PLoS medicine
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People with comorbidities are underrepresented in clinical trials. Empirical estimates of treatment effect modification by comorbidity are lacking, leading to uncertainty in treatment recommendations. We aimed to produce estimates of treatment effect modification by comorbidity using individual participant data (IPD). ⋯ Assessments of treatment effect modification rarely consider comorbidity. Our findings demonstrate that for trials included in this analysis, there was no empirical evidence of treatment effect modification by comorbidity. The standard assumption used in evidence syntheses is that efficacy is constant across subgroups, although this is often criticised. Our findings suggest that for modest levels of comorbidities, this assumption is reasonable. Thus, trial efficacy findings can be combined with data on natural history and competing risks to assess the likely overall benefit of treatments in the context of comorbidity.
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Reducing antibiotic treatment duration is a key component of hospital antibiotic stewardship interventions. However, its effectiveness in reducing antimicrobial resistance is uncertain and a clear theoretical rationale for the approach is lacking. In this study, we sought to gain a mechanistic understanding of the relation between antibiotic treatment duration and the prevalence of colonisation with antibiotic-resistant bacteria in hospitalised patients. ⋯ In this study, we found both theoretical and empirical evidence that reducing antibiotic treatment duration can reduce resistance carriage, though the mechanistic models also highlighted circumstances under which reducing treatment duration can, perversely, increase resistance. Future antibiotic duration trials should monitor antibiotic-resistant bacteria colonisation as an outcome to better inform antibiotic stewardship policies.
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In low- and middle-income countries (L&MICs), the biggest contributing factors to the global burden of disease in childhood are deaths due to respiratory illness and diarrhoea, both of which are closely related to use of water, sanitation, and hygiene (WASH) services by households. However, current estimates of the health impacts of WASH interventions use self-reported morbidity, which may fail to capture longer-term or more severe impacts. Reported mortality is thought to be less prone to bias than other reported measures. This study aimed to answer the question: What are the impacts of WASH interventions on reported childhood mortality in L&MICs? ⋯ The findings are congruent with theories of infectious disease transmission. Washing with water presents a barrier to respiratory illness and diarrhoea, which are the two biggest contributors to all-cause mortality in childhood in L&MICs. Community-wide sanitation halts the spread of diarrhoea. We observed that evidence synthesis can provide new findings, going beyond the underlying data from trials to generate crucial insights for policy. Transparent reporting in trials creates opportunities for research synthesis to answer questions about mortality, which individual studies of interventions cannot be reliably designed to address.
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HIV testing services (HTS) are the first steps in reaching the UNAIDS 95-95-95 goals to achieve and maintain low HIV incidence. Evaluating the effectiveness of different demand creation interventions to increase uptake of efficient and effective HTS is useful to prioritize limited programmatic resources. This review was undertaken to inform World Health Organization (WHO) 2019 HIV testing guidelines and assessed the research question, "Which demand creation strategies are effective for enhancing uptake of HTS?" focused on populations globally. ⋯ Mobilization, couple- and motivation-oriented counseling, peer-led interventions, conditional fixed value incentives, and SMS are high-impact demand creation interventions and should be prioritized for programmatic consideration. Reduced duration counseling and video-based interventions are an efficient and effective alternative to address staffing shortages. Investment in demand creation activities should prioritize those with undiagnosed HIV or ongoing HIV exposure. Selection of demand creation interventions must consider risks and benefits, context-specific factors, feasibility and sustainability, country ownership, and universal health coverage across disease areas.
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Meta Analysis
Prevalence and natural history of depression after stroke: A systematic review and meta-analysis of observational studies.
Depression is the most frequent psychiatric condition after stroke and is associated with negative health outcomes. We aim to undertake a systematic review and meta-analysis of the prevalence and natural history of depression after stroke. ⋯ In this study, we observed that stroke survivors with early-onset depression (within 3 months after stroke) are at high risks for remaining depressed and make up two-thirds of the incident cases during 1 year after stroke. This highlights the need for ongoing clinical monitoring of patients depressed shortly after stroke.