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The RNA-binding protein ATX-2 regulates cytokinesis through PAR-5 and ZEN-4

Wed, 02/15/2017 - 10:43am

The spindle midzone harbors both microtubules and proteins necessary for furrow formation and the completion of cytokinesis. However, the mechanisms that mediate the temporal and spatial recruitment of cell division factors to the spindle midzone and midbody remain unclear. Here we describe a mechanism governed by the conserved RNA-binding protein ATX-2/Ataxin-2, which targets and maintains ZEN-4 at the spindle midzone. ATX-2 does this by regulating the amount of PAR-5 at mitotic structures, particularly the spindle, centrosomes, and midbody. Preventing ATX-2 function leads to elevated levels of PAR-5, enhanced chromatin and centrosome localization of PAR-5-GFP, and ultimately a reduction of ZEN-4-GFP at the spindle midzone. Codepletion of ATX-2 and PAR-5 rescued the localization of ZEN-4 at the spindle midzone, indicating that ATX-2 mediates the localization of ZEN-4 upstream of PAR-5. We provide the first direct evidence that ATX-2 is necessary for cytokinesis and suggest a model in which ATX-2 facilitates the targeting of ZEN-4 to the spindle midzone by mediating the posttranscriptional regulation of PAR-5.

Distinct Differences on Neointima Formation in Immunodeficient and Humanized Mice after Carotid or Femoral Arterial Injury

Wed, 02/15/2017 - 10:43am

Percutaneous coronary intervention is widely adopted to treat patients with coronary artery disease. However, restenosis remains an unsolved clinical problem after vascular interventions. The role of the systemic and local immune response in the development of restenosis is not fully understood. Hence, the aim of the current study was to investigate the role of the human immune system on subsequent neointima formation elicited by vascular injury in a humanized mouse model. Immunodeficient NOD.Cg-PrkdcscidIL2rgtm1Wjl(NSG) mice were reconstituted with human (h)PBMCs immediately after both carotid wire and femoral cuff injury were induced in order to identify how differences in the severity of injury influenced endothelial regeneration, neointima formation, and homing of human inflammatory and progenitor cells. In contrast to non-reconstituted mice, hPBMC reconstitution reduced neointima formation after femoral cuff injury whereas hPBMCs promoted neointima formation after carotid wire injury 4 weeks after induction of injury. Neointimal endothelium and smooth muscle cells in the injured arteries were of mouse origin. Our results indicate that the immune system may differentially respond to arterial injury depending on the severity of injury, which may also be influenced by the intrinsic properties of the arteries themselves, resulting in either minimal or aggravated neointima formation.

www.common-metrics.org: a web application to estimate scores from different patient-reported outcome measures on a common scale

Wed, 02/15/2017 - 10:43am

BACKGROUND: Recently, a growing number of Item-Response Theory (IRT) models has been published, which allow estimation of a common latent variable from data derived by different Patient Reported Outcomes (PROs). When using data from different PROs, direct estimation of the latent variable has some advantages over the use of sum score conversion tables. It requires substantial proficiency in the field of psychometrics to fit such models using contemporary IRT software. We developed a web application ( http://www.common-metrics.org ), which allows estimation of latent variable scores more easily using IRT models calibrating different measures on instrument independent scales.

RESULTS: Currently, the application allows estimation using six different IRT models for Depression, Anxiety, and Physical Function. Based on published item parameters, users of the application can directly estimate latent trait estimates using expected a posteriori (EAP) for sum scores as well as for specific response patterns, Bayes modal (MAP), Weighted likelihood estimation (WLE) and Maximum likelihood (ML) methods and under three different prior distributions. The obtained estimates can be downloaded and analyzed using standard statistical software.

CONCLUSIONS: This application enhances the usability of IRT modeling for researchers by allowing comparison of the latent trait estimates over different PROs, such as the Patient Health Questionnaire Depression (PHQ-9) and Anxiety (GAD-7) scales, the Center of Epidemiologic Studies Depression Scale (CES-D), the Beck Depression Inventory (BDI), PROMIS Anxiety and Depression Short Forms and others. Advantages of this approach include comparability of data derived with different measures and tolerance against missing values. The validity of the underlying models needs to be investigated in the future.

