The Relative Value of Anti-Obesity Medications Compared to Similar Therapies.

Purpose: To demonstrate a need for improved health insurance coverage for anti-obesity medications (AOMs) by comparing clinical and economic benefits of obesity treatments to covered medications for selected therapeutic areas. Methods: Using a grey literature search, we identified and prioritized therapeutic areas and treatment analogues for comparison to obesity. A targeted literature review identified clinical and economic outcomes research across the therapeutic area analogues. Associated comorbidities, clinical evidence, indirect costs (ie, absenteeism and productivity loss), and direct medical costs were evaluated to determine the relative value of treating obesity. Results: Four therapeutic areas/treatment analogues were selected for comparison to obesity: smoking cessation (varenicline), daytime sleepiness (modafinil), migraines (erenumab), and fibromyalgia (pregabalin). Obesity was associated with 17 comorbidities, more than migraine (9), smoking (8), daytime sleepiness (5), and fibromyalgia (2). Economic burden was greatest for obesity, followed by smoking, with yearly indirect and direct medical costs totaling $676 and $345 billion, respectively. AOMs resulted in cost savings of $2586 in direct medical costs per patient per year (PPPY), greater than that for varenicline at $930 PPPY, modafinil at $1045 PPPY, and erenumab at $468 PPPY; pregabalin utilization increased costs by $924 PPPY. AOMs were covered by 10-16% of United States health insurance plans, compared to 45-59% for the four comparators. Conclusion: Compared to four therapeutic analogues, obesity represented the highest economic burden and was associated with more comorbidities. AOMs provide greater cost savings compared to selected analogues. However, AOMs have limited formulary coverage. Improved coverage of AOMs may increase access to these treatments and may help address the clinical and economic burden associated with obesity and its comorbidities.

Protocol for a two-arm pragmatic stepped-wedge hybrid effectiveness-implementation trial evaluating Engagement and Collaborative Management to Proactively Advance Sepsis Survivorship (ENCOMPASS).

BACKGROUND: Sepsis survivors experience high morbidity and mortality, and healthcare systems lack effective strategies to address patient needs after hospital discharge. The Sepsis Transition and Recovery (STAR) program is a navigator-led, telehealth-based multicomponent strategy to provide proactive care coordination and monitoring of high-risk patients using evidence-driven, post-sepsis care tasks. The purpose of this study is to evaluate the effectiveness of STAR to improve outcomes for sepsis patients and to examine contextual factors that influence STAR implementation. METHODS: This study uses a hybrid type I effectiveness-implementation design to concurrently test clinical effectiveness and gather implementation data. The effectiveness evaluation is a two-arm, pragmatic, stepped-wedge cluster randomized controlled trial at eight hospitals in North Carolina comparing clinical outcomes between sepsis survivors who receive Usual Care versus care delivered through STAR. Each hospital begins in a Usual Care control phase and transitions to STAR in a randomly assigned sequence (one every 4 months). During months that a hospital is allocated to Usual Care, all eligible patients will receive usual care. Once a hospital transitions to STAR, all eligible patients will receive STAR during their hospitalization and extending through 90 days from discharge. STAR includes centrally located nurse navigators using telephonic counseling and electronic health record-based support to facilitate best-practice post-sepsis care strategies including post-discharge review of medications, evaluation for new impairments or symptoms, monitoring existing comorbidities, and palliative care referral when appropriate. Adults admitted with suspected sepsis, defined by clinical criteria for infection and organ failure, are included. Planned enrollment is 4032 patients during a 36-month period. The primary effectiveness outcome is the composite of all-cause hospital readmission or mortality within 90 days of discharge. A mixed-methods implementation evaluation will be conducted before, during, and after STAR implementation. DISCUSSION: This pragmatic evaluation will test the effectiveness of STAR to reduce combined hospital readmissions and mortality, while identifying key implementation factors. Results will provide practical information to advance understanding of how to integrate post-sepsis management across care settings and facilitate implementation, dissemination, and sustained utilization of best-practice post-sepsis management strategies in other heterogeneous healthcare delivery systems. TRIAL REGISTRATION: NCT04495946 . Submitted July 7, 2020; Posted August 3, 2020.

Economic value of nonsurgical weight loss in adults with obesity.

