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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.

OBJECTIVES: To quantify the real-world survival benefit of re-resection vs no re-resection in patients diagnosed with T1 bladder cancer (BC) at the population level. PATIENTS AND METHODS: Retrospective population-wide observational cohort study based on pathology reports linked to health administrative data. We identified patients who were diagnosed with T1 BC in the province of Ontario (01/2001-12/2015) and used billing claims to ascertain whether they received re-resection within 2-10 weeks. The time-dependent effect of re-resection on survival outcomes was modelled by Cox proportional hazards regression (unadjusted and adjusted for numerous assumed patient- and surgeon-level confounding variables). Effect measures were presented as hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: We identified 7666 patients of which 2162 (28.7%) underwent re-resection after a median (interquartile range) time of 45 (35-56) days. Patients who received re-resection were less likely to die from any causes (HR 0.68, 95% CI 0.63-0.74, P

Background Several Canadian provinces have introduced reimbursement policies mandating substitution of innovator biologics with lower-cost biosimilars. We estimated the number of patients affected and cost implications if such policy changes were to be implemented in Ontario, Canada. Methods We conducted a cross-sectional time series analysis of Ontarians dispensed publicly funded biologics indicated for inflammatory diseases (rheumatic conditions, inflammatory bowel disease: infliximab, etanercept, adalimumab) between January 2018 and December 2019, and forecasted trends to Dec. 31, 2020. The primary source of data was pharmacy claims data for all biologics reimbursed by the public drug program. We modelled the number of patients affected and government expenditures (in nominal Canadian dollars) of several biosimilar policy options, including mandatory nonmedical biosimilar substitution, substitution in new users, introduction of a biosimilar for adalimumab, and price negotiations. In a secondary analysis, we included insulin glargine. Results In 2018, 14 089 individuals were prescribed a publicly funded biologic for inflammatory diseases. A mandatory nonmedical biosimilar substitution would potentially have affected 7209 patients and saved $238.6 million from 2018 to 2020. A new-user substitution would have affected 757 patients and saved $34.2 million. If an adalimumab biosimilar were to become available, 12 928 patients would be affected by a mandatory nonmedical substitution and the 3-year savings would increase to $645.9 million (all biosimilars priced at 25% of innovator biologics). Finally, an expanded nonmedical substitution policy including insulin glargine would affect 115 895 patients and save $288.7 million (not including adalimumab). Interpretation Policies designed to curb rising costs of biologics can have substantially different effects on patients and government expenditures. Such analyses warrant careful consideration of the balance between cost savings and effects on patients.

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.

The Standardized Reporting of Machine Learning Applications in Urology (STREAM-URO) framework was developed to provide a set of recommendations to help standardize how machine learning studies in urology are reported. This framework serves three purposes: (1) to promote high-quality studies and streamline the peer review process; (2) to enhance reproducibility, comparability, and interpretability of results; and (3) to improve engagement and literacy of machine learning within the urological community.

Opioids are commonly prescribed following childbirth, but data are lacking on trends in postpartum opioid prescribing over time. We examined whether a highly-publicized 2006 case report questioning the safety of codeine during lactation was associated with changes in postpartum opioid prescribing. We conducted a cross-sectional time series analysis of all publicly-funded prescriptions for opioids to postpartum women in Ontario, Canada from April 1, 2000 to March 31, 2017. The intervention was the publication of a case report in 2006 attributing the death of a breastfeeding neonate to maternal codeine use. The primary outcome was the rate of opioid prescribing to postpartum women. Among postpartum women eligible for prescription drug coverage, 17.5% filled an opioid prescription in the third quarter of 2006 (immediately prior to publication of the case report), with codeine representing 89.8% of all prescriptions. By the fourth quarter of 2010, only 12.2% of postpartum women filled an opioid prescription, representing a decline of 30% (p

RESUME CONTEXTE: Les caracteristiques des patients, les soins cliniques, l’utilisation des ressources et les issues cliniques des personnes atteintes de la maladie a coronavirus 2019 (COVID-19) hospitalisees au Canada ne sont pas bien connus. METHODES: Nous avons recueilli des donnees sur tous les adultes hospitalises atteints de la COVID-19 ou de l’influenza ayant obtenu leur conge d’unites medicales ou d’unites de soins intensifs medicaux et chirurgicaux entre le 1er novembre 2019 et le 30 juin 2020 dans 7 centres hospitaliers de Toronto et de Mississauga (Ontario). Nous avons compare les issues cliniques des patients a l’aide de modeles de regression multivariee, en tenant compte des facteurs sociodemographiques et de l’intensite des comorbidites. Nous avons valide le degre d’exactitude de 7 scores de risque mis au point a l’externe pour determiner leur capacite a predire le risque de deces chez les patients atteints de la COVID-19. RESULTATS: Parmi les hospitalisations retenues, 1027 patients etaient atteints de la COVID-19 (âge median de 65 ans, 59,1 % d’hommes) et 783 etaient atteints de l’influenza (âge median de 68 ans, 50,8 % d’hommes). Les patients âges de moins de 50 ans comptaient pour 21,2 % de toutes les hospitalisations dues a la COVID-19 et 24,0 % des sejours aux soins intensifs. Comparativement aux patients atteints de l’influenza, les patients atteints de la COVID-19 presentaient un taux de mortalite perhospitaliere (mortalite non ajustee 19,9 % c. 6,1 %; risque relatif [RR] ajuste 3,46 %, intervalle de confiance [IC] a 95 % 2,56–4,68) et un taux d’utilisation des ressources des unites de soins intensifs (taux non ajuste 26,4 % c. 18,0 %; RR ajuste 1,50, IC a 95 % 1,25–1,80) significativement plus eleves, ainsi qu’une duree d’hospitalisation (duree mediane non ajustee 8,7 jours c. 4,8 jours; rapport des taux d’incidence ajuste 1,45; IC a 95 % 1,25–1,69) significativement plus longue. Le taux de rehospitalisation dans les 30 jours n’etait pas significativement different (taux non ajuste 9,3 % c. 9,6 %; RR ajuste 0,98 %, IC a 95 % 0,70–1,39). Trois scores de risque utilisant un pointage pour predire la mortalite perhospitaliere ont montre une bonne discrimination (aire sous la courbe [ASC] de la fonction d’efficacite du recepteur [ROC] 0,72–0,81) et une bonne calibration. INTERPRETATION: Durant la premiere vague de la pandemie, l’hospitalisation des patients atteints de la COVID-19 etait associee a des taux de mortalite et d’utilisation des ressources des unites de soins intensifs et a une duree d’hospitalisation significativement plus importants que les hospitalisations des patients atteints de l’influenza. De simples scores de risque peuvent predire avec une bonne exactitude le risque de mortalite perhospitaliere des patients atteints de la COVID-19.

BACKGROUND AND AIMS: In June 2016, the Ontario, Canada government implemented the Ontario Naloxone Program for Pharmacies (ONPP), authorizing pharmacists to provide injectable naloxone kits at no charge to all Ontario residents. In March 2018, the program was amended to include intranasal naloxone and remove the requirement to present a government health card to the dispensing pharmacist. We examined whether these changes increased naloxone dispensing through the ONPP. DESIGN: Population-based time-series analysis using interventional autoregressive integrated moving average models. SETTING: Ontario, Canada. PARTICIPANTS: All Ontario residents between 1 July 2016 and 31 March 2020. MEASUREMENTS: Monthly rates of pharmacy naloxone dispensing. FINDINGS: Overall, 199 484 individuals were dispensed a naloxone kit during the study period. In the main analysis, the rate of pharmacy naloxone dispensing increased by 65.1% following program changes (55.6-91.8 kits per 100 000 population between February 2018 and May 2018; P = 0.01). In subgroup analyses, naloxone dispensing increased among individuals receiving opioid agonist therapy (OAT) (3374.9-7264.2 kits per 100 000 OAT recipients; P = 0.04) among individuals receiving other prescription opioids (192.8-381.8 kits per 100 000 population prescribed opioids; P

BackgroundVariations in inpatient medical care are typically attributed to system, hospital or patient factors. Little is known about variations at the physician level within hospitals. We described the physician-level variation in clinical outcomes and resource use in general internal medicine (GIM).MethodsThis was an observational study of all emergency admissions to GIM at seven hospitals in Ontario, Canada, over a 5-year period between 2010 and 2015. Physician-level variations in inpatient mortality, hospital length of stay, 30-day readmission and use of ‘advanced imaging’ (CT, MRI or ultrasound scans) were measured. Physicians were categorised into quartiles within each hospital for each outcome and then quartiles were pooled across all hospitals (eg, physicians in the highest quartile at each hospital were grouped together). We report absolute differences between physicians in the highest and lowest quartiles after matching admissions based on propensity scores to account for patient-level variation.ResultsThe sample included 103 085 admissions to 135 attending physicians. After propensity score matching, the difference between physicians in the highest and lowest quartiles for in-hospital mortality was 2.4% (95% CI 0.6% to 4.3%, pConclusionsPatient outcomes and resource use in inpatient medical care varied substantially across physicians in this study. Physician-level variations in length of stay and imaging use were unlikely to be explained by patient factors whereas differences in mortality and readmission should be interpreted with caution and could be explained by unmeasured confounders. Physician-level variations may represent practice differences that highlight quality improvement opportunities.

