Institute For Clinical Evaluative Sciences Research Articles

Treatment Patterns and Healthcare Resource Utilization Among Patients with Triple Class Exposed Multiple Myeloma: A Population-Based Cohort Study

Introduction: Outcomes of patients with relapsed or refractory multiple myeloma (MM) have improved substantially with access to novel therapeutic agents. However, patients with triple class exposed (TCE) MM continue to have poor outcomes. Though newer bispecific antibody and chimeric antigen receptor T-cell immunotherapies have improved outcomes of TCE patients, these therapies are inaccessible outside of clinical trials in many publicly funded healthcare systems, including Canada. This study aimed to describe treatment patterns, outcomes, unplanned health care utilization and quality-of-life impairments of TCE MM patients in Ontario, Canada. These data will provide a crucial benchmark to compare to as novel immunotherapies become available. Methods: This retrospective observational study utilized data from the Institute for Clinical Evaluative Sciences (IC/ES) administrative database, which contains all health records of patients treated within Ontario's publicly funded healthcare system. Drug exposure was determined using the Cancer Activity Level Reporting (ALR) and Ontario Drug Benefit Claims Registry (ODB) databases, housed within IC/ES, which contain data on intravenous and oral MM treatment exposure for standard of care and clinical trial regimens. Patients were defined as TCE if they had prior or current treatment with a regimen containing an immunomodulatory drug (lenalidomide or pomalidomide), a proteasome inhibitor (bortezomib, carfilzomib, or ixazomib), and an anti-CD38 monoclonal antibody (isatuximab or daratumumab). The TCE index regimen was identified as the treatment on which a patient was first identified as having met the TCE definition. Inpatient hospitalization visits did not include planned chemotherapy infusion visits. Quality of life was described using the Edmonton Symptom Assessment System Score with scores ³ 7 corresponding to severe symptoms. Overall survival (OS) was determined using the Kaplan-Meier method. Results: Of the 16,777 patients with a diagnosis of MM between 2007-2021 in Ontario, 1358 patients were classified as TCE during their treatment course. The TCE index regimen was a daratumumab-based regimen in most patients [daratumumab/velcade/dex (n=566, 42%), daratumumab/lenalidomide/dex (n=619, 46%)]. Of the TCE patients, 247 (18%) were still receiving treatment with the TCE index regimen at last follow up, 263 (19%) died without receiving any additional treatment, and 489 (36%) received a subsequent MM treatment after the TCE index regimen. Baseline characteristics of patients (n=489) treated with a subsequent MM regimen after post TCE are summarized in Table 1. The three most commonly administered therapies post TCE were carfilzomib-dexamethasone (n=111, 23%), pomalidomide-dexamethasone (n=77, 16%) and oral cyclophosphamide (n=49, 10%). The next-line treatment regimen was administered in an academic versus community treatment center in 235 (48%) versus 254 (52%) of patients, respectively. The next-line therapy was a clinical trial in only 37 (8%) patients. Regarding healthcare utilization, among TCE patients receiving subsequent therapy, 149 (30%) were evaluated in the emergency department (ED), 126 (26%) were admitted to hospital, and 48 (10%) were referred to palliative care while on treatment with the subsequent therapy. Among patients with available information, the most common severe patient-reported symptoms during the subsequent line of treatment included: tiredness (27%), pain (23%) and overall poor well-being (21%). Additionally, 35% of patients had a ECOG PS of ≥2 on next-line treatment. The median OS patients treated after the TCE index regimen was 1.05 year (95% CI 0.89-1.35) as shown in Figure 1. Of the patients that died during follow up, the majority died in hospital (n=147, 44%) and were referred to palliative care (217, 65%). Conclusion: In this real-world study, we showed that the overall outcomes of TCE MM patients remains poor in Canada, highlighting the urgent need for novel therapies. Furthermore, we demonstrated that TCE patients receiving subsequent therapy had significant unplanned health care utilization and poor quality of life. Future studies will need to assess whether the outcomes, healthcare utilization, and patient-reported quality of life improve as newer immunotherapies become accessible as standard of care treatments within our publicly funded healthcare system.

Comparison of the Efficacy in Clinical Trials Versus Effectiveness in the Real-World of Treatments for Multiple Myeloma: A Population-Based Cohort Study

