On the estimation of intracluster correlation for time-to-event outcomes in cluster randomized trials

Cluster randomized trials (CRTs) involve the random assignment of intact social units rather than independent subjects to intervention groups. Time-to-event outcomes often are endpoints in CRTs where the intracluster correlation coefficient (ICC) serves as a descriptive parameter to assess the similarity among outcomes in a cluster. However, estimating the ICC in CRTs with time-to-event outcomes is a challenge due to the presence of censored observations. The ICC is estimated for two CRTs using the censoring indicators and observed outcomes. A simulation study explores the effect of administrative censoring on estimating the ICC. Results show that the ICC estimators derived from censoring indicators and observed outcomes are negatively biased for positively correlated outcomes. Analytic work further supports these results. Censoring indicators may be preferred to estimate the ICC under moderate frequency of administrative censoring while the observed outcomes may be preferred under minimal frequency of administrative censoring

Trends in systematic recording errors of blood pressure and association with outcomes in Canadian and UK primary care data: a retrospective observational study

Introduction End digit preference (EDP) or systematic bias in the recording of blood pressure (BP) measurement is prevalent in primary care: up to 60% of BP readings end in zero. High blood pressure (BP) is a leading cause of increased morbidity in adults and errors in measurement may contribute to increased rate of adverse cardiovascular outcomes. Objectives and Approach We studied EDP trends, uptake of Automated Office BP (AOBP) measurement, and cardiovascular outcomes in the UK and Canada.This is a retrospective observational study using routinely collected Electronic Medical Record data for patients age 18 or more. We used bootstrap method to estimate the odds ratios where logistic regression was fitted on one thousand independently sampled replicates of the CPCSSN and RCGP datasets. We implemented the unsupervised algorithm of k-nearest neighbor across all sites to find the optimal decision boundary to classify the sites into the three categories: (1) strong EDP; (2) some EDP; (3) no EDP. Results The mean rate of end digit zero for both systolic and diastolic BP decreased from 26.6% in 2006 to 15.4% in 2015 in Canada and from 24.2% in 2001 to 17.3% in 2015 in the U.K. There was a gradual decline in EDP in the three years following the purchase of an AOBP machine. Sites categorized as having high levels of EDP had lower mean sBP levels than sites with potentially no EDP in both Canada and UK. Patients in sites with high levels of EDP had higher yearly prevalence of stroke (Standardized morbidity ration or SMR 1.11), myocardial infarcts (SMR 1.15), and angina (SMR 1.27) than patients in sites with no EDP. Conclusion/Implications There is systematic recording errors including rounding down of BP readings associated with higher rates of EDP and presumably more use of manual BP measurement. Higher rates of EDP were associated with greater prevalence of adverse cardiovascular outcomes. Consideration should be given to using AOBP machines in primary care

Would you like to add a weight after this blood pressure, doctor? Discovery of potentially actionable associations between the provision of multiple screens in primary care

The CPCSSN was funded through a contribution agreement with the Public Health Agency of Canada.Rationale, aims, and objective:  Guidelines recommend screening for risk factors associated with chronic diseases but current electronic prompts have limited effects. Our objective was to discover and rank associations between the presence of screens to plan more efficient prompts in primary care. Methods:  Risk factors with the greatest impact on chronic diseases are associated with blood pressure, body mass index, waist circumference, glycaemic and lipid levels, smoking, alcohol use, diet, and exercise. We looked for associations between the presence of screens for these in electronic medical records. We used association rule mining to describe relationships among items, factor analysis to find latent categories, and Cronbach α to quantify consistency within latent categories. Results:  Data from 92 140 patients in or around Toronto, Ontario, were included. We found positive correlations (lift >1) between the presence of all screens. The presence of any screen was associated with confidence greater than 80% that other data on items with high prevalence (blood pressure, glycaemic and lipid levels, or smoking) would also be present. A cluster of rules predicting the presence of blood pressure were ranked highest using measures of interestingness such as standardized lift. We found 3 latent categories using factor analysis; these were laboratory tests, vital signs, and lifestyle factors; Cronbach α ranged between .58 for lifestyle factors and .88 for laboratory tests. Conclusions:  Associations between the provision of important screens can be discovered and ranked. Rules with promising combinations of associated screens could be used to implement data driven alerts.Publisher PDFPeer reviewe

Data on Patient Record Trajectory for Linkage (DataPRinT Linkage).

