Background:The prevalence of true asymptomatic COVID-19 cases is critical to policy makers considering the effectiveness of mitigation measures against the SARS-CoV-2 pandemic. We aimed to synthesize all available research on the asymptomatic rates and transmission rates where possible. Methods:We searched PubMed, Embase, Cochrane COVID-19 trials, and European PMC for preprint platforms such as MedRxiv. We included primary studies reporting on asymptomatic prevalence where: (a) the sample frame includes at-risk population, and (b) there was sufficiently long follow up to identify pre-symptomatic cases. Meta-analysis used fixed effect and random effects models.Results: We screened 571 articles and included five low risk-of-bias studies from three countries (China (2), USA (2), Italy (1)) that tested 9,242 at-risk people, of which 413 were positive and 65 were asymptomatic. Diagnosis in all studies was confirmed using a RT-qPCR test. The proportion of asymptomatic cases ranged from 6% to 41%. Meta-analysis (fixed effect) found that the proportion of asymptomatic cases was 16% (95% CI: 12% -20%) overall; higher in non-aged care 19% (15% -24%), and lower in long-term aged care 8% (4% -14%). Two studies provided direct evidence of forward transmission of the infection by asymptomatic cases but suggested lower rates than symptomatic cases. Conclusion:Our estimates of the prevalence of asymptomatic COVID-19 cases are lower than many highly publicized studies, but still substantial. Further robust epidemiological evidence is urgently needed, including in sub-populations such as children, to better understand the importance of asymptomatic cases for driving spread of the pandemic.

Introduction: The decision to deprescribe medications used for both disease prevention and symptom control (dual-purpose medications or DPMs) is often challenging for clinicians. We aim to establish the impact of deprescribing DPMs on patient-related outcomes for older adults near end-of-life (EOL). Methods: This systematic review was conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guideline. Literature was searched on PubMed, EMBASE, CINAHL, PsycINFO and Google Scholar until December 2019 for studies on deprescribing intervention with a control group (with or without randomisation); targeting ⩾65-year olds, at EOL, with at least one life-limiting illness and at least one potentially inappropriate DPM. We were interested in any patient-related outcomes. Studies with similar outcome assessment criteria were subjected to meta-analysis and narrative synthesis otherwise. The risk of bias was assessed using Cochrane Risk of Bias and ROBINS-I tools for randomised controlled trials (RCTs) and quasi-experimental non-randomised controlled studies, respectively. Results: Five studies covering 689 participants with mean age 81.6–85.7 years, the majority (74.6–100%) with dementia were included. The risk of bias was moderate to low. The deprescribing of DPMs lowered the risk of mortality (risk ratio (RR) = 0.59, 95% confidence interval (CI) = 0.44–0.79) and referral to acute care facilities (RR = 0.40, 95% CI = 0.22–0.73), but did not have a significant impact on the risk of falls, non-vertebral fracture, emergency presentation, unplanned hospital admission, or general practitioner visits. No significant difference was observed in the quality of life, physical and cognitive functions between the intervention and control groups. Conclusion: There is some evidence that deprescribing of DPMs for older adults near the EOL can lower the risk of mortality and referral to acute care facilities, but there are insufficient good-quality studies powered to confirm a benefit in terms of quality of life, physical or cognitive function, health service utilisation and adverse events. Plain Language Summary What is the health impact of withdrawal or dose reduction of medication used for disease prevention and symptom control in older adults near end-of-life? Introduction: Older adults (aged ⩾ 65 years) with advanced diseases such as cancer, dementia, and organ failure tend to have a limited life expectancy. With the progression of these diseases towards the end-of-life, the intensity for day-to-day supportive care becomes increasingly necessary. The use of medications for symptom management is a critical part of such care, but the use of medications for long-term disease prevention can become irrelevant due to the already shortened life expectancy and may become harmful due to alterations in physiology and pharmacology associated with age and frailty. This necessitates the withdrawal or dose reduction of inappropriate medications, the process called deprescribing. The decision to deprescribe medications used for both disease prevention and symptom control (DPMs) in this population is often challenging for clinicians. In this context, whether deprescribing of DPMs can improve patient-related health outcomes is unknown. Methods: Evidence from the literature was reviewed and analysed, and the quality of studies was assessed. Five studies were identified, which had 689 participants with an average age above 80 years and mostly suffering from dementia. Results: The analysis of these studies showed deprescribing of DPMs lowered the risk of death and referral to acute care facilities at 12 months but had no significant impact on falls, non-vertebral fractures, emergency presentations, unplanned hospital admission, general practitioner visits, quality of life, physical and mental functions. Conclusion: In conclusion, there were insufficient numbers of high-quality studies powered to confirm whether deprescribing of DPMs reduces adverse events, health service use, or improves the quality of life or functioning in older adults near the end of life.

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Objective To identify and summarize the evidence about the extent of overuse of medications in low- and middle-income countries, its drivers, consequences and potential solutions. Methods We conducted a scoping review by searching the databases PubMed®, Embase®, APA PsycINFO® and Global Index Medicus using a combination of MeSH terms and free text words around overuse of medications and overtreatment. We included studies in any language published before 25 October 2021 that reported on the extent of overuse, its drivers, consequences and solutions. Findings We screened 3489 unique records and included 367 studies reporting on over 5.1 million prescriptions across 80 low- and middle-income countries – with studies from 58.6% (17/29) of all low-, 62.0% (31/50) of all lower-middle- and 60.0% (33/55) of all upper-middle-income countries. Of the included studies, 307 (83.7%) reported on the extent of overuse of medications, with estimates ranging from 7.3% to 98.2% (interquartile range: 30.2–64.5). Commonly overused classes included antimicrobials, psychotropic drugs, proton pump inhibitors and antihypertensive drugs. Drivers included limited knowledge of harms of overuse, polypharmacy, poor regulation and financial influences. Consequences were patient harm and cost. Only 11.4% (42/367) of studies evaluated solutions, which included regulatory reforms, educational, deprescribing and audit–feedback initiatives. Conclusion Growing evidence suggests overuse of medications is widespread within low- and middle-income countries, across multiple drug classes, with few data of solutions from randomized trials. Opportunities exist to build collaborations to rigorously develop and evaluate potential solutions to reduce overuse of medications.

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