Probabilistic bias analysis for exposure misclassification of household income by neighbourhood in a cohort of individuals with colorectal cancer.

INTRODUCTION: Despite poor agreement, neighbourhood income is used as a proxy for household income, due to a lack of data availability. We quantified misclassification between household and neighbourhood income and demonstrate quantitative bias analysis (QBA) in scenarios where only neighbourhood income is available in assessing income inequalities on colorectal cancer mortality. METHODS: This was a retrospective study of adults with colorectal cancer diagnosed 2006-14 from Statistics Canada's Canadian Census Health and Environment Cohort. Neighbourhood income quintiles from Statistics Canada were used. Census household income quintiles were used to determine bias parameters and confirm results of the QBA. We calculated positive and negative predictive values using multinomial models, adjusting for age, sex and rural residence. Probabilistic QBA was conducted to explore the implication of exposure misclassification when estimating the effect of income on 5-year mortality. RESULTS: We found poor agreement between neighbourhood and household income: positive predictive values ranged from 21% to 37%. The bias-adjusted risk of neighbourhood income on 5-year mortality was similar to the risk of mortality by household income. The bias-adjusted relative risk of the lowest income quintile compared with the highest was 1.42 [95% simulation interval (SI) 1.32-1.53] compared with 1.46 [95% confidence interval (CI) 1.39-1.54] for household income and 1.18 (95% CI 1.12-1.24) for neighbourhood income. CONCLUSION: QBA can be used to estimate adjusted effects of neighbourhood income on mortality which represent household income. The predictive values from our study can be applied to similar cohorts with only neighbourhood income to estimate the effects of household income on cancer mortality.

Development of a Canadian Guidance for Reporting Real-world Evidence for Regulatory and Health-Technology Assessment (HTA) Decision Making.

Real-world evidence (RWE) can complement and fill knowledge gaps from randomized controlled trials to assist in health-technology assessment (HTA) for regulatory decision-making. However, the generation of RWE is an intricate process with many sequential decision points, and different methods and approaches may impact the quality and reliability of evidence. Standardization and transparency in reporting these decisions is imperative to appraise RWE and incorporate it into HTA decision-making. A partnership between Canadian health system stakeholders, namely Health Canada and Canada's Drug Agency (formerly the Canadian Agency for Drugs and Technologies in Health (CADTH)), was established to develop a guidance for standardization of reporting of RWE for regulatory and HTA decision-making in Canada. In this article, we describe the methods to develop the Guidance for Reporting Real-World Evidence document and checklist for reporting RWE for regulatory and HTA decision-making in Canada. This guidance can be adapted for other jurisdictions and will have future extensions to incorporate emerging issues with RWE and HTA decision-making.

Paid Family Leave and Prevention of Acute Respiratory Infections in Young Infants.

Importance: Acute respiratory tract infections are the leading cause of emergency department visits and hospitalizations in US children, with highest risks in the first 2 months after birth. Out-of-home childcare settings increase the spread of respiratory tract infections. The study team hypothesized that access to state-paid family leave could reduce acute care encounters (hospital admissions or emergency department visits) for respiratory tract infections in young infants by reducing out-of-home childcare transmissions. Objective: To determine if the 2018 introduction of paid family leave in New York state reduced acute care encounters for respiratory tract infections in infants 8 weeks or younger. Design, Setting, and Participants: This population-based study of acute care encounters took place in New York state and New England control states (Maine, Massachusetts, New Hampshire, Vermont) from October 2015 through February 2020. Participants included infants aged 8 weeks or younger. Controlled time series analysis using Poisson regression was used to estimate the impact of paid family leave on acute care encounters for respiratory tract infections, comparing observed counts during respiratory virus season (October through March) with those predicted in the absence of the policy. Acute care encounters for respiratory tract infections in 1-year-olds (who would not be expected to benefit as directly from the policy) were modeled as a placebo test. Intervention: New York State Paid Family Leave policy, introduced on January 1, 2018, providing 8 weeks of paid leave for eligible parents. Main Outcomes and Measures: Emergency department visits or hospitalizations with International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD) codes for upper or lower respiratory tract infections or associated symptoms (ie, fever, cough), excluding newborn hospitalizations. The secondary outcome was acute care encounters for respiratory syncytial virus (RSV) bronchiolitis. Results: There were 52 943 acute care encounters for respiratory infection among infants 8 weeks or younger. There were 15 932 encounters that were hospitalizations (30%) and 33 304 of the encounters were paid for by Medicaid (63%). Encounters were 18% lower than predicted (relative percentage change = -17.9; 95% CI, -20.3 to -15.7) after the introduction of paid family leave. RSV encounters were 27.0% lower (95% CI, -30.9 to -23.5) than predicted. Similar reductions were not observed in 1-year-olds (relative percentage change = -1.5; 95% CI, -2.5 to -0.6). Conclusions: New York state's paid family leave policy was associated with reduced acute care encounters for respiratory tract infections in young infants. These findings may be useful for informing implementation of paid family leave federally and in the states that have not enacted paid family leave policies.

