Search

Objective The objectives of this study were to: 1) identify predictors of subsequent surgery following initial treatment of proximal humerus fractures (PHF); and 2) generate valid risk prediction tools to predict subsequent surgery. Methods We identified PHF patients ≥ 50 years from 2004 to 2015 using health datasets in Ontario, Canada. We used procedural codes to classify patients into treatment groups of: 1) surgical fixation; 2) shoulder replacement; and 3) conservative. We used procedural and diagnosis codes to capture subsequent surgery within two years post fracture. We developed regression models for two thirds of each group to identify predictors of subsequent surgery, and the regression equations to develop risk tools to predict subsequent surgery. We used the final third of each cohort to evaluate the discriminative ability of the risk tools using c-statistics. Results We identified 20,897 PHF patients, 2,414 treated with fixation, 1,065 with replacement, and 17,418 treated conservatively. Predictors of reoperation following fixation included bone grafting, and nail or wire fixation vs. plate fixation, while poor bone quality was associated with reoperation following initial replacement. In conservatively treated patients, more comorbidities were associated with subsequent surgery, while age 70+, and discharge home following presentation lowered the odds of subsequent surgery. The risk tools were able to discriminate with c-statistics of 0.75-0.88 (derivation) and 0.51-0.79 (validation). Conclusion Our risk tools showed good to strong discriminative ability for patients treated with fixation and conservatively. These data may be used as the foundation to develop a clinically informative tool. Level of evidence Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

OBJECTIVE School readiness is strongly associated with a child's future school success and well-being. The primary objective of this study was to determine whether meeting 24-hour movement guidelines (national physical activity, sedentary behaviors, and sleep recommendations) was associated with school readiness measured with mean scores in each of the 5 developmental domains of the Early Development Instrument (EDI) in Canadian children aged 4 to 6 years. Secondary objectives include examining the following: (1) the association between meeting 24-hour movement guidelines and overall vulnerability in school readiness and (2) the association between meeting individual physical activity, screen use and sleep recommendations, and overall school readiness. METHODS A prospective cohort study was performed using data from children (aged 4-6 years) who participated in a large-scale primary care practice-based research network. RESULTS Of the 739 participants (aged 5.9 + 0.12 years) in this prospective cohort study, 18.2% met the 24-Hour Movement Guidelines. Linear regression models (adjusted for child/family demographic characteristics, number of siblings, immigration status, and annual household income) revealed no evidence of an association between meeting all 24-hour movement guidelines and any of the 5 domains of the EDI (p > 0.05). Adjusted linear regression models revealed evidence of an association between meeting screen use guidelines and the "language and cognitive development" (β = 0.16, p = 0.004) domain, and for the sleep guideline, there was a statistically significant association with the "physical health and well-being" (β = 0.23, p = 0.001), the "language and cognitive development" (β = 0.10, p = 0.003), and the "communication skills and general knowledge" (β = 0.18, p < 0.001) domain. CONCLUSION Early lifestyle interventions targeting screen use and sleep may be beneficial for improving a child's readiness for school.

Opioid-related policies and guidelines increased the prevalence of rapid opioid dose tapering between 2016 and 2017 in Ontario, Canada, but instances were temporary and short-lived., Reports have emerged of abrupt tapering among recipients of long-term prescription opioids to conform new prescribing guidelines. We conducted a population-based, repeated cross-sectional time-series study among very high-dose (≥200 MME) opioid recipients in Ontario, Canada, to examine changes in the monthly prevalence of rapid tapering from 2014 to 2018, defined as recipients experiencing either a ≥50% reduction in daily doses or abrupt discontinuation sustained for 30 days. Interventional autoregressive integrated moving average models were used to test for significant changes following key guidelines and drug policies and programs. A sensitivity analysis examined rapid tapering sustained for 90 days. The monthly prevalence of rapid tapering events was stable from January 2014 to September 2016 (average monthly prevalence: 1.4%) but increased from 1.4% in October 2016 to 1.8% in April 2017 (P = 0.001), coincident with Ontario's Fentanyl Patch-for-Patch Return Program implementation. Transient spikes in the prevalence of rapid tapering also occurred 2 months after Ontario's delisting of publicly funded high-strength opioids and the release of updated Canadian Opioid Prescribing Guideline for Chronic Pain, reaching 2.3% in March 2017 and July 2017, respectively. However, this prevalence decreased to 1.2% in December 2018 (P < 0.0001). Although the prevalence of abrupt opioid discontinuation was lower, similar trends were observed. Our sensitivity analysis examining long-lasting rapid tapering found similar trends but lower prevalence, with no changes in complete discontinuation. These temporary increases in rapid tapering events highlight the need for improved communication and evidence-based resources for prescribers to minimize negative consequences of evolving policies and guidelines.

INTRODUCTION AND OBJECTIVE:A second transurethral resection within 2 to 6 weeks after the initial resection (i.e. re-resection) is recommended for patients diagnosed with primary T1 bladder cancer ...

