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Krithika Rajagopalan,1 Sean D Candrilli,2 Mayank Ajmera2 1Sunovion Pharmaceuticals Inc, Marlborough, MA 01752, USA; 2RTI Health Solutions, Research Triangle Park, NC 27709, USA Background: Complex titration requirements and dosing of antiepileptic drugs (AEDs) may pose a significant treatment burden for patients with epilepsy. This study evaluated health-care-resource utilization (HCRU) rates and costs by treatment burden, defined as number of daily pills and dosing frequency, among managed-care enrollees with epilepsy who initiated AED monotherapy. Methods: This retrospective longitudinal study examined administrative HC-claim data in patients aged ≥18 years with two or more pharmacy claims for an AED and two or more medical claims for epilepsy or afebrile convulsion. The number of daily AED pills was estimated at index as the total number of pills dispensed divided by the days supplied, and categorized as more than zero/one, one/two, two/three, and more than three per day. AED-dosing frequency was measured at index and categorized as one, two, three, or four times daily. Postindex 12-month all-cause and epilepsy-related HCRU and costs were estimated using multivariable Poisson regression models and generalized linear models, respectively. Results: Unadjusted total all-cause and epilepsy-related costs at 12 months postindex averaged US$26,015 per person and US$5,557 per person (2017 values), respectively. Adjusted all-cause and epilepsy-related costs were US$25,918 per person and US$5,602 per person, respectively. A pill burden of more than three a day was associated with a 6.7% increase in total annual HC costs compared with one pill/day. Patients receiving one/two, two/three, and more than three pills per day had 13.3%, 23.9%, and 38.3% higher epilepsy-related costs, respectively, than those receiving one pill per day (P

Mayank Ajmera,1 Amit D Raval,1 Chan Shen,2 Usha Sambamoorthi1 1Department of Pharmaceutical Systems and Policy, School of Pharmacy, School of Medicine, West Virginia University, Morgantown, WV, USA; 2Department of Biostatistics and Health Services Research, University of Texas MD Anderson Cancer Center, Houston, TX, USA Objective: To estimate excess health care expenditures associated with gastroesophageal reflux disease (GERD) among elderly individuals with chronic obstructive pulmonary disease (COPD) and examine the contribution of predisposing characteristics, enabling resources, need variables, personal health care practices, and external environment factors to the excess expenditures, using the Blinder-Oaxaca linear decomposition technique. Methods: This study utilized a cross-sectional, retrospective study design, using data from multiple years (2006-2009) of the Medicare Current Beneficiary Survey linked with fee-for-service Medicare claims. Presence of COPD and GERD was identified using diagnoses codes. Health care expenditures consisted of inpatient, outpatient, prescription drugs, dental, medical provider, and other services. For the analysis, t-tests were used to examine unadjusted subgroup differences in average health care expenditures by the presence of GERD. Ordinary least squares regressions on log-transformed health care expenditures were conducted to estimate the excess health care expenditures associated with GERD. The Blinder-Oaxaca linear decomposition technique was used to determine the contribution of predisposing characteristics, enabling resources, need variables, personal health care practices, and external environment factors, to excess health care expenditures associated with GERD. Results: Among elderly Medicare beneficiaries with COPD, 29.3% had co-occurring GERD. Elderly Medicare beneficiaries with COPD/GERD had 1.5 times higher ($36,793 vs $24,722 [P

Mayank Ajmera,1 Chan Shen,2 Xiaoyun Pan,1 Patricia A Findley,3 George Rust,4 Usha Sambamoorthi1 1Department of Pharmaceutical Systems and Policy, School of Pharmacy, West Virginia University, Morgantown, WV, USA; 2Department of Biostatistics, MD Anderson Cancer Center, University of Texas, Houston, TX, USA; 3School of Social Work, Rutgers University, New Brunswick, NJ, USA; 4Department of Family Medicine, Morehouse School of Medicine, Atlanta, GA, USA Background: The purpose of this study was to examine the association between use of inhaled anticholinergics and all-cause mortality among elderly individuals with chronic obstructive pulmonary disease (COPD), after controlling for demographic, socioeconomic, health, functional status, smoking, and obesity. Methods: We used a retrospective longitudinal panel data design. Data were extracted for multiple years (2002–2009) of the Medicare Current Beneficiary Survey (MCBS) linked with fee-for-service Medicare claims. Generic and brand names of inhaled anticholinergics were used to identify inhaled anticholinergic utilization from the self-reported prescription medication files. All-cause mortality was assessed using the vital status variable. Unadjusted group differences in mortality rates were tested using the chi-square statistic. Multivariable logistic regressions with independent variables entered in separate blocks were used to analyze the association between inhaled anticholinergic use and all-cause mortality. All analyses accounted for the complex design of the MCBS. Results: Overall, 19.4% of the elderly Medicare beneficiaries used inhaled anticholinergics. Inhaled anticholinergic use was significantly higher (28.5%) among those who reported poor health compared with those reporting excellent or very good health (12.7%). Bivariate analyses indicated that inhaled anticholinergic use was associated with significantly higher rates of all-cause mortality (18.7%) compared with nonusers (13.6%). However, multivariate analyses controlling for risk factors did not suggest an increased likelihood of all-cause mortality (adjusted odds ratio 1.26, 95% confidence interval 0.95–1.67). Conclusion: Use of inhaled anticholinergics among elderly individuals with COPD is potentially safe in terms of all-cause mortality when we adjust for baseline risk factors. Keywords: geriatrics, chronic obstructive pulmonary disease, inhaled anticholinergics, mortality, drug safety