Introduction: Improvements in outcomes of patients with multiple myeloma (MM) depend on the use of regimens approved based on results from large phase III randomized controlled trials (RCTs) demonstrating their efficacy. However, many real-world (RW) patients would not have met the stringent RCTs inclusion criteria. Therefore, the effectiveness of these drugs in the RW setting is unknown. Understanding this efficacy-effectiveness gap is important to contextualize the expected outcomes in the current RW setting. Therefore, we conducted a retrospective population-based study to compare the efficacy versus effectiveness of registration RCTs with RW patients using standard of care (SoC) MM regimens for the primary outcomes of 1) progression free survival [PFS]; 2) overall survival [OS] and 3) serious adverse events (AEs). Methods: RW data was obtained from the Institute for Clinical Evaluative Sciences, an administrative database capturing all health records in the publicly funded health care system in Ontario, Canada. Adult patients treated between Jan 2007 to Dec 2020 with SoC regimens were included. Only regimens with corresponding registrational phase III RCTs which led to the public reimbursement in Ontario were included (lenalidomide/dex [Rd] and bortezomib/Rd [VRd] for newly diagnosed transplant ineligible patients, and relapsed MM (RRMM) regimens included carfilzomib/Rd [KRd], carfilzomib/dex [Kd], daratumumab/Rd [DRd], daratumumab/bortezomib/dex [DVd], pomalidomide/dex [Pd]). In the RW cohort, PFS was defined as the time from initiation of index regimen to death, initiation of subsequent MM treatment, or last follow-up, and patients remaining on the index regimen as last follow up were censored. Kaplan-Meier curves from pivotal phase 3 RCTs were manually digitized to provide individual patient-level estimates of PFS and OS. Meta-analyses were performed to compare the gap of PFS and OS outcomes of RW versus RCT patients, and effect estimates were summarized using hazard ratios (HR). The frequency of serious AE data was abstracted from published RCTs. Given that serious AEs in RCTs would have resulted in hospitalization, hospital admission during treatment with the index regimen was used as a surrogate for serious AEs in the RW cohort. Differences in RW and RCT safety outcomes were reported descriptively. Results & Discussion: A total of 3951 RW MM patients, treated with 7 standard of care MM regimens, were included. Baseline characteristics of patients in the RW and RCT cohorts are shown in table 1. Overall, patients in the RW cohort were older than in the RCTs. For relapsed regimens, there was a longer time between MM diagnosis and start of the regimen in the real-world versus RCT. With regards to the efficacy-effectiveness gap, MM patients treated in routine practise in the RW had a worse PFS despite overestimated of RW PFS compared to highly selected RCT patients for 6 of the 7 MM regimens evaluated, with a pooled HR of 1.44 (95% CI 1.34-1.54) in the meta-analysis (Figure 1A). Similarly, RW patients had a worse OS compared to RCT patients treated with 6 of the 7 regimens, with a pooled HR of 1.75 (95% ci 1.63-1.88) in the meta-analysis (Figure 1B). RRMM patients in the RW had higher rates of prior lenalidomide exposure compared to RCT patients. The only regimen which showed a trend towards performing better in the RW as compared to RCTs was Pd. The reason for this is likely multifactorial but perhaps patients included in the MM-003 RCT may have had more refractory MM (given the higher prior immunomodulatory drug exposure and longer time from diagnosis to treatment among Pd RCT patient) compared to RW patients in this study. With regards to safety, the percentage of patients with inpatient hospitalization during treatment in the real-world cohort and reported serious AEs in RCT were comparable (VRD 57% vs not reported [NR]; Rd 64% vs NR; Kd 57% vs 59%; KRd 53% vs 60%; DVd 36% vs NR; DRd 46% vs 49%; Pd 59% vs 61%). Conclusion: This is one the largest population-level studies highlighting the significant efficacy-effectiveness gap between registrational RCTs and RW usage of these regimens, with RW patients experiencing 44% worse PFS and 75% worse OS compared to RCT patients. Our data emphasize the importance of ongoing evaluation of RW data to contextualize effectiveness and toxicity of selected regimens in the clinic, and better inform both clinicians and patients for shared treatment decision making.

Profiling medical specialties and informing aspiring physicians: a data-driven approach.

A detailed, unbiased perspective of the inter-relations among medical fields could help students make informed decisions on their future career plans. Using a data-driven approach, the inter-relations among different medical fields were decomposed and clustered based on the similarity of their working environments.Publicly available, aggregate databases were merged into a single rich dataset containing demographic, working environment and remuneration information for physicians across Canada. These data were collected from the Canadian Institute for Health Information, the Canadian Medical Association, and the Institute for Clinical Evaluative Sciences, primarily from 2018 to 2019. The merged dataset includes 25 unique medical specialties, each with 36 indicator variables. Latent Profile Analysis (LPA) was used to group specialties into distinct clusters based on relatedness.The 25 medical specialties were decomposed into seven clusters (latent variables) that were chosen based on the Bayesian Information Criterion. The Kruskal-Wallis test identified eight indicator variables that significantly differed between the seven profiles. These variables included income, work settings and payment styles. Variables that did not significantly vary between profiles included demographics, professional satisfaction, and work-life balance satisfaction.The 25 analyzed medical specialties were grouped in an unsupervised manner into seven profiles via LPA. These profiles correspond to expected and meaningful groups of specialties that share a common theme and set of indicator variables (e.g. procedurally-focused, clinic-based practice). These profiles can help aspiring physicians narrow down and guide specialty choice.

How do perceptions of Covid-19 risk impact pregnancy-related health decisions? A convergent parallel mixed-methods study protocol.

Pregnant people have a higher risk of severe COVID-19 disease. They have been disproportionately impacted by COVID-19 infection control policies, which exacerbated conditions resulting in intimate partner violence, healthcare access, and mental health distress. This project examines the impact of accumulated individual health decisions and describes how perinatal care and health outcomes changed during the COVID-19 pandemic. Quantitative strand: Describe differences between 2019, 2021, and 2022 birth groups related to maternal vaccination, perinatal care, and mental health care. Examine the differential impacts on racialized and low-income pregnant people.Qualitative strand: Understand how pregnant people's perceptions of COVID-19 risk influenced their decision-making about vaccination, perinatal care, social support, and mental health. This is a Canadian convergent parallel mixed-methods study. The quantitative strand uses a retrospective cohort design to assess birth group differences in rates of Tdap and COVID-19 vaccination, gestational diabetes screening, length of post-partum hospital stay, and onset of depression, anxiety, and adjustment disorder, using administrative data from ICES, formerly the Institute for Clinical Evaluative Sciences (Ontario) and PopulationData BC (PopData) (British Columbia). Differences by socioeconomic and ethnocultural status will also be examined. The qualitative strand employs qualitative description to interview people who gave birth between May 2020- December 2021 about their COVID-19 risk perception and health decision-making process. Data integration will occur during design and interpretation. This study received ethical approval from McMaster University and the University of British Columbia. Findings will be disseminated via manuscripts, presentations, and patient-facing infographics. Registration: Clinicaltrials.gov registration number: NCT05663762.

Postoperative buprenorphine continuation in stabilized buprenorphine patients: A population cohort study.

