Early genetic testing in pediatric epilepsy: Diagnostic and cost implications.

The identification of numerous genetically based epilepsies has resulted in the widespread use of genetic testing to inform epilepsy etiology. Our study aims to investigate whether a difference exists in the diagnostic evaluation and healthcare-related cost expenditures of pediatric patients with epilepsy of unknown etiology who receive a genetic diagnosis through multigene epilepsy panel (MEP) testing and comparing those who underwent early (EGT) versus late genetic testing (LGT). Testing was defined as early (less than 1 year), or late (more than 1 year), following clinical epilepsy diagnosis. A retrospective chart review of pediatric individuals (1-17 years) with epilepsy of unknown etiology who underwent multigene epilepsy panel (MEP) testing identified 28 of 226 (12%) individuals with a pathogenic epilepsy variant [EGT n = 8 (29%); LGT n = 20 (71%)]. The average time from clinical epilepsy diagnosis to genetic diagnosis was 0.25 years (EGT), compared with 7.1 years (LGT). The EGT cohort underwent fewer metabolic tests [EGT n = 0 (0%); LGT n = 16 (80%) (P < 0.01)] and invasive procedures [EGT n = 0 (0%); LGT n = 5 (25%) (P = 0.06)]. Clinical management changes implemented due to genetic diagnosis occurred in 10 (36%) patients [EGT n = 2 (25%); LGT n = 8 (40%) (P = 0.76)]. Early genetic testing with a MEP in pediatric patients with epilepsy of unknown etiology who receive a genetic diagnosis is associated with fewer non-diagnostic tests and invasive procedures and reduced estimated overall healthcare-related costs. PLAIN LANGUAGE SUMMARY: This study aims to investigate whether a difference exists in the diagnostic evaluation and cost expenditures of pediatric patients (1-17 years) with epilepsy of unknown cause who are ultimately diagnosed with a genetic cause of epilepsy through multigene epilepsy panel testing and comparing those who underwent early testing (less than 1 year) versus late testing (more than 1 year) after clinical epilepsy diagnosis. Of the 28 of 226 individuals with a confirmed genetic cause of epilepsy on multigene epilepsy panel testing, performing early testing was associated with fewer non-diagnostic tests, fewer invasive procedures and reduced estimated overall healthcare-related costs.

Relationship of COPD Exacerbation Severity and Frequency on Risks for Future Events and Economic Burden in the Medicare Fee-For-Service Population.

Purpose: To quantify the effects of moderate and/or severe chronic obstructive pulmonary disease (COPD) exacerbations on future exacerbations and healthcare costs in Medicare Fee-For-Service beneficiaries. Patients and Methods: A retrospective cohort study of patients ≥40 years of age, with continuous enrollment from 2015 to 2018, with an index COPD diagnosis defined as first hospitalization, emergency department visit, or first of two outpatient visits (≥30 days apart) in 2015 with a claim for chronic bronchitis, emphysema, or chronic airway obstruction. Patients were stratified by baseline exacerbation categories in year one (YR1) and subsequently evaluated in YR2 and YR3: (A) none; (B) 1 moderate; (C) ≥2 moderate; (D) 1 severe; and (E) ≥2, one being severe. Moderate exacerbations were defined as COPD-related outpatient/ED visits with a corticosteroid/antibiotic claim within ±7 days of the visit and severe exacerbations as hospitalizations with a primary COPD diagnosis. Total all-cause costs for Categories B-E were compared to reference Category A using generalized linear models and inflation adjusted to 2019 dollars. Results: A total of 1,492,108 patients met study criteria with a mean (±SD) age of 70.9±10.9. In YR1, nearly 40% of patients experienced ≥1 moderate and/or severe exacerbations. Patients having multiple exacerbations, regardless of severity were 2-4 times more likely to experience an exacerbation during YR2 and YR3. Adjusted costs ranged between $24,000 and $26,600 for all categories for YR2 and YR3. Adjusted YR2 costs for Category D and E were $1421 and $1548 higher than those without an exacerbation (Category A YR2 $25,084, YR3 $24,282; p<0.0001). The respective YR3 adjusted costs were $2062 and $2117 higher than those without an exacerbation (Category A; p<0.0001), representing an increase of 6-8% and 8-9% for YR2 and YR3. Conclusion: Medicare patients with recent moderate or severe exacerbations, or at least two exacerbations per year are at significant risk for future exacerbations and incur higher all-cause costs.

Continuity of Care Assessment Within a Vertically Integrated Care Management Organization Before and After COPD-Related Exacerbations.

