Implementation, Clinical Benefit and Safety of a D-Dimer-Focused Pulmonary Embolism Testing Pathway in the Emergency Department.

STUDY OBJECTIVE: Computed tomography pulmonary angiogram (CTPA) is overused during pulmonary embolism (PE) testing in the emergency department (ED), whereas prediction rules and D-dimer are underused. We report the adherence, clinical benefit, and safety of a D-dimer-only strategy to guide need for PE imaging in the ED. METHODS: This was a prospective multicenter implementation study in 2 EDs with historical and external controls. Patients with suspected PE underwent D-dimer testing and imaging (CTPA or ventilation-perfusion scan) when D-dimer levels were 500 ng/mL or more. PE was ruled out if D-dimer was less than 500 ng/mL or with negative imaging. The primary implementation outcome was the proportion of patients tested for PE in adherence with the pathway. The primary clinical benefit outcome was the proportion of patients tested for PE who received pulmonary imaging. The primary safety outcome was diagnosis of PE in the 30 days following negative PE testing postimplementation. RESULTS: Between January 2018 and June 2021, 16,155 patients were tested for PE, including 33.4% postimplementation, 30.7% preimplementation, and 35.9% in an external control site. Adherence with the D-dimer-only pathway was 97.6% (adjusted odds ratio (aOR) post- versus preimplementation 5.26 (95% confidence interval 1.70 to 16.26). There was no effect on the proportion undergoing PE imaging. Imaging yield increased aOR 4.89 (1.17 to 20.53). Two cases of PE (0.04%; 0.01% to 0.16%) were diagnosed within 30 days. CONCLUSION: In this Canadian ED study, the uptake of a D-dimer-only PE testing strategy was high. Implementation was associated with higher imaging yield and a D-dimer level of less than 500 ng/mL safely excluded PE.

Proton pump inhibitors for gastrointestinal bleeding prophylaxis in critically ill patients: A systematic review protocol.

BACKGROUND: Proton pump inhibitors (PPIs) are the most commonly prescribed drugs for preventing upper gastrointestinal bleeding in critically ill patients. However, concerns have arisen about the possible harms of using PPIs, including potentially increased risk of pneumonia, Clostridioides difficile infection, and more seriously, an increased risk of death in the most severely ill patients. Triggered by the REVISE trial, which is a forthcoming large randomized trial comparing pantoprazole to placebo in invasively mechanically ventilated patients, we will conduct this systematic review to evaluate the efficacy and safety of PPIs versus no prophylaxis for critically ill patients. METHODS: We will systematically search randomized trials that compared gastrointestinal bleeding prophylaxis with PPIs versus placebo or no prophylaxis in adults in the intensive care unit (ICU). Pairs of reviewers will independently screen the literature, and for those eligible trials, extract data and assess risk of bias. We will perform meta-analyses using a random-effects model, and calculate relative risks for dichotomous outcomes and mean differences for continuous outcomes, and the associated 95% confidence intervals. We will conduct subgroup analysis to explore whether the impact of PPIs on mortality differs in more and less severely ill patients. We will assess certainty of evidence using the GRADE approach. DISCUSSION: This systematic review will provide the most up-to-date evidence regarding the merits and limitations of stress ulcer prophylaxis with PPIs in critically ill patients in contemporary practice.

Effect of low dose denosumab on bone mineral density in postmenopausal women with osteoporosis after a transition from 60 mg dose: a prospective observational study.

INTRODUCTION: Denosumab is an effective antiresorptive molecule and reduces the risk of fracture in postmenopausal osteoporosis. Cessation of denosumab therapy however is associated with rapid declines in bone mineral density (BMD), rises in bone remodeling, and an increased risk of fracture. We evaluated the effect of low dose denosumab (30 mg every 6 months) on the prevention of bone loss following a switch from standard dose (60 mg of denosumab every 6 months) in a prospective observational study. METHODS: We recruited 114 women 50-90 years of age with postmenopausal osteoporosis at a moderate fracture risk without prior fragility fractures, who had been on denosumab 60 mg every 6 month. These women switched to low dose denosumab 30 mg every 6 months. Mean percentage change in lumbar spine (LS), femoral neck (FN), total hip (TH) and 1/3 distal radius (1/3RAD) BMD at 12 and 24 months were evaluated. Predictors for change in BMD were explored. Subgroup analysis for patients on denosumab 60 mg every 6 months for <3 years and for ≥3 years before switching to low dose denosumab 30 mg was evaluated. RESULTS: At 12 months following a switch from 60 mg to 30 mg of denosumab every 6 months we observed an increase in LS BMD mean percentage change (+2.03%, 95% CI 1.18-2.88, p < 0.001). BMD was stable at the hip and radial sites. Age was found to be a predictor of the mean percentage change in LS BMD for the overall sample. At 24 months, there was a further increase in LS BMD mean percentage change (+3.44%, 95% CI 1.74-5.12, p < 0.001), with stable BMD at other skeletal sites. The 12 month mean BMD percentage change at the LS (p = 0.015), FN (p < 0.001), TH (p < 0.001), and 1/3 RAD (p < 0.001) were found to be predictors of the 24 month mean BMD percentage change. No clinical fractures were reported during 24 months of follow up. CONCLUSION: We observed stable BMD following a switch from denosumab 60 mg every 6 months to 30 mg every 6 months in this prospective observational study conducted in postmenopausal women at a moderate fracture risk.

