Administrative Healthcare Databases Research Articles

The Intergenerational Transfer of Mental Disorders: A Population-Based Multigenerational Linkage Study: Le transfert intergénérationnel des troubles mentaux : une étude sur les liens multigénérationnels basée sur la population.

The aetiology of mental disorders involves genetic and environmental factors, both reflected in family health history. We examined the intergenerational transmission of multiple mental disorders from parents and grandparents using population-based, objectively measured family histories. This population-based retrospective cohort study used administrative healthcare databases in Manitoba, Canada and included adults living in Manitoba from 1977 to 2020 with linkages to at least one parent and one grandparent. Index date was when individuals turned 18 or 1 April 1977, whichever occurred later. Mental disorder diagnoses (mood and anxiety, substance use and psychotic disorders) were identified in individuals, parents and grandparents from hospitalization and outpatient records. Cox proportional hazards regression models included sociodemographic characteristics, individual's comorbidity and mental disorder history in a grandparent, mother and father. Of 109,359 individuals with no mental disorder prior to index date, 47.1% were female, 36.3% had a mental disorder during follow-up, and 90.9% had a parent or grandparent with a history of a mental disorder prior to the index date. Both paternal and maternal history of a mental disorder increased the risk of the disorder in individuals. Psychotic disorders had the strongest association with parental history and were mostly influenced by paternal (hazards ratio [HR] 3.73, 95% confidence interval [CI] 2.99 to 4.64) compared to maternal history (HR 2.23, 95% CI, 1.89 to 2.64). Grandparent history was independently associated with the risk of all mental disorders but had the strongest influence on substance use disorders (HR 1.42, 95% CI, 1.34 to 1.50). Parental history of mental disorders was associated with an increased risk of all mental disorders. Grandparent history of mental disorders was associated with a small risk increase of the disorders above and beyond parental history influence. This three-generation study further highlights the need for family-based interventional programs in families affected by mental disorders. The Intergenerational Transfer of Mental Illnesses.

Validation Study of Cardiovascular International Statistical Classification of Diseases and Related Health Problems, Tenth Edition, Australian Modification (ICD-10-AM) Codes in Administrative Healthcare Databases (ANZACS–QI 77)

Administrative healthcare databases can be utilised for research. The accuracy of the International Statistical Classification of Diseases and Related Health Problems, Tenth Edition, Australian Modification (ICD-10-AM) coding of cardiovascular conditions in New Zealand is not known and requires validation. International Statistical Classification of Diseases and Related Health Problems, Tenth Edition, Australian Modification coded discharges for acute coronary syndrome (ACS), heart failure (HF) and atrial fibrillation (AF), in both primary and secondary diagnostic positions, were identified from four district health boards between 1 January 2019 and 31 June 2019. A sample was randomly selected for retrospective clinician review for evidence of the coded diagnosis according to contemporary diagnostic criteria. Positive predictive values (PPVs) for ICD-10-AM coding vs clinician review were calculated. This study is also known as All of New Zealand, Acute Coronary Syndrome-Quality Improvement (ANZACS-QI) 77. A total of 600 cases (200 for each diagnosis, 5.0% of total identified cases) were reviewed. The PPV of ACS was 93% (95% confidence interval [CI] 89%-96%), HF was 93% (95% CI 89%-96%) and AF was 96% (95% CI 92%-98%). There were no differences in PPV between district health boards. PPV for ACS were lower in Māori vs non-Māori (72% vs 96%; p=0.004), discharge from non-Cardiology vs Cardiology services (89% vs 96%; p=0.048) and ICD-10-AM coding for unstable angina vs myocardial infarction (81% vs 95%; p=0.011). PPV for HF were higher in the primary vs secondary diagnostic position (100% vs 89%; p=0.001). The PPVs of ICD-10-AM coding for ACS, HF, and AF were high in this validation study. ICD-10-AM coding can be used to identify these diagnoses in administrative databases for the purposes of healthcare evaluation and research.

A study protocol for identifying aging trajectories toward chronic neurodegenerative diseases by means of Marche regional administrative databases - TREND project.

People are living longer but an increasing number of older people experience chronicity and disability in the latest years of their life. The Marche region is one of the Italian regions where people live the longest lives; therefore, the number of people with age-related chronic diseases is expected to be at least similar, if not higher, compared to the rest of Italy. The identification of the aging trajectories is of huge interest in the arena of public health. Administrative healthcare databases represent valuable reservoirs for reconstructing the trajectories of aging. Here, we present the protocol for a study (TREND project) aimed to integrate existing administrative databases into a Marche regional dataset in order to estimate the prevalence and incidence rates of age-related neurodegenerative diseases (ND), with a specific focus on Parkinsonism and Dementia. The TREND Project is a retrospective cross-sectional study. The source population includes permanent residents in the Marche region aged 40 years and older. A minimal dataset has been built up linking data on drug prescriptions, outpatient services, and diagnosis for hospital admission, from 2014 to 2021 in the Marche Region. Data on clinical outcomes (re-hospitalization, mortality, comorbidities), and therapeutic approaches (drugs and medicines) have been integrated with state-of-the-art statistical methods to define patients into different risk clusters and to analyze the aging trend by assessing the Comorbidity Index (CI) as a proxy for chronicity. Our research contributes to the integration of existing administrative databases on ND to create a Marche regional ND database, support regional health policy, and better understand patients' needs and their aging trajectories. This approach could be implemented also at the National level. Moreover, by linking different administrative data sources, this study sheds light on important issues related to ND, such as early-onset dementia; ethical aspects such as anticipated wills; problems of dementia in patients still in the job market, etc. The results of this study will contribute to the successful implementation of integrated care for patients affected by ND at regional or national levels.

