Real-world evidence of sotrovimab effectiveness for preventing severe outcomes in patients with COVID-19: A quality improvement propensity matched retrospective cohort study of a pan-provincial program in Alberta, Canada.

OBJECTIVE: Post-marketing surveillance of sotrovimab's effect during implementation in the Canadian population is limited. METHODS: The study used a propensity score matched retrospective cohort design. Follow-up began between the periods of December 15, 2021 to April 30 2022. The study assessed any severe outcome defined as all-cause hospital admission, or mortality within 30 days of a confirmed COVID-19 positive test. Covariate adjusted odds ratios between sotrovimab treatment and the severe outcome was conducted using logistic regression. RESULTS: There were 22,289 individuals meeting treatment criteria for sotrovimab. There were 1,603 treated and 6,299 untreated individuals included in the analysis. Outcome occurrence in the study was 5.49% (treated) and 4.21% (untreated), with a median time from diagnosis to treatment of 1.00 days (IQR = 2.00 days). In the propensity-matched cohort, sotrovimab was not associated with a lower odds of a severe outcome (OR = 1.20; 95% CI: 0.91, 1.58), adjusting for confounding variables. CONCLUSION: After adjusting for confounding variables, sotrovimab treatment was not associated with lower odds of a severe outcome within 30-days of COVID-19 positive date.

Excess deaths during the COVID-19 pandemic in Alberta, Canada.

Objectives: To determine if there was excess mortality in Alberta, Canada during the coronavirus disease 2019 (COVID-19) pandemic, to confirm if excess mortality affected all age groups equally, and to determine what proportions of excess deaths were directly related to COVID-19 and non-pharmaceutical drug poisoning. Methods: Weekly all-cause data used to estimate excess mortality were modelled against the pre-pandemic period (January 2015-February 2020). Age-adjusted weekly mortality rates for March 2020 to December 2021 were compared with the preceding 5 years. Results: From March 2020 to December 2021, there was an 11% excess mortality rate, corresponding to an average of 265 monthly excess deaths (maximum >30%). COVID-19-related deaths (n=3202) accounted for 54.9% of total excess deaths (n=5833) that occurred in the 22-month period. The increase in all-cause excess deaths was proportionately higher, and with significantly greater numbers, in younger age groups. Significant increases in monthly drug poisoning deaths occurred from March 2020 to April 2021, with a total of 1819 deaths. Eight hundred and 25 excess drug poisoning deaths, representing 25.4% of total all-cause excess deaths, occurred, mainly among those aged 25-60 years. Overall, 54.9% of all excess deaths were directly related to COVID-19 and 25.4% were related to drug poisoning. Conclusions: There was a significant increase in all-cause mortality during the COVID-19 pandemic. Although older adults are more likely to die of COVID-19, a massive increase in non-COVID-19-related mortality was observed among younger people. These factors should be considered in public policy decisions on epidemic/pandemic management.

Multicenter Postimplementation Assessment of the Positive Predictive Value of SARS-CoV-2 Antigen-Based Point-of-Care Tests Used for Screening of Asymptomatic Continuing Care Staff.

Frequent screening of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among asymptomatic populations using antigen-based point-of-care tests (APOCTs) is occurring globally with limited clinical performance data. The positive predictive value (PPV) of two APOCTs used in the asymptomatic screening of SARS-CoV-2 among health care workers (HCWs) at continuing care (CC) sites across AB, Canada, was evaluated. Between 22 February and 2 May 2021, CC sites implemented SARS-CoV-2 voluntary screening of their asymptomatic HCWs. On-site testing with Abbott Panbio or BD Veritor occurred on a weekly or twice-weekly basis. Positive APOCTs were confirmed with a real-time reverse transcriptase PCR (rRT-PCR) reference method. A total of 71,847 APOCTs (17,689 Veritor and 54,158 Panbio) were performed among 369 CC sites. Eighty-seven (0.12%) APOCTs were positive, of which 39 (0.05%) were confirmed as true positives using rRT-PCR. Use of the Veritor and Panbio resulted in 76.6% and 30.0% false-positive detection, respectively (P < 0.001). This corresponded to PPVs of 23.4 and 70.0% for the Veritor and Panbio, respectively. Frequent screening of SARS-CoV-2 among asymptomatic HCWs in CC, using APOCTs, resulted in a very low detection rate and a high rate of detection of false positives. Careful assessment of the risks versus benefits of APOCT programs and the prevalence of infection in this population needs to be thoroughly considered before implementation.

