Phenotyping healthcare use before pediatric-onset multiple sclerosis,including by sex and age: A matched cohort study

Abstract

Background:

Little is known about the prodrome in pediatric-onset multiple sclerosis (POMS), especially potential age and sex differences.

Objective:

To compare annual hospitalization and physician visit rates overall, and for physician visits, examine sex- and age-group (<12, 12–15, 16 to <18 years) differences, up to 18 years pre-first demyelinating event (pre-index) in 451 POMS and 1420 matched non–multiple sclerosis (MS) individuals.

Method:

Using Ontario administrative data (1991–2020), we estimated rate ratios (RRs) by visit-related diagnosis, sex, and age using over-dispersed-Poisson models.

Results:

The POMS cohort showed elevated rates by year 1 pre-index (“year −1”), for ill-defined, other-health-contact, mental-, and respiratory-related hospitalizations (RRs ⩾ 3.6). Elevated physician visits began at year −14 for respiratory (RRs ⩾ 1.3), year −13 for endocrine (RRs ⩾ 2.4) and injury-related (RRs ⩾ 1.2), year −12 for ill-defined (RRs ⩾ 1.3), and year −11 for nervous system (RRs ⩾ 4.0) and mental-related (RRs ⩾ 2.0). Nervous system visits showed the largest sex-gap; males with (vs without) MS had elevated RRs from year −12 and females from year −6; both peaked the year pre-index (males: RR = 47.2; 95% confidence interval (CI): 17.3–128.3; females: RR = 17.0; 95% CI: 8.9–32.3). Among 12- to 15-year-olds, elevated rates were sustained for respiratory-related (from year −12, except year −5), injury-related, and ill-defined (from year −13); (all RR ⩾ 1.3), while findings were more sporadic in the other age groups.

Conclusion:

Findings suggest prolonged, organ-specific healthcare use pre-POMS, with some sex- and age-related differences indicating pre-onset disease heterogeneity.

Keywords

Demyelinating disease healthcare utilization hospitalizations pediatric-onset multiple sclerosis physician visits prodrome sex

Introduction

Pediatric-onset multiple sclerosis (POMS) represents approximately 3%–10% of all multiple sclerosis (MS) cases¹ and is marked by higher relapse rates, greater inflammatory activity, and earlier cognitive involvement than adult-onset MS.^2,3 A symptomatic prodromal phase of MS may manifest as increased healthcare utilization, offering a potential window for earlier recognition and intervention. Mounting evidence suggests that neuroinflammatory processes begin years before clinical recognition.^4
–6

Although increased healthcare utilization has been reported preceding the first recognized demyelinating event (MS onset), in both adult and pediatric populations,^6
–10 few studies have characterized these patterns across different sexes and specific age groups. Consequently, the understanding of pre-onset healthcare patterns in pediatric populations is limited. Also, demographic factors such as sex and age influence disease expression and healthcare utilization patterns in MS and in other pediatric immune-mediated diseases.^11
–14 For instance, while females are at higher risk of MS, at least after puberty, biological sex may influence immune responses and neurodegeneration, potentially contributing to differences in disease progression and outcomes.^15,16 Similarly, age influences the clinical course of MS, including relapse rates and disability progression after MS onset.^2,17
–19 However, the longitudinal patterns of healthcare use before POMS, as well as potential sex- and age-related differences in these early encounters, remain insufficiently characterized. Therefore, to characterize healthcare use before POMS, we examined annual hospital and physician visit rates by diagnoses up to 18 years before the first demyelinating event in individuals with POMS versus a matched cohort without MS. Physician visit rates were also examined by sex and age.

Methods

Data sources

This matched cohort study was conducted using population-based data from Ontario, Canada, where publicly funded healthcare services are recorded in administrative databases maintained by ICES (formerly the Institute for Clinical and Evaluative Sciences). Supplemental Table S1 lists the utilized databases.

