screen performance for identification of previously unknown permanent hearing impairment, pending evidence-based policy decisions based on the research recommendations. Further research is needed into a number of important areas including the evaluation of an agreed national protocol for services delivering SES to make future studies and audits of screen performance more directly comparable. © Queen's Printer and Controller of HMSO 2007. All rights reserved.

Pharmacological relief of neuropathic pain is often insufficient. Electrical neurostimulation is efficacious in chronic neuropathic pain and other neurological diseases. European Federation of Neurological Societies (EFNS) launched a Task Force to evaluate the evidence for these techniques and to produce relevant recommendations. We searched the literature from 1968 to 2006, looking for neurostimulation in neuropathic pain conditions, and classified the trials according to the EFNS scheme of evidence for therapeutic interventions. Spinal cord stimulation (SCS) is efficacious in failed back surgery syndrome (FBSS) and complex regional pain syndrome (CRPS) type I (level B recommendation). High-frequency transcutaneous electrical nerve stimulation (TENS) may be better than placebo (level C) although worse than electro-acupuncture (level B). One kind of repetitive transcranial magnetic stimulation (rTMS) has transient efficacy in central and peripheral neuropathic pains (level B). Motor cortex stimulation (MCS) is efficacious in central post-stroke and facial pain (level C). Deep brain stimulation (DBS) should only be performed in experienced centres. Evidence for implanted peripheral stimulations is inadequate. TENS and r-TMS are non-invasive and suitable as preliminary or add-on therapies. Further controlled trials are warranted for SCS in conditions other than failed back surgery syndrome and CRPS and for MCS and DBS in general. These chronically implanted techniques provide satisfactory pain relief in many patients, including those resistant to medication or other means.

People receiving a renal transplant require long-term treatment with immunosuppressant drugs. Contemporary regimens usually include a calcineurin inhibitor (CI), either ciclosporin or tacrolimus, in conjunction with at least one other drug. The aim of this study was to review the economic literature relating to the choice of CIs in patients following renal transplantation, with the specific intention of highlighting the challenges in estimating their cost effectiveness.A systematic literature search and narrative analysis was carried out, and 12 studies of varying quality and complexity were reviewed. All of the studies compared ciclosporin, azathioprine and a corticosteroid (CAS) with tacrolimus, azathioprine and a corticosteroid (TAS) but only three also evaluated the costs and effects of other possible treatment regimens. A variety of different evaluative frameworks were employed, from single randomised controlled trial-based studies over relatively short-time periods (6 months) to more complex Bayesian modelling techniques.The studies were broadly consistent in concluding that TAS was more effective than CAS in terms of reducing the rate of acute rejection episodes. of the studies that undertook decision modelling, all but one estimated that TAS was associated with better graft-related outcomes such as rejection-free life-years, patient-survival and QALYs. Six of the studies concluded that the healthcare costs associated with TAS were lower than those for CAS. A seventh study suggested that TAS was the least costly option if costs were considered over a relatively long time period (14 years). Only one study clearly concluded that CAS was more cost effective than TAS.Clinical evidence clearly shows that TAS is more effective than CAS in terms of reducing the incidence of acute rejection following renal transplantation. The majority of published economic evaluations suggest that TAS is also the more cost-effective option. However, the economic evaluations contained a number of methodological limitations, undermining the confidence that can be attached to their results. Future economic evaluations of the CIs, and immunosuppressants in general, should address these issues in order to produce more robust cost-effectiveness estimates. Most importantly, they should evaluate a wider range of potential treatment options.

BACKGROUND: Home-based cardiac rehabilitation offers an alternative to traditional, hospital-based cardiac rehabilitation. AIM: to compare the cost effectiveness of home-based cardiac rehabilitation and hospital-based cardiac rehabilitation. METHODS: 104 patients with an uncomplicated acute myocardial infarction and without major comorbidity were randomized to receive home-based rehabilitation (n=60) i.e. nurse facilitated, self-help package of 6 weeks' duration (the Heart Manual) or hospital-based rehabilitation for 8-10 weeks (n=44). Complete economic data were available in 80 patients (48 who received home-based rehabilitation and 32 who received hospital-based rehabilitation). Healthcare costs, patient costs, and quality of life (EQ-5D4.13) were assessed over the 9 months of the study. RESULTS: the cost of running the home-based rehabilitation programme was slightly lower than that of the hospital-based programme (mean (95% confidence interval) difference - 30 pounds sterling (- 45 pounds sterling to - 12 pounds sterling) [-44 euro, -67 euro to -18 euro] per patient. The cost difference was largely the result of reduced personnel costs. Over the 9 months of the study, no significant difference was seen between the two groups in overall healthcare costs (78 pounds sterling, - 1102 pounds sterling to 1191 pounds sterling [-115 euro, -1631 euro to -1763 euro] per patient) or quality adjusted life-years (-0.06 (-0.15 to 0.02)). The lack of significant difference between home-based rehabilitation and hospital-based rehabilitation did not alter when different costs and different methods of analysis were used. CONCLUSIONS: the health gain and total healthcare costs of the present hospital-based and home-based cardiac rehabilitation programmes for patients after myocardial infarction appear to be similar. These initial results require affirmation by further economic evaluations of cardiac rehabilitation in different settings.

BACKGROUND: Participation in cardiac rehabilitation after acute myocardial infarction is sub-optimal. Offering home-based rehabilitation may improve uptake. We report the first randomized study of cardiac rehabilitation to include patient preference. AIM: to compare the clinical effectiveness of a home-based rehabilitation with hospital-based rehabilitation after myocardial infarction and to determine whether patient choice affects clinical outcomes. DESIGN: Pragmatic randomized controlled trial with patient preference arms. SETTING: Rural South West England. METHODS: Patients admitted with uncomplicated myocardial infarction were offered hospital-based rehabilitation classes over 8-10 weeks or a self-help package of six weeks' duration (the Heart Manual) supported by a nurse. Primary outcomes at 9 months were mean depression and anxiety scores on the Hospital Anxiety Depression scale, quality of life after myocardial infarction (MacNew) score and serum total cholesterol. RESULTS: of the 230 patients who agreed to participate, 104 (45%) consented to randomization and 126 (55%) chose their rehabilitation programme. Nine month follow-up data were available for 84/104 (81%) randomized and 100/126 (79%) preference patients. At follow-up no difference was seen in the change in mean depression scores between the randomized home and hospital-based groups (mean difference: 0; 95% confidence interval, -1.12 to 1.12) nor mean anxiety score (-0.07; -1.42 to 1.28), mean global MacNew score (0.14; -0.35 to 0.62) and mean total cholesterol levels (-0.18; -0.62 to 0.27). Neither were there any significant differences in outcomes between the preference groups. CONCLUSIONS: Home-based cardiac rehabilitation with the Heart Manual was as effective as hospital-based rehabilitation for patients after myocardial infarction. Choosing a rehabilitation programme did not significantly affect clinical outcomes.

Objectives: to assess the clinical effectiveness and cost-effectiveness of buprenorphine maintenance therapy (BMT) and methadone maintenance therapy (MMT) for the management of opioid-dependent individuals. Data sources: Major electronic databases were searched from inception to August 2005. Industry submissions to the National Institute for Health and Clinical Excellence were accessed. Review methods: the assessment of clinical effectiveness was based on a review of existing reviews plus an updated search for randomised controlled trials (RCTs). A decision tree with Monte Carlo simulation model was developed to assess the cost-effectiveness of BMT and MMT. Retention in treatment and opiate abuse parameters were sourced from the meta-analysis of RCTs directly comparing flexible MMT with flexible dose BMT. Utilities were derived from a panel representing a societal perspective. Results: Most of the included systematic reviews and RCTs were of moderate to good quality, and focused on short-term (up to 1-year follow-up) outcomes of retention in treatment and the level of opiate use (self-report or urinalysis). Most studies employed a trial design that compared a fixed-close strategy (i.e. all individuals received a standard dose) of MMT or BMT and were conducted in predominantly young men who fulfilled criteria as opiate-dependent or heroin-dependent users, without significant co-morbidities. RCT meta-analyses have shown that a fixed dose of MMT or BMT has superior levels of retention in treatment and opiate use than placebo or no treatment, with higher fixed doses being more effective than lower fixed doses. There was evidence, primarily from non-randomised observational studies, that fixed-dose MMT reduces mortality, HIV risk behavior and levels of crime compared with no therapy and one small RCT has shown the level of mortality with fixed-dose BMT to be significantly less than with placebo. Flexible dosing (i.e. individualised doses) of MMT and BMT is more reflective of real-world practice. Retention in treatment was superior for flexible MMT than flexible BMT dosing but there was no significant difference in opiate use. Indirect comparison of data from population cross-sectional studies suggests that mortality with BMT may be lower than that with MMT. A pooled RCT analysis showed no significant difference in serious adverse events with MMT compared with BMT. Although treatment modifier evidence was limited, adjunct psychosocial and contingency interventions (e.g. financial incentives for opiate-free urine samples) appeared to enhance the effects of both, MMT and BMT. Also, MMT and BMT appear to be similarly effective whether delivered in a primary care or outpatient clinic setting. Although most of the included economic evaluations were considered to be of high quality, none used all of the appropriate parameters, effectiveness data, perspective and comparators required to make their results generalisable to the NHS context. One company (Schering-Plough) submitted cost-effectiveness evidence based on an economic model that had a 1-year time horizon and sourced data from a single RCT of flexible-dose MMT compared with flexible-dose BMT and utility values obtained from the literature; the results showed that for MMT vs no drug therapy, the incremental cost-effectiveness ratio (ICER) was £12,584/quality-adjusted life-year (QALY), for BMT versus no drug therapy, the ICER was £30,048/QALY and in a direct comparison, MMT was found to be slightly more effective and less costly than BMT. The assessment group model found for MMT versus no drug therapy that the ICER was £13,697/QALY, for BMT versus no drug therapy that the ICER was £26,429/QALY and, as with the industry model, in direct comparison, MMT was slightly more effective and less costly than BMT. When considering social costs, both MMT and BMT gave more health gain and were less costly than no drug treatment. These findings were robust to deterministic and probabilistic sensitivity analyses. Conclusions: Both flexible-dose MMT and BMT are more clinically effective and more cost-effective than no drug therapy in dependent opiate users. In direct comparison, a flexible dosing strategy with MMT was found be somewhat more effective in maintaining individuals in treatment than flexible-dose BMT and therefore associated with a slightly higher health gain and lower costs. However, this needs to be balanced by the more recent experience of clinicians in the use of buprenorphine, the possible risk of higher mortality of MMT and individual opiate-dependent users' preferences. Future research should be directed towards the safety and effectiveness of MMT and BMT; potential safety concerns regarding methadone and buprenorphine, specifically mortality and key drug interactions; efficacy of substitution medications (in particular patient subgroups, such as within the criminal justice system, or within young people); and uncertainties in cost-effectiveness identified by current economic models. © Queen's Printer and Controller of HMSO 2007. All rights reserved.