The linkage of Electronic Medical Records, Administrative and other data sources is highly valuable for research and health system monitoring. Once linked, combined resources can be analyzed to provide the answers to a variety of health questions that otherwise could not be answered. However, legislative and administrative barriers, including lengthy processes for data sharing agreements, may preclude timely linkage which is a key requirement during pandemics. Objective To develop a method using a patient’s health trajectory to probabilistically link primary care Electronic Medical Record (EMR) data with administrative and other data, without the need to transfer large datasets or identifiable information. To determine the legislative feasibility, accuracy and validity of this linkage process. Study Design Identify data strings that do not directly identify patients and could be used as unique linkage variables. The data strings, which we are calling dataprints, are sufficiently similar over time in different databases. One example in Ontario, Canada, is the pattern of submitted health claims. For every patient seen by a family physician, there exists a unique pattern of dates/billing codes/diagnoses over time. These unique patterns are reasonably similar in EMR and administrative datasets. We will apply an algorithm which turns the string in the selected dataprints to an irreversibly hashed code for each person. The hashed code and no additional information will be provided by both data controllers to a trusted-third party who will determine which records match and send a mapping table to both. This enables analyses to be run in parallel, without divulging any direct person identifiers. Dataset Individuals contained in the University of Toronto Practice Based Research Network (UTOPIAN). Outcome Measures Linkage quality will be assessed by the number of true matches and represented by sensitivity, specificity and positive and negative predictive values. Results The method will be evaluated against a validated, deterministically linked reference standard at North York General Hospital using de-identified EMR and hospital data. Results will inform processes to enable analyses across datasets while adhering to privacy legislation

Impact of the Diabetes Canada Guideline Dissemination Strategy on the prescription of vascular protective medications : a retrospective cohort study, 2010-2015

Funding: Diabetes CanadaOBJECTIVE: The 2013 Diabetes Canada guidelines launched targeted dissemination tools and a simple assessment for vascular protection. We aimed to 1) examine changes associated with the launch of the 2013 guidelines and additional dissemination efforts in the rates of vascular protective medications prescribed in primary care for older patients with diabetes and 2) examine differences in the rates of prescriptions of vascular protective medications by patient and provider characteristics. RESEARCH DESIGN AND METHODS: The study population included patients (≥40 years of age) from the Canadian Primary Care Sentinel Surveillance Network with type 2 diabetes and at least one clinic visit from April 2010 to December 2015. An interrupted time series analysis was used to assess the proportion of eligible patients prescribed a statin, ACE inhibitor (ACEI)/angiotensin receptor blocker (ARB), or antiplatelet prescription in each quarter. Proton pump inhibitor (PPI) prescriptions were the reference control. RESULTS: A dynamic cohort was used where participants were enrolled each quarter using a prespecified set of conditions (range 25,985-70,693 per quarter). There were no significant changes in statin (P = 0.43), ACEI/ARB (P = 0.42), antiplatelet (P = 0.39), or PPI (P = 0.16) prescriptions at baseline (guideline intervention). After guideline publication, there was a significant change in slope for statin (-0.52% per quarter, SE 0.15, P < 0.05), ACEI/ARB (-0.38% per quarter, SE 0.13, P < 0.05) and reference PPI (-0.18% per quarter, SE 0.05, P < 0.05) prescriptions. CONCLUSIONS: There was a decrease in prescribing trends over time that was not specific to vascular protective medications. More effective knowledge translation strategies are needed to improve vascular protection in diabetes in order for patients to receive the most effective interventions.PostprintPeer reviewe

Over-use of thyroid testing in Canadian and UK primary care in frequent attenders : a cross-sectional study