Income differences in time to colon cancer diagnosis.

INTRODUCTION: People with low income have worse outcomes throughout the cancer care continuum; however, little is known about income and the diagnostic interval. We described diagnostic pathways by neighborhood income and investigated the association between income and the diagnostic interval. METHODS: This was a retrospective cohort study of colon cancer patients diagnosed 2007-2019 in Ontario using routinely collected data. The diagnostic interval was defined as the number of days from the first colon cancer encounter to diagnosis. Asymptomatic pathways were defined as first encounter with a colonoscopy or guaiac fecal occult blood test not occurring in the emergency department and were examined separately from symptomatic pathways. Quantile regression was used to determine the association between neighborhood income quintile and the conditional 50th and 90th percentile diagnostic interval controlling for age, sex, rural residence, and year of diagnosis. RESULTS: A total of 64,303 colon cancer patients were included. Patients residing in the lowest income neighborhoods were more likely to be diagnosed through symptomatic pathways and in the emergency department. Living in low-income neighborhoods was associated with longer 50th and 90th-percentile symptomatic diagnostic intervals compared to patients living in the highest income neighborhoods. For example, the 90th percentile diagnostic interval was 15 days (95% CI 6-23) longer in patients living in the lowest income neighborhoods compared to the highest. CONCLUSION: These findings reveal income inequities during the diagnostic phase of colon cancer. Future work should determine pathways to reducing inequalities along the diagnostic interval and evaluate screening and diagnostic assessment programs from an equity perspective.

Antenatal corticosteroids and newborn respiratory outcomes in twins: A regression discontinuity study.

OBJECTIVE: To estimate the effect of antenatal corticosteroids on newborn respiratory morbidity in twins. DESIGN: Regression discontinuity applied to population-based birth registry data. SETTING: British Columbia, Canada, 2008-2018. POPULATION: Twin pregnancies admitted for birth between 31+0 and 36+6 weeks of gestation. METHODS: During our study period, Canadian clinical practice guidelines recommended antenatal corticosteroid administration for imminent preterm birth up to 33+6 weeks. We used a logistic model to compare the predicted risks of our outcomes among pregnancies admitted for birth immediately before this clinical cut-point (higher probability of exposure to antenatal corticosteroids) versus immediately after it (lower probability). MAIN OUTCOME MEASURES: Our primary outcome was a composite of newborn respiratory distress or in-hospital death. Our secondary outcome was a composite of newborn respiratory intervention or in-hospital death. RESULTS: Among 2524 pregnancies (5035 liveborn twins), 47% of admissions before 34+0 weeks of gestation were exposed to antenatal corticosteroids but only 4.2% of admissions after this cut-point were exposed. The risk of newborn respiratory distress or in-hospital mortality increased abruptly at 34+0 weeks, corresponding to a protective effect of treatment (risk ratio [RR] 0.69, 95% CI 0.53-0.90; risk difference [RD] -12 cases per 100 births, 95% CI -20 to -4.1). There was no clear evidence for or against an effect on newborn respiratory intervention or in-hospital death (RR 0.89, 95% CI 0.70-1.13; RD -4.2 per 100, 95% CI -13 to +4.2). CONCLUSIONS: Our findings provide evidence for the effectiveness of antenatal corticosteroids in preventing adverse newborn respiratory outcomes in twins.

The impact of team-based primary care on medication-related outcomes in older adults: A comparative analysis of two Canadian provinces.

