Dynamic nitric oxide/drug codelivery system based on polyrotaxane architecture for effective treatment of Candida albicans infection.

The low permeability of antifungal agents to fungal biofilms, which allows the continued survival of the fungus inside, is a key issue that makes fungal infections difficult to cure. Inspired by the unique dynamic molecule motion properties of the polyrotaxane (PR) nanomedicine, herein, a dynamic delivery system Clo@mPRP/NONOate was fabricated by co-loading nitric oxide (NO) and the antifungal drug clotrimazole (Clo) onto the α-cyclodextrin (α-CD) PR modified mesoporous polydopamine (mPDA) nanoparticles, in which pentaethylenehexamine (PEHA) was grafted to α-CDs. The cationic α-CDs endowed this dynamic NO/Clo codelivery system with the ability to effectively attach to fungal biofilms through electrostatic interaction, while the introduction of PRs with flexible molecule motion (slide and rotation of CDs) enhanced the permeability of nanoparticles to biofilms. Meanwhile, NO could effectively inhibit the formation of fungal hyphae, showing an dissipating effect on mature biofilms, and could be further combined with Clo to completely eradicate fungi inside the biofilms. In addition, the dynamic system Clo@mPRP/NONOate could efficiently and synergistically eliminate planktonic Candida albicans (C. albicans) in a safe and no toxic side effect manner, and effectively cured C. albicans-induced vaginal infection in mice. Therefore, this dynamic NO/Clo codelivery system provided an effective solution to the clinical treatment of C. albicans-induced vaginal infection, and the application prospect could even be extended to other microbial infectious diseases. STATEMENT OF SIGNIFICANCE: A dynamic codelivery system based on cationized cyclodextrin polyrotaxane combining nitric oxide and antifungal drugs clotrimazole was prepared to deal with the issue of clinical fungal biofilm infection. This dynamic codelivery system could be attached to the Candida albicans biofilms and penetrate into biofilm via flexible molecular mobility to effectively eradicate the fungi. This dynamic codelivery system could synergistically and efficiently eliminate planktonic-state Candida albicans, but did not show significant cytotoxicity to normal somatic cells.

Dynamic Landscapes of tRNA Transcriptomes and Translatomes in Diverse Mouse Tissues.

Although the function of tRNA in the translational process is well established, it remains controversial whether tRNA abundance is tightly associated with translational efficiency (TE) in mammals. Moreover, how critically the expression of tRNAs contributes to the establishment of tissue-specific proteomes in mammals has not been well addressed. Here, we measured both tRNA expression using demethylase-tRNA sequencing (DM-tRNA-seq) and TE of mRNAs using ribosome-tagging sequencing (RiboTag-seq) in the brain, heart, and testis of mice. Remarkable variation in the expression of tRNA isodecoders was observed among different tissues. When the statistical effect of isodecoder-grouping on reducing variations is considered through permutating the anticodons, we observed an expected reduction in the variation of anticodon expression across all samples, an unexpected smaller variation of anticodon usage bias, and an unexpected larger variation of tRNA isotype expression at amino acid level. Regardless of whether or not they share the same anticodons, the isodecoders encoding the same amino acids are co-expressed across different tissues. Based on the expression of tRNAs and the TE of mRNAs, we find that the tRNA adaptation index (tAI) and TE are significantly correlated in the same tissues but not between tissues; and tRNA expression and the amino acid composition of translating peptides are positively correlated in the same tissues but not between tissues. We therefore hypothesize that the tissue-specific expression of tRNAs might be due to post-transcriptional mechanisms. This study provides a resource for tRNA and translation studies, as well as novel insights into the dynamics of tRNAs and their roles in translational regulation.

Effect of compliance with GOLD treatment recommendations on COPD health care resource utilization, cost, and exacerbations among patients with COPD on maintenance therapy.

