Clinformatics Data Mart Database Research Articles

Using Machine Learning Models to Identify Factors Associated With 30-Day Readmissions After Posterior Cervical Fusions: A Longitudinal Cohort Study.

Readmission rates after posterior cervical fusion (PCF) significantly impact patients and healthcare, with complication rates at 15%-5% and up to 12% 90-day readmission rates. In this study, we aim to test whether machine learning (ML) models that capture interfactorial interactions outperform traditional logistic regression (LR) in identifying readmission-associated factors. The Optum Clinformatics Data Mart database was used to identify patients who underwent PCF between 2004-2017. To determine factors associated with 30-day readmissions, 5 ML models were generated and evaluated, including a multivariate LR (MLR) model. Then, the best-performing model, Gradient Boosting Machine (GBM), was compared to the LACE (Length patient stay in the hospital, Acuity of admission of patient in the hospital, Comorbidity, and Emergency visit) index regarding potential cost savings from algorithm implementation. This study included 4,130 patients, 874 of which were readmitted within 30 days. When analyzed and scaled, we found that patient discharge status, comorbidities, and number of procedure codes were factors that influenced MLR, while patient discharge status, billed admission charge, and length of stay influenced the GBM model. The GBM model significantly outperformed MLR in predicting unplanned readmissions (mean area under the receiver operating characteristic curve, 0.846 vs. 0.829; p<0.001), while also projecting an average cost savings of 50% more than the LACE index. Five models (GBM, XGBoost [extreme gradient boosting], RF [random forest], LASSO [least absolute shrinkage and selection operator], and MLR) were evaluated, among which, the GBM model exhibited superior predictive performance, robustness, and accuracy. Factors associated with readmissions impact LR and GBM models differently, suggesting that these models can be used complementarily. When analyzing PCF procedures, the GBM model resulted in greater predictive performance and was associated with higher theoretical cost savings for readmissions associated with PCF complications.

Associations Between Neuroinflammation-Related Conditions and Alzheimer's Disease: A Study of US Insurance Claims Data.

Early detection of Alzheimer's disease (AD) is a key component for the success of the recently approved lecanemab and aducanumab. Patients with neuroinflammation-related conditions are associated with a higher risk for developing AD. Investigate the incidence of AD among patients with neuroinflammation-related conditions including epilepsy, hemorrhage stroke, multiple sclerosis (MS), and traumatic brain injury (TBI). We used Optum's de-identified Clinformatics Data Mart Database (CDM). We derived covariate-matched cohorts including patients with neuroinflammation-related conditions and controls without the corresponding condition. The matched cohorts were: 1) patients with epilepsy and controls (N = 67,825 matched pairs); 2) patients with hemorrhage stroke and controls (N = 81,510 matched pairs); 3) patients with MS and controls (N = 9,853 matched pairs); and 4) patients TBI and controls (N = 104,637 matched pairs). We used the Cox model to investigate the associations between neuroinflammation-related conditions and AD. We identified that epilepsy, hemorrhage stroke, and TBI were associated with increased risks of AD in both males and females (hazard ratios [HRs]≥1.74, p < 0.001), as well as in gender- and race-conscious subpopulations (HRs≥1.64, p < 0.001). We identified that MS was associated with increased risks of AD in both males and females (HRs≥1.47, p≤0.004), while gender- and race-conscious subgroup analysis shown mixed associations. Patients with epilepsy, hemorrhage stroke, MS, and/or TBI are associated with a higher risk of developing AD. More attention on cognitive status should be given to older patients with these conditions.

Active surveillance pharmacovigilance for Clostridioides difficile infection and gastrointestinal bleeding: an analytic framework based on case-control studies

Active surveillance pharmacovigilance is an emerging approach to identify medications with unanticipated effects. We previously developed a framework called pharmacopeia-wide association studies (PharmWAS) that limits false positive medication associations through high-dimensional confounding adjustment and set enrichment. We aimed to assess the transportability and generalizability of the PharmWAS framework by using medical claims data to reproduce known medication associations with Clostridioides difficile infection (CDI) or gastrointestinal bleeding (GIB). We conducted case-control studies using Optum's de-identified Clinformatics Data Mart Database of individuals enrolled in large commercial and Medicare Advantage health plans in the United States. Individuals with CDI (from 2010 to 2015) or GIB (from 2010 to 2021) were matched to controls by age and sex. We identified all medications utilized prior to diagnosis and analysed the association of each with CDI or GIB using conditional logistic regression adjusted for risk factors for the outcome and a high-dimensional propensity score. For the CDI study, we identified 55,137 cases, 220,543 controls, and 290 medications to analyse. Antibiotics with Gram-negative spectrum, including ciprofloxacin (aOR 2.83), ceftriaxone (aOR 2.65), and levofloxacin (aOR 1.60), were strongly associated. For the GIB study, we identified 450,315 cases, 1,801,260 controls, and 354 medications to analyse. Antiplatelets, anticoagulants, and non-steroidal anti-inflammatory drugs, including ticagrelor (aOR 2.81), naproxen (aOR 1.87), and rivaroxaban (aOR 1.31), were strongly associated. These studies demonstrate the generalizability and transportability of the PharmWAS pharmacovigilance framework. With additional validation, PharmWAS could complement traditional passive surveillance systems to identify medications that unexpectedly provoke or prevent high-impact conditions. U.S. National Institute of Diabetes and Digestive and Kidney Diseases.