BACKGROUND: Obesity imposes a substantial economic burden on the United States. The short-term value of nonsurgical weight loss (WL) and nonsurgical sustained WL (i.e., WL not resulting from bariatric surgery) is poorly understood. OBJECTIVES: To assess short-term (1 year) effect of nonsurgical WL and sustained nonsurgical WL (i.e., approximately 2 years) on per-patient-per-month (PPPM) total all-cause health care costs among adults with obesity in the United States. METHODS: In this retrospective cohort study, we analyzed data from the IBM MarketScan Explorys Claims-EMR Data Set from January 1, 2012, through June 30, 2018. Adults aged 18-64 years with a body mass index (BMI) measurement ≥ 30 kg/m2 on the index date and BMI measurements at 12, 24, and 36 months were classified into weight-gain (≥ 3%), no-weight-change (within ± 3%), and WL (≥ 3%-≤ 5%, > 5%-≤ 10%, and > 10%-≤ 20%) cohorts based on the change from first to second BMI measurements (baseline), and sustained nonsurgical WL based on WL during baseline and < 3% weight gain from second to third BMI measurement. PPPM all-cause health care costs were calculated for baseline, first year, and second year of follow-up. Generalized linear models were used to examine if PPPM all-cause health care cost change (ΔPPPM) from baseline to follow-up differed significantly between nonsurgical WL/sustained WL and no-weight-change cohorts. Analyses were stratified by index obesity class (class 1: BMI 30- < 34.9 kg/m2, class 2: BMI 35- < 39.9 kg/m2, class 3: BMI ≥ 40 kg/m2). Specific nonsurgical WL treatments used by individuals in the study were not studied. RESULTS: The sample included 20,488 adults who were grouped as follows: weight-gain cohort (24.8%), no-weight-change cohort (56.6%), ≥ 3%- ≤ 5% WL cohort (8.2%), > 5%- ≤ 10% WL cohort (7.7%), and > 10%- ≤ 20% WL cohort (2.8%). Compared with the no-weight-change cohort, adjusted mean ΔPPPM all-cause health care cost from baseline to first year of follow-up was lower in all WL cohorts (≥ 3%- ≤ 5% WL: -$57.36, > 5%- ≤ 10% WL: -$135.35 [P < 0.05], > 10%- ≤ 20% WL: -$193.54 [P < 0.05]). In the second year of follow-up (n = 15,307), the cohorts were weight-gain (43.4%), no-weight-change (59.4%), ≥ 3%- ≤ 5% sustained WL (7.3%), ≥ 5%- ≤ 10% sustained WL (6.3%), and > 10%- ≤ 20% sustained WL (1.8%). Adjusted mean ΔPPPM all-cause health care cost was lower in all sustained WL groups (-$26.38, -$157.41 [P < 0.05], and -$185.41 for ≥ 3%- ≤ 5%, ≥ 5%- ≤ 10%, and > 10%- ≤ 20% WL, respectively). Greater nonsurgical WL and sustained nonsurgical WL were generally associated with larger reduction in short-term all-cause health care costs. Results stratified by index obesity class were mixed, due to small samples. CONCLUSIONS: Substantial all-cause health care cost savings were observed 1 year after nonsurgical WL and after sustained (on average for 2 years) nonsurgical WL in adults with obesity, with greater nonsurgical WL and sustained nonsurgical WL associated with greater cost savings. Comprehensive solutions to chronic weight management, including improved access to antiobesity medications in combination with lifestyle interventions, could be valuable to patients, employers, and payers. DISCLOSURES: This study was sponsored by Novo Nordisk, which also purchased the data. Blanchette is an employee of Novo Nordisk. Smolarz and Ramasamy are employees of Novo Nordisk and hold equity in Novo Nordisk. Ding, Fan, and Weng were employees of Novo Nordisk at the time this study was conducted. The findings from this study were previously presented at Obesity Week 2019; November 3-7, 2019; Las Vegas, NV.

Comorbidity Associations with AATD Among Commercially Insured and Medicare Beneficiaries with COPD in the US.

Introduction: Alpha-1 antitrypsin deficiency (AATD) is often not identified in patients with chronic obstructive pulmonary disease (COPD) until advanced stages of disease, despite the availability of genetic testing. While clinical practice guidelines provide recommendations on patients who should be tested, more refined algorithms are needed to identify COPD patients who are likely candidates for AATD testing and to prevent delays in diagnosis and treatment. The objective of this study was to identify comorbid associations with AATD among patients diagnosed with COPD in the United States. Methods: Using data from the 2012-2017 PharMetrics Plus Administrative Claims Database and 2011-2014 Medicare Fee for Service 5% Sample, patients with COPD (ICD-9-CM: 491.xx, 492.xx, or 496, ICD-10-CM J41, J42, J43, J44) and AATD (ICD-9-CM: 273.4, ICD-10-CM: E88.01) were identified. Patient demographic and diagnostic characteristics were assessed. Logistic regression models were developed to identify significant predictors of AATD. Results: A cohort of 344,528 Medicare beneficiaries with COPD (of which 302 (0.09%) also had two diagnoses of AATD) and a cohort of 340,259 commercially insured patients with COPD (of which 1076 (0.3%) also had a diagnosis of AATD) were constructed. Associations with AATD identified in both models included ICD-9-CM and ICD-10-CM codes for chronic pulmonary heart disease, chronic liver disease and cirrhosis, and liver transplant. Discussion: Significant associations with a diagnosis of AATD among patients with COPD were consistently represented in each of the datasets evaluated, which suggests meaningful comorbidity implications in AATD patients. These findings reinforce the need to test individuals with COPD for AATD as early as possible to help reduce the development of associated comorbid conditions.