Sudden discontinuation of buprenorphine in the treatment of opioid use disorder can increase the risk of subsequent relapse and overdose. Little is known about buprenorphine use in the perioperative period. The aim of this study was to determine the rate of buprenorphine continuation after hospital discharge following surgery and factors associated with continuation. A population-based retrospective cohort study was conducted using administrative data from Ontario, Canada, between 2012 and 2018. The cohort included individuals on continuous buprenorphine prior to surgery. Logistic regression modeling was used to estimate the association of buprenorphine continuation with demographic, opioid agonist treatment, surgical and health service use factors. Administrative databases from Institute for Clinical Evaluative Sciences (ICES) were used, which capture the Ontario, Canada, population. The data sets describe physician billing, monitoring of controlled substances and hospital discharges. Adults (≥ 18 years, n = 2176) had received a buprenorphine/naloxone product continuously for at least 60 days for the treatment of opioid use disorder and subsequently underwent a surgical procedure. Continuation (versus discontinuation) of buprenorphine prescriptions in the 14 days after surgical discharge was recommended. Exposures included demographic, comorbidity, opioid agonist treatment, surgical and health service use characteristics. About 176 (8.1%) of the 2176 patients discontinued buprenorphine after surgery. Inpatient surgery (versus ambulatory) was associated with reduced odds of continuation, with an unadjusted odds ratio (OR) of 0.17 [95% confidence interval (CI) = 0.12-0.25] and an adjusted OR of 0.16 (95% CI = 0.11-0.23) after accounting for age, sex, rural residence, neighborhood income quintile, Charlson comorbidity index, psychiatric hospitalizations in the past 5 years and recent dispensed supply of buprenorphine (number needed to harm of 6.6). In Ontario, Canada, from 2012 to 2018, most patients receiving continuous preoperative buprenorphine therapy continued buprenorphine use after surgery. Inpatient surgery was a strong predictor of discontinuation compared with ambulatory procedures.

PD29-02 BENCHMARKING BLADDER CANCER CARE: A REAL-LIFE POPULATION-BASED STUDY

You have accessJournal of UrologyCME1 Apr 2023PD29-02 BENCHMARKING BLADDER CANCER CARE: A REAL-LIFE POPULATION-BASED STUDY Nicolas Vanin-Moreno, Marlo Whitehead, and Robert Siemens Nicolas Vanin-MorenoNicolas Vanin-Moreno More articles by this author , Marlo WhiteheadMarlo Whitehead More articles by this author , and Robert SiemensRobert Siemens More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003315.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Radical cystectomy (RC) is a complex oncological surgical procedure and population studies of routine surgical care have suggested suboptimal results compared to high-volume centers of excellence. A previous Canadian bladder cancer quality-of-care consensus led to adoption of multiple key quality-of-care indicators with associated benchmarks created utilizing available evidence and expert opinion to inform and measure future performance. Herein we report real-life benchmark performance for the management of muscle invasive bladder cancer (MIBC) relative to expert opinion guidance. METHODS: This is a population-based, retrospective, cohort study that used the Ontario Cancer Registry (OCR) to identify all incident patients who underwent RC from 2009 and 2013. Electronic records of treatment from 1,573 patients were linked to OCR; pathology records were obtained for all cases and reviewed by a team of trained data abstractors. The primary objective was to describe benchmarks for identified indicators first as median values obtained across hospitals or providers as well as a “pared-mean” approach to identify a benchmark population of "top performance" as defined as the best outcome accomplished for at least 10 percent of the population. RESULTS: Overall, performance in Ontario across all indicators fell short of expert-opinion determined benchmarks. Annual surgical volume by each surgeon performing a RC (benchmark>6, percent of institutions meeting benchmark =20%), percent of patients with MIBC referred pre-operatively to Medical Oncology (MO; benchmark >90%, percent of institutions meeting benchmark =2%) and Radiation Oncology (RO; benchmark >50%, percent of institutions meeting benchmark =0%), time to cystectomy within 6 weeks of TURBT in patients without neoadjuvant chemotherapy (benchmark <6 weeks, percent of institutions meeting benchmark =0%), percent of patients with adequate lymph node dissection (defined as >14 nodes, benchmark >85%, percent of institutions meeting benchmark =0%), percent of patients with positive margins post RC (benchmark <10%, percent of institutions meeting benchmark =46%), and 90 day mortality (benchmark <5%, percent of institutions meeting benchmark =37%) fell considerably short. Simply evaluating benchmarks across the province as median performance significantly under-estimated benchmarks that were possible by top-performing hospitals. CONCLUSIONS: Performance through the majority of BC quality of care indicators fall short of benchmarks proposed by expert-opinion. Different methodologies such as a pared-mean approach of top performers may provide more realistic benchmarking. Source of Funding: This study was supported by the Institute for Clinical Evaluative Sciences (ICES), which is funded by an annual grant from the Ontario Ministry of Health and Long-Term Care (MOHLTC). Parts of this material are based on data and information compiled and provided by CIHI. © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e824 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Nicolas Vanin-Moreno More articles by this author Marlo Whitehead More articles by this author Robert Siemens More articles by this author Expand All Advertisement PDF downloadLoading ...

Abstract P4-06-10: Is Anthracycline Chemotherapy Essential in the Treatment of Women with Breast Cancer? – A Real World Comparison in the Neoadjuvant Setting