Vasomotor symptoms (VMS) are the hallmark of menopause and negatively affect a large proportion of women over many years. However, studies evaluating the overall impact of VMS are limited. This systematic review (SR) aimed to examine epidemiological, clinical, humanistic, and economic outcomes of VMS among perimenopausal women and among women aged ≥65 years in the US. A systematic search of the MEDLINE and Embase databases was conducted to identify observational studies (2010-2022) reporting on these populations. Data reporting outcomes of interest were extracted and analyzed descriptively. Of 7,613 studies identified, 34 met inclusion criteria, of which 30 reported on perimenopausal women and 4 reported on VMS in women aged ≥ 65 years. VMS and severe/moderate-to-severe VMS were reported by 48.4-70.6 percent and 13.0-63.1 percent, respectively, of perimenopausal women. Mean VMS duration was 2.6 years, and median duration ranged from 7.4 to 10.1 years among women with onset in early perimenopause and from 3.8 to 6.1 years among those with onset in late perimenopause. Among women aged ≥65 years, 20.9-45.1 percent reported VMS; 2.0 percent reported severe symptoms, and 17.6 percent reported moderate symptoms. No studies reported VMS frequency and duration or the economic or humanistic burden among women aged ≥65 years. In conclusion, high VMS frequency and severity were observed among perimenopausal women and women aged ≥65 years in the US in this SR, highlighting the need for (1) better management of VMS to reduce frequency and severity and (2) further research to clarify the impact of VMS on disease burden, quality of life, and economic impact.

Background: In patients with heart failure with reduced ejection fraction (HFrEF), lower discharge heart rate (HR) is known to be associated with better outcomes. However, the effect of HR control on patient outcomes, and the demographic and clinical determinants of this association, are not well documented., Objectives: The purpose of this work was to evaluate the association between the HR control and the risk of post-discharge rehospitalization in patients hospitalized with HFrEF., Methods: Data were collected using a retrospective medical record review in the USA. Reduction in HR between admission and discharge ("HR control") defined the primary exposure, categorized as no reduction, > 0 to < 20% reduction, and ≥ 20% reduction. Time to first rehospitalization in the post-discharge follow-up defined the study outcome and was analyzed using multivariable Cox regression modeling., Results: A total of 1002 patients were analyzed (median age, 63 years; median follow-up duration, 24.2 months). At admission, 59.1% received beta-blockers, 57.4% received diuretics, and 47.5% received angiotensin-converting enzyme (ACE) inhibitors. Most patients (90.5%) achieved some HR control (38.4% achieved > 0 to < 20% reduction, and 52% achieved ≥ 20% reduction). Approximately 39% were rehospitalized during the follow-up (14% within 30 days). In multivariable analysis, patients with > 0 to < 20% reduction in HR had a 39% lower risk of rehospitalization [hazard ratio 0.61; 95% confidence interval (CI) 0.43-0.85]; patients with ≥ 20% reduction in HR had a 38% lower rehospitalization risk (hazard ratio 0.62; 95% CI 0.45-0.87) than those with no HR reduction., Conclusions: Reduction in HR between admission and discharge was associated with reduced risk for rehospitalization. Findings indicate HR control as an important goal in the management of patients hospitalized for HFrEF., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background and Aims: Limited real-world nontertiary care evidence on the patient therapeutic journey and disease burden of eosinophilic esophagitis (EoE) exists. The aim was to collect real-world data on the EoE patient journey across different age groups., Methods: This retrospective, real-world, cohort study used electronic medical records and claims data provided by a rural integrated US healthcare system. Eligibility criteria included ≥ 2 diagnoses of EoE (2009-2018), ≥ 1 endoscopy, and ≥ 12 months of data before and after the index date (the first endoscopy date during the 180 days before and the 365 days after the first EoE diagnosis). Clinical findings, all-cause healthcare resource utilization, specialists consulted, therapies, and markers of disease progression were analyzed., Results: Overall, 613 patients were enrolled: 0-11 (children, n = 182), 12-17 (adolescents, n = 146), 18-54 (adults, n = 244), and ≥ 55 years old (older adults, n = 41). Post index, the prevalence of signs and symptoms increased. At baseline, most endoscopies were abnormal (80.5%) and most peak eosinophil counts were > 15 eosinophils/high-power field (87.9%); post index, all age groups had endoscopic and histologic improvements. However, 3 years post index, abnormal endoscopic appearance (62.3%) and histologic activity (51.2%) were observed. Patients of all ages exhibited considerable all-cause healthcare resource utilization. During follow-up, 86.3% of patients consulted a specialist. Before and after index, proton pump inhibitors and corticosteroids were the most commonly used pharmacological therapies; 44.0% of patients discontinued their first treatment post index. Disease progression occurred in 13.9% of patients post index., Conclusion: In this setting, patients with EoE irrespective of age face difficult therapeutic journeys with substantial disease burden., (© 2024 The Authors.)