Two comparative assessments of intravenous immunoglobulin therapy switching patterns in the treatment of chronic inflammatory demyelinating polyneuropathy in the US.

Purpose: For chronic inflammatory demyelinating polyneuropathy (CIDP) patients, each branded intravenous immunoglobulin (IVIG) treatment differs in production processes, virus elimination, formulation, and composition. Given the limited availability of real-world data comparing IVIGs for CIDP, this study evaluated switching patterns between IVIG products in 2 separate retrospective databases. Patients and methods: Two independent analytic teams retrospectively evaluated IVIG treatment-naïve patients with an ICD diagnosis code for CIDP. Study 1 used integrated healthcare claims from IMS LifeLink PharMetrics Plus™ and Study 2 used the Truven MarketScan® Database. All analyses were descriptive, with outcomes assessed during the 2-year post-index period. Results: One-quarter of IVIG patients switched therapies within the 2-year study period. In both studies, switching rates were lowest for IVIG-G (Gamunex®-C) (Study 1: 9.8%, Study 2: 8.9%), followed by IVIG-F (Flebogamma®) (Study 1: 25.0%, Study 2: 18.2%), and highest for IVIG-other (Octagam®/Gammaplex®) (Study 1: 50.0%, Study 2: 33.3%). When patients were switched, most switched to IVIG-G (Study 1: 51.6%, Study 2: 54.3%). Conclusion: The small proportion of CIDP switchers in 2 independent studies suggests that IVIG therapy is generally well tolerated. However, differences existed in switch rates for different IVIG products. The reason for low switching rates could not be assessed in this study; therefore, further studies are required to detect possible relevant differences in effectiveness and tolerability.

Survival associated with chronic obstructive pulmonary disease among SEER-Medicare beneficiaries with non-small-cell lung cancer.

Objective: We investigated the impact of preexisting COPD and its subtypes, chronic bronchitis and emphysema, on overall survival among Medicare enrollees diagnosed with non-small-cell lung cancer (NSCLC). Methods: Using SEER-Medicare data, we included patients ≥66 years of age diagnosed with NSCLC at any disease stage between 2006 and 2010 and continuously enrolled in Medicare Parts A and B in the 12 months prior to diagnosis. Preexisting COPD in patients with NSCLC were identified using ICD-9 codes. Kaplan-Meier method and log-rank tests were used to examine overall survival by COPD status and COPD subtype. Multivariable Cox proportional hazards models were fit to assess the risk of death after cancer diagnosis. Results: We identified 66,963 lung cancer patients. Of these, 22,497 (33.60%) had documented COPD before NSCLC diagnosis. For each stage of NSCLC, median survival was shorter in the COPD compared to the non-COPD group (Stage I: 692 days vs 1,130 days, P<0.0001; Stage II: 473 days vs 627 days, P<0.0001; Stage III: 224 days vs 229 days; P<0.0001; Stage IV: 106 days vs 112 days, P<0.0001). For COPD subtype, median survival for patients with preexisting chronic bronchitis was shorter compared to emphysema across all stages of NSCLC (Stage I: 672 days vs 811 days, P<0.0001; Stage II 582 days vs 445 days, P<0.0001; Stage III: 255 days vs 229 days, P<0.0001; Stage IV: 105 days vs 112 days, P<0.0001). In Cox proportional hazard model, COPD patients exhibited 11% increase in risk of death than non-COPD patients (HR: 1.11, 95%CI: 1.09-1.13). Conclusion: NSCLC patients with preexisting COPD had shorter survival with marked differences in early stages of lung cancer. Chronic bronchitis demonstrated a greater association with time to death than emphysema.

Differences in Patient Demographics and Healthcare Costs of Patients with PIDD Receiving Intravenous or Subcutaneous Immunoglobulin Therapies in the United States.

