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Background: Studies of the neurovascular contribution to dementia have largely focused on cerebral small vessel disease (CSVD), but the role of intracranial atherosclerotic disease (ICAD) remains unknown in the general population. The objective of this study was to determine the risk of incident dementia from ICAD after adjusting for CSVD and cardiovascular risk factors in a US community-based cohort., Methods: We acquired brain magnetic resonance imaging examinations from 2011 through 2013 in 1980 Black and White participants in the ARIC study (Atherosclerosis Risk in Communities), a prospective cohort conducted in 4 US communities. Magnetic resonance imaging examinations included high-resolution vessel wall magnetic resonance imaging and magnetic resonance angiography to identify ICAD. Of these participants, 1590 without dementia, without missing covariates, and with adequate magnetic resonance image quality were followed through 2019 for incident dementia. Associations between ICAD and incident dementia were assessed using Cox proportional hazard ratios adjusted for CSVD (characterized by white matter hyperintensities, lacunar infarctions, and microhemorrhages), APOE4 genotype (apolipoprotein E gene ε4), and cardiovascular risk factors., Results: The mean age (SD) of study participants was 77.4 (5.2) years. ICAD was detected in 34.6% of participants. After a median follow-up of 5.6 years, 286 participants developed dementia. Compared with participants without ICAD, the fully adjusted hazard ratios (95% CIs) for incident dementia in participants with any ICAD, with ICAD only causing stenosis ≤50%, and with ICAD causing stenosis >50% in ≥1 vessel were 1.57 (1.17-2.11), 1.41 (1.02-1.95), and 1.94 (1.32-2.84), respectively. ICAD was associated with dementia even among participants with low white matter hyperintensities burden, a marker of CSVD., Conclusions: ICAD was associated with an increased risk of incident dementia, independent of CSVD, APOE4 genotype, and cardiovascular risk factors. The increased risk of dementia was evident even among participants with low CSVD burden, a group less likely to be affected by vascular dementia, and in participants with ICAD causing only low-grade stenosis. Our results suggest that ICAD may partially mediate the effect that cardiovascular risk factors have on the brain leading to dementia. Both ICAD and CSVD must be considered to understand the vascular contributions to cognitive decline., Competing Interests: None.

Purpose: Valbenazine is commonly used to treat tardive dyskinesia, and we conducted a pharmacovigilance analysis using the Food and Drug Administration Adverse Event Reporting System (FAERS) to evaluate neurological safety signals associated with valbenazine., Methods: Data was collected in FAERS from the second quarter of 2017 to the fourth quarter of 2023 for data cleaning. Neurological adverse event (AE) signals of valbenazine were mined by calculating reporting odds ratios (ROR), information component (IC) and empirical Bayesian geometric mean (EBGM). The serious and non-serious cases and signals were prioritized using a rating scale., Results: The number of neurological AE reports where the primary suspect (PS) drug was 8981 for valbenazine. Significant AE signals were identified by the preferred term (PT) analysis for valbenazine, including somnolence (ROR 19.69), tremor (ROR 15.17), and tardive dyskinesia (ROR 236.91), among which 18 AEs were identified as new signals. Patient age (p < 0.009) and sex (p = 0.197) might be associated with an increased risk of neurological AE severity. Notably, the association between valbenazine and neurological disorders remained when stratified by sex, age, and reporter type. AE timing analysis was performed for the drug and four moderate clinical priority signals [i.e., somnolence, balance disorder, parkinsonism, and akathisia (priorities 7)], showing the same early failure type profiles., Conclusions: The increase in neurological safety signals is identified in the post-marketing research of valbenazine. Clinicians need to pay attention to not only common AEs but also be alert to new neurological AE signals when using valbenazine., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Volatile organic compounds (VOCs) encompass hundreds of high production volume chemicals and have been reported to be associated with adverse respiratory outcomes such as chronic obstructive pulmonary disease (COPD). However, research on the combined toxic effects of exposure to various VOCs on COPD is lacking. We aimed to assess the effect of VOC metabolite mixture on COPD risk in a large population sample., Methods: We assessed the effect of VOC metabolite mixture on COPD risk in 5997 adults from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2020 (pre-pandemic) using multivariate logistic regression, Bayesian weighted quantile sum regression (BWQS), quantile-based g-Computation method (Qgcomp), and Bayesian kernel machine regression (BKMR). We explored whether these associations were mediated by white blood cell (WBC) count and total bilirubin., Results: In the logistic regression model, we observed a significantly increased risk of COPD associated with 9 VOC metabolites. Conversely, N-acetyl-S-(benzyl)-L-cysteine (BMA) and N-acetyl-S-(n-propyl)-L-cysteine (BPMA) showed insignificant negative correlations with COPD risk. The overall mixture exposure demonstrated a significant positive relationship with COPD in both the BWQS model (adjusted odds ratio (OR) = 1.30, 95% confidence interval (CI): 1.06, 1.58) and BKMR model, and with marginal significance in the Qgcomp model (adjusted OR = 1.22, 95% CI: 0.98, 1.52). All three models indicated a significant effect of the VOC metabolite mixture on COPD in non-current smokers. WBC count mediated 7.1% of the VOC mixture associated-COPD in non-current smokers., Conclusions: Our findings provide novel evidence suggesting that VOCs may have adverse associations with COPD in the general population, with N, N- Dimethylformamide and 1,3-Butadiene contributing most. These findings underscore the significance of understanding the potential health risks associated with VOC mixture and emphasize the need for targeted interventions to mitigate the adverse effects on COPD risk., (© 2024. The Author(s).)

Objectives: Previous studies suggest an association between central arterial stiffness (CAS) and intracranial atherosclerotic disease (ICAD) among Asian participants with stroke or hypertension; this association has not been evaluated in United States populations. We assessed the cross-sectional association of CAS with ICAD presence and burden in late-life, and differences in association by age, sex, and race., Materials and Methods: We conducted a cross-sectional analysis of 1,285 Atherosclerosis Risk in Communities Study participants [mean age 75 (standard deviation: 5) years, 38 % male, 20  % Black] at Visit 5 (2011-2013). CAS was measured as carotid-femoral pulse wave velocity (cfPWV) using the Omron VP-1000 Plus. ICAD was assessed using high-resolution vessel wall MRI and MR angiography. We evaluated associations of a 1 standard deviation (SD) cfPWV (3.02 m/s) and high vs. non-high cfPWV (≥ 13.57 m/s vs. < 13.57 m/s) with presence of plaques (yes/no) and plaque number (0, 1-2, and >2) using multivariable logistic and ordinal logistic regression models adjusted for covariates., Results: Each one SD greater cfPWV was associated with higher odds of plaque presence (odds ratio (OR)=1.32, 95 % confidence interval (CI): 1.22, 1.43), and an incrementally higher odds of number of plaques (OR 1-2 vs. 0 plaques = 1.21, 95 % CI: 1.10, 1.33; OR >2 vs. 0 plaques = 1.51, 95 % CI: 1.33,1.71). Results suggested differences by race, with greater magnitude associations among Black participants., Conclusions: CAS was positively associated with ICAD presence and burden; cfPWV may be a useful subclinical vascular measure for identification of individuals who are at high risk for cerebrovascular disease., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: No study has comprehensively quantified the individual and collective contributions of various risk factors to the growing burden of diabetes in the United States., Methods: This study aimed to determine the extent to which an increase in the prevalence of diabetes was related to concurrent changes in the distribution of diabetes-related risk factors among US adults (aged 20 years or above and not pregnant). Seven cycles of series of cross-sectional National Health and Nutrition Examination Survey data between 2005-2006 and 2017-2018 were included. The exposures were survey cycles and seven domains of risk factors, including genetic, demographic, social determinants of health, lifestyle, obesity, biological, and psychosocial domains. Using Poisson regressions, percent reduction in the β coefficient (the logarithm used to calculate the prevalence ratio for prevalence of diabetes in 2017-2018 vs. 2005-2006) was computed to assess the individual and collective contribution of the 31 prespecified risk factors and seven domains to the growing burden of diabetes., Results: Of the 16,091 participants included, the unadjusted prevalence of diabetes increased from 12.2% in 2005-2006 to 17.1% in 2017-2018 [prevalence ratio: 1.40 (95% CI, 1.14-1.72)]. Individually, genetic domain [17.3% (95% CI, 5.4%-40.8%)], demographic domain [41.5% (95% CI, 24.4%-76.8%)], obesity domain [35.3% (95% CI, 15.8%-70.2%)], biological domain [46.2% (95% CI, 21.6%-79.1%)], and psychosocial domain [21.3% (95% CI, 9.5%-40.1%)] were significantly associated with a different percent reduction in β. After adjusting for all seven domains, the percent reduction in β was 97.3% (95% CI, 62.7%-164.8%)., Conclusion: The concurrently changing risk factors accounted for the increasing diabetes prevalence. However, the contribution of each risk factor domain varied. Findings may inform planning cost-effective and targeted public health programs for diabetes prevention., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Huang, Xu, Qiao, Wang and Zhong.)