Diagnoses from physician and hospital visits were grouped by International Classification of Diseases (ICD) chapter (ICD-9 for physician visits (modified three-digit codes) and hospitalizations pre-2002 and ICD-10-CA for hospitalizations from 2002 onwards, Supplemental Table S2). These data covered the period from 1 April 1991 to 1 March 2020 and were linked for each person using their unique encoded health identifiers and analyzed at ICES.

Ethical considerations

Ethical approval was granted by the University of British Columbia’s Clinical Research Ethics Board. Data access via ICES was authorized under Section 45 of Ontario’s Personal Health Information Protection Act (PHIPA).

Study participants

The POMS cohort was previously established using Ontario health administrative data and has been described in detail elsewhere.⁹ Briefly, a validated algorithm with a sensitivity of 89.2% and specificity of 100% was used to identify individuals with POMS;²⁰ it required ⩾3 hospital or physician visits coded for MS (ICD-9/10-CA:340/G35). Once identified, an index date was established for each individual, defined as the earliest recorded ICD code in either the hospital or physician visit data for MS or a related demyelinating condition (Supplemental Table S3). The index date had to occur before age 18 years. Individuals were included if they had a valid healthcare registration number and maintained ⩾90% continuous Ontario health insurance coverage in each year for ⩾5 years pre-index date (or all years if <5 years) through until the third MS diagnostic code. Each individual with POMS was matched without replacement on sex, birth year, and three-digit postal code at index with up to five individuals with no MS/demyelination-related diagnostic codes. To ensure comparable observation windows, matched individuals were required to meet the same health insurance coverage criteria and have follow-up periods at least as long as their POMS counterparts before the index and through to the third diagnostic code for MS.

Analysis

We compared annual rates of hospital and physician visits by ICD chapter up to 18 years pre-index date and yearly physician visit rates by ICD chapter stratified by sex and age group between the POMS and matched cohorts. An overall description of physician visits by ICD-9 chapters for all years pre-index date combined is available elsewhere.⁹

Descriptive statistics were used to summarize characteristics of the POMS and non-MS cohorts. We estimated annual rate ratios (RRs) of hospital and physician visits by ICD chapter using overdispersed Poisson models with Pearson scale correction and the logarithm of person-time as the model offset. For physician visits only, we also estimated the yearly RRs by sex (female and male) and age group at the index date (<12, 12–15, 16 to <18 years). Results by ICD chapter were restricted to those with ⩾10 such visits with the relevant ICD code in any given year for both cohorts combined to meet privacy and data access requirements. The Benjamini–Hochberg procedure was applied to control for the false discovery rate at 5% across 1377 total comparisons. Analyses were conducted using SAS-Version-9.4 (SAS Institute, Cary, USA) and R version 4.0.5 (R Foundation, Vienna, Austria). The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) cohort reporting guidelines were used.

Results

A total of 451 POMS individuals were identified, with 1420 matched individuals without MS. Almost two-thirds of participants were female in both cohorts (Table 1). The mean (standard deviation) age at the index date for the POMS cohort = 14.3 (3.4); the non-MS cohort was well-matched to the POMS cohort. The mean follow-up pre-index was ≈11 years in both cohorts.

Table 1.

Characteristics of the pediatric-onset multiple sclerosis (POMS) cohort and matched cohort without MS at the index date.