BACKGROUND: Primary immune-deficiency disease (PIDD) is a rare, debilitating disease of the immune system that predisposes the affected individual to infection, autoimmune conditions, and neoplasm. A major component of the cost of treating PIDD is the high price of immunoglobulin drugs, which can be administered via an intravenous (IV) or subcutaneous (SC) route. OBJECTIVE: To compare real-world costs for patients with PIDD who are receiving IV immunoglobulin (IVIG) or SC immunoglobulin (SCIG) treatment, from a US payer perspective, using a large claims database. METHODS: Based on 2011 to 2013 data from the PharMetrics Plus database, a large national healthcare claims database, patients who were newly diagnosed with PIDD were included in the study if they had ≥2 claims for PIDD that were ≥90 days apart, and if they were treatment-naïve for a minimum of 1 year before the study period. Patients who switched the route of immunoglobulin administration were excluded, with the exception of patients who received SCIG who could initially receive ≤2 IV-loading infusions, as directed by treatment guidelines. We used propensity score analysis to match the patients in the SCIG cohort to patients in the IVIG cohort based on age, sex, and all Elixhauser comorbidities. We compared the patient characteristics and direct medical costs (all-cause, PIDD-related, and pharmacy-related) before and after matching, using t-tests for continuous variables, chi-square test for categorical variables, and Wilcoxon rank-sum test for differences in medians. RESULTS: A total of 1639 patients with PIDD (986 who received IVIG and 653 who received SCIG) met all the study inclusion criteria. Compared with the patients who received IVIG, the patients who received SCIG were predominantly female (58% vs 63%, respectively) and significantly younger (mean age, 49.1 vs 40.3 years, respectively). Significantly fewer patients who received SCIG than those receiving IVIG had claims with International Classification of Diseases, Ninth Revision codes for Elixhauser comorbidities, including cardiovascular and pulmonary conditions, diabetes, renal failure, liver disease, cancers, weight loss, fluid and electrolyte disorders, and psychoses (P <.05 for all), and their Charlson Comorbidity Index scores were lower than those receiving IVIG (1.74 vs 3.01, respectively; P ≤.05 for all). After matching the 2 cohorts (N = 553 in each), the 1-year postindex median total PIDD-related costs were significantly lower in the IVIG group than in the SCIG group ($38,064 vs $43,266, respectively; P = .002). CONCLUSIONS: In matched analyses, PIDD-related treatment costs were higher for patients who received SCIG than for those who received IVIG. Furthermore, patients who received SCIG were significantly younger and had significantly less comorbidities than their counterparts who received IVIG, suggesting that patient characteristics that reflect a desire and greater capacity for autonomy may affect physicians' choice of the route of administration for immunoglobulin.

Comorbidities and length of stay in chronic obstructive pulmonary disease patients.

Chronic Obstructive Pulmonary Disease (COPD) has a significant burden on patients and the healthcare system. There is a link between COPD and comorbidities such as congestive heart failure (CHF), fluid and electrolyte disorders, and renal failure. This adds to the complexity of healthcare in these patients. The objective of this study is to determine if certain comorbidities affect length of stay. A sample of 3,399 patients with COPD were assessed from the Premier© healthcare database. The cohort had a mean (standard deviation (SD)) age of 68.41 (10.85) years. The average number of comorbidities was 24.83 (10.46) with a mean length of stay (SD) of 11.64 (9.40) days. A negative binomial regression model was used to evaluate the impact that comorbidities have on the length of hospital stay. The authors found that the number of comorbidities was associated with an increased length of stay (r = .4596, p < .0001). Having at least one comorbidity was associated with a 13% greater length of stay (IRR = 1.13, 95% CI 1.11-1.15, p < 0.0001). CHF was associated with a 28% greater length of stay (IRR = 1.28, 95% CI 1.24-1.31, p < 0.0001). Fluid and electrolyte disorders were associated with a 2-fold greater length of stay (IRR = 2.57, 95% CI 2.52-2.62, p < 0.0001). Renal failure was associated with a 50% greater length of stay (IRR = 1.50, 95% CI 1.45-1.55, p < 0.0001). However, uncomplicated diabetes was associated with 13% shorter length of stay than not having uncomplicated diabetes (IRR = .87, 95% CI .82-.91, p < .0001). This study demonstrated that specific comorbidities have an impact on length of stay.

Healthcare utilization and costs associated with COPD among SEER-Medicare beneficiaries with NSCLC.

AIM: To estimate the healthcare utilization and costs in elderly lung cancer patients with and without pre-existing chronic obstructive pulmonary disease (COPD). METHODS: Using Surveillance, Epidemiology and End Results (SEER)-Medicare data, this study identified patients with lung cancer between 2006-2010, at least 66 years of age, and continuously enrolled in Medicare Parts A and B in the 12 months prior to cancer diagnosis. The diagnosis of pre-existing COPD in lung cancer patients was identified using ICD-9 codes. Healthcare utilization and costs were categorized as inpatient hospitalizations, skilled nursing facility (SNF) use, physician office visits, ER visits, and outpatient encounters for every stage of lung cancer. The adjusted analysis was performed using a generalized linear model for healthcare costs and a negative binomial model for healthcare utilization. RESULTS: Inpatient admissions in the COPD group increased for each stage of non-small cell lung cancer (NSCLC) compared to the non-COPD group per 100 person-months (Stage I: 14.67 vs 9.49 stays, p < .0001; Stage II: 14.13 vs 10.78 stays, p < .0001; Stage III: 28.31 vs 18.91 stays, p < .0001; Stage IV: 49.5 vs 31.24 stays, p < .0001). A similar trend was observed for outpatient visits, with an increase in utilization among the COPD group (Stage I: 1136.04 vs 796 visits, p < .0001; Stage II: 1325.12 vs 983.26 visits, p < .0001; Stage III: 2025.47 vs 1656.64 visits, p < .0001; Stage IV: 2825.73 vs 2422.26 visits, p < .0001). Total direct costs per person-month in patients with pre-existing COPD were significantly higher than the non-COPD group across all services ($54,799.16 vs $41,862.91). Outpatient visits represented the largest cost category across all services in both groups, with higher costs among the COPD group ($41,203 vs $31,140.08). CONCLUSION: Healthcare utilization and costs among lung cancer patients with pre-existing COPD was ∼2-3-times higher than the non-COPD group.

