PLoS medicine
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The fixed dose combination of artemether-lumefantrine (AL) is the most widely used treatment for uncomplicated Plasmodium falciparum malaria. Relatively lower cure rates and lumefantrine levels have been reported in young children and in pregnant women during their second and third trimester. The aim of this study was to investigate the pharmacokinetic and pharmacodynamic properties of lumefantrine and the pharmacokinetic properties of its metabolite, desbutyl-lumefantrine, in order to inform optimal dosing regimens in all patient populations. ⋯ Our findings suggest that revised AL dosing regimens for young children and pregnant women would improve drug exposure but would require longer or more complex schedules. These dosing regimens should be evaluated in prospective clinical studies to determine whether they would improve cure rates, demonstrate adequate safety, and thereby prolong the useful therapeutic life of this valuable antimalarial treatment.
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Randomized Controlled Trial Multicenter Study
Efficacy of melatonin with behavioural sleep-wake scheduling for delayed sleep-wake phase disorder: A double-blind, randomised clinical trial.
Delayed Sleep-Wake Phase Disorder (DSWPD) is characterised by sleep initiation insomnia when attempting sleep at conventional times and difficulty waking at the required time for daytime commitments. Although there are published therapeutic guidelines for the administration of melatonin for DSWPD, to our knowledge, randomised controlled trials are lacking. This trial tested the efficacy of 0.5 mg melatonin, combined with behavioural sleep-wake scheduling, for improving sleep initiation in clinically diagnosed DSWPD patients with a delayed endogenous melatonin rhythm relative to patient-desired (or -required) bedtime (DBT). ⋯ In this study, melatonin treatment 1 h prior to DBT combined with behavioural sleep-wake scheduling was efficacious for improving objective and subjective measures of sleep disturbances and sleep-related impairments in DSWPD patients with delayed circadian phase relative to DBT. Improvements were achieved largely through the sleep-promoting effects of melatonin, combined with behavioural sleep-wake scheduling.
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It has long been contested that trade rules and agreements are used to dispute regulations aimed at preventing noncommunicable diseases (NCDs). Yet most analyses of trade rules and agreements focus on trade disputes, potentially overlooking how a challenge to a regulation's consistency with trade rules may lead to 'policy or regulatory chill' effects whereby countries delay, alter, or repeal regulations in order to avoid the costs of a dispute. Systematic empirical analysis of this pathway to impact was previously prevented by a dearth of systematically coded data. ⋯ Policy makers appear to face significant pressure to design food, beverage, and tobacco regulations that other countries will deem consistent with trade rules. Trade-related influence on public health policy is likely to be understated by analyses limited to formal trade disputes.
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Medicare Advantage (MA) and Medicare fee-for-service (FFS) plans have different financial incentives. Medicare pays predetermined rates per beneficiary to MA plans for providing care throughout the year, while providers serving FFS patients are reimbursed per utilization event. It is unknown how these incentives affect post-acute care in skilled nursing facilities (SNFs). The objective of this study was to examine differences in rehabilitation service use, length of stay, and outcomes for patients following hip fracture between FFS and MA enrollees. ⋯ Compared to FFS patients, MA patients had a shorter course of rehabilitation but were more likely to be discharged to the community successfully and were less likely to experience a 30-day hospital readmission. Longer lengths of stay may not translate into better outcomes in the case of hip fracture patients in SNFs.
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Systematic reviews have described high rates of attrition in patients with HIV receiving antiretroviral therapy (ART). However, migration and clinical transfer may lead to an overestimation of attrition (death and loss to follow-up). Using a newly linked national laboratory database in South Africa, we assessed national retention in South Africa's national HIV program. ⋯ In this study, HIV care retention was substantially higher when viewed from a national perspective than from a facility perspective. Our results suggest that traditional clinical cohorts underestimate retention.