Comparison of YEARS and Adjust-Unlikely D-dimer Testing for Pulmonary Embolism in the Emergency Department.

STUDY OBJECTIVE: We prospectively assessed the diagnostic accuracy of YEARS and a modified age-adjusted clinical decision rule ("Adjust-Unlikely") for pulmonary embolism (PE) testing in the emergency department. METHODS: This study was conducted in tertiary care Canadian emergency departments. When the D-dimer was <500 ng/ml, PE was excluded. Pulmonary imaging for PE was performed when the D-dimer was ≥500 ng/ml. Patients were followed for 30 days, and PE outcomes were independently adjudicated. Physicians systematically recorded the presence or absence of YEARS items (PE most likely, hemoptysis, signs of deep venous thrombosis) prior to D-dimer testing and imaging. We analyzed the diagnostic accuracy of YEARS and the "Adjust-Unlikely" rule. Age adjustment (age x 10 in those >50 years old) was applied in patients where PE was not the most likely diagnosis and 500 ng/ml threshold when PE was most likely. RESULTS: One thousand seven hundred three patients were included, median age 62 (50, 74), 58% female, PE prevalence 8.0%. YEARS sensitivity for PE diagnosis was 92.6% (87.0, 96.0%) and specificity 45.0% (42.5, 47.5%). Adjust-Unlikely sensitivity was 100.0% (97.2, 100.0%) and specificity 32.4% (30.1, 34.8%). Posttest probability of PE in the group of patients with PE excluded by D-dimer between 500 ng/ml and the adjusted limit was 2.8% (1.6, 5.1%) for YEARS and 0.0% (0.0, 2.6%) for the "Adjust-Unlikely" rule. CONCLUSION: The "Adjust-Unlikely" rule would modestly reduce imaging and identify all cases of PE. YEARS would substantially reduce imaging but miss 1 in 14 cases of PE.

The Hospital at Home Model vs Routine Hospitalization for Acute Heart Failure: A Survey of Patients' Preferences.

Background: Patients with heart failure (HF) experience recurrent hospitalizations and may prefer a Hospital at Home (HaH) model over routine hospitalization. Methods: We administered a 9-item questionnaire on perceived effectiveness, safety, convenience, and acceptability of a HaH model among patients hospitalized for HF at 2 academic hospitals in Ontario. The primary outcome was HaH care acceptability, defined as a preference for or neutrality to HaH care over routine hospitalization. We used partial Spearman rank correlations (ρ) and multivariable logistic regression analyses to explore associations with outcomes. Results: Of 297 eligible patients, 269 (90.6%) completed the questionnaire. The mean age was 76.2 (standard deviation, 12.3) years; 48.3% were female; and 70.5% lived in their own home, commonly with a relative or caregiver (67.9%). As many as 211 patients (78.4%; 95% confidence interval [CI] 73.0%-83.2%) found HaH care acceptable, with 169 (62.8%; 95% CI, 56.8%-68.6%) preferring HaH care over routine hospitalization. Perceived convenience (ρ, 0.57; P < 0.001) and safety (ρ, 0.37; p < 0.001) were associated with HaH acceptability, whereas perceived effectiveness was not (ρ, 0.14; P = 0.021). A college (adjusted odds ratio [aOR], 5.96; 95% CI, 2.01-17.62; P = 0.001) or university (aOR, 3.58; 95% CI, 1.07-12.06; P = 0.039) education was associated with greater odds of HaH acceptability, whereas residing in a caregiver's home was associated with lower odds (aOR, 0.34; 95% CI 0.14-0.84; P = 0.019). Conclusions: A majority of patients with HF perceived HaH care to be an acceptable alternative to routine hospitalization, prioritizing perceived convenience and safety over effectiveness. Postsecondary education and living independently without caregiver support were associated with HaH acceptability.

Introduction: Puisque les patients atteints d'insuffisance cardiaque (IC) sont hospitalisés à répétition, ils peuvent préférer le modèle d'hospitalisation à domicile (HAD) à l'hospitalisation habituelle. Méthodes: Nous avons fait passer un questionnaire de neuf items sur l'efficacité, la sécurité, la commodité et l'acceptabilité perçues du modèle d'HAD aux patients hospitalisés atteints d'IC de deux hôpitaux universitaires de l'Ontario. Le critère de jugement principal était l'acceptabilité des soins en HAD, définie par la préférence ou la neutralité à l'égard des soins en HAD plutôt qu'à l'égard de l'hospitalisation habituelle. Nous avons utilisé les corrélations partielles sur les rangs de Spearman (ρ) et les analyses multivariées de régression logistique pour examiner les associations avec les résultats. Résultats: Au sein des 297 patients admissibles, 269 (90,6 %) ont rempli le questionnaire. L'âge moyen était de 76,2 (écart type, 12,3) ans; 48,3 % étaient des femmes et 70,5 % vivaient dans leur propre maison, généralement avec un parent ou un soignant (67,9 %). Jusqu'à 211 patients (78,4 %; intervalle de confiance [IC] à 95 %, 73,0 %-83,2 %) trouvaient les soins en HAD acceptables : 169 (62,8 %; IC à 95 %, 56,8 %-68,6 %) préféraient les soins en HAD à l'hospitalisation habituelle. La commodité (ρ, 0,57; P < 0,001) et la sécurité perçues (ρ, 0,37; p < 0,001) étaient associées à l'acceptabilité de l'HAD, tandis que l'efficacité perçue ne l'était pas (ρ, 0,14; P = 0,021). Une formation collégiale (ratio d'incidence ajusté [RIAa], 5,96; IC à 95 %, 2,01-17,62; P = 0,001) ou universitaire (RIAa, 3,58; IC à 95 %, 1,07-12,06; P = 0,039) était associée à une plus grande probabilité d'acceptabilité de l'HAD, tandis que le fait de vivre au domicile du soignant était associé à une plus faible probabilité (RIAa, 0,34; IC à 95 %, 0,14-0,84; P = 0,019). Conclusions: Une majorité de patients atteints d'IC considéraient que les soins en HAD étaient une alternative acceptable à l'hospitalisation habituelle, et accordaient la priorité à la commodité et à la sécurité perçues plutôt qu'à l'efficacité. La formation postsecondaire et le fait de vivre de façon indépendante sans l'aide d'un soignant étaient associés à l'acceptabilité de l'HAD.