BACKGROUND: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) report for the management of chronic obstructive pulmonary disease (COPD) focuses on reducing existing symptoms, decreasing the risk of future exacerbations, and improving health status by recommending specific drug therapy based on exacerbation risk and symptoms. However, disparities exist between evidence-based recommendations and clinical practice. Research that quantifies the real-world effect of COPD regimen alignment with the GOLD recommendations on clinical and economic outcomes is needed. OBJECTIVE: To compare COPD-related health care resource utilization (HRU) and costs, as well as exacerbation rates, among patients with COPD on maintenance therapy based on 2017 GOLD treatment recommendation compliance status per GOLD ABCD risk group classification in a U.S. commercially insured/Medicare Advantage population. METHODS: This retrospective cohort study utilized administrative claims data in the HealthCore Integrated Research Database. The COPD population was identified using a previously validated claims-based predictive model. Among this population, patients with ≥ 1 claim for a COPD maintenance medication (earliest maintenance fill-date = index date) between January 1, 2014, and March 31, 2017, were identified. Patients were required to be aged ≥ 40 years, have ≥ 12 months of pre-index and ≥ 30 days of post-index health plan enrollment, with no diagnosis for asthma, cystic fibrosis, and/or lung cancer at any time from January 1, 2013, to March 31, 2018. Patients were categorized into exacerbation risk/symptomatology groups according to the 2017 GOLD ABCD assessment recommendations and were then classified into treatment-compliance status based on their maintenance therapy. Multivariable analyses were conducted to examine post-index COPD-related HRU, costs, and exacerbations by compliance status. RESULTS: The primary analytical study sample included 38,382 patients in the GOLD A/B group and 6,525 in the GOLD C/D group. Patients were further categorized into GOLD A (n = 19,345), B (n = 19,037), C (n = 1,865), and D (n = 4,670). GOLD-compliant regimens were observed in 32.9% of patients in the GOLD A/B group and in 58.9% of patients in the GOLD C/D group. Inhaled corticosteroid-containing regimens were the most commonly observed noncompliant regimen. Patients on compliant regimens had significantly fewer COPD-related inpatient and emergency department visits and therefore had significantly lower COPD-related medical costs in both the GOLD A/B and C/D cohorts. Similar results were observed for individual GOLD cohorts B, C, and D. These savings were offset by increased pharmacy expenditures. Being on GOLD guideline-compliant regimens significantly reduced the risk of exacerbation by 8% (hazard ratio [HR] = 0.92; P < 0.0001) in the GOLD A/B cohort and by 12% (HR = 0.88; P = 0.0005) in the GOLD C/D cohort, and was also associated with a significantly reduced exacerbation rate in the GOLD A/B (rate ratio [RR] = 0.93; P < 0.0001) and GOLD C/D (RR = 0.93; P = 0.0129) groups. CONCLUSIONS: This study suggests a continuing trend of high prevalence of suboptimal prescriber compliance to GOLD treatment recommendations. Treatment regimens compliant with GOLD recommendations were associated with improvement in exacerbations, reduced COPD-related HRU, and COPD-related medical cost offsets. DISCLOSURES: This study was funded by Boehringer Ingelheim Pharmaceuticals, Inc. (BIPI). BIPI was given the opportunity to review the manuscript for medical and scientific accuracy as well as intellectual property considerations. Palli and Shaikh are employees of BIPI. Willey is an employee of HealthCore, which was contracted by BIPI to conduct this study. Zhou was an employee of HealthCore at the time of study execution. Data were presented in part during an AMCP webinar (recording not made public) held in lieu of the Spring 2020 AMCP conference, which was canceled due to the COVID-19 pandemic.

Effect of V-Go Versus Multiple Daily Injections on Glycemic Control, Insulin Use, and Diabetes Medication Costs Among Individuals with Type 2 Diabetes Mellitus.

BACKGROUND: Coping with discomfort and the uncertainties of daily adjustments are prominent challenges confronting individuals with type 2 diabetes mellitus (T2DM) who require multiple daily injections (MDI) of insulin. For this growing population, wearable, disposable devices capable of delivering consistent and sustained doses of basal-bolus therapy may help to alleviate concerns and improve outcomes. However, studies on the comparative effectiveness of new, innovative delivery systems versus MDI on insulin requirements, glycemic control, and health care costs are sparse. OBJECTIVE: To examine glycemic control, insulin use, and diabetes medication costs for users of the V-Go Wearable Insulin Delivery device compared with MDI insulin therapy among individuals with T2DM in a commercially insured population in the United States. METHODS: This retrospective cohort study queried administrative claims data from the HealthCore Integrated Research Database from July 1, 2011, through July 31, 2017. Cohorts included individuals with T2DM aged 21-80 years either newly initiating V-Go or using MDI for basal/bolus insulin. The date of earliest claim for V-Go prescription fill or for bolus insulin was defined as the index date, depending on the cohort. Previous insulin therapy was required in both cohorts. Baseline hemoglobin A1c (A1c) values were identified during the 6 months before and 15 days after the index date; results closest to 12 months after the index date were selected as follow-up. Insulin use and diabetes medication cost data were examined during the 6 months baseline and the second half of the 1-year follow-up. V-Go and MDI users were 1:1 matched on baseline insulin exposure, A1c level, and other characteristics of interest. Univariate and multivariate tests were used to compare follow-up outcomes. RESULTS: Matched cohorts included 118 well-balanced pairs (mean age: 56 years; mean baseline A1c: 9.2%). During follow-up, both cohorts experienced improvements in glycemic control relative to baseline (% with A1c ≤ 9%, baseline/follow-up: V-Go 49/69, P < 0.001; MDI 50/60, P = 0.046). With similar baseline insulin prescription fills and diabetes medication costs, V-Go users required fewer insulin prescription fills (mean change: -0.8 vs. +1.8 fills, P < 0.001; -17% vs. +38%); had a smaller increase in diabetes medication costs (mean change in 2016 USD: $341 vs. $1,628, P = 0.012; +10% vs. +47%); and a decrease in insulin total daily dose (mean change in insulin units per day: -29.2 vs. +5.8, P < 0.001; -21% vs. +4%), compared with MDI users, during the last 6 months of follow-up. CONCLUSIONS: This study was the first to evaluate clinical and economic outcomes associated with the use of V-Go for up to a 1-year follow-up period. Relative to MDI users, V-Go users had similar glycemic control but lower insulin use and lower diabetes medication costs during follow-up. V-Go therapy may provide an opportunity to improve quality measures more cost-effectively in people with T2DM who require basal-bolus therapy. DISCLOSURES: This study was funded by Valeritas. Nguyen is an employee of Valeritas. Zhou, Grabner, Barron, and Quimbo are employees of HealthCore, which received funding for this study from Valeritas. Raval was an employee of HealthCore at the time the study was conducted. Partial findings from this study were presented at the International Society of Pharmacoeconomics and Outcomes Research 23rd Annual International Meeting; May 19-23, 2018; Baltimore, MD; and the 54th European Association for the Study of Diabetes Annual Meeting; October 1-5, 2018; Berlin, Germany.

