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We aimed to examine a) the policies of national and international clinical trial registries regarding observational studies; b) the time trends of observational study registration; and c) the published arguments for and against observational study registration. Scoping review of registry practices and published arguments. We searched the websites and databases of all 19 members of the World Health Organization's Registry Network to identify policies relating to observational studies and the number of observational studies registered annually from the beginning of the registries to 2022. Regarding documents with arguments, we searched Medline, Embase, Google Scholar, and top medical and epidemiological journals from 2009 to 2023. We classified arguments as “main” based on the number (n ≥ 3) of documents they occurred in. Of 19 registries, 15 allowed observational study registration, of which seven (35%) had an explicit policy regarding what to register and two (11%) about when to register. The annual number of observational study registrations increased over time in all registries; for example, ClinicalTrials.gov increased from 313 in 1999 to 9775 in 2022. Fifty documents provided arguments concerning observational study registration: 31 argued for, 18 against, and one was neutral. Since 2012, 19 out of 25 documents argued for. We classified nine arguments as main: five for and four against. The two most prevalent arguments for were the prevention of selective reporting of outcomes (n = 16) and publication bias (n = 12), and against were that it will hinder exploration of new ideas (n = 17) and it will waste resources (n = 6). Few registries have policies regarding observational studies; an increasing number of observational studies were registered; there was a lively debate on the merits of registration of observational studies, which, since 2012, seems to converge toward proregistration. •Only 7 (35%) study registries had an explicit policy for observational studies.•Only 2 (11%) registries specified when to register observational studies.•The annual number of observational study registration increased in all registries.•The debate on observational study registration converges toward pro-registration.

In this paper, we discuss recent developments in econometrics that we view as important for empirical researchers working on policy evaluation questions. We focus on three main areas, in each case, highlighting recommendations for applied work. First, we discuss new research on identification strategies in program evaluation, with particular focus on synthetic control methods, regression discontinuity, external validity, and the causal interpretation of regression methods. Second, we discuss various forms of supplementary analyses, including placebo analyses as well as sensitivity and robustness analyses, intended to make the identification strategies more credible. Third, we discuss some implications of recent advances in machine learning methods for causal effects, including methods to adjust for differences between treated and control units in high-dimensional settings, and methods for identifying and estimating heterogenous treatment effects.

BackgroundDouble checking medication administration in hospitals is often standard practice, particularly for high-risk drugs, yet its effectiveness in reducing medication administration errors (MAEs) and improving patient outcomes remains unclear. We conducted a systematic review of studies evaluating evidence of the effectiveness of double checking to reduce MAEs.MethodsFive databases (PubMed, Embase, CINAHL, Ovid@Journals, OpenGrey) were searched for studies evaluating the use and effectiveness of double checking on reducing medication administration errors in a hospital setting. Included studies were required to report any of three outcome measures: an effect estimate such as a risk ratio or risk difference representing the association between double checking and MAEs, or between double checking and patient harm; or a rate representing adherence to the hospital’s double checking policy.ResultsThirteen studies were identified, including 10 studies using an observational study design, two randomised controlled trials and one randomised trial in a simulated setting. Studies included both paediatric and adult inpatient populations and varied considerably in quality. Among three good quality studies, only one showed a significant association between double checking and a reduction in MAEs, another showed no association, and the third study reported only adherence rates. No studies investigated changes in medication-related harm associated with double checking. Reported double checking adherence rates ranged from 52% to 97% of administrations. Only three studies reported if and how independent and primed double checking were differentiated.ConclusionThere is insufficient evidence that double versus single checking of medication administration is associated with lower rates of MAEs or reduced harm. Most comparative studies fail to define or investigate the level of adherence to independent double checking, further limiting conclusions regarding effectiveness in error prevention. Higher-quality studies are needed to determine if, and in what context (eg, drug type, setting), double checking produces sufficient benefits in patient safety to warrant the considerable resources required. CRD42018103436.

