Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Caring for individuals with concurrent mental health and opioid use disorder : a mixed-methods study with implications for health research, policy and practice

Background: The co-occurrence of opioid use disorder (OUD) and mental illness is common and may lead to poor negative health and social outcomes, as compared with having either illness alone. The body of evidence pertaining to best practices in person-centred care for those with concurrent OUD and mental illness remains in its infancy. The objective of this project is to generate evidence to guide improvements in the provision of concurrent OUD and mental health care for this population. Methods: This mixed-methods project begins with a rapid review which assesses the current landscape of health-related measurement for this population and provides recommendations for empirical work. For the empirical work, first, data were derived from two longstanding prospective cohort studies of people who use unregulated drugs. The impact of various factors on receipt of concurrent OUD and mental health care from a single provider were examined using generalized estimating equations. Second, guided by an interpretive descriptive methodology, data were collected via semi-structured interviews with physicians and persons with lived experience (PWLE). Findings were derived in a series of iterative steps including thematic analysis, as well as theme interrogation, and reflection on plausible associations or affiliations. Results: This project highlighted key concerns with current health-related measurement practices and identified strategies to improve the quality of and opportunities for health-related measurement among this population. It identified factors which may delay or inhibit receipt of concurrent OUD and mental health care from a single provider including daily non-injection opioid use and experience of a non-fatal overdose. It then drew attention to various concerns with the present quality of care currently being provided to individuals with a concurrent OUD and mental illness. This thesis also identified strategies that may ensure the provision of high quality, evidence-informed care for this population. Conclusion: Amidst North America’s worsening overdose crisis, a coronavirus pandemic, and an era where mental health has been increasingly threatened, findings from this project offer critical insights to help guide future research, policy, and practice decisions in an optimal way to support improvements in outcomes of persons living with concurrent OUD and mental illness.Medicine, Faculty ofGraduat

The association between COVID-19 infection and incident atrial fibrillation: results from a retrospective cohort study using a large US commercial insurance database

Background We sought to examine a 1-year incidence of atrial fibrillation (AF) among patients with SARS-CoV-2 virus (COVID-19) in comparison to those with non-COVID-19 acute upper respiratory infection (AURI).Methods Patients with a diagnosis of COVID-19 (in any setting) between April 2020 and June 2021 were identified in Optum Clinformatics. Two comparator cohorts were constructed: an ‘AURI pandemic’ cohort (AURI diagnosis between April 2020 and June 2021) and an ‘AURI prepandemic’ cohort (AURI diagnosis between January 2018 and December 2018). One-year incidence of AF was compared among: COVID-19 versus AURI pandemic cohort; COVID-19 versus AURI prepandemic cohort; and AURI pandemic versus AURI prepandemic cohort. For each comparison, we applied a matching weights technique to balance covariates. Logistic regression was used to compare the odds of incident AF among the matched cohorts.Results When comparing the matched COVID-19 (n=102 227) cohort with the AURI pandemic (n=102 101) cohort, higher incidence of AF was observed among the COVID-19 cohort (2.2% vs 1.2%; p<0.001; OR 1.83; 95% CI 1.72 to 1.95). Similar findings were observed for the COVID-19 (n=169 687) versus AURI prepandemic (n=169 486) comparison (2.7% vs 1.6%; p<0.001; OR 1.70; 95% CI 1.63 to 1.78). When comparing the AURI pandemic (n=1 26 392) versus AURI prepandemic (n=1 26 394) cohort, no significant differences in incident AF were observed (1.1% vs 1.2%; p=0.133; OR 0.95, 95% CI 0.90 to 1.01).Conclusion Patients diagnosed with COVID-19 were found to be at a higher risk of incident AF as compared with those with AURI. Timely diagnosis and appropriate treatment of AF may potentially mitigate the burden of AF conferred by COVID-19

Major depressive disorder and access to health services among people who use illicit drugs in Vancouver, Canada

Background: People who use illicit drugs (PWUD) are commonly diagnosed with major depressive disorder (MDD). However, little is known about whether PWUD living with MDD experience additional barriers to accessing health services compared to those without MDD. We sought to identify whether MDD symptoms were associated with perceived barriers to accessing health services among people who use illicit drugs (PWUD) in Vancouver, Canada. Methods: Data were collected through prospective cohorts of PWUD in Vancouver, Canada between 2005 and 2016. Using multiple logistic regression, we examined the relationship between MDD symptoms, defined as a Centre for Epidemiologic Studies Depression (CES-D) scale total score of ≥16, and barriers to access health services. We also used descriptive statistics to examine common barriers among participants who reported any barriers. Results: Among a total of 1529 PWUD, including 521 (34.1%) females, 415 (27.1%) reported barriers to accessing health services, and 956 (62.5%) reported MDD symptoms at baseline. In multiple logistic regression analyses, after adjusting for a range of potential confounders, MDD symptoms (adjusted odds ratio [AOR] = 1.40; 95% confidence interval [CI]: 1.03–1.92) were positively and significantly associated with barriers to accessing health services. Among those who reported MDD symptoms and barriers to access, commonly reported barriers included: long wait lists/times (38.1%); and treated poorly by health care professionals (30.0%). Conclusion: These findings show that the likelihood of experiencing barriers to accessing health services was higher among PWUD with MDD symptoms compared to their counterparts. Policies and interventions tailored to address these barriers are urgently needed for this subpopulation of PWUD.Medicine, Faculty ofOther UBCNon UBCMedicine, Department ofReviewedFacult

