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ObjectiveTo identify the factors that affect coronavirus disease 2019 (COVID-19) vaccine decision making among individuals diagnosed with a rheumatologic condition, given that previous international studies have demonstrated that a significant proportion of patients with rheumatic disease (RD) are vaccine hesitant.MethodsThis cross-sectional study involved an online survey with adult patients with RD from the Kaye Edmonton Clinic Rheumatology Clinic between June and August 2021. Quantitative results were descriptively analyzed, whereas qualitative thematic analysis was conducted for open-ended responses.ResultsThe survey had a response rate of 70.9% (N = 231). Regarding COVID-19 vaccines, patients with RD were most concerned about the possible effect of vaccination on their rheumatic condition (45.2%) and about vaccine effectiveness (45.1%). Most patients had discussed COVID-19 vaccination (75.9%) and its risks and benefits (66.1%) with their medical team, and 83.6% of respondents were confident in the information provided. Patients’ perceptions of the government’s role in handling the COVID-19 pandemic varied: 33% reported that they found government-instituted public health measures effective. Surprisingly, 9.7% of patients with RD still reported concerns that they could develop COVID-19 from an approved COVID-19 vaccine.ConclusionThis study describes factors implicated in COVID-19 vaccine decision making among patients with RD. Three important themes included possible adverse effects of the vaccine on RD control, reduced vaccine efficacy because of RD/treatment, and risk of contracting SARS-CoV-2 from the COVID-19 vaccine. Knowledge from this study can assist healthcare providers in looking after patients with RD to initiate discussions with patients to share evidence-based vaccine information and assist with informed decision making.

In Canada, published outcome data for COVID-19 come largely from the first 2 waves of the pandemic. We examined changes in demographics and 30-day outcomes after SARS-CoV-2 infection during the first 3 pandemic waves in Alberta and Ontario; for wave 3, we compared outcomes between those infected with a variant of concern and those infected with the original "wild-type" SARS-CoV-2.We conducted a population-based retrospective cohort study using linked health care data sets in Alberta and Ontario. We identified all-cause hospitalizations or deaths within 30 days after a positive result on a reverse transcription polymerase chain reaction test for SARS-CoV-2 in individuals of any age between Mar. 1, 2020, and June 30, 2021, with genomic confirmation of variants of concern. We compared outcomes in wave 3 (February 2021 to June 2021) with outcomes in waves 1 and 2 combined (March 2020 to January 2021) after adjusting for age, sex and Charlson Comorbidity Index score. Using wave 3 data only, we compared outcomes by vaccination status and whether or not the individual was infected with a variant of concern.Compared to those infected with SARS-CoV-2 during waves 1 and 2 (We observed a shift among those infected with SARS-CoV-2 toward younger patients with fewer comorbidities, a shorter length of hospital stay and lower mortality risk as the pandemic evolved in Alberta and Ontario; however, infection with a variant of concern was associated with a substantially higher risk of hospitalization or death. As variants of concern emerge, ongoing monitoring of disease expression and outcomes among vaccinated and unvaccinated individuals is important to understand the phenotypes of COVID-19 and the anticipated burdens for the health care system.

Importance Recent changes in guidelines for managing Clostridioides difficile infections (CDI) have placed fidaxomicin as a first-line treatment. Objective To estimate the net cost of first-line fidaxomicin compared to vancomycin in the American and Canadian healthcare systems and to estimate the price points at which fidaxomicin would become cost saving for the prevention of recurrence. Data sources and study selection We identified randomized, placebo-controlled trials directly comparing fidaxomicin with vancomycin that reported on recurrence. Medication costs were obtained from the Veterans Affairs Federal Supply Schedule (US) and the Quebec drug formulary (Canada). The average cost of a CDI recurrence was established through a systematic review for each country. Data extraction, synthesis and outcome measures For efficacy, data on CDI recurrence at day 40 were pooled using a restricted maximal likelihood random effects model. For the cost review, the mean cost across identified studies was adjusted to reflect May 2022 dollars. These were used to estimate the net cost per recurrence prevented with fidaxomicin and the price point below which fidaxomicin would be cost saving. Results The estimated mean system costs of a CDI recurrence were $15 147USD and $8806CAD, respectively. Preventing one recurrence by using first-line fidaxomicin over vancomycin would cost $38 222USD (95%CI $30 577–$57 332) and $13 760CAD (95%CI $11 008–$20 640), respectively. The probability that fidaxomicin was cost saving exceeded 95% if priced below $1140USD or $860CAD, respectively. Conclusions and Relevance An increased drug expenditure on fidaxomicin may not be offset through recurrence prevention unless the fidaxomicin price is negotiated.

BackgroundDue to COVID-19’s significant morbidity and mortality, identifying the most cost-effective pharmacologic treatment strategy is critical. As such, we determined the most cost-effective strategy for moderate to severe COVID-19 respiratory infections using the United States health care system as a representative model.MethodsA decision analytic model modelled a base case scenario of a 60-year-old patient admitted to hospital with COVID-19. Patients requiring oxygen were considered moderate severity, and patients with severe COVID-19 required intubation with intensive care. Strategies modelled included giving remdesivir to all patients, remdesivir in severe infections, remdesivir in moderate infections, dexamethasone to all patients, dexamethasone in severe infections, remdesivir in moderate/dexamethasone in severe infections, and best supportive care. Data for the model came from the published literature. The time horizon was 1 year; no discounting was performed due to the short duration. The perspective was of the payer in the United States health care system.ResultsSupportive care for moderate/severe COVID-19 cost $11,112.98/0.8256 QALY. Remdesivir in moderate/dexamethasone in severe infections was the most cost-effective with an incremental cost-effectiveness ratio of $19,764.56/QALY gained compared to supportive care. Probabilistic sensitivity analyses showed remdesivir for moderate/dexamethasone for severe COVID-19 infection was most cost-effective in 88.6% of scenarios and dexamethasone in moderate-severe infections in 11.4% of scenarios. With lower willingness to pay thresholds ($250-$37,500), dexamethasone for severe infections was favoured.ConclusionsRemdesivir for moderate/dexamethasone for severe COVID-19 infections was the0020most cost-effective strategy. Further data is required for remdesivir to better assess its cost effectiveness in treatment of COVID-19.

