Uptake of COVID-19 vaccination among community-dwelling individuals receiving healthcare for substance use disorder and major mental illness: a matched retrospective cohort study.

Introduction: Patients with major mental illness (MMI) and substance use disorders (SUD) face barriers in accessing healthcare. In this population-based retrospective cohort study, we investigated the uptake of COVID-19 vaccination in Ontario, Canada among community-dwelling individuals receiving healthcare for major mental illness (MMI) and/or substance use disorders (SUD), comparing them to matched general population controls. Methods: Using linked health administrative data, we identified 337,290 individuals receiving healthcare for MMI and/or SUD as of 14 December 2020, matched by age, sex, and residential geography to controls without such healthcare. Follow-up extended until 31 December 2022 to document vaccination events. Results: Overall, individuals receiving healthcare for MMI and/or SUD (N = 337,290) had a slightly lower uptake of first (cumulative incidence 82.45% vs. 86.44%; hazard ratio [HR] 0.83 [95% CI 0.82-0.83]) and second dose (78.82% vs. 84.93%; HR 0.77 [95% CI 0.77-0.78]) compared to matched controls. Individuals receiving healthcare for MMI only (n = 146,399) had a similar uptake of first (87.96% vs. 87.59%; HR 0.97 [95% CI 0.96-0.98]) and second dose (86.09% vs. 86.05%, HR 0.94 [95% CI 0.93-0.95]). By contrast, individuals receiving healthcare for SUD only (n = 156,785) or MMI and SUD (n = 34,106) had significantly lower uptake of the first (SUD 78.14% vs. 85.74%; HR 0.73 [95% CI 0.72-0.73]; MMI & SUD 78.43% vs. 84.74%; HR 0.76 [95% CI 0.75-0.77]) and second doses (SUD 73.12% vs. 84.17%; HR 0.66 [95% CI 0.65-0.66]; MMI & SUD 73.48% vs. 82.93%; HR 0.68 [95% CI 0.67-0.69]). Discussion: These findings suggest that effective strategies to increase vaccination uptake for future COVID-19 and other emerging infectious diseases among community-dwelling people with SUD are needed.

Premature Acute Myocardial Infarction Treated With Invasive Revascularization: Comparing STEMI With NSTEMI in a Population-Based Study of Young Patients.

BACKGROUND: Acute myocardial infarction (AMI) usually presents in older populations, in which there are established demographic and outcome differences for ST-elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI). No similar comparisons for AMI in the young population exist. METHODS: We compared all index NSTEMI and STEMI hospitalizations in young (18-45 years) patients who required revascularization in Alberta, Canada. Outcomes were survival to discharge, and a composite of heart failure hospitalization, cardiac arrest hospitalization, and all-cause mortality at 1 and 5 years. RESULTS: There were 1679 patients included with an index AMI who required revascularization: 655 (39.0%) NSTEMI and 1024 (61.0%) STEMI. The population was disproportionately male (86%), particularly in STEMI patients (87.3%). Marked dyslipidemia (35%) and active smoking (42%) were common, with similar rates among groups. Percutaneous coronary intervention was used in 98.7% of STEMI and 91.5% of NSTEMI patients (P < 0.001), with the remainder who underwent surgical revascularization. The in-hospital mortality rate during index AMI was higher in STEMI compared with NSTEMI patients (1.7% vs 0%; P < 0.001). The rates of the composite outcome were similar for both groups at 1 and 5 years of follow-up in patients who survived to index hospital discharge. After adjusting for sex, age, heart failure and/or cardiac arrest at index AMI, outcomes remained similar among groups at 1 and 5 years. CONCLUSIONS: In young patients with AMI, STEMI was a disproportionately male phenomenon and associated with higher mortality at index hospitalization. One-year and 5-year outcomes were similar among STEMI and NSTEMI patients in those discharged alive at index AMI. Smoking and dyslipidemia appear to be major risk factors in the young.

Alzheimer's disease associated isoforms of human CD33 distinctively modulate microglial cell responses in 5XFAD mice.

Microglia play diverse pathophysiological roles in Alzheimer's disease (AD), with genetic susceptibility factors skewing microglial cell function to influence AD risk. CD33 is an immunomodulatory receptor associated with AD susceptibility through a single nucleotide polymorphism that modulates mRNA splicing, skewing protein expression from a long protein isoform (CD33M) to a short isoform (CD33m). Understanding how human CD33 isoforms differentially impact microglial cell function in vivo has been challenging due to functional divergence of CD33 between mice and humans. We address this challenge by studying transgenic mice expressing either of the human CD33 isoforms crossed with the 5XFAD mouse model of amyloidosis and find that human CD33 isoforms have opposing effects on the response of microglia to amyloid-ß (Aß) deposition. Mice expressing CD33M have increased Aß levels, more diffuse plaques, fewer disease-associated microglia, and more dystrophic neurites compared to 5XFAD control mice. Conversely, CD33m promotes plaque compaction and microglia-plaque contacts, and minimizes neuritic plaque pathology, highlighting an AD protective role for this isoform. Protective phenotypes driven by CD33m are detected at an earlier timepoint compared to the more aggressive pathology in CD33M mice that appears at a later timepoint, suggesting that CD33m has a more prominent impact on microglia cell function at earlier stages of disease progression. In addition to divergent roles in modulating phagocytosis, scRNAseq and proteomics analyses demonstrate that CD33m+ microglia upregulate nestin, an intermediate filament involved in cell migration, at plaque contact sites. Overall, our work provides new functional insights into how CD33, as a top genetic susceptibility factor for AD, modulates microglial cell function.