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Intimate partner violence in the relationships of men with disabilities in the United States: relative prevalence and health correlates

Tue, 08/30/2016 - 3:16pm

Despite the growing literature on intimate partner violence (IPV) victimization against people with disabilities, few studies have examined IPV against men with disabilities. This study uses population-based data to examine the prevalence of past-year and lifetime IPV against men with disabilities in the United States in comparison with men without disabilities and women with and without disabilities, compare the demographic characteristics of men with disabilities who reported IPV to those of other men, and examine associations of IPV and disability status with mental and physical health and other health risks among men. Results indicate that, adjusting for demographic characteristics, men with disabilities were more likely to report lifetime IPV than men without disabilities and, among those reporting any lifetime IPV, men with disabilities were more likely to report past-year IPV than both nondisabled men and women. With few exceptions, comparisons of health indicators revealed that men with disabilities reporting lifetime IPV were more likely than other men to report poor health status and to report engaging in health risk behaviors. Directions for future research and programmatic and policy implications of these results are discussed.

Pregnancy outcomes among women with intellectual and developmental disabilities

Tue, 08/30/2016 - 3:16pm

BACKGROUND: There is currently no population-based research on the maternal characteristics or birth outcomes of U.S. women with intellectual and developmental disabilities (IDDs). Findings from small-sample studies among non-U.S. women indicate that women with IDDs and their infants are at higher risk of adverse health outcomes.

PURPOSE: To describe the maternal characteristics and outcomes among deliveries to women with IDDs and compare them to women with diabetes and the general obstetric population.

METHODS: Data from the 1998-2010 Massachusetts Pregnancy to Early Life Longitudinal database were analyzed between November 2013 and May 2014 to identify in-state deliveries to Massachusetts women with IDDs.

RESULTS: Of the 916,032 deliveries in Massachusetts between 1998 and 2009, 703 ( < 0.1%) were to women with IDDs. Deliveries to women with IDDs were to those who were younger, less educated, more likely to be black and Hispanic, and less likely to be married. They were less likely to identify the father on the infant's birth certificate, more likely to smoke during pregnancy, and less likely to receive prenatal care during the first trimester compared to deliveries to women in the control groups (p < 0.01). Deliveries to women with IDDs were associated with an increased risk of adverse outcomes, including preterm delivery, very low and low birth weight babies, and low Apgar scores.

CONCLUSIONS: Women with IDDs are at a heightened risk for adverse pregnancy outcomes. These findings highlight the need for a systematic investigation of the pregnancy-related risks, complications, costs, and outcomes of women with IDDs. Inc.

Pregnancy Outcomes Among U.S. Women With Intellectual and Developmental Disabilities

Tue, 08/30/2016 - 3:16pm

The existing research on pregnancy outcomes for women with intellectual and developmental disabilities (IDD) is sparse. This study analyzed the 2010 Healthcare Cost and Utilization Project Nationwide Inpatient Sample and compared deliveries among women with IDD (n = 340) to the general obstetric population. Women with IDD had longer hospital stays and were more likely to have Caesarean deliveries in contrast to other women. Rates of adverse pregnancy outcomes were elevated for women with IDD across a range of measures, including early labor, preterm birth, and preeclampsia, and their infants were more likely to have low birth weight, even after adjusting for age, race, ethnicity, and insurance type. Targeted interventions are needed to address these deleterious outcomes.

Changes in smoking-related symptoms during enforced abstinence of incarceration

Tue, 08/30/2016 - 3:16pm

BACKGROUND: Tobacco use among prisoners is much higher than among the general population. Little is known about changes in smoking-related symptoms during periods of incarceration. The objective of this study is to evaluate changes in smoking-related symptoms during incarceration.

METHODS: We recruited 262 inmates from a tobacco-free prison. At baseline, participants were asked about smoking-related symptoms prior to incarceration and then asked about recent symptoms.

RESULTS: All symptom scores on the American Thoracic Society Questionnaire (ATSQ) improved during incarceration. Higher ATSQ scores were associated with asthma, depressive symptoms, stress, higher addiction and more pack years of smoking. Greater improvement in symptoms was not associated with smoking status after release.