Introduction: Prognostication is a significant challenge early in the post-cardiac arrest period. Common prognostic factors for neurological survival are unreliable (high false positive rates) until 72 hours post-cardiac arrest. It is not known whether there are a combination of factors that can be utilized earlier in the post-cardiac arrest period to accurately predict patient outcome. Our objective was to predict neurological outcome utilizing a novel combination of patient factors early in the post-cardiac arrest period. Methods: We conducted a retrospective cohort study using data from our local registry. We included adult patients who obtained a return of spontaneous circulation (ROSC) after out-of-hospital cardiac arrest (OHCA). We excluded patients who did not survive for at least 24 hours post-ROSC and those who had a do not resuscitate (DNR) order within 2 hours of ROSC. We performed an ordinal regression analysis using the proportional odds model to predict neurological outcome (modified rankin score (mRS)). We included a good neurological outcome (mRS 0-2), poor neurological outcome (mRS 3-5), and dead (mRS 6) as an ordinal outcome. We included a number of patient demographics, intra- and post-cardiac arrest factors as covariates in our model. The predictive performance of our model was analyzed using receiver operating characteristic (ROC) curves for discrimination and Brier statistic for calibration. Results: We included 3448 patients in our analysis. We found that an initial shockable rhythm (odds ratio (OR) 4.1; 95% confidence interval (CI) 3.6, 5.4), the absence of pupillary reflexes (OR 3.5; 95% CI 2.4,4.8) and maximum motor score on the Glasgow Coma Scale (GCS) (OR 1.5; 95% CI 1.4,1.6) had the greatest association with improved neurologic outcome. Longer duration of resuscitation was associate with worse outcomes (OR 0.84, 95% CI 0.82,0.87). The overall performance of our model was excellent with an area under the ROC curve of 0.89 and a Brier statistic of 0.13. Conclusion: Our model predicted good neurological outcome with a high rate of accuracy, however external validation of the model is required. This model may be useful to provide risk stratification of patients in clinical practice and future research on post-cardiac arrest care.

Introduction: Diagnostic imaging reports contain important data for stroke surveillance and clinical research but converting a large amount of free-text data into structured data with manual chart abstraction is resource-intensive. We determined the accuracy of CHARTextract, a natural language processing (NLP) tool, to extract relevant stroke-related attributes from full reports of computed tomograms (CT), CT angiograms (CTA), and CT perfusion (CTP) performed at a tertiary stroke centre. Methods: We manually extracted data from full reports of 1,320 consecutive CT/CTA/CTP performed between October 2017 and January 2019 in patients presenting with acute stroke. Trained chart abstractors collected data on the presence of anterior proximal occlusion, basilar occlusion, distal intracranial occlusion, established ischemia, haemorrhage, the laterality of these lesions, and ASPECT scores, all of which were used as a reference standard. Reports were then randomly split into a training set (n= 921) and validation set (n= 399). We used CHARTextract to extract the same attributes by creating rule-based information extraction pipelines. The rules were human-defined and created through an iterative process in the training sample and then validated in the validation set. Results: The prevalence of anterior proximal occlusion was 12.3% in the dataset (n=86 left, n=72 right, and n=4 bilateral). In the training sample, CHARTextract identified this attribute with an overall accuracy of 97.3% (PPV 84.1% and NPV 99.4%, sensitivity 95.5% and specificity 97.5%). In the validation set, the overall accuracy was 95.2% (PPV 76.3% and NPV 98.5%, sensitivity 90.0% and specificity 96.0%). Conclusions: We showed that CHARTextract can identify the presence of anterior proximal vessel occlusion with high accuracy, suggesting that NLP can be used to automate the process of data collection for stroke research. We will present the accuracy of CHARTextract for the remaining neurological attributes at ISC 2020.

To the Editorsβ-Adrenergic blockers (β-blockers) are among the most widely prescribed drugs in the world, with more than 191 million prescriptions dispensed in the United States in 2010 alone.1 They are commonly used to manage hypertension, heart failure, and arrhythmias and for the secondary preven

INTRODUCTION AND OBJECTIVES:Mirabegron, a β-3 adrenoreceptor agonist, used to treat overactive bladder (OAB) has been shown in clinical trials to produce a minor increase in resting heart rate, blo...

This randomized trial compared (1) continuous femoral nerve block (cFNB), (2) single femoral nerve block (sFNB), and (3) local infiltration analgesia (LIA) with respect to analgesic and functional outcomes after primary tricompartmental knee arthroplasty (TKA).One hundred twenty patients undergoing primary tricompartmental knee arthroplasty were randomly assigned to 1 of 3 interventions for postoperative analgesia: (1) cFNB-preoperative bolus of ropivacaine 0.5% 20 mL followed by ropivacaine 0.2% 5 mL per hour for 48 hours; (2) sFNB-preoperative bolus of ropivacaine 0.5% 20 mL with placebo 0.9% saline 5 mL per hour for 48 hours; or (3) LIA-intraoperative tricompartmental injection of ropivacaine 0.2% (150 mL) with epinephrine (10 µg/mL) and ketorolac 30 mg with femoral placebo 0.9% saline 20 mL preoperative bolus and 0.9% saline placebo 5 mL per hour for 48 hours. All participants received an identical, standardized, postoperative multimodal analgesic regimen. Participants, health care providers, data collectors, and analysts were blinded. All participants received identical perineural catheters and perineural/LIA solution (depending on randomized intervention) to maintain blinding. The primary outcome measure was numeric rating scale for pain (NRS) during physiotherapy on postoperative day (POD) 2 at 9:00 AM. Secondary outcomes included opioid consumption, NRS on POD 1 (rest/physiotherapy/worst), functional outcomes, and block complications.For the primary outcome, pain during physiotherapy on POD 2 at 9:00 AM, the overall analysis of covariance (ANCOVA) was significant (P = .049), but pairwise comparisons did not demonstrate any significant differences between treatment arms. NRS was 4.6 (95% confidence interval [CI], 3.3-6.0) for the cFNB group, 4.6 (95% CI, 3.3-6.0) for the sFNB group, and 3.4 (95% CI, 2.2-4.8) for the LIA group. The following is the mean difference in NRS on POD 2 at 9:00 AM among groups: cFNB-LIA (1.2, 95% CI, -0.1 to 2.5; P = .073); sFNB-LIA (1.2, 95% CI, -0.2 to 2.5; P = .097); cFNB-sFNB (0.0, 95% CI, -1.3 to 1.4; P = .996). There were no statistically significant differences between groups in cumulative 48-hour opioid consumption or functional outcomes. cFNB and LIA were superior to sFNB for NRS on POD 1 for worst pain experienced and pain during physiotherapy, respectively. There were no adverse events associated with study procedures reported among participants in the 3 groups.Our findings suggest no clinically significant differences between cFNB, LIA, and sFNB for pain during physiotherapy on POD 2 after TKA. Secondary analyses suggest that cFNB and LIA are superior to sFNB for early analgesic outcomes (NRS on POD 1) after TKA.