Background and Purpose: Intracranial vessel wall MR imaging is an emerging technique for intracranial vasculopathy assessment. Our aim was to investigate intracranial vessel wall MR imaging use by the American Society of Neuroradiology (ASNR) members at their home institutions, including indications and barriers to implementation., Materials and Methods: The ASNR Vessel Wall Imaging Study Group survey on vessel wall MR imaging use, frequency, applications, MR imaging systems and field strength used, protocol development approaches, vendor engagement, reasons for not using vessel wall MR imaging, ordering-provider interest, and impact on clinical care, was distributed to the ASNR membership between April 2 and August 30, 2019., Results: There were 532 responses; 79 were excluded due to nonresponse and 42 due to redundant institutional responses, leaving 411 responses. Fifty-two percent indicated that their institution performs vessel wall MR imaging, with 71.5% performed at least 1-2 times/month, most frequently on 3T MR imaging, and 87.7% using 3D sequences. Protocols most commonly included were T1-weighted pre- and postcontrast and TOF-MRA; 60.6% had limited contributions from vendors or were still in protocol development. Vasculopathy differentiation (94.4%), cryptogenic stroke (41.3%), aneurysm (38.0%), and atherosclerosis (37.6%) evaluation were the most common indications. For those not performing vessel wall MR imaging, interpretation (53.1%) or technical (46.4%) expertise, knowledge of applications (50.5%), or limitations of clinician (56.7%) or radiologist (49.0%) interest were the most common reasons. If technical/expertise obstacles were overcome, 56.4% of those not performing vessel wall MR imaging indicated that they would perform it. Ordering providers most frequently inquiring about vessel wall MR imaging were from stroke neurology (56.5%) and neurosurgery (25.1%), while 34.3% indicated that no providers had inquired., Conclusions: More than 50% of neuroradiology groups use vessel wall MR imaging for intracranial vasculopathy characterization and differentiation, emphasizing the need for additional technical and educational support, especially as clinical vessel wall MR imaging implementation continues to grow., (© 2022 by American Journal of Neuroradiology.)

The aim of this study was to investigate the therapeutic effect of minimally invasive aspiration on intracerebral hemorrhage (ICH) and the value of artificial intelligence algorithm combined with computed tomography (CT) image evaluation. Ninety-two patients with intracerebral hemorrhage were divided into experimental group (46 cases, minimally invasive aspiration therapy) and control group (46 cases, traditional craniotomy therapy) according to different treatment methods, and CT image scanning was performed. In addition, a CT image segmentation model of intracerebral hemorrhage based on improved fuzzy C-means clustering algorithm (n-FCM) was proposed to process the CT images of the patients. The results showed that the Dice coefficient of n-FCM algorithm after the addition of salt and pepper noise was 0.89, which was higher than that of traditional algorithm; the average operation time of experimental group was 58.93 ± 5.33 min, which was significantly lower than that of control group (90.21 ± 16.24 min) ( P < 0.05); the overall response rate of experimental group was 93.48%, which was significantly higher than that of control group (76.09%) ( P < 0.05); one month after operation, the National Institutes of Health Stroke Scale (NIHSS) score of experimental group was 3.89 ± 1.95 points, and the Scandinavian Stroke Scale (SSS) score was 10.67 ± 1.76 points, which was significantly lower than that of control group ( P < 0.05); the incidence rate of complications in experimental group was significantly lower than that of control group ( P < 0.05). It showed that the n-FCM algorithm was superior to the traditional algorithm in CT image processing, with the advantages of good denoising effect and less running time. Minimally invasive aspiration treatment had the advantages of operation time, convenient operation, and less damage to patients, which was beneficial to postoperative recovery and prognosis of patients., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Junfeng Sun et al.)

Models that recapitulate the complexity of human tumors are urgently needed to develop more effective cancer therapies. We report a bank of human patient-derived xenografts (PDXs) and matched organoid cultures from tumors that represent the greatest unmet need: endocrine-resistant, treatment-refractory and metastatic breast cancers. We leverage matched PDXs and PDX-derived organoids (PDxO) for drug screening that is feasible and cost-effective with in vivo validation. Moreover, we demonstrate the feasibility of using these models for precision oncology in real time with clinical care in a case of triple-negative breast cancer (TNBC) with early metastatic recurrence. Our results uncovered a Food and Drug Administration (FDA)-approved drug with high efficacy against the models. Treatment with this therapy resulted in a complete response for the individual and a progression-free survival (PFS) period more than three times longer than their previous therapies. This work provides valuable methods and resources for functional precision medicine and drug development for human breast cancer., (© 2022. The Author(s).)

[Figure: see text].

Purpose: We previously developed an age-scalable 3D computational phantom that has been widely used for retrospective whole-body dose reconstructions of conventional two-dimensional historic radiation therapy (RT) treatments in late effects studies of childhood cancer survivors. This phantom is modeled in the FORTRAN programming language and is not readily applicable for dose reconstructions for survivors treated with contemporary RT whose treatment plans were designed using computed tomography images and complex treatment fields. The goal of this work was to adapt the current FORTRAN model of our age-scalable computational phantom into Digital Imaging and Communications in Medicine (DICOM) standard so that it can be used with any treatment planning system (TPS) to reconstruct contemporary RT. Additionally, we report a detailed description of the phantom's age-based scaling functions, information that was not previously published., Method: We developed a Python script that adapts our phantom model from FORTRAN to DICOM. To validate the conversion, we compared geometric parameters for the phantom modeled in FORTRAN and DICOM scaled to ages 1 month, 6 months, 1, 2, 3, 5, 8, 10, 15, and 18 years. Specifically, we calculated the percent differences between the corner points and volume of each body region and the normalized mean square distance (NMSD) between each of the organs. In addition, we also calculated the percent difference between the heights of our DICOM age-scaled phantom and the heights (50th percentile) reported by the World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC) for male and female children of the same ages. Additionally, we calculated the difference between the organ masses for our DICOM phantom and the organ masses for two reference phantoms (from International Comission on Radiation Protection (ICRP) 89 and the University of Florida/National Cancer Institute reference hybrid voxel phantoms) for ages newborn, 1, 5, 10, 15 and adult. Lastly, we conducted a feasibility study using our DICOM phantom for organ dose calculations in a commercial TPS. Specifically, we simulated a 6 MV photon right-sided flank field RT plan for our DICOM phantom scaled to age 3.9 years; treatment field parameters and age were typical of a Wilms tumor RT treatment in the Childhood Cancer Survivor Study. For comparison, the same treatment was simulated using our in-house dose calculation system with our FORTRAN phantom. The percent differences (between FORTRAN and DICOM) in mean dose and percent of volume receiving dose ⩾5 Gy were calculated for two organs at risk, liver and pancreas., Results: The percent differences in corner points and the volumes of head, neck, and trunk body regions between our phantom modeled in FORTRAN and DICOM agreed within 3%. For all of the ages, the NMSDs were negliglible with a maximum NMSD of 7.80 × 10 -2 mm for occiptital lobe of 1 month. The heights of our age-scaled phantom agreed with WHO/CDC data within 7% from infant to adult, and within 2% agreement for ages 5 years and older. We observed that organ masses in our phantom are less than the organ masses for other reference phantoms. Dose calculations done with our in-house calculation system (with FORTRAN phantom) and commercial TPS (with DICOM phantom) agreed within 7%., Conclusion: We successfully adapted our phantom model from the FORTRAN language to DICOM standard and validated its geometric consistency. We also demonstrated that our phantom model is representative of population height data for infant to adult, but that the organ masses are smaller than in other reference phantoms and need further refinement. Our age-scalable computational phantom modeled in DICOM standard can be scaled to any age at RT and used within a commercial TPS to retrospectively reconstruct doses from contemporary RT in childhood cancer survivors.

