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Surveillance for sulfadoxine-pyrimethamine resistant malaria parasites in the Lake and Southern Zones, Tanzania, using pooling and next-generation sequencing

Mon, 07/17/2017 - 7:36pm

BACKGROUND: Malaria in pregnancy (MiP) remains a major public health challenge in areas of high malaria transmission. Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is recommended to prevent the adverse consequences of MiP. The effectiveness of SP for IPTp may be reduced in areas where the dhps581 mutation (a key marker of high level SP resistance) is found; this mutation was previously reported to be common in the Tanga Region of northern Tanzania, but there are limited data from other areas. The frequency of molecular markers of SP resistance was investigated in malaria parasites from febrile patients at health centres (HC) in seven regions comprising the Lake and Southern Zones of mainland Tanzania as part of the ongoing efforts to generate national-wide data of SP resistance.

METHODS: A cross-sectional survey was conducted in the outpatient departments of 14 HCs in seven regions from April to June, 2015. 1750 dried blood spot (DBS) samples were collected (117 to 160 per facility) from consenting patients with positive rapid diagnostic tests for malaria, and no recent (within past 2 months) exposure to SP or related drugs. DNA was extracted from the DBS, pooled by HC, and underwent pooled targeted amplicon deep sequencing to yield estimates of mutated parasite allele frequency at each locus of interest.

RESULTS: The dhps540 mutation was common across all 14 sites, ranging from 55 to 98.4% of sequences obtained. Frequency of the dhps581 mutation ranged from 0 to 2.4%, except at Kayanga HC (Kagera Region, Lake Zone) where 24.9% of sequences obtained were mutated. The dhfr164 mutation was detected only at Kanyanga HC (0.06%).

CONCLUSION: By pooling DNA extracts, the allele frequency of mutations in 14 sites could be directly determined on a single deep-sequencing run. The dhps540 mutant was very common at all locations. Surprisingly, the dhps581 was common at one health center, but rare in all the others, suggesting that there is geographic micro-heterogeneity in mutant distribution and that accurate surveillance requires inclusion of multiple sites. A better understanding of the effect of the dhps581 mutant on the efficacy of IPTp-SP is needed.

CRISPR/Cas9-mediated genome editing induces exon skipping by alternative splicing or exon deletion

Mon, 07/17/2017 - 7:36pm

CRISPR is widely used to disrupt gene function by inducing small insertions and deletions. Here, we show that some single-guide RNAs (sgRNAs) can induce exon skipping or large genomic deletions that delete exons. For example, CRISPR-mediated editing of beta-catenin exon 3, which encodes an autoinhibitory domain, induces partial skipping of the in-frame exon and nuclear accumulation of beta-catenin. A single sgRNA can induce small insertions or deletions that partially alter splicing or unexpected larger deletions that remove exons. Exon skipping adds to the unexpected outcomes that must be accounted for, and perhaps taken advantage of, in CRISPR experiments.

Genome-Wide CRISPR Screen Identifies Regulators of Mitogen-Activated Protein Kinase as Suppressors of Liver Tumors in Mice

Mon, 07/17/2017 - 7:36pm

BACKGROUND and AIMS: It has been a challenge to identify liver tumor suppressors or oncogenes due to the genetic heterogeneity of these tumors. We performed a genome-wide screen to identify suppressors of liver tumor formation in mice, using CRISPR-mediated genome editing.