Variability in How Canadian Pediatric Weight Management Clinics Deliver Care: Evidence from the CANadian Pediatric Weight Management Registry.

Background: Clinical practice guidelines for pediatric weight management highlight the importance of family-based behavioral strategies to enhance health behaviors. Little is known, however, of how clinics implement these programs. The study objectives were to (1) describe how Canadian pediatric weight management clinics deliver care and (2) evaluate change in services over time. Methods: The CANadian Pediatric Weight management Registry (CANPWR) is a multisite prospective cohort study of participants enrolled in a Canadian pediatric weight management clinic. Clinical program characteristics (e.g., referral process, inclusion criteria, funding, program characteristics, patient interaction methods, and follow-up) were collected at the start and end of the CANPWR recruitment period (2015-2019). Results: Entrance into the nine clinics varied with limiting criteria based on geographic proximity, age, weight status, and presence of health conditions. The clinics varied in size (50-220 new patients/year). The planned length of intervention varied widely, from 10 weeks to open-ended (median 2 years). Behavior modification strategies were delivered with a mix of individual and group-based sessions and most were delivered in person, complemented by use of virtual care. Over time, more clinics saw patients under the age of 5 years and all clinics defined a program length. Conclusion: Although all clinics offered family-based behavioral weight management services, these varied considerably, especially in program entrance criteria, size of clinic, and the length of intervention. The influence of the variability in delivery of services on health outcomes will be addressed in future studies.

Global variations in the prevalence, treatment, and impact of atrial fibrillation in a multi-national cohort of 153 152 middle-aged individuals.

AIMS: To compare the prevalence of electrocardiogram (ECG)-documented atrial fibrillation (or flutter) (AF) across eight regions of the world, and to examine antithrombotic use and clinical outcomes. METHODS AND RESULTS: Baseline ECGs were collected in 153 152 middle-aged participants (ages 35-70 years) to document AF in two community-based studies, spanning 20 countries. Medication use and clinical outcome data (mean follow-up of 7.4 years) were available in one cohort. Cross-sectional analyses were performed to document the prevalence of AF and medication use, and associations between AF and clinical events were examined prospectively. Mean age of participants was 52.1 years, and 57.7% were female. Age and sex-standardized prevalence of AF varied 12-fold between regions; with the highest in North America, Europe, China, and Southeast Asia (270-360 cases per 100 000 persons); and lowest in the Middle East, Africa, and South Asia (30-60 cases per 100 000 persons) (P < 0.001). Compared with low-income countries (LICs), AF prevalence was 7-fold higher in middle-income countries (MICs) and 11-fold higher in high-income countries (HICs) (P < 0.001). Differences in AF prevalence remained significant after adjusting for traditional AF risk factors. In LICs/MICs, 24% of participants with AF and a CHADS2 score ≥1 received antithrombotic therapy, compared with 85% in HICs. AF was associated with an increased risk of stroke [hazard ratio (HR) 2.29; 95% confidence interval (CI) 1.49-3.52] and death (HR 2.97; 95% CI 2.25-3.93); with similar rates in different countries grouped by income level. CONCLUSIONS: Large variations in AF prevalence occur in different regions and countries grouped by income level, but this is only partially explained by traditional AF risk factors. Antithrombotic therapy is infrequently used in poorer countries despite the high risk of stroke associated with AF.

The Canadian Alliance for Healthy Hearts and Minds: How Well Does It Reflect the Canadian Population?

BACKGROUND: The intent of the Canadian Alliance for Healthy Hearts and Minds (CAHHM) cohort is to understand the early determinants of subclinical cardiac and vascular disease and progression in adults selected from existing cohorts-the Canadian Partnership for Tomorrow's Health, the Prospective Urban and Rural Evaluation (PURE) cohort, and the Montreal Heart Institute Biobank. We evaluated how well the CAHHM-Health Services Research (CAHHM-HSR) subcohort reflects the Canadian population. METHODS: A cross-sectional design was used among a prospective cohort of community-dwelling adults aged 35-69 years who met the CAHHM inclusion criteria, and a cohort of adults aged 35-69 years who responded to the 2015 Canadian Community Health Survey-Rapid Response module. The INTERHEART risk score was calculated at the individual level with means and proportions reported at the overall and provincial level. RESULTS: There are modest differences between CAHHM-HSR study participants and the 2015 Canadian Community Health Survey-Rapid Response respondents in age (56.3 vs 51.7 mean years), proportion of men (44.9% vs 49.3%), and mean INTERHEART risk score (9.7 vs 10.1). Larger differences were observed in postsecondary education (86.8% vs 70.2%), Chinese ethnicity (11.0% vs 3.3%), obesity (23.2% vs 29.3%), current smoker status (6.1% vs 18.4%), and having no cardiac testing (30.4% vs 55.9%). CONCLUSIONS: CAHHM-HSR participants are older, of higher socioeconomic status, and have a similar mean INTERHEART risk score, compared with participants in the Canadian Community Health Survey. Differing sampling strategies and missing data may explain some differences between the CAHHM-HSR cohort and Canadian community-dwelling adults and should be considered when using the CAHHM-HSR for scientific research.