Objective: To evaluate if access to team-based primary care is related to medication management outcomes for older adults. Methods: We completed two retrospective cohort studies using administrative health data for older adults (66+) in Ontario (n = 428,852) and Québec (n = 310,198) who were rostered with a family physician (FP) between the 2001/02 and 2017/18 fiscal years. We generated matched comparison groups of older adults rostered to an FP practicing in a team-based model, and older adults rostered to an FP in a non-team model. We compared the following outcomes between these groups: any adverse drug reactions (ADRs), any potentially inappropriate prescription (PIP), and polypharmacy. Average treatment effects of access to team-based care were estimated using a difference-in-differences estimator. Results: The risk of an ADR was 22 % higher (RR = 1.22, 95 % CI = 1.18, 1.26) for older adults rostered to a team-based FP in Québec and 6 % lower (RR = 0.943, 95 % CI = 0.907, 0.978) in Ontario. However, absolute risk differences were less than 0.5 %. Differences in the risk of polypharmacy were small in Québec (RR = 1.005, 95 % CI = 1.001, 1.009) and Ontario (RR = 1.004, 95 % CI = 1.001, 1.007) and had absolute risk differences of less than 1 % in both provinces. Effects on PIP were not statistically or clinically significant in adjusted models. Interpretation: We did not find evidence that access to team-based primary care in Ontario or Québec meaningfully improved medication management outcomes for older adults.

Cost modelling incorporating procalcitonin for the risk stratification of febrile infants ≤60 days old.

Objectives: Procalcitonin testing is recommended to discriminate febrile young infants at risk of serious bacterial infections (SBI). However, this test is not available in many clinical settings, limited largely by cost. This study sought to evaluate contemporary real-world costs associated with the usual care of febrile young infants, and estimate impact on clinical trajectory and costs when incorporating procalcitonin testing. Methods: We assessed hospital-level door-to-discharge costs of all well-appearing febrile infants aged ≤60 days, evaluated at a tertiary paediatric hospital between April/2016 and March/2019. Emergency Department and inpatient expense data for usual care were obtained from the institutional general ledger, validated by the provincial Ministry of Health. These costs were then incorporated into a probabilistic model of risk stratification for an equivalent simulated cohort, with the addition of procalcitonin. Results: During the 3-year study period, 1168 index visits were included for analysis. Real-world median costs-per-infant were the following: $3266 (IQR $2468 to $4317, n=93) for hospitalized infants with SBIs; $2476 (IQR $1974 to $3236, n=530) for hospitalized infants without SBIs; $323 (IQR $286 to $393, n=538) for discharged infants without SBIs; and, $3879 (IQR $3263 to $5297, n=7) for discharged infants subsequently hospitalized for missed SBIs. Overall median cost-per-infant of usual care was $1555 (IQR $1244 to $2025), compared to a modelled cost of $1389 (IQR $1118 to $1797) with the addition of procalcitonin (10.7% overall cost savings; $1,816,733 versus $1,622,483). Under pessimistic and optimistic model assumptions, savings were 5.9% and 14.9%, respectively. Conclusions: Usual care of febrile young infants is variable and resource intensive. Increased access to procalcitonin testing could improve risk stratification at lower overall costs.

Inequalities in survival and care across social determinants of health in a cohort of advanced lung cancer patients in Quebec (Canada): A high-resolution population-level analysis.

BACKGROUND: Advanced lung cancer patients exposed to breakthrough therapies like EGFR tyrosine kinase inhibitors (EGFR-TKI) may experience social inequalities in survival, partly from differences in care. This study examined survival by neighborhood-level socioeconomic and sociodemographic status, and geographical location of advanced lung cancer patients who received gefitinib, an EGFR-TKI, as first-line palliative treatment. Differences in the use and delay of EGFR-TKI treatment were also examined. METHODS: Lung cancer patients receiving gefitinib from 2001 to 2019 were identified from Quebec's health administrative databases. Accounting for age and sex, estimates were obtained for the median survival time from treatment to death, the probability of receiving osimertinib as a second EGFR-TKI, and the median time from biopsy to receiving first-line gefitinib. RESULTS: Among 457 patients who received first-line treatment with gefitinib, those living in the most materially deprived areas had the shortest median survival time (ratio, high vs. low deprivation: 0.69; 95% CI: 0.47-1.04). The probability of receiving osimertinib as a second EGFR-TKI was highest for patients from immigrant-dense areas (ratio, high vs. lowdensity: 1.95; 95% CI: 1.26-3.36) or from Montreal (ratio, other urban areas vs. Montreal: 0.39; 95% CI: 0.16-0.71). The median wait time for gefitinib was 1.27 times longer in regions with health centers peripheral to large centers in Quebec or Montreal in comparison to regions with university-affiliated centers (95% CI: 1.09-1.54; n = 353). CONCLUSION: This study shows that real-world variations in survival and treatment exist among advanced lung cancer patients in the era of breakthrough therapies and that future research on inequalities should also focus on this population.