Effect of V-Go Versus Multiple Daily Injections on Glycemic Control, Insulin Use, and Diabetes Medication Costs Among Individuals with Type 2 Diabetes Mellitus.

BACKGROUND: Coping with discomfort and the uncertainties of daily adjustments are prominent challenges confronting individuals with type 2 diabetes mellitus (T2DM) who require multiple daily injections (MDI) of insulin. For this growing population, wearable, disposable devices capable of delivering consistent and sustained doses of basal-bolus therapy may help to alleviate concerns and improve outcomes. However, studies on the comparative effectiveness of new, innovative delivery systems versus MDI on insulin requirements, glycemic control, and health care costs are sparse. OBJECTIVE: To examine glycemic control, insulin use, and diabetes medication costs for users of the V-Go Wearable Insulin Delivery device compared with MDI insulin therapy among individuals with T2DM in a commercially insured population in the United States. METHODS: This retrospective cohort study queried administrative claims data from the HealthCore Integrated Research Database from July 1, 2011, through July 31, 2017. Cohorts included individuals with T2DM aged 21-80 years either newly initiating V-Go or using MDI for basal/bolus insulin. The date of earliest claim for V-Go prescription fill or for bolus insulin was defined as the index date, depending on the cohort. Previous insulin therapy was required in both cohorts. Baseline hemoglobin A1c (A1c) values were identified during the 6 months before and 15 days after the index date; results closest to 12 months after the index date were selected as follow-up. Insulin use and diabetes medication cost data were examined during the 6 months baseline and the second half of the 1-year follow-up. V-Go and MDI users were 1:1 matched on baseline insulin exposure, A1c level, and other characteristics of interest. Univariate and multivariate tests were used to compare follow-up outcomes. RESULTS: Matched cohorts included 118 well-balanced pairs (mean age: 56 years; mean baseline A1c: 9.2%). During follow-up, both cohorts experienced improvements in glycemic control relative to baseline (% with A1c ≤ 9%, baseline/follow-up: V-Go 49/69, P < 0.001; MDI 50/60, P = 0.046). With similar baseline insulin prescription fills and diabetes medication costs, V-Go users required fewer insulin prescription fills (mean change: -0.8 vs. +1.8 fills, P < 0.001; -17% vs. +38%); had a smaller increase in diabetes medication costs (mean change in 2016 USD: $341 vs. $1,628, P = 0.012; +10% vs. +47%); and a decrease in insulin total daily dose (mean change in insulin units per day: -29.2 vs. +5.8, P < 0.001; -21% vs. +4%), compared with MDI users, during the last 6 months of follow-up. CONCLUSIONS: This study was the first to evaluate clinical and economic outcomes associated with the use of V-Go for up to a 1-year follow-up period. Relative to MDI users, V-Go users had similar glycemic control but lower insulin use and lower diabetes medication costs during follow-up. V-Go therapy may provide an opportunity to improve quality measures more cost-effectively in people with T2DM who require basal-bolus therapy. DISCLOSURES: This study was funded by Valeritas. Nguyen is an employee of Valeritas. Zhou, Grabner, Barron, and Quimbo are employees of HealthCore, which received funding for this study from Valeritas. Raval was an employee of HealthCore at the time the study was conducted. Partial findings from this study were presented at the International Society of Pharmacoeconomics and Outcomes Research 23rd Annual International Meeting; May 19-23, 2018; Baltimore, MD; and the 54th European Association for the Study of Diabetes Annual Meeting; October 1-5, 2018; Berlin, Germany.

