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Familial, Associational, & Incidental Relationships (FAIR)

Fri, 11/07/2014 - 11:00am

Identifying familial linkages in a phenotypic data warehouse can be valuable in cohort identification, and beginning to understand interactions of diseases among families. The goal of the Familial, Associational, & Incidental Relationships (FAIR) system is to identify an index set patients’ relationships through elements in a data warehouse. Using a test set of 500 children, we measured the sensitivity and specificity of available linkage algorithm (e.g.: insurance id and phone numbers) and validated this tool/algorithm through a manual chart audit. Sensitivity varied from 16% to 87%, and specificity from 70% to 100% using various combinations of identifiers. Using the “i2b2” warehouse infrastructure, we have now developed a web app that facilitates FAIR for any index population.

Cancer Surveillance and Outreach in Carlisle, Massachusetts: An Analysis of MDPH Cancer and Environmental Health Data in a Small Town Context

Fri, 11/07/2014 - 11:00am

Introduction: The Carlisle Board of Health (BOH) sought to understand how cancer affects its town (population under 5,000), using data on expected and observed cancer incidence provided by the Massachusetts Cancer Registry (MCR). This project examined cancer incidence data summarized by city/town in five-year intervals, evaluated demographic and environmental factors that could contribute to cancer, and provided recommendations for cancer outreach. Methods: MCR city/town reports from 1995-2009 were examined to identify community cancer trends. A literature review focused on cancers of concern to guide outreach efforts. Data on contributing environmental exposures and health behaviors were explored to identify potential risk factors in Carlisle. Individual- and community-level recommendations were issued based on the data and literature. Results: Observed cases of breast cancer and melanoma in women and colorectal cancer and prostate cancer in men exceeded the number of expected cases. Bladder cancer in men and lung cancer in men and women were somewhat lower than expected. There was insufficient evidence of causation by local environmental exposure. Discussion: Excess cancer cases in Carlisle cannot be interpreted as a cancer cluster. Individuals should be aware of important risk factors and control lifestyle-related factors for common types of cancer. The BOH can monitor data on potential environmental exposures and provide ongoing communication with Carlisle residents about cancer in the community through social media, the local newspaper, and town events. Broad educational outreach on specific risk factors, including sun exposure, arsenic in drinking water, and youth tobacco use should be considered to foster healthy behaviors.

A Nurse Practitioner Model for Delivering Primary and Coordinated Care to Adults with Disabilities - CLASS Inc., Lawrence, MA and Academic Partners, Brandeis University and University of Massachusetts Lowell

Fri, 11/07/2014 - 11:00am

The project will (1) design and plan the implementation of a nurse practitioner model for delivering primary and coordinated care to adults with disabilities who are receiving day habilitation services, and (2) evaluate the design and planning processes using a participatory and iterative approach. The project is a collaborative effort between a university-based research center, provider agencies, a nursing school, and government officials. Products include a logic model of the intervention, materials for training nurses to provide care and service coordination, and an analysis of the process to disseminate lessons learned, support a demonstration project and encourage replication efforts.

Building a Coalition to Promote Health Literacy in Central Massachusetts

Fri, 11/07/2014 - 11:00am

Founded by graduate nursing students at Worcester State University (WSU), the Central Massachusetts Health Literacy Project (CMHLP) is an academic-community partnership with the vision of a healthier Central Massachusetts through health literacy efforts. Current health indicators of the greater Worcester area suggest that there is great need for building health literacy capacity. Although students are considered learners, many WSU graduate nursing students have roots in Central Massachusetts and have years of experience as health care providers. They come from diverse cultural, linguistic, and health care backgrounds. Their combined health care experiences and ability to interpret and perform scholarly work contribute to their ability to assess health literacy needs of local residents, identify the best health literacy practices, and formulate innovative solutions to poor heath literacy. CMHLP members have worked with Worcester Refugee Assistance Program, Elder Services of Worcester, and Central Mass/MetroWest Transitions in Care Collaborative. CMHLP members are not outsiders who come into a community to study and leave. Their commitment to the Worcester area not only helps sustain the collaborative but provides the important everlasting connection between the university and local community.

