A Canadian Simulation Model for Major Depressive Disorder: Study Protocol.

BACKGROUND: Major depressive disorder (MDD) is a common, often recurrent condition and a significant driver of healthcare costs. People with MDD often receive pharmacological therapy as the first-line treatment, but the majority of people require more than one medication trial to find one that relieves symptoms without causing intolerable side effects. There is an acute need for more effective interventions to improve patients' remission and quality of life and reduce the condition's economic burden on the healthcare system. Pharmacogenomic (PGx) testing could deliver these objectives, using genomic information to guide prescribing decisions. With an already complex and multifaceted care pathway for MDD, future evaluations of new treatment options require a flexible analytic infrastructure encompassing the entire care pathway. Individual-level simulation models are ideally suited for this purpose. We sought to develop an economic simulation model to assess the effectiveness and cost effectiveness of PGx testing for individuals with major depression. Additionally, the model serves as an analytic infrastructure, simulating the entire patient pathway for those with MDD. METHODS AND ANALYSIS: Key stakeholders, including patient partners, clinical experts, researchers, and modelers, designed and developed a discrete-time microsimulation model of the clinical pathways of adults with MDD in British Columbia (BC), including all publicly-funded treatment options and multiple treatment steps. The Simulation Model of Major Depression (SiMMDep) was coded with a modular approach to enhance flexibility. The model was populated using multiple original data analyses conducted with BC administrative data, a systematic review, and an expert panel. The model accommodates newly diagnosed and prevalent adult patients with MDD in BC, with and without PGx-guided treatment. SiMMDep comprises over 1500 parameters in eight modules: entry cohort, demographics, disease progression, treatment, adverse events, hospitalization, costs and quality-adjusted life-years (payoff), and mortality. The model predicts health outcomes and estimates costs from a health system perspective. In addition, the model can incorporate interactive decision nodes to address different implementation strategies for PGx testing (or other interventions) along the clinical pathway. We conducted various forms of model validation (face, internal, and cross-validity) to ensure the correct functioning and expected results of SiMMDep. CONCLUSION: SiMMDep is Canada's first medication-specific, discrete-time microsimulation model for the treatment of MDD. With patient partner collaboration guiding its development, it incorporates realistic care journeys. SiMMDep synthesizes existing information and incorporates provincially-specific data to predict the benefits and costs associated with PGx testing. These predictions estimate the effectiveness, cost-effectiveness, resource utilization, and health gains of PGx testing compared with the current standard of care. However, the flexible analytic infrastructure can be adapted to support other policy questions and facilitate the rapid synthesis of new data for a broader search for efficiency improvements in the clinical field of depression.

Validation of the Passive Surveillance Stroke Severity Score in Three Canadian Provinces.

BACKGROUND: Stroke outcomes research requires risk-adjustment for stroke severity, but this measure is often unavailable. The Passive Surveillance Stroke SeVerity (PaSSV) score is an administrative data-based stroke severity measure that was developed in Ontario, Canada. We assessed the geographical and temporal external validity of PaSSV in British Columbia (BC), Nova Scotia (NS) and Ontario, Canada. METHODS: We used linked administrative data in each province to identify adult patients with ischemic stroke or intracerebral hemorrhage between 2014-2019 and calculated their PaSSV score. We used Cox proportional hazards models to evaluate the association between the PaSSV score and the hazard of death over 30 days and the cause-specific hazard of admission to long-term care over 365 days. We assessed the models' discriminative values using Uno's c-statistic, comparing models with versus without PaSSV. RESULTS: We included 86,142 patients (n = 18,387 in BC, n = 65,082 in Ontario, n = 2,673 in NS). The mean and median PaSSV were similar across provinces. A higher PaSSV score, representing lower stroke severity, was associated with a lower hazard of death (hazard ratio and 95% confidence intervals 0.70 [0.68, 0.71] in BC, 0.69 [0.68, 0.69] in Ontario, 0.72 [0.68, 0.75] in NS) and admission to long-term care (0.77 [0.76, 0.79] in BC, 0.84 [0.83, 0.85] in Ontario, 0.86 [0.79, 0.93] in NS). Including PaSSV in the multivariable models increased the c-statistics compared to models without this variable. CONCLUSION: PaSSV has geographical and temporal validity, making it useful for risk-adjustment in stroke outcomes research, including in multi-jurisdiction analyses.

