Administrative Healthcare Databases Research Articles

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.

Real-world antifibrotic treatment patterns in patients with idiopathic pulmonary fibrosis: retrospective analyses of two large healthcare administrative databases in the United States.

Real-world data on the use, healthcare resource utilization (HCRU), and associated costs of antifibrotic therapies in patients with idiopathic pulmonary fibrosis (IPF) are limited. To assess the prevalence of antifibrotic treatment, characteristics of patients receiving treatment, discontinuation rates, and HCRU and costs associated with treatment. This retrospective study analyzed de-identified longitudinal and cross-sectional data, respectively, from two US claims databases: Optum's de-identified Clinformatics® Data Mart Database (CDM; commercial claims, Medicare Advantage) and the Veterans Health Administration (VHA) database. The study periods were October 1, 2013-March 31, 2019 and October 1, 2014-September 30, 2019, respectively. Eligible individuals were adults with ⩾1 diagnosis claim for IPF. Antifibrotic prevalence, patient demographics, treatment discontinuation rates, and HCRU and costs were determined separately for each cohort and described using summary statistics. Bivariate comparisons were analyzed using Chi-square and Student's t-tests for categorical and continuous variables, respectively. Overall, 4223 and 4459 eligible patients were identified in the CDM and VHA databases, respectively. Prevalence of antifibrotic uptake was 9.2% and 29.1% and the rate of index treatment discontinuation was 47% and 66% during follow-up in the CDM and VHA cohorts, respectively. Antifibrotic-treated patients were significantly younger (p < 0.0001) with lower mean Charlson Comorbidity Index scores at baseline versus untreated patients in both cohorts. In the CDM cohort, the number of outpatient and pharmacy visits was significantly higher in treated versus untreated patients during follow-up (both p < 0.0001). A similar trend was observed for the VHA cohort. Total follow-up costs in both cohorts were significantly higher in treated versus untreated patients due to higher pharmacy costs (CDM; p < 0.0001) or higher outpatient and pharmacy costs (VHA; p < 0.0001). The low prevalence of antifibrotic usage in both cohorts, together with the high rate of antifibrotic discontinuation, and increased HCRU and costs in treated versus untreated patients, support the need for novel treatment options for IPF. Not applicable.

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.

Economic burden due to COVID-19 in a Colombian Caribbean state, 2020 and 2021.

To estimate the economic burden associated with COVID-19 in Córdoba, Colombia, 2020 and 2021. Economic burden study. Direct costs were analyzed from the third-party payer perspective using healthcare administrative databases and interviews from a cohort of confirmed COVID-19 cases from Córdoba. Costing aggregation was performed by the bottom-up method. Indirect costs were estimated using the productivity loss approach. Contrast tests and statistical models were estimated at 5% significance. We studied 1,800 COVID-19 cases. The average economic cost of COVID-19 per episode was estimated at US$ 2,519 (95%CI 1,980;3,047). The direct medical cost component accounted for 92.9% of the total; out-of-pocket and indirect costs accounted for 2% and 5.1%, respectively. COVID-19 economic cost was mainly due to direct medical costs. This study provided evidence of the economic burden faced by households due to COVID-19, with the most vulnerable households bearing much of the burden on their income.

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

Pulmonary 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.

Association Between the Dialysate Bicarbonate and the Pre-dialysis Serum Bicarbonate Concentration in Maintenance Hemodialysis: A Retrospective Cohort Study.

It is unclear whether the use of higher dialysate bicarbonate concentrations is associated with clinically relevant changes in the pre-dialysis serum bicarbonate concentration. The objective is to examine the association between the dialysate bicarbonate prescription and the pre-dialysis serum bicarbonate concentration. This is a retrospective cohort study. The study was performed using linked administrative health care databases in Ontario, Canada. Prevalent adults receiving maintenance in-center hemodialysis as of April 1, 2020 (n = 5414) were included. Patients were grouped into the following dialysate bicarbonate categories at the dialysis center-level: individualized (adjustment based on pre-dialysis serum bicarbonate concentration) or standardized (>90% of patients received the same dialysate bicarbonate concentration). The standardized category was stratified by concentration: 35, 36 to 37, and ≥38 mmol/L. The primary outcome was the mean outpatient pre-dialysis serum bicarbonate concentration at the patient level. We examined the association between dialysate bicarbonate category and pre-dialysis serum bicarbonate using an adjusted linear mixed model. All dialysate bicarbonate categories had a mean pre-dialysis serum bicarbonate concentration within the normal range. In the individualized category, 91% achieved a pre-dialysis serum bicarbonate ≥22 mmol/L, compared to 87% in the standardized category. Patients in the standardized category tended to have a serum bicarbonate that was 0.25 (95% confidence interval [CI] = -0.93, 0.43) mmol/L lower than patients in the individualized category. Relative to patients in the 35 mmol/L category, patients in the 36 to 37 and ≥38 mmol/L categories tended to have a serum bicarbonate that was 0.70 (95% CI = -0.30, 1.70) mmol/L and 0.87 (95% CI = 0.14, 1.60) mmol/L higher, respectively. There was no effect modification by age, sex, or history of chronic lung disease. We could not directly confirm that all laboratory measurements were pre-dialysis. Data on prescribed dialysate bicarbonate concentrations for individual dialysis sessions were not available, which may have led to some misclassification, and adherence to a practice of individualization could not be measured. Residual confounding is possible. We found no significant difference in the pre-dialysis serum bicarbonate concentration irrespective of whether an individualized or standardized dialysate bicarbonate was used. Dialysate bicarbonate concentrations ≥38 mmol/L (vs 35 mmol/L) may increase the pre-dialysis serum bicarbonate concentration by 0.9 mmol/L.