Incidence and Risk Factors Epilepsy in Patients with Dementia: A Population-Based Study Using Regional Healthcare Databases in Umbria.

Dementia is prevalent among the elderly, also representing a risk for seizures/epilepsy. Estimations of epilepsy risk in dementia patients are not widely available. Our research aims to ascertain the incidence of epilepsy and its associated risk factors in subjects with dementia in the Umbria region, based on data from healthcare databases. In this retrospective study based on the healthcare administrative database of Umbria, we identified all patients diagnosed with dementia from 2013 to 2017, based on ICD-9-CM codes. For epilepsy ascertainment, we used a validated algorithm that required an EEG and the prescription of one or more anti-seizure medications post-dementia diagnosis. A case-control analysis was conducted, matching five non-dementia subjects by gender and age to each dementia patient. Cox proportional hazards models were then utilized in the analysis. We identified 7,314 dementia cases, also including 35,280 age- and sex-matched control subjects. Out of patients with dementia, 148 individuals (2.02%) were diagnosed with epilepsy. We observed a progressive increase in the cumulative incidence of seizures over time, registering 1.45% in the first year following the diagnosis, and rising to 1.96% after three years. Analysis using Cox regression revealed a significant association between the development of epilepsy and dementia (HR = 4.58, 95% CI = 3.67-5.72). Additional risk factors were male gender (HR = 1.35, 95% CI = 1.07-1.69) and a younger age at dementia onset (HR = 1.03, 95% CI=1.02-1.04). Dementia increases epilepsy risk, especially with early onset and male gender. Clinicians should have a low threshold to suspect seizures in dementia cases.

Study protocol for the development and validation of a clinical prediction tool to estimate the risk of 1-year mortality among hospitalized patients with dementia.

Patients with dementia and their caregivers could benefit from advance care planning though may not be having these discussions in a timely manner or at all. A prognostic tool could serve as a prompt to healthcare providers to initiate advance care planning among patients and their caregivers, which could increase the receipt of care that is concordant with their goals. Existing prognostic tools have limitations. We seek to develop and validate a clinical prediction tool to estimate the risk of 1-year mortality among hospitalized patients with dementia. The derivation cohort will include approximately 235,000 patients with dementia, who were admitted to hospital in Ontario from April 1st, 2009, to December 31st, 2017. Predictor variables will be fully prespecified based on a literature review of etiological studies and existing prognostic tools, and on subject-matter expertise; they will be categorized as follows: sociodemographic factors, comorbidities, previous interventions, functional status, nutritional status, admission information, previous health care utilization. Data-driven selection of predictors will be avoided. Continuous predictors will be modelled as restricted cubic splines. The outcome variable will be mortality within 1 year of admission, which will be modelled as a binary variable, such that a logistic regression model will be estimated. Predictor and outcome variables will be derived from linked population-level healthcare administrative databases. The validation cohort will comprise about 63,000 dementia patients, who were admitted to hospital in Ontario from January 1st, 2018, to March 31st, 2019. Model performance, measured by predictive accuracy, discrimination, and calibration, will be assessed using internal (temporal) validation. Calibration will be evaluated in the total validation cohort and in subgroups of importance to clinicians and policymakers. The final model will be based on the full cohort. We seek to develop and validate a clinical prediction tool to estimate the risk of 1-year mortality among hospitalized patients with dementia. The model would be integrated into the electronic medical records of hospitals to automatically output 1-year mortality risk upon hospitalization. The tool could serve as a trigger for advance care planning and inform access to specialist palliative care services with prognosis-based eligibility criteria. Before implementation, the tool will require external validation and study of its potential impact on clinical decision-making and patient outcomes. NCT05371782.

Applicability and impact of the COMPASS trial in a Canadian population of patients with atherosclerotic disease

Background and aimsIn the COMPASS trial, low-dose rivaroxaban with aspirin improved cardiovascular outcomes in patients with atherosclerotic cardiovascular disease (ASCVD). We aimed to assess the potential clinical implications of this therapy in a generalizable population. Methods and ResultsA retrospective cohort of adults with ASVCD was formed using healthcare administrative databases in Alberta, Canada (population 4.4 million). Patients with a new diagnosis between 2008 and 2019 formed the epidemiological cohort (n = 224,600) and those with long-term follow-up (>5 years) formed the outcomes cohort (n = 232,460). The primary outcome of major adverse cardiovascular events (MACE) was assessed and categorized based on the COMPASS trial eligibility. In the outcomes cohort, 77% had only coronary artery disease, 15% had only peripheral artery disease, and 8% had both. Of those, 37% met the COMPASS trial eligibility criteria, 36% met exclusion criteria and 27% did not meet inclusion criteria. Over a median of 7.8 years, the COMPASS exclusion group demonstrated the highest rate of MACE (5.9 per 100 person-years), following by the eligible group and the group that did not meet COMPASS inclusion criteria (3.1 and 1.4 per 100 person-years respectively). The expected net clinical benefit of antithrombotic therapy in the eligible group was 5.6 fewer events per 1000 person-years. ConclusionsIn a real-world population of 4.4 million adults, there are roughly 20,000 new cases of ASVCD diagnosed yearly, with ∼40% being eligible for the addition of low-dose rivaroxaban therapy to antiplatelet therapy. The theoretical implementation of dual antithrombotic treatment in this population could result in a substantial reduction in cardiovascular morbidity and mortality.

