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Objectives Antidepressants increase the risk of falls and fracture in older adults. However, risk estimates vary considerably even in comparable populations, limiting the usefulness of current evidence for clinical decision making. Our aim was to apply a common protocol to cohorts of older antidepressant users in multiple jurisdictions to estimate fracture risk associated with different antidepressant classes, drugs, doses, and potential treatment indications. Design Retrospective (2009-2014) cohort study. Setting Five jurisdictions in the United States, Canada, United Kingdom, and Taiwan. Participants Older antidepressant users-subjects were followed from first antidepressant prescription or dispensation to first fracture or until the end of follow-up. Measurements The risk of fractures with antidepressants was estimated by multivariable Cox proportional hazards models using time-varying measures of antidepressant dose and use vs nonuse, adjusting for patient characteristics. Results Between 42.9% and 55.6% of study cohorts were 75 years and older, and 29.3% to 45.4% were men. Selective serotonin reuptake inhibitors (SSRIs) (48.4%-60.0%) were the predominant class used in North America compared with tricyclic antidepressants (TCAs) in the United Kingdom and Taiwan (49.6%-53.6%). Fracture rates varied from 37.67 to 107.18 per 1,000. The SSRIs citalopram (hazard ratio [HR] = 1.23; 95% confidence interval [CI] = 1.11-1.36 to HR = 1.43; 95% CI = 1.11-1.84) and sertraline (HR = 1.36; 95% CI = 1.10-1.68), the SNRI duloxetine (HR = 1.41; 95% CI = 1.06-1.88), TCAs doxepin (HR = 1.36; 95% CI = 1.00-1.86) and imipramine (HR = 1.16; 95% CI = 1.05-1.28), and atypicals (HR = 1.34; 95% CI = 1.14-1.58) increased fracture risk in some but not all jurisdictions. In the United States and the United Kingdom, fracture risk with all classes was higher when prescribed for depression than chronic pain, a trend that is likely explained by drug choice. Conclusion The fracture risk for patients may be reduced by selecting paroxetine, an SSRI with lower risk than citalopram, the SNRI venlafaxine over duloxetine, and the TCA amitriptyline over imipramine or doxepin. There is uncertainty about the risk associated with the atypical antidepressants. J Am Geriatr Soc 68:1494-1503, 2020.

Rehabilitation post-stroke is critical for maximizing patient outcomes. This study assessed the feasibility of implementing and evaluating a continuing professional development (CPD) intervention aimed at increasing the uptake of stroke best practice guidelines among physiotherapists (PTs), occupational therapists (OTs) and speech-language pathologists (SLPs) in six university-affiliated stroke rehabilitation centers in Quebec, Canada.Twelve stroke best practice recommendations with reflective tools were sent weekly by e-mail. Participants' eligibility criteria included: a) profession; b) practicing more than 1 year in a stroke rehabilitation program; c) fluency in French or English; and d) basic computer literacy. Feasibility (operationalized via participation, satisfaction and relevance), cognitive impact, perceived application in practice and expected patient outcomes were measured over 24 weeks using three questionnaires and analyzed using descriptive statistics.The sample totaled 62 of 133 eligible (47%) clinicians. Satisfaction, relevance and cognitive impact of delivered information varied across disciplines and recommendations. Agreement with the recommendations was high across disciplines. On average, three-interdisciplinary recommendations (related to post-stoke depression, post-stoke fatigue and patients' and caregivers' learning needs) were rated as the most relevant for at least one patient. The majority of clinicians would use the recommendations for a specific patient and expected health benefits by applying those recommendations.This study demonstrated the feasibility of assessing the impact of a CPD intervention in stroke rehabilitation uptake and informed the design of a research program aimed at increasing the use of stroke evidence-based rehabilitation interventions.

