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Objective: Pituitary adenylate-cyclase activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) are two neuropeptides that exhibit anti-inflammatory and neuroprotective properties, modulating the production of cytokines and chemokines, and the behavior of immune cells. However, the relationship between PACAP and VIP levels and Parkinson’s disease (PD) are not clear. The aim of the current study was to evaluate serum PACAP and VIP levels in PD patients and to analysis the correlation between neuropeptide levels and non-motor symptoms.Methods: In this cross-sectional study, we enrolled 72 patients with idiopathic PD and 71 healthy volunteers. Serum PACAP and VIP levels were measured using an enzyme-linked immunosorbent assay (ELISA) kit. Non-motor symptoms were assessed with the Non-Motor Symptoms Scale (NMSS) for PD, including total and single-item scores.Results: The serum PACAP levels of PD patients were significantly lower than those of healthy controls [(76.02 ± 43.78) pg/ml vs. (154.96 ± 76.54) pg/ml, P < 0.001]; and the serum VIP levels of PD patients were also significantly lower than those of healthy controls [(109.56 ± 15.39) pg/ml vs. (136.46 ± 24.16) pg/ml, P < 0.001]. PACAP levels were inversely correlated only with the score on NMSS item five, assessing Attention/memory (r = −0.276, P < 0.05) and lower serum PACAP levels were detected in the cognitive dysfunction subgroup than in the cognitively intact subgroup [(61.87 ± 32.66) pg/ml vs. (84.51 ± 47.59) pg/ml, P < 0.05]; meanwhile, VIP levels were inversely correlated with the NMSS total score (r = −0.285, P < 0.05) and the single-item scores for item one, assessing Cardiovascular (r = −0.257, P < 0.05) and item three, assessing Mood/cognition (r = −0.373, P < 0.05), and lower serum VIP levels were detected in the anxiety subgroup and depression subgroup than in the non-anxiety subgroup and non-depression subgroup, respectively [(107.45 ± 15.40) pg/ml vs. (116.41 ± 13.67) pg/ml, P < 0.05]; [(104.45 ± 15.26) pg/ml vs. (113.43 ± 14.52) pg/ml, P < 0.05].Conclusion: The serum PACAP and VIP levels of PD patients were significantly lower than those of healthy controls. The non-motor symptoms significantly negatively correlated with serum PACAP level was cognitive dysfunction, while mood disorder was significantly correlated with serum VIP level.

Aims: Many new mobile technologies are available to assist people in managing chronic conditions, but data on the association between the use of these technologies and medical spending remains limited. As the available digital technology offerings to aid in diabetes management increase, it is important to understand their impact on medical spending. The aim of this study was to investigate the financial impact of a remote digital diabetes management program using medical claims and real-time blood glucose data. Materials and methods: A retrospective analysis of multivariate difference-in-difference and instrumental variables regression modeling was performed using data collected from a remote digital diabetes management program. All employees with diabetes were invited, in a phased introduction, to join the program. Data included blood glucose (BG) values captured remotely from members via connected BG meters and medical spending claims. Participants included members (those who accepted the invitation, n = 2,261) and non-members (n = 8,741) who received health insurance benefits from three self-insured employers. Medical spending was compared between people with well-controlled (BG ≤ 154 mg/dL) and poorly controlled (BG > 154 mg/dL) diabetes. Results: Program access was associated with a 21.9% (p p p p = 0.03) lower medical spending. Limitations and conclusions: Remote digital diabetes management is associated with decreased medical spending at 1 year. Reductions in spending increased with active utilization. It will be beneficial for future studies to analyze the long-term effects of the remote diabetes management program and assess impacts on patient health and well-being.

Introduction: Heme oxygenase-1 (HO-1) is a 32 kDa stress-response protein implicated in the pathogenesis of Parkinson’s disease (PD). Biliverdin is derived from heme through a reaction mediated by HO-1 and protects cells from oxidative stress. However, iron and carbon monoxide produced by the catabolism of HO-1 exert detrimental effects on patients with PD. The purpose of this study was to determine whether plasma HO-1 levels represent a biomarker of PD and to further explore the underlying mechanism of increased HO-1 levels by applying voxel-based morphometry (VBM).Methods: We measured plasma HO-1 levels using an enzyme-linked immunosorbent assay (ELISA) in 156 subjects, including 81 patients with early- and advanced-stage PD and 75 subjects without PD. The analyses were adjusted to control for confounders such as age, sex, and medication. We analyzed T1-weighted magnetic resonance imaging (MRI) data from 74 patients with PD using VBM to elucidate the association between altered brain volumes and HO-1 levels. Then, we compared performance on MMSE sub-items between PD patients with low and high levels of HO-1 using Mann-Whitney U tests.Results: Plasma HO-1 levels were significantly elevated in PD patients, predominantly those with early-stage PD, compared with controls (p < 0.05). The optimal cutoff value for patients with early PD was 2.245 ng/ml HO-1 [area under the curve (AUC) = 0.654]. Plasma HO-1 levels were unaffected by sex, age, and medications (p > 0.05). The right hippocampal volume was decreased in the subset of PD patients with high HO-1 levels (p < 0.05). A weak correlation was observed between right hippocampal volume and plasma HO-1 levels (r = −0.273, p = 0.018). There was no difference in total MMSE scores between the low- and high-HO-1 groups (p > 0.05), but the high-HO-1 group had higher language scores than the low-HO-1 group (p < 0.05).Conclusions: Plasma HO-1 levels may be a promising biomarker of early PD. Moreover, a high plasma concentration of the HO-1 protein is associated with a reduction in right hippocampal volume.

Background Evidence suggests that insulin therapy of patients with type 2 diabetes mellitus (T2DM) is frequently discontinued. However, the reasons for discontinuing insulin and factors associated with insulin discontinuation in this patient population are not well understood. Methods We conducted a retrospective cohort study of adults with T2DM prescribed insulin between 2010 and 2017 at Partners HealthCare. Reasons for discontinuing insulin and factors associated with insulin discontinuation were studied using electronic medical records (EMR) data. Natural language processing (NLP) was applied to identify reasons from unstructured clinical notes. Factors associated with insulin discontinuation were extracted from structured EMR data and evaluated using multivariable logistic regression. Results Among 7009 study patients, 2957 (42.2%) discontinued insulin within 12 months after study entry. Most patients who discontinued insulin (2121 / 71.7%) had reasons for discontinuation documented. The most common reasons were improving blood glucose control (33.2%), achieved weight loss (18.5%) and initiation of non-insulin diabetes medications (16.7%). In multivariable analysis adjusted for demographics and comorbidities, patients were more likely to discontinue either basal or bolus insulin if they were on a basal-bolus regimen (OR 1.6, 95% CI 1.3 to 1.8; p p Conclusions In this large real-world evidence study conducted in an area with a high penetration of health insurance, insulin discontinuation countenanced by healthcare providers was common. In most cases it was linked to achievement of glycemic control, achieved weight loss and initiation of other diabetes medications. Factors associated with and stated reasons for insulin discontinuation were different from those previously described for non-adherence to insulin therapy, identifying it as a distinct clinical phenomenon.