CONCLUSION: Forced tobacco abstinence leads to significant improvements in smoking-related symptoms. However, improvements in symptoms are not associated with smoking behavior changes. Addressing changes in symptoms during incarceration will require further evaluation in smoking cessation interventions for incarcerated populations.

Vision Stations: Addressing Corrective Vision Needs With Low-cost Technologies

Tue, 08/30/2016 - 3:16pm

Eyeglasses, required for functional vision by nearly half the world's population, are still needed by more than a billion people. There are a number of constraints on the provision of eyeglasses: product cost, durability, and appearance; traditional approaches to evaluating refraction; and sustainably scaling potential distribution methods. We offer our experience with an immigrant population in a US urban setting using a "Vision Station." The station allowed for immediate provision of adjustable glasses using self-refraction, ordering of custom lenses from a low-cost website, and referral to primary and eye care physicians for those with medical eye concerns. As with models in development by other groups, Vision Stations connect people with the life-changing provision of functional vision.

Frequent Emergency Department Visits and Hospitalizations Among Homeless People With Medicaid: Implications for Medicaid Expansion

Tue, 08/30/2016 - 3:16pm

OBJECTIVES: We examined factors associated with frequent hospitalizations and emergency department (ED) visits among Medicaid members who were homeless.

METHODS: We included 6494 Massachusetts Medicaid members who received services from a health care for the homeless program in 2010. We used negative binomial regression to examine variables associated with frequent utilization.

RESULTS: Approximately one third of the study population had at least 1 hospitalization and two thirds had 1 or more ED visits. More than 70% of hospitalizations and ED visits were incurred by only 12% and 21% of these members, respectively. Homeless individuals with co-occurring mental illness and substance use disorders were at greatest risk for frequent hospitalizations and ED visits (e.g., incidence rate ratios [IRRs] = 2.9-13.8 for hospitalizations). Individuals living on the streets also had significantly higher utilization (IRR = 1.5).

CONCLUSIONS: Despite having insurance coverage, homeless Medicaid members experienced frequent hospitalizations and ED visits. States could consider provisions under the Patient Protection and Affordable Care Act (e.g., Medicaid expansion and Health Homes) jointly with housing programs to meet the needs of homeless individuals, which may improve the quality and cost effectiveness of care.

Performance of the GRACE Risk Score 2.0 Simplified Algorithm for Predicting 1-Year Death After Hospitalization for an Acute Coronary Syndrome in a Contemporary Multiracial Cohort

Mon, 08/29/2016 - 9:07am

The GRACE Risk Score is a well-validated tool for estimating short- and long-term risk in acute coronary syndrome (ACS). GRACE Risk Score 2.0 substitutes several variables that may be unavailable to clinicians and, thus, limit use of the GRACE Risk Score. GRACE Risk Score 2.0 performed well in the original GRACE cohort. We sought to validate its performance in a contemporary multiracial ACS cohort, in particular in black patients with ACS. We evaluated the performance of the GRACE Risk Score 2.0 simplified algorithm for predicting 1-year mortality in 2,131 participants in Transitions, Risks, and Actions in Coronary Events Center for Outcomes Research and Education (TRACE-CORE), a multiracial cohort of patients discharged alive after an ACS in 2011 to 2013 from 6 hospitals in Massachusetts and Georgia. The median age of study participants was 61 years, 67% were men, and 16% were black. Half (51%) of the patients experienced a non-ST-segment elevation myocardial infarction (NSTEMI) and 18% STEMI. Eighty patients (3.8%) died within 12 months of discharge. The GRACE Risk Score 2.0 simplified algorithm demonstrated excellent model discrimination for predicting 1-year mortality after hospital discharge in the TRACE-CORE cohort (c-index = 0.77). The c-index was 0.94 in patients with STEMI, 0.78 in those with NSTEMI, and 0.87 in black patients with ACS. In conclusion, the GRACE Risk Score 2.0 simplified algorithm for predicting 1-year mortality exhibited excellent model discrimination across the spectrum of ACS types and racial/ethnic subgroups and, thus, may be a helpful tool to guide routine clinical care for patients with ACS.