CONTEXTE: L'étude Alliance canadienne cœurs et cerveaux sains (CAHHM) vise à mieux comprendre les facteurs déterminants précoces et la progression de l'atteinte cardiovasculaire subclinique chez des adultes sélectionnés au sein de cohortes existantes ­ soit celles de l'étude menée par le Partenariat canadien pour la santé de demain, de l'étude PURE (Prospective Urban and Rural Evaluation) et de la biobanque de l'Institut de cardiologie de Montréal. Nous avons évalué la mesure dans laquelle la sous-cohorte du volet de recherche sur l'utilisation des services de santé de la CAHHM (CAHHM-HSR) représente la population canadienne. MÉTHODOLOGIE: Nous avons adopté une approche transversale pour étudier une cohorte prospective d'adultes vivant dans la communauté âgés de 35 à 69 ans et répondant aux critères d'inclusion de l'étude CAHHM, ainsi qu'une cohorte d'adultes âgés de 35 à 69 ans ayant participé au volet de réponse rapide de l'Enquête sur la santé dans les collectivités canadiennes (ESCC) de 2015. Le score de risque INTERHEART individuel des participants a été calculé à partir des moyennes et des proportions rapportées à l'échelle globale et à l'échelle provinciale. RÉSULTATS: Les différences entre les participants du volet CAHHM-HSR et ceux du volet de réponse rapide de l'ESCC de 2015 étaient minimes quant à l'âge (56,3 ans vs 51,7 ans en moyenne), à la proportion d'hommes (44,9 % vs 49,3 %) et au score de risque INTERHEART moyen (9,7 vs 10,1). On a toutefois noté des différences plus importantes en ce qui concerne les caractéristiques suivantes : éducation postsecondaire (86,8 % vs 70,2 %), origine ethnique chinoise (11,0 % vs 3,3 %), obésité (23,2 % vs 29,3 %), tabagisme actuel (6,1 % vs 18,4 %) et absence d'antécédents d'examen cardiaque (30,4 % vs 55,9 %). CONCLUSIONS: Les participants du volet CAHHM-HSR sont plus âgés et ont un statut socioéconomique plus élevé que ceux du volet de réponse rapide de l'ESCC, mais ont un score de risque INTERHEART moyen comparable. Les différences quant aux stratégies d'échantillonnage et des données manquantes pourraient expliquer certains des écarts observés entre la cohorte CAHHM-HSR et celle des adultes canadiens vivant dans la communauté; il conviendrait d'en tenir compte lorsqu'on utilise les données du volet CAHHM-HSR à des fins de recherche scientifique.

Efficacité et innocuité des agents antiviraux contre le SRAS-CoV-2, selon des données d'études sur la COVID-19 et d'autres infections virales aiguës : revue systématique et méta-analyse.

CONTEXTE: On donne de façon empirique des agents antiviraux à certains patients atteints de la maladie à coronavirus 2019 (COVID-19). Dans le but d'appuyer la rédaction de lignes directrices sur la prise en charge de la COVID-19, nous avons réalisé une revue systématique des bénéfices et des préjudices associés à 7 traitements antiviraux contre cette infection. MÉTHODES: Nous avons effectué des recherches dans MEDLINE, Embase, le Cochrane Central Register of Controlled Trials (CENTRAL), PubMed et 3 bases de données chinoises (CNKI, Wanfang Data et SinoMed) jusqu'au 19 avril 2020, dans medRxiv et ChinaXiv jusqu'au 27 avril 2020, ainsi que dans Chongqing VIP jusqu'au 30 avril 2020. Nous avons sélectionné des études sur la ribavirine, la chloroquine, l'hydroxychloroquine, l'umifénovir (Arbidol), le favipiravir, l'interféron et le lopinavir/ritonavir. Lorsqu'il n'y avait pas de données directes d'études sur la COVID-19, nous avons retenu des données indirectes d'études sur le syndrome respiratoire aigu sévère (SRAS) et le syndrome respiratoire du Moyen-Orient (SRMO) pour l'analyse de l'efficacité, et d'études sur d'autres infections respiratoires virales aiguës pour l'analyse de l'innocuité. RÉSULTATS: Le taux de décès chez les patients atteints d'une forme sans signe clinique de gravité de COVID-19 était extrêmement bas, ce qui ne permet pas de conclure à un effet important sur la mortalité. Nous n'avons obtenu que des données de très faible qualité indiquant que la plupart des traitements avaient peu ou pas de bénéfices sur les paramètres à l'étude, quelle que soit la gravité de la COVID-19. Seule exception : le traitement au lopinavir/ritonavir, pour lequel nous avons obtenu des données de faible qualité faisant état d'une réduction de la durée du séjour en unité de soins intensifs (différence des risques [DR] 5 jours de moins, intervalle de confiance [IC] de 95 % 0 à 9 jours) et de la durée d'hospitalisation (DR 1 jour de moins, IC de 95 % 0 à 2 jours). En ce qui concerne l'innocuité, les données étaient de faible ou de très faible qualité, sauf pour le traitement au lopinavir/ritonavir, où des données de qualité moyenne laissaient supposer une augmentation probable de la diarrhée, des nausées et des vomissements. INTERPRÉTATION: À l'heure actuelle, rien ne prouve de façon convaincante que les traitements antiviraux apportent des bénéfices importants dans la lutte contre la COVID-19, bien que les données propres à chaque traitement n'excluent pas cette possibilité. D'autres essais randomisés et contrôlés menés auprès de patients atteints de la COVID-19 sont nécessaires avant de pouvoir recourir à ces traitements en toute confiance.

