Sarah Walker

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.

BACKGROUND: The findings from observational studies, reviews and meta-analyses, supported by biological theories, that circumcised men appear less likely to acquire human immunodeficiency virus (HIV) has contributed to the recent ground swell of support for considering male circumcision as a strategy for preventing sexually acquired infection. We sought to elucidate and appraise the global evidence from published and unpublished studies that circumcision can be used as an intervention to prevent HIV infection. OBJECTIVES: 1) To assess the evidence of an interventional effect of male circumcision for preventing acquisition of HIV-1 and HIV-2 by men through heterosexual intercourse 2) To examine the feasibility and value of performing individual person data (IPD) meta-analysis SEARCH STRATEGY: We searched online for published and unpublished studies in The Cochrane Library (issue 2, 2002), MEDLINE (April 2002), EMBASE (February 2002) and AIDSLINE (August 2001). We also searched databases listing conference abstracts, scanned reference lists of articles and contacted authors of included studies. SELECTION CRITERIA: We searched for randomized and quasi-randomized controlled trials of male circumcision or, in their absence, observational studies that compare acquisition rates of HIV-1 and HIV-2 infection in circumcised and uncircumcised heterosexual men. DATA COLLECTION AND ANALYSIS: Independent reviewers selected studies, assessed study quality and extracted data. We stratified studies based on study design and on whether they included participants from the general population or high-risk groups (such as patients treated for sexually transmitted infections). We expressed findings as crude and adjusted odds ratios (OR) together with their 95% confidence intervals (CI) and conducted a sensitivity analysis to explore the effect of adjustment on study results. We investigated whether the method of circumcision ascertainment influenced study outcomes. MAIN RESULTS: We identified no completed randomized controlled trials. Three randomized controlled trials are currently underway or commencing shortly. We found 34 observational studies: 16 conducted in the general population and 18 in high-risk populations. It seems unlikely that potential confounding factors were completely accounted for in any of the included studies. In particular, important risk factors, such as religion and sexual practices, were not adequately accounted for in many of the included studies. General population study results:The single cohort study (N = 5516) showed a significant difference in HIV transmission rates between circumcised and uncircumcised men [OR = 0.58; 95% CI: 0.36 to 0.96]. Results for the 14 cross-sectional studies were inconsistent, with point estimates for unadjusted odds ratios varying between 0.28 and 1.73. Six studies had statistically significant results, four in the direction of benefit and two in the direction of harm. The test for heterogeneity between the cross-sectional studies was highly significant (chi-square = 77.59; df = 13; P-value < 0.00001). Nine studies reported adjusted odds ratios with eight in the direction of benefit, ranging from 0.26 to 0.80. Use of adjusted results tended to show stronger evidence of an association although they remained heterogenous (chi-square = 75.2; df = 13; P-value < 0.00001). Only one case-control study was found (N = 51) which had a non-significant result [OR = 1.90; 95% CI: 0.50 to 7.20]. High-risk group study results:The four cohort studies identified found a protective effect from circumcision with point estimates for unadjusted odds ratios varying from 0.10 to 0.39. Two of these studies had statistically significant results. Two studies reported adjusted odds ratios, both protective with one being significant. The chi-square test for between-study heterogeneity was not significant (chi-square = 5.21; df = 3; P-value = 0.16). All eleven cross-sectional studies reporting unadjusted results found benefit from circumcision, eight of which had statistically significant results. Estimates of effnal studies reporting unadjusted results found benefit from circumcision, eight of which had statistically significant results. Estimates of effect varied from an unadjusted odds ratio of 0.10 to 0.66. Between-study heterogeneity was significant with the chi-square = 29.77; df = 10; P-value = 0.0009. Four of these studies reported adjusted odds ratios ranging from 0.20 to 0.59 and all were significant. One additional cross-sectional study only reported an adjusted odds ratio in the direction of benefit which was statistically significant. All three case-control studies found a protective effect of circumcision on HIV status, two being statistically significant. Point estimates varied from unadjusted odds ratios of 0.37 to 0.88. One reported an adjusted odds ratio showing a significant protective effect. Adverse effects:No studies reported on the adverse effects of circumcision. In most studies, circumcision had taken place during childhood or adolescence before the studies commenced. REVIEWER'S CONCLUSIONS: We found insufficient evidence to support an interventional effect of male circumcision on HIV acquisition in heterosexual men. The results from existing observational studies show a strong epidemiological association between male circumcision and prevention of HIV, especially among high-risk groups. However, observational studies are inherently limited by confounding which is unlikely to be fully adjusted for. In the light of forthcoming results from RCTs, the value of IPD analysis of the included studies is doubtful. The results of these trials will need to be carefully considered before circumcision is implemented as a public health intervention for prevention of sexually transmitted HIV.

OBJECTIVES: To 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. DESIGN: Cross-sectional single-arm service evaluation of real-time user data. SETTING: 31 post-COVID-19 clinics in the UK. PARTICIPANTS: 3754 adults diagnosed with PCS in primary or secondary care deemed suitable for rehabilitation. INTERVENTION: Patients using the Living With Covid Recovery digital health intervention registered between 30 November 2020 and 23 March 2022. PRIMARY AND SECONDARY OUTCOME MEASURES: The 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. RESULTS: 3541 (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. CONCLUSION: A 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.