KEY POINTS Concern about imbalances between the demand and the supply of vaccinations for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been raised, given worldwide demand, centralized manufacturing and limitations in the infrastructure for vaccine delivery and administration in

POINTS CLES Compte tenu de la demande mondiale, de la fabrication centralisee et des limites de l’infrastructure de livraison et d’administration des vaccins au Canada, plusieurs s’inquietent d’un possible desequilibre entre l’offre et la demande de vaccins contre le coronavirus du

Background The prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among asymptomatic patients admitted to hospital has implications for personal protective equipment use, testing strategy and confidence in the safety of acute care services. Our aim was to estimate the positivity rate of reverse transcription polymerase chain reaction (RT-PCR) testing among people admitted to hospital without symptoms of coronavirus disease 2019 (COVID-19) in Alberta, Canada. Methods Between Apr. 9 and May 24, 2020, we screened for COVID-19 symptoms and tested for SARS-CoV-2 infection in all consecutive adult patients (≥ 18 yr) admitted via emergency department to 3 Alberta hospitals. We summarized the parameters of the epidemic curve and assessed the performance of symptom screening versus RT-PCR results on nasopharyngeal or oropharyngeal swab samples. Results The study period encompassed Alberta's initial epidemic curve, with peak active cases per 100 000 of 71.4 (0.07%) on Apr. 30, 2020, and 14.7 and 14.6 at the beginning (Apr. 9, 2020) and end (May 24, 2020), respectively. Testing for SARS-CoV-2 infection (64.9% throat and 35.1% nasopharyngeal swabs) was done on 3375 adults (mean age 51, standard deviation 21, yr; 51.5% men). None of the asymptomatic patients (n = 1814) tested positive, and 71 of those with symptoms tested positive (n = 1561; 4.5%, 95% confidence interval [CI] 3.6%-5.7%). Sensitivity of symptom screening (v. RT-PCR) was 100% (95% CI 95%-100%), and specificity was 55% (95% CI 53%-57%). Posttest probabilities for prevalence of SARS-CoV-2 infection ranging from 1.5 to 14 times the peak prevalence of active cases during the study did not change when we assumed lower sensitivity (92%). Interpretation In a region with low disease prevalence where protocolized symptom assessment was in place during the admission process, we did not identify people admitted to hospital without COVID-19 symptoms who were RT-PCR positive. There may not be additive benefit to universal testing of asymptomatic patients on hospital admission in a setting of low pretest probability and strong public health containment.

ObjectivesThe four SARS-CoV-2 variants of concern (VOC; Alpha, Beta, Gamma and Delta) identified by May 2021 are highly transmissible, yet little is known about their impact on public health measures. We aimed to synthesise evidence related to public health measures and VOC.DesignA rapid scoping review.Data sourcesOn 11 May 2021, seven databases (MEDLINE, Embase, the Cochrane Database of Systematic Reviews, Central Register of Controlled Trials, Epistemonikos’ L-OVE on COVID-19, medRxiv, bioRxiv) were searched for terms related to VOC, public health measures, transmission and health systems. No limit was placed on date of publication.Eligibility criteriaStudies were included if they reported on any of the four VOCs and public health measures, and were available in English. Only studies reporting on data collected after October 2020, when the first VOC was reported, were included.Data extraction and synthesisTitles, abstracts and full-text articles were screened by two independent reviewers. Data extraction was completed by two independent reviewers using a standardised form. Data synthesis and reporting followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines.ResultsOf the 37 included studies, the majority assessed the impact of Alpha (n=32) and were conducted in Europe (n=12) or the UK (n=9). Most were modelling studies (n=28) and preprints (n=28). The majority of studies reported on infection control measures (n=17), followed by modifying approaches to vaccines (n=13), physical distancing (n=6) and either mask wearing, testing or hand washing (n=2). Findings suggest an accelerated vaccine rollout is needed to mitigate the spread of VOC.ConclusionsThe increased severity of VOC requires proactive public health measures to control their spread. Further research is needed to strengthen the evidence for continued implementation of public health measures in conjunction with vaccine rollout. With no studies reporting on Delta, there is a need for further research on this and other emerging VOC on public health measures.

