PLoS medicine
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Multicenter Study Observational Study
Age and the association between apolipoprotein E genotype and Alzheimer disease: A cerebrospinal fluid biomarker-based case-control study.
The ε4 allele of apolipoprotein E (APOE) gene and increasing age are two of the most important known risk factors for developing Alzheimer disease (AD). The diagnosis of AD based on clinical symptoms alone is known to have poor specificity; recently developed diagnostic criteria based on biomarkers that reflect underlying AD neuropathology allow better assessment of the strength of the associations of risk factors with AD. Accordingly, we examined the global and age-specific association between APOE genotype and AD by using the A/T/N classification, relying on the cerebrospinal fluid (CSF) levels of β-amyloid peptide (A, β-amyloid deposition), phosphorylated tau (T, pathologic tau), and total tau (N, neurodegeneration) to identify patients with AD. ⋯ In this study, we found that AD diagnosis based on biomarkers was associated with APOE ε4 carrier status, with a higher OR than previously reported from studies based on only clinical AD criteria. This association differs according to age, with the strongest effect at 65-70 years. These findings highlight the need for early interventions for dementia prevention to mitigate the effect of APOE ε4 at the population level.
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Randomized Controlled Trial
Evaluation of the effectiveness of topical repellent distributed by village health volunteer networks against Plasmodium spp. infection in Myanmar: A stepped-wedge cluster randomised trial.
The World Health Organization has yet to endorse deployment of topical repellents for malaria prevention as part of public health campaigns. We aimed to quantify the effectiveness of repellent distributed by the village health volunteer (VHV) network in the Greater Mekong Subregion (GMS) in reducing malaria in order to advance regional malaria elimination. ⋯ In this study, we observed apparent protection against new infections associated with the large-scale distribution of repellent by VHVs. Incorporation of repellent into national strategies, particularly in areas where bed nets are less effective, may contribute to the interruption of malaria transmission. Further studies are warranted across different transmission settings and populations, from the GMS and beyond, to inform WHO public health policy on the deployment of topical repellents for malaria prevention.
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Inflammation during pregnancy is hypothesized to influence fetal growth. Eicosanoids, an important class of lipid mediators derived from polyunsaturated fatty acids, can act as both direct influences and biomarkers of inflammation through a variety of biological pathways. However, quantifying these distinct inflammatory pathways has proven difficult. We aimed to characterize a comprehensive panel of plasma eicosanoids longitudinally across gestation in pregnant women and to determine whether levels differed by infant size at delivery. ⋯ In this nested case-control study, we found that eicosanoids and fatty acids systematically change in maternal plasma over pregnancy. Eicosanoids from specific inflammation-related pathways were higher in mothers of SGA cases and mostly similar in mothers of LGA cases compared to controls. These findings can provide deeper insight into etiologic mechanisms of abnormal fetal growth outcomes.
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Randomized Controlled Trial
Safety and parasite clearance of artemisinin-resistant Plasmodium falciparum infection: A pilot and a randomised volunteer infection study in Australia.
Artemisinin resistance is threatening malaria control. We aimed to develop and test a human model of artemisinin-resistant (ART-R) Plasmodium falciparum to evaluate the efficacy of drugs against ART-R malaria. ⋯ We developed the first (to our knowledge) human model of ART-R malaria. The delayed clearance profile of ART-R parasites after AS aligns with field study observations. Although based on a relatively small sample size, results indicate that this model can be safely used to assess new drugs against ART-R P. falciparum.
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Comparative Study Observational Study
Disparities in United States hospitalizations for serious infections in patients with and without opioid use disorder: A nationwide observational study.
Patients with opioid use disorder (OUD) who are hospitalized for serious infections requiring prolonged intravenous antibiotics may face barriers to discharge, which could prolong hospital length of stay (LOS) and increase financial burden. We investigated differences in LOS, discharge disposition, and charges between hospitalizations for serious infections in patients with and without OUD. ⋯ Our findings suggest that among hospitalizations for some serious infections, those involving patients with OUD were associated with longer LOS, higher odds of discharge to post-acute care facilities or patient-directed discharge, and similar total hospital charges, despite lower daily charges. These findings highlight opportunities to improve care for patients with OUD hospitalized with serious infections, and to reduce the growing associated costs.