Evaluating methods for risk prediction of Covid-19 mortality in nursing home residents before and after vaccine availability: a retrospective cohort study.

BACKGROUND: SARS-CoV-2 vaccines are effective in reducing hospitalization, COVID-19 symptoms, and COVID-19 mortality for nursing home (NH) residents. We sought to compare the accuracy of various machine learning models, examine changes to model performance, and identify resident characteristics that have the strongest associations with 30-day COVID-19 mortality, before and after vaccine availability. METHODS: We conducted a population-based retrospective cohort study analyzing data from all NH facilities across Ontario, Canada. We included all residents diagnosed with SARS-CoV-2 and living in NHs between March 2020 and July 2021. We employed five machine learning algorithms to predict COVID-19 mortality, including logistic regression, LASSO regression, classification and regression trees (CART), random forests, and gradient boosted trees. The discriminative performance of the models was evaluated using the area under the receiver operating characteristic curve (AUC) for each model using 10-fold cross-validation. Model calibration was determined through evaluation of calibration slopes. Variable importance was calculated by repeatedly and randomly permutating the values of each predictor in the dataset and re-evaluating the model's performance. RESULTS: A total of 14,977 NH residents and 20 resident characteristics were included in the model. The cross-validated AUCs were similar across algorithms and ranged from 0.64 to 0.67. Gradient boosted trees and logistic regression had an AUC of 0.67 pre- and post-vaccine availability. CART had the lowest discrimination ability with an AUC of 0.64 pre-vaccine availability, and 0.65 post-vaccine availability. The most influential resident characteristics, irrespective of vaccine availability, included advanced age (≥ 75 years), health instability, functional and cognitive status, sex (male), and polypharmacy. CONCLUSIONS: The predictive accuracy and discrimination exhibited by all five examined machine learning algorithms were similar. Both logistic regression and gradient boosted trees exhibit comparable performance and display slight superiority over other machine learning algorithms. We observed consistent model performance both before and after vaccine availability. The influence of resident characteristics on COVID-19 mortality remained consistent across time periods, suggesting that changes to pre-vaccination screening practices for high-risk individuals are effective in the post-vaccination era.

Potentially Modifiable Risk Factors for Dementia and Mild Cognitive Impairment: An Umbrella Review and Meta-Analysis.

INTRODUCTION: The prevalence of mild and major neurocognitive disorders (NCDs), also referred to as mild cognitive impairment and dementia, is rising globally. The prevention of NCDs is a major global public health interest. We sought to synthesize the literature on potentially modifiable risk factors for NCDs. METHODS: We conducted an umbrella review using a systematic search across multiple databases to identify relevant systematic reviews and meta-analyses. Eligible reviews examined potentially modifiable risk factors for mild or major NCDs. We used a random-effects multi-level meta-analytic approach to synthesize risk ratios for each risk factor while accounting for overlap in the reviews. We further examined risk factors for major NCD due to two common etiologies: Alzheimer's disease and vascular dementia. RESULTS: A total of 45 reviews with 212 meta-analyses were synthesized. We identified fourteen broadly defined modifiable risk factors that were significantly associated with these disorders: alcohol consumption, body weight, depression, diabetes mellitus, diet, hypertension, less education, physical inactivity, sensory loss, sleep disturbance, smoking, social isolation, traumatic brain injury, and vitamin D deficiency. All 14 factors were associated with the risk of major NCD, and five were associated with mild NCD. We found considerably less research for vascular dementia and mild NCD. CONCLUSION: Our review quantifies the risk associated with 14 potentially modifiable risk factors for mild and major NCDs, including several factors infrequently included in dementia action plans. Prevention strategies should consider approaches that reduce the incidence and severity of these risk factors through health promotion, identification, and early management.

Validating the Emergency Department Avoidability Classification (EDAC): A cluster randomized single-blinded agreement study.