Changes in the Appropriateness of US Outpatient Antibiotic Prescribing After the Coronavirus Disease 2019 Outbreak: An Interrupted Time Series Analysis of 2016–2021 Data

Abstract Background No national study has evaluated changes in the appropriateness of US outpatient antibiotic prescribing across all conditions and age groups after the coronavirus disease 2019 (COVID-19) outbreak in March 2020. Methods This was an interrupted time series analysis of Optum's de-identified Clinformatics Data Mart Database, a national commercial and Medicare Advantage claims database. Analyses included prescriptions for antibiotics dispensed to children and adults enrolled during each month during 2017–2021. For each prescription, we applied our previously developed antibiotic appropriateness classification scheme to International Classification of Diseases, Tenth Revision, Clinical Modification diagnosis codes on medical claims occurring on or during the 3 days prior to dispensing. Outcomes included the monthly proportion of antibiotic prescriptions that were inappropriate and the monthly proportion of enrollees with ≥1 inappropriate prescription. Using segmented regression models, we assessed for level and slope changes in outcomes in March 2020. Results Analyses included 37 566 581 enrollees, of whom 19 154 059 (51.0%) were female. The proportion of enrollees with ≥1 inappropriate prescription decreased in March 2020 (level decrease: −0.80 percentage points [95% confidence interval {CI}, −1.09% to −.51%]) and subsequently increased (slope increase: 0.02 percentage points per month [95% CI, .01%–.03%]), partly because overall antibiotic dispensing rebounded and partly because the proportion of antibiotic prescriptions that were inappropriate increased (slope increase: 0.11 percentage points per month [95% CI, .04%–.18%]). In December 2021, the proportion of enrollees with ≥1 inappropriate prescription equaled the corresponding proportion in December 2019. Conclusions Despite an initial decline, the proportion of enrollees exposed to inappropriate antibiotics returned to baseline levels by December 2021. Findings underscore the continued importance of outpatient antibiotic stewardship initiatives.

Financial Viability of the No Surprises Act Independent Dispute Resolution Process: Radiology and Other Hospital-Based Specialties.

BACKGROUND. The federal No Surprises Act (NSA), designed to eliminate surprise medical billing for out-of-network (OON) care for circumstances beyond patients' control, established the independent dispute resolution (IDR) process to settle clinician-payer payment disputes for OON care. OBJECTIVE. The purpose of our study was to assess the fraction of OON claims for which radiologists and other hospital-based specialists can expect to at least break even when challenging payer-determined payments through the NSA IDR process, as a measure of the process's financial viability. METHODS. This retrospective study extracted claims from a national commercial database (Optum's deidentified Clinformatics Data Mart) for hospital-based specialties occurring on the same day as in-network emergency department (ED) visits or inpatient stays from January 2017 to December 2021. OON claims were identified. OON claims batching was simulated using IDR rules. Maximum potential recovered payments from the IDR process were estimated as the difference between the charges and the allowed amount. The percentages of claims for which the maximum potential payment and one-quarter of this amount (a more realistic payment recovery estimate) would exceed IDR fees were determined, using US$150 and US$450 fee thresholds to approximate the range of final 2024 IDR fees. These values represented the percentage of OON claims that would be financially viable candidates for IDR submission. RESULTS. Among 76,221,264 claims for hospital-based specialties associated with in-network ED visits or inpatient stays, 1,482,973 (1.9%) were OON. The maximum potential payment exceeded fee thresholds of US$150 and US$450 for 55.0% and 32.1%, respectively, of batched OON claims for radiologists and 76.8% and 61.3% of batched OON claims for all other hospital-based specialties combined. At payment of one-quarter of that amount, these values were 26.9% and 10.6%, respectively, for radiologists and 56.6% and 38.4% for all other hospital-based specialties combined. CONCLUSION. The IDR process would be financially unviable for a substantial fraction of OON claims for hospital-based specialists (more so for radiology than for other such specialties). CLINICAL IMPACT. Although the NSA enacted important patient protections, IDR fees limit clinicians' opportunities to dispute payer-determined payments and potentially undermine their bargaining power in contract negotiations. Therefore, IDR rulemaking may negatively impact patient access to in-network care.

Perinatal Posttraumatic Stress Disorder Diagnoses Among Commercially Insured People Increased, 2008-20.