Objective To examine the career outcomes of 20 years of PhD graduates from Canadian health services and policy research (HSPR) doctoral training programs. Methods The deans of the doctoral training programs were invited to participate in this national cohort study. A standardized career-tracking template was developed. Internet searches of publicly accessible sources were used to track graduates' employment. Descriptive analyses summarized PhD program characteristics and current employment. Results Of the 1,208 trainees who graduated during our study period, 884 (73.2% of 1,208, or 90.3% of the 979 with complete data) could be successfully tracked. HSPR PhD graduates are highly employable, but employment trends have changed over time. Today's graduates are more likely to enter careers in a wider variety of sectors and roles and are less likely to be employed in academia than previous graduates. However, over 50% of graduates are currently employed in professorial positions within the academic sector or in research roles or departments within healthcare delivery organizations. Conclusions This article provides an initial descriptive profile of the career outcomes of HSPR PhD graduates in Canada from 10 university-based doctoral training programs. To ensure that PhD graduates are prepared to contribute fully within diverse sectors and roles, doctoral training must evolve to keep pace with employment trends and encompass, in addition to research skills, the professional skills demanded in the public, private, not-for-profit and healthcare delivery sectors.

Background Administrative health data are increasingly used to detect adverse drug events (ADEs). However, the few studies evaluating diagnostic codes for ADE detection demonstrated low sensitivity, likely due to narrow code sets, physician under-recognition of ADEs, and underreporting in administrative data. The objective of this study was to determine if combining an expanded ICD code set in administrative data with e-prescribing data improves ADE detection. Methods We conducted a prospective cohort study among patients newly prescribed antidepressant or antihypertensive medication in primary care and followed for 2 months. Gold standard ADEs were defined as patient-reported symptoms adjudicated as medication-related by a clinical expert. Potential ADEs in administrative data were defined as physician, ED, or hospital visits during follow-up for known adverse effects of the study medication, as identified by ICD codes. Potential ADEs in e-prescribing data were defined as study drug discontinuations or dose changes made during follow-up for safety or effectiveness reasons. Results Of 688 study participants, 445 (64.7%) were female and mean age was 64.2 (SD 13.9). The study drug for 386 (56.1%) patients was an antihypertensive, and for 302 (43.9%) an antidepressant. Using the gold standard definition, 114 (16.6%) patients experienced an ADE, with 40 (10.4%) among antihypertensive users and 74 (24.5%) among antidepressant users. The sensitivity of the expanded ICD code set was 7.0%, of e-prescribing data 9.7%, and of the two combined 14.0%. Specificities were high (86.0–95.0%). The sensitivity of the combined approach increased to 25.8% when analysis was restricted to the 27% of patients who indicated having reported symptoms to a physician. Conclusion Combining an expanded diagnostic code set with e-prescribing data improves ADE detection. As few patients report symptoms to their physician, higher detection rates may be achieved by collecting patient-reported outcomes via emerging digital technologies such as patient portals and mHealth applications.

Objectives Opioid-related medication errors (MEs) can have a significant impact on patient health and contribute to opioid misuse. The objective of this study was to estimate the incidence of and variables associated with the receipt of an opioid prescription and opioid-related MEs (omissions, duplications, or dose changes) at hospital discharge. We also determined rates of adverse drug events and risks of emergency department visits, readmissions, or death 30 days and 90 days post discharge associated with MEs. Methods A cohort of hospitalized patients discharged from the McGill University Health Centre between 2014 and 2016 was assembled. The impact of opioid-related MEs was assessed in a propensity score–adjusted logistic regression models. Multivariable logistic regression was used to determine characteristics associated with MEs and discharge opioid prescription. Results A total of 1530 (43.9%) of 3486 patients were prescribed opioids, of which 13.4% (n = 205) of patients had at least 1 opioid-related ME. Rates of MEs were higher in handwritten prescriptions compared to the electronic reconciliation discharge prescription group (20.6% vs 1.2%). Computer-based prescriptions were associated with a 69% lower risk of opioid-related MEs (adjusted odds ratio: 0.31, 95% confidence interval: 0.14-0.65) as well as 63% lower risk of receiving an opioid prescription. Opioid-related MEs were associated with a 2.3 times increased risk of healthcare utilization in the 30 days postdischarge period (adjusted odds ratio: 2.32, 95% confidence interval: 1.24-4.32). Conclusions Opioid-related MEs are common in handwritten discharge prescriptions. Our findings highlight the need for computer-based prescribing platforms and careful review of medications during critical periods of care such as hospital transitions.