Challenges in Research and Health Technology Assessment of Rare Disease Technologies: Report of the ISPOR Rare Disease Special Interest Group.

BACKGROUND: Successful development of new treatments for rare diseases (RDs) and their sustainable patient access require overcoming a series of challenges related to research and health technology assessment (HTA). These impediments, which may be unique to RDs or also apply to common diseases but are particularly pertinent in RDs, are diverse and interrelated. OBJECTIVE: To develop for the first time a catalog of primary impediments to RD research and HTA, and to describe the cause and effect of individual challenges. METHODS: Challenges were identified by an international 22-person expert working group and qualitative outreach to colleagues with relevant expertise. A broad range of stakeholder perspectives is represented. Draft results were presented at annual European and North American International Society for Pharmacoeconomics and Outcomes Research (ISPOR) congresses, and written comments were received by the 385-strong ISPOR Rare Disease Review Group from two rounds of review. Findings were refined and confirmed via targeted literature search. RESULTS: Research-related challenges linked to the low prevalence of RDs were categorized into those pertaining to disease recognition and diagnosis, evaluation of treatment effect, and patient recruitment for clinical research. HTA-related challenges were classified into issues relating to the lack of a tailored HTA method for RD treatments and uncertainty for HTA agencies and health care payers. CONCLUSIONS: Identifying and highlighting diverse, but interrelated, key challenges in RD research and HTA is an essential first step toward developing implementable and sustainable solutions. A collaborative multistakeholder effort is required to enable faster and less costly development of safe, efficacious, and appropriate new RD therapies that offer value for money.

Shared decision making and time to exacerbation in children with asthma.

Objective: Although shared decision making (SDM) is a promising approach for improving outcomes for patients with chronic diseases, no evidence currently supports the use of SDM to delay asthma exacerbations. We evaluated the impact of an SDM intervention implemented by providers in a real-world setting on time to exacerbation in children with asthma. Methods: This study used a prospective cohort observed between 2011 and 2013 at five primary care practices that serve vulnerable populations (e.g., Medicaid and uninsured patients) in Charlotte, NC. Patients aged 2 to 17 receiving SDM were matched to those receiving usual care using propensity scores. Time to asthma exacerbation (asthma hospitalization, emergency department visit or oral steroid prescription in the outpatient setting) was compared between groups using Kaplan-Meier curves and conditional Cox proportional hazards models. Results: The cohort included 746 children, 60.5% male and 54.2% African American, with a mean age of 8.6 years. Of these, 625 received usual care and 121 received SDM. The final analysis included 100 matched pairs of children. Kaplan-Meier curves showed longer exacerbation-free time for patients in the SDM intervention compared to those in usual care (p = 0.005). The difference in risk of experiencing an exacerbation was marginally significant between the two groups (HR = 0.56, 95% C.I. = 0.29-1.08, p = 0.08). Conclusions: SDM was found to delay exacerbations among children with asthma. Clinicians should consider incorporating patient preferences in treatment decisions through SDM as a means for longer exacerbation-free time among children with poor asthma control.

The value of self-medication: summary of existing evidence.

AIM: The aim of this review was to identify the international evidence that is currently available on the economic value of self-care through responsible self-medication, in terms of the measures related to access to treatment, time, and productivity. METHODS: A targeted literature search was conducted for 1990-2016, including data gathered from members of the World Self-Medication Industry and searches on PubMed, EBSCOHost, and Google Scholar. Specific searches of individual drug classes known to be switched to non-prescription status in this period were also conducted. RESULTS: A total of 71 articles were identified, of which 17 (11 modeling studies, six retrospective analyses) were included in the review. Evidence from modeling studies and retrospective analyses of grouped data across a range of common conditions for which non-prescription medications are available in different countries/regions showed that the use of non-prescription products for the treatment of common conditions or for symptom management (e.g. allergies, chronic pain, migraine, vaginitis, gastrointestinal symptoms, or common cold symptoms) had considerable value to patients, payers, and employers alike in terms of cost savings and improved productivity. Potential benefits of self-medication were also identified in preventative healthcare strategies, such as those for cardiovascular health and osteoporosis. LIMITATIONS: This review was limited by a targeted, but non-systematic approach to literature retrieval, as well as the inclusion of unpublished reports/white papers and patient self-reported data. CONCLUSIONS: The evidence identified in this literature review shows that responsible, appropriate self-medication with non-prescription products can provide significant economic benefits for patients, employers, and healthcare systems worldwide.