A molecular signature of preclinical rheumatoid arthritis triggered by dysregulated PTPN22

Wed, 02/15/2017 - 10:43am

A unique feature of rheumatoid arthritis (RA) is the presence of anti-citrullinated protein antibodies (ACPA). Several risk factors for RA are known to increase the expression or activity of peptidyl arginine deiminases (PADs), which catalyze citrullination and, when dysregulated, can result in hypercitrullination. However, the consequence of hypercitrullination is unknown and the function of each PAD has yet to be defined. Th cells of RA patients are hypoglycolytic and hyperproliferative due to impaired expression of PFKFB3 and ATM, respectively. Here, we report that these features are also observed in peripheral blood mononuclear cells (PBMCs) from healthy at-risk individuals (ARIs). PBMCs of ARIs are also hypercitrullinated and produce more IL-2 and Th17 cytokines but fewer Th2 cytokines. These abnormal features are due to impaired induction of PTPN22, a phosphatase that also suppresses citrullination independently of its phosphatase activity. Attenuated phosphatase activity of PTPN22 results in aberrant expression of IL-2, ATM, and PFKFB3, whereas diminished nonphosphatase activity of PTPN22 leads to hypercitrullination mediated by PADs. PAD2- or PAD4-mediated hypercitrullination reduces the expression of Th2 cytokines. By contrast, only PAD2-mediated hypercitrullination can increase the expression of Th17 cytokines. Taken together, our data depict a molecular signature of preclinical RA that is triggered by impaired induction of PTPN22.

A gene-centered C. elegans protein-DNA interaction network provides a framework for functional predictions

Wed, 02/15/2017 - 10:43am

Transcription factors (TFs) play a central role in controlling spatiotemporal gene expression and the response to environmental cues. A comprehensive understanding of gene regulation requires integrating physical protein-DNA interactions (PDIs) with TF regulatory activity, expression patterns, and phenotypic data. Although great progress has been made in mapping PDIs using chromatin immunoprecipitation, these studies have only characterized ~10% of TFs in any metazoan species. The nematode C. elegans has been widely used to study gene regulation due to its compact genome with short regulatory sequences. Here, we delineated the largest gene-centered metazoan PDI network to date by examining interactions between 90% of C. elegans TFs and 15% of gene promoters. We used this network as a backbone to predict TF binding sites for 77 TFs, two-thirds of which are novel, as well as integrate gene expression, protein-protein interaction, and phenotypic data to predict regulatory and biological functions for multiple genes and TFs.

A Pilot Competency Matrix for Data Management Skills: A Step toward the Development of Systematic Data Information Literacy Programs

Wed, 02/15/2017 - 10:42am

Initial work in identifying data management or data information literacy skills generally went as far as identifying a list of proposed competencies without further differentiation between those competencies, whether by discipline, complexity, or use case. This article describes a significant innovation upon existing competencies by identifying a scaffolding (built upon existing competencies) that moves students progressively from undergraduate training through post graduate coursework and research to post-doctoral work and into the early years of data stewardship. The scaffolding ties together existing research that has been completed in research data management skills and data information literacy with research into the outcomes that are desirable for individuals to present in data management at each of the levels of education. Competencies are aligned according to application (personal, team, research enterprise) in such a way that the skills attained at the undergraduate level give students moving on to graduate work greater familiarity with data management and therefore greater likelihood of success at the graduate and then post graduate and data steward levels.

Vitamin D status in pediatric irritable bowel syndrome

Tue, 02/14/2017 - 9:59am

IMPORTANCE: Irritable bowel syndrome (IBS) is associated with significant morbidity in children and adolescents, and the therapeutic efficacy of available treatment options is limited. The role of vitamin D supplementation in pediatric IBS is unclear as the vitamin D status of pediatric patients with IBS is unknown. Equally, the relationship of vitamin D status with psychosomatic symptoms in children and adolescents is unclear.