Risk of serious infection associated with different classes of targeted therapies used in psoriatic arthritis: a nationwide cohort study from the French Health Insurance Database (SNDS)

ObjectiveTo assess the risk of serious infection associated with different targeted therapies for psoriatic arthritis (PsA) in real-world settings.MethodsThis nationwide cohort study used the administrative healthcare database of the French...

Defining pre-emptive living kidney donor transplantation as a quality indicator

Quality indicators in kidney transplants are needed to identify care gaps and improve access to transplants. We used linked administrative health care databases to examine multiple ways of defining pre-emptive living donor kidney transplants, including different patient cohorts and censoring definitions. We included adults from Ontario, Canada with advanced chronic kidney disease between January 1, 2013, to December 31, 2018. We created 4 unique incident patient cohorts, varying the eligibility by the risk of progression to kidney failure and whether individuals had a recorded contraindication to kidney transplant (eg, home oxygen use). We explored the effect of 4 censoring event definitions. Across the 4 cohorts, size varied substantially from 20 663 to 9598 patients, with the largest reduction (a 43% reduction) occurring when we excluded patients with ≥1 recorded contraindication to kidney transplantation. The incidence rate (per 100 person-years) of pre-emptive living donor kidney transplant varied across cohorts from 1.02 (95% CI: 0.91-1.14) for our most inclusive cohort to 2.21 (95% CI: 1.96-2.49) for the most restrictive cohort. Our methods can serve as a framework for developing other quality indicators in kidney transplantation and monitoring and improving access to pre-emptive living donor kidney transplants in health care systems.

P986 Effectiveness of the adjuvanted recombinant zoster vaccine (RZV) in preventing herpes zoster (HZ) among patients ≥50 years of age with Inflammatory Bowel Disease in the United States: A retrospective real-world database analysis from 2018 to 2021

Abstract Background Patients with inflammatory bowel disease (IBD) are at higher risk of developing HZ compared to general population.1 The US Food and Drug Administration (FDA) approved RZV for adults ≥50 years of age (YOA) in Oct 2017 and for adults ≥18 YOA who are or will be at increased risk of HZ due to immunodeficiency or immunosuppression, as patients with IBD, in Jul 2021. This study addresses an information gap for RZV vaccine effectiveness (VE) in preventing HZ among IBD patients ≥50 YOA. Methods We conducted a retrospective matched cohort study using the Optum Clinformatics Data Mart healthcare administrative claims database from Jan 2018 to Dec 2021. Patients ≥50 YOA with IBD who received 2 RZV doses with dose interval ≥28 days (RZV [2-dose] cohort) were 1:3 matched to their unvaccinated counterparts (non-RZV cohort) by age, medication category, and other confounders (propensity score). The index date for RZV cohort was the date of the second dose and for non-RZV cohort was the same index date as their vaccinated match. Follow-up started from index date +30 days until earliest date of HZ occurrence, end of enrolment, death, receipt of HZ vaccine, or study end. The first HZ episode during follow-up was identified using an algorithm that included ICD-10 diagnosis code, inpatient or outpatient claims and/or HZ antiviral medication used within 7 days pre/post-HZ diagnosis. Incidence rates (IRs) of HZ were calculated overall, stratified by condition (ulcerative colitis [UC], Crohn’s disease [CD]) and age. Cox hazards models were used to estimate overall and stratified hazard ratios (HRs). VE (%) was calculated as (1−HR) × 100. A similar approach was used to evaluate VE for patients who received 1 RZV dose. Results We identified 6501 RZV vaccinated and 19962 matched unvaccinated IBD patients who were included in the 2-dose analysis (Table). The IR of HZ was 2.92/1000 person-years (PY) in the RZV cohort and 10.96/1000 PY in the non-RZV cohort, resulting in a VE of 73.4% (95% confidence intervals [CIs]: 60.8-82.0) for IBD patients (Figure). VE against HZ was 63.5% (95%CIs: 43.0-76.6) and 85.7% (95%CIs: 69.5-93.3) in UC and CD 2-dose cohorts. IRs and VE stratified by condition and age are presented in Figure. Adjusted VE for IBD patients who received 1 RZV dose was 63.4% (95%CIs: 24.9-82.2). Conclusion Our analysis provides real-world evidence that RZV vaccination is effective in preventing HZ in IBD patients ≥50 YOA and reduce the burden in this population with increased risk of HZ. These findings are consistent with the available literature on RZV effectiveness in patients with IBD, suggesting that this population could greatly benefit from RZV vaccination. 1. Yun H et al, Arthritis Rheumatol 2016;68:2328-37 Funding GSK

Patterns of opioid use in New Zealand older adults, 2007-2018.

