COVID-19 vaccine effectiveness among South Asians in Canada.

We evaluated the effectiveness of COVID-19 vaccines among South Asians living in Ontario, Canada compared to non-South Asians and compared the odds of symptomatic COVID-19 infection and related hospitalizations and deaths among non-vaccinated South Asians and non-South Asians. This was a test negative design study conducted in Ontario, Canada between December 14, 2020 and November 15, 2021. All eligible individuals >18 years with symptoms of COVID-19 were subdivided by ethnicity (South Asian vs other) and vaccination status (vaccinated versus not). The primary outcome was vaccine effectiveness as defined by COVID-19 infections, hospitalizations, and deaths, and secondary outcome was the odds of COVID-19 infections, hospitalizations, and death comparing non-vaccinated South Asians to non-vaccinated non-South Asians. 883,155 individuals were included. Among South Asians, two doses of COVID-19 vaccine prevented 93.8% (95% CI 93.2, 94.4) of COVID-19 infections and 97.5% (95% CI 95.2, 98.6) of hospitalizations and deaths. Among non-South Asians, vaccines prevented 86.6% (CI 86.3, 86.9) of COVID-19 infections and 93.1% (CI 92.2, 93.8) of hospitalizations and deaths. Non-vaccinated South Asians had higher odds of symptomatic SARS-CoV-2 infection compared to non-vaccinated non-South Asians (OR 2.35, 95% CI 2.3, 2.4), regardless of their immigration status. COVID-19 vaccines are effective in preventing infections, hospitalizations and deaths among South Asians living in Canada. The observation that non-vaccinated South Asians have higher odds of symptomatic COVID-19 infection warrants further investigation.

Low-Dose Rivaroxaban Plus Aspirin in Fragile Patients After Lower Extremity Revascularization.

BACKGROUND: Rivaroxaban 2.5 mg plus aspirin reduced limb and cardiovascular events and increased bleeding in patients with symptomatic peripheral artery disease (PAD) after lower extremity revascularization in the VOYAGER PAD (Efficacy and Safety of Rivaroxaban in Reducing the Risk of Major Thrombotic Vascular Events in Subjects With Symptomatic Peripheral Artery Disease Undergoing Peripheral Revascularization Procedures of the Lower Extremities) study. Fragile patients are at heightened risk for ischemic and bleeding events. OBJECTIVES: The purpose of this study was to investigate the safety and efficacy of rivaroxaban 2.5 mg in fragile patients from VOYAGER PAD. METHODS: Patients were categorized as fragile based on prespecified criteria (age >75 years, weight ≤50 kg, or baseline estimated glomerular filtration rate <50 mL/min/1.73 m2). The primary efficacy outcome was the composite of acute limb ischemia, major amputation of a vascular etiology, myocardial infarction, ischemic stroke, or cardiovascular death. The principal safety outcome was TIMI major bleeding. RESULTS: Of 6,564 randomized patients, a total of 1,674 subjects were categorized as fragile at baseline. In the placebo arm, fragile patients were at higher risk of the primary outcome (HR: 1.34; 95% CI: 1.12-1.61) and TIMI major bleeding (HR: 1.57; 95% CI: 0.83-2.96), compared with nonfragile patients. The effect of rivaroxaban on the primary endpoint was not modified by frailty status (fragile HR: 0.93; 95% CI: 0.75-1.15; nonfragile HR: 0.83; 95% CI: 0.72-0.97; P interaction = 0.37). Rivaroxaban increased TIMI major bleeding in fragile (HR: 1.54; 95% CI: 0.82-2.91) and nonfragile patients (HR: 1.37; 95% CI: 0.84-2.23; P interaction = 0.65). CONCLUSIONS: Patients with PAD after lower extremity revascularization meeting fragile criteria are at higher risk of ischemic complications and bleeding. Rivaroxaban reduces ischemic risk and increases bleeding regardless of frailty status. These data may assist in personalization of antithrombotic therapy in fragile population.

Rivaroxaban for Patients with Intermittent Claudication.