Importance: The neurokinin 3 receptor antagonist fezolinetant 45 mg/d significantly reduced frequency/severity of moderate to severe vasomotor symptoms (VMS) of menopause compared with placebo in two phase 3 randomized controlled trials. Its efficacy relative to available therapies is unknown., Objective: We conducted a systematic review and Bayesian network meta-analysis to compare efficacy with fezolinetant 45 mg and hormone therapy (HT) and non-HT for VMS in postmenopausal women., Evidence Review: Using OvidSP, we systematically searched multiple databases for phase 3 or 4 randomized controlled trials in postmenopausal women with ≥7 moderate to severe VMS per day or ≥50 VMS per week published/presented in English through June 25, 2021. Mean change in frequency and severity of moderate to severe VMS from baseline to week 12 and proportion of women with ≥75% reduction in VMS frequency at week 12 were assessed using fixed-effect models., Findings: The network meta-analysis included data from the pooled phase 3 fezolinetant trials plus 23 comparator publications across the outcomes analyzed (frequency, 19 [34 regimens]; severity, 6 [7 regimens]; ≥75% response, 9 [15 regimens]). Changes in VMS frequency did not differ significantly between fezolinetant 45 mg and any of the 27 HT regimens studied. Fezolinetant 45 mg reduced the frequency of moderate to severe VMS events per day significantly more than all non-HTs evaluated: paroxetine 7.5 mg (mean difference [95% credible interval {CrI}], 1.66 [0.63-2.71]), desvenlafaxine 50 to 200 mg (mean differences [95% CrI], 1.12 [0.10-2.13] to 2.16 [0.90-3.40]), and gabapentin ER 1800 mg (mean difference [95% CrI], 1.63 [0.48-2.81]), and significantly more than placebo (mean difference, 2.78 [95% CrI], 1.93-3.62]). Tibolone 2.5 mg (the only HT regimen evaluable for severity) significantly reduced VMS severity compared with fezolinetant 45 mg. Fezolinetant 45 mg significantly reduced VMS severity compared with desvenlafaxine 50 mg and placebo and did not differ significantly from higher desvenlafaxine doses or gabapentin ER 1800 mg. For ≥75% responder rates, fezolinetant 45 mg was less effective than tibolone 2.5 mg (not available in the United States) and conjugated estrogens 0.625 mg/bazedoxifene 20 mg (available only as 0.45 mg/20 mg in the United States), did not differ significantly from other non-HT regimens studied and was superior to desvenlafaxine 50 mg and placebo., Conclusions: The only HT regimens that showed significantly greater efficacy than fezolinetant 45 mg on any of the outcomes analyzed are not available in the United States. Fezolinetant 45 mg once daily was statistically significantly more effective than other non-HTs in reducing the frequency of moderate to severe VMS., Relevance: These findings may inform decision making with regard to the individualized management of bothersome VMS due to menopause., Competing Interests: Financial disclosure/conflicts of interest: R.K. is a consultant to Astellas Pharma, Avion Pharma, Pharmavite, Pfizer, and TherapeuticsMD. E.G. and O.P.-L. are employees of Analysis Group, Inc., which received funding from Astellas to conduct this analysis. A.Z., S.M., and M.A. are employees of Astellas Pharma, Inc. A.M. and E.S. are employees of Astellas Pharma Europe Ltd., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The Menopause Society.)

Introduction: Urothelial carcinoma (UC) is a malignancy of the urothelium that encompasses the renal pelvis, bladder, and urethra. Current treatment guidelines for advanced (ie, locally advanced or metastatic) UC recommend using avelumab maintenance therapy in patients with nonprogressive disease following first-line platinum-based chemotherapy. This study aimed to assess the representativeness of the patient population in the JAVELIN Bladder 100 (JB-100) trial, which examined the efficacy and safety of avelumab first-line maintenance, vs. real-world patients with advanced UC that had not progressed with first-line platinum-based chemotherapy treated between 2015 and 2018 by reviewing demographic and clinical characteristics., Patients and Methods: A medical chart review (MCR) study collected demographics and treatment characteristics for patients with advanced UC in the United States, the United Kingdom, and France. Data were analyzed descriptively for review with data collected from patients enrolled in JB-100., Results: Clinical characteristics were consistent between JB-100 and the MCR. Most patients were male, received 4 to 6 cycles of platinum-based chemotherapy, and had an Eastern Cooperative Oncology Group performance status of 0 or 1. All patients in the MCR had either stable disease or a response with platinum-based chemotherapy (∼75% achieved a complete or partial response). Fewer than half (42.5%) of all patients in the MCR received subsequent therapy., Conclusion: Patient demographics, clinical characteristics, and treatment patterns from a MCR of patients with advanced UC that had not progressed following first-line platinum-based chemotherapy appeared similar to data from patients enrolled in JB-100. Future studies should examine whether real-world outcomes are consistent with findings from JB-100., Gov Identifier: NCT02603432., Competing Interests: Disclosure JB has served in consulting or advisory roles for Astellas Pharma, AstraZeneca/MedImmune, Bristol Myers Squibb, Genentech, Novartis, Pfizer, Pierre Fabre, and the healthcare business of Merck KGaA, Darmstadt, Germany; has received travel and accommodation expenses from Ipsen, Merck & Co, Kenilworth, NJ, and Pfizer; has stock and other ownership interests in Rainier Therapeutics; has received honoraria from UpToDate; has received institutional research funding from Millennium, Pfizer, Sanofi, and the healthcare business of Merck KGaA, Darmstadt, Germany; and is an Editorial Board Member of this journal, but was not involved in the peer-review process nor had access to any information regarding its peer review. JC is an employee of Pfizer and holds stock in Bayer, Bristol Myers Squibb, and Pfizer. MP-K is an employee of Pfizer. JCC is an employee and a stockholder of Pfizer. NC is an employee of, has stock and other ownership interests in, and reports honoraria from Pfizer. EE, AH, and SDC are full-time employees of RTI Health Solutions, an independent nonprofit research organization, which was a paid consultant to Pfizer and the healthcare business of Merck KGaA, Darmstadt, Germany in connection with the research for and development of this manuscript. Their compensation is unconnected to the studies on which they work. MK is an employee of the healthcare business of Merck KGaA, Darmstadt, Germany. MA was an employee of RTI Health Solutions, which was a paid consultant to Pfizer and the healthcare business of Merck KGaA, Darmstadt, Germany in connection with the research for and development of this manuscript, when this study was conducted., (Copyright © 2023. Published by Elsevier Inc.)

