Development and electronic health record validation of an algorithm for identifying patients with Duchenne muscular dystrophy in US administrative claims.

BACKGROUND: Muscular dystrophies (MDs) comprise a heterogenous group of genetically inherited conditions characterized by progressive muscle weakness and increasing disability. The lack of separate diagnosis codes for Duchenne MD (DMD) and Becker MD, 2 of the most common forms of MD, has limited the conduct of DMD-specific real-world studies. OBJECTIVE: To develop and validate administrative claims-based algorithms for identifying patients with DMD and capturing their nonambulatory and ventilation-dependent status. METHODS: This was a retrospective cohort study using the statistically deidentified Optum Market Clarity Database (including patient claims linked with electronic health records [EHRs] data) to develop and validate the following algorithms: DMD diagnosis, nonambulatory status, and ventilation-dependent status. The initial study sample consisted of US patients in the database who had a diagnosis code for Duchenne/Becker MD (DBMD) between October 1, 2018, and September 30, 2020, who were male, aged 40 years or younger on their first DBMD diagnosis, and met continuous enrollment and 1-day minimal clinical activities requirement in a 12-month measurement period between October 1, 2017, and September 30, 2020. The algorithms, developed by a cross-functional team of DMD specialists (including patient advocates), were based on administrative claims data with International Classification of Diseases, Tenth Revision, Clinical Modifications coding, using information of diagnosis codes for DBMD, sex, age, treatment, and disease severity (eg, evidence of ambulation assistance/support and/or evidence of ventilation support or dependence). Patients who met each algorithm and had EHR notes available were then validated against structured fields and unstructured provider notes from their own linked EHR to confirm patients' DMD diagnoses, nonambulatory status, and ventilation-dependent status. Algorithm performance was assessed by positive predictive value with 95% CIs. RESULTS: A total of 1,300 patients were included in the initial study sample. Of these, EHR were available and reviewed for 303 patients. The mean age of the 303 patients was 14.8 years, with 61.7% being non-Hispanic White. A majority had a Charlson comorbidity index score of 0 (59.4%) or 1-2 (27.7%). Positive predictive value (95% CI) was 91.6% (85.8%-95.6%) for the DMD diagnosis algorithm, 88.4% (80.2%-94.1%) for the nonambulatory status algorithm, and 77.8% (62.9%-88.8%) for the ventilation-dependent status algorithm. CONCLUSIONS: This work provides the means to more accurately identify patients with DMD from administrative claims data without a specific diagnosis code. The algorithms validated in this study can be applied to assess treatment effectiveness and other outcomes among patients with DMD treated in clinical practice. DISCLOSURES: This study was funded by Pfizer, which contracted with Optum to perform the study and provide medical writing assistance. Ms Schrader reports being an employee of Parent Project Muscular Dystrophy. Mr Posner reports being an employee and stockholder of Pfizer and receiving support from Pfizer for attending conferences not related to this manuscript. Dr Dorling reports being an employee and stockholder of Pfizer at the time the study was conducted and is a current employee of Chiesi USA, Inc. Ms Senerchia reports being an employee of Optum and owning stock in Pfizer and UnitedHealth Group, the parent company of Optum. Dr Chen reports being an employee and stockholder of Pfizer. Ms Beaverson reports being an employee of Pfizer and owning stock in Pfizer and Amicus Therapeutics. Dr Seare reports being an employee of Optum at the time the study was conducted. Dr Garnier and Ms Merla report being employees of Pfizer. Ms Walker reports being an employee of Optum. Dr Alvir reports being an employee and stockholder of Pfizer. Dr Mahn reports being an employee and stockholder of Pfizer. Dr Zhang reports being an employee of Optum. Ms Landis reports being an employee of Optum. Ms Buikema reports being an employee of Optum and holding stock in UnitedHealth Group, the parent company of Optum.

Risk of relapse and readmission among hospitalized adults with carbapenem non-susceptible gram-negative infections.