BACKGROUND: The combination of rivaroxaban plus aspirin compared with aspirin alone reduces the risk of major adverse cardiovascular and limb events for high-risk patients with peripheral artery disease. It is unknown whether rivaroxaban plus aspirin improves intermittent claudication for adults with lower-risk peripheral arterial disease. METHODS: In this randomized, open-label, multicenter, 24-week clinical trial, we randomly assigned patients with peripheral artery disease and intermittent claudication to receive either 2.5 mg of rivaroxaban twice daily plus 100 mg of aspirin once daily or 100 mg of aspirin once daily. The primary outcome was a 24-week change in total walking distance, measured by the 6-minute walking test. The primary safety outcome was the incidence of major bleeding or clinically relevant nonmajor bleeding. RESULTS: Eighty-eight patients were randomly assigned to either rivaroxaban plus aspirin (n=46) or aspirin alone (n=42). The mean age was 67 years, and 54% were female. The total walking distance measured by 6-minute walk test improved by 89 ± 18 m (mean±standard error) in the rivaroxaban-plus-aspirin group versus 21 ± 16 m in the aspirin-alone group. This corresponded to an absolute difference of 68 ± 24 m (95% confidence interval [CI], 19 to 116 m; P=0.007) and a relative improvement over the aspirin-alone group of 327% (95% CI, 94 to 560%). No major bleeding events were observed in either group. CONCLUSIONS: In patients with peripheral artery disease and intermittent claudication, 2.5 mg of rivaroxaban twice daily plus 100 mg of aspirin daily improved the total walking distance by a 6-minute walking test compared with 100 mg of aspirin daily alone. (Funded by Bayer S.A.; Clinicaltrials.gov number, NCT04853719.).

Maternal smoking DNA methylation risk score associated with health outcomes in offspring of European and South Asian ancestry.

Background: Maternal smoking has been linked to adverse health outcomes in newborns but the extent to which it impacts newborn health has not been quantified through an aggregated cord blood DNA methylation (DNAm) score. Here, we examine the feasibility of using cord blood DNAm scores leveraging large external studies as discovery samples to capture the epigenetic signature of maternal smoking and its influence on newborns in White European and South Asian populations. Methods: We first examined the association between individual CpGs and cigarette smoking during pregnancy, and smoking exposure in two White European birth cohorts (n=744). Leveraging established CpGs for maternal smoking, we constructed a cord blood epigenetic score of maternal smoking that was validated in one of the European-origin cohorts (n=347). This score was then tested for association with smoking status, secondary smoking exposure during pregnancy, and health outcomes in offspring measured after birth in an independent White European (n=397) and a South Asian birth cohort (n=504). Results: Several previously reported genes for maternal smoking were supported, with the strongest and most consistent association signal from the GFI1 gene (6 CpGs with p<5 × 10-5). The epigenetic maternal smoking score was strongly associated with smoking status during pregnancy (OR = 1.09 [1.07, 1.10], p=5.5 × 10-33) and more hours of self-reported smoking exposure per week (1.93 [1.27, 2.58], p=7.8 × 10-9) in White Europeans. However, it was not associated with self-reported exposure (p>0.05) among South Asians, likely due to a lack of smoking in this group. The same score was consistently associated with a smaller birth size (-0.37±0.12 cm, p=0.0023) in the South Asian cohort and a lower birth weight (-0.043±0.013 kg, p=0.0011) in the combined cohorts. Conclusions: This cord blood epigenetic score can help identify babies exposed to maternal smoking and assess its long-term impact on growth. Notably, these results indicate a consistent association between the DNAm signature of maternal smoking and a small body size and low birth weight in newborns, in both White European mothers who exhibited some amount of smoking and in South Asian mothers who themselves were not active smokers. Funding: This study was funded by the Canadian Institutes of Health Research Metabolomics Team Grant: MWG-146332.

A single dose of radiation elicits comparable acute salivary gland injury to fractionated radiation.