INTRODUCTION: The Emergency Department Avoidability Classification (EDAC) retrospectively classifies emergency department (ED) visits that could have been safely managed in subacute primary care settings, but has not been validated against a criterion standard. A validated EDAC could enable accurate and reliable quantification of avoidable ED visits. We compared agreement between the EDAC and ED physician judgements to specify avoidable ED visits. MATERIALS AND METHODS: We conducted a cluster randomized, single-blinded agreement study in an academic hospital in Hamilton, Canada. ED visits between January 1, 2019, and December 31, 2019 were clustered based on EDAC classes and randomly sampled evenly. A total of 160 ED visit charts were randomly assigned to ten participating ED physicians at the academic hospital for evaluation. Physicians judged if the ED visit could have been managed appropriately in subacute primary care (an avoidable visit); each ED visit was evaluated by two physicians independently. We measured interrater agreement between physicians with a Cohen's kappa and 95% confidence intervals (CI). We evaluated the correlation between the EDAC and physician judgements using a Spearman rank correlation and ordinal logistic regression with odds ratios (ORs) and 95% CIs. We examined the EDAC's precision to identify avoidable ED visits using accuracy, sensitivity and specificity. RESULTS: ED physicians agreed on 139 visits (86.9%) with a kappa of 0.69 (95% CI 0.59-0.79), indicating substantial agreement. Physicians judged 96.2% of ED visits classified as avoidable by the EDAC as suitable for management in subacute primary care. We found a high correlation between the EDAC and physician judgements (0.64), as well as a very strong association to classify avoidable ED visits (OR 80.0, 95% CI 17.1-374.9). The EDACs avoidable and potentially avoidable classes demonstrated strong accuracy to identify ED visits suitable for management in subacute care (82.8%, 95% CI 78.2-86.8). DISCUSSION: The EDAC demonstrated strong evidence of criterion validity to classify avoidable ED visits. This classification has important potential for accurately monitoring trends in avoidable ED utilization, measuring proportions of ED volume attributed to avoidable visits and informing interventions intended at reducing ED use by patients who do not require emergency or life-saving healthcare.

Primary care quality for older adults: Practice-based quality measures derived from a RAND/UCLA appropriateness method study.

We established consensus on practice-based metrics that characterize quality of care for older primary care patients and can be examined using secondary health administrative data. We conducted a two-round RAND/UCLA Appropriateness Method (RAM) study and recruited 10 Canadian clinicians and researchers with expertise relevant to the primary care of elderly patients. Informed by a literature review, the first RAM round evaluated the appropriateness and importance of candidate quality measures in an online questionnaire. Technical definitions were developed for each endorsed indicator to specify how the indicator could be operationalized using health administrative data. In a virtual synchronous meeting, the expert panel offered feedback on the technical specifications for the endorsed indicators. Panelists then completed a second (final) questionnaire to rate each indicator and corresponding technical definition on the same criteria (appropriateness and importance). We used statistical integration to combine technical expert panelists' judgements and content analysis of open-ended survey responses. Our literature search and internal screening resulted in 61 practice-based quality indicators for rating. We developed technical definitions for indicators endorsed in the first questionnaire (n = 55). Following the virtual synchronous meeting and second questionnaire, we achieved consensus on 12 practice-based quality measures across four Priority Topics in Care of the Elderly. The endorsed indicators provide a framework to characterize practice- and population-level encounters of family physicians delivering care to older patients and will offer insights into the outcomes of their care provision. This study presented a case of soliciting expert feedback to develop measurable practice-based quality indicators that can be examined using administrative data to understand quality of care within population-based data holdings. Future work will refine and operationalize the technical definitions established through this process to examine primary care provision for older adults in a particular context (Ontario, Canada).

Examining the "Potentially Preventable Emergency Department Transfer" Indicator Among Nursing Home Residents.