Abstract Background: Breast cancer is the second most commonly diagnosed cancer in North American women. The administration of neoadjuvant chemotherapy (NAC) is the mainstay of treatment for individuals with high risk disease in an effort to reduce the extent of surgery, evaluate the role of additional adjuvant therapies (based on pathologic response to NAC), and improve disease-free and overall survival (OS). Anthracyclines have been shown to increase response rates leading to a greater likelihood of pathologic complete response compared to non-anthracycline regimens. However, for some individuals anthracyclines are omitted from the NAC regimen due to toxicities including greater immunosuppression, cardiac toxicity and risk of acute leukemia. We established a population-based cohort of individuals treated with NAC for breast cancer. We report the outcomes of women selected for treatment with non-anthracycline NAC compared to those treated with anthracyclines. Methods: This is a retrospective population-based cohort study using linked health administrative data held at the Institute for Clinical Evaluative Sciences (ICES) in Ontario, Canada. We identified adult women diagnosed with stage I-III breast cancer (ICD-10 C50^) between 2012 and 2020 who received NAC. Administration of at least 50% of the planned chemotherapy regimen was required. We excluded patients with bilateral breast cancer, previous malignancy and male sex. NAC regimens were classified as anthracycline and non-anthracycline-containing regimens. To address confounding between those receiving anthracycline and other regimens, we built a propensity score model including patient and disease characteristics. The association with OS was calculated using Cox proportional hazards models, and breast cancer-specific survival (BCSS) was calculated using cause-specific Cox proportional hazards models. Models were adjusted for the propensity score, radiation treatment as a time-varying covariate, age, socioeconomic status, breast cancer stage and receptor sub-type, as well as Charlson comorbidity index. Results: A total of 4,180 women were identified with a median follow up of 62 months (IQR 44 – 85). Of these, 279 (6.7%) were treated with non-anthracycline regimens compared to 3,901 treated with anthracycline. Patients who received non-anthracyclines were older (median 62 years vs. 50 years; p &amp;lt; 0.001), and less likely to have stage III disease (33.0% vs. 48.7%; p &amp;lt; 0.001), and harbor triple-negative breast cancer (TNBC) (14.0% vs. 24.4%; p &amp;lt; 0.001). They were more likely to have no recorded comorbidities (89.2% vs. 96.5%; p &amp;lt; 0.001), undergo mastectomy (82.1% vs. 71.9%; p &amp;lt; 0.001), and sentinel lymph node biopsy (44.4% vs. 32.3%; p &amp;lt; 0.001). After propensity score and multivariable adjustment, women selected for treatment with non-anthracycline regimens had similar OS (HR 0.85, 95% CI 0.60-1.21) and BCSS (cause-specific HR 0.76, 95% CI 0.46-1.25) compared to those treated with anthracyclines. When stratified by stage, women treated with non-anthracycline regimens did not have significantly higher incidences of breast cancer death or death from any cause (stages I, II, and III Gray’s Test p-value all &amp;gt; 0.1). The mean OS was 7.2 years for women who received non-anthracycline regimens (95% CI 7.0 – 7.4) compared to 7.9 years for those who received anthracycline (95% CI 7.9 – 8.0) (log-rank p = 0.100). Conclusions: Women with stage I-III breast cancer treated with non-anthracycline NAC regimens are a highly selected population. These patients were older and healthier, with earlier stage disease and more favorable subtype (i.e. non-TNBC) when compared to those treated with anthracycline NAC. Our results demonstrate that women were well selected to omit anthracyclines and did not have worse survival outcomes. Further research is needed to better understand in whom anthracycline can be safely omitted. Citation Format: Danilo Giffoni M. M. Mata, Matthew Castelo, Rinku Sutradhar, Lena Nguyen, Neil Faught, Danielle Rodin, Ezra Hahn, Omolara Fatiregun, Cindy Fong, Sabina Trebinjac, Andrea Eisen, Lawrence Paszat, Katarzyna Jerzak, Eileen Rakovitch. Is Anthracycline Chemotherapy Essential in the Treatment of Women with Breast Cancer? – A Real World Comparison in the Neoadjuvant Setting [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-06-10.

Identifying the effect of inherited bleeding disorders on the development of postpartum hemorrhage: a population-based, retrospective cohort study

BackgroundWomen with inherited bleeding disorders (IBDs) are at an increased risk of postpartum hemorrhage (PPH). However, the impact of other maternal predelivery risk factors, including anemia, on the association between IBD and maternal bleeding remains poorly understood. Additionally, studies examining potential pathways linking IBD and PPH are limited. ObjectivesWe aimed to determine the risk of PPH associated with IBD. MethodsA retrospective cohort study was conducted using data held within ICES (formerly the Institute for Clinical Evaluative Sciences). Women with an in-hospital, live, or stillborn delivery between January 2014 and December 2019 were included. Poisson regression with robust error variance was used to determine the risk (RR) and 95% CIs of PPH among women with or without an IBD diagnosis. Models were stratified for primiparous and multiparous women. ResultsAmong the total population of 601,773 women, 29,661 (4.93%) experienced PPH. Multivariate models demonstrated that IBD was an independent risk factor for PPH among both the total cohort (adjusted RR [aRR] = 1.26; 95% CI: 1.08, 1.46) and primiparous women (aRR = 1.36; 95% CI: 1.12, 1.66). Among multiparous women, prior PPH was associated with an increased risk of PPH (aRR = 8.65; 95% CI: 8.32, 8.99), whereas IBD had no effect (aRR = 1.1; 95% CI: 0.86, 1.4). Predelivery anemia, placental conditions, multifetal gestation, and induction of labor were associated with increased PPH risk among all cohorts. ConclusionsIBD significantly increases the risk of PPH. The management of delivery should be based on individualized assessment of risk factors to ensure optimal maternal outcomes.

Total hip arthroplasty versus hemiarthroplasty for treatment of femoral neck fractures : a population-based analysis of practice variation in Ontario, Canada.

This study aimed to describe practice variation in the use of total hip arthroplasty (THA) for older patients with femoral neck fracture and to determine the association between patient, surgeon, and institution factors and treatment with THA. We performed a cross-sectional analysis of 49,597 patients aged 60 years and older from Ontario, Canada, who underwent hemiarthroplasty or THA for femoral neck fracture between 2002 and 2017. This population-based study used routinely collected healthcare databases linked through ICES (formerly known as the Institute for Clinical Evaluative Sciences). Multilevel logistic regression modelling was used to quantify the association between patient, surgeon, and institution-level variables and whether patients were treated with THA. Variance partition coefficient and median odds ratios were used to estimate the variation attributable to higher-level variables and the magnitude of effect of higher-level variables, respectively. Over the study period, 9.4% of patients (n = 4,638) were treated with THA. Patient factors associated with higher likelihood of treatment by THA included: younger age, male sex, and diagnosis with rheumatoid arthritis. Long-term care residence, use of home care services prior to hip fracture, diagnosis of dementia, higher comorbidity burden, and the most marginalized group were negatively associated with treatment by THA. Treating surgeon and institution accounted for 54.2% and 17.8% of the total variation in treatment with THA, respectively. Surgeon volume of THA procedures in the 365 days prior to surgery was the strongest higher-level predictor of treatment with THA. Specific treating surgeons and institutions still accounted for significant proportions of the variability in treatment with THA (40.3% and 19.5% of total observed variation, respectively) after controlling for available patient, surgeon, and institution-level variables. The strongest predictors for treatment of patients with femoral neck fracture with THA were patient age, treating surgeon, and treating institution. This practice variation highlights differential access to care for patients.Cite this article: Bone Joint J2023;105-B(2):180-189.