Prevalence and burden of illness of treated hemolytic neonatal hyperbilirubinemia in a privately insured population in the United States.

BACKGROUND: Prevalence of hemolytic neonatal hyperbilirubinemia (NHB) is not well characterized, and economic burden at the population level is poorly understood. This study evaluated the prevalence, clinical characteristics, and economic burden of hemolytic NHB newborns receiving treatment in U.S. real-world settings. METHODS: This cohort study used administrative claims from 01/01/2011 to 08/31/2017. The treated cohort had hemolytic NHB diagnosis and received phototherapy, intravenous immunoglobulin, and/or exchange transfusions. They were matched with non-NHB newborns who had neither NHB nor related treatments on the following: delivery hospital/area, gender, delivery route, estimated gestational age (GA), health plan eligibility, and closest date of birth within 5 years. Inferential statistics were reported. RESULTS: The annual NHB prevalence was 29.6 to 31.7%; hemolytic NHB, 1.8 to 2.4%; treated hemolytic NHB, 0.46 to 0.55%, between 2011 and 2016. The matched analysis included 1373 pairs ≥35 weeks GA. The treated hemolytic NHB cohort had significantly more birth trauma and hemorrhage (4.5% vs. 2.4%, p = 0.003), vacuum extractor affecting newborn (1.9% vs. 0.8%, p = 0.014), and polycythemia neonatorum (0.8% vs. 0%, p = 0.001) than the matched non-NHB cohort. The treated hemolytic NHB cohort also had significantly longer mean birth hospital stays (4.5 vs. 3.0 days, p < 0.001), higher level 2-4 neonatal intensive care admissions (15.7% vs. 2.4, 15.9% vs. 2.8 and 10.6% vs. 2.5%, respectively, all p < 0.001) and higher 30-day readmission (8.7% vs. 1.7%, p < 0.001). One-month and one-year average total costs of care were significantly higher for the treated hemolytic NHB cohort vs. the matched non-NHB cohort, $14,405 vs. $5527 (p < 0.001) and $21,556 vs. $12,986 (p < 0.001), respectively. The average costs for 30-day readmission among newborns who readmitted were $13,593 for the treated hemolytic NHB cohort and $3638 for the matched non-NHB cohort, p < 0.001. The authors extrapolated GA-adjusted prevalence of treated hemolytic NHB in the U.S. newborn population ≥ 35 weeks GA and estimated an incremental healthcare expenditure of $177.0 million during the first month after birth in 2016. CONCLUSIONS: The prevalence of treated hemolytic NHB was 4.6-5.5 patients per 1000 newborns. This high-risk hemolytic NHB imposed substantial burdens of healthcare resource utilization and incremental costs on newborns, their caregivers, and the healthcare system.

Utilization of High-Cost Interventions for Targeted Clinical Conditions During the Early Stages of ACO Development in a Commercially Insured Population.

This study compared utilization patterns of high-cost services and medications for patients receiving care from Accountable Care Organization (ACO)-participating physicians and those receiving care from non-ACO physicians during the initial phases of ACO development in a commercially insured environment. Patients ≥18 years (≥40 years for chronic obstructive pulmonary disease [COPD]) with prevalent rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, type 2 diabetes, COPD, or chronic low back pain between January 1, 2012, and August 31, 2014 were identified in the HealthCore Integrated Research DatabaseSM. Patients were assigned to the ACO cohort if their primary treating physician was contracted to the health plan through an ACO agreement. Each clinical condition was stratified for severity of illness. Cohort utilization patterns were compared for the 12-month period following the index encounter. The primary outcome measures show that there was no statistically significant utilization difference between the ACO and non-ACO cohorts for 90% of the 82 comparisons made. It is expected that some measures will achieve significant difference simply because of having this many comparisons, but no clear pattern was identified. This study did not observe statistically significant differences in utilization of high-cost services and medications between ACO and non-ACO cohorts with limited experience in the ACO model. Future analyses with longer study durations, at later stages of ACO development, tracking a more granular level of physician organizational structure, and with designs that integrate clinical and administrative data are essential to better understand the impact of payment innovation strategies using an ACO structure.

Commercial Claims-Based Comparison of Survival and Toxic Effects of Definitive Radiotherapy vs Primary Surgery in Patients With Oropharyngeal Squamous Cell Carcinoma.

