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.

severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected more than 16 000 000 individuals worldwide and caused over 600 000 deaths from COVID-19. Despite advances in pharmacological treatment and early vaccine development, reducing transmission of the virus with the use of facemasks (referring to medical or surgical masks, N-95 and similar respirators, cloth masks, and bandannas) by health-care workers and the public alike remains a hotly debated topic due to politicisation of discourse and decision making.At the beginning of the pandemic, many experts advised against the use of facemasks by the public due to a sense that their potential risks, such as self-contamination, could outweigh the potential benefits, and that public use would lead to depletion of the supply needed for healthcare workers. Experts then shifted their thinking about potential benefits of masks to include protecting others against infection with SARS-CoV-2 (source control), similar to how surgical masks in the operating room protect patients. However, self-protection is the main reason why infection prevention and control experts recommend health-care workers to wear a facemask when entering a patient's room who may have a viral respiratory infection. With COVID-19, however, facemasks might be beneficial for protection of both health-care workers and the public.On Jan 30, 2020, Rothe and colleagues described SARS-CoV-2 in a number of individuals infected by a person reported to be asymptomatic who had travelled from China. This report was questioned because the index case had taken acetaminophen for jetlag, which could have masked COVID-19 symptoms. Hence, the scientific community became and remained doubtful about transmission by presymptomatic and asymptomatic individuals for some time. It has since become evident that people are infectious for at least 48 h before symptom onset (presymptomatic), that some people have only minor symptoms (paucisymptomatic), and others remain entirely asymptomatic. These individuals can transmit the virus without knowing they are infectious-the main argument for use of facemasks as a source control. In addition, there continues to be disagreement about the risk of transmission through aerosolised SARS-CoV-2. These perceived conflicts, in turn, continue to fuel the conflicting advice about the potential role and type of facemasks in the COVID-19 pandemic for health-care workers and the public.Systematic reviews of facemask use suggest relative risk (RR) reductions for infection ranging from 6-80%, including for betacoronavirus infection (eg, COVID-19, SARS, MERS). This inconsistency might be a result of different inclusion and exclusion criteria of the type of studies; the type of included population-eg, health-care workers or the general public; possibly the type of facemask used; the outcomes

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 arrival at the tertiary care hospital, our initial evaluation showed irritability, lethargy and hypersalivation. After 48 hours, the patient exhibited multifocal myoclonus and decorticate posturing. Intubation and mechanical ventilation were performed with fluid resuscitation and therapy with vasopressors, corticosteroids and broad-spectrum antibiotics. A computed tomography scan of his brain was unremarkable. An electroencephalogram showed diffuse abnormalities consistent with metabolic encephalopathy. We investigated potential rabies exposure, and his family confirmed that he had sustained a bat bite on his left shoulder 6 months previously but had not sought treatment.We performed a nuchal skin biopsy and obtained saliva and serum samples for rabies virologic and serologic testing. Direct fluorescent antibody staining indicated that the skin biopsy contained rabies virus antigen, and reverse-transcriptase polymerase chain reaction indicated that both the skin and saliva samples contained the rabies virus. Diagnostic tests available for suspected rabies cases in Canada are described in Box 1. The patient received an intramuscular injection of 1200 IU of human rabies immune globulin.We started the Milwaukee Protocol 15 days after symptom onset (3 days after diagnosis). The Protocol consisted of inducing a therapeutic coma (infusions of ketamine, midazolam and propofol titrated to burst-suppression pattern on the electroencephalogram) and antiviral therapy (ribavirin, amantadine).1 We also provided metabolic supplementation (with tetrahydrobiopterin and L-arginine). We monitored regional cerebral perfusion using transcranial Doppler ultrasonography. Serial serum, saliva and cerebrospinal fluid samples were assessed weekly for immune response and viral clearance.Over time, rabies virus-specific IgM and IgG and total antibody titres rose and viral excretion in the saliva fell. We stopped sedation on day 42, 3 weeks after initiation of the Milwaukee Protocol. Direct fluorescent antibody staining indicated that the repeat nuchal biopsy performed on day 43 was only weakly positive for rabies virus antigen, and reverse-transcriptase polymerase chain reaction was negative. On the same day, transcranial Doppler ultrasonography showed only minor perfusion abnormalities, and the electroencephalogram was near isoelectric. By day 56, results of serial rabies virus tests suggested viral clearance; however, our patient's saliva still contained a low level of the virus. He remained comatose for 4 weeks after we stopped sedation. A neurologic examination on day 64, including apnea testing, was consistent with brain death. However, a nuclear medicine perfusion scan showed preservation of cerebral blood flow. Neuroimaging showed diffuse ...

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.

Despite COVID-19’s significant morbidity and mortality, considering cost-effectiveness of pharmacologic treatment strategies for hospitalized patients remains critical to support healthcare resource decisions within budgetary constraints. As such, we calculated the cost-effectiveness of using remdesivir and dexamethasone for moderate to severe COVID-19 respiratory infections using the United States health care system as a representative model. A 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 only moderate and only severe 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. Supportive care for moderate/severe COVID-19 cost $11,112.98 with 0.7155 quality adjusted life-year (QALY) obtained. Using dexamethasone for all patients was the most-cost effective with an incremental cost-effectiveness ratio of $980.84/QALY; all remdesivir strategies were more costly and less effective. Probabilistic sensitivity analyses showed dexamethasone for all patients was most cost-effective in 98.3% of scenarios. Dexamethasone for moderate-severe COVID-19 infections was the most cost-effective strategy and would have minimal budget impact. Based on current data, remdesivir is unlikely to be a cost-effective treatment for COVID-19.

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.

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The Canadian Nosocomial Infection Surveillance Program has been performing surveillance of antibiotic-resistant organisms in Canada since 1994. The authors of this study compared two point-prevalence surveys of antimicrobial use that were conducted in hospitals that were participating in the program in 2002 and 2009. The authors compared the use of antimicrobials between these two surveys. The changes in antimicrobial use over time are presented, in addition to potential reasons for and consequences of these changes.