Search

Background Prior randomized clinical trials have reported benefit of fluvoxamine ≥200 mg/d vs placebo for patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods This randomized, double-blind, placebo-controlled, fully remote multisite clinical trial evaluated whether fluvoxamine prevents clinical deterioration in higher-risk outpatients with acute coronavirus disease 2019 (COVID-19). Between December 2020 and May 2021, nonhospitalized US and Canadian participants with confirmed symptomatic infection received fluvoxamine (50 mg on day 1, 100 mg twice daily thereafter) or placebo for 15 days. The primary modified intent-to-treat (mITT) population included participants who started the intervention within 7 days of symptom onset with a baseline oxygen saturation ≥92%. The primary outcome was clinical deterioration within 15 days of randomization, defined as having both (1) shortness of breath (severity ≥4 on a 0–10 scale or requiring hospitalization) and (2) oxygen saturation <92% on room air or need for supplemental oxygen. Results A total of 547 participants were randomized and met mITT criteria (n = 272 fluvoxamine, n = 275 placebo). The Data Safety Monitoring Board recommended stopping early for futility related to lower-than-predicted event rates and declining accrual concurrent with vaccine availability in the United States and Canada. Clinical deterioration occurred in 13 (4.8%) participants in the fluvoxamine group and 15 (5.5%) participants in the placebo group (absolute difference at day 15, 0.68%; 95% CI, −3.0% to 4.4%; log-rank P =.91). Conclusions This trial did not find fluvoxamine efficacious in preventing clinical deterioration in unvaccinated outpatients with symptomatic COVID-19. It was stopped early and underpowered due to low primary outcome rates. Clinical Trials Registration ClinicalTrials.gov Identifier: NCT04668950. [ABSTRACT FROM AUTHOR]

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a rapidly emerging virus causing the ongoing coronavirus disease 2019 (COVID-19) pandemic with no known effective prophylaxis. We investigated whether hydroxychloroquine could prevent SARS-CoV-2 in healthcare workers at high risk of exposure. Methods We conducted a randomized, double-blind, placebo-controlled clinical trial of healthcare workers with ongoing exposure to persons with SARS-CoV-2, including those working in emergency departments, intensive care units, COVID-19 hospital wards, and first responders. Participants across the United States and in the Canadian province of Manitoba were randomized to hydroxychloroquine loading dose then 400 mg once or twice weekly for 12 weeks. The primary endpoint was confirmed or probable COVID-19–compatible illness. We measured hydroxychloroquine whole-blood concentrations. Results We enrolled 1483 healthcare workers, of whom 79% reported performing aerosol-generating procedures. The incidence of COVID-19 (laboratory-confirmed or symptomatic compatible illness) was 0.27 events/person-year with once-weekly and 0.28 events/person-year with twice-weekly hydroxychloroquine compared with 0.38 events/person-year with placebo. For once-weekly hydroxychloroquine prophylaxis, the hazard ratio was.72 (95% CI,.44–1.16; P =.18) and for twice-weekly was.74 (95% CI,.46–1.19; P =.22) compared with placebo. Median hydroxychloroquine concentrations in whole blood were 98 ng/mL (IQR, 82–120) with once-weekly and 200 ng/mL (IQR, 159–258) with twice-weekly dosing. Hydroxychloroquine concentrations did not differ between participants who developed COVID-19–compatible illness (154 ng/mL) versus participants without COVID-19 (133 ng/mL; P =.08). Conclusions Pre-exposure prophylaxis with hydroxychloroquine once or twice weekly did not significantly reduce laboratory-confirmed COVID-19 or COVID-19–compatible illness among healthcare workers. Clinical Trials Registration Clinicaltrials.gov NCT04328467. [ABSTRACT FROM AUTHOR]

Background Bloodstream infections (BSIs) with methicillin-susceptible Staphylococcus aureus (MSSA) are associated with significant morbidity and mortality. Our objective in this study was to determine the efficacy of synergistic treatment with daptomycin when given with either cefazolin or cloxacillin for the treatment of MSSA BSI. Methods A randomized, double-blind, placebo-controlled trial was performed at 2 academic hospitals in Montreal, Canada. Patients aged ≥18 years with MSSA BSI receiving either cefazolin or cloxacillin monotherapy were considered for inclusion. In addition to the standard-of-care treatment, participants received a 5-day course of adjunctive daptomycin or placebo. The primary outcome was the duration of MSSA BSI in days. Results Of 318 participants screened, 115 were enrolled and 104 were included in the intention-to-treat analysis (median age, 67 years; 34.5% female). The median duration of bacteremia was 2.04 days among patients who received daptomycin vs 1.65 days in those who received placebo (absolute difference, 0.39 days; P  = .40). In a modified intention-to-treat analysis that involved participants who remained bacteremic at the time of enrollment, we found a median duration of bacteremia of 3.06 days among patients who received daptomycin vs 3.0 days in those who received placebo (absolute difference, 0.06 days; P  = .77). Ninety-day mortality in the daptomycin arm was 18.9% vs 17.7% in the placebo arm (P  = 1.0). Conclusions Among patients with MSSA BSIs, the administration of adjunctive daptomycin therapy to standard-of-care treatment did not shorten the duration of bacteremia and should not be routinely considered. Clinical Trials Registration NCT02972983. [ABSTRACT FROM AUTHOR]

When faced with a new and therefore frightening disease such as coronavirus disease 2019 (COVID-19), and given concerns over a potentially high case fatality rate, clinicians and patients will be strongly compelled to try unproven therapies. As the number of severely ill patients with coronavirus disease 2019 (COVID-19) continues to increase, we must learn as much as possible about this disease, as quickly as possible, to inform patient care. [Extracted from the article]

Background: Syndromic surveillance through web or phone-based polling has been used to track the course of infectious diseases worldwide. Our study objective was to describe the characteristics, symptoms, and self-reported testing rates of respondents in three different COVID-19 symptom surveys in Canada. Methods: This was a cross-sectional study using three distinct Canada-wide web-based surveys, and phone polling in Ontario. All three sources contained self-reported information on COVID-19 symptoms and testing. In addition to describing respondent characteristics, we examined symptom frequency and the testing rate among the symptomatic, as well as rates of symptoms and testing across respondent groups. Results: We found that over March- April 2020, 1.6% of respondents experienced a symptom on the day of their survey, 15% of Ontario households had a symptom in the previous week, and 44% of Canada-wide respondents had a symptom in the previous month. Across the three surveys, SARS-CoV-2-testing was reported in 2–9% of symptomatic responses. Women, younger and middle-aged adults (versus older adults) and Indigenous/First nations/Inuit/Métis were more likely to report at least one symptom, and visible minorities were more likely to report the combination of fever with cough or shortness of breath. Interpretation: The low rate of testing among those reporting symptoms suggests significant opportunity to expand testing among community-dwelling residents of Canada. Syndromic surveillance data can supplement public health reports and provide much-needed context to gauge the adequacy of SARS-CoV-2 testing rates. [ABSTRACT FROM AUTHOR]

