IntroductionLow high-density lipoprotein (HDL) is widely used as a marker of cardiovascular disease risk, although this relationship is not causal and is likely mediated through associations with other risk factors. Low HDL is extremely common in sub-Saharan African populations, and this has often been interpreted to indicate that these populations will have increased cardiovascular risk. We aimed to determine whether the association between HDL and other cardiovascular risk factors differed between populations in sub-Saharan Africa and the UK.MethodsWe compared data from adults living in Uganda and Malawi (n=26 216) and in the UK (n=8747). We examined unadjusted and adjusted levels of HDL and applied the WHO recommended cut-offs for prevalence estimates. We used spline and linear regression to assess the relationship between HDL and other cardiovascular risk factors.ResultsHDL was substantially lower in the African than in the European studies (geometric mean 0.9–1.2 mmol/L vs 1.3–1.8 mmol/L), with African prevalence of low HDL as high as 77%. Total cholesterol was also substantially lower (geometric mean 3.3–3.9 mmol/L vs 4.6–5.4 mmol/L). In comparison with European studies the relationship between HDL and adiposity (body mass index, waist to hip ratio) was greatly attenuated in African studies and the relationship with non-HDL cholesterol reversed: in African studies low HDL was associated with lower non-HDL cholesterol. The association between sex and HDL was also different; using the WHO sex-specific definitions, low HDL was substantially more common among women (69%–77%) than men (41%–59%) in Uganda/Malawi.ConclusionThe relationship between HDL and sex, adiposity and non-HDL cholesterol in sub-Saharan Africa is different from European populations. In sub-Saharan Africans low HDL is a marker of low overall cholesterol and sex differences are markedly attenuated. Therefore low HDL in isolation is unlikely to indicate raised cardiovascular risk and the WHO sex-based cut-offs are inappropriate.

Abstract
. Background
. Type 2 diabetes (T2D) is common and increasing in prevalence. It is possible to prevent or delay T2D using lifestyle intervention programmes. Entry to these programmes is usually determined by a measure of glycaemia in the ‘intermediate’ range. This paper investigated the relationship between HbA1c and future diabetes risk and determined the impact of varying thresholds to identify those at high risk of developing T2D.
.
. Methods
. We studied 4227 participants without diabetes aged ≥ 40 years recruited to the Exeter 10,000 population cohort in South West England. HbA1c was measured at study recruitment with repeat HbA1c available as part of usual care. Absolute risk of developing diabetes within 5 years, defined by HbA1c ≥ 48 mmol/mol (6.5%), according to baseline HbA1c, was assessed by a flexible parametric survival model.
.
. Results
. The overall absolute 5-year risk (95% CI) of developing T2D in the cohort was 4.2% (3.6, 4.8%). This rose to 7.1% (6.1, 8.2%) in the 56% (n = 2358/4224) of participants classified ‘high-risk’ with HbA1c ≥ 39 mmol/mol (5.7%; ADA criteria). Under IEC criteria, HbA1c ≥ 42 mmol/mol (6.0%), 22% (n = 929/4277) of the cohort was classified high-risk with 5-year risk 14.9% (12.6, 17.2%). Those with the highest HbA1c values (44–47 mmol/mol [6.2–6.4%]) had much higher 5-year risk, 26.4% (22.0, 30.5%) compared with 2.1% (1.5, 2.6%) for 39–41 mmol/mol (5.7–5.9%) and 7.0% (5.4, 8.6%) for 42–43 mmol/mol (6.0–6.1%). Changing the entry criterion to prevention programmes from 39 to 42 mmol/mol (5.7–6.0%) reduced the proportion classified high-risk by 61%, and increased the positive predictive value (PPV) from 5.8 to 12.4% with negligible impact on the negative predictive value (NPV), 99.6% to 99.1%. Increasing the threshold further, to 44 mmol/mol (6.2%), reduced those classified high-risk by 59%, and markedly increased the PPV from 12.4 to 23.2% and had little impact on the NPV (99.1% to 98.5%).
.
. Conclusions
. A large proportion of people are identified as high-risk using current thresholds. Increasing the risk threshold markedly reduces the number of people that would be classified as high-risk and entered into prevention programmes, although this must be balanced against cases missed. Raising the entry threshold would allow limited intervention opportunities to be focused on those most likely to develop T2D.
.

