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Previous research linking opioid prescribing to adverse drug events has failed to properly account for the time-varying nature of opioid exposure. This study aimed to explore how the risk of opioid-related emergency department visits, readmissions, or deaths (composite outcome) varies with opioid dose and duration, comparing different novel modeling techniques. A prospective cohort of 1,511 hospitalized patients discharged from 2 McGill-affiliated hospitals in Montreal, 2014–2016, was followed from the first postdischarge opioid dispensation until 1 year after discharge. Marginal structural Cox proportional hazards models and their flexible extensions were used to explore the association between time-varying opioid use and the composite outcome. Weighted cumulative exposure models assessed cumulative effects of past use and explored how its impact depends on the recency of exposure. The patient mean age was 69.6 (standard deviation = 14.9) years; 57.7% were male. In marginal structural model analyses, current opioid use was associated with a 71% increase in the hazard of opioid-related adverse events (adjusted hazard ratio = 1.71, 95% confidence interval: 1.21, 2.43). The weighted cumulative exposure results suggested that the risk cumulates over the previous 50 days of opioid consumption. Flexible modeling techniques helped assess how the risk of opioid-related adverse events may be associated with time-varying opioid exposures while accounting for nonlinear relationships and the recency of past use. [ABSTRACT FROM AUTHOR]

Aims: We describe an innovative research protocol to: (a) examine patient‐level longitudinal associations between nurse staffing practices and the risk of adverse events in acute care hospitals and; (b) determine possible thresholds for safe nurse staffing. Design: A dynamic cohort of adult medical, surgical and intensive care unit patients admitted to 16 hospitals in Quebec (Canada) between January 2015–December 2019. Methods: Patients in the cohort will be followed from admission until 30‐day postdischarge to assess exposure to selected nurse staffing practices in relation to the subsequent occurrence of adverse events. Five staffing practices will be measured for each shift of an hospitalization episode, using electronic payroll data, with the following time‐varying indicators: (a) nursing worked hours per patient; (b) skill mix; (c) overtime use; (d) education mix and; and (e) experience. Four high‐impact adverse events, presumably associated with nurse staffing practices, will be measured from electronic health record data retrieved at the participating sites: (a) failure‐to‐rescue; (b) in‐hospital falls; (c) hospital‐acquired pneumonia and; and (d) venous thromboembolism. To examine the associations between the selected nurse staffing exposures and the risk of each adverse event, separate multivariable Cox proportional hazards frailty regression models will be fitted, while adjusting for patient, nursing unit and hospital characteristics, and for clustering. To assess for possible staffing thresholds, flexible non‐linear spline functions will be fitted. Funding for the study began in October 2019 and research ethics/institutional approval was granted in February 2020. Discussion: To our knowledge, this study is the first multisite patient‐level longitudinal investigation of the associations between common nurse staffing practices and the risk of adverse events. It is hoped that our results will assist hospital managers in making the most effective use of the scarce nursing resources and in identifying staffing practices that minimize the occurrence of adverse events. [ABSTRACT FROM AUTHOR]

To propose statistical measures to identify different longitudinal patterns of change in quantitative health indicators.The authors propose several simple measures to discriminate between stable–unstable, increasing–decreasing, linear–nonlinear, monotonic–nonmonotonic patterns of change. They then suggest using factor analysis to select the subset of nonredundant measures, and cluster analysis, based on the selected measures, to identify subgroups of patients with similar longitudinal trajectories. The proposed approach is illustrated using data on osteoarthritis disability from a longitudinal study undertaken in Toronto, Ontario, in 1996–2001. Disability was measured at four points in time for 835 patients, using the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index.The proposed measures allowed the detection of individual patients with specific patterns of change and identification of four different groups of patients with WOMAC scores that are (1) regularly increasing, (2) regularly decreasing, (3) stable over time, or (4) highly unstable, with abrupt changes or short-term fluctuations.The proposed approach may be used to (1) screen even large databases to identify particular patterns of change; or (2) summarize different patterns of change by classifying patients into groups with similar trajectories. Once identified, the groups can be investigated to determine whether there are differences in patient characteristics or outcomes. [Copyright &y& Elsevier]

