Metronidazole-associated Neurologic Events: A Nested Case-control Study.

BACKGROUND: Case reports have described instances of peripheral and central nervous system toxicity during treatment with metronidazole; however, no large-scale studies have examined this association. METHODS: We conducted a population-based nested case-control study of adults aged 66 years or older living in Ontario, Canada, between 1 April 2003 and 31 March 2017. Cases were individuals who attended hospital for any of cerebellar dysfunction, encephalopathy, or peripheral neuropathy within 100 days of a prescription for either metronidazole or clindamycin. We matched each case patient with up to 10 event-free control subjects who also received metronidazole or clindamycin. We used conditional logistic regression to test the association between metronidazole exposure and neurologic events, with clindamycin as the reference exposure. RESULTS: We identified 1212 cases with recent use of either metronidazole or clindamycin and 12 098 controls. Neurologic adverse events were associated with an increased odds of metronidazole exposure compared to clindamycin (odds ratio [OR], 1.72 [95% confidence interval {CI}, 1.53-1.94]), which persisted after accounting for patient demographics, comorbidities, and other medication exposures (adjusted odds ratio [aOR], 1.43 [95% CI, 1.26-1.63]). We found a consistent association limited to either central (aOR, 1.46 [95% CI, 1.27-1.68]) or peripheral (aOR, 1.34 [95% CI, 1.02-1.76]) nervous system events. Among metronidazole recipients, the overall incidence of neurologic events at 100 days was approximately 0.25%. CONCLUSIONS: Metronidazole is associated with an increased risk of adverse peripheral and central nervous system events relative to clindamycin. Clinicians and patients should be aware of these rare but potentially serious adverse events.

Population-Wide Peer Comparison Audit and Feedback to Reduce Antibiotic Initiation and Duration in Long-Term Care Facilities with Embedded Randomized Controlled Trial.

BACKGROUND: Antibiotic overprescribing in long-term care settings is driven by prescriber preferences and is associated with preventable harms for residents. We aimed to determine whether peer comparison audit and feedback reporting for physicians reduces antibiotic overprescribing among residents. METHODS: We employed a province wide, difference-in-differences study of antibiotic prescribing audit and feedback, with an embedded pragmatic randomized controlled trial (RCT) across all long-term care facilities in Ontario, Canada, in 2019. The study year included 1238 physicians caring for 96 185 residents. In total, 895 (72%) physicians received no feedback; 343 (28%) were enrolled to receive audit and feedback and randomized 1:1 to static or dynamic reports. The primary outcomes were proportion of residents initiated on an antibiotic and proportion of antibiotics prolonged beyond 7 days per quarter. RESULTS: Among all residents, between the first quarter of 2018 and last quarter of 2019, there were temporal declines in antibiotic initiation (28.4% to 21.3%) and prolonged duration (34.4% to 29.0%). Difference-in-differences analysis confirmed that feedback was associated with a greater decline in prolonged antibiotics (adjusted difference -2.65%, 95% confidence interval [CI]: -4.93 to -.28%, P = .026), but there was no significant difference in antibiotic initiation. The reduction in antibiotic durations was associated with 335 912 fewer days of treatment. The embedded RCT detected no differences in outcomes between the dynamic and static reports. CONCLUSIONS: Peer comparison audit and feedback is a pragmatic intervention that can generate small relative reductions in the use of antibiotics for prolonged durations that translate to large reductions in antibiotic days of treatment across populations. Clinical Trials Registration. NCT03807466.

Incidence and prevalence of giant cell arteritis in Ontario, Canada.

OBJECTIVE: To estimate trends in the incidence and prevalence of GCA over time in Canada. METHODS: We performed a population-based study of Ontario health administrative data using validated case definitions for GCA. Among Ontario residents ≥50 years of age we estimated the annual incidence and prevalence rates between 2000 and 2018. We performed sensitivity analyses using alternative validated case definitions to provide comparative estimates. RESULTS: Between 2000 and 2018 there was a relatively stable incidence over time with 25 new cases per 100 000 people >50 years of age. Age-standardized incidence rates were significantly higher among females than males [31 cases (95% CI: 29, 34) vs 15 cases (95% CI: 13, 18) per 100 000 in 2000]. Trends in age-standardized incidence rates were stable among females but increased among males over time. Incidence rates were highest among those ≥70 years of age. Standardized prevalence rates increased from 125 (95% CI 121, 129) to 235 (95% CI 231, 239) cases per 100 000 from 2000 to 2018. The age-standardized rates among males rose from 76 (95% CI 72, 81) cases in 2000 to 156 (95% CI 151, 161) cases per 100 000 population in 2018. Between 2000 and 2018, the age-standardized rates among females similarly increased over time, from 167 (95% CI 161, 173) to 304 (95% CI 297, 310) cases per 100 000 population. CONCLUSION: The incidence and prevalence of GCA in Ontario is similar to that reported in the USA and northern Europe and considerably higher than that reported for southern Europe and non-European populations.