BACKGROUND: There is currently little research describing patient experience and continuity of care immediately prior, during, and following an acute exacerbation of chronic obstructive pulmonary disease (AECOPD). This analysis examined clinical characteristics, chronic obstructive pulmonary disease (COPD)­related medication patterns and outpatient visits before and after an AECOPD. METHODS: This retrospective analysis used electronic health records, medical claims, and pharmacy dispensing data for patients within the Kaiser Permanente Northwest Health System. Patients with ≥1 AECOPD between January 1, 2015 and December 31, 2017 were identified. The most recent AECOPD was considered the index date. An AECOPD was defined as an inpatient hospitalization with a primary diagnosis of COPD, or respiratory failure with a secondary diagnosis of COPD, or an outpatient visit with a primary diagnosis of COPD and dispensing of respiratory-related antibiotics and/or oral corticosteroids ±5 days of the visit. Eligible patients were: ≥40 years old; ≥2 encounters within 12 months of each other or ≥1 hospitalization with primary or secondary COPD diagnosis, chronic bronchitis, or emphysema prior to index; and continuously enrolled ±90 days relative to index. COPD-related inhaled maintenance medication, rescue inhalers, oral corticosteroid use, and ambulatory visits were assessed 90-days pre- and post-index. RESULTS: There were 2829 patients included (mean [standard deviation] age: 69.0 [10.5] years) who had an AECOPD (7% severe; 93% moderate). The percentage of patients on inhaled maintenance therapy increased from 60.6% pre-AECOPD to 68.8% post-AECOPD and increased from 60.0% to 87.4% among patients who experienced a severe AECOPD. COPD-related ambulatory visits increased more than four-fold for primary care and more than doubled for pulmonologist visits in the post-AECOPD period. CONCLUSION: The low proportion of patients observed with changes to controller and rescue medication (particularly following a moderate AECOPD), yet higher utilization of COPD-related ambulatory visits before and after an AECOPD suggests that there is opportunity to improve pharmacotherapy management.

Time-to-first exacerbation, adherence, and medical costs among US patients receiving umeclidinium/vilanterol or tiotropium as initial maintenance therapy for chronic obstructive pulmonary disease: a retrospective cohort study.

BACKGROUND: Adherence to chronic obstructive pulmonary disease (COPD) maintenance medication is important for managing symptoms and exacerbation risk, and is associated with reduced mortality, hospitalizations, and costs. This study compared on-treatment exacerbations, medical costs, and medication adherence in patients with COPD initiating treatment with umeclidinium/vilanterol (UMEC/VI) or tiotropium (TIO). METHODS: This retrospective matched cohort study selected patients from Optum's de-identified Clinformatics Data Mart database who initiated maintenance treatment with UMEC/VI or TIO between 01/01/2014 and 12/31/2017 (index date defined as the first dispensing). Eligible patients were ≥ 40 years of age and had ≥ 12 months continuous health plan coverage pre- and post-index; ≥ 1 medical claim for COPD pre-index or on the index date; no moderate/severe COPD-related exacerbations on the index date; no asthma diagnosis pre- or post-index; no maintenance medication fills containing inhaled corticosteroids, long-acting ß2-agonists, or long-acting muscarinic antagonists pre-index or on the index date; and no fills for both UMEC/VI and TIO on the index date. Outcomes included time-to-first (Kaplan-Meier analysis) and rates of on-treatment COPD-related moderate/severe exacerbations, medication adherence (proportion of days covered [PDC] and proportion of adherent patients [PDC ≥ 0.8]), and COPD-related medical costs per patient per month (PPPM). Propensity score matching was used to adjust for potential confounders. RESULTS: Each cohort included 3929 matched patients. Kaplan-Meier rates of on-treatment COPD-related exacerbations were similar between cohorts (hazard ratio at 12 months; overall: 0.93, moderate: 0.92, severe: 1.07; all p > 0.05). UMEC/VI versus TIO initiators had significantly higher adherence (mean PDC: 0.44 vs 0.37; p < 0.001; proportion with PDC ≥ 0.8: 22.0% vs 16.4%; p< 0.001) and significantly lower mean on-treatment COPD-related total medical costs ($867 vs $1095 PPPM; p = 0.028), driven by lower outpatient visit costs. CONCLUSIONS: These findings provide valuable information for physicians considering UMEC/VI or TIO as initial maintenance therapy options for patients with COPD.

Umeclidinium/Vilanterol Compared with Fluticasone Propionate/Salmeterol, Budesonide/Formoterol, and Tiotropium as Initial Maintenance Therapy in Patients with COPD Who Have High Costs and Comorbidities.