The SARS-CoV-2 variant of concern, omicron, appears to be less severe than delta. We aim to quantify the differences in symptom prevalence, risk of hospital admission, and symptom duration among the vaccinated population. In this prospective longitudinal observational study, we collected data from participants who were self-reporting test results and symptoms in the ZOE COVID app (previously known as the COVID Symptoms Study App). Eligible participants were aged 16–99 years, based in the UK, with a body-mass index between 15 and 55 kg/m2, had received at least two doses of any SARS-CoV-2 vaccine, were symptomatic, and logged a positive symptomatic PCR or lateral flow result for SARS-CoV-2 during the study period. The primary outcome was the likelihood of developing a given symptom (of the 32 monitored in the app) or hospital admission within 7 days before or after the positive test in participants infected during omicron prevalence compared with those infected during delta prevalence. Between June 1, 2021, and Jan 17, 2022, we identified 63 002 participants who tested positive for SARS-CoV-2 and reported symptoms in the ZOE app. These patients were matched 1:1 for age, sex, and vaccination dose, across two periods (June 1 to Nov 27, 2021, delta prevalent at >70%; n=4990, and Dec 20, 2021, to Jan 17, 2022, omicron prevalent at >70%; n=4990). Loss of smell was less common in participants infected during omicron prevalence than during delta prevalence (16·7% vs 52·7%, odds ratio [OR] 0·17; 95% CI 0·16–0·19, p<0·001). Sore throat was more common during omicron prevalence than during delta prevalence (70·5% vs 60·8%, 1·55; 1·43–1·69, p<0·001). There was a lower rate of hospital admission during omicron prevalence than during delta prevalence (1·9% vs 2·6%, OR 0·75; 95% CI 0·57–0·98, p=0·03). The prevalence of symptoms that characterise an omicron infection differs from those of the delta SARS-CoV-2 variant, apparently with less involvement of the lower respiratory tract and reduced probability of hospital admission. Our data indicate a shorter period of illness and potentially of infectiousness which should impact work–health policies and public health advice. Wellcome Trust, ZOE, National Institute for Health Research, Chronic Disease Research Foundation, National Institutes of Health, and Medical Research Council

Objective To contextualise the degree of harm that comes from unsafe medical care compared with individual health conditions using the global burden of disease (GBD), a metric to determine how much suffering is caused by individual diseases. Design Analytic modelling of observational studies investigating unsafe medical care in countries’ inpatient care settings, stratified by national income, to identify incidence of seven adverse events for GBD modelling. Observational studies were generated through a comprehensive search of over 16 000 articles written in English after 1976, of which over 4000 were appropriate for full text review. Results The incidence, clinical outcomes, demographics and costs for each of the seven adverse events were collected from each publication when available. We used disability-adjusted life years (DALYs) lost as a standardised metric to measure morbidity and mortality due to specific adverse events. We estimate that there are 421 million hospitalisations in the world annually, and approximately 42.7 million adverse events. These adverse events result in 23 million DALYs lost per year. Approximately two-thirds of all adverse events, and the DALYs lost from them, occurred in low-income and middle-income countries. Conclusions This study provides early evidence that adverse events due to medical care represent a major source of morbidity and mortality globally. Though suffering related to the lack of access to care in many countries remains, these findings suggest the importance of critically evaluating the quality and safety of the care provided once a person accesses health services. While further refinements of the estimates are needed, these data should be a call to global health policymakers to make patient safety an international priority.

Evaluating complex interventions is complicated. The Medical Research Council's evaluation framework (2000) brought welcome clarity to the task. Now the council has updated its guidance