The salivary glands are often damaged during head and neck cancer radiotherapy. This results in chronic dry mouth, which adversely affects quality of life and for which there is no long-term cure. Mouse models of salivary gland injury are routinely used in regenerative research. However, there is no clear consensus on the radiation regime required to cause injury. Here, we analysed three regimes of γ-irradiation of the submandibular salivary gland. Transcriptional analysis, immunofluorescence and flow cytometry was used to profile DNA damage, gland architecture and immune cell changes 3 days after single doses of 10 or 15 Gy or three doses of 5 Gy. Irrespective of the regime, radiation induced comparable levels of DNA damage, cell cycle arrest, loss of glandular architecture, increased pro-inflammatory cytokines and a reduction in tissue-resident macrophages, relative to those observed in non-irradiated submandibular glands. Given these data, coupled with the fact that repeated anaesthetic can negatively affect animal welfare and interfere with saliva secretion, we conclude that a single dose of 10 Gy irradiation is the most refined method of inducing acute salivary gland injury in a mouse model.

Effect of Peripheral Interventions in Patients with Peripheral Artery Disease Receiving Rivaroxaban and Aspirin: Analyses from the XATOA Registry.

OBJECTIVE: To assess the characteristics and clinical outcomes of patients with lower extremity peripheral artery disease (PAD) in XATOA receiving dual pathway inhibition (DPI) with rivaroxaban 2.5 mg twice daily plus aspirin according to lower extremity revascularisation (LER) history. METHODS: XATOA is an international, multicentre, prospective, single arm registry study. This subanalysis investigated patients with lower extremity PAD according to LER history. Patients with coronary artery disease, PAD, or both, receiving DPI were followed for 12 or more months. Baseline characteristics and clinical outcomes were assessed according to LER history. A time dependency analysis assessed outcomes by time between the most recent LER procedure and the start of DPI. A multivariate analysis assessed the influence of patient characteristics on clinical outcomes. RESULTS: In XATOA (n = 5 532), 2 820 (51.0%) patients had lower extremity PAD, of whom 1 736 (61.6%) had prior LER and 1 084 (38.4%) had no prior LER. Baseline characteristics were generally similar between patients with or without prior LER. A higher proportion of patients with prior LER experienced any treatment emergent clinical events compared with those without prior LER (15.0% vs. 9.4%, respectively), with greater differences observed between incidence rates of limb events, including major adverse limb events (9.06 vs. 4.09 events per 100 patient years, respectively). Similar rates of myocardial infarction, stroke, and major bleeding were observed in both subgroups. Clinical event rates were generally higher in patients who had previous LER for six months or less compared with patients who had previous LET for more than six months before starting DPI, regardless of LER type. Multivariate analyses showed that prior LER was predictive of limb events. CONCLUSION: This subanalysis of XATOA found that prior LER was associated with increased rates of limb events, consistent with results of COMPASS and VOYAGER PAD. Rates of bleeding were also low regardless of LER history and consistent with the findings from these trials.

Therapeutic Role of Nusinersen on Respiratory Progression in Pediatric Patients With Spinal Muscular Atrophy Type 2 and Nonambulant Type 3.

Background and Objectives: Nusinersen has shown significant functional motor benefit in the milder types of spinal muscular atrophy (SMA). Less is known on the respiratory outcomes in patients with nusinersen-treated SMA. The aim of this study was to describe changes in respiratory function in pediatric patients with SMA type 2 and 3 on regular treatment with nusinersen within the iSMAc international cohort and to compare their trajectory with the natural history (NH) data published by the consortium in 2020. Methods: This is a 5-year retrospective observational study of pediatric SMA type 2 and nonambulant type 3 (age ≤18 years) treated with nusinersen. The primary objective was to compare the slopes of decline in forced vital capacity % predicted (FVC% pred.), FVC, and age when FVC dropped below 60% between the treated patients and a control group from the natural history cohort. Data on peak cough flow and the use of noninvasive ventilation (NIV) and cough assist were collected. Results: Data were available for 69 treated patients, 53 were SMA type 2 and 16 type 3. The mean (SD) age at first injection was 8.5 (3.2) and 9.7 (3.7) years, respectively. The median (interquartile range) treatment duration was 1 (0.7; 1.9) and 1.2 (0.9; 1.9) years, respectively. At the time of the first nusinersen injection, 24 of 52 (46%) patients with SMA type 2 and 2 of 16 (13%) patients with SMA type 3 were on NIV. Forty-three of 53 (81%) and 4 of 16 (25%) patients used cough device. FVC% pred. in treated patients with SMA type 2 declined annually by 2.3% vs 3.9% in NH (p = 0.08) and in treated patients with type 3 by 2.6% vs 3.4% NH (p = 0.59). Patients treated reached FVC <60% later than untreated (12.1 vs 10 years, p = 0.05). A higher percentage of treated vs untreated patients maintained FVC% pred. equal/above their baseline after 12 (65% vs 36%) and 24 (50% vs 24%) months, respectively. NIV use among treated did not significantly change throughout 1-year follow-up. Discussion: This study included the largest real-world cohort of pediatric patients with milder SMA types. The results suggest a positive role of nusinersen in delaying the respiratory decline in patients treated longer than 1 year when compared with natural history. Larger cohorts and longer observation are planned. Classification of Evidence: This study provided Class III evidence that nusinersen slows progression for patients with SMA types 2 and 3 compared with a natural history cohort.