Agreement between individual and neighborhood income measures in patients with colorectal cancer in Canada.

INTRODUCTION: With increasing interest in income-related differences in cancer outcomes, accurate measurement of income is imperative. Misclassification of income can result in wrong conclusions as to the presence of income inequalities. We determined misclassification between individual- and neighborhood-level income and their association with overall survival among colorectal cancer (CRC) patients. METHODS: The Canadian Census Health and Environment Cohorts were used to identify CRC patients diagnosed from 1992 to 2017. We used neighborhood income quintiles from Statistics Canada and created individual income quintiles from the same data sources to be as similar as possible. Agreement between individual and neighborhood income quintiles was measured using cross-tabulations and weighted kappa statistics. Cox proportional hazards and Lin semiparametric hazards models were used to determine the effects of individual and neighborhood income independently and jointly on survival. Analyses were also stratified by rural residence. RESULTS: A total of 103 530 CRC patients were included in the cohort. There was poor agreement between individual and neighborhood income with only 17% of respondents assigned to the same quintile (weighted kappa = 0.18). Individual income had a greater effect on relative and additive survival than neighborhood income when modeled separately. The interaction between individual and neighborhood income demonstrated that the most at risk for poor survival were those in the lowest individual and neighborhood income quintiles. Misclassification was more likely to occur for patients residing in rural areas. CONCLUSION: Cancer researchers should avoid using neighborhood income as a proxy for individual income, especially among patients with cancers with demonstrated inequalities by income.

Team-based primary care reforms and older adults: a descriptive assessment of sociodemographic trends and prescribing endpoints in two Canadian provinces.

BACKGROUND: Team-based primary care reforms aim to improve care coordination by involving multiple interdisciplinary health professionals in patient care. Team-based primary care may support improved medication management for older adults with polypharmacy and multiple points of contact with the healthcare system. However, little is known about this association. This study compares sociodemographic and prescribing trends among older adults in team-based vs. traditional primary care models in Ontario and Quebec. METHODS: We constructed two provincial cohorts using population-level health administrative data from 2006-2018. Our primary exposure was enrollment in a team-based model of care. Key endpoints included adverse drug events (ADEs), potentially inappropriate prescriptions (PIPs), and polypharmacy. We plotted prescribing trends across the observation period (stratified by model of care) in each province. We used standardized mean differences to compare characteristics of older adults and providers, as well as prescribing endpoints. RESULTS: Formal patient/physician enrollment increased in both provinces since the time of policy implementation; team-based enrollment among older adults was higher in Quebec (47%) than Ontario (33%) by the end of our observation period. The distribution of sociodemographic characteristics was reasonably comparable between team-based and non-team-based patients in both provinces, aside from a persistently higher share of rural patients in team-based care. Most PIPs assessed either declined or remained relatively steady over time, regardless of model of care and province. Several PIPs were more common among team-based patients than non-team-based patients, particularly in Quebec. We did not detect notable trends in ADEs or polypharmacy in either province. CONCLUSIONS: Our findings offer encouraging evidence that many PIPs are declining over time in this population, regardless of patients' enrollment in team-based care. Rates of decline appear similar across models of care, suggesting these models may not meaningfully influence prescribing endpoints. Additional efforts are needed to understand the impact of team-based care among older adults and improve primary care prescribing practices.

Human resource implications of expanding latent tuberculosis patient care activities.

Introduction: The World Health Organization (WHO) declared increasing services for latent tuberculosis infection (LTBI) a priority to eliminate tuberculosis (TB) by 2035. Yet, there is little information about thehuman resource needs required to implement LTBI treatment scale-up. Our study aimed to estimate the change in healthcare workers (HCW) time spent on different patient care activities, following an intervention to strengthen LTBI services. Methods: We conducted a time and motion (TAM) study, observing HCW throughout a typical workday before and after the intervention (Evaluation and Strengthening phases, respectively) at 24 health facilities in five countries. The precise time spent on pre-specified categories of work activities was recorded. Time spent on direct patient care was subcategorized as relating to one of three conditions: LTBI, active or suspected TB, and non-TB (i.e., patients with any other medical condition). A linear mixed model (LMM) was fit to estimate the change in HCW time following the intervention. Results: A total of 140 and 143 HCW participated in the TAMs during the Evaluation and Strengthening phases, respectively. Results from intervention facilities showed an increase of 9% (95% CI: 3%, 15%) in the proportion of HCW time spent on LTBI-related services, but with a corresponding change of -11% (95% CI: -21%, -1%) on active TB services. There was no change in the proportion of time spent on LTBI care in control facilities; this remained low in both phases of the study. Discussion: Our findings suggest that additional HCW personnel will be required for expansion of LTBI services to ensure that this expansion does not reduce the time available for care of active TB patients.