Objective: To evaluate the hypothesis that nonadherence to medication changes made at hospital discharge is associated with an increased risk of adverse events in the 30 days postdischarge.Study Setting: Patients admitted to hospitals in Montreal, Quebec, between 2014 and 2016.Study Design: Prospective cohort study.Data Collection: Nonadherence to medication changes was measured by comparing medications dispensed in the community with those prescribed at hospital discharge. Patient, health system, and drug regimen-level covariates were measured using medical services and pharmacy claims data as well as data abstracted from the patient's hospital chart. Multivariable Cox models were used to determine the association between nonadherence to medication changes and the risk of adverse events.Principal Findings: Among 2655 patients who met our inclusion criteria, mean age was 69.5 years (SD 14.7) and 1581 (60%) were males. Almost half of patients (n = 1161, 44%) were nonadherent to at least one medication change, and 860 (32%) were readmitted to hospital, visited the emergency department, or died in the 30 days postdischarge. Patients who were not adherent to any of their medication changes had a 35% higher risk of adverse events compared to those who were adherent to all medication changes (1.41 vs 1.27 events/100 person-days, adjusted hazard ratio: 1.35, 95% CI: 1.06-1.71).Conclusions: Almost half of all patients were not adherent to some or all changes made to their medications at hospital discharge. Nonadherence to all changes was associated with an increased risk of adverse events. Interventions addressing barriers to adherence should be considered moving forward. [ABSTRACT FROM AUTHOR]

Background: Recent studies show that paternal depression negatively impacts children's behavioral and emotional development. This study determined the prevalence of depressed mood in first-time fathers at 2 and 6 months postpartum and identified associated risk factors.Methods: A prospective cohort study with 622 men who completed sociodemographic and psychosocial questionnaires during their partner's third trimester of pregnancy. Fathers completed measures again at 2 and 6 months postpartum and partners completed the depressed mood measure at all three timepoints. A cutoff of ≥10 for the Edinburgh Postnatal Depression Scale identified depressed mood status.Results: The prevalence of depressive symptoms in fathers was 13.76% at 2 months and 13.60% at 6 months postpartum. Men who were depressed during their partner's pregnancy were 7 times more likely to be depressed at 2 months postpartum. Depressed mood status at both the antenatal and 2 month postpartum assessment was associated with increased risk of depressed mood at 6 months postpartum. Older age, poor sleep quality at study entry, worse couple adjustment, having a partner experiencing antenatal depressive symptoms and elevated parental stress were associated with depressive symptoms at 2 months postpartum. Poor sleep quality, financial stress and a decline in couple adjustment were independently associated to depressive symptoms at 6 months postpartum.Limitations: This sample was fairly well-educated and predominately middle-class. Depressive symptoms were assessed using a self-report questionnaire.Conclusions: The psychosocial risk factors identified provide opportunities for early screening and targeted prevention strategies for fathers at risk for depression during the transition to parenthood. [ABSTRACT FROM AUTHOR]

Objective To quantify the risk of incident diabetes mellitus (DM) associated with the dosage, duration, and timing of glucocorticoid (GC) use in patients with rheumatoid arthritis (RA). Methods We undertook a cohort study using 2 databases: a UK primary care database (the Clinical Practice Research Datalink [CPRD]) including 21,962 RA patients (1992-2009) and the US National Data Bank for Rheumatic Diseases (NDB) including 12,657 RA patients (1998-2013). Information on the dosage and timing of GC use was extracted. DM in the CPRD was defined using Read codes, at least 2 prescriptions for oral antidiabetic medication, or abnormal blood test results. DM in the NDB was defined through patient self-reports. Data were analyzed using time-dependent Cox models and a novel weighted cumulative dose (WCD) model that accounts for dosage, duration, and timing of treatment. Results The hazard ratio (HR) was 1.30 (95% confidence interval [95% CI] 1.17-1.45) and 1.61 (95% CI 1.37-1.89) in current GC users compared to nonusers in the CPRD and the NDB, respectively. A range of conventional statistical models consistently confirmed increases in risk with the GC dosage and duration. The WCD model showed that recent GC use contributed the most to the current risk of DM, while doses taken >6 months previously did not influence current risk. In the CPRD, 5 mg of prednisolone equivalent dose for the last 1, 3, and 6 months was significantly associated with HRs of 1.20, 1.43, and 1.48, respectively, compared to nonusers. Conclusion GC use is a clinically important and quantifiable risk factor for DM. Risk is influenced by the dosage and treatment duration, although only for GC use within the last 6 months. [ABSTRACT FROM AUTHOR]