Costs of major depression covered / not covered in British Columbia, Canada.

BACKGROUND: Major depressive disorder (MDD) is one of the world's leading causes of disability. Our purpose was to characterize the total costs of MDD and evaluate the degree to which the British Columbia provincial health system meets its objective to protect people from the financial impact of illness. METHODS: We performed a population-based cohort study of adults newly diagnosed with MDD between 2015 and 2020 and followed their health system costs over two years. The expenditure proportion of MDD-related, patient paid costs relative to non-subsistence income was estimated, incidences of financial hardship were identified and the slope index of inequality (SII) between the highest and lowest income groups compared across regions. RESULTS: There were 250,855 individuals diagnosed with MDD in British Columbia over the observation period. Costs to the health system totalled >$1.5 billion (2020 CDN), averaging $138/week for the first 12 weeks following a new diagnosis and $65/week to week 52 and $55/week for weeks 53-104 unless MDD was refractory to treatment ($125/week between week 12-52 and $101/week over weeks 53-104). The proportion of MDD-attributable costs not covered by the health system was 2-15x greater than costs covered by the health system, exceeding $700/week for patients with severe MDD or MDD that was refractory to treatment. Population members in lower-income groups and urban homeowners had disadvantages in the distribution of financial protection received by the health system (SII reached - 8.47 and 15.25, respectively); however, financial hardship and inequities were mitigated province-wide if MDD went into remission (SII - 0.07 to 0.6). CONCLUSIONS: MDD-attributable costs to health systems and patients are highest in the first 12 weeks after a new diagnosis. During this time, lower income groups and homeowners in urban areas run the risk of financial hardship.

Change in Hospital Risk-standardized Stroke Mortality Performance With and Without the Passive Surveillance Stroke Severity Score.

BACKGROUND: Adjustment for baseline stroke severity is necessary for accurate assessment of hospital performance. We evaluated whether adjusting for the Passive Surveillance Stroke SeVerity (PaSSV) score, a measure of stroke severity derived using administrative data, changed hospital-specific estimated 30-day risk-standardized mortality rate (RSMR) after stroke. METHODS: We used linked administrative data to identify adults who were hospitalized with ischemic stroke or intracerebral hemorrhage across 157 hospitals in Ontario, Canada between 2014 and 2019. We fitted a random effects logistic regression model using Markov Chain Monte Carlo methods to estimate hospital-specific 30-day RSMR and 95% credible intervals with adjustment for age, sex, Charlson comorbidity index, and stroke type. In a separate model, we additionally adjusted for stroke severity using PaSSV. Hospitals were defined as low-performing, average-performing, or high-performing depending on whether the RSMR and 95% credible interval were above, overlapping, or below the cohort's crude mortality rate. RESULTS: We identified 65,082 patients [48.0% were female, the median age (25th,75th percentiles) was 76 years (65,84), and 86.4% had an ischemic stroke]. The crude 30-day all-cause mortality rate was 14.1%. The inclusion of PaSSV in the model reclassified 18.5% (n=29) of the hospitals. Of the 143 hospitals initially classified as average-performing, after adjustment for PaSSV, 20 were reclassified as high-performing and 8 were reclassified as low-performing. Of the 4 hospitals initially classified as low-performing, 1 was reclassified as high-performing. All 10 hospitals initially classified as high-performing remained unchanged. CONCLUSION: PaSSV may be useful for risk-adjusting mortality when comparing hospital performance. External validation of our findings in other jurisdictions is needed.

Cost-effectiveness of pharmacogenomic-guided treatment for major depression.