Opioid use has increased globally, dramatically increasing opioid overdose, dependence, abuse and mortality. Limited research is available on opioid use patterns in older adults in New Zealand and internationally. This study aims to address this gap by determining the incidence and prevalence of opioid use among older adults (age ≥65 years) in New Zealand from 2007 to 2018. This was a population-based retrospective cohort study conducted using New Zealand national administrative healthcare databases. The annual opioid use incidence (2008-2018) and prevalence (2007-2018) in older adults were determined and stratified by sex, age, and opioid type and strength. We used descriptive statistics to summarise the patterns of opioid dispensing. Data analysis was conducted using MS Excel, and data linking was performed using SQL software. A total of 820,349 older adults were initiated on opioids during the study period. The overall incidence of opioid use in older adults showed a steady increase from 2008 to 2015; similarly, the prevalence steadily increased from 2007 to 2015, and thereafter, both rates fluctuated. A slight decrease in both prevalence and incidence rates was observed in 2018. Codeine and tramadol were the most commonly dispensed opioids during the study period. Females had a higher incidence and prevalence of all opioids than males. The incidence and prevalence of opioid dispensing increased in New Zealand older adults over time. Monitoring the trends of opioid use in older adults is critical to enable clinicians and policymakers to deliver early interventions to prevent future opioid-related adverse events.

Clinical evaluation of code‐based algorithms to identify patients with pulmonary arterial hypertension in healthcare databases

AbstractPulmonary arterial hypertension (PAH) is a rare subgroup of pulmonary hypertension (PH). Claims and administrative databases can be particularly important for research in rare diseases; however, there is a lack of validated algorithms to identify PAH patients using administrative codes. We aimed to measure the accuracy of code‐based PAH algorithms against the true clinical diagnosis by right heart catheterization (RHC). This study evaluated algorithms in patients who were recorded in two linkable data assets: the Stanford Healthcare administrative electronic health record database and the Stanford Vera Moulton Wall Center clinical PH database (which records each patient's RHC diagnosis). We assessed the sensitivity and specificity achieved by 16 algorithms (six published). In total, 720 PH patients with linked data available were included and 558 (78%) of these were PAH patients. Algorithms consisting solely of a P(A)H‐specific diagnostic code classed all or almost all PH patients as PAH (sensitivity >97%, specificity <12%) while multicomponent algorithms with well‐defined temporal sequences of procedure, diagnosis and treatment codes achieved a better balance of sensitivity and specificity. Specificity increased and sensitivity decreased with increasing algorithm complexity. The best‐performing algorithms, in terms of fewest misclassified patients, included multiple components (e.g., PH diagnosis, PAH treatment, continuous enrollment for ≥6 months before and ≥12 months following index date) and achieved sensitivities and specificities of around 95% and 38%, respectively. Our findings help researchers tailor their choice and design of code‐based PAH algorithms to their research question and demonstrate the importance of including well‐defined temporal components in the algorithms.

Comparison of Acute Health Care Utilization Between Patients Receiving In-Center Hemodialysis and the General Population: A Population-Based Matched Cohort Study From Ontario, Canada.

Patients receiving maintenance hemodialysis have multiple comorbidities and are at high risk of presenting to the hospital. However, the incidence and cost of acute health care utilization in the in-center hemodialysis population and how this compares with other populations is poorly understood. To determine the rate, pattern, and cost of emergency department visits and hospitalizations in patients receiving in-center hemodialysis compared with a matched general population. Population-based matched cohort study. We used linked administrative health care databases from Ontario, Canada. We included 25 379 patients (incident and prevalent) receiving in-center hemodialysis between January 1, 2010, and December 31, 2018. Patients were matched on birth date (±2 years), sex, and cohort entry date using a 1:4 ratio to 101 516 individuals from the general population. Our primary outcomes were emergency department visits (allowing for multiple visits per individual) and hospital admissions from the emergency department. We also assessed all-cause hospitalizations, all-cause readmissions within 30 days of discharge from the original hospitalization, length of stay for hospital admissions (including multiple visits per individual), and the financial cost of these admissions. We presented the rate, percentage, median (25th, 75th percentiles), and incidence rate per 1000 person-years for emergency department visits and hospitalizations. Individual-level health care costs for emergency department visits and all-cause hospitalization were estimated using resource intensity weights multiplied by the cost per weighted case. Patients receiving in-center hemodialysis had substantially more comorbidities (eg, diabetes) than the matched general population. Eighty percent (n = 20 309) of patients receiving in-center hemodialysis had at least 1 emergency department visit compared with 56% (n = 56 452) of individuals in the matched general population, over a median follow-up of 1.8 years (25th, 75th percentiles: 0.7, 3.6) and 5.2 (2.5, 8.4) years, respectively. The incidence rate of emergency department visits, allowing for multiple visits per individual, was 2274 per 1000 person-years (95% confidence interval [CI]: 2263, 2286) for patients receiving in-center hemodialysis, which was almost 5 times as high as the matched general population (471 per 1000 person-years; 95% CI: 469, 473). The rate of hospital admissions from the emergency department and the rate of all-cause hospital admissions in the in-center hemodialysis population was more than 7 times as high as the matched general population (hospital admissions from the emergency department: 786 vs 101 per 1000 person-years; all-cause hospital admissions: 1056 vs 139 per 1000 person-years). The median number of all-cause hospitalization days per patient year was 4.0 (0, 16.5) in the in-center hemodialysis population compared with 0 (0, 0.5) in the matched general population. The cost per patient-year for emergency department visits in the in-center hemodialysis population was approximately 5.5 times as high as the matched general population while the cost of hospitalizations in the in-center hemodialysis population was approximately 11 times as high as the matched general population (emergency department visits: CAN$ 1153 vs CAN$ 209; hospitalizations: CAN$ 21 151 vs CAN$ 1873 [all costs in 2023 CAN$]). External generalizability and we could not determine whether emergency department visits and hospitalizations were preventable. Patients receiving in-center hemodialysis have high acute health care utilization. These results improve our understanding of the burden of disease and the associated costs in the in-center hemodialysis population, highlight the need to improve acute outcomes, and can aid health care capacity planning. Additional research is needed to address the risk of hospitalization after controlling for patient comorbidities. This is not applicable as this is a population-based matched cohort study and not a clinical trial.