Objectives: To distribute the EMPOWER patient education brochure and use hospitalization as an opportunity to reduce inappropriate sedatives. Design: Participants were sequentially recruited until we achieved 30‐day follow‐up telephone and pharmacy records for 50 individuals. The proportion meeting the primary outcome was compared with that of a control cohort and with rates of cessation achieved in the community. Setting: Fifty‐two‐bed medical clinical teaching unit in Montréal, Canada. Participants: Inpatients aged 65 and older who were chronic, regular sedative users. Measurements: The primary outcome was short‐term sustained cessation 30‐days after discharge. As a secondary outcome, we compared self‐reported sleep disturbance before and after the intervention. Results: Sedatives were deprescribed in 32 of 50 (64%) participants who received the EMPOWER brochure, which was significantly higher than our historical rate of 21% (p<.001). Participants did not report significant worsening in their quality of sleep after sedative cessation. Conclusion: Hospitalized individuals are willing to deprescribe, and contact with the healthcare system provides the opportunity to initiate the process with educational brochures. This type of intervention requires few resources and is feasible and inexpensive. [ABSTRACT FROM AUTHOR]

Background: Evolocumab, a proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitor, has been shown to reduce low-density lipoprotein levels by up to 60%. Despite the absence of a reduction in overall or cardiovascular mortality in the Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk (FOURIER) trial, some believe that, with longer treatment, such a benefit might eventually be realized. Our aim was to estimate the potential mortality benefit over a patient's lifetime and the cost per year of life saved (YOLS) for an average Canadian with established coronary artery disease. We also sought to estimate the price threshold at which evolocumab might be considered cost-effective for secondary prevention in Canada. Methods: We calibrated the Cardio-metabolic Model, a well-validated tool for predicting cardiovascular events and life expectancy, to the reduction in nonfatal events seen in the FOURIER trial. Assuming that long-term treatment will eventually result in mortality benefits, we estimated YOLSs and cost per YOLS with evolocumab treatment plus a statin compared to a statin alone. We then estimated the annual drug costs that would provide a 50% chance of being cost-effective at willingness-to-pay values of $50 000 and $100 000. Results: In secondary prevention in patients similar to those in the FOURIER study, evolocumab treatment would save an average of 0.34 (95% confidence interval [CI] 0.27-0.41) life-years at a cost of $101 899 (95% CI $97 325-$106 473), yielding a cost per YOLS of $299 482. We estimate that to have a 50% probability of achieving a cost per YOLS below $50 000 and $100 000 would require annual drug costs below $1200 and $2300, respectively. Interpretation: At current pricing, the use of evolocumab for secondary prevention is unlikely to be cost-effective in Canada. [ABSTRACT FROM AUTHOR]

Background: The performance and availability of invasive and non-invasive investigations for the diagnosis of Pneumocystis jirovecii pneumonia (PCP) vary across clinical settings. Estimating the pre-test probability of PCP is essential to the optimal selection and interpretation of diagnostic tests, such as the 1,3-β-D-glucan assay (BDG), for the prioritization of bronchoscopy, and to guide empiric treatment decisions. We aimed to develop a multivariable risk score to estimate the pre-test probability of PCP., Methods: The score was developed from a cohort of 626 individuals who underwent bronchoscopy for the purposes of identifying PCP in a Canadian tertiary-care centre, between 2015 and 2018. We conducted a nested case-control study of 57 cases and 228 unmatched controls. Demographic, clinical, laboratory, and radiological data were included in a multivariable logistic regression model to estimate adjusted odds ratios for PCP diagnosis. A clinical risk score was derived from the multivariable model and discrimination was assessed by estimating the score's receiver operating characteristic curve., Results: Participants had a median age of 60 years (interquartile range [IQR] 49-68) and 115 (40%) were female; 40 (14%) had HIV and 49 (17%) had a solid organ transplant (SOT). The risk score included prior SOT or HIV with CD4 ≤ 200/µL (+ 2), serum lactate dehydrogenase ≥ 265.5 IU/mL (+ 2), radiological pattern typical of PCP on chest x-ray (+ 2) or CT scan (+ 2.5), and PCP prophylaxis with trimethoprim-sulfamethoxazole (-3) or other antimicrobials (-2). The median score was 4 points (IQR, 2-4.5) corresponding to a 28% probability of PCP. The risk prediction model had good discrimination with a c-statistic of 0.79 (0.71-0.84). Given the operating characteristics of the BDG assay, scores ≤ 3 in patients without HIV, and ≤ 5.5 in those with HIV, paired with a negative BDG, would be expected to rule out PCP with 95% certainty., Conclusion: We propose the PCP Score to estimate pre-test probability of PCP. Once validated, it should help clinicians determine which patients to refer for invasive investigations, when to rely on serological testing, and in whom to consider pre-emptive treatment., (© 2024. The Author(s).)