AIM: To characterize the vitamin D status of pediatric patients with IBS using a case-control study design.

HYPOTHESIS: Serum 25-hydroxyvitamin D [25(OH)D] concentration will be similar between patients with IBS and controls.

SUBJECTS AND METHODS: A retrospective case-controlled study of 116 controls (age 14.6 ± 4.3 y), female (n = 67; 58%) and 55 subjects with IBS (age 16.5 ± 3.1y), female (n = 44; 80%). Overweight was defined as BMI of ≥85th but <95th >percentile, and obesity as BMI ≥95th percentile. Vitamin D deficiency was defined as 25(OH)D of/L, while seasons of vitamin D draw were categorized as summer, winter, spring, and fall. Major psychosomatic manifestations included in the analysis were depression, anxiety, and migraine.

RESULTS: More than 50% of IBS subjects had vitamin D deficiency at a cut-off point of/L (53% vs. 27%, p = 0.001); and >90% of IBS subjects had vitamin D deficiency at a cut-off point of/L (93% vs. 75%, p = 0.006). IBS subjects had significantly lower mean 25(OH)D: 53.2 ± 15.8 nmol/L vs. 65.2 ± 28.0 nmol/L, p = 0.003; and albumin: 6.2 ± 0.6 vs. 6.5 ± 0.6 μmol/L, p = 0.0.01. IBS subjects with migraine had significantly lower mean 25(OH)D concentration compared to controls (p = 0.01). BMI z-score was similar between the controls and IBS subjects (0.5 ± 1.4 vs. 1.2 ± 2.9, p = 0.11).

CONCLUSIONS: Pediatric patients with IBS had significantly lower 25(OH)D concentration compared to controls despite having similar mean BMI values as controls. Only 7% of the children and adolescents with IBS were vitamin D sufficient, and >50% of the subjects with IBS had vitamin D deficiency. This is a much higher prevalence of vitamin D deficiency compared to IBD and other malabsorption syndromes. Monitoring for vitamin D deficiency should be part of the routine care for patients with IBS. Randomized control trials are warranted to determine the role of adjunctive vitamin D therapy in pediatric IBS.

Agreement between Rheumatologist and Patient-reported Adherence to Methotrexate in a US Rheumatoid Arthritis Registry

Mon, 02/13/2017 - 4:00pm

OBJECTIVE: Rheumatologists have limited tools to assess medication adherence. The extent to which methotrexate (MTX) adherence is overestimated by rheumatologists is unknown.

METHODS: We deployed an Internet survey to patients with rheumatoid arthritis (RA) participating in a US registry. Patient self-report was the gold standard compared to MTX recorded in the registry.

RESULTS: Response rate to the survey was 44%. Of 228 patients whose rheumatologist reported current MTX at the time of the most recent registry visit, 45 (19.7%) had discontinued (n = 19, 8.3%) or missed > /= 1 dose in the last month (n = 26, 11.4%). For the subgroup whose rheumatologist also confirmed at the next visit that they were still taking MTX (n = 149), only 2.6% reported not taking it, and 10.7% had missed at least 1 dose.

CONCLUSION: MTX use was misclassified for 13%-20% of patients, mainly because of 1 or more missed doses rather than overt discontinuation. Clinicians should be aware of suboptimal adherence when assessing MTX response.

Differences in Problems Paying Medical Bills between African Americans and Whites from 2007 and 2009: the Underlying Role of Health Status

Mon, 02/13/2017 - 4:00pm

OBJECTIVES: Although the proportion of people reporting problems paying medical bills has declined in the aftermath of the Great Recession, it is unclear if this decline has been caused by self-rationing of care, particularly among disadvantaged groups. We examined African American-White differences in problems paying medical bills prevalence along with factors which may account for observed differences.

DESIGN: We used cross-sectional data from 2007 (N = 13,064) and 2010 (N = 11,873) waves of the nationally representative, Health Tracking Household Survey. Logistic regression analyses, accounting for complex survey design and weights, were performed to compute population-based estimates.