OBJECTIVE: To determine if nursing home (NH) resident characteristics associated with potentially preventable emergency department transfers (PPEDs) are similarly associated with non-potentially preventable emergency department transfers (non-PPEDs). DESIGN: We conducted a population-level retrospective cohort study using linked administrative data reported using the Resident Assessment Instrument-Minimum Data Set Version 2.0 and the National Ambulatory Care Reporting System for emergency department transfers. SETTING AND PARTICIPANTS: We assessed all NH residents transferred to the emergency department within 92 days after admission. The cohort included 56,433 NH resident admissions assessment of which 3498 NH residents experienced PPEDs, and 9331 residents experienced non-PPEDs. METHODS: We assessed Ontario NH residents admission assessments collected between January 1, 2017, and December 31, 2018. We used cumulative incidence functions and Cox regression to compare resident characteristics between residents experiencing PPEDs and non-PPEDs. PPEDs were defined based on the International Classification of Diseases, 10th Revision. RESULTS: Approximately 23% of residents experienced an emergency department transfer within 92 days of NH admission. The cumulative incidence of PPEDs was 6.3% and non-PPEDs was 16.8%. After adjusting for clinically relevant features, 14 of 18 resident admission characteristics were associated with both types of transfers. Resident admission characteristics associated with a greater risk of PPEDs solely were pneumonia [hazard ratio (HR) 1.48; CI 1.25-1.70] and oxygen therapy (HR 1.88; CI 1.69-2.10). Resident admission characteristics associated with a greater risk of non-PPEDs solely are experiencing a change in mood (HR 1.09; CI 1.01-1.18) and delirium (HR 1.08; CI 1.04-1.13). CONCLUSIONS AND IMPLICATIONS: PPEDs were associated with a similar cluster of NH resident characteristics as those transferred for non-ambulatory reasons, suggesting that the clinical distinction between PPEDs vs non-PPEDs within the NH might be unclear. These findings highlight that the PPED indicator could be revised to improve specificity.

The association between frailty, long-term care home characteristics and COVID-19 mortality before and after SARS-CoV-2 vaccination: a retrospective cohort study.

BACKGROUND: The relative contributions of long-term care (LTC) resident frailty and home-level characteristics on COVID-19 mortality has not been well studied. We examined the association between resident frailty and home-level characteristics with 30-day COVID-19 mortality before and after the availability of SARS-CoV-2 vaccination in LTC. METHODS: We conducted a population-based retrospective cohort study of LTC residents with confirmed SARS-CoV-2 infection in Ontario, Canada. We used multi-level multivariable logistic regression to examine associations between 30-day COVID-19 mortality, the Hubbard Frailty Index (FI), and resident and home-level characteristics. We compared explanatory models before and after vaccine availability. RESULTS: There were 11,179 and 3,655 COVID-19 cases in the pre- and post-vaccine period, respectively. The 30-day COVID-19 mortality was 25.9 and 20.0% during the same periods. The median odds ratios for 30-day COVID-19 mortality between LTC homes were 1.50 (95% credible interval [CrI]: 1.41-1.65) and 1.62 (95% CrI: 1.46-1.96), respectively. In the pre-vaccine period, 30-day COVID-19 mortality was higher for males and those of greater age. For every 0.1 increase in the Hubbard FI, the odds of death were 1.49 (95% CI: 1.42-1.56) times higher. The association between frailty and mortality remained consistent in the post-vaccine period, but sex and age were partly attenuated. Despite the substantial home-level variation, no home-level characteristic examined was significantly associated with 30-day COVID-19 mortality during either period. INTERPRETATION: Frailty is consistently associated with COVID-19 mortality before and after the availability of SARS-CoV-2 vaccination. Home-level characteristics previously attributed to COVID-19 outcomes do not explain significant home-to-home variation in COVID-19 mortality.

Validation of a classification to identify emergency department visits suitable for subacute and virtual care models: a randomised single-blinded agreement study protocol.

INTRODUCTION: Redirecting suitable patients from the emergency department (ED) to alternative subacute settings may assist in reducing ED overcrowding while delivering equivalent care. The Emergency Department Avoidance Classification (EDAC) was constructed to retrospectively classify ED visits that may have been suitable for safe management in a subacute or virtual clinical setting. The EDAC has established face and content validity but has not been tested against a reference standard as a criterion. OBJECTIVES: Our primary objective is to examine the agreement between the EDAC and ED physician judgements in retrospectively identifying ED visits suitable for subacute care management. Our secondary objective is to assess the validity of ED physicians' judgement as a criterion standard. Our tertiary objective is to examine how the ED physician's perception of a virtual ED care alternative correlates with the EDAC. METHODS AND ANALYSIS: A randomised single-centre, single-blinded agreement study. We will randomly select ED charts between 1 January and 31 December 2019 from an academic hospital in Hamilton, Canada. ED charts will be randomly assigned to participating ED physicians who will evaluate if this ED visit could have been managed appropriately and safely in a subacute and/or virtual model of care. Each chart will be reviewed by two physicians independently. We compute our needed sample size to be 79 charts. We will use kappa statistics to measure inter-rater agreement. A repeated measures regression model of physician ratings will provide variance estimates that we will use to assess the intraclass correlation of ED physician ratings and the EDAC. ETHICS AND DISSEMINATION: This study has been approved by the Hamilton Integrated Research Ethics Board (2022-14625). If validated, the EDAC may provide an ED-based classification to identify potentially avoidable ED visits, monitor ED visit trends, and proactively delineate those best suited for subacute or virtual care models.