BACKGROUND: Infections caused by carbapenem-nonsusceptible gram-negative (C-NS) pathogens are associated with increased mortality and high treatment costs. Identification of potentially modifiable factors that may improve patient outcomes is important for better management of C-NS GN infections. METHODS: This was a retrospective study of hospitalized adults with electronic health record evidence of complicated urinary tract infection (cUTI), bacterial pneumonia (BP), complicated intra-abdominal infection (cIAI), or bacteremia (BAC) due to C-NS GN organisms from January 2013 to March 2018. Treatment patterns and clinical characteristics during the index hospitalization were analyzed descriptively and stratified by infection site(s). The effect of patient characteristics on index infection relapse during the postdischarge period and on readmission with 30 days was modeled using logistic regression. RESULTS: The study included 2,862 hospitalized patients with C-NS GN infections. Index infection sites were 38.4% cUTI ± BAC, 21.5% BP ± BAC, 18.7% cUTI + BP ± BAC, 14.7% any cIAI, and 6.7% BAC only. The majority of patients (83.6%) received an antibiotic during their index hospitalization; among these, the most common classes given were penicillins (52.9%), fluoroquinolones (50.7%), and carbapenems (38.9%). During the postdischarge period, 21.7% of patients had a relapse of the index infection and 63.9% of patients were readmitted to the hospital. Factors associated with increased adjusted odds ratio (OR) for relapse or readmission included Charlson comorbidity score of ≥3 relative to 0 (relapse: OR [95% CI] = 1.34 [1.01-1.76], p = .040; readmission: OR [95% CI] 1.92 [1.50-2.46], p < .001), preindex immunocompromised status (relapse: OR [95% CI] 1.37 [1.05-1.79], p = .019; readmission: OR [95% CI] = 1.60 [1.27-2.02], p < .001), and preindex carbapenem use (relapse: OR [95% CI] = 1.35 [1.07-1.72], p = .013; readmission: OR [95% CI] = 1.25 [1.00-1.57], p = .048). CONCLUSIONS: Adverse postdischarge outcomes were common among hospitalized patients with C-NS GN infections and were significantly associated with previous carbapenem use and patient clinical characteristics such as higher comorbidity burden and immunocompromised status. Adoption of antimicrobial stewardship and consideration of individual patient risk factors in making treatment decisions may help improve clinical outcomes.

Racial and ethnic disparity in clinical outcomes among patients with confirmed COVID-19 infection in a large US electronic health record database.

BACKGROUND: Racial and ethnic minority groups have been disproportionately affected by the US coronavirus disease 2019 (COVID-19) pandemic; however, nationwide data on COVID-19 outcomes stratified by race/ethnicity and adjusted for clinical characteristics are sparse. This study analyzed the impacts of race/ethnicity on outcomes among US patients with COVID-19. METHODS: This was a retrospective observational study of patients with a confirmed COVID-19 diagnosis in the electronic health record from 01 February 2020 through 14 September 2020. Index encounter site, hospitalization, and mortality were assessed by race/ethnicity (Hispanic, non-Hispanic Black [Black], non-Hispanic White [White], non-Hispanic Asian [Asian], or Other/unknown). Associations between racial/ethnic categories and study outcomes adjusted for patient characteristics were evaluated using logistic regression. FINDINGS: Among 202,908 patients with confirmed COVID-19, patients from racial/ethnic minority groups were more likely than White patients to be hospitalized on initial presentation (Hispanic: adjusted odds ratio 1·690, 95% CI 1·620-1·763; Black: 1·810, 1·743-1·880; Asian: 1·503, 1·381-1·636) and during follow-up (Hispanic: 1·700, 1·638-1·764; Black: 1·578, 1·526-1·633; Asian: 1·391, 1·288-1·501). Among hospitalized patients, adjusted mortality risk was lower for Black patients (0·881, 0·809-0·959) but higher for Asian patients (1·205, 1·000-1·452). INTERPRETATION: Racial/ethnic minority patients with COVID-19 had more severe disease on initial presentation than White patients. Increased mortality risk was attenuated by hospitalization among Black patients but not Asian patients, indicating that outcome disparities may be mediated by distinct factors for different groups. In addition to enacting policies to facilitate equitable access to COVID-19-related care, further analyses of disaggregated population-level COVID-19 data are needed.