Background: Machine learning (ML) is a rapidly advancing field with increasing utility in health care. We conducted a systematic review and critical appraisal of ML applications in vascular surgery. Methods: MEDLINE, Embase, and Cochrane CENTRAL were searched from inception to March 1, 2021. Study screening, data extraction, and quality assessment were performed by two independent reviewers, with a third author resolving discrepancies. All original studies reporting ML applications in vascular surgery were included. Publication trends, disease conditions, methodologies, and outcomes were summarized. Critical appraisal was conducted using the PROBAST risk-of-bias and TRIPOD reporting adherence tools. The PROSPERO registration number is CRD42021240310. Findings: We included 212 studies from a pool of 2,235 unique articles. ML techniques were used for diagnosis, prognosis, and image segmentation in carotid stenosis, aortic aneurysm/dissection, peripheral artery disease, diabetic foot ulcer, venous disease, and renal artery stenosis. The number of publications on ML in vascular surgery increased from 1 (1991-1996) to 118 (2016-2021). Most studies were retrospective and single center, with no randomized controlled trials. Area under the receiver operating characteristic curve (AUROC) ranged from 0.61-1.00, with 79.5% [62/78] studies reporting AUROC ≥ 0.80. Out of 22 studies comparing ML techniques to existing prediction tools, clinicians, or traditional regression models, 20 performed better and 2 performed similarly. Overall, 94.8% (201/212) studies had high risk-of-bias and adherence to reporting standards was poor with a rate of 41.4%. Interpretation: Machine learning has been increasingly applied to a broad range of vascular surgical conditions with good predictive value. However, overall risk-of-bias and reporting adherence are suboptimal. Future studies should consider standardized tools such as PROBAST and TRIPOD to improve study quality and clinical applicability. Funding: None. Declaration of Interest: All authors declare no competing interests

Background The capacity of general internal medicine (GIM) clinical teaching units has been strained by decreasing resident supply and increasing patient demand. The objective of our study was to compare the number of residents (supply) with the volume and duration of patient care activities (demand) to identify inefficiency. Methods Using the most recently available data from an academic teaching hospital in Toronto, Ontario, we identified each occurrence of a set of patient care activities that took place on the clinical teaching unit from 2015 to 2019. We completed a descriptive analysis of the frequencies of these activities and how the frequencies varied by hour, day, week, month and year. Patient care activities included admissions, rounds, responding to pages, meeting with patients and their families, patient transfers, discharges and responding to cardiac arrests. The estimated time to complete each task was based on the available data in our electronic medical record system and interviews with GIM physicians and trainees. To calculate resident utilization, the person-hours of patient care tasks was divided by the person-hours of resident supply. Resident utilization was computed for 3 scenarios corresponding to varying levels of resident absenteeism. Results During the study period, there were 14 581 consultations to GIM from the emergency department. Patient volumes tended to be highest during January and lowest during May and June, and highest on Monday morning and lowest on Friday night. Daily admissions to hospital from the emergency department were higher on weekdays than on weekends, and hourly admissions peaked at 8 am and between 3 pm and 1 am. Weekday resident utilization was generally highest between 8 am and 2 pm, and lowest between 1 am and 8 am. In a scenario in which all residents were present apart from those who were post-call, resident utilization generally never exceeded 100%; in scenarios in which at least 1 resident was absent owing to illness or vacation, it was common for resident utilization to approach or exceed 100%, particularly during daytime working hours. Interpretation Analyzing supply and demand on a GIM ward has allowed us to identify periods when supply and demand are not aligned and to demonstrate empirically the vulnerability of current staffing models. These data have the potential to inform and optimize scheduling on an internal medicine ward.

Background Cerebral protection remains the cornerstone of successful aortic surgery; however, there is no consensus as to the optimal strategy. Objective To compare the safety and efficacy of innominate to axillary artery cannulation for delivering antegrade cerebral protection during proximal aortic arch surgery. Methods This randomized controlled trial (The Aortic Surgery Cerebral Protection Evaluation CardioLink-3 Trial, ClinicalTrials.gov Identifier: NCT02554032 ), conducted across 6 Canadian centers between January 2015 and June 2018, allocated 111 individuals to innominate or axillary artery cannulation. The primary safety outcome was neuroprotection per the appearance of new severe ischemic lesions on the postoperative diffusion-weighted-magnetic resonance imaging. The primary efficacy outcome was the difference in total operative time. Secondary outcomes included 30-day all-cause mortality and postoperative stroke. Results One hundred two individuals (mean age, 63 ± 11 years) were in the primary safety per-protocol analysis. Baseline characteristics between the groups were similar. New severe ischemic lesions occurred in 19 participants (38.8%) in the axillary versus 18 (34%) in the innominate group (P for noninferiority = .0009). Total operative times were comparable (median, 293 minutes; interquartile range, 222-411 minutes) for axillary versus (298 minutes; interquartile range, 231-368 minutes) for innominate (P for superiority = .47). Stroke/transient ischemic attack occurred in 4 (7.1%) participants in the axillary versus 2 (3.6%) in the innominate group (P = .43). Thirty-day mortality, seizures, delirium, and duration of mechanical ventilation were similar in both groups. Conclusions diffusion-weighted magnetic resonance imaging assessments indicate that antegrade cerebral protection with innominate cannulation is safe and affords similar neuroprotection to axillary cannulation during aortic surgery, although the burden of new neurological lesions is high in both groups.

Background Identifying venous thromboembolism (VTE) from large clinical and administrative databases is important for research and quality improvement. Objective To develop and validate natural language processing (NLP) algorithms to identify VTE from radiology reports among general internal medicine (GIM) inpatients. Methods This cross-sectional study included GIM hospitalizations between April 1, 2010 and March 31, 2017 at 5 hospitals in Toronto, Ontario, Canada. We developed NLP algorithms to identify pulmonary embolism (PE) and deep venous thrombosis (DVT) from radiologist reports of thoracic computed tomography (CT), extremity compression ultrasound (US), and nuclear ventilation-perfusion (VQ) scans in a training dataset of 1551 hospitalizations. We compared the accuracy of our NLP algorithms, the previously-published “simpleNLP” tool, and administrative discharge diagnosis codes (ICD-10-CA) for PE and DVT to the “gold standard” manual review in a separate random sample of 4000 GIM hospitalizations. Results Our NLP algorithms were highly accurate for identifying DVT from US, with sensitivity 0.94, positive predictive value (PPV) 0.90, and Area Under the Receiver-Operating-Characteristic Curve (AUC) 0.96; and in identifying PE from CT, with sensitivity 0.91, PPV 0.89, and AUC 0.96. Administrative diagnosis codes and the simple NLP tool were less accurate for DVT (ICD-10-CA sensitivity 0.63, PPV 0.43, AUC 0.81; simpleNLP sensitivity 0.41, PPV 0.36, AUC 0.66) and PE (ICD-10-CA sensitivity 0.83, PPV 0.70, AUC 0.91; simpleNLP sensitivity 0.89, PPV 0.62, AUC 0.92). Conclusions Administrative diagnosis codes are unreliable in identifying VTE in hospitalized patients. We developed highly accurate NLP algorithms to identify VTE from radiology reports in a multicentre sample and have made the algorithms freely available to the academic community with a user-friendly tool ( https://lks-chart.github.io/CHARTextract-docs/ ).

