Systematic review and network meta-analysis comparing the efficacy of fezolinetant with hormone and nonhormone therapies for treatment of vasomotor symptoms due to menopause.

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.

Retrospective Analysis of the Burden of Illness of Eosinophilic Granulomatosis With Polyangiitis (EGPA) Versus Asthma in Commercially Insured US Patients.

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 ß2-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.

Evaluating Real-World Characteristics of Patients With Advanced Urothelial Carcinoma Eligible for Avelumab Maintenance Therapy: A Multicountry Retrospective Medical Chart Review.

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.

A real-world study of treatment patterns among patients with osteoporotic fracture: analysis of a Japanese hospital database.

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 D3, 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 D3 (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 D3 (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.

Real-world clinical outcomes of patients with myelofibrosis treated with ruxolitinib: a medical record review.

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.

An evaluation of costs associated with overall organ damage in patients with systemic lupus erythematosus in the United States.

INTRODUCTION: Approximately 33-50% of patients with systemic lupus erythematosus (SLE) develop organ damage within 5 years of diagnosis. Real-world studies that capture the healthcare resource utilization (HCRU) and costs associated with SLE-related organ damage are limited. The aim of this study was to evaluate HCRU and costs associated with organ damage in patients with SLE in the USA. METHODS: This retrospective study (GSK study 208380) used the PharMetrics Plus administrative claims database from 1 January 2008 to 30 June 2019. Patients with SLE and organ damage were identified using International Classification of Diseases (ICD)-9/10 codes derived from the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index. The first observed diagnosis of organ damage was designated as the index date. Selection criteria included: ≥18 years of age; ≥1 inpatient or ≥2 outpatient claims for SLE (≥30 days apart before the index date; ICD-9: 710.0 or ICD-10: M32, excluding M32.0); ≥1 inpatient or ≥3 outpatient claims for organ damage within 6 months for the same organ system code; continuous enrollment of 12 months both pre- and post-index date. The proportion of patients with new organ damage, disease severity, SLE flares, SLE-related medication patterns, HCRU and all-cause costs (2018 US$) were assessed 12 months pre- and post-index date. RESULTS: Of the 360,803 patients with a diagnosis of SLE, 8952 patients met the inclusion criteria for the presence of new organ damage. Mean (standard deviation (SD)) age was 46.4 (12.2) years and 92% of patients were female. The most common sites of organ damage were neuropsychiatric (22.0%), ocular (12.9%), and cardiovascular (11.4%). Disease severity and proportion of moderate/severe flare episodes significantly increased from pre- to post-index date (p < 0.0001). Overall, SLE-related medication patterns were similar pre- versus post-index date. Inpatient, emergency department and outpatient claims increased from pre- to post-index date and mean (SD) all-cause costs were 71% higher post- versus pre-index date ($26,998 [57,982] vs $15,746 [29,637], respectively). CONCLUSIONS: The economic impact associated with organ damage in patients with SLE is profound and reducing or preventing organ damage will be pivotal in alleviating the burden for patients and healthcare providers.

Use of Antifungals and Outcomes Among Inpatients at Risk of Invasive Aspergillosis or Mucormycosis in the USA: A Retrospective Cohort Study.

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.

Clinical implications of prolonged hyperglycaemia before basal insulin initiation in type 2 diabetes patients: An electronic medical record database analysis.

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.

What's Been The Bang For The Buck? Cost-Effectiveness Of Health Care Spending Across Selected Conditions In The US.

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.

Impact of antiepileptic-drug treatment burden on health-care-resource utilization and costs.

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<0.0001). Increase in dosing frequency was associated with greater total HCRU and higher costs, but only patients with twice-daily dosing had significantly higher epilepsy-related costs. CONCLUSION: Findings from this study suggest that increased treatment burden is associated with greater HCRU and higher overall and epilepsy-related costs. Reducing treatment burden via selection of AED therapy with reduced pill numbers and dosing frequency should be considered to improve health and economic outcomes.

Treatment Intensification in Type 2 Diabetes: A Real-World Study of 2-OAD Regimens, GLP-1 RAs, or Basal Insulin.

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.

Evaluation of comorbidities and health care resource use among patients with highly active neuromyelitis optica.

BACKGROUND: Neuromyelitis optica (NMO) is characterized by unpredictable attacks on the optic nerves and spinal cord, causing accumulations of neurological disability that may lead to blindness and paralysis. We examined comorbidities and health care use among patients with highly active NMO, defined as at least two relapses within 12months of the patient's first NMO encounter in the database. METHODS: This retrospective study of a US administrative claims database compared patients with highly active NMO to matched individuals without NMO. All outcomes, including Charlson Comorbidity Index (CCI) score, hospitalizations, and emergency department visits, were measured over the 12-month period following the patient's first NMO encounter in the database. RESULTS: A total of 1349 patients with NMO were identified. Of these, 134 had highly active NMO (80% female, mean age 45.6years) and were matched to 670 non-NMO controls. Patients with highly active NMO had significantly greater comorbidity burden than non-NMO controls (mean CCI score: 4.1 versus 0.6; P<0.0001) and greater proportions of hospitalization (53.7% versus 4.0%; P<0.0001) and emergency department visits (60.5% versus 9.7%; P<0.0001). CONCLUSIONS: High occurrence of several acute and chronic conditions and extensive health care use highlight the significant medical burden among patients with highly active NMO.

Concomitant Medication Use and New-Onset Diabetes Among Medicaid Beneficiaries with Chronic Obstructive Pulmonary Disease.

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.

Association Between Statin Medications and COPD-Specific Outcomes: A Real-World Observational Study.

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.

Prescription Drug Use and Polypharmacy Among Medicaid-Enrolled Adults with Autism: A Retrospective Cross-Sectional Analysis.

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.

A Real-World Observational Study of Time to Treatment Intensification Among Elderly Patients with Inadequately Controlled Type 2 Diabetes Mellitus.

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.

Multimorbidity and COPD Medication Receipt Among Medicaid Beneficiaries With Newly Diagnosed COPD.

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.

A real-world study of the effect of timing of insulin initiation on outcomes in older medicare beneficiaries with type 2 diabetes mellitus.

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.

Use of antidepressants and statins and short-term risk of new-onset diabetes among high risk adults.

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.

Explaining the increased health care expenditures associated with gastroesophageal reflux disease among elderly Medicare beneficiaries with chronic obstructive pulmonary disease: a cost-decomposition analysis.

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<0.001]) expenditures than did those with COPD/no GERD. Ordinary least squares regression revealed that individuals with COPD/GERD had 36.3% (P<0.001) higher expenditures than did those with COPD/no GERD. Overall, 30.9% to 43.6% of the differences in average health care expenditures were explained by differences in predisposing characteristics, enabling resources, need variables, personal health care practices, and external environment factors between the two groups. Need factors explained up to 41% of the differences in average health care expenditures between the two groups. CONCLUSION: Among elderly Medicare beneficiaries with COPD, the presence of GERD was associated with higher expenditures. Need factors primarily contributed to the differences in average health care expenditures, suggesting that the comanagement of chronic conditions may reduce excess health care expenditures associated with GERD.