High-Throughput Computing to Automate Population-Based Studies to Detect the 30-Day Risk of Adverse Outcomes After New Outpatient Medication Use in Older Adults with Chronic Kidney Disease: A Clinical Research Protocol.

Safety issues are detected in about one third of prescription drugs in the years following regulatory agency approval. Older adults, especially those with chronic kidney disease, are at particular risk of adverse reactions to prescription drugs. This protocol describes a new approach that may identify credible drug-safety signals more efficiently using administrative health care data. To use high-throughput computing and automation to conduct 700+ drug-safety cohort studies in older adults in Ontario, Canada. Each study will compare 74 acute (30-day) outcomes in patients who start a new prescription drug (new users) to a group of nonusers with similar baseline health characteristics. Risks will be assessed within strata of baseline kidney function. The studies will be population-based, new-user cohort studies conducted using linked administrative health care databases in Ontario, Canada (January 1, 2008, to March 1, 2020). The source population for these studies will be residents of Ontario aged 66 years or older who filled at least one outpatient prescription through the Ontario Drug Benefit (ODB) program during the study period (all residents have universal health care, and those aged 65+ have universal prescription drug coverage through the ODB). We identified 3.2 million older adults in the source population during the study period and built 700+ initial medication cohorts, each containing mutually exclusive groups of new users and nonusers. Nonusers were randomly assigned cohort entry dates that followed the same distribution of prescription start dates as new users. Eligibility criteria included a baseline estimated glomerular filtration rate (eGFR) measurement within 12 months before the cohort entry date (median time was 71 days before cohort entry in the new user group), no prior receipt of maintenance dialysis or a kidney transplant, and no prior prescriptions for drugs in the same subclass as the study drug. New users and nonusers will be balanced on ~400 baseline health characteristics using inverse probability of treatment weighting on propensity scores within 3 strata of baseline eGFR: ≥60, 45 to <60, <45 mL/min per 1.73 m2. We will compare new user and nonuser groups on 74 clinically relevant outcomes (17 composites and 57 individual outcomes) in the 30 days after cohort entry. We used a prespecified approach to identify these 74 outcomes. In each cohort, we will obtain eGFR-stratum-specific weighted risk ratios and risk differences using modified Poisson regression and binomial regression, respectively. Additive and multiplicative interaction by eGFR category will be examined. Drug-outcome associations that meet prespecified criteria (identified signals) will be further examined in additional analyses (including survival, negative-control exposure, and E-value analyses) and visualizations. The initial medication cohorts had a median of 6120 new users per cohort (interquartile range: 1469-38 839) and a median of 1 088 301 nonusers (interquartile range: 751 697-1 267 009). Medications with the largest number of new users were amoxicillin trihydrate (n = 1 000 032), cephalexin (n = 571 566), prescription acetaminophen (n = 571 563), and ciprofloxacin (n = 504,374); 19% to 29% of new users in these cohorts had an eGFR <60 mL/min per 1.73 m2. Despite our use of robust techniques to balance baseline indicators and to control for confounding by indication, residual confounding will remain a possibility. Only acute (30-day) outcomes will be examined. Our data sources do not include nonprescription (over-the-counter) drugs or drugs prescribed in hospitals and do not include outpatient prescription drug use in children or adults <65 years. This accelerated approach to conducting postmarket drug-safety studies has the potential to more efficiently detect drug-safety signals in a vulnerable population. The results of this protocol may ultimately help improve medication safety.

Effectiveness of a Fourth COVID-19 mRNA Vaccine Dose Against the Omicron Variant in Solid Organ Transplant Recipients.