Germline CDH1 Variants and Lifetime Cancer Risk.

Importance: Approximately 1% to 3% of gastric cancers and 5% of lobular breast cancers are hereditary. Loss of function CDH1 gene variants are the most common gene variants associated with hereditary diffuse gastric cancer and lobular breast cancer. Previously, the lifetime risk of gastric cancer was estimated to be approximately 25% to 83% and for breast cancer it was estimated to be approximately 39% to 55% in individuals with loss of function CDH1 gene variants. Objective: To describe gastric and breast cancer risk estimates for individuals with CDH1 variants. Design, Setting, and Participants: Multicenter, retrospective cohort and modeling study of 213 families from North America with a CDH1 pathogenic or likely pathogenic (P/LP) variant in 1 or more family members conducted between January 2021 and August 2022. Main Outcomes and Measures: Hazard ratios (HRs), defined as risk in variant carriers relative to noncarriers, were estimated for each cancer type and used to calculate cumulative risks and risks per decade of life up to age 80 years. Results: A total of 7323 individuals from 213 families were studied, including 883 with a CDH1 P/LP variant (median proband age, 53 years [IQR, 42-62]; 4% Asian; 4% Hispanic; 85% non-Hispanic White; 50% female). In individuals with a CDH1 P/LP variant, the prevalence of gastric cancer was 13.9% (123/883) and the prevalence of breast cancer among female carriers was 26.3% (144/547). The estimated HR for advanced gastric cancer was 33.5 (95% CI, 9.8-112) at age 30 years and 3.5 (95% CI, 0.4-30.3) at age 70 years. The lifetime cumulative risk of advanced gastric cancer in male and female carriers was 10.3% (95% CI, 6%-23.6%) and 6.5% (95% CI, 3.8%-15.1%), respectively. Gastric cancer risk estimates based on family history indicated that a carrier with 3 affected first-degree relatives had a penetrance of approximately 38% (95% CI, 25%-64%). The HR for breast cancer among female carriers was 5.7 (95% CI, 2.5-13.2) at age 30 years and 3.9 (95% CI, 1.1-13.7) at age 70 years. The lifetime cumulative risk of breast cancer among female carriers was 36.8% (95% CI, 25.7%-62.9%). Conclusions and Relevance: Among families from North America with germline CDH1 P/LP variants, the cumulative risk of gastric cancer was 7% to 10%, which was lower than previously described, and the cumulative risk of breast cancer among female carriers was 37%, which was similar to prior estimates. These findings inform current management of individuals with germline CDH1 variants.

Consistent cord blood DNA methylation signatures of gestational age between South Asian and white European cohorts.