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) down-regulates angiotensin-converting enzyme 2, potentially increasing angiotensin II. We hypothesized that losartan compared to usual care decreases mortality and is safe in patients hospitalized with coronavirus disease 2019 (COVID-19). We aimed to evaluate the effect of losartan versus usual care on 28-day mortality in patients hospitalized for acute COVID-19., Methods: Eligibility criteria included adults admitted for acute COVID-19. Exclusion criteria were hypotension, hyperkalemia, acute kidney injury, and use of angiotensin receptor blockers (ARBs) or angiotensin-converting enzyme inhibitors within 7 days. Participants were randomized to losartan 25-100 mg/day orally for the hospital duration or 3 months or the control arm (usual care) in 29 hospitals in Canada and France. The primary outcome was 28-day mortality. Secondary outcomes were hospital mortality, organ support, and serious adverse events (SAEs)., Results: The trial was stopped early because of a serious safety concern with losartan. In 341 patients, any SAE and hypotension were significantly higher in the losartan versus usual care groups (any SAE: 39.8% vs 27.2%, respectively, P = .01; hypotension: 30.4% vs 15.3%, respectively, P < .001) in both ward and intensive care patients. The 28-day mortality did not differ between losartan (6.5%) versus usual care (5.9%) (odds ratio, 1.11 [95% confidence interval, .47-2.64]; P = .81), nor did organ dysfunction or secondary outcomes., Conclusions: Caution is needed in deciding which patients to start or continue using ARBs in patients hospitalized with pneumonia to mitigate risk of hypotension, acute kidney injury, and other side effects. ARBs should not be added to care of patients hospitalized for acute COVID-19., Clinical Trials Registration: NCT04606563., Competing Interests: Potential conflicts of interest . J. A. R. reports patents owned by the University of British Columbia that are related to (i) the use of PCSK9 inhibitor(s) in sepsis, (ii) the use of vasopressin in septic shock, and (iii) a patent owned by Ferring for use of selepressin in septic shock; J. A. R. is an inventor on these patents. J. A. R. was a founder, director, and shareholder in Cyon Therapeutics Inc (now closed) and is a shareholder in Molecular You Corp; is the Senior Research Advisor of the British Columbia, Canada Post COVID–Interdisciplinary Clinical Care Network (PC-ICCN); reports receiving consulting fees in the last 3 years as a funded member of the data and safety monitoring board of a National Institutes of Health–sponsored trial of plasma in COVID-19 (PASS-IT-ON; 2020–2021); has received grants for COVID-19 and for pneumonia research from CIHR and the St Paul's Foundation; and was a nonfunded science advisor and member of the government of Canada COVID-19 Therapeutics Task Force (June 2020–2021). All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Bronchoalveolar lavage is usually employed for molecular diagnosis of Pneumocystis jirovecii but requires a specialized procedure. By contrast, nasopharyngeal (NP) specimens are easily obtained. In this retrospective study of 35 patients with paired NP and bronchoscopy specimens, NP specimens had a 100% negative percent agreement (95% CI 80.5-100) but only 72.2% positive percent agreement (95% CI 46.5-90.3)., Competing Interests: The authors declare no conflict of interest.

Background: The role of remdesivir in the treatment of hospitalized patients with COVID-19 remains ill-defined. We conducted a cost-effectiveness analysis alongside the Canadian Treatments for COVID-19 (CATCO) open-label, randomized clinical trial evaluating remdesivir., Methods: Patients with COVID-19 in Canadian hospitals from Aug. 14, 2020, to Apr. 1, 2021, were randomly assigned to receive remdesivir plus usual care versus usual care alone. Taking a public health care payer's perspective, we collected in-hospital outcomes and health care resource utilization alongside estimated unit costs in 2020 Canadian dollars over a time horizon from randomization to hospital discharge or death. Data from 1281 adults admitted to 52 hospitals in 6 Canadian provinces were analyzed., Results: The total mean cost per patient was $37 918 (standard deviation [SD] $42 413; 95% confidence interval [CI] $34 617 to $41 220) for patients randomly assigned to the remdesivir group and $38 026 (SD $46 021; 95% CI $34 480 to $41 573) for patients receiving usual care (incremental cost -$108 [95% CI -$4953 to $4737], p > 0.9). The difference in proportions of in-hospital deaths between remdesivir and usual care groups was -3.9% (18.7% v. 22.6%, 95% CI -8.3% to 1.0%, p = 0.09). The difference in proportions of incident invasive mechanical ventilation events between groups was -7.0% (8.0% v. 15.0%, 95% CI -10.6% to -3.4%, p = 0.006), whereas the difference in proportions of total mechanical ventilation events between groups was -5.7% (16.4% v. 22.1%, 95% CI -10.0% to -1.4%, p = 0.01). Remdesivir was the dominant intervention (but only marginally less costly, with mildly lower mortality) with an incalculable incremental cost effectiveness ratio; we report results of incremental costs and incremental effects separately. For willingness-to-pay thresholds of $0, $20 000, $50 000 and $100 000 per death averted, a strategy using remdesivir was cost-effective in 60%, 67%, 74% and 79% of simulations, respectively. The remdesivir costs were the fifth highest cost driver, offset by shorter lengths of stay and less mechanical ventilation., Interpretation: From a health care payer perspective, treating patients hospitalized with COVID-19 with remdesivir and usual care appears to be preferrable to treating with usual care alone, albeit with marginal incremental cost and small clinical effects. The added cost of remdesivir was offset by shorter lengths of stay in the intensive care unit and less need for ventilation., Study Registration: ClinicalTrials. gov, no. NCT04330690., Competing Interests: Competing interests: Robert Fowler is the H. Barrie Fairley Professor of Critical Care Medicine at the University Health Network and the University of Toronto Interdepartmental Division of Critical Care Medicine. Robert Fowler declares a Canadian Institutes of Health Research (CIHR) operating grant. John Conly declares grants from the CIHR, Pfizer and the World Health Organization (WHO). He declares a peer-reviewed research grant on acute and primary care preparedness for COVID-19 in Alberta, Canada; he was a primary local investigator for the STRIVE Staphylococcus aureus vaccine randomized controlled trial in vertebral spinal surgery with instrumentation for which all funding was provided only to the University of Calgary; he was a co-investigator on a WHO-funded study using integrated human factors and ethnography approaches to identify and scale innovative infection prevention and control (IPC) guidance implementation supports in primary care with a focus on low-resource settings and using drone aerial systems to deliver medical supplies and personal protective equipment to remote First Nations communities during the COVID-19 pandemic. John Conly also reports receiving accommodations and airfare from the Centers for Disease Control and Prevention to attend a meeting in 2019. He is a member and chair of the WHO Infection Prevention and Control Research and Development Expert Group for COVID-19 and a member of the WHO Health Emergencies Programme Ad-hoc COVID-19 IPC Guidance Development Group, both of which provide multidisciplinary advice to the WHO, for which no funding is received and from which no funding recommendations are made for any WHO contracts or grants. He is also a member of the Cochrane Acute Respiratory Infections Group. Darrell Tan is supported by a Tier 2 Canada Research Chair in HIV Prevention and STI Research. Ryan Zarychanski reports grants from the CIHR, the Peter Munk Cardiac Centre, the Thistledown Foundation and the National Institutes of Health. He is a WHO thrombostasis technical advisory member. Ryan Zarychanski is the recipient of the Lyonel G. Israels Research Chair in Hematology at the University of Manitoba. Todd Lee reports a CATCO operating grant from the CIHR as a co–principal investigator and a co-investigator. He reports various operating grants from the CIHR, a technical development grant from the Centre for Aging + Brain Health Innovation and research salary support from the Fonds de recherche du Québec — Santé. He is the co-owner of a company that is bringing Med-Safer to market. Srinivas Murthy is the Innovative Medicines Canada and Health Research Foundation Chair in Pandemic Preparedness Research. Srinivas Murthy reports a grants from the CIHR and Health Research Foundation and Innovative Medicines Canada., (© 2022 CMA Impact Inc. or its licensors.)