Advanced Lung Cancer Patients' Use of EGFR Tyrosine Kinase Inhibitors and Overall Survival: Real-World Evidence from Quebec, Canada.

EGFR tyrosine kinase inhibitors (EGFR-TKIs) are breakthrough palliative treatments for advanced lung cancer patients with tumors harboring mutations in the EGFR gene. Using healthcare administrative data, three cohorts were created to describe the use of three EGFR-TKIs that are publicly funded in Quebec for specific indications (i.e., 1st-line gefitinib, 1st-line afatinib, and post-EGFR-TKI osimertinib). The main objective was to compare overall survival (OS) among patients receiving these treatments to those in previous experimental and real-world studies. The patients who received EGFR-TKIs for indications of interest between 1 April 2001, and 31 March 2019 (or 31 March 2020, for post-EGFR-TKI osimertinib) were included to estimate the Kaplan-Meier-based median OS for each cohort. An extensive literature search was conducted to include comparable studies. For the gefitinib 1st-line (n = 457), the afatinib 1st-line (n = 80), and the post-EGFR-TKI osimertinib (n = 119) cohorts, we found a median OS (in months) of 18.9 (95%CI: 16.3-21.9), 26.6 (95%CI: 13.7-NE) and 19.9 (95%CI: 17.4-NE), respectively. Out of the 20 studies that we retained from the literature review and where comparisons were feasible, 17 (85%) had similar OS results, which further confirms the value of these breakthrough therapies in real-world clinical practice.

Health care services use, stillbirth, and neonatal and infant survival following implementation of the Maternal Health Voucher Scheme in Bangladesh: A difference-in-differences analysis of Bangladesh Demographic and Health Survey data, 2000 to 2016.

BACKGROUND: Starting in 2006 to 2007, the Government of Bangladesh implemented the Maternal Health Voucher Scheme (MHVS). This program provides pregnant women with vouchers that can be exchanged for health services from eligible public and private sector providers. In this study, we examined whether access to the MHVS was associated with maternal health services utilization, stillbirth, and neonatal and infant mortality. METHODS AND FINDINGS: We used information on pregnancies and live births between 2000 to 2016 reported by women 15 to 49 years of age surveyed as part of the Bangladesh Demographic and Health Surveys. Our analytic sample included 23,275 pregnancies lasting at least 7 months for analyses of stillbirth and between 15,125 and 21,668 live births for analyses of health services use, neonatal, and infant mortality. With respect to live births occurring prior to the introduction of the MHVS, 31.3%, 14.1%, and 18.0% of women, respectively, reported receiving at least 3 antenatal care visits, delivering in a health institution, and having a skilled birth attendant at delivery. Rates of neonatal and infant mortality during this period were 40 and 63 per 1,000 live births, respectively, and there were 32 stillbirths per 1,000 pregnancies lasting at least 7 months. We applied a difference-in-differences design to estimate the effect of providing subdistrict-level access to the MHVS program, with inverse probability of treatment weights to address selection into the program. The introduction of the MHVS program was associated with a lagged improvement in the probability of delivering in a health facility, one of the primary targets of the program, although associations with other health services were less evident. After 6 years of access to the MHVS, the probabilities of reporting at least 3 antenatal care visits, delivering in a health facility, and having a skilled birth attendant present increased by 3.0 [95% confidence interval (95% CI) = -4.8, 10.7], 6.5 (95% CI = -0.6, 13.6), and 5.8 (95% CI = -1.8, 13.3) percentage points, respectively. We did not observe evidence consistent with the program improving health outcomes, with probabilities of stillbirth, neonatal mortality, and infant mortality decreasing by 0.7 (95% CI = -1.3, 2.6), 0.8 (95% CI = -1.7, 3.4), and 1.3 (95% CI = -2.5, 5.1) percentage points, respectively, after 6 years of access to the MHVS. The sample size was insufficient to detect smaller associations with adequate precision. Additionally, we cannot rule out the possibility of measurement error, although it was likely nondifferential by treatment group, or unmeasured confounding by concomitant interventions that were implemented differentially in treated and control areas. CONCLUSIONS: In this study, we found that the introduction of the MHVS was positively associated with the probability of delivering in a health facility, but despite a longer period of follow-up than most extant evaluations, we did not observe attendant reductions in stillbirth, neonatal mortality, or infant mortality. Further work and engagement with stakeholders is needed to assess if the MHVS has affected the quality of care and health inequalities and whether the design and eligibility of the program should be modified to improve maternal and neonatal health outcomes.