Background and aim Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare inflammatory disorder associated with the presence of blood and tissue eosinophilia, extravascular granulomas, and asthma. Currently, the burden of EGPA on the patient and the healthcare system is not well characterized. This study aimed to assess the real-world clinical and economic burden of disease in adult patients with EGPA compared with matched patients with asthma without EGPA. Methods This retrospective cohort study used medical, pharmacy, enrolment, and demographic data from a US administrative claims database (PharMetrics Plus). Patients ≥18 years old, with ≥six months of continuous health plan enrolment in the baseline period, and ≥12 months of continuous health plan enrolment in the follow-up period were eligible for this analysis. Patients with EGPA and patients with asthma without EGPA were identified using diagnosis codes and were subsequently matched 1:5 (e.g., one patient with EGPA matched with five patients with asthma, without EGPA) based on baseline characteristics. The primary outcome measure was all-cause healthcare costs; secondary outcomes included healthcare resource utilization, medication usage, and clinical characteristics. Results In the final matched cohorts, there were 7183 patients with EGPA and 35,915 patients with asthma without EGPA. During the follow-up period, mean total all-cause healthcare costs were significantly higher in patients with EGPA than in those with asthma without EGPA (mean {standard deviation}: $44,405 {$82,060} vs $24,487 {$54,691}; p<0.0001). Patients with EGPA had mean total all-cause healthcare costs that were 73.9% greater than those in patients with asthma without EGPA, even after applying a multivariable analysis to adjust for differences in demographic and clinical characteristics. Medication usage was consistently higher in the EGPA population than in the asthma population (excepting short-acting β 2 -agonists). The majority of patients in the EGPA population (83.1%) also experienced ≥one relapse during the study period, with 26.3% of patients in the EGPA population experiencing a major relapse. Conclusions There is a significantly greater economic and clinical burden associated with EGPA compared with asthma without EGPA in adults. These results underscore the unmet need in this patient population for improved disease control strategies that will reduce the burden of EGPA on patients and the healthcare system., Competing Interests: The authors have declared financial relationships, which are detailed in the next section., (Copyright © 2023, Bell et al.)

Health records of patients hospitalized for osteoporotic fracture were analyzed. Prior to the index hospital admission, most patients were not receiving any antiosteoporotic treatment. During the index hospitalization visit, 25.5% of patients received antiosteoporotic treatment. The most common treatment regimens were active vitamin D 3 , bisphosphonates, and teriparatide., Purpose: To examine the real-world treatment patterns and factors associated with receipt of treatment among Japanese patients with osteoporotic fracture., Methods: We retrospectively analyzed health records of patients who were hospitalized for osteoporotic fracture between February 2016 and February 2018 in Japan. The type and duration of treatment with antiosteoporotic medications prescribed during hospital stays and after discharge were examined using descriptive statistics. Demographic and clinical factors (e.g., age, previous diagnoses, Charlson Comorbidity Index scores) associated with osteoporotic treatment were explored using multivariable logistic regression., Results: A total of 112,275 patient medical records were evaluated, including 56,574 records from patients with hip fracture, 26,681 records from patients with vertebrae fracture, and 29,020 patients with non-vertebral non-hip fractures. Prior to the index hospital admission, most patients (91.7%, n = 102,919) were not receiving any antiosteoporotic treatment. For those receiving treatment, active vitamin D 3 (51.1%, n = 4778) and bisphosphonates (47.5%, n = 4441) were the most common. During the index hospitalization visit, 25.5% (n = 28,678) of patients received treatment for their fracture, including active vitamin D 3 (n = 17,074), bisphosphonates (n = 10,007), and teriparatide (n = 4561). Upon discharge, 41.5% (n = 46,536) of patients returned to their home and 34.3% (n = 38,542) of patients were transferred to a different hospital or medical care facility. Variables associated with receipt of treatment at follow-up included older age, previous diagnoses of osteoporosis and fracture, and higher Charlson Comorbidity Index scores., Conclusion: Despite osteoporotic fracture being a major health concern within older Japanese populations, treatment with antiosteoporotic medication regimens remains generally low., (© 2023. The Author(s).)

Aim: To assess real-world ruxolitinib treatment patterns and outcomes in patients diagnosed with primary or secondary myelofibrosis. Materials & methods: Patient medical records were reviewed in six countries. Results: Eligible patients (n = 469) had a mean age of 63.5 years, and most were male (66.5%) with primary myelofibrosis (78.5%). Median duration of ruxolitinib treatment was 13.1 months; 40% of patients initiated treatment at the recommended dose. The Kaplan-Meier estimate of median survival from ruxolitinib initiation was 44.4 months (95% CI, 38.8-50.2 months). Approximately one quarter (23%) of patients continued ruxolitinib after progression. Conclusion: These results suggest an unmet need for more effective treatments for patients with myelofibrosis who failed ruxolitinib.

Introduction: Prophylaxis and treatment of invasive aspergillosis (IA) and mucormycosis (IM) within a real-world US inpatient setting is undocumented since the introduction of isavuconazole. This retrospective medical record review aimed to describe characteristics, triazole use, and outcomes among inpatients across the USA who initiated antifungal monotherapy (AFMT) as prophylaxis or treatment of IA/IM., Methods: A convenience sample of US physicians abstracted data from randomly selected records of hospitalized patients aged ≥ 18 years initiating AFMT (amphotericin B, isavuconazole, voriconazole, or posaconazole) as prophylaxis or treatment of IA/IM between 2013 and 2017. Retrieved data included background characteristics, dosage and duration of AFMT, healthcare resource use, and survival. Characteristics and outcomes were compared (prophylaxis vs treatment) using Fisher's exact and one-way analysis of variance tests where applicable. Exploratory Kaplan-Meier analyses described overall and inpatient survival., Results: Physicians (n = 23) retrieved 124 patient records (43 prophylaxis; 81 treatment). Median duration of first-line AFMT was 14 days (range 1-603 days) and 19 days (range 3-351 days) in the prophylaxis and treatment groups, respectively. One patient received second-line therapy. Median duration of hospitalization was 29 days (range 4-259 days) and 31 days (range 6-980 days) in the prophylaxis and treatment groups, respectively. Admission to intensive care occurred in 14% and 52% of patients in the prophylaxis and treatment groups, respectively. At the time of data retrieval, overall and inpatient survival rates in the prophylaxis group were 88% and 87%, respectively, and in the treatment group were 66% and 76%, respectively., Conclusions: This study documented real-world prophylactic and therapeutic AFMT use for IA/IM and associated outcomes among hospitalized patients in the USA since approval of isavuconazole. IA/IM were associated with lengthy hospital stays commonly requiring intensive care. Prophylactic and therapeutic AFMT dosages and duration generally followed recommendations and switching between agents was rare., Funding: Astellas Pharma Global Development, Inc., Northbrook, IL, USA.