ImportanceRecent changes in the Infectious Diseases and Healthcare Epidemiology Societies of America (IDSA-SHEA) guidelines for managing Clostridioides difficile infections (CDI) have placed fidaxomicin as first-line treatment.ObjectiveTo estimate the net cost of first line fidaxomicin compared to vancomycin in the American and Canadian healthcare systems and to estimate the price points at which fidaxomicin would become cost saving. In Canada, net costs were from the public payer perspective. In the US, costs were from a healthcare and payer perspective.Data sourcesWe identified all randomized controlled trials comparing fidaxomicin with vancomycin through the 2021 IDSA-SHEA guideline update. Medication costs were obtained from internet prices (US) and the Quebec drug formulary (Canada). The average cost of a CDI recurrence was established through a systematic review for each country.Study selectionFor fidaxomicin efficacy, we included double-blind and placebo-controlled trials. For the systematic review of recurrence costs, studies were included if they were primary research articles, had a cost-analysis of CDI, included cases of recurrent CDI, and were calculated with cost parameters from American or Canadian healthcare systems. Studies were excluded if the population was solely pediatric or hospitalized.Data extraction and SynthesisFor the efficacy meta-analysis, data was pooled using a restricted maximal likelihood random effects model. For the cost review, the mean cost across identified studies was adjusted to reflect July 2022 dollars.Main Outcomes and MeasuresThe primary outcome of the meta-analysis was CDI recurrence at Day 40. The primary outcome of the systematic review was the average cost of a CDI recurrence in the American and Canadian healthcare systems. The objective was to estimate the net cost per recurrence prevented and the price point below which fidaxomicin would be cost saving to either the public payer (Canada) or the insurer (US).ResultsThe estimated mean system cost of a CDI recurrence was $15147USD and $8806CAD, respectively. At current drug pricing, to prevent one recurrence by using first line fidaxomicin over vancomycin would cost $43904USD (95%CI $35123-$65856) and $13,760CAD (95%CI $11,008-$20,640), respectively. The likelihood of fidaxomicin offering cost savings varies by country, with a 95% probability of fidaxomicin being cost saving if priced below $1180USD or $860CAD respectively.Conclusions and RelevanceAn increased drug expenditure on fidaxomicin will not be offset through recurrence prevention unless the fidaxomicin price is negotiated.

Fecal microbiota transplantation (FMT) is highly effective in recurrent Clostridioides difficile infection (CDI), increasing evidence supports FMT in severe or fulminant Clostridioides difficile infection (SFCDI). However, the multifactorial mechanisms that underpin the efficacy of FMT are not fully understood. Systems biology approaches using high-throughput technologies may help with mechanistic dissection of host-microbial interactions. Here, we have undertaken a deep phenomics study on four adults receiving sequential FMT for SFCDI, in which we performed a longitudinal, integrative analysis of multiple host factors and intestinal microbiome changes. Stool samples were profiled for changes in gut microbiota and metabolites and blood samples for alterations in targeted epigenomic, metabonomic, glycomic, immune proteomic, immunophenotyping, immune functional assays, and T-cell receptor (TCR) repertoires, respectively. We characterised temporal trajectories in gut microbial and host immunometabolic data sets in three responders and one non-responder to sequential FMT. A total of 562 features were used for analysis, of which 78 features were identified, which differed between the responders and the non-responder. The observed dynamic phenotypic changes may potentially suggest immunosenescent signals in the non-responder and may help to underpin the mechanisms accompanying successful FMT, although our study is limited by a small sample size and significant heterogeneity in patient baseline characteristics. Our multi-omics integrative longitudinal analytical approach extends the knowledge regarding mechanisms of efficacy of FMT and highlights preliminary novel signatures, which should be validated in larger studies.

Although co-design has made important contributions to practice in many fields, healthcare has only recently employed it for shaping best practices. This paper explores an aspect of medical practice that challenges many hospitals: the decision-making process for ordering urine testing and the use of antibiotics, specifically, in treating Urinary Tract Infections (UTI) and Asymptomatic Bacteriuria (ASB). The case investigates how physicians and nurses make decisions about testing urine for infection and the use of antibiotics. To explore the issue, the researchers conducted three co-design workshops to (1) uncover the medical decision-making process in ordering urine testing and treating UTI and ASB, (2) determine the needs of clinicians as they make such decisions, and (3) collectively design a decision aid that would fit users’ cognitive, emotional and physical needs. The case shows how human-centered design approach led to an evidence-based decision-making tool – guiding clinicians to improve their practices by reconsidering when and if to order urine testing and prescribe antibiotics.

ImportanceWith the emergence of more transmissible SARS-CoV-2 variants of concern (VOC), there is an urgent need for evidence about disease severity and the health care impacts of VOC in North America, particularly since a substantial proportion of the population have declined vaccination thus far.ObjectiveTo examine 30-day outcomes in Canadians infected with SARS-CoV-2 in the first year of the pandemic and to compare event rates in those with VOC versus wild-type infection.DesignRetrospective cohort study using linked healthcare administrative datasets.SettingAlberta and Ontario, the two Canadian provinces that experienced the largest third wave in the spring of 2021.ParticipantsAll individuals with a positive SARS-CoV-2 reverse transcriptase polymerase chain reaction swab from March 1, 2020 until March 31, 2021, with genomic confirmation of VOC screen-positive tests during February and March 2021 (wave 3).Exposure of InterestVOC versus wild type SARS-CoV-2Main Outcomes and MeasuresAll-cause hospitalizations or death within 30 days after a positive SARS-CoV-2 swab.ResultsCompared to the 372,741 individuals with SARS-CoV-2 infection between March 2020 and January 2021 (waves 1 and 2 in Canada), there was a shift in transmission towards younger patients in the 104,232 COVID-19 cases identified in wave 3. As a result, although third wave patients were more likely to be hospitalized (aOR 1.34 [1.29-1.39] in Ontario and aOR 1.53 [95%CI 1.41-1.65] in Alberta), they had shorter lengths of stay (median 5 vs. 7 days, pConclusions and RelevanceOn a population basis, the shift towards younger age groups as the COVID-19 pandemic has evolved translates into more hospitalizations but shorter lengths of stay and lower mortality risk than seen in the first 10 months of the pandemic in Canada. However, on an individual basis, infection with a VOC is associated with a higher risk of hospitalization or death than the original wild-type SARS-CoV-2 – this is important information to address vaccine hesitancy given the increasing frequency of VOC infections now.