Leaders Care: Mitigating Violence against Emergency Department Staff

Fri, 11/07/2014 - 11:00am

Engaging Emergency Department clinicians in identifying fears and challenges about safety will support a more secure environment. Identifying staff perceptions regarding safety guided intervention development to maximize security. A survey identified staff perceptions of security, and was repeated after the implementation of mitigation interventions in a New Hampshire community hospital Emergency Department. Staff members, Security Officers, and Patient Registrars were invited to participate in anonymous online surveys pre- and post- mitigation intervention implementation. Data were analyzed for significant differences in responses pre- and post- interventions. Following the initial survey, interventions addressing staff concerns were developed and implemented. In the post-intervention survey, significant differences were noted in 5 of 11 staff concerns. Staff security is a moving target in this environment. Leaders must look at the team as a whole. Interventions designed will drive ongoing educational initiatives, policy revision, and clarification of responsibilities among team members in order to improve safety.

Acceptability of a Novel Smartphone Application for Rhythm Evaluation in Patients with Atrial Fibrillation

Fri, 11/07/2014 - 11:00am

Background: Investigators at UMass Medical School and WPI co-developed a novel smartphone application (app), PULSESMART, that detects atrial fibrillation (AF). AF is the world’s most common, serious heart rhythm problem. In its early stages, most cases of AF are paroxysmal (pAF), making them difficult to identify early in the course of disease. Long-term cardiac monitoring is frequently needed to diagnose and prevent complications from AF, such as stroke. Home monitoring for AF can be clinically impactful but existing technologies have cost or methodological limitations. Data are needed on the potential acceptability and usability of heart rhythm monitoring applications.

Aim: Our aim was to examine patient acceptability of using a pAF detection app.

Methods: 52 patients with pAF underwent rhythm assessment using the app and completed a standardized questionnaire. We looked specifically at responses to 3 questions: 1) how easy was it to use? 2) How important could it be for you? And 3) to what extent does it fit into your daily life?

Results: The mean age was 68.5 years and 69% female. The majority of patients reported the app was easy to use (73%), could be important to them and their health (84%), and would fit into their daily lives (78%).

Conclusions: After use of the pAF detection app, most patients reported positively. The results suggest that older persons with, or at risk for, pAF may benefit from smartphone-based arrhythmia detection platforms. Further work is needed to assess the feasibility of at-home or in-clinic app use.

Symposium Breakout Sessions: 2014 Community Engagement and Research Symposium

Fri, 11/07/2014 - 11:00am

Complete list of Breakout Sessions with descriptions for the 4th annual Community Engagement and Research Symposium, held Friday, November 7, 2014 at the University of Massachusetts Medical School, Worcester, MA.

Symposium Agenda: 2014 Community Engagement and Research Symposium

Fri, 11/07/2014 - 11:00am

Agenda for the 4th annual Community Engagement and Research Symposium, held Friday, November 7, 2014 at the University of Massachusetts Medical School, Worcester, MA.

Symposium Poster Session Presentations: 2014 Community Engagement and Research Symposium

Fri, 11/07/2014 - 10:00am

Complete list of Poster Session presentations with abstracts for the 4th annual Community Engagement and Research Symposium, held Friday, November 7, 2014 at the University of Massachusetts Medical School, Worcester, MA.

Id2 complexes with the SNAG domain of Snai1 inhibiting Snai1-mediated repression of integrin beta4

Tue, 11/04/2014 - 9:56am

The epithelial-mesenchymal transition (EMT) is a fundamental process that underlies development and cancer. Although the EMT involves alterations in the expression of specific integrins that mediate stable adhesion to the basement membrane, such as alpha6beta4, the mechanisms involved are poorly understood. Here, we report that Snai1 inhibits beta4 transcription by increasing repressive histone modification (trimethylation of histone H3 at K27 [H3K27Me3]). Surprisingly, Snai1 is expressed and localized in the nucleus in epithelial cells, but it does not repress beta4. We resolved this paradox by discovering that Id2 complexes with the SNAG domain of Snai1 on the beta4 promoter and constrains the repressive function of Snai1. Disruption of the complex by depleting Id2 resulted in Snai1-mediated beta4 repression with a concomitant increase in H3K27Me3 modification on the beta4 promoter. These findings establish a novel function for Id2 in regulating Snai1 that has significant implications for the regulation of epithelial gene expression.