Prior research has shown that concordance with the guideline-endorsed recommendation to re-resect patients diagnosed with primary T1 bladder cancer (BC) is suboptimal. Therefore, the aim of this population-based study was to identify factors associated with re-resection in T1 BC.We linked province-wide BC pathology reports (January 2001 to December 2015) with health administrative data sources to derive an incident cohort of patients diagnosed with T1 BC in the province of Ontario, Canada. Re-resection was ascertained by a billing claim for transurethral resection within 2 to 8 weeks after the initial resection, accounting for system-related wait times. Multivariable logistic regression analysis accounting for the clustered nature of the data was used to identify various patient-level and surgeon-level factors associated with re-resection. P values0.05 were considered statistically significant (2-sided).We identified 7,373 patients who fulfilled the inclusion criteria. Overall, 1,678 patients (23%) underwent re-resection. Patients with a more aggressive tumor profile and individuals without sufficiently sampled muscularis propria as well as younger, healthier and socioeconomically advantaged patients were more likely to receive re-resection (all p0.05). In addition, more senior, lower volume and male surgeons were less likely to perform re-resection for their patients (all p0.05).Only a minority of all patients received re-resection within 2 to 8 weeks after initial resection. To improve the access to care for potentially underserved patients, we suggest specific knowledge translation/exchange interventions that also include equity aspects besides further promotion of evidence-based instead of eminence-based medicine.

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 ...

Mortality rates in our fracture liaison service ranged from 2.7% at year 1 to 14.8% at year 5 post-screening. Presentation with multiple simultaneous fractures at screening was associated with higher risk of death. This finding indicates the need for increased focus on this high-risk group. To examine all-cause mortality rates in a provincial fracture liaison service (FLS) and the association between the index fracture type, particularly multiple simultaneous fractures, and the risk of death at follow-up. This cohort study includes fragility fracture patients aged 50+, enrolled in a provincial FLS in Ontario, Canada, between 2007 and 2010. All-cause mortality was assessed using administrative data. Multivariable Cox proportional hazards model was used to examine the risk of death 5 years after screening. Crude mortality rates for 6543 fragility fracture patients were 2.7% at year 1, 5.6% at year 2, and 14.8% at year 5 after screening. After adjusting for age and sex, and relative to distal radius fracture, patients with multiple (simultaneous) fractures at screening had a higher risk of dying (HR = 1.8, 95%CI 1.3–2.4), followed by those with a hip fracture (HR = 1.5, 95%CI 1.3–1.8), a proximal humerus fracture (HR = 1.4, 95%CI 1.2–1.7), and other single fractures (HR = 1.4, 95%CI 1.1–1.7). Having an index ankle fracture was not associated with the risk of death over a distal radius fracture. As compared to the 50–65 age group, patients 66 years and older had a higher risk of death (for 66–70 age group: HR = 2.5, 95%CI 1.9–3.3; for 71–80: HR = 4.3, 95%CI 3.5–5.4; and for 81+: HR = 10.6, 95%CI 8.7–13.0). Females had a lower risk of death (HR = 0.5, 95%CI 0.5–0.6) than males. Presenting with multiple fractures was an indicator of higher risk of death relative to a distal radius fracture. This finding indicates the need for increased focus on this high-risk group.

Background Although it is known that women do not participate in trials as frequently as men, there are limited recent data examining how women recruitment has changed over time. Methods We conducted MEDLINE search using a validated strategy for randomized trials published in New England Journal of Medicine, Lancet, and Journal of the American Medical Association between 1986 and 2015, and included trials evaluating pharmacologic or nonpharmacologic therapies. We abstracted data on demographics, intervention type, clinical indication, and trial design characteristics, and examined their relationships with women enrollment. Results In total, 598 trials met inclusion criteria. Women enrollment increased significantly over time (21% between 1986 and 1990 to 33% between 2011 and 2015; Pfor trend Conclusions Although enrollment of women has increased over time, it remains lower than the relative proportion in the disease population. Future studies should elucidate the reasons for persistent under-representation of women in clinical trials.

Objectives The uptake of endovascular aortic repair for elective and ruptured abdominal aortic aneurysm repair is not well studied. We aimed to examine the trends in open surgical repair and endovascular aortic repair of eAAA and rAAA and to examine the effects of randomized trial publications on elective open surgical repair and endovascular aortic repair rates. Methods We conducted a population-based time-series analysis of eAAA and rAAA repairs in Ontario, Canada from 2003 to 2016. We examined changes in overall and approach-specific rates of eAAA and rAAA repair using exponential smoothing models. Interventional autoregressive integrated moving average models were fit to the eAAA rates to examine the impact of randomized trial results on these rates. Results We identified 19,489 eAAA (12,232 open (63%) and 7257 endovascular (37%)) and 2732 rAAA (2466 open (90%) and 266 endovascular (10%)) repairs from 2003 to 2016. The rate of eAAA repair declined from 6.39/100,000 in 2003 to 5.59/100,000 in 2016 (13% decrease, p = 0.17). The rate of elective open surgical repair decreased nearly three-fold from 6.07/100,000 to 2.12/100,000 ( p Conclusions While elective open surgical repair use has significantly decreased from 2003 to 2016, elective endovascular aortic repair use has significantly increased. The DREAM and EVAR-1 results significantly impacted the observed rates of elective open surgical repair only. The reasons for these trends require further characterization.

Purpose High‐strength opioid formulations were delisted (removed) from Ontario's public drug formulary in January 2017, except for palliative patients. We evaluated the impact of this policy on opioid utilization and dosing. Methods We conducted a longitudinal study among patients receiving publicly funded, high‐strength opioids from August 2016 to July 2017. The primary outcome measure was weekly median daily opioid dose (in milligrams of morphine or equivalent; MME) of (1) publicly funded and (2) all opioid prescriptions irrespective of funding source, evaluated using interrupted time series analyses and stratified by palliative care status. Results Following policy implementation, the weekly median daily dose of publicly funded opioids decreased immediately among non‐palliative patients by 10 MME (95% confidence limit [CL], −16.8 to −3.1) from a pre‐intervention dose of 424.5 MME (95% CL, 417.8‐431.2) and fell gradually among palliative patients by 3.9 MME per week (95% CL, −5.5 to −2.3) from a pre‐intervention dose of 450.1 MME (95% CL, 432.5‐467.7). In contrast, among all opioid prescriptions, gradual reductions in weekly median daily doses were observed only for non‐palliative patients, which decreased by 0.7 MME per week (95% CL, −1.3 to −0.2) from a pre‐intervention dose of 426.2 MME (95% CL, 420.9‐431.5). Conclusion The delisting of publicly‐funded, high‐strength opioids was accompanied by changes in funding source and small reductions in the weekly median daily doses dispensed. Although observed dose reductions of less than 1 MME weekly are likely not clinically relevant, safety implications of these changes require further monitoring.

We sought to assess temporal trends in peripheral artery disease (PAD)-related hospitalization rates in Ontario. Trends in quarterly rates of PAD hospitalization per 100,000 Ontarians between 2006 and 2019 were assessed using autocorrelated linear regression. Stratified analyses according to age, sex, and most responsible diagnosis code type (with vs without diabetes-specific PAD codes) were performed. From 2006 to 2019, overall PAD hospitalizations did not decrease significantly when diabetes-specific codes were included. A significant decrease was observed among women and those older than 65 years old. Future studies of PAD epidemiology and outcomes using administrative data should include diabetic angiopathy.

BackgroundThe capacity of the general internal medicine clinical teaching units has been strained by decreasing resident supply and increasing patient demand. The objective of our study was to quantitatively compare the number of residents (supply) with the volume and duration of patient care activities (demand) to identify inefficiency.MethodsUsing the most recently available data from an academic teaching hospital, we identified each occurrence of a set of patient care activities that took place on the clinical teaching unit. We completed a descriptive analysis of the frequencies of these activities and how the frequencies varied by hour, day, week, month, and year. Patient care activities included admissions, rounds, responding to pages, meeting with patients and their families, patient transfers, discharges, and responding to cardiac arrests. The estimated time to complete each task was based on the available data in our electronic healthcare system and interviews with general internal medicine physicians or trainees. To calculate resident utilization, the person-hours of patient care tasks was divided by the person-hours of resident supply. Resident utilization was computed for three scenarios corresponding to varying levels of resident absenteeism.ResultsBetween 2015 and 2019 there were 14,581 consultations to general internal medicine from the emergency department. Patient volumes tended to be highest during January and lowest during May and June; and highest on Monday morning and lowest on Friday night. Daily admissions into hospital from the emergency department were higher on weekdays than on weekends, and hourly admissions peaked at 8:00 AM and between 3:00 PM and 1:00 AM. Weekday resident utilization was generally highest between 8:00 AM and 2:00 PM and lowest between 1:00 AM and 8:00 AM. In a scenario where all residents were present apart from those who were post-call, resident utilization generally never exceeded 100%; in scenarios where at least one resident was absent due to illness and/or vacation, it was common for resident utilization to approach or exceed 100%, particularly during daytime working hours.InterpretationAnalyzing supply and demand on a general internal medicine ward has allowed us to identify periods where supply and demand are not aligned and to empirically demonstrate the vulnerability of current staffing models. These data have the potential to inform and optimize scheduling on an internal medicine ward.

