A Biomechanical Analysis of Oblique Metacarpal Metadiaphyseal Fracture Fixation in a Cadaver Model.

PURPOSE: Although metacarpal fractures are typically managed nonoperatively, when surgical management is indicated, metacarpal fractures are commonly treated with crossed Kirschner wires (K-wires), which may limit early range of motion. Intramedullary implants are increasing in use with the potential advantage of early range of motion; however, stability in oblique metacarpal neck fractures remains a theoretical concern. The purpose of this study was to determine the biomechanical stability of noncompressive intramedullary fixation for oblique metacarpal neck fractures compared with crossed K-wire fixation. METHODS: The index, long, and small metacarpals were harvested from three matched pairs of fresh-frozen cadavers. Oblique fractures at the metadiaphyseal region were created in each metacarpal. Each metacarpal was randomized to noncompressive, threaded intramedullary nail fixation or fixation with two crossed K-wires. Specimens were mounted in a Materials Testing System load frame and axially loaded until failure. Load to failure (LTF), stiffness, and load to 2 mm displacement were calculated from load-displacement curves. Differences in peak LTF, stiffness, and load to 2 mm displacement between noncompressive intramedullary fixation and crossed K-wire fixation were evaluated. RESULTS: The noncompressive intramedullary fixation cohort had a significantly higher LTF (1,190.9 ± 534.7 N vs 297.0 ± 156.0 N) and stiffness (551.3 ± 164.6 N/mm vs 283.0 ± 194.5 N/mm) when compared with the crossed K-wire fixation cohort. Load at 2 mm displacement was greater in the noncompressive intramedullary fixation cohort compared with crossed K-wire fixation (820.5 ± 203.9 vs 514.1 ± 259.6). CONCLUSIONS: For oblique metadiaphyseal metacarpal fractures, noncompressive intramedullary fixation provides a biomechanically superior construct under axial loading in terms of LTF, stiffness, and load to 2 mm of displacement compared with crossed K-wire fixation. CLINICAL RELEVANCE: Noncompressive intramedullary nails may be an alternative to K-wire fixation for the treatment of oblique metadiaphyseal metacarpal fractures.

High and Low Dosage of Vancomycin in Polymethylmethacrylate Cements: Efficacy and Mechanical Properties.

INTRODUCTION: Prosthetic joint infections (PJIs) are difficult to treat and represent a significant burden to the healthcare system. Two-stage revision surgery with placement of an antibiotic-loaded cement spacer is currently the gold standard for treatment in the United States for late-onset infections. We evaluate the efficacy of varying doses of vancomycin added to antibiotic-containing acrylic cement spacers and discuss the biomechanical and antimicrobial properties of using high versus low doses of vancomycin in cement spacers in the hip and knee. MATERIALS AND METHODS: Commercially available Copal cement containing either gentamicin and clindamycin (G + C) or gentamicin and vancomycin (G + V) was prepared with the manual addition of low (2 g) and high (6 g) doses of vancomycin. In vitro mechanical testing was then carried out according to ISO 5833 and DIN 53435, as well as inhibition zone assays against common PJI pathogens. Additionally, inhibition zone assays were conducted on two commercially available prefabricated spacers containing gentamicin: Copal Exchange G and Cemex Spacer-K. RESULTS: In biomechanical testing, Copal G + V with the addition of 6 g of vancomycin failed to meet the ISO standard. Copal G + C and Copal G + V with low and high dosages of vancomycin were all effective against the tested pathogens and displayed constant efficacy for a duration of 42 days. High doses of vancomycin showed significantly lower mechanical stability. Moreover, Copal Exchange G showed significantly larger inhibition zones across 42 days. DISCUSSION: While higher concentrations of vancomycin appear to improve the antimicrobial efficacy of cement, they also reduce its mechanical stability. Despite its smoother surface, the Copal Exchange G spacer exhibits large inhibition zones after 1 day and maintains consistently large inhibition zones over 6 weeks. Thus, it may be preferred for use in two-stage revision surgery. CONCLUSION: Copal Exchange G is more effective than Cemex Spacer K against S. aureus and E. coli. The manual addition of vancomycin to cement containing double antibiotics is very effective. The influence on ISO compression is low, the ISO bending modulus is increased, and ISO bending, DIN bending, and DIN impact, are reduced.

Effectiveness of modified vaccinia Ankara-Bavarian Nordic vaccine against mpox infection: emulation of a target trial.