BACKGROUND: Pharmacogenomic testing to identify variations in genes that influence metabolism of antidepressant medications can enhance efficacy and reduce adverse effects of pharmacotherapy for major depressive disorder. We sought to establish the cost-effectiveness of implementing pharmacogenomic testing to guide prescription of antidepressants. METHODS: We developed a discrete-time microsimulation model of care pathways for major depressive disorder in British Columbia, Canada, to evaluate the effectiveness and cost-effectiveness of pharmacogenomic testing from the public payer's perspective over 20 years. The model included unique patient characteristics (e.g., metabolizer phenotypes) and used estimates derived from systematic reviews, analyses of administrative data (2015-2020) and expert judgment. We estimated incremental costs, life-years and quality-adjusted life-years (QALYs) for a representative cohort of patients with major depressive disorder in BC. RESULTS: Pharmacogenomic testing, if implemented in BC for adult patients with moderate-severe major depressive disorder, was predicted to save the health system $956 million ($4926 per patient) and bring health gains of 0.064 life-years and 0.381 QALYs per patient (12 436 life-years and 74 023 QALYs overall over 20 yr). These savings were mainly driven by slowing or avoiding the transition to refractory (treatment-resistant) depression. Pharmacogenomic-guided care was associated with 37% fewer patients with refractory depression over 20 years. Sensitivity analyses estimated that costs of pharmacogenomic testing would be offset within about 2 years of implementation. INTERPRETATION: Pharmacogenomic testing to guide antidepressant use was estimated to yield population health gains while substantially reducing health system costs. These findings suggest that pharmacogenomic testing offers health systems an opportunity for a major value-promoting investment.

Epidemiology and treatment of heart failure with chronic obstructive pulmonary disease in Canadian primary care.

AIMS: Heart failure (HF) and chronic obstructive pulmonary disease (COPD) are largely managed in primary care, but their intersection in terms of disease burden, healthcare utilization, and treatment is ill-defined. METHODS AND RESULTS: We examined a retrospective cohort including all patients with HF or COPD in the Canadian Primary Care Sentinel Surveillance Network from 2010 to 2018. The population size in 2018 with HF, COPD, and HF with COPD was 15 778, 27 927, and 4768 patients, respectively. While disease incidence declined, age-sex-standardized prevalence per 100 population increased for HF alone from 2.33 to 3.63, COPD alone from 3.44 to 5.96, and COPD with HF from 12.70 to 15.67. Annual visit rates were high and stable around 8 for COPD alone but declined significantly over time for HF alone (9.3-8.1, P = 0.04) or for patients with both conditions (14.3-11.9, P = 0.006). For HF alone, cardiovascular visits were common (29.4%), while respiratory visits were infrequent (3.5%), with the majority of visits being non-cardiorespiratory. For COPD alone, respiratory and cardiovascular visits were common (16.4% and 11.3%) and the majority were again non-cardiorespiratory. For concurrent disease, 39.0% of visits were cardiorespiratory. The commonest non-cardiorespiratory visit reasons were non-specific symptoms or signs, endocrine, musculoskeletal, and mental health. In patients with HF with and without COPD, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker/angiotensin receptor-neprilysin inhibitor use was similar, while mineralocorticoid receptor antagonist use was marginally higher with concurrent COPD. Beta-blocker use was initially lower with concurrent COPD compared with HF alone (69.3% vs. 74.0%), but this progressively declined by 2018 (74.5% vs. 73.5%). CONCLUSIONS: The prevalence of HF and COPD continues to rise. Although patients with either or both conditions are high utilizers of primary care, the majority of visits relate to non-cardiorespiratory comorbidities. Medical therapy for HF was similar and the initially lower beta-blocker utilization disappeared over time.

Productivity Decline or Administrative Avalanche? Examining Factors That Shape Changing Workloads in Primary Care.

Background: In Canada, family physicians (FPs) per capita have increased but so have access challenges. We explored changes in population characteristics, service delivery and FP practice that may help understand these trends. Methods: We used linked administrative data in British Columbia to describe changes in patient ages and comorbidities, hospitalizations and receipt of services that may require FP coordination, review and/or follow-up: prescriptions dispensed, laboratory tests, diagnostic imaging (radiology and ultrasound), specialist visits and emergency department visits. We estimate the number of FPs delivering community-based comprehensive care and report changes in service volume per community-based FP visit. Results: Between 1999/2000 and 2017/2018, people experienced fewer days in hospital, but the number of treated comorbidities, day surgeries and other services requiring FP coordination increased over and above the expected levels attributed to population aging. While the total number of FPs per capita have increased, numbers in community-based care have not and visits per physician have fallen. Increases in services that may involve FP coordination per community-based FP visit ranged from 32.2% for diagnostic radiology to 122.1% for lab tests. Conclusion: Findings suggest substantially increased coordination workload per FP visit. Ongoing impacts of population aging and changing service delivery on primary care workload require further examination.