The effectiveness of booster doses of COVID-19 vaccines in solid organ transplant recipients is unclear. We conducted a population-based matched cohort study using linked administrative healthcare databases from Ontario, Canada to estimate the marginal vaccine effectiveness of a fourth versus third dose of the BNT162b2 and mRNA-1273 vaccines against clinically important outcomes (ie, hospitalization or death) and infection during the era of the Omicron variant. We matched 3120 solid organ transplant recipients with a third COVID-19 vaccine dose (reference) to 3120 recipients with a fourth dose. Recipients were matched on the third dose date (±7 d). We used a multivariable Cox proportional hazards model to estimate the marginal vaccine effectiveness with outcomes occurring between December 21, 2021 and April 30, 2022. The cumulative incidence of COVID-19-related hospitalization or death was 2.8% (95% confidence interval [CI], 2.0-3.7) in the third dose group compared with 1.1% (95% CI, 0.59-1.8) in the fourth dose group after 84 d of follow-up (P < 0.001). The adjusted marginal vaccine effectiveness was 70% (95% CI, 47-83) against clinically important outcomes and 39% (95% CI, 21-52) against SARS-CoV-2 infection. Compared with a third dose, a fourth dose of the COVID-19 vaccine was associated with improved protection against hospitalization, death, and SARS-CoV-2 infection during the Omicron era. Results highlight the importance of a booster COVID-19 vaccine dose in solid organ transplant recipients.

Influence of sex on the persistence of different classes of targeted therapies for psoriatic arthritis: a cohort study of 14 778 patients from the French health insurance database (SNDS)

BackgroundSex differences in phenotype presentation, disease trajectory and treatment response in psoriatic arthritis (PsA) have been reported. Nevertheless, whether classes of targeted therapies differentially affect men and women with PsA...

Increased mortality in patients with RA-associated interstitial lung disease: data from a French administrative healthcare database

ObjectivesInterstitial lung disease (ILD) is a severe extra-articular manifestation of rheumatoid arthritis (RA). The objectives of this study were to estimate mortality rate in patients with RA-ILD and identify factors...

Assessing the Impact of Marginalization on Survival for Patients Undergoing Allogeneic Stem Cell Transplant in Ontario, Canada

Background Allogeneic hematopoietic stem cell transplants (allo-SCT) are potentially life-saving interventions used to treat hematologic disorders. Recent studies have shown that living in rural areas may predict worse outcomes after allo-SCT. Marginalization, a term that encompasses social and health-related factors affecting individuals, is predictive of adverse health outcomes. The Ontario Marginalization Index (ON-Marg), an administrative index using variables obtained from census data, was used to identify marginalization status (quintile 1-least marginalized; quintile 5-most marginalized) encompassing four domains: residential instability (area-level concentrations of people who experience high rates of family or housing instability), material deprivation (area-level concentrations of inability for individuals and communities to access and attain basic material needs), dependency (area-level concentrations of people who do not have income from employment), and ethnic concentration (area-level concentrations of people who are recent immigrants and/or a visible minority). In a publicly-funded healthcare context, it is important to know how marginalization impacts survival for patients undergoing allo-SCT. Methods We performed a retrospective population-based study using administrative healthcare databases from Ontario, Canada. Patients were included if they were 18 years or older at the time of allo-SCT, and had undergone allo-SCT for acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) or acute lymphoblastic leukemia (ALL) between 2010 and 2022. Patients were excluded if they were a non-Ontario resident at the time of allo-SCT and as a result lacked ON-Marg data. Patients who received allo-SCT for a different indication were excluded. The primary outcome of this study was 2-year overall survival (OS) from time of transplant to death or end of the study period, based on ON-Marg quintiles. Multivariable Cox regression analysis was used to identify baseline characteristics associated with OS, with ON-Marg as the main exposure. Results A total of 1961 patients underwent allo-SCT for AML/MDS/ALL. The median age of patients undergoing allo-SCT was 55 years (IQR 43-63), and 55% of patients were male. 40% of patients had high aggregated diagnosis group (ADG) comorbidity burden, and a majority of patients (64%) lived within 50 kilometers (km) from the transplant center, with a mean distance of 33 km in the entire study population. The distribution of patients across each quintile of marginalization was not always uniform. For ethnic concentration, 24% of patients were in quintile 5, with 17% of patients in quintile 1. For dependency, 19% of patients were in quintile 5, and 25% of patients were in quintile 1. During the follow-up period, 43% of patients (n = 842) died. 2-year OS was not significantly different across all quintiles of the ethnic concentration domain of marginalization ( Figure 1A). 2-year OS was worse (HR 1.27, 95% CI 1.02-1.57) for patients in quintile 4 compared to quintile 1 of the dependency domain of marginalization ( Figure 1B). This effect persisted in multivariable logistic regression analyses accounting for other demographic variables ( Table 1). Increased age and a higher comorbidity index were significantly associated with worse survival across all domains. Patients with ALL had worse outcomes compared to patients with AML/MDS across all domains of marginalization. There was also a trend toward patients living &amp;gt;200 km from the transplant center having an increased risk of death compared to patients living less than 50 km from the center (HR 1.24, 95% CI 1.00-1.54). Conclusion This study shows that 2-year OS after allo-SCT for AML/MDS/ALL was not affected by marginalization quintile of ethnic concentration. This is in keeping with other published data suggesting that outcomes after allo-SCT are not impacted by socioeconomic factors such as race. Patients in quintile 4 of dependency had worse outcomes than patients in quintile 1, suggesting that employment and income support are crucial to successful patient outcomes. A majority of patients who underwent allo-SCT lived in close proximity to the transplant center. Transplant outcomes in general do not appear to vary based on marginalization status, and it is therefore crucial that all patients who may benefit receive allo-SCT regardless of demographics or distance to treatment centers.

