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The annual cut-off date of birth for entry to school in British Columbia, Canada, is Dec. 31. Thus, children born in December are typically the youngest in their grade. We sought to determine the influence of relative age within a grade on the diagnosis and pharmacologic treatment of attention-deficit/hyperactivity disorder (ADHD) in children. We conducted a cohort study involving 937 943 children in British Columbia who were 6–12 years of age at any time between Dec. 1, 1997, and Nov. 30, 2008. We calculated the absolute and relative risk of receiving a diagnosis of ADHD and of receiving a prescription for a medication used to treat ADHD (i.e., methylphenidate, dextroamphetamine, mixed amphetamine salts or atomoxetine) for children born in December compared with children born in January. Boys who were born in December were 30% more likely (relative risk [RR] 1.30, 95% confidence interval [CI] 1.23–1.37) to receive a diagnosis of ADHD than boys born in January. Girls born in December were 70% more likely (RR 1.70, 95% CI 1.53–1.88) to receive a diagnosis of ADHD than girls born in January. Similarly, boys were 41% more likely (RR 1.41, 95% CI 1.33–1.50) and girls 77% more likely (RR 1.77, 95% CI 1.57–2.00) to be given a prescription for a medication to treat ADHD if they were born in December than if they were born in January. The results of our analyses show a relative-age effect in the diagnosis and treatment of ADHD in children aged 6–12 years in British Columbia. These findings raise concerns about the potential harms of overdiagnosis and overprescribing. These harms include adverse effects on sleep, appetite and growth, in addition to increased risk of cardiovascular events.

•Industry sponsors in some cases influence decisions on whether to report trials.•Companies may influence reporting through owning and controlling access to data.•Trial agreements may only weakly protect the right of site investigators to publish.•Early phase internal company trials are a source of unpublished clinical trials.•Small biotech firms may cease operations without publishing their results. Approximately 40% of randomized controlled trials are not published, leading to publication bias and less informed clinical decision-making. Qualitative interviews were conducted to understand whether and how industry sponsors of clinical trials of drugs and biologics in Canada influence decisions to report trial results. Participants eligible for an interview included clinical trial investigators and research coordinators with experience in drug research, research ethics board members with at least 1 year of experience in ethical review of trials, research administrators with knowledge of dissemination of clinical trial findings or relations with trial sponsors, and trial participants who had taken part in a drug trial as an adult in the 5 years before their interview. Semi-structured interviews were held in person or by telephone between March 2019 and April 2021 with participants in Alberta, British Columbia, and Ontario, Canada. Qualitative analysis included coding of interview transcripts and identification of key themes. Interviews were conducted with 34 participants, including 17 clinical trial investigators, 1 clinical research coordinator, 3 research administrators, 3 research ethics board members, and 10 clinical trial participants. Participants involved in the conduct, administration, or ethical review of trials represented a range of medical disciplines. Interview participant accounts indicated that in some cases, industry sponsors influence whether results are reported. A core theme was that companies have a weaker incentive to publish trials with unfavorable findings and trials for products that they have decided not to develop further. Companies may influence reporting in various ways, including stopping trials early and not reporting results of stopped trials, owning and controlling access to data, and negotiating clinical trial agreements in multicenter trials that do not fully protect the ability of investigators to publish. Internal company trials represent an additional source of unpublished trials. More broadly, the research system creates a dependency on funding from industry sponsors that may weaken the ability of researchers and research institutions to negotiate terms with industry sponsors that would fully protect publication rights. Interviews with trial investigators and others connected to trial research indicate that in some cases, industry sponsors of clinical trial research in Canada influence whether results are reported. Policies aiming to bring about full reporting of trials could benefit from considering the commercial incentives of companies and the ways in which industry sponsors may influence clinical trial reporting. Future research could examine the generalizability of these findings to other jurisdictions.

