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Background Whole genome sequencing (WGS) studies can enhance our understanding of the role of patients with asymptomatic Clostridium difficile colonization in transmission. Methods Isolates obtained from patients with Clostridium difficile infection (CDI) and colonization identified in a study conducted during 2006–2007 at 6 Canadian hospitals underwent typing by pulsed-field gel electrophoresis, multilocus sequence typing, and WGS. Isolates from incident CDI cases not in the initial study were also sequenced where possible. Ward movement and typing data were combined to identify plausible donors for each CDI case, as defined by shared time and space within predefined limits. Proportions of plausible donors for CDI cases that were colonized, infected, or both were examined. Results Five hundred fifty-four isolates were sequenced successfully, 353 from colonized patients and 201 from CDI cases. The NAP1/027/ST1 strain was the most common strain, found in 124 (62%) of infected and 92 (26%) of colonized patients. A donor with a plausible ward link was found for 81 CDI cases (40%) using WGS with a threshold of ≤2 single nucleotide polymorphisms to determine relatedness. Sixty-five (32%) CDI cases could be linked to both infected and colonized donors. Exclusive linkages to infected and colonized donors were found for 28 (14%) and 12 (6%) CDI cases, respectively. Conclusions Colonized patients contribute to transmission, but CDI cases are more likely linked to other infected patients than colonized patients in this cohort with high rates of the NAP1/027/ST1 strain, highlighting the importance of local prevalence of virulent strains in determining transmission dynamics. [ABSTRACT FROM AUTHOR]

Background: Community clinics offer potential for timelier outbreak detection and monitoring than emergency departments. However, the accuracy of syndrome definitions used in surveillance has never been evaluated in community settings. This study's objective was to assess the accuracy of syndrome definitions based on diagnostic codes in physician claims for identifying 5 syndromes (fever, gastrointestinal, neurological, rash, and respiratory including influenza-like illness) in community clinics. Methods: We selected a random sample of 3,600 community-based primary care physicians who practiced in the fee-for-service system in the province of Quebec, Canada in 2005-2007. We randomly selected 10 visits per physician from their claims, stratifying on syndrome type and presence, diagnosis, and month. Double-blinded chart reviews were conducted by telephone with consenting physicians to obtain information on patient diagnoses for each sampled visit. The sensitivity, specificity, and positive predictive value (PPV) of physician claims were estimated by comparison to chart review. Results: 1,098 (30.5%) physicians completed the chart review. A chart entry on the date of the corresponding claim was found for 10,529 (95.9%) visits. The sensitivity of syndrome definitions based on diagnostic codes in physician claims was low, ranging from 0.11 (fever) to 0.44 (respiratory), the specificity was high, and the PPV was moderate to high, ranging from 0.59 (fever) to 0.85 (respiratory). We found that rarely used diagnostic codes had a higher probability of being false-positives, and that more commonly used diagnostic codes had a higher PPV. Conclusions: Future research should identify physician, patient, and encounter characteristics associated with the accuracy of diagnostic codes in physician claims. This would enable public health to improve syndromic surveillance, either by focusing on physician claims whose diagnostic code is more likely to be accurate, or by using all physician claims and weighing each according to the likelihood that its diagnostic code is accurate. [ABSTRACT FROM AUTHOR]

To evaluate the validity of the Identification of Seniors at Risk (ISAR) screening tool for detecting severe functional impairment and depression and predicting increased depressive symptoms and increased utilization of health services. Four university-affiliated hospitals in Montreal. Data from two previous studies were available: Study 1, in which the ISAR scale was developed (n=1,122), and Study 2, in which it was used to identify patients for a randomized trial of a nursing intervention (n=1,889 with administrative data, of which 520 also had clinical data). Patients aged 65 and older who were to be released from an emergency department (ED). Baseline validation criteria included premorbid functional status in both studies and depression in Study 2 only. Increase in depressive symptoms at 4-month follow-up was assessed in Study 2. Information on health services utilization during the 5 months after the ED visit (repeat ED visits and hospitalization in both studies, visits to community health centers in Study 2) was available by linkage with administrative databases. Estimates of the area under the receiver operating characteristic curve (AUC) for concurrent validity of the ISAR scale for severe functional impairment and depression ranged from 0.65 to 0.86. Estimates of the AUC for predictive validity for increased depressive symptoms and high utilization of health services ranged from 0.61 to 0.71. The ISAR scale has acceptable to excellent concurrent and predictive validity for a variety of outcomes, including clinical measures and utilization of health services. [ABSTRACT FROM AUTHOR]