Background and Purpose— There is no consensus on the comparative efficacy and safety of carotid artery stenting (CAS) versus carotid endarterectomy (CEA) in patients with asymptomatic carotid artery stenosis. To evaluate CAS versus CEA in asymptomatic patients, we conducted a systematic review and meta-analysis of randomized controlled trials. Methods— We systematically searched EMBASE, PubMed, MEDLINE, and the Cochrane Library for randomized controlled trials comparing CAS to CEA in asymptomatic patients using a pre-specified protocol. Two independent reviewers identified randomized controlled trials meeting our inclusion/exclusion criteria, extracted relevant data, and assessed quality using the Cochrane risk of bias tool. Random effects models with inverse-variance weighting were used to estimate pooled risk ratios (RRs) comparing the incidences of periprocedural and long-term outcomes between CAS and CEA. Results— We identified 11 reports of 5 randomized controlled trials for inclusion (n=3019) asymptomatic patients. The pooled incidences of any periprocedural stroke (RR, 1.84; 95% confidence interval [CI], 0.99–3.40), periprocedural nondisabling stroke (RR, 1.95; 95% CI, 0.98–3.89), and any periprocedural stroke or death (RR, 1.72; 95% CI, 0.95–3.11) trended toward an increased risk after CAS. We could not rule out clinically significant differences between treatments for long-term stroke (RR, 1.24; 95% CI, 0.76–2.03) and the composite outcome of periprocedural stroke, death or myocardial infarction, or long-term ipsilateral stroke (RR, 0.92; 95% CI, 0.70–1.21). Conclusions— Although uncertainty surrounds the long-term outcomes of CAS versus CEA, the potential for increased risks of periprocedural stroke and periprocedural stroke or death with CAS suggests that CEA is the preferred option for the management of asymptomatic carotid stenosis.

Context Treatment guidelines recommend the use of combination therapies for smoking cessation, particularly behavioral therapy (BT) as an adjunct to pharmacotherapy. However, these guidelines rely on previous reviews with important limitations. This study's objective was to evaluate the efficacy of combination therapies compared with monotherapies, using the most rigorous data available. Evidence acquisition A systematic review and meta-analysis of RCTs of pharmacotherapies, BTs, or both were conducted. The Cochrane Library, Embase, PsycINFO, and PubMed databases were systematically searched from inception to July 2015. Inclusion was restricted to RCTs reporting biochemically validated abstinence at 12 months. Direct and indirect comparisons were made in 2015 between therapies using hierarchical Bayesian models. Evidence synthesis The search identified 123 RCTs meeting inclusion criteria (60,774 participants), and data from 115 (57,851 participants) were meta-analyzed. Varenicline with BT increased abstinence more than other combinations of a pharmacotherapy with BT (varenicline versus bupropion: OR=1.56, 95% credible interval [CrI]=1.07, 2.34; varenicline versus nicotine patch: OR=1.65, 95% CrI=1.10, 2.51; varenicline versus short-acting nicotine-replacement therapies: OR=1.68, 95% CrI=1.15, 2.53). Adding BT to any pharmacotherapy compared with pharmacotherapy alone was inconclusive, owing to wide CrIs (OR=1.17, CrI=0.60, 2.12). Nicotine patch with short-acting nicotine-replacement therapy appears safe and increases abstinence versus nicotine-replacement monotherapy (OR=1.63, CrI=1.06, 3.03). Data are limited concerning other pharmacotherapy combinations and their safety and tolerability. Conclusions Evidence suggests that combination therapy benefits may be less than previously thought. Combined with BT, varenicline increases abstinence more than other pharmacotherapy with BT combinations.