Several studies have reported smaller hippocampal volume in patients with depression. However, the temporality of the association is undetermined. One hypothesis is that hippocampal atrophy might be a susceptibility factor for depression. In the present study, we assessed whether hippocampal atrophy was associated with subsequent depressive symptoms in a cohort of older French adults (n = 1,309) who were 65–80 years of age and enrolled into the study in 1999–2001 in Dijon, France. Subjects were followed for more than 10 years. Participants underwent 2 cerebral magnetic resonance imaging scans, one at baseline and one at the 4-year follow-up. We used linear mixed models to estimate the associations of hippocampal atrophy with 1) the average depressive symptom scores over follow-up (using the Center for Epidemiologic Studies-Depression scale) measured biennially over the subsequent 6 years and 2) changes in symptom scores over follow-up. In women, a 2-standard-deviation increase in annual hippocampal atrophy was associated with a 1.67-point (95% confidence interval: 0.59, 2.77) increase in the average depressive symptom score over follow-up and with a 1.97-point (95% confidence interval: 0.68, 3.24) increase in scores over the 2 subsequent years but not with later changes in symptoms. No association was detected in men. Accounting for potential selective attrition (using inverse probability weights) did not alter results. Hippocampal atrophy was associated with more subsequent depressive symptoms and with shorter-term worsening of symptoms in women. [ABSTRACT FROM PUBLISHER]

The response of immigrants to new societies is dynamic. There may be an initial period of happiness followed by peaks of stressful periods. These reactions along with socio-economic changes are likely to influence their health, which may start converging towards the average health of the host population. We used a longitudinal analysis to assess the differences in health outcomes (mental health and self-rated health), separately in men and women, in Canadian born and immigrants over a 12-year period (and the associated socio-economic factors). We used random effects logistic regression models for evaluation of these health outcomes in 3,081 men and 4,187 women from the National Population Health Survey (1994/95 to 2006/07). After adjusting for all the covariates, non-white immigrants were less likely to have severe psychological distress compared with the Canadian born individuals [odds ratio (OR) Men: 0.49, 95% confidence intervals (CI) 0.24-1.00, Women-OR: 0.54; 95% CI: 0.32-0.92]. Immigrant women (white and non-white) were more likely to rate their health as poor through this 12-year period than the Canadian born women (White-OR: 1.64, 95% CI: 1.17-2.64; Non-white-OR: 1.82, 95% CI: 1.01-3.28). Immigrants in the lowest income adequacy category reported higher psychological distress and poorer health than those in the highest income categories. We did not find any significant differences in the mental health and self-rated health of Canadian men and white male immigrants throughout this 12-year period. Though, non-white immigrant women were less likely to have severe psychological distress through this 12 year period, they were the ones most likely to rate their health as poor. [ABSTRACT FROM AUTHOR]

