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ImportanceThere are limited efficacious treatments for Alzheimer disease.ObjectiveTo assess efficacy and adverse events of donanemab, an antibody designed to clear brain amyloid plaque.Design, Setting, and ParticipantsMulticenter (277 medical research centers/hospitals in 8 countries), randomized, double-blind, placebo-controlled, 18-month phase 3 trial that enrolled 1736 participants with early symptomatic Alzheimer disease (mild cognitive impairment/mild dementia) with amyloid and low/medium or high tau pathology based on positron emission tomography imaging from June 2020 to November 2021 (last patient visit for primary outcome in April 2023).InterventionsParticipants were randomized in a 1:1 ratio to receive donanemab (n = 860) or placebo (n = 876) intravenously every 4 weeks for 72 weeks. Participants in the donanemab group were switched to receive placebo in a blinded manner if dose completion criteria were met.Main Outcomes and MeasuresThe primary outcome was change in integrated Alzheimer Disease Rating Scale (iADRS) score from baseline to 76 weeks (range, 0-144; lower scores indicate greater impairment). There were 24 gated outcomes (primary, secondary, and exploratory), including the secondary outcome of change in the sum of boxes of the Clinical Dementia Rating Scale (CDR-SB) score (range, 0-18; higher scores indicate greater impairment). Statistical testing allocated α of .04 to testing low/medium tau population outcomes, with the remainder (.01) for combined population outcomes.ResultsAmong 1736 randomized participants (mean age, 73.0 years; 996 [57.4%] women; 1182 [68.1%] with low/medium tau pathology and 552 [31.8%] with high tau pathology), 1320 (76%) completed the trial. Of the 24 gated outcomes, 23 were statistically significant. The least-squares mean (LSM) change in iADRS score at 76 weeks was −6.02 (95% CI, −7.01 to −5.03) in the donanemab group and −9.27 (95% CI, −10.23 to −8.31) in the placebo group (difference, 3.25 [95% CI, 1.88-4.62]; P < .001) in the low/medium tau population and −10.2 (95% CI, −11.22 to −9.16) with donanemab and −13.1 (95% CI, −14.10 to −12.13) with placebo (difference, 2.92 [95% CI, 1.51-4.33]; P < .001) in the combined population. LSM change in CDR-SB score at 76 weeks was 1.20 (95% CI, 1.00-1.41) with donanemab and 1.88 (95% CI, 1.68-2.08) with placebo (difference, −0.67 [95% CI, −0.95 to −0.40]; P < .001) in the low/medium tau population and 1.72 (95% CI, 1.53-1.91) with donanemab and 2.42 (95% CI, 2.24-2.60) with placebo (difference, −0.7 [95% CI, −0.95 to −0.45]; P < .001) in the combined population. Amyloid-related imaging abnormalities of edema or effusion occurred in 205 participants (24.0%; 52 symptomatic) in the donanemab group and 18 (2.1%; 0 symptomatic during study) in the placebo group and infusion-related reactions occurred in 74 participants (8.7%) with donanemab and 4 (0.5%) with placebo. Three deaths in the donanemab group and 1 in the placebo group were considered treatment related.Conclusions and RelevanceAmong participants with early symptomatic Alzheimer disease and amyloid and tau pathology, donanemab significantly slowed clinical progression at 76 weeks in those with low/medium tau and in the combined low/medium and high tau pathology population.Trial RegistrationClinicalTrials.gov Identifier: NCT04437511
Introduction South Asia has had a dynamic response to the ongoing COVID-19 pandemic. The overall burden and response have remained comparable across highly-burdened countries within the South Asian Region. Methodology Using a population-based observational design, all eight South Asian countries were analyzed using a step-wise approach. Data were obtained from government websites and publicly-available repositories for population dynamics and key variables. Results South Asian countries have a younger average age of their population. Inequitable distribution of resources centered in urban metropolitan cities within South Asia is present. Certain densely populated regions in these countries have better testing and healthcare facilities that correlate with lower COVID-19 incidence per million populations. Trends of urban-rural disparities are unclear given the lack of clear reporting of the gaps within these regions. COVID-19 vaccination lag has become apparent in South Asian countries, with the expected time to complete the campaign being unfeasible as the COVID-19 pandemic progresses. Conclusion With a redesigning of governance policies on preventing the rise of COVID-19 promptly, the relief on the healthcare system and healthcare workers will allow for adequate time to roll out vaccination campaigns with equitable distribution. Capacity expansion of public health within the Region is required to ensure a robust healthcare response to the ongoing pandemic and future infectious disease outbreaks.
BACKGROUND: Percutaneous coronary intervention (PCI) is the most commonly performed procedure for treating coronary artery disease (CAD), however, relatively little is known regarding the quality of PCI in Canada. We have previously assembled a panel of cardiovascular experts to develop a set of quality indicators that is suitable for implementation in the Canadian health care system. In this study, we evaluated the quality of care of PCI in Ontario by measuring the adherence of established PCI quality indicators in routine clinical practice. METHODS: A chart abstraction study was conducted at hospitals with the capability to perform PCI in Ontario, Canada from 2009 and 2010. A target study sample of approximately 200 PCI procedures were taken from each site in order to obtain a representative sample of patients with stable coronary artery disease (CAD) and acute coronary syndrome (ACS). Process indicators assessed included prescription of aspirin, dual anti-platelet therapy, statins, smoking cessation, and others. Outcome indicators included death, myocardial infarction, and other adverse PCI complications. RESULTS: Our study sample included 3,041 patients, of which 18% had stable CAD and 82% had an ACS. Their mean age was 63 AE 12.4 years and 29% of the patients were female. Among them, 89% were prescribed aspirin prior to PCI, 98.7% were prescribed aspirin after PCI, 95.1% were prescribed dual antiplatelet therapy for 12 months after drug eluting stents, and 94.9% were prescribed statins. The lowest performing quality indicator was smoking cessation counseling, which was observed in 42% of patients (18% in stable CAD and 47% in ACS; p<0.001). PCI outcomes stratified by stable CAD vs ACS are shown in Table 1. CONCLUSION: This current study demonstrates high levels of adherence to quality indicators and relatively low rates of adverse events for patients undergoing PCI procedures in Ontario.Smoking cessation counseling was not consistently performed and could represent a focus for future quality improvement efforts.
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