Thomas P Power,1 Xuehua Ke,2 Zhenxiang Zhao,3 Nicole Gidaya Bonine,2 Mark J Cziraky,2 Michael Grabner,2 John J Barron,2 Ralph Quimbo,2 Burkhard Vangerow,3 Peter P Toth4,5 1AIM Specialty Health, Chicago, IL, 2HealthCore, Inc., Wilmington, DE, 3Eli Lilly and Company, Indianapolis, IN, 4CGH Medical Center, Sterling, IL, 5Johns Hopkins University School of Medicine, Baltimore, MD, USA Purpose: The aim of this study was to investigate real-world patient characteristics, medication use, and health care resource utilization (HCRU) and costs among patients with clinical atherosclerotic cardiovascular disease (ASCVD) as defined by 2013 American College of Cardiology/American Heart Association (ACC/AHA) guidelines, to examine burden of disease and unmet needs, such as potential undertreatment.Patients and methods: This retrospective cohort study utilized a nationally representative managed care database to identify newly diagnosed ASCVD patients between January 1, 2007, and November 30, 2012 (index = first ASCVD diagnosis date) in the USA. Patients had ≥12-month pre-index (baseline) and ≥12-month post-index (follow-up) health plan enrollment and no baseline lipid-lowering medication (LLM). Patient characteristics, LLM utilization patterns, HCRU, and costs were examined for all patients and by subgroups based on LLM use pattern and/or follow-up low-density lipoprotein cholesterol (LDL-C) levels.Results: A total of 128,017 ASCVD patients were identified with a mean (SD) age of 59 (13) years, 43.1% female, and 48.8% with ≥36-month follow-up. Within 12-month follow-up, 10.6% had high-intensity statins and 56.9% had no LLM fills. Baseline mean (SD) all-cause costs were $8,852 ($25,608). At 12-month follow-up, mean (SD) all-cause and ASCVD-related costs were $31,443 ($54,040) and $20,289 ($45,159), respectively. The 36-month analyses showed similar distributions. Multivariable analyses showed that age, gender, region, health insurance type, baseline comorbidities, baseline use of specific medications, baseline lipid profiles, and index ASCVD type were significantly associated with all-cause and ASCVD-related health care costs.Conclusion: Patients have nonoptimal treatment for ASCVD and substantial HCRU and costs associated with residual risk. Unmet needs and cost burdens of ASCVD patients merit additional investigation. Keywords: ASCVD, low-density lipoprotein cholesterol, lipid-lowering medications, health care resource utilization and costs, statins, treatment patterns, guidelines, real-world evidence

To compare 30 and 90 day real-world acute myocardial infarction (AMI) and bleeding related rehospitalization rates in acute coronary syndrome (ACS) patients receiving percutaneous coronary intervention (PCI; ACS-PCI) treated with clopidogrel or prasugrel.Using the Premier hospital database, ACS-PCI patients receiving a drug-eluting (DES) or bare-metal (BMS) stent and clopidogrel or prasugrel from July 2009 to June 2011 were analyzed. Patients were included based on the prasugrel US prescribing information (USPI), excluding patients with a history of transient ischemic attack/stroke and patients ≥75 years without diabetes or prior MI. The primary endpoint was 30 day adjusted AMI rehospitalization rate. Secondary endpoints included 90 day AMI and 30 and 90 day bleeding-related rehospitalization rates. Treatment comparisons were adjusted using propensity score stratification.At the index event, prasugrel patients (N = 9404) differed from clopidogrel patients (N = 74,163) by having a lower risk of comorbid conditions associated with bleeding, being more likely younger and male, having ST-elevation MI and receiving a DES. For clopidogrel and prasugrel, respectively, the observed AMI-related rehospitalization rates were 4.7% and 3.9% at 30 days (p 0.0001) and 6.3% and 5.1% at 90 days (p 0.0001). After adjustment, prasugrel was associated with ∼10% lower odds of AMI-related rehospitalization (30 days: OR = 0.892 [95% CI: 0.798, 0.998]; 90 days, OR = 0.901 [95% CI: 0.817, 0.994]). Adjusted bleeding-related rehospitalization rates were similar to each other (OR = 1.035 at 30 days [95% CI: 0.765, 1.399]; OR = 0.922 at 90 days [95% CI: 0.725, 1.172]).Treatment adherence was not assessed. Bleeding events not resulting in a hospitalization (e.g. office, outpatient, or emergency room visits), deaths outside the hospital, or readmissions to a hospital outside of the Premier alliance were not captured in the database.The different patient characteristics between prasugrel- and clopidogrel-treated patients suggest physicians are more selective in choosing patients for prasugrel than recommended in the prasugrel USPI. However, after adjustment for these differences, 30 and 90 day AMI rehospitalization rates were lower for prasugrel-treated patients compared to clopidogrel-treated patients, with no difference in adjusted bleeding-related rehospitalization rates.

BackgroundNon-motor symptoms are common in Parkinson’s disease (PD) and can even be used as part of the supportive criteria for diagnosis. Chronic inflammation is involved in every stage of PD. Disorders of the immune system affect the peripheral blood. Whether the humoral immune response is associated with the non-motor symptoms of PD remains unknown.MethodsMann–Whitney tests and Bonferroni correction were used to compare the serum levels of IgG, IgA, IgM, C3, and C4 between 180 sporadic PD patients and 187 healthy controls. Multiple regression models were conducted to assess the associations among these indicators of humoral immunity and the clinical features of PD patients.ResultsMale PD patients had lower levels of C3 and C4 than healthy controls [0.87 (0.22) vs. 0.96 (0.19); 0.19 (0.06) vs. 0.22 (0.07), respectively, Pc < 0.01] and lower levels of C3 than female PD patients [0.87 (0.22) vs. 1.02 (0.23), Pc < 0.01]. Patients suffering from attention/memory problems had significantly lower levels of IgA and C3 than those without these problems [1.92 (1.21) vs. 2.57 (0.76); 0.89 (0.24) vs. 0.97 (0.24), respectively, Pc < 0.04]. In addition, serum IgG levels were negatively associated with mood/cognition problem scores and were positively associated with gastrointestinal tract problem scores (adjusted R2 = 0.063, F = 1.805, p = 0.038). Serum C3 levels were negatively associated with being male, age, and sleep/fatigue problem scores (adjusted R2 = 0.123, F = 2.678, p = 0.001).ConclusionThe peripheral humoral immune response might be correlated with the non-motor symptoms of PD.