The authors sought to investigate trends in the incidence of human immunodeficiency virus (HIV) infection, evaluate changes in risk behavior, and assess associations between syringe access programs and HIV seroconversion among injection drug users (IDUs) in Montreal, Canada, who were recruited and followed for a prospective cohort study between 1992 and 2008. Methods included Kaplan-Meier survival analysis and time-varying Cox regression models. Of 2,137 HIV-seronegative IDUs at enrollment, 148 became HIV-positive within 4 years (incidence: 3.3 cases/100 person-years; 95% confidence interval: 2.8, 3.9). An annual HIV incidence decline of 0.06 cases/100 person-years prior to 2000 was followed by a more rapid annual decline of 0.24 cases/100 person-years during and after 2000. Behavioral trends included increasing cocaine and heroin use and decreasing proportions of IDUs reporting any syringe-sharing or sharing a syringe with an HIV-positive person. In multivariate analyses, HIV seroconversion was associated with male gender, unstable housing, intravenous cocaine use, and sharing syringes or having sex with an HIV-positive partner. Always acquiring syringes from safe sources conferred a reduced risk of HIV acquisition among participants recruited after 2004, but this association was not statistically significant for participants recruited earlier. In conclusion, HIV incidence has declined in this cohort, with an acceleration of the reduction in HIV transmission after 2000. [ABSTRACT FROM AUTHOR]

Abstract: Using a multi-level random effects logistic model, we examine the contribution of source country, individual characteristics and post-migration experiences to the self-rated health (SRH) of 2468 male and 2614 female immigrants from the Longitudinal Survey of Immigrants to Canada (2001–2005). Sex/gender differences were found for all categories of health determinants. Source country characteristics explained away some ethnic differentials in health and had independent negative effects, particularly among women. Thus, women from countries lower on the development index appear at greater risk of poor SRH, and should be at the forefront of public health programmes aimed at new immigrants in Canada. [Copyright &y& Elsevier]

Immigrants often lose their health advantage as they start adapting to the ways of the new society. Having access to care when it is needed is one way that individuals can maintain their health. We assessed the healthcare access in Canadian immigrants and the socioeconomic factors associated with access over a 12-year period. We compared two measures of healthcare access (having a regular doctor and reporting an unmet healthcare need in the past 12 months) among immigrants and Canadian-born men and women, aged more than 18 years. We applied a logistic random effects model to evaluate these outcomes separately, in 3081 males and 4187 females from the National Population Health Survey (1994-2006). Adjusting for all covariates, immigrant men and women (white and non-white) had similar odds of having a regular doctor than the Canadian-born individuals (white immigrants: males OR: 1.32, 95% C.I.: 0.89-1.94, females OR: 1.14, 95% C.I.: 0.78-1.66; non-white immigrants: males OR: 1.28, 95% C.I.: 0.73-2.23, females OR: 1.23, 95% C.I.: 0.64-2.36). Interestingly, non-white immigrant women had significantly fewer unmet health needs (OR: 0.32, 95% C.I.: 0.17-0.59). Among immigrants, time since immigration was associated with having access to a regular doctor (OR per year: 1.02, 95% C.I.: 1.00-1.04). Visible minority female immigrants were least likely to report an unmet healthcare need. In general, there is little evidence that immigrants have worse access to health-care than the Canadian-born population. [ABSTRACT FROM AUTHOR]