Mapping Canadian Data Assets to Generate Real-World Evidence: Lessons Learned from Canadian Real-World Evidence for Value of Cancer Drugs (CanREValue) Collaboration's RWE Data Working Group.

Canadian provinces routinely collect patient-level data for administrative purposes. These real-world data (RWD) can be used to generate real-world evidence (RWE) to inform clinical care and healthcare policy. The CanREValue Collaboration is developing a framework for the use of RWE in cancer drug funding decisions. A Data Working Group (WG) was established to identify data assets across Canada for generating RWE of oncology drugs. The mapping exercise was conducted using an iterative scan with informant surveys and teleconference. Data experts from ten provinces convened for a total of three teleconferences and two in-person meetings from March 2018 to September 2019. Following each meeting, surveys were developed and shared with the data experts which focused on identifying databases and data elements, as well as a feasibility assessment of conducting RWE studies using existing data elements and resources. Survey responses were compiled into an interim data report, which was used for public stakeholder consultation. The feedback from the public consultation was used to update the interim data report. We found that databases required to conduct real-world studies are often held by multiple different data custodians. Ninety-seven databases were identified across Canada. Provinces held on average 9 distinct databases (range: 8-11). An Essential RWD Table was compiled that contains data elements that are necessary, at a minimal, to conduct an RWE study. An Expanded RWD Table that contains a more comprehensive list of potentially relevant data elements was also compiled and the availabilities of these data elements were mapped. While most provinces have data on patient demographics (e.g., age, sex) and cancer-related variables (e.g., morphology, topography), the availability and linkability of data on cancer treatment, clinical characteristics (e.g., morphology and topography), and drug costs vary among provinces. Based on current resources, data availability, and access processes, data experts in most provinces noted that more than 12 months would be required to complete an RWE study. The CanREValue Collaboration's Data WG identified key data holdings, access considerations, as well as gaps in oncology treatment-specific data. This data catalogue can be used to facilitate future oncology-specific RWE analyses across Canada.

Patient characteristics associated with enrolment under voluntary programs implemented within fee-for-service systems in British Columbia and Quebec: a cross-sectional study.

BACKGROUND: There is a paucity of information on patient characteristics associated with enrolment under voluntary programs (e.g. incentive payments) implemented within fee-for-service systems. We explored patient characteristics associated with enrolment under these programs in British Columbia and Quebec. METHODS: We used linked administrative data and a cross-sectional design to compare people aged 40 years or more enrolled under voluntary programs to those who were eligible but not enrolled. We examined 2 programs in Quebec (enrolment of vulnerable patients with qualifying conditions [implemented in 2003] and enrolment of the general population [2009]) and 3 in BC (Chronic disease incentive [2003], Complex care incentive [2007] and enrolment of the general population [A GP for Me, 2013]). We used logistic regression to estimate the odds of enrolment by neighbourhood income, rural versus urban residence, previous treatment for mental illness, previous treatment for substance use disorder and use of health care services before program implementation, controlling for characteristics linked to program eligibility. RESULTS: In Quebec, we identified 1 569 010 people eligible for the vulnerable enrolment program (of whom 505 869 [32.2%] were enrolled within the first 2 yr of program implementation) and 2 394 923 for the general enrolment program (of whom 352 380 [14.7%] were enrolled within the first 2 yr). In BC, we identified 133 589 people eligible for the Chronic disease incentive, 47 619 for the Complex care incentive and 1 349 428 for A GP for Me; of these, 60 764 (45.5%), 28 273 (59.4%) and 1 066 714 (79.0%), respectively, were enrolled within the first 2 years. The odds of enrolment were higher in higher-income neighbourhoods for programs without enrolment criteria (adjusted odds ratio [OR] comparing highest to lowest quintiles 1.21 [95% confidence interval (CI) 1.20-1.23] in Quebec and 1.67 [95% CI 1.64-1.69] in BC) but were similar across neighbourhood income quintiles for programs with health-related eligibility criteria. The odds of enrolment by urban versus rural location varied by program. People treated for substance use disorders had lower odds of enrolment in all programs (adjusted OR 0.60-0.72). Compared to people eligible but not enrolled, those enrolled had similar or higher numbers of primary care visits and longitudinal continuity of care in the year before enrolment. INTERPRETATION: People living in lower-income neighbourhoods and those treated for substance use disorders were less likely than people in higher-income neighbourhoods and those not treated for such disorders to be enrolled in programs without health-related eligibility criteria. Other strategies are needed to promote equitable access to primary care.