To examine the trends in antiepileptic drug (AED) use among individuals living in Manitoba with and without a history of epilepsy.Using data obtained from administrative health databases in Manitoba, we assessed the quarterly prevalence of AED use between 1998 and 2013 among individuals with and without a history of epilepsy using cross-sectional time series analysis.Over the study period, the number of individuals prescribed AEDs increased more than 3-fold, from 8,883 to 27,246. The prevalence of AED use among patients with epilepsy increased by 3%, from 789.6 per 1,000 in 1998/1999 to 813.9 per 1,000 in 2012/2013 (p0.001 after 2006). In contrast, we observed a 210% increase in AED use among patients without epilepsy from 6.8 to 21.1 per 1,000 over the same period (p0.001). We observed a 55-fold rise in gabapentin use among patients without a seizure disorder (from 0.2 to 11.1 per 1,000; p0.001), while gabapentin use among those with epilepsy increased only 2-fold, from 21.6 to 41.3 per 1,000 (p0.001).There has been a marked increase in the prevalence of AED users over the last 15 years, with a large shift towards the use of newer antiepileptic agents (primarily gabapentin) among those without epilepsy. Further research on the effect of these trends on health and economic outcomes will be of interest for clinicians and policymakers.

Background There are no recognized pharmacological treatments for abdominal aortic aneurysms ( AAA ), although statins are suggested to be beneficial. We sought to summarize the literature regarding the effects of statins on human AAA growth, rupture, and 30‐day mortality. Methods and Results We conducted a systematic review and meta‐analysis of randomized and observational studies using the Cochrane CENTRAL database, MEDLINE , and EMBASE up to June 15, 2018. Review, abstraction, and quality assessment were conducted by 2 independent reviewers, and a third author resolved discrepancies. Pooled mean differences and odds ratios with 95% confidence intervals were calculated using random effects models. Heterogeneity was quantified using the I 2 statistic, and publication bias was assessed using funnel plots. Our search yielded 911 articles. One case‐control and 21 cohort studies involving 80 428 patients were included. The risk of bias was low to moderate. Statin use was associated with a mean AAA growth rate reduction of 0.82 mm/y (95% confidence interval 0.33, 1.32, P =0.001, I 2 =86%). Statins were also associated with a lower rupture risk (odds ratio 0.63, 95% confidence interval 0.51, 0.78, P 2 =27%), and preoperative statin use was associated with a lower 30‐day mortality following elective AAA repair (odds ratio 0.55, 95% confidence interval 0.36, 0.83, P =0.005, I 2 =57%). Conclusions Statin therapy may be associated with reduction in AAA progression, rupture, and lower rates of perioperative mortality following elective AAA repair. These data argue for widespread statin use in AAA patients. Clinical Trial Registration URL : www.crd.york.ac.uk . Unique identifier: CRD 42017056480.

Background Statins are commonly used for the prevention of cardiovascular events; however, statins are underutilized in patients with noncoronary atherosclerosis. We sought to establish the rates of statin use in patients with carotid artery disease and to examine the association between statin therapy and outcomes after carotid revascularization. Methods and Results In this population‐level retrospective cohort study, we identified all individuals aged ≥66 years who underwent carotid endarterectomy or stenting in Ontario, Canada (2002–2014). The primary outcome was a composite of 1‐year stroke, myocardial infarction, or death (major adverse cardiac and cerebrovascular events). Five‐year risks were also examined. Adjusted hazard ratios were computed using inverse probability of treatment weighting based on propensity scores. A total of 7893 of 10 723 patients (73.6%) who underwent carotid revascularization were on preprocedural statin therapy; moderate‐ or high‐dose therapy was utilized by 7384 patients (68.9%). The composite rate of 1‐year major adverse cardiac and cerebrovascular events was lower among statin users (adjusted hazard ratio: 0.76; 95% confidence interval, 0.70–0.83). Patients who were on persistent long‐term statin therapy after the carotid procedure continued to experience significantly lower risk of major adverse cardiac and cerebrovascular events at 5 years (adjusted hazard ratio: 0.75, 95% confidence interval, 0.71–0.80). The beneficial associations with statin use were observed regardless of type of carotid revascularization procedure, carotid artery symptom status, or statin dose. Conclusions Continuous statin therapy was associated with a 25% lower risk of long‐term adverse cardiovascular events in patients with significant carotid disease. Along with other supportive evidence, statins should be considered in patients undergoing carotid revascularization, and efforts are required to increase statin use in this undertreated population.

Supplemental digital content is available in the text., Small studies suggest that prescription stimulants can precipitate psychosis and mania. We conducted a population-based case-crossover study to examine whether hospitalization for psychosis or mania was associated with initiation of stimulant therapy. Between October 1, 1999 and March 31, 2013, we studied 12,856 young people who received a stimulant prescription and were subsequently hospitalized for psychosis or mania. Of these, 183 commenced treatment during 1 of 2 prespecified 60-day intervals (defined as the “risk interval” and “control interval,” respectively) prior to admission. We found that stimulant initiation was associated with an increased risk of hospitalization for psychosis or mania in the subsequent 60 days (odds ratio, 1.86; 95% confidence interval, 1.39–2.56). The risk was marginally higher in patients treated with antipsychotic drugs (odds ratio, 2.06; 95% confidence interval, 1.38–3.28), but remained in patients with no such history (odds ratio, 1.66; 95% confidence interval, 1.09–2.66). One third of subjects received another stimulant prescription after hospital discharge. Of these, 45% were readmitted with psychosis or mania shortly thereafter. We conclude that initiation of prescription stimulants is associated with an increased risk of hospitalization for psychosis or mania. Resumption of therapy is common, which may reflect a lack of awareness of the potential causative role of these drugs.