Prognostic value of dynamic electrocardiographic T wave changes in non-ST elevation acute coronary syndrome

Mon, 08/29/2016 - 9:07am

OBJECTIVE: To assess the relationship between the evolution of T wave inversion (TWI) on the 24-48 h postadmission ECG and the patient characteristics, management and clinical outcomes among those with non-ST elevation acute coronary syndrome (NSTE-ACS).

METHODS: We evaluated admission and 24-48 h follow-up ECGs of 7201 patients with NSTE-ACS from the prospective, multicentre Global Registry of Acute Coronary Events (GRACE) and Canadian ACS Registry I. We performed multivariable analyses to determine the association between new TWI (on follow-up ECG only), resolved TWI (on admission ECG only) and persistent TWI (on both admission and follow-up ECG) and inhospital and cumulative 6-month all-cause mortality.

RESULTS: Patients with TWI were older, more likely to have cardiovascular risk factors, higher Killip class and GRACE risk scores. After adjustment for known prognostic factors, compared with patients presenting without TWI, new TWI was associated with significantly lower inhospital mortality (OR=0.60, 95% CI 0.38 to 0.95, p=0.029), whereas resolved (OR=1.06, 95% CI 0.65 to 1.75, p=0.81) and persistent (OR=0.73, 95% CI 0.48 to 1.11, p=0.14) TWI did not predict inhospital mortality. No TWI pattern independently predicted inhospital adverse cardiovascular events or cumulative 6-month mortality. In contrast, ST depression on the admission and follow-up ECG were independent predictors of inhospital and 6-month mortality.

CONCLUSIONS: Across the spectrum of NSTE-ACS, TWI within 48 h of presentation was associated with high-risk clinical features, but its presence or dynamic change did not provide additional prognostic value beyond other established clinical predictors.

Clinical Characteristics, Management, and Outcomes of Acute Coronary Syndrome in Patients With Right Bundle Branch Block on Presentation

Mon, 08/29/2016 - 9:07am

We examined the relations between right bundle branch block (RBBB) and clinical characteristics, management, and outcomes among a broad spectrum of patients with acute coronary syndrome (ACS). Admission electrocardiograms of patients enrolled in the Global Registry of Acute Coronary Events (GRACE) electrocardiogram substudy and the Canadian ACS Registry I were analyzed independently at a blinded core laboratory. We performed multivariable logistic regression analysis to assess the independent prognostic significance of admission RBBB on in-hospital and 6-month mortality. Of 11,830 eligible patients with ACS (mean age 65; 66% non-ST-elevation ACS), 5% had RBBB. RBBB on admission was associated with older age, male sex, more cardiovascular risk factors, worse Killip class, and higher GRACE risk score (all p < 0.01). Patients with RBBB less frequently received in-hospital cardiac catheterization, coronary revascularization, or reperfusion therapy (all p < 0.05). The RBBB group had higher unadjusted in-hospital (8.8% vs 3.8%, p < 0.001) and 6-month mortality rates (15.1% vs 7.6%, p < 0.001). After adjusting for established prognostic factors in the GRACE risk score, RBBB was a significant independent predictor of in-hospital death (odds ratio 1.45, 95% CI 1.02 to 2.07, p = 0.039), but not cumulative 6-month mortality (odds ratio 1.29, 95% CI 0.95 to 1.74, p = 0.098). There was no significant interaction between RBBB and the type of ACS for either in-hospital or 6-month mortality (both p > 0.50). In conclusion, across a spectrum of ACS, RBBB was associated with preexisting cardiovascular disease, high-risk clinical features, fewer cardiac interventions, and worse unadjusted outcomes. After adjusting for components of the GRACE risk score, RBBB was a significant independent predictor of early mortality.

Temporal trends in all-cause mortality according to smoking status: Insights from the Global Registry of Acute Coronary Events

Mon, 08/29/2016 - 9:06am

Objective

Smoking has been shown to be a risk factor for heart disease. However, it was recently reported that despite the evolution in therapy for acute coronary syndrome (ACS), smokers have not demonstrated improved outcomes.

