Stratified Estimates Research Articles

P-59. Tdap Vaccination Coverage During Pregnancy, 2016 Through 2023

Abstract Background The Advisory Committee on Immunization Practices recommends tetanus-diphtheria-acellular pertussis (Tdap) vaccination during every pregnancy, preferably between gestational weeks 27 and 36. Estimates of Tdap vaccination coverage among pregnant people for the period overlapping the COVID-10 pandemic are limited. Our objective was to assess Tdap vaccination coverage during pregnancy within the Vaccine Safety Datalink (VSD) before and during the COVID-19 pandemic, to examine the potential impact of the pandemic on Tdap coverage. Tdap vaccination coverage during pregnancy, overall and by age group – 2016 through 2023, Vaccine Safety Datalink Tdap vaccination coverage among pregnant people ages 12--54 years, overall and stratified by age group. Ages 12--17 and 45--54 years have been excluded from stratified estimates due to low numbers, but are included in the overall estimate. Eligible pregnancies had a live birth of at least 26 weeks’ gestation during the study period and were continuously enrolled at their Vaccine Safety Datalink site for the duration of their pregnancy. Age was determined as of pregnancy start. Data available and presented here are limited to one VSD site; data from eight other VSD sites are being collected. Methods We examined Tdap vaccination coverage among pregnant people ages 12—54 years with a live birth of ≥ 26 weeks’ gestation from January 2016 through December 2023; pregnancies were identified using a validated algorithm. We captured Tdap, influenza, COVID-19, and respiratory syncytial virus (RSV) vaccination during the pregnancy using electronic medical records linked to immunization registries. We assessed annual crude Tdap vaccination coverage and demographics associated with Tdap vaccination. Among people who received Tdap, we examined gestational age at Tdap receipt and described uptake of other vaccines recommended during pregnancy (influenza, COVID-19, RSV). Data available and presented here are limited to one VSD site; data from eight other VSD sites are being collected. Tdap vaccination coverage during pregnancy, by race and ethnicity – 2016 through 2023, Vaccine Safety Datalink Tdap vaccination coverage among pregnant people ages 12-54 years, stratified by race and ethnicity. Eligible pregnancies had a live birth of at least 26 weeks’ gestation during the study period and were continuously enrolled at their Vaccine Safety Datalink site for the duration of their pregnancy. Race and ethnicity were assessed using electronic health record data. The following race and ethnicity categories were combined into “Another race, NH” due to low numbers: non-Hispanic (NH) multiple race [3.7%], NH Native Hawaiian or Pacific Islander [0.8%], NH Middle Eastern or North African [0.7%], NH American Indian or Alaskan Native [0.4%]. Data available and presented here are limited to one VSD site; data from eight other VSD sites are being collected. Results An average of 4,143 births were included in each of the eight calendar years. The population was, on average, 64% non-Hispanic (NH) White, 13% Hispanic, 9% NH Asian, 6% NH multiracial, 5% unknown race and ethnicity, and 4% NH Black; 62% of pregnant people were 25—34 years old. Crude Tdap vaccination coverage was 90% among those with births in 2016 and 87% among those with births in 2023. Coverage was consistently lowest among those aged 18—24 (Figure 1). In all years, NH Asian pregnant people had the highest Tdap coverage; coverage was lowest among NH Black pregnant people in six of eight years, with a sharp drop in coverage in 2023 (Figure 2). Patterns of vaccination among pregnant people who received Tdap are shown in Figure 3. Patterns of Tdap, influenza, COVID-19, and RSV vaccine uptake during pregnancy among those who received Tdap during pregnancy – 2016 through 2023, Vaccine Safety Datalink Tdap, influenza, COVID-19, and RSV vaccination during pregnancy among individuals who received Tdap during pregnancy. Eligible pregnancies had a live birth of at least 26 weeks’ gestation during the study period and were continuously enrolled at their Vaccine Safety Datalink site for the duration of their pregnancy. Data available and presented here are limited to one VSD site; data from eight other VSD sites are being collected. Conclusion Between 2016 and 2023, 87—90% of pregnant people with live births received the Tdap vaccine each year. However, we identified consistent disparities in coverage by age, race, and ethnicity; racial disparities widened in later years. Disclosures Darios Gethaun, MD, PhD, MPH, HOLOGIC Inc.: Grant/Research Support|Johnson & Johnson: Grant/Research Support Nicola P. Klein, MD, PhD, CSL Seqirus: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Merck: Grant/Research Support|Pfizer: Grant/Research Support|Sanofi Pasteur: Grant/Research Support

Networking in biological and physical retrospective dosimetry in Europe and beyond.