Objectives: Significant literature exists on the effects of medication adherence on reducing healthcare costs, but less is known about the effect of medication adherence among Medicare low-income subsidy (LIS) recipients. This study examined the effects of medication adherence on healthcare costs among LIS recipients with diabetes, hypertension, and/or heart failure., Methods: This retrospective study analyzed Medicare claims data (2012-2013) linked to the Area Health Resources Files. Using measures developed by the Pharmacy Quality Alliance, adherence to 11 medication classes was studied among patients with 7 possible combinations of the diseases mentioned. Adherence was measured in 8 categories of proportion of days covered (PDC): ≥95%, 90% to <95%, 85% to <90%, 80% to <85%, 75% to <80%, 50% to <75%, 25% to <50%, and <25%. Annual Medicare costs were compared across adherence categories. A generalized linear model was used to control for patient/community characteristics., Results: Among patients with only one disease, such as diabetes, patients with the lowest adherence (PDC < 25%) had $3152/year higher Medicare costs than patients with the highest adherence (PDC ≥ 95%; $11 101 vs $7949; P < .05). The adjusted costs among patients with PDC < 25% was $1893 higher than patients with PDC ≥ 95% ($9919 vs $8026; P < .05). Among patients with multiple chronic conditions, patients' adherence to medications for fewer diseases had higher costs., Conclusions: Greater medication adherence is associated with lower Medicare costs in the Medicare LIS population. Future policy affecting the LIS program should encourage better medication adherence among patients with chronic diseases., (Copyright © 2020 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Background: Significant racial and ethnic disparities in statin prescribing and utilization have been constantly documented., Objective: To examine whether racial/ethnic disparities in statin treatment have decreased among the diabetic population after the release of the 2013 American College of Cardiology/American Heart Association (ACC/AHA) guidelines., Methods: This retrospective study analyzed patients with diabetes aged 40-75 years old in the Medicare Expenditure Panel Survey (2011-2012 and 2014-2015). Racial and ethnic disparities in the likelihood of statin use and number of statin prescriptions were compared before and after the guideline release. Logistic and negative binomial regressions were used to adjust for patient characteristics. A difference-in-difference model (DID) was used to examine disparity changes., Results: This study included 2584 patients from 2011 to 2012 and 2610 from 2014 to 2015. During 2011-2012, racial/ethnic disparities were significant for the likelihood of statin use. For the number of statin prescriptions, racial disparity was significant, but not for the ethnic disparity. During 2014-2015, racial/ethnic disparities were significant for the likelihood of statin use but were not significant for the number of statin prescriptions. The DID model found that the 2013 guidelines were not associated with a reduction in racial and ethnic disparities in statin treatment., Conclusions: This study found persistent disparities in the likelihood of statin use. The 2013 ACC/AHA guidelines were not associated with a reduction in racial and ethnic disparities in statin treatment., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: The role of palliative gastrectomy in the management of metastatic gastric cancer remains inadequately clarified., Methods: We analyzed patients with metastatic gastric cancer enrolled in the Surveillance, Epidemiology, and End Results registry from January 2004 to December 2012. Propensity score (PS) analysis with 1:1 matching and the nearest neighbor matching method was performed to ensure well-balanced characteristics of the groups of patients who undergone gastrectomy and those without gastrectomy. Data were analyzed by Kaplan-Meier and Cox proportional hazards regression models to evaluate the overall survival and cancer-specific survival rates with corresponding 95% confidence intervals (CIs)., Results: In general, receiving any kind of gastrectomy was associated with an improvement in survival in the multivariate analyses (hazard ratio [HR]os = 0.64, 95% CI = 0.59-0.70, HRcss = 0.63, 95% CI = 0.57-0.68) and PS matching (PSM) analyses (HRos = 0.63, 95% CI = 0.56-0.70, HRcss = 0.62, 95% CI = 0.55-0.70). After PSM, palliative gastrectomy was found to be associated with remarkably improved survival for patients with stage M1 with only 1 metastasis but not associated with survival of patients with stage M1 with extensive metastasis (≥2 metastatic sites)., Discussion: The results obtained from the Surveillance, Epidemiology, and End Results database suggest that patients with metastatic gastric cancer might benefit from palliative gastrectomy on the basis of chemotherapy. However, a PSM cohort study of this kind still has a strong selection bias and cannot replace a properly conducted randomized controlled trial.

Objectives: To compare viewpoints of nationally certified and noncertified technicians and explore the perceived value of technician certification in the job performance domains of medication safety, skills and abilities, experience, engagement and satisfaction, and productivity., Methods: A cross-sectional survey of pharmacy technicians, from 6 states representing 4 regions of the United States, was conducted. Technician mailing lists were purchased from Boards of Pharmacy, and randomly selected technicians were sent survey invitations. Surveys were completed via Qualtrics and analyzed with the use of SAS., Results: Six hundred seventy-six technicians (547 certified, 103 noncertified, and 26 previously certified) responded to the survey (9.4% response rate). Certified technicians reported significantly higher confidence rating for desire to take on new responsibilities (P < 0.01; Cohen d 0.45) and plans to remain in the pharmacy field (P = 0.01, Cohen d 0.35), lower rating for leaving the job in the next 12 months (P < 0.01; Cohen d 0.35), and perceived lower rate of medication errors (P < 0.01; Cohen d 0.35) compared with other technicians in the work setting. The majority of respondents stated confidence in performing the "final check" on another technician's preparation of a new or refill medication if allowed. Both certified and noncertified technicians noted dissatisfaction with pay. The majority of respondents reported that they spent none of or less than 10% of their workday assisting pharmacists with medication therapy management (MTM) sessions, immunizations, or point-of-care tests; however, 71 respondents specifically described how they assist pharmacists with MTM., Conclusion: Results from our survey sample indicate that certified technicians have a stronger organizational and career commitment and desire to take on new roles. A majority of respondents noted dissatisfaction with pay but feel a sense of pride in their work. Both groups were confident in their abilities needed for tech-check-tech product verification., (Copyright © 2019 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Background/objectives: Previous research indicates that eligibility criteria for medication therapy management (MTM) services in Medicare prescription drug (Part D) plans, defined under the Medicare Modernization Act (MMA), are associated with racial/ethnic disparities and ineffective in identifying individuals with medication utilization issues. Our study's objective was to determine the comparative effectiveness of MTM eligibility criteria under MMA and in the Affordable Care Act (ACA) in identifying patients with medication utilization issues across racial/ethnic groups., Design: ACA and MMA MTM eligibility criteria were compared on proportions of eligible individuals among patients with medication utilization issues. Multinomial logistic regression was conducted to control for patient/community characteristics. Need-based and demand-based analyses were used to determine disparities due to need and demand for healthcare. Main/sensitivity analyses were conducted for the range of eligibility thresholds., Setting: Medicare data (2012-2013) linked to Area Health Resources Files., Participants: A total of 964 610 patients 65 years or older., Measurements: Medication safety/adherence measures, developed primarily by the Pharmacy Quality Alliance, were used to determine medication utilization issues., Results: Higher proportions of patients were eligible based on ACA than MMA MTM eligibility criteria. For example, in 2013, proportions based on ACA and MMA MTM eligibility criteria would be 99.7% and 26.2%, respectively, in the main analysis (p < .001); in the demand-based main analysis, ACA criteria were associated with 13.6% and 9.8%, respectively, higher effectiveness than MMA criteria among non-Hispanic blacks and Hispanics than non-Hispanic whites., Conclusion: ACA MTM eligibility criteria are more effective than MMA criteria in identifying older patients needing MTM, particularly among minorities. J Am Geriatr Soc 67:581-587, 2019., (© 2019 The American Geriatrics Society.)