The Association of COPD Exacerbations with New Onset Type 2 Diabetes among Medicare Patients.

Objective: Chronic obstructive pulmonary disease (COPD) is highly prevalent in the elderly population and typically reduces overall quality of life. Exacerbations of COPD are commonly treated with corticosteroids, a class of drug known to cause insulin resistance. The objective of this study was to assess the rate of exacerbations requiring emergency room visits, hospitalizations or any medical encounter (a combination of emergency room and hospitalizations) between COPD patients who did and did not develop type 2 diabetes. Research Design and Methods: A case-control study of COPD patients from the 2011-2012 Medicare 5% sample Limited Data Set (LDS) was conducted. Beneficiaries with at least 1 year of continuous enrollment and evidence of > 2 COPD-related claims (>1 primary diagnosis) were included in the study. Cases were defined as a beneficiary with a new claim for type 2 diabetes, whereas controls lacked evidence of type 2 diabetes (beneficiaries with evidence of non-incident type 2 diabetes were excluded). Results: Of 27 456 COPD beneficiaries, 1274 developed incident type 2 diabetes (4.6%). After matching, 2536 beneficiaries were assigned as cases (n = 1268) and controls (n = 1268). Cases in the emergency room (1.97 claims per person) (p = <0.001) and hospitalizations (2.02 claims per person) (p = <0.001) had a higher rate of exacerbations. Conclusion: Our findings suggest that patients that were hospitalized and visited the emergency room for COPD exacerbations had a greater likelihood of type 2 diabetes. Type 2 diabetes may be associated with exposure to corticosteroids as a result of the treatment for exacerbations. Future work should investigate the risk for type 2 diabetes in COPD patients treated with corticosteroids.

Healthcare Cost and Utilization before and after Diagnosis of Pseudomonas aeruginosa among Patients with Non-Cystic Fibrosis Bronchiectasis in the U.S.

Non-cystic fibrosis bronchiectasis (NCFBE) is a rare, chronic lung disease characterized by bronchial inflammation and permanent airway dilation. Chronic infections with P. aeruginosa have been linked to higher morbidity and mortality. To understand the impact of P. aeruginosa in NCFBE on health care costs and burden, we assessed healthcare costs and utilization before and after P. aeruginosa diagnosis. Using data from 2007 to 2013 PharMetrics Plus administrative claims, we included patients with ≥2 claims for bronchiectasis and >1 claim for P. aeruginosa; then excluded those with a claim for cystic fibrosis. Patients were indexed at first claim for P. aeruginosa and were required to have >12 months before and after the index P. aeruginosa. The mean differences in utilization and costs were assessed using paired Student's t-tests for statistical significance. Mean total healthcare costs per patient were $36,213 pre-P. aeruginosa diagnosis versus $67,764 post-P. aeruginosa, an increase of 87% (p < 0.0001). Inpatient costs represented the largest proportion of total healthcare costs post-P. aeruginosa (54%) with an increase of four hospitalizations per patient (p < 0.0001). NCFBE patients with evidence of P. aeruginosa incur substantially greater healthcare costs and utilization after P. aeruginosa diagnosis. Future research should explore methods of earlier identification of NCFBE patients with P. aeruginosa, as this may lead to fewer severe exacerbations, thereby resulting in a reduction in hospitalizations and healthcare costs.

One-year Prevalence, Comorbidities, and Cost of Hospitalizations for Alpha-1 Antitrypsin Deficiency among Patients with Chronic Obstructive Pulmonary Disease in the United States.