Posttraumatic stress disorder (PTSD) is a burdensome disorder, affecting 3-4percent of delivering people in the US, with higher rates seen among Black and Hispanic people. The extent of clinical diagnosis remains unknown. We describe the temporal and racial and ethnic trends in perinatal PTSD diagnoses among commercially insured people with live-birth deliveries during the period 2008-20, using administrative claims from Optum's Clinformatics Data Mart Database. Predicted probabilities from our logistic regression analysis showed a 394percent increase in perinatal PTSD diagnoses, from 37.7 per 10,000 deliveries in 2008 to 186.3 per 10,000 deliveries in 2020. White people had the highest diagnosis rate at all time points (208.0 per 10,000 deliveries in 2020), followed by Black people, people with unknown race, Hispanic people, and Asian people (188.7, 171.9, 146.9, and 79.8 per 10,000 deliveries in 2020, respectively). The significant growth in perinatal PTSD diagnosis rates may reflect increased awareness, diagnosis, or prevalence of the disorder. However, these rates fall well below the estimated prevalence of PTSD in the perinatal population.

Real-world association between systemic corticosteroid exposure and complications in US patients with severe asthma

BackgroundSystemic corticosteroid (SCS) use remains widespread among patients with severe asthma, despite associated complications.ObjectiveEvaluate the association between cumulative SCS exposure and SCS-related complications in severe asthma.MethodsThis retrospective, longitudinal study used claims data from the Optum Clinformatics Data Mart database (GSK ID: 214469). Eligible patients (≥ 12 years old) had an asthma diagnosis and were divided into two cohorts: SCS use and non/burst-SCS use. Patients in the SCS use cohort had a claim for a daily prednisone-equivalent dose ≥ 5 mg SCS following ≥ 6 months of continuous SCS use; those in the non/burst-SCS cohort had no evidence of continuous SCS use and had a non-SCS controller/rescue medication initiation claim. For each cohort, the date of the qualifying claim was the index date. SCS users were further stratified by SCS use during each quarter of follow-up: low (≤ 6 mg/day), medium (> 6–12 mg/day), high (> 12 mg/day), and continuous high (≥ 20 mg/day for 90 days). SCS-related complications were evaluated in the quarter following SCS exposure. The adjusted odds ratios (OR) of experiencing SCS-related complications during follow-up in each of the SCS use groups versus the non/burst SCS cohort were calculated using generalized estimating equations models.ResultsSCS and non/burst-SCS use cohorts included 7473 and 89,281 patients (mean follow-up: 24.6 and 24.2 months), respectively. Compared with the non/burst-SCS use cohort, medium, high, and continuous high SCS use was associated with greater odds of any SCS-related complication (adjusted OR [95% confidence interval]: 1.30 [1.21, 1.39], 1.49 [1.35, 1.64] and 1.63 [1.40, 1.89], respectively) including increased acute gastrointestinal, cardiovascular, and immune system-related complications, and chronic cardiovascular, metabolic/endocrine, central nervous system, bone-/muscle-related, ophthalmologic, and hematologic/oncologic complications. Low-dose SCS use was also associated with significantly increased odds of acute gastrointestinal and immune system-related complications, and chronic bone-/muscle-related and hematologic/oncologic complications versus the non/burst-SCS use cohort.ConclusionSCS use, even at low doses, is associated with increased risk of SCS-related complications among patients with severe asthma.

Association between social vulnerability index and admission urgency for transcatheter aortic valve replacement

BackgroundTranscatheter aortic valve replacement (TAVR) are not offered equitably to vulnerable population groups. Adequate levels of insurance may narrow gaps among patients with higher social vulnerability index (SVI). Among a national population of individuals with commercial or Medicare insurance, we sought to determine whether SVI was associated with urgency of receipt of TAVR for aortic stenosis. Methods and resultsUsing Optum's de-identified Clinformatics Data Mart Database (CDM), we identified admissions for TAVR with aortic stenosis between January 2018 and March 2022. Admission urgency was identified by CDM claims codes. SVI was cross-referenced to patient zip codes and grouped into quintiles. Generalized linear mixed effects models were used to predict the probability of a TAVR admission being urgent based on SVI quintiles, adjusting for patient and hospital-level covariates. ResultsAmong 6680 admissions for TAVR [median age 80 years (interquartile range 75–85), 43.9 % female], 8.5 % (n = 567) were classified as urgent. After adjusting for patient and hospital-level variables, there were no significant differences in the odds of urgent admission for TAVR according to SVI quintiles [OR 5th (greatest social vulnerability) vs 1st quintile (least social vulnerability): 1.29 (95 % CI: 0.90–1.85)]. ConclusionsAmong commercial or Medicare beneficiaries with aortic stenosis, SVI was not associated with admission urgency for TAVR. To clarify whether cardiovascular care delivery is improved across SVI with higher paying beneficiaries, future investigation should identify whether relationships between SVI and TAVR urgency vary for Medicaid beneficiaries compared to commercial beneficiaries.

Dynamic Prognosis Prediction for Patients on DAPT After Drug-Eluting Stent Implantation: Model Development and Validation.