Objectives: To determine whether angiotensin receptor blockers (ARBs) or angiotensin-converting enzyme (ACE) inhibitors are associated with improved outcomes in hospitalized patients with COVID-19 according to sex and to report sex-related differences in renin-angiotensin system (RAS) components., Design: Prospective observational cohort study comparing the effects of ARB or ACE inhibitors versus no ARBs or ACE inhibitors in males versus females. Severe acute respiratory syndrome coronavirus 2 downregulates ACE-2, potentially increasing angiotensin II (a pro-inflammatory vasoconstrictor). Sex-based differences in RAS dysregulation may explain sex-based differences in responses to ARBs because the ACE2 gene is on the X chromosome. We recorded baseline characteristics, comorbidities, prehospital ARBs or ACE inhibitor treatment, use of organ support and mortality, and measured RAS components at admission and days 2, 4, 7, and 14 in a subgroup ( n = 46), recorded d -dimer ( n = 967), comparing males with females., Setting: ARBs CORONA I is a multicenter Canadian observational cohort of patients hospitalized with acute COVID-19. This analysis includes patients admitted to 10 large urban hospitals across the four most populated provinces., Patients: One-thousand six-hundred eighty-six patients with polymerase chain reaction-confirmed COVID-19 (February 2020 to March 2021) for acute COVID-19 illness were included., Interventions: None., Measurements and Main Results: Males on ARBs before admission had decreased use of ventilation (adjusted odds ratio [aOR] = 0.52; p = 0.007) and vasopressors (aOR = 0.55; p = 0.011) compared with males not on ARBs or ACE inhibitors. No significant effects were observed in females for these outcomes. The test for interaction was significant for use of ventilation ( p = 0.006) and vasopressors ( p = 0.044) indicating significantly different responses to ARBs according to sex. Males had significantly higher plasma ACE-1 at baseline and angiotensin II at day 7 and 14 than females., Conclusions: ARBs use was associated with less ventilation and vasopressors in males but not females. Sex-based differences in RAS dysregulation may contribute to sex-based differences in outcomes and responses to ARBs in COVID-19., Competing Interests: Drs. Rocheleau’s, Cheng’s, Lee’s, Haljan’s, Vinh’s, Mann’s, Donohoe’s, and Russell’s institutions received funding from the Canadian Institutes for Health Research. Dr. Mohammed’s institution received funding from Genome Canada and Genome British Colombia. Dr. Goodlett disclosed that he is the founder of Pataigin LLC and Deurion LLC and that the University of Victoria Genome British Columbia Proteome Centre (for which he is a director) received funding from Genome Canada and Genome British Colombia. Dr. Burns disclosed that he is a consultant to JN Nova Pharma. Dr. Cheng’s institution received funding from McGill Interdisciplinary Initiative in Infection and Immunity; he received funding from GEn1E Lifesciences and NPlex Biosciences; he disclosed that he is the cofounder of Kanvas Biosciences and owns equity in the company; and he disclosed that he is a named coinventor on a pending patent entitled “Methods for assessing the severity and progression of SARS-CoV2 infections using cell-free DNA.” Dr. Slutsky received funding from Apeiron, GlaxoSmithKline, Baxter, Cellenkos, Diffusion, Edesa, Exvastat, Faron, and Novalung. Dr. Lee received funding from the Fonds de recherche du Quebec santé (FRQS). Dr. Haljan’s institution received funding from Michael Smith Foundation for Health Research and Surrey Hospital Foundation. Dr. Vinh’s institution received funding from the Jeffrey Modell Foundation and FRQS; he received funding from CSL Behring, Astra Zeneca, Moderna, Takeda, QU Biologics, Merck Canada, Novartis Canada, and the COVID Immunity Task Force (Public Health Agency of Canada); he disclosed he has patent applications pending (Encrypting File System Identification [EFS ID] 40101099; EFS ID 44321620). Dr. Russell reports patents owned by the University of British Columbia (UBC) that are related to the use of proprotein convertase subtilisin/kexin type 9 inhibitor(s) in sepsis and related to the use of vasopressin in septic shock and a patent owned by Ferring for use of selepressin in septic shock; he is an inventor on these patents; he was a founder, director, and shareholder in Cyon Therapeutics and is a shareholder in Molecular You Corp; he reports receiving consulting fees in the last 3 years from: Asahi Kesai Pharmaceuticals of America (was developing recombinant thrombomodulin in sepsis), SIB Therapeutics LLC (developing a sepsis drug), and Ferring Pharmaceuticals (manufactures vasopressin and developing selepressin); he is no longer actively consulting for the following: La Jolla Pharmaceuticals (developing angiotensin II; Dr. Russell chaired the Data Safety Monitoring Board of a trial of angiotensin II from 2015 to 2017), PAR Pharma (sells prepared bags of vasopressin); and he reports having received an investigator-initiated grant from Grifols (entitled “Is HBP a mechanism of albumin’s efficacy in human septic shock?”) that was provided to and administered by UBC. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and Wolters Kluwer Health, Inc.)