OBJECTIVE: To estimate the real world effectiveness of modified vaccinia Ankara-Bavarian Nordic (MVA-BN) vaccine against mpox infection. DESIGN: Emulation of a target trial. SETTING: Linked databases in Ontario, Canada. PARTICIPANTS: 9803 men aged ≥18 years with a history of being tested for syphilis and a laboratory confirmed bacterial sexually transmitted infection (STI) in the previous year, or who filled a prescription for HIV pre-exposure prophylaxis in the previous year. On each day between 12 June 2022 and 27 October 2022, those who had been vaccinated 15 days previously were matched 1:1 with unvaccinated men by age, geographical region, past HIV diagnosis, number of bacterial STI diagnoses in the previous three years, and receipt of any non-MVA-BN vaccine in the previous year. MAIN OUTCOME MEASURE: The main outcome measure was vaccine effectiveness ((1-hazard ratio)×100) of one dose of subcutaneously administered MVA-BN against laboratory confirmed mpox infection. A Cox proportional hazards model was used to estimate hazard ratios to compare the rate of laboratory confirmed mpox between the two groups. RESULTS: 3204 men who received the vaccine were matched to 3204 unvaccinated controls. A total of 71 mpox infections were diagnosed, with 0.09 per 1000 person days (95% confidence interval (CI) 0.05 to 0.13) in the vaccinated group and 0.20 per 1000 person days (0.15 to 0.27) in the unvaccinated group over the study period of 153 days. Estimated vaccine effectiveness of one dose of MVA-BN against mpox infection was 58% (95% CI 31% to 75%). CONCLUSION: The findings of this study, conducted in the context of a targeted vaccination programme and evolving outbreak of mpox, suggest that one dose of MVA-BN is moderately effective in preventing mpox infection.

Goal Concordant Care: A Cross-Sectional Study Evaluating Correlates of Concordant Care and Association With Satisfaction and Outcomes.

BACKGROUND: The concordance between patient and physician goals has been associated with improved outcomes in many chronic diseases. The purpose of this study was to evaluate the association between goal concordant care, patient satisfaction, and patient experience and to analyze factors associated with goal concordant care in hand and upper extremity surgery. METHODS: New patients who were 18 years or older were invited to participate. Goal concordant care was defined as the patient's previsit treatment goal matching the primary treatment received. The χ2 tests were used to evaluate the association between goal concordant care and patient satisfaction and patient experience. We conducted univariable logistic regression to evaluate variables for their association with concordance and multivariable logistic regression for variables that were significantly associated in the initial analyses to evaluate their aggregate influence on concordance. RESULTS: In total, 169 patients enrolled. The rate of goal concordant care was 62%; concordance was not associated with patient satisfaction or experience. Age, sex, English proficiency, health literacy, education level, employment and relationship status, pain self-efficacy, symptom duration, functional disability, and patient-centered decision-making were not associated with concordant care. Patients with annual income less than $50,000 had significantly higher odds of goal discordant care. CONCLUSION: Patients with lower income had more than 3 times the odds of receiving discordant care. However, discordant care was not associated with patient satisfaction or experience. Further studies on other pertinent outcomes are needed in orthopedic surgery (eg, treatment adherence). Known care disparities based on socioeconomic status may be mediated through care discordance and should be investigated.

The Clinical Severity of COVID-19 Variants of Concern: Retrospective Population-Based Analysis.

BACKGROUND: SARS-CoV-2 variants of concern (VOCs) emerged and rapidly replaced the original strain worldwide. The increased transmissibility of these new variants led to increases in infections, hospitalizations, and mortality. However, there is a scarcity of retrospective investigations examining the severity of all the main VOCs in presence of key public health measures and within various social determinants of health (SDOHs). OBJECTIVE: This study aims to provide a retrospective assessment of the clinical severity of COVID-19 VOCs in the context of heterogenous SDOHs and vaccination rollout. METHODS: We used a population-based retrospective cohort design with data from the British Columbia COVID-19 Cohort, a linked provincial surveillance platform. To assess the relative severity (hospitalizations, intensive care unit [ICU] admissions, and deaths) of Gamma, Delta, and Omicron infections during 2021 relative to Alpha, we used inverse probability treatment weighted Cox proportional hazard modeling. We also conducted a subanalysis among unvaccinated individuals, as assessed severity differed across VOCs and SDOHs. RESULTS: We included 91,964 individuals infected with a SARS-CoV-2 VOC (Alpha: n=20,487, 22.28%; Gamma: n=15,223, 16.55%; Delta: n=49,161, 53.46%; and Omicron: n=7093, 7.71%). Delta was associated with the most severe disease in terms of hospitalization, ICU admissions, and deaths (hospitalization: adjusted hazard ratio [aHR] 2.00, 95% CI 1.92-2.08; ICU: aHR 2.05, 95% CI 1.91-2.20; death: aHR 3.70, 95% CI 3.23-4.25 relative to Alpha), followed generally by Gamma and then Omicron and Alpha. The relative severity by VOC remained similar in the unvaccinated individual subanalysis, although the proportion of individuals infected with Delta and Omicron who were hospitalized was 2 times higher in those unvaccinated than in those fully vaccinated. Regarding SDOHs, the proportion of hospitalized individuals was higher in areas with lower income across all VOCs, whereas among Alpha and Gamma infections, 2 VOCs that cocirculated, differential distributions of hospitalizations were found among racially minoritized groups. CONCLUSIONS: Our study provides robust severity estimates for all VOCs during the COVID-19 pandemic in British Columbia, Canada. Relative to Alpha, we found Delta to be the most severe, followed by Gamma and Omicron. This study highlights the importance of targeted testing and sequencing to ensure timely detection and accurate estimation of severity in emerging variants. It further sheds light on the importance of vaccination coverage and SDOHs in the context of pandemic preparedness to support the prioritization of allocation for resource-constrained or minoritized groups.