Drug treatments for covid-19: living systematic review and network meta-analysis

OBJECTIVE: To compare the effects of treatments for coronavirus disease 2019 (covid-19). DESIGN: Living systematic review and network meta-analysis. DATA SOURCES: WHO covid-19 database, a comprehensive multilingual source of global covid-19 literature, up to 3 December 2021 and six additional Chinese databases up to 20 February 2021. Studies identified as of 1 December 2021 were included in the analysis. STUDY SELECTION: Randomised clinical trials in which people with suspected, probable, or confirmed covid-19 were randomised to drug treatment or to standard care or placebo. Pairs of reviewers independently screened potentially eligible articles. METHODS: After duplicate data abstraction, a bayesian network meta-analysis was conducted. Risk of bias of the included studies was assessed using a modification of the Cochrane risk of bias 2.0 tool, and the certainty of the evidence using the grading of recommendations assessment, development, and evaluation (GRADE) approach. For each outcome, interventions were classified in groups from the most to the least beneficial or harmful following GRADE guidance. RESULTS: 463 trials enrolling 166 581 patients were included; 267 (57.7%) trials and 89 814 (53.9%) patients are new from the previous iteration; 265 (57.2%) trials evaluating treatments with at least 100 patients or 20 events met the threshold for inclusion in the analyses. Compared with standard care, three drugs reduced mortality in patients with mostly severe disease with at least moderate certainty: systemic corticosteroids (risk difference 23 fewer per 1000 patients, 95% credible interval 40 fewer to 7 fewer, moderate certainty), interleukin-6 receptor antagonists when given with corticosteroids (23 fewer per 1000, 36 fewer to 7 fewer, moderate certainty), and Janus kinase inhibitors (44 fewer per 1000, 64 fewer to 20 fewer, high certainty). Compared with standard care, two drugs probably reduce hospital admission in patients with non-severe disease: nirmatrelvir/ritonavir (36 fewer per 1000, 41 fewer to 26 fewer, moderate certainty) and molnupiravir (19 fewer per 1000, 29 fewer to 5 fewer, moderate certainty). Remdesivir may reduce hospital admission (29 fewer per 1000, 40 fewer to 6 fewer, low certainty). Only molnupiravir had at least moderate quality evidence of a reduction in time to symptom resolution (3.3 days fewer, 4.8 fewer to 1.6 fewer, moderate certainty); several others showed a possible benefit. Several drugs may increase the risk of adverse effects leading to drug discontinuation; hydroxychloroquine probably increases the risk of mechanical ventilation (moderate certainty). CONCLUSION: Corticosteroids, interleukin-6 receptor antagonists, and Janus kinase inhibitors probably reduce mortality and confer other important benefits in patients with severe covid-19. Molnupiravir and nirmatrelvir/ritonavir probably reduce admission to hospital in patients with non-severe covid-19. SYSTEMATIC REVIEW REGISTRATION: This review was not registered. The protocol is publicly available in the supplementary material. READERS' NOTE: This article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication. This is the fifth version of the original article published on 30 July 2020 (BMJ 2020;370:m2980), and previous versions can be found as data supplements. When citing this paper please consider adding the version number and date of access for clarity.

Comparison of two frailty identification tools for critically ill patients: A post-hoc analysis of a multicenter prospective cohort study.

PURPOSE: We aimed to describe the association of two frailty screening tools, the validated Clinical Frailty Scale (CFS) score and the recently described modified Frailty Index (mFI) in critically ill patients. MATERIALS AND METHODS: We performed a post-hoc analysis of a multicenter cohort of patients admitted to six Canadian Intensive Care Units (ICU) between 2010 and 2011. Frailty was screened using the CFS and the mFI. Concordance between these tools was evaluated, as well as discrimination and predictive ability for clinical outcomes after adjustments. RESULTS: The cohort included 421 patients. Prevalence of frailty was 32.8% with the CFS and 39.2% with the mFI. However, concordance between the two tools was low [(intraclass correlation of 0.37; 95% confidence interval [CI] 0.29-0.45) and partial Spearman rank correlation of 0.38 (95% CI 0.29-0.47)]. Hospital and 1-year mortality, as well as dependency after discharge and hospital readmission, were greater for frail compared to non-frail patients screened with the use of both tools. CONCLUSION: While the CFS and mFI showed low concordance, both showed good discrimination and predictive validity for hospital mortality. Both tools identify a subgroup of frail patients more likely to have worse clinical outcomes.