Purpose To compare common carotid artery (CCA) wall thickness measured manually by using US and semiautomatically by using MRI, and to examine their associations with incident coronary heart disease and stroke. Materials and Methods This prospective study enrolled 698 participants without a history of clinical cardiovascular disease (CVD) from the Multi-Ethnic Study of Atherosclerosis (MESA) from July 2000 to December 2013 (mean age, 63 years; range, 45 to 84 years; same for men and women). All participants provided written informed consent. CCA wall thickness was measured with US as well as both noncontrast proton-density-weighted and intravenous gadolinium-enhanced MRI. Cox proportional hazards models were used to assess the associations between wall thickness measurements by using US and MRI with CVD outcomes. Results The adjusted hazard ratios for coronary heart disease, stroke, and CVD associated with per standard deviation increase in intima-media thickness were 1.10, 1.08, and 1.14, respectively. The corresponding associations for mean wall thickness measured with proton-density-weighted MRI were 1.32, 1.48, and 1.37, and for mean wall thickness measured with gadolinium-enhanced MRI were 1.27, 1.58, and 1.38. When included simultaneously in the same model, MRI wall thickness, but not intima-media thickness, remained associated with outcomes. Conclusion For individuals without known cardiovascular disease at baseline, wall thickness measurements by using MRI were more consistently associated with incident cardiovascular disease, particularly stroke, than were intima-media thickness by using US. © RSNA, 2018 Online supplemental material is available for this article.

Our recent study revealed recurrent chromosomal losses and somatic mutations of genes in the Hippo pathway in mucinous tubular and spindle cell carcinoma (MTSCC). Here, we performed an integrative analysis of 907 renal cell carcinoma (RCC) samples (combined from The Cancer Genome Atlas and in-house studies) and the Knepper data set of microdissected rat nephrons. We identified VSTM2A and IRX5 as novel cancer-specific and lineage-specific biomarkers in MTSCC. We then assessed their expression by RNA in situ hybridization (ISH) in 113 tumors, including 33 MTSCC, 40 type 1 papillary RCC, 8 type 2 papillary RCC, 2 unclassified RCC, 15 clear cell RCC, and 15 chromophobe RCC. Sensitivity and specificity were calculated as the area under the receiver operating characteristics curve (AUC). All MTSCC tumors demonstrated moderate to high expression of VSTM2A (mean ISH score=255). VSTM2A gene expression assessed by RNA sequencing strongly correlated with VSTM2A ISH score (r(2)=0.81, P=0.00016). The majority of non-MTSCC tumors demonstrated negative or low expression of VSTM2A. IRX5, nominated as a lineage-specific biomarker, showed moderate to high expression in MTSCC tumors (mean ISH score=140). IRX5 gene expression assessed by RNA sequencing strongly correlated with IRX5 ISH score (r(2)=0.69, P=0.00291). VSTM2A (AUC: 99.2%) demonstrated better diagnostic efficacy than IRX5 (AUC: 87.5%), and may thus serve as a potential diagnostic marker to distinguish tumors with overlapping histology. Furthermore, our results suggest MTSCC displays an overlapping phenotypic expression pattern with the loop of Henle region of normal nephrons.

Objective: To demonstrate whether radiotherapy has an effect on the survival of patients with stage IVb (M1) cervical cancer, as it has not been adequately clarified., Methods: We analyzed International Federation of Gynecology and Obstetrics (FIGO) stage M1 cervical cancer diagnosed in patients between 1992 and 2013 using population-based data from the Surveillance, Epidemiology, and End Results registry. Propensity score (PS) analysis with 1:1 matching and the nearest neighbor matching method was performed to ensure well-balanced characteristics of comparison groups. Data were analyzed by Kaplan-Meier and Cox proportional hazards regression models to evaluate the overall survival (OS) and cancer-specific survival (CSS) months with corresponding 95% confidence intervals (95% CIs)., Results: In general, receiving radiotherapy significantly improved OS and CSS both before and after PS matching (PSM) (P < 0.001), with significantly improved OS (hazard ratio, 0.69; 95% CI, 0.62-0.76) and CSS (hazard ratio, 0.79; 95% CI, 0.70-0.89) after PSM in patients with stage M1 cervical cancer. Before PSM, radiotherapy was found to be associated with improved survival even for the patients with stage M1 cervical cancer with extensive metastasis (≥2 metastatic sites) (P < 0.001). Although P value was not significant for brain metastasis, the survival month was numerically improved before PSM (OS and CSS, 1 month vs 4 months). Overall, radiotherapy still significantly improved survival for patients with one metastatic site (ie, oligometastases) either before or after PSM (P < 0.05), with the survival month improved more than 6 months., Conclusions: The large Surveillance, Epidemiology, and End Results results support that radiotherapy might improve the survival of patients with metastatic cervical cancer. It might be prudent to carefully select suitable patients for radiation therapy for metastatic cervical cancer.

Background: Both hypertensive and atherosclerotic processes contribute to common carotid artery intima-media thickness (CCA-IMT). Elevated CCA-IMT may be indicative of subclinical cerebrovascular disease; however, its role in the absence of concomitant carotid artery plaque is uncertain, and few studies have examined associations in Black populations., Materials and Methods: At cohort visit 3 (1993-1995) a subset of stroke-free participants (641 Blacks and 702 Whites, mean age 63) from the Atherosclerosis Risk in Communities (ARIC) study was imaged by brain MRI and carotid ultrasound. A CCA-IMT >0.9 mm was considered elevated. Asymptomatic brain lesions ≥3 mm were considered silent brain infarctions (SBI). Subcortical SBI measuring 3 to <20 mm were considered lacunes. Associations between elevated CCA-IMT and SBI were analyzed with Poisson regression., Results: Elevated CCA-IMT was identified in 168 participants (16% of Blacks, 10% of Whites), and SBI were observed in 156 (15% of Blacks, 8% of Whites). Elevated CCA-IMT was strongly related to anterior circulation SBI, posterior circulation SBI, and lacunes. After adjustments, elevated CCA-IMT remained associated with greater number of lacunes in Blacks ([prevalence ratio, PR] = 1.60; 95% confidence interval [CI]: 1.02-2.51), but not Whites (PR = 0.85; 95% CI: 0.35-2.04); P value for interaction = 0.12. Among Black participants without concomitant carotid plaque, elevated CCA-IMT was associated with twice the number of lacunes (PR = 2.00; 95% CI: 1.05-3.82)., Conclusions: In older Black adults, elevated CCA-IMT is independently associated with lipohyalinosis of the cerebral small vessels, irrespective of concomitant carotid plaque and vascular risk factors.