ObjectivesThis is an update of a previous report that examined literature published up to March 11th, 2021. Sixteen additional studies have been included in this update. The objective of this report is to identify comparative observational studies and randomized controlled trials (RCTs) evaluating the efficacy and effectiveness of COVID-19 vaccination in reducing forward transmission from vaccinated people, and studies examining the biological plausibility of vaccination-induced transmission reduction.MethodA search of databases, MEDLINE, Embase, L-OVE and the Cochrane Central Register of Controlled Trials was conducted to identify RCTs or comparative observational studies evaluating the efficacy and effectiveness of COVID-19 vaccination in the prevention of transmission, asymptomatic infections and transmissibility of COVID-19 among vaccinated persons. An additional search of grey literature was conducted. This search is current to May 4th, 2021.ResultsIn this update, 16 additional studies, including 9 human and 7 animal studies, were included. Therefore, this review examines a total of 33 included studies: 21 human studies and 12 preclinical animal studies. Evidence from two large household surveillance studies from the UK suggests that a single or full dose of AstraZeneca (AZ) and Pfizer-BioNtech (PfBnT) vaccines may prevent household transmission of COVID-19 after 14 days of vaccination by up to 54%. The AZ vaccine trials in the general population suggest that an initial low dose followed by a standard dose may provide up to 59% protection against asymptomatic or unknown infection, although efficacy against these outcomes was not demonstrated following two standard doses. PfBnT vaccine observational studies in the general population suggest up to 90% effectiveness against asymptomatic infection after seven or more days of full dose vaccination. Up to 75% effectiveness against asymptomatic infection was reported after full- dose in healthcare workers. Across RCTs examining asymptomatic infection in the general population, one dose of Moderna was shown to provide an efficacy of 61.4% against asymptomatic infection 21 days after the first dose; in another trial, the J&J vaccine had an efficacy of 74% 28 days after the first dose. Lastly, seven of eight studies found significantly increased cycle threshold, suggestive of lower viral load, in PfBnT or AZ vaccinated individuals compared with those who were unvaccinated.ConclusionThe AZ and PfBnT vaccines may prevent household transmission of COVID-19 after 14 days of vaccination. More studies have found the vaccines to significantly reduce the risk of asymptomatic infection and significantly increase cycle threshold, suggestive of lower viral load. Further research is needed to evaluate post-vaccination infectivity and transmission of both the wild type COVID-19 virus and the variants of concern from other jurisdictions.

Objectives:To measure the impact of an antimicrobial stewardship initiative on the rate of urine culture testing and antimicrobial prescribing for urinary tract infections (UTIs) between control and intervention sites. Secondary objectives included evaluation of potential harms of the intervention and identifying characteristics of the population prescribed antimicrobials for UTI.Design:Cluster randomized controlled trial.Setting:Nursing homes in rural Alberta, Canada.Participants:The study included 42 nursing homes ranging from 8 to 112 beds.Methods/interventions:Intervention sites received on-site staff education, physician academic detailing, and integrated clinical decision-making tools. Control sites provided standard care. Data were collected for 6 months prior to and 12 months after the intervention.Results:Resident age (83.0 vs 83.8 years) and sex distribution (female, 62.5% vs 64.5%) were similar between the groups. Statistically significant decreases in the rate of urine culture testing (−2.1 tests per 1,000 resident days [RD]; 95% confidence interval [CI], −2.5 to −1.7;P< .001) and antimicrobial prescribing for UTIs (−0.7 prescriptions per 1,000 RD; 95% CI, −1.0 to −0.4;P< .001) were observed in the intervention group. There was no difference in hospital admissions (0.00 admissions per 1,000 RD; 95% CI, −0.4 to 0.3;P= .76), and the mortality rate decreased by 0.2 per 1,000 RD in the intervention group (95% CI, −0.5 to −0.1;P= .002). Chart reviews indicated that UTI symptoms were charted in 16% of cases and that urine culture testing occurred in 64.5% of cases.Conclusion:A multimodal antimicrobial stewardship intervention in rural nursing homes significantly decreased the rate of urine culture testing and antimicrobial prescriptions for UTI, with no increase in hospital admissions or mortality.

Background As of November 25th 2021, four SARS-CoV − 2 variants of concern (VOC: Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), and Delta (B.1.617.2)) have been detected. Variable degrees of increased transmissibility of the VOC have been documented, with potential implications for hospital and health system capacity and control measures. This rapid review aimed to provide a synthesis of evidence related to health system responses to the emergence of VOC worldwide. Methods Seven databases were searched up to September 27, 2021, for terms related to VOC. Titles, abstracts, and full-text documents were screened independently by two reviewers. Data were extracted independently by two reviewers using a standardized form. Studies were included if they reported on at least one of the VOC and health system outcomes. Results Of the 4877 articles retrieved, 59 studies were included, which used a wide range of designs and methods. Most of the studies reported on Alpha, and all except two reported on impacts for capacity planning related to hospitalization, intensive care admissions, and mortality. Most studies (73.4%) observed an increase in hospitalization, but findings on increased admission to intensive care units were mixed (50%). Most studies (63.4%) that reported mortality data found an increased risk of death due to VOC, although health system capacity may influence this. No studies reported on screening staff and visitors or cohorting patients based on VOC. Conclusion While the findings should be interpreted with caution as most of the sources identified were preprints, evidence is trending towards an increased risk of hospitalization and, potentially, mortality due to VOC compared to wild-type SARS-CoV − 2. There is little evidence on the need for, and the effect of, changes to health system arrangements in response to VOC transmission.