ObjectivesWe used an international pharmacosurveillance network to estimate the rate and characteristics of antidepressant use in older adults in countries with more conservative (UK) and liberal depression guidelines (Canada, USA).SettingElectronic health records and population-based administrative data from six jurisdictions in four countries (UK, Taiwan, USA and Canada).ParticipantsA historical cohort of older adults (≥65 years) who had a new episode of antidepressant use between 2009 and 2014.Outcome measuresThe age and sex-standardised cumulative incidence of new episodes of antidepressant use in older adults was measured. Descriptive statistics were used to compare the proportion of new users by the antidepressant prescribed, therapeutic class, potential treatment indication and country, as well as the characteristics of the first treatment episode (standardised daily doses, duration and changes).ResultsThe incidence of antidepressant use between 2009 and 2014 varied from 4.7% (Montreal and Quebec City) to 18.6% (Taiwan). Tricyclic antidepressants (TCAs) were the most commonly used class in the UK (48.8%) and Taiwan (52.4%) compared with selective serotonin reuptake inhibitors (SSRIs) in North American jurisdictions (42.3%–53.3%). Chronic pain was the most common potential treatment indication (41.2%–68.2%). Among users with chronic pain, TCAs were used most frequently in the UK and Taiwan (55.2%–60.4%), whereas SSRIs were used most frequently in North America (33.5%–46.4%). Treatment was longer (252–525 vs 169–437 days), standardised doses were higher (0.7–1.3 vs 0.5–1.0) and treatment was more likely to be changed (31%–46% vs 21%–34%) among patients with depression (9.1%–43%) than those with chronic pain.ConclusionAntidepressant use in older adults varied 24-fold by country, with the UK, which has the most conservative treatment guidelines, being among the lowest. Chronic pain was the most common potential treatment indication. Evaluation of real-world risks of TCAs is a priority for future research, given high rates of use and the potential for increased toxicity in older adults because of potent anticholinergic effects.

American College of Cardiology Foundation/American Heart Association guidelines no longer recommend the use of routine aspiration thrombectomy during primary percutaneous coronary intervention (PCI). This is based on evidence from recent randomized controlled trials (RCTs) that suggests that the long-term benefits of aspiration thrombectomy were previously overestimated. We conducted a systematic review and meta-analysis of RCTs to examine the effect of routine aspiration thrombectomy during primary PCI versus primary PCI alone on markers of reperfusion immediately after PCI and on clinical outcomes at ≥6 months. We systematically searched Medline, EMBASE, and the Cochrane Library of Clinical trials for RCTs published in English or French with follow-up ≥6 months. Data were pooled using random-effects models. Eighteen publications (containing data from 14 RCTs, n = 20,285) met our inclusion criteria. Aspiration thrombectomy was associated with higher rates of ST-segment resolution (relative risk [RR] 1.22, 95% CI 1.07 to 1.40) and myocardial blush grade 3 (RR 1.30, 95% CI 1.01 to 1.67) and a reduced risk of no reflow immediately after PCI (RR 0.63, 95% CI 0.40 to 0.98). However, thrombectomy was not associated with our primary outcome of all-cause mortality at longest available follow-up (RR 0.92, 95% CI 0.81 to 1.04). Similar results were obtained for myocardial infarction and target vessel/lesion revascularization. Thrombectomy also increased the risk of stroke (RR 1.59, 95% CI 1.07 to 2.35). In conclusion, routine aspiration thrombectomy during primary PCI has some short-term clinical benefits but does not improve outcomes ≥6 months and increases the risk of stroke.

Depression is common among cardiac patients and associated with adverse cardiovascular outcomes. Bright light therapy has emerged as a promising treatment for depressive symptoms, however it has not yet been investigated in this population. We conducted a double-blind, randomized, placebo-controlled pilot trial to assess the feasibility of a larger-scale trial testing bright light therapy for depressive symptoms in cardiac patients. Patients hospitalized for an acute coronary syndrome or undergoing cardiac surgery were randomized to either bright light (10,000 lux) or dim light placebo (500 lux) lamps for 30 minutes each day over 4 weeks, beginning in-hospital. Depression was quantified using the Patient Health Questionnaire 9 (PHQ-9) and Depression Anxiety and Stress Scales (DASS-21). The Short-Form Health Survey 36 (SF-36) was used to measure quality of life. A total of 175 patients were screened and 15 were randomized (8 treatment, 7 placebo) (8.6%) over 10 months. Despite protocol amendments which broadened the inclusion criteria, the trial was terminated early for infeasibility based on the rate of enrollment (1–2 participants/month), with 39.5% of the target sample (38 participants) enrolled. Future trials should take into account the timing of the onset of depressive symptoms in these patients, and consider a less conservative approach to eligibility as well as ways to increase the acceptability of bright light therapy in hospitalized cardiac patients. Once enrolled, our findings suggest that most participants will adhere to the assigned treatment and complete follow-up.