Objectives: To determine the association between the implementation of an antimicrobial stewardship program at a local PICU and to determine the association between the presence of an antimicrobial stewardship programs and antimicrobial use across three Canadian PICUs, among critically ill children with bronchiolitis., Design: A multicenter retrospective cohort study., Setting: Three Canadian PICUs over two winter seasons., Interventions: An antimicrobial stewardship program was implemented at PICU 1 at the end of season 1., Patients: Patients less than or equal to 2 years old admitted with bronchiolitis., Measurements and Main Results: We used regression models with an interaction term between site (PICU 1 and PICU 2) and season (1 and 2) as the primary analysis to determine the association between implementation of an antimicrobial stewardship program at PICU 1 and 1) the proportion of antimicrobials discontinued 72 hours after hospital admission (logistic regression), 2) antimicrobial treatment duration (negative binomial regression), and 3) antimicrobial prescriptions within 48 hours of hospital admission (logistic regression). As a secondary analysis, we determined the association between having an antimicrobial stewardship program present and the aforementioned outcomes across the three PICUs. A total of 372 patients were included. During seasons 1 and 2, median age was 2.2 months (interquartile range, 1.2-6.2 mo) and 2.1 months (interquartile range, 1.3-6.8 mo), respectively. Among patients with viral bronchiolitis, implementation of an antimicrobial stewardship program at PICU 1 was associated with increased odds of discontinuing antimicrobials (odds ratio, 25.63; 95% CI, 2.86-326.29), but not with antimicrobial duration (odds ratio, 0.56; 95% CI, 0.31-1.02) or antimicrobial prescriptions (odds ratio, 0.33; 95% CI, 0.10-1.04). The presence of an antimicrobial stewardship program was similarly associated with antimicrobial discontinuation among patients with viral bronchiolitis (odds ratio, 20.79; 95% CI, 2.46-244.92), but not with antimicrobial duration (odds ratio, 0.57; 95% CI, 0.32-1.03) or antimicrobial prescriptions (odds ratio, 0.37; 95% CI, 0.12-1.11)., Conclusions: Antimicrobial stewardship programs were associated with increased likelihood of discontinuing antimicrobial treatments in the PICU patients with viral bronchiolitis. However, larger studies are needed to further determine the role of an antimicrobial stewardship programs in reducing unnecessary antimicrobial use in this patient population., Competing Interests: Dr. Papenburg’s institution received funding from MedImmune; he received funding from AbbVie, Cepheid, BD Diagnostics, MedImmune, Sanofi Pasteur, Seegene, and Janssen Pharmaceutical. Dr. Quach’s institution received funding from the McGill University Health Centre, Research Institute. Dr. Jouvet received funding from the Mallinckrodt. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Objectives: Antivirals are recommended for children hospitalized with influenza but are underutilized. We describe antiviral prescribing during influenza admissions in Canadian pediatric centers and identify factors associated with antiviral use., Methods: We performed active surveillance for laboratory-confirmed influenza hospitalizations among children ≤16 years old at the 12 Canadian Immunization Monitoring Program Active hospitals, from 2010-2011 to 2018-2019. Logistic regression analyses were used to identify factors associated with antiviral use., Results: Among 7545 patients, 57.4% were male; median age was 3 years (interquartile range: 1.1-6.3). Overall, 41.3% received antiviral agents; 72.8% received antibiotics. Antiviral use varied across sites (range, 10.2% to 81.1%) and influenza season (range, 19.9% to 59.6%) and was more frequent in children with ≥1 chronic health condition (52.7% vs 36.7%; P < .001). On multivariable analysis, factors associated with antiviral use included older age (adjusted odds ratio [aOR] 1.04 [95% confidence interval (CI), 1.02-1.05]), more recent season (highest aOR 9.18 [95% CI, 6.70-12.57] for 2018-2019), admission during peak influenza period (aOR 1.37 [95% CI, 1.19-1.58]), availability of local treatment guideline (aOR 1.54 [95% CI, 1.17-2.02]), timing of laboratory confirmation (highest aOR 2.67 [95% CI, 1.97-3.61] for result available before admission), presence of chronic health conditions (highest aOR 4.81 [95% CI, 3.61-6.40] for cancer), radiographically confirmed pneumonia (aOR 1.39 [95% CI, 1.20-1.60]), antibiotic treatment (aOR 1.51 [95% CI, 1.30-1.76]), respiratory support (1.57 [95% CI, 1.19-2.08]), and ICU admission (aOR 3.62 [95% CI, 2.88-4.56])., Conclusions: Influenza antiviral agents were underused in Canadian pediatric hospitals, including among children with high-risk chronic health conditions. Prescribing varied considerably across sites, increased over time, and was associated with patient and hospital-level characteristics. Multifaceted hospital-based interventions are warranted to strengthen adherence to influenza treatment guidelines and antimicrobial stewardship practices., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2021 by the American Academy of Pediatrics.)