METHODS: We performed a genome-wide CRISPR/Cas9-based knockout screen of P53-null mouse embryonic liver progenitor cells that overexpressed MYC. We infected p53-/-;Myc;Cas9 hepatocytes with the mGeCKOa lentiviral library of 67,000 single-guide RNAs (sgRNAs), targeting 20,611 mouse genes, and transplanted the transduced cells subcutaneously into nude mice. Within 1 month, all the mice that received the sgRNA library developed subcutaneous tumors. We performed high-throughput sequencing of tumor DNA and identified sgRNAs increased at least 8-fold compared to the initial cell pool. To validate the top 10 candidate tumor suppressors from this screen, we collected data from patients with hepatocellular carcinoma (HCC) using the Cancer Genome Atlas and COSMIC databases. We used CRISPR to inactivate candidate tumor suppressor genes in p53-/-;Myc;Cas9 cells and transplanted them subcutaneously into nude mice; tumor formation was monitored and tumors were analyzed by histology and immunohistochemistry. Mice with liver-specific disruption of p53 were given hydrodynamic tail-vein injections of plasmids encoding Myc and sgRNA/Cas9 designed to disrupt candidate tumor suppressors; growth of tumors and metastases was monitored. We compared gene expression profiles of liver cells with vs without tumor suppressor gene disrupted by sgRNA/Cas9. Genes found to be up-regulated after tumor suppressor loss were examined in liver cancer cell lines; their expression was knocked down using small hairpin RNAs, and tumor growth was examined in nude mice. Effects of the MEK inhibitors AZD6244, U0126, and trametinib, or the multi-kinase inhibitor sorafenib, were examined in human and mouse HCC cell lines.

RESULTS: We identified 4 candidate liver tumor suppressor genes not previously associated with liver cancer (Nf1, Plxnb1, Flrt2, and B9d1). CRISPR-mediated knockout of Nf1, a negative regulator of RAS, accelerated liver tumor formation in mice. Loss of Nf1 or activation of RAS up-regulated the liver progenitor cell markers HMGA2 and SOX9. RAS pathway inhibitors suppressed the activation of the Hmga2 and Sox9 genes that resulted from loss of Nf1 or oncogenic activation of RAS. Knockdown of HMGA2 delayed formation of xenograft tumors from cells that expressed oncogenic RAS. In human HCCs, low levels of NF1 messenger RNA or high levels of HMGA2 messenger RNA were associated with shorter patient survival time. Liver cancer cells with inactivation of Plxnb1, Flrt2, and B9d1 formed more tumors in mice and had increased levels of mitogen-activated protein kinase phosphorylation.

CONCLUSIONS: Using a CRISPR-based strategy, we identified Nf1, Plxnb1, Flrt2, and B9d1 as suppressors of liver tumor formation. We validated the observation that RAS signaling, via mitogen-activated protein kinase, contributes to formation of liver tumors in mice. We associated decreased levels of NF1 and increased levels of its downstream protein HMGA2 with survival times of patients with HCC. Strategies to inhibit or reduce HMGA2 might be developed to treat patients with liver cancer.

GUIDEseq: a bioconductor package to analyze GUIDE-Seq datasets for CRISPR-Cas nucleases

Mon, 07/17/2017 - 7:36pm

BACKGROUND: Genome editing technologies developed around the CRISPR-Cas9 nuclease system have facilitated the investigation of a broad range of biological questions. These nucleases also hold tremendous promise for treating a variety of genetic disorders. In the context of their therapeutic application, it is important to identify the spectrum of genomic sequences that are cleaved by a candidate nuclease when programmed with a particular guide RNA, as well as the cleavage efficiency of these sites. Powerful new experimental approaches, such as GUIDE-seq, facilitate the sensitive, unbiased genome-wide detection of nuclease cleavage sites within the genome. Flexible bioinformatics analysis tools for processing GUIDE-seq data are needed.

RESULTS: Here, we describe an open source, open development software suite, GUIDEseq, for GUIDE-seq data analysis and annotation as a Bioconductor package in R. The GUIDEseq package provides a flexible platform with more than 60 adjustable parameters for the analysis of datasets associated with custom nuclease applications. These parameters allow data analysis to be tailored to different nuclease platforms with different length and complexity in their guide and PAM recognition sequences or their DNA cleavage position. They also enable users to customize sequence aggregation criteria, and vary peak calling thresholds that can influence the number of potential off-target sites recovered. GUIDEseq also annotates potential off-target sites that overlap with genes based on genome annotation information, as these may be the most important off-target sites for further characterization. In addition, GUIDEseq enables the comparison and visualization of off-target site overlap between different datasets for a rapid comparison of different nuclease configurations or experimental conditions. For each identified off-target, the GUIDEseq package outputs mapped GUIDE-Seq read count as well as cleavage score from a user specified off-target cleavage score prediction algorithm permitting the identification of genomic sequences with unexpected cleavage activity.