VEGF targets the tumour cell

Tue, 11/04/2014 - 9:56am

The function of vascular endothelial growth factor (VEGF) in cancer is not limited to angiogenesis and vascular permeability. VEGF-mediated signalling occurs in tumour cells, and this signalling contributes to key aspects of tumorigenesis, including the function of cancer stem cells and tumour initiation. In addition to VEGF receptor tyrosine kinases, the neuropilins are crucial for mediating the effects of VEGF on tumour cells, primarily because of their ability to regulate the function and the trafficking of growth factor receptors and integrins. This has important implications for our understanding of tumour biology and for the development of more effective therapeutic approaches.

Regulated splicing of the alpha6 integrin cytoplasmic domain determines the fate of breast cancer stem cells

Tue, 11/04/2014 - 9:56am

Although the alpha6beta1 integrin has been implicated in the function of breast and other cancer stem cells (CSCs), little is known about its regulation and relationship to mechanisms involved in the genesis of CSCs. We report that a CD44(high)/CD24(low) population, enriched for CSCs, is comprised of distinct epithelial and mesenchymal populations that differ in expression of the two alpha6 cytoplasmic domain splice variants: alpha6A and alpha6B. alpha6Bbeta1 expression defines the mesenchymal population and is necessary for CSC function, a function that cannot be executed by alpha6A integrins. The generation of alpha6Bbeta1 is tightly controlled and occurs as a consequence of an autocrine vascular endothelial growth factor (VEGF) signaling that culminates in the transcriptional repression of a key RNA-splicing factor. These data alter our understanding of how alpha6beta1 contributes to breast cancer, and they resolve ambiguities regarding the use of total alpha6 (CD49f) expression as a biomarker for CSCs.

IMP3 expression is associated with poor outcome and epigenetic deregulation in intrahepatic cholangiocarcinoma

Tue, 11/04/2014 - 9:56am

IMP3 is a fetal protein not expressed in normal adult tissues. IMP3 is an oncoprotein and a useful biomarker for a variety of malignancies and is associated with reduced overall survival of a number of them. IMP3 expression and its prognostic value for patients with intrahepatic cholangiocarcinoma (ICC) have not been well investigated. The molecular mechanism underlying IMP3 expression in human cancer cells remains to be elucidated. Here we investigated IMP3 expression in ICC and adjacent nonneoplastic liver in 72 unifocal primary ICCs from a single institute by immunohistochemistry, immunoblotting, and real-time polymerase chain reaction. IMP3 was specifically expressed in cancer cells but not in the surrounding normal tissue, and 59 (82%) of 72 ICCs were IMP3 positive by immunohistochemistry. Among 35 cases with lymphovascular invasion, 26 (74%) showed IMP3 positivity in lymph node metastases. IMP3 expression was significantly correlated with tumor size, pathological grade, metastasis, and clinical stage. Kaplan-Meier analysis demonstrated an inverse correlation between IMP3 expression and overall survival rate. Multivariate analysis revealed that IMP3 was the only risk factor associated with survival. To further explore the mechanism of IMP3 expression in cancers, we identified 2 CpG islands at IMP3 proximal promoter. Interestingly, the IMP3 promoter was almost completely demethylated in ICCs in contrast to densely methylated promoter in normal liver tissues. IMP3 expression is a useful biomarker for ICCs and can provide an independent prognostic value for patients with ICC. To our knoweldge, this is the first direct evidence of epigenetic deregulation of IMP3 in human cancer.

Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Availability of Tanning Beds on US College Campuses

Thu, 10/30/2014 - 7:20am

Importance. Indoor tanning is widespread among young adults in the United States despite evidence establishing it as a risk factor for skin cancer. The availability of tanning salons on or near college campuses has not been formally evaluated.

Objective. To evaluate the availability of indoor tanning facilities on US college and university campuses (colleges) and in off-campus housing surrounding but not owned by the college.

Design, Setting, and Participants. This observational study sampled the top 125 US colleges and universities listed in US News and World Report. Investigators searched websites of the colleges and nearby housing and contacted them by telephone inquiring about tanning services.

Main Outcomes and Measures. Frequency of indoor tanning facilities on college campus and in off-campus housing facilities, as well as payment options for tanning.