OBJECTIVES: to assess the clinical effectiveness and cost-effectiveness of buprenorphine maintenance therapy (BMT) and methadone maintenance therapy (MMT) for the management of opioid-dependent individuals. DATA SOURCES: Major electronic databases were searched from inception to August 2005. Industry submissions to the National Institute for Health and Clinical Excellence were accessed. REVIEW METHODS: the assessment of clinical effectiveness was based on a review of existing reviews plus an updated search for randomised controlled trials (RCTs). A decision tree with Monte Carlo simulation model was developed to assess the cost-effectiveness of BMT and MMT. Retention in treatment and opiate abuse parameters were sourced from the meta-analysis of RCTs directly comparing flexible MMT with flexible dose BMT. Utilities were derived from a panel representing a societal perspective. RESULTS: Most of the included systematic reviews and RCTs were of moderate to good quality, and focused on short-term (up to 1-year follow-up) outcomes of retention in treatment and the level of opiate use (self-report or urinalysis). Most studies employed a trial design that compared a fixed-dose strategy (i.e. all individuals received a standard dose) of MMT or BMT and were conducted in predominantly young men who fulfilled criteria as opiate-dependent or heroin-dependent users, without significant co-morbidities. RCT meta-analyses have shown that a fixed dose of MMT or BMT has superior levels of retention in treatment and opiate use than placebo or no treatment, with higher fixed doses being more effective than lower fixed doses. There was evidence, primarily from non-randomised observational studies, that fixed-dose MMT reduces mortality, HIV risk behaviour and levels of crime compared with no therapy and one small RCT has shown the level of mortality with fixed-dose BMT to be significantly less than with placebo. Flexible dosing (i.e. individualised doses) of MMT and BMT is more reflective of real-world practice. Retention in treatment was superior for flexible MMT than flexible BMT dosing but there was no significant difference in opiate use. Indirect comparison of data from population cross-sectional studies suggests that mortality with BMT may be lower than that with MMT. A pooled RCT analysis showed no significant difference in serious adverse events with MMT compared with BMT. Although treatment modifier evidence was limited, adjunct psychosocial and contingency interventions (e.g. financial incentives for opiate-free urine samples) appeared to enhance the effects of both MMT and BMT. Also, MMT and BMT appear to be similarly effective whether delivered in a primary care or outpatient clinic setting. Although most of the included economic evaluations were considered to be of high quality, none used all of the appropriate parameters, effectiveness data, perspective and comparators required to make their results generalisable to the NHS context. One company (Schering-Plough) submitted cost-effectiveness evidence based on an economic model that had a 1-year time horizon and sourced data from a single RCT of flexible-dose MMT compared with flexible-dose BMT and utility values obtained from the literature; the results showed that for MMT vs no drug therapy, the incremental cost-effectiveness ratio (ICER) was pound 12,584/quality-adjusted life-year (QALY), for BMT versus no drug therapy, the ICER was pound 30,048/QALY and in a direct comparison, MMT was found to be slightly more effective and less costly than BMT. The assessment group model found for MMT versus no drug therapy that the ICER was pound 13,697/QALY, for BMT versus no drug therapy that the ICER was pound 26,429/QALY and, as with the industry model, in direct comparison, MMT was slightly more effective and less costly than BMT. When considering social costs, both MMT and BMT gave more health gain and were less costly than no drug treatment. These findings were robust to deterministic and probabilistic sensitivity analyses. CONCLUSIONS: Both flexible-dose MMT and BMT are more clinically effective and more cost-effective than no drug therapy in dependent opiate users. In direct comparison, a flexible dosing strategy with MMT was found be somewhat more effective in maintaining individuals in treatment than flexible-dose BMT and therefore associated with a slightly higher health gain and lower costs. However, this needs to be balanced by the more recent experience of clinicians in the use of buprenorphine, the possible risk of higher mortality of MMT and individual opiate-dependent users' preferences. Future research should be directed towards the safety and effectiveness of MMT and BMT; potential safety concerns regarding methadone and buprenorphine, specifically mortality and key drug interactions; efficacy of substitution medications (in particular patient subgroups, such as within the criminal justice system, or within young people); and uncertainties in cost-effectiveness identified by current economic models.

To assess the clinical effectiveness and cost-effectiveness of buprenorphine maintenance therapy (BMT) and methadone maintenance therapy (MMT) for the management of opioid-dependent individuals. Major electronic databases were searched from inception to August 2005. Industry submissions to the National Institute for Health and Clinical Excellence were accessed. The assessment of clinical effectiveness was based on a review of existing reviews plus an updated search for randomised controlled trials (RCTs). A decision tree with Monte Carlo simulation model was developed to assess the cost-effectiveness of BMT and MMT. Retention in treatment and opiate abuse parameters were sourced from the meta-analysis of RCTs directly comparing flexible MMT with flexible dose BMT. Utilities were derived from a panel representing a societal perspective. Most of the included systematic reviews and RCTs were of moderate to good quality, and focused on short-term (up to 1-year follow-up) outcomes of retention in treatment and the level of opiate use (self-report or urinalysis). Most studies employed a trial design that compared a fixed-dose strategy (i.e. all individuals received a standard dose) of MMT or BMT and were conducted in predominantly young men who fulfilled criteria as opiate-dependent or heroin-dependent users, without significant co-morbidities. RCT meta-analyses have shown that a fixed dose of MMT or BMT has superior levels of retention in treatment and opiate use than placebo or no treatment, with higher fixed doses being more effective than lower fixed doses. There was evidence, primarily from non-randomised observational studies, that fixed-dose MMT reduces mortality, HIV risk behaviour and levels of crime compared with no therapy and one small RCT has shown the level of mortality with fixed-dose BMT to be significantly less than with placebo. Flexible dosing (i.e. individualised doses) of MMT and BMT is more reflective of real-world practice. Retention in treatment was superior for flexible MMT than flexible BMT dosing but there was no significant difference in opiate use. Indirect comparison of data from population cross-sectional studies suggests that mortality with BMT may be lower than that with MMT. A pooled RCT analysis showed no significant difference in serious adverse events with MMT compared with BMT. Although treatment modifier evidence was limited, adjunct psychosocial and contingency interventions (e.g. financial incentives for opiate-free urine samples) appeared to enhance the effects of both MMT and BMT. Also, MMT and BMT appear to be similarly effective whether delivered in a primary care or outpatient clinic setting. Although most of the included economic evaluations were considered to be of high quality, none used all of the appropriate parameters, effectiveness data, perspective and comparators required to make their results generalisable to the NHS context. One company (Schering-Plough) submitted cost-effectiveness evidence based on an economic model that had a 1-year time horizon and sourced data from a single RCT of flexible-dose MMT compared with flexible-dose BMT and utility values obtained from the literature; the results showed that for MMT vs no drug therapy, the incremental cost-effectiveness ratio (ICER) was pound 12,584/quality-adjusted life-year (QALY), for BMT versus no drug therapy, the ICER was pound 30,048/QALY and in a direct comparison, MMT was found to be slightly more effective and less costly than BMT. The assessment group model found for MMT versus no drug therapy that the ICER was pound 13,697/QALY, for BMT versus no drug therapy that the ICER was pound 26,429/QALY and, as with the industry model, in direct comparison, MMT was slightly more effective and less costly than BMT. When considering social costs, both MMT and BMT gave more health gain and were less costly than no drug treatment. These findings were robust to deterministic and probabilistic sensitivity analyses. Both flexible-dose MMT and BMT are more clinically effective and more cost-effective than no drug therapy in dependent opiate users. In direct comparison, a flexible dosing strategy with MMT was found be somewhat more effective in maintaining individuals in treatment than flexible-dose BMT and therefore associated with a slightly higher health gain and lower costs. However, this needs to be balanced by the more recent experience of clinicians in the use of buprenorphine, the possible risk of higher mortality of MMT and individual opiate-dependent users' preferences. Future research should be directed towards the safety and effectiveness of MMT and BMT; potential safety concerns regarding methadone and buprenorphine, specifically mortality and key drug interactions; efficacy of substitution medications (in particular patient subgroups, such as within the criminal justice system, or within young people); and uncertainties in cost-effectiveness identified by current economic models.

Patients with neuropathic pain secondary to failed back surgery syndrome (FBSS) typically experience persistent pain, disability, and reduced quality of life. We hypothesised that spinal cord stimulation (SCS) is an effective therapy in addition to conventional medical management (CMM) in this patient population. We randomised 100 FBSS patients with predominant leg pain of neuropathic radicular origin to receive spinal cord stimulation plus conventional medical management (SCS group) or conventional medical management alone (CMM group) for at least 6 months. The primary outcome was the proportion of patients achieving 50% or more pain relief in the legs. Secondary outcomes were improvement in back and leg pain, health-related quality of life, functional capacity, use of pain medication and non-drug pain treatment, level of patient satisfaction, and incidence of complications and adverse effects. Crossover after the 6-months visit was permitted, and all patients were followed up to 1 year. In the intention-to-treat analysis at 6 months, 24 SCS patients (48%) and 4 CMM patients (9%) (p

OBJECTIVE: We analyzed the cost-effectiveness and cost-utility of treating failed back-surgery syndrome using spinal cord stimulation (SCS) versus reoperation. MATERIALS AND METHODS: a disinterested third party collected charge data for the first 42 patients in a randomized controlled crossover trial. We computed the difference in cost with regard to success (cost-effectiveness) and mean quality-adjusted life years (cost-utility). We analyzed the patient-charge data with respect to intention to treat (costs and outcomes as a randomized group), treated as intended (costs as randomized; crossover failure assigned to a randomized group), and final treatment costs and outcomes. RESULTS: By mean 3.1-year follow-up, 13 of 21 patients (62%) crossed from reoperation versus 5 of 19 patients (26%) who crossed from SCS (P < 0.025) [corrected]. The mean cost per success was US $117,901 for crossovers to SCS. No crossovers to reoperation achieved success despite a mean per-patient expenditure of US $260,584. The mean per-patient costs were US $31,530 for SCS versus US $38,160 for reoperation (intention to treat), US $48,357 for SCS versus US $105,928 for reoperation (treated as intended), and US $34,371 for SCS versus US $36,341 for reoperation (final treatment). SCS was dominant (more effective and less expensive) in the incremental cost-effectiveness ratios and incremental cost-utility ratios. A bootstrapped simulation for incremental costs and quality-adjusted life years confirmed SCS's dominance, with approximately 72% of the cost results occurring below US policymakers' "maximum willingness to pay" threshold. CONCLUSION: SCS was less expensive and more effective than reoperation in selected failed back-surgery syndrome patients, and should be the initial therapy of choice. SCS is most cost-effective when patients forego repeat operation. Should SCS fail, reoperation is unlikely to succeed.

Objectives: to evaluate the relative effectiveness and cost-effectiveness of a home-based programme of cardiac rehabilitation using the Heart Manual, with centre-based programmes. It also sought to explore the reasons for non-adherence to cardiac rehabilitation programmes. Design: an individually randomised trial, with minimisation for age, gender, ethnicity, initial diagnosis and hospital of recruitment. Participants were followed up after 6, 12 and 24 months by questionnaire and clinical assessment. Individual semistructured interviews were undertaken in the homes of a purposive sample of patients who did not adhere to their allocated programme, and focus groups were undertaken with groups of patients who adhered to the programmes. Setting: Four hospitals in predominantly inner-city, multi-ethnic, socio-economically deprived areas of the West Midlands in England, for 2 years from 1 February 2002. Participants: a total of 525 patients who had experienced a myocardial infarction (MI) or coronary revascularisation within the previous 12 weeks. Interventions: all the rehabilitation programmes included exercise, relaxation, education and lifestyle counselling. All patients were seen by a cardiac rehabilitation nurse prior to hospital discharge and provided with information about their condition and counselling about risk factor modification. The four centre-based programmes varied in length from nine sessions at weekly intervals of education, relaxation and circuit training to 24 individualised sessions over 12 weeks of mainly walking, fixed cycling and rowing with group-based education. The home-based programme consisted of an appropriate version of the Heart Manual, home visits and telephone contact. The Heart Manual was introduced to patients on an individual basis, either in hospital or on a home visit. Home visits by a nurse took place at approximately 1, 6 and 12 weeks after recruitment, with a telephone call at 3 weeks. At the final visit, patients were encouraged to maintain their lifestyle changes and to continue with their exercise programme. Where needed, follow-up was made by a rehabilitation nurse who spoke Punjabi. An audiotape of an abridged version of the Heart Manual in Punjabi accompanied the manual for patients with a limited command of English. Main outcome measures: Primary outcomes were smoking cessation, blood pressure, total and high-density lipoprotein cholesterol, exercise capacity measured by the incremental shuttle walking test and psychological status measured by the Hospital Anxiety and Depression Scale (HADS). Secondary outcomes included self-reported diet, physical activity, cardiac symptoms and quality of life. Health service resource use and costs of rehabilitation programmes from health service and societal perspectives were also measured. Adherence to the physical activity element of the rehabilitation programmes was measured by questionnaire 6, 9 and 12 weeks. Results: No clinically or statistically significant differences were found in any of the primary or secondary outcome measures between the home- and centre-based groups. Significant improvements in total cholesterol, smoking prevalence, the HADS anxiety score, self-reported physical activity and diet were seen in both arms between baseline and the 6-month follow-up. Five or more contacts with a cardiac rehabilitation nurse were received by 96% of home-based participants, whereas only 56% of centre-based participants attended this many rehabilitation classes. The direct rehabilitation costs to the health service were significantly higher for the home-based programme (mean cost £198 versus £157 for the centre-based programme), but when patient costs were included the mean cost of the centre-based arm rose to £182. Patients' reasons for not taking up or adhering to cardiac rehabilitation were multifactorial and very individual. Other health problems limited some patients' ability to exercise. Most non-adherers found some aspects of their cardiac rehabilitation programme helpful. Many had adapted advice on rehabilitation and were continuing to exercise in other ways and had made lifestyle changes, particularly to their diet. The home-based patients' lack of motivation to exercise on their own at home was a major factor in non-adherence. The focus groups revealed little diversity of views among patients from each programme. Patients in the hospital programme enjoyed the camaraderie of group exercise and the home-based patients valued the wealth of information and advice in the Heart Manual. Conclusions: a home-based cardiac rehabilitation programme for low- to moderate-risk patients does not produce inferior outcomes compared with the traditional centre-based programmes. With the level of home visiting in this trial, the home-based programme was more costly to the health service, but with the difference in costs borne by patients attending centre-based programmes. Different reasons were given by home and hospital cardiac rehabilitation patients for not taking up or adhering to cardiac rehabilitation, with home-based patients often citing a lack of motivation to exercise at home. Social characteristics, individual patient needs and the location of cardiac rehabilitation programmes need to be taken into account in programme design to maximise participation. Research is recommended into cardiac rehabilitation in patients from ethnic minority groups; measurement tools to assess physical activity and dietary change; evaluating the Heart Manual in patients who decline centre-based cardiac rehabilitation; the implementation of home-based programmes in the UK; and strategies that sustain physical activity in the long term. © Queen's Printer and Controller of HMSO 2007. All rights reserved.