Ionizing radiation is of huge benefit to society; however, the risks of radiation overexposure in occupational settings or due to accidents or other incidents are of growing concern, not least due to the potential implications for exposed individuals in terms of acute high dose (e.g. ARS) and/or longer term low dose health effects such as cancer or genetic effects. This manuscript considers the state of the art for biological and 'fortuitous' physical retrospective dose estimation either in blood or in materials being carried by suspected exposed individuals, respectively, in support of routine and emergency radiation incident response, and the potential future progress in this fascinating and active field. In recent years, international experts in this field have engaged in active collaboration and networking on support of these goals, and continued efforts in this area will ensure the global community remains ready to respond to radiation accidents and incidents. In addition, over and above improved dose and exposure characterization in the field of radiation emergency medicine, scientific developments in biological markers may contribute to potential contributions to individualized or stratified risk estimation in molecular epidemiology to assess long term, low dose radiation risk; in personalized medical dosimetry for better justification and optimization for use of radiation in such settings, and even perhaps for potential future situations involving radiation exposure, for example protection of individuals traveling to space.

Material, Psychological, and Behavioral Financial Hardship Among Lesbian, Gay, and Bisexual Cancer Survivors in the United States.

Driven by anti-LGBTQ+ stigma, emerging literature suggests that lesbian, gay, and bisexual (LGB) cancer survivors experience financial hardship (FH) more frequently than heterosexual survivors. However, few studies have used nationally representative samples to estimate this inequity. National Health Interview Survey data from 2019 to 2022 were pooled and weighted. Outcomes included material, psychological, and behavioral FH. The behavioral domain was further broken down into subdomains including medical care, prescription medications, and mental health care. Multivariable logit models controlling for a variety of factors were used to generate LGB and heterosexual predicted probabilities and differential effects for each FH outcome. Stratified estimates were generated by sex and age groups. A total of N = 374 LGB and N = 12,757 heterosexual cancer survivors were included in this analysis. In adjusted analyses, LGB cancer survivors had significantly higher material (19%, 95% CI, 15 to 24 v 12%, 95% CI, 11 to 13; P = .004), psychological (44%, 95% CI, 38 to 51 v 37%, 95% CI, 36 to 38; P = .035), and behavioral (23%, 95% CI, 18 to 28 v 13%, 95% CI, 13 to 14; P < .0001) FH than heterosexual survivors. LGB cancer survivors also had higher medical behavioral (11%, 95% CI, 7 to 15 v 7%, 95% CI, 6 to 7; P = .030), prescription medication behavioral (14%, 95% CI, 10 to 19 v 10%, 95% CI, 9 to 10; P = .032), and mental health behavioral (9%, 95% CI, 6 to 13 v 3%, 95% CI, 3 to 4; P < .0001) FH than heterosexual survivors. Stratified estimates revealed young LGB cancer survivors had the highest probability of each outcome (material: 31%, 95% CI, 23 to 40; psychological: 58%, 95% CI, 50 to 66; behavioral: 45%, 95% CI, 36 to 53). In this nationally representative analysis, LGB cancer survivors experience substantial inequities in all FH outcomes. It is crucial that future FH interventional work should prioritize populations at the highest risk of FH, such as LGB cancer survivors.

An Enhanced Exponential Dual to Ratio-cum-Product Type Estimator of Population mean under Stratified Random Sampling

This article investigates an exponential estimator in dual form for the population mean in stratified random sampling using two auxiliary variates that are modified from the ratio-cum-product type estimators. The formulae for bias and mean squared error (MSE) have been determined for the suggested stratified random sample estimator. Additionally, in a stratified sample scheme, the propounded estimator has been practically and conceptually compared to current ones. It is proven that the improved estimator that has been presented is more effective than all other competing population mean estimators. . KEYWORDS :Ratio-cum-Product estimator, Stratified sample scheme, Population mean, Mean squared error, Bias.

Gender, Ethnicity, and Socioeconomic Inequalities in Physical Activity Throughout the Life Course: A Systematic Review of Cohort Studies.