BOugie or stylet in patients UnderGoing Intubation Emergently (BOUGIE): protocol and statistical analysis plan for a randomised clinical trial.

INTRODUCTION: Intubation-related complications are less frequent when intubation is successful on the first attempt. The rate of first attempt success in the emergency department (ED) and intensive care unit (ICU) is typically less than 90%. The bougie, a semirigid introducer that can be placed into the trachea to facilitate a Seldinger-like technique of tracheal intubation and is typically reserved for difficult or failed intubations, might improve first attempt success. Evidence supporting its use, however, is from a single academic ED with frequent bougie use. Validation of these findings is needed before widespread implementation. METHODS AND ANALYSIS: The BOugie or stylet in patients Undergoing Intubation Emergently trial is a prospective, multicentre, non-blinded randomised trial being conducted in six EDs and six ICUs in the USA. The trial plans to enrol 1106 critically ill adults undergoing orotracheal intubation. Eligible patients are randomised 1:1 for the use of a bougie or use of an endotracheal tube with stylet for the first intubation attempt. The primary outcome is successful intubation on the first attempt. The secondary outcome is severe hypoxaemia, defined as an oxygen saturation less than 80% between induction until 2 min after completion of intubation. Enrolment began on 29 April 2019 and is expected to be completed in 2021. ETHICS AND DISSEMINATION: The trial protocol was approved with waiver of informed consent by the Central Institutional Review Board at Vanderbilt University Medical Center or the local institutional review board at an enrolling site. The results will be submitted for publication in a peer-reviewed journal and presented at scientific conferences. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT03928925).

Protocol and statistical analysis plan for the PREventing cardiovascular collaPse with Administration of fluid REsuscitation during Induction and Intubation (PREPARE II) randomised clinical trial.

INTRODUCTION: Cardiovascular collapse is a common complication during tracheal intubation of critically ill adults. Whether administration of an intravenous fluid bolus prevents cardiovascular collapse during tracheal intubation remains uncertain. A prior randomised trial found fluid bolus administration to be ineffective overall but suggested potential benefit for patients receiving positive pressure ventilation during tracheal intubation. METHODS AND ANALYSIS: The PREventing cardiovascular collaPse with Administration of fluid REsuscitation during Induction and Intubation (PREPARE II) trial is a prospective, multi-centre, non-blinded randomised trial being conducted in 13 academic intensive care units in the USA. The trial will randomise 1065 critically ill adults undergoing tracheal intubation with planned use of positive pressure ventilation (non-invasive ventilation or bag-mask ventilation) between induction and laryngoscopy to receive 500 mL of intravenous crystalloid or no intravenous fluid bolus. The primary outcome is cardiovascular collapse, defined as any of: systolic blood pressure <65 mm Hg, new or increased vasopressor administration between induction and 2 min after intubation, or cardiac arrest or death between induction and 1 hour after intubation. The primary analysis will be an unadjusted, intention-to-treat comparison of the primary outcome between patients randomised to fluid bolus administration and patients randomised to no fluid bolus administration using a χ2 test. The sole secondary outcome is 28-day in-hospital mortality. Enrolment began on 1 February 2019 and is expected to conclude in June 2020. ETHICS AND DISSEMINATION: The trial was approved by either the central institutional review board at Vanderbilt University Medical Center or the local institutional review board at each trial site. Results will be submitted for publication in a peer-reviewed journal and presented at scientific conferences. TRIAL REGISTRATION NUMBER: NCT03787732.

Comparing methods to estimate incremental inpatient costs and length of stay due to methicillin-resistant Staphylococcus aureus in Alberta, Canada.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is an opportunistic bacterial organism resistant to first line antibiotics. Acquisition of MRSA is often classified as either healthcare-associated or community-acquired. It has been shown that both healthcare-associated and community-acquired infections contribute to the spread of MRSA within healthcare facilities. The objective of this study was to estimate the incremental inpatient cost and length of stay for individuals colonized or infected with MRSA. Common analytical methods were compared to ensure the quality of the estimate generated. This study was performed at Alberta Ministry of Health (Edmonton, Alberta), with access to clinical MRSA data collected at two Edmonton hospitals, and ministerial administrative data holdings. METHODS: A retrospective cohort study of patients with MRSA was identified using a provincial infection prevention and control database. A coarsened exact matching algorithm, and two regression models (semilogarithmic ordinary least squares model and log linked generalized linear model) were evaluated. A MRSA-free cohort from the same facilities and care units was identified for the matched method; all records were used for the regression models. Records span from January 1, 2011 to December 31, 2015, for individuals 18 or older at discharge. RESULTS: Of the models evaluated, the generalized linear model was found to perform the best. Based on this model, the incremental inpatient costs associated with hospital-acquired cases were the most costly at $31,686 (14,169 - 60,158) and $47,016 (23,125 - 86,332) for colonization and infection, respectively. Community-acquired MRSA cases also represent a significant burden, with incremental inpatient costs of $7397 (2924 - 13,180) and $14,847 (8445 - 23,207) for colonization and infection, respectively. All costs are adjusted to 2016 Canadian dollars. Incremental length of stay followed a similar pattern, where hospital-acquired infections had the longest incremental stays of 35.2 (16.3-69.5) days and community-acquired colonization had the shortest incremental stays of 3.0 (0.6-6.3) days. CONCLUSIONS: MRSA, and in particular, hospital-acquired MRSA, places a significant but preventable cost burden on the Alberta healthcare system. Estimates of cost and length of stay varied by the method of analysis and source of infection, highlighting the importance of selecting the most appropriate method.