Opioid addiction is recognized as a critical health care issue that has increased in recent years due to the advent and subsequent abuse of slow release opioids such as oxycodone (Dhalla et al., 2009; Dhalla et al., 2011; Juurlink et al., 2013). Across the province of Ontario (Canada), opioid use and subsequent addiction is seen as a major health crisis (Gomes et al., 2011; Kiepek et al., 2012; Lynas, 2013a, 2013b). For example, Gomes et al. (2014) recently reported that approximately 12% of deaths in patients between the ages of 25 and 34 years occur due to opioid-related overdoes. Despite the severity of opioid dependence in Ontario and a rapid expansion in access to treatment over the past 20 years, access to addiction therapy is not uniformly distributed across all regions of the province (Brands, 2000). Clinical practice guidelines state that methadone maintenance therapy (MMT) is the standard of care for treating patients with opioid dependence (Health Canada, 2002; Centre for Addiction and Mental Health, 2011). Methadone maintenance therapy is a substitution/maintenance treatment model whereby the patient receives methadone in a structured treatment environment to reduce or eliminate the uncontrolled use of illicit opioids (Connock et al., 2007). With substance use disorders as a primary driver of opiate-related overdoses, expanding access to addiction treatment services is recognized to be an important goal of treatment programming and policy throughout North America and Europe (Volkow et al., 2014). In Ontario, patients receiving MMT will frequently commence treatment at a specialized addiction clinic where a nurse or pharmacist will observe medication intake on a daily basis during initial treatment, with the future possibility of treatment in a family physician's office or community pharmacy following stabilization (Health Canada, 2002; Bell et al., 2006). It is a noteworthy difference from the American mode such that, in Ontario, observed dosing can be administered at several types of approved locations including a family physician's office, addiction clinic, or local pharmacy. By contrast, the American model of directly observed therapy is considerably more restrictive only allowing methadone dosing to occur at regulated opioid treatment programs. Best results for MMT, including reduced mortality rate and improved psychosocial function, are linked to continuous treatment, often over the course of several years or even decades, with gradual reduction in the level of observed medication (Health Canada, 2002; Peles et al., 2008; Bell et al., 2006; Nosyk et al., 2009, 2010, 2012; Degenhardt et al., 2011; Tetrault and Fiellin, 2012). Maintenance treatment is fundamentally different from weaning strategies because patients may remain on methadone or buprenorphine for extended periods (Peles et al., 2010). A key element of treatment is that patients receive frequent and detailed care by an addiction-trained physician including urine drug screening, counseling, and general medical care (Health Canada, 2002). In northern regions of Ontario, patients are subject to several barriers in accessing care. For example, northern patients may have difficulty enrolling in treatment due to the well-documented lack of primary care physicians, and they may also have to travel longer distances to reach a nurse or pharmacist prepared to provide observed dosing (Aird and Kerr, 2007; Canadian Mental Health Association, 2009; Kiepek et al., 2012). Currently, there is a gap in knowledge with respect to MMT retention and mortality rates for patients residing in differing geographies, especially where access to addiction services are markedly reduced. Here, we evaluate the relationship between location of residence and both treatment retention and mortality among first time MMT patients across Ontario, Canada.

Purpose We determined if the USPSTF recommendation against prostate specific antigen screening was associated with a change in biopsy and cancer detection rates. Materials and Methods We conducted a time series analysis (October 2008 to June 2013) of prostate biopsies performed at University Health Network (Toronto). Biopsies for active surveillance or solely targeting magnetic resonance imaging detected lesions were excluded from study. Interventional ARIMA models with step functions were used to examine changes in the number of biopsies performed and cancers detected per month. Low risk prostate cancer was defined as no Gleason pattern 4 or greater, 3 or fewer cores involved, or 1/3 or less of the total number of cores involved, and no core with greater than 50% cancer involvement. Intermediate to high grade prostate cancer was defined as Gleason 7-10. Results A total of 3,408 biopsies were performed and 1,601 (47.0%) prostate cancers were detected (low risk prostate cancer 563 [16.5%], intermediate to high grade prostate cancer 914 [26.8%]). The median number of biopsies per month decreased from 58.0 (IQR 54.5–63.0) before the recommendations to 35.5 (IQR 27.0–41.0) afterward (p=0.003), while the median number of patients undergoing first-time biopsy decreased from 42.5 (IQR 37.5–45.5) to 24.0 (IQR 19.0–32.5, p=0.025). The median number of low risk prostate cancers detected per month decreased from 8.5 (IQR 6.5–10.5) to 5.5 (IQR 4.0–7.0, p=0.012), while the median number of intermediate to high grade prostate cancers per month decreased from 17.5 (IQR 14.5–21.5) to 10.0 (IQR 9.0–12.0, p Conclusions After the USPSTF recommendation the number of biopsies performed (total and first-time), based on referrals from our catchment area, has decreased. This is likely due to decreased use of prostate specific antigen screening. Although it is encouraging that fewer low risk prostate cancers are being diagnosed, the sudden decrease in the detection rate of Gleason 7-10 prostate cancers is concerning.