Impact of the coronavirus disease 2019 pandemic on equity of access to hip and knee replacements: a population-level study.

The COVID-19 pandemic had innumerable impacts on healthcare delivery. In Canada, this included limitations on inpatient capacity, which resulted in an increased focus on outpatient surgery for non-emergent cases such as joint replacements. The objective of this study was to assess whether the pandemic and the shift towards outpatient surgery had an impact on access to joint replacement for marginalized patients. Data from Ontario's administrative healthcare databases were obtained for all patients undergoing an elective hip or knee replacement between January 1, 2018 and August 31, 2021. All surgeries performed before March 15, 2020 were classified as "pre-COVID," while all procedures performed after that date were classified as "post-COVID." The Ontario Marginalization Index domains were used to analyze proportion of marginalized patients undergoing surgery pre- and post-COVID. A total of 102,743 patients were included-42,812 hip replacements and 59,931 knee replacements. There was a significant shift towards outpatient surgery during the post-COVID period (1.1% of all cases pre-COVID to 13.2% post-COVID, p < 0.001). In the post-COVID cohort, there were significantly fewer patients from some marginalized groups, as well as fewer patients with certain co-morbidities, such as congestive heart failure and chronic obstructive pulmonary disease. The most important finding of this population-level database study is that, compared to before the COVID-19 pandemic, there has been a change in the profile of patients undergoing hip and knee replacements in Ontario, specifically across a range of indicators. Fewer marginalized patients are undergoing joint replacement surgery since the COVID-19 pandemic. Further monitoring of access to joint replacement surgery is required in order to ensure that surgery is provided to those who are most in need.

Assessing the Impact of Marginalization on Survival for Patients Undergoing Autologous Stem Cell Transplant in Ontario, Canada

Background Autologous hematopoietic stem cell transplants (ASCT) are potentially life-saving interventions used to treat hematologic disorders. However, it is unclear if socioeconomic disparities impact the patient benefit from ASCT. Recent evidence suggests lower rates of ASCT for patients living in rural settings and for ethnic minority groups. Few population-based studies have assessed comprehensive indices of marginalization as predictors of outcomes after ASCT. In a publicly funded healthcare setting, it is crucial to understand if various aspects of marginalization interact to ultimately impact survival for patients undergoing ASCT. Methods We performed a retrospective population-based study using administrative healthcare databases from Ontario, Canada. Patients were included if they had undergone auto-SCT for lymphoma or myeloma between 2010 and 2022. The Ontario Marginalization Index (ON-Marg), created using Canadian census data, explores four key aspects of marginalization: residential instability (referring to housing instability), material deprivation (referring to individual and community abilities to access basic material needs), dependency (referring to lack of income from employment), and ethnic concentration (referring to individuals who are recent immigrants or belonging to a visible minority group). The primary outcome was 2-year overall survival (OS) from time of transplant to death or end of the study period stratified by ON-Marg quintiles. Multivariable Cox regression analyses were used to identify baseline characteristics associated with OS. Results A total of 1886 patients underwent ASCT for lymphoma and 2842 patients underwent ASCT for myeloma. The median age of patients undergoing ASCT for lymphoma was 56 years (IQR 44-63) and 64% of patients were male. 22% of patients had high aggregated diagnosis group (ADG) comorbidity scores and 15% had a prior history of cancer. 2-year OS for patients in the fifth quintile of marginalization of the ethnic concentration index was 80.4% (95% CI 75.9-84.1%), compared to 72.3% (95% CI 67.5-76.5%) in the first quintile ( Figure 1A). This survival advantage (HR 0.71, 95% CI 0.52-0.99) persisted after adjusting for age, comorbidity burden, and distance to hospital ( Table 1). Patients who lived 150-200 km from the transplant center had a lower risk of death compared to patients who lived within 50km of the hospital (HR 0.53, 95% CI 0.30-0.94). 2-year OS was not significantly different for patients in quintile 5 of marginalization of the dependency index compared to quintile 1 (HR 1.25, 95% CI 0.93-1.67), with similarly no significant difference across residential instability or material deprivation. The median age of patients undergoing ASCT for myeloma was 61 years (IQ 55-66), and 25% of patients had high ADG comorbidity scores. OS was not significantly different across all domains of marginalization, with a 2-year OS of 88.8% (95% CI 85.8-91.2%) in quintile 1 of ethnic deprivation and 87.5% (95% CI 84.7-89.8%) in quintile 5 ( Figure 1B). Higher comorbidity scores were associated with an increased risk of death compared to lower comorbidity scores (HR 2.17, 95% CI 1.58-2.98), as shown in Table 1. Living 150-200 km from the transplant center was associated with worse OS (HR 1.74, 95% CI 1.24-2.45). Conclusion This is one of the first studies to examine the effect of marginalization on outcomes after ASCT in a publicly-funded healthcare system. For patients undergoing ASCT for lymphoma, patients in quintile 5 of ethnic concentration had improved 2-year OS compared to patients in quintile 1. One possible explanation is the healthy immigrant effect, whereby immigrant patients are healthier than their Canadian-born counterparts. Cultural factors may also have a protective role. Patients undergoing ASCT for lymphoma who lived farther from the transplant center had a lower risk of death; these patients may be more highly selected based on fitness and disease biology to be referred for transplant compared to patients who live within close proximity. For patients undergoing ASCT for myeloma, 2-year OS was not affected by ethnic concentration quintile. The decision for referral for ASCT for myeloma is not as subjective, with ASCT commonly used in the first-line setting for eligible patients regardless of distance, which likely accounts for this difference. Further work is needed to ensure that all eligible patients receive ASCT.