Background: Growth differentiation factor 15 (GDF15) has been shown to be protective for dopaminergic neurons in animal and ex vivo experiments. However, little is known about its effect on the human body. Objective: This study investigated associations between serum GDF15 levels and clinical parameters in patients with Parkinson disease (PD). Methods: Idiopathic PD patients (n = 104) and age-matched controls (n = 88) were enrolled. Serum GDF15 levels were measured by human enzyme-linked immunosorbent assay. Univariate and multivariate analyses investigated correlations between GDF15 and clinical characteristics, including disease severity by the Unified PD Rating Scale (UPDRS)-III. The diagnostic value of GDF15 was evaluated by receiver-operating characteristic curve (ROC) analysis. Results: The serum GDF15 levels of the PD patients were significantly higher than those of the healthy controls. In PD patients, serum GDF15 levels in men were significantly higher than in women. GDF15 levels correlated with age, gender, disease duration, and UPDRS-III score. After adjusting for confounding factors, multiple linear regression analysis showed that the serum GDF15 level (β = 0.015, p = 0.001) was an independent risk factor for UPDRS-III score. In ROC analysis, GDF15 achieved an area under the curve of 0.86 for the identification of PD, with a sensitivity of 71.15% and a specificity of 87.50%. Conclusion: GDF15 may be a potential biomarker for the diagnosis and monitoring of motor severity in PD.

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

Background Orexin, a neuropeptide primarily secreted by neurons in the lateral hypothalamus, has been implicated in Parkinson’s disease (PD). Studies on the relationship between plasma orexin-A levels and PD are rare. Objectives This study aimed to assess levels of plasma orexin-A in the progression of PD and to evaluate the correlation between orexin-A levels and non-motor symptoms. Methods Enzyme-linked immunosorbent assay was used to determine plasma orexin-A levels in 117 healthy controls and 121 PD patients, including those with early (n = 68), medium (n = 40) and advanced (n = 13) stages of the disease. Evaluation of motor symptoms and non-motor symptoms in PD patients, such as sleep disorders, cognitive dysfunction, neuropsychiatric symptoms, autonomic nervous dysfunction, hyposmia and PD-related pain, were assessed by the associated scales. Results Plasma orexin-A levels were significantly higher in PD patients compared to healthy controls. Orexin-A levels were elevated in early-stage and medium-stage PD compared to healthy controls, but were decreased in advanced-stage PD. Orexin-A levels were negatively correlated with the Unified Parkinson’s Disease Rating Scale Part III scores, disease duration, and dopamine receptor agonist doses, and were positively correlated with the Pittsburgh Sleep Quality Index, REM-sleep Behavior Disorder Questionnaire, 14-item Hamilton Anxiety Scale, Mini-Mental State Examination, and Non-motor Symptom Scale items 22–24 scores. Conclusions We found for the first time that plasma orexin-A levels were increased in early-stage and medium-stage PD and were decreased in advanced-stage PD. Furthermore, orexin-A levels were correlated with the non-motor symptoms of insomnia, REM-sleep behavior disorder, anxiety, cognitive dysfunction, and renal dysfunction.

AIMS: To describe global patterns of insulin treatment and to assess the impact of patient, provider, health system and economic influences on treatment decisions for patients with insulin-treated type 2 diabetes (T2D). METHODS: This prospective cohort study of insulin-treated patients with T2D was conducted across 18 countries categorized as high, upper-middle or lower-middle income regions. Information collected from patients included knowledge of diabetes, experiences and interactions with their healthcare provider. Physician information included specialty, practice size, availability of diabetes support services, volume of diabetes patients treated and time spent per patient. Physicians determined an individualized haemoglobin A1c (HbA1c) target for each patient by the start of the study. Changes in T2D therapies and HbA1c were recorded for 2 years. RESULTS: Complete treatment data were available for 2528 patients. Median age was 61 years and median duration of diabetes was 11.4 years. Changes to treatment regimen occurred in 90.0% of patients, but changes were less common in countries with a higher economic status (P

This study explored the treatment pattern of newly diagnosed type 2 diabetes (T2D) patients in 2015 using the Commercial and Medicare MarketScan databases. Therapy lines were defined in Table 1. A total of 115,091 adult patients with newly diagnosed (Dx) T2D were identified. Of patients who had antidiabetic drug (ADD) claims within a year after first T2D Dx (n = 53,041), about 20% progressed to second line. The average time from initial Dx to first line and from first to second line were 53 and 117 days respectively. The proportion of combination therapy (≥ 2 ADDs) was increased from 12% in first line to 63% in second line. Table 1 captured the top 20 therapies in each line. About 76% of patients started with metformin (MET) as monotherapy or in combination with sulfonylurea (SU). Substantial variation exists in second line therapies with SU leading the top monotherapy (8.7%). A very small number of patients received newer drugs such as dapagliflozin, dulaglutide and empagliflozin. In line with ADA recommendations, the majority of patients initiated MET-based regimens in first line. SUs were widely used in second line. Despite ongoing research and drug development, little has changed in prescribing of ADD, suggesting a need for better understanding of the gaps in diabetes management and/or education on use and benefits of newer drugs. This study most likely underestimated ADD therapy due to lack of prescriptions filled without pharmacy benefits. Disclosure J. Wu: None. J. Xie: None. S. Wong-Jacobosn: None. V.S. Haynes: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. Z. Zhao: None.

Understanding the natural progression of type 2 diabetes mellitus (T2DM) is crucial in determining the appropriate approaches to care and effective management among these patients. Patients with a diagnosis for T2DM between January 2012 to December 2013 and treated with a non-insulin glucose-lowering medication were identified from a large national health plan using medical and pharmacy claims. The first occurring diagnosis for T2DM was considered the index date. Patients were required to be enrolled ≥ 6 months prior to index and be 18-89 years at index. Based on presence or absence of diagnosis for T2DM during the pre-index period, patients were categorized as prevalent or incident. Patients were followed for a maximum of five years allowing longitudinal assessment of T2DM progression and trends in comorbidities, treatment regimens, and laboratory outcomes. The quarterly cohorts declined from 147,900 and 20,066 in 2Q2012 to 52,091 and 11,454 in 2Q2017 in the prevalent and incident cohorts, respectively. Despite the increasing utilization of glucose-lowering medications, glycemic control remained suboptimal, with increasing prevalence of complications such as kidney disease in both prevalent and incident cohorts as patients progressed through their diabetes. Disclosure R. Nair: Other Relationship; Self; Eli Lilly and Company. Z. Zhao: None. P. Gandhi: Employee; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Y. Li: None. K. Brodovicz: Employee; Self; Boehringer Ingelheim Pharmaceuticals, Inc. Y.A. Meah: Employee; Self; Humana Inc. S. Kalirai: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. C. Moretz: None. M. MacKenzie: Other Relationship; Self; Boehringer Ingelheim GmbH. B. Curtis: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. T.G. Prewitt: None.