Introduction: Pneumocystis jirovecii pneumonia (PJP) is an opportunistic infection of immunocompromised hosts with significant morbidity and mortality. The current standard of care, trimethoprim-sulfamethoxazole (TMP-SMX) at a dose of 15-20 mg/kg/day, is associated with serious adverse drug events (ADE) in 20%-60% of patients. ADEs include hypersensitivity reactions, drug-induced liver injury, cytopenias and renal failure, all of which can be treatment limiting. In a recent meta-analysis of observational studies, reduced dose TMP-SMX for the treatment of PJP was associated with fewer ADEs, without increased mortality., Methods and Analysis: A phase III randomised, placebo-controlled, trial to directly compare the efficacy and safety of low-dose TMP-SMX (10 mg/kg/day of TMP) with the standard of care (15 mg/kg/day of TMP) among patients with PJP, for a composite primary outcome of change of treatment, new mechanical ventilation, or death. The trial will be undertaken at 16 Canadian hospitals. Data will be analysed as intention to treat. Primary and secondary outcomes will be compared using logistic regression adjusting for stratification and presented with 95% CI., Ethics and Dissemination: This study has been conditionally approved by the McGill University Health Centre; Ethics approval will be obtained from all participating centres. Results will be submitted for publication in a peer-reviewed journal., Trial Registration Number: NCT04851015., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The role of remdesivir in the treatment of patients in hospital with COVID-19 remains ill defined in a global context. The World Health Organization Solidarity randomized controlled trial (RCT) evaluated remdesivir in patients across many countries, with Canada enrolling patients using an expanded data collection format in the Canadian Treatments for COVID-19 (CATCO) trial. We report on the Canadian findings, with additional demographics, characteristics and clinical outcomes, to explore the potential for differential effects across different health care systems., Methods: We performed an open-label, pragmatic RCT in Canadian hospitals, in conjunction with the Solidarity trial. We randomized patients to 10 days of remdesivir (200 mg intravenously [IV] on day 0, followed by 100 mg IV daily), plus standard care, or standard care alone. The primary outcome was in-hospital mortality. Secondary outcomes included changes in clinical severity, oxygen- and ventilator-free days (at 28 d), incidence of new oxygen or mechanical ventilation use, duration of hospital stay, and adverse event rates. We performed a priori subgroup analyses according to duration of symptoms before enrolment, age, sex and severity of symptoms on presentation., Results: Across 52 Canadian hospitals, we randomized 1282 patients between Aug. 14, 2020, and Apr. 1, 2021, to remdesivir ( n = 634) or standard of care ( n = 648). Of these, 15 withdrew consent or were still in hospital, for a total sample of 1267 patients. Among patients assigned to receive remdesivir, in-hospital mortality was 18.7%, compared with 22.6% in the standard-of-care arm (relative risk [RR] 0.83 (95% confidence interval [CI] 0.67 to 1.03), and 60-day mortality was 24.8% and 28.2%, respectively (95% CI 0.72 to 1.07). For patients not mechanically ventilated at baseline, the need for mechanical ventilation was 8.0% in those assigned remdesivir, and 15.0% in those receiving standard of care (RR 0.53, 95% CI 0.38 to 0.75). Mean oxygen-free and ventilator-free days at day 28 were 15.9 (± standard deviation [SD] 10.5) and 21.4 (± SD 11.3) in those receiving remdesivir and 14.2 (± SD 11) and 19.5 (± SD 12.3) in those receiving standard of care ( p = 0.006 and 0.007, respectively). There was no difference in safety events of new dialysis, change in creatinine, or new hepatic dysfunction between the 2 groups., Interpretation: Remdesivir, when compared with standard of care, has a modest but significant effect on outcomes important to patients and health systems, such as the need for mechanical ventilation. Trial registration : ClinicalTrials.gov, no. NCT04330690., Competing Interests: Competing interests: Alexandra Binnie reports receiving research grants from the Canadian Institutes of Health Research (CIHR) and the Physicians Services Incorporated Foundation. Sergio Borgia reports receiving honoraria from Gilead Sciences and GSK. Yiorgos Alexandros Cavayas reports receiving a grant from CIHR. Matthew Cheng reports receiving grants from the McGill Interdisciplinary Initiative in Infection and Immunity and from CIHR, during the conduct of the study (payments made to the institution). Dr. Cheng also reports receiving personal fees from AstraZeneca, outside the submitted work; and from Nplex Biosciences and GEn1E lifesciences (in the form of stock options for being a member of the scientific advisory board) outside the submitted work. Dr. Cheng co-founded Kanvas Biosicences and owns equity in the company, and reports 3 patents pending. John Conly reports receiving grants from CIHR, Pfizer, the World Health Organization (WHO), Sunnybrook Research Institute, University of Calgary, and the Calgary Health Foundation. Dr. Conly also reports receiving support to attend the Think Tank Meeting 2019. Dr. Conly is a member and Chair of the WHO Infection Prevention and Control Research and Development Expert Group for COVID-19, a member of the WHO Health Emergencies Programme (WHE) Ad-hoc COVID-19 IPC Guidance Development Group, and a member of the Cochrane Acute Respiratory Infections Group. Madeleine Durand reports receiving grants from CIHR and the Fonds Recherche du Québec–Santé (FRQS). Rob Fowler reports receiving a grant from CIHR for the CATCO trial and is the H. Barrie Fairley Professor of Critical Care at the University Health Network. Michael Fralick reports receiving multiple grants from CIHR and support from grants from the Canadian military for clinical trials to identify treatments for COVID-19 (payments made to institution). Dr. Fralick is a paid consultant for a start-up company called Proof DiagnosticsDx, which has created a point-of-care testing device using CRISPR for COVID-19. Holly Hoang reports receiving payment from CATCO Sunnybrook to fund research assistant (payment made to institution) and a research grant from Covenant Health Research Centre. Marina Klein reports receiving grants from Gilead, ViiV Healthcare, Merck and AbbVie for investigator-initiated studies, and consulting fees from Gilead, ViiV Healthcare, Merck and AbbVie, all outside the submitted work. Todd Lee reports receiving operating grants from CIHR and McGill Interdisciplinary Initiative in Infection and Immunity (MI4), and research salary support from FRQS. Alexandra Lostun reports receiving per-case funding to cover the costs of enrolling patients (paid to institution, North York General Hospital). François Carrier reports receiving grants from the Instituts de recherche en santé du Canada and the Canadian Donation and Transplantation Research Program, and a grant and salary support from FRQS. Marlee McGuinty reports receiving speaking fees from Merck. Srinivas Murthy reports receiving a grant from CIHR, during the conduct of the study, and is the Health Research Foundation and Innovative Medicines Canada Chair in Pandemic Preparedness Research. Conar O’Neil reports receiving conference sponsorship from Gilead Sciences, and is a member of a Gilead Sciences advisory board. Jesse Papenburg reports receiving a grant from CIHR, during the conduct of the study, as well as research grants and contracts from AbbVie and research contracts (site investigator for clinical trial) from MedImmune, Merck and Sanofi Pasteur. Dr. Papenburg has received consulting fees from Merck for an ad hoc advisory board meeting, and honoraria for presentations from Seegene, AbbVie and AstraZeneca. Dr. Papenburg is also a voting member of the National Advisory Committee on Immunization. Ken Kuljit S. Parhar reports receiving a CIHR project grant, Alberta Innovates grant and Alberta Health Innovation Implementation and Spread grant (all paid to institution). Seema Nair Parvathy reports receiving funding from St. Joseph’s Health Care Foundation and London Health Sciences Foundation. Moira Rushton-Marovac reports receiving advisory board honoraria from Gilead. Marina Salvadori reports being an employee of the Public Health Agency of Canada. Makeda Semret reports receiving support from the McGill MI4 for the clinical research platform through which CATCO was supported at the McGill University Health Centre. Ameeta Singh reports receiving consulting fees from Gilead for membership of an advisory board. Ranjani Somayaji reports receiving contract research funding from Sunnybrook Research Institute, University of Calgary and Calgary Health Foundation, and clinical research funding from CIHR and the Cystic Fibrosis Foundation. Dr. Somayaji also reports participation on an oncovir data monitoring safety board. Darrell Tan reports receiving grants from AbbVie (in-kind drug only) and Gilead (in-kind drug and grants to institution), and a contract between GSK and the institution for clinical trials. Alain Tremblay reports receiving contract research funding from the Sunnybrook Research Institute, and grants for COVID-19 clinical trials from the University of Calgary and Calgary Health Foundation. Alexis Turgeon reports receiving a grant from CIHR. Jason Weatherald reports receiving grants (paid to institution) and consulting fees (paid to Dr. Weatherald) from Janssen and Actelion, as well as honoraria and travel support from Janssen. Dr. Weatherald has served on advisory boards for Janssen and Acceleron (paid) and on a Data Safety Monitoring Board for Université Laval (unpaid). Dr. Weatherald also reports membership of the Medical Advisory Committee of the Pulmonary Hypertension Association of Canada, and is a shareholder of Precision Lung Consultants and Diagnostics. Cedric Yansouni reports receiving grants from FRQS and consulting fees from Medicago Inc. Dr. Yansouni also reports participation in a Medicago Inc. Independent Data Monitoring Committee and held the role of scientific advisor for the COVID-19 Immunity Task Force. No other competing interests were declared., (© 2022 CMA Impact Inc. or its licensors.)