The Impact of Primary Care Practice Models on Indicators of Unplanned Health Care Utilization for Ontario Adults Newly Diagnosed With Chronic Obstructive Pulmonary Disease: A Retrospective Cohort Study.

Chronic obstructive pulmonary disease (COPD) is a highly prevalent chronic disease. Most of the care for this population occurs within the primary care setting; however, the extent to which different primary care practice models influence the outcomes of patients with COPD remains unclear. The study aimed to compare and analyze the influence of different primary care practice models on indicators of unplanned health care utilization among newly diagnosed COPD patients in Ontario. A retrospective cohort study was conducted using health administrative database within the Institute for Clinical Evaluative Sciences. The cohort included persons who were 35 years and older with physician-diagnosed COPD between January 1, 2014 and December 31, 2019. Patients were assigned into 3 practice models: team-based, traditional, and no enrolment. The primary outcomes examined was unplanned health care utilization, specifically emergency department (ED) visits and hospitalizations. To account for excessive zero values, the zero inflated negative binomial (ZINB) models were used to analyze the association between different practice models and unplanned health care utilization. Among 57,145 individuals who met the inclusion criteria, 55,994 were included in the regression analysis. Of the included participants, 62.8% of patients were in the traditional group, 30.3% were in the team-based group, and 6.9% were in the no enrolment group. Between 2014 and 2019, 70.7% of the cohort had at least 1 all-cause ED visit without hospitalization. The adjusted ZINB models showed no significant difference in risks of experiencing an unplanned health care utilization between the team-based and traditional groups. However, patients in the no enrolment group had a significantly higher risk of ED visit without hospitalization regardless of cause, ED visit with hospitalization regardless of cause, and 30-day readmissions regardless of cause. Primary care practice models are complex, influenced by remuneration and organizational structures, reinforcing the need for further research to enhance our understanding of primary care reforms. Furthermore, given the growing shortage of primary care providers, patients with COPD and other chronic conditions are particularly vulnerable.

Young adults with intellectual and developmental disabilities who participate in Special Olympics are less likely to be diagnosed with depression.

People with intellectual and developmental disabilities (IDD) experience high rates of depression. Evidence indicates that physical activity, or participation in a sports club, in a supportive social environment has mental and physical health benefits. Adults with IDD, on average, engage in low levels of physical activity. The purpose of this study was to compare the rates of depression among young adult Special Olympics participants with IDD compared to non-participants with IDD. This was a 20-year retrospective cohort study of young adults (19-29years) with IDD in the province of Ontario, Canada that compared rates of depression among Special Olympics participants (n = 8710) to non-participants (n = 42,393) using administrative health databases housed at ICES (formerly the Institute for Clinical Evaluative Sciences). Using cox proportional hazard models, the crude hazard ratios were calculated for the association between each independent variable and the dependent variable. After controlling for other variables, the hazard rate for depression among Special Olympics participants compared to the hazard rate for depression among non-participants generated an adjusted hazard ratio of 0.51. Over the 20-year follow-up, the participants were 0.51 times as likely to develop depression as non-participants; this represents a 49% reduction in risk among Special Olympics participants. This result was statistically significant and represents a medium effect size. Future research is needed on how much of this risk reduction is related to a physiological response to physical activity/exercise, and how much is related to the social connectedness of being part of a group participating in Special Olympics.

Personalised cooler dialysate for patients receiving maintenance haemodialysis (MyTEMP): a pragmatic, cluster-randomised trial

Haemodialysis centres have conventionally provided maintenance haemodialysis using a standard dialysate temperature (eg, 36·5°C) for all patients. Many centres now use cooler dialysate (eg, 36·0°C or lower) for potential cardiovascular benefits. We aimed to assess whether personalised cooler dialysate, implemented as centre-wide policy, reduced the risk of cardiovascular-related death or hospital admission compared with standard temperature dialysate. MyTEMP was a pragmatic, two-arm, parallel-group, registry-based, open-label, cluster-randomised, superiority trial done at haemodialysis centres in Ontario, Canada. Eligible centres provided maintenance haemodialysis to at least 15 patients a week, and the medical director of each centre had to confirm that their centre would deliver the assigned intervention. Using covariate-constrained randomisation, we allocated 84 centres (1:1) to use either personalised cooler dialysate (nurses set the dialysate temperature 0·5-0·9°C below each patient's measured pre-dialysis body temperature, with a lowest recommended dialysate temperature of 35·5°C), or standard temperature dialysate (36·5°C for all patients and treatments). Patients and health-care providers were not masked to the group assignment; however, the primary outcome was recorded in provincial databases by medical coders who were unaware of the trial or the centres' group assignment. The primary composite outcome was cardiovascular-related death or hospital admission with myocardial infarction, ischaemic stroke, or congestive heart failure during the 4-year trial period. Analysis was by intention to treat. The study is registered at ClinicalTrials.gov, NCT02628366. We assessed all of Ontario's 97 centres for inclusion into the study. Nine centres had less than 15 patients and one director requested that four of their seven centres not participate. 84 centres were recruited and on Feb 1, 2017, these centres were randomly assigned to administer personalised cooler dialysate (42 centres) or standard temperature dialysate (42 centres). The intervention period was from April 3, 2017, to March 31, 2021, and during this time the trial centres provided outpatient maintenance haemodialysis to 15 413 patients (about 4·3 million haemodialysis treatments). The mean dialysate temperature was 35·8°C in the cooler dialysate group and 36·4°C in the standard temperature group. The primary outcome occurred in 1711 (21·4%) of 8000 patients in the cooler dialysate group versus 1658 (22·4%) of 7413 patients in the standard temperature group (adjusted hazard ratio 1·00, 96% CI 0·89 to 1·11; p=0·93). The mean drop in intradialytic systolic blood pressure was 26·6 mm Hg in the cooler dialysate group and 27·1 mm Hg in the standard temperature group (mean difference -0·5 mm Hg, 99% CI -1·4 to 0·4; p=0·14). Centre-wide delivery of personalised cooler dialysate did not significantly reduce the risk of major cardiovascular events compared with standard temperature dialysate. The rising popularity of cooler dialysate is called into question by this study, and the risks and benefits of cooler dialysate in some patient populations should be clarified in future trials. Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Ontario Renal Network, Ontario Strategy for Patient-Oriented Research Support Unit, Dialysis Clinic, Inc., ICES (formerly known as the Institute for Clinical Evaluative Sciences), Lawson Health Research Institute, and Western University.