Background— Rehospitalizations after acute myocardial infarction for unplanned coronary revascularization and unstable angina (UA) are common. However, despite the inclusion of these events in composite end points of many clinical trials, their association with health status has not been studied. Methods and Results— We included 3283 patients with acute myocardial infarction enrolled in a prospective, 24-center US study who had rehospitalizations independently classified by experienced cardiologists. Health status was assessed using Seattle Angina Questionnaire and EuroQol-5D Visual Analog Scale. In the propensity-matched cohorts, 1-year health status was compared between those who did and did not experience rehospitalization for UA or revascularization using a hierarchical linear model. Overall, mean age was 59 years, 33% were women, and 70% were white. Rehospitalization rates for UA and unplanned revascularization at 1 year were 4.3% and 4.7%. One-year Seattle Angina Questionnaire summary scores were worse in patients with rehospitalizations for UA (mean difference, −10.1; 95% confidence interval, −12.4 to −7.9) and unplanned revascularization (mean difference, −5.7; 95% confidence interval, −8.8 to −2.5) when compared with patients without such rehospitalizations. Similarly, EuroQol-5D Visual Analog Scale scores were worse among patients with such readmissions. Individual Seattle Angina Questionnaire domains indicated worse 1-year angina and quality of life outcomes among patients rehospitalized for UA or unplanned revascularization. Conclusions— Within the first year after acute myocardial infarction, rehospitalizations for UA and unplanned revascularization are associated with worse health status. These findings highlight the impact of such events from a patient’s perspective, beyond their economic impact and support the use of UA and unplanned revascularization as elements of composite end points.

// Bin Song 1,2,3,* , Heyang Cui 1,2,* , Yaoping Li 1,4,* , Caixia Cheng 1,2,5,* , Bin Yang 1,4,* , Fang Wang 1,2,* , Pengzhou Kong 1,2,* , Hongyi Li 1,2 , Ling Zhang 1,2 , Zhiwu Jia 1,2 , Yanghui Bi 1,2 , Jiaqian Wang 6 , Yong Zhou 6 , Jing Liu 1,7 , Juan Wang 1,2 , Zhenxiang Zhao 1,2 , Yanyan Zhang 1,7 , Xiaoling Hu 1,2 , Ruyi Shi 1,2 , Jie Yang 1,2 , Haiyan Liu 1,2,8 , Ting Yan 1,2 , Yike Li 1,7 , Enwei Xu 1,2,9 , Yu Qian 1,2 , Yanfeng Xi 9 , Shiping Guo 4 , Yunqing Chen 4 , Jinfen Wang 9 , Guodong Li 9 , Jianfang Liang 5 , Junmei Jia 3 , Xing Chen 10 , Jiansheng Guo 7 , Tong Wang 11 , Yanbo Zhang 11 , Qingshan Li 12 , Chuangui Wang 13 , Xiaolong Cheng 1,2 , Qimin Zhan 14 and Yongping Cui 1,2 1 Translational Medicine Research Center, Shanxi Medical University, Taiyuan, Shanxi, China 2 Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi, China 3 Department of Oncology, The First Hospital, Shanxi Medical University, Taiyuan, Shanxi, China 4 Department of Tumor Surgery, Shanxi Cancer Hospital, Taiyuan, Shanxi, China 5 Department of Pathology, The First Hospital, Shanxi Medical University, Taiyuan, Shanxi, China 6 BGI-Shenzhen, Shenzhen, Guangdong, China 7 Department of General Surgery, the First Hospital, Shanxi Medical University, Taiyuan, Shanxi, China 8 Department of Nuclear medicine, the First Hospital, Shanxi Medical University, Taiyuan, Shanxi, China 9 Department of Pathology, Shanxi Cancer Hospital, Taiyuan, Shanxi, China 10 Department of Endoscopy, Shanxi Provincial People’s Hospital, Taiyuan, Shanxi, China 11 Department of Statistics, Shanxi Medical University, Taiyuan, Shanxi, China 12 School of Pharmaceutical Sciences, Shanxi Medical University, Taiyuan, Shanxi, China 13 Key Laboratory of Medical Cell Biology, College of Translational Medicine, China Medical University, Shenyang, China 14 State Key Laboratory of Molecular Oncology, Cancer Institute and Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China * Authors share co-first authorship Correspondence to: Yongping Cui, email: // Qimin Zhan, email: // Keywords : esophageal cancer, significantly mutated genes, mutational exclusivity, oncogene Received : August 05, 2015 Accepted : September 24, 2015 Published : October 29, 2015 Abstract Background: Recurrent genetic abnormalities that correlate with clinical features could be used to determine patients’ prognosis, select treatments and predict responses to therapy. Esophageal squamous cell carcinoma (ESCC) contains genomic alterations of undefined clinical significance. We aimed to identify mutually exclusive mutations that are frequently detected in ESCCs and characterized their associations with clinical variables. Methods: We analyzed next-generation-sequencing data from 104 ESCCs from Taihang Mountain region of China; 96 pairs were selected for deep target-capture-based validation and analysis of clinical and pathology data. We used model proposed by Szczurek to identify exclusive mutations and to associate these with pathology findings. Univariate and multivariate analyses with Cox proportional hazards model were used to examine the association between mutations and overall survival and response to chemotherapy. Findings were validated in an analysis of samples from 89 patients with ESCC from Taihang Mountain. Results: We identified statistically significant mutual exclusivity between mutations in NOTCH1 and PIK3CA in ESCC samples. Mutations in NOTCH1 were associated with well-differentiated, early-stage malignancy and less metastasis to regional lymph nodes. Nonetheless, patients with NOTCH1 mutations had shorter survival times than patients without NOTCH1 mutations, and failed to respond to chemotherapy. In contrast, patients with mutations in PIK3CA had better responses to chemotherapy and longer survival times than patients without PIK3CA mutations. Conclusions: In a genetic analysis of ESCCs from patients in China, we identified mutually exclusive mutations in NOTCH1 and PIK3CA . These findings might increase our understanding of ESCC development and be used as prognostic factors.