Importance: Definitive radiotherapy (RT) and primary surgery (PS) are considered to be equally viable local therapy modalities for oropharyngeal squamous cell carcinoma (OPSCC). The comparative effectiveness of these therapies is often debated, and treatment decisions are based on a paucity of comparative data. Objective: To examine the differences in overall survival and key toxic effects in patients with OPSCC treated with RT and PS. Design, Setting, and Participants: This retrospective cohort analysis used the HealthCore Integrated Research Database to identify 884 patients diagnosed with OPSCC from January 1, 2007, to December 31, 2014. Patients were categorized as receiving definitive RT (with or without chemotherapy) or PS (with or without adjuvant RT or chemoradiotherapy). Administrative claims data were linked with state cancer registries from California, Connecticut, Georgia, Kentucky, New York, and Ohio. Data analysis was performed from February 29, 2016, to February 6, 2018. Exposures: Definitive RT or PS. Main Outcomes and Measures: Overall survival was analyzed using Cox proportional hazards regression. Risks of gastrostomy dependence, esophageal stricture, and osteoradionecrosis were determined through claims and analyzed using logistic regression. Results: A total of 884 patients (608 [68.8%] in the RT group and 276 [31.2%] in the PS group; mean [SD] age, 61.5 [10.7] years; 727 [82.2%] male; 842 [95.3%] white) were included in this study. The 3-year overall survival was 76% among patients treated with RT and 81% among patients treated with PS (hazard ratio, 0.76; 95% CI, 0.54-1.01). On multivariable analysis, increasing age, female sex, and low income were associated with inferior survival; treatment type was not. Patients treated with RT were more likely to have gastrostomy dependence within the first year (391 [64.3%] vs 127 [46.0%]; adjusted OR, 0.57; 95% CI, 0.42-0.77). After treating chemotherapy as an effect modifier, there was no difference between modalities. Treatment type was not associated with esophageal stricture or osteoradionecrosis risk. Mean costs were approximately $100 000 for payers and $5000 for patients, with no adjusted differences between RT and PS. Conclusions and Relevance: This study suggests that RT and PS are equally viable treatment options for OPSCC; therefore, local therapy decisions may be individualized to each patient. However, the frequent addition of chemotherapy was associated with increased gastrostomy dependence among patients undergoing RT, which may be relevant in clinical decision making.

Initiation Patterns of Statins in the 2 Years After Release of the 2013 American College of Cardiology/American Heart Association (ACC/AHA) Cholesterol Management Guideline in a Large US Health Plan.

BACKGROUND: The purpose of this study was to characterize changes in statin utilization patterns in patients newly initiated on therapy in the 2 years following the release of the 2013 American College of Cardiology/American Heart Association (ACC/AHA) cholesterol management guideline in a large US health plan population. METHODS AND RESULTS: This retrospective, observational study used administrative medical and pharmacy claims data to identify patients newly initiated on statin therapy over 4 quarters prior to and 8 quarters following the release of the guideline (average N/quarter=3596). Patients were divided into the 4 statin benefit groups (SBGs) based on risk factors and laboratory lipid levels as defined in the guideline: SBG1 (with atherosclerotic cardiovascular disease [ASCVD]; N=1046/quarter), SBG2 (without ASCVD, with low-density lipoprotein cholesterol ≥190 mg/dL; N=454/quarter), SBG3 (without ASCVD, aged 40-75 years, with diabetes mellitus, low-density lipoprotein cholesterol 70-189 mg/dL; N=1391/quarter), SBG4 (no ASCVD or diabetes mellitus, age 40-75 years, low-density lipoprotein cholesterol 70-189 mg/dL, estimated 10-year ASCVD risk of ≥7.5%; N=705/quarter). Demographic variables, statin utilization patterns, lipid levels, and comorbidities were analyzed for pre- and postguideline periods. Postguideline, gradually increased high-intensity statin initiation occurred in SBG1, SBG2, and in SBG3 patients with 10-year ASCVD risk ≥7.5%. Moderate- to high-intensity statin initiation gradually increased among SBG4 patients. Recommended-intensity statin choice changed to a greater degree among patients treated by specialty care physicians. Regarding sex, target-intensity statin initiation was lower in women in all groups before and after guideline release. CONCLUSIONS: Prescriber implementation of the guideline recommendations has gradually increased, with the most marked change in the increased initiation of high-intensity statins in patients with ASCVD and in those treated by a specialist.

Comparative effectiveness of budesonide/formoterol combination and tiotropium bromide among COPD patients new to these controller treatments.