Aims: To assess the effect of duration of hyperglycaemia before basal insulin (BI) initiation on clinical outcomes in type 2 diabetes (T2D)., Materials and Methods: Patients with T2D who initiated BI during 2009-2013, had continuous enrolment for ≥2 years preceding and ≥1 year following BI initiation ("index date"), and had ≥1 glycated haemoglobin (A1C) measure not at target (ie, ≥7.0%) within 6 months preindex date were included in the study. Patients were stratified by preindex-date duration of A1C ≥7.0%. Longitudinal A1C, weight, BMI, and diabetes medication were compared between cohorts for up to 15-month follow-up., Results: Of 37 053 patients who initiated BI, 40.7%, 15.3%, 16.0%, and 28.0%, respectively, had uncontrolled A1C for <6, 6-<12, 12-<18 and 18-24 months preindex date. Baseline characteristics were similar between cohorts. Baseline A1C values were similar across cohorts (9.2%-9.6%). Mean follow-up A1C values were higher with longer preindex-date duration of uncontrolled A1C (8.0 ± 1.7%, 8.2 ± 1.6%, 8.5 ± 1.7%, and 8.6 ± 1.7% for <6, 6-<12, 12-<18, and 18-24 months); attainment of A1C <7.0% worsened with increasing preindex-date duration of A1C ≥7.0% (29.6%, 20.0%, 14.6%, and 11.5% for <6, 6-<12, 12-<18, and 18-24 months)., Conclusions: These data suggest that longer duration of uncontrolled A1C before BI initiation increases the risk of not reaching glycaemic targets. However, target attainment was poor in all cohorts, highlighting inadequate glycaemic control as an important unmet need in US patients with T2D., Competing Interests: EL and AS are employees and shareholders of Sanofi. LB has received grant/research support from AstraZeneca, Janssen Pharmaceuticals, Inc, Lexicon Pharmaceuticals, Inc, Merck & Co., Novo Nordisk, and Sanofi; speaker honoraria from AstraZeneca, Janssen Pharmaceuticals, Inc, Merck & Co., Novo Nordisk, Sanofi; consultant honoraria from AstraZeneca, GSK, Intarcia Therapeutics, Inc, Janssen Pharmaceuticals, Inc, Merck & Co., Inc, Novo Nordisk, Sanofi. BG is an advisory panel/board member for Sanofi, Eli Lilly, Novo Nordisk, Novartis, GSK, MSD, Boehringer Ingelheim, AstraZeneca, Abbott, Medtronic, Roche Diagnostics; a clinical investigator for Sanofi, Eli Lilly, Novo Nordisk, GSK, BMS, AstraZeneca, Medtronic, Abbott, Roche Diagnostics, MSD, Novartis, Janssen, Boehringer Ingelheim; has received research support from Medtronic, Vitalaire, Sanofi, Eli Lilly, Novo Nordisk; the GetGoal‐Duo2 trial (NCT01768559) was sponsored by Sanofi. JM, KD, and MA are employees of RTI Health Solutions, which received funding from Sanofi. DR is a member of advisory boards/speaker during symposia for AstraZeneca, Janssen, Lilly, Novartis, Novo Nordisk, Sanofi.

The continued rise in health care spending has led to an intense debate among policy makers and other health care stakeholders on how to best manage increasing costs, leading to a focus on cost increases with little consideration of the associated change in outcomes. We identified the extent to which increased medical intervention spending on seven prevalent chronic conditions in the US over a twenty-year period has been a good investment. The results provide disease-level cost-effectiveness ratios for comparing changes in medical care spending to changes in health outcomes for patients diagnosed with one of the conditions. This study has two key findings: First, dollars spent on medical care can be a source of high value creation, and such investment should continue. Second, significant variability in value exists across diseases, which highlights the need for disease-specific spending approaches.

Introduction: Treatment guidelines recommend a stepwise approach to glycemia management in patients with type 2 diabetes (T2D), but this may result in uncontrolled glycated hemoglobin A1c (HbA1c) between steps. This retrospective analysis compared clinical and economic outcomes among patients with uncontrolled T2D initiating two oral antidiabetes drugs (OADs), glucagon-like peptide-1 receptor agonists (GLP-1 RAs), or basal insulin in a real-world setting., Methods: Adults with T2D on OAD monotherapy were identified in the MarketScan claims database (2007-2014). Those initiating two OADs (simultaneously or sequentially), GLP-1 RAs, or basal insulin were selected (date of initiation was termed the 'index date'); patients were required to have HbA1c > 7.0% in the 6 months pre-index date. HbA1c was compared from 6 months pre- to 1-year post-index. Annual all-cause healthcare utilization and costs were reported over the 1-year follow-up period., Results: Data for 6054 patients were analyzed (2-OAD, n = 4442; GLP-1 RA, n = 361; basal insulin, n = 1251). Baseline HbA1c was high in all cohorts, but highest in the basal-insulin cohort. Treatment initiation resulted in reductions in HbA1c in all cohorts, which was generally maintained throughout the follow-up period. Average HbA1c reductions from the 6 months pre- to 1 year post-index date were -1.2% for GLP-1 RA, -1.6% for OADs, and -1.8% for basal insulin. HbA1c < 7.0% at 1 year occurred in 32.6%, 47.5%, and 41.1% of patients, respectively. Annual healthcare costs (mean [SD]) were lowest for OAD (US$10,074 [$22,276]) followed by GLP-1 RA (US$14,052 [$23,829]) and basal insulin (US$18,813 [$37,332])., Conclusion: Despite robust HbA1c lowering following treatment initiation, many patients did not achieve HbA1c < 7.0%. Basal insulin, generally prescribed for patients with high baseline HbA1c, was associated with a large reduction in HbA1c and with higher costs. Therapy intensification at an appropriate time could lead to clinical and economic benefits and should be investigated further., Funding: Sanofi U.S., Inc.