This study aimed to assess longitudinal changes in physical activity inequalities according to gender, socioeconomic status, and ethnicity throughout the life course. We searched PubMed, Embase, Web of Science, and Scopus databases for cohort studies addressing trajectories or monitoring physical activity at a minimum of 2 time points, presenting stratified estimates for at least 1 dimension of inequality (gender, socioeconomic status, or ethnicity). Main methodological characteristics and physical activity point estimates were extracted, enabling interpretation of the stability or increasing/decreasing inequalities over time. Out of the 22 included studies in the review, none were designed or presented with specific aims addressing changes in physical activity according to the dimension of inequalities throughout the life course. Therefore, the main results and interpretation were performed according to available information. Males consistently showed a higher prevalence of physical activity than females. We observed both an increase and stability in gender inequality during childhood, followed by an increase in the transition from childhood to adolescence. During adolescence, both increase and stability in gender inequality were identified, with mixed results observed during adulthood, and in later life stages, in a limited number of studies. There is no or very limited evidence regarding ethnicity and socioeconomic status inequalities throughout the life course. Although none of the studies directly measured inequalities, an early emergence of gender inequalities was observed. Future research should include these dimensions as well as other social identities to enhance the understanding of inequalities throughout the life course.

How to interpret patient-reported outcomes? - Stratified adjusted minimal important changes for the EQ-5D-3L in hip and knee replacement patients

BackgroundAs one of the main goals of hip and knee replacements is to improve patients’ health-related quality of life, a meaningful evaluation can be achieved by calculating minimal important changes (MICs) for improvements in patient-reported outcome measures (PROMs). This study aims at providing MICs adjusted for patient characteristics for EQ-5D-3L index score improvements after hip and knee replacements. It adds to existing literature by relying on a large national sample and precise clustering algorithms, and by employing a state-of-the-art methodology for the calculation of improved adjusted MICs.MethodologyA retrospective observational study was conducted using the publicly available National Health Service (NHS) PROMs dataset for primary hip and knee replacements. We used information on 252,331 hip replacements and 279,668 knee replacements from all NHS-funded providers in England between 2013 and 2020. Clusters of patients were created based on pre-operative EQ-VAS, depression status, and sex. Unstratified and stratified estimates for meaningful EQ-5D-3L improvements were obtained through anchor-based predictive MICs corrected for the proportion of improved patients and the reliability of transition ratings.ResultsStratifying patients showed that MICs varied across subgroups based on pre-operative EQ-VAS, depression status, and sex. MICs were larger for patients with worse pre-operative EQ-VAS scores, while patients with better pre-operative scores required smaller MICs to achieve a meaningful change. We show how after stratification the percentage of patients achieving their stratified MIC was better in line with the actual share of improved patients. Larger MICs were found for patients with depression and for female patients. MICs calculated for knee replacements were consistently lower than those for hip replacements.ConclusionsOur findings show the importance of adjusting MICs for patients’ characteristics and should be considered for quality-related choices and policy initiatives.

Incorporating Forest Mapping-Related Uncertainty into the Error Propagation of Wall-to-Wall Biomass Maps: A General Approach for Large and Small Areas

The sources of uncertainty in wall-to-wall AGB maps propagate from the tree to pixel, but uncertainty due to forest cover mapping is rarely incorporated into the error propagation process. This study aimed to (1) elaborate an analytical procedure to incorporate forest-mapping-related uncertainty into the error propagation from plot and pixel predictions; (2) develop a stratified estimator with a model-assisted estimator for small and large areas; and (3) estimate the effect of ignoring the mapping uncertainty on the confidence intervals (CIs) for totals. Data consist of a subset of the Brazilian national forest inventory (NFI) database, comprising 75 counties that, once aggregated, served as strata for the stratified estimator. On-ground data were gathered from 152 clusters (plots) and remotely sensed data from Landsat-8 scenes. Four major contributions are highlighted. First, we describe how to incorporate forest-mapping-related uncertainty into the CIs of any forest attribute and spatial resolution. Second, stratified estimators perform better than non-stratified estimators for forest area estimation when the response variable is forest/non-forest. Comparing our stratified estimators, this study indicated greater precision for the stratified estimator than for the regression estimator. Third, using the ratio estimator, we found evidence that the simple field plot information provided by the NFI clusters is sufficient to estimate the proportion forest for large regions as accurately as remote-sensing-based methods, albeit with less precision. Fourth, ignoring forest-mapping-related uncertainty erroneously narrows the CI width as the estimate of proportion forest area decreases. At the small-area level, forest-mapping-related uncertainty led to CIs for total AGB as much as 63% wider in extreme cases. At the large-area level, the CI was 5–7% wider.