An unusual case of Erysipelothrix rhusiopathiae prosthetic joint infection from the Canadian Arctic: whole genome sequencing unable to identify a zoonotic source.

BACKGROUND: Erysipelothrix rhusiopathiae is a zoonotic pathogen that causes erysipeloid and is most frequently associated with exposure to domestic swine. Infection of native and prosthetic joints is a rarely reported manifestation. CASE PRESENTATION: We describe a case of E. rhusiopathiae prosthetic joint infection in a woman with a history of exposure to wild animals in the Canadian Arctic. Patient management involved a 1-stage surgical revision exchange with an antibiotic impregnated cement spacer and 6 weeks of intravenous penicillin G followed by 6 weeks of oral amoxicillin. Ten previously reported cases of E. rhusiopathiae joint infection are reviewed. Recent increases in mortality due to infection with this organism among host animal populations in the Canadian Arctic have generated concern regarding a potential increase in human infections. However, whole genome sequencing (WGS) of the organism was unable to identify a zoonotic origin for this case. CONCLUSIONS: Consideration should be given to E. rhusiopathiae as a cause of joint infections if the appropriate epidemiologic and host risk factors exist. Expanded use of WGS in other potential animal hosts and environmental sources may provide important epidemiologic information in determining the source of human infections.

Correction to: Comparing methods to estimate incremental inpatient costs and length of stay due to methicillin-resistant Staphylococcus aureus in Alberta, Canada.

In the original publication of this article [1], the authors want to add the following sentence in the Acknowledgement section.

Preventing transmission of bloodborne viruses from infected healthcare workers to patients: Summary of a new Canadian Guideline.

BACKGROUND: Although it is well documented that bloodborne viruses (BBVs), including human immunodeficiency virus (HIV), hepatitis C virus (HCV) and hepatitis B virus (HBV) have been transmitted from patients to healthcare workers (HCWs), there has also been reported transmission from HCWs to patients during the provision of health care. With remarkable progress in infection prevention, diagnosis tools, treatment regimens and major improvements in guideline development methodology, there was a need to develop an evidence-based guideline to replace the 1998 Canadian consensus document for managing HCWs infected with BBVs. PURPOSE: This article summarizes the Canadian Guideline on the Prevention of Transmission of Bloodborne Viruses from Infected Healthcare Workers in Healthcare Settings. METHODS: A Guideline Development Task Group was established and key questions developed to inform the guideline content. Systematic reviews were conducted to evaluate the risk of HCW-to-patient transmission of HIV, HCV and HBV. Environmental scans were used to provide information on Expert Review Panels, disclosure of a HCW's serologic status and lookback investigations. Federal, provincial and territorial partners and key stakeholder organizations were consulted on the Guideline. RESULTS: The risk of HCW-to-patient BBV transmission was found to be negligible, except during exposure-prone procedures, where there is a risk that injury to the HCW may result in exposure of a patient's open tissues to the HCW's blood. Risk of ensuing transmission and the rate of transmission varied by BBV, and were lowest with HIV and highest with HBV. The Guideline provides key content, including recommendations regarding criteria to determine if a procedure is an exposure-prone procedure, management of HCWs infected with a BBV, including considerations for the HCW's fitness for practice, Expert Review Panels, HCW disclosure obligations and right to privacy and lookback investigations. CONCLUSION: This new Guideline provides a pan-Canadian approach for managing HCWs infected with a BBV, with recommendations related to preventing HCW-to-patient transmission of BBVs during the provision of care.

Mycobacterium chimaera Infection After Aortic Valve Replacement Presenting With Aortic Dissection and Pseudoaneurysm.