Characteristics, n (%)	MS (N = 451)	Non-MS (N = 1420)
Female	293 (65.0%)	900 (63.4%)
Age at index date, years^a
<12	69 (15.3%)	202 (14.2%)
12 to 15	153 (33.9%)	517 (36.4%)
16 to <18	229 (50.8%)	701 (49.4%)
Mean age at index date, years (SD)	14.3 (3.4)	14.4 (3.2)
Index year
1991–2000	128 (28.4%)	454 (32.0%)
2001–2010	200 (44.3%)	647 (45.6%)
2011–2020	123 (27.3%)	319 (22.5%)
Area-based income quintile
5 (most affluent)	106 (23.5%)	341 (24.0%)
4	96 (21.3%)	334 (23.5%)
3	81 (18.0%)	260 (18.3%)
2	80 (17.7%)	265 (18.7%)
1 (least affluent)	88 (19.5%)	220 (15.5%)
Area of residence
Urban	398 (88.2%)	1253 (88.2%)
Rural	53 (11.8%)	167 (11.8%)

Key: SES = Socioeconomic status, based on each individual’s residential postal code linked to their neighborhood-level income; SD = standard deviation

Anti-myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) could not be directly identified in the administrative data used in this study. As a result, some individuals in the youngest age group (<12 years) may have been misclassified.

Annual hospital and physician visit rates by ICD chapter

As there were fewer hospital visits, these limited yearly rate estimates; however, respiratory-related visits were among the earliest to rise (from 16 years pre-index: “year −16”), although they were only significant in years −8, −2, and −1 (RR: 2.4–3.7). Visits related to “other health system contacts” (which can include “general medical examinations,” Supplemental Table S2) were significantly elevated years −16, −13, −11, −10, −2, and −1 (RRs: 3.4–11.6) and ill-defined signs/symptoms (from years −3 to −1; RRs: 3.8–12.1). In the year pre-index date, hospital visits for ill-defined signs/symptoms (RR = 12.1; 95% confidence interval (CI): 3.6–40.5), other health system contact (RR = 11.6; 95% CI: 3.1–43.6), mental disorders (RR = 4.2; 95% CI: 1.3–14.1), and respiratory system (RR = 3.6; 95% CI: 1.3–10.4) were significantly elevated (Figure 1(a); Supplemental Figure S1).

Figure 1.

Rate ratios by ICD chapter for hospital (a) and physician (b) visits over time in individuals with pediatric-onset MS (POMS) compared with matched non-MS controls. Results span up to 18 years before the index demyelinating event.

Physician visit rates were higher in the POMS than the non-MS cohort for most ICD chapters starting from year −14 (Figure 1(b), Supplemental Figure S2). These included respiratory (from year −14, except year −7; RRs: 1.3–1.7), nervous system (from year −11; RRs: 4.0–22.6), mental disorders (from year −11, except years −10 to −8; RRs: 2.0–4.0), ill-defined signs/symptoms (from year −12, except years −11 and −7; RRs: 1.3–4.2), endocrine/metabolic conditions (periodically elevated from years −13 to −7, then consistently from year −6 to −1; RRs: 2.4–5.4), and injury-related visits (sporadically from years −13 to −1; RRs: 1.2–2.4). Physician visit rates were higher in the POMS than the non-MS cohort for other conditions over a more limited duration. For example, visit rates were higher in 4 to 7 (in total) of the 18 years pre-index for sense organs (years −18, −11, −7, and −3 to −1; RRs: 1.3–3.4), circulatory system (years −6, −5, −2, and −1; RRs: 2.7–29.1), digestive (years −7 to −4 and −2; RRs: 2.2–4.2), genitourinary (years −11, −6 to −3 and −1; RRs: 1.7–2.9), congenital anomalies (years −10, −9, and −3 to −1; RRs: 3.4–31.3), and conditions originating in the perinatal period (years −15, −14, −12, −4, and −1; RRs: 9.5–22.8). Visit rates differed between the two cohorts for only 2 years for infection-related visit rates (years −5 and −2; RRs: 1.6), neoplasms (years −3 and −1; RRs: 2.7–4.5), and blood-related (years −5 and −1; RRs: 2.4–4.7).