Background Adherence to medicines is low for a variety of reasons, including the cost borne by patients. Some jurisdictions publicly fund medicines for the general population, but many jurisdictions do not, and such policies are contentious. To our knowledge, no trials studying free access to a wide range of medicines have been conducted. Methods and findings We randomly assigned 786 primary care patients who reported not taking medicines due to cost between June 1, 2016 and April 28, 2017 to either free distribution of essential medicines (n = 395) or to usual medicine access (n = 391). The trial was conducted in Ontario, Canada, where hospital care and physician services are publicly funded for the general population but medicines are not. The trial population was mostly female (56%), younger than 65 years (83%), white (66%), and had a low income from wages as the primary source (56%). The primary outcome was medicine adherence after 2 years. Secondary outcomes included control of diabetes, blood pressure, and low-density lipoprotein (LDL) cholesterol in patients taking relevant treatments and healthcare costs over 2 years. Adherence to all appropriate prescribed medicines was 38.7% in the free distribution group and 28.6% in the usual access group after 2 years (absolute difference 10.1%; 95% confidence interval (CI) 3.3 to 16.9, p = 0.004). There were no statistically significant differences in control of diabetes (hemoglobin A1c 0.27; 95% CI −0.25 to 0.79, p = 0.302), systolic blood pressure (−3.9; 95% CI −9.9 to 2.2, p = 0.210), or LDL cholesterol (0.26; 95% CI −0.08 to 0.60, p = 0.130) based on available data. Total healthcare costs over 2 years were lower with free distribution (difference in median CAN$1,117; 95% CI CAN$445 to CAN$1,778, p = 0.006). In the free distribution group, 51 participants experienced a serious adverse event, while 68 participants in the usual access group experienced a serious adverse event (p = 0.091). Participants were not blinded, and some outcomes depended on participant reports. Conclusions In this study, we observed that free distribution of essential medicines to patients with cost-related nonadherence substantially increased adherence, did not affect surrogate health outcomes, and reduced total healthcare costs over 2 years. Trial registration ClinicalTrials.gov NCT02744963., Author summary Why was this study done? Medicine nonadherence is common globally, and costs borne by patients is a major barrier. More than 100 countries have an essential medicines list to help meet the priority health needs of the population. Publicly funding essential medicines is contentious in part due to the potential cost to governments. What did the researchers do and find? We conducted a randomized controlled trial of free essential medicines distribution in 786 people who reported trouble affording medicines in a setting where healthcare services are publicly funded. Free medicine distribution improved adherence to medicines appropriately prescribed after 2 years (absolute risk difference, 10.1%; 95% confidence interval (CI) 3.3 to 16.9, p = 0.004). Free distribution had inconsistent effects on surrogate health outcomes over 2 years and lowered total healthcare costs by a median of CAN$1,117 (95% CI CAN$445 to CAN$1,778, p = 0.006). What do these findings mean? Distributing a comprehensive set of essential medicines at no charge to primary care patients improved medicine adherence and reduce healthcare costs. These findings could help inform policy changes in countries planning to implement universal healthcare that includes access to medicines.

Fractures of the cervical spine are a medical emergency and may lead to permanent paralysis and even death. Accurate diagnosis in patients with suspected fractures by computed tomography (CT) is critical to patient management. In this paper, we propose a deep convolutional neural network (DCNN) with a bidirectional long-short term memory (BLSTM) layer for the automated detection of cervical spine fractures in CT axial images. We used an annotated dataset of 3,666 CT scans (729 positive and 2,937 negative cases) to train and validate the model. The validation results show a classification accuracy of 70.92% and 79.18% on the balanced (104 positive and 104 negative cases) and imbalanced (104 positive and 419 negative cases) test datasets, respectively., This paper is accepted for presentation at the IEEE International Symposium on Biomedical Imaging (ISBI) 2021

Objective Trauma-related vascular injuries are major contributors to morbidity and mortality worldwide. We conducted a retrospective, population-based, cross-sectional study to examine temporal trends and factors associated with traumatic vascular injury-related in-hospital mortality in Ontario, Canada from 1991 to 2009. Methods We obtained data on Ontario hospital admissions for traumatic vascular injury, including injury mechanism and body region; and patient age, sex, socioeconomic status, and residence from the Canadian Institute for Health Information Discharge Abstract Database and Registered Persons Database from fiscal years 1991 to 2009. We performed time series analysis of vascular injury-related in-hospital mortality rates and multivariable logistic regression analysis to identify significant mortality-associated factors. Results The overall in-hospital mortality rate for trauma-related vascular injury was 5.5%. A slight but non-significant decline in mortality occurred over time. The likelihood of vascular injury-related in-hospital mortality was significantly higher for patients involved in transport-related accidents (odds ratio [OR[=2.21, 95% confidence interval [CI], 1.76–2.76), age ≥65 years (OR = 4.34, 95% CI, 2.25–8.38), or with thoracic (OR = 2.24, 95% CI, 1.56–3.20) or abdominal (OR = 2.45, 95% CI, 1.75–3.42) injuries. Conclusions In-hospital mortality from traumatic vascular injury in Ontario was low and stable from 1991 to 2009.

Diabetic foot ulcers (DFUs) are common and disabling, necessitating lengthy hospitalizations. In this study we sought to identify potentially modifiable determinants of high-intensity hospital care use among adults with DFUs.Three related case-control studies were conducted using Canada-wide cohorts of adults hospitalized with a DFU from 2011 to 2015. In study 1, cases comprised the top 10% with the highest cumulative 1-year acute care hospital costs; controls were randomly selected from those below the top 10%. Study 2 comprised cases/controls within/below the top 10% for cumulative acute care hospital length of stay (LOS). Study 3 included cases/controls within/below the top 10% for cumulative number of acute care hospitalizations. Using generalized linear models, predictor variables were tested between cases and controls, while adjusting for age and sex.In study 1, mean acute care costs among 8,971 cases and 3,174 controls were $71,757 and $13,687, respectively. Sepsis conferred the greatest excess cost (mean, $38,790; 95% confidence interval [CI], $34,597 to $43,508), followed by chronic kidney disease (mean, $30,607; 95% CI, $28,389 to $32,825) and major lower limb amputation (mean, $30,884; 95% CI, $28,613 to $33,155). In study 2, mean LOS was higher among 8,477 cases (69 days) than 3,467 controls (12 days). Lower limb amputation conferred the greatest adjusted excess in mean LOS (mean, 28 days; 95% CI, 27 to 28 days). In study 3, there was a mean of 3 hospitalizations among 10,341 cases and 1 among 5,509 controls. Peripheral artery disease conferred the greatest excess number of hospitalizations (1.3 more hospitalizations; 1.2 to 1.4).Early aggressive treatment of chronic kidney disease and peripheral artery disease, alongside guideline-based amputation prevention strategies, may reduce high-intensity hospital care use among adults with DFUs.

BackgroundPatient characteristics, clinical care, resource use, and outcomes associated with hospitalization for coronavirus disease (COVID-19) in Canada are not well described.MethodsWe described all adult discharges from inpatient medical services and medical-surgical intensive care units (ICU) between November 1, 2019 and June 30, 2020 at 7 hospitals in Toronto and Mississauga, Ontario. We compared patients hospitalized with COVID-19, influenza and all other conditions using multivariable regression models controlling for patient age, sex, comorbidity, and residence in long-term-care.ResultsThere were 43,462 discharges in the study period, including 1,027 (3.0%) with COVID-19 and 783 (2.3%) with influenza. Patients with COVID-19 had similar age to patients with influenza and other conditions (median age 65 years vs. 68 years and 68 years, respectively, SDInterpretationAdults hospitalized with COVID-19 during the first wave of the pandemic used substantial hospital resources and suffered high mortality. COVID-19 was associated with significantly greater mortality, ICU use, and hospital length-of-stay than influenza.