Background: Clinical data on patients admitted to hospital with coronavirus disease 2019 (COVID-19) provide clinicians and public health officials with information to guide practice and policy. The aims of this study were to describe patients with COVID-19 admitted to hospital and intensive care, and to investigate predictors of outcome to characterize severe acute respiratory infection., Methods: This observational cohort study used Canadian data from 32 selected hospitals included in a global multisite cohort between Jan. 24 and July 7, 2020. Adult and pediatric patients with a confirmed diagnosis of COVID-19 who received care in an intensive care unit (ICU) and a sampling of up to the first 60 patients receiving care on hospital wards were included. We performed descriptive analyses of characteristics, interventions and outcomes. The primary analyses examined in-hospital mortality, with secondary analyses of the length of hospital and ICU stay., Results: Between January and July 2020, among 811 patients admitted to hospital with a diagnosis of COVID-19, the median age was 64 (interquartile range [IQR] 53-75) years, 495 (61.0%) were men, 46 (5.7%) were health care workers, 9 (1.1%) were pregnant, 26 (3.2%) were younger than 18 years and 9 (1.1%) were younger than 5 years. The median time from symptom onset to hospital admission was 7 (IQR 3-10) days. The most common symptoms on admission were fever, shortness of breath, cough and malaise. Diabetes, hypertension and cardiac, kidney and respiratory disease were the most common comorbidities. Among all patients, 328 received care in an ICU, admitted a median of 0 (IQR 0-1) days after hospital admission. Critically ill patients received treatment with invasive mechanical ventilation (88.8%), renal replacement therapy (14.9%) and extracorporeal membrane oxygenation (4.0%); 26.2% died. Among those receiving mechanical ventilation, 31.2% died. Age was an influential predictor of mortality (odds ratio per additional year of life 1.06, 95% confidence interval 1.03-1.09)., Interpretation: Patients admitted to hospital with COVID-19 commonly had fever, respiratory symptoms and comorbid conditions. Increasing age was associated with the development of critical illness and death; however, most critically ill patients in Canada, including those requiring mechanical ventilation, survived and were discharged from hospital., Competing Interests: Competing interests: See the end of the article. Competing interests: Todd Lee reports salary support from Fonds de recherche du Québec – Santé. Deepali Kumar reports grants and personal fees from Roche. Michelle Kho reports grants from Canada Research Chairs. Matthew Cheng reports grants from the McGill Interdisciplinary Initiative in Infection and Immunity and personal fees from GEn1E Lifesciences (as a member of the scientific advisory board) and personal fees from nplex biosciences (as a member of the scientific advisory board). Philippe Jouvet reports consulting for Mallinckrodt Pharmaceuticals and grants to his institution from VitalTracer and Evolucare. Patrick Archambault is a co-investigator in the Canadian Institutes of Health Research (CIHR)–funded Canadian COVID-19 Emergency Department Rapid Response Network (https://canadiancovid19ednetwork.org). No other competing interests were declared., (© 2021 Joule Inc. or its licensors.)

Introduction: The optimal treatment for extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae bloodstream infections has yet to be defined. Retrospective studies have shown conflicting results, with most data suggesting the non-inferiority of beta-lactam-beta-lactamase inhibitor combinations compared with carbapenems. However, the recently published MERINO trial failed to demonstrate the non-inferiority of piperacillin-tazobactam to meropenem. The potential implications of the MERINO trial are profound, as widespread adoption of carbapenem treatment will have detrimental effects on antimicrobial stewardship in areas endemic for ESBL and carbapenem-resistant bacteria. Therefore, we believe that it is justified to re-examine the comparison in a second randomised controlled trial prior to changing clinical practice., Methods and Analysis: PeterPen is a multicentre, investigator-initiated, open-label, randomised controlled non-inferiority trial, comparing piperacillin-tazobactam with meropenem for third-generation cephalosporin-resistant Escherichia coli and Klebsiella bloodstream infections. The study is currently being conducted in six centres in Israel and one in Canada with other centres from Israel, Italy and Canada expected to join. The two primary outcomes are all-cause mortality at day 30 from enrolment and treatment failure at day seven (death, fever above 38°C in the last 48 hours, continuous symptoms, increasing Sequential Organ Failure Assessment Score or persistent blood cultures with the index pathogen). A sample size of 1084 patients was calculated for the mortality endpoint assuming a 12.5% mortality rate in the control group with a 5% non-inferiority margin and assuming 100% follow-up for this outcome., Ethics and Dissemination: The study is approved by local and national ethics committees as required. Results will be published, and trial data will be made available., Trial Registration Numbers: ClinicalTrials.gov Registry (NCT03671967); Israeli Ministry of Health Trials Registry (MOH&#95;2018-12-25&#95;004857)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Coronavirus disease 2019 (Covid-19) occurs after exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). For persons who are exposed, the standard of care is observation and quarantine. Whether hydroxychloroquine can prevent symptomatic infection after SARS-CoV-2 exposure is unknown., Methods: We conducted a randomized, double-blind, placebo-controlled trial across the United States and parts of Canada testing hydroxychloroquine as postexposure prophylaxis. We enrolled adults who had household or occupational exposure to someone with confirmed Covid-19 at a distance of less than 6 ft for more than 10 minutes while wearing neither a face mask nor an eye shield (high-risk exposure) or while wearing a face mask but no eye shield (moderate-risk exposure). Within 4 days after exposure, we randomly assigned participants to receive either placebo or hydroxychloroquine (800 mg once, followed by 600 mg in 6 to 8 hours, then 600 mg daily for 4 additional days). The primary outcome was the incidence of either laboratory-confirmed Covid-19 or illness compatible with Covid-19 within 14 days., Results: We enrolled 821 asymptomatic participants. Overall, 87.6% of the participants (719 of 821) reported a high-risk exposure to a confirmed Covid-19 contact. The incidence of new illness compatible with Covid-19 did not differ significantly between participants receiving hydroxychloroquine (49 of 414 [11.8%]) and those receiving placebo (58 of 407 [14.3%]); the absolute difference was -2.4 percentage points (95% confidence interval, -7.0 to 2.2; P = 0.35). Side effects were more common with hydroxychloroquine than with placebo (40.1% vs. 16.8%), but no serious adverse reactions were reported., Conclusions: After high-risk or moderate-risk exposure to Covid-19, hydroxychloroquine did not prevent illness compatible with Covid-19 or confirmed infection when used as postexposure prophylaxis within 4 days after exposure. (Funded by David Baszucki and Jan Ellison Baszucki and others; ClinicalTrials.gov number, NCT04308668.)., (Copyright © 2020 Massachusetts Medical Society.)