Bridging Hepatitis C Care Gaps: A Modeling Approach for Achieving the WHO's Targets in Ontario, Canada.

BACKGROUND: The World Health Organization (WHO) has set hepatitis C (HCV) elimination targets for 2030. Understanding existing gaps in the "HCV care-cascade" is essential for meeting these targets. We aimed to identify the level of service scale-up needed along the "HCV care-cascade" to achieve the WHO's HCV elimination targets in Ontario, Canada. METHODS: By employing a decision analytic model, we projected the quality-adjusted life years (QALYs) and healthcare costs for individuals with HCV in Ontario. We increased RNA testing and treatment rates to 98%, followed by increasing antibody testing uptake until we achieved the WHO's mortality target (i.e., a 65% reduction in liver-related mortality by 2030 vs. 2015). RESULTS: Without scaling up by 2030, the expected QALYs and costs per person were 9.156 and CAD 48,996, respectively. Improved RNA testing and treatment rates reduced liver-related deaths to 3.3/100,000, a 57% reduction from 2015. Further doubling the antibody testing rates can achieve the WHO's mortality target in 2035, but not in 2030. Compared to the status quo, such program would be cost-effective considering a 50,000 CAD/QALY gained threshold if annual implementation costs stayed under 2.3 M CAD/100,000 people. CONCLUSIONS: Doubling the antibody testing rates, along with increased RNA testing and treatment rates, showed promise in meeting the WHO's goals by 2035.

Seroprevalence of SARS-CoV-2 antibodies among children receiving primary care in Toronto, Ontario.

OBJECTIVE: Characterizing the seroprevalence of SARS-CoV-2 antibodies in children is needed to optimize the COVID-19 public health response. We quantified the seroprevalence of SARS-CoV-2 infection-acquired antibodies and vaccine-acquired antibodies among children receiving primary care in Toronto, Canada. METHODS: We conducted a longitudinal cohort study between January 2021 and November 2022 in healthy children aged 0-16 years receiving primary care in Toronto. The primary and secondary outcomes were seroprevalence of SARS-COV-2 infection-acquired antibodies and vaccine-acquired antibodies ascertained from finger-prick dried blood spots. Samples were tested using an enzyme-linked immunosorbent assay for antibodies to full-length spike trimer and nucleocapsid. We explored sociodemographic differences with Firth's penalized generalized estimating equations. RESULTS: Of the 475 participants, 50.1% were girls and mean age was 6.4 years (SD = 3.2). We identified 103 children seropositive for infection-acquired antibodies, with a crude seroprevalence that rose from 2.6% (95%CI 1.39-4.92) from January to July 2021 to 50.7% (95%CI 39.5-61.8) by July to November 2022. Seroprevalence of vaccine-acquired antibodies was 45.2% by July to November 2022 (95%CI 34.3-56.58). No differences in sociodemographic factors (age, sex, income, or ethnicity) were identified for infection-acquired antibodies; however, children with vaccine-acquired antibodies were more likely to be older, have mothers with university education, and have mothers who had also been vaccinated. CONCLUSION: Our results provide a benchmark for seroprevalence of SARS-CoV-2 antibodies in children in Toronto. Ongoing monitoring of the serological status of children is important, particularly with the emergence of new variants of concern, low vaccine coverage, and discontinuation of PCR testing.