Physician visits by sex

Nervous system–related physician visits exhibited the most pronounced sex differences; males with (vs without) MS had consistently elevated RRs starting at year −12 (RR = 8.0; 95% CI: 4.0–22.1), while for females, the earliest was in year −6 (RR = 4.3; 95% CI: 1.5–12.5). Both peaked in the year pre-index, with RRs among males (RR = 47.2; 95% CI: 17.3–128.3) and among females (RR = 17.0; 95% CI: 8.9–32.3) (Figure 2, Supplemental Figure S3). The relative increase in visit rates in the POMS versus non-MS cohort was higher among females than males for infection-related and genitourinary visits, but in specific years only; year −12 for infections (RR (females)= 1.5; 95% CI: 1.1–2.2; males = 0.5; 95% CI: 0.3–1.0) and year −6 for genitourinary visits (RR (females)= 3.7; 95% CI: 1.8–7.4; males = 0.5; 95% CI: 0.2–1.8).

Figure 2.

Rate ratio by ICD chapter for physician visit rates over time in individuals with pediatric-onset MS (POMS) compared with matched non-MS controls, stratified by sex.

Physician visits by age

Some age-related differences for the POMS versus non-MS cohorts were identified for the infection and injury-related ICD chapters, with a higher physician visit RR in the 12- to 15-year-old age group relative to those aged 16 to <18 years. However, these were rather sporadic and limited to certain years. For example, for infection-related visits, the RR at year −16 was 5.2 (95% CI: 1.4–18.6) among the 12- to 15-year-olds versus 0.8 (95% CI: 0.6–1.3) for the 16- to <18-year-olds. For injury-related visits, the year −12 RR = 1.6 (95% CI: 1.2–2.3) among 12- to 15-year-olds versus 0.8 (95% CI: 0.5–1.1) among 16- to <18-year-olds (Figure 3 and Supplemental Figure S4).

Figure 3.

Rate ratio by ICD chapter for physician visit rates over time in individuals with pediatric-onset MS (POMS) compared with matched non-MS cohort, stratified by age at index date.

Other differences included a sustained period pre-index date in which the physician visit RRs were elevated among the 12- to 15-year-olds with (vs without) MS relative to similar comparisons among the other age groups, although this pattern should be interpreted cautiously given the non-uniform changes in sample size across age groups over time. For example, for respiratory-related visits, elevated RRs among the 12- to 15-year-olds were observed from year −12 to −1 (except year −5), with RRs ranging from 1.3 to 2.1. In contrast, the 16- to <18-year-olds showed elevated RRs only in years −13, −9, −4, and −2 (RRs: 1.3–1.5), and the <12-year-olds in years −6 and −2 (RRs: 1.6–1.8). Similarly, the 12- to 15-year-olds showed more sustained elevations, starting from years −13 for ill-defined signs/symptoms (for 10 years out of the total observed period), injury-related (for 10 years of the observed period), and endocrine/metabolic (for 8 years of the observed period) chapters while increases in the <12 and 16 to <18 year groups were more sporadic and limited to fewer pre-index years. For all these age-related findings, comparisons with the youngest age group (<12 years at index) were limited due to the smaller number of individuals and fewer years lived, leading to a shorter observation period. Overall temporal patterns were preserved after multiple comparison adjustment (see figures).

Discussion

Our study examined healthcare utilization patterns before the first demyelinating event, revealing higher rates of physician visits across multiple ICD chapters among 451 individuals with POMS compared to 1420 matched non-MS individuals. Respiratory system–related physician visits rates were the first to rise in a consistent and sustained manner, being elevated from year −14 and for almost all subsequent years through until year −1. Next to rise were physician visits related to the endocrine system and injury-related (elevated from year −13), followed by ill-defined signs/symptoms (from year −12), nervous system and mental disorders (elevated from year −11). Some sex- and age-related differences were observed, with nervous system–related visits showing earlier increases in males (from year −12) than females (from year −6). Age-related differences were less consistent, but 12- to 15-year-olds had sustained elevations in respiratory, injury-related, and ill-defined visits from as early as year −13, unlike the other age groups, which exhibited more sporadic elevations pre-index. Collectively, these patterns of elevated healthcare use long before the index date indicate an early disease phase in POMS that may differ in timing and presentation by age and sex.

