BACKGROUND: Major depression represents a pressing challenge for health care. In England, Increasing Access to Psychological Therapies (IAPT) services provide evidence-based psychological therapies in a stepped-care approach to patients with depression. While introduction of these services has successfully increased access to therapy, estimates suggest that about 50% of depressed patients who have come to the end of the IAPT pathway still show significant levels of symptoms. This study will investigate whether Mindfulness-Based Cognitive Therapy (MBCT), a group intervention combining training in mindfulness meditation and elements from cognitive therapy, can have beneficial effects in depressed patients who have not responded to high-intensity therapy in IAPT. It will seek to establish the effectiveness and cost-effectiveness of MBCT as compared to the treatment these patients would usually receive. METHODS: in a 2-arm randomised controlled trial, patients who currently meet the criteria for major depressive disorder and who have not sufficiently responded to at least 12 sessions of IAPT high-intensity therapy will be allocated, at a ratio of 1:1, to receive either MBCT (in addition to treatment as usual [TAU]) or continue with TAU only. Assessments will take place at baseline, 10 weeks and 34 weeks post-randomisation. The primary outcome will be reduction in depression symptomatology 34 weeks post-randomisation as assessed using the Public Health Questionnaire-9 (PHQ-9). Secondary outcomes will include depressive symptomatology at 10 weeks post-randomisation and other clinical outcomes measured at 10-week and 34-week follow-up, along with a series of binarised outcomes to indicate clinically significant and reliable change. Evaluations of cost-effectiveness will be based on assessments of service use costs collected using the Adult Service Use Schedule and health utilities derived from the EQ-5D. DISCUSSION: This trial will add to the evidence base for the use of MBCT in depressed treatment non-responders. It will constitute the first trial to test MBCT following non-response to psychological therapy, with results providing a direct estimate of efficacy within the IAPT pathway. As such, its results will offer an important basis for decisions regarding the adoption of MBCT for non-responders within IAPT. TRIAL REGISTRATION: ClinicalTrials.gov NCT05236959. Registered on 11 February 2022. ISRCTN 17755571. Registered on 2 February 2021.

INTRODUCTION: Medical patients, admitted acutely to hospital, are at risk of venous thromboembolism (VTE). Clinical guidelines advise thromboprophylaxis prophylaxis for those at high risk of VTE. VTE is a common sequela of cancer, but guidelines take little consideration of cancer as an independent risk factor and their utility in palliative care patients is unclear. The hospice inpatient deep vein thrombosis (DVT) detection study (HIDDen) reported a 28% prevalence of asymptomatic iliofemoral DVT in hospice patients of poor performance status (PS) and prognosis, calling into question the utility of thromboprophylaxis in the palliative care setting. However, the majority of cancer inpatients receiving palliative care are admitted to hospital through the acute medical setting, yet their risk factors for VTE may differ from those admitted to hospices. OBJECTIVE: to better understand the prevalence and behaviours of VTE in patients with cancer receiving palliative care who are admitted as an acute medical emergency. DESIGN: Multicentre, observational cohort study. SETTING: Secondary care acute hospitals in South Wales, UK. PATIENTS: We plan to recruit 232 patients≥18 years old with a diagnosis of incurable cancer, and/or receiving palliative or best supportive care who are admitted acutely to hospital. Patients will be followed up for a maximum of 6 months following registration. PRIMARY OUTCOME: Presence of lower extremity DVT. SECONDARY OUTCOMES: Symptom burden attributed to DVT or pulmonary embolism, patient PS, patient demographics and development of new VTE within 90 days of registration. ANALYSIS: the study statistical analysis plan will document analysis, methodology and procedures. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Wales Research Ethics Committee, reference 22/WA/0037 (IRAS 306352)-the main trial results will be analysed as soon as practically possible and the publication shared with investigators and on sponsor website; applications to access trial data will be subject to sponsor review process.