BACKGROUND: Comorbidities in patients with chronic obstructive pulmonary disease (COPD) are associated with increased medical costs and risk of exacerbations. This study compared COPD-related medical costs and exacerbations in high-cost, high-comorbidity patients with COPD receiving initial maintenance treatment (IMT) with umeclidinium/vilanterol (UMEC/VI) versus fluticasone propionate/salmeterol (FP/SAL), budesonide/formoterol (B/F), or tiotropium (TIO). METHODS: This retrospective, matched cohort study identified patients from Optum's de-identified Clinformatics Data Mart database who initiated UMEC/VI, FP/SAL, B/F, or TIO between January 1, 2014 and December 31, 2018 (index date defined as date of the first fill). Eligibility criteria included age ≥40 years at index, ≥1 pre-index COPD diagnosis, no pre-index asthma diagnosis, 12 months of continuous insurance coverage pre-index, and high pre-index costs (≥80th percentile of IMT population) and comorbidities (Quan-Charlson comorbidity index ≥3). Propensity score matching was used to control for potential confounders. On-treatment COPD-related medical costs (primary endpoint) and exacerbations were evaluated. RESULTS: Matched cohorts were well balanced on baseline characteristics (UMEC/VI vs FP/SAL: n=1194 each; UMEC/VI vs B/F: n=1441 each; UMEC/VI vs TIO: n=1277 each). Patients receiving UMEC/VI had significantly lower COPD-related medical costs versus FP/SAL (difference: $6587 per patient per year; P=0.048), and numerically lower costs versus B/F and TIO. Patients initiating UMEC/VI had significantly lower risk of COPD-related severe exacerbation versus FP/SAL (hazard ratio [95% CI]: 0.78 [0.62, 0.98]; P=0.032), B/F (0.77 [0.63, 0.95]; P=0.016), and TIO (0.79 [0.64, 0.98]; P=0.028). The rate of COPD-related severe exacerbations was significantly lower with UMEC/VI versus FP/SAL (rate ratio [95% CI]: 0.73 [0.59, 0.91]; P=0.008) and B/F (0.73 [0.59, 0.93]; P=0.012), and numerically lower versus TIO (0.83 [0.68, 1.04]; P=0.080). CONCLUSION: These findings suggest that high-cost, high-comorbidity patients with COPD receiving UMEC/VI compared with FP/SAL, B/F, and TIO as IMT may have lower medical costs and exacerbation risk.

Incremental Costs Associated with Length of Hospitalization Due to Viral Pneumonia: Impact of Intensive Care and Economic Implications of Reducing the Length of Stay in the Era of COVID-19.

BACKGROUND: Emerging trial data for treatment of COVID-19 suggest that in addition to improved clinical outcomes, these treatments reduce length of hospital stay (LOS). However, the economic value of a shortened LOS is unclear. OBJECTIVE: To estimate incremental costs per day of hospitalization for a patient with influenza or viral pneumonia, as a proxy for COVID-19; ICU costs associated with invasive mechanical ventilation (iMV) were also determined. METHODS: Retrospective analysis of claims-based data was conducted using the IBM MarketScan® Commercial Claims and Encounters and Medicare Supplemental and Coordination of Care and the Medicare Fee-for-Service claims databases for hospitalizations due to influenza/viral pneumonia between January 2018 and June 2019. Cases were stratified as uncomplicated hospitalizations or with ICU. Ordinary least squares regression, excluding LOS or costs exceeding the 99th percentile (base case), was used to estimate incremental costs per day; a sensitivity analysis included all qualified hospitalizations. Additional sensitivity analyses used weighting methodology. RESULTS: Among 6055 and 118,419 hospitalizations in the commercially insured and Medicare databases, respectively, 5958 and 116,552 hospitalizations, respectively, represented the base case. Estimated incremental base case costs per additional inpatient day were $2158 and $3900 in the commercial population for uncomplicated hospitalizations and hospitalizations with ICU, respectively, and $475 and $668, respectively in the Medicare population. Estimated incremental base case costs per additional ICU day were $5254 and $608 for Commercial and Medicare populations, respectively. Higher absolute costs were estimated in the sensitivity analysis on all qualified hospitalizations; the weighted sensitivity analyses generally showed that estimates were stable. Use of iMV increased costs by $35,482 and $13,101 in the commercial and Medicare populations, respectively. CONCLUSION: The incremental daily cost of a hospitalization is substantial for US patients with commercial insurance and for Medicare patients. These findings may help quantify the economic value of COVID-19 treatments that reduce LOS.

Symptom Burden and GOLD Classification in Medicare Advantage Patients with COPD Initiating Umeclidinium/Vilanterol or Fluticasone Propionate/Salmeterol Therapy.

Background: Long-acting muscarinic antagonist/long-acting ß2-agonist (LAMA/LABA) provide greater improvements in lung function and symptoms than inhaled corticosteroid (ICS)/LABA in patients with chronic obstructive pulmonary disease (COPD). This study evaluated symptom burden and Global Initiative for Obstructive Lung Disease (GOLD) categorization among patients who recently initiated umeclidinium/vilanterol (UMEC/VI; LAMA/LABA) or fluticasone propionate/salmeterol (FP/SAL; ICS/LABA) single-inhaler dual therapy. Methods: COPD-diagnosed Medicare Advantage enrollees aged ≥65 years were identified from the Optum Research Database (ORD). Eligible patients had ≥1 pharmacy claim for UMEC/VI or FP/SAL in the 6-month period before sample identification, with no evidence of triple therapy (ICS/LAMA/LABA), asthma, or lung cancer. Symptom burden was assessed via cross-sectional surveys using the COPD Assessment Test (CAT) and modified Medical Research Council (mMRC) dyspnea scale. Patients were classified into GOLD categories using patient-reported symptoms and claims-based exacerbation history. Treatment groups were balanced on potential confounders using inverse probability of treatment weighting (IPTW). CAT and mMRC scores were analyzed with generalized linear regression models using IPTW propensity scores. Results: The final analytic sample included 789 respondents (UMEC/VI: N=392; FP/SAL: N=397). Approximately 66% patients were classified as GOLD B when assessing symptoms with CAT and mMRC together, or CAT alone; more patients were classified as GOLD A (~40%) than GOLD B (~36%) using mMRC alone. Proportions of patients in each GOLD group were similar between treatment cohorts. Post-IPTW multivariable modeling showed similar symptom burden between treatment groups. Conclusion: After controlling for baseline characteristics, symptom burden was similar between patients receiving UMEC/VI or FP/SAL. GOLD classification using mMRC produced more conservative results compared with CAT, potentially underestimating patient symptoms. Many patients receiving FP/SAL were classified as GOLD A or B, despite GOLD recommending non-ICS-containing therapy in these patients. These findings support the need for routine assessment of symptoms in patients with COPD.