Validation of a claims-based algorithm to identify patients with chronic thromboembolic pulmonary hypertension using electronic health record data.

This study aimed to validate an algorithm developed to identify chronic thromboembolic pulmonary hypertension (CTEPH) among patients with a history of pulmonary embolism. Validation was halted because too few patients had gold-standard evidence of CTEPH in the administrative claims/electronic health records database, suggesting that CTEPH is underdiagnosed.

Economic Outcomes of First-Line Regimen Switching Among Stable Patients with HIV.

BACKGROUND: Although switching of antiretroviral therapy (ART) is a valid approach for addressing treatment failure in patients with human immunodeficiency virus (HIV), ART changes among those who are well maintained on their current regimens may lead to the development of new side effects or resistance. OBJECTIVE: To examine the effect of first-line regimen switching on subsequent health care utilization and cost among stable HIV patients. METHODS: This was a retrospective claims data study of adult patients with HIV who initiated ART between 2007 and 2013 and had been treated with their initial regimens for at least 6 continuous months. Those with evidence of pregnancy or HIV-2 were excluded. Patients who underwent an ART change were assigned to a switcher cohort; a nonswitcher cohort was then generated by matching up to 20 nonswitchers for each switcher, with replacement. The index date was the date of the first ART change for switchers and was the claim date closest to the corresponding switcher's switch date for nonswitchers. Patient characteristics at baseline and post-index annualized health care utilization and costs were analyzed descriptively and with multivariable models. Analyses were performed in the full population and among patients designated as virologically stable (had undetectable viral ribonucleic acid [RNA] for 90 days pre-index) and virologically and clinically stable (had undetectable viral RNA and no apparent clinical reason for switching ART). RESULTS: The study population consisted of 6,983 individuals, which included 927 switchers (168 virologically stable; 55 virologically+clinically stable), who were matched with replacement with 18,511 nonswitcher comparators. The switcher cohort was 88.8% male (mean age 43.8 years). Mean preindex and follow-up treatment durations for switchers and nonswitchers were 1.8 years and 1.5 years, respectively; demographic characteristics, pre-index treatment duration, and follow-up duration were similar between cohorts. Significantly more nonswitchers than switchers had a first-line efavirenz-based regimen (67.2% vs. 47.8%, P < 0.001). In the virologically stable subset, follow-up annualized health care utilization for switchers versus nonswitchers, respectively, was 14.8 versus 12.3 ambulatory visits (P < 0.05), 0.8 versus 0.9 emergency department visits (P = 0.652), and 0.05 versus 0.05 inpatient hospitalizations (P = 0.915). Follow-up annualized health care costs were $37,120 for switchers versus $31,771 for nonswitchers (P < 0.05), with the difference driven largely by pharmacy costs. Multivariable-adjusted follow-up annualized health care costs were 8.9% higher among switchers versus nonswitchers (P < 0.01), and switchers also had a shorter time to subsequent ART regimen change (P < 0.001). Results were similar for the virologically+clinically stable subset. CONCLUSIONS: In this large, real-world population, stable patients with HIV who switched from their first-line ART regimens had significantly higher health care costs than those who did not change therapies, suggesting that ART regimen changes may be costly and should be undertaken only when clinically warranted. DISCLOSURES: This work was funded by Bristol-Myers Squibb (BMS), which participated in the design of the study, interpretation of the data, revision of the manuscript, and the decision to submit the manuscript for publication. Rosenblatt is an employee and stock owner of BMS; Villasis-Keever was an employee of BMS at the time this study was conducted and is currently an employee of Janssen. Buikema is an employee and stock owner of Optum, and Seare, Bengston, Johnson, and Cao are employees of Optum, which was contracted by BMS to conduct the study. Optum contracts with pharmaceutical companies, such as Janssen, Merck, EMD Serano, GlaxoSmithKline, and Gilead, to conduct research in HIV. Optum is also a subsidiary of a health plan that has interest in managing the health and associated costs of patients with HIV. Study concept and design were contributed by Rosenblatt and Buikema, along with the other authors. Cao and Johnson took the lead in data collection, along with Buikema, Seare, and Bengston. Data interpretation was performed by Buikema, Seare, Bengston, and Villasis-Keever. The manuscript was written by Buikema and Bengston, along with Rosenblatt, Seare, Johnson and Villasis-Keever, and revised by Rosenblatt, Villasis-Keever, and Johnson, along with the other authors.