Changes in comprehensiveness of services delivered by Canadian family physicians: Analysis of population-based linked data in 4 provinces.

OBJECTIVE: To describe changes in the comprehensiveness of services delivered by family physicians across service settings and service areas in 4 Canadian provinces, to identify which settings and areas have changed the most, and to compare the magnitude of changes by physician characteristics. DESIGN: Descriptive analysis of province-wide, population-based billing data linked to population and physician registries. SETTING: British Columbia, Manitoba, Ontario, and Nova Scotia. PARTICIPANTS: Family physicians registered to practise in the 1999-2000 and 2017-2018 fiscal years. MAIN OUTCOME MEASURES: Comprehensiveness was measured across 7 service settings (home care, long-term care, emergency departments, hospitals, obstetric care, surgical assistance, anesthesiology) and in 7 service areas consistent with office-based practice (prenatal and postnatal care, Papanicolaou testing, mental health, substance use, cancer care, minor surgery, palliative home visits). The proportion of physicians with activity in each setting and area are reported and the average number of service settings and areas by physician characteristics is described (years in practice, sex, urban or rural practice setting, and location of medical degree training). RESULTS: Declines in comprehensiveness were observed across all provinces studied. Declines were greater for comprehensiveness of settings than for areas consistent with office-based practice. Changes were observed across all physician characteristics. On average across provinces, declines in the number of service settings and service areas were highest among physicians in practice 20 years or longer, male physicians, and physicians practising in urban areas. CONCLUSION: Declining comprehensiveness was observed across all physician characteristics, pointing to changes in the practice and policy contexts in which all family physicians work.

Confirmation of Insertion, Deletion, and Deletion-Insertion Variants Detected by Next-Generation Sequencing.

BACKGROUND: Despite clinically demonstrated accuracy in next generation sequencing (NGS) data, many clinical laboratories continue to confirm variants with Sanger sequencing, which increases cost of testing and turnaround time. Several studies have assessed the accuracy of NGS in detecting single nucleotide variants; however, less has been reported about insertion, deletion, and deletion-insertion variants (indels). METHODS: We performed a retrospective analysis from 2015-2022 of indel results from a subset of NGS targeted gene panel tests offered through the Mayo Clinic Genomics Laboratories. We compared results from NGS and Sanger sequencing of indels observed in clinical runs and during the intra-assay validation of the tests. RESULTS: Results demonstrated 100% concordance between NGS and Sanger sequencing for over 490 indels (217 unique), ranging in size from 1 to 68 basepairs (bp). The majority of indels were deletions (77%) and 1 to 5 bp in length (90%). Variant frequencies ranged from 11.4% to 67.4% and 85.1% to 100% for heterozygous and homozygous variants, respectively, with a median depth of coverage of 2562×. A subset of indels (7%) were located in complex regions of the genome, and these were accurately detected by NGS. We also demonstrated 100% reproducibility of indel detection (n = 179) during intra-assay validation. CONCLUSIONS: Together this data demonstrates that reportable indel variants up to 68 bp can be accurately assessed using NGS, even when they occur in complex regions. Depending on the complexity of the region or variant, Sanger sequence confirmation of indels is usually not necessary if the variants meet appropriate coverage and allele frequency thresholds.

Pan-Canadian study of psychiatric care (PCPC): protocol for a mixed-methods study.