Evaluation of Medication Adherence and Rescue Medication Use in Non-Exacerbating Patients with COPD Receiving Umeclidinium/Vilanterol or Budesonide/Formoterol as Initial Maintenance Therapy.

Background: Adherence to inhaled maintenance therapy is critical to managing chronic obstructive pulmonary disease (COPD), while increasing rescue medication usage may indicate worsening symptoms. This study evaluated adherence and rescue medication use in patients with COPD without a history of exacerbation who initiated combination therapy with budesonide/formoterol (B/F) or umeclidinium/vilanterol (UMEC/VI). Methods: Retrospective observational study of commercially insured and Medicare Advantage with Part D enrollees who initiated UMEC/VI or B/F between January 1, 2014 and December 31, 2017 (earliest fill defined as index date). Eligibility criteria included age ≥40 years, 12 months continuous enrollment pre- and post-index, ≥1 pre-index COPD diagnosis, no pre-index asthma diagnosis, COPD-related exacerbations, or medication fills containing inhaled corticosteroids, long-acting ß2-agonists, or long-acting muscarinic antagonists. Inverse probability of treatment weighting (IPTW) was used to balance treatment groups on potential confounders. Medication adherence (primary endpoint) was evaluated by the proportion of days covered (PDC). Rescue medication use (secondary endpoint) was standardized to canister equivalents (1 metered dose inhaler [200 puffs] or ~100 nebulized doses of short-acting ß2-agonist- and/or short-acting muscarinic agonist-containing medication). Results: After IPTW, covariates were balanced between cohorts (UMEC/VI: N=4082; B/F: N=9529). UMEC/VI initiators had a significantly greater mean PDC (UMEC/VI: 0.47 [0.33]; B/F: 0.38 [0.30]; P<0.001) and significantly higher rates of adherence (PDC≥0.80) than B/F initiators (UMEC/VI: n=1004 [25%], B/F: n=1391 [15%]; relative risk: 1.68, 95% CI: 1.57, 1.81; P<0.001). In the year following initiation, UMEC/VI initiators filled significantly fewer rescue medication canister equivalents than B/F initiators (predicted mean [95% CI]: 1.78 [1.69, 1.88] vs 2.15 [2.08, 2.23]; mean difference [95% CI]: -0.37 [-0.50, -0.24]; P<0.001), corresponding to 17% less (estimated) rescue medication use (incidence rate ratio [95% CI]: 0.83 [0.78, 0.88]). Conclusion: Among non-exacerbating patients with COPD initiating dual therapy, UMEC/VI demonstrated improved adherence and reduced rescue medication use compared with B/F.

Health care resource utilization among patients with T2D and cardiovascular-, heart failure-, or renal-related hospitalizations.

OBJECTIVES: In patients with type 2 diabetes (T2D), comorbidity-related hospitalizations can have significant impact on longitudinal care. This study aimed to estimate incremental all-cause health care resource utilization (HCRU) and costs between patients with T2D who experienced cardiovascular (CV)-, heart failure (HF)-, or renal-related hospitalizations vs those who did not. STUDY DESIGN: This was a retrospective cohort study using data from a large national health plan. METHODS: Patients with T2D aged 18 to 90 years with CV, HF, or renal hospitalizations were identified from the Humana claims database from October 1, 2009, to September 30, 2015, and separated into CV, HF, and renal cohorts. Patients had 12 months of continuous enrollment prior to the date of first hospitalization (index) and were followed for up to 12 months. Per-patient per-month (PPPM) all-cause HCRU and costs for hospitalized patients were compared with those of no-CV, no-HF, and no-renal cohorts. Differences in baseline characteristics between cohorts were controlled for using generalized linear models. RESULTS: A total of 221,229, 68,126, and 120,105 patients were included in the CV, HF, and renal cohorts, respectively; these patients were older and had higher Deyo-Charlson Comorbidity Index scores than patients in the no-CV, no-HF, and no-renal cohorts. Adjusted for baseline covariates, they had higher mean PPPM inpatient stays, outpatient visits, emergency department visits, and total health care costs. CONCLUSIONS: Among patients with T2D, concurrent CV, HF, or renal events present significant disease burden leading to poor quality of life. This information can be used to guide disease management strategies and interventions aimed at reducing comorbidity-related hospitalizations and health care costs, thus providing improved quality of life for these patients.