The rapid evolution of artificial intelligence (AI) in conjunction with recent updates in dual antiplatelet therapy (DAPT) management guidelines emphasizes the necessity for innovative models to predict ischemic or bleeding events after drug-eluting stent implantation. Leveraging AI for dynamic prediction has the potential to revolutionize risk stratification and provide personalized decision support for DAPT management. We developed and validated a new AI-based pipeline using retrospective data of drug-eluting stent-treated patients, sourced from the Cerner Health Facts data set (n=98 236) and Optum's de-identified Clinformatics Data Mart Database (n=9978). The 36 months following drug-eluting stent implantation were designated as our primary forecasting interval, further segmented into 6 sequential prediction windows. We evaluated 5 distinct AI algorithms for their precision in predicting ischemic and bleeding risks. Model discriminative accuracy was assessed using the area under the receiver operating characteristic curve, among other metrics. The weighted light gradient boosting machine stood out as the preeminent model, thus earning its place as our AI-DAPT model. The AI-DAPT demonstrated peak accuracy in the 30 to 36 months window, charting an area under the receiver operating characteristic curve of 90% [95% CI, 88%-92%] for ischemia and 84% [95% CI, 82%-87%] for bleeding predictions. Our AI-DAPT excels in formulating iterative, refined dynamic predictions by assimilating ongoing updates from patients' clinical profiles, holding value as a novel smart clinical tool to facilitate optimal DAPT duration management with high accuracy and adaptability.

Treatment Patterns, Healthcare Resource Utilization, and Costs of Patients With Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma in the US.

Chronic lymphocytic leukemia (CLL) is the most common type of leukemia among US adults and has experienced a rapidly evolving treatment landscape; yet current data on treatment patterns in clinical practice and economic burden are limited. This study aimed to provide an up-to-date description of real-world characteristics, treatments, and costs of patients with CLL or small lymphocytic lymphoma (SLL). Using retrospective data from the Optum Clinformatics DataMart database (January 2013 to December 2021), adults with diagnosis codes for CLL/SLL on two different dates were selected. An adapted algorithm identified lines of therapy (LOT). Treatment patterns were stratified by the index year pre- and post-2018. Healthcare resource utilization and costs were evaluated per patient-years. A total of 18 418 patients with CLL/SLL were identified, 5226 patients (28%) were treated with ≥1 LOT and 1728 (9%) with ≥2 LOT. Among patients diagnosed with CLL in 2014-2017 and ≥1 LOT (N = 2585), 42% used targeted therapy and 30% used chemoimmunotherapy in first line (1L). The corresponding proportions of patients diagnosed with CLL in 2018-2021 (N = 2641) were 54% and 16%, respectively. Total costs were numerically 3.5 times higher and 4.9 times higher compared with baseline costs among patients treated with 1L+ and 3L+, respectively. This study documented the real-world change in CLL treatment landscape and the substantial economic burden of patients with CLL/SLL. Specifically, targeted therapies were increasingly used as 1L treatments and they were part of more than half of 1L regimens in recent years (2018-2021).

Characteristics of Patients Receiving Novel Muscular Dystrophy Drugs in Trials vs Routine Care

The US Food and Drug Administration approved eteplirsen for Duchenne muscular dystrophy (DMD) in 2016 based on a controversial pivotal study that demonstrated a limited effect on the surrogate measure of dystrophin production. Other DMD treatments in the same class followed. To assess how patients receiving novel DMD treatments in postapproval clinical settings compare with patients in the clinical trials. This cross-sectional study collected data on patients who initiated 1 of 4 novel DMD treatments (eteplirsen, golodirsen, viltolarsen, and casimersen) using national claims databases of commercially insured (Merative MarketScan and Optum's Clinformatics Data Mart Database [CDM]) and Medicaid patients between September 19, 2016, and March 31, 2022. Patients were followed for 1 year after the date of first use of any novel DMD treatment. In addition, patients in pivotal DMD drug trials were identified for comparison. Age, sex, race and ethnicity, region, and DMD stage of patients receiving novel DMD treatment. The main outcome was health care costs and drug discontinuation as measured using descriptive statistics. A total of 223 routine care patients initiating novel DMD drugs (58 in MarketScan, 35 in CDM, and 130 in Medicaid) were identified. Among the 106 patients in the pivotal trials, the mean (SD) age was 8.5 (2.0) years (range, 4.0-13.0 years), which was younger than the mean age of patients in routine care (MarketScan: 13.7 [7.0] years [range, 1.8-33.3 years; P < .001]; CDM: 11.9 [5.7] years [range, 0.6-23.6 years; P < .001]; Medicaid: 13.4 [6.5] years [range, 1.8-46.1 years; P < .001]). The proportion of female patients identified in postapproval clinical settings was 2.9% (n = 1) in CDM (vs 34 male patients [97.1%]) and 1.5% (n = 2) in Medicaid (vs 128 male patients [98.5%]), which was not different from the pivotal trials. While nearly all patients in the pivotal trials had DMD disease stage 1 or 2 when initiating the DMD treatments (103 [97.2%]), in the postapproval clinical setting, slightly more than one-third of patients were in disease stage 3 or 4 (MarketScan, 17 [36.2%; P < .001]; CDM, 13 [41.9%; P < .001]; Medicaid, 54 [47.0%; P < .001]). The payer's cost for novel DMD treatments varied across the databases, with a mean (SD) of $634 764 ($607 101) in MarketScan, $482 749 ($582 350) in CDM, and $384 023 ($1 165 730) in Medicaid. Approximately one-third of routine care patients discontinued the treatments after approximately 7 months (mean [SD], 6.1 [4.4], 6.9 [3.9], and 7.2 [4.3] months in MarketScan, CDM, and Medicaid, respectively). These findings raise questions about the translation of DMD drug trial findings to routine care settings, with patients in routine care discontinuing the treatment within 1 year and payers incurring substantial expenses for these medications. More data are needed on whether these high costs are accompanied by corresponding clinical benefits.