The aim of the present study was to evaluate the temporal trends in the treatments and outcomes across a broad spectrum of ACS patients (STEMI and non-ST-elevation ACS [NSTEACS]) according to smoking status on presentation in the Global Registry of Acute Coronary Events (GRACE). Methods

Our cohort was stratified into 3 groups: current smokers, former smokers and never smokers. We evaluated trends in demographics, treatment modalities and outcomes in these 3 groups from 1999 to 2007. Results

The study population comprised a total of 63,015 patients admitted to hospital with an ACS and with identifiable baseline smoking status. Smokers presented with STEMI more often than non-smokers. There was an unadjusted decline in 30-day mortality in all 3 groups. However, the adjusted decline was not statistically significant among current smokers (HR = 0.98 per study year, 95% CI 0.94–1.01, p = 0.20). A subgroup analysis of 22,894 STEMI patients demonstrated no reduction in annual adjusted 30-day mortality rates among smokers (HR = 1.01, 95% CI 0.96–1.06 (Table 5), whereas former and never smokers' mortality declined. Conclusions

Over the years 1999–2007, 30-day mortality declined in patients presenting with acute coronary syndrome. However, smokers presenting with STEMI did not demonstrate a reduction in mortality.

Increase in Fracture Risk Following Unintentional Weight Loss in Postmenopausal Women: The Global Longitudinal Study of Osteoporosis in Women

Fri, 08/26/2016 - 3:13pm

Increased fracture risk has been associated with weight loss in postmenopausal women, but the time course over which this occurs has not been established. The aim of this study was to examine the effects of unintentional weight loss of ≥10 lb (4.5 kg) in postmenopausal women on fracture risk at multiple sites up to 5 years after weight loss. Using data from the Global Longitudinal Study of Osteoporosis in Women (GLOW), we analyzed the relationships between self-reported unintentional weight loss of ≥10 lb at baseline, year 2, or year 3 and incident clinical fracture in the years after weight loss. Complete data were available in 40,179 women (mean age ± SD 68 ± 8.3 years). Five-year cumulative fracture rate was estimated using the Kaplan-Meier method, and adjusted hazard ratios for weight loss as a time-varying covariate were calculated from Cox multiple regression models. Unintentional weight loss at baseline was associated with a significantly increased risk of fracture of the clavicle, wrist, spine, rib, hip, and pelvis for up to 5 years after weight loss. Adjusted hazard ratios showed a significant association between unintentional weight loss and fracture of the hip, spine, and clavicle within 1 year of weight loss, and these associations were still present at 5 years. These findings demonstrate increased fracture risk at several sites after unintentional weight loss in postmenopausal women. This increase is found as early as 1 year after weight loss, emphasizing the need for prompt fracture risk assessment and appropriate management to reduce fracture risk in this population. © 2016 American Society for Bone and Mineral Research.

Know Your Chances: Understanding Health Statistics Book Discussion Final Report

Fri, 08/26/2016 - 8:45am

The Know Your Chances: Understanding Health Statistics Book Discussion Project evolved from a webinar held by the National Network of Libraries of Medicine New England Region’s (NN/LM NER) on March 4, 2014. Following the webinar, Margot Malachowski, NER’s Healthy Communities COI (Community of Interest) Leader, shared a vision for a book discussion group project.

In June 2014, the NN/LM NER Healthy Communities, Community of Interest (COI) invited network members to apply to participate in a health statistics book discussion project. The nine libraries and organizations selected to participate were required to: host and lead a book discussion at least once; attend planning teleconferences, and provide a brief post-project report to share their experiences. Participants were asked to select an audience for a book discussion, ideally public libraries, high school students, health professions students, caregivers, teachers, support groups or patient educators. Project participants lead book discussions that helped consumers learn how to calculate risk, put risk in perspective, and develop a healthy skepticism.