CONCLUSION: The GUIDEseq package enables analysis of GUIDE-data from various nuclease platforms for any species with a defined genomic sequence. This software package has been used successfully to analyze several GUIDE-seq datasets. The software, source code and documentation are freely available at http://www.bioconductor.org/packages/release/bioc/html/GUIDEseq.html .

IRaPPA: information retrieval based integration of biophysical models for protein assembly selection

Mon, 07/17/2017 - 7:36pm

Motivation: In order to function, proteins frequently bind to one another and form 3D assemblies. Knowledge of the atomic details of these structures helps our understanding of how proteins work together, how mutations can lead to disease, and facilitates the designing of drugs which prevent or mimic the interaction.

Results: Atomic modeling of protein-protein interactions requires the selection of near-native structures from a set of docked poses based on their calculable properties. By considering this as an information retrieval problem, we have adapted methods developed for Internet search ranking and electoral voting into IRaPPA, a pipeline integrating biophysical properties. The approach enhances the identification of near-native structures when applied to four docking methods, resulting in a near-native appearing in the top 10 solutions for up to 50% of complexes benchmarked, and up to 70% in the top 100.

Availability and Implementation: IRaPPA has been implemented in the SwarmDock server ( http://bmm.crick.ac.uk/ approximately SwarmDock/ ), pyDock server ( http://life.bsc.es/pid/pydockrescoring/ ) and ZDOCK server ( http://zdock.umassmed.edu/ ), with code available on request.

Contact: moal@ebi.ac.uk.

Supplementary information: Supplementary data are available at Bioinformatics online.

Testing U.S. State-Based Training Models to Meet Health Workforce Needs in Long-Term Care

Mon, 07/17/2017 - 9:50am

As the United States health care system grows, so does the need for trained medical professionals - especially in the form of in home care aides. The US Bureau of of Labor Statistics projects a 26 percent increase in demand for these kinds of health workers by 2024 - and with rising demand comes new need for proper medical education. This study presents case studies of six state-based training models for new home care aides and discusses the recruitment process, curriculum design and delivery methods of all six methods.

The data researches collected to perform this case study came from state-level demonstration project reports, demographic data compiled by national evaluators and collaborative topic-based analysis conducted by individual teams. By comparing this information from state to state, they were able to identify methods they deemed successful for training in home care aides.

Researchers concluded government funded, evidence-based and person-centered home care aide training programs like the ones they studied could produce well equipped home care workers that were prepared to work with the elderly and individuals with disabilities. However, further research is still needed nationally and internationally to analyze the actual effects these new workers have on patients.

Substance Use Disorder Privacy Law Limits Both Payers, Prescribers

Mon, 07/17/2017 - 9:50am

We should reform or align 42 CFR Part 2 with HIPAA to better serve patients with substance use disorder, UMass Medical School pharmacists Kimberly Lenz and Tyson Thompson write in an opinion piece for Managed Healthcare Executive.

The Effect of a Federal Controlled Substance Act Schedule Change on Hydrocodone Combination Products Claims in a Medicaid Population

Mon, 07/17/2017 - 9:50am

BACKGROUND: In 2012, hydrocodone combination products (HCPs) were the most prescribed medications in the United States. Under the Controlled Substance Act of 1970, hydrocodone alone was classified as a Schedule II drug, while HCPs were classified as Schedule III, indicating a lower risk for abuse and misuse. However, according to a Drug Enforcement Agency analysis, the addition of nonopioids has not been shown to diminish abuse potential of hydrocodone. In response to concerns for drug abuse and overdose, the Drug Enforcement Agency rescheduled HCPs to Schedule II in October 2014, with the intent of limiting overprescribing and increasing awareness of their abuse potential. However, it is unknown whether this has affected the overall claims for HCPs in a Medicaid population.

OBJECTIVES: To (a) compare the trend in HCP prescription claims with select non-HCP (opioid and nonopioid) analgesic claims before and after the HCP schedule change in the Massachusetts Medicaid fee-for-service/Primary Care Clinician plan population and (b) identify if there was a change in HCP new start member and claim characteristics before and after the HCP schedule change.