Background: Previous research found racial and ethnic disparities in meeting medication therapy management (MTM) eligibility criteria implemented by the Centers for Medicare & Medicaid Services (CMS) in accordance with the Medicare Modernization Act (MMA)., Objective: To examine whether alternative MTM eligibility criteria based on the CMS Part D star ratings quality evaluation system can reduce racial and ethnic disparities., Methods: This study analyzed the Beneficiary Summary File and claims files for Medicare beneficiaries linked to the Area Health Resource File. Three million Medicare beneficiaries with continuous Parts A, B, and D enrollment in 2012-2013 were included. Proposed star ratings criteria included 9 existing medication safety and adherence measures developed mostly by the Pharmacy Quality Alliance. Logistic regression and the Blinder-Oaxaca approach were used to test disparities in meeting MMA and star ratings eligibility criteria across racial and ethnic groups. Multinomial logistic regression was used to examine whether there was a disparity reduction by comparing individuals who were MTM-eligible under MMA but not under star ratings criteria and those who were MTM-eligible under star ratings criteria but not under the MMA. Concerning MMA-based MTM criteria, main and sensitivity analyses were performed to represent the entire range of the MMA eligibility thresholds reported by plans in 2009, 2013, and proposed by CMS in 2015. Regarding star ratings criteria, meeting any 1 of the 9 measures was examined as the main analysis, and various measure combinations were examined as the sensitivity analyses., Results: In the main analysis, adjusted odds ratios for non-Hispanic blacks (backs) and Hispanics to non-Hispanic whites (whites) were 1.394 (95% CI = 1.375-1.414) and 1.197 (95% CI = 1.176-1.218), respectively, under star ratings. Blacks were 39.4% and Hispanics were 19.7% more likely to be MTM-eligible than whites. Blacks and Hispanics were less likely to be MTM-eligible than whites in some sensitivity analyses. Disparities were not completely explained by differences in patient characteristics based on the Blinder-Oaxaca approach. The multinomial logistic regression of each main analysis found significant adjusted relative risk ratios (RRR) between whites and blacks for 2009 (RRR = 0.459, 95% CI = 0.438-0.481); 2013 (RRR = 0.449, 95% CI = 0.434-0.465); and 2015 (RRR = 0.436, 95% CI = 0.425-0.446) and between whites and Hispanics for 2009 (RRR = 0.559, 95% CI = 0.528-0.593); 2013 (RRR = 0.544, 95% CI = 0.521-0.569); and 2015 (RRR = 0.503, 95% CI = 0.488-0.518). These findings indicate a significant reduction in racial and ethnic disparities when using star ratings eligibility criteria; for example, black-white disparities in the likelihood of meeting MTM eligibility criteria were reduced by 55.1% based on star ratings compared with MMA in 2013. Similar patterns were found in most sensitivity and disease-specific analyses., Conclusions: This study found that minorities were more likely than whites to be MTM-eligible under the star ratings criteria. In addition, MTM eligibility criteria based on star ratings would reduce racial and ethnic disparities associated with MMA in the general Medicare population and those with specific chronic conditions., Disclosures: Research reported in this publication was supported by the National Institute on Aging of the National Institutes of Health under award number R01AG049696. The content of this study is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Cushman reports an Eli Lilly grant and uncompensated consulting for Takeda Pharmaceuticals outside this work. The other authors have no potential conflicts of interest to report. Study concept and design were contributed by Wang and Shih, along with Wan, Kuhle, Spivey, and Cushman. Wang, Qiao, and Wan took the lead in data collection, with assistance from the other authors. Data interpretation was performed by Wang, Kuhle, and Qiao, with assistance from the other authors. The manuscript was written by Spivey and Qiao, along with the other authors, and revised by Cushman, Dagogo-Jack, and Chisholm-Burns, along with the other authors.

Identification of carotid artery atherosclerosis is conventionally based on measurements of luminal stenosis and surface irregularities using in vivo imaging techniques including sonography, CT and MR angiography, and digital subtraction angiography. However, histopathologic studies demonstrate considerable differences between plaques with identical degrees of stenosis and indicate that certain plaque features are associated with increased risk for ischemic events. The ability to look beyond the lumen using highly developed vessel wall imaging methods to identify plaque vulnerable to disruption has prompted an active debate as to whether a paradigm shift is needed to move away from relying on measurements of luminal stenosis for gauging the risk of ischemic injury. Further evaluation in randomized clinical trials will help to better define the exact role of plaque imaging in clinical decision-making. However, current carotid vessel wall imaging techniques can be informative. The goal of this article is to present the perspective of the ASNR Vessel Wall Imaging Study Group as it relates to the current status of arterial wall imaging in carotid artery disease., (© 2018 by American Journal of Neuroradiology.)

The objective of this study was to examine positive predictive value (PPV) of medication therapy management (MTM) eligibility criteria under Medicare Modernization Act (MMA) and Affordable Care Act (ACA) in identifying patients with medication utilization issues across racial and ethnic groups. The study analyzed Medicare data (2012-2013) for 2 213 594 beneficiaries. Medication utilization issues were determined based on medication utilization measures mostly developed by Pharmacy Quality Alliance. MMA was associated with higher PPV than ACA in identifying individuals with medication utilization issues among non-Hispanic blacks (blacks) and Hispanics than non-Hispanic whites (whites). For example, odds ratio for having medication utilization issues to whites when examining MMA in 2013 and ACA were 1.09 (95% confidence interval [CI] = 1.04-1.15) among blacks, and 1.17 (95% CI = 1.10-1.24) among Hispanics, in the main analysis. Therefore, MMA was associated with 9% and 17% higher PPV than ACA in identifying patients with medication utilization issues among blacks and Hispanics, respectively, than whites.

Importance: Intracranial atherosclerotic disease (ICAD) is an important cause of stroke; however, little is known about racial differences in ICAD prevalence and its risk factors., Objective: To determine racial differences in ICAD prevalence and the risk factors (both midlife and concurrent) associated with its development in a large, US community-based cohort., Design, Setting, and Participants: Analysis of 1752 black and white participants recruited from the Atherosclerosis Risk in Communities (ARIC) cohort study who underwent 3-dimensional intracranial vessel wall magnetic resonance imaging from October 18, 2011 to December 30, 2013; data analysis was performed from October 18, 2011 to May 13, 2015., Exposures: Midlife and concurrent cardiovascular risk factors., Main Outcomes and Measures: Intracranial plaque presence, size (maximum normalized wall index) and number were assessed by vessel wall magnetic resonance imaging. Midlife and concurrent vascular risk factor associations were determined by Poisson regression (plaque presence), negative binominal regression (plaque number), and linear regression (plaque size), and compared between races., Results: Of the 1752 study participants (mean [SD] age, 77.6 [5.3] years; range, 67-90 years), 1023 (58.4%) were women and 518 (29.6%) were black. Black men had the highest prevalence (50.9% vs 35.9% for black women, 35.5% for white men, and 30.2% for white women; P < .001) and the highest frequency (22.4% vs 12.1% for black women, 10.7% for white men, and 8.7% for white women; P < .01) of multiple plaques. Prevalence increased with age, reaching 50% before ages 68, 84, and 88 years in black men, white men, and white women, respectively (ICAD prevalence remained <50% in black women). Midlife hypertension and hyperlipidemia were associated with 29% (prevalence ratio [PR], 1.29; 95% CI, 1.08-1.55) and 18% (PR, 1.18; 95% CI, 0.98-1.42), respectively, increased ICAD prevalence with no significant differences between races. Midlife hypertension was also associated with larger plaques (1.11 higher mean maximum normalized wall index; 95% CI, 0.21-2.01). Midlife smoking and diabetes were associated with increased risk of ICAD in black individuals (102% [PR, 2.02; 95% CI, 1.12-3.63] and 57% [PR, 1.57; 95% CI, 1.13- 2.19], respectively), but not in white participants (P < .05 interaction by race)., Conclusions and Relevance: The prevalence of ICAD was highest in black men. Midlife smoking and diabetes were strongly associated with late-life ICAD in blacks only, whereas midlife hypertension and hyperlipidemia were associated with late-life ICAD in both races. These associations may help to explain racial differences in US stroke rates and offer insight into preventive risk-factor management strategies.