Use of multiple prescription medications is common among individuals with chronic obstructive pulmonary disease (COPD) because of coexisting inflammatory-related conditions. Specifically, the use of antidepressants, inhaled corticosteroids (ICSs), and statins may place individuals with COPD at high risk for new-onset diabetes. The objective was to examine the relationship between the use of antidepressants, ICSs, and statins and new-onset diabetes among Medicaid beneficiaries with COPD. This study used a retrospective longitudinal cohort design using multiple years (2005-2008) of Medicaid claims for beneficiaries with newly diagnosed COPD (n = 15,287), who were diabetes free at baseline. National Drug Codes were used to determine the receipt of antidepressants, ICSs, and statins, and International Classification of Diseases, Ninth Revision, Clinical Modification codes were used to define new-onset diabetes (250.x2). Multivariable logistic regression was used to examine the adjusted relationship between medication use and new-onset diabetes. Overall, 6.3% of the study population was diagnosed with new-onset diabetes. After controlling for baseline characteristics, individuals using ICSs (adjusted odds ratio [AOR]: 1.23; 95% confidence interval [CI]: 1.07, 1.47) or statins (AOR: 1.48; 95% CI: 1.27, 1.72) had a greater risk of new-onset diabetes compared to those not given ICSs, statins, or antidepressants. Analyses using combined medication categories revealed that adults using statins in combination with both antidepressants and ICSs, or when combined with ICS, were more likely to have new-onset diabetes. These findings indicate that multiple medication use (ICSs and statins) was associated with increased rates of new-onset diabetes. Further research is warranted to understand this association.

Background: Disease-modifying drugs are not yet available for the management of chronic obstructive pulmonary disease (COPD). HMG-CoA reductase inhibitors (statins) have anti-inflammatory properties and are therefore being considered for use in the management of COPD., Objective: Our objective was to examine the association between statin use and COPD-specific outcomes in a real-world setting., Methods: This was a retrospective longitudinal dynamic cohort study that used Medicaid claims data from multiple years (2005-2008) to identify patients with newly diagnosed COPD. Statin therapy was determined from the prescription drug file using National Drug Codes (NDCs). COPD-specific outcomes such as hospitalizations and emergency room and outpatient visits were identified based on a primary diagnosis of COPD. Multivariable logistic regressions with inverse probability treatment weights (IPTWs) were used to examine the relationship between statin therapy and COPD-specific outcomes., Results: The study included 19,060 Medicaid beneficiaries with newly diagnosed COPD, 30.3% of whom received statins during the baseline period. Adults who received statins had significantly lower rates of COPD-specific hospitalizations (4.7 vs. 5.2%; p < 0.05), emergency room visits (13.4 vs. 15.4%; p < 0.001), and outpatient visits (41.4 vs. 44.7%; p < 0.001) than those who did not receive statin therapy. Even after adjusting for observed selection bias with IPTWs, adults receiving statins were less likely to have COPD-specific hospitalizations [adjusted odds ratio (AOR) 0.76; 95% confidence interval (CI) 0.66-0.87], emergency room visits (AOR 0.81; 95% CI 0.75-0.89), and outpatient visits (AOR 0.86; 95% CI 0.80-0.91) than those not receiving statins., Conclusions: Findings from this study suggest statins have beneficial effects in patients with newly diagnosed COPD and warrant further clinical trial investigation.

Background: A lack of gold standard treatment for autism spectrum disorders (ASD), no clear ASD management guidelines, and lack of evidence-based pharmacological interventions other than aripiprazole and risperidone elevate the risk of off-label prescribing and adverse effects among individuals with ASD, more so among adults., Objective: The aim of this study was to identify and compare the types of prescription drug use, rates of polypharmacy, and characteristics associated with polypharmacy among adults with and without ASD in a retrospective cross-sectional analysis of a three-state Medicaid Analytic eXtract database (2000-2008)., Methods: Adults aged 22-64 years with ASD (ICD9-CM code: 299.xx) were propensity score-matched to 'no ASD' controls by age, sex, and race. General polypharmacy (≥6 unique classes of prescription drugs in a year) and psychotropic polypharmacy (≥3 unique prescription drug classes of psychotropic medications within a 90-day period) were the main study outcomes. Chi-square tests for rates, t tests for mean number of claims, and multivariate logistic regressions for likelihood of prescription drug use and polypharmacy were run., Results: Annually, almost 75% of adults with ASD had >20 prescription drug claims compared with 33% of adults without ASD. Around 85% of adults with ASD used at least one psychotropic drug class compared with 42% of adults without ASD. Highly common psychotropics were antipsychotics (66% ASD vs 20% noASD ), anticonvulsants (59% ASD vs 20% noASD ), and anxiolytics/hypnotics/sedatives (21% ASD vs 11% noASD ). Other than psychotropics, many adults with ASD used medical prescription drugs such as antimicrobials (47%), dermatologic agents (48%), respiratory agents (38%), gastrointestinal agents (31%), alternative medications (25%), antiparkinsonian agents (22.6%), antihyperlipidemics/statins (7.3%), and immunologics (2.0%). Rates of general (48% ASD vs 32% noASD ) and psychotropic polypharmacy (19% ASD vs 6% noASD ) were significantly higher in the ASD group., Conclusion: Prescription drug use and polypharmacy rates among adults with ASD are substantially higher than those in an age-, sex-, and race-matched cohort of adults without ASD. Adults with ASD frequently use therapeutic treatments other than psychotropics. Healthcare providers, who usually report low confidence in treating patients with ASD, should play an active role in constant monitoring of prescription drug use patterns and patient response to interventions. Prescribers and caregivers are encouraged to make decisions after weighing the benefits and risks associated with a pharmacological treatment. Further investigations into the common use of any alternative treatments that can affect a patient's response to core treatments should also be conducted., Competing Interests: Compliance with Ethical Standards Informed consent Informed consent was not required for the current study which did not involve direct patient data collection. The study was exempted from the West Virginia Institutional Review Board. The research proposal for Medicaid database use was reviewed and successfully approved by Centers of Medicare and Medicaid Services under a data user agreement policy. Funding Authors SM and US were partially funded by an IDeA-CTR award from the National Institute of General Medical Sciences, U54GM104942. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or the policy or position of West Virginia University (WVU) or any other affiliated organizations. All authors approved the final manuscript as submitted. Conflict of interests All authors, including RV, SM, US, CS, SP, ND, and MA, declare that there are no conflicts of interest for this research work.