METHODS: This quasi-experimental, retrospective study used enrollment and pharmacy claims data to evaluate all members in the study population 1 year before and after the HCP schedule change. The number of claims for HCPs and select non-HCP analgesics was reported as the monthly rate per total population, and an interrupted time series analysis compared the change in the monthly rate of claims across groups. Members with 1 or more pharmacy claims for a new HCP prescription during a 5-month period before or after the HCP schedule change were analyzed to determine member demographics (age, gender, and number of claims) and claim characteristics (average daily dose, average quantity per claim, and days supply).

RESULTS: The rate of HCP claims increased before and decreased after the HCP schedule change. Controlling for the trend during the period before the HCP schedule change, the rate of HCP claims per 1,000 members per month decreased at a greater rate than non-HCP analgesics in the period after the HCP schedule change (P < 0.001). The percentage of HCP claims for new start members decreased after the HCP schedule change (44.9% vs. 34.1% of all HCP claims pre- to post-schedule change; P < 0.001). In the group of new starts, there was not a significant difference in the average daily dose (26.3 mg vs. 26.4 mg; P = 0.69), while there was a decrease in average number of tablets dispensed per claim (from 37.1 to 20.3 tablets; P < 0.001) and an increase in the percentage of claims for a shorter days supply (from 57.7% to 81.6%; P < 0.001).

CONCLUSIONS: The findings of this study suggest that the HCP schedule change may have contributed to the decrease in claims for HCPs in a Medicaid population. After the HCP schedule change, there was a trend towards decreased HCP use among new starts.

DISCLOSURES: No outside funding supported this study. The authors have nothing to disclose. Study concept and design were contributed by all authors except for Arnold and Clements. Tran, Arnold, and Clements took the lead in data collection, along with Peristere, and data interpretation was performed by all the authors, except Arnold. The manuscript was written primarily by Tran, along with Lavitas, Stevens, and Greenwood, and revised by all the authors except Arnold and Peristere. A poster of this research project was presented at the Academy of Managed Care Pharmacy's 2016 Annual Meeting in San Francisco, California, April 2016.

Patient navigation and financial incentives to promote smoking cessation in an underserved primary care population: A randomized controlled trial protocol

Mon, 07/17/2017 - 8:16am

Despite the high risk of tobacco-related morbidity and mortality among low-income persons, few studies have connected low-income smokers to evidence-based treatments. We will examine a smoking cessation intervention integrated into primary care. To begin, we completed qualitative formative research to refine an intervention utilizing the services of a patient navigator trained to promote smoking cessation. Next, we will conduct a randomized controlled trial combining two interventions: patient navigation and financial incentives. The goal of the intervention is to promote smoking cessation among patients who receive primary care in a large urban safety-net hospital. Our intervention will encourage patients to utilize existing smoking cessation resources (e.g., quit lines, smoking cessation groups, discussing smoking cessation with their primary care providers). To test our intervention, we will conduct a randomized controlled trial, randomizing 352 patients to the intervention condition (patient navigation and financial incentives) or an enhanced traditional care control condition. We will perform follow-up at 6, 12, and 18 months following the start of the intervention. Evaluation of the intervention will target several implementation variables: reach (participation rate and representativeness), effectiveness (smoking cessation at 12 months [primary outcome]), unintended consequences (e.g., purchase of illicit substances with incentive money), adoption (use of intervention across primary care suites), implementation (delivery of intervention), and maintenance (smoking cessation after conclusion of intervention). Improving the implementation of smoking cessation interventions in primary care settings serving large underserved populations could have substantial public health impact, reducing cancer-related morbidity/mortality and associated health disparities.

Impact of Type 2 Diabetes and Postmenopausal Hormone Therapy on Incidence of Cognitive Impairment in Older Women

Mon, 07/17/2017 - 8:16am

OBJECTIVE: In older women, higher levels of estrogen may exacerbate the increased risk for cognitive impairment conveyed by diabetes. We examined whether the effect of postmenopausal hormone therapy (HT) on cognitive impairment incidence differs depending on type 2 diabetes.

RESEARCH DESIGN AND METHODS: The Women's Health Initiative (WHI) randomized clinical trials assigned women to HT (0.625 mg/day conjugated equine estrogens with or without [i.e., unopposed] 2.5 mg/day medroxyprogesterone acetate) or matching placebo for an average of 4.7-5.9 years. A total of 7,233 women, aged 65-80 years, were classified according to type 2 diabetes status and followed for probable dementia and cognitive impairment (mild cognitive impairment or dementia).