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.

Background Stigma and high-care needs can present barriers to the provision of high-quality primary care for people with opioid use disorder (OUD) and those prescribed opioids for chronic pain. We explored the likelihood of securing a new primary care provider (PCP) among people with varying histories of opioid use who had recently lost access to their PCP. Methods and findings We conducted a retrospective cohort study using linked administrative data among residents of Ontario, Canada whose enrolment with a physician practicing in a primary care enrolment model (PEM) was terminated between January 2016 and December 2017. We assigned individuals to 3 groups based upon their opioid use on the date enrolment ended: long-term opioid pain therapy (OPT), opioid agonist therapy (OAT), or no opioid. We fit multivariable models assessing the primary outcome of primary care reattachment within 1 year, adjusting for demographic characteristics, clinical comorbidities, and health services utilization. Secondary outcomes included rates of emergency department (ED) visits and opioid toxicity events. Among 154,970 Ontarians who lost their PCP, 1,727 (1.1%) were OAT recipients, 3,644 (2.4%) were receiving long-term OPT, and 149,599 (96.5%) had no recent prescription opioid exposure. In general, OAT recipients were younger (median age 36) than those receiving long-term OPT (59 years) and those with no recent prescription opioid exposure (44 years). In all exposure groups, the majority of individuals had their enrolment terminated by their physician (range 78.1% to 88.8%). In the primary analysis, as compared to those not receiving opioids, OAT recipients were significantly less likely to find a PCP within 1 year (adjusted hazard ratio [aHR] 0.55, 95% confidence interval [CI] 0.50 to 0.61, p < 0.0001). We observed no significant difference between long-term OPT and opioid unexposed individuals (aHR 0.96; 95% CI 0.92 to 1.01, p = 0.12). In our secondary analysis comparing the period of PCP loss to the year prior, we found that rates of ED visits were elevated among people not receiving opioids (adjusted rate ratio (aRR) 1.20, 95% CI 1.18 to 1.22, p < 0.0001) and people receiving long-term OPT (aRR 1.37, 95% CI 1.28 to 1.48, p < 0.0001). We found no such increase among OAT recipients, and no significant increase in opioid toxicity events in the period following provider loss for any exposure group. The main limitation of our findings relates to their generalizability outside of PEMs and in jurisdictions with different financial incentives incorporated into primary care provision. Conclusions In this study, we observed gaps in access to primary care among people who receive prescription opioids, particularly among OAT recipients. Ongoing efforts are needed to address the stigma, discrimination, and financial disincentives that may introduce barriers to the healthcare system, and to facilitate access to high-quality, consistent primary care services for chronic pain patients and those with OUD., In a retrospective cohort study, Tara Gomes and colleagues study associations between opioid use history and reattachment to a primary care provider following termination of enrollment among residents of Ontario, Canada., Author summary Why was this study done? Primary care is an important component of healthcare systems; however, inequities in access have been documented among some patient populations. In particular, research suggests that people with substance use disorders or chronic pain can be flagged as “undesirable” by physicians, creating barriers to care for patients who often have complex medical needs. Research is needed to understand whether these barriers are reflected in patients’ ability to secure a primary care provider (PCP) in the community. What did the researchers do and find? We created a cohort of people who had previously been enrolled with a PCP and were subsequently unenrolled, and compared the likelihood of finding another PCP among those being treated for an opioid use disorder (OUD), those receiving opioids for chronic pain, and people from the general population unexposed to opioids. We found that people treated for an OUD had a much lower rate of finding another PCP within a year compared to opioid unexposed individuals. Although people treated with opioids for chronic pain did not experience a lower rate of primary care reenrollment overall, they were less likely to gain access to collaborative primary care models that can provide high-quality continuity of care. This population also had elevated rates of emergency department visits during their period of provider loss. What do these findings mean? Gaps in access to primary care exist for people with OUD and chronic pain, which may be influenced by stigma, discrimination, and financial disincentives within the healthcare system. There is a need for focused efforts to provide high-quality, accessible healthcare to people who use drugs and chronic pain patients, many of whom have multiple chronic conditions that would benefit from consistent primary care.

Introduction Dentists are a common source of opioid exposure. This study investigates the association between initial dental opioid prescription characteristics and subsequent persistent use and examines the rate of opioid overdose after initiation. Methods A retrospective cohort study was conducted among Ontario residents who were dispensed an initial opioid prescription originating from a dentist between October 2014 and September 2018 (data were analyzed in October 2019–May 2020). Exposures were characterized on the basis of the average daily dose in milligram morphine equivalents and the duration and formulation (long versus short acting) of the initial prescription. New, persistent use was defined as ≥1 opioid prescription within 90 days and another within 91–365 days after the initial prescription. The rate of an opioid overdose within 90 days after initiation was examined. Results Among 786,125 Ontarians who initiated a dentist-prescribed opioid, 34,880 (4.4%) developed persistent use, whereas 140 (0.72 per 1,000 person-years) had evidence of an overdose within 90 days. People dispensed an initial daily dose >90 milligram morphine equivalents (n=5,644, 0.7%) had significantly greater odds of persistence (AOR=1.20, 95% CI=1.07, 1.34) than those dispensed ≤20 milligram morphine equivalents (n=179,884, 22.9%). Persistence was also significantly associated with receiving longer prescription durations and a long-acting opioid on initiation. Conclusions Among people who initiated a dentist-prescribed opioid, 1 in 23 experienced persistent use, and persistence was associated with the characteristics of the prescription. Prescribing lower doses, prescribing for shorter durations, and avoiding long-acting formulations may be an opportunity to lessen the risk of persistent opioid use.

Opioids have been increasingly associated with suicide, but whether they are independent contributors is unclear. Oxycodone and hydromorphone are commonly prescribed high-potency opioids that can differentially affect mood. The objective of this study was to explore whether oxycodone and hydromorphone are differentially associated with suicide. We conducted a retrospective population-based case-control study in Ontario, Canada, from 1992 to 2014. Using coronial data, we defined case subjects as individuals who died by suicide involving an opioid overdose. Each of these was matched with up to four controls who died of accidental opioid overdose. We ascertained exposure to oxycodone, hydromorphone, and other opioids from postmortem toxicology testing. We used odds ratios and 95% confidence intervals to examine whether opioid-related suicide was disproportionately associated with oxycodone relative to hydromorphone. We identified 438 suicides and 1212 accidental deaths, each of which involved either oxycodone or hydromorphone but not both. The median age at death was 49 years and 51% were men. After adjusting for a history of self-harm, psychiatric illness, and exposure to other opioids, we found that oxycodone was more strongly associated with suicide than hydromorphone (adjusted odds ratio 1.59; 95% confidence interval 1.20–2.11). In a secondary analysis, we observed a trend of similar magnitude in which combined exposure to oxycodone and hydromorphone was more strongly associated with suicide than hydromorphone alone (adjusted odds ratio 1.68; 95% confidence interval 0.92–3.09). While preliminary, these findings support the possibility that some high-potency opioids might independently influence the risk of suicide in susceptible individuals.

Objective In the present study, we compared the outcomes of elective abdominal aortic aneurysm (AAA) repair in patients with and without rheumatoid arthritis (RA) stratified by the type of surgery. Methods A retrospective population-based cohort study was conducted from 2003 to 2016. Linked administrative health data from Ontario, Canada were used to identify all patients aged ≥65 years who had undergone elective open or endovascular AAA repair during the study period. Patients were identified using validated procedure and billing codes and matching using propensity scores. The primary outcome was survival. The secondary outcomes were major adverse cardiovascular events (MACE)-free survival (defined as freedom from death, myocardial infarction, and stroke), reintervention, and secondary rupture. Results Of 14,816 patients undergoing elective AAA repair, a diagnosis of RA was present for 309 (2.0%). The propensity-matched cohort included 234 pairs of RA and control patients. The matched cohort was followed up for a mean ± standard deviation of 4.93 ± 3.35 years, and the median survival was 6.76 and 7.31 years for the RA and control groups, respectively. Cox regression analysis demonstrated no statistically significant differences in the hazards for death, MACE, reintervention, or secondary rupture. Analysis of the differences in outcomes stratified by repair approach also showed no statistically significant differences in the hazards for death, MACE, reintervention, or secondary rupture. Conclusions We found no statistically significant differences in survival, MACE, reintervention, or secondary rupture among patients with RA undergoing elective AAA repair compared with controls. Further studies are required to evaluate the impact of comorbidities and antirheumatic medications on the outcomes of elective AAA repair.

