Attenuated traumatic axonal injury and improved functional outcome after traumatic brain injury in mice lacking Sarm1
Axonal degeneration is a critical, early event in many acute and chronic neurological disorders. It has been consistently observed after traumatic brain injury, but whether axon degeneration is a driver of traumatic brain injury remains unclear. Molecular pathways underlying the pathology of traumatic brain injury have not been defined, and there is no efficacious treatment for traumatic brain injury. Here we show that mice lacking the mouse Toll receptor adaptorSarm1(sterile alpha/Armadillo/Toll-Interleukin receptor homology domain protein) gene, a key mediator of Wallerian degeneration, demonstrate multiple improved traumatic brain injury-associated phenotypes after injury in a closed-head mild traumatic brain injury model.Sarm1(-/-)mice developed fewer beta-amyloid precursor protein aggregates in axons of the corpus callosum after traumatic brain injury as compared toSarm1(+/+)mice. Furthermore, mice lackingSarm1had reduced plasma concentrations of the phophorylated axonal neurofilament subunit H, indicating that axonal integrity is maintained after traumatic brain injury. Strikingly, whereas wild-type mice exibited a number of behavioural deficits after traumatic brain injury, we observed a strong, early preservation of neurological function inSarm1(-/-)animals. Finally, usingin vivoproton magnetic resonance spectroscopy we found tissue signatures consistent with substantially preserved neuronal energy metabolism inSarm1(-/-)mice compared to controls immediately following traumatic brain injury. Our results indicate that the SARM1-mediated prodegenerative pathway promotes pathogenesis in traumatic brain injury and suggest that anti-SARM1 therapeutics are a viable approach for preserving neurological function after traumatic brain injury.
Developing a Community-Based Participatory Research Approach to Understanding of the Repeat Use of Psychiatric Emergency Services
Psychiatric emergency services (PES) remain a critical and under-examined component of the community mental health system. We describe how a unique community-academic partnership came together to examine repeat use of PES through the design and conduct of a qualitative study using a CBPR approach. The goals of the project were to: (1) develop a model of research which promoted the inclusion of people who use mental health services in the research process; and (2) design and conduct a study to examine the repeat use of PES through the inclusion of the perspectives and experiences of people who use these services.
Infertility and perinatal loss are common, and associated with lower quality of life, marital discord, complicated grief, major depressive disorder, anxiety disorders, and post-traumatic stress disorder. Young women, who lack social supports, have experienced recurrent pregnancy loss or a history of trauma and / or preexisting psychiatric illness are at a higher risk of experiencing psychiatric illnesses or symptoms after a perinatal loss or during infertility. It is especially important to detect, assess, and treat depression, anxiety, or other psychiatric symptoms because infertility or perinatal loss may be caused or perpetuated by such symptoms. Screening, psychoeducation, provision of resources and referrals, and an opportunity to discuss their loss and plan for future pregnancies can facilitate addressing mental health concerns that arise. Women at risk of or who are currently experiencing psychiatric symptoms should receive a comprehensive treatment plan that includes the following: (1) proactive clinical monitoring, (2) evidence-based approaches to psychotherapy, and (3) discussion of risks, benefits, and alternatives of medication treatment during preconception and pregnancy.
Most women with perinatal depression do not receive depression treatment. The authors describe the development and beta testing of a new program, PRogram In Support of Moms (PRISM), to improve treatment of perinatal depression in obstetric practices. A multidisciplinary work group of seven perinatal and behavioral health professionals was convened to design, refine, and beta-test PRISM in an obstetric practice. Iterative feedback and problem solving facilitated development of PRISM components, which include provider training and a toolkit, screening procedures, implementation assistance, and access to immediate psychiatric consultation. Beta testing with 50 patients over two months demonstrated feasibility and suggested that PRISM may improve provider screening rates and self-efficacy to address depression. On the basis of lessons learned, PRISM will be enhanced to integrate proactive patient engagement and monitoring into obstetric practices. PRISM may help overcome patient-, provider-, and system-level barriers to managing perinatal depression in obstetric settings.