Background: In clinical trials, the two anti-interleukin (IL)-5 monoclonal antibodies (mAbs: mepolizumab and reslizumab) approved to treat severe eosinophilic asthma reduce exacerbations by ∼50-60%., Objective: To observe response to anti-IL-5 mAbs in a real-life clinical setting, and to evaluate predictors of suboptimal response., Methods: In four Canadian academic centres, predefined clinical end-points in 250 carefully characterised moderate-to-severe asthmatic patients were collected prospectively to assess response to the two anti-IL-5 mAbs. Suboptimal response was determined based on failure to reduce maintenance corticosteroid (MCS) or asthma symptoms scores (Asthma Control Questionnaire (ACQ)) or exacerbations, in addition to persistence of sputum/blood eosinophils. Worsening in suboptimal responders was assessed based on reduced lung function by 25% or increase in MCS/ACQ. A representative subset of 39 patients was evaluated for inflammatory mediators, autoantibodies and complement activation in sputum (by ELISA) and for immune-complex deposition by immunostaining formalin-fixed paraffin-embedded sputum plugs., Results: Suboptimal responses were observed in 42.8% (107 out of 250) patients treated with either mepolizumab or reslizumab. Daily prednisone requirement, sinus disease and late-onset asthma diagnoses were the strongest predictors of suboptimal response. Asthma worsened in 13.6% (34 out of 250) of these patients. The majority (79%) of them were prednisone-dependent. Presence of sputum anti-eosinophil peroxidase immunoglobulin (Ig)G was a predictor of suboptimal response to an anti-IL-5 mAb. An increase in sputum C3c (marker of complement activation) and deposition of C1q-bound/IL-5-bound IgG were observed in the sputa of those patients who worsened on therapy, suggesting an underlying autoimmune-mediated pathology., Conclusion: A significant number of patients who meet currently approved indications for anti-IL5 mAbs show suboptimal response to them in real-life clinical practice, particularly if they are on high doses of prednisone. Monitoring blood eosinophil count is not helpful to identify these patients. The concern of worsening of symptoms associated with immune-complex mediated complement activation in a small proportion of these patients highlights the relevance of recognising airway autoimmune phenomena and this requires further evaluation., Competing Interests: Conflict of interest: M. Mukherjee reports grants from Canadian Institutes of Health Research and Canadian Allergy, Asthma, and Immunology Foundation, grants and personal fees from Methapharm Specialty Pharmaceuticals, and personal fees from Astrazeneca, outside the submitted work. Conflict of interest: D.F. Forero has nothing to disclose. Conflict of interest: S. Tran has nothing to disclose. Conflict of interest: M-E. Boulay has nothing to disclose. Conflict of interest: M. Bertrand has nothing to disclose. Conflict of interest: A. Bhalla has nothing to disclose. Conflict of interest: J. Cherukat has nothing to disclose. Conflict of interest: H. Al-Hayyan has nothing to disclose. Conflict of interest: A. Ayoub has nothing to disclose. Conflict of interest: S.D. Revill has nothing to disclose. Conflict of interest: T. Javkar has nothing to disclose. Conflict of interest: K. Radford has nothing to disclose. Conflict of interest: M. Kjarsgaard has nothing to disclose. Conflict of interest: C. Huang has nothing to disclose. Conflict of interest: A. Dvorkin-Gheva has nothing to disclose. Conflict of interest: K. Ask reports grants from Canadian Pulmonary Fibrosis Foundation, Ontario Thoracic Society, Synairgen, GSK, Indalo, Unity, Avalyn, Canadian Institutes of Health Research and Synairgen, grants and personal fees from Boehringer Ingelheim, outside the submitted work. Conflict of interest: R. Olivenstein has nothing to disclose. Conflict of interest: N. Dendukuri has nothing to disclose. Conflict of interest: C. Lemiere reports grants and personal fees for advisory board work from AstraZeneca and TEVA Innovation, personal fees for advisory board work from GlaxoSmithKline, Sanofi and Novartis, outside the submitted work. Conflict of interest: L-P. Boulet has nothing to disclose. Conflict of interest: J.G. Martin has nothing to disclose. Conflict of interest: P. Nair reports grants and personal fees for lectures from AZ and Teva, grants from Novartis and Sanofi, grants and personal fees for consultancy from Roche, personal fees for lectures from Novartis, personal fees advisory board work from Merck and Equillium, outside the submitted work., (Copyright ©ERS 2020.)