We found relatively few studies examining healthcare use over such an extended period before POMS with which to compare our findings.^7
–9,21 For example, a German study, focusing on the 5 years before the first demyelinating event, found higher healthcare visits among 1091 children and adolescents with MS compared to 10,910 without MS, especially for infectious diseases and respiratory, digestive, and musculoskeletal conditions.⁸ A more recent Swedish study examined outpatient care in 233 individuals with POMS and 1151 without MS over the 17 years pre-onset, reporting elevated visits predominantly 1–10 years before onset. In the year immediately before onset, higher rates were observed for neoplasms, nervous system disorders, sense organ conditions, ill-defined symptoms, and other health system contacts.⁷ However, their focus was on hospital outpatient and prescription data, with no information on primary care use. In contrast, our study captured primary and specialized care visits, providing a potentially more comprehensive picture of early healthcare use.

Respiratory-related physician visits were among the most persistently elevated across the pre-index period in our POMS cohort. In a sub-cohort of this study participants (230 POMS and 621 non-MS individuals), respiratory-related emergency department visits were also higher in the POMS cohort, starting 12 years before the index date.¹⁰ Further work was needed to clarify whether these elevated visits reflect prodromal manifestations of MS, underlying risk factors that precede biologic onset, or some interplay between the two. A South Korean cohort study of 49,937 children hospitalized with Mycoplasma pneumoniae and 499,370 matched children without the infection found an increased autoimmune risk, suggesting early infections may act as immune-priming events.²² Similarly, adolescents with hospital-diagnosed infections, including respiratory, showed elevated MS risk in adulthood.²³ Findings are also consistent with observations following MS diagnosis. A Swedish registry-based study reported that respiratory diseases were among the most common comorbidities, even among youth with (vs without) MS.²⁴

Physician visits related to endocrine and metabolic conditions and ill-defined signs/symptoms displayed parallel patterns in the years preceding the index date in our study. Non-specific symptoms, such as fatigue and metabolic disturbances, may originate from early neuroendocrine dysfunction in MS.²⁵ Structural and functional abnormalities in the hypothalamic–pituitary axis, including pituitary enlargement and impaired hormonal responses, have been documented even in MS patients without overt endocrine disease, pointing to a preclinical phase of dysregulation.^25,26 These physiological changes may contribute to the multisystem, diagnostically ambiguous complaints captured within these ICD chapters.

The elevated neoplasm-related physician visit rates observed in the closest pre-index years, while relatively rare (data not shown), may reflect a trend that warrants further investigation. These visits reflect encounters coded for neoplasms rather than confirmed cancer diagnoses, and the specific details of neoplasms-related visits were not known. Although these events were also infrequent in a Swedish POMS study, authors similarly showed increased outpatient visits for neoplasms across several years before symptom onset, with statistical significance reached in years 1 and 4 pre-index.⁷ Such patterns may reflect shared inflammatory pathways between immune dysregulation and tissue growth regulation.²⁷ It is also possible that MS was identified due to heightened health surveillance in these individuals. The particularly high RRs observed in years –2 and –1 for both physician and hospital visits, spanning multiple ICD chapters in this study, suggest a period of escalating clinical activity in the lead-up to the first demyelinating event. The increased visits in our POMS cohort likely reflect rising clinical complexity as symptoms accumulate across body systems. It may also drive repeated healthcare encounters and contribute to delays in recognizing the first demyelinating event. A study in the United States based on phone interviews with 42 parents of 41 children with MS found an average of 3.6 medical visits occurred before a diagnosis of MS was confirmed.²⁸