OBJECTIVE: Perinatal depression is common and associated with poor birth, infant and child outcomes. Screening for perinatal depression alone does not improve treatment rates or patient outcomes. This paper describes the development, implementation and outcomes of a new and low-cost population-based program to help providers address perinatal depression, the Massachusetts Child Psychiatry Access Project (MCPAP) for Moms.
METHOD: MCPAP for Moms builds providers' capacity to address perinatal depression through (1) trainings and toolkits on depression screening, assessment and treatment; (2) telephonic access to perinatal psychiatric consultation for providers serving pregnant and postpartum women; and (3) care coordination to link women with individual psychotherapy and support groups.
RESULTS: In the first 18 months, MCPAP for Moms enrolled 87 Ob/Gyn practices, conducted 100 trainings and served 1123 women. Of telephone consultations provided, 64% were with obstetric providers/midwives and 16% were with psychiatrists. MCPAP for Moms costs $8.38 per perinatal woman per year ($0.70 per month) or $600,000 for 71,618 deliveries annually in Massachusetts.
CONCLUSION: The volume of encounters, number of women served and low cost suggest that MCPAP for Moms is a feasible, acceptable and sustainable approach that can help frontline providers effectively identify and manage perinatal depression.
Promotional flyer for the e-Science Portal for New England Librarians. The e-Science portal is a resource for librarians, library students, information professionals, and interested individuals to learn about and discuss library roles in e-Science, fundamentals of domain sciences, and emerging trends in supporting networked scientific research.
Priorities of Municipal Policy Makers in Relation to Physical Activity and the Built Environment: A Latent Class Analysis
OBJECTIVE: To examine policy makers' public policy priorities related to physical activity and the built environment, identify classes of policy makers based on priorities using latent class analysis, and assess factors associated with class membership.
DESIGN: Cross-sectional survey data from municipal officials in 94 cities and towns across 6 US states were analyzed.
PARTICIPANTS: Participants (N = 423) were elected or appointed municipal officials spanning public health, planning, transportation/public works, community and economic development, parks and recreation, and city management.
MAIN OUTCOME MEASURES: Participants rated the importance of 11 policy areas (public health, physical activity, obesity, economic development, livability, climate change, air quality, natural resource conservation, traffic congestion, traffic safety, and needs of vulnerable populations) in their daily job responsibilities. Latent class analysis was used to determine response patterns and identify distinct classes based on officials' priorities. Logistic regression models assessed participant characteristics associated with class membership.
RESULTS: Four classes of officials based on policy priorities emerged: (1) economic development and livability; (2) economic development and traffic concerns; (3) public health; and (4) general (all policy areas rated as highly important). Compared with class 4, officials in classes 1 and 3 were more likely to have a graduate degree, officials in class 2 were less likely to be in a public health job/department, and officials in class 3 were more likely to be in a public health job/department.
CONCLUSIONS: Findings can guide public health professionals in framing discussions with policy makers to maximize physical activity potential of public policy initiatives, particularly economic development.
Did Medicare Part D Affect National Trends in Health Outcomes or Hospitalizations? A Time-Series Analysis
BACKGROUND: Medicare Part D increased economic access to medications, but its effect on population-level health outcomes and use of other medical services remains unclear.
OBJECTIVE: To examine changes in health outcomes and medical services in the Medicare population after implementation of Part D.
DESIGN: Population-level longitudinal time-series analysis with generalized linear models.
PATIENTS: Nationally representative sample of Medicare beneficiaries (n = 56,293 [unweighted and unique]) from 2000 to 2010.
MEASUREMENTS: Changes in self-reported health status, limitations in activities of daily living (ADLs) (ADLs and instrumental ADLs), emergency department visits and hospital admissions (prevalence, counts, and spending), and mortality. Medicare claims data were used for confirmatory analyses.
RESULTS: Five years after Part D implementation, no clinically or statistically significant reductions in the prevalence of fair or poor health status or limitations in ADLs or instrumental ADLs, relative to historical trends, were detected. Compared with trends before Part D, no changes in emergency department visits, hospital admissions or days, inpatient costs, or mortality after Part D were seen. Confirmatory analyses were consistent.
LIMITATIONS: Only total population-level outcomes were studied. Self-reported measures may lack sensitivity.
CONCLUSION: Five years after implementation, and contrary to previous reports, no evidence was found of Part D's effect on a range of population-level health indicators among Medicare enrollees. Further, there was no clear evidence of gains in medical care efficiencies.