Sex Disparities in Longitudinal Use and Intensification of Guideline-Directed Medical Therapy Among Patients With Newly Diagnosed Heart Failure With Reduced Ejection Fraction.

Guideline-directed medical therapies (GDMTs) are the mainstay of treatment for heart failure with reduced ejection fraction (HFrEF), but they are underused. Whether sex differences exist in the initiation and intensification of GDMT for newly diagnosed HFrEF is not well established. Patients with incident HFrEF were identified from the 2016 to 2020 Optum deidentified Clinformatics Data Mart Database, which is derived from a database of administrative health claims for members of large commercial and Medicare Advantage health plans. The primary outcome was the use of optimal GDMT within 12 months of HFrEF diagnosis. Consistent with the guideline recommendations during the time period of the study, optimal GDMT was defined as ≥50% of the target dose of evidence-based beta-blocker plus ≥50% of the target dose of angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, or any dose of angiotensin receptor neprilysin inhibitor plus any dose of mineralocorticoid receptor antagonist. The probability of achieving optimal GDMT on follow-up and predictors of optimal GDMT were evaluated with time-to-event analysis with adjusted Cox proportional hazard models. The study cohort included 63 759 patients (mean age, 71.3 years; 15.2% non-Hispanic Black race; 56.6% male). Optimal GDMT use was achieved by 6.2% of patients at 12 months after diagnosis. Female (compared with male) patients with HFrEF had lower use across every GDMT class and lower use of optimal GDMT at each time point at follow-up. In an adjusted Cox model, female sex was associated with a 23% lower probability of achieving optimal GDMT after diagnosis (hazard ratio [HR], 0.77 [95% CI, 0.71-0.83]; P<0.001). The sex disparities in GDMT use after HFrEF diagnosis were most pronounced among patients with commercial insurance (females compared with males; HR, 0.66 [95% CI, 0.58-0.76]) compared with Medicare (HR, 0.85 [95% CI, 0.77-0.92]); Pinteraction sex×insurance status=0.005) and for younger patients (age <65 years: HR, 0.65 [95% CI, 0.58-0.74]) compared with older patients (age ≥65 years: HR, 87 [95% CI, 80-96]) Pinteraction sex×age=0.009). Overall use of optimal GDMT after HFrEF diagnosis was low, with significantly lower use among female (compared with male) patients. These findings highlight the need for implementation efforts directed at improving GDMT initiation and titration.

Radiologists’ Out-of-Network Billing Trends, 2007 to 2021

PurposeGiven the financial hardships of surprise billing for patients, the aim of this study was to assess the degree to which radiologists effectively participate in commercial insurance networks by examining the trend in the share of radiologists’ imaging claims that are out of network (OON). MethodsA retrospective study over a 15-year period (2007-2021) was conducted using claims from Optum’s deidentified Clinformatics Data Mart Database to assess the share of radiologists’ imaging claims that are OON. Radiologists’ annual OON rate was assessed overall as well as for claims associated with inpatient stays and emergency department (ED) visits. Rates were assessed for all imaging studies as well as by modality. Linear regression was conducted to assess OON rate time trends. ResultsFrom 2007 to 2021, 5,039,142 of radiologists’ imaging claims (6.3%) were OON. This rate declined from 12.6% in 2007 to 1.1% in 2021. Over the study period, the OON rate was 5.0% during an inpatient stay and 2.1% on the same day as an ED visit that did not lead to an inpatient admission. The linear trend in the overall OON rate declined 0.74 percentage points annually (95% confidence interval [CI], −0.90 to −0.58 percentage points) over the study period. Likewise, the annual declines were 0.54 percentage points (95% CI, −0.71 to −0.36) and 0.26 percentage points (95% CI, −0.33 to −0.20 percentage points) for imaging claims associated with inpatient stays and ED visits, respectively. ConclusionsRadiologists’ imaging claims that are OON has significantly declined from 2007 to a minimal level in 2021. This may indicate effective negotiations between radiologists and commercial payers and new state-level surprise billing laws.