Background: Among elderly patients, the management of type 2 diabetes mellitus (T2DM) is complicated by population heterogeneity and elderly-specific complexities. Few studies have been done to understand treatment intensification among elderly patients failing multiple oral antidiabetic drugs (OADs)., Objective: To examine the association between time to treatment intensification of T2DM and elderly-specific patient complexities., Methods: In this observational, retrospective cohort study, elderly (aged ≥ 65 years) Medicare beneficiaries (n = 16,653) with inadequately controlled T2DM (hemoglobin A1c ≥ 8.0% despite 2 OADs) were included. Based on the consensus statement for diabetes care in elderly patients published by the American Diabetes Association and the American Geriatric Society, elderly-specific patient complexities were defined as the presence or absence of 5 geriatric syndromes: cognitive impairment; depression; falls and fall risk; polypharmacy; and urinary incontinence., Results: Overall, 48.7% of patients received intensified treatment during follow-up, with median time to intensification 18.5 months (95% CI = 17.7-19.3). Median time to treatment intensification was shorter for elderly patients with T2DM with polypharmacy (16.5 months) and falls and fall risk (12.7 months) versus those without polypharmacy (20.4 months) and no fall risk (18.6 months). Elderly patients with urinary incontinence had a longer median time to treatment intensification (18.6 months) versus those without urinary incontinence (14.6 months). The median time to treatment intensification did not significantly differ by the elderly-specific patient complexities that included cognitive impairment and depression. However, after adjusting for demographic, insurance, clinical characteristics, and health care utilization, we found that only polypharmacy was associated with time to treatment intensification (adjusted hazard ratio, 1.10; 95% CI = 1.04-1.15; P = 0.001)., Conclusions: Less than half of elderly patients with inadequately controlled T2DM received treatment intensification. Elderly-specific patient complexities were not associated with time to treatment intensification, emphasizing a positive effect of the integrated health care delivery model. Emerging health care delivery models that target integrated care may be crucial in providing appropriate treatment for elderly T2DM patients with complex conditions.

Background: Multimorbidity is highly prevalent among patients with COPD. The association between multimorbidity and COPD medication management is not well researched. The aim of this study was to examine the association between multimorbidity and COPD medication receipt among Medicaid beneficiaries with newly diagnosed COPD., Methods: A retrospective longitudinal dynamic cohort design was used, and data were extracted from Medicaid Analytic eXtract files from 2005 to 2008. Medicaid beneficiaries with newly diagnosed COPD (N = 19,060) were identified using the International Classification of Diseases, 9th Revision, Clinical Modification, for COPD. This code (for commonly co-occurring conditions with COPD) was used to create a multimorbidity variable. These conditions included anxiety, arthritis, bipolar disorder, cardiovascular diseases, depression, diabetes, hypertension, hyperlipidemia osteoporosis, and schizophrenia. Medicaid beneficiaries with newly diagnosed COPD were categorized as: (1) physical multimorbidity only, (2) psychiatric multimorbidity only, (3) both physical and psychiatric multimorbidity, and (4) no multimorbidity. Receipt of COPD medications (short- or long-acting bronchodilators, inhaled corticosteroids) was identified using National Drug Codes. Bivariate relationships between multimorbidity and COPD medication receipt were tested using the chi-square test of independence. The associations between multimorbidity and COPD medication receipt were analyzed with logistic and multinomial logistic regression analyses., Results: Among Medicaid beneficiaries with newly diagnosed COPD, 81.9% had at least one co-occurring chronic condition. After controlling for subject characteristics, adults with multimorbidity were less likely to receive COPD medications compared with those without any inflammation-related multimorbidity. For example, those with physical multimorbidity were less likely to receive short-acting bronchodilators (adjusted odds ratio [OR] 0.76, 95% CI 0.69-0.83), long-acting bronchodilators (adjusted OR 0.84, 95% CI 0.76-0.92), and inhaled corticosteroids (adjusted OR 0.75, 95% CI 0.68-0.82) compared with those with no inflammation-related multimorbidity., Conclusions: The prevalence of multimorbidity is very high among Medicaid beneficiaries with newly diagnosed COPD. Our findings indicate poor COPD medication management among those with multimorbidity., (Copyright © 2015 by Daedalus Enterprises.)

Objectives: To compare clinical and economic outcomes of early insulin initiation with those of delayed initiation in older adults with type 2 diabetes mellitus (T2DM)., Design: Retrospective cohort study., Setting: Humana Medicare Advantage health insurance plan., Participants: Older (≥65) Medicare beneficiaries with T2DM., Measurements: Subjects were grouped according to number of classes of oral antidiabetes drugs (OADs) they had taken before initiation of insulin: one (early insulin initiators), two, or three or more (delayed insulin initiators). One-year follow-up outcomes included change in glycosylated hemoglobin (HbA1c), percentage of older adults with HbA1c less than 8.0%, hypoglycemic events, and total healthcare costs., Results: Overall, 14,669 individuals were included in the analysis. Baseline and 1-year follow-up HbA1c levels were available for 4,028 (27.5%) individuals. Insulin was initiated early in 32% and delayed in 20%. At follow-up, unadjusted reduction in HbA1c was 0.9±3.7% for the group with one OAD, 0.7±2.4% for those with two, and 0.5±3.6% for those with three or more. Early insulin initiation was associated with significantly greater reduction in HbA1c (0.4%; adjusted P<.001), 30% greater likelihood of achieving HbA1c less than 8.0% (adjusted odds ratio=1.30, 95% confidence interval=1.18-1.43), and no significant differences in total costs or hypoglycemia events (11.5% of early initiators vs 10.2% of delayed initiators; P=.32)., Conclusion: This study suggests beneficial effects of early insulin initiation in older adults with T2DM who do not have adequate glycemic control, without increasing the risk of hypoglycemia or greater total direct healthcare costs., (© 2015, Copyright the Authors Journal compilation © 2015, The American Geriatrics Society.)