Outcomes of Transplant-Eligible and Transplant-Ineligible Patients with Mantle Cell Lymphoma in Ontario, Canada

Background The frontline treatment of patients with symptomatic mantle cell lymphoma (MCL) requiring treatment varies in practice. In Ontario, Canada, transplant-eligible (TE) patients have been treated with chemoimmunotherapy followed by autologous stem cell transplant (ASCT). In 2013, R-CHOP alternating with R-DHAP prior to ASCT replaced R-CHOP alone as standard of care based on the European MCL Younger trial (Hermine JCO 2022). Although this regimen improves progression-free survival, there remains concern about its toxicity. For transplant-ineligible (TI) patients, the standard of care has evolved over time. Evidence in support of bendamustine-rituximab (BR) efficacy in indolent lymphoma resulted in its increased use in TI patients with MCL over the last decade. However, real-world data are lacking on toxicities of this regimen compared to other chemoimmunotherapy. We aimed to characterize survival and healthcare utilization outcomes of patients with MCL using current treatment approaches. Methods We conducted a retrospective population-based study of patients with MCL using healthcare administrative databases from Ontario, Canada, from 2005 to 2020. Patients were defined as TE if they were less than 70 years old at the time of treatment initiation, and received either R-CHOP or R-CHOP/R-DHAP. Patients were defined as TI if they were 70 years or greater at the time of treatment initiation, and treated with BR or other forms of chemoimmunotherapy. The primary outcome was 5-year overall survival (OS), from the time of first treatment to death or end of the study period. Secondary outcomes were toxicities of treatment and healthcare utilization. Cox regression analyses were used to assess the impact of demographic and treatment variables on OS. Results A total of 918 patients with MCL were included in this study; 426 were TE and 492 TI. For TE patients, 254 were treated with R-CHOP, and 172 with R-CHOP/R-DHAP. The median age of patients in both groups was 60 years (range 36-70 years, p=0.37). Patients treated with R-CHOP alone were followed for a mean of 6.01 years, and patients treated with R-CHOP/R-DHAP for a mean of 3.38 years. Maintenance rituximab (MR) was used in 70.5% of patients treated with R-CHOP and 77.3% of patients treated with R-CHOP/R-DHAP (p=0.12). ASCT was received by 53.5% of patients treated with R-CHOP and 83.7% of patients treated with R-CHOP/R-DHAP (p&amp;lt;0.01). 5-year OS of patients treated with R-CHOP/R-DHAP was 70.5% vs 62.0% for patients treated with R-CHOP regardless of transplant status ( Figure 1A hazard ratio [HR] 0.75, 95% CI 0.51-1.10). Of the 270 patients who received ASCT within 1 year of treatment initiation, survival was not impacted by prior receipt of R-CHOP alone or R-CHOP/R-DHAP (HR for R-CHOP/R-DHAP vs. R-CHOP 0.76, 95% CI 0.42-1.39). A higher proportion of patients treated with R-CHOP/R-DHAP required hospital admissions for fever, infection, neutropenia, and renal toxicity, compared to R-CHOP alone ( Table 1). There was no difference between regimens in the number of patients requiring emergency department (ED) visits between regimens (p=0.39). 492 TI patients were included; 303 treated with BR and 189 treated with other regimens, most commonly R-CHOP (n=62) or R-CVP (n=108). The median age of patients in both groups was 77 years (range 71-94 years, p=0.17), and there was no significant difference in comorbidities (p=0.23). MR was more commonly used after BR compared to historical regimens (72.6% vs. 54.5%, p&amp;lt;0.01). 5-year unadjusted OS of patients treated with BR was 40.3% and 27.5% for patients treated with R-CHOP/R-CVP ( Figure 1B), with significantly lower mortality with the use of BR (HR 0.68, 95% CI 0.51-0.89). After adjusting for age, sex, comorbidities, and MR, this was no longer significant (HR 0.86, 95% CI 0.65-1.14). MR use was associated with significantly lower mortality (HR 0.33, 95% CI 0.24-0.44). More patients treated with BR had hospital admissions for neutropenia and febrile neutropenia ( Table 1). Conclusion In this large population-based study of patients with MCL, R-CHOP/R-DHAP prior to ASCT showed a trend toward improved 5-year OS, though not significant. For TI patients, BR resulted in superior OS compared to other regimens with similar rates of toxicities, however this was not significant after adjusting for use of MR, suggesting other regimens followed by MR may be a reasonable alternatives.