Radiation Dose, Technique and Use of Brain Radiation on Overall Survival in Patients with Limited-Stage Small Cell Lung Cancer

<h3>Purpose/Objective(s)</h3> The standard of care for limited-stage small cell lung cancer (LS-SCLC) currently involves concurrent chemoradiation +/- prophylactic cranial irradiation (PCI). Previous research has presented conflicting data regarding the optimal radiation therapy (RT) technique, RT dosage, and impact of brain RT on long term overall survival (OS). This study aimed to explore prognostic factors of OS in LS-SCLC cancer patients using a population-based cohort. <h3>Materials/Methods</h3> Data on all patients diagnosed with LS-SCLC in Ontario, Canada from 2005-2017 was obtained using the Institute for Clinical Evaluative Sciences (IC/ES) Data and Analytic Services. Eligible patients received curative intent chemoradiation, and OS was estimated from a landmark date of 6 months post-diagnosis to avoid survivor bias. Kaplan-Meier methods and Cox regression were used to estimate OS and explore differences between RT dose (40-49, 50-59, 60+ Gy), RT technique (3DCRT, IMRT, VMAT), and use of brain RT (PCI – 25 Gy, whole brain RT – 20 or 30 Gy, other brain RT, no brain RT). Multivariate analyses adjusted for sex, age, income quintile, Charlson comorbidity index, disease stage, prior history of cardiac disease, brain RT dose, and laterality. <h3>Results</h3> A total of 1360 LS-SCLC patients who received chemoradiation were included. Median OS (95% CI) was 18.1 months (16.6-19.4). Higher RT dose had significantly improved OS when compared to 40-49 Gy on univariate analysis (HR=0.83, 0.71-0.95, 60+ Gy), however, this did not persist when adjusting for other prognostic factors on multivariate analysis (HR=0.90, 0.77-1.06, 60+ Gy). The use of whole brain RT was associated with worse OS on both univariate (HR=1.47, 1.24-1.74) and multivariate (HR=1.42, 1.18-1.70) analyses. OS (95% CI) at 5-years for RT dose were 40-49 Gy: 16% (13-19%), 50-59 Gy: 23% (18-29), and 60+ Gy: 20% (16-25). For RT technique, OS (95% CI) at 5-years were 3DCRT: 19% (13-22), IMRT: 18% (13-23), and VMAT: 12% (4-25). Multivariate analyses demonstrated that male sex (HR=1.36, 1.20-1.55), more advanced stage disease (HR=1.35/1.94/3.08/1.67 for stage 2/3/4/Unknown vs 1), and older age were prognostic for worse OS. <h3>Conclusion</h3> Analyses of population-based data demonstrated that male sex, older age, and more advanced disease stage were notable predictors of OS in LS-SCLC. RT dose, when adjusting for other important prognostic variables did not predict for improved OS. However, use of whole brain RT (versus PCI or no PCI) was associated with worse OS. Use of PCI versus no PCI did not influence survival in this cohort, nor did RT technique.

Determining the influence of the primary and specialist network of care on patient and system outcomes among patients with a new diagnosis of chronic obstructive pulmonary disease (COPD)

IntroductionCare for patients with chronic obstructive pulmonary disease (COPD) is provided by both family physicians (FP) and specialists. Ideally, patients receive comprehensive and coordinated care from this provider team. The objectives for this study were: 1) to describe the family and specialist physician network of care for Ontario patients newly diagnosed with COPD and 2) to determine the associations between selected characteristics of the physician network and unplanned healthcare utilization.MethodsWe conducted a retrospective cohort study using Ontario health administrative data housed at ICES (formerly the Institute for Clinical Evaluative Sciences). Ontario patients, ≥ 35 years, newly diagnosed with COPD were identified between 2005 and 2013. The FP and specialist network of care characteristics were described, and the relationship between selected characteristics (i.e., continuity of care) with unplanned healthcare utilization during the first 5 years after COPD diagnosis were determined in multivariate models.ResultsOur cohort consisted of 450,837 patients, mean age 61.5 (SD 14.6) years. The FP was the predominant provider of care for 86.4% of the patients. Using the Bice-Boxerman’s Continuity of Care Index (COCI), a measure reflecting care across different providers, 227,082 (50.4%) were categorized in a low COCI group based on a median cut-off. In adjusted analyses, patients in the low COCI group were more likely to have a hospital admission (OR = 2.27, 95% CI 2.20,2.22), 30-day readmission (OR = 2.44, 95% CI 2.39, 2.49) and ER visit (OR = 2.27, 95% CI 2.25, 2.29).ConclusionHigher indices of continuity of care are associated with reduced unplanned hospital use for patients with COPD. Primary care-based practice models to enhance continuity through coordination and integration of both primary and specialist care have the potential to enhance the health experience for patients with COPD and should be a health service planning priority.

Measuring the Predictive Accuracy of Preoperative Clinical Frailty Instruments Applied to Electronic Health Data in Older Patients Having Emergency General Surgery: A Retrospective Cohort Study.