Estimation of Environmental Burden of Disease related to Arsenic exposure in European Populations

Abstract Background Arsenic (As) exposure poses significant health risks to exposed populations, with exposure occurring predominantly via diet for the general population as recently referred by the European Food Safety Authority. This study assesses the environmental burden of disease (EBD) for three cancer types related to arsenic, across Europe. Methods A literature review was conducted to 1) identify the dose-response function (DRF) to assess the cancer risk in European populations, and 2) define EBD approaches applicable to the available data. Country-specific data (Belgium, Denmark, Portugal) for EBD calculation (exposure, socioeconomic status, health outcomes) were gathered. Disability-Adjusted Life Years (DALY) estimations were performed by calculating attributable cases (AC). Results Two main references are used for DRF: the United States Food and Drug Administration DRF for assessing bladder and lung cancer risks, and the United States Environmental Protection Agency DRF for skin cancer. Preliminary results for Belgium indicate that inorganic arsenic dietary exposure ranges from 0.084 [0.080 - 0.088] to 0.102 [0.097 - 0.107] µg/kg body weight per day, varying with education level. Stratified estimates suggest that individuals with higher educational attainment (ISCED levels 5 &amp; 6) have a marginally higher average daily intake of arsenic compared to those with lower educational attainment (ISCED levels 0, 1 &amp; 2). DALY attributable to inorganic arsenic exposure follow the same trend as exposure levels, i.e. individuals with a higher education level bear a higher burden of disease than individuals of the low education stratum. This concerns the three studied cancers. Conclusions This study quantifies DALY related to inorganic arsenic from dietary exposure for different European countries. Our findings will contribute to better target public health policies and interventions for arsenic risk mitigation. Key messages • Exposure to inorganic arsenic is confirmed in European countries. • EBD studies guide action priorities to tackle chemical risk factors.

Characteristics of men and women with medically diagnosed cluster headache in a national integrated healthcare system: A Veterans Health Administration cohort study.

Describe the epidemiology of cluster headache (CH) using Veterans Health Administration (VHA) Electronic Health Record (EHR) data. Epidemiologic studies of CH at the population level are difficult because it has a prevalence of ~0.1%. Hospital system-wide studies are an attractive alternative as they have large numbers of patients and broader populations than headache or neurology clinic-based studies. The VHA is an ideal hospital-based system in which to study CH because it is nationwide, predominantly male, has a strong focus on mood disorders and suicidality, and has accessible individual medical records. Here, we report the first headache study based on an ongoing longitudinal cohort of patients with CH using VHA EHR data. The VHA EHR data were accessed from Fiscal Year 2008 to 2019. Patients with CH consisted of all patients with at least one outpatient visit containing a CH diagnosis code from the International Classification of Diseases (ICD)-9 or -10. We extracted data on demographic features, incidence, and prevalence, as well as pain and psychiatric comorbidities. Of the 1,524,960 distinct patients who presented for headache treatment in the VHA between Fiscal Year 2008-2019, 24,131 had at least one visit with a CH diagnosis. The 1-year period prevalence of a CH diagnosis in the VHA ranges from 0.08% to 0.10% for women and 0.10% to 0.18% for men. A larger proportion of women versus men received a diagnosis of unspecified CH (59.6% [1412/2368] vs. 53.6% [11,663/21,763], p < 0.001). Most patients with CH had both comorbid headache and non-headache pain diagnoses. Headache not-otherwise-specified was the most common comorbid headache disorder at 70.0% (16,885/24,131) and was more common in women (76.1%, 1801/2368) compared to men (69.3%, 15,084/21,763). Other common comorbidities included migraine, depression, tobacco use, and obstructive sleep apnea. Rates of suicidal ideation or attempt were almost 50% higher in women (5-year proportion 9.4%, 222/2368) with CH compared to men (6.6%, 1433/21,763). To our knowledge this is the largest hospital system study of CH to date and reinforces several previous studies. Pain, mental health, and sleep disorders comorbidities are particularly prevalent in this group and were often more common in women compared to men with CH. Future work should examine gender and race stratified prevalence estimates within the VHA and other healthcare systems.