Aims: We evaluated the association of combined use of antidepressants and statins and the risk of new-onset diabetes among high-risk adults., Methods: We used a retrospective, observational, longitudinal design among adults (age ≥ 22 years) who were diabetes free at baseline and had reported hypertension or hyperlipidemia or heart disease. We used data were from 2004 to 2009 Medical Expenditure Panel Survey and identified from self-reported diabetes or insulin use. We categorized antidepressants and statins use into four groups: antidepressants only, statins only, combined use of antidepressants and statins (antidepressants-statins), and neither antidepressant nor statins. We conducted chi-square and multivariable logistic regressions to examine the association between use of antidepressants-statins and new-onset diabetes after controlling for demographic and economic characteristics, health-status, access to care, presence of depression, and lifestyle risk factors., Results: In our study sample, 9.3% used antidepressants only, 10.7% used statins only and 2.4% adults reported use of antidepressants-statins. Nearly 2% of the study sample reported new-onset diabetes. In unadjusted analyses, significantly higher proportion of adults using antidepressants-statins (3.2%) reported new-onset diabetes compared to those using neither antidepressants nor statins (1.1%). However, after controlling for all other variables in multivariable regression we did not observe a statistically significant association between use of antidepressants-statins and new-onset diabetes., Conclusions: Our study results do not suggest that use of antidepressants-statins may increase the risk of new-onset diabetes. Future research needs to examine this relationship with specific combinations of these drug classes and using longer follow up periods., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Objective: Breast cancer is the most common cancer among women worldwide. Given the advances in extending survival, the number of recently diagnosed breast cancer patients and longer-term breast cancer survivors is growing. The goals of this study were to better understand (1) perceptions of provider cancer recurrence risk communication, (2) perceived risk of breast cancer recurrence in cancer patients and survivors, and (3) accuracy of perceived risk., Methods: A survey was conducted on women with a prior breast cancer (n=141)., Results: Approximately 40% of women perceived that providers had not talked about their breast cancer recurrence risk; although only 1 person reported not wanting a physician to talk to her about her risk. Women were largely inaccurate in their assessments of risk. Greater worry, living in a rural area, and longer time since diagnosis were associated with greater inaccuracy. Women tended to think about distal recurrence of cancer as often of local recurrence., Conclusions: Perceived risk of breast cancer recurrence was inaccurate, and patients desired more communication about recurrence risk., Practice Implications: Consistent with findings from other studies, greater efforts are needed to improve the communication of cancer recurrence risk to patients. Attention should be paid to those from rural areas and to distal cancer recurrence in women with a previous history of breast cancer., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Background. Individuals with multimorbidity are vulnerable to poor quality of care due to issues related to care coordination. Ambulatory care sensitive hospitalizations (ACSHs) are widely accepted quality indicators because they can be avoided by timely, appropriate, and high-quality outpatient care. Objective. To examine the association between multimorbidity, mental illness, and ACSH. Study Design. We used a longitudinal panel design with data from multiple years (2000-2005) of Medicare Current Beneficiary Survey. Individuals were categorized into three groups: (1) multimorbidity with mental illness (MM/MI); (2) MM/no MI; (3) no MM. Multivariable logistic regressions were used to analyze the association between multimorbidity and ACSH. Results. Any ACSH rates varied from 10.8% in MM/MI group to 8.8% in MM/No MI group. Likelihood of any ACSH was higher among beneficiaries with MM/MI (AOR = 1.62; 95% CI = 1.14, 2.30) and MM (AOR = 1.54; 95% CI = 1.12, 2.11) compared to beneficiaries without multimorbidity. There was no statistically significant difference in likelihood of ACSH between MM/MI and MM/No MI groups. Conclusion. Multimorbidity (with or without MI) had an independent and significant association with any ACSH. However, presence of mental illness alone was not associated with poor quality of care as measured by ACSH.

Objective: The objective of the study is to examine the association between ambulatory care sensitive hospitalizations (ACSH) and dual Medicare/Veteran Health Administration use., Participants: A nationally representative sample of Medicare beneficiaries, who participated in the Medicare Current Beneficiary Survey (MCBS)., Design/measurements: Cross-sectional analyses (N = 44,988) of linked fee-for-service Medicare claims and survey data from multiple years of the MCBS (2001-2005). Any ACSH and specific types of ACSH were measured using the list of prevention quality indicators developed by the Agency for Healthcare Research and Quality. Among veterans, dual Medicare/VHA use was defined as having inpatient or outpatient visits paid by VHA and consisted of three categories: 1) predominant-VHA use; 2) some VHA use and no VHA use. Unadjusted group differences in any ACSH were tested using chi-square tests. Logistic regressions were used to analyze the association between dual Medicare/VHA use and ACSH after controlling for demographic, socio-economic status, health status, functional status, smoking status and obesity. All analyses accounted for the complex design of the MCBS., Results: Among inpatient users, 10.1% had ACSH events for acute conditions and 15.8% for chronic conditions. Among all survey respondents, 5% had any ACSH event. Among predominant-VHA users the rate was 4.9% and among veterans with some VHA use it was 3.7%. In bivariate and multivariate analyses, dual Medicare/VHA use was not significantly associated with any ACSH., Conclusion: In a representative sample of Medicare beneficiaries, despite low income and health status, veterans with dual Medicare/VHA use were as likely as veterans without dual use to have any ACSH, perhaps due to expanded healthcare access and emphasis on primary care in the VHA system.