Know Your Chances is a quick read and is freely available online on the PubMed Health bookshelf at: http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0050876/

Analysis of apoptosis of memory T cells and dendritic cells during the early stages of viral infection or exposure to toll-like receptor agonists

Thu, 08/25/2016 - 1:13pm

Profound type I interferon (IFN-I)-dependent attrition of memory CD8 and CD4 T cells occurs early during many infections. It is dramatic at 2 to 4 days following lymphocytic choriomeningitis virus (LCMV) infection of mice and can be elicited by the IFN-inducing Toll receptor agonist poly(I:C). We show that this attrition occurs in many organs, indicating that it is due to T cell loss rather than redistribution. This loss correlated with elevated intracellular staining of T cells ex vivo for activated caspases but with only low levels of ex vivo staining with annexin V, probably due to the rapid clearance of apoptotic cells in vivo. Instead, a high frequency of annexin V-reactive CD8alpha(+) dendritic cells (DCs), which are known to be highly phagocytic, accumulated in the spleen as the memory T cell populations disappeared. After short in vitro incubation, memory phenotype T cells isolated from LCMV-infected mice (day 3) or mice treated with poly(I:C) (12 h) displayed substantial DNA fragmentation, as detected by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) assay, compared to T cells isolated from uninfected mice, indicating a role for apoptosis in the memory T cell attrition. This apoptosis of memory CD8 T cells early during LCMV infection was reduced in mice lacking the proapoptotic molecule Bim. Evidence is presented showing that high levels of T cell attrition, as found in young mice, correlate with reduced immunodomination by cross-reactive memory cells.

Microtubule stabilization by bone morphogenetic protein receptor-mediated scaffolding of c-Jun N-terminal kinase promotes dendrite formation

Thu, 08/25/2016 - 1:13pm

Neuronal outgrowth occurs via coordinated remodeling of the cytoskeleton involving both actin and microtubules. Microtubule stabilization drives the extending neurite, yet little is known of the molecular mechanisms whereby extracellular cues regulate microtubule dynamics. Bone morphogenetic proteins (BMPs) play an important role in neuronal differentiation and morphogenesis, and BMP7 in particular induces the formation of dendrites. Here, we show that BMP7 induces stabilization of microtubules in both a MAP2-dependent neuronal cell culture model and in dendrites of primary cortical neurons. BMP7 rapidly activates c-Jun N-terminal kinases (JNKs), known regulators of microtubule dynamics, and we show that JNKs associate with the carboxy terminus of the BMP receptor, BMPRII. Activation and binding of JNKs to BMPRII is required for BMP7-induced microtubule stabilization and for BMP7-mediated dendrite formation in primary cortical neurons. These data indicate that BMPRII acts as a scaffold to localize and coordinate cytoskeletal remodeling and thereby provides an efficient means for extracellular cues, such as BMPs, to control neuronal dendritogenesis.

Platelet JNK1 is involved in secretion and thrombus formation

Thu, 08/25/2016 - 1:12pm

The role of c-Jun NH(2)-terminal kinase 1 (JNK1) in hemostasis and thrombosis remains unclear. We show here, with JNK1-deficient (JNK1(-/-)) mice, that JNK1 plays an important role in platelet biology and thrombus formation. In tail-bleeding assays, JNK1(-/-) mice exhibited longer bleeding times than wild-type mice (396 +/- 39 seconds vs 245 +/- 32 seconds). We also carried out in vitro whole-blood perfusion assays on a collagen matrix under arterial shear conditions. Thrombus formation was significantly reduced for JNK1(-/-) platelets (51%). In an in vivo model of thrombosis induced by photochemical injury to cecum vessels, occlusion times were 4.3 times longer in JNK1(-/-) arterioles than in wild-type arterioles. Moreover, in vitro studies carried out in platelet aggregation conditions demonstrated that, at low doses of agonists, platelet secretion was impaired in JNK1(-/-) platelets, leading to altered integrin alphaIIbbeta3 activation and reduced platelet aggregation, via a mechanism involving protein kinase C. JNK1 thus appears to be essential for platelet secretion in vitro, consistent with its role in thrombus growth in vivo. Finally, we showed that ERK2 and another isoform of JNK affect platelet aggregation through 2 pathways, one dependent and another independent of JNK1.

c-Jun NH2-terminal kinase is required for lineage-specific differentiation but not stem cell self-renewal