To evaluate the relative effectiveness and cost-effectiveness of a home-based programme of cardiac rehabilitation using the Heart Manual, with centre-based programmes. It also sought to explore the reasons for non-adherence to cardiac rehabilitation programmes. An individually randomised trial, with minimisation for age, gender, ethnicity, initial diagnosis and hospital of recruitment. Participants were followed up after 6, 12 and 24 months by questionnaire and clinical assessment. Individual semistructured interviews were undertaken in the homes of a purposive sample of patients who did not adhere to their allocated programme, and focus groups were undertaken with groups of patients who adhered to the programmes. Four hospitals in predominantly inner-city, multi-ethnic, socio-economically deprived areas of the West Midlands in England, for 2 years from 1 February 2002. A total of 525 patients who had experienced a myocardial infarction (MI) or coronary revascularisation within the previous 12 weeks. All the rehabilitation programmes included exercise, relaxation, education and lifestyle counselling. All patients were seen by a cardiac rehabilitation nurse prior to hospital discharge and provided with information about their condition and counselling about risk factor modification. The four centre-based programmes varied in length from nine sessions at weekly intervals of education, relaxation and circuit training to 24 individualised sessions over 12 weeks of mainly walking, fixed cycling and rowing with group-based education. The home-based programme consisted of an appropriate version of the Heart Manual, home visits and telephone contact. The Heart Manual was introduced to patients on an individual basis, either in hospital or on a home visit. Home visits by a nurse took place at approximately 1, 6 and 12 weeks after recruitment, with a telephone call at 3 weeks. At the final visit, patients were encouraged to maintain their lifestyle changes and to continue with their exercise programme. Where needed, follow-up was made by a rehabilitation nurse who spoke Punjabi. An audiotape of an abridged version of the Heart Manual in Punjabi accompanied the manual for patients with a limited command of English. Primary outcomes were smoking cessation, blood pressure, total and high-density lipoprotein cholesterol, exercise capacity measured by the incremental shuttle walking test and psychological status measured by the Hospital Anxiety and Depression Scale (HADS). Secondary outcomes included self-reported diet, physical activity, cardiac symptoms and quality of life. Health service resource use and costs of rehabilitation programmes from health service and societal perspectives were also measured. Adherence to the physical activity element of the rehabilitation programmes was measured by questionnaire 6, 9 and 12 weeks. No clinically or statistically significant differences were found in any of the primary or secondary outcome measures between the home- and centre-based groups. Significant improvements in total cholesterol, smoking prevalence, the HADS anxiety score, self-reported physical activity and diet were seen in both arms between baseline and the 6-month follow-up. Five or more contacts with a cardiac rehabilitation nurse were received by 96% of home-based participants, whereas only 56% of centre-based participants attended this many rehabilitation classes. The direct rehabilitation costs to the health service were significantly higher for the home-based programme (mean cost 198 pounds versus 157 pounds for the centre-based programme), but when patient costs were included the mean cost of the centre-based arm rose to 182 pounds. Patients' reasons for not taking up or adhering to cardiac rehabilitation were multifactorial and very individual. Other health problems limited some patients' ability to exercise. Most non-adherers found some aspects of their cardiac rehabilitation programme helpful. Many had adapted advice on rehabilitation and were continuing to exercise in other ways and had made lifestyle changes, particularly to their diet. The home-based patients' lack of motivation to exercise on their own at home was a major factor in non-adherence. The focus groups revealed little diversity of views among patients from each programme. Patients in the hospital programme enjoyed the camaraderie of group exercise and the home-based patients valued the wealth of information and advice in the Heart Manual. A home-based cardiac rehabilitation programme for low- to moderate-risk patients does not produce inferior outcomes compared with the traditional centre-based programmes. With the level of home visiting in this trial, the home-based programme was more costly to the health service, but with the difference in costs borne by patients attending centre-based programmes. Different reasons were given by home and hospital cardiac rehabilitation patients for not taking up or adhering to cardiac rehabilitation, with home-based patients often citing a lack of motivation to exercise at home. Social characteristics, individual patient needs and the location of cardiac rehabilitation programmes need to be taken into account in programme design to maximise participation. Research is recommended into cardiac rehabilitation in patients from ethnic minority groups; measurement tools to assess physical activity and dietary change; evaluating the Heart Manual in patients who decline centre-based cardiac rehabilitation; the implementation of home-based programmes in the UK; and strategies that sustain physical activity in the long term.

OBJECTIVES: to evaluate the relative effectiveness and cost-effectiveness of a home-based programme of cardiac rehabilitation using the Heart Manual, with centre-based programmes. It also sought to explore the reasons for non-adherence to cardiac rehabilitation programmes. DESIGN: an individually randomised trial, with minimisation for age, gender, ethnicity, initial diagnosis and hospital of recruitment. Participants were followed up after 6, 12 and 24 months by questionnaire and clinical assessment. Individual semistructured interviews were undertaken in the homes of a purposive sample of patients who did not adhere to their allocated programme, and focus groups were undertaken with groups of patients who adhered to the programmes. SETTING: Four hospitals in predominantly inner-city, multi-ethnic, socio-economically deprived areas of the West Midlands in England, for 2 years from 1 February 2002. PARTICIPANTS: a total of 525 patients who had experienced a myocardial infarction (MI) or coronary revascularisation within the previous 12 weeks. INTERVENTIONS: all the rehabilitation programmes included exercise, relaxation, education and lifestyle counselling. All patients were seen by a cardiac rehabilitation nurse prior to hospital discharge and provided with information about their condition and counselling about risk factor modification. The four centre-based programmes varied in length from nine sessions at weekly intervals of education, relaxation and circuit training to 24 individualised sessions over 12 weeks of mainly walking, fixed cycling and rowing with group-based education. The home-based programme consisted of an appropriate version of the Heart Manual, home visits and telephone contact. The Heart Manual was introduced to patients on an individual basis, either in hospital or on a home visit. Home visits by a nurse took place at approximately 1, 6 and 12 weeks after recruitment, with a telephone call at 3 weeks. At the final visit, patients were encouraged to maintain their lifestyle changes and to continue with their exercise programme. Where needed, follow-up was made by a rehabilitation nurse who spoke Punjabi. An audiotape of an abridged version of the Heart Manual in Punjabi accompanied the manual for patients with a limited command of English. MAIN OUTCOME MEASURES: Primary outcomes were smoking cessation, blood pressure, total and high-density lipoprotein cholesterol, exercise capacity measured by the incremental shuttle walking test and psychological status measured by the Hospital Anxiety and Depression Scale (HADS). Secondary outcomes included self-reported diet, physical activity, cardiac symptoms and quality of life. Health service resource use and costs of rehabilitation programmes from health service and societal perspectives were also measured. Adherence to the physical activity element of the rehabilitation programmes was measured by questionnaire 6, 9 and 12 weeks. RESULTS: No clinically or statistically significant differences were found in any of the primary or secondary outcome measures between the home- and centre-based groups. Significant improvements in total cholesterol, smoking prevalence, the HADS anxiety score, self-reported physical activity and diet were seen in both arms between baseline and the 6-month follow-up. Five or more contacts with a cardiac rehabilitation nurse were received by 96% of home-based participants, whereas only 56% of centre-based participants attended this many rehabilitation classes. The direct rehabilitation costs to the health service were significantly higher for the home-based programme (mean cost 198 pounds versus 157 pounds for the centre-based programme), but when patient costs were included the mean cost of the centre-based arm rose to 182 pounds. Patients' reasons for not taking up or adhering to cardiac rehabilitation were multifactorial and very individual. Other health problems limited some patients' ability to exercise. Most non-adherers found some aspects of their cardiac rehabilitation programme helpful. Many had adapted advice on rehabilitation and were continuing to exercise in other ways and had made lifestyle changes, particularly to their diet. The home-based patients' lack of motivation to exercise on their own at home was a major factor in non-adherence. The focus groups revealed little diversity of views among patients from each programme. Patients in the hospital programme enjoyed the camaraderie of group exercise and the home-based patients valued the wealth of information and advice in the Heart Manual. CONCLUSIONS: a home-based cardiac rehabilitation programme for low- to moderate-risk patients does not produce inferior outcomes compared with the traditional centre-based programmes. With the level of home visiting in this trial, the home-based programme was more costly to the health service, but with the difference in costs borne by patients attending centre-based programmes. Different reasons were given by home and hospital cardiac rehabilitation patients for not taking up or adhering to cardiac rehabilitation, with home-based patients often citing a lack of motivation to exercise at home. Social characteristics, individual patient needs and the location of cardiac rehabilitation programmes need to be taken into account in programme design to maximise participation. Research is recommended into cardiac rehabilitation in patients from ethnic minority groups; measurement tools to assess physical activity and dietary change; evaluating the Heart Manual in patients who decline centre-based cardiac rehabilitation; the implementation of home-based programmes in the UK; and strategies that sustain physical activity in the long term.

OBJECTIVES: to assess the clinical effectiveness and cost-effectiveness of cardiac resynchronisation therapy (CRT) for people with heart failure and evidence of dyssynchrony by comparing cardiac resynchronisation therapy devices, CRT-P and CRT with defibrillation (CRT-D), each with optimal pharmaceutical therapy (OPT), and with each other. DATA SOURCES: Electronic databases were searched up to June 2006. Manufacturer submissions to the National Institute for Health and Clinical Excellence (NICE) were also searched for additional evidence. REVIEW METHODS: Relevant data from selected studies were extracted, narrative reviews were undertaken and meta-analyses of the clinical trial data were conducted. A Markov model was developed. Incremental costs and quality-adjusted life-years (QALYs) were calculated. Extensive one-way sensitivity analyses, threshold analyses, probabilistic sensitivity analyses and value of information analyses were carried out. RESULTS: Five randomised controlled trials met the inclusion criteria, recruiting 3434 participants. Quality was good to moderate. Meta-analyses showed that both CRT-P and CRT-D devices significantly reduced the mortality and level of heart failure hospitalisations and they improved health-related quality of life in people with New York Heart Association (NYHA) class III and IV heart failure and evidence of dyssynchrony (QRS interval >120 ms) who were also receiving OPT. A single direct comparison indicated that the effects of CRT-P and CRT-D were similar, with the exception of an additional reduction in sudden cardiac death (SCD) associated with CRT-D. On average, implanting a CRT device in 13 people would result in the saving of one additional life over a 3-year period compared with OPT. The NHS device and procedure cost of implanting a new CRT-P system (pulse generator unit and required leads) was estimated to be 5074 British pounds and that of a CRT-D system 17,266 British pounds. The discounted lifetime costs of OPT, CRT-P and CRT-D were estimated as 9375 British pounds, 20,804 British pounds and 32,689 British pounds, respectively. The industry submissions to NICE contained four cost-effectiveness analyses, of which two were more appropriate as reference cases. One used a discrete event simulation model that gave estimated incremental cost-effectiveness ratios (ICERs) of CRT-P vs OPT of 15,645 British pounds per QALY. The other analysis was based on the results of the COMPANION trial and estimated an ICER of 2818 British pounds per QALY gained by CRT-P vs OPT and a cost per QALY gained of 22,384 British pounds for CRT-D vs OPT. Compared with OPT, the Markov model base case analysis estimated that CRT-P conferred an additional 0.70 QALYs for an additional 11,630 British pounds per person, giving an estimated ICER of 16,735 British pounds per QALY gained for a mixed age cohort (range 14,630-20,333 British pounds). CRT-D vs CRT-P conferred an additional 0.29 QALYs for an additional 11,689 British pounds per person, giving an ICER of 40,160 British pounds per QALY for a mixed age cohort (range 26,645-59,391 British pounds). The authors' ICERs are higher than those from the industry-submitted analysis. Probabilistic sensitivity analysis based on 1000 simulated trials showed that, at a willingness-to-pay (WTP) threshold of 30,000 British pounds per QALY, in CRT-P versus OPT, CRT-P was likely to be cost-effective in 91.3% of simulations and that CRT-P was negatively dominated in 0.4% of simulations. It also showed that in CRT-P versus CRT-D, CRT-D was likely to be cost-effective in 26.3% of simulations and that CRT-P dominated CRT-D in 7.8% of simulations. The relative risk for SCD when CRT-D is compared with OPT is 0.44 in the base case. This treatment becomes cost-ineffective at a WTP threshold of 30,000 British pounds when this value is greater than 0.65. When both CRT-P and CRT-D were considered as competing technologies with each other and OPT (three-way probabilistic analysis), and at the same WTP, there was a 68% probability that CRT-P provided the highest expected net benefit. The WTP threshold would need to be above 40,000 British pounds before CRT-D provided the highest expected net benefit. CONCLUSIONS: the study found that CRT-P and CRT-D devices reduce mortality and hospitalisations due to heart failure, improve quality of life and reduce SCD in people with heart failure NYHA classes III and IV, and evidence of dyssynchrony. When measured using a lifetime time horizon and compared with optimal medical therapy, the devices are estimated to be cost-effective at a WTP threshold of 30,000 British pounds per QALY; CRT-P is cost-effective at a WTP threshold of 20,000 British pounds per QALY. When the cost and effectiveness of all three treatment strategies are compared, the estimated net benefit from CRT-D is less than with the other two strategies, until the WTP threshold exceeds 40,160 British pounds/QALY. Further research is needed into the identification of those patients unlikely to benefit from this therapy, the appropriate use of CRT-D devices, the differences in mortality and heart failure hospitalisation for NYHA classes I and II, as well as the long-term implications of using this therapy.