Pregnancy Outcomes in Living Kidney Donors: Protocol of a Population-Based Cohort Study in Three Canadian Provinces.

A substantial proportion of living kidney donors are women of childbearing age. Some prior studies report a higher risk of gestational hypertension and pre-eclampsia in living kidney donors compared with nondonors. Further research is needed to better quantify the risk of adverse maternal, fetal/infant, and neonatal outcomes attributable to living kidney donation. To determine the risk of hypertensive disorders of pregnancy, including gestational hypertension, pre-eclampsia, and eclampsia, and other maternal and fetal/infant outcomes in living kidney donors compared with a matched group of nondonors of similar baseline health. Protocol for a population-based, matched cohort study using Canadian administrative health care databases. The protocol will be run separately in 3 provinces, Ontario, Alberta, and British Columbia, and results will be combined statistically using meta-analysis. The cohort will include women aged 18 to 48 years who donated a kidney between July 1992 and March 2022 and had at least one postdonation singleton pregnancy of ≥20 weeks gestation between January 1993 and February 2023. We expect to include at least 150 living kidney donors with over 200 postdonation pregnancies from Ontario and a similar number of donors and pregnancies across Alberta and British Columbia combined. Nondonors will include women from the general population with at least one pregnancy of ≥20 weeks gestation between January 1993 and February 2023. Nondonors will be randomly assigned cohort entry dates based on the distribution of nephrectomy dates in donors. The sample of nondonors will be restricted to those aged 18 to 48 years on their cohort entry dates with delivery dates at least 6 months after their assigned entry dates. A concern with donor and nondonor comparisons is that donors are healthier than the general population. To reduce this concern, we will also apply 30+ exclusion criteria to further restrict the nondonor group so that they have similar health measures at cohort entry as the donors. Donor and nondonor pregnancies will then be matched (1:4) on 5 potential confounders: delivery date, maternal age at delivery date, time between cohort entry and delivery date, neighborhood income quintile, and parity at delivery date. The primary outcome will be a composite of maternal gestational hypertension, preeclampsia, or eclampsia. Secondary maternal outcomes will include components of the primary outcome, early pre-eclampsia, severe maternal morbidity, cesarean section, postpartum hemorrhage, and gestational diabetes. Fetal/infant/neonatal outcomes will include premature birth/low birth weight, small for gestational age, neonatal intensive care unit admission, stillbirth, and neonatal death. The primary unit of analysis will be the pregnancy. We will compute the risk ratio of the primary composite outcome in donors versus nondonors using a log-binomial mixed regression model with random effects to account for the correlation within women with multiple pregnancies and within matched sets of donors and nondonors. We will perform the statistical analyses within each province and then combine aggregated results using meta-analytic techniques to produce overall estimates of the study outcomes. Due to regulations that prevent individual-level records from being sent to other provinces, we cannot pool individual-level data from all 3 provinces. Compared to prior studies, this study will better estimate the donation-attributable risk of adverse maternal, fetal/infant, and neonatal outcomes. Transplant centers can use the results to counsel female living donor candidates of childbearing age and to inform recommended practices for the follow-up and care of living kidney donors who become pregnant.

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.

Risk of motor vehicle accidents with profound injuries in patients with ankylosing spondylitis: a nationwide, population-based cohort study.