Background Whereas composite end points are often used in clinical trials of percutaneous coronary interventions ( PCI ), the impact of individual components on subsequent survival is incompletely defined. We evaluated the association of subsequent acute coronary syndromes ( ACS ) and unplanned coronary revascularization post‐ PCI with long‐term survival. Methods and Results From 2009 to 2011, the Ki CS ‐ PCI (Keio interhospital Cardiovascular Studies) consecutively enrolled patients undergoing PCI in 14 Japanese teaching hospitals. We identified patients who experienced ACS or unplanned coronary revascularization following their index PCI and compared subsequent survival during the 2‐year follow‐up period using propensity‐matched cohorts of patients who did and did not experience these events. Cox proportional hazard models were used to assess 2‐year all‐cause mortality. Because unstable angina is less severe than acute myocardial infarction, we also generated a separate propensity‐matched cohort for UA post‐ PCI . Among 3348 PCI patients (mean age, 67.5±10.7 years; 79.7% male), 214 (6.4%) experienced a subsequent ACS (168 events [78.5%] were unstable angina), and 198 (5.9%) underwent unplanned revascularization. In the propensity‐matched cohorts, patients with a subsequent ACS admission had an increased risk of mortality as compared with those without (hazard ratio, 4.73; 95% confidence interval=1.35–16.6; P =0.015), whereas those with an unplanned revascularization did not have significantly higher risk (hazard ratio, 2.97; 95% confidence interval=0.57–14.3; P =0.19). Among unstable angina events, no association with mortality was observed (hazard ratio, 1.39; 95% confidence interval=0.48–4.00; P =0.54). Conclusions In the Ki CS ‐ PCI registry, the incidence of a subsequent ACS was associated with higher mortality, but this association was less apparent after unplanned coronary revascularization or unstable angina. The prognostic implications of different outcomes in a composite end point should be considered when interpreting the results of clinical trials in PCI .

Background— Intensive statins are superior to moderate statins in reducing morbidity and mortality after an acute myocardial infarction. Although studies have documented rates of statin prescription as a quality performance measure, variations in hospitals’ rates of initiating, intensifying, and maximizing statin therapy after acute myocardial infarction are unknown. Methods and Results— We assessed statin use at admission and discharge among 4340 acute myocardial infarction patients from 24 US hospitals (2005–2008). Hierarchical models estimated site variation in statin initiation in naïve patients, intensification in those undergoing submaximal therapy, and discharge on maximal therapy (defined as a statin with expected low-density lipoprotein cholesterol lowering ≥50%) after adjustment for patient factors, including low-density lipoprotein cholesterol level. Site variation was explored with a median rate ratio, which estimates the relative difference in risk ratios of 2 hypothetically identical patients at 2 different hospitals. Among statin-naïve patients, 87% without a contraindication were prescribed a statin, with no variability across sites (median rate ratio, 1.02). Among patients who arrived on submaximal statins, 26% had their statin therapy intensified, with modest site variability (median rate ratio, 1.47). Among all patients without a contraindication, 23% were discharged on maximal statin therapy, with substantial hospital variability (median rate ratio, 2.79). Conclusions— In a large, multicenter acute myocardial infarction cohort, statin therapy was begun in nearly 90% of patients during hospitalization, with no variability across sites; however, rates of statin intensification and maximization were low and varied substantially across hospitals. Given that more intense statin therapy is associated with better outcomes, changing the existing performance measures to include the intensity of statin therapy may improve care.

Background Rehospitalizations following acute myocardial infarction for unplanned coronary revascularization and unstable angina ( UA ) are often included as parts of composite end points in clinical trials. Although clearly costly, the clinical relevance of these individual components has not been described. Methods and Results Patients enrolled in a prospective, 24‐center, US acute myocardial infarction registry were followed for 1 year after an acute myocardial infarction for rehospitalizations, that were independently adjudicated by experienced cardiologists. Patients who did and did not experience UA or revascularization rehospitalization were propensity matched using greedy matching. Among 3283 patients with acute myocardial infarction who were included, mean age was 59 years, 33% were female, and 70% were white. Rehospitalization rates for UA and unplanned revascularization at 1 year were 5.0% and 4.1%, respectively. After propensity matching, we included 2433 patients in the UA rehospitalization group and 2410 in the unplanned revascularization group. Using weighted proportional hazards Cox regression, there was no significant association between a rehospitalization for UA and 5‐year all‐cause mortality (9.6% versus 13.8%; adjusted hazard ratio 0.87, 95% CI 0.60–1.16). Patients rehospitalized for unplanned revascularization had a lower 5‐year mortality risk (7.0% versus 15.1%; hazard ratio 0.68, 95% CI 0.50–0.92) compared with those without such rehospitalizations. Nevertheless, patients with UA and unplanned revascularization had a substantially greater hazard of subsequent rehospitalizations compared with patients without such events ( UA : hazard ratio 4.36, 95% CI 3.48–5.47; revascularization: hazard ratio 4.38, 95% CI 3.53–5.44). Conclusions Rehospitalizations for UA and unplanned revascularization in the year after an acute myocardial infarction are associated with higher risks of subsequent rehospitalizations but not with mortality.

Objectives: Several pharmacologic therapies have been recommended for managing fibromyalgia. However, the factors associated with each treatment initiation have not been well established. This study assessed factors that were associated with the use of duloxetine vs. other pain medications among patients with fibromyalgia. Research Design and Methods: Administrative claims from a large, U.S. commercially insured population were analyzed using a retrospective cohort design. Patients with fibromyalgia who were 18 to 64 years old and initiated duloxetine vs. selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), venlafaxine, gabapentin, pregabalin, tramadol, or nontramadol opioids between January 1, 2007 and December 12, 2008 were selected. Treatment initiation was defined as no access to the same medication over the previous 90 days, with the most recent initiation date as the index date. All patients selected had at least one fibromyalgia diagnosis (ICD-9-CM: 729.1) in the 12 months prior to initiation of each study medication. Multiple logistic regression models were estimated to assess the predictors of initiating duloxetine vs. each of the other medications. Results: The study included 117,305 patients with fibromyalgia (48 years of age on average; 76% women) who initiated duloxetine (n = 5,827), SSRIs (n = 8,620), TCAs (n = 5,424), venlafaxine (n = 2,038), gabapentin (n = 5,733), pregabalin (n = 11,152), tramadol (n = 7,312), or nontramadol opioids (n = 71,199). Common fibromyalgia-related comorbidities were low back pain (31% to 49%), osteoarthritis (14% to 21%), and sleep disturbance (10% to 15%). Controlling for demographic and clinical characteristics, patients who received pregabalin in the prior 12-month period were more likely to initiate duloxetine. Patients from other treatment cohorts, except for those in the pregabalin and nontramadol opioid cohorts, were more likely to re-initiate the same prior medication than to begin treatment with duloxetine. Other predictors of duloxetine initiation included history of rheumatoid and sleep disturbance. Conclusions: The presence of select comorbidities and prior use of certain medications were associated with the duloxetine initiation among working-age, commercially insured patients with fibromyalgia.