An adaptation of a macroscale methodology to assess the direct economic losses caused by Tropical Cyclone Idai in Zimbabwe.

Tropical cyclones are among the costliest disasters in the world, with reported losses amounting to billions of US dollars on an annual basis. To reduce the impact of disasters including cyclones, Zimbabwe signed the Sendai Framework whose Target C is aimed at reducing the direct economic losses of disasters. Under the direction of the United Nations Office for Disaster Risk Reduction (UNDRR), an open-ended intergovernmental expert working group (OIEWG) developed a simple methodology for estimating direct disaster-economic loss. Therefore, this study tested the applicability of the OIEWG methodology in assessing the direct economic losses induced by Tropical Cyclone Idai (TCI) in Zimbabwe. The results revealed that TCI inflicted huge losses in most sectors of the economy, notably the housing, agriculture and the critical infrastructure. The sectoral analysis approach of the OIEWG methodology worked well in distinguishing direct and indirect loses as well as in underlining the need to adopt and effectively implement adequate risk reduction strategies in the built environment. Strengthening such strategies such as the 'build back better' principle, cyclone forecasting and warning systems and constructing cyclone-resilient infrastructure is critical in order to minimise direct losses attributed to cyclones.

Mental Health Condition among University Students of Bangladesh during the Critical COVID-19 Period.

Bangladesh's education sector has been in a state of flux since COVID-19. During the pandemic, all university campuses were closed. There was a mental health issue among the students. This study aims to examine the mental health condition and the determinants that contribute to adverse mental health conditions among university students of Bangladesh. A survey was performed online among university students in Bangladesh, in mid-June 2020 when averaging 3345 affected cases of the population daily. The convenience sampling technique was used and the survey gathered data from 365 university students. The relationship between general information and Depression, Anxiety, and Stress Scale 21 (DASS-21) subscales of university students was determined. The questionnaire was administered to respondents during the pandemic, which ensured fast replies. Linear regression models were used for statistical analysis. University students indicated normal levels of depression (30.41%), anxiety (43.29%), and stress (47.40%). However, a disproportionate number of extremely depressed, anxious, and stressed university students suggested a mental health status of concern. There were significant connections between the individual's opinion of social satisfaction, mental health concerns, and the present location's safety with an undesirable mental health condition. Female students were shown to be much more anxious and stressed than male students. Capital Dhaka city students were more depressed and anxious than students outside of Dhaka. Financial and psychological support for students may help mitigate the psychological impact. Authorities should make effective efforts to reduce mental health problems among these students. This research may aid organizations, health care providers, and social workers in their attempts to prepare for and respond to pandemics.

Nursing Home Resident Admission Characteristics and Potentially Preventable Emergency Department Transfers.

OBJECTIVES: To determine which nursing home (NH) resident-level admission characteristics are associated with potentially preventable emergency department (PPED) transfers. DESIGN: We conducted a population-level retrospective cohort study on NH resident data collected using the Resident Assessment Instrument-Minimum Data Set Version 2.0 and linked to the National Ambulatory Care Reporting System for ED transfers. SETTING: We used all NH resident admission assessments from January 1, 2017, to December 31, 2018, in Ontario. PARTICIPANTS: The cohort included the admission assessment of 56,433 NH residents. METHODS: PPED transfers were defined based on the International Classification of Disease, Version 10 (Canadian) We used logistic regression with 10-fold cross-validation and computed average marginal effects to identify the association between resident characteristics at NH admission and PPED transfers within 92 days after admission. RESULTS: Overall, 6.2% of residents had at least 1 PPED transfer within 92 days of NH admission. After adjustment, variables that had a prevalence of 10% or more that were associated with a 1% or more absolute increase in the risk of a PPED transfer included polypharmacy [of cohort (OC) 84.4%, risk difference (RD) 2.0%], congestive heart failure (OC 29.0%, RD 3.0%), and renal failure (OC 11.6%, RD 1.2%). Female sex (OC 63.2%, RD -1.3%), a do not hospitalize directive (OC 24.4%, RD -2.6%), change in mood (OC 66.9%, RD -1.2%), and Alzheimer's or dementia (OC 62.1%, RD -1.2%) were more than 10% prevalent and associated with a 1% or more absolute decrease in the risk of a PPED. CONCLUSIONS AND IMPLICATIONS: Though many routinely collected resident characteristics were associated with a PPED transfer, the absence of sufficiently discriminating characteristics suggests that emergency department visits by NH residents are multifactorial and difficult to predict. Future studies should assess the clinical utility of risk factor identification to prevent transfers.