Health Service Use among Individuals with Depression and Psychological Distress: A Population-Based Cohort Study in Ontario, Canada: Utilisation des services de santé par les personnes souffrant de dépression et de détresse psychologique : une étude de cohorte dans la population de l'Ontario, Canada.

OBJECTIVES: Relatively little is known about how health-care utilization differs among individuals with psychological distress compared to those with major depressive disorder (MDD). METHODS: Ontario participants of the Canadian Community Health Survey Cycle 1.2 (2002) were linked to health administrative data to follow their health-care utilization patterns for up to 15 years. Based on their survey responses, we classified individuals hierarchically into Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria MDD, psychological distress (Kessler-6: 8 to 24), or an unexposed group with neither condition. We compared the rates of outpatient and acute care mental and nonmental health-related visits across the 3 groups over time using Poisson regression. RESULTS: Among the 430 individuals with MDD, 668 with psychological distress, and 9,089 in the unexposed group, individuals with MDD and psychological distress had higher rates of health-care utilization than the unexposed overall and across time. The rates of psychiatrist visits for the MDD group were significantly higher than the other groups initially but declined over the follow-up. Conversely, the rates of psychiatrist visits among the psychological distress group increased over time and converged with that of the MDD group by the end of follow-up (rate ratioMDD vs. psychological distress at 1 year: 4.20 [1.97 to 11.40]; at 15 years: 1.53 [0.54 to 4.08]). Acute care visits were similar between the MDD and psychological distress groups at all time points. CONCLUSIONS: Individuals with psychological distress required mental health care rivalling that of individuals with MDD over time, suggesting that even a cross-sectional assessment of significant psychological distress is a serious clinical concern.

Primary Care Provider and Child Characteristics Associated with Age of Diagnosis of Autism Spectrum Disorder: A Population-Based Cohort Study.

In a cohort of kindergarten children in Ontario, Canada with Autism Spectrum Disorder (ASD) (n = 1522), we tested the association of age at ASD diagnosis and characteristics of (1) the child's primary care provider and, (2) the child using health administrative databases. We tested the association of primary care practice model and time from developmental delay identification to age at ASD diagnosis. Older age of diagnosis was associated with provider foreign training (vs. domestic) (adjusted Hazard Ratio [aHR] 1.17, 95% CI 1.03, 1.33) but not sex, care model, and years of practice. After developmental delay identification, children with paediatricians had longer time to diagnosis than children with providers in care models (aHR 0.68, 95% CI 0.54, 0.86). Findings can be used to inform primary care provider ASD training.

Association of Early Physician Follow-up With Readmission Among Patients Hospitalized for Acute Myocardial Infarction, Congestive Heart Failure, or Chronic Obstructive Pulmonary Disease.