BACKGROUND: Inhaled corticosteroid/long-acting ß2-agonist combinations and/or long-acting muscarinic antagonists are recommended first-line therapies for preventing chronic obstructive pulmonary disease (COPD) exacerbation. Comparative effectiveness of budesonide/formoterol combination (BFC, an inhaled corticosteroid/long-acting ß2-agonist combination) vs tiotropium (long-acting muscarinic antagonist) in the US has not yet been studied. METHODS: Using US claims data from the HealthCore Integrated Research Environment, COPD patients (with or without comorbid asthma) ≥40 years old initiating BFC or tiotropium between March 1, 2009 and February 28, 2012 and at risk for exacerbation were identified and followed for 12 months. Patients were propensity score matched on demographics and COPD disease severity indicators. The primary outcome was time to first COPD exacerbation. Secondary outcomes included COPD exacerbation rate, health care resource utilization, and costs. RESULTS: The Cox proportional hazards model for time to first exacerbation yielded a hazard ratio (HR) of 0.78 (95% CI =[0.70, 0.87], P<0.001), indicating a 22% reduction in risk of COPD exacerbation associated with initiation of BFC versus tiotropium. A post hoc sensitivity analysis found similar effects in those who had a prior asthma diagnosis (HR =0.72 [0.61, 0.86]) and those who did not (HR =0.83 [0.72, 0.96]). BFC initiation was associated with lower COPD-related health care resource utilization and costs ($4,084 per patient-year compared with $5,656 for tiotropium patients, P<0.001). CONCLUSION: In COPD patients new to controller therapies, initiating treatment with BFC was associated with improvements in health and economic outcomes compared with tiotropium.

Asthma and Chronic Obstructive Pulmonary Disease Overlap Syndrome: Doubled Costs Compared with Patients with Asthma Alone.

BACKGROUND: Patients with asthma and chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) have more rapid disease progression and more exacerbations than do those with either condition alone. Little research has been performed, however, in these patients. OBJECTIVE: The objective was to summarize the health care utilization, costs, and comorbidities of patients with uncontrolled asthma and patients with ACOS. METHODS: This retrospective analysis used medical and pharmacy claims from large commercial health plans. The study included patients 6 years or older with a diagnosis of asthma and one or more asthma exacerbation (index event). Patients were classified as having asthma alone or ACOS, and the two groups were matched for age, sex, region, index year, index month, and health plan type. Outcomes included rates of comorbid disease, health care utilization, and costs during the 12 months before and after the index exacerbation. RESULTS: Among the matched patients with asthma (6,505 ACOS; 26,060 without COPD), mean annual all-cause health care costs were twice as high as for patients with ACOS ($22,393 vs. $11,716; P < 0.0001). Asthma-related costs, representing 29% of total costs, were nearly twice as high among patients with ACOS ($6,319 vs. 3,356; P < 0.0001). Cost differences were driven by large differences in the proportions of patients with an inpatient hospitalization (34.0% vs. 14.6%; P < 0.0001) or emergency department visit (29.6% vs. 19.9%; P < 0.0001). Nearly all prespecified comorbid conditions were more prevalent in the ACOS group. CONCLUSIONS: Patients with asthma and COPD had nearly double the health care costs as did patients with asthma without COPD. The overall disease profile of patients with asthma should be considered when managing patients, rather than treating asthma as a solitary condition.

Healthcare utilization and costs associated with S. aureus and P. aeruginosa pneumonia in the intensive care unit: a retrospective observational cohort study in a US claims database.

BACKGROUND: Staphylococcus aureus and Pseudomonas aeruginosa are major causes of pneumonia in intensive care unit (ICU) patients. Limited data exist regarding the health economic impact of S. aureus and P. aeruginosa pneumonias in the ICU setting. METHODS: We conducted a retrospective observational cohort study using a 29.6 million enrollee US medical and pharmacy administrative claims database. ICU patients with S. aureus or P. aeruginosa infection per International Classification of Diseases, 9th ed. coding between 01/01/2007-8/31/2012 were compared with ICU patients without any pneumonia or infections of interest. Primary outcomes were costs in 2012 US dollars, healthcare utilization and all-cause mortality associated with hospital-acquired S. aureus or P. aeruginosa pneumonia, and the relative odds of incurring higher costs due to a comorbid condition. RESULTS: Patients with S. aureus or P. aeruginosa pneumonia had longer mean hospital (37.9 or 55.4 vs 7.2 days, P < .001) and ICU stays (6.9 or 14.8 vs 1.1 days, P < .001), a higher rate of mechanical ventilation (62.6 % or 62.3 % vs 7.4 %, P < .001), higher mortality (16.0 % or 20.2 % vs 3.1 %, P < .001), and higher total mean hospitalization costs ($146,978 or $213,104 vs $33,851, P < .001) vs controls. Pneumonia survivors had significantly increased risk of rehospitalization within 30 days (27.2 % or 31.1 % vs 15.3 %, P < .001). Comorbid conditions were not associated with increased cost in the pneumonia cohorts. CONCLUSIONS: Healthcare costs and resource utilization were high among ICU patients with S. aureus or P. aeruginosa pneumonia. Reducing the incidence of these infections could lead to substantial cost savings in the United States.