RESULTS: Through a maximum of 18 years of follow-up, women with diabetes had increased risk of probable dementia (hazard ratio [HR] 1.54 [95% CI 1.16-2.06]) and cognitive impairment (HR 1.83 [1.50-2.23]). The combination of diabetes and random assignment to HT increased their risk of dementia (HR 2.12 [1.47-3.06]) and cognitive impairment (HR 2.20 [1.70-2.87]) compared with women without these conditions, interaction P = 0.09 and P = 0.08. These interactions appeared to be limited to women assigned to unopposed conjugated equine estrogens.

CONCLUSIONS: These analyses provide additional support to a prior report that higher levels of estrogen may exacerbate risks that type 2 diabetes poses for cognitive function in older women. The role estrogen plays in suppressing non-glucose-based energy sources in the brain may explain this interaction. long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Impact of Risk Adjustment for Socioeconomic Status on Risk-adjusted Surgical Readmission Rates

Mon, 07/17/2017 - 8:16am

OBJECTIVE: To assess whether differences in readmission rates between safety-net hospitals (SNH) and non-SNHs are due to differences in hospital quality, and to compare the results of hospital profiling with and without SES adjustment.

BACKGROUND: In response to concerns that quality measures unfairly penalizes SNH, NQF recently recommended that performance measures adjust for socioeconomic status (SES) when SES is a risk factor for poor patient outcomes.

METHODS: Multivariate regression was used to examine the association between SNH status and 30-day readmission after major surgery. The results of hospital profiling with and without SES adjustment were compared using the CMS Hospital Compare and the Hospital Readmissions Reduction Program (HRRP) methodologies.

RESULTS: Adjusting for patient risk and SES, patients admitted to SNHs were not more likely to be readmitted compared with patients in in non-SNHs (AOR 1.08; 95% CI:0.95-1.23; P = 0.23). The results of hospital profiling based on Hospital Compare were nearly identical with and without SES adjustment (ICC 0.99, kappa 0.96). Using the HRRP threshold approach, 61% of SNHs were assigned to the penalty group versus 50% of non-SNHs. After adjusting for SES, 51% of SNHs were assigned to the penalty group.

CONCLUSIONS: Differences in surgery readmissions between SNHs and non-SNHs are due to differences in the patient case mix of low-SES patients, and not due to differences in quality. Adjusting readmission measures for SES leads to changes in hospital ranking using the HRRP threshold approach, but not using the CMS Hospital Compare methodology. CMS should consider either adjusting for the effects of SES when calculating readmission thresholds for HRRP, or replace it with the approach used in Hospital Compare.

Adaptation of community health worker-delivered behavioral activation for torture survivors in Kurdistan, Iraq

Mon, 07/17/2017 - 8:16am

BACKGROUND: Growing evidence supports the use of Western therapies for the treatment of depression, trauma, and stress delivered by community health workers (CHWs) in conflict-affected, resource-limited countries. A recent randomized controlled trial (Bolton et al. 2014a) supported the efficacy of two CHW-delivered interventions, cognitive processing therapy (CPT) and brief behavioral activation treatment for depression (BATD), for reducing depressive symptoms and functional impairment among torture survivors in the Kurdish region of Iraq.

METHODS: This study describes the adaptation of the CHW-delivered BATD approach delivered in this trial (Bolton et al.2014a), informed by the Assessment-Decision-Administration-Production-Topical experts-Integration-Training-Testing (ADAPT-ITT) framework for intervention adaptation (Wingood and DiClemente, 2008). Cultural modifications, adaptations for low-literacy, and tailored training and supervision for non-specialist CHWs are presented, along with two clinical case examples to illustrate delivery of the adapted intervention in this setting.

RESULTS: Eleven CHWs, a study psychiatrist, and the CHW clinical supervisor were trained in BATD. The adaptation process followed the ADAPT-ITT framework and was iterative with significant input from the on-site supervisor and CHWs. Modifications were made to fit Kurdish culture, including culturally relevant analogies, use of stickers for behavior monitoring, cultural modifications to behavioral contracts, and including telephone-delivered sessions to enhance feasibility.