Prevalence and Costs of Eosinophilic Esophagitis in the United States

Background and AimsEosinophilic esophagitis (EoE) has been continually increasing in prevalence but current estimates are lacking. We aimed to determine updated estimates of the prevalence and medical costs associated with EoE in the United States. MethodsWe used two large administrative databases, MarketScan and Medicare, and International Classification of Disease codes to calculate annual prevalence of EoE, as well as age- and sex- stratified estimates, standardized to the U.S. population. Health care utilization, including medications and endoscopic procedures was quantified, and annual EoE-associated costs were estimated. ResultsWe identified 20,435 EoE cases in MarketScan in 2022 and 1,913 EoE cases in Medicare in 2017. This translated to prevalences of 163.08 cases/100,000 and 64.83 cases/ 100,000 in MarketScan and Medicare, respectively. There was a 5-fold increase in prevalence in both databases since 2009. In MarketScan, prevalence was higher among males (204.45/100,000 vs 122.06/100,000 among females); for both sexes, peak prevalence was from 40–44years. Standardized to the U.S. population, the prevalence of EoE was 142.5/100,000, extrapolating to 472,380 cases. Total EoE-associated healthcare costs were estimated to be $1.32 billion in 2024 dollars after accounting for inflation. ConclusionsThe prevalence of EoE continues to increase, with a rate of 1 in 617 in 2022 in those <65 years of age, and 1 in 1562 in 2017 those ≥65 years. Standardized to the U.S. population, the overall prevalence was approximately 1 in 700. EoE-associated annual costs were estimated to be $1.3 billion in 2024 dollars, representing a substantial financial burden.

Age, sex, and multi-morbidity stratified mortality risk estimates for adults with cerebral palsy to inform clinical decision making

BackgroundWhile research has provided key insights into mortality rates and risks for individuals with cerebral palsy (CP), clinically useable mortality risk estimates remain unreported for adults with CP, especially by key patient-level factors. ObjectiveThe objective of this study was to generate clinically useable mortality risk estimates among adults with CP to inform clinical decision making. MethodsThis retrospective cohort study, using a fee-for-service Medicare database, identified adults ≥18-years-old with CP from 01/01/2008-12/31/2010 and followed through 12/31/2019 for death. Mortality risk at 1-, 3-, 5-, and 9-year intervals were selected based on common clinical length of time to reasonably benefit from preventive care. Sex-stratified analyses assessed risk estimates by narrow age group (18–25/26-34/35–44/45-54/55–64/65-74/≥75 years old) and multi-morbidity group (Whitney Comorbidity Index score 0–2/3/4–6/≥7). ResultsOf 24,767 adults with CP, n = 12,962 were men (mean [SD] age = 48.3 [15.0] years) and n = 11,805 were women (age = 49.7 [15.8] years). Loss to follow-up was rare. 1-year risk was similar between men and women (3.4 % vs. 3.3 %), but increased slightly more for men than women through 9-years (30.1 % vs. 28.0 %). As expected, the mortality risk increased with older age and higher WCI scores. The probability of death (and survival) is presented per age and multi-morbidity group for men and women with CP. ConclusionsMortality risk estimates were reported at clinically relevant intervals by age, sex, and multi-morbidity status. This information can be used to weigh harm-to-benefit ratios of screening and treatment strategies based on mortality expectancy estimates.

REALM-DCM: A Phase 3, Multinational, Randomized, Placebo-Controlled Trial of ARRY-371797 in Patients With Symptomatic LMNA-Related Dilated Cardiomyopathy.