RéSUMé: OBJECTIF: Caractériser la séroprévalence des anticorps du SRAS-CoV-2 chez les enfants est nécessaire pour optimiser la réponse de santé publique à COVID-19. Nous avons quantifié la séroprévalence des anticorps acquis par l'infection au SRAS-CoV-2 et des anticorps acquis par le vaccin chez les enfants recevant des soins primaires à Toronto, au Canada. MéTHODES: Nous avons mené une étude de cohorte longitudinale entre janvier 2021 et novembre 2022 auprès d'enfants en bonne santé âgés de 0 à 16 ans recevant des soins primaires à Toronto. Les résultats principaux et secondaires étaient la séroprévalence des anticorps acquis par l'infection du SRAS-CoV-2 et des anticorps acquis par le vaccin déterminés à partir de taches de sang séché par piqûre au doigt. Les échantillons ont été testés à l'aide d'un test immuno-enzymatique pour détecter les anticorps dirigés contre le trimère de pointe complet et la nucléocapside. Nous avons exploré les différences sociodémographiques à l'aide des équations d'estimation généralisées pénalisées de Firth. RéSULTATS: Sur les 475 participants, 50,1 % étaient des filles et l'âge moyen était de 6,4 ans (ET = 3,2). Nous avons identifié 103 enfants séropositifs aux anticorps acquis lors d'une infection, avec une séroprévalence non ajusté qui est passée de 2,6 % (IC 95% : 1,39­4,92) de janvier à juillet 2021 à 50,7 % (IC 95% : 39,5­61,8) de juillet à novembre 2022. La séroprévalence des anticorps acquis par le vaccin était de 45,2 % de juillet à novembre 2022 (IC à 95% : 34,3­56,58). Aucune différence dans les facteurs sociodémographiques (âge, sexe, revenu ou appartenance ethnique) n'a été identifiée pour les anticorps acquis lors d'une infection; cependant, les enfants avec des anticorps acquis par le vaccin étaient plus susceptibles d'être plus âgés, d'avoir des mères ayant fait des études universitaires et d'avoir des mères également vaccinées. CONCLUSION: Nos résultats fournissent une référence pour la séroprévalence des anticorps du SRAS-CoV-2 chez les enfants de Toronto. La surveillance continue du statut sérologique des enfants est importante, en particulier avec l'émergence de nouveaux variants préoccupants, la faible couverture vaccinale et l'arrêt des tests PCR.

Effectiveness of Influenza Vaccination During Pregnancy Against Laboratory-Confirmed Seasonal Influenza Among Infants Under 6 Months of Age in Ontario, Canada.

BACKGROUND: Randomized trials conducted in low- and middle-income settings demonstrated efficacy of influenza vaccination during pregnancy against influenza infection among infants <6 months of age. However, vaccine effectiveness (VE) estimates from settings with different population characteristics and influenza seasonality remain limited. METHODS: We conducted a test-negative study in Ontario, Canada. All influenza virus tests among infants <6 months from 2010 to 2019 were identified and linked with health databases to ascertain information on maternal-infant dyads. VE was estimated from the odds ratio for influenza vaccination during pregnancy among cases versus controls, computed using logistic regression with adjustment for potential confounders. RESULTS: Among 23 806 infants tested for influenza, 1783 (7.5%) were positive and 1708 (7.2%) were born to mothers vaccinated against influenza during pregnancy. VE against laboratory-confirmed infant influenza infection was 64% (95% confidence interval [CI], 50%-74%). VE was similar by trimester of vaccination (first/second, 66% [95% CI, 40%-80%]; third, 63% [95% CI, 46%-74%]), infant age at testing (0 to <2 months, 63% [95% CI, 46%-75%]; 2 to <6 months, 64% [95% CI, 36%-79%]), and gestational age at birth (≥37 weeks, 64% [95% CI, 50%-75%]; < 37 weeks, 61% [95% CI, 4%-86%]). VE against influenza hospitalization was 67% (95% CI, 50%-78%). CONCLUSIONS: Influenza vaccination during pregnancy offers effective protection to infants <6 months, for whom vaccines are not currently available.

Effect modification by statin use status on the association between fine particulate matter (PM2.5) and cardiovascular mortality.