Importance: A better understanding of the association between early physician follow-up after discharge and adverse outcomes among hospitalized patients may inform interventions aimed at reducing readmission for common chronic conditions. Objective: To assess whether hospitalized patients with early physician follow-up after discharge had lower rates of overall and condition-specific readmissions within 30 days and 90 days of discharge. Design, Setting, and Participants: This cohort study was conducted among Ontario, Canada, adults with first admission for acute myocardial infarction (AMI), congestive heart failure (CHF), or chronic obstructive pulmonary disease (COPD) during 2005 to 2019. The exposure was follow-up visit with a primary care physician or relevant specialist within 7 days of discharge. Cox proportional hazards models were used to compare patients with vs without early follow-up, adjusting for sociodemographic factors and comorbidities, weighting by propensity score-based overlap weights. Data were analyzed from January through July 2021. Main Outcomes and Measures: Primary outcomes were 30-day and 90-day readmissions, cardiac readmissions (readmission for AMI, CHF, or angina) for patients with cardiac conditions, and COPD-related readmissions for patients with COPD. Mortality at 30 days and 90 days was a secondary outcome. All percentages reported in Results are unweighted. Results: The study cohort comprised 450 746 patients, including 198 854 patients with AMI, 133 058 patients with CHF, and 118 834 patients with COPD; the median (IQR) age was 66 (56-77) years for AMI, 78 (68-85) years for CHF, and 73 (64-81) years for COPD, and there were 64 339 (32.35%) women, 62 575 (47.03%) women, and 59 179 (49.80%) women, respectively. There were 91 182 patients (45.85%), 56 491 patients (42.46%), and 40 159 patients (33.79%), respectively, who received an early follow-up visit. Overall, patients with early follow-up had higher rates of collaborative care (eg, CHF: 20 931 patients [37.85%] vs 11 101 of 76 567 patients [14.85%]) and visits to a specialist within 30 days (eg, CHF: 25 797 patients [45.67%] vs 20 548 patients [26.84%]). Those with early follow-up had lower 90-day readmission rates among patients with CHF (15 934 patients [28.21%] vs 23 121 patients [30.20%]; adjusted hazard ratio [aHR], 0.98; 95% CI, 0.96-0.99) and among those with COPD (8784 patients [21.87%] vs 18 097 of 78 675 patients [23.00%]; aHR, 0.95; 95% CI, 0.93-0.98). Among patients with COPD, those with early follow-up had lower 90-day COPD-related readmission rates (4015 patients [10.00%] vs 8449 patients [10.74%]; aHR, 0.93; 95% CI, 0.89-0.96), and among patients with CHF, those with early follow-up had lower 90-day mortality rates (4044 patients [7.16%] vs 6281 patients [8.20%]; aHR, 0.93; 95% CI, 0.90-0.97). There were no significant benefits at 30 days or for patients with AMI. Conclusions and Relevance: These findings suggest that early follow-up in conjunction with a comprehensive transitional care strategy for hospitalized patients with medically complex conditions coupled with ongoing effective chronic disease management may be associated with reduced 90-day readmissions.

Behavioral Nudges to Improve Audit and Feedback Report Opening Among Antibiotic Prescribers: A Randomized Controlled Trial.

Background: Peer comparison audit and feedback has demonstrated effectiveness in improving antibiotic prescribing practices, but only a minority of prescribers view their reports. We rigorously tested 3 behavioral nudging techniques delivered by email to improve report opening. Methods: We conducted a pragmatic randomized controlled trial among Ontario long-term care prescribers enrolled in an ongoing peer comparison audit and feedback program which includes data on their antibiotic prescribing patterns. Physicians were randomized to 1 of 8 possible sequences of intervention/control allocation to 3 different behavioral email nudges: a social peer comparison nudge (January 2020), a maintenance of professional certification incentive nudge (October 2020), and a prior participation nudge (January 2021). The primary outcome was feedback report opening; the primary analysis pooled the effects of all 3 nudging interventions. Results: The trial included 421 physicians caring for >28 000 residents at 450 facilities. In the pooled analysis, physicians opened only 29.6% of intervention and 23.9% of control reports (odds ratio [OR], 1.51 [95% confidence interval {CI}, 1.10-2.07], P = .011); this difference remained significant after accounting for physician characteristics and clustering (adjusted OR [aOR], 1.74 [95% CI, 1.24-2.45], P = .0014). Of individual nudging techniques, the prior participation nudge was associated with a significant increase in report opening (OR, 1.62 [95% CI, 1.06-2.47], P = .026; aOR, 2.16 [95% CI, 1.33-3.50], P = .0018). In the pooled analysis, nudges were also associated with accessing more report pages (aOR, 1.28 [95% CI, 1.14-1.43], P < .001). Conclusions: Enhanced nudging strategies modestly improved report opening, but more work is needed to optimize physician engagement with audit and feedback. Clinical Trials Registration: NCT04187742.

Long-term macrolide therapy for chronic obstructive pulmonary disease: a population-based time series analysis.

BACKGROUND: Macrolides are recommended as an adjunctive treatment for patients with moderate to severe chronic obstructive pulmonary disease (COPD) who experience recurrent exacerbations. The objective of this study was to examine temporal trends in the provision of long-term macrolide therapy, specifically before and after publication of the landmark MACRO trial in August 2011 showing efficacy of macrolides for this indication. METHODS: We performed an interrupted time series analysis using population-level health administrative data. The study cohort consisted of all Ontario residents who had COPD, were using at least 1 long-acting inhaler, and were aged 65 years and older between Apr. 1, 2004, and Mar. 31, 2018. We compared the baseline characteristics of eligible patients before and after publication of the MACRO trial. Our primary outcome was overall prevalence of long-term macrolide therapy; secondary outcomes were incidence of COPD-related hospitalizations, emergency department visits and outpatient exacerbations requiring high-dose steroids in each quarter. We performed an interrupted time series analysis to assess for changes in the incidence of macrolide prophylaxis by quarter-year over the study period. RESULTS: The rate of long-term macrolide use increased from 0.8 per 1000 people in 2004 to 13.8 per 1000 people in 2018 (in the severe COPD group, the rate increased from 1.3 to 32.3 per 1000 people). The interrupted time series analysis showed that, before 2011, the prevalence of macrolide prophylaxis increased at a rate of 0.44 (95% confidence interval [CI] 0.39-0.50) per 1000 people per year; after 2011, the rate of increase grew by 1.18 (95% CI 1.07-1.29) per 1000 people to 1.63 (95% CI 1.56-1.69) per 1000 people per year. The seasonal pattern of COPD-related health care visits remained stable over the study period, and there was no detectable reduction in hospitalizations or emergency department visits at the population level. INTERPRETATION: In the past decade, there has been a significant rise in the use of long-term macrolide therapy for patients with COPD. As this practice becomes increasingly common, it will be important to monitor its potential benefits on COPD exacerbations but also its potential effects on adverse events and antimicrobial resistance patterns.