Vertical transmission risk of SARS-CoV-2 infection in the third trimester: a systematic scoping review.

BACKGROUND: Studies on COVID-19 infection in pregnancy thus far have largely focused on characterizing maternal and neonatal clinical characteristics. However, another evolving focus is assessing and mitigating the risk of vertical transmission amongst COVID-19-positive mothers. The objective of this review was to summarize the current evidence on the vertical transmission potential of COVID-19 infection in the third trimester and its effects on the neonate. METHODS: OVID MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trial (CENTRAL) were searched from January 2020 to May 2020, with continuous surveillance. RESULTS: 18 studies met the inclusion criteria, consisting of 157 mothers and 160 neonates. The mean age of the pregnant patients was 30.8 years and the mean gestational period was 37 weeks and 1 d. Currently, there is currently no conclusive evidence to suggest that vertical transmission of SARS-CoV-2 occurs. Amongst 81 (69%) neonates who were tested for SARS-CoV-2, 5 (6%) had a positive result. However, amongst these 5 neonates, the earliest test was performed at 16 h after birth, and only 1 neonate was positive when they were later re-tested. However, this neonate initially tested negative at birth, suggesting that the SARS-CoV-2 infection was likely hospital-acquired rather than vertically transmitted. 13 (8%) neonates had complications or symptoms. CONCLUSIONS: The findings of this rapid descriptive review based on early clinical evidence suggest that vertical transmission of SARS-CoV-2 from mother to neonate/newborn did not occur. Future studies are needed to determine the optimal management of neonates born to COVID-19-positive mothers.

Characteristics and quality of systematic reviews and meta-analyses of observational nutritional epidemiology: a cross-sectional study.

BACKGROUND: Dietary recommendations and policies should be guided by rigorous systematic reviews. Reviews that are of poor methodological quality may be ineffective or misleading. Most of the evidence in nutrition comes from nonrandomized studies of nutritional exposures (usually referred to as nutritional epidemiology studies), but to date methodological evaluations of the quality of systematic reviews of such studies have been sparse and inconsistent. OBJECTIVES: We aimed to investigate the quality of recently published systematic reviews and meta-analyses of nutritional epidemiology studies and to propose guidance addressing major limitations. METHODS: We searched MEDLINE (January 2018-August 2019), EMBASE (January 2018-August 2019), and the Cochrane Database of Systematic Reviews (January 2018-February 2019) for systematic reviews of nutritional epidemiology studies. We included a random sample of 150 reviews. RESULTS: Most reviews were published by authors from Asia (n = 49; 32.7%) or Europe (n = 43; 28.7%) and investigated foods or beverages (n = 60; 40.0%) and cancer morbidity and mortality (n = 54; 36%). Reviews often had important limitations: less than one-quarter (n = 30; 20.0%) reported preregistration of a protocol and almost one-third (n = 42; 28.0%) did not report a replicable search strategy. Suboptimal practices and errors in the synthesis of results were common: one-quarter of meta-analyses (n = 30; 26.1%) selected the meta-analytic model based on statistical indicators of heterogeneity and almost half of meta-analyses (n = 50; 43.5%) did not consider dose-response associations even when it was appropriate to do so. Only 16 (10.7%) reviews used an established system to evaluate the certainty of evidence. CONCLUSIONS: Systematic reviews of nutritional epidemiology studies often have serious limitations. Authors can improve future reviews by involving statisticians, methodologists, and researchers with substantive knowledge in the specific area of nutrition being studied and using a rigorous and transparent system to evaluate the certainty of evidence.