Patients with ankylosing spondylitis (AS) suffer from impaired physical activity and are prone to motor vehicle accidents (MVA), but definite instruction regarding the relationship between disease evolvement and MVA and potential risk factors is lacking. To explore the risk factors and their impact on recorded MVA with profound injuries in AS patients with prescriptions. Nationwide, population-based, matched retrospective cohort study. Using Taiwanese administrative healthcare databases, with available claims data from 2003 to 2013, we selected 30,911 newly diagnosed adult AS patients with concurrent prescriptions from 2006 to 2012 as AS patients, along with 309,110 non-AS individuals as the control group, matched in gender, age at index date and year of the index date. The risk of recorded MVA with profound injuries was compared between the two groups in terms of incidence rate ratio (IRR) and log-rank test p-value. Using Cox regression analysis, we studied associations between the risk and AS diagnosis. The risk of recorded MVA with profound injuries in AS patients was significantly higher than in non-AS individuals, specifically 2 years after AS diagnosis (IRR, 2.00; 95% confidence interval (CI), 1.42-2.81). For patients with follow-up periods >2 years, the adjusted risk was positively associated with suburban residence (adjusted hazard ratio (aHR), 2.18; 95% CI, 1.55-3.06), rural residence (aHR, 1.89; 95% CI, 1.27-2.80), lower insured income (aHR, 1.35; 95% CI, 1.01-1.81) and recorded MVA with profound injuries before AS diagnosis (aHR, 6.16; 95% CI, 2.53-14.96). AS diagnosis (aHR, 1.81; 95% CI, 1.27-2.59) and frequency of ambulatory visits (aHR, 1.01; 95% CI, 1.004--1.02) were specific associated factors for them compared with those with follow-up periods ⩽2 years. For adult AS patients in Taiwan, factors such as AS disease evolution and frequent ambulatory visits for disease control in the second year of the disease course may significantly increase the risk of recorded MVA with profound injuries beyond 2 years after AS diagnosis.

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...

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.

An italian real-world analysis of obstructive hypertrophic cardiomyopathy through a large administrative healthcare database

Abstract Background The obstructive hypertrophic cardiomyopathy (HCM) is still not curable. Pharmacological treatments and removal of excess cardiac tissue are recommended to manage symptoms. Purpose The study aimed to identify and describe patients with obstructive HCM, from the perspective of the Italian National Health Service (INHS). Methods From the Fondazione ReS (Ricerca e Salute) database (∼5 million inhabitants/year), adults with ≥1 in-hospital main/secondary diagnosis of obstructive HCM (ICD9-CM code: 425.1) and surgical resection between 01/01/2013 and 12/31/2018 (accrual period), were identified. They are characterized by age, sex, comorbidities and implantation of cardiac devices/revascularization performance, at the baseline. Within 2 years from 01/01/2019 (index date), mortality and related causes, pharmacological therapy (obstructive HCM-related drugs, other cardiovascular "CV" and non-CV drugs), overnight hospitalizations due to CV causes of interest (i.e., obstructive HCM/heart failure/coronary artery disease/hypertension/cerebrovascular disease), other CV, and non-CV diagnoses, local outpatient specialist care, and healthcare integrated costs charged to the INHS, were assessed. Results Out of 640 adults (incidence 16.2x100,000 inhabitants; 55% males; mean age 70±14) with obstructive HCM, 60 (9.4%) underwent resection. The most common comorbidities were hypertension (95%), arrhythmia (53%), and dyslipidaemia (50%). A mean of 2 implantations of cardiac devices/revascularizations are performed in 36% (229/640) patients with obstructive HCM. Within 2 years, 65/640 (10.2%) patients died. Among in-hospital deaths (40/65): 2.5% are due to obstructive HCM, 27.5% to CV and 70% to non-CV causes. During follow-up: ∼90% of patients received ≥1 obstructive HCM-related drug (∼80% β-blockers), 88% ≥1 other CV drug and ∼92% ≥1 non-CV medication. Within the 1st and 2nd follow-up years, respectively, 28% and 22% are hospitalized at least once: 14% and 10% for CV causes of interest, ∼2% for other CV events, and 17% and 13% for non-CV causes; on average, ∼10 days of in-hospital stay. From 85% to 80% of patients received ≥1 local outpatient specialist service, during 1st and 2nd years, respectively. On average, the 1st and 2nd year, respectively, the INHS spent per patient €4362 and €3791: pharmaceuticals accounted for 35% and 40% (mostly concomitant drugs), hospitalizations for 57% and 52%, specialist care for 9% and 8% of the total cost. Conclusion Despite the low prevalence of obstructive HCM, this study shows its high overall burden on the INHS, particularly due to concomitant pharmacological treatments and overnight hospitalizations.

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.

Cohort profile: the United Kingdom Childhood Cancer Study (UKCCS) – a UK-wide population-based study examining the health of cancer survivors

PurposeThe United Kingdom Childhood Cancer Study’s (UKCCS’s) matched cohort was established to examine the longer term morbidity and mortality of individuals previously diagnosed with cancer before 15 years of age,...