PLoS medicine
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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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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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Observational Study
Major trauma presentations and patient outcomes in English hospitals during the COVID-19 pandemic: An observational cohort study.
Single-centre studies suggest that successive Coronavirus Disease 2019 (COVID-19)-related "lockdown" restrictions in England may have led to significant changes in the characteristics of major trauma patients. There is also evidence from other countries that diversion of intensive care capacity and other healthcare resources to treating patients with COVID-19 may have impacted on outcomes for major trauma patients. We aimed to assess the impact of the COVID-19 pandemic on the number, characteristics, care pathways, and outcomes of major trauma patients presenting to hospitals in England. ⋯ This national evaluation of the impact of COVID on major trauma presentations to English hospitals has observed important public health findings: The large reduction in overall numbers injured has been primarily driven by reductions in road traffic collisions, while numbers of older people injured at home increased over the second lockdown. Future research is needed to better understand the initial reduction in likelihood of survival after major trauma observed with the implementation of the first lockdown.
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Randomized Controlled Trial
Same-day testing with initiation of antiretroviral therapy or tuberculosis treatment versus standard care for persons presenting with tuberculosis symptoms at HIV diagnosis: A randomized open-label trial from Haiti.
Same-day HIV testing and antiretroviral therapy (ART) initiation is being widely implemented. However, the optimal timing of ART among patients with tuberculosis (TB) symptoms is unknown. We hypothesized that same-day treatment (TB treatment for those diagnosed with TB; ART for those not diagnosed with TB) would be superior to standard care in this population. ⋯ In patients with TB symptoms at HIV diagnosis, we found that same-day treatment was not associated with superior retention and viral suppression. In this study, a short delay in ART initiation did not appear to compromise outcomes.
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An increased risk of myocarditis or pericarditis after priming with mRNA Coronavirus Disease 2019 (COVID-19) vaccines has been shown but information on the risk post-booster is limited. With the now high prevalence of prior Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, we assessed the effect of prior infection on the vaccine risk and the risk from COVID-19 reinfection. ⋯ We observed an increased risk of myocarditis within the first week after priming and booster doses of mRNA vaccines, predominantly in males under 40 years with the highest risks after a second dose. The risk difference between the second and the third doses was particularly marked for the mRNA-1273 vaccine that contains half the amount of mRNA when used for boosting than priming. The lower risk in those with prior SARS-CoV-2 infection, and lack of an enhanced effect post-booster, does not suggest a spike-directed immune mechanism. Research to understand the mechanism of vaccine-associated myocarditis and to document the risk with bivalent mRNA vaccines is warranted.