Thu, 08/25/2016 - 1:12pm

The c-Jun NH(2)-terminal kinase (JNK) is implicated in proliferation. Mice with a deficiency of either the Jnk1 or the Jnk2 genes are viable, but a compound deficiency of both Jnk1 and Jnk2 causes early embryonic lethality. Studies using conditional gene ablation and chemical genetic approaches demonstrate that the combined loss of JNK1 and JNK2 protein kinase function results in rapid senescence. To test whether this role of JNK was required for stem cell proliferation, we isolated embryonic stem (ES) cells from wild-type and JNK-deficient mice. We found that Jnk1(-/-) Jnk2(-/-) ES cells underwent self-renewal, but these cells proliferated more rapidly than wild-type ES cells and exhibited major defects in lineage-specific differentiation. Together, these data demonstrate that JNK is not required for proliferation or self-renewal of ES cells, but JNK plays a key role in the differentiation of ES cells.

Differential activation of p38MAPK isoforms by MKK6 and MKK3

Thu, 08/25/2016 - 1:12pm

All four members of the mammalian p38 mitogen-activated protein kinase (MAPK) family (p38alpha, p38beta, p38gamma and p38delta) are activated by dual phosphorylation in the TGY motif in the activation loop. This phosphorylation is mediated by three kinases, MKK3, MKK6 and MKK4, at least in vitro. The role of these MKK in the activation of p38alpha has been demonstrated in studies using fibroblasts that lack MKK3 and/or MKK6. Nonetheless, the physiological upstream activators of the other p38MAPK isoforms have not yet been reported using MKK knockout cells. In this study, we examined p38beta, gamma and delta activation by MKK3 and MKK6, in cells lacking MKK3, MKK6 or both. We show that MKK3 and MKK6 are both essential for the activation of p38gamma and p38beta induced by environmental stress, whereas MKK6 is the major p38gamma activator in response to TNFalpha. In contrast, p38delta activation by ultraviolet radiation, hyperosmotic shock, anisomycin or by TNFalpha is mediated by MKK3. Moreover, in response to osmotic stress, MKK3 and MKK6 are crucial in regulating the phosphorylation of the p38gamma substrate hDlg and its activity as scaffold protein. These data indicate that activation of distinct p38MAPK isoforms is regulated by the selective and synchronized action of two kinases, MKK3 and MKK6, in response to cell stress.

Role of the hypothalamic-pituitary-thyroid axis in metabolic regulation by JNK1

Thu, 08/25/2016 - 1:12pm

The cJun N-terminal kinase 1 (JNK1) is implicated in diet-induced obesity. Indeed, germline ablation of the murine Jnk1 gene prevents diet-induced obesity. Here we demonstrate that selective deficiency of JNK1 in the murine nervous system is sufficient to suppress diet-induced obesity. The failure to increase body mass is mediated, in part, by increased energy expenditure that is associated with activation of the hypothalamic-pituitary-thyroid axis. Disruption of thyroid hormone function prevents the effects of nervous system JNK1 deficiency on body mass. These data demonstrate that the hypothalamic-pituitary-thyroid axis represents an important target of metabolic signaling by JNK1.

Functional cooperation of the proapoptotic Bcl2 family proteins Bmf and Bim in vivo

Thu, 08/25/2016 - 1:12pm

Bcl2-modifying factor (Bmf) is a member of the BH3-only group of proapoptotic proteins. To test the role of Bmf in vivo, we constructed mice with a series of mutated Bmf alleles that disrupt Bmf expression, prevent Bmf phosphorylation by the c-Jun NH(2)-terminal kinase (JNK) on Ser(74), or mimic Bmf phosphorylation on Ser(74). We report that the loss of Bmf causes defects in uterovaginal development, including an imperforate vagina and hydrometrocolpos. We also show that the phosphorylation of Bmf on Ser(74) can contribute to a moderate increase in levels of Bmf activity. Studies of compound mutants with the related gene Bim demonstrated that Bim and Bmf exhibit partially redundant functions in vivo. Thus, developmental ablation of interdigital webbing on mouse paws and normal lymphocyte homeostasis require the cooperative activity of Bim and Bmf.