Spirometry evaluation to assess performance of a claims-based predictive model identifying patients with undiagnosed COPD.

BACKGROUND: A claims-based model to predict patients likely to have undiagnosed COPD was developed by Moretz et al in 2015. This study aims to assess the performance of the aforementioned model using prospectively collected spirometry data. METHODS: A study population aged 40-89 years enrolled in a Medicare Advantage plan with prescription drug coverage or commercial health plan and without a claim for COPD diagnosis was identified from April 1, 2012 to March 31, 2016 in the Humana claims database. This population was stratified into subjects likely or unlikely to have undiagnosed COPD using the claims-based predictive model. Subjects were randomly selected for spirometry evaluation of FEV1 and FVC. The predictive model was validated using airflow limitation ratio (FEV1/FVC <0.70). RESULTS: A total of 218 subjects classified by the predictive model as likely and 331 not likely to have undiagnosed COPD completed spirometry evaluation. Those predicted to have undiagnosed COPD had a higher mean age (70.2 vs 67.9 years, P=0.0012) and a lower mean FEV1/FVC ratio (0.724 vs 0.753, P=0.0002) compared to those predicted not to have undiagnosed COPD. Performance metrics for the predictive model were: area under the curve =0.61, sensitivity =52.5%, specificity =64.6%, positive predictive value =33.5%, and negative predictive value =80.1%. CONCLUSION: The claims-based predictive model identifies those not at risk of having COPD eight out of ten times, and those who are likely to have COPD one out of three times.

Factors influencing dabigatran or warfarin medication persistence in patients with nonvalvular atrial fibrillation.

Factors influencing differences in persistence between dabigatran and warfarin in patients with nonvalvular atrial fibrillation (NVAF) remain unclear. AIM: Compare differences in persistence between new dabigatran and warfarin users in patients newly diagnosed with NVAF, adjusting for sociodemographics, clinical characteristics, patient out-of-pocket cost and other covariates. METHODS: A retrospective matched-cohort study was conducted using a US claims database of Medicare and commercially insured patients with NVAF aged≥ 18 years. Persistence and monthly out-of-pocket costs for dabigatran or warfarin were calculated and adjusted for covariates using Cox proportional hazard models. RESULTS & CONCLUSION: Unadjusted persistence was significantly lower among dabigatran users (n = 1025) compared with matched warfarin users (38 vs 46%). Adjusting for covariates rendered this difference insignificant (hazard ratio = 0.930).

Healthcare utilization and costs for patients initiating Dabigatran or Warfarin.

BACKGROUND: Novel oral anticoagulants (NOAC) such as dabigatran, when compared to warfarin, have been shown to potentially reduce the risk of stroke in patients with non-valvular atrial fibrillation (NVAF) together with lower healthcare resource utilization (HCRU) and similar total costs. This study expands on previous work by comparing HCRU and costs for patients newly diagnosed with NVAF and newly initiated on dabigatran or warfarin, and is the first study specifically in a Medicare population. METHODS: A retrospective matched-cohort study was conducted using data from administrative health care claims during the study period 01/01/2010-12/31/2012. Cox regression analyses were used to compare all-cause risk of first hospitalizations and emergency room (ER) visits. Medical, pharmacy, and total costs per-patient-per-month (PPPM) were compared between dabigatran and warfarin users. RESULTS: A total of 1110 patients initiated on dabigatran were propensity score-matched with corresponding patients initiated on warfarin. The mean number of hospitalizations (0.92 vs. 1.13, P = 0.012), ER visits (1.32 vs. 1.56, P < 0.01), office visits (21.43 vs. 29.41; P < 0.01), and outpatient visits (10.86 vs. 22.02; P < 0.01) were lower among dabigatran compared to warfarin users. Patients initiated on dabigatran had significantly lower risk of first all-cause ER visits [hazard ratio (HR): 0.84, 95% confidence interval (CI): 0.73-0.98] compared to those initiated on warfarin. Adjusted mean pharmacy costs PPPM were significantly greater for dabigatran users ($510 vs. $250, P < 0.001); however, mean medical costs PPPM ($1912 vs. $1956, P = 0.55) and mean total costs PPPM ($2381 vs. $2183, P = 0.10) were not significantly different compared to warfarin users. CONCLUSIONS: Dabigatran users had significantly lower HCRU compared to warfarin users. In addition, dabigatran users had lower risk of all-cause ER visits. Despite higher pharmacy costs, the two cohorts did not differ significantly in medical or total all-cause costs.