ObjectiveTo understand how the experiences and views of trial participants, trial investigators and others connected to clinical trial research relate to whether researchers have a duty to participants to publicly report research findings.DesignQualitative interview study.SettingSemistructured interviews held in person or by telephone between March 2019 and April 2021 with participants in the Canadian provinces of Alberta, British Columbia and Ontario.Participants34 participants, including 10 clinical trial participants, 17 clinical trial investigators, 1 clinical research coordinator, 3 research administrators and 3 research ethics board members.AnalysisWe conducted a thematic analysis, including qualitative coding of interview transcripts and identification of key themes.Main outcome measuresKey themes identified through qualitative coding of interview data.ResultsMost clinical trial participants felt that reporting clinical trial results is important. Accounts of trial participants suggest their contributions are part of a reciprocal relationship involving the expectation that research will advance medical knowledge. Similarly, comments from trial investigators suggest that reporting trial results is part of reciprocity with trial participants and is a necessary part of honouring informed consent. Accounts of trial investigators suggest that when drug trials are not reported, this may undermine informed consent in subsequent trials by withholding information on harms or efficacy relevant to informed decisions on whether to conduct or enroll in future trials of similar drugs.ConclusionThe views of trial participants, trial investigators and others connected to clinical trial research in Canada suggest that researchers have an obligation to participants to publicly report clinical trial results and that reporting results is necessary for honouring informed consent.

The COVID-19 pandemic disrupted progress towards global HCV elimination goals by interrupting essential health services in Canada and globally. We aimed to evaluate the effect of the pandemic on hepatitis C virus (HCV) testing rates in a population-based cohort study in Ontario using health administrative data. All residents with records of either HCV antibody or ribonucleic acid (RNA) tests were included. Monthly testing rate per 1000 population were compared during the pre-pandemic (01/01/2015–29/02/2020) and pandemic (01/03/2020–31/12/2022) periods using interrupted time series models, stratified by sex, homelessness, human immunodeficiency virus (HIV), and immigration status, and people who inject drugs (PWID). The HCV testing rate followed a statistically significant upward trend before the pandemic, dropping at its onset with 1.38/1000 fewer individuals initiating testing monthly. Compared to counterfactual estimates, the observed monthly number of people tested per 1000 population was lower by 1.41 (95% CI: 1.18–1.64) in 2020 (May–Dec), 1.17 (95% CI: 0.99–1.36) in 2021, and 1.41 (95% CI: 1.22–1.59) in 2022, corresponding to relative reductions of 47%, 34%, and 41%, respectively. Testing rates remained below expected levels across all subgroups throughout 2020–2022, with the greatest absolute declines observed among people co-infected with HIV, people experiencing homelessness, and PWID. Tailored, equity-focused interventions are needed to address these persistent gaps in HCV testing, without which Canada’s progress toward its 2030 elimination targets remains at risk.

We investigated the impacts of the COVID-19 pandemic on hepatitis C (HCV) treatment initiation, including by birth cohort and injection drug use status, in British Columbia (BC), Canada. Using population data from the BC COVID-19 Cohort, we conducted interrupted time series analyses, estimating changes in HCV treatment initiation following the introduction of pandemic-related policies in March 2020. The study included a pre-policy period (April 2018 to March 2020) and three follow-up periods (April to December 2020, January to December 2021, and January to December 2022). The level of HCV treatment initiation decreased by 26% in April 2020 (rate ratio 0.74, 95% confidence interval [CI] 0.60 to 0.91). Overall, no statistically significant difference in HCV treatment initiation occurred over the 2020 and 2021 post-policy periods, and an increase of 34.4% (95% CI 0.6 to 75.8) occurred in 2022 (equating to 321 additional people initiating treatment), relative to expectation. Decreases in HCV treatment initiation occurred in 2020 for people born between 1965 and 1974 (25.5%) and people who inject drugs (24.5%), relative to expectation. In summary, the pandemic was associated with short-term disruptions in HCV treatment initiation in BC, which were greater for people born 1965 to 1974 and people who inject drugs.