BACKGROUND: Epigenetic modifications, particularly DNA methylation (DNAm) in cord blood, are an important biological marker of how external exposures during gestation can influence the in-utero environment and subsequent offspring development. Despite the recognized importance of DNAm during gestation, comparative studies to determine the consistency of these epigenetic signals across different ethnic groups are largely absent. To address this gap, we first performed epigenome-wide association studies (EWAS) of gestational age (GA) using newborn cord blood DNAm comparatively in a white European (n = 342) and a South Asian (n = 490) birth cohort living in Canada. Then, we capitalized on established cord blood epigenetic GA clocks to examine the associations between maternal exposures, offspring characteristics and epigenetic GA, as well as GA acceleration, defined as the residual difference between epigenetic and chronological GA at birth. RESULTS: Individual EWASs confirmed 1,211 and 1,543 differentially methylated CpGs previously reported to be associated with GA, in white European and South Asian cohorts, respectively, with a similar distribution of effects. We confirmed that Bohlin's cord blood GA clock was robustly correlated with GA in white Europeans (r = 0.71; p = 6.0 × 10-54) and South Asians (r = 0.66; p = 6.9 × 10-64). In both cohorts, Bohlin's clock was positively associated with newborn weight and length and negatively associated with parity, newborn female sex, and gestational diabetes. Exclusive to South Asians, the GA clock was positively associated with the newborn ponderal index, while pre-pregnancy weight and gestational weight gain were strongly predictive of increased epigenetic GA in white Europeans. Important predictors of GA acceleration included gestational diabetes mellitus, newborn sex, and parity in both cohorts. CONCLUSIONS: These results demonstrate the consistent DNAm signatures of GA and the utility of Bohlin's GA clock across the two populations. Although the overall pattern of DNAm is similar, its connections with the mother's environment and the baby's anthropometrics can differ between the two groups. Further research is needed to understand these unique relationships.

Managing greenhouse gas emissions in the terminal year of life in an overwhelmed health system: a paradigm shift for people and our planet.

Health care contributes 4·4% of global net carbon emissions. Hospitals are resource-intensive settings, using a large amount of supplies in patient care and have high energy, ventilation, and heating needs. This Viewpoint investigates emissions related to health care in a patient's last year of life. End of life (EOL) is a period when health-care use and associated emissions production increases exponentially due primarily to hospital admissions, which are often at odds with patients' values and preferences. Potential solutions detailed within this Viewpoint are facilitating advanced care plans with patients to ensure their EOL wishes are clear, beginning palliative care interventions earlier when treating a life-limiting illness, deprescribing unnecessary medications because medications and their supply chains make up a significant portion of health-care emissions, and, enhancing access to low-intensity community care settings (eg, hospices) within the last year of life if home care is not available. Our analysis was done using Canadian data, but the findings can be applied to other high-income countries.

Effect of Milk-Feeding Frequency and Calcium Gluconate Supplementation on Growth, Health, and Reproductive and Metabolic Features of Holstein Heifers at a Rearing Farm.

We compared the effects of milk-feeding in 288 Holstein calves (72 per group) which were fed twice (2F) or thrice (3F) daily, with or without the addition of hydrogenated fat-embedded calcium gluconate (G) supplemented in the starter food and in the daily diet up to the age of 9 months, on the calves' metabolism, growth, health, and reproductive efficiency up to first pregnancy. The calves received 6 L of milk replacer (130 g/L) and had ad libitum access to water and textured calf starter with or without gluconate. Gluconate supplementation promoted a "catch-up" in growth in supplemented calves compared to their counterparts that did not receive gluconate. Gluconate appeared to reduce animal metabolic stress during key events, such as weaning and transfer into open-door pens, reducing fructosamine (352.61 vs. 303.06 in 3FG and 3F, respectively; p = 0.028) and urea (3F revealed the highest values compared with the other three groups: 19.06 for 3F vs. 13.9 (2F), 13.7 (2FG), and 14.3 (3FG), respectively, p = 0.002) from weaning onwards. The feeding of dairy calves with milk replacer three rather than two times per day tended to be associated with better health from weaning to 4 months old; parameters such as ultrasound lung score and calf health score improved over time (p < 0.001). Thrice-daily feeding with milk replacer tended to reduce the number of artificial inseminations per pregnancy in heifers by 0.2 points (p = 0.092). We confirmed significant correlations between early health and growth parameters and reproductive efficiency and a positive correlation between body weight and average daily weight gain and the thickness of the back fat layer in young heifers (r = 0.245; p < 0.0001; r = 0.214; p < 0.0001 respectively). Our study was conducted on a commercial farm with reasonably effective animal management, so baseline welfare was likely satisfactory.