BACKGROUND: Numerous studies have linked fine particulate matter (PM2.5) to increased cardiovascular mortality. Less is known how the PM2.5-cardiovascular mortality association varies by use of cardiovascular medications. This study sought to quantify effect modification by statin use status on the associations between long-term exposure to PM2.5 and mortality from any cardiovascular cause, coronary heart disease (CHD), and stroke. METHODS: In this nested case-control study, we followed 1.2 million community-dwelling adults aged ≥66 years who lived in Ontario, Canada from 2000 through 2018. Cases were patients who died from the three causes. Each case was individually matched to up to 30 randomly selected controls using incidence density sampling. Conditional logistic regression models were used to estimate odds ratios (ORs) for the associations between PM2.5 and mortality. We evaluated the presence of effect modification considering both multiplicative (ratio of ORs) and additive scales (the relative excess risk due to interaction, RERI). RESULTS: Exposure to PM2.5 increased the risks for cardiovascular, CHD, and stroke mortality. For all three causes of death, compared with statin users, stronger PM2.5-mortality associations were observed among non-users [e.g. for cardiovascular mortality corresponding to each interquartile range increase in PM2.5, OR = 1.042 (95% CI, 1.032-1.053) vs OR = 1.009 (95% CI, 0.996-1.022) in users, ratio of ORs = 1.033 (95% CI, 1.019-1.047), RERI = 0.039 (95% CI, 0.025-0.050)]. Among users, partially adherent users exhibited a higher risk of PM2.5-associated mortality than fully adherent users. CONCLUSIONS: The associations of chronic exposure to PM2.5 with cardiovascular and CHD mortality were stronger among statin non-users compared to users.

Leveraging a clinical emergency department dataset to estimate two-dose COVID-19 vaccine effectiveness and duration of protection in Canada.

BACKGROUND: During the COVID-19 pandemic, clinical care shifted toward virtual and Emergency Department care. We explored the feasibility of mRNA vaccine effectiveness (VE) estimation against SARS-CoV-2-related Emergency Department visits and hospitalizations using prospectively collected Emergency Department data. METHODS: We estimated two-dose VE using a test-negative design and data from 10 participating sites of the Canadian COVID-19 Emergency Department Rapid Response Network (CCEDRRN). We included Emergency Department patients presenting with COVID-19 symptoms and nucleic acid amplification testing for SARS-CoV-2 between July 19 and December 31, 2021. We excluded patients with unclear vaccination and one or more than 2 vaccine doses by their Emergency Department visit. RESULTS: Among 3,405 eligible patients, adjusted two-dose mRNA VE against SARS-CoV-2-related Emergency Department visits was 93.3 % (95 % CI 87.9-96.3 %) between 7-55 days, sustained over 80 % through 139 days post-vaccination. In stratified analyses, VE was similar among patients with select immune-compromising conditions, chronic kidney disease, lung disease, unstable housing, and reported illicit substance use. CONCLUSIONS: Two-dose mRNA VE against SARS-CoV-2-related Emergency Department visit was high and sustained, including among vulnerable subgroups. Compared to administrative datasets, active Emergency Department enrolment enables standardization for testing access and indication and supports separate VE assessment among special population subgroups. Compared to other active enrolment settings, Emergency Departments more consistently function during crises when alternate healthcare sectors become variably closed. TRIAL REGISTRATION: Clinicaltrials.gov, NCT0470294.

Pediatric Respiratory Syncytial Virus Hospitalizations, 2017-2023.

Importance: Respiratory syncytial virus (RSV) transmission was disrupted worldwide following the COVID-19 pandemic, and further study is required to better understand these changes. Objective: To compare observed and expected RSV hospital and intensive care unit (ICU) admission rates and characteristics of admitted children during the 2021-2022 and 2022-2023 seasons. Design, Setting, and Participants: A population-based cohort study of all children aged younger than 5 years in Ontario, Canada, July 1, 2017, through March 31, 2023, was conducted. Exposures: Individual and neighborhood-level sociodemographic and clinical characteristics were identified from administrative data, including age, palivizumab eligibility, complex medical conditions, rurality, and living in a marginalized neighborhood. Main Outcomes and Measures: The main outcome was RSV-associated hospitalization. Secondary outcomes included ICU admissions, mechanical ventilation, extracorporeal membrane oxygenation, and in-hospital death. Poisson generalized estimating equations were used to model weekly age- and sex-specific hospitalization rates and estimate expected rates in the postpandemic era; adjusted rate ratios (RRs) and 95% CIs are reported. Results: This cohort study included approximately 700 000 children per study year. Compared with prepandemic years (2017-2018, 2018-2019, and 2019-2020), the 2021-2022 RSV season peaked slightly earlier, but overall admission rates were comparable (289.1 vs 281.4-334.6 per 100 000, or approximately 2000 admissions). The 2022-2023 season peaked a month earlier and resulted in more than twice as many hospitalizations (770.0 per 100 000; n = 4977 admissions). The proportion of children admitted to an ICU in 2022-2023 (13.9%) was slightly higher than prepandemic (9.6%-11.4%); however, the population-based rate was triple the prepandemic levels (106.9 vs 27.6-36.6 per 100 000 children in Ontario). With the exception of palivizumab-eligible children, all sociodemographic and health status characteristics were associated with lower-than-expected RSV hospitalization rates in 2021-2022. In contrast, older age of patients was associated with higher-than-expected rates in 2022-2023 (ie, 24-59 months: RR, 1.90; 95% CI, 1.35-2.66). Conclusions and Relevance: There were notable differences in RSV epidemiologic characteristics in Ontario following the COVID-19 pandemic. It is not yet clear whether and how long atypical RSV epidemics may persist. Clinicians and program planners should consider the potential for ongoing impacts to health care capacity and RSV immunization programs.