Background: Asthma is one of the most frequently targeted chronic diseases in the medication therapy management (MTM) programs of the Medicare prescription drug (Part D) benefits. Although racial and ethnic disparities in meeting eligibility criteria for MTM services have been reported, little is known about whether there would be similar disparities among adults with asthma in the United States., Methods: Adult patients with asthma (age ≥ 18) from Medical Expenditure Panel Survey (2011-2012) were analyzed. Bivariate analyses were conducted to compare the proportions of patients who would meet Medicare MTM eligibility criteria between non-Hispanic Blacks (Blacks), Hispanics and non-Hispanic Whites (Whites). Survey-weighted logistic regression was performed to adjust for patient characteristics. Main and sensitivity analyses were conducted to cover the entire range of the eligibility thresholds used by Part D plans in 2011-2012., Results: The sample included 4,455 patients with asthma, including 2,294 Whites, 1,218 Blacks, and 943 Hispanics. Blacks and Hispanics had lower proportions of meeting MTM eligibility criteria than did Whites (P < 0.001). According to the main analysis, Blacks and Hispanics had 36% and 32% lower, respectively, likelihood of MTM eligibility than Whites (odds ratio [OR]: 0.64, 95% confidence interval [CI]: 0.45-0.90; OR: 0.68, 95% CI: 0.47-0.98, respectively). Similar results were obtained in sensitivity analyses., Conclusions: There are racial and ethnic disparities in meeting Medicare Part D MTM eligibility criteria among adult patients with asthma. Future studies should examine the implications of such disparities on health outcomes of patients with asthma and explore alternative MTM eligibility criteria.

Background: People living with chronic health conditions exhibit higher risk for developing severe complications from influenza according to the Centers for Diseases Control and Prevention. Although racial and ethnic disparities in influenza vaccination have been documented, it has not been comprehensively determined whether similar disparities are present among the adult population with at least one such condition., Objective: To study if racial and ethnic disparities in relation to influenza vaccination are present in adults suffering from at least one chronic condition and if such inequalities differ between age groups., Methods: The Medical Expenditure Panel Survey (2011-2012) was used to study the adult population (age ≥18) who had at least one chronic health condition. Baseline differences in population traits across racial and ethnic groups were identified using a chi-square test. This was conducted among various age groups. In addition, survey logistic regression was utilized to produce odds ratios of receiving influenza vaccination annually between racial and ethnic groups., Results: The total sample consisted of 15,499 adults living with at least one chronic health condition. The numbers of non-Hispanic whites (whites), non-Hispanic blacks (blacks), and Hispanics were 8,658, 3,585, and 3,256, respectively. Whites (59.93%) were found to have a higher likelihood of self-reporting their receipt of the influenza vaccine in comparison to the black (48.54%) and Hispanic (48.65%) groups (P<0.001). When examining persons aged 50-64 years and ≥65 years, it was noted that the black (54.99%, 62.72%) and Hispanic (53.54%, 64.48%) population had lower rates of influenza vaccine coverage than the white population (59.22%, 77.89) (both P<0.0001). No significant differences between whites and the blacks or Hispanics were found among the groups among adults between 18 and 49 inclusive (P>0.05). After controlling for patient characteristics, the difference in influenza vaccine coverage between whites and the minority groups were no longer significant for adults aged 50-64 years. However, the difference were still statistically significant for those aged ≥65 years., Conclusions: In the United States, there are significant disparities in influenza vaccination by race and ethnicity for adults over 65 years with at least one chronic health condition. Future research is needed to help develop more targeted interventions to address these issues and improve influenza vaccination rates., Competing Interests: The authors have declared that no competing interests exist.

Background: The Medicare Prescription Drug, Improvement, and Modernization Act requires Part D plans to establish programs to provide medication therapy management (MTM) services starting from 2006. MTM services have been found to improve patient outcomes from pharmacotherapy, reduce emergency room visits and hospitalizations, and reduce health care costs in a cost-effective fashion. However, previous research found that non-Hispanic blacks (blacks) and Hispanics may be less likely to be eligible for MTM services than non-Hispanic whites (whites) among the Medicare population, according to current Medicare MTM eligibility criteria. This finding is because Medicare MTM eligibility criteria are predominantly based on medication use and costs, and blacks and Hispanics tend to use fewer prescription medications and incur lower prescription medication costs. The Patient Protection and Affordable Care Act (PPACA) laid out a set of MTM eligibility criteria for eligible entities to target patients for MTM services: "(1) take 4 or more prescribed medications ...; (2) take any 'high risk' medications; (3) have 2 or more chronic diseases ... or (4) have undergone a transition of care, or other factors ... that are likely to create a high risk of medication-related problems.", Objectives: To (a) examine racial/ethnic disparities in meeting the eligibility criteria for MTM services in PPACA among the Medicare population and (b) determine whether there would be greater disparities in health and economic outcomes among MTM-ineligible than MTM-eligible groups., Methods: This was a retrospective cross-sectional analysis of the Medicare Current Beneficiaries Survey (2007-2008). To determine medication characteristics, the U.S. Food and Drug Administration's Electronic Orange Book was also used. Proportions of the population eligible for MTM services based on PPACA MTM eligibility criteria were compared across racial and ethnic groups using a chi-square test; a logistic regression model was used to adjust for population sociodemographic and health characteristics. Health and economic outcomes examined included health status (self-perceived good health status, number of chronic diseases, activities of daily living [ADLs], and instrumental activities of daily living [IADLs]), health services utilization and costs (physician visits, emergency room visits, and total health care costs), and medication use patterns (generic dispensing ratio). To determine difference in disparities across MTM eligibility categories, difference-in-differences regressions of various functional forms were employed, depending on the nature of the dependent variables. Interaction terms between the dummy variables for minority groups (e.g., blacks or Hispanics) and MTM eligibility were included to test whether disparity patterns varied between MTM-ineligible and MTM-eligible individuals., Results: The sample consisted of 12,966 Medicare beneficiaries, of which 11,161 were white, 930 were black, and 875 were Hispanic. Of the study sample, 9,992 whites (86.4%), 825 blacks (86.3%), and 733 Hispanics (80.6%) were eligible for MTM. The difference between whites and Hispanics was significant (P  less than  0.050), and the difference between whites and blacks was not significant (P  greater than 0.050). In multivariate analyses, significant disparity in eligibility for MTM services was found only between Hispanics and whites (odds ratio [OR] = 0.59; 95% CI = 0.43-0.82) but not between blacks and whites (OR = 0.78; 95% CI = 0.55-1.09). Disparities were greater among the MTM-ineligible than the MTM-eligible populations in self-perceived health status, ADLs, and IADLs for both blacks and Hispanics compared with whites. When analyzing the number of chronic conditions, the number and costs of physician visits, and total health care costs, the authors of this study found lower racial and ethnic disparities among the ineligible population than the eligible population., Conclusions: Hispanics are significantly less likely than whites to qualify for MTM among the Medicare population, according to MTM eligibility criteria stipulated in the PPACA. PPACA MTM eligibility criteria may aggravate existing racial and ethnic disparities in health status but may remediate racial and ethnic disparities in health services utilization. Alternative MTM eligibility criteria other than PPACA MTM eligibility criteria may be needed to improve the efficiency and equity of access to Medicare Part D MTM programs.