Objective To evaluate compliance with hyperlipidaemia screening guidelines for cardiovascular disease prevention in RA compared with the general population. Methods We conducted a longitudinal study of a population-based RA cohort including all prevalent cases in British Columbia between 1996 and 2006, followed up until 2010, with matched general population controls. Using administrative data, we measured compliance with general population guidelines (testing lipids every 5 years for women ⩾50 and men ⩾40), after excluding individuals with previous diabetes, coronary artery disease or hyperlipidaemia. Compliance was measured as the proportion of 5-year eligibility periods with one or more lipid test. Compliance rates in RA and controls were compared by Chi-square test. Odds ratio (95% CI) of compliance in RA (vs controls) was estimated using generalized estimating equation models, adjusting for age and sex. Mean compliance rate per patient was also calculated and compared using Mann-Whitney U test. Results Analyses included 5587 RA individuals and 5613 controls, contributing 6993 and 7208 5-year eligibility periods, respectively. Lipids were measured in 56.6 and 59.5% of eligibility periods in RA and controls, respectively [adjusted odds ratio (95% CI): 0.97 (0.90, 1.06)]. Screening improved over time in RA relative to the general population, but remained suboptimal even after 2003, at 65.8%. Mean (s. d.) compliance rate per patient was 56.6 (47.2)% for RA and 59.5 (46.6)% for controls. Family physicians ordered almost all the lipid tests. Conclusion Compliance with general population guidelines for hyperlipidaemia screening in RA was poor and did not differ from the general population, despite a higher risk of cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Background: With potent antiretroviral drugs, HIV infection is becoming a chronic disease. Emergence of comorbidities, particularly cardiovascular disease (CVD) has become a leading concern for patients living with the infection. We hypothesized that the chronic and persistent inflammation and immune activation associated with HIV disease leads to accelerated aging, characterized by CVD. This will translate into higher incidence rates of CVD in HIV infected participants, when compared to HIV negative participants, after adjustment for traditional CVD risk factors. When characterized further using cardiovascular imaging, biomarkers, immunological and genetic profiles, CVD associated with HIV will show different characteristics compared to CVD in HIV-negative individuals.Methods/design: The Canadian HIV and Aging cohort is a prospective, controlled cohort study funded by the Canadian Institutes of Health Research. It will recruit patients living with HIV who are aged 40 years or older or have lived with HIV for 15 years or more. A control population, frequency matched for age, sex, and smoking status, will be recruited from the general population. Patients will attend study visits at baseline, year 1, 2, 5 and 8. At each study visit, data on complete medical and pharmaceutical history will be captured, along with anthropometric measures, a complete physical examination, routine blood tests and electrocardiogram. Consenting participants will also contribute blood samples to a research biobank. The primary outcome is incidence of a composite of: myocardial infarction, coronary revascularization, stroke, hospitalization for angina or congestive heart failure, revascularization or amputation for peripheral artery disease, or cardiovascular death. Preplanned secondary outcomes are all-cause mortality, incidence of the metabolic syndrome, incidence of type 2 diabetes, incidence of renal failure, incidence of abnormal bone mineral density and body fat distribution. Patients participating to the cohort will be eligible to be enrolled in four pre-planned sub-studies of cardiovascular imaging, glucose metabolism, immunological and genetic risk profile.Discussion: The Canadian HIV and Aging Cohort will provide insights on pathophysiological pathways leading to premature CVD for patients living with HIV. [ABSTRACT FROM AUTHOR]

The Saguenay Youth Study (SYS) is a two-generational study of adolescents and their parents (n = 1029 adolescents and 962 parents) aimed at investigating the aetiology, early stages and trans-generational trajectories of common cardiometabolic and brain diseases. The ultimate goal of this study is to identify effective means for increasing healthy life expectancy. The cohort was recruited from the genetic founder population of the Saguenay Lac St Jean region of Quebec, Canada. The participants underwent extensive (15-h) phenotyping, including an hour-long recording of beat-by-beat blood pressure, magnetic resonance imaging of the brain and abdomen, and serum lipidomic profiling with LC-ESI-MS. All participants have been genome-wide genotyped (with ∼ 8 M imputed single nucleotide polymorphisms) and a subset of them (144 adolescents and their 288 parents) has been genome-wide epityped (whole blood DNA, Infinium HumanMethylation450K BeadChip). These assessments are complemented by a detailed evaluation of each participant in a number of domains, including cognition, mental health and substance use, diet, physical activity and sleep, and family environment. The data collection took place during 2003-12 in adolescents (full) and their parents (partial), and during 2012-15 in parents (full). All data are available upon request. [ABSTRACT FROM AUTHOR]