Understanding the impact of maternal and infant nutrition on infant/child health: multiethnic considerations, knowledge translation, and future directions for equitable health research.

A mother's intrauterine environment influences her health and that of her offspring, at birth and in the future. Herein, we present an overview of our Canadian Institutes of Health Research (CIHR)-funded grant "Understanding the impact of maternal and infant nutrition on infant/child health"-set within The NutriGen Birth Cohort Alliance. NutriGen is a consortium of four Canadian prospective birth cohorts representing >5000 mother-child pairs of diverse ethnic groups including South Asians, White Europeans, and Indigenous peoples. We summarize our objectives and main findings on outcomes of maternal diet, gestational diabetes, birth weight, cardiometabolic health, the microbiome, and epigenetic modifications. We append this work with 10 key messages when conducting multiethnic research and review our knowledge translation products. We describe the clinical impact of our research on maternal and child health and conclude with future directions on biomarker discovery, expansion to other ethnic groups, and interventions for high-risk populations.

The association of red and processed meat with gestational diabetes mellitus: Results from 2 Canadian birth cohort studies.

OBJECTIVE: Red and processed meat is considered risk factors of gestational diabetes mellitus (GDM), but the evidence is inconclusive. We aimed to examine the association between red and processed meat intake and odds of GDM among South Asian and White European women living in Canada. METHODS: This is a cross-sectional analysis of pregnant women from two birth cohorts: SouTh Asian biRth cohorT (START; n = 976) and Family Atherosclerosis Monitoring In earLY life (FAMILY; n = 581). Dietary intake was assessed using a validated 169-item semi-quantitative food-frequency questionnaire (FFQ). Multivariate logistic regression models were used to examine the associations between gestational diabetes and: 1) total red and processed meat; 2) unprocessed red meat; 3) processed meat and GDM after adjustment for potential confounders. RESULTS: There were 241 GDM cases in START and 91 in FAMILY. The median total red and processed meat intake were 1.5 g/d (START) and 52.8 g/d (FAMILY). In START, the multivariable-adjusted odds ratio (OR) showed neither lower nor higher intakes of unprocessed red meat (p-trend = 0.68), processed meat (p-trend = 0.90), or total red and processed meat (p-trend = 0.44), were associated with increased odds of GDM, when compared with medium intake. Similar results were observed in FAMILY except for processed meat intake [OR = 0.94 (95% CI 0.47-1.91), for medium versus low and OR = 1.51 (95% CI 0.77-2.29) for medium versus high; p-trend = 0.18] after adjusting for additional dietary factors such as the diet quality score, total fiber, saturated fat and glycemic load. CONCLUSION: Medium compared with low or high red and processed meat intake is not associated with GDM in White Europeans and South Asians living in Canada.

Sociodemographic factors associated with vaccine hesitancy in the South Asian community in Canada.

OBJECTIVE: South Asians represent the largest non-white ethnic group in Canada and were disproportionately impacted by the COVID-19 pandemic. We sought to determine the factors associated with vaccine hesitancy in South Asian Canadians. METHODS: We conducted a cross-sectional analysis of vaccine hesitancy using data collected at the baseline assessment of a prospective cohort study, COVID CommUNITY South Asian. Participants (18 + years) were recruited from the Greater Toronto and Hamilton Area in Ontario (ON) and the Greater Vancouver Area in British Columbia (BC) between April and November 2021. Demographic characteristics and vaccine attitudes measured by the Vaccine Attitudes Examination (VAX) scale were collected. Each item is scored on a 6-point Likert scale, and higher scores reflect greater hesitancy. A multivariable linear mixed effects model was used to identify sociodemographic factors associated with vaccine hesitancy, adjusting for multiple covariates. RESULTS: A total of 1496 self-identified South Asians (52% female) were analyzed (mean age = 38.5 years; standard deviation (SD): 15.3). The mean VAX score was 3.2, SD: 0.8 [range: 1.0‒6.0]. Factors associated with vaccine hesitancy included: time since immigration (p = 0.04), previous COVID-19 infection (p < 0.001), marital status (p < 0.001), living in a multigenerational household (p = 0.03), age (p = 0.02), education (p < 0.001), and employment status (p = 0.001). CONCLUSION: Among South Asians living in ON and BC, time since immigration, prior COVID-19 infection, marital status, living in a multigenerational household, age, education, and employment status were associated with vaccine hesitancy. This information can be used to address vaccine hesitancy in the South Asian population in future COVID-19 waves or pandemics.