In the treatment of chronic obstructive pulmonary disease (COPD), tiotropium bromide has a longer duration of action than ipratropium bromide; however, tiotropium bromide is a more expensive alternative treatment. At issue is whether tiotropium reduces the risk for hospital readmissions for COPD compared with ipratropium. A population-based cohort study was conducted to assess whether tiotropium reduces the risk for hospital readmissions for COPD compared with ipratropium. British Columbia (BC) linked provincial administrative health databases were used to identify new patients with COPD (aged ≥45 years) with a first hospital admission for COPD from 2003 to 2011. The study period was defined as the 30-day tiotropium or ipratropium treatment-initiation period after hospital discharge. Patients were followed up for ≤6 months from drug initiation to hospital readmission for COPD. In a subanalysis, the 2 treatment groups were matched on age, sex, and high-dimensional propensity scores derived from 200 empirically identified and predefined covariates. The risk for hospital readmission was estimated using multivariate Cox proportional hazards and logistic regression analyses. In total, 3723 patients with COPD were dispensed tiotropium (n = 992) or ipratropium (n = 2731) within 30 days from the index hospital admission for COPD. The mean age of these patients was 72.8 years, and 50.8% were women. Tiotropium-treated patients were more likely to be in a higher income category and were more likely to use a greater number of medications compared with ipratropium-treated patients. Among the subset of 1500 matched patients, 215 (14.3%) were readmitted to hospital within 6 months. There was no statistically significant group difference in hospital readmissions using either analytical approach (hazard ratio = 0.98 [95% CI, 0.72–1.34]; odds ratio = 0.97 [95% CI, 0.70–1.36]). In this select group of patients, neither tiotropium nor ipratropium was effective in significantly decreasing the risk for rehospitalization for COPD within 6 months.

ObjectivesTo study the association between accidental opioid overdose and neurological, respiratory, cardiac and other serious adverse events and whether risk of these adverse events was elevated during hospital readmissions compared with initial admissions.DesignRetrospective cohort study.SettingPopulation-based study using linked administrative data in British Columbia, Canada.ParticipantsThe primary analysis included 2433 patients with 2554 admissions for accidental opioid overdose between 2006 and 2015, including 121 readmissions within 1 year of initial admission. The secondary analysis included 538 patients discharged following a total of 552 accidental opioid overdose hospitalizations and 11 040 matched controls from a cohort of patients with ≥180 days of prescription opioid use.Outcome measuresThe primary outcome was encephalopathy; secondary outcomes were adult respiratory distress syndrome, respiratory failure, pulmonary haemorrhage, aspiration pneumonia, cardiac arrest, ventricular arrhythmia, heart failure, rhabdomyolysis, paraplegia or tetraplegia, acute renal failure, death, a composite outcome of encephalopathy or any secondary outcome and total serious adverse events (all-cause hospitalisation or death). We analysed these outcomes using generalised linear models with a logistic link function.Results3% of accidental opioid overdose admissions included encephalopathy and 25% included one or more adverse events (composite outcome). We found no evidence of increased risk of encephalopathy (OR 0.57; 95% CI 0.13 to 2.49) or other outcomes during readmissions versus initial admissions. In the secondary analysis, <5 patients in each cohort experienced encephalopathy. Risk of the composite outcome (OR 2.15; 95% CI 1.48 to 3.12) and all-cause mortality (OR 2.13; 95% CI 1.18 to 3.86) were higher for patients in the year following overdose relative to controls.ConclusionsWe found no evidence that risk of encephalopathy or other adverse events was higher in readmissions compared with initial admissions for accidental opioid overdose. Risk of serious morbidity and mortality may be elevated in the year following an accidental opioid overdose.