Consensus recommendations for the use of novel antiretrovirals in persons with HIV who are heavily treatment-experienced and/or have multidrug-resistant HIV-1: Endorsed by the American Academy of HIV Medicine, American College of Clinical Pharmacy: An executive summary.

Treatment options are currently limited for persons with HIV-1 (PWH) who are heavily treatment-experienced and/or have multidrug-resistant HIV-1. Three agents have been approved by the U.S. Food and Drug Administration (FDA) since 2018, representing a significant advancement for this population: ibalizumab, fostemsavir, and lenacapavir. However, there is a paucity of recommendations endorsed by national and international guidelines describing the optimal use (e.g., selection and monitoring after initiation) of these novel antiretrovirals in this population. To address this gap, a modified Delphi technique was used to develop these consensus recommendations that establish a framework for initiating and managing ibalizumab, fostemsavir, or lenacapavir in PWH who are heavily treatment-experienced and/or have multidrug-resistant HIV-1. In addition, future areas of research are also identified and discussed in the main document.

Consensus recommendations for the use of novel antiretrovirals in persons with HIV who are heavily treatment-experienced and/or have multidrug-resistant HIV-1: Endorsed by the American Academy of HIV Medicine, American College of Clinical Pharmacy.

Treatment options are currently limited for persons with HIV-1 (PWH) who are heavily treatment-experienced and/or have multidrug-resistant HIV-1. Three agents have been approved by the U.S. Food and Drug Administration (FDA) since 2018, representing a significant advancement for this population: ibalizumab, fostemsavir, and lenacapavir. However, there is a paucity of recommendations endorsed by national and international guidelines describing the optimal use (e.g., selection and monitoring after initiation) of these novel antiretrovirals in this population. To address this gap, a modified Delphi technique was used to develop these consensus recommendations that establish a framework for initiating and managing ibalizumab, fostemsavir, or lenacapavir in PWH who are heavily treatment-experienced and/or have multidrug-resistant HIV-1. In addition, future areas of research are also identified and discussed.

COVID-19 vaccination safety and associated health care utilization among adults with inflammatory bowel disease - a population-based self-controlled case series analysis.

BACKGROUND AND AIMS: There is an incomplete understanding of the full safety profiles of repeated COVID-19 vaccinations in patients with inflammatory bowel disease (IBD). Among individuals with IBD, we assessed whether COVID-19 vaccines were associated with serious adverse events of special interest (AESI) and health care utilization [all-cause hospitalizations, Emergency Department (ED) visits, gastroenterology visits, IBD-related visits]. METHODS: Using comprehensive administrative health data from Ontario, Canada, adults with IBD who received at least one COVID-19 vaccine from December 2020-January 2022 were included. Self-controlled case series analyses were conducted to evaluate the relative incidence rates of AESI and health care utilization outcomes across post-vaccination risk and control periods. RESULTS: Among 88,407 IBD patients, 99.7% received mRNA vaccines and 75.9% received ≥ 3 doses. Relative to control periods, we did not detect an increase in AESI. IBD patients had fewer all-cause hospitalizations during post-vaccination risk periods. Patients experienced more all-cause ED visits after dose 2 [Relative Incidence (RI):1.08(95%CI:1.04-1.12)] but fewer visits after doses 3 [RI:0.85 (95%CI:0.81-0.90)] and 4 [RI:0.73 (95%CI:0.57-0.92)]. There was no increase in gastroenterologist visits or IBD-related health care utilization post-vaccination. There were fewer IBD-related hospitalizations after dose 1 [RI:0.84 (95%CI:0.72-0.98)] and 3 [RI:0.63 (95%CI:0.52-0.76)], fewer IBD-related ED visits after dose 3 [RI:0.81 (95%CI:0.71-0.91)] and 4 [RI:0.55 (95%CI:0.32-0.96)], and fewer outpatient visits after dose 2 [RI:0.91 (95%CI:0.90-0.93)] and 3 [RI:0.87 (95%CI:0.86-0.89)]. CONCLUSION: This population-based study did not detect increased AESI, all-cause or IBD-related health care utilization following COVID-19 vaccination, suggesting a lack of association between vaccination and increased disease activity.