Impact of comorbid conditions in COPD patients on health care resource utilization and costs in a predominantly Medicare population.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) often have multiple underlying comorbidities, which may lead to increased health care resource utilization (HCRU) and costs. OBJECTIVE: To describe the comorbidity profiles of COPD patients and examine the associations between the presence of comorbidities and HCRU or health care costs. METHODS: A retrospective cohort study utilizing data from a large US national health plan with a predominantly Medicare population was conducted. COPD patients aged 40-89 years and continuously enrolled for 12 months prior to and 24 months after the first COPD diagnosis during the period of January 01, 2009, through December 31, 2010, were selected. Eleven comorbidities of interest were identified 12 months prior through 12 months after COPD diagnosis. All-cause and COPD-related hospitalizations and costs were assessed 24 months after diagnosis, and the associations with comorbidities were determined using multivariate statistical models. RESULTS: Ninety-two percent of 52,643 COPD patients identified had at least one of the 11 comorbidities. Congestive heart failure (CHF), coronary artery disease, and cerebrovascular disease (CVA) had the strongest associations with all-cause hospitalizations (mean ratio: 1.56, 1.32, and 1.30, respectively; P<0.0001); other comorbidities examined had moderate associations. CHF, anxiety, and sleep apnea had the strongest associations with COPD-related hospitalizations (mean ratio: 2.01, 1.32, and 1.21, respectively; P<0.0001); other comorbidities examined (except chronic kidney disease [CKD], obesity, and osteoarthritis) had moderate associations. All comorbidities assessed (except obesity and CKD) were associated with higher all-cause costs (mean ratio range: 1.07-1.54, P<0.0001). CHF, sleep apnea, anxiety, and osteoporosis were associated with higher COPD-related costs (mean ratio range: 1.08-1.67, P<0.0001), while CVA, CKD, obesity, osteoarthritis, and type 2 diabetes were associated with lower COPD-related costs. CONCLUSION: This study confirms that specific comorbidities among COPD patients add significant burden with higher HCRU and costs compared to patients without these comorbidities. Payers may use this information to develop tailored therapeutic interventions for improved management of patients with specific comorbidities.

Association between adherence to medications for COPD and medications for other chronic conditions in COPD patients.

BACKGROUND: Patients with COPD often have multiple comorbidities requiring use of multiple medications, and adherence rates for maintenance COPD (mCOPD) medications are already known to be suboptimal. Presence of comorbidities in COPD patients, and use of medications used to treat those comorbidities (non-COPD medications), may have an adverse impact on adherence to mCOPD medications. OBJECTIVE: The objective of the study was to evaluate the association between non-adherence to mCOPD medications and non-COPD medications in COPD patients. METHODS: COPD patients were identified using a large administrative claims database. Selected patients were 40-89 years old and continuously enrolled for 12 months prior to and 24 months after the first identified COPD diagnosis (index date) during January 1, 2009 to December 31, 2010. Patients were required to have ≥1 prescription for a mCOPD medication within 365 days of the index date and ≥1 prescription for one of 12 non-COPD medication classes within ±30 days of the first COPD prescription. Adherence (proportion of days covered [PDC]) was measured during 365 days following the first COPD prescription. The association between non-adherence (PDC <0.8) to mCOPD and non-adherence to non-COPD medications was determined using logistic regression, controlling for baseline patient characteristics. RESULTS: A total of 14,117 patients, with a mean age of 69.9 years, met study criteria. Of these, 40.9% were males and 79.2% were non-adherent to mCOPD medications with a mean PDC of 0.47. Non-adherence to mCOPD medications was associated with non-adherence to 10 of 12 non-COPD medication classes (odds ratio 1.38-1.78, all P<0.01). CONCLUSION: Adherence to mCOPD medications is low. Non-adherence (or adherence) to mCOPD medications is positively related to non-adherence (or adherence) to non-COPD medications, implying that the need to take medications prescribed for comorbid conditions does not adversely impact adherence to mCOPD medications.

A Historical Retrospective Analysis of the Impact of Diabetes Quality Measure Attainment on Outcomes in Medicare Advantage Members.

The objective of this study was to assess achievement of 4 diabetes mellitus (DM)-related quality measures (QMs) and examine the relationship between QM attainment, concurrent health care costs, and DM complications over 1 year by conducting a retrospective analysis of claims data for Medicare Advantage Prescription Drug plan members with DM. Claims and member-level quality data were used to assess QM achievement, concurrent health care costs, and presence of new or worsening DM complications during the QM year. Multivariable regression models were used to examine the relationship between QM achievement and outcome measures controlling for potentially confounding baseline characteristics. QM attainment rates ranged from 54.2% for DM Treatment measure to 83.4% for Cholesterol Screening measure. Odds of new or worsening complications were greater for members who did not meet the Blood Sugar Controlled performance goal (odds ratio [OR]: 1.12, P < 0.001), DM Treatment goal (OR: 1.40, P < 0.001), or Cholesterol Screening goal (OR: 1.32, P < 0.001). Failure to attain the DM Medication Adherence goal was associated with lower odds of new or worsening complications (OR: 0.94, P < 0.001). In the regression models, all-cause health care costs were greater for members who achieved the Blood Sugar Controlled quality goal (P < 0.001), but lower for members who attained DM Treatment (P < 0.001) and low-density lipoprotein Cholesterol Screening goals (P < 0.001). There was no statistically significant relationship between attaining the DM Medication Adherence measure and all-cause costs. Achievement rates for individual QMs varied across the study population and relationships between QM attainment, health care costs, and DM complications during the QM measurement year were mixed.