LMNA (lamin A/C)-related dilated cardiomyopathy is a rare genetic cause of heart failure. In a phase 2 trial and long-term extension, the selective p38α MAPK (mitogen-activated protein kinase) inhibitor, ARRY-371797 (PF-07265803), was associated with an improved 6-minute walk test at 12 weeks, which was preserved over 144 weeks. REALM-DCM (NCT03439514) was a phase 3, randomized, double-blind, placebo-controlled trial in patients with symptomatic LMNA-related dilated cardiomyopathy. Patients with confirmed LMNA variants, New York Heart Association class II/III symptoms, left ventricular ejection fraction ≤50%, implanted cardioverter-defibrillator, and reduced 6-minute walk test distance were randomized to ARRY-371797 400 mg twice daily or placebo. The primary outcome was a change from baseline at week 24 in the 6-minute walk test distance using stratified Hodges-Lehmann estimation and the van Elteren test. Secondary outcomes using similar methodology included change from baseline at week 24 in the Kansas City Cardiomyopathy Questionnaire-physical limitation and total symptom scores, and NT-proBNP (N-terminal pro-B-type natriuretic peptide) concentration. Time to a composite outcome of worsening heart failure or all-cause mortality and overall survival were evaluated using Kaplan-Meier and Cox proportional hazards analyses. REALM-DCM was terminated after a planned interim analysis suggested futility. Between April 2018 and October 2022, 77 patients (aged 23-72 years) received ARRY-371797 (n=40) or placebo (n=37). No significant differences (P>0.05) between groups were observed in the change from baseline at week 24 for all outcomes: 6-minute walk test distance (median difference, 4.9 m [95% CI, -24.2 to 34.1]; P=0.82); Kansas City Cardiomyopathy Questionnaire-physical limitation score (2.4 [95% CI, -6.4 to 11.2]; P=0.54); Kansas City Cardiomyopathy Questionnaire-total symptom score (5.3 [95% CI, -4.3 to 14.9]; P=0.48); and NT-proBNP concentration (-339.4 pg/mL [95% CI, -1131.6 to 452.7]; P=0.17). The composite outcome of worsening heart failure or all-cause mortality (hazard ratio, 0.43 [95% CI, 0.11-1.74]; P=0.23) and overall survival (hazard ratio, 1.19 [95% CI, 0.23-6.02]; P=0.84) were similar between groups. No new safety findings were observed. Findings from REALM-DCM demonstrated futility without safety concerns. An unmet treatment need remains among patients with LMNA-related dilated cardiomyopathy. URL: https://classic.clinicaltrials.gov; Unique Identifiers: NCT03439514, NCT02057341, and NCT02351856.

층화 조건부 양적속성 무관질문모형

In this paper, when we want to obtain information, which is a sensitive quantitative attribute, from a stratified population, we propose a stratified conditional quantitative attribute unrelated question model capable of stratified estimation for sensitive attributes by using the quantitative attribute unrelated question model of Greenberg et al. (1971). In proposed model, only persons who answered “yes” through a randomization device composed of less sensitive attributes and forced questions are required to use the Greenberg et al.'s (1971) quantitative attribute unrelated question model. In addition, the sample allocation problem of each stratum is dealt with by considering proportional allocation and optimum one. We also propose a stratified conditional two sample quantitative attribute unrelated question model that can estimate sensitive quantitative attributes by stratification using two independent samples when there is no information about unrelated variables in proposed stratified conditional quantitative attribute unrelated question model. Lastly, the efficiency of the proposed model and the stratified quantitative attribute unrelated question model which applied the stratified sampling method to Greenberg et al.'s (1971) quantitative attribute unrelated question model are compared. And the efficiency of the conditional stratified two sample quantitative unrelated question model and the stratified two sample quantitative unrelated question model are compared.

Minor Genetic Overlap Among Rheumatoid Arthritis, Myocardial Infarction, and Myocardial Infarction Risk Determinants.

The aim of this study was to investigate whether a shared genetic susceptibility exists between individuals with rheumatoid arthritis (RA) and individuals with myocardial infarction (MI)-including major MI risk factors-and to quantify the degree of any such overlap. Genome-wide association study (GWAS) data for individuals with RA were constructed from a sample of 26,637 Swedish patients with RA and controls without RA. For patients with MI, GWAS data were obtained from a previously published meta-analysis. Genome-wide genetic correlation was estimated via linkage disequilibrium score regression. LAVA was employed to estimate local genetic correlations in ~2,500 nonoverlapping loci, including the major histocompatibility complex. The controls without RA were used for reference panel data. We also assessed stratified estimates of both genome-wide and local genetic correlation based on subsamples of individuals with seropositive RA and those with seronegative RA. Furthermore, genome-wide genetic correlation was estimated between RA and selected cardiovascular risk factors to elucidate pleiotropic relationships. Following quality control, our GWAS of patients with RA consisted of 25,826 individuas. Genome-wide genetic correlation between patients with RA and MI was estimated to 0.13 (95% confidence interval -0.03 to 0.29). Six regions exhibited significant local genetic correlation, though none harbored any known risk single-nucleotide polymorphisms for either of the two traits. Estimates were similar in both individuals with seropositive RA and those with seronegative RA. No statistically significant genetic correlations were observed between RA risk factors and any of the MI risk factors. Our findings indicate that genetic overlap between patients with RA and MI is minor. Furthermore, genetic overlap between RA and MI risk factors seem unlikely to provide a major contribution to the increased risk of MI observed in patients with RA.