We present a case of Mycobacterium chimaera infection presenting with aortic dissection and pseudoaneuysm in a 22-year-old man with a past history of aortic valve replacement. Clinicians should consider M. chimaera infection in those presenting with aortic dissection as a late complication of cardiovascular surgery.

Influenza outbreak in a Canadian correctional facility.

Correctional facilities face increased risk of communicable disease transmission and outbreaks. We describe the progression of an influenza outbreak in a Canadian remand facility and suggest strategies for preventing, identifying and responding to outbreaks in this setting. In total, six inmates had laboratory-confirmed influenza resulting in 144 exposed contacts. Control measures included enhanced isolation precautions, restricting admissions to affected living units, targeted vaccination and antiviral prophylaxis. This report highlights the importance of setting specific outbreak guidelines in addressing population and environmental challenges, as well as implementation of effective infection prevention and control (IPAC) and public health measures when managing influenza and other communicable disease outbreaks.

Health-related quality of life with long-term retention of the PROSthesis of Antibiotic Loaded Acrylic Cement system following infection resolution in low demand patients.

BACKGROUND: The study purpose was to (1) evaluate health-related quality of life (HRQL) with the PROSthesis of Antibiotic Loaded Acrylic Cement (PROSTALAC) in situ for infected total hip arthroplasty (THA), (2) determine infection resolution, and (3) compare subjects who underwent second stage surgery with those who retained the PROSTALAC on a longer term basis. METHODS: Demographics, physical demand level, and comorbidities were recorded prospectively in 29 subjects followed to at least 24 months after initial PROSTALAC insertion. HRQL was evaluated using the Western Ontario McMaster Osteoarthritis Index (WOMAC) and RAND 36-Item Health Survey. Infection resolution was determined using a pre-specified clinical definition. RESULTS: Twenty-five of 29 (86%) subjects' infections resolved. Three subjects died, of whom two had resolved infections. For survivors, 22/26 (85%) completed HRQL evaluations. After PROSTALAC insertion, pain and function improved within 3-6 months and was retained at 24 months. Of those followed to 24 months, 7/22 (32%) subjects underwent second stage surgery. They were higher physical demand subjects ( p = 0.03) than those not undergoing second stage surgery. We found no difference in WOMAC scores at 24 months between those who underwent second stage surgery and those who retained the PROSTALAC ( p > 0.32). DISCUSSION: The PROSTALAC system for THA appears to allow acceptable HRQL while in situ for at least 2 years in low physical demand patients. Subjects with higher physical demand levels are more likely to undergo second stage surgery. CONCLUSION: Further evaluation is required to determine whether longer term PROSTALAC retention may be appropriate for specific patient groups.

Use of ward closure to control outbreaks among hospitalized patients in acute care settings: a systematic review.

BACKGROUND: Though often used to control outbreaks, the efficacy of ward closure is unclear. This systematic review sought to identify studies defining and describing ward closure in outbreak control and to determine impact of ward closure as an intervention on outbreak containment. METHODS: We searched these databases with no language restrictions: MEDLINE, 1946 to 7 July 2014; EMBASE, 1974 to 7 July 2014; CINAHL, 1937 to 8 July 2014; and Cochrane Database of Systematic Reviews, 2005 to May 2014. We also searched the following: IndMED; LILACS; reference lists from retrieved articles; conference proceedings; and websites of the CDCP, the ICID, and the WHO. We included studies of patients hospitalized in acute care facilities; used ward closure as a control measure; used other control measures; and discussed control of the outbreak(s) under investigation. A component approach was used to assess study quality. RESULTS: We included 97 English and non-English observational studies. None included a controlled comparison between ward closure and other interventions. We found that ward closure was often used as part of a bundle of interventions but could not determine its direct impact separate from all the other interventions whether used in parallel or in sequence with other interventions. We also found no universal definition of ward closure which was widely accepted. CONCLUSIONS: With no published controlled studies identified, ward closure for control of outbreaks remains an intervention that is not evidence based and healthcare personnel will need to continue to balance the competing risks associated with its use, taking into consideration the nature of the outbreak, the type of pathogen and its virulence, mode of transmission, and the setting in which it occurs. Our review has identified a major research gap in this area.

Effectiveness of safety-engineered devices in reducing sharp object injuries.