Efficacy and safety of antiviral treatment for COVID-19 from evidence in studies of SARS-CoV-2 and other acute viral infections: a systematic review and meta-analysis.

BACKGROUND: Antiviral medications are being given empirically to some patients with coronavirus disease 2019 (COVID-19). To support the development of a COVID-19 management guideline, we conducted a systematic review that addressed the benefits and harms of 7 antiviral treatments for COVID-19. METHODS: We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), PubMed and 3 Chinese databases (CNKI, WANFANG and SinoMed) through Apr. 19, medRxiv and Chinaxiv through Apr. 27, and Chongqing VIP through Apr. 30, 2020. We included studies of ribavirin, chloroquine, hydroxychloroquine, umifenovir (arbidol), favipravir, interferon and lopinavir/ritonavir. If direct evidence from COVID-19 studies was not available, we included indirect evidence from studies of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) for efficacy outcomes and other acute respiratory viral infections for safety outcomes. RESULTS: In patients with nonsevere COVID-19 illness, the death rate was extremely low, precluding an important effect on mortality. We found only very low-quality evidence with little or no suggestion of benefit for most treatments and outcomes in both nonsevere and severe COVID-19. An exception was treatment with lopinavir/ritonavir, for which we found low-quality evidence for a decrease in length of stay in the intensive care unit (risk difference 5 d shorter, 95% confidence interval [CI] 0 to 9 d) and hospital stay (risk difference 1 d shorter, 95% CI 0 to 2 d). For safety outcomes, evidence was of low or very low quality, with the exception of treatment with lopinavir/ritonavir for which moderate-quality evidence suggested likely increases in diarrhea, nausea and vomiting. INTERPRETATION: To date, persuasive evidence of important benefit in COVID-19 does not exist for any antiviral treatments, although for each treatment evidence has not excluded important benefit. Additional randomized controlled trials involving patients with COVID-19 will be needed before such treatments can be administered with confidence.

High-flow nasal cannula for acute hypoxemic respiratory failure in patients with COVID-19: systematic reviews of effectiveness and its risks of aerosolization, dispersion, and infection transmission.

PURPOSE: We conducted two World Health Organization-commissioned reviews to inform use of high-flow nasal cannula (HFNC) in patients with coronavirus disease (COVID-19). We synthesized the evidence regarding efficacy and safety (review 1), as well as risks of droplet dispersion, aerosol generation, and associated transmission (review 2) of viral products. SOURCE: Literature searches were performed in Ovid MEDLINE, Embase, Web of Science, Chinese databases, and medRxiv. Review 1: we synthesized results from randomized-controlled trials (RCTs) comparing HFNC to conventional oxygen therapy (COT) in critically ill patients with acute hypoxemic respiratory failure. Review 2: we narratively summarized findings from studies evaluating droplet dispersion, aerosol generation, or infection transmission associated with HFNC. For both reviews, paired reviewers independently conducted screening, data extraction, and risk of bias assessment. We evaluated certainty of evidence using GRADE methodology. PRINCIPAL FINDINGS: No eligible studies included COVID-19 patients. Review 1: 12 RCTs (n = 1,989 patients) provided low-certainty evidence that HFNC may reduce invasive ventilation (relative risk [RR], 0.85; 95% confidence interval [CI], 0.74 to 0.99) and escalation of oxygen therapy (RR, 0.71; 95% CI, 0.51 to 0.98) in patients with respiratory failure. Results provided no support for differences in mortality (moderate certainty), or in-hospital or intensive care length of stay (moderate and low certainty, respectively). Review 2: four studies evaluating droplet dispersion and three evaluating aerosol generation and dispersion provided very low certainty evidence. Two simulation studies and a crossover study showed mixed findings regarding the effect of HFNC on droplet dispersion. Although two simulation studies reported no associated increase in aerosol dispersion, one reported that higher flow rates were associated with increased regions of aerosol density. CONCLUSIONS: High-flow nasal cannula may reduce the need for invasive ventilation and escalation of therapy compared with COT in COVID-19 patients with acute hypoxemic respiratory failure. This benefit must be balanced against the unknown risk of airborne transmission.