PURPOSE As clinical practice moves towards more judicious opioid prescribing, physicians require information on how to safely initiate opioids. The objective of this study was to examine the association between initial opioid prescription characteristics and risks of harm and long-term use. METHODS We conducted a population-based retrospective cohort study among Ontario residents newly dispensed an opioid for pain between July 2013 and March 2016. The primary exposure was the average daily opioid dose dispensed at initiation (in milligram morphine equivalents; MME), with secondary exposures including the initial prescription's duration and formulation. The primary outcome was fatal or non-fatal opioid overdose. A secondary analysis studied continued opioid use for at least 1 year. RESULTS Among the 2 021 371 individuals meeting our inclusion criteria, 1121 (0.56 per 1000 person-years) experienced an opioid overdose within 1 year and 64 013 (3.17%) continued treatment for at least 1 year. Higher initial daily dose, longer prescription duration, and receipt of a long-acting formulation at initiation were significantly associated with higher hazard of overdose. Compared to daily doses of 20 MME or lower, initial doses exceeding 200 MME daily were associated with a particularly high hazard of overdose (aHR 2.97, 95% confidence interval [CI] 1.62 to 5.44). In the secondary analysis, there were similar associations between initial dose, duration, and formulation and long-term use. CONCLUSIONS Although the absolute risk of an opioid overdose within the first year of prescription opioid use is low, better alignment of opioid initiation practices with guidelines may reduce opioid-related harm.

Background Accurate assessment of functional capacity, a predictor of postoperative morbidity and mortality, is essential to improving surgical planning and outcomes. We assessed if all 12 items of the Duke Activity Status Index (DASI) were equally important in reflecting exercise capacity. Methods In this secondary cross-sectional analysis of the international, multicentre Measurement of Exercise Tolerance before Surgery (METS) study, we assessed cardiopulmonary exercise testing and DASI data from 1455 participants. Multivariable regression analyses were used to revise the DASI model in predicting an anaerobic threshold (AT) >11 ml kg−1 min−1 and peak oxygen consumption (VO2 peak) >16 ml kg−1 min−1, cut-points that represent a reduced risk of postoperative complications. Results Five questions were identified to have dominance in predicting AT>11 ml kg−1 min−1 and VO2 peak>16 ml.kg−1min−1. These items were included in the M-DASI-5Q and retained utility in predicting AT>11 ml.kg−1.min−1 (area under the receiver-operating-characteristic [AUROC]-AT: M-DASI-5Q=0.67 vs original 12-question DASI=0.66) and VO2 peak (AUROC-VO2 peak: M-DASI-5Q 0.73 vs original 12-question DASI 0.71). Conversely, in a sensitivity analysis we removed one potentially sensitive question related to the ability to have sexual relations, and the ability of the remaining four questions (M-DASI-4Q) to predict an adequate functional threshold remained no worse than the original 12-question DASI model. Adding a dynamic component to the M-DASI-4Q by assessing the chronotropic response to exercise improved its ability to discriminate between those with VO2 peak>16 ml.kg−1.min−1 and VO2 peak Conclusions The M-DASI provides a simple screening tool for further preoperative evaluation, including with cardiopulmonary exercise testing, to guide perioperative management.

OBJECTIVEIntracranial hemorrhage (ICH) associated with cerebral hyperperfusion syndrome is a rare but major complication of carotid artery revascularization. The objective of this study was to compare the rate of ICH after carotid artery stenting (CAS) with that after endarterectomy (CEA).METHODSThe authors performed a retrospective population-based cohort study of patients who underwent carotid artery revascularization in the province of Ontario, Canada, between 2002 and 2015. The primary outcome was the rate of ICH that occurred within 90 days after carotid artery intervention among patients who underwent CAS versus that of those who underwent CEA. The authors used inverse probability of treatment weighting and propensity scores to account for selection bias. In sensitivity analyses, patients who had postprocedure ischemic stroke were excluded, and the following subgroups were examined: patients with symptomatic and asymptomatic carotid artery stenosis, patients treated between 2010 and 2015, and patients aged ≥ 66 years (to account for antiplatelet and anticoagulant use).RESULTSA total of 16,688 patients underwent carotid artery revascularization (14% CAS, 86% CEA). Patients with more comorbid illnesses, symptomatic carotid artery stenosis, or cardiac disease and those who were taking antiplatelet agents or warfarin before surgery were more likely to undergo CAS. Among the overall cohort, 80 (0.48%) patients developed ICH within 90 days (0.85% after CAS, 0.42% after CEA). The 180-day mortality rate after ICH in the overall cohort was 2.7%, whereas the 180-day mortality rate among patients who suffered ICH was 42.5% (40% for CAS-treated patients, 43.3% for CEA-treated patients). In the adjusted analysis, patients who underwent CAS were significantly more likely to have ICH than those who underwent CEA (adjusted OR 1.77; 95% CI 1.32–2.36; p < 0.001). These results were consistent after excluding patients who developed postprocedure ischemic stroke (adjusted OR 1.90; 95% CI 1.41–2.56) and consistent among symptomatic (adjusted OR 1.74; 95% CI 1.16–2.63) and asymptomatic (adjusted OR 1.75; 95% CI 1.16–2.63) patients with carotid artery stenosis, among patients treated between 2010 and 2015 (adjusted OR 2.21; 95% CI 1.45–3.38), and among the subgroup of patients aged ≥ 66 years (adjusted OR 1.53; 95% CI 1.05–2.24) after adjusting for medication use.CONCLUSIONSCAS is associated with a rare but higher risk of ICH relative to CEA. Future research is needed to devise strategies that minimize the risk of this serious complication after carotid artery revascularization.

Background The Canadian opioid crisis is a complex, multifaceted problem involving prescribed, diverted and illicitly manufactured opioids. This study sought to characterize the contribution of prescribed opioids to opioid-related hospitalizations in Canada. Methods We conducted a cross-sectional study of all individuals who were admitted to hospital for opioid toxicity in British Columbia (BC), Manitoba and Ontario between April 2015 and March 2016. We used prescription claims to ascertain active prescription opioid use at time of hospital admission. In secondary analyses, we defined recent opioid prescriptions as those that were dispensed in the 30 and 180 days up to and including admission, and the prevalence of active co-prescription of benzodiazepines with opioids at time of overdose. Results We identified 2599 instances of opioid toxicity over the study period. In BC, 34.1% of hospital visits for overdose occurred in people with an active opioid prescription, compared to 52.2% (47 of 90) in Manitoba and 52.8% (804 of 1524) in Ontario. However, active opioid prescriptions prior to overdose varied significantly by age and sex. Co-prescription of opioids and benzodiazepines prior to overdose ranged from 17.1% in BC to 35.6% in Manitoba. Conclusions There remains an important ongoing contribution of prescribed opioids to overdoses across Canada, but non-prescribed opioids play a growing role, particularly in BC. These findings underscore the importance of more judicious opioid prescribing, harm reduction programs, and improved access to addiction care for people with an opioid use disorder.

Purpose: To determine the positive predictive values (PPV) of Ontario administrative data codes for the identification of open (OSR) and endovascular (EVAR) repairs of elective (eAAA) and ruptured (rAAA) abdominal aortic aneurysms. Methods: We randomly identified 319 eAAA and rAAA repairs at two Toronto hospitals between April 2003 and March 2015, using administrative health data in Ontario, Canada. International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10) codes I71.3 and I71.4, were used to identify rAAA and eAAA patients, respectively. A blinded retrospective chart review was conducted and served as the gold standard comparator. Re-abstracted records were compared to Canadian Classification of Health Interventions (CCI) and Ontario Health Insurance Plan (OHIP) codes in the Canadian Institute for Health Information Discharge Abstract Database (CIHI-DAD) and OHIP databases. We calculated the PPV and 95% confidence intervals (95% CI) of individual and combined procedure and billing codes for elective and ruptured OSR and EVAR (eOSR, eEVAR, rOSR, and rEVAR). Results: Permutation of codes allowed identification of eOSR with 95% PPV (95% CI 88, 98), eEVAR with 96% PPV (95% CI 90, 99), rOSR with 87% PPV (95% CI 79, 93) and rEVAR with 91% PPV (95% CI 59, 100). Conclusions: Diagnostic, procedure and billing code combinations allow identification of eOSR, eEVAR, rOSR and rEVAR patients in Ontario administrative data with a high degree of certainty.