To examine medication dosing patterns of duloxetine and pregabalin among patients with fibromyalgia.From a large US administrative claims database, commercially insured fibromyalgia patients aged 18-64 who initiated duloxetine or pregabalin in 2006 were selected. Initiation was defined as a 90-day medication gap, with the dispense date of the first initiation as the index date. All patients selected had continuous enrollment over the 12-month pre- and post-index periods, and were classified into the duloxetine or pregabalin cohorts based on their index agent. Initial daily dose, average daily dose over the 12-month post-index period, mean and median daily doses and daily costs of each of the first 12 prescriptions were examined for both the duloxetine and pregabalin cohorts.Both the duloxetine (n = 3773) and pregabalin (n = 4189) cohorts had a mean age of 50 years (median age: 52 vs. 53). The average initial daily dose was 55.7 mg for duloxetine and 161.5 mg for pregabalin. Over the 12-month post-index period, the average daily dose per patient was 55.6 mg for duloxetine and 195.7 mg for pregabalin. The average daily doses for the first 12 duloxetine prescriptions ranged 55.7-60.3 mg, with the mean daily costs between $3.77 and $4.59. For the first 12 pregabalin prescriptions, the average daily dose increased from 161.5 mg to 282.4 mg, while the average daily costs ranged between $4.30-4.61.Among patients with fibromyalgia, duloxetine and pregabalin initiators had different dosing patterns. The average daily dose for duloxetine was relatively stable over time, while pregabalin patients had significant dose increase over the 12-month post-index period.

Recent guidelines recommend use of aspirin and either clopidogrel or prasugrel for at least 12 months following use of drug-eluting or bare metal stents in patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI). This study evaluated factors associated with clopidogrel use and adherence in ACS patients following PCI.The US employer-based MarketScan commercial claims database was used to examine factors associated with clopidogrel use and adherence. Adherence was defined as a medication possession ratio of 80% or higher. Multivariate logistic regression analyses were conducted to identify factors associated with clopidogrel use and adherence and included patient demographics, comorbidities, and prior beta-blocker, statin, and angiotensin converting enzyme inhibitor (BSI) use as factors.A total of 10,465 patients aged 18-65 years who met inclusion criteria were hospitalized for ACS and underwent PCI between 01/01/2005 and 12/31/2006. Overall, the rate of clopidogrel use was 92.8% for ACS-PCI patients and 66.8% of the clopidogrel users were adherent. Receiving PCI without stenting (Odds Ratio [OR] = 3.28), comorbid hypertension (OR = 1.50), diabetes (OR = 1.49), and atrial fibrillation (OR = 1.91) were associated with decreased filled prescriptions for clopidogrel. Younger age (OR = 0.83) and prior use of clopidogrel (OR = 0.54) or other BSI medications (OR = 0.44) were associated with increased use of clopidogrel (all p values 0.05). Factors significantly associated with non-adherence of clopidogrel were prior use of clopidogrel (OR = 1.40), prior hospitalization (OR = 1.34), chronic pulmonary disease (OR = 1.31), PCI without stenting (OR = 1.32), diabetes (OR = 1.17), and younger age (OR = 1.29). Prior use of BSI medications (OR = 0.82) increased adherence to clopidogrel.Prior use of clopidogrel, comorbid conditions such as diabetes and chronic pulmonary disease, prior hospitalization, PCI without stenting, and younger age had a negative impact on clopidogrel adherence. These findings may assist programs to improve thienopyridine compliance through a better understanding of patients' disease profiles and concomitant medication use.

To assess the demographic and clinical characteristics associated with initiation of duloxetine therapy compared with other pharmacologic therapies for treatment of diabetic peripheral neuropathic pain (DPNP).This study used administrative claims databases for commercially-insured individuals aged 18-64 years to examine factors associated with treatment among DPNP patients who initiated duloxetine versus tricyclic antidepressants (TCAs), venlafaxine, gabapentin, pregabalin, or opioids between 7/1/2005 and 12/31/2007. Treatment initiation was defined as no pill coverage of the same medication over the previous 90 days. Multiple logistic regression models were estimated to assess factors associated with initiating duloxetine versus each of the other DPNP therapies.The study included 11,060 DPNP patients with average age of 55 years old. Cardiovascular disease (63-70%), cerebrovascular/peripheral vascular disease (26-33%), low back pain (24-39%), and osteoarthritis (17-26%) were the most common diabetes- and pain-related comorbidities. Controlling for demographic and clinical characteristics, patients who received duloxetine or pregabalin in the prior 12-month period were more likely to initiate duloxetine. Patients from other DPNP treatment cohorts, except for those in the pregabalin cohort, were more likely to re-initiate the same prior therapy than begin treatment with duloxetine (all p0.05). A history of anxiety disorder was significantly associated with initiation of all DPNP treatments other than duloxetine (all p0.05), except for TCAs. Patients with low back pain were more likely to initiate duloxetine than TCAs or venlafaxine, but less likely to initiate duloxetine than pregabalin or opioids. Patients with infections related to diabetes were less likely to initiate duloxetine than venlafaxine, gabapentin, or opioids.Because a retrospective administrative claims database was used, this study is subject to selection bias due to unobservable confounders, inability to measure prescriber preferences or characteristics or disease severity.Among commercially-insured DPNP patients, those with prior use of duloxetine or pregabalin were more likely to initiate duloxetine than other treatments. The presence of select comorbidities was also associated with specific medication initiation.

There are no published studies on physical dating violence in college students in Chile, and campuses across the country currently lack systematized programs to prevent or respond to this public health problem. This is the first study to examine prevalence and predictors of physical dating violence victimization with a sample of female college students in Chile.A closed-ended questionnaire was administered to students enrolled in general education courses at a major public university. The prevalence of women's physical dating violence victimization was calculated, and generalized ordered logit models were used to estimate risk factors for such victimization (n = 441). Ancillary analyses examined associations of dating violence victimization with experiences of unwanted sexual contact and forced condom nonuse.Approximately 21% of subjects reported one or more incidents of physical dating violence not involving physical injury since age 14, and another 5% reported at least one incident resulting in physical injury during this time period. Risk factors identified in five sequential models were sexual abuse and witnessing of domestic violence in childhood, low parental education, residence away from the parental home, urban residence, and having had sexual intercourse. Maternal employment and religious participation had protective effects. Dating violence victimization was found to be significantly associated with experiences of unwanted sexual contact and forced condom nonuse.The study findings show a high prevalence of physical dating violence, strong associations between several sociodemographic factors and dating violence, and links between dating violence and sexual/reproductive risk. Our results indicate a need to expand attention to this public health problem in Chile as well as other developing countries, where research and prevention/response initiatives have generally been similarly limited. The findings also have important implications for the content of dating violence, HIV/sexually transmitted infection (STI), and pregnancy prevention programs for adolescents and young adults.