RéSUMé: OBJECTIF: Nous avons réalisé deux comptes rendus sur commande de l'Organisation mondiale de la santé pour guider l'utilisation de canules nasales à haut débit (CNHD) chez les patients ayant contracté le coronavirus (COVID-19). Nous avons synthétisé les données probantes concernant leur efficacité et leur innocuité (compte rendu 1), ainsi que les risques de dispersion des gouttelettes, de génération d'aérosols, et de transmission associée d'éléments viraux (compte rendu 2). SOURCE: Des recherches de littérature ont été réalisées dans les bases de données Ovid MEDLINE, Embase, Web of Science, ainsi que dans les bases de données chinoises et medRxiv. Compte rendu 1 : nous avons synthétisé les résultats d'études randomisées contrôlées (ERC) comparant les CNHD à une oxygénothérapie conventionnelle chez des patients en état critique atteints d'insuffisance respiratoire hypoxémique aiguë. Compte rendu 2 : nous avons résumé sous forme narrative les constatations d'études évaluant la dispersion de gouttelettes, la génération d'aérosols ou la transmission infectieuse associées aux CNHD. Pour les deux comptes rendus, des réviseurs appariés ont réalisé la sélection des études, l'extraction des données et l'évaluation du risque de biais de manière indépendante. Nous avons évalué la certitude des données probantes en nous fondant sur la méthodologie GRADE. CONSTATATIONS PRINCIPALES: Aucune étude éligible n'incluait de patients atteints de COVID-19. Compte rendu 1 : 12 ERC (n = 1989 patients) ont fourni des données probantes de certitude faible selon lesquelles les CNHD réduiraient la ventilation invasive (risque relatif [RR], 0,85; intervalle de confiance [IC] 95 %, 0,74 à 0,99) et l'intensification de l'oxygénothérapie (RR, 0,71; IC 95 %, 0,51 à 0,98) chez les patients atteints d'insuffisance respiratoire. Les résultats n'ont pas démontré de différences en matière de mortalité (certitude modérée), ni de durée du séjour hospitalier ou à l'unité des soins intensifs (certitude modérée et faible, respectivement). Compte rendu 2 : quatre études évaluant la dispersion de gouttelettes et trois évaluant la génération et la dispersion d'aérosols ont fourni des données probantes de très faible certitude. Deux études de simulation et une étude croisée ont donné des résultats mitigés quant à l'effet des CNHD sur la dispersion des gouttelettes. Bien que deux études de simulation n'aient rapporté aucune augmentation associée concernant la dispersion d'aérosols, l'une a rapporté que des taux de débit plus élevés étaient associés à des régions à densité d'aérosols élevée plus grandes. CONCLUSION: Les canules nasales à haut débit pourraient réduire la nécessité de recourir à la ventilation invasive et l'escalade des traitements par rapport à l'oxygénothérapie conventionnelle chez les patients atteints de COVID-19 souffrant d'insuffisance respiratoire hypoxémique aiguë. Cet avantage doit être soupesé contre le risque inconnu de transmission atmosphérique.

Variability in deceased donor care in Canada: a report of the Canada-DONATE cohort study.

PURPOSE: Canadian donor management practices have not been reported. Our aim was to inform clinicians and other stakeholders about the range of current practices. METHODS: This prospective observational cohort study enrolled consecutive, newly consented organ donors from August 1 2015 to July 31 2018 at 27 academic and five community adult intensive care units in British Columbia, Alberta, Ontario, and Quebec. Research staff prospectively recorded donor management data. Provincial organ donation organizations verified the organs donated. We formally compared practices across provinces. RESULTS: Over a median collection period of eight months, 622 potential donors were classified at baseline as having neurologic determination of death (NDD donors; n = 403) or circulatory death (DCD donors; n = 219). Among NDD donors, 85.6% underwent apnea testing (rarely with carbon dioxide insufflation), 33.2% underwent ancillary testing, and subsequent therapeutic hypothermia (34-35°C) was rare. Neurologic determination of death donors were more hemodynamically unstable with most having received vasopressin and norepinephrine infusions, with a large majority having received high-dose corticosteroids and intravenous thyroxine. Among DCD donors, 61.6% received corticosteroids, and 8.9% received thyroxine. Most donors did not receive lung-protective ventilation strategies. Invasive procedures after donation consent included bronchoscopy (71.7%), cardiac catheterization (NDD donors only; 21.3%), and blood transfusions (19.3%). Physicians ordered intravenous antemortem heparin for 94.8% of DCD donors. The cohort donated 1,629 organs resulting in 1,532 transplants. Case selection, death determinations, and hormone, nutrition and heparin practices all varied across provinces. CONCLUSION: These study findings highlight areas for knowledge translation and further clinical research. Interprovincial discrepancies will likely pose unique challenges to national randomized trials. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT03114436); registered 10 April, 2017.

RéSUMé: OBJECTIF: Les pratiques canadiennes de prise en charge des donneurs n'ont pas été rapportées. Notre objectif était d'informer les cliniciens et autres parties intéressées quant à l'éventail des pratiques actuelles. MéTHODE: Cette étude de cohorte observationnelle et prospective a recruté des donneurs d'organes consécutifs ayant récemment consenti au don entre le 1er août 2015 et le 31 juillet 2018 dans 27 unités de soins intensifs universitaires et cinq unités de soins intensifs pour adultes en milieu communautaire en Colombie-Britannique, en Alberta, en Ontario et au Québec. Le personnel de recherche a enregistré de manière prospective les données de prise en charge des donneurs. Les organismes de dons d'organes provinciaux ont vérifié les organes donnés. Nous avons formellement comparé les pratiques d'une province à l'autre. RéSULTATS: Sur une période médiane de collecte de huit mois, 622 donneurs potentiels ont été catégorisés au départ comme ayant un diagnostic de décès neurologique (donneurs DDN; n = 403) ou un décès cardiocirculatoire (donneurs DDC; n = 219). Parmi les donneurs DDN, 85,6 % ont subi un test d'apnée (rarement avec insufflation de dioxyde de carbone), 33,2 % ont subi des tests complémentaires, et une hypothermie thérapeutique subséquente (34-35°C) était rare. Les donneurs par diagnostic de décès neurologique étaient plus instables hémodynamiquement, la plupart ayant reçu des perfusions de vasopressine et de norépinéphrine, et une vaste majorité de ces donneurs ont reçu des corticostéroïdes à forte dose ainsi que de la thyroxine intraveineuse. Parmi les donneurs par DDC, 61,6 % avaient reçu des corticostéroïdes, et 8,9 % de la thyroxine. La plupart des donneurs n'avaient pas bénéficié de stratégies de ventilation protectrice des poumons. Les interventions invasives réalisées après le consentement au don comprenaient la bronchoscopie (71,7 %), le cathétérisme cardiaque (donneurs DDN seulement; 21,3 %) et les transfusions sanguines (19,3 %). Les médecins ont prescrit de l'héparine intraveineuse ante mortem chez 94,8 % des donneurs DDC. La cohorte a donné 1629 organes, résultant en 1532 greffes. La sélection de cas, la détermination de décès et les pratiques hormonales, nutritionnelles et hépariniques variaient toutes d'une province à l'autre. CONCLUSION: Ces résultats soulignent des domaines propices à la transmission de connaissances et aux recherches cliniques plus poussées. Les différences interprovinciales poseront probablement des défis uniques pour les études randomisées nationales. Enregistrement de l'étude : www.clinicaltrials.gov (NCT03114436); enregistrée le 10 avril 2017.