Dr Greiver is supported through the Gordon F. Cheesbrough Research Chair in Family and Community Medicine from North York General Hospital.Background Thyroid stimulating hormone (TSH) is a common test used to detect and monitor clinically significant hypo- and hyperthyroidism. Population based screening of asymptomatic adults for thyroid disorders is not recommended. Objective The research objectives were to determine patterns of TSH testing in Canadian and English primary care practices, as well as patient and physician practice characteristics associated with testing TSH for primary care patients with no identifiable indication. Methods In this two-year cross-sectional observational study, Canadian and English electronic medical record databases were used to identify patients and physician practices. Cohorts of patients aged 18 years or older, without identifiable indications for TSH testing, were generated from these databases. Analyses were performed using a random-effects logistic regression to determine patient and physician practice characteristics associated with increased testing. We determined the proportion of TSH tests done concurrently with at least one common screening blood test (lipid profile or hemoglobin A1c). Standardized proportions of TSH test per family practice were used to examine the heterogeneity in the populations. Results At least one TSH test was done in 35.97 % (N=489,663) of Canadian patients and 29.36% (N=1,030,489) of English patients. Almost all TSH tests in Canada and England (95.69% and 99.23% respectively) were within the normal range (0.40-5.00 mU/L). A greater number of patient-physician encounters was the strongest predictor of TSH testing. 51.40% of TSH tests in Canada and 76.55% in England were done on the same day as at least one other screening blood test. There was no association between practice size and proportion of asymptomatic patients tested. Conclusions This comparative binational study found TSH patterns suggestive of over-testing and potentially thyroid disorder screening in both countries. There may be significant opportunities to improve appropriateness of TSH ordering in Canada and England and therefore improve allocation of limited system resources.PostprintPeer reviewe

Agreement between primary care and hospital diagnosis of schizophrenia and bipolar disorder : a cross-sectional, observational study using record linkage

Funding: Support for this project was provided by North York General Hospital.People with serious mental illness die 10–25 years sooner than people without these conditions. Multiple challenges to accessing and benefitting from healthcare have been identified amongst this population, including a lack of coordination between mental health services and general health services. It has been identified in other conditions such as diabetes that accurate documentation of diagnosis in the primary care chart is associated with better quality of care. It is suspected that if a patient admitted to the hospital with serious mental illness is then discharged without adequate identification of their diagnosis in the primary care setting, follow up (such as medication management and care coordination) may be more difficult. We identified cohorts of patients with schizophrenia and bipolar disorder who accessed care through the North York Family Health Team (a group of 77 family physicians in Toronto, Canada) and North York General Hospital (a large community hospital) between January 1, 2012 and December 31, 2014. We identified whether labeling for these conditions was concordant between the two settings and explored predictors of concordant labeling. This was a retrospective cross-sectional study using de-identified data from the Health Databank Collaborative, a linked primary care-hospital database. We identified 168 patients with schizophrenia and 370 patients with bipolar disorder. Overall diagnostic concordance between primary care and hospital records was 23.2% for schizophrenia and 15.7% for bipolar disorder. Concordance was higher for those with multiple (2+) inpatient visits (for schizophrenia: OR 2.42; 95% CI 0.64–9.20 and for bipolar disorder: OR 8.38; 95% CI 3.16–22.22). Capture-recapture modeling estimated that 37.4% of patients with schizophrenia (95% CI 20.7–54.1) and 39.6% with bipolar disorder (95% CI 25.7–53.6) had missing labels in both settings when adjusting for patients’ age, sex, income quintiles and co-morbidities. In this sample of patients accessing care at a large family health team and community hospital, concordance of diagnostic information about serious mental illness was low. Interventions should be developed to improve diagnosis and continuity of care across multiple settings.Publisher PDFPeer reviewe

Perivoj dvorca Batthyany

The authors are grateful to the North York General Foundation for financial support through the Exploration Fund. Dr. Greiver holds an investigator award from the Department of Family and Community Medicine, University of Toronto and was supported by a research stipend from North York General Hospital.Patients with chronic obstructive pulmonary disease (COPD) or heart failure (HF) are frequently cared for in hospital and in primary care settings. We studied labeling agreement for COPD and HF for patients seen in both settings in Toronto, Canada. This was a retrospective observational study using linked hospital-primary care electronic data from 70 family physicians. Patients were 20 years of age or more and had at least one visit in both settings between 1 January 2012 and 31 December 2014. We recorded labeling concordance and associations with clinical factors. We used capture-recapture models to estimate the size of the populations. COPD concordance was 34%; the odds ratios (ORs) of concordance increased with aging (OR 1.84 for age 75+ vs. <65, 95% CI 0.92–3.69) and more inpatient admissions (OR 2.89 for 3+ visits vs. 0 visits, 95% CI 1.59–5.26). HF concordance was 33%; the ORs of concordance decreased with aging (OR 0.39 for 75+ vs. <65, 95% CI 0.18–0.86) and increased with more admissions (OR = 2.39; 95% CI 1.33–4.30 for 3+ visits vs. 0 visits). Based on capture-recapture models, 21–24% additional patients with COPD and18–20% additional patients with HF did not have a label in either setting. The primary care prevalence was estimated as 748 COPD patients and 834 HF patients per 100,000 enrolled adult patients. Agreement levels for COPD and HF were low and labeling was incomplete. Further research is needed to improve labeling for these conditions.Publisher PDFPeer reviewe