The ongoing pandemic of Novel Coronavirus Disease 2019 (COVID-19) infection has created a global emergency. Despite the infection causes a mild illness to most people, some patients are severely affected, demanding an urgent need to better understand how to risk-stratify infected subjects. This is a meta-analysis of observational studies evaluating cardiovascular (CV) complications in hospitalized COVID-19 patients and the impact of cardiovascular risk factors (RF) or comorbidities on mortality. Data sources: PubMed, Scopus, and ISI from 1 December 2019 through 11 June 2020; references of eligible studies; scientific session abstracts; cardiology web sites. We selected studies reporting clinical outcomes of hospitalized patients with COVID-19. The main outcome was death. Secondary outcomes were cardiovascular symptoms and cardiovascular events developed during the COVID-19-related hospitalization. Extracted data were recorded in excel worksheets and analysed using statistical software (MedCalc, OpenMetanalyst, R). We used the proportion with 95% CI as the summary measure. A Freeman-Tukey transformation was used to calculate the weighted summary proportion under the random-effects model. Heterogeneity was assessed by using the Cochran Q test and I2 values. Among 77317 hospitalized patients from 21 studies, 12.86% had cardiovascular comorbidities or RF. Cardiovascular complications were registered in 14.09% of cases during hospitalization. At meta-regression analysis, pre-existing cardiovascular comorbidities or RF were significantly associated to cardiovascular complications in COVID-19 patients (p = 0.019). Pre-existing cardiovascular comorbidities or RF (p<0.001), older age (p<0.001), and the development of cardiovascular complications during the hospitalization (p = 0.038) had a significant interaction with death. Cardiovascular complications are frequent among COVID-19 patients, and might contribute to adverse clinical events and mortality, together with pre-existing cardiovascular comorbidities and RF. Clinicians worldwide should be aware of this association, to identifying patients at higher risk.

Vitamin D deficiency co-exists in patients with COVID-19. At this time, dark skin color, increased age, the presence of pre-existing illnesses and vitamin D deficiency are features of severe COVID disease. Of these, only vitamin D deficiency is modifiable. Through its interactions with a multitude of cells, vitamin D may have several ways to reduce the risk of acute respiratory tract infections and COVID-19: reducing the survival and replication of viruses, reducing risk of inflammatory cytokine production, increasing angiotensin-converting enzyme 2 concentrations, and maintaining endothelial integrity. Fourteen observational studies offer evidence that serum 25-hydroxyvitamin D concentrations are inversely correlated with the incidence or severity of COVID-19. The evidence to date generally satisfies Hill’s criteria for causality in a biological system, namely, strength of association, consistency, temporality, biological gradient, plausibility (e.g., mechanisms), and coherence, although experimental verification is lacking. Thus, the evidence seems strong enough that people and physicians can use or recommend vitamin D supplements to prevent or treat COVID-19 in light of their safety and wide therapeutic window. In view of public health policy, however, results of large-scale vitamin D randomized controlled trials are required and are currently in progress.

Observational studies are increasingly used to inform health decision-making when randomised trials are not feasible, ethical or timely. The target trial approach provides a framework to help minimise common biases in observational studies that aim to estimate the causal effect of interventions. Incomplete reporting of studies using the target trial framework limits the ability for clinicians, researchers, patients and other decision-makers to appraise, synthesise and interpret findings to inform clinical and public health practice and policy. This paper describes the methods that we will use to develop the TrAnsparent ReportinG of observational studies Emulating a Target trial (TARGET) reporting guideline. The TARGET reporting guideline will be developed in five stages following recommended guidance. The first stage will identify target trial reporting practices by systematically reviewing published studies that explicitly emulated a target trial. The second stage will identify and refine items to be considered for inclusion in the TARGET guideline by consulting content experts using sequential online surveys. The third stage will prioritise and consolidate key items to be included in the TARGET guideline at an in-person consensus meeting of TARGET investigators. The fourth stage will produce and pilot-test both the TARGET guideline and explanation and elaboration document with relevant stakeholders. The fifth stage will disseminate the TARGET guideline and resources via journals, conferences and courses. Ethical approval for the survey has been attained (HC220536). The TARGET guideline will be disseminated widely in partnership with stakeholders to maximise adoption and improve reporting of these studies.

Influenza virus infections are believed to spread mostly by close contact in the community. Social distancing measures are essential components of the public health response to influenza pandemics. The objective of these mitigation measures is to reduce transmission, thereby delaying the epidemic peak, reducing the size of the epidemic peak, and spreading cases over a longer time to relieve pressure on the healthcare system. We conducted systematic reviews of the evidence base for effectiveness of multiple mitigation measures: isolating ill persons, contact tracing, quarantining exposed persons, school closures, workplace measures/closures, and avoiding crowding. Evidence supporting the effectiveness of these measures was obtained largely from observational studies and simulation studies. Voluntary isolation at home might be a more feasible social distancing measure, and pandemic plans should consider how to facilitate this measure. More drastic social distancing measures might be reserved for severe pandemics.