Correction: The association between temperature, rainfall and humidity with common climate-sensitive infectious diseases in Bangladesh.

[This corrects the article DOI: 10.1371/journal.pone.0199579.].

Relationship between diet and acculturation among South Asian children living in Canada.

INTRODUCTION: Diet and South Asian ethnicity are both associated with early onset of cardiovascular risk factors. Among youth of South Asian origin, little is known about the role of culture in determining healthy dietary patterns. We aimed to assess dietary patterns and their relationships with acculturation to Western and traditional lifestyles among South Asian youth in Canada. METHODS: The Research in Cardiovascular Health - Lifestyles, Environments and Genetic Attributes in Children and Youth (RICH LEGACY) study targeted South Asian children and adolescents aged 7-8 and 14-15 years in two Canadian cities. In this cross-sectional study, acculturation questionnaires and food frequency questionnaires were administered to assess the correlations between Western and traditional culture scores, immigration status (generation and length of residency) in Canada and intake frequency of various foods. RESULTS: Among 759 youth, those who ate fruits and vegetables more often consumed dairy and whole grains more often (all r = 0.17-0.22, all p < 0.001), while those who ate fast food more often consumed meat, sweets and sugared drinks more often (all r 0.24-0.38, all p < 0.001). Traditional culture scores were weakly positively correlated with whole grain intake frequency (r = 0.12, p = 0.001), and negatively with meat intake frequency (r = -0.14, p < 0.001). Western culture scores positively correlated with high intake frequency of meat (r = 0.23, p < 0.001), fast food (r = 0.14, p < 0.001) and sweets (r = 0.14, p < 0.001). DISCUSSION: Children who are more acculturated with Western lifestyle consumed foods associated with increased metabolic risk. However, whether this eating pattern translates into increased risk of obesity and cardiovascular diseases needs to be further explored.

Obesity class versus the Edmonton Obesity Staging System for Pediatrics to define health risk in childhood obesity: results from the CANPWR cross-sectional study.

BACKGROUND: Disease severity in paediatric obesity is usually defined using the body-mass index (BMI). Although informative at the population level, its usefulness on an individual level has limitations. The use of a clinical staging system-Edmonton Obesity Staging System for Pediatrics (EOSS-P)-in identifying health risk has been proposed. This study aimed to examine the association between BMI class and EOSS-P stage. METHODS: This cross-sectional study was done in children with obesity aged 5-17 years who enrolled in the Canadian Pediatric Weight Management Registry (CANPWR) between May 31, 2013, and Oct 27, 2017, involving ten multidisciplinary paediatric weight management clinics in Canada. We classified participants into WHO BMI classes (class I as 2-3 SD scores, class II as >3 SD scores, and class III as >4 SD scores above the WHO growth standard median), and applied the EOSS-P staging system (stages 0, 1, and 2/3) based on the clinical assessment of coexisting metabolic, mechanical, mental health, and social milieu issues. Clinical information was extracted from medical records and reported using standardised case report forms. Associations of BMI class with EOSS-P stage were examined in children with complete data. FINDINGS: Of the 847 children with complete data, 546 (64%) had severe obesity based on BMI class (ie, class II or III) and 678 (80%) were EOSS-P stage 2/3. Stage 2/3 obesity-related health issues were common; mental health concerns were most common (520 [61%] of 847 children), followed by metabolic (349 [41%] of 847 children), social milieu (179 [21%] of 847 children), and mechanical (86 [10%] of 847 children) health issues. Mental health issues (eg, anxiety and attention-deficit hyperactivity disorder) were equally distributed across BMI classes, metabolic health issues were slightly more common in higher BMI classes, and mechanical (eg, musculoskeletal issues and sleep apnoea) and social milieu (eg, bullying and low household income) issues increased with increasing BMI class. Of children with class I obesity, 206 (76%) of 270 had overall EOSS-P stage 2/3, compared with 195 (85%) of 229 with class III obesity. INTERPRETATION: Physical and mental health issues were highly prevalent among children with obesity irrespective of BMI class. Participants with class III obesity carried the greatest health risk across subcategories of the EOSS-P. As BMI class increased, a concomitant increased disease burden in mechanical and social milieu issues was observed, whereas metabolic and mental health risks were high across BMI classes. FUNDING: Canadian Institutes of Health Research, Ontario Ministry of Health, McMaster University, and McMaster Children's Hospital.

Publisher Correction: Pathways to eating in children and adolescents with obesity.

In the original version of this Article the following were listed as authors; however, they should have only been referred to in the Acknowledgments section and not listed in this way.