Trends in end digit preference for blood pressure and associations with cardiovascular outcomes in Canadian and UK primary care : a retrospective observational study

This study received funding through a grant by the North York Genera Hospital Foundation’s Exploration Fund. MG held an investigator award from the Department of Family and Community Medicine, University of Toronto and was supported by a research stipend from North York General Hospital. The Canadian Primary Care Sentinel Surveillance Network was a committee of the College of Family Physicians of Canada and was funded through a contribution agreement with the Public Health Agency of Canada.Objectives: To study systematic errors in recording blood pressure (BP) as measured by end digit preference (EDP); to determine associations between EDP, uptake of Automated Office BP (AOBP) machines and cardiovascular outcomes. Design: Retrospective observational study using routinely collected electronic medical record data from 2006 to 2015 and a survey on year of AOBP acquisition in Toronto, Canada in 2017. Setting: Primary care practices in Canada and the UK. Participants: Adults aged 18 years or more. Main outcome measures: Mean rates of EDP and change in rates. Rates of EDP following acquisition of an AOBP machine. Associations between site EDP levels and mean BP. Associations between site EDP levels and frequency of cardiovascular outcomes. Results:  707 227 patients in Canada and 1 558 471 patients in the UK were included. From 2006 to 2015, the mean rate of BP readings with both systolic and diastolic pressure ending in zero decreased from 26.6% to 15.4% in Canada and from 24.2% to 17.3% in the UK. Systolic BP readings ending in zero decreased from 41.8% to 32.5% in the 3 years following the purchase of an AOBP machine. Sites with high EDP had a mean systolic BP of 2.0 mm Hg in Canada, and 1.7 mm Hg in the UK, lower than sites with no or low EDP. Patients in sites with high levels of EDP had a higher frequency of stroke (standardised morbidity ratio (SMR) 1.15, 95% CI 1.12 to 1.17), myocardial infarction (SMR 1.16, 95% CI 1.14 to 1.19) and angina (SMR 1.25, 95% CI 1.22 to 1.28) than patients in sites with no or low EDP. Conclusions:  Acquisition of an AOBP machine was associated with a decrease in EDP levels. Sites with higher rates of EDP had lower mean BPs and a higher frequency of adverse cardiovascular outcomes. The routine use of manual office-based BP measurement should be reconsidered.Publisher PDFPeer reviewe

Marginal structural models using calibrated weights with SuperLearner: application to longitudinal diabetes cohort.

Although machine learning has permeated many disciplines, the convergence of causal methods and machine learning remains sparse in the existing literature. Our aim was to formulate a marginal structural model in which we envisioned hypothetical (i.e. counterfactual) dynamic treatment regimes using a combination of drug therapies to manage diabetes: metformin, sulfonylurea and SGLT-2. We were interested in estimating “diabetes care provision” in next calendar year using a composite measure of chronic disease prevention and screening elements. We demonstrated the application of dynamic treatment regimes using the National Diabetes Action Canada Repository in which we applied a collection of mainstream statistical learning algorithms. We generated an ensemble of statistical learning algorithms using the SuperLearner based on the following base learners: (i) least absolute shrinkage and selection operator, (ii) ridge regression, (iii) elastic net, (iv) random forest, (v) gradient boosting machines, (vi) neural network. Each statistical learning algorithm was fitted using the pseudo-population with respect to the marginalization of the time-dependent confounding process. The covariate balance was assessed using the longitudinal (i.e. cumulative-time product) stabilized weights with calibrated restrictions. Our results indicated that the treatment drop-in cohorts (with respect to metformin, sulfonylurea and SGLT-2) may improve diabetes care provision in relation to treatment naïve cohort. As a clinical utility, we hope that this article will facilitate discussions around the prevention of adverse chronic outcomes associated with diabetes through the improvement of diabetes care provisions in primary care