Background
Bacterial infections of the upper and lower respiratory tract are a frequent complication of influenza and contribute to the widespread use of antibiotics. Influenza vaccination may help reduce both appropriate and inappropriate prescribing of antibiotics. Electronic health records provide a rich source of information for assessing secondary effects of influenza vaccination.


Methods
We conducted a retrospective study to estimate effects of influenza vaccine on antibiotic (amoxicillin) prescription in the elderly based on data from the Clinical Practice Research Datalink. The introduction of UK policy to recommend the influenza vaccine to older adults in 2000 led to a substantial increase in uptake, creating a natural experiment. of 259,753 eligible patients that were unvaccinated in 1999 and aged≥65y by January 2000, 88,519 patients received influenza vaccination in 2000. These were propensity score matched 1:1 to unvaccinated patients. Time-to-amoxicillin was analysed using the Prior Event Rate Ratio (PERR) Pairwise method to address bias from time-invariant measured and unmeasured confounders. A simulation study and negative control outcome were used to help strengthen the validity of results.


Results
Compared to unvaccinated patients, those from the vaccinated group were more likely to be prescribed amoxicillin in the year prior to vaccination: hazard ratio (HR) 1.90 (95% confidence interval 1.83, 1.98). Following vaccination, the vaccinated group were again more likely to be prescribed amoxicillin, HR 1.64 (1.58,1.71). After adjusting for prior differences between the two groups using PERR Pairwise, overall vaccine effectiveness was 0.86 (0.81, 0.92). Additional analyses suggested that provided data meet the PERR assumptions, these estimates were robust.


Conclusions
Once differences between groups were taken into account, influenza vaccine had a beneficial effect, lowering the frequency of amoxicillin prescribing in the vaccinated group. Ensuring successful implementation of national programmes of vaccinating older adults against influenza may help contribute to reducing antibiotic resistance.

Information received by women regarding physical activity during and after pregnancy often lacks clarity and may be conflicting and confusing. Without clear, engaging, accessible guidance centred on the experiences of pregnancy and parenting, the benefits of physical activity can be lost. We describe a collaborative process to inform the design of evidence-based, user-centred physical activity resources which reflect diverse experiences of pregnancy and early parenthood. Two iterative, collaborative phases involving patient and public involvement (PPI) workshops, a scoping survey (n = 553) and stakeholder events engaged women and maternity, policy and physical activity stakeholders to inform pilot resource development. These activities shaped understanding of challenges experienced by maternity and physical activity service providers, pregnant women and new mothers in relation to supporting physical activity. Working collaboratively with women and stakeholders, we co-designed pilot resources and identified important considerations for future resource development. Outcomes and lessons learned from this process will inform further work to support physical activity during pregnancy and beyond, but also wider health research where such collaborative approaches are important. We hope that drawing on our experiences and sharing outcomes from this work provide useful information for researchers, healthcare professionals, policy makers and those involved in supporting physical activity behaviour.