ObjectivesTo describe self-reported characteristics and symptoms of treatment-seeking patients with post-COVID-19 syndrome (PCS). To assess the impact of symptoms on health-related quality of life (HRQoL) and patients’ ability to work and undertake activities of daily living.DesignCross-sectional single-arm service evaluation of real-time user data.Setting31 post-COVID-19 clinics in the UK.Participants3754 adults diagnosed with PCS in primary or secondary care deemed suitable for rehabilitation.InterventionPatients using the Living with Covid Recovery digital health intervention registered between 30 November 2020 and 23 March 2022.Primary and secondary outcome measuresThe primary outcome was the baseline Work and Social Adjustment Scale (WSAS). WSAS measures the functional limitations of the patient; scores of ≥20 indicate moderately severe limitations. Other symptoms explored included fatigue (Functional Assessment of Chronic Illness Therapy–Fatigue), depression (Patient Health Questionnaire–Eight Item Depression Scale), anxiety (Generalised Anxiety Disorder Scale, Seven-Item), breathlessness (Medical Research Council Dyspnoea Scale and Dyspnoea-12), cognitive impairment (Perceived Deficits Questionnaire, Five-Item Version) and HRQoL (EQ-5D). Symptoms and demographic characteristics associated with more severe functional limitations were identified using logistic regression analysis.Results3541 (94%) patients were of working age (18-65); mean age (SD) 48 (12) years; 1282 (71%) were female and 89% were white. 51% reported losing ≥1 days from work in the previous 4 weeks; 20% reported being unable to work at all. Mean WSAS score at baseline was 21 (SD 10) with 53% scoring ≥20. Factors associated with WSAS scores of ≥20 were high levels of fatigue, depression and cognitive impairment. Fatigue was found to be the main symptom contributing to a high WSAS score.ConclusionA high proportion of this PCS treatment-seeking population was of working age with over half reporting moderately severe or worse functional limitation. There were substantial impacts on ability to work and activities of daily living in people with PCS. Clinical care and rehabilitation should address the management of fatigue as the dominant symptom explaining variation in functionality.

IntroductionLong COVID-19 is a distressing, disabling and heterogeneous syndrome often causing severe functional impairment. Predominant symptoms include fatigue, cognitive impairment (‘brain fog’), breathlessness and anxiety or depression. These symptoms are amenable to rehabilitation delivered by skilled healthcare professionals, but COVID-19 has put severe strain on healthcare systems. This study aims to explore whether digitally enabled, remotely supported rehabilitation for people with long COVID-19 can enable healthcare systems to provide high quality care to large numbers of patients within the available resources. Specific objectives are to (1) develop and refine a digital health intervention (DHI) that supports patient assessment, monitoring and remote rehabilitation; (2) develop implementation models that support sustainable deployment at scale; (3) evaluate the impact of the DHI on recovery trajectories and (4) identify and mitigate health inequalities due to the digital divide.Methods and analysisMixed-methods, theoretically informed, single-arm prospective study, combining methods drawn from engineering/computer science with those from biomedicine. There are four work packages (WP), one for each objective. WP1 focuses on identifying user requirements and iteratively developing the intervention to meet them; WP2 combines qualitative data from users with learning from implementation science and normalisation process theory, to promote adoption, scale-up, spread and sustainability of the intervention; WP3 uses quantitative demographic, clinical and resource use data collected by the DHI to determine illness trajectories and how these are affected by use of the DHI; while WP4 focuses on identifying and mitigating health inequalities and overarches the other three WPs.Ethics and disseminationEthical approval obtained from East Midlands – Derby Research Ethics Committee (reference 288199). Our dissemination strategy targets three audiences: (1) Policy makers, Health service managers and clinicians responsible for delivering long COVID-19 services; (2) patients and the public; (3) academics.Trial registration numberResearch Registry number: researchregistry6173.