Objectives: We hypothesized that antibiotic use in PICUs is based on criteria not always supported by evidence. We aimed to describe determinants of empiric antibiotic use in PICUs in eight different countries., Design: Cross-sectional survey., Setting: PICUs in Canada, the United States, France, Italy, Saudi Arabia, Japan, Thailand, and Brazil., Subjects: Pediatric intensivists., Interventions: None., Measurements and Main Results: We used literature review and focus groups to develop the survey and its clinical scenarios (pneumonia, septic shock, meningitis, and intra-abdominal infections) in which cultures were unreliable due to antibiotic pretreatment. Data analyses included descriptive statistics and linear regression with bootstrapped SEs. Overall response rate was 39% (482/1,251), with individual country response rates ranging from 25% to 76%. Respondents in all countries prolonged antibiotic duration based on patient characteristics, disease severity, pathogens, and radiologic findings (from a median increase of 1.8 d [95% CI, 0.5-4.0 d] to 9.5 d [95% CI, 8.5-10.5 d]). Younger age, severe disease, and ventilator-associated pneumonia prolonged antibiotic treatment duration despite a lack of evidence for such practices. No variables were reported to shorten treatment duration for all countries. Importantly, more than 39% of respondents would use greater than or equal to 7 days of antibiotics for patients with a positive viral polymerase chain reaction test in all scenarios, except in France for pneumonia (29%), septic shock (13%), and meningitis (6%). The use of elevated levels of inflammatory markers to prolong antibiotic treatment duration varied among different countries., Conclusions: Antibiotic-related decisions are complex and may be influenced by cultural and contextual factors. Evidence-based criteria are necessary to guide antibiotic duration and ensure the rational use of antibiotics in PICUs.

Objective: To i) estimate how large the mortality reductions would be if women were offered screening from age 50 until age 69; ii) to do so using the same trials and participation rates considered by the Canadian Task Force; iii) but to be guided in our analyses by the critical differences between cancer screening and therapeutics, by the time-pattern that characterizes the mortality reductions produced by a limited number of screens, and by the year-by-year mortality data in the appropriate segment of follow-up within each trial; and thereby iv) to avoid the serious underestimates that stem from including inappropriate segments of follow-up, i.e., too soon after study entry and too late after discontinuation of screening., Methods: We focused on yearly mortality rate ratios in the follow-up years where, based on the screening regimen employed, mortality deficits would be expected. Because the regimens differed from trial to trial, we did not aggregate the yearly data across trials. To avoid statistical extremes arising from the small numbers of yearly deaths in each trial, we calculated rate ratios for 3-year moving windows., Results: We were able to extract year-specific data from the reports of five of the trials. The data are limited for the most part by the few rounds of screening. Nevertheless, they suggest that screening from age 50 until age 69 would, at each age from 55 to 74, result in breast cancer mortality reductions much larger than the estimate of 21% that the Canadian Task Force report is based on., Discussion: By ignoring key features of cancer screening, several of the contemporary analyses have seriously underestimated the impact to be expected from such a program of breast cancer screening.

Background: While many North American healthcare institutions are switching from Tuberculin Skin Test (TST) to Interferon-gamma release assays (IGRAs), there is relatively limited data on association between occupational tuberculosis (TB) risk factors and test positivity and/or patterns of test discordance., Methods: We recruited a cohort of Canadian health care workers (HCWs) in Montreal, and performed both TST and QuantiFERON-TB Gold In Tube (QFT) tests, and assessed risk factors and occupational exposure., Results: In a cross-sectional analysis of baseline results, the prevalence of TST positivity using the 10 mm cut-off was 5.7% (22/388, 95%CI: 3.6-8.5%), while QFT positivity was 6.2% (24/388, 95%CI: 4-9.1%). Overall agreement between the tests was poor (kappa=0.26), and 8.3% of HCWs had discordant test results, most frequently TST-/QFT+ (17/388, 4.4%). TST positivity was associated with total years worked in health care, non-occupational exposure to TB and BCG vaccination received after infancy or on multiple occasions. QFT positivity was associated with having worked as a HCW in a foreign country., Conclusions: Our results suggest that LTBI prevalence as measured by either the TST or the QFT is low in this HCW population. Of concern is the high frequency of unexplainable test discordance, namely: TST-/QFT+ subjects, and the lack of any association between QFT positivity and clear-cut recent TB exposure. If these discordant results are indeed false positives, the use of QFT in lieu of TST in low TB incidence settings could result in overtreatment of uninfected individuals.

The literature suggests that improvements in nurses' work environments may improve the quality of patient care. Furthermore, monitoring the work environment through staff surveys may be a feasible method of identifying opportunities for quality improvement. This study aimed to confirm five proposed sub-scales from the Nursing Work Index - Revised (NWI-R) to assess the nursing work environment and the performance of these sub-scales across different units in a hospital. Data were derived from a cross-sectional survey of 243 nurses from 13 units of a 300-bed university-affiliated hospital in Quebec, Canada, during 2001. Using confirmatory factor analysis, the five subscales were confirmed; three of the sub-scales had greater ability to discriminate between units. Using hierarchical regression models, "resource adequacy" was the sub-scale most strongly associated with the perceived quality of care at the last shift. The NWI-R sub-scales are potentially useful for comparison of work environments of different nursing units at the same hospital.