Assessing the validity of administrative health data for the identification of children and youth with autism spectrum disorder in Ontario.

Population-level identification of children and youth with ASD is essential for surveillance and planning for required services. The objective of this study was to develop and validate an algorithm for the identification of children and youth with ASD using administrative health data. In this retrospective validation study, we linked an electronic medical record (EMR)-based reference standard, consisting 10,000 individuals aged 1-24 years, including 112 confirmed ASD cases to Ontario administrative health data, for the testing of multiple case-finding algorithms. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and corresponding 95% confidence intervals (CI) were calculated for each algorithm. The optimal algorithm was validated in three external cohorts representing family practice, education, and specialized clinical settings. The optimal algorithm included an ASD diagnostic code for a single hospital discharge or emergency department visit or outpatient surgery, or three ASD physician billing codes in 3 years. This algorithm's sensitivity was 50.0% (95%CI 40.7-88.7%), specificity 99.6% (99.4-99.7), PPV 56.6% (46.8-66.3), and NPV 99.4% (99.3-99.6). The results of this study illustrate limitations and need for cautious interpretation when using administrative health data alone for the identification of children and youth with ASD. LAY SUMMARY: We tested algorithms (set of rules) to identify young people with ASD using routinely collected administrative health data. Even the best algorithm misses more than half of those in Ontario with ASD. To understand this better, we tested how well the algorithm worked in different settings (family practice, education, and specialized clinics). The identification of individuals with ASD at a population level is essential for planning for support services and the allocation of resources. Autism Res 2021, 14: 1037-1045. © 2021 The Authors. Autism Research published by International Society for Autism Research published by Wiley Periodicals LLC.

Identifying Children and Youth With Autism Spectrum Disorder in Electronic Medical Records: Examining Health System Utilization and Comorbidities.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder requiring significant health and educational resources for affected individuals. A reference standard for ASD was generated from an existing population-based cohort of 10,000 children and youth aged 1-24 years who were randomly selected for chart abstraction from 29,256 patients from 119 family physicians. We developed and validated an algorithm to identify children and youth with ASD within an electronic medical record system (N = 80,237, aged 1-24 years) in order to examine the prevalence of comorbidities and quantify health system utilization within the cohort. We identified 1,062 children and youth with ASD representing a prevalence of 1.32%. Compared to individuals without ASD, those with ASD had a higher prevalence of asthma, were more likely to visit a specialist, undergo surgery, and be hospitalized for psychiatric reasons. Children and youth with ASD in Ontario have complex health system needs, illustrated through a significant burden of comorbidities and increased health system utilization. LAY SUMMARY: Our paper generates population-based estimates of health system use by children and youth with ASD, who have a higher burden of comorbidities than the general population. We developed a case-finding algorithm and applied it in electronic medical records to create a cohort of children and youth with ASD, thereby generating an important resource to further study the health care needs of individuals with ASD.

Health system costs for cancer medications and radiation treatment in Ontario for the 4 most common cancers: a retrospective cohort study.