Estimating disease burden using national linked electronic health records: a study using an English population-based cohort.

Electronic health records (EHRs) have the potential to be used to produce detailed disease burden estimates. In this study we created disease estimates using national EHR for three high burden conditions, compared estimates between linked and unlinked datasets and produced stratified estimates by age, sex, ethnicity, socio-economic deprivation and geographical region. EHRs containing primary care (Clinical Practice Research Datalink), secondary care (Hospital Episode Statistics) and mortality records (Office for National Statistics) were used. We used existing disease phenotyping algorithms to identify cases of cancer (breast, lung, colorectal and prostate), type 1 and 2 diabetes, and lower back pain. We calculated age-standardised incidence of first cancer, point prevalence for diabetes, and primary care consultation prevalence for low back pain. 7.2 million people contributing 45.3 million person-years of active follow-up between 2000-2014 were included. CPRD-HES combined and CPRD-HES-ONS combined lung and bowel cancer incidence estimates by sex were similar to cancer registry estimates. Linked CPRD-HES estimates for combined Type 1 and Type 2 diabetes were consistently higher than those of CPRD alone, with the difference steadily increasing over time from 0.26% (2.99% for CPRD-HES vs. 2.73 for CPRD) in 2002 to 0.58% (6.17% vs. 5.59) in 2013. Low back pain prevalence was highest in the most deprived quintile and when compared to the least deprived quintile the difference in prevalence increased over time between 2000 and 2013, with the largest difference of 27% (558.70 per 10,000 people vs 438.20) in 2013. We use national EHRs to produce estimates of burden of disease to produce detailed estimates by deprivation, ethnicity and geographical region. National EHRs have the potential to improve disease burden estimates at a local and global level and may serve as more automated, timely and precise inputs for policy making and global burden of disease estimation.

Claims and cost responsibility trends for high-deductible insurance plan participants with breast and prostate cancer in the New Hampshire Limited Use Commercial Health Care Claims data.

e23148 Background: High-deductible health plans (HDHPs) are popular in the US due to their potential to curb rising healthcare costs and involve higher out-of-pocket costs for consumers which are associated with lower utilization of health services. Data on longitudinal trends for claims and cost responsibility for adult HDHP participants with cancer is scarce, which was the motivation for our study. Methods: We used multivariable Poisson regression models with the Huber/White/Sandwich linearized estimator of variance and predictive margins [reported as counts with 95% confidence intervals (CI)] to examine the effect of HDHP status on select stratified estimates of (a) the average number of claims per enrollee (claims), and (b) the average total participant responsibility per enrollee visit (cost in $; i.e., the sum of in-network and out-of-network values), for adult (age &gt; / = 18 years) participants in the New Hampshire Limited Use Commercial Health Care Claims data, with breast and prostate cancer (BC/PC) diagnoses for the 10-year period 2010-19. Final models were fully adjusted for other plan types, year, age, and quintile of ecologic income, and our final dataset consisted of 945,281 claim records. Results: Overall, BC and PC HDHP participants had significantly fewer claims over the 10-year period [average counts: (BC: -242.2; -244.6, -239.8); (PC: -445.3; -450.3, -440.4)]. In addition, BC and PC HDHP participants had significantly lower participant responsibility over the 10-year period [average $: (BC: -85.4; -87.5, -83.2); (PC: -104.9; -115.5, -94.2)]. Overall trends for claims across the entire time period for HDHP vs. non-HDHP BC/PC participants were consistently lower, and flat trends were observed for BC from 2014-19 and for PC from 2012-19; however, there was steady increase in claims for both BC/PC non-HDHP participants across the same late periods. The trend for participant responsibility for BC HDHP participants was also lower compared with non-HDHP for all years except 2014; and after 2014 increases were seen for both BC HDHP and non-HDHP participants with the latter showing the steepest increases. The trend for participant responsibility for PC HDHP participants was lower compared with non-HDHP between 2010-17; but this relationship inverted for 2018-19 with HDHP participants showing the highest participant responsibility levels. Conclusions: Our findings show discordance in claims trends for HDHP vs. non-HDHP participants with BC/PC; durable trends of reduced claims are observed for HDHP participants, but for non-HDHP participants claim trends show steady increases in later periods.