BackgroundAs of April 2021, three SARS-CoV-2 variants of concern (VOC: B.1.1.7, B.1.351 and P.1) have been detected in over 132 countries. Increased transmissibility of VOC has implications for public health measures and health system arrangements. This rapid scoping review aims to provide a synthesis of current evidence related to public health measures and health system arrangements associated with VOC.MethodsRapid scoping review. Seven databases were searched up to April 7, 2021 for terms related to VOC, transmission, public health and health systems. A grey literature search was conducted up to April 14, 2021. Title, abstracts and full text were screened independently by two reviewers. Data were double extracted using a standardized form. Studies were included if they reported on at least one of the VOC and public health or health system outcomes.ResultsOf the 2487 articles and 59 grey literature sources retrieved, 37 studies and 21 guidance documents were included. Included studies used a wide range of designs and methods. Most of the studies and guidance documents reported on B.1.1.7, and 18 studies and 4 reports provided data for consideration in relation to public health measures. Public health measures, including lockdowns, physical distancing, testing and contact tracing, were identified as critical adjuncts to a comprehensive vaccination campaign. No studies reported on handwashing or masking procedures related to VOC. For health system arrangements, 17 studies were identified. Some studies found an increase in hospitalization due to B.1.1.7 but no difference in length of stay or ICU admission. Six studies found an increased risk of death ranging from 15-67% with B.1.1.7 compared non-B.1.1.7, but three studies reported no change. One study reported on the effectiveness of personal protective equipment in reducing VOC transmission in the hospital. No studies reported on screening staff and visitors, adjusting service provisions, or adjusting patient accommodations and shared spaces, which is a significant gap in the literature. Guidance documents did not tend to cite any evidence and were thus assumed to be based on expert opinion.ConclusionWhile the findings should be interpreted with caution as most of the sources identified were preprints, findings suggest a combination of non-pharmaceutical interventions (e.g., masking, physical distancing, lockdowns, testing) should be employed alongside a vaccine strategy to improve population and health system outcomes. While the findings are mixed on the impact of VOC on health system arrangements, the evidence is trending towards increased hospitalization and death.

Summary Background The classic geographical range of histoplasmosis in North America primarily includes the states and provinces adjacent to the Ohio, Mississippi, and St Lawrence riverways. Although Alberta, Canada is not typically considered a region of risk for histoplasmosis, cases with suspected local acquisition have been reported. We aimed to investigate the epidemiology and geographical distribution of cases of histoplasmosis in Alberta to assess evidence for local acquisition of infections, using genomic analysis for corroboration. Methods We did an epidemiological and genomic investigation, in which laboratory-confirmed cases of histoplasmosis were reviewed in Alberta from 2011, when the disease became reportable, until 2018. We used data attained from Alberta Health. Travel and exposure histories and clinical features were reviewed. Definite local acquisition was defined as a case without previous travel outside Alberta or associated with a common-source outbreak within the province, whereas probable local acquisition was a sporadic case with travel outside Alberta but compelling local exposures. Genomes of selected case isolates were analysed, including those from cases suspected to have been locally acquired and imported. Findings Between Jan 1, 2011, and June 30, 2018, 45 cases of histoplasmosis were identified. Participants had a median age of 53 years (range 17–77) and 32 [71%] were male. Among 34 patients with documented travel histories, ten (29%) had never left the province. 11 cases were of definite local acquisition, including eight cases from three common-source outbreaks and three sporadic cases in patients who had never travelled outside Alberta. The common-source outbreaks all involved exposure to bats or their droppings in chimneys or attics of private dwellings or churches. Four patients had travelled outside Alberta but compelling evidence was seen for local exposure to bat guano. Genome sequencing showed that isolates from cases of definite and probable local acquisition clustered together and were genetically distinct from isolates from suspected imported cases and other published isolates. Interpretation Using epidemiological and genomic analyses, we established that cases of histoplasmosis have been acquired in Alberta, thus expanding the geographical range of Histoplasma spp much further northwest than was previously appreciated. Histoplasmosis should be considered in patients with compatible symptoms outside areas of classic geographical risk. Funding None.

Background Severe and fulminant Clostridioides Difficile infection(CDI) is associated with increased mortality and morbidity. Current guidelines recommend high dose vancomycin with metronidazole for treatment. Surgery is a high risk for patients failing medical therapy partly due to multiple comorbidities. Emerging evidence suggests efficacy of sequential fecal microbiota transplantation(FMT) by colonoscopy combined with vancomycin in patients failing maximal medical therapy. Fidaxomicin is non-inferior to vancomycin in treating CDI; however, it has not been studied in severe/fulminant cases. It is not known if FMT by enema combined with fidaxomicin is efficacious and safe in this patient population. Aims This single center, prospective, open-label pilot study aimed to determine the efficacy and safety of combined sequential FMT by enema plus fidaxomicin in severe or fulminant CDI not responding to maximal medical therapy. Primary outcome was resolution of diarrhea 2 weeks following final FMT. Secondary outcomes were resolution of diarrhea 8 weeks following final FMT, safety of proposed treatment protocol and colectomy rate. Methods Consecutive patients with severe or fulminant CDI, who fulfilled study inclusion criteria were recruited. Sequential cycles of FMT, administered by enema daily over three days(720cc followed by 360cc and 180cc), plus fidaxomicin 200mg PO BID were given. Clinical symptoms and inflammatory markers were monitored during the study and subsequent cycles of FMT were administered when clinical or biochemical improvement plateaued. A final FMT was administered with CDI resolution. Results A total of three patients were enrolled between Jan 22 to Aug 8, 2019, shown in Table 1. One patient had fulminant CDI due to shock, and the others had severe CDI. All had severe pseudomembranous colitis seen on endoscopy at enrollment. Two of three patients reached both primary and secondary outcomes with 2 FMT cycles. The only patient who did not reach the primary was successfully managed with long term vancomycin suppression. This patient had failed multiple FMTs prior to enrollment. There were no adverse events noted and no colectomy was required during this study. Conclusions This pilot study is the first to demonstrate efficacy and safety of combined sequential FMT by enema and fidaxomicin in treating severe or fulminant CDI patients. An adequately powered study is required to validate these findings. Funding Agencies CIHRAlberta Health Services, University of Alberta Hospital Foundation