RESULTS: Overall, the prevalence of problems paying medical bills was 18.3 % in 2007 and 19.8 % in 2010. African Americans more frequently reported having problems paying medical bills than Whites. Among African Americans, problems paying medical bills decreased from 30 % in 2007 to 25 % in 2010, which was largely explained by fewer problems reported by those in poor/fair health. Problems paying medical bills significantly declined from 44 % in 2007 to 33 % in 2010 for African Americans in poor/fair health, but remained almost constant for those in good health and very good/excellent health.

CONCLUSION: Our findings suggest that African Americans in poor health may be rationing or forgoing necessary care as a result of the recession, which could increase existing health disparities and future health spending. Efforts to reduce racial/ethnic disparities may depend on the extent to which the lingering effects of the Great Recession are mitigated.

Girls and Boys Born before 28 Weeks Gestation: Risks of Cognitive, Behavioral, and Neurologic Outcomes at Age 10 Years

Mon, 02/13/2017 - 4:00pm

OBJECTIVES: To compare the prevalence of cognitive, neurologic, and behavioral outcomes at 10 years of age in 428 girls and 446 boys who were born extremely preterm.

STUDY DESIGN: A total of 889 of 966 eligible children previously enrolled in the multicenter Extremely Low Gestational Age Newborns Study from 2002-2004 were evaluated at 10 years of age. Children underwent a neuropsychological battery and testing for autism spectrum disorder (ASD), and parents reported on their child's behavior, development, and seizures.

RESULTS: Of the children, 28% of boys and 21% of girls exhibited moderate to severe impairment on summary measures of cognitive abilities. Boys had a higher prevalence of impairment than girls in nearly all measures of cognition, were more than twice as likely to have microcephaly (15% in boys, 8% in girls), and require more often assistive devices to ambulate (6% in boys, 4% in girls). In contrast, boys and girls had comparable risk for a history of seizure (identified in 10% of the cohort) or epilepsy (identified in 7% of the cohort). The boy-to-girl ratio of ASD (9% in boys, 5% in girls) was lower than expected compared with the overall US autism population.

CONCLUSIONS: In this contemporary cohort of children born extremely premature and evaluated at school age, boys had higher prevalence of cognitive, neurologic, and behavioral deficits than girls. The ratio of boys to girls among those with ASD deserves further study as does the perinatal environmental-genetic interactions that might contribute to male preponderance of deficits in this high-risk sample.

Decade-Long Trends in Liver Transplant Waitlist Removal Due to Illness Severity: The Impact of Centers for Medicare and Medicaid Services Policy

Mon, 02/13/2017 - 4:00pm

BACKGROUND: The central tenet of liver transplant organ allocation is to prioritize the sickest patients first. However, a 2007 Centers for Medicare and Medicaid Services regulatory policy, Conditions of Participation (COP), which mandates publically reported transplant center performance assessment and outcomes-based auditing, critically altered waitlist management and clinical decision making. We examine the extent to which COP implementation is associated with increased removal of the "sickest" patients from the liver transplant waitlist.

STUDY DESIGN: This study included 90,765 adult (aged 18 years and older) deceased donor liver transplant candidates listed at 102 transplant centers from April 2002 through December 2012 (Scientific Registry of Transplant Recipients). We quantified the effect of COP implementation on trends in waitlist removal due to illness severity and 1-year post-transplant mortality using interrupted time series segmented Poisson regression analysis.

RESULTS: We observed increasing trends in delisting due to illness severity in the setting of comparable demographic and clinical characteristics. Delisting abruptly increased by 16% at the time of COP implementation, and likelihood of being delisted continued to increase by 3% per quarter thereafter, without attenuation (p < 0.001). Results remained consistent after stratifying on key variables (ie, Model for End-Stage Liver Disease and age). The COP did not significantly impact 1-year post-transplant mortality (p = 0.38).

CONCLUSIONS: Although the 2007 Centers for Medicare and Medicaid Services COP policy was a quality initiative designed to improve patient outcomes, in reality, it failed to show beneficial effects in the liver transplant population. Patients who could potentially benefit from transplantation are increasingly being denied this lifesaving procedure while transplant mortality rates remain unaffected. Policy makers and clinicians should strive to balance candidate and recipient needs from a population-benefit perspective when designing performance metrics and during clinical decision making for patients on the waitlist.