Healthcare Resource Utilization and Costs Associated with Autosomal Dominant Polycystic Kidney Disease.

Background: Autosomal dominant polycystic kidney disease (ADPKD), a hereditary nephropathy, eventually leads to end-stage renal disease (ESRD), typically by mid-life. Objectives: The objective of this study was to assess real-world healthcare resource utilization and cost among commercially insured (COM) and Medicare Advantage (MAPD) ADPKD patients in addition to the cost profile by chronic kidney disease (CKD) stage. Methods: Patients diagnosed with ADPKD (two or more claims) with ≥30 days of continuous medical and pharmacy benefits and no evidence of autosomal recessive polycystic kidney disease were selected (Optum Research Database and Impact National Benchmarking Database: 1/1/06-8/31/12). Plan and patient paid healthcare costs and resource utilization per patient per month (PPPM) were described in total and by insurance type. CKD stage was established based on serum creatinine laboratory values or dialysis-related codes. Adjusted, CKD stage-specific costs were predicted for 4 years using regression models. Results: Of the 36,253,096 patients in the databases (1/1/06-8/31/12), 5,051 had evidence of ADPKD. Following exclusion criteria, 4,356 COM and 468 MAPD ADPKD patients remained. Total healthcare resource utilization and costs were high, and costs increased substantially from CKD stage 1-5. PPPM healthcare costs were 37% for ADPKD management and 52% for dialysis services. Predicted 4-year healthcare costs by CKD stage were $40,164 (stage 1), $33,397 (stage 2), $42,686 (stage 3), $148,402 (stage 4), and $207,548 (stage 5). Conclusions: Healthcare resource utilization and costs associated with ADPKD were substantial, irrespective of payer type, and primarily driven by CKD stage. Of the total healthcare costs, 88% were ADPKD- and dialysis-related. Most impactful was the spike in predicted cost when patients progressed from CKD stage 3 to stage 4 (by 348%) after multivariate adjustment. These stage 4-associated costs are primarily due to ultimate progression into stage 5 and ESRD within the 4-year time frame.

Association of RSV-related hospitalization and non-compliance with palivizumab among commercially insured infants: a retrospective claims analysis.

BACKGROUND: Palivizumab has been shown to decrease the incidence of hospitalization due to respiratory syncytial virus (RSV) in infants at risk of severe RSV disease. We examined the association between compliance with palivizumab dosing throughout the RSV season and risk of RSV-related hospitalization in clinical practice. METHODS: Subjects who were born and discharged from the hospital before the RSV season and received ≥1 palivizumab dose during their first RSV season were identified from a large US commercial health insurance database between 01/01/03 and 12/31/09. Subjects were deemed compliant if they received ≥5 palivizumab doses without gaps (>35 days) and their first dose was received by November 30. RSV-related hospitalizations were identified using ICD-9-CM diagnosis codes and examined over 2 observation periods: post-index dose and RSV season. A Cox proportional hazard model was used to evaluate the association between non-compliance and RSV-related hospitalization. RESULTS: Of the 5,003 subjects who received palivizumab, 62% were deemed non-compliant. Non-compliant subjects had significantly higher unadjusted rates of RSV-related hospitalizations compared to compliant subjects during both observation periods (post-index: 6.1 vs. 2.8 per 100 infant seasons, p < 0.001; RSV season: 5.9% vs. 2.3%; p < 0.001). In multivariate analyses, non-compliance was significantly associated with higher risk of RSV-related hospitalization (HR = 2.01; p < 0.001). Of the 225 RSV-related hospitalizations observed during the RSV season, 61 (27%) occurred before the first dose of palivizumab. CONCLUSIONS: Subjects who did not receive monthly dosing of palivizumab throughout the RSV season had significantly higher rates of RSV-related hospitalizations. The RSV-related hospitalizations prior to the first dose of palivizumab suggest some dosing was started too late.