Spinal cord stimulation (SCS) is an established treatment of chronic neuropathic pain. Although a temporary SCS screening trial is widely used to determine whether a patient should receive permanent SCS implant, its evidence base is limited. We aimed to establish the clinical utility, diagnostic accuracy, and cost-effectiveness of an SCS screening trial. A multicentre single-blind, parallel two-group randomised controlled superiority trial was undertaken at 3 centres in the United Kingdom. Patients were randomised 1:1 to either SCS screening trial strategy (TG) or no trial screening strategy (NTG). Treatment was open label, but outcome assessors were masked. The primary outcome measure was numerical rating scale (NRS) pain at 6-month follow-up. Between June 2017 and September 2018, 105 participants were enrolled and randomised (TG = 54, NTG = 51). Mean numerical rating scale pain decreased from 7.47 at baseline (before SCS implantation) to 4.28 at 6 months in TG and from 7.54 to 4.49 in NTG (mean group difference: 0.2, 95% confidence interval [CI]: -1.2 to 0.9, P = 0.89). We found no difference between TG and NTG in the proportion of pain responders or other secondary outcomes. Spinal cord stimulation screening trial had a sensitivity of 100% (95% CI: 78-100) and specificity of 8% (95% CI: 1-25). The mean incremental cost-effectiveness ratio of TG vs NTG was £78,895 per additional quality-adjusted life-year gained. In conclusion, although the SCS screening trial may have some diagnostic utility, there was no evidence that an SCS screening TG provides superior patient outcomes or is cost-effective compared to a no trial screening approach.

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.

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

There are approximately 3,000 new UK diagnoses of cervical cancer annually, with many women presenting symptomatically. We aimed to identify and quantify features of cervical cancer in primary care in a case-control study in the UK. Putative features of cervical cancer were identified, and odd ratios and positive predictive values (PPVs) were calculated. About 1,006 women aged ≥40 years diagnosed with cervical cancer and 4,992 age-, sex- and practice-matched controls were selected from the Clinical Practice Research Datalink. Median age at diagnosis was 61 years (interquartile range 51-75). Seven symptoms and two abnormal investigations were associated with cervical cancer: post-menopausal bleeding, odds ratio 43 (95% confidence interval 25, 75); vaginal discharge or vaginitis 8.8 (5.2, 15), intermenstrual bleeding 4.7 (1.6, 14); haematuria 4.6 (2.1, 10); irregular menstruation 3.8 (1.6, 9.0); urinary tract infection 1.9 (1.3, 2.8); abdominal pain 1.8 (1.4, 2.5); high white cell count 5.1 (2.9, 8.8) and low haemoglobin 2.6 (1.8, 3.8): all p 

BACKGROUND: Breast cancer is the most common cancer in the UK. GPs are encouraged to refer all women whose symptoms may represent cancer, rather than selecting those at highest risk. AIM: to identify and quantify features of breast cancer in primary care. DESIGN AND SETTING: a UK case-control study using the Clinical Practice Research Database (CPRD). METHOD: Possible features of breast cancer were identified in the year before diagnosis, and odds ratios calculated using conditional logistic regression. Positive predictive values (PPVs) were estimated for consulting women. RESULTS: a total of 3994 women aged ≥40 years with breast cancer between 2000 and 2009, and 16 873 age-, sex-, and practice-matched controls were studied. Median age at diagnosis was 63 years (interquartile range 55-74 years). Four features were significantly associated with breast cancer: breast lump (odds ratio [OR] 110; 95% confidence interval [CI] = I88 to 150), breast pain (OR = 4.2; 95% CI = 3.0 to 6.0), nipple retraction (OR = 26; 95% CI = 10 to 64), nipple discharge (OR = 19; 95% CI = 8.6 to 41): all P-values 70 years. PPVs were lower in women who also reported breast pain. CONCLUSION: Generally, the figures support current referral practice. However, the low likelihood of cancer for all the non-lump symptoms means that the current guidance recommends investigation for possible cancer at a more liberal risk threshold than for other cancers. Although supported by patients, this may not meet current NHS criteria for cost-benefit.