OBJECTIVE: the impact of taking oral glucose-lowering medicines intermittently, rather than as recommended, is unclear. We conducted a retrospective cohort study using community-acquired U.K. clinical data (Clinical Practice Research Database [CPRD] and GoDARTS database) to examine the prevalence of nonadherence to treatment for type 2 diabetes and investigate its potential impact on HbA1c reduction stratified by type of glucose-lowering medication. RESEARCH DESIGN AND METHODS: Data were extracted for patients treated between 2004 and 2014 who were newly prescribed metformin, sulfonylurea, thiazolidinedione, or dipeptidyl peptidase 4 inhibitors and who continued to obtain prescriptions over 1 year. Cohorts were defined by prescribed medication type, and good adherence was defined as a medication possession ratio ≥0.8. Linear regression was used to determine potential associations between adherence and 1-year baseline-adjusted HbA1c reduction. RESULTS: in CPRD and GoDARTS, 13% and 15% of patients, respectively, were nonadherent. Proportions of nonadherent patients varied by the oral glucose-lowering treatment prescribed (range 8.6% [thiazolidinedione] to 18.8% [metformin]). Nonadherent, compared with adherent, patients had a smaller HbA1c reduction (0.4% [4.4 mmol/mol] and 0.46% [5.0 mmol/mol] for CPRD and GoDARTs, respectively). Difference in HbA1c response for adherent compared with nonadherent patients varied by drug (range 0.38% [4.1 mmol/mol] to 0.75% [8.2 mmol/mol] lower in adherent group). Decreasing levels of adherence were consistently associated with a smaller reduction in HbA1c. CONCLUSIONS: Reduced medication adherence for commonly used glucose-lowering therapies among patients persisting with treatment is associated with smaller HbA1c reductions compared with those taking treatment as recommended. Differences observed in HbA1c responses to glucose-lowering treatments may be explained in part by their intermittent use.

We discuss inference for longitudinal clinical trials subject to possibly informative dropout. A selection of available methods is reviewed for the simple case of trials with two timepoints. Using data from two such clinical trials, each with two treatments, we demonstrate that different analysis methods can at times lead to quite different conclusions from the same data. We investigate properties of complete-case estimators for the type of trials considered, with emphasis on interpretation and meaning of parameters. We contrast longitudinal and crossover designs and argue that for crossover studies there are often good reasons to prefer a complete case analysis. More generally, we suggest that there is merit in an approach in which no untestable assumptions are made. Such an approach would combine a dropout analysis, an analysis of complete-case data only, and a careful statement of justified conclusions.

Objective: to determine the effectiveness of mindfulness-based stress reduction (MBSR) and mindfulness-based cognitive therapy (MBCT) on psychological and physical outcomes for people with vascular disease. Design: Systematic review and meta-analysis of randomised controlled trials. Data sources: AMED, CINAHL, EMBASE, British Nursing Index, Medline, Web of Science, PsycINFO, Cochrane Database of Systematic Reviews, Central, Social Sciences Citation Index, Social Policy and Practice, and HMIC from inception to January 2013. Review methods: Articles were screened for inclusion independently by two reviewers. Data extraction and quality appraisal were performed by one reviewer and checked by a second with discrepancies resolved by discussion with a third if necessary. Random-effects meta-analyses were performed. Results: Nine articles (from eight original randomised controlled trials) met eligibility criteria and were included in the final review. In total, 578 participants were enrolled across the trials, with participants presenting with prehypertension/hypertension (n. = 3 trials), type 1 or 2 diabetes (n. = 2), heart disease (n. = 2) and stroke (n. = 1). Meta-analyses, using standardised mean differences, showed evidence of reductions in stress (- 0.36; 95% CI - 0.67 to - 0.09; p. = 0.01), depression (- 0.35; 95% CI - 0.53 to - 0.16; p. = 0.003) and anxiety (- 0.50; 95% CI - 0.70 to - 0.29; p. < 0.001). Effects on physical outcomes (blood pressure, albuminuria, stress hormones) were mixed. Conclusion: Whilst populations with vascular disease appear to derive a range of psychological benefits from MBSR/MBCT intervention, the effects on physical parameters of disease are not yet established. More robust studies, with longer term follow-up, are required to ascertain full effectiveness of such intervention. © 2014.

Background: the Strengths and Difficulties Added Value Score (SDQ AVS) uses a large epidemiological study to predict follow-up parental SDQ scores for the evaluation of routine outcomes. Method: We tested the prediction of the SDQ AVS derived from a national population survey separately on scores for the waiting list control and intervention groups in a randomised controlled trial. If the SDQ AVS is to be clinically useful, it needs to function as expected across different populations. Results: in the control arm, the SDQ AVS predicted an effect size of 0.15 (95% CI -0.01-0.30) compared to an expected effect size of 0, as the children in this arm received no treatment. In the experimental arm, the SDQ AVS predicted an effect size of 0.62 (95% CI 0.42-0.83) compared to the study effect size of 0.53. Change scores overestimated the effect size in both arms (control 0.50 95% CI 0.34-0.66, intervention 0.85 95% CI 0.66-1.04). Conclusion: Our findings suggest that the SDQ AVS adjusts for spontaneous improvement, regression to the mean and attenuation.