Comparative resource utilization and costs for patients with acute coronary syndrome managed with percutaneous coronary intervention and treated with clopidogrel or prasugrel.

PURPOSE: Results of a study of bleeding events and other inhospital outcomes with the use of clopidogrel versus prasugrel in patients with acute coronary syndrome (ACS) managed with percutaneous coronary intervention (PCI) are reported. METHODS: Demographic and clinical data on adults hospitalized for ACS, managed with PCI, and treated with clopidogrel or prasugrel during a two-year period were extracted from a large hospital claims database. Bleeding rates, hospital length of stay (LOS), and total hospital costs during the index hospitalization were evaluated. RESULTS: The study sample consisted of 75,297 patients who received clopidogrel and 9,477 who received prasugrel. The unadjusted bleeding rates were 5.7% with clopidogrel use and 3.2% with prasugrel use (p < 0.0001). After propensity score stratification to adjust for selection bias, rates of bleeding events were not significantly different between clopidogrel- and prasugrel-treated patients (odds ratio, 0.90; 95% confidence interval [CI], 0.80-1.02; p = 0.0949). The adjusted mean ± S.D. hospital LOS was 0.22 day lower (95% CI, 0.15-0.28; p < 0.001) with the use of prasugrel versus clopidogrel, and adjusted total mean hospital costs were $375 less for prasugrel-treated patients (p = 0.003). CONCLUSION: After adjustments for demographic and clinical characteristics, rates of inhospital bleeding in patients who received prasugrel and those who received clopidogrel were not significantly different. The adjusted analyses showed that the mean hospital LOS was shorter and total mean hospital costs were lower for patients treated with prasugrel.

Early treatment revisions by addition or switch for type 2 diabetes: impact on glycemic control, diabetic complications, and healthcare costs.

BACKGROUND: The study examined the prevalence of early treatment revisions after glycosylated hemoglobin (HbA1c) ≥9.0% (75 mmol/mol) and estimated the impact of early treatment revisions on glycemic control, diabetic complications, and costs. RESEARCH DESIGN AND METHODS: A retrospective cohort study of administrative claims data of plan members with type 2 diabetes and HbA1c ≥9.0% (75 mmol/mol) was completed. Treatment revision was identified as treatment addition or switch. Glycemic control was measured as HbA1c during 6-12 months following the first qualifying HbA1c ≥9.0% (75 mmol/mol) laboratory result. Complications severity (via Diabetes Complication Severity Index (DCSI)) and costs were measured after 12, 24, and 36 months. Unadjusted comparisons and multivariable models were used to examine the relationship between early treatment revision (within 90 days of HbA1c) and outcomes after controlling for potentially confounding factors measured during a 12-month baseline period. RESULTS: 8463 participants were included with a mean baseline HbA1c of 10.2% (75 mmol/mol). Early treatment revision was associated with greater reduction in HbA1c at 6-12 months (-2.10% vs -1.87%; p<0.001). No significant relationship was observed between early treatment revision and DCSI at 12, 24, or 36 months (p=0.931, p=0.332, and p=0.418). Total costs, medical costs, and pharmacy costs at 12, 24, or 36 months were greater for the early treatment revision group compared with the delayed treatment revision group (all p<0.05). CONCLUSIONS: The findings suggest that in patients with type 2 diabetes mellitus, treatment revision within 90 days of finding an HbA1c ≥9.0% is associated with a greater level of near-term glycemic control and higher cost. The impact on end points such as diabetic complications may not be realized over relatively short time frames.

Development and Validation of a Predictive Model to Identify Individuals Likely to Have Undiagnosed Chronic Obstructive Pulmonary Disease Using an Administrative Claims Database.

BACKGROUND: Despite the importance of early detection, delayed diagnosis of chronic obstructive pulmonary disease (COPD) is relatively common. Approximately 12 million people in the United States have undiagnosed COPD. Diagnosis of COPD is essential for the timely implementation of interventions, such as smoking cessation programs, drug therapies, and pulmonary rehabilitation, which are aimed at improving outcomes and slowing disease progression. OBJECTIVE: To develop and validate a predictive model to identify patients likely to have undiagnosed COPD using administrative claims data. METHODS: A predictive model was developed and validated utilizing a retro-spective cohort of patients with and without a COPD diagnosis (cases and controls), aged 40-89, with a minimum of 24 months of continuous health plan enrollment (Medicare Advantage Prescription Drug [MAPD] and commercial plans), and identified between January 1, 2009, and December 31, 2012, using Humana's claims database. Stratified random sampling based on plan type (commercial or MAPD) and index year was performed to ensure that cases and controls had a similar distribution of these variables. Cases and controls were compared to identify demographic, clinical, and health care resource utilization (HCRU) characteristics associated with a COPD diagnosis. Stepwise logistic regression (SLR), neural networking, and decision trees were used to develop a series of models. The models were trained, validated, and tested on randomly partitioned subsets of the sample (Training, Validation, and Test data subsets). Measures used to evaluate and compare the models included area under the curve (AUC); index of the receiver operating characteristics (ROC) curve; sensitivity, specificity, positive predictive value (PPV); and negative predictive value (NPV). The optimal model was selected based on AUC index on the Test data subset. RESULTS: A total of 50,880 cases and 50,880 controls were included, with MAPD patients comprising 92% of the study population. Compared with controls, cases had a statistically significantly higher comorbidity burden and HCRU (including hospitalizations, emergency room visits, and medical procedures). The optimal predictive model was generated using SLR, which included 34 variables that were statistically significantly associated with a COPD diagnosis. After adjusting for covariates, anticholinergic bronchodilators (OR = 3.336) and tobacco cessation counseling (OR = 2.871) were found to have a large influence on the model. The final predictive model had an AUC of 0.754, sensitivity of 60%, specificity of 78%, PPV of 73%, and an NPV of 66%. CONCLUSIONS: This claims-based predictive model provides an acceptable level of accuracy in identifying patients likely to have undiagnosed COPD in a large national health plan. Identification of patients with undiagnosed COPD may enable timely management and lead to improved health outcomes and reduced COPD-related health care expenditures.