Dysfunctional error-related processing in incarcerated youth with elevated psychopathic traits

Mon, 02/13/2017 - 4:00pm

Adult psychopathic offenders show an increased propensity towards violence, impulsivity, and recidivism. A subsample of youth with elevated psychopathic traits represent a particularly severe subgroup characterized by extreme behavioral problems and comparable neurocognitive deficits as their adult counterparts, including perseveration deficits. Here, we investigate response-locked event-related potential (ERP) components (the error-related negativity [ERN/Ne] related to early error-monitoring processing and the error-related positivity [Pe] involved in later error-related processing) in a sample of incarcerated juvenile male offenders (n=100) who performed a response inhibition Go/NoGo task. Psychopathic traits were assessed using the Hare Psychopathy Checklist: Youth Version (PCL:YV). The ERN/Ne and Pe were analyzed with classic windowed ERP components and principal component analysis (PCA). Using linear regression analyses, PCL:YV scores were unrelated to the ERN/Ne, but were negatively related to Pe mean amplitude. Specifically, the PCL:YV Facet 4 subscale reflecting antisocial traits emerged as a significant predictor of reduced amplitude of a subcomponent underlying the Pe identified with PCA. This is the first evidence to suggest a negative relationship between adolescent psychopathy scores and Pe mean amplitude.

Validation of the HOOS, JR: A Short-form Hip Replacement Survey

Mon, 02/13/2017 - 4:00pm

BACKGROUND: Patient-reported outcome measures (PROMs) are increasingly in demand for outcomes evaluation by hospitals, administrators, and policymakers. However, assessing total hip arthroplasty (THA) through such instruments is challenging because most existing measures of hip health are lengthy and/or proprietary.

QUESTIONS/PURPOSES: The objective of this study was to derive a patient-relevant short-form survey based on the Hip disability and Osteoarthritis Outcome Score (HOOS), focusing specifically on outcomes after THA.

METHODS: We retrospectively evaluated patients with hip osteoarthritis who underwent primary unilateral THA and who had completed preoperative and 2-year postoperative PROMs using our hospital's hip replacement registry. The 2-year followup in this population was 81% (4308 of 5351 patients). Of these, 2371 completed every item on the HOOS before surgery and at 2 years, making them eligible for the formal item reduction analysis. Through semistructured interviews with 30 patients, we identified items in the HOOS deemed qualitatively most important to patients with hip osteoarthritis. The original HOOS has 40 items, the four quality-of-life items were excluded a priori, five were excluded for being redundant, and one was excluded based on patient-relevance surveys. The remaining 30 items were evaluated using Rasch modeling to yield a final six-item HOOS, Joint Replacement (HOOS, JR), representing a single construct of "hip health." We calculated HOOS, JR scores for the Hospital for Special Surgery (HSS) cohort and validated this new score for internal consistency, external validity (versus HOOS and WOMAC domains), responsiveness to THA, and floor and ceiling effects. Additional external validation was performed using calculated HOOS, JR scores in collaboration with the Function and Outcomes Research for Comparative Effectiveness in Total Joint Replacement (FORCE-TJR) nationally representative joint replacement registry (n = 910).

RESULTS: The resulting six-item PROM (HOOS, JR) retained items only from the pain and activities of daily living domains. It showed high internal consistency (Person Separation Index, 0.86 [HSS]; 0.87 [FORCE]), moderate to excellent external validity against other hip surveys (Spearman's correlation coefficient, 0.60-0.94), very high responsiveness (standardized response means, 2.03 [95% CI, 1.84-2.22] [FORCE]; and 2.38 [95% CI, 2.27-2.49] [HSS]), and favorable floor (0.6%-1.9%) and ceiling (37%-46%) effects. External validity was highest for the HOOS pain (Spearman's correlation coefficient, 0.87 [95% CI, 0.86-0.89] [HSS]; and 0.87 [95% CI, 0.84-0.90] [FORCE]) and HOOS activities of daily living (Spearman's correlation coefficient, 0.94 [95% CI, 0.93-0.95] [HSS]; and 0.94 [95% CI, 0.93-0.96] [FORCE]) domains in the HSS validation cohort and the FORCE-TJR cohort.