KEY POINTS An 82-year-old man was transferred from Inuvik (Northwest Territories, Canada) to a tertiary hospital in Alberta for evaluation of an infection at a permanent pacemaker site. The pacemaker had been inserted in 2005 to treat third-degree heart block. The patient had experienced increasing

Background: Prior studies using reverse transcriptase inhibitors to treat a human betaretrovirus (HBRV) in patients with primary biliary cholangitis (PBC) resulted in a 21% reduction in alkaline phosphatase (ALP). Herein, we studied the safety and efficacy of combination tenofovir-emtricitabine (TDF/FTC) and lopinavir-ritonavir (LPRr) in PBC patients unresponsive to ursodeoxycholic acid (UDCA). Methods: A double-blind randomized controlled trial was performed in patients on UDCA for 6 months or more with ALP levels greater than two-fold the upper limit of normal or bilirubin greater than the upper limit of normal. Patients were randomized to daily TDF/FTC 300/200 mg and LPRr 800/200 mg versus identical placebo for 6 months. The primary endpoint was reduction of ALP below 1.67 × ULN or normalization of bilirubin. HBRV DNA levels were assessed in peripheral blood mononuclear cells (PBMC) using digital droplet polymerase chain reaction. Results: The enrolment was limited to 13 patients because most patients were unable to tolerate LPRr due to the development of gastrointestinal symptoms. No difference in the primary endpoint was achieved. A significant reduction was observed in ALP by 25% ( P < 0.05) and in HBRV proviral load ( P < 0.05) after 6 months of combination antiretroviral therapy. The majority of patients had diminished levels of LPRr after 6 months’ therapy suggesting inadequate intake of protease inhibitor toward the end of the study. Conclusions: Combination anti-retroviral therapy resulted in improvement in hepatic biochemistry with reduction in proviral load. The frequency of side effects from LPRr in patients with PBC exceeds the frequency reported for HIV, warranting the search for better tolerated combinations in future studies.

Protistan parasites have an undisputed global health impact. However, outside of a few key exceptions, e.g. the agent of malaria, most of these infectious agents are neglected as important health threats. The Symposium entitled "Free-living amoebae and neglected pathogenic protozoa: health emergency signals?" held at the European Congress of Protistology in Rome, July 2019, brought together researchers addressing scientific and clinical questions about some of these fascinating organisms. Topics presented included the molecular basis of pathogenicity in Acanthamoeba; genomics of Naegleria fowleri; and epidemiology of poorly diagnosed enteric protistan species, including Giardia, Cryptosporidium, Blastocystis, Dientamoeba. The Symposium aim was to excite the audience about the opportunities and challenges of research in these underexplored organisms and to underline the public health implications of currently under-appreciated protistan infections. The major take home message is that any knowledge that we gain about these organisms will allow us to better address them, in terms of monitoring and treatment, as sources of future health emergencies.

BACKGROUND: Overuse of investigations, treatments, and procedures contribute to rising health care costs and may cause patient harm. In an attempt to promote higher-value health care, the Choosing Wisely Canada campaign has encouraged professional societies to develop statements that are directly actionable by their members. Currently, there are variations in infectious diseases practice that lead some patients to receive therapies and investigations that lack benefit and are potentially harmful. METHODS: The Association of Medical Microbiology and Infectious Disease Canada (AMMI) Canada established its Choosing Wisely Canada top five list of recommendations using the framework put forward by Choosing Wisely Canada. Following an electronic survey of its members regarding low-value practices within infectious diseases, AMMI Canada convened a working group that developed a list of draft recommendations and ranked the top five recommendations by consensus. This list was shared with the AMMI Canada membership electronically and during a national open forum. Following revisions based on feedback received, the AMMI Canada Executive Council and Guidelines Committee endorsed the final list, which was disseminated online. RESULTS: The top five declarative statements on infectious diseases practices that physicians and patients should question include: do not routinely prescribe intravenous forms of highly bioavailable antimicrobial agents for patients who can reliably take and absorb oral medications; do not prescribe alternative second-line antimicrobials to patients reporting nonsevere reactions to penicillin when beta-lactams are the recommended first-line therapy; do not routinely repeat CD4 measurements in patients with HIV infection with HIV-1 RNA suppression for >2 years and CD4 counts >500/μL, unless virological failure occurs or intercurrent opportunistic infection develops; do not routinely repeat radiologic imaging in patients with osteomyelitis demonstrating clinical improvement following adequate antimicrobial therapy; and do not prescribe aminoglycosides for synergy to patients with bacteremia or native valve infective endocarditis caused by Staphylococcus aureus. CONCLUSIONS: The Choosing Wisely Canada statements in infectious diseases endorsed by AMMI Canada represent a starting point to engage AMMI Canada members in broader discussions related to resource stewardship within infectious diseases practice and to take action.

We report the cases of 3 patients with fatal, disseminated Mycobacterium chimaera infections following cardiac surgeries. Progressive neurocognitive decline and death were explained by active granulomatous encephalitis, with widespread involvement of other organs. This syndrome is clinically elusive and, thus, may have caused deaths in prior reported series.