INTRODUCTION: The Canadian population has poor and inequitable access to psychiatric care despite a steady per-capita supply of psychiatrists in most provinces. There is some quantitative evidence that practice style and characteristics vary substantially among psychiatrists. However, how this compares across jurisdictions and implications for workforce planning require further study. A qualitative exploration of psychiatrists' preferences for practice style and the practice choices that result is also lacking. The goal of this study is to inform psychiatrist workforce planning to improve access to psychiatric care by: (1) developing and evaluating comparable indicators of supply of psychiatric care across provinces, (2) analysing variations and changes in the characteristics of the psychiatrist workforce, including demographics and practice style and (3) studying psychiatrist practice choices and intentions, and the factors that lead to these choices. METHODS AND ANALYSIS: A cross-provincial mixed-methods study will be conducted in the Canadian provinces of British Columbia, Manitoba, Ontario and Nova Scotia. We will analyse linked-health administrative data within three of the four provinces to develop comparable indicators of supply and characterise psychiatric services at the regional level within provinces. We will use latent profile analysis to estimate the probability that a psychiatrist is in a particular practice style and map the geographical distribution of psychiatrist practices overlayed with measures of need for psychiatric care. We will also conduct in-depth, semistructured qualitative interviews with psychiatrists in each province to explore their preferences and practice choices and to inform workforce planning. ETHICS AND DISSEMINATION: This study was approved by Ontario Tech University Research Ethics Board (16637 and 16795) and institutions affiliated with the study team. We built a team comprising experienced researchers, psychiatrists, medical educators and policymakers in mental health services and workforce planning to disseminate knowledge that will support effective human resource policies to improve access to psychiatric care in Canada.

Determination of the Duplicated CYP2D6 Allele Using Real-Time PCR Signal: An Alternative Approach.

CYP2D6 duplication has important pharmacogenomic implications. Reflex testing with long-range PCR (LR-PCR) can resolve the genotype when a duplication and alleles with differing activity scores are detected. We evaluated whether visual inspection of plots from real-time-PCR-based targeted genotyping with copy number variation (CNV) detection could reliably determine the duplicated CYP2D6 allele. Six reviewers evaluated QuantStudio OpenArray CYP2D6 genotyping results and the TaqMan Genotyper plots for seventy-three well-characterized cases with three copies of CYP2D6 and two different alleles. Reviewers blinded to the final genotype visually assessed the plots to determine the duplicated allele or opt for reflex sequencing. Reviewers achieved 100% accuracy for cases with three CYP2D6 copies that they opted to report. Reviewers did not request reflex sequencing in 49-67 (67-92%) cases (and correctly identified the duplicated allele in each case); all remaining cases (6-24) were marked by at least one reviewer for reflex sequencing. In most cases with three copies of CYP2D6, the duplicated allele can be determined using a combination of targeted genotyping using real-time PCR with CNV detection without need for reflex sequencing. In ambiguous cases and those with >3 copies, LR-PCR and Sanger sequencing may still be necessary for determination of the duplicated allele.

SARS-CoV-2 testing and COVID-19-related primary care use among people with citizenship, permanent residency, and temporary immigration status: an analysis of population-based administrative data in British Columbia.

OBJECTIVES: Having temporary immigration status affords limited rights, workplace protections, and access to services. There is not yet research data on impacts of the COVID-19 pandemic for people with temporary immigration status in Canada. METHODS: We use linked administrative data to describe SARS-CoV-2 testing, positive tests, and COVID-19 primary care service use in British Columbia from January 1, 2020 to July 31, 2021, stratified by immigration status (citizen, permanent resident, temporary resident). We plot the rates of people tested and confirmed positive for COVID-19 by week from April 19, 2020 to July 31, 2021 across immigration groups. We use logistic regression to estimate adjusted odds ratios of a positive SARS-CoV-2 test, access to testing, and primary care among people with temporary status or permanent residency, compared with people who hold citizenship. RESULTS: A total of 4,146,593 people with citizenship, 914,089 people with permanent residency, and 212,215 people with temporary status were included. Among people with temporary status, 52.1% had "male" administrative sex and 74.4% were ages 20-39, compared with 50.1% and 24.4% respectively among those with citizenship. Of people with temporary status, 4.9% tested positive for SARS-CoV-2 over this period, compared with 4.0% among people with permanent residency and 2.1% among people with citizenship. Adjusted odds of a positive SARS-CoV-2 test among people with temporary status were almost 50% higher (aOR 1.42, 95% CI 1.39, 1.45), despite having half the odds of access to testing (aOR 0.53, 95% CI 0.53, 0.54) and primary care (aOR 0.50, 95% CI 0.49, 0.52). CONCLUSION: Interwoven immigration, health, and occupational policies place people with temporary status in circumstances of precarity and higher health risk. Reducing precarity accompanying temporary status, including regularization pathways, and decoupling access to health care from immigration status can address health inequities.