Of the few published studies exploring healthcare use before POMS, we were unable to find any that specifically examined sex- and age-related differences. The early, prolonged, and elevated burden of nervous system-, injury-, genitourinary-, and infection-related physician visits, differing by sex and age, may reflect heterogeneous prodromal manifestations influenced by developmental, hormonal, or immune system changes. One study in a general MS cohort found that males with (vs without) MS had significantly more nervous system–related visits in the 5 years preceding their first demyelinating event than females with (vs without) MS.²⁹ Age-related prodromal patterns may also be at play in our study, as the 12–15 age group showed a more consistent and longer pre-index period of elevated healthcare use compared with both the younger and older groups. Although the shorter follow-up time and smaller sample size in the <12 group warrant cautious interpretation. Nonetheless, previous studies suggest that prepuberty and puberty may influence prodromal MS activity and presentation, potentially linked to shifts in immune and neural function, particularly in females.^14,30,31 This echoes patterns seen in another autoimmune disease—type 1 diabetes—in which disease onset during early adolescence (aged 11–15 years) was associated with a higher risk of acute complications compared with onset before age 11 or after 15.³² These findings may underscore puberty as a critical window for prodromal-related disease expression.

This study offers a population-based lens into healthcare utilization extending up to 18 years pre-POMS, capturing routinely collected interactions with the health system. A key strength is the longitudinal, granular design, enabling the examination of age- and sex-specific patterns, factors often underexplored in pediatric MS, while minimizing recall bias. Nonetheless, limitations warrant caution. POMS is relatively rare, such that some of the sex- and age-related subgroups, particularly beyond the 5-year window before the first demyelinating event, were small. While administrative data enable capture of health care use for the entire population, we were not able to access specific biological exposures, such as viral infections, obesity metrics, or endocrine-related factors. Our study predated the first international diagnostic criteria for myelin oligodendrocyte glycoprotein antibody (MOGAb)–associated disease.³³ We did not have access to MOGAb tests, which are now recommended for <12-year-olds in the revised MS diagnostic criteria.³⁴ While this may have resulted in some misclassification of the <12-year-olds, this group was relatively small (n = 69; 15.3% of the cohort), and our age-stratified analyses enabled visualization of results in the two older groups (without those <12 years old). Finally, utilization reflects more than disease burden; it may also be shaped by other factors such as health-seeking behavior, which our design could not fully capture.

Conclusion

In this population-based study, respiratory-related physician visits were the first to show a consistent and prolonged increase, beginning 14 years before the first demyelinating event. Subsequent increases emerged across endocrine, injury-related, ill-defined, nervous system, and mental health visits. Sex differences were most evident for nervous system visits, where males with versus without MS showed elevated RRs earlier and over a more extended period relative to females. Age-related differences were less consistent, but 12- to 15-year-olds had sustained elevations in respiratory, injury-related, and ill-defined visits from as early as year −13, unlike the other age groups. Our findings highlight the value of longitudinal administrative data in identifying prodromal healthcare patterns and support the potential for earlier recognition of POMS.

Supplemental Material

sj-docx-1-msj-10.1177_13524585261445372 – Supplemental material for Phenotyping healthcare use before pediatric-onset multiple sclerosis, including by sex and age: A matched cohort study

Supplemental material, sj-docx-1-msj-10.1177_13524585261445372 for Phenotyping healthcare use before pediatric-onset multiple sclerosis, including by sex and age: A matched cohort study by Farahnaz Amini, Karl Everett, Feng Zhu, Ping Li, Kyla A McKay, Yinshan Zhao, Colleen J Maxwell, Ruth Ann Marrie and Helen Tremlett in Multiple Sclerosis Journal

Footnotes

Acknowledgements

The authors would like to acknowledge the members of the team who facilitated gaining funding for the wider program of work related to the MS prodrome (Dr. M. Ehsan Karim, Dr. José Wijnands, and Dr. Fardowsa L.A. Yusuf). J.W. also contributed to designing the technical plan while a research associate at the University of British Columbia, Canada.