Background: We have designed a prospective adverse event (AE) surveillance method. We performed this study to evaluate this method's performance in several hospitals simultaneously., Objectives: To compare AE rates obtained by prospective AE surveillance in different hospitals and to evaluate measurement factors explaining observed variation., Methods: We conducted a multicentre prospective observational study. Prospective AE surveillance was implemented for 8 weeks on the general medicine wards of five hospitals. To determine if population factors may have influenced results, we performed mixed-effects logistic regression. To determine if surveillance factors may have influenced results, we reassigned observers to different hospitals midway through surveillance period and reallocated a random sample of events to different expert review teams., Results: During 3560 patient days of observation of 1159 patient encounters, we identified 356 AEs (AE risk per encounter=22%). AE risk varied between hospitals ranging from 9.9% of encounters in Hospital D to 35.8% of encounters in Hospital A. AE types and severity were similar between hospitals-the most common types were related to clinical procedures (45%), hospital-acquired infections (21%) and medications (19%). Adjusting for age and comorbid status, we observed an association between hospital and AE risk. We observed variation in observer behaviour and moderate agreement between clinical reviewers, which could have influenced the observed rate difference., Conclusion: This study demonstrated that it is possible to implement prospective surveillance in different settings. Such surveillance appears to be better suited to evaluating hospital safety concerns within rather than between hospitals as we could not definitively rule out whether the observed variation in AE risk was due to population or surveillance factors., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Importance: Adverse drug events (ADEs) account for up to 16% of emergency department (ED) visits and 7% of hospital admissions. Medication reconciliation is required for hospital accreditation because it can reduce medication discrepancies, but there is no evidence that reducing discrepancies reduces ADEs or other adverse outcomes., Objective: To evaluate whether electronic medication reconciliation reduces ADEs, medication discrepancies, and other adverse outcomes compared with usual care., Design, Setting, and Participants: This cluster randomized trial involved 3491 patients who were discharged from 2 medical units and 2 surgical units at the McGill University Health Centre, Montreal, Quebec, Canada, between October 2014 and November 2016. Data analysis took place from July 2017 to July 2019., Intervention: The RightRx intervention electronically retrieved community drugs from the provincial insurer and aligned them with in-hospital drugs to facilitate reconciliation and communication at care transitions., Main Outcomes and Measures: The primary outcome was ADEs in 30 days after discharge. Secondary outcomes included medication discrepancies, ED visits, hospital readmissions, and a composite outcome of ED visits, readmissions, and death up to 90 days after discharge., Results: Of 4656 eligible patients, 3567 (76.6%) consented to participate (2060 [57.8%] men; mean [SD] age, 69.8 [14.9] years). Overall, 76 patients died during the hospital stay, so 3491 patients were included in the analysis. There was no significant difference in the risk of ADEs between intervention and control groups (76 [4.6%] vs 73 [4.0%]; OR, 0.97; 95% CI, 0.33-1.48), ED visits (433 [26.2%] vs 488 [26.6%]; OR, 0.83; 95% CI, 0.36-1.42), hospital readmission (170 [10.3%] vs 261 [14.2%]; OR, 0.22; 95% CI, 0.06-1.14), or the composite outcome (447 [27.0%] vs 506 [27.6%]; OR, 0.75; 95% CI, 0.34-1.27) at 30 days. Medication discrepancies were significantly reduced in the intervention group compared with the control group (437 [26.4%] vs 1029 [56.0%]; OR, 0.24; 95% CI, 0.12-0.57). Changes made to community medications (OR, 1.05; 95% CI, 1.01-1.10) and new medications (OR, 1.09; 95% CI, 1.01-1.18) were significant risk factors for ADEs., Conclusions and Relevance: Electronic medication reconciliation reduced medication discrepancies but did not reduce ADEs or other adverse outcomes. Hospital accreditation should focus on interventions that reduce the risk of adverse events for patients with multiple changes to community medications., Trial Registration: ClinicalTrials.gov identifier: NCT01179867.

Over 3 million hospitalizations and 17 million ER visits occur in Canada each year. A substantial proportion of these encounters are preventable and attributable to medication non- adherence. Non-adherence to medication changes during discharge increases the risk of adverse events post-discharge. A mobile application was developed to improve medication management of post-discharge patients. A pilot randomized controlled trial was conducted to assess the application's usability and efficacy in decreasing non-adherence to medication changes made at discharge.