To assess the clinical effectiveness and cost-effectiveness of cardiac resynchronisation therapy (CRT) for people with heart failure and evidence of dyssynchrony by comparing cardiac resynchronisation therapy devices, CRT-P and CRT with defibrillation (CRT-D), each with optimal pharmaceutical therapy (OPT), and with each other. Electronic databases were searched up to June 2006. Manufacturer submissions to the National Institute for Health and Clinical Excellence (NICE) were also searched for additional evidence. Relevant data from selected studies were extracted, narrative reviews were undertaken and meta-analyses of the clinical trial data were conducted. A Markov model was developed. Incremental costs and quality-adjusted life-years (QALYs) were calculated. Extensive one-way sensitivity analyses, threshold analyses, probabilistic sensitivity analyses and value of information analyses were carried out. Five randomised controlled trials met the inclusion criteria, recruiting 3434 participants. Quality was good to moderate. Meta-analyses showed that both CRT-P and CRT-D devices significantly reduced the mortality and level of heart failure hospitalisations and they improved health-related quality of life in people with New York Heart Association (NYHA) class III and IV heart failure and evidence of dyssynchrony (QRS interval. > 120 ms) who were also receiving OPT. A single direct comparison indicated that the effects of CRT-P and CRT-D were similar, with the exception of an additional reduction in sudden cardiac death (SCD) associated with CRT-D. On average, implanting a CRT device in 13 people would result in the saving of one additional life over a 3-year period compared with OPT. The NHS device and procedure cost of implanting a new CRT-P system (pulse generator unit and required leads) was estimated to be 5074 British pounds and that of a CRT-D system 17,266 British pounds. The discounted lifetime costs of OPT, CRT-P and CRT-D were estimated as 9375 British pounds, 20,804 British pounds and 32,689 British pounds, respectively. The industry submissions to NICE contained four cost-effectiveness analyses, of which two were more appropriate as reference cases. One used a discrete event simulation model that gave estimated incremental cost-effectiveness ratios (ICERs) of CRT-P vs OPT of 15,645 British pounds per QALY. The other analysis was based on the results of the COMPANION trial and estimated an ICER of 2818 British pounds per QALY gained by CRT-P vs OPT and a cost per QALY gained of 22,384 British pounds for CRT-D vs OPT. Compared with OPT, the Markov model base case analysis estimated that CRT-P conferred an additional 0.70 QALYs for an additional 11,630 British pounds per person, giving an estimated ICER of 16,735 British pounds per QALY gained for a mixed age cohort (range 14,630-20,333 British pounds). CRT-D vs CRT-P conferred an additional 0.29 QALYs for an additional 11,689 British pounds per person, giving an ICER of 40,160 British pounds per QALY for a mixed age cohort (range 26,645-59,391 British pounds). The authors' ICERs are higher than those from the industry-submitted analysis. Probabilistic sensitivity analysis based on 1000 simulated trials showed that, at a willingness-to-pay (WTP) threshold of 30,000 British pounds per QALY, in CRT-P versus OPT, CRT-P was likely to be cost-effective in 91.3% of simulations and that CRT-P was negatively dominated in 0.4% of simulations. It also showed that in CRT-P versus CRT-D, CRT-D was likely to be cost-effective in 26.3% of simulations and that CRT-P dominated CRT-D in 7.8% of simulations. The relative risk for SCD when CRT-D is compared with OPT is 0.44 in the base case. This treatment becomes cost-ineffective at a WTP threshold of 30,000 British pounds when this value is greater than 0.65. When both CRT-P and CRT-D were considered as competing technologies with each other and OPT (three-way probabilistic analysis), and at the same WTP, there was a 68% probability that CRT-P provided the highest expected net benefit. The WTP threshold would need to be above 40,000 British pounds before CRT-D provided the highest expected net benefit. The study found that CRT-P and CRT-D devices reduce mortality and hospitalisations due to heart failure, improve quality of life and reduce SCD in people with heart failure NYHA classes III and IV, and evidence of dyssynchrony. When measured using a lifetime time horizon and compared with optimal medical therapy, the devices are estimated to be cost-effective at a WTP threshold of 30,000 British pounds per QALY; CRT-P is cost-effective at a WTP threshold of 20,000 British pounds per QALY. When the cost and effectiveness of all three treatment strategies are compared, the estimated net benefit from CRT-D is less than with the other two strategies, until the WTP threshold exceeds 40,160 British pounds/QALY. Further research is needed into the identification of those patients unlikely to benefit from this therapy, the appropriate use of CRT-D devices, the differences in mortality and heart failure hospitalisation for NYHA classes I and II, as well as the long-term implications of using this therapy.

OBJECTIVES: to review the clinical and cost-effectiveness of basiliximab, daclizumab, tacrolimus, mycophenolate mofetil (MMF), mycophenolate sodium (MPS) and sirolimus as possible immunosuppressive therapies for renal transplantation in children. DATA SOURCES: Electronic databases were searched up to November 2004. REVIEW METHODS: Data from selected studies were extracted and quality assessed. An economic model [Birmingham Sensitivity Analysis paediatrics (BSAp)] was produced based on an adaptation of a model previously developed for the assessment of the cost-effectiveness of immunosuppressants in adults following renal transplant. RESULTS: for the addition of basiliximab, one unpublished paediatric randomised control trial (RCT), reported that the addition of basiliximab to tacrolimus-based triple therapy (BTAS) failed to significantly improve 6-month biopsy-proven acute rejection (BPAR), graft function, graft loss and all-cause mortality. No significant difference between groups was seen in 6-month or 1-year or longer graft loss, all-cause mortality and side-effects. In a meta-analysis of adult RCTs, the addition of basiliximab to a ciclosporin, azathioprine and steroid regimen (CAS) significantly reduced short-term BPAR. There was no significant difference in short- or long-term graft loss, all-cause mortality or side-effects. One adult RCT was included for the addition of daclizumab to CAS, which reported reduced 1-year BPAR, although no difference between groups was seen in either 1- or 3-year graft loss, all-cause mortality and side-effects. For tacrolimus versus ciclosporin, one unpublished paediatric RCT found that a regimen of tacrolimus, azathioprine and a steroid (TAS) reduced 6-month BPAR and improved graft function [glomerular filtration rate (GFR)] compared with CAS. This improvement in BPAR with tacrolimus was as shown in the meta-analysis of adult RCTs. There was evidence, particularly in children, that in comparison with ciclosporin, tacrolimus may reduce long-term graft loss, although there is no benefit on total mortality. The total level of withdrawal in children was reduced in children receiving tacrolimus. Adult RCTs showed an increase in post-transplant diabetes mellitus with tacrolimus. For MMF versus azathioprine, a meta-analysis of adult RCTs showed MMF [regimen of ciclosporin, MMF and a steroid (CMS)] to reduce 1-year BPAR compared with azathioprine (CAS). There was evidence, particularly in children, that in comparison with azathioprine, tacrolimus may reduce long-term graft loss, although there is no benefit on total mortality. There was an increase in the level of cytomegalovirus infection with MMF, although the overall level of withdrawal due to adverse events was not different to that of azathioprine-treated adults. No study comparing MPS with azathioprine (CAS) was identified. In an adult RCT comparing MMF with MPS, there was no significant difference between groups in 1-year efficacy or side-effects. One unpublished paediatric RCT assessed the addition of sirolimus to CAS. BPAR, graft loss and all-cause mortality were not reported. In two adult RCTs, compared with azathioprine, sirolimus reduced 1-year BPAR, reduced graft function (as assessed by an increased serum creatinine) and increased the level of hyperlipidaemia. No significant differences were seen in other efficacy and side-effect outcomes. On an adult RCT comparing sirolimus with ciclosporin, there were no significant differences between groups in 1-year efficacy or side-effects with the exception of an increased level of hyperlipidaemia with sirolimus substitution. Both the assessment group and drug companies assessed the cost-effectiveness of the newer renal immunosuppressants currently licensed in children using an adaptation (BSAp) of the Birmingham Sensitivity Analysis (BSA) model. This model is based on a 10-year extrapolation of 1-year BPAR results sourced from paediatric RCTs or adult RCTs (where paediatric RCTs were not available). The addition of basiliximab and that of daclizumab to CAS was found to increase quality-adjusted life-years (QALYs) and decreased overall costs, a finding that was robust to sensitivity analyses. The incremental cost-effectiveness ratio (ICER) of replacing ciclosporin with tacrolimus was highly sensitive to the selection of the hazard ratio for graft loss from acute rejection, dialysis costs and the incorporation (or not) of side-effects. The ICERs for tacrolimus versus ciclosporin ranged from about 46,000 pounds/QALY to about 146,000 pounds/QALY. Although sensitive to varying the hazard ratio for graft loss with acute rejection, the ICER for replacing azathioprine with MMF remained in excess of 55,000 pounds/QALY. CONCLUSIONS: in general, compared with a regimen of ciclosporin, azathioprine and steroid, the newer immunosuppressive agents consistently reduced the incidence of short-term biopsy-proven acute rejection. However, evidence of the impact on side-effects, long-term graft loss, compliance and overall health-related quality of life is limited. Cost-effectiveness was estimated based on the relationship between short-term acute rejection levels from RCTs and long-term graft loss. Both the addition of daclizumab and that of basiliximab were found to be dominant strategies, that is, regarding cost savings and increased QALYs. The incremental cost-effectiveness of tacrolimus relative to ciclosporin was highly sensitive to key model parameter values and therefore may well be a cost-effective strategy. The incremental cost-effectiveness of MMF compared with azathioprine, although also sensitive to model parameter, was unattractive. There is a particular need for RCTs to assess the use of MMF, MPS and daclizumab for renal transplantation in children where no such evidence currently exists. Future comparative studies need to report not only on the impact of the newer immunosuppressants on short- and long-term clinical outcomes but also on side-effects, compliance, healthcare resource, costs and health-related quality of life.