Declaration of conflicting interests

The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Farahnaz Amini has nothing to disclose. Feng Zhu has nothing to disclose. Karl Everett has nothing to disclose. Ping Li has nothing to disclose. Yinshan Zhao has nothing to disclose. Kyla A McKay is funded by the Swedish Research Council, Bjarne Ahlström’s Foundation, and a salary award from Karolinska Institute. She has received speaker honoraria from Biogen (2022) and Sanofi-Aventis (2023). Colleen Maxwell receives research funding from a University of Waterloo Research Chair, CIHR, Multiple Sclerosis Society of Canada, National Multiple Sclerosis Society, CMSC, and the Public Health Agency of Canada. Ruth Ann Marrie receives research funding from: CIHR, MS Canada, National Multiple Sclerosis Society, CMSC, The Arthritis Society, US Department of Defense, Pfizer Foundation, Public Health Agency of Canada, MMSF, and Brain Canada. She is a co-investigator on a study funded in part by Biogen Idec and Roche (no funds to her) and is supported by the Multiple Sclerosis Clinical Research Chair (Dalhousie University). Helen Tremlett has, in the last 5 years, received research support from the Canada Research Chair Program, the National Multiple Sclerosis Society, the Canadian Institutes of Health Research, MS Canada, the Multiple Sclerosis Scientific Research Foundation, and the EDMUS Foundation (“Fondation EDMUS contre la sclérose en plaques”). In addition, in the last 5 years, has had travel expenses or registration fees prepaid or reimbursed to present at CME conferences or attend meetings (as a member of the International Advisory Committee on Clinical Trials in Multiple Sclerosis) from the Consortium of MS Centres (2023), the Canadian Neurological Sciences Federation (2023), National MS Society (2022–2025), ECTRIMS/ACTRIMS (2017–2025), and American Academy of Neurology (2019). Speaker honoraria are either declined or donated to an MS charity or to an unrestricted grant for use by HT’s research group.

Funding

The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The study was funded in part by the National MS Society and MS Canada (RG5063A4/1/RFA-2103-37392; EGID: P002/903124; PI: Tremlett). The study funders had no role in the methods, analyses, writing of the manuscript, or the decision to submit it for publication. This study was in part supported by ICES (formerly the “Institute for Clinical Evaluative Sciences”), which is funded by an annual grant from the Ontario Ministry of Health (MOH) and the Ministry of Long-Term Care (MLTC).

ORCID iDs

Ruth Ann Marrie

Helen Tremlett

Data availability statement

The use of data in this project is authorized under Section 45 of Ontario’s Personal Health Information Protection Act (PHIPA) and approved by ICES’ Privacy and Legal Office. ICES is an independent, non-profit research institute whose legal status under Ontario’s health information privacy law allows it to collect and analyze healthcare and demographic data, without consent, for health system evaluation and improvement. This document used data adapted from the Statistics Canada Postal Code^OM Conversion File, which is based on data licensed from Canada Post Corporation, and/or data adapted from the Ontario Ministry of Health Postal Code Conversion File, which contains data copied under license from ©Canada Post Corporation and Statistics Canada. Parts of this material are based on data and/or information compiled and provided by the Ontario Ministry of Health and the Canadian Institute for Health Information (CIHI). The analyses, conclusions, opinions, and statements expressed herein are solely those of the authors and do not reflect those of the funding or data sources; no endorsement is intended or should be inferred.

The data set from this study is held securely in coded form at ICES. While legal data sharing agreements between ICES and data providers (e.g. healthcare organizations and government) prohibit ICES from making the data set publicly available, access may be granted to those who meet pre-specified criteria for confidential access, available at (email: das@ices.on.ca). The full data set creation plan and underlying analytic code are available from the authors upon request, understanding that the computer programs may rely upon coding templates or macros that are unique to ICES and are, therefore, either inaccessible or may require modification.

Supplemental material

Supplemental material for this article is available online.

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