Antenatal corticosteroid administration and attention-deficit/hyperactivity disorder in childhood: a regression discontinuity study.

BACKGROUND: Antenatal corticosteroids reduce respiratory morbidity in preterm infants, but their use during late preterm gestation (34-36 weeks) is limited because their safety for longer-term child neurodevelopment is unclear. We sought to determine if fetuses with higher probability of exposure to antenatal corticosteroids had increased rates of prescriptions for attention-deficit/hyperactivity disorder (ADHD) medication in childhood, using a quasiexperimental design that better controls for confounding than existing observational studies. METHODS: We identified 16 358 children whose birthing parents were admitted for delivery between 31 + 0 (31 weeks, 0 days) and 36 + 6 weeks' gestation in 2000-2013, using a perinatal data registry from British Columbia, Canada, and linked their records with population-based child ADHD medication data (2000-2018). We used a regression discontinuity design to capitalize on the fact that pregnancies presenting for delivery immediately before and immediately after the clinical cut-off for antenatal corticosteroid administration of 34 + 0 weeks' gestation have very different levels of exposure to corticosteroids, but are otherwise similar with respect to confounders. RESULTS: Over a median follow-up period of 9 years, 892 (5.5%) children had 1 or more dispensations of ADHD medication. Children whose birthing parents were admitted for delivery just before the corticosteroid clinical cut-off of 34 + 0 weeks' gestation did not appear to be more likely to be prescribed ADHD medication than those admitted just after the cut-off (rate ratio 1.1, 95% confidence interval [CI] 0.8 to 1.6; 1.3 excess cases per 100 children, 95% CI -2.5 to 5.7). INTERPRETATION: We found little evidence that children with higher probability of exposure to antenatal corticosteroids have higher rates of ADHD prescriptions in childhood, supporting the safety of antenatal corticosteroids for this neurodevelopmental outcome.

The effects of early pregnancy loss on health outcomes and health care utilization and costs.

OBJECTIVE: To evaluate the effects of early pregnancy loss on subsequent health care use and costs. DATA SOURCES: Linked administrative health databases from Manitoba, Canada. STUDY DESIGN: This was a population-based cohort study. The exposure of interest was first recorded ectopic pregnancy or miscarriage (EPM). Outcomes included visits to all ambulatory care providers, family physicians (FPs), specialists, and hospitals, as well as the costs associated with these visits. We also assessed the impact of EPM on a global measure of health service utilization and the incidence and costs of psychotropic medications. DATA COLLECTION/EXTRACTION METHODS: We identified women who experienced their first recorded loss (EPM) from 2003-2012 and created a propensity score model to match these women to women who experienced a live birth, with outcome measures available through 31 December 2014. We used a difference in differences approach with multivariable negative binomial models and generalized estimating equations (GEE) to assess the impact of EPM on the aforementioned health care utilization indicators. PRINCIPAL FINDINGS: EPM was associated with a short-term increase in visits to, and costs associated with, certain ambulatory care providers. These findings were driven in large part by increased visits/costs to FPs (rate difference [RD]: $19.92 [95% CI: $16.33, $23.51]) and obstetrician-gynecologists (OB-GYNs) (RD $9.41 [95% CI: $8.42, $10.40]) in the year immediately following the loss, excluding care associated with the loss itself. We also detected an increase in hospital stays and costs and a decrease in the use of psychotropic medications relative to matched controls. CONCLUSION: Pregnancy loss may lead to subsequent increases in certain types of health care utilization. While the absolute costs associated with post-EPM care are relatively small, the observed patterns of service utilization are informative for providers and policy makers seeking to support women following a loss.