Treatment patterns, healthcare utilization, and costs of chronic opioid treatment for non-cancer pain in the United States.

OBJECTIVES: To evaluate treatment patterns, healthcare resource utilization, and costs among patients within a large managed care population chronically using opioids for non-cancer pain. STUDY DESIGN: Retrospective cohort study. METHODS: Patients aged ≥18 years with ≥1 prescription initiating opioids between January 1, 2007, and December 31, 2011, who also had 12 months of continuous pre-index health plan enrollment, were identified. Patients with pre-index opioid use or cancer diagnosis were excluded. Opioid exposure was stratified by treatment duration-short-term (30-182 days) versus chronic (≥183 days)-and by index opioid type (weak vs strong). RESULTS: A total of 2.9 million patients initiating opioids were identified, of which 257,602 had at least 30 days of continuous use and were included in the study. The mean age was 51 years and 52% were female. Overall, 239,998 (93%) patients had short-term opioid use, and 17,604 (7%) had chronic use; 215,424 (84%) initiated treatment with a weak opioid, and 44,712 (17%) with a strong opioid. The specialty most associated with the use of less potent opioids was general/family practice (28%), and for more potent opioids it was surgery (22%). Large increases in health-care utilization were reported between the pre-index and first 6-month post initiation periods for chronic users. Utilization rates decreased after the first 6 months but never reverted to baseline levels. Costs mirrored utilization trends, more than doubling between baseline and the first 6 months of treatment for pharmacy ($2029 vs $4331) and all-cause medical ($11,430 vs $27,365). Costs declined after the first 6 months of opioid use but remained above pre-index levels. CONCLUSIONS: These results demonstrated that healthcare resource utilization and costs increased during the first 6 months following clinical scenarios that necessitated opioid initiation and subsequently declined, suggesting the need to monitor patients beyond the acute care period.

Comparative effectiveness of budesonide-formoterol combination and fluticasone-salmeterol combination for asthma management: a United States retrospective database analysis.

BACKGROUND: Comparative effectiveness of the budesonide-formoterol fumarate dihydrate combination (BFC) and the fluticasone propionate-salmeterol combination (FSC) therapy on asthma exacerbation has not been assessed in real-world settings in the United States. OBJECTIVE: To compare exacerbation rates and health care utilization for patients with asthma who initiate BFC versus FSC therapy. METHODS: This retrospective cohort comparative effectiveness study queried medical and pharmacy data for patients with asthma from a large managed care data repository that covers major US population centers. The patients were 12 to 64 years old, with ≥12 months of pre- and postindex enrollment and ≥1 pharmacy claim(s) for BFC or FSC initiated during June 1, 2007, and September 30, 2010; the first prescription fill date was defined as the index date. Patients with other respiratory diseases and/or cancer were excluded. Exacerbation was defined as asthma-related hospitalization, emergency department visit, and/or oral corticosteroid prescription fill. Cohorts were matched by using propensity scores. RESULTS: A total of 3043 patients per cohort were matched and balanced. During the 12 months following the initiation the BFC cohort had lower adjusted exacerbations per person year versus the FSC cohort (0.85 vs 0.93; RR 0.92, 95% CI [0.85-0.99]), lower oral corticosteroid fill rates, and fewer asthma-related emergency department visits but comparable asthma-related hospitalization. CONCLUSIONS: Asthma exacerbation was lower for BFC versus FSC initiators due to lower rates of oral corticosteroid use and asthma-related emergency department visits, which indicate better treatment effectiveness of those patients initiated with BFC compared with FSC.

Description of cardiovascular event rates in patients initiating chronic opioid therapy for noncancer pain in observational cohort studies in the US, UK, and Germany.

INTRODUCTION: Previous observational studies in the US suggest that opioid analgesic use increases the risk of cardiovascular (CV) events. The current study provides additional background event rates for five prespecified CV outcomes of interest in patients from three countries. METHODS: Three observational cohort studies were conducted in patients from the US (N = 17,604), the UK (N = 9,823), and Germany (N = 9,412). Patients were new opioid users who had undergone ≥6 months of chronic, continuous therapy. De-identified data were collated from electronic healthcare databases in the respective countries. Demographics, clinical characteristics, and opioid use were examined. Overall rates, prevalence rates in patients with established CV disease, and incidence rates in patients without established CV disease were determined for myocardial infarction (MI), stroke, transient ischemic attack, unstable angina, and congestive heart failure (CHF). RESULTS: Cardiovascular disease at baseline was more prevalent in US and German patients. Back pain and depression were prevalent preexisting comorbidities. The majority of patients were using various weak opioids (based on receptor affinities), CV medications, and antidepressants. Overall rates by individual CV outcome per 1,000 patient-years by country were greatest for CHF (US 37.2, 95% CI 24.1-40.5), unstable angina (UK 8.2, 95% CI 7.0-9.6), and stroke (Germany 5.3, 95% CI 4.1-6.7). Overall rates for MI were: US, 10.7 (95% CI 9.1-12.5), UK, 6.7 (95% CI 5.6-8.0), and Germany, 2.7 (95% CI 1.9-3.7). Overall rates for each CV outcome, prevalence rates in patients with preexisting CV disease, and incidence rates in patients without established CV disease differed by country. Rates were higher in patients with preexisting CV disease. CONCLUSIONS: CV risk for new opioid users with ≥6 months of therapy was increased in patients with established CV disease compared with those without established CV disease, and the risk for specific outcomes differed by country. Assessment of CV safety events of new therapies introduced to chronic opioid users should consider sample size and population heterogeneity in the design of an observational study.