CONCLUSIONS: The HOOS, JR provides a valid, reliable, and responsive measure of hip health for patients undergoing THA. This short-form PROM is patient relevant and efficient.

LEVEL OF EVIDENCE: Level III, diagnostic study.

Validation of the KOOS, JR: A Short-form Knee Arthroplasty Outcomes Survey

Mon, 02/13/2017 - 4:00pm

BACKGROUND: Medicare is rapidly moving toward using patient-reported outcome measures (PROMs) for outcomes assessment and justification of orthopaedic and other procedures. Numerous measures have been developed to study knee osteoarthritis (OA); however, many of these surveys are long, disruptive to clinic flow, and result in incomplete data capture and/or low followup rates. The Knee injury and Osteoarthritis Outcome (KOOS) physical function short-form (KOOS-PS), while shorter, ignores pain, which is a primary concern of patients with advanced knee OA.

QUESTIONS/PURPOSES: Our objective was to derive and validate a short-form survey focused on the patient with end-stage knee OA undergoing TKA.

METHODS: Using our hospital's knee replacement registry, we retrospectively identified 2291 patients with knee OA who underwent primary unilateral TKA and had completed preoperative and 2-year postoperative PROMs. We assessed 30 items from the 42-item KOOS that were quantitatively most difficult for patients to perform before TKA and qualitatively most relevant to patients with end-stage knee OA. Rasch analysis identified the KOOS, JR, a seven-item instrument, representing a single dimension, which we define as "knee health" because it reflects aspects of pain, symptom severity, and activities of daily living (ADL) including movements or activities that are directly relevant and difficult for patients with advanced knee OA. We assessed the internal consistency, external validity (versus KOOS and WOMAC domains), responsiveness, and floor and ceiling effects of the KOOS, JR. External validation was performed using calculated KOOS, JR scores in collaboration with a nationally representative joint replacement registry, the Function and Outcomes Research for Comparative Effectiveness in Total Joint Replacement (FORCE-TJR).

RESULTS: Internal consistency for the KOOS, JR was high (Person Separation Index, 0.84; and 0.85 [FORCE]), external validity against other validated knee surveys was excellent (Spearman correlation coefficient, rho 0.54-0.91), particularly for the KOOS pain (rho 0.89 [95% CI, 0.88-0.91] Hospital for Special Surgery [HSS]; and 0.91 [95% CI, 0.90-0.93] [FORCE]) and KOOS ADL (rho 0.87 [95% CI, 0.85-0.88] [HSS]; and 0.84 [95% CI, 0.81-0.87] [FORCE]). The KOOS, JR responsiveness (standardized response means, 1.79 [95% CI, 1.70-1.88] [HSS]; and 1.70 [95% CI, 1.54-1.86] [FORCE]) was high and floor 0.4-1.2%) and ceiling (18.8-21.8%) effects were favorable.

CONCLUSIONS: The new short knee PROM, the KOOS, JR, provides a single score representing "knee health" as it combines pain, symptoms, and functional limitations in a single score. This short-form PROM is patient-relevant and efficient.

LEVEL OF EVIDENCE: Level III, diagnostic study.

High Prevalence and Heterogeneity of Diabetes in Patients With TB in South India: A Report from the Effects of Diabetes on Tuberculosis Severity (EDOTS) Study

Mon, 02/13/2017 - 4:00pm

BACKGROUND: Previous studies reported an association of diabetes mellitus (DM) with TB susceptibility. Many studies were retrospective, had weak diagnostic criteria for DM, and did not assess other comorbidities. The Effects of Diabetes on Tuberculosis Severity (EDOTS) study is addressing these limitations with a longitudinal comparison of patients with TB who are classified as diabetic or normoglycemic according to World Health Organization criteria. We report interim findings after enrolling 159 of a planned 300 subjects.

