Metropolitan Social Environments and Pre-HAART/HAART Era Changes in Mortality Rates (per 10,000 Adult Residents) among Injection Drug Users Living with AIDS

Background Among the largest US metropolitan areas, trends in mortality rates for injection drug users (IDUs) with AIDS vary substantially. Ecosocial, risk environment and dialectical theories suggest many metropolitan areas characteristics that might drive this variation. We assess metropolitan area characteristics associated with decline in mortality rates among IDUs living with AIDS (per 10,000 adult MSA residents) after highly active antiretroviral therapy (HAART) was developed. Methods This is an ecological cohort study of 86 large US metropolitan areas from 1993–2006. The proportional rate of decline in mortality among IDUs diagnosed with AIDS (as a proportion of adult residents) from 1993–1995 to 2004–2006 was the outcome of interest. This rate of decline was modeled as a function of MSA-level variables suggested by ecosocial, risk environment and dialectical theories. In multiple regression analyses, we used 1993–1995 mortality rates to (partially) control for pre-HAART epidemic history and study how other independent variables affected the outcomes. Results In multivariable models, pre-HAART to HAART era increases in ‘hard drug’ arrest rates and higher pre-HAART income inequality were associated with lower relative declines in mortality rates. Pre-HAART per capita health expenditure and drug abuse treatment rates, and pre- to HAART-era increases in HIV counseling and testing rates, were weakly associated with greater decline in AIDS mortality. Conclusions Mortality among IDUs living with AIDS might be decreased by reducing metropolitan income inequality, increasing public health expenditures, and perhaps increasing drug abuse treatment and HIV testing services. Given prior evidence that drug-related arrest rates are associated with higher HIV prevalence rates among IDUs and do not seem to decrease IDU population prevalence, changes in laws and policing practices to reduce such arrests while still protecting public order should be considered

Forced Smoking Abstinence: Not Enough for Smoking Cessation

Importance: Millions of Americans are forced to quit smoking as they enter tobacco-free prisons and jails, but most return to smoking within days of release. Interventions are needed to sustain tobacco abstinence after release from incarceration. Objective: To evaluate the extent to which the WISE intervention (Working Inside for Smoking Elimination), based on motivational interviewing (MI) and cognitive behavioral therapy (CBT), decreases relapse to smoking after release from a smoke-free prison. Design: Participants were recruited approximately 8 weeks prior to their release from a smoke-free prison and randomized to 6 weekly sessions of either education videos (control) or the WISE intervention. Setting: A tobacco-free prison in the United States. Participants: A total of 262 inmates (35% female). Main Outcome Measure: Continued smoking abstinence was defined as 7-days point-prevelance abstinence validated by urine cotinine measurement. Results: At the 3-week follow-up, 25% of the participants in the WISE intervention (31 of 122) and 7% of the control participants (9 of 125) continued to be tobacco-abstinent (odds ration [OR], 4.4; 95% CI, 2.0-9.7). In addition to the intervention, Hispanic ethnicity, a plan to remain abstinent, and being incarcerated for more than 6 months were all associated with increased likelihood of remaining abstinent. In the logistical regression analysis, participants randomized to the WISE intervention were 6.6 times more likely to remain tobacco abstinent at the 3-week follow up than those randomized to the control condition (95% CI, 2.5-17.0). Nonsmokers at the 3-week follow-up had an additional follow-up 3 months after release, and overall 12% of the participants in the WISER intervention (14 of 122) and 2% of the control participants (3 of 125) were tobacco free at 3 months, as confirmed by urine cotinine measurement (OR, 5.3; 95% CI, 1.4-23.8). Conclusions and Relevance: Forced tobacco abstinence alone during incarceration has little impact on postrelease smoking status. A behavioral intervention provided prior to release greatly improves cotinine-confirmed smoking cessation in the community. Trial Registration: clinicaltrials.gov Identifier: NCT0112258

Biallelic mutations in valyl-tRNA synthetase gene VARS are associated with a progressive neurodevelopmental epileptic encephalopathy.

Aminoacyl-tRNA synthetases (ARSs) function to transfer amino acids to cognate tRNA molecules, which are required for protein translation. To date, biallelic mutations in 31 ARS genes are known to cause recessive, early-onset severe multi-organ diseases. VARS encodes the only known valine cytoplasmic-localized aminoacyl-tRNA synthetase. Here, we report seven patients from five unrelated families with five different biallelic missense variants in VARS. Subjects present with a range of global developmental delay, epileptic encephalopathy and primary or progressive microcephaly. Longitudinal assessment demonstrates progressive cortical atrophy and white matter volume loss. Variants map to the VARS tRNA binding domain and adjacent to the anticodon domain, and disrupt highly conserved residues. Patient primary cells show intact VARS protein but reduced enzymatic activity, suggesting partial loss of function. The implication of VARS in pediatric neurodegeneration broadens the spectrum of human diseases due to mutations in tRNA synthetase genes