Validation of the Waterpipe Tolerance Questionnaire Among Jordanian School-Going Adolescent Waterpipe Users
INTRODUCTION: Waterpipe use among adolescents has been increasing progressively. Yet no studies were reported to assess the validity and reliability of nicotine dependence scale. The current study aims to assess the validity and reliability of an Arabic version of the modified Waterpipe Tolerance Questionnaire WTQ among school-going adolescent waterpipe users.
METHODS: In a cross-sectional study conducted in Jordan, information on waterpipe use among 333 school-going adolescents aged 11-18 years was obtained using the Arabic version of the WTQ. An exploratory factor analysis and correlation matrices were conducted to assess validity and reliability of the WTQ.
RESULTS: The WTQ had a 0.73 alpha of internal consistency indicating moderate level of reliability. The scale showed multidimensionality with items loading on two factors, namely waterpipe consumption and morning smoking.
CONCLUSION: This study report nicotine dependence level among school-going adolescents who identify themselves as waterpipe users using the WTQ.
Associations of lifetime active and passive smoking with spontaneous abortion, stillbirth and tubal ectopic pregnancy: a cross-sectional analysis of historical data from the Women's Health Initiative
OBJECTIVE: To examine the associations between tobacco exposure and adverse pregnancy outcomes using quantitative measures of lifetime active smoking and secondhand smoke (SHS) exposure.
METHODS: Historical reproductive data on 80 762 women who participated in the Women's Health Initiative Observational Study were examined with a cross-sectional analysis. We assessed self-reported lifetime active and passive tobacco smoke exposure, self-reported spontaneous abortions, stillbirths and ectopic pregnancies.
RESULTS: When compared with never-smoking women, participants who were ever active smokers during their reproductive years had ORs (OR) of 1.16 (95% CI 1.08 to 1.26) for 1 or more spontaneous abortions, 1.44 (95% CI 1.20 to 1.73) for 1 or more stillbirths, and 1.43 (95% CI 1.10 to 1.86) for 1 or more ectopic pregnancies. Never-smoking women participants with the highest levels of lifetime SHS exposure, including childhood > 10 years, adult home > 20 years and adult work exposure > 10 years, when compared with never-smoking women with no SHS exposure had adjusted ORs of 1.17 (95% CI 1.05 to 1.30) for spontaneous abortion, 1.55 (95% CI 1.21 to 1.97) for stillbirth, and 1.61 (95% CI 1.16 to 2.24) for ectopic pregnancy.
CONCLUSIONS: Women who were ever-smokers during their reproductive years had significantly greater estimates of risk for spontaneous abortion, stillbirth and tubal ectopic pregnancy. Never-smoking women with the highest levels of lifetime exposure to SHS had significantly increased estimates of risk for spontaneous abortion, stillbirth and tubal ectopic pregnancy.
Inflammation contributes to the pathogenesis of most acute and chronic liver diseases. Inflammasomes are multiprotein complexes that can sense danger signals from damaged cells and pathogens and assemble to mediate caspase-1 activation, which proteolytically activates the cytokines IL-1beta and IL-18. In contrast to other inflammatory responses, inflammasome activation uniquely requires two signals to induce inflammation, therefore setting an increased threshold. IL-1beta, generated upon caspase-1 activation, provides positive feed-forward stimulation for inflammatory cytokines, thereby amplifying inflammation. Inflammasome activation has been studied in different human and experimental liver diseases and has been identified as a major contributor to hepatocyte damage, immune cell activation and amplification of liver inflammation. In this Review, we discuss the different types of inflammasomes, their activation and biological functions in the context of liver injury and disease progression. Specifically, we focus on the triggers of inflammasome activation in alcoholic steatohepatitis and NASH, chronic HCV infection, ischaemia-reperfusion injury and paracetamol-induced liver injury. The application and translation of these discoveries into therapies promises novel approaches in the treatment of inflammation in liver disease.
IMPORTANCE: Massachusetts introduced health care reform (HCR) in 2006, expecting to expand health insurance coverage and improve outcomes. Because traumatic injury is a common acute condition with important health, disability, and economic consequences, examination of the effect of HCR on patients hospitalized following injury may help inform the national HCR debate.