CONCLUSIONS: BATD was delivered by CHWs in a resource-poor, conflict-affected area in Kurdistan, Iraq, with some important modifications, including low-literacy adaptations, increased cultural relevancy of clinical materials, and tailored training and supervision for CHWs. Barriers to implementation, lessons learned, and recommendations for future efforts to adapt behavioral therapies for resource-limited, conflict-affected areas are discussed.

Navigating to health: Evaluation of a community health center patient navigation program

Mon, 07/17/2017 - 8:16am

Patient Navigators are trained, lay health care workers who guide patients in overcoming barriers to health care access and utilization. Little evidence exists regarding reach and impact of Patient Navigators for chronic disease management. This study evaluated a Patient Navigator program aimed at optimizing health care utilization among ethnically diverse patients with diabetes and/or hypertension at a community health center (CHC). Trained Patient Navigators contacted eligible patients who had not seen a primary care provider (PCP) for > /= 6 months. Outcomes included number of patients reached by Patient Navigators and seen by PCPs after Patient Navigator contact. Distributions and frequencies of outcomes pre- and post-call were compared. A total of 215 patients had > /= 1 call attempt from Patient Navigators. Of these, 74 were additionally contacted via mailed letters or at the time of a CHC visit. Among the 45 patients reached, 77.8% scheduled an appointment through the Patient Navigator. These patients had higher rates of PCP visits 6 months post-call (90%) than those not reached (42.2%) (p < 0.0001). Findings emphasize the value of direct telephone contact in patient health care re-engagement and may inform the development of future Patient Navigator programs to improve reach and effectiveness.

Patient navigation and financial incentives to promote smoking cessation in an underserved primary care population: A randomized controlled trial protocol

Mon, 07/17/2017 - 8:16am

Despite the high risk of tobacco-related morbidity and mortality among low-income persons, few studies have connected low-income smokers to evidence-based treatments. We will examine a smoking cessation intervention integrated into primary care. To begin, we completed qualitative formative research to refine an intervention utilizing the services of a patient navigator trained to promote smoking cessation. Next, we will conduct a randomized controlled trial combining two interventions: patient navigation and financial incentives. The goal of the intervention is to promote smoking cessation among patients who receive primary care in a large urban safety-net hospital. Our intervention will encourage patients to utilize existing smoking cessation resources (e.g., quit lines, smoking cessation groups, discussing smoking cessation with their primary care providers). To test our intervention, we will conduct a randomized controlled trial, randomizing 352 patients to the intervention condition (patient navigation and financial incentives) or an enhanced traditional care control condition. We will perform follow-up at 6, 12, and 18 months following the start of the intervention. Evaluation of the intervention will target several implementation variables: reach (participation rate and representativeness), effectiveness (smoking cessation at 12 months [primary outcome]), unintended consequences (e.g., purchase of illicit substances with incentive money), adoption (use of intervention across primary care suites), implementation (delivery of intervention), and maintenance (smoking cessation after conclusion of intervention). Improving the implementation of smoking cessation interventions in primary care settings serving large underserved populations could have substantial public health impact, reducing cancer-related morbidity/mortality and associated health disparities.

Assessing Medical Students' Tobacco Dependence Treatment Skills Using a Detailed Behavioral Checklist

Mon, 07/17/2017 - 8:16am

CONSTRUCT: This article describes the development and implementation of an assessment intended to provide objective scores that would be valid indications of medical students' abilities to counsel patients about tobacco dependence.

BACKGROUND: Assessing medical students' advanced communication skills, particularly in the context of providing tobacco-dependence treatment, consistently and accurately is challenging; doing so across multiple medical schools is even more difficult.

APPROACH: Ten medical schools implemented a tobacco-dependence treatment case as part of an Objective Structured Clinical Examination for 3rd-year medical students. A 33-item checklist with detailed criteria and examples was developed for scoring students' performances. Trained coders viewed and coded 660 videotaped encounters; approximately 10% also were coded by the coding supervisor to check accuracy.