ENSEMBLE PLUS: final results of shorter ocrelizumab infusion from a randomized controlled trial

IntroductionOcrelizumab is an approved intravenously administered anti-CD20 antibody for multiple sclerosis (MS). The safety profile and patient preference for conventional versus shorter ocrelizumab infusions were investigated in the ENSEMBLE PLUS study.MethodsENSEMBLE PLUS was a randomized, double-blind substudy to the single-arm ENSEMBLE study (NCT03085810), comparing outcomes in patients with early-stage relapsing–remitting MS receiving ocrelizumab 600 mg over the approved 3.5-h (conventional) versus 2-h (shorter) infusion. The primary endpoint was the proportion of patients with infusion-related reactions (IRRs) following the first randomized dose (RD); the secondary endpoint included IRR frequency at subsequent RDs.ResultsAt first RD, the number of patients with an IRR in the conventional (101/373; 27.1%) versus shorter (107/372; 28.8%) infusion group was similar (difference, stratified estimates [95% CI]: 1.9% [− 4.4, 8.2]). Most IRRs (conventional: 99.4%; shorter: 97.7%) were mild/moderate. IRR frequency decreased over the course of RDs; three patients discontinued from the shorter infusion arm but continued with conventional infusion. Overall, > 98% of IRRs resolved without sequelae in both groups. Pre-randomization throat irritation was predictive of future throat irritation as an IRR symptom. Adverse events (AEs) and serious AEs were consistent with the known ocrelizumab safety profile. On completion of ENSEMBLE PLUS, most patients chose to remain on (95%) or switch to (80%) shorter infusion.ConclusionENSEMBLE PLUS demonstrates the safety and tolerability of shorter ocrelizumab infusions. Most patients remained on/switched to shorter infusion after unblinding; IRRs did not strongly influence patient decisions.Clinical Trials Registration: Substudy of ENSEMBLE (NCT03085810). Registration: March 21, 2017.

A stratified estimation for sensitive variable using correlated scrambling variables

In this article, when the population is composed of several strata, we deal with the problem of stratified estimation for sensitive variables by applying stratified sampling to Murtaza et al.’s model using correlated scrambling variables. When the size of each stratum is accurately known, the sensitive variable is estimated by stratification, and the proportional and optimal allocations are examined as a method of allocating samples to each stratum. Also, in the case of not knowing the size of each stratum, a sensitive variable is estimated by using two-phase sampling, and the method of allocating samples to each stratum is also examined. Also, the efficiency between the proposed stratified model of Murtaza et al.’s and the existing model of Murtaza et al.’s is compared.

Using Stratified Sampling to Improve LIME Image Explanations

We investigate the use of a stratified sampling approach for LIME Image, a popular model-agnostic explainable AI method for computer vision tasks, in order to reduce the artifacts generated by typical Monte Carlo sampling. Such artifacts are due to the undersampling of the dependent variable in the synthetic neighborhood around the image being explained, which may result in inadequate explanations due to the impossibility of fitting a linear regressor on the sampled data. We then highlight a connection with the Shapley theory, where similar arguments about undersampling and sample relevance were suggested in the past. We derive all the formulas and adjustment factors required for an unbiased stratified sampling estimator. Experiments show the efficacy of the proposed approach.

Optimal allocation strategies in platform trials with continuous endpoints.

Platform trials are randomized clinical trials that allow simultaneous comparison of multiple interventions, usually against a common control. Arms to test experimental interventions may enter and leave the platform over time. This implies that the number of experimental intervention arms in the trial may change as the trial progresses. Determining optimal allocation rates to allocate patients to the treatment and control arms in platform trials is challenging because the optimal allocation depends on the number of arms in the platform and the latter typically varies over time. In addition, the optimal allocation depends on the analysis strategy used and the optimality criteria considered. In this article, we derive optimal treatment allocation rates for platform trials with shared controls, assuming that a stratified estimation and a testing procedure based on a regression model are used to adjust for time trends. We consider both, analysis using concurrent controls only as well as analysis methods using concurrent and non-concurrent controls and assume that the total sample size is fixed. The objective function to be minimized is the maximum of the variances of the effect estimators. We show that the optimal solution depends on the entry time of the arms in the trial and, in general, does not correspond to the square root of allocation rule used in classical multi-arm trials. We illustrate the optimal allocation and evaluate the power and type 1 error rate compared to trials using one-to-one and square root of allocations by means of a case study.