RéSUMé: OBJECTIFS: Le statut d'immigration temporaire confère des droits, des mesures de protection au travail et un accès aux services limités. Il n'y a pas encore de données de recherche sur les impacts de la pandémie de COVID-19 chez les personnes ayant un statut d'immigration temporaire au Canada. MéTHODE: Nous utilisons des données administratives maillées pour décrire le dépistage du SRAS-CoV-2, les tests positifs et l'utilisation des services de soins de première ligne liés à la COVID-19 en Colombie-Britannique entre le 1er janvier 2020 et le 31 juillet 2021, stratifiées selon le statut d'immigration (citoyenneté, résidence permanente, résidence temporaire). Nous reportons sur des graphiques les taux hebdomadaires de personnes testées et confirmées positives pour la COVID-19 entre le 19 avril 2020 et le 31 juillet 2021 dans les groupes d'immigration. Nous utilisons la régression logistique pour estimer les rapports de cotes ajustés d'un test positif pour le SRAS-CoV-2, de l'accès au dépistage et de l'accès aux soins primaires chez les personnes ayant le statut de résidents temporaires ou permanents comparativement aux personnes ayant la citoyenneté canadienne. RéSULTATS: En tout, 4 146 593 citoyens, 914 089 résidents permanents et 212 215 résidents temporaires ont été inclus. Chez les personnes ayant le statut de résidents temporaires, 52,1 % étaient de sexe administratif « masculin ¼ et 74,4 % avaient entre 20 et 39 ans, contre 50,1 % et 24,4 % respectivement chez les personnes ayant la citoyenneté. Chez les résidents temporaires, 4,9 % avaient obtenu un test positif pour le SRAS-CoV-2 au cours de la période de l'étude, contre 4 % chez les résidents permanents et 2,1 % chez les citoyens. La probabilité ajustée d'un test positif pour le SRAS-CoV-2 chez les personnes ayant le statut de résidents temporaires était près de 50 % plus élevée (RCa 1,42, IC de 95 % 1,39, 1,45), même si leurs probabilités d'accès au dépistage (RCa 0,53, IC de 95 % 0,53, 0,54) et aux soins primaires (RCa 0,50, IC de 95 % 0,49, 0,52) étaient moitié moindres. CONCLUSION: La conjugaison des politiques d'immigration, de santé et de main-d'œuvre met les personnes ayant le statut de résidents temporaires en situation de précarité et de risques accrus pour la santé. La réduction de la précarité qui accompagne le statut temporaire, dont les voies de régularisation, et le découplage entre l'accès aux soins de santé et le statut d'immigration pourraient répondre aux iniquités en santé.

Declining Comprehensiveness of Services Delivered by Canadian Family Physicians Is Not Driven by Early-Career Physicians.

We describe changes in the comprehensiveness of services delivered by family physicians in 4 Canadian provinces (British Columbia, Manitoba, Ontario, Nova Scotia) during the periods 1999-2000 and 2017-2018 and explore if changes differ by years in practice. We measured comprehensiveness using province-wide billing data across 7 settings (home, long-term care, emergency department, hospital, obstetrics, surgical assistance, anesthesiology) and 7 service areas (pre/postnatal care, Papanicolaou [Pap] testing, mental health, substance use, cancer care, minor surgery, palliative home visits). Comprehensiveness declined in all provinces, with greater changes in number of service settings than service areas. Decreases were no greater among new-to-practice physicians.

Changes over time in patient visits and continuity of care among graduating cohorts of family physicians in 4 Canadian provinces.

BACKGROUND: Lack of patient access to family physicians in Canada is a concern. The role of recent physician graduates in this problem of supply of primary care services has not been established. We sought to establish whether career stage or graduation cohort were related to family physician practice volume and continuity of care over time. METHODS: We conducted a retrospective cohort study of family physician practice from 1997/98 to 2017/18. We collected administrative health and physician claims data in British Columbia, Manitoba, Ontario and Nova Scotia. We included all physicians who registered with their respective provincial regulatory colleges as having a medical specialty of family practice or who had billed the provincial health insurance system for patient care as family physicians, or both. We used regression models to isolate the effects of 3-year categories of years in practice (at all career stages), time period and cohort on patient contacts and physician-level continuity of care. RESULTS: Between 1997/98 and 2017/18, the median number of patient contacts per provider per year fell by between 515 and 1736 contacts in the 4 provinces examined. Median contacts peaked at 27-29 years in practice in all provinces, and median physician-level continuity of care increased until 30 or more years in practice. We found no association between graduation cohort and patient contacts or physician-level continuity of care. INTERPRETATION: Recent cohorts of family physicians practise similarly to their predecessors in terms of practice volumes and continuity of care. Because family physicians of all career stages showed declining patient contacts, we suggest that system-wide solutions to recent challenges in the accessibility of primary care in Canada are needed.