Aim To assess the prevalence of high-risk atherosclerotic cardiovascular disease (ASCVD, defined as history of acute coronary syndrome [hACS], cerebrovascular atherosclerotic disease [CeVAD], peripheral artery disease [PAD], or coronary artery disease w/diabetes [CADD]) and associated costs and cardiovascular (CV) events in Japan. Methods A retrospective analysis was conducted using the Japan Medical Data Center (JMDC) database (2006-2011). ASCVD prevalence was estimated on the basis of diagnoses for CeVAD, PAD, CADD, and hACS (ACS claim ＞ 30-≤ 365 days after ACS-related hospitalization) during 1/1/ 2008-12/31/2009. Population denominators used in the prevalence estimations were provided by JMDC. A subcohort with an insurance coverage for ≥ 12 months before and ≥ 24 months after first/index ASCVD claim during 1/1/2008-12/31/2009 were analyzed on the basis of costs (in 2012 US dollars) and events. Results ASCVD prevalence was 1,869/100,000 population. In total, 8,112 patients met inclusion criteria for the cost and CV event analyses. Among these patients, 4.0% experienced any event (myocardial infarction, stroke, coronary revascularization, hospitalization for unstable angina) in the year after ASCVD diagnosis, which decreased to 2.2% in year 2. First-year event rates were highest (22%) in patients with hACS. Mean [SD] all-cause costs per patient in year 1 were $7,031 [$14,359] for all patients with ASCVD combined. Extrapolated to the entire employed population, total first-year costs were estimated at $8.2 billion. Conclusions ASCVD is not rare in Japan, even within a relatively young population of employed persons. Further, the total direct first-year cost burden of ASCVD in the employed Japanese population is high. These data may inform future economic assessments of new ASCVD treatments.

Patients with coronary artery disease with diabetes, a history of acute coronary syndromes, cerebrovascular atherosclerotic disease, or peripheral arterial disease are at particularly high risk for a cardiovascular (CV) event and can be defined as having high-risk atherosclerotic cardiovascular disease (ASCVD). The objective of this study is to examine healthcare resource utilization (HRU) and total healthcare costs (THC) for patients with ASCVD in a commercially insured population.A retrospective cohort study was conducted using a large, US employer-based, claims database. Patients with an ASCVD diagnosis between October 1, 2008 to September 30, 2009 who met eligibility requirements were included. All-cause and ASCVD-related HRU and THC for the first and second year of follow-up were examined for all patients and by the number of arterial beds affected. Adjusted THC were compared across groups with and without polyvascular disease.The analysis included 152,290 patients with ASCVD. Use of CV-related medications, hospitalizations, and office visits were highest among patients with three arterial beds affected. Mean all-cause THC for patients with ASCVD were ∼$19,000 per patient in Year 1 or Year 2, with medical costs as the main driver. ASCVD-related THC were also similar for Year 1 ($8699) and Year 2 ($7925) across all patients. Adjusted all-cause and ASCVD-related THC for both years were greatest for patients with three affected arterial beds compared with one or two affected beds (p 0.001 for each comparison).This is the first study in a managed care setting to systematically estimate all-cause and ASCVD-related THC for an aggregated population of ASCVD patients at high risk for a CV event. The economic burden of ASCVD in working-age patients in the US is substantial. Significantly higher HRU and costs were found in patients with polyvascular disease compared with those with only one affected bed.

Rationale: Parkinsonism can be secondary to many internal diseases, in some certain conditions, it seems that the clinical manifestations of parkinsonism presenting reversible. We report a case of patient with parkinsonism secondary to pseudohypoparathyroidism, who improved markedly after the supplement of serum calcium. Patient concerns and diagnoses: A 52-year-old woman with acute parkinsonism was diagnosed as pseudohypoparathyroidism after the conducting of brain computed tomography, laboratory examinations, and gene detection. The son of the patient was also examined and was diagnosed as pseudohypoparathyroidism, who had ever complained of the history of epilepsy. The clinical manifestations of parkinsonism of the patient was reevaluated after the supplement of serum calcium according to the diagnosis. Interventions and outcomes: The brain computed tomography revealed the basal ganglia calcification of the patient, accompanying by serum hypocalcemia and hyperphosphatemia. Loss of function mutation also confirmed the diagnosis. Five days after the therapy targeting at correction of serum hypocalcemia, the patient improved greatly in dyskinesia. Lessons: This study reported a patient presenting as acute reversible parkinsonism, who was finally diagnosed as pseudohypoparathyroidism. It indicated us that secondary parkinsonism should be carefully differentiated for its dramatic treatment effect. And the family history of seizures might be an indicator for the consideration of pseudohypoparathyroidism.

Aggressively managing low-density lipoprotein cholesterol (LDL-C) after myocardial infarction (MI) is a cornerstone of secondary prevention. The changes in LDL-C after MI and the factors associated with LDL-C levels are unknown. Therefore, we directly measured fasting LDL-C levels in 797 MI patients from 24 US hospitals from 2005 to 2008. Mean LDL-C levels at discharge, 1 month, and 6 months were 95.1, 81.9, and 87.1 mg/dL, respectively. In a hierarchical, multivariable, repeated measures model, older age, male sex, and hypertension were associated with lower LDL-C levels, whereas self-reported avoidance of health care because of cost was associated with higher LDL-C. Both the presence and intensity of statin therapy at discharge were strongly associated with LDL-C levels, with adjusted mean 6-month changes of -3.4 mg/dL (95% confidence interval (CI): -12.1, 5.3) for no statins; 1.7 mg/dL (95% CI: -4.7, 8.1) for low statins; -10.2 mg/dL (95% CI: -14.5, -6.0) for moderate statins; and -13.9 mg/dL (95% CI: -19.7, -8.0) for intensive statins (P < 0.001). In conclusion, we found that greater reductions in LDL-C levels after MI were strongly associated with the presence and intensity of statin therapy, older age, male sex, hypertension, and better socioeconomic status. These findings support the use of intensive statin therapy in post-MI patients and provide estimates of the expected LDL-C changes after MI in a real-world population.