To review the clinical and cost-effectiveness of basiliximab, daclizumab, tacrolimus, mycophenolate mofetil (MMF), mycophenolate sodium (MPS) and sirolimus as possible immunosuppressive therapies for renal transplantation in children. Electronic databases were searched up to November 2004. Data from selected studies were extracted and quality assessed. An economic model [Birmingham Sensitivity Analysis paediatrics (BSAp)] was produced based on an adaptation of a model previously developed for the assessment of the cost-effectiveness of immunosuppressants in adults following renal transplant. For the addition of basiliximab, one unpublished paediatric randomised control trial (RCT), reported that the addition of basiliximab to tacrolimus-based triple therapy (BTAS) failed to significantly improve 6-month biopsy-proven acute rejection (BPAR), graft function, graft loss and all-cause mortality. No significant difference between groups was seen in 6-month or 1-year or longer graft loss, all-cause mortality and side-effects. In a meta-analysis of adult RCTs, the addition of basiliximab to a ciclosporin, azathioprine and steroid regimen (CAS) significantly reduced short-term BPAR. There was no significant difference in short- or long-term graft loss, all-cause mortality or side-effects. One adult RCT was included for the addition of daclizumab to CAS, which reported reduced 1-year BPAR, although no difference between groups was seen in either 1- or 3-year graft loss, all-cause mortality and side-effects. For tacrolimus versus ciclosporin, one unpublished paediatric RCT found that a regimen of tacrolimus, azathioprine and a steroid (TAS) reduced 6-month BPAR and improved graft function [glomerular filtration rate (GFR)]. compared with CAS. This improvement in BPAR with tacrolimus was as shown in the meta-analysis of adult RCTs. There was evidence, particularly in children, that in comparison with ciclosporin, tacrolimus may reduce long-term graft loss, although there is no benefit on total mortality. The total level of withdrawal in children was reduced in children receiving tacrolimus. Adult RCTs showed an increase in post-transplant diabetes mellitus with tacrolimus. For MMF versus azathioprine, a meta-analysis of adult RCTs showed MMF [regimen of ciclosporin, MMF and a steroid (CMS)] to reduce 1-year BPAR compared with azathioprine (CAS). There was evidence, particularly in children, that in comparison with azathioprine, tacrolimus may reduce long-term graft loss, although there is no benefit on total mortality. There was an increase in the level of cytomegalovirus infection with MMF, although the overall level of withdrawal due to adverse events was not different to that of azathioprine-treated adults. No study comparing MPS with azathioprine (CAS) was identified. In an adult RCT comparing MMF with MPS, there was no significant difference between groups in 1-year efficacy or side-effects. One unpublished paediatric RCT assessed the addition of sirolimus to CAS. BPAR, graft loss and all-cause mortality were not reported. In two adult RCTs, compared with azathioprine, sirolimus reduced 1-year BPAR, reduced graft function (as assessed by an increased serum creatinine) and increased the level of hyperlipidaemia. No significant differences were seen in other efficacy and side-effect outcomes. On an adult RCT comparing sirolimus with ciclosporin, there were no significant differences between groups in 1-year efficacy or side-effects with the exception of an increased level of hyperlipidaemia with sirolimus substitution. Both the assessment group and drug companies assessed the cost-effectiveness of the newer renal immunosuppressants currently licensed in children using an adaptation (BSAp) of the Birmingham Sensitivity Analysis (BSA) model. This model is based on a 10-year extrapolation of 1-year BPAR results sourced from paediatric RCTs or adult RCTs (where paediatric RCTs were not available). The addition of basiliximab and that of daclizumab to CAS was found to increase quality-adjusted life-years (QALYs) and decreased overall costs, a finding that was robust to sensitivity analyses. The incremental cost-effectiveness ratio (ICER) of replacing ciclosporin with tacrolimus was highly sensitive to the selection of the hazard ratio for graft loss from acute rejection, dialysis costs and the incorporation (or not) of side-effects. The ICERs for tacrolimus versus ciclosporin ranged from about 46,000 pounds/QALY to about 146,000 pounds/QALY. Although sensitive to varying the hazard ratio for graft loss with acute rejection, the ICER for replacing azathioprine with MMF remained in excess of 55,000 pounds/QALY. In general, compared with a regimen of ciclosporin, azathioprine and steroid, the newer immunosuppressive agents consistently reduced the incidence of short-term biopsy-proven acute rejection. However, evidence of the impact on side-effects, long-term graft loss, compliance and overall health-related quality of life is limited. Cost-effectiveness was estimated based on the relationship between short-term acute rejection levels from RCTs and long-term graft loss. Both the addition of daclizumab and that of basiliximab were found to be dominant strategies, that is, regarding cost savings and increased QALYs. The incremental cost-effectiveness of tacrolimus relative to ciclosporin was highly sensitive to key model parameter values and therefore may well be a cost-effective strategy. The incremental cost-effectiveness of MMF compared with azathioprine, although also sensitive to model parameter, was unattractive. There is a particular need for RCTs to assess the use of MMF, MPS and daclizumab for renal transplantation in children where no such evidence currently exists. Future comparative studies need to report not only on the impact of the newer immunosuppressants on short- and long-term clinical outcomes but also on side-effects, compliance, healthcare resource, costs and health-related quality of life.

Objective: the primary aim of this analysis was to prospectively assess the full economic costs associated with implementing Newborn Hearing Screening Programme (NHSP) based on a two-stage screen, transient evoked otoacoustic emissions followed, if there is no clear response, by automated auditory brainstem response. Economic data were also collected from the Infant Distraction Test Screening (IDTS) service performed by health visitors at around eight months of age, which was being phased out. A comparison of costs and outcomes associated with NHSP and IDTS was conducted. Design: 20 NHSP sites were invited to provide detailed cost data on NHSP implementation and 14 of these sites were selected to provide costs on the IDTS service that was being supplanted. Results: There was marked variability in the costs. Given the higher yield of NHSP sites, the average cost per case detected across NHSP sites (£31,410/case) was approximately half that of IDTS sites (£69,919/case). Including family costs, the average total cost per case of NHSP (£34,826/case) was almost a quarter of IDTS (£117,942/case). Conclusions: Family costs and cost per case associated with NHSP are considerably less than that with IDTS. These findings support the policy of implementation of NHSP and the phasing out of the IDTS.

STUDY DESIGN: Systematic review and meta-regression. OBJECTIVES: to compare the efficacy and safety of balloon kyphoplasty and vertebroplasty for the treatment of vertebral compression fractures, and to examine the prognostic factors that predict outcome. SUMMARY OF BACKGROUND DATA: a previous systematic review of vertebroplasty by Levine et al in 2000 identified seven case series studies and no controlled studies. METHODS: a number of electronic databases were searched through March 1, 2004. Citation searches of included studies were undertaken and contact was made with experts in the field. No language restrictions were applied. All controlled and uncontrolled studies were included with the exception of case reports. Prognostic factors responsible for pain relief and cement leakage were examined using meta-regression. RESULTS: the following studies were included: balloon kyphoplasty (three nonrandomized comparative studies against conventional medical therapy and 13 case series), vertebroplasty (one nonrandomized comparative study against conventional medical care and 57 cases series), balloon kyphoplasty versus vertebroplasty (one nonrandomized comparative study). The majority of studies were undertaken in older women with osteoporotic vertebral compression fractures with long-term pain that was refractory to medical treatment. At this time, there is no good quality direct comparative evidence of balloon kyphoplasty versus vertebroplasty. From indirect comparison of case series evidence, the procedures appear to provide similar gains in pain relief while for balloon kyphoplasty there is better documentation of gains in patient functionality and quality of life. The level of cement leakage and number of reported adverse events (pulmonary emboli and neurologic injury) in balloon kyphoplasty was significantly lower than for vertebroplasty. These findings were confirmed by meta-regression analysis. CONCLUSIONS: There is Level III evidence to support balloon kyphoplasty and vertebroplasty as effective therapies in the management of patients with symptomatic osteoporotic vertebral compression fractures refractory to conventional medical therapy. Although there was a good ratio of benefit to harm for both procedures, balloon kyphoplasty appears to offer the better adverse event profile. These conclusions need to be updated on the basis of the findings of ongoing randomized controlled trials.

The study's objective was to determine the effectiveness of a joint NHS/Social Services rehabilitation unit (a form of intermediate care) for older people on discharge from community hospital, compared with 'usual' community services. This was a controlled clinical trial in a practice setting. The intervention was 6 weeks in a rehabilitation unit where individuals worked with care/rehabilitation assistants and occupational therapists to regain independence. Controls went home with the health/social care services they would ordinarily receive. Participants were from two matched geographical areas in Devon: one with a rehabilitation unit, one without. Recruitment was from January 1999 to October 2001 in 10 community hospitals. Study eligibility was assessed using the unit's inclusion/exclusion criteria: 55 years or older and 'likely to benefit from a short-term rehabilitation programme' ('potential to improve', 'realistic and achievable goals' and 'motivation to participate'). Ninety-four people were recruited to the intervention and 112 to the control. The mean (standard deviation) age was 81.8 (8.0) years. The main outcome measure was prevention of institutionalisation assessed by the number of days from baseline interview to admission to residential/nursing care or death ('survival-at-home time'). Secondary outcome measures were time to hospital re-admission over 12 months, quality of life and coping ability. There were no significant differences between the groups on any outcome measure. Adjusted hazard ratio (95% CI) for 'survival-at-home time' was 1.13 (0.70-1.84), and 0.84 (0.53-1.33) for 'time to hospital re-admission'. However, attending the unit was associated with earlier hospital discharge. Median (interquartile range) days in hospital for the intervention graph was 27 (20, 40), and for the control graph was 35 (22, 47) (U = 4234, P = 0.029). These findings suggest a stay in a rehabilitation unit is no more effective than 'usual' care at diverting older people from hospital/long-term care. Alternative service configurations may be as effective, having implications for tailoring services more specifically to individual need and/or user preferences. However, the unit did appear to facilitate earlier discharges from community hospital.

The study's aim was to investigate the cost-effectiveness of an NHS/Social Services short-term residential rehabilitation unit (a form of intermediate care) for older people on discharge from community hospital compared with 'usual' community services. An economic evaluation was conducted alongside a prospective controlled trial, which explored the effectiveness of a rehabilitation unit in a practice setting. The aim of the unit was to help individuals regain independence. A matched control group went home from hospital with the health/social care services they would ordinarily receive. The research was conducted in two matched geographical areas in Devon: one with a rehabilitation unit, one without. Participants were recruited from January 1999 to October 2000 in 10 community hospitals and their eligibility determined using the unit's strict inclusion/exclusion criteria, including 55 years or older and likely to benefit from a short-term rehabilitation programme: potential to improve, realistic, achievable goals, motivation to participate. Ninety-four people were recruited to the intervention and 112 to the control group. Details were collated of the NHS and Social Services resources participants used over a 12-month follow-up. The cost of the resource use was compared between those who went to the unit and those who went straight home. Overall, costs were very similar between the two groups. Aggregated mean NHS/Social Services costs for the 12 months of follow-up were pound 8542.28 for the intervention group and pound 8510.68 for the control. However, there was a clear 'seesaw' effect between the NHS and Social Services: the cost of the unit option fell more heavily on Social Services (pound 5011.56, whereas pound 3530.72 to the NHS), the community option more so on the NHS (pound 5146.74, whereas pound 3363.94 to Social Services). This suggests that residential rehabilitation for older people is no more cost-effective over a year after discharge from community hospital than usual community services. The variability in cost burden between the NHS and Social Services has implications for 'who pays' and being sure that agencies share both pain and gain.

OBJECT: the long-term success of spinal cord stimulation is impeded by the high incidence of adverse events. The cost of complications to the healthcare budget is influenced by the time course needed to reverse the effect, and by the type of corrective measures required. Understanding the mechanism of complications and reducing them can improve the overall success rate and the cost factor. METHODS: the authors performed a retrospective analysis of data obtained in 160 patients treated during a 10-year period. For each category of complication, the level of healthcare resource use was assessed for each case and a unit cost was applied. The total cost of each complication was determined by summing across healthcare resource headings. All cost calculations were performed in Canadian dollars at 2005 prices. To understand the mechanics of various hardware-related complications and how to avoid them, the authors have utilized the results of bench tests conducted at Medtronic, Inc. Fifty-one adverse events occurred in 42 of the 160 patients. The complications were classified as either hardware related (39 events) or biological (12 events). The mean cost of complications during the 10-year study period was dollar 7092 (range dollar 130 - dollar 22,406). CONCLUSIONS: Complications not only disrupt the effect of pain control but also pose an added expense to the already high cost of therapy. It is possible to reduce the complication rate, and thus improve the long-term success rate, by following the suggestions made in this paper, which are supported by the biomechanics of the human body and the implanted material.

Although neuropathic pain can be acute in nature, in most patients the pain is persistent (or "refractory"). Patients with chronic neuropathic pain are seen most often in clinical practice. It consists of a number of different disease-specific indications, each of which can have differing diagnostic definitions and cutoffs. Consequently, it is difficult to estimate precisely the prevalence and incidence of neuropathic pain. The limited currently available epidemiological literature is reviewed in this article. The burden of neuropathic pain on patients and healthcare systems appears to be potentially large, with an estimated prevalence of 1.5%. Patients with neuropathic pain experience a poor health-related quality of life and consume a high level of healthcare resources, and costs. The future prioritization by healthcare policy makers for neuropathic pain treatment funding requires further data to clarify its epidemiology, the burden on the health of patients, and the demand on healthcare budgets.

Faced with rapidly escalating costs, healthcare policy makers are increasingly turning to research evidence to serve as a basis for their population-based decisions on access and funding of new and existing therapies-health technology assessment. A two-stage approach is often used to arrive at a policy recommendation for a given treatment. First, following a systematic review of literature, the "level of evidence" for the treatment is assessed according to epidemiological principles. Then a grade of policy recommendation is provided based on both the level of evidence and the applicability of the evidence to current clinical practice. To assess the current evidence basis for refractory neuropathic pain, a comprehensive search was undertaken for systematic reviews of pharmacological interventions and interventional procedures (ie, spinal cord stimulation, therapeutic blocks, radiofrequency procedures, and surgery). of the 33 systematic reviews identified, the majority provided evidence for the use of drugs and spinal cord stimulation in the management of various neuropathic pain indications. Little evidence was found for either radiofrequency procedures or therapeutic blocks. By including randomized controlled trials, a number of these systematic reviews indicate a high grade of evidence. Nevertheless, more pragmatic clinical trials are needed to address the evidence needs of healthcare policy makers. These trials should address a direct comparison of the relative effectiveness of neuropathic pain therapies, particularly in combination with other therapies and at different points in the disease course.

