PLoS medicine
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Giorgia Sulis and Madhukar Pai discuss the global distribution, and approaches to diagnosis and treatment, of isoniazid-resistant tuberculosis.
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Comparative Study Observational Study
Comparison of aggregate and individual participant data approaches to meta-analysis of randomised trials: An observational study.
It remains unclear when standard systematic reviews and meta-analyses that rely on published aggregate data (AD) can provide robust clinical conclusions. We aimed to compare the results from a large cohort of systematic reviews and meta-analyses based on individual participant data (IPD) with meta-analyses of published AD, to establish when the latter are most likely to be reliable and when the IPD approach might be required. ⋯ In this study we found that HRs from published AD were most likely to agree with those from IPD when the information size was large. Based on these findings, we provide guidance for determining systematically when standard AD meta-analysis will likely generate robust clinical conclusions, and when the IPD approach will add considerable value.
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Randomized Controlled Trial Multicenter Study
Evaluation of a clinical decision rule to guide antibiotic prescription in children with suspected lower respiratory tract infection in The Netherlands: A stepped-wedge cluster randomised trial.
Optimising the use of antibiotics is a key component of antibiotic stewardship. Respiratory tract infections (RTIs) are the most common reason for antibiotic prescription in children, even though most of these infections in children under 5 years are viral. This study aims to safely reduce antibiotic prescriptions in children under 5 years with suspected lower RTI at the emergency department (ED), by implementing a clinical decision rule. ⋯ In this multicentre ED study, we observed that a clinical decision rule for childhood pneumonia did not reduce overall antibiotic prescription, but that it was non-inferior to usual care. Exploratory analyses showed fewer strategy failures and that fewer antibiotics were prescribed in low/intermediate-risk children, suggesting improved targeting of antibiotics by the decision rule.
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Randomized Controlled Trial
Effectiveness of a scalable group-based education and monitoring program, delivered by health workers, to improve control of hypertension in rural India: A cluster randomised controlled trial.
New methods are required to manage hypertension in resource-poor settings. We hypothesised that a community health worker (CHW)-led group-based education and monitoring intervention would improve control of blood pressure (BP). ⋯ While the durability of the effect is uncertain, this trial provides evidence that a low-cost program using CHWs to deliver an education and monitoring intervention is effective in controlling BP and is potentially scalable in resource-poor settings globally.
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Observational Study
Dysregulation of multiple metabolic networks related to brain transmethylation and polyamine pathways in Alzheimer disease: A targeted metabolomic and transcriptomic study.
There is growing evidence that Alzheimer disease (AD) is a pervasive metabolic disorder with dysregulation in multiple biochemical pathways underlying its pathogenesis. Understanding how perturbations in metabolism are related to AD is critical to identifying novel targets for disease-modifying therapies. In this study, we test whether AD pathogenesis is associated with dysregulation in brain transmethylation and polyamine pathways. ⋯ In this study, we observed broad dysregulation of transmethylation and polyamine synthesis/catabolism, including abnormalities in neurotransmitter signaling, urea cycle, aspartate-glutamate metabolism, and glutathione synthesis. Our results implicate alterations in cellular methylation potential and increased flux in the transmethylation pathways, increased demand on antioxidant defense mechanisms, perturbations in intermediate metabolism in the urea cycle and aspartate-glutamate pathways disrupting mitochondrial bioenergetics, increased polyamine biosynthesis and breakdown, as well as abnormalities in neurotransmitter metabolism that are related to AD.