To compare predictive accuracy of frailty instruments operationalizable in electronic data for prognosticating outcomes among older adults undergoing emergency general surgery (EGS). Older patients undergoing EGS are at higher risk of perioperative morbidity and mortality. Preoperative frailty is a common and strong perioperative risk factor in this population. Despite this, existing barriers preclude routine preoperative frailty assessment. We conducted a retrospective cohort study of adults above 65 undergoing EGS from 2012 to 2018 using Institute for Clinical Evaluative Sciences (ICES) provincial healthcare data in Ontario, Canada. We compared 4 frailty instruments: Frailty Index (FI), Hospital Frailty Risk Score (HFRS), Risk Analysis Index-Administrative (RAI), ACG Frailty-defining diagnoses indicator (ACG). We compared predictive accuracy beyond baseline risk models (age, sex, American Society of Anesthesiologists' score, procedural risk). Predictive performance was measured using discrimination, calibration, explained variance, net reclassification index and Brier score (binary outcomes); using explained variance, root mean squared error and mean absolute prediction error (continuous outcomes). Primary outcome was 30-day mortality. Secondary outcomes were 365-day mortality, nonhome discharge, days alive at home, length of stay, and 30-day and 365-day health systems cost. A total of 121,095 EGS patients met inclusion criteria. Of these, 11,422 (9.4%) experienced death 30 days postoperatively. Addition of FI, HFRS, and RAI to the baseline model led to improved discrimination, net reclassification index, and R2 ; RAI demonstrated the largest improvements. Adding 4 frailty instruments to typically assessed preoperative risk factors demonstrated strong predictive performance in accurately prognosticating perioperative outcomes. These findings can be considered in developing automated risk stratification systems among older EGS patients.

Direct Oral Anticoagulation Versus Warfarin in Patients with Atrial Fibrillation and Bioprosthetic Heart Valves: a Retrospective, Real-World Cohort Study.

In this retrospective cohort study of consecutive patients with atrial fibrillation and surgical or transcatheter bioprosthetic valve, we compared the efficacy and safety of direct oral anticoagulants withwarfarin. Using linked health administrative databases housed at the Institute for Clinical Evaluative Sciences, we identified consecutive patients in Ontario (Canada) 65years of age or older with AF who underwent bioprosthetic valve replacement between 1 April 2012 and 31 March 2017. We created a time-varying Cox model to examine the relationship between the type of anticoagulant and time to thrombotic or bleeding events after adjustment for baseline risk of thrombosis using the CHA2DS2-VASc score and risk ofbleeding using the HAS-BLED scores. We conductedprespecified subgroup analyses according to whether valve implantation was surgical or transcatheter. We identified 2245 eligible patients. The mean age was 79years, 41% were female, and 39% had transcatheter aortic valve replacement. Risk of death or thrombosis was not differentbetween direct oral anticoagulants and warfarin after adjustment for CHA2DS2-VASc score (hazard ratio [HR] 1.02, 95% confidence interval [CI], 0.83-1.25). Risk of death or bleeding was not differentbetween direct oral anticoagulants and warfarin after adjustment for HAS-BLED score (HR 0.89, 95% CI 0.75-1.07). Subgroup analyses of surgical or transcatheter valves were consistent with overall results. In a real-world population of patients with atrial fibrillation and bioprosthetic valve replacement, we foundno difference between direct oral anticoagulants and warfarin with regard to the risk of thrombosis or bleeding.

Determining the incidence of postpartum haemorrhage among Ontario women with and without inherited bleeding disorders: A population-based cohort study.

At a population level, there is a poor understanding of the incidence and pre-disposing risk factors of postpartum haemorrhage (PPH) among women with inherited bleeding disorders (IBD). To determine the incidence of PPH, and identify maternal factors associated with risk of PPH among women with IBD. We conducted a retrospective cohort study using data housed within ICES (formerly known as the Institute for Clinical Evaluative Sciences). The cohort included women with an in-hospital, live or stillborn delivery, between January 2014 and December 2019. The primary outcome was PPH (identified by ICD-10 code O72). PPH incidence and risk factors were compared between women with and without IBD. Temporal trends were assessed using the Cochrane-Armitage test. Between group differences were assessed using standardised differences (std. difference). Total 601,773 women were included; 2002 (.33%) had an IBD diagnosis. PPH incidence was 1.5 times higher (7.3 vs. 4.9 cases/100 deliveries, std. difference .1) among women with IBD compared to women without. Women with IBD were slightly older (31.7 vs. 30.7 years), had higher rates of hypertension, previous PPH, and induction of labour. Women with IBD were more frequently diagnosed with anaemia (4.8% vs. 1.8%; std difference .17) and had lower haemoglobin levels at admission for delivery compared to women without IBD. This study contributes to the literature regarding obstetric bleeding among women with IBD, showing that anaemia at delivery may be an important risk factor for PPH. Given their predisposition to anaemia, clarifying this relationship will optimise management and outcomes.

The real-world experience of adjuvant docetaxel and cyclophosphamide (TC) chemotherapy in HER-2 negative breast cancer.

538 Background: Adjuvant chemotherapy in breast cancer (BC) substantially improves overall survival (OS) and the risk of recurrence. The short and long-term side effects of anthracycline, and its modest benefits in the adjuvant setting, led to controversy about its role in comparison with TC. We aim to compare the OS of TC with anthracycline-based regimens in Ontario, the most populous province in Canada. Methods: We conducted a retrospective population-based cohort study using the Institute for Clinical Evaluative Sciences (ICES) database, involving females with stage I-III BC HER2-negative. Patients were treated with adjuvant chemotherapy between January 2009 to December 2017. The anthracycline regimens for comparison were as follows, FEC-D: Fluorouracil, Epirubicin, Cyclophosphamide, followed by Docetaxel; and ACT: Doxorubicin, Cyclophosphamide, followed by Docetaxel or Paclitaxel. Exclusion criteria included missing baseline characteristics, a prior history of malignancy or chemotherapy starting more than 120 days from breast surgery. The end of follow-up was March 31st, 2018. Adjusted analyses to compare OS by positive axillary lymph nodes (LN) and chemotherapy regimens were conducted with Cox proportional hazards models. Results: Of a total 10634 female patients with BC, 60% were ≥ 50 years-old, with 19.6% stage I, 61.1% stage II, and 19.3% stage III and 7130 (67%) women were classified as ER+ and 2379 (22.4%) as ER-. Among 5764 (54.2%) patients with positive LN, 4300 (40.4%) had LN 1-3 and 1464 (13.8%) had LN ≥ 4. There were 4945 (46.5%) high-grade cases. There were 2487 (23.5%) patients treated with TC, 2981 (28%) with ACT, and 5166 (48.5%) with FEC-D. With a median follow-up of 5.5 years, the OS comparison for the entire study population showed hazard ratio (HR) of TC vs ACT was 1.47 (95% CI 1.14 – 1.90), p = 0.0027 and TC vs FEC-D HR was 1.48 (95% CI 1.18 – 1.86), p = 0.0007. For ER+ patients treated with TC, the OS comparison of LN 1-3 and LN ≥ 4 vs. LN 0 showed HR 1.34 (95% CI 0.81 – 2.21), p = 0.26, and HR 4.29 (95% CI 2.09 – 8.79), p &lt; 0.0001, respectively. For ER+ LN 0 patients, the OS HR of TC vs. ACT was 1.15 (95% CI 0.58 – 2.35), p = 0.67, and TC vs. FEC-D HR was 1.38 (95% CI 0.81 – 2.33), p = 0.23. For ER- patients treated with TC, the OS comparison of LN 1-3 and LN ≥ 4 vs. LN 0 showed HR 1.12 (95% CI 0.42 – 3.01), p = 0.82 and HR 4.41 (95% CI 1.33 – 14.59), p = 0.015, respectively. For ER- LN 0 patients, the OS HR for TC vs. ACT was 2.04 (95% CI 1.09 – 3.81), p = 0.025, and TC vs. FEC-D HR was 2.05 (95% CI 1.08 – 3.90), p = 0.028. Conclusions: Patients treated with adjuvant TC who had four or more axillary LN had significantly lower OS when compared to patients with LN 0. For women with ER- disease, TC demonstrated a significant unfavourable survival outcome when compared to anthracycline-based treatments.