Advancing virtual primary care for people with opioid use disorder (VPC OUD): a mixed-methods study protocol.

INTRODUCTION: The emergence of COVID-19 introduced a dual public health emergency in British Columbia, which was already in the fourth year of its opioid-related overdose crisis. The public health response to COVID-19 must explicitly consider the unique needs of, and impacts on, communities experiencing marginalisation including people with opioid use disorder (PWOUD). The broad move to virtual forms of primary care, for example, may result in changes to healthcare access, delivery of opioid agonist therapies or fluctuations in co-occurring health problems that are prevalent in this population. The goal of this mixed-methods study is to characterise changes to primary care access and patient outcomes following the rapid introduction of virtual care for PWOUD. METHODS AND ANALYSIS: We will use a fully integrated mixed-methods design comprised of three components: (a) qualitative interviews with family physicians and PWOUD to document experiences with delivering and accessing virtual visits, respectively; (b) quantitative analysis of linked, population-based administrative data to describe the uptake of virtual care, its impact on access to services and downstream outcomes for PWOUD; and (c) facilitated deliberative dialogues to co-create educational resources for family physicians, PWOUD and policymakers that promote equitable access to high-quality virtual primary care for this population. ETHICS AND DISSEMINATION: Approval for this study has been granted by Research Ethics British Columbia. We will convene PWOUD and family physicians for deliberative dialogues to co-create educational materials and policy recommendations based on our findings. We will also disseminate findings via traditional academic outputs such as conferences and peer-reviewed publications.

Primary care for individuals with serious mental illness (PriSMI): protocol for a convergent mixed methods study.

INTRODUCTION: People with serious mental illness (SMI) have poor health outcomes, in part because of inequitable access to quality health services. Primary care is well suited to coordinate and manage care for this population; however, providers may feel ill-equipped to do so and patients may not have the support and resources required to coordinate their care. We lack a strong understanding of prevention and management of chronic disease in primary care among people with SMI as well as the context-specific barriers that exist at the patient, provider and system levels. This mixed methods study will answer three research questions: (1) How do primary care services received by people living with SMI differ from those received by the general population? (2) What are the experiences of people with SMI in accessing and receiving chronic disease prevention and management in primary care? (3) What are the experiences of primary care providers in caring for individuals with SMI? METHODS AND ANALYSIS: We will conduct a concurrent mixed methods study in Ontario and British Columbia, Canada, including quantitative analyses of linked administrative data and in-depth qualitative interviews with people living with SMI and primary care providers. By comparing across two provinces, each with varying degrees of mental health service investment and different primary care models, results will shed light on individual and system-level factors that facilitate or impede quality preventive and chronic disease care for people with SMI in the primary care setting. ETHICS AND DISSEMINATION: This study was approved by the University of Ottawa Research Ethics Board and partner institutions. An integrated knowledge translation approach brings together researchers, providers, policymakers, decision-makers, patient and caregiver partners and knowledge users. Working with this team, we will develop policy-relevant recommendations for improvements to primary care systems that will better support providers and reduce health inequities.

Implementation of preemptive DNA sequence-based pharmacogenomics testing across a large academic medical center: The Mayo-Baylor RIGHT 10K Study.