Controlled trial of the impact of a BC adult mental health practice support program (AMHPSP) on primary health care professionals’ management of depression

Background: Depression affects over 400 million people globally. The majority are seen in primary care. Barriers in providing adequate care are not solely related to physicians’ knowledge/skills deficits, but also time constraints, lack of confidence/avoidance, which need to be addressed in mental health-care redesign. We hypothesized that family physician (FP) training in the Adult Mental Health Practice Support Program (AMHPSP) would lead to greater improvements in patient depressive symptom ratings (a priori primary outcome) compared to treatment as usual. Methods: From October 2013 to May 2015, in a controlled trial 77 FP practices were stratified on the total number of physicians/practice as well as urban/rural setting, and randomized to the British Columbia AMHPSP⎯a multi-component contact-based training to enhance FPs’ comfort/skills in treating mild-moderate depression (intervention), or no training (control) by an investigator not operationally involved in the trial. FPs with a valid license to practice in NS were eligible. FPs from both groups were asked to identify 3–4 consecutive patients > 18 years old, diagnosis of depression, Patient Health Questionnaire (PHQ-9) score ≥ 10, able to read English, intact cognitive functioning. Exclusion criteria: antidepressants within 5 weeks and psychotherapy within 3 months of enrollment, and clinically judged urgent/emergent medical/psychiatric condition. Patients were assigned to the same arm as their physician. Thirty-six practices recruited patients (intervention n = 23; control n = 13). The study was prematurely terminated at 6 months of enrollment start-date due to concomitant primary health-care transformation by health-system leaders which resulted in increased in-office demands, and recruitment failure. We used the PHQ-9 to assess between-group differences at baseline, 1, 2, 3, and 6 months follow-up. Outcome collectors and assessors were blind to group assignment. Results: One hundred-and-twenty-nine patients (intervention n = 72; control n = 57) were analysed. A significant improvement in depression scores among intervention group patients emerged between 3 and 6 months, time by treatment interaction, likelihood ratio test (LR) chi2(3) = 7.96, p = .047. Conclusions: This novel skill-based program shows promise in translating increased FP comfort and skills managing depressed patients into improved patient clinical outcomes⎯even in absence of mental health specialists availability. Trial registration #NCT01975948 .Medicine, Faculty ofOther UBCNon UBCPsychiatry, Department ofReviewedFacult

Is expected substance type associated with timing of drug checking service utilization?: A cross-sectional study

Background Drug checking is a harm reduction intervention aiming to reduce substance use-related risks by improving drug user knowledge of the composition of unregulated drugs. With increasing fears of fentanyl adulteration in unregulated drugs, this study sought to examine whether the expected type of drug checked (stimulant vs. opioid) was associated with timing of drug checking service utilization (pre-consumption vs. post-consumption). Methods Data were derived from drug checking sites in British Columbia between October 31, 2017 and December 31, 2019. Pearson’s Chi-square test was used to examine the relationship between expected sample type (stimulant vs. opioid) and timing of service utilization. Odds ratios (OR) were calculated to assess the strength of this relationship. The Mantel–Haenszel (MH) test was used to adjust for service location. Results A total of 3561 unique stimulant and opioid samples were eligible for inclusion, including 691 (19.40%) stimulant samples; and 2222 (62.40%) samples that were tested pre-consumption. Results indicated a positive association between testing stimulant samples and testing pre-consumption (OR = 1.45; 95% CI 1.21–1.73). Regions outside of the epicenter of the province’s drug scene showed a stronger association with testing pre-consumption (ORMH = 2.33; 95% CI 1.51–3.56) than inside the epicenter (ORMH = 1.33; 95% CI 1.09–1.63). Conclusion Stimulant samples were more likely to be checked pre-consumption as compared with opioid samples, and stimulant samples were more likely to be tested pre-consumption in regions outside the epicenter of the province’s drug scene. This pattern may reflect a concern for fentanyl-adulterated stimulant drugs.Medicine, Faculty ofMedicine, Department ofPopulation and Public Health (SPPH), School ofReviewedFacultyResearche