A US database study characterizing patients initiating a budesonide-formoterol combination versus tiotropium bromide as initial maintenance therapy for chronic obstructive pulmonary disease.

OBJECTIVE: To compare clinical and demographic characteristics, resource utilization and costs of chronic obstructive pulmonary disease (COPD) patients prior to initiating budesonide-formoterol combination (BFC) or tiotropium-maintenance therapy. MATERIALS AND METHODS: This cross-sectional study used claims-based diagnosis to identify COPD patients in the HealthCore Integrated Research Database who initiated BFC or tiotropium therapy between March 1, 2009 and January 31, 2012 (intake period); the index date was defined as the initial prescription fill for either agent. Patients diagnosed with respiratory tract cancer or receiving inhaled corticosteroids/long-acting ß2-adrenergic agonists or tiotropium in 12 months prior to index date were excluded. Categorical variables were evaluated with χ(2) tests; mean cost differences were evaluated using γ-regression. RESULTS: Overall, 6,940 BFC and 10,831 tiotropium patients were identified. The BFC group was younger (mean age 64 versus 67 years), with a greater proportion of females (54% versus 51%). BFC-treated patients had more comorbid respiratory conditions, including asthma (25% versus 13%), but fewer comorbid cardiovascular conditions, including atherosclerosis (7% versus 10%) and myocardial infarction (4% versus 6%). A greater proportion of BFC patients received prior respiratory medication, including oral corticosteroids (46% versus 35%) and short-acting ß2-agonists (44% versus 35%). Tiotropium-treated patients had a greater mean number of COPD-related outpatient visits (4.6 versus 4.1). BFC-treated patients had lower total all-cause ($17,259 versus $17,926) and COPD-related ($1,718 versus $1,930) health care costs, driven by lower all-cause and COPD-related inpatient expenditures. CONCLUSION: Initiators of BFC or tiotropium showed differences in clinical and demographic characteristics and health care utilization and costs prior to starting COPD maintenance therapy.

Community pharmacy practice in China: past, present and future.

BACKGROUND: In 2009, China launched a new healthcare system, with reform of the primary healthcare system as its foundation and focus, to enable residents to access primary healthcare for simple health problems instead of seeking help at hospitals. Community pharmacies and pharmacists were to have increased responsibility in primary healthcare by delivering pharmaceutical care services in China in addition to their traditional roles of dispensing prescriptions and selling medicines. AIM OF THE REVIEW: To describe the current status of Chinese community pharmacy education and practice, and discuss future directions. METHOD: A literature search was conducted using MEDLINE and International Pharmaceutical Abstracts. Additional articles were identified through the cross-referencing of articles and books. Additional data were found from relevant websites. RESULTS: From the 313 publications identified, 98 were included. China currently has 388,000 retail pharmacies, corresponding to one pharmacy per 3,532 population. All pharmacies provide prescription and over-the-counter products, as well as prescription dispensing and patient counselling. However, the lack of reimbursement mechanisms reduces the willingness of pharmacists to offer high-quality dispensing and counselling services. There is a shortage of qualified pharmacists to meet increasing patient needs. This, coupled with a shortage of pharmacist training, has resulted in pharmaceutical care being a low priority for delivery in routine pharmacy practice. To meet the increasing demand for pharmacists, 25 universities have been allowed to offer BS, MS and PhD degrees (3-7 years in length) in clinical pharmacy since 2008. The adoption of Good Pharmacy Practice as a recommended standard for community pharmacy practice provides pharmacists with a framework to aid them in service delivery. CONCLUSION: A number of undertakings still require development, including the enactment of the Chinese Pharmacist Law, development of a standard for pharmaceutical care activities, development of the pharmacy workforce, increasing public awareness of pharmacists, and proper reimbursement for care provision. Although pharmaceutical care services are underdeveloped in China, they will become an integral part of the professional work of all pharmacists in the future, particularly in community pharmacy settings.