Objectives: Little is known about severe chronic obstructive pulmonary disease (COPD) exacerbations among patients with Alpha-1 Antitrypsin Deficiency (AATD). We assessed inpatients with AATD and COPD among a sample of COPD inpatients to ascertain demographic, clinical and economic differences in the course of disease and treatment. Methods: Using data from the 2009 Nationwide Inpatient Sample (NIS), we identified COPD (ICD-9-CM: 491.xx, 492.xx, or 496.xx) patients with AATD (273.4). We compared patient demographics and healthcare outcomes (eg, length of stay, inpatient death, type and number of procedures, and cost of care) between COPD patients with and without alpha-1 antitrypsin deficiency. Frequencies and percentages for patient demographics were compared using bivariate statistics (eg, chi-square test). Recognizing the non-parametric nature of length of stay and cost, we calculated median values and interquartile ranges for these variables for each group of patients. Finally, the risk of inpatient death was estimated using logistic regression. Results: Of 840 242 patients with COPD (10.8% of the NIS sample population), 0.08% (684) had a primary or secondary diagnosis code for AATD. COPD+AATD were younger (56 vs 70, p<0.0001) and as a result, less likely to be covered by Medicare (44% vs 62%, p<0.0001). AATD patients were also more likely to have comorbid non-alcoholic liver disease (7% vs 2%, p<0.0001), depression (17% vs 13%, p=0.0328), and pulmonary circulation disorders (7% vs 4%, p=0.0299). Patients with AATD had a 14% longer length of stay (IRR = 1.14, 95% CI 1.07, 1.21) and a mean cost of $1487 (p=0.0251) more than COPD inpatients without AATD. Conclusions: AATD is associated with increased mean length of stay and cost, as well as higher frequency of comorbid non-alcoholic liver disease, depression, and pulmonary circulation disorders. Future research should assess other differences between AATD and the general COPD population such as natural history of disease, treatment responsiveness and disease progression.

Evaluating cost benefits of combination therapies for advanced melanoma.

BACKGROUND: Although a number of monoimmunotherapies and targeted therapies are available to treat BRAF+ advanced melanoma, response rates remain relatively low in the range of 22-53% with progression-free survival (PFS) in the range of 4.8-8.8 months. Recently, combination targeted therapies have improved response rates to about 66-69%, PFS to 11.0-12.6 months and overall survival (OS) to 25.1-25.6 months. While combination immunotherapies have improved response rates of 67 compared with 19-29% with monotherapies and improved PFS of 11.7 compared with 4.4-5.8 months with monotherapies, the OS benefit is yet to be established in phase 3 trials. As healthcare costs continue to rise, US payers have a predominant interest in assessing the value of available treatments. Therefore, a cost-benefit model was developed to evaluate the value of treating BRAF+ advanced melanoma with two combination therapies: nivolumab + ipilimumab (N+I) and dabrafenib + trametinib (D+T). SCOPE: The model was used to estimate total costs, total costs by expenditure category, cost per month of PFS and cost per responder for the payer, and societal perspectives of treating advanced melanoma patients with the BRAF V600 mutation using combination targeted therapy (D+T) or combination immunotherapy (N+I). The model followed patients from initiation of treatment to the point of progression or death. Deterministic and probabilistic sensitivity analyses were conducted to evaluate the robustness of the results and to understand the dispersion of simulated results. FINDINGS: Based on a hypothetical payer with one million covered lives, it was expected that fourteen metastatic melanoma patients with the BRAF V600 mutation would be treated each year. Cost-benefit with N+I and D+T was simulated from the payer perspective. The cost per month of PFS for N+I was $22,162, while that for D+T was $17,716 (-$4,446 cost difference); the cost per responder for N+I was $388,746 and that for D+T was $282,429 (-$106,316 cost difference). The cost per month of PFS and per responder from the societal perspective resembled the patterns observed from the payer's perspective: the cost per month of PFS for N+I was $22,843, while that for D+T was $18,283 (-$4,560 cost difference). The cost per responder for N+I was $400,695 and that for D+T was $291,473 (-$109,222 cost difference). The totals of travel and treatment time for N+I and D+T were 58 hours and 3.9 hours per patient, respectively, of which total infusion time for N+I accounted for a majority - 59% - of the 58 hours. Sensitivity analyses indicated that results were most sensitive to model inputs for median PFS, body weight, and drug cost. Moreover, D+T is likely associated with a lower cost per month of PFS and cost per responder than N+I, except at low body weights (less than 57 kg). CONCLUSION: The model presented in this study was used to analyze the clinical and economic benefit of using combination therapies in advanced melanoma patients with the BRAF V600 mutation. This analysis suggests D+T therapy is associated with less patient time and lower costs relative to N+I to gain similar PFS and overall response rate (ORR) benefits.

The dilemma of diabetes in chronic inflammatory demyelinating polyneuropathy.