Background and Purpose— Many ischemic strokes or transient ischemic attacks are labeled cryptogenic but may have undetected atrial fibrillation (AF). We sought to identify those most likely to have subclinical AF. Methods— We prospectively studied patients with cryptogenic stroke or transient ischemic attack aged ≥55 years in sinus rhythm, without known AF, enrolled in the intervention arm of the 30 Day Event Monitoring Belt for Recording Atrial Fibrillation After a Cerebral Ischemic Event (EMBRACE) trial. Participants underwent baseline 24-hour Holter ECG poststroke; if AF was not detected, they were randomly assigned to 30-day ECG monitoring with an AF auto-detect external loop recorder. Multivariable logistic regression assessed the association between baseline variables (Holter-detected atrial premature beats [APBs], runs of atrial tachycardia, age, and left atrial enlargement) and subsequent AF detection. Results— Among 237 participants, the median baseline Holter APB count/24 h was 629 (interquartile range, 142–1973) among those who subsequently had AF detected versus 45 (interquartile range, 14–250) in those without AF ( P P P =0.0017) and 2 years ( P =0.0027). Compared with the 16% overall 90-day AF detection rate, the probability of AF increased from Conclusions— Among older cryptogenic stroke or transient ischemic attack patients, the number of APBs on a routine 24-hour Holter ECG was a strong dose-dependent independent predictor of prevalent subclinical AF. Those with frequent APBs have a high probability of AF and represent ideal candidates for prolonged ECG monitoring for AF detection. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00846924.

We examined temporal changes in the demographics of patients undergoing definitive treatment for kidney stones during a 20-year period in Ontario, Canada.Using the Ontario Health Insurance Plan physician claims database and the Canadian Institute for Health Information Discharge Abstract Database we performed a population based cross-sectional time series analysis by identifying all kidney stone treatments done between July 1, 1991 and December 31, 2010. The demographics assessed were patient gender, age and socioeconomic status. The rate and/or proportion of kidney stone treatments per strata of these demographics were calculated for each 1-year block of the study period. We used time series analysis with exponential smoothing and autoregressive integrated moving average models to assess for trends with time.We identified 116,115 patients who underwent treatment for kidney stones during the study period. The rate of stone procedures performed per year increased steadily from 85/100,000 to 126/100,000 population. With time the rate of females who were treated increased significantly from 40/100,000 to 53/100,000 (p0.0001). In contrast, the rate of males who were treated remained stable, increasing from 82/100,000 to 83/100,000 (p = 0.11). In regard to age the rate of patients older than 64 years increased significantly with time from 67/100,000 to 89/100,000 (p0.0001). In regard to socioeconomic status approximately 20% of the patients were in each of the 5 income quintiles during the entire study period.Our population based study shows an increased rate of females and of patients older than 64 years undergoing definitive treatment for kidney stones with time.

Background— Cardiovascular mortality has decreased over the past 5 decades, making it increasingly difficult to demonstrate significant benefits of new therapies in randomized clinical trials. We sought to determine whether the use of composite end points in major cardiovascular trials has changed over time and examine temporal trends in the clinical importance of individual components of these composite end points. Methods and Results— Using a validated search strategy, we searched MEDLINE for randomized trials of therapies for primary or secondary cardiovascular prevention published in New England Journal of Medicine , The Lancet , and the Journal of the American Medical Association between 1986 and 2015. We abstracted and categorized study population demographics, type of intervention, and primary and secondary outcomes. Composite end point components were ranked according to importance (minor, moderate, major, critical, and death) and temporal trends analyzed. In total, 604 of 2607 trials retrieved met inclusion criteria. Use of composite end points increased significantly over time from 18.8% between 1986 and 1990 to 83.0% between 2011 and 2015 ( P P P P Conclusions— Contemporary cardiovascular randomized clinical trials are more likely to use primary composite end points that contain a larger number of components. Furthermore, these composite end points have increasingly incorporated components of lesser clinical importance. Clinicians and policymakers interpreting results of randomized trials should recognize that the significance of individual components in a composite end point is often heterogeneous.

Purpose: We evaluate population based trends in the use of extracorporeal shock wave lithotripsy, ureteroscopy and percutaneous nephrolithotomy during the last 20 years, as well as assess the re-treatment rate and morbidity from treatment over time.Materials and Methods: Using administrative databases in the province of Ontario, Canada, a population based cross-sectional time series analysis was performed between July 1, 1991 and December 31, 2010. All extracorporeal shock wave lithotripsy, ureteroscopy and percutaneous nephrolithotomy procedures were identified, along with all hospital readmissions and emergency department visits within 7 days of treatment. The primary outcome was treatment use, and secondary outcomes were the need for ancillary treatment and hospital readmission or emergency department visit after treatment. Exponential smoothing and autoregressive integrated moving average (ARIMA) models were used to assess trends over time.Results: We identified 194,781 kidney stone treatments perform...

Harassment and discrimination include a wide range of behaviors that medical trainees perceive as being humiliating, hostile, or abusive. To understand the significance of such mistreatment and to explore potential preventive strategies, the authors conducted a systematic review and meta-analysis to examine the prevalence, risk factors, and sources of harassment and discrimination among medical trainees.In 2011, the authors identified relevant studies by searching MEDLINE and EMBASE, scanning reference lists of relevant studies, and contacting experts. They included studies that reported the prevalence, risk factors, and sources of harassment and discrimination among medical trainees. Two reviewers independently screened all articles and abstracted study and participant characteristics and study results. The authors assessed the methodological quality in individual studies using the Newcastle-Ottawa Scale. They also conducted a meta-analysis.The authors included 57 cross-sectional and 2 cohort studies in their review. The meta-analysis of 51 studies demonstrated that 59.4% of medical trainees had experienced at least one form of harassment or discrimination during their training (95% confidence interval [CI]: 52.0%-66.7%). Verbal harassment was the most commonly cited form of harassment (prevalence: 63.0%; 95% CI: 54.8%-71.2%). Consultants were the most commonly cited source of harassment and discrimination, followed by patients or patients' families (34.4% and 21.9%, respectively).This review demonstrates the surprisingly high prevalence of harassment and discrimination among medical trainees that has not declined over time. The authors recommend both drafting policies and promoting cultural change within academic institutions to prevent future abuse.