METHODS: A cohort study of patients with TB in South India with DM or normoglycemia defined by oral glucose tolerance test (OGTT) and fasting glucose. Glycohemoglobin (HbA1c), serum creatinine, lipids, and 25-hydroxyvitamin D were measured at enrollment. Patients were monitored monthly during TB treatment, and HbA1c measurement was repeated after 3 months.

RESULTS: Of 209 eligible patients, 113 (54.1%) were classified as diabetic, 44 (21.0%) with impaired glucose tolerance, and 52 (24.9%) as normoglycemic. More patients with diabetes were detected by OGTT than by HbA1c. Diabetes was a newly received diagnosis for 37 (32.7%) in the DM group, and their median HbA1c (6.8%) was significantly lower than in those with previously diagnosed DM (HbA1c, 10.4%). Among 129 patients monitored for 3 months, HbA1c declined in all groups, with the greatest difference in patients with a newly received diagnosis of DM.

CONCLUSIONS: Early EDOTS study results reveal a strikingly high prevalence of glycemic disorders in South Indian patients with pulmonary TB and unexpected heterogeneity within the patient population with diabetes and TB. This glycemic control heterogeneity has implications for the TB-DM interaction and the interpretation of TB studies relying exclusively on HbA1c to define diabetic status.

Impact of residential UV exposure in childhood versus adulthood on skin cancer risk in Caucasian, postmenopausal women in the Women's Health Initiative

Mon, 02/13/2017 - 4:00pm

BACKGROUND: Sun exposure is a major risk factor for skin cancer; however, the relative contribution of ultraviolet (UV) exposure during childhood versus adulthood on skin cancer risk remains unclear.

OBJECTIVE: Our goal was to determine the impact of residential UV, measured by AVerage daily total GLObal solar radiation (AVGLO), exposure during childhood (birth, 15 years) versus adulthood (35, 50 years, and present) on incident non-melanoma skin cancer (NMSC) and malignant melanoma (MM) in postmenopausal women.

METHODS: Women were followed with yearly surveys throughout the duration of their participation in the Women's Health Initiative Observational study, a multicenter study from 1993 to 2005. A total of 56,557 women had data on all observations and were included in the baseline characteristics. The main exposure, residential UV (as measured by AVGLO), was measured by geographic residence during childhood and adulthood. Outcome was risk of incident NMSC and MM.

RESULTS: Over 11.9 years (median follow-up), there were 9,195 (16.3 %) cases of NMSC and 518 (0.92 %) cases of MM. Compared with the reference group (women with low childhood and low adulthood UV), women with low childhood and high adulthood UV had a 21 % increased risk of NMSC (odds ratio 1.21, 95 % confidence interval 1.12, 1.31). Women with high childhood and high adulthood UV had a 19 % increased risk of NMSC (odds ratio 1.19, 95 % confidence interval 1.11, 1.27). Surprisingly, women with high childhood UV and low adulthood UV did not have a significant increase in NMSC risk compared with the reference group (odds ratio 1.08, 95 % confidence interval 0.91, 1.28) in multivariable models. Residential UV exposure in childhood or adulthood was not associated with increased melanoma risk.

CONCLUSION: This study reveals an increase in NMSC risk associated with adulthood residential UV exposure, with no effect for childhood UV exposure.

A systematic review and meta-analysis of meditative interventions for informal caregivers and health professionals

Mon, 02/13/2017 - 4:00pm

BACKGROUND: Burnout, stress and anxiety have been identified as areas of concern for informal caregivers and health professionals, particularly in the palliative setting. Meditative interventions are gaining acceptance as tools to improve well-being in a variety of clinical contexts, however, their effectiveness as an intervention for caregivers remains unknown.

AIM: To explore the effect of meditative interventions on physical and emotional markers of well-being as well as job satisfaction and burnout among informal caregivers and health professionals.

DESIGN: Systematic review of randomised clinical trials and pre-post intervention studies with meditative interventions for caregivers.