Results. Of the 125 colleges, 48.0% had indoor tanning facilities either on campus or in off-campus housing, and 14.4% of colleges allow campus cash cards to be used to pay for tanning. Indoor tanning was available on campus in 12.0% of colleges and in off-campus housing in 42.4% of colleges. Most off-campus housing facilities with indoor tanning (96%) provide it free to tenants. Midwestern colleges had the highest prevalence of indoor tanning on campus (26.9%), whereas Southern colleges had the highest prevalence of indoor tanning in off-campus housing facilities (67.7%). Presence of on-campus tanning facilities was significantly associated with enrollment (P = .01), region (P = .02), and presence of a school of public health (P = .01) but not private vs public status (P = .18) or presence of a tobacco policy (P = .16). Presence of tanning facilities in off-campus housing was significantly associated with region (P = .002) and private vs public status (P = .01) but not enrollment (P = .38), tobacco policy (P = .80), or presence of a school of public health (P = .69).

Conclusions and Relevance. Reducing the availability of indoor tanning on and around college campuses is an important public health target.

Doing the best with what we have: we need better: informing obstetric policy with administrative data

Tue, 10/28/2014 - 2:06pm

In this issue of Medical Care, Backes Kozhimannil and colleagues present data from the National Inpatient Sample on differences between rural and urban obstetric care. We applaud their efforts in examining this issue and agree that all women should be afforded safe deliveries, and ideally each woman’s experience would not be different. That being said, there are some practical considerations that must be applied to their analyses and recommendations. We would like to take this opportunity to capitalize on their efforts and speak to 2 other highly related implications for policy and practice.

Attitudes of women in their forties toward the 2009 USPSTF mammogram guidelines: a randomized trial on the effects of media exposure

Tue, 10/28/2014 - 2:06pm

OBJECTIVE: The objective of the study was to assess women's attitudes toward 2009 US Preventive Services Task Force mammography screening guideline changes and evaluate the role of media in shaping opinions.

STUDY DESIGN: Two hundred forty-nine women, aged 39-49 years, presenting for annual examinations randomized to read 1 of 2 articles, and survey completion comprised the design of the study.

RESULTS: Eighty-eight percent overestimated the lifetime breast cancer (BrCa) risk. Eighty-nine percent want yearly mammograms in their 40s. Eighty-six percent felt the changes were unsafe, and even if the changes were doctor recommended, 84% would not delay screening until age 50 years. Those with a friend/relative with BrCa were more likely to want annual mammography in their forties (92% vs 77%, P = .001), and feel changes unsafe (91% vs 69%, P ≤ .0001). Participants with previous false-positive mammograms were less likely to accept doctor-recommended screening delay until age 50 years (8% vs 21%, P = .01).

CONCLUSION: Women overestimate BrCa risk. Skepticism of new mammogram guidelines exists, and is increased by exposure to negative media. Those with prior false-positive mammograms are less likely to accept changes.

Copyright © 2011 Mosby, Inc. All rights reserved.

Role of multiple births in very low birth weight and infant mortality

Tue, 10/28/2014 - 2:06pm

OBJECTIVE: To determine the percentage of very-low-birth-weight (VLBW) infants (g) and infant deaths attributable to multiple births in the general population and in women aged 35+.

STUDY DESIGN: The year 2000 Massachusetts birth certificate database with linked births-deaths was examined. Etiologic fractions (EF) for VLBW and infant mortality attributable to multiples were calculated for the general population and the 35+ age group. The percentages of multiples occurring in the 35+ age group were calculated. Infant deaths due to congenital anomalies and "perinatal conditions" were calculated.

RESULTS: There were 81,582 resident births in Massachusetts in 2000. Of them 4.3% were multiples. Of the 1090 VLBW infants, 26.1% (95% CI: 23.5-28.8) were in twins and 7.7% (95% CI: 6.2-9.5) in higher-order multiples, yielding an EF of 30.8% for multiples in VLBW. In the 35+ age group, the multiple birth ratio was 6.6% (95% CI: 6.3-7.0). The EF for multiples and VLBW in this age group was 33.7%. The 35+ age group accounted for 32.4% (95% CI: 30.8-34.0) of twins and 45.5% (95% CI: 39.1-52.0) of higher-order multiples born in 2000. Of the 392 infant deaths, 57 (14.6%; 95% CI: 11.2-18.4) were attributed to congenital anomalies, and 236 (60.2%; 95% CI: 55.2-65.0) to "perinatal conditions." Multiples were responsible for 8 (14%; 95% CI: 6.3-25.8) of deaths due to anomalies, and 73 (30.9%; 95% CI: 25.1-37.3) due to "perinatal conditions."