RESULTS: Average time required to code an encounter was approximately 31 minutes; accuracy (i.e., agreement with the gold standard coder) was excellent. Overall, students performed an average of 1 in 4 of the 33 behaviors included on the checklist, and only 1 in 10 discussed setting a quit date. Most students (almost 9 in 10) asked how much the patient smoked in a day, and just over 7 in 10 informed the patient that the cough was due to smoking.

CONCLUSIONS: The authors developed and implemented a rigorous assessment that will be used to evaluate medical students' tobacco-dependence treatment skills. Operationalizing the specific counseling behaviors, training coders to accurately capture students' performances using a structured checklist, and conducting the coding all required substantial time commitments but will provide confidence in the objectivity of the assessment results. In addition, this assessment can be used to provide formative information on medical students' tobacco-dependence treatment skills and to tailor ongoing training for medical students in this area.

Disparities in access to healthy and unhealthy foods in central Massachusetts: implications for public health policy

Mon, 07/17/2017 - 8:16am

OBJECTIVES: To analyze geographic and income disparities in access to healthy foods in central Massachusetts.

METHODS: We surveyed 106 (92% of all) food stores longitudinally in the study area between 2007 and 2010. We analyzed the geographic and temporal variations in community- and store-level healthy food availability indices (HFAI) and unhealthy food availability indices (UFAI) overall and by select store and community characteristics.

RESULTS: Twenty-seven of 68 communities in the study area (39.7%) had no food store and 5 (8.3%) had one or few stores with very limited availability of healthy foods, affecting 23.7% of the county population. Lack of food stores was associated strongly with lower housing density and upper tertile of median household income. About 45% of the surveyed stores had inadequate availabilities of healthy food. Store-level HFAI and UFAI scores were highly correlated, and higher among larger stores affiliated with a chain (vs independent). Though healthy foods were usually most available in larger stores, unhealthy foods were widely available in all stores.

CONCLUSIONS: Over half of central Massachusetts communities, mostly rural and small, had either no food store or few stores with limited availabilities of healthy foods. Immediate policy interventions on the food environment are necessary in these communities. Further, without examining what is actually sold in stores, analysis of disparities in access to healthy food relies on the number of food stores, which can lead to a distorted picture of accessibility and mislead community health policies.

Fostering multiple healthy lifestyle behaviors for primary prevention of cancer

Mon, 07/17/2017 - 8:16am

The odds of developing cancer are increased by specific lifestyle behaviors (tobacco use, excess energy and alcohol intakes, low fruit and vegetable intake, physical inactivity, risky sexual behaviors, and inadequate sun protection) that are established risk factors for developing cancer. These behaviors are largely absent in childhood, emerge and tend to cluster over the life span, and show an increased prevalence among those disadvantaged by low education, low income, or minority status. Even though these risk behaviors are modifiable, few are diminishing in the population over time. We review the prevalence and population distribution of these behaviors and apply an ecological model to describe effective or promising healthy lifestyle interventions targeted to the individual, the sociocultural context, or environmental and policy influences. We suggest that implementing multiple health behavior change interventions across these levels could substantially reduce the prevalence of cancer and the burden it places on the public and the health care system. We note important still-unresolved questions about which behaviors can be intervened upon simultaneously in order to maximize positive behavioral synergies, minimize negative ones, and effectively engage underserved populations. We conclude that interprofessional collaboration is needed to appropriately determine and convey the value of primary prevention of cancer and other chronic diseases.

Risk of heart failure among postmenopausal women: a secondary analysis of the randomized trial of vitamin D plus calcium of the women's health initiative

Mon, 07/17/2017 - 8:16am

BACKGROUND: Vitamin D supplementation may be an inexpensive intervention to reduce heart failure (HF) incidence. However, there are insufficient data to support this hypothesis. This study evaluates whether vitamin D plus calcium (CaD) supplementation is associated with lower rates of HF in postmenopausal women and whether the effects differ between those at high versus low risk for HF.