Potential upstream determinants of coronary heart disease (CHD) include life-course socioeconomic position (e.g., childhood socioeconomic circumstances, own education and occupation); however, several plausible biological mechanisms by which socioeconomic position (SEP) may influence CHD are poorly understood. Several CHD risk factors appear to be more strongly associated with SEP in women than in men; little is known as to whether any CHD risk factors may be more strongly associated with SEP in men. Objectives were to evaluate whether cumulative life-course SEP is associated with a measurement of subclinical atherosclerosis, the ankle–brachial index (ABI), in men and women. This study was a prospective analysis of 1,454 participants from the Framingham Heart Study Offspring Cohort (mean age 57 years, 53.8% women). Cumulative SEP was calculated by summing tertile scores for father''s education, own education, and own occupation. ABI was dichotomized as low (≤1.1) and normal (>1.1 to 1.4). After adjustment for age and CHD risk factors cumulative life-course SEP was associated with low ABI in men (odds ratio [OR] 2.04, 95% confidence interval [CI] 1.22 to 3.42, for low vs high cumulative SEP score) but not in women (OR 0.86, 95% CI 0.56 to 1.33). Associations with low ABI in men were substantially driven by their own education (OR 4.13, 95% CI 1.86 to 9.16, for lower vs higher than high school education). In conclusion, cumulative life-course SEP was associated with low ABI in men but not in women. [ABSTRACT FROM AUTHOR]

Evidence is lacking on whether the duration and timing of low socioeconomic position (SEP) across a person's life course may be associated with incidence of type 2 diabetes mellitus (T2D). The authors’ objectives were to investigate associations between cumulative SEP and the incidence of T2D in the Framingham Offspring Study (n = 1,893; 52% women; mean baseline age = 34 years). Pooled logistic regression analyses demonstrated that age-adjusted cumulative SEP was associated with T2D in women (for low vs. high cumulative SEP, odds ratio (OR) = 1.92, 95% confidence interval (CI): 1.08, 3.42). Age-adjusted analyses for young-adulthood SEP (7.85 for ≤12 vs. >16 years of education, OR = 2.84, 95% CI: 1.03), active professional life SEP (for laborer vs. professional/executive/supervisory/technical occupations, OR = 2.40, 95% CI: 1.05, 5.47), and social-mobility frameworks (for declining life-course SEP, OR = 2.99, 95% CI: 1.39, 6.44; for stable low vs. stable high life-course SEP, OR = 1.85, 95% CI: 1.02, 3.35) all demonstrated associations between low SEP and T2D incidence in women. No association was observed between childhood SEP and T2D in women for father's education (some high school or less vs. any postsecondary education, OR = 1.26, 95% CI: 0.72, 2.22). In men, there was little evidence of associations between life-course SEP and T2D incidence. These findings suggest that cumulative SEP is inversely associated with incidence of T2D in women, and that this association may be primarily due to the women's educational levels and occupations. [ABSTRACT FROM PUBLISHER]

Background: Glycerophosphocholine (GPC) metabolites modulate atherosclerosis and thus risk for cardiovascular disease (CVD). Preclinical CVD may start during adolescence. Here, we used targeted serum lipidomics to identify a new panel of GPCs, and tested whether any of these GPCs are associated, in adolescence, with classical risk factors of CVD, namely excess visceral fat (VF), elevated blood pressure, insulin resistance, and atherogenic dyslipidemia.Methods: We studied a population-based sample of 990 adolescents (12-18 years, 48% male), as part of the Saguenay Youth Study. Using liquid chromatography-electrospray ionization-mass spectrometry, we identified 69 serum GPCs within the 450 to 680 m/z range. We measured VF with MRI.Results: We identified several novel GPCs that were associated with multiple CVD risk factors. Most significantly, PC16:0/2:0 was negatively associated with VF (P=1.4×10-19), blood pressure (P=7.7×10-5), and fasting triacylglycerols (P=9.0×10-5), and PC14:1/0:0 was positively associated with VF (P=3.0×10-7), fasting insulin (P=5.4×10-32), and triacylglycerols (P=1.4×10-29). The Sobel test of mediation revealed that both GPCs mediated their respective relations between VF (as a potential primary exposure) and CVD risk factors (as outcomes, P values<1.3×10-3). Furthermore, a GPC shown recently to predict incident coronary heart disease in older adults, PC18:2/0:0, was associated with several CVD risk factors in adolescents; these associations were less strong than those with the newly identified GPCs.Conclusions: We identified novel GPCs strongly associated with multiple CVD risk factors in adolescents. These GPCs may be sensitive indicators of obesity-related risk for CVD outcomes in adults, and may improve biological understanding of CVD risk. [ABSTRACT FROM AUTHOR]