Assessments of risk of bias in systematic reviews of observational nutritional epidemiologic studies are often not appropriate or comprehensive: a methodological study.

BACKGROUND: An essential component of systematic reviews is the assessment of risk of bias. To date, there has been no investigation of how reviews of non-randomised studies of nutritional exposures (called 'nutritional epidemiologic studies') assess risk of bias. OBJECTIVE: To describe methods for the assessment of risk of bias in reviews of nutritional epidemiologic studies. METHODS: We searched MEDLINE, EMBASE and the Cochrane Database of Systematic Reviews (Jan 2018-Aug 2019) and sampled 150 systematic reviews of nutritional epidemiologic studies. RESULTS: Most reviews (n=131/150; 87.3%) attempted to assess risk of bias. Commonly used tools neglected to address all important sources of bias, such as selective reporting (n=25/28; 89.3%), and frequently included constructs unrelated to risk of bias, such as reporting (n=14/28; 50.0%). Most reviews (n=66/101; 65.3%) did not incorporate risk of bias in the synthesis. While more than half of reviews considered biases due to confounding and misclassification of the exposure in their interpretation of findings, other biases, such as selective reporting, were rarely considered (n=1/150; 0.7%). CONCLUSION: Reviews of nutritional epidemiologic studies have important limitations in their assessment of risk of bias.

Older Emergency Department Patients: Does Baseline Care Status Matter?

BACKGROUND: Little is known about the prognostic differences between older emergency department (ED) patients who present with different formal support requirements in the community. We set out to describe and compare the patient profiles and patterns of health service use among three older ED cohorts: home care clients, nursing home residents and those receiving no formal support. METHODS: We conducted a secondary analysis of the Canadian cohort from the interRAI multinational ED study. Data were collected using interRAI ED contact assessment on patients 75 years of age and older (n = 2,274), in eight ED sites across Canada. A series of descriptive statistics were reported. Adjusted associations were determined using logistic regression. RESULTS: Older adults receiving no formal support services were most stable. However, they were most likely to be hospitalized. Older home care clients were most likely to report depressive symptoms and distressed caregivers. They also had the greatest odds of frequent ED visitation post-discharge (OR=1.9; 95% CI=1.39-2.59). Older adults transferred from a nursing home were the frailest but had the lowest odds of hospital admission (OR=0.14; 95% CI=0.09-0.23). CONCLUSION: We demonstrated the importance of inquiring about community-based formal support services and provide data to support decision-making in the ED.

Interferon beta-1a for patients with moderate to severe acute respiratory distress syndrome: a systematic review and meta-analysis of randomized trials.

INTRODUCTION: Acute respiratory distress syndrome (ARDS) is a life-threatening disease characterized by respiratory failure with rapidly progressing inflammation. Currently, no effective pharmacological treatment for ARDS is available. OBJECTIVES: We conducted this systematic review and meta­ analysis to examine the use of interferon beta-1a in patients with ARDS. METHODS: Data sources included the following databases: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials. We retained trials from 1996 to February 25, 2020 that comparatively examined the use of interferon beta-1a in patients with ARDS. Two reviewers identified eligible studies, independently extracted study data, and assessed the risk of bias. The authors evaluated the certainty of evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. RESULTS: We included 2 trials (n = 392 patients). No significant differences in 28-day hospital mortality (risk ratio [RR], 0.59; 95% CI, 0.13-2.67; P = 0.49; very low certainty) and the number of ventilator-free days (mean difference, 4.85 days; 95% CI, -3.25 to 12.93; P = 0.24, very low certainty) were observed in patients treated with interferon beta-1a compared with those not receiving this drug. Interferon beta-1a also had no significant impact on the risk of adverse events (RR, 0.98%; 95% CI, 0.94-1.03; P = 0.47; low certainty). CONCLUSIONS: The use of interferon beta-1a does not appear to improve mortality or reduce the number of ventilator-free days and adverse events in patients with ARDS. This review is based on 2 small studies reporting a limited number of events, which raises questions regarding the true effects of interferon beta-1a. The analysis of 1 study revealed increased mortality with the concomitant use of corticosteroids and interferon beta-1a, suggesting a need for careful consideration of this drug-drug interaction.

COVID-19 coronavirus research has overall low methodological quality thus far: case in point for chloroquine/hydroxychloroquine.