Anti-depressants are among the most widely-prescribed medications. It is unknown whether the risk of seizure during therapeutic use differs by drug. We ranked the seizure risk of popular anti-depressants.We conducted a population-based case-control study between April 2002 and March 2015 in Ontario, Canada. Cases were Ontario residents aged ≥65 years hospitalized for a first-ever seizure within 60 d of filling a prescription for one of nine second-generation anti-depressants, each dispensed more than 1 million times (range: 1,196,810 [fluvoxamine] to 19,849,930 [citalopram]) during the study period. For each case, we identified up to four seizure-free controls receiving a similar anti-depressant, and matched on age, sex, date and a pre-defined seizure-specific disease risk index.We identified 5701 patients hospitalized with a first-ever seizure and matched them with 21,872 controls. Relative to bupropion, the risk of new-onset seizure during therapeutic use was highest for escitalopram (adjusted odds ratio [OR] 1.79; 95% confidence interval [CI] 1.42-2.25) and citalopram (OR 1.67; 95% CI 1.35-2.07), while no incremental risk was found for fluoxetine (OR 1.02; 95%CI 0.78-1.33) and duloxetine (OR 0.94; 95%CI 0.75-1.22). Other anti-depressants were associated with modest increase in seizure risk.The risk of seizure during therapeutic use among elderly patients varies among second-generation anti-depressants. Escitalopram and citalopram are associated with the highest risk. Prescribers should consider the seizure risk of individual anti-depressants and use discretion when selecting an anti-depressant, especially for patients with other risk factors for seizure. Frontline clinicians should be cognizant of this differential risk.

Objectives To examine whether postpartum treatment with oxycodone is associated with an increased risk of new persistent opioid use relative to codeine. Methods Population-based retrospective cohort study of opioid-naive women who gave birth in Ontario, Canada between September 1, 2012 and March 31, 2018. Using linked administrative healthcare databases, women prescribed oxycodone postpartum were compared to those prescribed codeine postpartum. The primary outcome was persistent opioid use at 90 days following the initial postpartum prescription, with codeine as the reference exposure. Persistent use at 90 days was defined as any filled prescription in the 28-days (76-104 days), and 56-days (62-118 days) surrounding the 90-day mark. Relative risks (aRR) were adjusted for maternal, delivery, and prescription characteristics. Results We identified 21,365 postpartum women newly prescribed codeine and 43,767 newly prescribed oxycodone. Compared to codeine, an initial prescription for oxycodone was not associated with persistent opioid use at 90 days, whether a 28-day (aRR 1.12; 95%CI 0.92-1.36) or 56-day (aRR 1.06; 95%CI 0.91-1.24) window around the 90-day outcome was considered. Results were unchanged in a propensity-score matched analysis. A prescription containing greater than 225 milligrams of morphine equivalents was associated with an increased risk of persistent use (aRR 1.87; 95%CI 1.43-2.44), as was an initial prescription duration longer than 7 days (aRR 1.59; 95%CI 1.26-2.03). Conclusions The risk of new, persistent opioid use after delivery was similar for oxycodone and codeine. Limiting the volume and duration of the initial opioid prescription may be important interventions to reduce the risk of persistent opioid use in postpartum women.

Importance Use of stimulants continues to increase among older adults for a variety of indications. An association between stimulant use and increased risk of cardiovascular (CV) events has been established among children and young adults, but few studies have explored the risk of CV events among older patients, a group with increased baseline risk. Objective To evaluate the association between stimulant use and risk of CV events among older adults. Design, setting, and participants This propensity score-matched cohort study, with 4 nonusers per 1 user, was conducted from July 1, 2017, to June 27, 2019, using data from population-based health care databases from Ontario, Canada, from January 1, 2002, to December 31, 2016. Included individuals were outpatients aged 66 years or older. Exposures Initiation of a prescription stimulant. Main outcomes and measures The primary outcome was a CV event, defined as a composite of emergency department visit or hospitalization for myocardial infarction, stroke or transient ischemic attack (TIA), or ventricular arrhythmia. Risk of CV event was assessed at 30 days, 180 days, and 365 days after initiation of stimulants from Cox proportional hazard models. A secondary analysis assessed each component of the primary outcome separately. Results Among 6457 older adults who initiated a prescription stimulant (ie, the exposed group) and 24 853 older adults who did not initiate such treatment (ie, the unexposed group), the distribution of baseline patient characteristics was well balanced after matching (sex: 3173 [49.1%] men vs 12 112 [48.7%] men; standardized difference, 0.01; median [IQR] age: 74 [69-80] years vs 74 [69-80] years; standardized difference, 0.01). Within this cohort, there were 932 CV events during the 365-day follow-up (5.11 events per 100 person-years among individuals who initiated stimulants). In the primary analysis, stimulant initiation was associated with increased risk of CV events at 30 days (hazard ratio [HR], 1.4; 95% CI, 1.1-1.8) but not at 180 days (HR, 1.2; 95% CI, 0.9-1.6) or 365 days (HR, 1.0; 95% CI, 0.6 to 1.8). In the secondary analysis, stimulant initiation was associated with increased risk of ventricular arrhythmias (HR, 3.0; 95% CI, 1.1-8.7) and stroke or TIA (HR, 1.6; 95% CI, 1.1-2.1) at 30 days. Conclusions and relevance This cohort study found that stimulant use was associated with an early increase in CV events among older adults with no association for long-term use.

Background The precise scope of hospital care delivered under general internal medicine services remains poorly quantified. The purpose of this study was to describe the demographic characteristics, medical conditions, health outcomes and resource use of patients admitted to general internal medicine at 7 hospital sites in the Greater Toronto Area. Methods This was a retrospective cohort study involving all patients who were admitted to or discharged from general internal medicine at the study sites between Apr. 1, 2010, and Mar. 31, 2015. Clinical data from hospital electronic information systems were linked to administrative data from each hospital. We examined trends in resource use and patient characteristics over the study period. Results There were 136 208 admissions to general internal medicine involving 88 121 unique patients over the study period. General internal medicine admissions accounted for 38.8% of all admissions from the emergency department and 23.7% of all hospital bed-days. Over the study period, the number of admissions to general internal medicine increased by 32.4%; there was no meaningful change in the median length of stay or cost per hospital stay. The median patient age was 73 (interquartile range [IQR] 57-84) years, and the median number of coexisting conditions was 6 (IQR 3-9). The median acute length of stay was 4.6 (IQR 2.5-8.6) days, and the median total cost per hospital stay was $5850 (IQR $3915-$10 061). Patients received at least 1 computed tomography scan in 52.2% of admissions. The most common primary discharge diagnoses were pneumonia (5.0% of admissions), heart failure (4.7%), chronic obstructive pulmonary disease (4.1%), urinary tract infection (4.0%) and stroke (3.6%). Interpretation Patients admitted to general internal medicine services represent a large, heterogeneous, resource-intensive and growing population. Understanding and improving general internal medicine care is essential to promote a high-quality, sustainable health care system.

BACKGROUND: Timely follow-up after hospital discharge may decrease readmission to hospital. Financial incentives to improve follow-up have been introduced in the United States and Canada, but it is unknown whether they are effective. Our objective was to evaluate the impact of an incentive program on timely physician follow-up after hospital discharge. METHODS: We conducted an interventional time series analysis of all medical and surgical patients who were discharged home from hospital between Apr. 1, 2002, and Jan. 30, 2015, in Ontario, Canada. The intervention was a supplemental billing code for physician follow-up within 14 days of discharge from hospital, introduced in 2006. The primary outcome was an outpatient visit within 14 days of discharge. Secondary outcomes were 7-day follow-up and a composite of emergency department visits, nonelective hospital readmission and death within 14 days. RESULTS: We included 8 008 934 patient discharge records. The incentive code was claimed in 31% of eligible visits by 51% of eligible physicians, and cost $17.5 million over the study period. There was no change in the average monthly rate of outcomes in the year before the incentive was introduced compared with the year following introduction: 14-day follow-up (66.5% v. 67.0%, overall p = 0.5), 7-day follow-up (44.9% v. 44.9%, overall p = 0.5) and composite outcome (16.7% v. 16.9%, overall p = 0.2). INTERPRETATION: Despite uptake by physicians, a financial incentive did not alter follow-up after hospital discharge. This lack of effect may be explained by features of the incentive or by extra-physician barriers to follow-up. These barriers should be considered by policymakers before introducing similar initiatives.