Background: Use of warfarin is standard of care for stroke prevention in patients with atrial fibrillation (AF). However, AF patients experience high rates of warfarin discontinuation/interruption, resulting in increased health risks and health care costs. As such, it is important to study the rates and predictors of warfarin discontinuation/interruption in this population., Objectives: To determine (a) rates of warfarin discontinuation and interruption and (b) demographic, clinical, and health care-related factors associated with discontinuation and interruption in patients with nonvalvular AF (NVAF) in the usual clinical practice settings in the United States., Methods: This retrospective cohort study used the MarketScan Database and included patients (aged ≥ 18 years) with NVAF who were initiated on warfarin. The study period was January 1, 2008, to June 30, 2012. To be included, patients were required to have at least 2 claims with AF diagnosis separated by ≥ 30 days and ≤ 12 months and at least 1 outpatient claim. Warfarin initiation had to occur within 30 days of the AF diagnosis. Patients also had to have continuous enrollment in prescription drug plans from 6 months prior to warfarin use to at least 12 months after warfarin initiation. Patients were followed for 1 year after warfarin initiation. Persistence was defined as warfarin therapy without a gap ≥ 45 days between the end date of the former prescription and the start date of the current prescription or with international normalized ratio (INR) monitoring at least every 42 days. Interruption was defined as a gap in warfarin therapy ≥ 45 days and ≤ 90 days between the end date of the former prescription and the start date of the current prescription and without INR monitoring at least every 42 days. Discontinuation was defined as greater than 90 days without warfarin therapy between the end date of the former prescription and the start date of the current prescription and without INR monitoring at least every 42 days. Chi-square tests were used to analyze categorical variables, and independent samples t-tests were used for continuous variables. Cox proportional hazards regression model was performed to determine factors associated with warfarin discontinuation/interruption, including demographic (e.g., age, gender); clinical (e.g., comorbidities, CHADS2 score); and health care-related (e.g., hospitalizations or emergency room visits) characteristics. Sensitivity analyses were conducted by varying prescription gaps by 7, 14, and 30 days., Results: A total of 58,593 patients with NVAF were included. The mean age was approximately 71 years (SD = 12.00) and mean CHADS2 score was 1.66 (SD = 1.23). The majority of patients were male (60%). During 12 months after warfarin initiation, 45% of patients were persistent with warfarin; 12% had interruption without discontinuation; and 43% had discontinuation. The risk of warfarin interruption or discontinuation was significantly greater in patients who were younger than 65 years (HR = 1.22; 95% CI = 1.19-1.25), lived in the West (HR = 1.07; 95% CI = 1.03-1.11), had history of anemia (HR = 1.10; 95% CI = 1.06-1.14), had history of bleeding (HR = 1.10; 95% CI = 1.06-1.14), or had history of hospitalization or emergency room visits (HR = 1.11; 95% CI = 1.08-1.13). The significant factors associated with interruption and discontinuation were similar. In the sensitivity analyses, the significant factors associated with discontinuation/interruption were similar across different prescription gaps., Conclusions: In the U.S. clinical practice setting, more than 50% of NVAF patients discontinued or interrupted warfarin within 1 year after initiation. Aged less than  65 years, history of anemia, and history of hospitalization/emergency room visits were associated with increased risk of discontinuation/interruption. Given the high prevalence of warfarin discontinuation/interruption, health care providers should take a more active role in understanding and addressing the reasons behind patient discontinuation/interruption.

Objective: To examine the association of dietary quality and risk of incident diabetes overall and by race/ethnicity among postmenopausal women enrolled in the Women's Health Initiative (WHI)., Research Methods and Procedures: The WHI recruited 161,808 postmenopausal women between 1993 and 1998, and followed them until 2005. Incident diabetes was determined annually over an average of 7.6 years from enrollment. At baseline, all participants completed a Food Frequency Questionnaire (FFQ). Dietary quality was assessed by the Alternate Healthy Eating Index (AHEI), calculated from the baseline FFQ responses., Results: There were 10,307 incident cases of self-reported treated diabetes over 1,172,761 person-years of follow-up. Most participants did not meet the AHEI dietary goals; that is, only 0.1% of women met or exceeded the recommended consumption of vegetables, and few (17.3%) met or exceeded the recommended level for total fiber. After adjusting for potential confounders, women in the highest quintile of the AHEI score were 24% less likely to develop diabetes relative to women in the lowest quintile of AHEI [hazard ratio (HR)=0.76 (95% CI: 0.70-0.82)]. This association was observed in Whites [HR=0.74 (95% CI: 0.68-0.82)] and Hispanics [HR=0.68 (95% CI: 0.46-0.99)], but not in Blacks [HR=0.85 (95% CI: 0.69-1.05)] or Asians [HR=0.88 (95% CI: 0.57-1.38)]., Conclusion: These findings support a protective role of healthful eating choices in reducing the risk of developing diabetes, after adjusting for other lifestyle factors, in White and Hispanic postmenopausal women. Future studies are needed to investigate the relationship between dietary quality and risk of diabetes among Blacks and Asians in relationship to other lifestyle factors.