Non-tuberculous mycobacterium encephalitis is rare. Since 2013, a global outbreak of Mycobacterium chimaera infection has been attributed to point-source contamination of heater cooler units used in cardiac surgery. Disseminated M. chimaera infection has presented many unique challenges, including non-specific clinical presentations with delays in diagnosis, and a high mortality rate among predominantly immunocompetent adults. Here, we describe three patients with fatal disseminated Mycobacterium chimaera infection showing initially non-specific, progressively worsening neurocognitive decline, including confusion, delirium, depression and apathy. Autopsy revealed widespread granulomatous encephalitis of the cerebrum, brain stem and spinal cord, along with granulomatous chorioretinitis. Cerebral involvement and differentiation between mycobacterial granulomas and microangiopathic changes can be assessed best on MRI with contrast enhancement. The prognosis of M. chimaera encephalitis appears to be very poor, but might be improved by increased awareness of this new syndrome and timely antimicrobial treatment.LEARNING OBJECTIVESThis presentation will enable the learner to:1.Describe the clinical, radiological and neuropathological findings of Mycobacterium chimaera encephalitis2.Be aware of this rare form of encephalitis, and explain its diagnosis, prognosis and management

Current guidelines recommend antibiotic prophylaxis in all patients presenting with cirrhosis and acute variceal hemorrhage (AVH). We aimed to evaluate the characteristics and clinical impact of "early" infections (developing within 14 days) of AVH in a real-world setting.We analyzed retrospective data from a cohort of 371 adult patients with cirrhosis and AVH all of whom had received antibiotic prophylaxis (74% men; mean age 56 years), admitted to tertiary care hospitals in Edmonton, Alberta, Canada, and Barcelona, Spain. Sensitivity analyses were presented for culture-positive (confirmed) infections.The mean MELD was 16. Fifty-two percent of patients received quinolones, 45% third-generation cephalosporins and 3% other antibiotics. Fourteen percent (51/371) developed an infection within 14 days of AVH. Seventy-five percent of infections were culture positive and occurred at a mean of six days from AVH. When all infections were considered, respiratory infections were the most common (53%) followed by urinary tract infections (17%) and bacteremia (16%). Resistance patterns differed between countries. Outpatient antibiotic prophylaxis (OR 5.4) and intubation (OR 2.6) were independent predictors of bacterial infection. Bacterial infection (OR 2.6) and the MELD (OR 1.2) were independent predictors of six-week mortality.Early bacterial infections develop in 14% of cirrhotic patients with AVH despite antibiotic prophylaxis, and have a negative impact on six-week mortality. Intubation and outpatient antibiotic prophylaxis are associated with increased risk of early bacterial infections. Patients at risk should be followed closely with prompt infection workup and local antibiogram-based expansion of antibiotic therapy in case of clinical decline.

Background Histoplasmosis is a serious fungal infection caused by the geographically restricted, dimorphic fungus Histoplasma capsulatum. In Canada, the geographic range of H. capsulatum is classically thought to be restricted to southern parts of Ontario and Quebec. Over the past decade, histoplasmosis has occasionally been diagnosed in patients in Alberta without travel to areas of known geographic risk (Figure 1). We studied the epidemiology and geographic distribution of histoplasmosis in Alberta to assess evidence for locally-acquired infections. Methods We retrospectively reviewed all laboratory-confirmed (culture, antigen and/or immunodiffusion positive) cases of histoplasmosis diagnosed from January 1, 2011 to June 30, 2018. Data collected by public health and clinical charts were reviewed for clinical presentation, exposure and travel histories, and geographic distribution of cases. Cases of histoplasmosis in patients who had not left Alberta or associated with a local point source were classified as definite local acquisition; cases in patients with remote travel but with local exposures and appropriate timing of disease onset were deemed “probable” cases of local infection. University of Alberta’s Research Ethics Board approved this study. Results We identified 45 laboratory-confirmed cases of histoplasmosis, including 17 cases that were locally acquired. Among these, there were 12 cases of definite local acquisition, including 8 patients from 3 point-source outbreaks—all involving exposure to bats and/or their droppings in chimneys or attics of private dwellings or churches—and 4 sporadic cases in patients who had never traveled. Of the other 5 cases probably acquired in Alberta, patients had previously traveled (n = 4) or travel history was incomplete (n = 1) but local exposures preceding infection were considered compelling. The mean incidence rate of locally acquired infection was 0.062/100,000 population with incidence increasing since 2014. Table 1 shows features of locally acquired cases. Conclusion This study, for the first time, establishes Alberta as a region of geographic risk for histoplasmosis. The diagnosis should be considered in patients with compatible symptoms and exposure history, even in the absence of travel. Disclosures All authors: No reported disclosures.

Background In primary biliary cirrhosis (PBC), biochemical criteria at 1 year are considered surrogates of response to ursodeoxycholic acid (UDCA). However, due to the slow natural history of PBC, evaluation at 1 year may be suboptimal to assess the therapeutic response, particularly in early disease. Aim To determine whether evaluation of biochemical criteria at 1 year is a reliable surrogate of UDCA response in early PBC. Methods We analysed the prospectively collected data of 215 patients (untreated = 129; UDCA-treated = 86) with early PBC (normal baseline bilirubin/albumin) and a median follow-up of 8 years (range: 1–29.1). The 1-year attainment rates of the Barcelona, Paris-I, Paris-II and Toronto definitions, and their predictive relevance for a poor outcome (death, transplantation, complications of cirrhosis), were assessed either as a result of UDCA or no treatment. Independent associations with attaining each UDCA response definition were identified by multivariate analysis. Results Untreated patients displayed 1-year biochemical features compatible with ‘treatment response’ at rates (Barcelona: 36.4%, Paris-I: 66.7%, Toronto: 59.7%, Paris-II: 40.3%) similar to those obtained under UDCA. Depending on the definition, baseline ALP≤3xULN (OR: 4.80–35.90), AST≤2xULN (OR: 5.63–9.34) and early histological stage (OR: 3.67–3.87) were the stronger predictors for attaining the criteria. UDCA treatment was associated with attaining Barcelona (OR = 2.16) and Paris-II (OR = 2.84), but not Paris-I, and not Toronto definition when excluding late histological cases. Paris-I criteria were significantly predictive of long-term outcomes (HR = 2.83) in untreated patients. Conclusions In early PBC, biochemical criteria at 1 year reflect severity of the disease rather than the therapeutic response to UDCA.