Association of Late Preterm Birth and Size for Gestational Age With Cardiometabolic Risk in Childhood

The long-term cardiometabolic consequences of late preterm birth (34-36 weeks' gestation) are not well understood. To assess whether late preterm birth and size for gestational age are associated with cardiometabolic risk (CMR) in childhood. This retrospective cohort study included 1742 children born in Ontario, Canada, between April 1, 2006, and September 30, 2014, and followed up until September 30, 2019. Data from children enrolled in The Applied Research Group for Kids (TARGet Kids!) primary care practice-based research network were linked to administrative health care data at ICES (formerly known as the Institute for Clinical Evaluative Sciences). Participants were excluded if they had conditions affecting growth (eg, failure to thrive or cystic fibrosis), any acute or chronic conditions (other than asthma and high-functioning autism), severe developmental delay, or families who were unable to communicate in English. Late preterm birth, gestational age as a continuous measure, and size for gestational age. The primary outcome was composite CMR score (overall age- and sex-standardized z score of CMR components, including waist circumference, log triglyceride level, glucose level, systolic blood pressure, and high-density lipoprotein cholesterol level). Secondary outcomes were the individual CMR components. Multivariable linear regression analysis was used to separately evaluate the associations of late preterm birth, continuous gestational age, and size for gestational age with CMR at ages 3 to 12 years. Among 2440 eligible children, 1742 (mean [SD] age, 5.6 [2.2] years; 951 boys [54.6%]) were included in the final cohort. Overall, 87 children (5.0%) were born moderately preterm (<34 weeks' gestation), 145 (8.3%) were born late preterm (34-36 weeks' gestation), 455 (26.1%) were born early term (37-38 weeks' gestation), and 1055 (60.6%) were born full term (≥39 weeks' gestation). Compared with children born full term, those born moderately preterm (adjusted β = 0.50; 95% CI, 0.24-0.75) and late preterm (adjusted β = 0.27; 95% CI, 0.06-0.47) had higher CMR scores. Each additional gestational week was associated with a 0.06 U (adjusted β; 95% CI, -0.08 to -0.03 U) decrease in CMR. In this study, children born late preterm and moderately preterm had higher CMR. These results suggest that screening and early-life interventions for these children may prevent cardiometabolic outcomes.

Are Income-based Differences in TKA Use and Outcomes Reduced in a Single-payer System? A Large-database Comparison of the United States and Canada.

Income-based differences in the use of and outcomes in TKA have been studied; however, it is not known if different healthcare systems affect this relationship. Although Canada's single-payer healthcare system is assumed to attenuate the wealth-based differences in TKA use observed in the United States, empirical cross-border comparisons are lacking. (1) Does TKA use differ between Pennsylvania, USA, and Ontario, Canada? (2) Are income-based disparities in TKA use larger in Pennsylvania or Ontario? (3) Are TKA outcomes (90-day mortality, 90-day readmission, and 1-year revision rates) different between Pennsylvania and Ontario? (4) Are income-based disparities in TKA outcomes larger in Pennsylvania or Ontario? We identified all patients hospitalized for primary TKA in this cross-border retrospective analysis, using administrative data for 2012 to 2018, and we found a total of 161,244 primary TKAs in Ontario and 208,016 TKAs in Pennsylvania. We used data from the Pennsylvania Health Care Cost Containment Council, Harrisburg, PA, USA, and the ICES (formally the Institute for Clinical Evaluative Sciences), Toronto, Ontario, Canada. We linked patient-level data to the respective census data to determine community-level income using ZIP Code or postal code of residence and stratified patients into neighborhood income quintiles. We compared TKA use (age and gender, standardized per 10,000 population per year) for patients residing in the highest-income versus the lowest-income quintile neighborhoods. Similarly secondary outcomes 90-day mortality, 90-day readmission, and 1-year revision rates were compared between the two regions and analyzed by income groups. TKA use was higher in Pennsylvania than in Ontario overall and for all income quintiles (lowest income quartile: 31 versus 18 procedures per 10,000 population per year; p < 0.001; highest income quartile: 38 versus 23 procedures per 10,000 population per year; p < 0.001). The relative difference in use between the highest-income and lowest-income quintile was larger in Ontario (28% higher) than in Pennsylvania (23% higher); p < 0.001. Patients receiving TKA in Pennsylvania were more likely to be readmitted within 90 days and were more likely to undergo revision within the first year than patients in Ontario, but there was no difference in mortality at 1 year. When comparing income groups, there were no differences between the countries in 90-day mortality, readmission, or 1-year revision rates (p > 0.05). These results suggest that universal health insurance through a single-payer may not reduce the income-based differences in TKA access that are known to exist in the United States. Future studies are needed determine if our results are consistent across other geographic regions and other surgical procedures. Level III, therapeutic study.