The Effect of COVID-19 Vaccination on Outpatient Antibiotic Prescribing in Older Adults: A Self-Controlled Risk-Interval Study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) vaccination has been associated with reduced outpatient antibiotic prescribing among older adults with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We assessed the impact of COVID-19 vaccination on outpatient antibiotic prescribing in the broader population of older adults, regardless of SARS-CoV-2 infection status. METHODS: We included adults aged ≥65 years who received their first, second, and/or third COVID-19 vaccine dose from December 2020 to December 2022. We used a self-controlled risk-interval design and included cases who received an antibiotic prescription 2-6 weeks before vaccination (pre-vaccination or control interval) or after vaccination (post-vaccination or risk interval). We used conditional logistic regression to estimate the odds of being prescribed (1) any antibiotic, (2) a typical "respiratory" infection antibiotic, or (3) a typical "urinary tract" infection antibiotic (negative control) in the post-vaccination interval versus the pre-vaccination interval. We accounted for temporal changes in antibiotic prescribing using background monthly antibiotic prescribing counts. RESULTS: 469 923 vaccine doses met inclusion criteria. The odds of receiving any antibiotic or a respiratory antibiotic prescription were lower in the post-vaccination versus pre-vaccination interval (aOR, .973; 95% CI, .968-.978; aOR, .961; 95% CI, .953-.968, respectively). There was no association between vaccination and urinary antibiotic prescriptions (aOR, .996; 95% CI, .987-1.006). Periods with high (>10%) versus low (<5%) SARS-CoV-2 test positivity demonstrated greater reductions in antibiotic prescribing (aOR, .875; 95% CI, .845-.905; aOR, .996; 95% CI, .989-1.003, respectively). CONCLUSIONS: COVID-19 vaccination was associated with reduced outpatient antibiotic prescribing in older adults, especially during periods of high SARS-CoV-2 circulation.

Characteristics of primary care practices by proportion of patients unvaccinated against SARS-CoV-2: a cross-sectional cohort study.

BACKGROUND: Variations in primary care practices may explain some differences in health outcomes during the COVID-19 pandemic. We sought to evaluate the characteristics of primary care practices by the proportion of patients unvaccinated against SARS-CoV-2. METHODS: We conducted a population-based, cross-sectional cohort study using linked administrative data sets in Ontario, Canada. We calculated the percentage of patients unvaccinated against SARS-CoV-2 enrolled with each comprehensive-care family physician, ranked physicians according to the proportion of patients unvaccinated, and identified physicians in the top 10% (v. the other 90%). We compared characteristics of family physicians and their patients in these 2 groups using standardized differences. RESULTS: We analyzed 9060 family physicians with 10 837 909 enrolled patients. Family physicians with the largest proportion (top 10%) of unvaccinated patients (n = 906) were more likely to be male, to have trained outside of Canada, to be older, and to work in an enhanced fee-for-service model than those in the remaining 90%. Vaccine coverage (≥ 2 doses of SARS-CoV-2 vaccine) was 74% among patients of physicians with the largest proportion of unvaccinated patients, compared with 87% in the remaining patient population. Patients in the top 10% group tended to be younger and live in areas with higher levels of ethnic diversity and immigration and lower incomes. INTERPRETATION: Primary care practices with the largest proportion of patients unvaccinated against SARS-CoV-2 served marginalized communities and were less likely to use team-based care models. These findings can guide resource planning and help tailor interventions to integrate public health priorities within primary care practices.

Ongoing Gaps in the Hepatitis C Care Cascade during the Direct-Acting Antiviral Era in a Large Retrospective Cohort in Canada: A Population-Based Study.