Background Direct oral anticoagulants (DOACs) have expanded the armamentarium for antithrombotic therapy. Although DOAC-related major bleeding was associated with favorable outcomes compared with warfarin in clinical trials, warfarin effects were reversed in Methods Consecutive patients ≥ 66 years presented to five tertiary care hospitals across three cities in Ontario, Canada from October 2010 to March 2015 with diagnoses that included hemorrhage. Charts were screened for association with DOAC or warfarin use; eligible cases were abstracted and linked to administrative databases. Results Among 19,061 records screened, 2,002 (460 receiving DOAC, 1,542 receiving warfarin) were eligible. Reversal agents (72.9% vitamin K, 40.7% prothrombin complex concentrates) were frequently used in warfarin bleeding events. Red blood cell transfusions occurred more often in DOAC bleeding events than in warfarin events (52.0% vs 39.5%; adjusted relative risk [aRR], 1.32; 95% CI, 1.19-2.47). However, units of blood products transfused were not different between the two groups. Thirty-four DOAC cases (7.4%) received activated prothrombin complex concentrates or recombinant factor VIIa. In-hospital mortality was lower following DOAC bleeding events (9.8% vs 15.2%; aRR, 0.66; 95% CI, 0.49-0.89), although differences in 30-day mortality did not reach statistical significance (12.6% vs 16.3%; aRR, 0.79; 95% CI, 0.61-1.03). Conclusions In this unselected cohort of patients with oral anticoagulant-related hemorrhage with high rates of warfarin reversal, in-hospital mortality was lower among DOAC-associated bleeding events. These findings support the safety of DOACs in routine care and present useful baseline measures for evaluations of DOAC-specific reversal agents.

Background A randomized controlled trial of adults with empyema recently demonstrated decreased length of stay in hospital in patients treated with intrapleurally administered dornase alfa and fibrinolytics compared to fibrinolytics alone. Whether this treatment strategy is safe and effective in children remains unknown. Methods/design This study protocol is for a superiority, placebo-controlled, parallel-design, multicenter randomized controlled trial. The participants are previously well children admitted to a children’s hospital with a diagnosis of empyema requiring chest tube insertion and fibrinolytics administered intrapleurally. Children will be randomized after the treating physician has decided that pleural drainage is required but prior to chest tube insertion. After chest tube insertion, participants in the treatment group will receive intrapleurally administered tissue plasminogen activator (tPA) 4 mg followed by dornase alfa 5 mg. Participants in the placebo group will receive tPA 4 mg followed by normal saline. Study treatments will be administered once daily for 3 days. All participants, parents or caregivers, clinicians, and research personnel will remain blinded. The primary outcome is length of stay from chest tube insertion to discharge from hospital. Secondary outcomes include time to meeting discharge criteria, chest tube duration, fever duration, need for additional procedures, adverse events, hospital readmission, cost of hospitalization, and mortality. Discussion This multicenter randomized controlled trial will assess the safety, effectiveness, and cost-effectiveness of combined treatment with dornase alfa and fibrinolytics compared to fibrinolytics alone for the treatment of empyema in children. Trial registration ClinicalTrials.gov: NCT01717742. Registered on 8 October 2012. Electronic supplementary material The online version of this article (doi:10.1186/s13063-017-2026-0) contains supplementary material, which is available to authorized users.

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

Background Hyponatremia may occur after initiation of a second-generation antidepressant drug. However, the magnitude of this risk among older adults in routine care is not well characterized. Study Design Retrospective, population-based, matched-cohort study. Setting & Participants In Ontario, Canada, 2003 to 2012, we compared older adults with a mood or anxiety disorder who were dispensed 1 of 9 second-generation antidepressant drugs with matched adults with comparable indicators of baseline health who were not dispensed an antidepressant drug (n=138,246 per group). A similar comparison was made in a subpopulation with available laboratory data (n=4,186 per group). Predictor Second-generation antidepressant prescription versus no antidepressant prescription. Outcomes The primary outcome was hospitalization with hyponatremia. A secondary outcome was hospitalization with both hyponatremia and delirium. Measurements We assessed hospitalization with hyponatremia using a diagnosis code and, in the subpopulation, serum sodium values. We assessed hospitalization with hyponatremia and delirium using a combination of diagnosis codes. Results Second-generation antidepressant use versus nonuse was associated with higher 30-day risk for hospitalization with hyponatremia (450/138,246 [0.33%] vs 84/138,246 [0.06%]; relative risk [RR], 5.46 [95% CI, 4.32-6.91]). This association was consistent in the subpopulation with serum sodium values (73/4,186 [1.74%] vs 18/4,186 [0.43%]; RR, 4.23 [95% CI, 2.50-7.19]; absolute risk increase, 1.31% [95% CI, 0.87%-1.75%]). Second-generation antidepressant use versus nonuse was also associated with higher 30-day risk for hospitalization with both hyponatremia and delirium (28/138,246 [0.02%] vs 7/138,246 [0.005%]; RR, 4.00 [95% CI, 1.75-9.16]). Limitations Measures of serum sodium could be ascertained in only a subpopulation. Conclusions Use of a second-generation antidepressant in routine care by older adults is associated with an approximate 5-fold increase in 30-day risk for hospitalization with hyponatremia compared to nonuse. However, the absolute increase in 30-day incidence is low.

This work is supported by grant 381409 from the Canadian Institutes for Health Research, the Ontario SPOR Support Unit that is supported by the Canadian Institutes of Health Research and the Province of Ontario, the Canada Research Chairs program, and the St Michael’s Hospital Foundation. Importance: Nonadherence to treatment with medicines is common globally, even for life-saving treatments. Cost is one important barrier to access, and only some jurisdictions provide medicines at no charge to patients. Objective: To determine whether providing essential medicines at no charge to outpatients who reported not being able to afford medicines improves adherence. Design, Setting, and Participants: A multicenter, unblinded, parallel, 2-group, superiority, outcomes assessor-blinded, individually randomized clinical trial conducted at 9 primary care sites in Ontario, Canada, enrolled 786 patients between June 1, 2016, and April 28, 2017, who reported cost-related nonadherence. Follow-up occurred at 12 months. The primary analysis was performed using an intention-to-treat principle. Interventions: Patients were randomly allocated to receive free medicines on a list of essential medicines in addition to otherwise usual care (n = 395) or usual medicine access and usual care (n = 391). Main Outcomes and Measures: The primary outcome was adherence to treatment with all medicines that were appropriately prescribed for 1 year. Secondary outcomes were hemoglobin A1c level, blood pressure, and low-density lipoprotein cholesterol levels 1 year after randomization in participants taking corresponding medicines. Results: Among the 786 participants analyzed (439 women and 347 men; mean [SD] age, 51.7 [14.3] years), 764 completed the trial. Adherence to treatment with all medicines was higher in those randomized to receive free distribution (151 of 395 [38.2%]) compared with usual access (104 of 391 [26.6%]; difference, 11.6%; 95% CI, 4.9%-18.4%). Control of type 1 and 2 diabetes was not significantly improved by free distribution (hemoglobin A1c, -0.38%; 95% CI, -0.76% to 0.00%), systolic blood pressure was reduced (-7.2 mm Hg; 95% CI, -11.7 to -2.8 mm Hg), and low-density lipoprotein cholesterol levels were not affected (-2.3 mg/dL; 95% CI, -14.7 to 10.0 mg/dL). Conclusions and Relevance: The distribution of essential medicines at no charge for 1 year increased adherence to treatment with medicines and improved some, but not other, disease-specific surrogate health outcomes. These findings could help inform changes to medicine access policies such as publicly funding essential medicines. Trial Registration: ClinicalTrials.gov identifier: NCT02744963. Publisher PDF