Introduction and Objective: Diagnostic testing for Clostridioides difficile infection (CDI) by nucleic acid amplification test (NAAT) cannot distinguish between colonization and infection. A positive NAAT may therefore represent a false positive for infection, since diarrhea due to various aetiologies may occur in hospitalized patients. Our objective was to help answer the question: "does this medical inpatient with diarrhea have CDI?", Design: We conducted a retrospective cohort study (n = 248) on the Clinical Teaching Units of the Royal Victoria Hospital (Montréal, Canada). Patients were included if they had a NAAT between January 2014 and September 2015 and their admission diagnosis was not CDI. CDI cases and non-CDI cases were compared, and independent predictors of CDI were determined by logistic regression., Results: Several factors were independently associated with CDI, including: hemodialysis (OR: 13.5, 95% CI: 2.85-63.8), atrial fibrillation (OR: 3.70, 95% CI: 1.52-9.01), whether the patient received empiric treatment (OR: 3.01, 95% CI: 1.04-8.68), systemic antibiotic therapy prior to testing (OR: 4.23, 95% CI: 1.71-10.5), previous positive NAAT (OR: 3.70, 95% CI: 1.41-9.72), and a leukocyte count of 11x109/L or higher (OR: 3.43, 95% CI: 1.42-8.26). The area under the curve was 0.80., Conclusion: For patients presenting with hospital-onset diarrhea, various parameters can help differentiate between CDI and other causes. A clinical prediction calculator derived from our cohort (http://individual.utoronto.ca/leet/cdiff.html) might assist clinicians in estimating the risk of CDI for inpatients; those with low pre-test probability may not require immediate testing, treatment, nor prolonged isolation., Competing Interests: The authors have declared that no competing interests exist.

Importance: Clostridium difficile infection (CDI) is associated with significant morbidity, mortality, and a high risk of recurrence. Proton pump inhibitor (PPI) use is associated with an initial episode of CDI, and PPIs are frequently overprescribed. For many, the use of PPIs could likely be discontinued before CDI recurrence., Objectives: To determine whether PPI use was associated with a risk of initial CDI recurrence, to assess what proportion of patients who developed CDI were taking a PPI for a non-evidence-based indication, and to evaluate whether physicians discontinued unnecessary PPIs in the context of CDI., Design, Setting, and Participants: We conducted a retrospective cohort study of incident health care-associated CDI cases to determine the association between continuous PPI use and CDI recurrence within 90 days. The setting was 2 university-affiliated hospitals, the 417-bed Montreal General Hospital (Montreal, Quebec, Canada) and the 517-bed Royal Victoria Hospital (Montreal, Quebec, Canada). The cohort consisted of 754 patients who developed health care-associated CDI between January 1, 2010, and January 30, 2013, and who survived for a minimum of 15 days after their initial episode of nosocomial CDI., Exposure: Continuous PPI use., Main Outcomes and Measures: Recurrence of CDI within 15 to 90 days of the initial episode., Results: Using a multivariable Cox proportional hazards model, the cause-specific hazard ratios for recurrence were 1.5 (95% CI, 1.1-2.0) for age older than 75 years, 1.5 (95% CI, 1.1-2.0) for continuous PPI use, 1.003 (95% CI, 1.002-1.004) per day for length of stay, and 1.3 (95% CI, 0.9-1.7) for antibiotic reexposure. The use of PPIs was common (60.7%), with only 47.1% of patients having an evidence-based indication. Proton pump inhibitors were discontinued in only 3 patients with CDI., Conclusions and Relevance: After adjustment for other independent predictors of recurrence, patients with continuous PPI use remained at elevated risk of CDI recurrence. We suggest that the cessation of unnecessary PPI use should be considered at the time of CDI diagnosis.

Background: Antibiotic use is an important quality improvement target. Nearly 50% of antibiotic use is unnecessary or inappropriate. To combat overuse, the Centers for Disease Control and Prevention (CDC) proposed "time-outs" to reevaluate antibiotics., Objective: To optimize antibiotic use through trainee-led time-outs., Design: Before-after study., Setting: Internal medicine (2 units, 46 beds) at a university hospital., Patients: Inpatients (n = 679)., Intervention: From January 2012 until June 2013, while receiving monthly education on antimicrobial stewardship, resident physicians adjusted patients' antibiotic therapy through twice-weekly time-out audits using a structured electronic checklist., Measurements: Antibiotic costs were standardized and compared in the year before and after the audits. Use was measured as World Health Organization defined daily doses (DDDs) per 1000 patient-days. Total antibiotic use and the use of moxifloxacin, carbapenems, antipseudomonal penicillins, and vancomycin were compared by using interrupted time series. Rates of nosocomial Clostridium difficile infection were compared by using incidence rate ratios., Results: Total costs in the units decreased from $149,743CAD (January 2011 to January 2012) to $80,319 (January 2012 to January 2013), for a savings of $69,424 (46% reduction). Of the savings, $54,150 (78%) was related to carbapenems and $15,274 (22%) was due to other antibiotic classes. Adherence with the auditing process was 80%. In the time-series analyses, the only reliable and statistically significant change was a reduction in the rate of moxifloxicin use, by -1.9 DDDs per 1000 patient-days per month (95% CI, -3.8 to -0.02; P = 0.048). Rates of C. difficile infection decreased from 24.2 to 19.6 per 10,000 patient-days (incidence rate ratio, 0.8 [CI, 0.5 to 1.3])., Limitation: Other temporal factors may confound the findings., Conclusions: An antibiotic self-stewardship bundle to implement the CDC's suggested time-outs seems to have reduced overall costs and targeted antibiotic use., Primary Funding Source: None.

Objective: Identifying features that differentiate patients with H1N1 influenza infection from those with other conditions may assist clinical decision making during waves of pandemic influenza activity., Methods: From April 27 to June 15, 2009, nasopharyngeal swabs were obtained from all adults presenting to two urban emergency departments (EDs) with illness including fever or respiratory symptoms. H1N1 infection was detected by reverse transcriptase-polymerase chain reaction. Chart review was performed to compare cases of H1N1 influenza (n  =  117) to matched controls., Results: The median age of cases was 35 years versus 50 years for controls (p < .001). In those with pre-existing conditions, asthma was present in 31% of cases versus 14% of controls (OR 2.6, 95% CI 1.3-5.4). Cough (OR 7.8, 95% CI 3.2-19), fever (OR 3.0, 95% CI 1.7-5.4), headache (OR 2.0, 95% CI 1.2-3.2), and myalgias (OR 1.9, 95% CI 1.2-3.1) were significantly more common in H1N1 cases. The median white blood cell count was 5.7 × 109/mL versus 10.9 × 109/mL (p < .001). The combination of fever and cough had an OR of 5.3. Fever, cough, low white blood cell (WBC) count, and tachycardia had the highest OR at 11. The absence of both fever and cough had a negative predictive value of 99%, but this occurred in only 8% of controls., Conclusion: In patients presenting to the ED, the combination of fever, cough, tachycardia, and WBC count < 10 × 109/mL was suggestive of H1N1 influenza infection. However, clinical features could not reliably distinguish influenza from other acute respiratory illnesses in adult ED patients.