The Neiman Imaging Comorbidity Index: Development and Validation in a National Commercial Claims Database

ObjectiveTo build the Neiman Imaging Comorbidity Index (NICI), based on variables available in claims datasets, which provides good discrimination of an individual’s chance of receiving advanced imaging (CT, MR, PET), and thus, utility as a control variable in research. MethodsThis retrospective study used national commercial claims data from Optum’s deidentified Clinformatics Data Mart database from the period January 1, 2018 to December 31, 2019. Individuals with continuous enrollment during this 2-year study period were included. Lasso (least absolute shrinkage and selection operator) regression was used to predict the chance of receiving advanced imaging in 2019 based on the presence of comorbidities in 2018. A numerical index was created in a development cohort (70% of the total dataset) using weights assigned to each comorbidity, based on regression β coefficients. Internal validation of assigned scores was performed in the remaining 30% of claims, with comparison to the commonly used Charlson Comorbidity Index. ResultsThe final sample (development and validation cohorts) included 10,532,734 beneficiaries, of whom 2,116,348 (20.1%) received advanced imaging. After model development, the NICI included nine comorbidities. In the internal validation set, the NICI achieved good discrimination of receipt of advanced imaging with a C statistic of 0.709 (95% confidence interval [CI] 0.708-0.709), which predicted advanced imaging better than the CCI (C 0.692, 95% CI 0.691-0.692). Controlling for age and sex yielded better discrimination (C 0.748, 95% CI 0.748-0.749). DiscussionThe NICI is an easily calculated measure of comorbidity burden that can be used to adjust for patients’ chances of receiving advanced imaging. Future work should explore external validation of the NICI.

Real-World Patterns of Targeted Therapy Use in Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma in the United States: A Longitudinal Study

Introduction: Clinical guidelines and practice have shifted toward increasing use of novel Bruton's tyrosine kinase inhibitors (BTKi) or B-cell lymphoma 2 inhibitor (BCL2i) for treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). To highlight recent changes in clinical practice, this study evaluated real-world treatment sequences, with a focus on sequential novel targeted therapy, among patients with CLL/SLL in the US over time. Methods: Adult patients with ≥2 medical claims for CLL/SLL diagnosis on distinct days and ≥1 claim for CLL/SLL therapy were identified in the Optum Clinformatics DataMart database (2014-2021). The index date was the date of initiation of the first observed line of therapy (LOT) following the first observed CLL/SLL diagnosis. The observation period spanned from index to the earliest of end of eligibility, data availability, or death. LOTs were identified using a claims-based algorithm adapted from published literature during the observation period. Each LOT spanned from the initiation of a new agent to discontinuation of all agents in the LOT (i.e., 90-day gap without any dispensing), a switch to another agent, or the addition of a new agent. The proportion of patients receiving sequential targeted therapy in the first 2 LOTs (i.e., BTKi/BCL2i as first-line [1L] and second-line [2L] treatments in any order) was described. For sequential BTKi in 1L and 2L, treatments were also described by agent (i.e., ibrutinib, acalabrutinib, zanubrutinib, and combinations thereof). To assess longitudinal patterns, Sankey plots were created for 2 temporal data cohorts: patients with a 1L in 2014-2017 and patients with a 1L in 2018-2021. Results: We identified 7,146 eligible patients, 40.6% female, median age 73 years, with a median follow-up of 2 years after 1L initiation. The most common 1L treatment was BTKi (36.8%), then chemoimmunotherapy (CIT; 27.4%), CD20 (22.2%), chemotherapy (7.6%), and BCL2i (5.4%). In the first 2 LOTs, 22.3% of patients had sequential targeted therapy, comprising 70.0% BTKi→BTKi (i.e., BTKi retreated), 23.8% BTKi→BCL2i, 3.6% BCL2i→BCL2i, and 2.6% BCL2i→BTKi. The most common BTKi sequences by agent were ibrutinib→ibrutinib (61.6%) and ibrutinib→acalabrutinib (28.4%). Among patients with a 1L in 2014-2017 (N=2,612; median follow-up=3 years; Figure A), the most common 1L treatment class was CIT (44.6%), followed by CD20 (25.2%), BTKi (21.7%), chemotherapy (7.6%), and BCL2i (0.3%). For those receiving a 2L treatment (N=905), the 3 most common treatment classes were BTKi (37.6%), CD20 (30.2%), and CIT (17.2%). The proportion of patients receiving sequential targeted therapy in the first 2 LOTs was 11.2%; among these patients, 80.2% had BTKi→BTKi; 17.8% had BTKi→BCL2i; 2.0% had BCL2i→BCL2i; and 0% had BCL2i→BTKi. The most common BTKi sequences by agent were ibrutinib→ibrutinib (81.5%) and ibrutinib→acalabrutinib (17.3%). Among patients with a 1L in 2018-2021 (N=4,534; median follow-up=1 year; Figure B), the most common 1L treatment class was BTKi (45.5%), followed by CD20 (20.4%), CIT (17.5%), BCL2i (8.3%), and chemotherapy (7.6%). For 2L (N=833), the 3 most common treatment classes were BTKi (40.9%), CD20 (24.4%), and BCL2i (14.9%). The proportion of patients receiving sequential targeted therapy in the first 2 LOTs was 34.3%, comprising 66.4% BTKi→BTKi; 25.9% BTKi→BCL2i; 4.2% BCL2i→BCL2i; and 3.5% BCL2i→BTKi). Among those receiving sequential BTKi, the most common sequences by agent were ibrutinib→ibrutinib (53.2%), ibrutinib→acalabrutinib (33.2%), and acalabrutinib→acalabrutinib (5.3%). Conclusions: This longitudinal real-world study found a substantial increase in patients with CLL/SLL receiving targeted therapies in 1L over time. In particular, the proportion receiving BTKi in 1L doubled in 2018-2021 relative to 2014-2017 and accounted for almost half of the recent 1L CLL/SLL initiations. A third of patients with 1L observed in 2018-2021 also received a targeted agent in 2L, relative to about 1 in 10 patients in 2014-2017, with BTKi→BTKi being the most common sequence. Surprisingly, patients who received a BTKi in 1L were more likely to receive a BTKi in 2L than they were to switch to a BCL2i. Future studies should assess clinical outcomes to determine optimal sequences for CLL/SLL as well as the reasons for re-treatment with BTKi.