BACKGROUND: to determine the effectiveness of home-based cardiac rehabilitation programmes compared with (i) usual care and (ii) supervised centre-based cardiac rehabilitation on mortality, health related quality of life and modifiable cardiac risk factors of patients with coronary heart disease. METHODS: Systematic review and meta-analysis of randomised controlled trials. MAIN OUTCOME MEASURES: mortality, smoking cessation, exercise capacity, systolic blood pressure, total cholesterol, psychological status, and health related quality of life. RESULTS: Eighteen included trials for home versus usual rehabilitation and six trials of home versus supervised centre-based rehabilitation were identified. The home-based interventions were clinically heterogeneous, trials often small, with quality poorly reported. Compared with usual care, home-based cardiac rehabilitation had a 4 mm Hg (95% CI 6.5, 1.5) greater reduction in systolic blood pressure, and a reduced relative risk of being a smoker at follow-up (RR 0.71, 95% CI 0.51, 1.00). Differences in exercise capacity, total cholesterol, anxiety and depression were all in favour of the home-based group. In patients post-myocardial infarction exercise capacity was significantly improved in the home rehabilitation group by 1.1 METS (95% CI 0.2, 2.1) compared to usual care. The comparison of home-based with supervised centre-based cardiac rehabilitation revealed no significant differences in exercise capacity, systolic blood pressure and total cholesterol. CONCLUSIONS: Current evidence does not show home-based cardiac rehabilitation to be significantly inferior to centre-based rehabilitation for low-risk cardiac patients. However, the numbers of patients included are less than 750 and ongoing trials will contribute to the debate on the acceptability, effectiveness and cost-effectiveness of home-based cardiac rehabilitation.

It is unclear how much of the reduction in cardiac mortality in coronary heart disease (CHD) patients with exercise training is the result of direct effects on the heart and coronary vasculature, or to indirect effects, via primary risk factors. The aim of this article was to quantify the cardiac mortality benefits of exercise-based rehabilitation attributable to risk factor reductions versus the direct effects on the heart and vasculature. The IMPACT coronary heart disease model was used to examine the reduction in cardiac mortality attributable to changes in risk factors from a meta-analysis of cardiac rehabilitation randomized, controlled trials. Patients were receiving rehabilitation following an acute myocardial infarction, angina pectoris or revascularization. Outcomes considered were primary risk factors (total cholesterol, systolic blood pressure and smoking behaviour) and cardiac mortality. Nineteen exercise-only cardiac rehabilitation trials (including 2984 patients) were identified. Across these trials, exercise training reduced pooled cardiac mortality by 28% (relative risk, 0.72, 95% confidence interval 0.55–0.95), with 30 fewer deaths than in the control group. Applying the CHD model, approximately 17 (58%) of these 30 fewer deaths were attributable to reductions in major cardiovascular risk factors: 7.1 deaths (minimum estimate 6.2, maximum estimate 9.5) attributable to an 18% reduction in smoking prevalence; 5.9 deaths (minimum −0.6, maximum 12.6) to a 0.11 mmol/l reduction in cholesterol, and 4.4 deaths (−1.0 minimum, 6.7 maximum) to a 2.0 mmHg reduction in systolic blood pressure. Approximately half of the 28% reduction in cardiac mortality achieved with exercise-based cardiac rehabilitation may be attributed to reductions in major risk factors, particularly smoking. © 2004, European Society of Cardiology. All rights reserved.

BACKGROUND: it is unclear how much of the reduction in cardiac mortality in coronary heart disease (CHD) patients with exercise training is the result of direct effects on the heart and coronary vasculature, or to indirect effects, via primary risk factors. OBJECTIVE: the aim of this article was to quantify the cardiac mortality benefits of exercise-based rehabilitation attributable to risk factor reductions versus the direct effects on the heart and vasculature. METHODS: the IMPACT coronary heart disease model was used to examine the reduction in cardiac mortality attributable to changes in risk factors from a meta-analysis of cardiac rehabilitation randomized, controlled trials. Patients were receiving rehabilitation following an acute myocardial infarction, angina pectoris or revascularization. Outcomes considered were primary risk factors (total cholesterol, systolic blood pressure and smoking behaviour) and cardiac mortality. RESULTS: Nineteen exercise-only cardiac rehabilitation trials (including 2984 patients) were identified. Across these trials, exercise training reduced pooled cardiac mortality by 28% (relative risk, 0.72, 95% confidence interval 0.55-0.95), with 30 fewer deaths than in the control group. Applying the CHD model, approximately 17 (58%) of these 30 fewer deaths were attributable to reductions in major cardiovascular risk factors: 7.1 deaths (minimum estimate 6.2, maximum estimate 9.5) attributable to an 18% reduction in smoking prevalence; 5.9 deaths (minimum -0.6, maximum 12.6) to a 0.11 mmol/l reduction in cholesterol, and 4.4 deaths (-1.0 minimum, 6.7 maximum) to a 2.0 mmHg reduction in systolic blood pressure. CONCLUSIONS: Approximately half of the 28% reduction in cardiac mortality achieved with exercise-based cardiac rehabilitation may be attributed to reductions in major risk factors, particularly smoking.

BACKGROUND: Children with congenital hearing impairment benefit from early detection and management of their hearing loss. These and related considerations led to the recommendation of universal newborn hearing screening. In 2001 the first phase of a national Newborn Hearing Screening Programme (NHSP) was implemented in England. Objective of this study was to assess costs and effectiveness for hospital and community-based newborn hearing screening systems in England based on data from this first phase with regard to the effects of alterations to parameter values. METHODS:. DESIGN: Clinical effectiveness analysis using a Markov Model. OUTCOME MEASURE: quality weighted detected child months (QCM). RESULTS: Both hospital and community programmes yielded 794 QCM at the age of 6 months with total costs of 3,690,000 pound sterling per 100,000 screened children in hospital and 3,340,000 pound sterling in community. Simulated costs would be lower in hospital in 48% of the trials. Any statistically significant difference between hospital and community in prevalence, test sensitivity, test specificity and costs would result in significant differences in cost-effectiveness between hospital and community. CONCLUSION: This modelling exercise informs decision makers by a quantitative projection of available data and the explicit and transparent statements about assumptions and the degree of uncertainty. Further evaluation of the cost-effectiveness should focus on the potential differences in test parameters and prevalence in these two settings.

The drive for good quality evidence has highlighted the importance of well-conducted systematic reviews and meta-analyses that critically evaluate and grade studies for new or existing therapies. A systematic review and meta-analysis was performed to review the efficacy, safety, and cost effectiveness of spinal cord stimulation (SCS) in complex regional pain syndrome (CRPS) and refractory neuropathic back and leg pain/failed back surgery syndrome (FBSS). The results support the use of SCS in patients with refractory neuropathic back and leg pain/FBSS (Grade B evidence) and CRPS type I (Grade a evidence)/type II (Grade D evidence). SCS not only reduces pain, improves quality of life, reduces analgesic consumption, and allows some patients to return to work, with minimal significant adverse events, but may also result in significant cost savings over time. © 2006 U.S. Cancer Pain Relief Committee.

OBJECTIVE: to review the clinical and cost-effectiveness of spinal cord stimulation (SCS) in the management of patients with complex regional pain syndrome (CRPS) and identify the potential predictors of SCS outcome. DESIGN: Systematic review of the literature and meta-regression. METHODS: Electronic databases were searched for controlled and uncontrolled studies and economic evaluations relating to the use of SCS in patients with either CRPS type I or II. RESULTS: One randomised controlled trial, 25 case series and one cost-effectiveness study were included. In the randomised controlled trial in type I CRPS patients, SCS therapy lead to a reduction in pain intensity at 24 months of follow-up (mean change in VAS score -2.0), whereas pain was unchanged in the control group (mean change in VAS score 0.0) (p

The drive for good quality evidence has highlighted the importance of well-conducted systematic reviews and meta-analyses that critically evaluate and grade studies for new or existing therapies. A systematic review and meta-analysis was performed to review the efficacy, safety, and cost effectiveness of spinal cord stimulation (SCS) in complex regional pain syndrome (CRPS) and refractory neuropathic back and leg pain/failed back surgery syndrome (FBSS). The results support the use of SCS in patients with refractory neuropathic back and leg pain/FBSS (Grade B evidence) and CRPS type I (Grade a evidence)/type II (Grade D evidence). SCS not only reduces pain, improves quality of life, reduces analgesic consumption, and allows some patients to return to work, with minimal significant adverse events, but may also result in significant cost savings over time.

BACKGROUND: Physical activity may be associated with reduced risk of colorectal cancer. The main aim of this paper is to review the available evidence for a link between exercise and large bowel cancer. METHODS: a Cochrane-type methodology was performed. Data extracted included, type of study, type of physical activity measured and the numerical results. The risk ratios (RR) of the studies have been pooled according to the type of study, type of exercise, type of cancer and sex. Pooling was undertaken using fixed effect meta-analysis. A random effect meta-analysis was used where substantial heterogeneity existed. RESULT: Data from 19 cohort studies showed a statistically significant reduction in the risk of colon cancer in physically active males, RR being 0.79 (95% CI 0.72-0.87) and 0.78 (95% CI 0.68-0.91) for occupational and recreational activities, respectively. In women only recreational activities are protective against colon cancer (RR = 0.71, 95%CI 0.57-0.88). Case-control studies showed significantly reduced risks of colon cancer in both sexes irrespective of the type of activity. No protection against rectal cancer is seen in either sex. CONCLUSION: There is considerable evidence that physical activity is associated with reduced risk of colon cancer in both males and females.

Objectives: to examine the clinical effectiveness and cost-effectiveness of the newer immunosuppressive drugs for renal transplantation: basiliximab, daclizumab, tacrolimus, mycophenolate (mofetil and sodium) and sirolimus. Data sources: Electronic databases. Industry submissions. Current Clinical Trials register. Cochrane Collaboration Renal Disease Group. Review methods: the review followed the InterTASC standards. Each of the five company submissions to the National Institute for Clinical Excellence (NICE) contained cost-effectiveness models, which were evaluated by using a critique covering (1) model checking, (2) a detailed model description and (3) model rerunning. Results: for induction therapy, three randomised controlled trials (RCTs) found that daclizumab significantly reduced the incidence of biopsy-confirmed acute rejection and patient survival at 6 months/1 year compared with placebo, but not compared with the monoclonal antibody OKT3. There was no significant gain in patient survival or graft loss at 3 years. The incidence of side-effects with daclizumab reduced compared to OKT3. Eight RCTs found that basiliximab significantly improved 6-month/1-year biopsy-confirmed acute rejection compared to placebo, but not compared to either ATG or OKT3. There was no significant gain in either 1-year patient survival or graft loss. The incidence of side-effects with basiliximab was not significantly different compared to OKT3/ATG. For initial/maintenance therapy, 13 RCTs found that tacrolimus reduced the 6-month/1-year incidence of biopsy-proven acute rejection compared to ciclosporin. There was no significant improvement in either 1-year or long-term (up to 5 years) graft loss or patient survival. The acute rejection benefit of tacrolimus over ciclosporin appeared to be equivalent for Sandimmun and Neoral. There were important differences in the side-effect profile of tacrolimus and ciclosporin. Seven RCTs found that mycophenolate mofetil (MMF) reduced the incidence of acute rejection. There was no significant difference in patient survival or graft loss at 1-year or 3-year follow-up. There appeared to be differences in the side-effect profiles of MMF and azathioprine (AZA). No RCTs comparing MMF with AZA were identified. One RCT compared mycophenolate sodium (MPS) to MMF and reported no difference between the two drugs in 1-year acute rejection rate, graft survival, patient survival or side-effect profile. Two RCTs suggest that addition of sirolimus to a ciclosporin-based initial/maintenance therapy reduces 1-year acute rejections in comparison to a ciclosporin (Neoral) dual therapy alone and substituting azathioprine with sirolimus in initial/maintenance therapy reduces the incidence of acute rejection. Graft and patient survival were not significantly different with either sirolimus regimen. Adding sirolimus increases the incidence of side-effects. The side-effect profiles of azathioprine and sirolimus appear to be different. For the treatment of acute rejection, three RCTs suggested that both tacrolimus and MMF reduce the incidence of subsequent acute rejection and the need for additional drug therapy. Only one RCT and one subgroup analysis in children ( <. 18 years) were identified comparing ciclosporin to tacrolimus and sirolimus, respectively. Conclusions: the newer immunosuppressant drugs (basiliximab, daclizumab, tacrolimus and MMF) consistently reduced the incidence of short-term (1-year) acute rejection compared with conventional immunosuppressive therapy. The independent use of basiliximab, daclizumab, tacrolimus and MMF was associated with a similar absolute reduction in 1-year acute rejection rate (approximately 15%). However, the effects of these drugs did not appear to be additive (e.g. benefit of tacrolimus with adjuvant MMF was 5% reduction in acute rejection rate compared with 15% reduction with adjuvant AZA). Thus, the addition of one of these drugs to a baseline immunosuppressant regimen was likely to affect adversely the incremental cost-effectiveness of the addition of another. The trials did not assess how the improvement in short-term outcomes (e.g. acute rejection rate or measures of graft function), together with the side-effect profile associated with each drug, translated into changes in patient-related quality of life. Moreover, given the relatively short duration of trials, the impact of the newer immunosuppressants on long-term graft loss and patient survival remains uncertain. The absence of both long-term outcome and quality of life from trial data makes assessment of the clinical and cost-effectiveness on the newer immunosuppressants contingent on modelling based on extrapolations from short-term trial outcomes. The choice of the most appropriate short-term outcome (e.g. acute rejection rate or measures of graft function) for such modelling remains a matter of clinical and scientific debate. The decision to use acute rejection in the meta-model in this report was based on the findings of a systematic review of the literature of predictors of long-term graft outcome. Only a very small proportion of the RCTs identified in this review assessed patient-focused outcomes such as quality of life. Since immunosuppressive drugs have both clinical benefits and specific side-effects, the balance of these harms and benefits could best be quantified through future trials using quality of life measures. The design of future trials should be considered with a view to the impact of drugs on particular renal transplant groups, particularly higher risk individuals and children. Finally there is a need for improved reporting of methodological details of future trials, such as the method of randomisation and allocation concealment. A number of issues exist around registry data, for example the use of multiple drug regimens and the need to assess the long-term outcomes. An option is the use of observational registry data including, if possible, prospective data on all consecutive UK renal transplant patients. Data capture for each patient should include immunosuppressant regimens, clinical and patient-related outcomes and patient demographics. © Queen's Printer and Controller of HMSO 2005. All rights reserved.