RéSUMé: OBJECTIF: Les Asiatiques du Sud, qui représentent le plus grand groupe ethnique non-blanc au Canada, ont été démesurément touchés par la pandémie de COVID-19. Nous avons cherché à déterminer les facteurs associés à l'hésitation vaccinale chez les Canadiennes et les Canadiens asiatiques du Sud. MéTHODE: Nous avons mené une analyse transversale de l'hésitation vaccinale à l'aide des données collectées durant l'évaluation préliminaire d'une étude de cohorte prospective du nom de COVID CommUNITY South Asian. Les personnes participantes (18 ans et plus) ont été recrutées dans la région du grand Toronto et de Hamilton, en Ontario, et dans la région du Grand Vancouver, en Colombie-Britannique, entre avril et novembre 2021. Le profil démographique et les attitudes face aux vaccins, mesurées selon l'échelle Vaccine Attitudes Examination (VAX), ont été obtenus. Chaque élément a été noté selon une échelle de Likert en 6 points (plus la note est élevée, plus l'hésitation vaccinale est importante). Un modèle linéaire multivarié à effets mixtes a servi à identifier les facteurs sociodémographiques associés à l'hésitation vaccinale, en rajustant les données pour tenir compte de plusieurs covariables. RéSULTATS: En tout, 1 496 personnes s'identifiant comme étant Asiatiques du Sud (dont 52 % de femmes) ont été analysées (âge moyen = 38,5 ans; écart-type [S] : 15,3). La note VAX moyenne était de 3,2, S : 0,8 [intervalle : 1,0‒6,0]. Les facteurs associés à l'hésitation vaccinale étaient : le temps écoulé depuis l'immigration (p = 0,04), une infection antérieure par la COVID-19 (p < 0,001), l'état matrimonial (p < 0,001), le fait de vivre dans un ménage multigénérationnel (p = 0,03), l'âge (p = 0,02), l'instruction (p < 0,001) et la situation d'emploi (p = 0,001). CONCLUSION: Chez les Asiatiques du Sud vivant en Ontario et en Colombie-Britannique, le temps écoulé depuis l'immigration, une infection antérieure par la COVID-19, l'état matrimonial, le fait de vivre dans un ménage multigénérationnel, l'âge, l'instruction et la situation d'emploi étaient associés à l'hésitation vaccinale. Ces informations peuvent être utilisées pour aborder l'hésitation vaccinale dans la population asiatique du Sud lors de vagues de COVID-19 ou de pandémies futures.

COVID-19 is associated with early emergence of preeclampsia: results from a large regional collaborative.