Background— Largely on the basis of 2 randomized trials published in the 1990s, β-blockers were initially promoted as an evidence-based intervention for preventing cardiac complications of noncardiac surgery. However, subsequent studies raised concerns about a widespread use of perioperative β-blockade. Little is known regarding how this changing evidence influenced the use of perioperative β-blockers in clinical practice. Methods and Results— We conducted a population-based, time-series analysis (April 1999 to March 2010) among residents of Ontario, Canada (age 66 years and older), to evaluate the influence of research publications and practice guidelines on rates of new β-blocker prescriptions before major elective noncardiac surgery. In an analysis of 249 828 procedures, the rate of new β-blocker prescriptions increased from 26.3 per 1000 procedures in April 1999 to 62.7 per 1000 procedures in the first quarter of 2005, after which it decreased to 19.7 per 1000 procedures by March 2010. We observed a marked decrease in prescriptions ( P =0.004) during early 2005, without any preceding publications that raised concerns about perioperative β-blockade. There was no change ( P =0.98) in prescription rates after the May 2008 publication of a multicenter, randomized trial that showed increased mortality from perioperative β-blockade. Prescribing trends remain unchanged after revisions of related practice guidelines in 2002 ( P =0.28) and 2006 ( P =0.53). Conclusions— After a period characterized by increasing adoption of preoperative β-blockade between 1999 and 2005, prescriptions rates subsequently fell from 2005 to 2010. Further research is needed to understand the basis for these changes, which are only partially explained by evidence of potential harm.

Background and Purpose— Tools to predict the clinical response after intravenous thrombolytic therapy (tPA) are scarce. The iScore is an existing validated tool to estimate outcomes after an acute ischemic stroke. The purpose of this study was to determine the ability of the iScore to predict clinical response and risk of hemorrhagic transformation after tPA. Methods— We applied the iScore ( www.sorcan.ca/iscore ) to patients presenting with an acute ischemic stroke at 11 stroke centers in Ontario, Canada, between 2003 and 2009 identified from the Registry of the Canadian Stroke Network. A cohort of patients with stroke treated at 154 centers in Ontario was used for external validation. We compared outcomes between patients receiving and not receiving tPA after adjusting for differences in baseline characteristics using propensity-score matching. Patients were stratified into 3 a priori defined groups according to stroke severity using the iScore. Results— Among 12 686 patients with an acute ischemic stroke, 1696 (13.4%) received intravenous thrombolysis. Higher iScores were associated with poor outcomes in both the tPA and non-tPA groups ( P Conclusion— The iScore may be used to predict clinical response and risk of hemorrhagic complications after tPA for an acute ischemic stroke. Patients with high iScores may not have a clinically meaningful benefit from intravenous tPA at the time of carrying a higher risk of hemorrhagic complications.

Background— A predictive model of stroke mortality may be useful for clinicians to improve communication with and care of hospitalized patients. Our aim was to identify predictors of mortality and to develop and validate a risk score model using information available at hospital presentation. Methods and Results— This retrospective study included 12 262 community-based patients presenting with an acute ischemic stroke at multiple hospitals in Ontario, Canada, between 2003 and 2008 who had been identified from the Registry of the Canadian Stroke Network (8223 patients in the derivation cohort, 4039 in the internal validation cohort) and the Ontario Stroke Audit (3720 for the external validation cohort). The mortality rates for the derivation and internal validation cohorts were 12.2% and 12.6%, respectively, at 30 days and 22.5% and 22.9% at 1 year. Multivariable predictors of 30-day and 1-year mortality included older age, male sex, severe stroke, nonlacunar stroke subtype, glucose ≥7.5 mmol/L (135 mg/dL), history of atrial fibrillation, coronary artery disease, congestive heart failure, cancer, dementia, kidney disease on dialysis, and dependency before the stroke. A risk score index stratified the risk of death and identified low- and high- risk individuals. The c statistic was 0.850 for 30-day mortality and 0.823 for 1-year mortality for the derivation cohort, 0.851 for the 30-day model and 0.840 for the 1-year mortality model in the internal validation set, and 0.790 for the 30-day model and 0.782 for the 1-year model in the external validation set. Conclusion— Among patients with ischemic stroke, factors identifiable within hours of hospital presentation predicted mortality risk at 30 days and 1 year. The predictive score may assist clinicians in estimating stroke mortality risk and policymakers in providing a quantitative tool to compare facilities.

Background and Purpose— Hemiparesis resulting in functional limitation of an upper extremity is common among stroke survivors. Although existing evidence suggests that increasing intensity of stroke rehabilitation therapy results in better motor recovery, limited evidence is available on the efficacy of virtual reality for stroke rehabilitation. Methods— In this pilot, randomized, single-blinded clinical trial with 2 parallel groups involving stroke patients within 2 months, we compared the feasibility, safety, and efficacy of virtual reality using the Nintendo Wii gaming system (VRWii) versus recreational therapy (playing cards, bingo, or “Jenga”) among those receiving standard rehabilitation to evaluate arm motor improvement. The primary feasibility outcome was the total time receiving the intervention. The primary safety outcome was the proportion of patients experiencing intervention-related adverse events during the study period. Efficacy, a secondary outcome measure, was evaluated with the Wolf Motor Function Test, Box and Block Test, and Stroke Impact Scale at 4 weeks after intervention. Results— Overall, 22 of 110 (20%) of screened patients were randomized. The mean age (range) was 61.3 (41 to 83) years. Two participants dropped out after a training session. The interventions were successfully delivered in 9 of 10 participants in the VRWii and 8 of 10 in the recreational therapy arm. The mean total session time was 388 minutes in the recreational therapy group compared with 364 minutes in the VRWii group ( P =0.75). There were no serious adverse events in any group. Relative to the recreational therapy group, participants in the VRWii arm had a significant improvement in mean motor function of 7 seconds (Wolf Motor Function Test, 7.4 seconds; 95% CI, −14.5, −0.2) after adjustment for age, baseline functional status (Wolf Motor Function Test), and stroke severity. Conclusions— VRWii gaming technology represents a safe, feasible, and potentially effective alternative to facilitate rehabilitation therapy and promote motor recovery after stroke.