Identifying adolescents at risk for suboptimal adherence to tuberculosis treatment: A prospective cohort study

Adolescents account for an estimated 800,000 incident tuberculosis (TB) cases annually and are at risk for suboptimal adherence to TB treatment. Most studies of adolescent TB treatment adherence have used surveillance data with limited psychosocial information. This prospective cohort study aimed to identify risk factors for suboptimal adherence to rifampicin-susceptible TB treatment among adolescents (10-19 years old) in Lima, Peru. We collected psychosocial data using self-administered surveys and clinical data via medical record abstraction. Applying k-means cluster analysis, we grouped participants by psychosocial characteristics hypothesized to impact adherence. Then, we conducted mixed effects regression to compare suboptimal adherence-defined as 10% of doses)-between clusters. Treatment setting (facility vs. home) and drug formulation (single drug vs. fixed dose combination) were interaction terms. Of 249 participants, 90 (36.1%) were female. Median age was 17 (IQR: 15, 16.6) years. We identified three clusters-A, B, and C-of participants based on psychosocial characteristics. Cluster C had the lowest support from caregivers, other family members, and friends; had the weakest motivation to complete TB treatment; were least likely to live with their mothers; and had experienced the most childhood adversity. Among the 118 (47.4%) participants who received facility-based treatment with single drug formulations, adherence did not differ between Clusters A and B, but Cluster C had six-fold odds of suboptimal adherence compared to Cluster A. In Clusters B and C, adherence worsened over time, but only in Cluster C did mean adherence fall below 90% within six months. Our findings have implications for the care of adolescents with TB. When caring for adolescents with low social support and other risk factors, clinicians should take extra measures to reinforce adherence, such as identifying a community health worker or peer to provide treatment support. Implementing newly recommended shorter regimens also may facilitate adherence.Revisión por pare

A LASSO-based approach to analyzing rare variants in genetic association studies

Genetic markers with rare variants are spread out in the genome, making it necessary and difficult to consider them in genetic association studies. Consequently, wisely combining rare variants into “composite” markers may facilitate meaningful analyses. In this paper, we propose a novel approach of analyzing rare variant data by incorporating the least absolute shrinkage and selection operator technique. We applied this method to the Genetic Analysis Workshop 17 data, and our results suggest that this new approach is promising. In addition, we took advantage of having 200 phenotype replications and assessed the performance of our approach by means of repeated classification tree analyses. Our method and analyses were performed without knowledge of the underlying simulating model. Our method identified 38 markers (in 65 genes) that are significantly associated with the phenotype Affected and correctly identified two causal genes, SIRT1 and PDGFD

Strengthening the integration of eye care into the health system: methodology for the development of the WHO package of eye care interventions.

OBJECTIVE: To describe the rational for, and the methods that will be employed to develop, the WHO package of eye care interventions (PECI). METHODS AND ANALYSIS: The development of the package will be conducted in four steps: (1) selection of eye conditions (for which interventions will be included in the package) based on epidemiological data on the causes of vision impairment and blindness, prevalence estimates of eye conditions and health facility data; (2) identification of interventions and related evidence for the selected eye conditions from clinical practice guidelines and high-quality systematic reviews by a technical working group; (3) expert agreement on the inclusion of eye care interventions in the package and the description of resources required for the provision of the selected interventions; and (4) peer review. The project will be led by the WHO Vision Programme in collaboration with Cochrane Eyes and Vision. A Technical Advisory Group, comprised of public health and clinical experts in the field, will provide technical input throughout all stages of development. RESULTS: After considering the feedback of Technical Advisory Group members and reviewing-related evidence, a final list of eye conditions for which interventions will be included in the package has been collated. CONCLUSION: The PECI will support Ministries of Health in prioritising, planning, budgeting and integrating eye care interventions into health systems. It is anticipated that the PECI will be available for use in 2021

Sloan Digital Sky Survey Imaging of Low Galactic Latitude Fields: Technical Summary and Data Release

The Sloan Digital Sky Survey (SDSS) mosaic camera and telescope have obtained five-band optical-wavelength imaging near the Galactic plane outside of the nominal survey boundaries. These additional data were obtained during commissioning and subsequent testing of the SDSS observing system, and they provide unique wide-area imaging data in regions of high obscuration and star formation, including numerous young stellar objects, Herbig-Haro objects and young star clusters. Because these data are outside the Survey regions in the Galactic caps, they are not part of the standard SDSS data releases. This paper presents imaging data for 832 square degrees of sky (including repeats), in the star-forming regions of Orion, Taurus, and Cygnus. About 470 square degrees are now released to the public, with the remainder to follow at the time of SDSS Data Release 4. The public data in Orion include the star-forming region NGC 2068/NGC 2071/HH24 and a large part of Barnard's loop.Comment: 31 pages, 9 figures (3 missing to save space), accepted by AJ, in press, see http://photo.astro.princeton.edu/oriondatarelease for data and paper with all figure