OBJECTIVE: To examine the effect of Massachusetts HCR on survival rates of injured patients.
DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study of 1,520,599 patients hospitalized following traumatic injury in Massachusetts or New York during the 10 years (2002-2011) surrounding Massachusetts HCR using data from the State Inpatient Databases. We assessed the effect of HCR on mortality rates using a difference-in-differences approach to control for temporal trends in mortality.
INTERVENTION: Health care reform in Massachusetts in 2006.
MAIN OUTCOME AND MEASURE: Survival until hospital discharge.
RESULTS: During the 10-year study period, the rates of uninsured trauma patients in Massachusetts decreased steadily from 14.9% in 2002 to 5.0.% in 2011. In New York, the rates of uninsured trauma patients fell from 14.9% in 2002 to 10.5% in 2011. The risk-adjusted difference-in-difference assessment revealed a transient increase of 604 excess deaths (95% CI, 419-790) in Massachusetts in the 3 years following implementation of HCR.
CONCLUSIONS AND RELEVANCE: Health care reform did not affect health insurance coverage for patients hospitalized following injury but was associated with a transient increase in adjusted mortality rates. Reducing mortality rates for acutely injured patients may require more comprehensive interventions than simply promoting health insurance coverage through legislation.
Dissemination of Evidence-Based Antipsychotic Prescribing Guidelines to Nursing Homes: A Cluster Randomized Trial
OBJECTIVES: To evaluate the effectiveness of efforts to translate and disseminate evidence-based guidelines about atypical antipsychotic use to nursing homes (NHs).
DESIGN: Three-arm, cluster randomized trial.
PARTICIPANTS: NHs in the state of Connecticut.
MEASUREMENTS: Evidence-based guidelines for atypical antipsychotic prescribing were translated into a toolkit targeting NH stakeholders, and 42 NHs were recruited and randomized to one of three toolkit dissemination strategies: mailed toolkit delivery (minimal intensity); mailed toolkit delivery with quarterly audit and feedback reports about facility-level antipsychotic prescribing (moderate intensity); and in-person toolkit delivery with academic detailing, on-site behavioral management training, and quarterly audit and feedback reports (high intensity). Outcomes were evaluated using the Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) framework.
RESULTS: Toolkit awareness of 30% (7/23) of leadership of low-intensity NHs, 54% (19/35) of moderate-intensity NHs, and 82% (18/22) of high-intensity NHs reflected adoption and implementation of the intervention. Highest levels of use and knowledge among direct care staff were reported in high-intensity NHs. Antipsychotic prescribing levels declined during the study period, but there were no statistically significant differences between study arms or from secular trends.
CONCLUSION: RE-AIM indicators suggest some success in disseminating the toolkit and differences in reach, adoption, and implementation according to dissemination strategy but no measurable effect on antipsychotic prescribing trends. Further dissemination to external stakeholders such as psychiatry consultants and hospitals may be needed to influence antipsychotic prescribing for NH residents.
Adherence to evidence-based secondary prevention pharmacotherapy in patients after an acute coronary syndrome: A systematic review
OBJECTIVE: To synthesize current evidence on medication adherence rates and associated risk factors in patients after an acute coronary syndrome (ACS).
METHODS: A systematic review was conducted. Five electronic databases and article bibliographies were searched for publications from 1990 to 2013 which assessed adherence to secondary prevention pharmacotherapy in adults after hospital discharge for an ACS. Identified studies were screened using pre-defined criteria for eligibility. A standardized form was used for data abstraction. Methodological quality was assessed using modified criteria for quantitative studies.
RESULTS: Sixteen studies met our inclusion criteria. Post-discharge medication adherence rates at 1-year ranged between 54% and 86%. There were no consistent predictors of non-adherence across all cardiac medication classes examined.
CONCLUSIONS: Adherence to secondary prevention pharmacotherapy was suboptimal in patients after hospital discharge for an ACS. Risk factors associated with non-adherence were examined in a limited number of studies, and the associations varied between these investigations.