Use of Disease-Modifying Treatments in Patients With Sickle Cell Disease

Despite hydroxyurea being an established treatment for sickle cell disease (SCD), it remains underused. The recent approval of the disease-modifying treatments (DMTs) l-glutamine, crizanlizumab, and voxelotor underscores the need to understand the uptake of DMTs in the current treatment landscape. To explore characteristics that may be associated with DMT use and to describe observed patterns of yearly DMT use from 2014 to 2021. This cross-sectional study used administrative claims data from Optum's deidentified Clinformatics Data Mart Database from January 1, 2014, to September 30, 2021, to identify adults and children with SCD. Data were analyzed from August 1, 2022, to August 28, 2023. Use of DMTs. Patient characteristics across groups with varying patterns of DMT use and yearly patterns of prescription fills for hydroxyurea, crizanlizumab, voxelotor, and l-glutamine. A total of 5022 beneficiaries with SCD (2081 [41.4%] aged 18-45 years; 2929 [58.3%] female) were included in sample A (144 [2.9%] inconsistent users, 274 [5.5%] incident users, 892 [17.8%] consistent users, and 3712 [73.9%] non-DMT users). Inconsistent users had a higher prevalence of vaso-occlusive crises (mean [SD], 3.7 [4.7]), splenic complications (6 of 144 [4.2%]), pulmonary complications (36 of 144 [25.0%]), kidney disease (21 of 144 [14.6%]), acute chest syndrome (18 of 144 [12.5%]), and health care visits (eg, mean [SD] inpatient visits, 7.0 [10.7]) compared with the other use groups. Non-DMT users had the lowest prevalence of vaso-occlusive crises (mean [SD], 0.8 [2.4]), acute chest syndrome (109 of 3712 [2.9%]), and inpatient (mean [SD], 2.0 [6.6]) and emergency department (mean [SD], 0.7 [3.1]) visits and the highest proportion of adults 65 years and older (593 of 3712 [16.0%]). In sample B (6387 beneficiaries with SCD), hydroxyurea use modestly increased from 428 of 2188 participants (19.6%) in 2014 to 701 of 2880 (24.3%) in 2021. Use of l-glutamine increased briefly but gradually decreased throughout the study period. In 2021, out of 2880 participants, 102 (3.5%) had at least 1 fill for crizanlizumab and 131 (4.6%) had at least 1 fill for voxelotor. Overall, total DMT use increased from 428 of 2188 participants (19.6%) in 2014 to 815 of 2880 patients (28.3%) in 2021. In this cross-sectional analysis of adults and children with SCD, uptake of DMTs remained low from 2014 to 2021, despite the approval of newer therapies. Notable differences in patient characteristics across varied DMT exposure types necessitate further exploration into factors that facilitate DMT use and the creation of strategies to enhance DMT uptake.

Comparative Safety and Effectiveness of Warfarin or Rivaroxaban Versus Apixaban in Patients With Advanced CKD and Atrial Fibrillation: Nationwide US Cohort Study

Head-to-head data comparing the effectiveness and safety of oral anticoagulants in patients with atrial fibrillation (AF) and advanced chronic kidney disease (CKD) are lacking. We compared the safety and effectiveness of warfarin or rivaroxaban versus apixaban in patients with AF and non-dialysis-dependent CKD stage 4/5. Propensity score-matched cohort study. 2 nationwide US claims databases, Medicare and Optum's deidentified Clinformatics Data Mart Database, were searched for the interval from January 1, 2013, through March 31, 2022, for patients with nonvalvular AF and CKD stage 4/5 who initiated warfarin versus apixaban (matched cohort, n=12,488) and rivaroxaban versus apixaban (matched cohort, n= 5,720). Warfarin, rivaroxaban, or apixaban. Primary outcomes included major bleeding and ischemic stroke. Secondary outcomes included all-cause mortality, major gastrointestinal bleeding, and intracranial bleeding. Cox regression was used to estimate HRs, and 1:1 propensity-score matching was used to adjust for 80 potential confounders. Compared with apixaban, warfarin initiation was associated with a higher rate of major bleeding (HR, 1.85; 95% CI, 1.59-2.15), including major gastrointestinal bleeding (1.86; 1.53-2.25) and intracranial bleeding (2.15; 1.42-3.25). Compared with apixaban, rivaroxaban was also associated with a higher rate of major bleeding (1.69; 1.33-2.15). All-cause mortality was similar for warfarin (1.08; 0.98-1.18) and rivaroxaban (0.94; 0.81-1.10) versus apixaban. Furthermore, no statistically significant differences for ischemic stroke were observed for warfarin (1.14; 0.83-1.57) or rivaroxaban (0.71; 0.40-1.24) versus apixaban, but the CIs were wide. Similar results were observed for warfarin versus apixaban in the positive control cohort of patients with CKD stage 3, consistent with randomized trial findings. Few ischemic stroke events, potential residual confounding. In patients with AF and advanced CKD, rivaroxaban and warfarin were associated with higher rates of major bleeding compared with apixaban, suggesting a superior safety profile for apixaban in this high-risk population. Different anticoagulants have been shown to reduce the risk of stroke in patients with atrial fibrillation, such as warfarin and direct oral anticoagulants like apixaban and rivaroxaban. Unfortunately, the large-scale randomized trials that compared direct anticoagulants versus warfarin excluded patients with advanced chronic kidney disease. Therefore, the comparative safety and effectiveness of warfarin, apixaban, and rivaroxaban are uncertain in this population. In this study, we used administrative claims data from the United States to answer this question. We found that warfarin and rivaroxaban were associated with increased risks of major bleeding compared with apixaban. There were few stroke events, with no major differences among the 3 drugs in the risk of stroke. In conclusion, this study suggests that apixaban has a better safety profile than warfarin and rivaroxaban.