COPD exacerbation frequency and its association with health care resource utilization and costs.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) exacerbations account for a substantial proportion of COPD-related costs. OBJECTIVE: To describe COPD exacerbation patterns and assess the association between exacerbation frequency and health care resource utilization (HCRU) and costs in patients with COPD in a Medicare population. METHODS: A retrospective cohort study utilizing data from a large US national health plan was conducted including patients with a COPD diagnosis during January 1, 2007 to December 31, 2012, aged 40-89 years and continuously enrolled in a Medicare Advantage Prescription Drug plan. Exacerbation frequency, HCRU, and costs were assessed during a 24-month period following the first COPD diagnosis (follow-up period). Four cohorts were created based on exacerbation frequency (zero, one, two, and ≥three). HCRU and costs were compared among the four cohorts using chi-square tests and analysis of variance, respectively. A trend analysis was performed to assess the association between exacerbation frequency and costs using generalized linear models. RESULTS: Of the included 52,459 patients, 44.3% had at least one exacerbation; 26.3%, 9.5%, and 8.5% had one, two, and ≥three exacerbations in the 24-month follow-up period, respectively. HCRU was significantly different among cohorts (all P<0.001). In patients with zero, one, two, and ≥three exacerbations, the percentages of patients experiencing all-cause hospitalizations were 49.7%, 66.4%, 69.7%, and 77.8%, respectively, and those experiencing COPD-related hospitalizations were 0%, 40.4%, 48.1%, and 60.5%, respectively. Mean all-cause total costs (medical and pharmacy) were more than twofold greater in patients with ≥three exacerbations compared to patients with zero exacerbations ($27,133 vs $56,033; P<0.001), whereas a greater than sevenfold difference was observed in mean COPD-related total costs ($1,605 vs $12,257; P<0.001). CONCLUSION: COPD patients frequently experience exacerbations. Increasing exacerbation frequency is associated with a multiplicative increase in all-cause and COPD-related costs. This underscores the importance of identifying COPD patients at risk of having frequent exacerbations for appropriate disease management.

Type 2 Diabetes Mellitus Patients' Healthcare Costs Related to Inpatient Hospitalizations: A Retrospective Administrative Claims Database Study.

INTRODUCTION: Diabetes-related healthcare costs are increasing in the United States, with inpatient hospitalization the largest component of medical expenditures. The aims of this study were to characterize hospitalized type 2 diabetes mellitus (T2DM) patients, understand the relationship between hospitalization and healthcare costs, and explore treatment modification after inpatient hospitalization. METHODS: A retrospective cohort analysis of Humana Medicare Advantage and commercial members with T2DM was conducted. T2DM members were identified and assigned to three groups: (1) inpatient hospitalization (IPH) without a 30-day readmit (IPH group); (2) IPH with a 30-day readmission (IPH readmission group); and, (3) matched non-IPH group. Demographics, clinical characteristics, comorbidities and healthcare costs were measured based on enrollment data and claims. Descriptive statistics were used and the relationship between IPH and costs was assessed using generalized linear models. RESULTS: A total of 15,555 IPH patients, 1757 IPH readmission patients, and 17,312 matched non-IPH patients were included in the study. The IPH readmission group had the highest adjusted mean all-cause total costs ($76,806), followed by the IPH group ($42,011), and the non-IPH group ($9624). A similar trend was observed for adjusted all-cause mean medical and pharmacy costs. DM-related total healthcare costs were highest for the IPH readmission group ($13,714), followed by the IPH group ($7477), and non-IPH group ($1620). While overall therapy modification (discontinuation, addition, switch) was low, T2DM patients with an IPH (with or without a readmission) had greater rates of therapy modification relative to the non-IPH patients. CONCLUSION: Adjusted all-cause and DM-related total costs were greatest for IPH readmission patients. Rates of treatment modification within 10 days of discharge after IPH were generally low. Identifying T2DM patients at high risk of readmission and employing methods to decrease that risk during the index hospitalization could have a significant impact on health system costs. FUNDING: Novo Nordisk.