To examine risk factors for lower respiratory tract infections (LRTI) hospital admission in the Canadian Arctic.This was a case-control study during a 14-month period among children less than 2 years of age. Cases were admitted to the Baffin Regional Hospital in Iqaluit, Nunavut with LRTI. Controls were age matched and came from Iqaluit and 2 communities. Odds ratios (ORs) of hospital admission for LRTI were estimated through multivariate conditional logistic regression modeling for following risk factors: smoking in pregnancy, Inuit race, prematurity, adoption status, breast-feeding, overcrowding, and residing outside of Iqaluit. Viruses in nasophayngeal aspirates were sought at the time of each hospital admission.There were 101 age-matched cases and controls. The following risk factors were significantly associated with an increased risk of admission for LRTI (adjusted OR): smoking in pregnancy (OR = 4.0; 95% CI: 1.1-14.6), residence outside of Iqaluit (OR = 2.7; 95% CI: 1.0 -7.2), full Inuit race (OR = 3.8; 95% CI: 1.1-12.8), and overcrowding (OR = 2.5, 95% CI: 1.1- 6.1). Non-breast-fed children had a 3.6-fold risk of being admitted for LRTI (95% CI: 1.2-11.5) and non-breast-fed adopted children had a 4.4-fold increased risk (95% CI: 1.1-17.6) when compared with breast-fed, nonadopted children. Prematurity was not associated with an increased risk of admission. Viruses were identified in 88 (72.7%) of admissions, with respiratory syncytial virus being identified in the majority of admissions, 62 (51.2%). Multiple viruses were isolated in 19 (15.7%) admissions.Smoking during pregnancy, place of residence, Inuit race, lack of breast-feeding, and overcrowding were all independently associated with increased risk of hospital admission for LRTI among Inuit children less than 2 years of age. Future research on the role of adoption and genetics on the health of Inuit children are required.

Background. Knowledge of any harm associated with living kidney donation guides informed consent and living donor follow-up. Risk estimates in the literature are variable, and most studies did not use a healthy control group to assess outcomes attributable to donation. Methods. We observed a retrospective cohort using health administrative data for donations which occurred in Ontario, Canada between the years 1993 and 2005. There were a total of 1278 living donors and 6359 healthy adults who acted as a control group. Individuals were followed for a mean of 6.2 years (range, 1-13 years) after donation. The primary outcome was a composite of time to death or first cardiovascular event (myocardial infarction, stroke, angioplasty, and bypass surgery). The secondary outcome was time to a diagnosis of hypertension. Results. There was no significant difference in death or cardiovascular events between donors and controls (1.3% vs. 1.7%; hazard ratio 0.7,95% confidence interval 0.4-1.2). Donors were more frequently diagnosed with hypertension than controls (16.3% vs. 11.9%, hazard ratio 1.4, 95% confidence interval 1.2-1.7) but were also seen more often by their primary care physicians (median [interquartile range] 3.6 [1.9-6.1] vs. 2.6 [1.4-4.3] visits per person year, P

Introduction: Patients with peripheral arterial disease (PAD) are often undertreated for cardiovascular (CV) risk factors, and they are at high risk for CV events. Hypothesis: A program that focuses on guideline-based risk factor management reduces adverse CV and limb events in PAD patients. Methods: A propensity-score matched observational cohort study with up to 7 years of follow-up was conducted using administrative databases in Ontario, Canada. Symptomatic PAD patients that were enrolled in the Systematic Assessment of Vascular Risk (SAVR) program between July 2004 and April 2007 were matched with up to 2 (control) patients with PAD from other Ontario tertiary vascular centers not enrolled in the program. The primary outcome was a composite of death, stroke or myocardial infarction (MI). Secondary outcomes included lower limb amputation and revascularization procedures. Cox proportional hazards regression analysis was used to compare outcomes between the groups. Results: A total of 791 patients were studied. During follow-up, the SAVR group (n=290) experienced the primary outcome at a significantly lower rate than the control group (adjusted HR, 0.64 [95% CI, 0.52 to 0.78]; P Conclusions: A multifactor risk reduction program targeted to patients with PAD is associated with fewer adverse CV and limb events over the long-term. Greater focus is needed on developing structured programs for risk factor control in these high-risk patients.

Background: Case reports suggest that some selective serotonin reuptake inhibitors can interact with warfarin to increase the likelihood of bleeding. We speculated that, among patients receiving warfarin, initiation of selective serotonin reuptake inhibitor treatment would be associated with an increased risk of hospitalization for upper gastrointestinal tract bleeding (UGIB). Methods: We conducted a population-based, nested, case-control study involving Ontario residents 66 years or older continuously treated with warfarin for at least 1 year. Cases admitted with UGIB were compared with matched controls (1:10) to explore the odds ratio for initiation of various antidepressants within 42, 90, and 180 days before the index admission. Results: From January 1994 to December 2002, we identified 98,784 elderly patients continuously receiving warfarin for at least 1 year; of whom 1538 (0.6%) were admitted to hospital for UGIB. The adjusted odds ratio for fluoxetine/fluvoxamine exposure in 90 days before UGIB hospitalization is 1.2 (95% confidence interval, 0.8-1.7), and the adjusted odds ratio for other selective serotonin reuptake inhibitors in the same period was 1.1 (95% confidence interval, 0.9-1.4). The odds ratios for exposure to antidepressants in 180 days before UGIB hospitalization were similar. Conclusion: The initiation of selective serotonin reuptake inhibitor treatment in patients receiving warfarin was not associated with a significant increase in the risk of hospitalization for UGIB.