BACKGROUND: Uterine cancer is the fourth most common cancer in women in the UK, with approximately 7700 new diagnoses and 1700 deaths annually. AIM: to identify and quantify features of uterine cancer in primary care. DESIGN AND SETTING: Case-control study using electronic primary care records in primary care in the UK. METHOD: Putative features of uterine cancer were identified in the year before diagnosis, and odds ratios (ORs) calculated using conditional logistic regression. Positive predictive values (PPVs) were calculated for women who consulted. RESULTS: a total of 2732 women aged ≥40 years with uterine cancer between 2000 and 2009, and 9537 age-, sex- and practice-matched controls were selected from the General Practice Research Database. The median age at diagnosis was 67 years. Nine features were significantly associated with uterine cancer: postmenopausal bleeding (OR = 160; 95% confidence interval [CI] = 100 to 240), excessive vaginal bleeding (OR = 22; 95% CI = 12 to 42), irregular menstruation (OR = 42; 95% CI = 27 to -63), vaginal discharge (OR = 14; 95% CI = 10 to 21), haematuria (OR = 8.7; 95% CI = 5.0 to 15), abdominal pain (OR = 2.0; 95% CI = 1.4 to 2.8), low haemoglobin (OR = 2.1; 95% CI = 1.5 to 2.9), raised platelets (OR = 1.5; 95% CI = 1.0 to 2.3), and raised glucose (OR = 1.4; 95% CI = 1.1 to 1.8); all P

Background: Hungary previously had one of the highest suicide rates in the world, but experienced major social and economic changes from 1990 onwards. We aimed to investigate the antecedents of suicide in Hungary. We hypothesised that suicide in Hungary would be associated with both risk factors for suicide as identified in Western studies, and experiences related to social and economic restructuring. Methods: We carried out a controlled psychological autopsy study. Informants for 194 cases (suicide deaths in Budapest and Pest County 2002-2004) and 194 controls were interviewed by clinicians using a detailed schedule. Results: Many of the demographic and clinical risk factors associated with suicide in other settings were also associated with suicide in Hungary; for example, being unmarried or having no current relationship, lack of other social contacts, low educational attainment, history of self-harm, current diagnosis of affective disorder (including bipolar disorder) or personality disorder, and experiencing a recent major adverse life event. A number of variables reflecting experiences since economic restructuring were also associated with suicide; for example, unemployment, concern over work propects, changes in living standards, practising religion. Just 20% of cases with evidence of depression at the time of death had received antidepressants. Conclusion: Suicide rates in Hungary are falling. Our study identified a number of risk factors related to individual-level demographic and clinical characteristics, and possibly recent societal change. Improved management of psychiatric disorder and self-harm may result in further reductions in suicide rates. © 2009 Almasi et al; licensee BioMed Central Ltd.

BACKGROUND: Concern exists that antidepressants can cause suicidality in youths with depression. AIMS: to determine the pooled risk of self-harm and suicidal behaviour from randomised trials of newer antidepressants. METHOD: a meta-analysis was carried out to calculate odds ratios for the combined data. RESULTS: Self-harm or suicide-related events occurred in 71 of 1487 (4.8%) of depressed youths treated with antidepressants v. 38 of 1254 (3.0%) of those given placebo (fixed effects odds ratio 1.70, 95% CI 1.13-2.54, P=0.01). There was a trend for individual suicidal thoughts, attempts and self-harm to occur more often in youths taking antidepressants than in those given placebo, but none of these differences was statistically significant. CONCLUSIONS: Antidepressants may cause a small short-term risk of self-harm or suicidal events in children and adolescents with major depressive disorder.

OBJECTIVES: to compare the effectiveness of cognitive behaviour therapy delivered by telephone with the same therapy given face to face in the treatment of obsessive compulsive disorder. DESIGN: Randomised controlled non-inferiority trial. SETTING: Two psychology outpatient departments in the United Kingdom. PARTICIPANTS: 72 patients with obsessive compulsive disorder. INTERVENTION: 10 weekly sessions of exposure therapy and response prevention delivered by telephone or face to face. MAIN OUTCOME MEASURES: Yale Brown obsessive compulsive disorder scale, Beck depression inventory, and client satisfaction questionnaire. RESULTS: Difference in the Yale Brown obsessive compulsive disorder checklist score between the two treatments at six months was -0.55 (95% confidence interval -4.26 to 3.15). Patient satisfaction was high for both forms of treatment. CONCLUSION: the clinical outcome of cognitive behaviour therapy delivered by telephone was equivalent to treatment delivered face to face and similar levels of satisfaction were reported. TRIAL REGISTRATION: Current Controlled Trials ISRCTN500103984 [controlled-trials.com].