BACKGROUND: Previous costing and resource estimates for cancer have not been complete owing to lack of comprehensive data on cancer-related medication and radiation treatment. Our objective was to calculate the mean overall costs per patient of cancer-related medications and radiation, as well as by disease subtype and stage, in the first year after diagnosis for the 4 most prevalent cancers in Ontario. METHODS: We conducted a retrospective cohort study using provincial health administrative databases to identify population health system resources and costs for all patients diagnosed with breast, colorectal, lung or prostate cancer between Jan. 1, 2010, and Dec. 31, 2015 in Ontario. The primary outcome measure was the overall average cost per patient in the 365 days after diagnosis for cancer-related medications and radiation treatment, calculated with the use of 2 novel costing algorithms. We determined the cost by disease, disease subtype and stage as secondary outcomes. RESULTS: There were 168 316 Ontarians diagnosed with cancer during the study period, 50 141 with breast cancer, 38 108 with colorectal cancer, 34 809 with lung cancer and 45 258 with prostate cancer. The mean per-patient cost for cancer-related medications was $8167 (95% confidence interval [CI] $8023-$8311), $6568 (95% CI $6446-$6691), $2900 (95% CI $2816-$2984) and $1211 (95% CI $1175-$1247) for breast, colorectal, lung and prostate cancer, respectively. The corresponding mean radiation treatment costs were $18 529 (95% CI $18 415-$18 643), $15 177 (95% CI $14 899-$15 456), $10 818 (95% CI $10 669-$10 966) and $16 887 (95% CI $16 648-$17 125). In general, stage III and IV cancers were the most expensive stages for both medications and radiation across all 4 disease sites. INTERPRETATION: Our work updates previous costing estimates to help understand costs and resources critical to health care system planning in a single-payer system. More refined costing estimates are useful as inputs to allow for more robust health economic modelling and health care system planning.

Demographic characteristics and cost of treatment among oncology patients in a publicly funded system, the Ontario Trillium Drug Program: a retrospective cohort study.

BACKGROUND: The aim of this study was to characterize the demographic characteristics and investigate the cost of a publicly funded system, the Ontario Trillium Drug Program (TDP), for an oncology patient population. METHODS: We ascertained all TDP claims between April 1997 and December 2016 from the Ontario Drug Benefit database to assess use and cost. Each drug was classified as a cancer treatment drug, cancer supportive therapy drug or noncancer drug. We also identified a cohort of patients with cancer with least 1 TDP claim, for whom we examined demographic and claims-related characteristics. RESULTS: Over the study period, 50 975 293 TDP claims totalling $4.8 billion were made. Although the proportion of cancer claims among all TDP claims remained constant between 1997 and 2016, the total annual cost of cancer treatment drugs increased nearly 40-fold. Imatinib and lenalidomide together accounted for nearly half of the cost of all cancer treatment drugs. We identified a cohort of 49 892 patients with cancer, of whom 18 631 (37.3%) were enrolled in the TDP before their cancer diagnosis and 31 261 (62.7%) were enrolled after their diagnosis. The former were more likely than the latter to be in lower income quintiles and to have more chronic conditions. Significant differences were also found in the distribution of cancer diagnoses between the 2 groups. INTERPRETATION: In the TDP, use increased over time and differed across cancer diagnoses and drugs. These results have public health and policy implications as antineoplastic drug costs continue to rise and place a burden on patients.

The Association of Resident Communication Abilities and Antibiotic Use in Long-Term Care.

OBJECTIVES: To determine whether decreased communication ability among long-term care residents is associated with increased antibiotic exposure. DESIGN: Retrospective cohort study. SETTING: All long-term care homes in Ontario, Canada. PARTICIPANTS: All adults aged 66 years or older residing in long-term care and undergoing a full assessment between January 1 and December 31, 2016 (N = 87,947). MEASUREMENTS: Data were obtained from linkable, population-wide administrative data sets. Residents were identified, and characteristics were abstracted from the Resident Assessment Instrument Minimum Dataset version 2.0. The primary predictors of interest were residents' ability to make themselves understood and ability to understand others. The primary outcome was antibiotic days of treatment per 1000 resident days in the 90 days following assessment (obtained from the Ontario Drug Benefits Database). RESULTS: Those who were sometimes/rarely/never able to make themselves understood received 50.7 antibiotic days per 1000 person-days of follow-up, compared to 62.1 received by those who were able to make themselves understood. Those who were sometimes/rarely/never able to understand others received 50.0 antibiotic days per 1000 person-days of follow-up, compared to 61.4 by those who were able to understand others. Multivariable Poisson regression, accounting for resident characteristics, confirmed that compared to those with highest levels of communication ability, those who could sometimes/rarely/never make themselves understood had significantly fewer days on antibiotics (rate ratio [RR] = 0.76; confidence interval [95% CI] = 0.73-0.79) as did those who could sometimes/rarely/never understand others (RR = 0.76; 95% CI = 0.74-0.79). CONCLUSION: Poor resident communication ability is not a driver of antibiotic overuse in long-term care. In fact, lower ability to understand others and/or be understood by others is associated with less antibiotic exposure. Further work is needed to optimize antibiotic use in long-term care residents across the entire spectrum of communication skills.