Limited evidence suggests that isotretinoin may be associated with inflammatory bowel disease (IBD). To explore this association, we conducted a retrospective population-based cohort study in British Columbia, Canada, among participants who were newly treated with isotretinoin or topical acne medications. The entire population of untreated provincial residents aged 12–29 years served as the reference group. During the 12-year study period, we identified 46,922 participants treated with isotretinoin, 184,824 treated with a topical acne medication, and 1,526,946 untreated individuals. Compared with untreated individuals, we observed no significant association between isotretinoin use and IBD (rate ratio (RR) 1.14; 95% confidence interval (CI) 0.92–1.41). As expected, we found no association with topical acne medications (RR 1.11; 95% CI 0.99–1.24). In prespecified secondary analyses, isotretinoin was associated with IBD among individuals aged 12–19 years (RR 1.39; 95% CI 1.03–1.87) and topical acne medications were associated with ulcerative colitis (RR 1.19; 95% CI 1.00–1.42). Our primary analyses found no association between isotretinoin and IBD. In prespecified secondary analyses, some evidence was found of associations with isotretinoin as well as topical acne medications, suggesting a possible association between IBD and acne itself. Additional research is needed to explore this possibility.

ObjectiveTo evaluate the association between regulatory drug safety advisories and changes in drug utilisation.DesignWe conducted controlled, interrupted times series analyses with administrative prescription claims data to estimate changes in drug utilisation following advisories. We used random-effects meta-analysis with inverse-variance weighting to estimate the average postadvisory change in drug utilisation across advisories.Study populationWe included advisories issued in Canada, Denmark, the UK and the USA during 2009–2015, mainly concerning drugs in common use in primary care. We excluded advisories related to over-the-counter drugs, drug-drug interactions, vaccines, drugs used primarily in hospital and advisories with co-interventions within ±6 months.Main outcome measuresChange in drug utilisation, defined as actual versus predicted percentage change in the number of prescriptions (for advisories without dose-related advice), or in the number of defined daily doses (for dose-related advisories), per 100 000 population.ResultsAmong advisories without dose-related advice (n=20), the average change in drug utilisation was −5.83% (95% CI −10.93 to –0.73; p=0.03). Advisories with dose-related advice (n=4) were not associated with a statistically significant change in drug utilisation (−1.93%; 95% CI −17.10 to 13.23; p=0.80). In a post hoc subgroup analysis of advisories without dose-related advice, we observed no statistically significant difference between the change in drug utilisation following advisories with explicit prescribing advice, such as a recommendation to consider the risk of a drug when prescribing, and the change in drug utilisation following advisories without such advice.ConclusionsAmong safety advisories issued on a wide range of drugs during 2009–2015 in 4 countries (Canada, Denmark, the UK and the USA), the association of advisories with changes in drug utilisation was variable, and the average association was modest.

Introduction Regulatory advisories on hydroxyzine and risk of QT prolongation and Torsade de pointes (TdP) were issued in the UK in April 2015 and Canada in June 2016. We hypothesized patients with risk factors for QT prolongation and TdP, compared with those without risk factors, would be less likely to initiate hydroxyzine in the UK and in British Columbia (BC), Canada, following advisories. Methods We conducted a longitudinal study with repeated measures, and evaluated hydroxyzine initiation in a UK cohort and a concurrent BC control cohort (April 2013–March 2016) as well as in a BC advisory cohort (June 2014–May 2017). Results This study included 247,665 patients in the UK cohort, 297,147 patients in the BC control cohort, and 303,653 patients in the BC advisory cohort. Over a 12-month post-advisory period, hydroxyzine initiation decreased by 21% in the UK (rate ratio 0.79, 95% confidence interval 0.66–0.96) relative to the expected level of initiation based on the pre-advisory trend. Hydroxyzine initiation did not change in the BC control cohort or following the Canadian advisory in the BC advisory cohort. The decrease in hydroxyzine initiation in the UK in the 12 months after the advisories was not significantly different for patients with risk factors compared with those without risk factors. Conclusion Hydroxyzine initiation decreased in the UK, but not in BC, in the 12 months following safety advisories. The decrease in hydroxyzine initiation in the UK was not significantly different for patients with versus without risk factors for QT prolongation and TdP.