Evaluating Montréal's harm reduction interventions for people who inject drugs: protocol for observational study and cost-effectiveness analysis.

INTRODUCTION: The main harm reduction interventions for people who inject drugs (PWID) are supervised injection facilities, needle and syringe programmes and opioid agonist treatment. Current evidence supporting their implementation and operation underestimates their usefulness by excluding skin, soft tissue and vascular infections (SSTVIs) and anoxic/toxicity-related brain injury from cost-effectiveness analyses (CEA). Our goal is to conduct a comprehensive CEA of harm reduction interventions in a setting with a large, dispersed, heterogeneous population of PWID, and include prevention of SSTVIs and anoxic/toxicity-related brain injury as measures of benefit in addition to HIV, hepatitis C and overdose morbidity and mortalities averted. METHODS AND ANALYSIS: This protocol describes how we will develop an open, retrospective cohort of adult PWID living in Québec between 1 January 2009 and 31 December 2020 using administrative health record data. By complementing this data with non-linkable paramedic dispatch records, regional monthly needle and syringe dispensation counts and repeated cross-sectional biobehavioural surveys, we will estimate the hazards of occurrence and the impact of Montréal's harm reduction interventions on the incidence of drug-use-related injuries, infections and deaths. We will synthesise results from our empirical analyses with published evidence to simulate infections and injuries in a hypothetical population of PWID in Montréal under different intervention scenarios including current levels of use and scale-up, and assess the cost-effectiveness of each intervention from the public healthcare payer's perspective. ETHICS AND DISSEMINATION: This study was approved by McGill University's Institutional Review Board (Study Number: A08-E53-19B). We will work with community partners to disseminate results to the public and scientific community via scientific conferences, a publicly accessible report, op-ed articles and open access peer-reviewed journals.

Avoidable Hospitalizations in Persons with Dementia: a Population-Wide Descriptive Study (2000-2015).

BACKGROUND: Whether avoidable hospitalizations in community-dwelling persons with dementia have decreased during primary care reforms is unknown. METHODS: We described the prevalence and trends in avoidable hospitalizations in population-based repeated yearly cohorts of 192,144 community-dwelling persons with incident dementia (Quebec, 2000-2015) in the context of a province-wide primary care reform, using the provincial health administrative database. RESULTS: Trends in both types of Ambulatory Care Sensitive Condition (ACSC) hospitalization (general and older population) and 30-day readmission rates remained constant with average rates per 100 person-years: 20.5 (19.9-21.1), 31.7 (31.0-32.4), 20.6 (20.1-21.2), respectively. Rates of delayed hospital discharge (i.e., alternate level of care (ALC) hospitalizations) decreased from 23.8 (21.1-26.9) to 17.9 (16.1-20.1) (relative change -24.6%). CONCLUSIONS: These figures shed light on the importance of the phenomenon, its lack of improvement for most outcomes over the years, and the need to develop evidence-based policies to prevent avoidable hospitalizations in this vulnerable population.

Development and Validation of an Instrument to Measure Health-Related Out-of-Pocket Costs: The Cost for Patients Questionnaire.

OBJECTIVE: The growth of healthcare spending is a major concern for insurers and governments but also for patients whose health problems may result in costs going beyond direct medical costs. To develop a comprehensive tool to measure direct and indirect costs of a health condition for patients and their families to various outpatient contexts. METHODS: We conducted a content and face validation including results of a systematic review to identify the items related to direct and indirect costs for patients or their families and an online Delphi to determine the cost items to retain. We conducted a pilot test-retest with 18 naive participants and analyzed data calculating intraclass correlation and kappa coefficients. RESULTS: An initial list of 34 items was established from the systematic review. Each round of the Delphi panel incorporated feedback from the previous round until a strong consensus was achieved. After 4 rounds of the Delphi to reach consensus on items to be included and wording, the questionnaire had a total of 32 cost items. For the test-retest, kappa coefficients ranged from -0.11 to 1.00 (median = 0.86), and intraclass correlation ranged from -0.02 to 0.99 (median = 0.62). CONCLUSIONS: A rigorous process of content and face development was implemented for the Cost for Patients Questionnaire, and this study allowed to set a list of cost elements to be considered from the patient's perspective. Additional research including a test-retest with a larger sample will be part of a subsequent validation strategy.