Real-World Incidence of Adverse Clinical Outcomes Among People With Coronary Artery Disease and/or Peripheral Artery Disease in Relation to Vascular Risk in the United States

Presence of polyvascular disease, diabetes, heart failure, or renal insufficiency in patients with chronic coronary artery disease (CAD) and peripheral artery disease (PAD) are associated with increased risks of adverse events, including major adverse cardiovascular events (MACEs) and major adverse limb events (MALEs). In this retrospective observational study using administrative claims data from Optum's deidentified Clinformatics Data Mart Database from January 2016 to September 2021, we described the incidence rates of MACEs, MALEs, and major thrombotic vascular events in patients with CAD or PAD stratified by the presence of risk factors (i.e., polyvascular disease, diabetes, heart failure, or renal insufficiency). A total of 1,435,241 patients (77% CAD and 34% PAD) met the inclusion and exclusion criteria. Patients with 0 risk factors were deemed the low-risk group (47%; n=681,333) and patients with ≥1 risk factor were deemed the high-risk group (53%; n=753,908). The mean age was 71.8 and 73.6years, and 42% and 44% were female in the low- and high-risk groups, respectively. Compared with the low-risk group, the high-risk group had a 72% higher hazard of developing MACEs (adjusted hazard ratio 1.72, 95% confidence interval 1.70 to 1.74), 82% higher hazard of developing major thrombotic vascular events (1.82, 1.80 to 1.84), and 146% higher hazard of developing MALEs (2.46, 2.39 to 2.53) (all p <0.001). In conclusion, in patients with CAD or PAD, the presence of 1 or more risk factors was associated with higher risks of MACEs, MALEs, and major thrombotic vascular events, underscoring the need to improve management of underlying diseases in this population.

Association of patient copayment and medication adherence in systemic lupus erythematosus

ObjectiveTo investigate the association of medication copayment and treatment adherence to hydroxychloroquine and immunosuppressants for SLE.MethodsWe conducted a retrospective analysis of health claims data using Optum’s de-identified Clinformatics Data Mart...

Real-World Treatment Effectiveness of Disease-Modifying Antirheumatic Drugs by Serostatus Among Patients With Rheumatoid Arthritis.

The objective of this study was to compare the clinical effectiveness of biologic disease-modifying antirheumatic drugs (bDMARDs) or Janus kinase inhibitors (JAKi) among seropositive versus seronegative patients with rheumatoid arthritis (RA) in a real-world setting. We used Optum's deidentified Clinformatics Data Mart Database (January 1, 2004, to March 31, 2021) linked with outpatient laboratory test results. The study population was adult patients with RA who initiated a bDMARD or JAKi. The index date was the dispensing of the first-ever study drug. At least 1-year continuous enrollment before and after the index date was required. Disenrollment due to death after the index date was allowed. Serostatus was defined using laboratory test results or the International Classification of Diseases, 10th Revision code M05x or M06.0x any time prior to the index date. Treatment effectiveness was measured based on a claims-based composite endpoint at 1-year post index, including nonoccurrence of any of the following: addition of conventional synthetic DMARDs, addition of or switching tonew bDMARDs/JAKi, initiation of glucocorticoids, increased glucocorticoid dose, or death. Log-binomial regression models were constructed to estimate the risk ratio (RR) with 95% confidence interval (CI) comparing seropositive patients with seronegative patients, adjusting for more than 60 baseline covariates. We identified a total of 7813 seropositive patients and 4202 seronegative patients. The mean (±SD) age was 56.7 (±14.0) years; 77.9% were female. The risk of 1-year treatment effectiveness was 70.2% among seropositive patients and 69.8% among seronegative patients. The adjusted RR (95% CI) was 1.00 (0.98-1.02). In this real-world cohort study, seropositive and seronegative patients with RA had similar 1-year treatment effectiveness after initiating a bDMARD/JAKi.