PURPOSE: The Mayo-Baylor RIGHT 10K Study enabled preemptive, sequence-based pharmacogenomics (PGx)-driven drug prescribing practices in routine clinical care within a large cohort. We also generated the tools and resources necessary for clinical PGx implementation and identified challenges that need to be overcome. Furthermore, we measured the frequency of both common genetic variation for which clinical guidelines already exist and rare variation that could be detected by DNA sequencing, rather than genotyping. METHODS: Targeted oligonucleotide-capture sequencing of 77 pharmacogenes was performed using DNA from 10,077 consented Mayo Clinic Biobank volunteers. The resulting predicted drug response-related phenotypes for 13 genes, including CYP2D6 and HLA, affecting 21 drug-gene pairs, were deposited preemptively in the Mayo electronic health record. RESULTS: For the 13 pharmacogenes of interest, the genomes of 79% of participants carried clinically actionable variants in 3 or more genes, and DNA sequencing identified an average of 3.3 additional conservatively predicted deleterious variants that would not have been evident using genotyping. CONCLUSION: Implementation of preemptive rather than reactive and sequence-based rather than genotype-based PGx prescribing revealed nearly universal patient applicability and required integrated institution-wide resources to fully realize individualized drug therapy and to show more efficient use of health care resources.

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.

Targeted Genotyping in Clinical Pharmacogenomics: What Is Missing?

Clinical pharmacogenomic testing typically uses targeted genotyping, which only detects variants included in the test design and may vary among laboratories. To evaluate the potential patient impact of genotyping compared with sequencing, which can detect common and rare variants, an in silico targeted genotyping panel was developed based on the variants most commonly included in clinical tests and applied to a cohort of 10,030 participants who underwent sequencing for CYP1A2, CYP2C19, CYP2C9, CYP2D6, CYP3A4, CYP3A5, DPYD, SLCO1B1, TPMT, UGT1A1, and VKORC1. The results of in silico targeted genotyping were compared with the clinically reported sequencing results. Of the 10,030 participants, 2780 (28%) had at least one potentially clinically relevant variant/allele identified by sequencing that would not have been detected in a standard targeted genotyping panel. The genes with the largest number of participants with variants only detected by sequencing were SLCO1B1, DPYD, and CYP2D6, which affected 13%, 6.3%, and 3.5% of participants, respectively. DPYD (112 variants) and CYP2D6 (103 variants) had the largest number of unique variants detected only by sequencing. Although targeted genotyping detects most clinically significant pharmacogenomic variants, sequencing-based approaches are necessary to detect rare variants that collectively affect many patients. However, efforts to establish pharmacogenomic variant classification systems and nomenclature to accommodate rare variants will be required to adopt sequencing-based pharmacogenomics.

Control of Cardiovascular Risk Factors in Patients with Chronic Obstructive Pulmonary Disease.

Rationale: Cardiovascular disease accounts for one-third of deaths in patients with chronic obstructive pulmonary disease (COPD). Better control of cardiovascular risk factors in primary care could improve outcomes. Objectives: To define the prevalence, monitoring, treatment, and control of risk factors in patients with COPD. Methods: Repeated cross-sectional analysis of primary care electronic medical records for all patients with COPD in the Canadian Primary Care Sentinel Surveillance Network from 2013 to 2018 (n = 32,695 in 2018). A control group was matched 1:1 for age, sex, and rural residence (n = 32,638 in 2018). Five risk factors were defined using validated definitions including laboratory results: hypertension, dyslipidemia, diabetes, obesity, and smoking. Results: All risk factors were more common in patients with COPD compared with matched control subjects, including hypertension (52.3% vs. 44.9%), dyslipidemia (62.0% vs. 57.8%), diabetes (25.0% vs. 20.2%), obesity (40.8% vs. 36.8%), and smoking (40.9% vs. 11.4%), respectively. The mean Framingham risk score was 20.6% versus 18.6%, with 53.8% of patients with COPD being high risk (⩾20%). Monitoring of risk factors within the last year in patients with COPD in 2018 was suboptimal: 71.8% hypertension, 39.4% dyslipidemia, 74.5% diabetes, 52.3% obesity. Smoking status was infrequently recorded in the electronic record. In those monitored, guideline recommended targets were achieved in 60.8%, 46.6%, 57.4%, 10.6% and 12.0% for each risk factor. Cardiovascular therapies including angiotensin-converting enzyme inhibitors (69%), statins (69%), and smoking cessation therapies (27%) were underused. Conclusions: In patients with COPD, major cardiovascular risk factors are common, yet inadequately monitored, undertreated, and poorly controlled. Strategies are needed to improve comprehensive risk factor management proven to reduce cardiovascular morbidity and mortality.