BACKGROUND: High risk vascular disease (HRVD defined as cerebrovascular disease [CVD], coronary artery disease with diabetes [CADD], history of acute coronary syndrome [ACS], or peripheral artery disease [PAD]) is among the biggest health problems affecting Japanese, with CVD and coronary artery disease (CAD) being the 2nd and 3rd most common causes of death. Despite proven efficacy of statins in reducing CV mortality, limited research is available to systematically study statin adherence and persistence for HRVD patients in Japan. OBJECTIVE: Examine statin adherence and persistence in HRVD patients. METHOD: A retrospective cohort study was conducted using the Japan Medical Data Center (JMDC) database, a large Japanese administrative claims database with 10 insurance societies (payers), and integrated inpatient, outpatient, and pharmacy claims of approximately 0.8 million covered lives from 2006-2011. Patients > 18 years with HRVD (CVD, PAD, CADD or history of ACS [≥30days through 365 days after discharge for ACS]) between 01/01/2008 to 12/31/2009, were identified for this study with minimum 12-month pre- and 24-month post-index insurance eligibility. Statin use was measured during the 12-month baseline period and the 24-month follow-up period. The date of the first HRVD claim(s) satisfying the above inclusion criteria was defined as the index date. Statin use was examined for the overall HRVD group as well as subgroups of patients with CVD only, PAD only, CADD only, history of ACS only, and patients with multiple HRVDs. Statin adherence, calculated using the medication possession ratio [MPR], and statin persistence, assessed with survival analysis techniques using a ≥30-day gap to define discontinuation, were measured in the 24-month follow-up period for the overall HRVD patient group. RESULTS: There were 10,400 HRVD patients identified in the JMDC database. Mean age was 52.8 and 57.1% were male. Statin use during the baseline period showed 12.1% of HRVD patients taking statins (CVD only: 10.2%; PAD only: 9.6%; CADD only: 14.6%; history of ACS only: 46.7%; CADD and a history of ACS: 48.3%; 2 affected artery beds: 17.8%; 3 affected artery beds: 19.5%). Statin use increased to 32.9% during the 24-month follow-up period (CVD only: 27.6%; PAD only: 26.6%; CADD only: 45.1%; history of ACS only: 54.4%; CADD and a history of ACS: 58.3%; 2 affected artery beds: 49.3%; 3 affected artery beds: 45.5%). For Japanese HRVD patients who used a statin, mean/median MPR was 0.89/0.94 and 82.1% of statin users were adherent (MPR ≥80%) to their statin therapy during the 24-month follow up period. The median time to statin discontinuation was 679 days during the 24-month follow up period. CONCLUSION: Statin use after HRVD diagnosis was modest and highest in ACS patients and patients with multiple affected vascular beds. Statin adherence was high among patients with HRVD in Japan.

Given the availability of several statins in the United States, it is important to understand patient characteristics associated with their initiation. We analyzed demographic and clinical factors associated with statin selection among new statin users.This retrospective cohort study examined factors associated with statin selection among patients newly initiated on therapy between 1/1/2007 and 12/31/2007. Commercial and Medicare patient cohorts were evaluated separately and comparisons were made between pravastatin (PS) and other statins including simvastatin (SS), atorvastatin (AS), or rosuvastatin (RS). Multiple logistic regression models were employed to assess factors associated with PS initiation versus other statins.In commercially insured patients, patients initiating PS were more likely to be older, female, and have diabetes mellitus, liver dysfunction, human immunodeficiency virus (HIV) infection, or hypertension and use calcium channel blockers, protease inhibitors, or additional lipid-modifying agents (p0.01 for each comparison). In Medicare-age patients, a higher percentage of PS initiators were aged 75-85, female, had atrial fibrillation, and were prescribed warfarin or triazole antifungals (p0.01 for each comparison). Presence of atrial fibrillation or HIV infection, or use of calcium channel blockers or additional lipid-modifying agents was associated with PS initiation compared with AS and SS. Use of warfarin was significantly associated with initiating PS compared with SS, AS, and RS in Medicare-age patients.Older age and female gender were associated with PS initiation. In addition, selected comorbidities and use of certain medications including warfarin or protease inhibitors were associated with PS initiation, which may reflect the tolerability of PS and its reduced risk of significant drug-drug interactions for certain patients. Because this study is a retrospective analysis of US healthcare claims, the findings are limited to only those factors captured within claims data and may not be generalizable to all patient populations in which statin therapy is initiated.

This study compared differences in healthcare costs and resource utilization for acute coronary syndrome (ACS) patients with and without diabetes mellitus (DM).A retrospective cohort study of a large, US employer-based claims database identified adults hospitalized for ACS between 01/01/2005 and 12/31/2006 and categorized them based on DM status. Resource utilization and costs during the index hospitalization and in the 12-month follow-up period were compared for ACS patients with and without DM using the propensity score stratification bootstrapping method, adjusting for differences in demographic and clinical characteristics.Of 12,502 patients who met selection criteria, 3,040 (24%) had a history of DM and 9,462 (76%) did not. Patients with DM were older, female, and had higher rates of previous cardiovascular and renal diseases. After the propensity score stratification, patients with DM incurred higher index hospitalization costs ($32,577 vs. $29,150, p0.01) as well as higher total follow-up healthcare costs ($35,400 vs. $24,080, p0.01), including higher inpatient ($17,278 vs. $11,247, p0.01), outpatient ($12,357 vs. $8,853, p0.01), and pharmacy costs ($5,765 vs. $3,980, p0.01).General limitations exist with any retrospective claims database analysis including potential diagnostic or procedural coding inaccuracies. Additionally, the patient population was representative of a working-age population with employer-sponsored health insurance and results may not be generalizable to other patient populations.DM is significantly associated with increased healthcare resource utilization and costs for ACS patients.

Background The significant economic burden associated with acute coronary syndromes (ACS) provides a need to evaluate both medical costs and productivity costs, according to evolving guideline-driven ACS treatment strategies, medical management (MM), percutaneous coronary intervention (PCI), or coronary artery bypass graft (CABG). Methods Commercially insured individuals, aged 18-64, with an emergency room (ER) visit or hospitalization accompanied by an ACS diagnosis (index event) were identified from a large claims database between 01/2004 and 12/2005 with a 1-year follow-up period. Patients who had an ACS diagnosis in the 12 months prior to their index event were excluded. Patients were divided into 3 groups according to treatment strategies during the index event: MM, PCI, or CABG. A subset of patients was identified for the productivity cost analysis exploring short-term disability and absenteeism costs. Multivariate generalized linear models were performed to examine the ACS costs by 3 different treatment strategies. Results A total of 10,487 patients were identified for the medical cost analysis. The total 1-year medical costs (index event costs plus the 1-year follow-up costs) were lowest for MM patients ($34,087), followed by PCI patients ($52,673) and CABG patients ($86,914). Of the 3,080 patients in the productivity costs analysis, 2,454 patients were identified in the short-term disability cohort and 626 patients were identified in the absenteeism cohort. Both the estimated mean total 1-year short-term disability and absenteeism costs were highest for CABG patients ($17,335, $14,960, respectively) compared to MM patients ($6,048, $9,826, respectively) and PCI patients ($9,221, $9,460, respectively). Conclusions Both total 1-year medical costs and 1-year productivity costs are substantial for working-aged individuals with ACS. These costs differ according to the type of treatment strategy, with CABG having higher costs compared to either PCI or MM.