METHODS AND RESULTS: Analyses were restricted to 35 983 (of original 36 282) women aged 50 to 79 years old in the Women's Health Initiative randomized trial of CaD supplementation who were randomized 1:1 in a double-blinded fashion to receive 1000 mg/d of calcium plus 400 IU/d of vitamin D3 or placebo. Overall, 744 adjudicated incident HF cases (intervention, 363; control, 381) occurred during a median follow-up of 7.1 (interquartile range, 1.6) years. CaD supplementation, compared with placebo, was not associated with reduced HF risk in the overall population, hazard ratio, 0.95; P=0.46. However, CaD supplementation had differential effects (P interaction=0.005) in subgroups stratified by baseline risk status of HF defined by the presence (high risk=17 449) or absence (low risk=18 534) of pre-existing HF precursors including coronary heart diseases, diabetes mellitus, or hypertension: 37% (hazard ratio, 0.63 [95% confidence interval, 0.46-0.87]) lower risk of HF in the low-risk versus hazard ratio, 1.06; P=0.51, in the high-risk subgroups.

CONCLUSIONS: CaD supplementation did not significantly reduce HF incidence in the overall cohort, however, it was beneficial among postmenopausal women without major HF precursors while of little value in high-risk subgroups. Additional studies are warranted to confirm these findings and investigate the underlying mechanism.

CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000611.

Municipal Officials' Participation in Built Environment Policy Development in the United States

Mon, 07/17/2017 - 8:16am

PURPOSE: This study examined municipal officials' participation in built environment policy initiatives focused on land use design, transportation, and parks and recreation.

DESIGN: Web-based cross-sectional survey.

SETTING: Eighty-three municipalities with 50,000 or more residents in eight states.

SUBJECTS: Four hundred fifty-three elected and appointed municipal officials.

MEASURES: Outcomes included self-reported participation in land use design, transportation, and parks and recreation policy to increase physical activity. Independent variables included respondent position; perceptions of importance, barriers, and beliefs regarding physical activity and community design and layout; and physical activity partnership participation.

ANALYSIS: Multivariable logistic regression models.

RESULTS: Compared to other positions, public health officials had lower participation in land use design (78.3% vs. 29.0%), transportation (78.1% vs. 42.1%), and parks and recreation (67.1% vs. 26.3%) policy. Perceived limited staff was negatively associated with participation in each policy initiative. Perceptions of the extent to which physical activity was considered in community design and physical activity partnership participation were positively associated with participation in each. Perceived lack of collaboration was associated with less land use design and transportation policy participation, and awareness that community design affects physical activity was associated with more participation. Perceived lack of political will was associated with less parks and recreation policy participation.

CONCLUSION: Public health officials are underrepresented in built environment policy initiatives. Improving collaborations may improve municipal officials' policy participation.

Diet quality and survival after ovarian cancer: results from the Women's Health Initiative

Mon, 07/17/2017 - 8:15am

BACKGROUND: Survival after an ovarian cancer diagnosis is poor. Given the high mortality in these patients, efforts to identify modifiable lifestyle behaviors that could influence survival are needed. Earlier evidence suggests a protective role for vegetables, but no prior studies have evaluated overall dietary quality and ovarian cancer survival. The purpose of this analysis was to evaluate the role of prediagnosis diet quality in ovarian cancer survival.

METHODS: We identified 636 centrally adjudicated cases of ovarian cancer within the Women's Health Initiative Observational Study or Clinical Trials of 161808 postmenopausal women followed from 1995 to 2012. Dietary quality was assessed for the Healthy Eating Index (2005) using a food frequency questionnaire, covariables were obtained from standardized questionnaires, and adiposity was measured by clinic-based measurements of height, weight, and waist circumference. The association between diet quality and mortality was analyzed using Cox proportional hazards regression, adjusted for potential confounders, and stratified by waist circumference, physical activity level, and diabetes status. Tests of statistical significance were two-sided.

RESULTS: Overall, higher diet quality was associated with lower all-cause mortality after ovarian cancer (hazard ratio [HR] for highest vs lowest tertile = 0.73; 95% confidence interval [CI] = 0.55 to 0.97, P(trend) = .03). The effect was strongest among women with waist circumference of 88 cm or less and with no history of diabetes (HR = 0.73, 95% CI = 0.54 to 0.98). Physical activity level did not modifythe association between diet quality and survival.

CONCLUSION: Our results suggest that overall higher prediagnosis diet quality may protect against mortality after ovarian cancer.