Background: Previous studies have found that racial and ethnic minorities would be less likely to meet the Medicare eligibility criteria for medication therapy management (MTM) services than their non-Hispanic White counterparts., Objectives: To examine whether racial and ethnic disparities in health status, health services utilization and costs, and medication utilization patterns among MTM-ineligible individuals differed from MTM-eligible individuals., Methods: This study analyzed Medicare beneficiaries in 2004-2005 Medicare Current Beneficiary Survey. Various multivariate regressions were employed depending on the nature of dependent variables. Interaction terms between the dummy variables for Blacks (and Hispanics) and MTM eligibility were included to test whether disparity patterns varied between MTM-ineligible and MTM-eligible individuals. Main and sensitivity analyses were conducted for MTM eligibility thresholds for 2006 and 2010., Results: Based on the main analysis for 2006 MTM eligibility criteria, the proportions for self-reported good health status for Whites and Blacks were 82.82% vs. 70.75%, respectively (difference = 12.07%; P < 0.001), among MTM-ineligible population; and 56.98% vs. 52.14%, respectively (difference = 4.84%; P = 0.31), among MTM-eligible population. The difference between these differences was 7.23% (P < 0.001). In the adjusted logistic regression, the interaction effect for Blacks and MTM eligibility had an OR of 1.57 (95% Confidence Interval, or CI = 0.98-2.52) on multiplicative term and difference in odds of 2.38 (95% CI = 1.54-3.22) on additive term. Analyses for disparities between Whites and Hispanics found similar disparity patterns. All analyses for 2006 and 2010 eligibility criteria generally reported similar patterns. Analyses of other measures did not find greater racial or ethnic disparities among the MTM-ineligible than MTM-eligible individuals., Conclusions: Disparities in MTM eligibility may aggravate existing racial and ethnic disparities in health outcomes. However, disparities in MTM eligibility may not aggravate existing disparities in health services utilization and costs and medication utilization patterns. Future studies should examine the effects of Medicare Part D on these disparities., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Non-Hispanic Blacks (Blacks) and Hispanics have a lower likelihood of being eligible for medication therapy management (MTM) services than do non-Hispanic Whites (Whites) based on Medicare MTM eligibility criteria., Objectives: To determine whether MTM eligibility criteria would perform differently over time, this study examined the trend of MTM disparities from 1996-1997 to 2007-2008., Methods: The study populations were Medicare beneficiaries from the Medical Expenditure Panel Survey. Proportions and the odds of MTM eligibility were compared between Whites and ethnic minorities. The trend of disparities was examined by including in logistic regression models interaction terms between dummy variables for the minority groups and 2007-2008. MTM eligibility thresholds for 2008 and 2010-2011 were analyzed. Main and sensitivity analyses were conducted to represent the entire range of the eligibility criteria., Results: This study found no statistical significant racial or ethnic disparities associated with the MTM eligibility criteria for 2008 among the Medicare population during 1996-1997. However, racial disparities associated with 2010-2011 MTM eligibility criteria were significant according to multivariate analyses among the Medicare population during 1996-1997. During 2007-2008, both racial and ethnic disparities associated with both 2008 MTM eligibility criteria and 2010-2011 eligibility criteria were generally significant. Disparity patterns did not exhibit a statistically significant change from 1996-1997 to 2007-2008., Conclusions: Racial and ethnic disparities in meeting MTM eligibility criteria may not decrease over time unless MTM eligibility criteria are changed., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Context: Peroxisome proliferator-activated receptor-γ (PPARG) plays a pivotal role in adipogenesis and glucose homeostasis., Objective: We investigated whether PPARG gene variants were associated with type 2 diabetes (T2D) risk in the multiethnic Women's Health Initiative (WHI)., Research Design and Methods: We assessed PPARG single-nucleotide polymorphisms (SNPs) in a case-control study nested in the prospective WHI observational study (WHI-OS) (1543 T2D cases and 2170 matched controls). After identifying 24 tagSNPs, we used multivariable logistic regression models and haplotype-based analyses to estimate these tagSNP-T2D associations. Single-SNP analyses were also conducted in another study of 5642 African American and Hispanic American women in the WHI SNP Health Association Resource (WHI-SHARe)., Results: We found a borderline significant association between the Pro12Ala (rs1801282) variant and T2D risk in WHI-OS [odds ratio (OR) 0.51, 95% confidence interval (CI) 0.31-0.83, P = .01, combined group, additive model; P = .04, Hispanic American] and WHI-SHARe (OR 0.25, 95% CI 0.08-0.77, P = .02, Hispanic American) participants. In promoter region, rs6809631, rs9817428, rs10510411, rs12629293, and rs12636454 were also associated with T2D risk (range ORs 0.68-0.78, 95% CIs 0.52-0.91 to 0.60-1.00, P ≤ .05) in WHI-OS, in which rs9817428 was replicated in then WHI-SHARe Hispanic American group (P = .04)., Conclusions: The association between PPARG Pro12Ala SNP and increased T2D susceptibility was confirmed, with Pro12 as risk allele. Additional significant loci included 5 PPARG promoter variants.

Objective: To examine determinants of racial/ethnic differences in diabetes incidence among postmenopausal women participating in the Women's Health Initiative., Research Design and Methods: Data on race/ethnicity, baseline diabetes prevalence, and incident diabetes were obtained from 158,833 women recruited from 1993-1998 and followed through August 2009. The relationship between race/ethnicity, other potential risk factors, and the risk of incident diabetes was estimated using Cox proportional hazards models from which hazard ratios (HRs) and 95% CIs were computed., Results: Participants were aged 63 years on average at baseline. The racial/ethnic distribution was 84.1% non-Hispanic white, 9.2% non-Hispanic black, 4.1% Hispanic, and 2.6% Asian. After an average of 10.4 years of follow-up, compared with whites and adjusting for potential confounders, the HRs for incident diabetes were 1.55 for blacks (95% CI 1.47-1.63), 1.67 for Hispanics (1.54-1.81), and 1.86 for Asians (1.68-2.06). Whites, blacks, and Hispanics with all factors (i.e., weight, physical activity, dietary quality, and smoking) in the low-risk category had 60, 69, and 63% lower risk for incident diabetes. Although contributions of different risk factors varied slightly by race/ethnicity, most findings were similar across groups, and women who had both a healthy weight and were in the highest tertile of physical activity had less than one-third the risk of diabetes compared with obese and inactive women., Conclusions: Despite large racial/ethnic differences in diabetes incidence, most variability could be attributed to lifestyle factors. Our findings show that the majority of diabetes cases are preventable, and risk reduction strategies can be effectively applied to all racial/ethnic groups.

Background: This study investigates whether the incidence of new-onset diabetes mellitus (DM) is associated with statin use among postmenopausal women participating in the Women's Health Initiative (WHI)., Methods: The WHI recruited 161,808 postmenopausal women aged 50 to 79 years at 40 clinical centers across the United States from 1993 to 1998 with ongoing follow-up. The current analysis includes data through 2005. Statin use was captured at enrollment and year 3. Incident DM status was determined annually from enrollment. Cox proportional hazards models were used to estimate the risk of DM by statin use, with adjustments for propensity score and other potential confounding factors. Subgroup analyses by race/ethnicity, obesity status, and age group were conducted to uncover effect modification., Results: This investigation included 153,840 women without DM and no missing data at baseline. At baseline, 7.04% reported taking statin medication. There were 10,242 incident cases of self-reported DM over 1,004,466 person-years of follow-up. Statin use at baseline was associated with an increased risk of DM (hazard ratio [HR], 1.71; 95% CI, 1.61-1.83). This association remained after adjusting for other potential confounders (multivariate-adjusted HR, 1.48; 95% CI, 1.38-1.59) and was observed for all types of statin medications. Subset analyses evaluating the association of self-reported DM with longitudinal measures of statin use in 125,575 women confirmed these findings., Conclusions: Statin medication use in postmenopausal women is associated with an increased risk for DM. This may be a medication class effect. Further study by statin type and dose may reveal varying risk levels for new-onset DM in this population.

While the popularity of and expenditures for herbal therapies (aka "ethnomedicines") have increased globally in recent years, their efficacy, safety, mechanisms of action, potential as novel therapeutic agents, cost-effectiveness, or lack thereof, remain poorly defined and controversial. Moreover, published clinical trials evaluating the efficacy of herbal therapies have rightfully been criticized, post hoc, for their lack of quality assurance and reproducibility of study materials, as well as a lack of demonstration of plausible mechanisms and dosing effects. In short, clinical botanical investigations have suffered from the lack of a cohesive research strategy which draws on the expertise of all relevant specialties. With this as background, US and Chinese co-investigators with expertise in Traditional Chinese Medicine (TCM), botany, chemistry and drug discovery, have jointly established a prototype library consisting of 202 authenticated medicinal plant and fungal species that collectively represent the therapeutic content of the majority of all commonly prescribed TCM herbal prescriptions. Currently housed at Harvard University, the library consists of duplicate or triplicate kilogram quantities of each authenticated and processed species, as well as "detanninized" extracts and sub-fractions of each mother extract. Each species has been collected at 2-3 sites, each separated geographically by hundreds of miles, with precise GPS documentation, and authenticated visually and chemically prior to testing for heavy metals and/or pesticides contamination. An explicit decision process has been developed whereby samples with the least contamination were selected to undergo ethanol extraction and HPLC sub-fractionation in preparation for high throughput screening across a broad array of biological targets including cancer biology targets. As envisioned, the subfractions in this artisan collection of authenticated medicinal plants will be tested for biological activity individually and in combinations (i.e., "complex mixtures") consistent with traditional ethnomedical practice. This manuscript summarizes the rationale, methods and preliminary "proof of principle" for the establishment of this prototype, authenticated medicinal plant library. It is hoped that these methods will foster scientific discoveries with therapeutic potential and enhance efforts to systematically evaluate commonly used herbal therapies worldwide., (Copyright © 2010 Elsevier B.V. All rights reserved.)