Objective: To investigate the relationship between preeclampsia and SARS-CoV-2 infection during pregnancy. Methods: This was a retrospective cohort study of pregnant women between March and October 2020. Pregnant patients admitted to 14 obstetrical centers in Michigan, USA formed the study population. Of the N = 1458 participants, 369 had SARS-CoV-2 infection (cases). Controls were uninfected pregnancies that were delivered in the same obstetric unit within 30 days of the index case. Robust Poisson regression was used to estimate relative risk (RR) of preterm and term preeclampsia and preeclampsia involving placental lesions. The analysis included adjustment for relevant clinical and demographic risk factors.Results: SARS-CoV-2 infection during pregnancy increased the risk of preeclampsia [adjusted aRR = 1.69 (1.26-2.26)], preeclampsia involving placental lesions [aRR = 1.97(1.14-3.4)] and preterm preeclampsia 2.48(1.48-4.17). Although the highest rate of preeclampsia was observed in patients infected with SARS-CoV-2 who were symptomatic (18.4%), there was increased risk even in asymptomatic SARS-CoV-2 infected patients (14.2%) relative to non-infected controls (8.7%) (p < 0.05). This association with symptomatology was also noted with preterm preeclampsia for which the rate doubled from 2.7% in controls to 5.2% in asymptomatic cases and reached 11.8% among symptomatic cases (p < 0.05). The rate of preterm preeclampsia among cases of pregnant people self-identified as Black reached 10.1% and was almost double the rate of the reminder of the group of infected pregnancies (5.3%), although the rate among uninfected was almost the same (2.7%) for both Black and non-Black groups (interaction p = 0.05).Conclusions: Infection with SARS-CoV-2 increases the risk of preeclampsia even in the absence of symptoms, although symptomatic persons are at even higher risk. Racial disparities in the development of preterm preeclampsia after SARS-CoV-2 infection may explain discrepancies in prematurity between different populations.

The role of family history in predicting germline pathogenic variant carriers who develop pancreatic cancer: Results of a multicenter collaboration.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) surveillance is recommended for some individuals with a pathogenic or likely pathogenic variant (PV/LPV) in a PDAC susceptibility gene; the recommendation is often dependent on family history of PDAC. This study aimed to describe PDAC family history in individuals with PDAC who underwent genetic testing to determine the appropriateness of including a family history requirement in these recommendations. METHODS: Individuals with PDAC with a germline heterozygous PV/LPV in ATM, BRCA1, BRCA2, EPCAM, MLH1, MSH2, MSH6, PALB2, or PMS2 (PV/LPV carriers) were assessed for family history of PDAC in first-degree relatives (FDRs) or second-degree relatives (SDRs) from nine institutions. A control group of individuals with PDAC without a germline PV/LPV was also assessed. RESULTS: The study included 196 PV/LPV carriers and 1184 controls. In the PV/LPV carriers, 25.5% had an affected FDR and/or SDR compared to 16.9% in the control group (p = .004). PV/LPV carriers were more likely to have an affected FDR compared to the controls (p = .003) but there was no statistical difference when assessing only affected SDRs (p = .344). CONCLUSIONS: Most PV/LPV carriers who developed PDAC did not have a close family history of PDAC and would not have met most current professional societies' recommendations for consideration of PDAC surveillance before diagnosis. However, PV/LPV carriers were significantly more likely to have a family history of PDAC, particularly an affected FDR. These findings support family history as a risk modifier in PV/LPV carriers, and highlight the need to identify other risk factors.

Structure and composition of microbial communities in the water column from Southern Gulf of Mexico and detection of putative hydrocarbon-degrading microorganisms.

This study assessed the bacterioplankton community and its relationship with environmental variables, including total petroleum hydrocarbon (TPH) concentration, in the Yucatan shelf area of the Southern Gulf of Mexico. Beta diversity analyses based on 16S rRNA sequences indicated variations in the bacterioplankton community structure among sampling sites. PERMANOVA indicated that these variations could be mainly related to changes in depth (5 to 180 m), dissolved oxygen concentration (2.06 to 5.93 mg L-1), and chlorophyll-a concentration (0.184 to 7.65 mg m3). Moreover, SIMPER and one-way ANOVA analyses showed that the shifts in the relative abundances of Synechococcus and Prochlorococcus were related to changes in microbial community composition and chlorophyll-a values. Despite the low TPH content measured in the studied sites (0.01 to 0.86 µL L-1), putative hydrocarbon-degrading bacteria such as Alteromonas, Acinetobacter, Balneola, Erythrobacter, Oleibacter, Roseibacillus, and the MWH-UniP1 aquatic group were detected. The relatively high copy number of the alkB gene detected in the water column by qPCR and the enrichment of hydrocarbon-degrading bacteria obtained during lab crude oil tests exhibited the potential of bacterioplankton communities from the Yucatan shelf to respond to potential hydrocarbon impacts in this important area of the Gulf Mexico.