BACKGROUND: Sharps injuries remain a common factor in occupational exposure of healthcare workers to blood-borne viruses. The extent to which the introduction of safety-engineered devices has been effective in reducing such injuries among healthcare workers is unclear. AIMS: To investigate the incidence of sharp object injury among healthcare workers in the Capital Health Region of Alberta, Canada and to determine the effectiveness of the introduction of safety- engineered devices in preventing these. METHODS: All reports of sharp object injuries to Capital Region Workplace Health and Safety offices from healthcare workers 2003-10 were analysed. Rates of sharp object injury were compared before (2006), during (2007-08) and after (2009-10) the introduction of safety-engineered devices, adjusting for other potential risk factors using Poisson regression and log-linear models. RESULTS: Between 2003 and 2010, a total of 4707 sharp object injuries were reported from 15 healthcare facilities. The sharp object injury rate per 1000 full-time equivalent employees per year declined from 35 before the introduction period to 30 during the introduction period (rate ratio [RR]: 0.88, 95% confidence interval [CI]: 0.78, 0.99) among most healthcare workers, but then rebounded again slightly after the intervention. Physician risks showed little change during the period of introduction (odds ratio [OR]: 0.99, 95% CI: 0.85, 1.14) but decreased significantly after the intervention (OR: 0.83, 95% CI: 0.71, 0.97). CONCLUSIONS: The introduction of safety-engineered devices was associated with a modest reduction in reported sharp object injuries but this appeared to be relatively short-lived for most workers.

A consensus development conference model for establishing health policy for surveillance and screening of antimicrobial-resistant organisms.

The Canadian Consensus Development Conference on Surveillance and Screening for Antimicrobial-Resistant Organisms (AROs) was sponsored by the Alberta Ministry of Health to provide evidence to update policies for ARO screening in acute care settings. A rigorous evidence-based literature review completed before the conference concluded that that neither universal nor targeted screening of patients was associated with a reduction in hospital-acquired ARO colonization, infection, morbidity, or mortality. Leading international clinicians, scientists, academics, policy makers, and administrators presented current evidence and clinical experience, focusing on whether and how hospitals should screen patients for AROs as part of broader ARO control strategies. An unbiased and independent "jury" with a broad base of expertise from complementary disciplines considered the evidence and released a consensus statement of 22 recommendations. Policy highlights included developing an integrated "One Health" strategy, fully resourcing basic infection control practices, not performing universal screening, and focusing original research to determine what works.

In vitro evaluation of diffusion of lidocaine and alkalinized lidocaine through the polyurethane membrane of the endotracheal tube.

OBJECTIVES: Endotracheal tube (ETT) and its inflated cuff are likely to induce specific reactivity at the emergence time. In ICU, the tolerance of the ETT cuff could be a part of patient agitation and increased of sedation. MATERIALS AND METHODS: Using specific ICU ETT cuff (thin polyurethane cuff), we perform an in vitro evaluation of diffusion of lidocaine and alkalinized lidocaine (L-B) across the PU cuff for a long duration. We evaluate the safety of this procedure by a daily injection into the cuff. RESULTS: With lidocaine alone, we observed a low rate of diffusion through the cuff (<8% over 24h), whereas the L-B solution had a high diffusion (>90% over 24h). The released profiles were similar from day 0 to day 8, and no cuff rupture was reported over the 8-day study. CONCLUSION: The safety, controlled release, and lack of deleterious effects on cuff membrane were confirmed. In case of unexpected cuff rupture, an adequate determination of the mixture allows to obtain a safe solution with the achievement of a physiological pH (7.4) and the small dose of lidocaine (40 mg).

Gram-negative bacteria that produce carbapenemases causing death attributed to recent foreign hospitalization.

Overseas travel, as a risk factor for the acquisition of infections due to antimicrobial-resistant organisms, has recently been linked to carbapenemase-producing Gram-negative bacteria. Multiresistant Klebsiella pneumoniae, Escherichia coli, and Acinetobacter baumannii strains were isolated from a wound of a Canadian patient with a recent history of hospitalization in India. This resulted in the initiation of outbreak management that included surveillance cultures. Epidemiological and molecular investigations showed that NDM-1-producing K. pneumoniae ST16 and OXA-23-producing A. baumannii ST10 strains were transmitted to 5 other patients, resulting in the colonization of 4 patients and the death of 1 patient due to septic shock caused by the OXA-23-producing A. baumannii strain. The high rate of false positivity of the screening cultures resulted in additional workloads and increased costs for infection control and clinical laboratory work. We believe that this is the first report of an infection with carbapenemase-producing Gram-negative bacteria resulting in death attributed to a patient with recent foreign hospitalization. We recommend routine rectal and wound screening for colonization with multiresistant bacteria for patients who have recently been admitted to hospitals outside Canada.