The case: A healthy 73-year-old man had pain in his left shoulder. He presented to a regional hospital 1 week later with fever, dysphagia, muscle spasms and progressive generalized weakness. His neurologic status deteriorated, which prompted transfer to a tertiary care hospital. Upon the patient's

Objectives: The purpose of this study was to determine the biological stability of heparin and to test for physical compatibility in heparin/antibiotic solutions in concentrations suitable for antibiotic lock therapy. Methods: Solutions were prepared with heparin 5000 U/mL or heparin 10 U/mL and cefazolin 10 mg/mL, ampicillin 10 mg/mL, or piperacillin 40 mg/mL. Solutions of vancomycin 2.5 mg/mL with heparin 5000 U/mL and vancomycin 2 mg/mL with heparin 10 U/mL were also prepared. The ability of each solution to elevate the activated partial thromboplastin time (APTT) of pooled normal plasma and the physical compatibility of the solutions were assessed for 14 days. Results: The APTT levels never varied by more than 16.4% from baseline. Physical incompatibility never occurred before day 14 in any of the solutions. Conclusions: Mixing of antibiotics in the concentrations chosen for the study had no clinically significant effect on biological heparin activity, and all solutions were physically compatible for at least 14 days.

OBJECTIVE To describe 2 recent cases of suspected immunoglobulin-mediated interference with the Beckman Coulter particle–enhanced turbidimetric inhibition immunoassay (PETINIA) used to measure vancomycin serum or plasma concentrations and to review the existing literature. CASE SUMMARY A 64-year-old woman with a history of multiple immune-related comorbidities received vancomycin for treatment of a prosthetic joint infection growing coagulase-negative Staphylococcus spp. A 33-year-old man with a history of Felty syndrome received vancomycin for the treatment of methicillin-resistant Staphylococcus aureus pneumonia. Both patients had multiple vancomycin trough concentrations determined using the Beckman Coulter PETINIA method and had measured concentrations reported as less than 4 mg/L despite appropriate vancomycin dosing for their size, age, and organ function. The patients' serum was then tested by alternative methods, which reported vancomycin concentrations consistent with those expected with the patients' dosing regimens. DISCUSSION Immunoglobulins are well known for interfering with chemistry assays. It is suspected that high levels of immunoglobulins in these 2 patients interfered with the accurate measurement of serum vancomycin concentrations. An objective causality assessment supported the interactions as being definite and probable, respectively. Two other cases of suspected immunoglobulin interference with vancomycin measurement have been reported in the literature when vancomycin concentrations were initially measured using the Beckman Coulter PETINIA method. In vitro studies support the hypothesis that immunoglobulin interference with vancomycin measurement by this method occurs and is a graded phenome non. CONCLUSIONS These cases suggest a high likelihood of immunoglobulin-mediated interference with the Beckman Coulter PETINIA method, which results in the reporting of falsely low vancomycin serum concentrations. When vancomycin concentrations do not correlate with what would be expected clinically, clinicians should have a high index of suspicion for potential assay interference.

A32-year-old woman with systemic lupus erythematosus (SLE) on immunosuppressive medications presented to the Walter C Mackenzie Health Sciences Centre, Edmonton, Alberta, with a three-day history of right wrist swelling. She also complained of chronic midthoracic back pain in the setting of documented steroid-induced osteoporosis. Her back pain had increased over the six months before admission. She had also developed bilateral radicular pain, limited mobility, leg weakness, urinary hesitancy and a subjective change in light touch sensation of the legs. Bowel function was normal. She had night sweats but no fever or weight loss. There was no history of travel outside Alberta nor was there animal exposure. When well, the patient worked as a teacher’s aide. There was no personal or exposure history to suggest past tuberculosis (TB) infection. She was admitted for investigation, pain control and wrist aspiration. Past medical history was notable for Staphylococcus aureus joint infections, steroid-induced diabetes, shingles, remote pulmonary embolism, chronic recurrent skin and soft tissue infections, and a Salmonella dublin bacteremia 10 months before this admission. Medications at admission included prednisone, chloroquine, cyclophosphamide, metformin and hydromorphone. Physical examination revealed a pale, afebrile woman in moderate discomfort. Respiratory, cardiac and abdominal examinations were within normal limits. Musculoskeletal examination revealed an ‘exaggerated thoracic kyphosis’ at approximately T8. Joint examination was normal with the exception of decreased range of motion at the right wrist secondary to swelling, with minimal erythema and tenderness. Limb strength and reflexes were equal, with downgoing plantar responses. Admission laboratory data were as follows: hemoglobin 107 g/L, platelets 400×10/L, white blood cells 4.3×10/L with lymphocytes of 0.4×10/L. Serum urea and creatinine were normal. Serum transaminases, bilirubin and the international normalized ratio were within normal limits and the alkaline phosphatase was elevated at 157 IU. Complement levels were low and the sedimentation rate was 43 (mm/h). On admission and subsequently, the blood cultures were all negative. The right wrist aspirate revealed a small amount of noninflammatory fluid, which was negative on Gram stain and culture. A bone scan was performed, which revealed diffuse increased uptake in both wrists, consistent with an ‘arthritic process’, and there was ‘intensely increased’ uptake in the