PURPOSE: We reviewed the literature on chronic inflammatory demyelinating polyneuropathy (CIDP) in diabetes mellitus (DM) and explored real-world data on the prevalence and treatment of CIDP within DM. METHODS: A literature search of Scopus was performed for the terms chronic inflammatory demyelinating polyradiculoneuropathy, chronic inflammatory demyelinating polyneuropathy, CIDP, and prevalence, incidence, epidemiology, or diabetes; peripheral neuropathy and prevalence or diabetes. We also searched through the reference lists of the resulting publications for additional findings that may have been missed. Additional publications on guidelines for the diagnosis of CIDP and diabetic neuropathy were also included. A descriptive analysis of the 2009-2013 PharMetrics Plus™ Database was performed to estimate the prevalence and treatment of CIDP within the DM population. RESULTS: There is an increasing body of literature suggesting that the prevalence of CIDP tends to be higher in diabetic patients, especially in those of older age. Our real-world data seem to support published findings from the literature. For the total cohort (N=101,321,694), the percent prevalence of CIDP (n=8,173) was 0.008%; DM (n=4,026,740) was 4%. The percent prevalence of CIDP without DM (n=5,986) was 0.006%; CIDP with DM (n=2,187) was 9-fold higher at 0.054%. For patients >50years old, there was a significantly higher percentage of CIDP with DM than CIDP without DM. Approximately 50% of CIDP patients were treated with IVIg, 23%-24% with steroids, 1%-2% with PE, and 20%-23% received no treatment. CONCLUSIONS: In addition to the growing evidence of higher prevalence of CIDP in DM, our findings reinforce the need for heightened awareness of the association of CIDP and DM.

Incidence and Cost of Ankle Sprains in United States Emergency Departments.

BACKGROUND: Ankle sprains represent a common injury in emergency departments, but little is known about common complications, procedures, and charges associated with ankle sprains in emergency departments. HYPOTHESIS: There will be a higher incidence of ankle sprains among younger populations (≤25 years old) and in female patients. Complications and procedures will differ between ankle sprain types. Lateral ankle sprains will have lower health care charges relative to medial and high ankle sprains. STUDY DESIGN: Descriptive epidemiological study. LEVEL OF EVIDENCE: Level 3. METHODS: A cross-sectional study of the 2010 Nationwide Emergency Department Sample was conducted. Outcomes such as charges, complications, and procedures were compared using propensity score matching between lateral and medial as well as lateral and high ankle sprains. RESULTS: The sample contained 225,114 ankle sprains. Female patients sustained more lateral ankle sprains (57%). After propensity score adjustment, lateral sprains incurred greater charges than medial ankle sprains (median [interquartile range], $1008 [$702-$1408] vs $914 [$741-$1108]; P < 0.01). Among complications, pain in the limb (1.92% vs 0.52%, P = 0.03), sprain of the foot (2.96% vs 0.70%, P < 0.01), and abrasion of the hip/leg (1.57% vs 0.35%, P = 0.03) were more common in lateral than medial ankle sprain events. Among procedures, medial ankle sprains were more likely to include diagnostic radiology (97.91% vs 83.62%, P < 0.01) and less likely to include medications than lateral ankle sprains (0.87% vs 2.79%, P < 0.01). Hospitalizations were more common following high ankle sprains than lateral ankle sprains (24 [6.06%] vs 1 [0.25%], P < 0.01). CONCLUSION: Ankle sprain emergency department visits account for significant health care charges in the United States. Age- and sex-related differences persist among the types of ankle sprains. CLINICAL RELEVANCE: The health care charges associated with ankle sprains indicate the need for additional preventive measures. There are age- and sex-related differences in the prevalence of ankle sprains that suggest these demographics may be risk factors for ankle sprains.

Estimated incidence of pertussis in people aged <50 years in the United States.

The introduction of pertussis vaccination in the United States (US) in the 1940s has greatly reduced its burden. However, the incidence of pertussis is difficult to quantify, as many cases are not laboratory-confirmed or reported, particularly in adults. This study estimated pertussis incidence in a commercially insured US population aged <50 years. Data were extracted from IMS' PharMetrics Plus claims database for patients with a diagnosis of pertussis or cough illness using International Classification of Diseases (ICD-9) codes, a commercial outpatient laboratory database for patients with a pertussis laboratory test, and the Centers for Disease Control influenza surveillance database. US national pertussis incidence was projected using 3 methods: (1) diagnosed pertussis, defined as a claim for pertussis (ICD-9 033.0, 033.9, 484.3) during 2008-2013; (2) based on proxy pertussis predictive logistic regression models; (3) using the fraction of cough illness (ICD-9 033.0, 033.9, 484.3, 786.2, 466.0, 466.1, 487.1) attributed to laboratory-confirmed pertussis, estimated by time series linear regression models. Method 1 gave a projected annual incidence of diagnosed pertussis of 9/100,000, which was highest in those aged <1 year. Method 2 gave an average annual projected incidence of 21/100,000. Method 3 gave an overall regression-estimated weighted annual incidence of pertussis of 649/100,000, approximately 58-93 times higher than method 1 depending on the year. These estimations, which are consistent with considerable underreporting of pertussis in people aged <50 years and provide further evidence that the majority of cases go undetected, especially with increasing age, may aid in the development of public health programs to reduce pertussis burden.