Objectives: to examine the clinical effectiveness and cost-effectiveness of the newer immunosuppressive drugs for renal transplantation: basiliximab, daclizumab, tacrolimus, mycophenolate (mofetil and sodium) and sirolimus. Data sources: Electronic databases. Industry submissions. Current Clinical Trials register. Cochrane Collaboration Renal Disease Group. Review methods: the review followed the InterTASC standards. Each of the five company submissions to the National Institute for Clinical Excellence (NICE) contained cost-effectiveness models, which were evaluated by using a critique covering (1) model checking, (2) a detailed model description and (3) model rerunning. Results: for induction therapy, three randomised controlled trials (RCTs) found that daclizumab significantly reduced the incidence of biopsy-confirmed acute rejection and patient survival at 6 months/1 year compared with placebo, but not compared with the monoclonal antibody OKT3. There was no significant gain in patient survival or graft loss at 3 years. The incidence of side-effects with daclizumab reduced compared to OKT3. Eight RCTs found that basiliximab significantly improved 6-month/1-year biopsy-confirmed acute rejection compared to placebo, but not compared to either ATG or OKT3. There was no significant gain in either 1-year patient survival or graft loss. The incidence of side-effects with basiliximab was not significantly different compared to OKT3/ATG. For initial/maintenance therapy, 13 RCTs found that tacrolimus reduced the 6-month/1-year incidence of biopsy-proven acute rejection compared to ciclosporin. There was no significant improvement in either 1-year or long-term (up to 5 years) graft loss or patient survival. The acute rejection benefit of tacrolimus over ciclosporin appeared to be equivalent for Sandimmun and Neoral. There were important differences in the side-effect profile of tacrolimus and ciclosporin. Seven RCTs found that mycophenolate mofetil (MMF) reduced the incidence of acute rejection. There was no significant difference in patient survival or graft loss at 1-year or 3-year follow-up. There appeared to be differences in the side-effect profiles of MMF and azathioprine (AZA). No RCTs comparing MMF with AZA were identified. One RCT compared mycophenolate sodium (MPS) to MMF and reported no difference between the two drugs in 1-year acute rejection rate, graft survival, patient survival or side-effect profile. Two RCTs suggest that addition of sirolimus to a ciclosporin-based initial/maintenance therapy reduces 1-year acute rejections in comparison to a ciclosporin (Neoral) dual therapy alone and substituting azathioprine with sirolimus in initial/maintenance therapy reduces the incidence of acute rejection. Graft and patient survival were not significantly different with either sirolimus regimen. Adding sirolimus increases the incidence of side-effects. The side-effect profiles of azathioprine and sirolimus appear to be different. For the treatment of acute rejection, three RCTs suggested that both tacrolimus and MMF reduce the incidence of subsequent acute rejection and the need for additional drug therapy. Only one RCT and one subgroup analysis in children (< 18 years) were identified comparing ciclosporin to tacrolimus and sirolimus, respectively. Conclusions: the newer immunosuppressant drugs (basiliximab, daclizumab, tacrolimus and MMF) consistently reduced the incidence of short-term (1-year) acute rejection compared with conventional immunosuppressive therapy. The independent use of basiliximab, daclizumab, tacrolimus and MMF was associated with a similar absolute reduction in 1-year acute rejection rate (approximately 15%). However, the effects of these drugs did not appear to be additive (e.g. benefit of tacrolimus with adjuvant MMF was 5% reduction in acute rejection rate compared with 15% reduction with adjuvant AZA). Thus, the addition of one of these drugs to a baseline immunosuppressant regimen was likely to affect adversely the incremental cost-effectiveness of the addition of another. The trials did not assess how the improvement in short-term outcomes (e.g. acute rejection rate or measures of graft function), together with the side-effect profile associated with each drug, translated into changes in patient-related quality of life. Moreover, given the relatively short duration of trials, the impact of the newer immunosuppressants on long-term graft loss and patient survival remains uncertain. The absence of both long-term outcome and quality of life from trial data makes assessment of the clinical and cost-effectiveness on the newer immunosuppressants contingent on modelling based on extrapolations from short-term trial outcomes. The choice of the most appropriate short-term outcome (e.g. acute rejection rate or measures of graft function) for such modelling remains a matter of clinical and scientific debate. The decision to use acute rejection in the meta-model in this report was based on the findings of a systematic review of the literature of predictors of long-term graft outcome. Only a very small proportion of the RCTs identified in this review assessed patient-focused outcomes such as quality of life. Since immunosuppressive drugs have both clinical benefits and specific side-effects, the balance of these harms and benefits could best be quantified through future trials using quality of life measures. The design of future trials should be considered with a view to the impact of drugs on particular renal transplant groups, particularly higher risk individuals and children. Finally there is a need for improved reporting of methodological details of future trials, such as the method of randomisation and allocation concealment. A number of issues exist around registry data, for example the use of multiple drug regimens and the need to assess the long-term outcomes. An option is the use of observational registry data including, if possible, prospective data on all consecutive UK renal transplant patients. Data capture for each patient should include immunosuppressant regimens, clinical and patient-related outcomes and patient demographics. © Queen's Printer and Controller of HMSO 2005. All rights reserved.

OBJECTIVES: to examine the clinical effectiveness and cost-effectiveness of the newer immunosuppressive drugs for renal transplantation: basiliximab, daclizumab, tacrolimus, mycophenolate (mofetil and sodium) and sirolimus. DATA SOURCES: Electronic databases. Industry submissions. Current Clinical Trials register. Cochrane Collaboration Renal Disease Group. REVIEW METHODS: the review followed the InterTASC standards. Each of the five company submissions to the National Institute for Clinical Excellence (NICE) contained cost-effectiveness models, which were evaluated by using a critique covering (1) model checking, (2) a detailed model description and (3) model rerunning. RESULTS: for induction therapy, three randomised controlled trials (RCTs) found that daclizumab significantly reduced the incidence of biopsy-confirmed acute rejection and patient survival at 6 months/1 year compared with placebo, but not compared with the monoclonal antibody OKT3. There was no significant gain in patient survival or graft loss at 3 years. The incidence of side-effects with daclizumab reduced compared to OKT3. Eight RCTs found that basiliximab significantly improved 6-month/1-year biopsy-confirmed acute rejection compared to placebo, but not compared to either ATG or OKT3. There was no significant gain in either 1-year patient survival or graft loss. The incidence of side-effects with basiliximab was not significantly different compared to OKT3/ATG. For initial/maintenance therapy, 13 RCTs found that tacrolimus reduced the 6-month/1-year incidence of biopsy-proven acute rejection compared to ciclosporin. There was no significant improvement in either 1-year or long-term (up to 5 years) graft loss or patient survival. The acute rejection benefit of tacrolimus over ciclosporin appeared to be equivalent for Sandimmun and Neoral. There were important differences in the side-effect profile of tacrolimus and ciclosporin. Seven RCTs found that mycophenolate mofetil (MMF) reduced the incidence of acute rejection. There was no significant difference in patient survival or graft loss at 1-year or 3-year follow-up. There appeared to be differences in the side-effect profiles of MMF and azathioprine (AZA). No RCTs comparing MMF with AZA were identified. One RCT compared mycophenolate sodium (MPS) to MMF and reported no difference between the two drugs in 1-year acute rejection rate, graft survival, patient survival or side-effect profile. Two RCTs suggest that addition of sirolimus to a ciclosporin-based initial/maintenance therapy reduces 1-year acute rejections in comparison to a ciclosporin (Neoral) dual therapy alone and substituting azathioprine with sirolimus in initial/maintenance therapy reduces the incidence of acute rejection. Graft and patient survival were not significantly different with either sirolimus regimen. Adding sirolimus increases the incidence of side-effects. The side-effect profiles of azathioprine and sirolimus appear to be different. For the treatment of acute rejection, three RCTs suggested that both tacrolimus and MMF reduce the incidence of subsequent acute rejection and the need for additional drug therapy. Only one RCT and one subgroup analysis in children (

AIMS: This paper presents a comprehensive systematic review of literature carried out to identify studies of interventions to improve uptake, adherence and professional compliance in cardiac rehabilitation. BACKGROUND: Guidelines recommend that cardiac rehabilitation should be offered to patients following acute myocardial infarction and revascularization. Uptake and adherence are low, particularly in women, older people, and socially deprived and ethnic minority patients. Although patient, service and professional barriers to rehabilitation uptake have been described, no attempt has been made to evaluate systematically interventions aimed at improving uptake and adherence in cardiac rehabilitation. METHODS: a comprehensive search strategy identified studies of cardiac rehabilitation, using the terms uptake, adherence and compliance. The search included grey literature, hand searching of specialist journals and conference abstracts. No language restriction was applied. Studies were summarized in three qualitative overviews and assessed by quality of evidence. RESULTS: from 3261 publications identified, 957 were acquired on the basis of title or abstract. Few studies were of sufficient quality to make specific recommendations. Six, 12 and five studies, respectively, provided adequate information on methods to improve uptake, adherence or professional compliance. A minority of studies were randomized controlled trials. Studies of motivational and self-management strategies and use of lay volunteers showed some promise in improving rehabilitation uptake or lifestyle change. Nurse-led coordination of care after hospital discharge may have a role in improving rehabilitation uptake. Limited information was provided on resource implications, and there was a lack of studies with under-represented groups. The literature contained numerous suggested interventions which merit evaluation in appropriately designed studies. CONCLUSIONS: Little research has been reported evaluating interventions to improve uptake, adherence and professional compliance in cardiac rehabilitation. A wide range of possible interventions was identified and further evaluations of methods are indicated.