The UK prevalence of parent-reported autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD) were estimated from the Millennium Cohort Study. Case definition was if a doctor or health care professional had ever told parents that their child had ASD and/or ADHD. Data were collected in 2008/2009 for 14,043 children. 1.7 % of children were reported as having ASD (95 % CI 1.4-2.0) at mean age 7.2 years (SD = 0.2; range = 6.3-8.2). 1.4 % reportedly had ADHD (95 % CI 1.2-1.7), and 0.3 % had both ASD and ADHD (95 % CI 0.2-0.5). After adjusting for socio-economic disadvantage, only male sex (p 

Increases in the sensitivity of DNA profiling technology now allow profiles to be obtained from smaller and more degraded DNA samples than was previously possible. The resulting profiles can be highly informative, but the subjective elements in the interpretation make it problematic to achieve the valid and efficient evaluation of evidential strength required in criminal cases. The problems arise from stochastic phenomena such as "dropout" (absence of an allele in the profile that is present in the underlying DNA) and experimental artefacts such as "stutter" that can generate peaks of ambiguous allelic status. Currently in the UK, evidential strength evaluation uses an approach in which the complex signals in the DNA profiles are interpreted in a semi-manual fashion by trained experts aided by a set of guidelines, but also relying substantially on professional judgment. We introduce a statistical model to calculate likelihood ratios for evaluating DNA evidence arising from multiple known and unknown contributors that allows for such stochastic phenomena by incorporating peak heights. Efficient use of peak heights allows for more crime scene profiles to be reported to courts than is currently possible. The model parameters are estimated from experimental data incorporating multiple sources of variability in the profiling system. We report and analyse experimental results from the SGMPlus system, run at 28 amplification cycles with no enhancements, currently used in the UK. Our methods are readily adapted to other DNA profiling systems provided that the experimental data for the parameter estimation is available. © 2013 Elsevier Ireland Ltd. All rights reserved.

Missing data arise in crossover trials, as they do in any form of clinical trial. Several papers have addressed the problems that missing data create, although almost all of these assume that the probability that a planned observation is missing does not depend on the value that would have been observed; that is, the data are missing at random (MAR). In many applications, this assumption is likely to be untenable; in which case, the data are missing not at random (MNAR). We investigate the effect on estimates of the treatment effect that assume data are MAR when data are actually MNAR. We also propose using the assumption of no carryover treatment effect, which is usually required for this design, to permit the estimation of a treatment effect when data are MNAR. The results are applied to a trial comparing two treatments for neuropathic pain and show that the estimate of treatment effect is sensitive to the assumption of MAR.

Currently practitioners use a binary approach to DNA profile interpretation. However it is recognised that methods considering peak heights/areas are preferable. In this paper we give an example that shows how peaks in stutter position and preferential amplification can be included in a calculation of likelihood ratios using a model that takes into account peak heights. © 2009 Elsevier Ireland Ltd.

Background Resurfacing is a popular alternative to a standard hip replacement in young arthritic patients. Despite bone preservation around the femoral component, there is little information regarding the bone quality. Patients and methods 32 patients underwent consecutive Birmingham hip resurfacing. The bone density of the femoral neck was measured preoperatively and then at 6 weeks, 3 months, 1 year, and 2 years. The femoral neck was divided into regions of interest. Results were available for 27 hips in 26 patients. Results the overall femoral neck bone density showed a trend towards a decrease at 6 weeks and 3 months but returned to the preoperative level at 1 year, and was maintained at 2 years. The combined superior regions of the neck showed a statistically significant decrease in bone density at 6 weeks and 3 months. This returned to preoperative levels at 1 year and was maintained at 2 years. Interpretation Bone density appears to decrease at 6 weeks and 3 months, suggesting that care is necessary until bone density begins to recover. © Nordic Orthopedic Federation.