To achieve hepatitis C virus (HCV) elimination, high uptake along the care cascade steps for all will be necessary. We mapped engagement with the care cascade overall and among priority groups in the post-direct-acting antivirals (DAAs) period and assessed if this changed relative to pre-DAAs. We created a population-based cohort of all reported HCV diagnoses in Quebec (1990-2018) and constructed the care cascade [antibody diagnosed, RNA tested, RNA positive, genotyped, treated, sustained virologic response (SVR)] in 2013 and 2018. Characteristics associated with RNA testing and treatment initiation were investigated using marginal logistic models via generalized estimating equations. Of the 31,439 individuals HCV-diagnosed in Quebec since 1990 and alive as of 2018, there was significant progress in engagement with the care cascade post- vs. pre-DAAs; 86% vs. 77% were RNA-tested, and 64% vs. 40% initiated treatment. As of 2018, a higher risk of not being RNA-tested or treated was observed among individuals born <1945 vs. >1965 [hazard ratio (HR); 95% CI; 1.35 (1.16-1.57)], those with material and social deprivation [1.21 (1.06-1.38)], and those with alcohol use disorder [1.21 (1.08-1.360]. Overall, non-immigrants had lower rates of RNA testing [0.76 (0.67-0.85)] and treatment initiation [0.63 (0.57-0.70)] than immigrants. As of 2018, PWID had a lower risk of not being RNA tested [0.67 (0.61-0.85)] but a similar risk of not being treated, compared to non-PWID. Engagement in the HCV care cascade have improved in the post-DAA era, but inequities remain. Vulnerable subgroups, including certain older immigrants, were less likely to have received RNA testing or treatment as of 2018 and would benefit from focused interventions to strengthen these steps.

Validation of case-ascertainment algorithms using health administrative data to identify people who inject drugs in Ontario, Canada.

OBJECTIVES: Health administrative data can be used to improve the health of people who inject drugs by informing public health surveillance and program planning, monitoring, and evaluation. However, methodological gaps in the use of these data persist due to challenges in accurately identifying injection drug use (IDU) at the population level. In this study, we validated case-ascertainment algorithms for identifying people who inject drugs using health administrative data in Ontario, Canada. STUDY DESIGN AND SETTING: Data from cohorts of people with recent (past 12 months) IDU, including those participating in community-based research studies or seeking drug treatment, were linked to health administrative data in Ontario from 1992 to 2020. We assessed the validity of algorithms to identify IDU over varying look-back periods (ie, all years of data [1992 onwards] or within the past 1-5 years), including inpatient and outpatient physician billing claims for drug use, emergency department (ED) visits or hospitalizations for drug use or injection-related infections, and opioid agonist treatment (OAT). RESULTS: Algorithms were validated using data from 15,241 people with recent IDU (918 in community cohorts and 14,323 seeking drug treatment). An algorithm consisting of ≥1 physician visit, ED visit, or hospitalization for drug use, or OAT record could effectively identify IDU history (91.6% sensitivity and 94.2% specificity) and recent IDU (using 3-year look back: 80.4% sensitivity, 99% specificity) among community cohorts. Algorithms were generally more sensitive among people who inject drugs seeking drug treatment. CONCLUSION: Validated algorithms using health administrative data performed well in identifying people who inject drugs. Despite their high sensitivity and specificity, the positive predictive value of these algorithms will vary depending on the underlying prevalence of IDU in the population in which they are applied.

Hepatitis C Attributable Healthcare Costs and Mortality among Immigrants: A Population-Based Matched Cohort Study.

Background: Data on the economic burden of chronic hepatitis C (CHC) among immigrants are limited. Our objective was to estimate the CHC-attributable mortality and healthcare costs among immigrants in Ontario, Canada. Methods: We conducted a population-based matched cohort study among immigrants diagnosed with CHC between May 31, 2003, and December 31, 2018, using linked health administrative data. Immigrants with CHC (exposed) were matched 1 : 1 to immigrants without CHC (unexposed) using a combination of hard (index date, sex, and age) and propensity-score matching. Net costs (2020 Canadian dollars) collected from the healthcare payer perspective were calculated using a phase-of-care approach and used to estimate long-term costs adjusted for survival. Results: We matched 5,575 exposed individuals with unexposed controls, achieving a balanced match. The mean age was 47 years, and 52% was male. On average, 10.5% of exposed and 3.5% of unexposed individuals died 15 years postindex (relative risk = 2.9; 95% confidence interval (CI): 2.6-3.5). The net 30-day costs per person were $88 (95% CI: 55 to 122) for the prediagnosis, $324 (95% CI: 291 to 356) for the initial phase, $1,016 (95% CI: 900 to 1,132) for the late phase, and $975 (95% CI: -25 to 1,974) for the terminal phase. The mean net healthcare cost adjusted for survival at 15 years was $90,448. Conclusions: Compared to unexposed immigrants, immigrants infected with CHC have higher mortality rates and greater healthcare costs. These findings will support the planning of HCV elimination efforts among key risk groups in the province.