Background Smoking cessation and weight management are recommended after acute coronary syndrome ( ACS ); however, little is known about the effects of smoking cessation on weight change after ACS . We aimed to assess the effect of smoking cessation after ACS on weight over a 12‐month follow‐up period. Methods and Results Data were prospectively collected from the EVITA (Evaluation of Varenicline in Smoking Cessation for Patients Post‐Acute Coronary Syndrome) trial. Weight change was compared among 3 groups of patients: those who were completely abstinent (n=70), those who smoked intermittently (n=68), and those who smoked persistently (n=34). Patients' mean baseline weight was 83.9 kg ( SD 17.7) with a mean body mass index of 28.5 ( SD 5.4). Patients smoked a mean of 37.7 years ( SD 17.7) and a mean of 21.0 cigarettes ( SD 9.0) per day prior to their ACS . Weight change varied across groups, with abstainers gaining a mean of 4.8 kg ( SD 8.6), intermittent smokers gaining a mean of 2.0 kg ( SD 8.9) and persistent smokers losing a mean of 0.7 kg ( SD 7.4). At 52 weeks, abstainers were more likely to gain weight than persistent smokers (difference in means 5.5 kg; 95% CI 2.3–8.8). This weight gain was not associated with an increase in the use of antihypertensive or antidiabetic medications. Conclusions Following an ACS , significant weight is gained by patients who quit smoking. Weight‐management interventions among smokers who quit after ACS should be a focus of investigation in future research so that the cardiovascular benefits achieved by smoking cessation are not offset by weight gain in this high‐risk population. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 00794573.

Importance Adverse drug events (ADEs) account for up to 16% of emergency department (ED) visits and 7% of hospital admissions. Medication reconciliation is required for hospital accreditation because it can reduce medication discrepancies, but there is no evidence that reducing discrepancies reduces ADEs or other adverse outcomes. Objective To evaluate whether electronic medication reconciliation reduces ADEs, medication discrepancies, and other adverse outcomes compared with usual care. Design, Setting, and Participants This cluster randomized trial involved 3491 patients who were discharged from 2 medical units and 2 surgical units at the McGill University Health Centre, Montreal, Quebec, Canada, between October 2014 and November 2016. Data analysis took place from July 2017 to July 2019. Intervention The RightRx intervention electronically retrieved community drugs from the provincial insurer and aligned them with in-hospital drugs to facilitate reconciliation and communication at care transitions. Main Outcomes and Measures The primary outcome was ADEs in 30 days after discharge. Secondary outcomes included medication discrepancies, ED visits, hospital readmissions, and a composite outcome of ED visits, readmissions, and death up to 90 days after discharge. Results Of 4656 eligible patients, 3567 (76.6%) consented to participate (2060 [57.8%] men; mean [SD] age, 69.8 [14.9] years). Overall, 76 patients died during the hospital stay, so 3491 patients were included in the analysis. There was no significant difference in the risk of ADEs between intervention and control groups (76 [4.6%] vs 73 [4.0%]; OR, 0.97; 95% CI, 0.33-1.48), ED visits (433 [26.2%] vs 488 [26.6%]; OR, 0.83; 95% CI, 0.36-1.42), hospital readmission (170 [10.3%] vs 261 [14.2%]; OR, 0.22; 95% CI, 0.06-1.14), or the composite outcome (447 [27.0%] vs 506 [27.6%]; OR, 0.75; 95% CI, 0.34-1.27) at 30 days. Medication discrepancies were significantly reduced in the intervention group compared with the control group (437 [26.4%] vs 1029 [56.0%]; OR, 0.24; 95% CI, 0.12-0.57). Changes made to community medications (OR, 1.05; 95% CI, 1.01-1.10) and new medications (OR, 1.09; 95% CI, 1.01-1.18) were significant risk factors for ADEs. Conclusions and Relevance Electronic medication reconciliation reduced medication discrepancies but did not reduce ADEs or other adverse outcomes. Hospital accreditation should focus on interventions that reduce the risk of adverse events for patients with multiple changes to community medications. Trial Registration ClinicalTrials.gov identifier:NCT01179867