Background - Chronic heart failure (CHF) is a major cause of morbidity and mortality that requires a novel approach to therapy. Perhexiline is an antianginal drug that augments glucose metabolism by blocking muscle mitochondrial free fatty acid uptake, thereby increasing metabolic efficiency. We assessed the effects of perhexiline treatment in CHF patients. Methods and Results - in a double-blind fashion, we randomly assigned patients with optimally medicated CHF to either perhexiline (n=28) or placebo (n=28). The primary end point was peak exercise oxygen consumption (V̇O 2max), an important prognostic marker. In addition, the effect of perhexiline on myocardial function and quality of life was assessed. Quantitative stress echocardiography with tissue Doppler measurements was used to assess regional myocardial function in patients with ischemic CHF. 31P magnetic resonance spectroscopy was used to assess the effect of perhexiline on skeletal muscle energetics in patients with nonischemic CHF. Treatment with perhexiline led to significant improvements in V̇O 2max (16.1±0.6 to 18.8±1.1 mL·kg -1·min -1; P

Chronic heart failure (CHF) is a common condition and is associated with excess morbidity and mortality, in spite of the many advances in its treatment. Chronic stable heart failure is also associated with an increased incidence of sleep-related breathing disorders, such as central sleep apnoea (CSA) and Cheyne Stokes respiration (CSR). Continuous positive airways pressure (CPAP) has been shown to alleviate the symptoms of CHF, improve left ventricular function and oxygenation. To a certain extent, CPAP also abolishes sleep-related breathing disorders in patients with chronic heart failure. In patients with acute pulmonary oedema, the use of positive pressure ventilation improves cardiac haemodynamic indices, as well as symptoms and oxygenation, and is associated with a lower need for intubation. However, some studies have cast doubts about its safety and suggest a higher rate of myocardial infarction associated with its use. In our opinion, non-invasive positive pressure ventilation and CPAP offers an adjunctive mode of therapy in patients with acute pulmonary oedema and chronic heart failure, who may not be suitable for intubation and in those not responsive to conventional therapies. Non-invasive ventilation also helps to improve oxygenation in those patients with exhaustion and respiratory acidosis. Many trials are still ongoing and the results of these studies would throw more light on the present role of non-invasive ventilation in the management of CHF.

BACKGROUND: Concerns have been raised about low participation rates of people from minority ethnic groups in clinical trials. However, the evidence is unclear as many studies do not report the ethnicity of participants and there is insufficient information about the reasons for ineligibility by ethnic group. Where there are data, there remains the key question as to whether ethnic minorities more likely to be ineligible (e.g. due to language) or decline to participate. We have addressed these questions in relation to the Birmingham Rehabilitation Uptake Maximisation (BRUM) study, a randomized controlled trial (RCT) comparing a home-based with a hospital-based cardiac rehabilitation programme in a multi-ethnic population in the UK. METHODS: Analysis of the ethnicity, age and sex of presenting and recruited subjects for a trial of cardiac rehabilitation in the West-Midlands, UK. PARTICIPANTS: 1997 patients presenting post-myocardial infarction, percutaneous transluminal coronary angioplasty or coronary artery bypass graft surgery. DATA COLLECTED: Exclusion rates, reasons for exclusion and reasons for declining to participate in the trial by ethnic group. RESULTS: Significantly more patients of South Asian ethnicity were excluded (52% of 'South Asian' v 36% 'White European' and 36% 'Other', p < 0.001). This difference in eligibility was primarily due to exclusion on the basis of language (i.e. the inability to speak English or Punjabi). of those eligible, similar proportions were recruited from the different ethnic groups (white, South Asian and other). There was a marked difference in eligibility between people of Indian, Pakistani or Bangladeshi origin. CONCLUSION: Once eligible for this trial, people from different ethnic groups were recruited in similar proportions. The reason for ineligibility in the BRUM study was the inability to support the range of minority languages.

OBJECTIVES: Are behavioural interventions effective in reducing the rate of sexually transmitted infections (STIs) among genitourinary medicine (GUM) clinic patients? DESIGN: Systematic review and meta-analysis of published articles. DATA SOURCES: Medline, CINAHL, Embase, PsychINFO, Applied Social Sciences Index and Abstracts, Cochrane Library Controlled Clinical Trials Register, National Research Register (1966 to January 2004). REVIEW METHODS: Randomised controlled trials of behavioural interventions in sexual health clinic patients were included if they reported change to STI rates or self reported sexual behaviour. Trial quality was assessed using the Jadad score and results pooled using random effects meta-analyses where outcomes were consistent across studies. RESULTS: 14 trials were included; 12 based in the United States. Experimental interventions were heterogeneous and most control interventions were more structured than typical UK care. Eight trials reported data on laboratory confirmed infections, of which four observed a greater reduction in their intervention groups (in two cases this result was statistically significant, p < 0.05). Seven trials reported consistent condom use, of which six observed a greater increase among their intervention subjects. Results for other measures of sexual behaviour were inconsistent. Success in reducing STIs was related to trial quality, use of social cognition models, and formative research in the target population. However, effectiveness was not related to intervention format or length. CONCLUSIONS: While results were heterogeneous, several trials observed reductions in STI rates. The most effective interventions were developed through extensive formative research. These findings should encourage further research in the United Kingdom where new approaches to preventing STIs are urgently required.

Previously, we reported significantly reduced pain and improved mobility persisting for 6 months after kyphoplasty of chronically painful osteoporotic vertebral fractures in the first prospective controlled trial. Since improvement of spinal biomechanics by restoration of vertebral morphology may affect the incidence of fracture, long-term clinical benefit and thereby cost-effectiveness, here we extend our previous work to assess occurrence of new vertebral fractures and clinical parameters 1 year after kyphoplasty compared with a conservatively treated control group. Sixty patients with osteoporotic vertebral fractures due to primary osteoporosis were included: 40 patients were treated with kyphoplasty, 20 served as controls. All patients received standard medical treatment. Morphological characteristics, new vertebral fractures, pain (visual analog scale), physical function [European Vertebral Osteoporosis Study (EVOS) score] (range 0-100 each) and back-pain-related doctors' visits were re-assessed 12 months after kyphoplasty. There were significantly fewer patients with new vertebral fractures of the thoracic and lumbar spine, after 12-months, in the kyphoplasty group than in the control group (P=0.0084). Pain scores improved from 26.2 to 44.4 in the kyphoplasty group and changed from 33.6 to 34.3 in the control group (P=0.008). Kyphoplasty treated patients required a mean of 5.3 back-pain-related doctors' visits per patient compared with 11.6 in the control group during 12 months follow-up (P=0.006). Kyphoplasty as an addition to medical treatment and when performed in appropriately selected patients by an interdisciplinary team persistently improves pain and reduces occurrence of new vertebral fractures and healthcare utilization for at least 12 months in individuals with primary osteoporosis.

BACKGROUND: There is widespread use of peak flow meters in both hospitals and general practice. Previous studies to assess peak flow meter accuracy have shown significant differences in the values obtained from different meters. However, many of these studies did not use human subjects for peak flow measurements and did not compare meters of varying usage. In this study human subjects have been used with meters of varying usage. METHODS: Participants were tested using two new (meters a and C) and one old peak flow meter (meter B) in random order. The study was double-blinded. Participants were recruited from the university campus. RESULTS: Four hundred and nine individuals participated. The difference between peak flow means of a and B was -9.93 l/min (95% CI: -12.37 to -7.48, P

Introduction.  Since its first application in 1967, numerous case series indicate that spinal cord stimulation (SCS) is an effective treatment for the management of failed back surgery syndrome (FBSS). However, only one randomized controlled trial has demonstrated that SCS provides more effective pain relief than re-operation and conventional medical management. The PROCESS randomized, controlled, multicenter trial aims to assess the clinical effectiveness and cost-effectiveness of SCS when added to conventional medical management compared to conventional medical management alone in patients with FBSS. Methods/Design.  a total of 100 FBSS patients with predominantly neuropathic leg pain will be recruited from 12 centers and randomized to receive either conventional medical management alone or in combination with SCS for a period of 24 months. Patients will be evaluated at 1, 3, 6, 9, 12, 18, and 24 months. At the 6-month visit, patients will be classified as successful (≥  50% pain relief in the legs) or unsuccessful (

STUDY DESIGN: Systematic review. OBJECTIVES: to assess efficacy and safety of spinal cord stimulation in patients with chronic leg and back pain and failed back surgery syndrome and to examine prognostic factors that predict spinal cord stimulation outcome. SUMMARY OF BACKGROUND DATA: a previous systematic review of spinal cord stimulation in patients with chronic back and leg pain and failed back surgery syndrome by Turner et al in 1995 identified 39 case studies and no controlled studies. METHODS: a number of electronic databases were searched through January 2002. Citation searching of included papers was undertaken, and gray literature was sought through contact with clinical experts. No language restrictions were applied. All controlled and noncontrolled study designs were included. Study selection was carried out independently by two reviewers. Prognostic factors (age, sex, duration of pain, time post surgery, follow-up duration, publication year, data collection year, indication, data collection country, study setting, and quality score) responsible for pain relief outcome across case series were examined using univariate and multivariate metaregression. RESULTS: One randomized controlled trial, one cohort study, and 72 case studies were included. The randomized controlled trial reported a significant benefit (P = 0.047) in the proportion of patients with failed back surgery syndrome reporting 50% or more pain relief with spinal cord stimulation (37.5%) compared with patients undergoing back reoperation (11.5%). There was evidence of substantial statistical heterogeneity (P < 0.0001) in the level of pain relief following spinal cord stimulation reported across case series studies. The four principal prognostic factors found to be predictive of increased level of pain relief with spinal cord stimulation were poor study quality score, short follow-up duration, multicenter (versus single center) studies, and the inclusion of patients with failed back surgery syndrome (versus chronic back and leg pain). Overall, 43% of patients with chronic back and leg pain/failed back surgery syndrome experienced one or more complications following a spinal cord stimulation implant, although no major adverse events were reported. CONCLUSIONS: Despite an increase in the number of studies over the last 10 years, the level of evidence for the efficacy of spinal cord stimulation in chronic back and leg pain/failed back surgery syndrome remains "moderate." Prognostic factors found to be predictive of the level of pain relief following spinal cord stimulation were study quality, follow-up duration, study setting, and patient indication.

OBJECTIVES: the aim of this study was to develop a decision-analytic model to assess the cost-effectiveness of spinal cord stimulation (SCS), relative to nonsurgical conventional medical management (CMM), for patients with failed back surgery syndrome (FBSS). METHODS: a decision tree and Markov model were developed to synthesize evidence on both health-care costs and outcomes for patients with FBSS. Outcome data of SCS and CMM were sourced from 2-year follow-up data of two randomized controlled trials (RCTs). Treatment effects were measured as levels of pain relief. Short- and long-term health-care costs were obtained from a detailed Canadian costing study in FBSS patients. Results are presented as incremental cost per quality adjusted life year (QALY) and expressed in 2003 Euros. Costs were discounted at 6 percent and outcomes at 1.5 percent. RESULTS: over the lifetime of the patient, SCS was dominant (i.e. SCS is cost-saving and gives more health gain relative to CMM); a finding that was robust across sensitivity analyses. At a 2-year time horizon, SCS gave more health gain but at an increased cost relative to CMM. Given the uncertainty in effectiveness and cost parameters, the 2-year cost-effectiveness of SCS ranged from 30,370 Euros in the base case to 63,511 Euros in the worst-case scenario. CONCLUSIONS: SCS was found to be both more effective and less costly than CMM, over the lifetime of a patient. In the short-term, although SCS is potentially cost-effective, the model results are highly sensitive to the choice of input parameters. Further empirical data are required to improve the precision in the estimation of short-term cost-effectiveness.

OBJECTIVE: to compare the positive and negative effects of tacrolimus and ciclosporin as initial treatment for renal transplant recipients. DESIGN: Systematic review. DATA SOURCES AND STUDY SELECTION: Reports of comparative randomised trials of tacrolimus and ciclosporin identified by searches of Medline, Embase, the Cochrane Register of Controlled Trials, the Cochrane Renal Group Specialist Register, and conference proceedings. DATA EXTRACTION AND SYNTHESIS: Two reviewers assessed trials for eligibility and quality and extracted data independently. Data were synthesised (random effects model) and results expressed as relative risk (RR), with values < 1 favouring tacrolimus. Subgroup analysis and meta-regression were used to examine potential effect modification by differences in trial design and immunosuppressive co-interventions. RESULTS: 123 reports from 30 trials (4102 patients) were included. At six months, graft loss was significantly reduced in tacrolimus treated recipients (RR = 0.56, 95% confidence interval 0.36 to 0.86), and this effect persisted up to three years. The relative reduction in graft loss with tacrolimus diminished with higher concentrations of tacrolimus (P = 0.04) but did not vary with ciclosporin formulation (P = 0.97) or ciclosporin concentration (P = 0.38). At one year, tacrolimus treated patients had less acute rejection (RR = 0.69, 0.60 to 0.79) and less steroid resistant rejection (RR = 0.49, 0.37 to 0.64) but more diabetes mellitus requiring insulin (RR = 1.86, 1.11 to 3.09), tremor, headache, diarrhoea, dyspepsia, and vomiting. The relative excess of diabetes increased with higher concentrations of tacrolimus (P = 0.003). Ciclosporin treated recipients had significantly more constipation and cosmetic side effects. No differences were seen in infection or malignancy. CONCLUSIONS: Treating 100 recipients with tacrolimus instead of ciclosporin for the first year after transplantation avoids 12 patients having acute rejection and two losing their graft but causes an extra five patients to develop insuli