OBJECTIVES/BACKGROUND AND OBJECTIVES: Prior epidemics of high-mortality human coronaviruses, such as the acute respiratory syndrome coronavirus (SARS-CoV or SARS-1) in 2003, have driven the characterization of compounds that could be possibly active against the currently emerging novel coronavirus SARS-CoV-2 (COVID-19). Presently, no approved treatment or prophylaxis is available for COVID-19. We comment on the existing COVID-19 research methodologies in general and the published reporting. Given the media attention and claims of effectiveness, we chose chloroquine and hydroxychloroquine, in combination with azithromycin, as an area of COVID-19 research to examine. METHODS/STUDY DESIGN AND SETTING: MEDLINE and EMBASE electronic databases were searched from 2019 to present (April 3rd, 2020) using a mix of keywords such as COVID-19 and chloroquine and hydroxychloroquine. We also searched the largest clinical medicine preprint repository, medRxiv.org. RESULTS: We found 6 studies, 3 randomized control trials and 3 observational studies, focusing on chloroquine and hydroxychloroquine (with azithromycin). We critically appraised the evidence. CONCLUSION: We found that the COVID-19 research methodology is very poor in the area of chloroquine/hydroxychloroquine research. In screening the literature, we observed the same across COVID-19 research in relation to potential treatments. The reporting is very poor and sparse, and patient-important outcomes needed to discern decision-making priorities are not reported. We do understand the barriers to perform rigorous research in health care settings overwhelmed by a novel deadly disease. However, this emergency pandemic situation does not transform flawed methods and data into credible results. The adequately powered, comparative, and robust clinical research that is needed for optimal evidence-informed decision-making remains absent in COVID-19.

Corticosteroids for patients with acute respiratory distress syndrome: a systematic review and meta-analysis of randomized trials.

INTRODUCTION: Acute respiratory distress syndrome (ARDS) is a rapidly progressing, inflammatory lung disease with a high mortality rate and no specific pharmacological treatment available. OBJECTIVES: We conducted a systematic review and meta­analysis on corticosteroid use in ARDS. METHODS: We searched 4 medical literature databases and retained randomized controlled trials on the use of corticosteroids in hospitalized adults with ARDS, which could be found there until February 2020. Two reviewers identified eligible studies, independently extracted data, and evaluated the risk of bias. The authors assessed the certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. RESULTS: We included 7 randomized controlled trials involving 851 patients. They showed that corticosteroids reduced all­cause mortality (risk ratio [RR], 0.75; 95% CI, 0.59-0.95; P = 0.02; moderate certainty) and the duration of mechanical ventilation (mean difference [MD], -4.93 days; 95% CI; -7.81 to -2.06; P <0.001; low certainty), and increased the number of ventilator­free days (MD, 4.28 days; 95% CI, 2.67-5.88; P <0.001; moderate certainty), as compared with placebo. Corticosteroids also increased the risk of hyperglycemia (RR, 1.12%; 95% CI, 1.01-1.24; P = 0.03; moderate certainty), and the effect on neuromuscular weakness was unclear (RR, 1.3; 95% CI, 0.8-2.11; P = 0.28; low certainty). CONCLUSIONS: These results suggest that systemic corticosteroids may potentially improve mortality, shorten ventilation times, and increase the number of ventilator­free days in patients with ARDS. However, the studies included different corticosteroid classes and initiated drug administration at different times, as well as used various dosing regimens. Thus, caution in the actual clinical application of these results is recommended.

Local-level governance of risk and resilience in Nepal.

This paper explores the circumstances in which communities may effectively reduce risks. It draws on the example of two 'Risk and Resilience Committees' (RRCs) that were established in Nepal as part of an action research project: one in Panchkhal in the central region, operating as a community-based organisation (CBO); and the other in Dhankuta in the eastern region, embedded in municipal government. In-depth interviews were conducted with RRC members. Wider community preferences for risk reduction were examined through a questionnaire survey. In Dhankuta, the RRC obtained further funding, developed strong upward and downward institutional links, and applied a 'disaster risk reduction lens' to existing local government responsibilities. In Panchkhal, RRC activities have been limited by funding and have focused on the strengthening of livelihoods. It may be concluded tentatively that community-based disaster risk reduction activities are more successful when they are institutionally embedded in local government structures.