CONCLUSION: Over 30% of VLBW infants, nearly 20% of infant mortality and >30% of infant mortality due to perinatal conditions could be attributed to multiples. Multiple pregnancy is a significant public health problem.

Role of smoking in low birth weight

Tue, 10/28/2014 - 2:06pm

OBJECTIVE: To assess the role of smoking on low birth weight (LBW).

STUDY DESIGN: From Massachusetts for 1998, 79,904 birth certificates were reviewed. Birth weight, gestational age, plurality and maternal race were analyzed in relation to the mother's smoking status during the pregnancy. The etiologic fraction (EF) was calculated for smoking and LBW for the group as a whole as well as for various subgroups.

RESULTS: A total of 11.7% of women acknowledged smoking during pregnancy. The overall LBW rate was 6.83%. The relative risk (RR) of LBW among smokers was 1.58. For all births the EF for smoking was 6.4% (95% CI: 5.4-7.3). For singleton pregnancies it was 10.9% (95% CI: 9.6-12.1) (14% for singleton whites and 7.2 for singleton blacks). At term, the EF of smoking on LBW was 13.4% (95% CI: 11.5-15.3), with an EF of 16.7% (95% CI: 14.5-18.7) for term singletons (21.4% among whites and 14.6% among blacks). Among very LBW infants, smoking accounted for 1.7% (95% CI:--0.5-3.8) of the outcome (5.8% among singletons). When stratifying for the effect of smoking, the rate of LBW was 6.38% among nonsmokers, 9.5% (RR 1.48, 1.38-1.61) among light smokers, 11.67% (RR 1.82, 1.63-2.05) among moderate smokers and 11.72% (RR 1.84, 1.33-2.54) among heavy smokers. Sixty percent of the overall population effect of smoking on LBW was in the category of light smokers.

CONCLUSION: The amount of LBW attributable to smoking was 6.4% in this sample. Among those who smoked, LBW was 58% more likely than among nonsmokers, and 60% of the overall population effect of smoking on LBW was noted among light smokers.

XK aprosencephaly and anencephaly in sibs

Tue, 10/28/2014 - 2:06pm

Recent studies have suggested a causal and pathogenetic relationship between holoprosencephaly and anencephaly. In support of the proposed relationship we report a sibship that includes anencephalic male twins and a female infant with a severe form of alobar holoprosencephaly, radial aplasia, and oligodactyly. The upper limb and brain malformations are considered to represent aprosencephaly syndrome. The coexistence of anencephaly and aprosencephaly within a sibship suggests that XK aprosencephaly syndrome may be an autosomal recessive disorder.

Genome-wide association study of proneness to anger

Fri, 10/17/2014 - 11:48am

BACKGROUND: Community samples suggest that approximately 1 in 20 children and adults exhibit clinically significant anger, hostility, and aggression. Individuals with dysregulated emotional control have a greater lifetime burden of psychiatric morbidity, severe impairment in role functioning, and premature mortality due to cardiovascular disease.

METHODS: With publically available data secured from dbGaP, we conducted a genome-wide association study of proneness to anger using the Spielberger State-Trait Anger Scale in the Atherosclerosis Risk in Communities (ARIC) study (n = 8,747).

RESULTS: Subjects were, on average, 54 (range 45-64) years old at baseline enrollment, 47% (n = 4,117) were male, and all were of European descent by self-report. The mean Angry Temperament and Angry Reaction scores were 5.8 +/- 1.8 and 7.6 +/- 2.2. We observed a nominally significant finding (p = 2.9E-08, lambda = 1.027 - corrected pgc = 2.2E-07, lambda = 1.0015) on chromosome 6q21 in the gene coding for the non-receptor protein-tyrosine kinase, Fyn.

CONCLUSIONS: Fyn interacts with NDMA receptors and inositol-1,4,5-trisphosphate (IP3)-gated channels to regulate calcium influx and intracellular release in the post-synaptic density. These results suggest that signaling pathways regulating intracellular calcium homeostasis, which are relevant to memory, learning, and neuronal survival, may in part underlie the expression of Angry Temperament.