Marriage and parenthood are associated with weight gain and residential mobility. Little is known about how obesity-relevant environmental contexts differ according to family structure. We estimated trajectories of neighborhood poverty, population density, and density of fast food restaurants, supermarkets, and commercial and public physical activity facilities for adults from a biracial cohort (CARDIA, n=4,174, aged 25-50) over 13 years (1992-93 through 2005-06) using latent growth curve analysis. We estimated associations of marriage, parenthood, and race with the observed neighborhood trajectories. Married participants tended to live in neighborhoods with lower poverty, population density, and availability of all types of food and physical activity amenities. Parenthood was similarly but less consistently related to neighborhood characteristics. Marriage and parenthood were more strongly related to neighborhood trajectories in whites (versus blacks), who, in prior studies, exhibit weaker associations between neighborhood characteristics and health. Greater understanding of how interactive family and neighborhood environments contribute to healthy living is needed.
Autism spectrum disorder (ASD) affects 1 in 50 children between the ages of 6 and 17 years. The etiology of ASD is not precisely known. ASD is an umbrella term, which includes both low- (IQ < 70) and high-functioning (IQ > 70) individuals. A better understanding of the disorder and how it manifests in individual subjects can lead to more effective intervention plans to fulfill the individual's treatment needs.Magnetic resonance imaging (MRI) is a non-invasive investigational tool that can be used to study the ways in which the brain develops or deviates from the typical developmental trajectory. MRI offers insights into the structure, function, and metabolism of the brain. In this article, we review published studies on brain connectivity changes in ASD using either resting state functional MRI or diffusion tensor imaging.The general findings of decreases in white matter integrity and in long-range neural coherence are well known in the ASD literature. Nevertheless, the detailed localization of these findings remains uncertain, and few studies link these changes in connectivity with the behavioral phenotype of the disorder. With the help of data sharing and large-scale analytic efforts, however, the field is advancing toward several convergent themes, including the reduced functional coherence of long-range intra-hemispheric cortico-cortical default mode circuitry, impaired inter-hemispheric regulation, and an associated, perhaps compensatory, increase in local and short-range cortico-subcortical coherence.
Alcoholic hepatitis (AH) is a clinical syndrome that was classically characterized by increasing jaundice, hepatomegaly, fever, neutrophilia, and an aspartate aminotransferase (AST):alanine aminotransferase (ALT) ratio of >2. It is a major cause of liver-related hospitalizations in those with a history of heavy alcohol consumption and is also a leading etiology associated with recurrent hospitalizations. Unfortunately, despite its clinical relevance, there are many gaps in knowledge related to this syndrome that represent barriers to the development of effective preventive surveillance, early detection, and therapeutic strategies. This article summarizes the gaps in knowledge and identifies research priorities to fill these gaps.
Recent national trends in acute myocardial infarction hospitalizations in Medicare: shrinking declines and growing disparities
We looked at trends in AMI (acute myocardial infarction) hospitalization rates among elderly Medicare beneficiaries over the 10-year period 2002 to 2011, focusing specifically on whether the post-2007 declines are also more modest for blacks than for whites, potentially reflecting a growing gap in care.
OBJECTIVES: The goal of this study was to determine whether endosomal Toll-like receptors (TLRs) contribute to the clinical manifestation of systemic autoimmunity exhibited by mice that lack the lysosomal nuclease DNaseII.
METHODS: DNaseII/IFNaR double deficient mice were intercrossed with Unc93b13d/3d mice to generate DNaseII-/-mice with non-functional endosomal TLRs. The resulting triple deficient mice were evaluated for arthritis, autoantibody production, splenomegaly, and extramedullary haematopoiesis. B cells from both strains were evaluated for their capacity to respond to endogenous DNA by using small oligonucleotide based TLR9D ligands and a novel class of bifunctional anti-DNA antibodies.
RESULTS: Mice that fail to express DNaseII, IFNaR, and Unc93b1 still develop arthritis but do not make autoantibodies, develop splenomegaly, or exhibit extramedullary haematopoiesis. DNaseII-/- IFNaR-/- B cells can respond to synthetic ODNs, but not to endogenous dsDNA.
CONCLUSIONS: RNA-reactive TLRs, presumably TLR7, are required for autoantibody production, splenomegaly, and extramedullary haematopoiesis in the DNaseII-/- model of systemic autoimmunity.