DATA SOURCES: PubMed, EMBASE, CINAHL and PsycINFO were searched up to November 2013. Of 1561 abstracts returned, 68 studies were examined in full text with 27 eligible for systematic review.

RESULTS: Controlled trials of informal caregivers showed statistically significant improvement in depression (effect size 0.49 (95% CI 0.24 to 0.75)), anxiety (effect size 0.53 (95% CI 0.06 to 0.99)), stress (effect size 0.49 (95% CI 0.21 to 0.77)) and self-efficacy (effect size 0.86 (95% CI 0.5 to 1.23)), at an average of 8 weeks following intervention initiation. Controlled trials of health professionals showed improved emotional exhaustion (effect size 0.37 (95% CI 0.04 to 0.70)), personal accomplishment (effect size 1.18 (95% CI 0.10 to 2.25)) and life satisfaction (effect size 0.48 (95% CI 0.15 to 0.81)) at an average of 8 weeks following intervention initiation.

CONCLUSIONS: Meditation provides a small to moderate benefit for informal caregivers and health professionals for stress reduction, but more research is required to establish effects on burnout and caregiver burden.

Medical Debt and Related Financial Consequences Among Older African American and White Adults

Mon, 02/13/2017 - 4:00pm

OBJECTIVES: To evaluate African American-White differences in medical debt among older adults and the extent to which economic and health factors explained these.

METHODS: We used nationally representative data from the 2007 and 2010 US Health Tracking Household Survey (n = 5838) and computed population-based estimates of medical debt attributable to economic and health factors with adjustment for age, gender, marital status, and education.

RESULTS: African Americans had 2.6 times higher odds of medical debt (odds ratio = 2.62; 95% confidence interval = 1.85, 3.72) than did Whites. Health status explained 22.8% of the observed disparity, and income and insurance explained 19.4%. These factors combined explained 42.4% of the observed disparity. In addition, African Americans were more likely to be contacted by a collection agency and to borrow money because of medical debt, whereas Whites were more likely to use savings.

CONCLUSIONS: African Americans incur substantial medical debt compared with Whites, and more than 40% of this is mediated by health status, income, and insurance disparities. Public health implications. In Medicare, low-income beneficiaries, especially low-income African Americans with poor health status, should be protected from the unintended financial consequences of cost-reduction strategies.

Asymmetric dimethylarginine, related arginine derivatives, and incident atrial fibrillation

Mon, 02/13/2017 - 4:00pm

BACKGROUND: Oxidative stress plays an important role in the development of atrial fibrillation (AF). Arginine derivatives including asymmetric dimethylarginine (ADMA) are central to nitric oxide metabolism and nitrosative stress. Whether blood concentrations of arginine derivatives are related to incidence of AF is uncertain.

METHODS AND RESULTS: In 3,310 individuals (mean age 58 +/- 10 years, 54% women) from the community-based Framingham Study, we prospectively examined the relations of circulating levels of ADMA, l-arginine, symmetric dimethylarginine (SDMA), and the ratio of l-arginine/ADMA to incidence of AF using proportional hazards regression models. Over a median follow-up time of 10 years, 247 AF cases occurred. Using age- and sex-adjusted regression models, ADMA was associated with a hazard ratio of 1.15 per 1-SD increase in loge-biomarker concentration (95% CI 1.02-1.29, P = .02) for AF, which was no longer significant after further risk factor adjustment (hazard ratio 1.09, 95% CI 0.97-1.23, P = .15). Neither l-arginine nor SDMA was related to new-onset AF. A clinical model comprising clinical risk factors for AF (for age, sex, height, weight, systolic blood pressure, diastolic blood pressure, current smoking, diabetes, hypertension treatment, myocardial infarction, and heart failure; c statistic = 0.781; 95% CI 0.753-0.808) was not improved by the addition of ADMA (0.782; 95% CI 0.755-0.809).

CONCLUSIONS: Asymmetric dimethylarginine and related arginine derivatives were not associated with incident AF in the community after accounting for other clinical risk factors and confounders. Its role in the pathogenesis of AF needs further refinement.