The use of outpatient laboratory databases to identify people with a low GFR may be part of an effective strategy to increase their use of treatments to prevent kidney failure. All renal function data from 17 independent outpatient laboratories in Eastern Ontario were combined to determine the proportion of adults with at least one serum creatinine measurement during a 1-yr period. The detection rates of low GFR were measured using different algorithms, and what proportion of identified low GFR was transient was considered. Canadian census data were used to calculate rates and proportions. Renal function testing was common. Of the 1,090,000 adult residents, 32% of the entire population and 63% of seniors had at least one serum creatinine measured during the study year. Sixteen percent of the population (49% of those with tests performed) had at least one GFR80 ml/min per 1.73 m2, 5% (16%) had at least one GFR60 ml/min per 1.73 m2, and 0.6% (1.7%) had at least one GFR30 ml/min per 1.73 m2. Low GFR were usually not transient: 68% of individuals with subsequent testing at least 30 d later had a similar or worse GFR. Ambulatory laboratory database case finding, particularly in older patients, seems to be a promising method for easily identifying large segments of the population with persistent reductions in GFR. Whether such identification leads to improved health outcomes warrants further study.

Background: With an aging population, patients are increasingly likely to present with stroke and pre-existing dementia, which may lead to greater death and disability. Objective: To assess the risk of all-cause mortality and poor functional outcomes after ischemic stroke in patients with and without pre-existing dementia. Design, Participants, and Setting: We conducted a multicenter cohort study of all patients presenting to 12 tertiary care institutions participating in the Registry of the Canadian Stroke Network (RCSN) with a first ischemic stroke between 2003 and 2008. Individuals with pre-existing dementia were matched using propensity score methods with patients without dementia during their index hospitalization based on these characteristics: age (within 3 years), sex, stroke severity, stroke subtype (lacunar vs. non-lacunar), level of consciousness, vascular risk factors, dysphagia, glucose and creatinine on admission, Charlson index, residence prior to hospitalization (home vs. other), pre-admission dependency, hospital arrival via ambulance, admission to stroke unit, thrombolysis, and palliative care. A propensity score model for dementia was estimated that balanced prognostically-important baseline covariates between subjects with and without dementia. Data Sources: Registry of the Canadian Stroke Network (RCSN) and Registered Persons Database (RPDB) Main Outcome Measures: The primary outcome was all cause mortality at 30-days. Secondary outcomes included mortality at discharge and at 1 year, disability at discharge (modified Rankin scale ≥3), medical complications (pneumonia), and discharge disposition. A subgroup analysis assessing the risk of intracerebral hemorrhage among those receiving thrombolysis was also conducted. Results: We matched 877 patients with an acute ischemic stroke and pre-existing dementia to 877 stroke patients without dementia. Patients were well-matched. The mean age was 82 years and 58% were women. Mortality at discharge, 30 days and one year after stroke was similar in patients with and without dementia [for mortality at discharge: RR 0.88 (95% confidence interval (CI) 0.74 to 1.05); mortality at 30-days: RR 0.88 (95%CI 0.75 to 1.03) and mortality at 1 year: RR 1.01; 95%CI 0.92 to 1.11). Patients with pre-existing dementia had similar disability at discharge and home disposition. In the subgroup of patients who received thrombolysis, there were no differences between those with and without dementia in the risk intracerebral hemorrhage (RR 1.27; 95%CI 0.69- 2.35) and no differences in mortality or disability at discharge. Conclusions: Pre-existing dementia is not independently associated with mortality, disability, or institutionalization after ischemic stroke. Pre-existing dementia should not necessarily preclude access to thrombolytic therapy and specialized stroke care.

36 Background: Socioeconomic status has been associated with increased mortality from ischemic heart disease as well as decreased access to interventions such as coronary angiography, even in countries with universal health care. We undertook a study to determine whether a similar association between socioeconomic status and mortality exists in the setting of stroke. Methods: We linked hospital discharge abstracts and vital-status data for all patients with acute stroke who were admitted to hospitals in Ontario between April 1994 and March 1997. Socioeconomic status for each patient was imputed based on their median neighborhood income as documented in Canada’s 1996 census. We determined the risk of death at thirty days and one year based on neighborhood income. Secondary analyses compared use of medications and carotid endarterectomy by income level. We used multivariate analyses to adjust for age, sex, stroke type, comorbid conditions and hospital and physician characteristics. Results: Overall, 39,545 patients were admitted with stroke during the study time frame. The crude 30-day and 1-year mortality rates were 19% and 33%, respectively. Thirty-day mortality was higher in those in the lowest income quintile than in the highest quintile (20% vs. 17%, P=0.002), with an adjusted hazard ratio of 1.1. One-year mortality was also higher in the lowest compared to the highest income quintile (34% vs. 31%, P=0.001), with an adjusted hazard ratio of 1.1. Each $10,000 increase in median neighborhood income was associated with a 9% reduction in the risk of death at 30 days (adjusted hazard ratio 0.91) and a 5% reduction in the risk of death at one year (adjusted hazard ratio 0.95). There were no differences in the use of medications (aspirin, ticlopidine, warfarin) or carotid endarterectomy based on socioeconomic status. However, waiting times for carotid surgery were significantly longer in the lowest income quintile compared to the highest (90 days vs. 60 days, P=0.001). Conclusion: Socioeconomic status affects mortality following stroke, even in a province with universal health care. The exact reasons for this effect on survival remain topics for future research.