Population and Noncompartmental Pharmacokinetics of Sodium Oxybate Support Weight‐Based Dosing in Children and Adolescents With Narcolepsy With Cataplexy

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Disease Prevalence and Use of Health Care among a National Sample of Black and White Male State Prisoners

U.S. prisons have a court-affirmed mandate to provide health care to prisoners. Given this mandate, we sought to determine whether use of prison health care was equitable across race using a nationally-representative sample of Black and White male state prisoners. We first examined the prevalence of health conditions by race. Then, across all health conditions and for each of 15 conditions, we compared the proportion of Black and White male prisoners with the condition who received health care. For most conditions including cancer, heart disease, and liver-related disorders, the age-adjusted prevalence of disease among Blacks was lower than among Whites (

Opt-Out HIV Testing of Inmates in North Carolina Prisons: Factors Associated with not Wanting a Test and not Knowing They Were Tested

Opt-out HIV testing is recommended for correctional settings but may occur without inmates’ knowledge or against their wishes. Through surveying inmates receiving opt-out testing in a large prison system, we estimated the proportion unaware of being tested or not wanting a test, and associations (prevalence ratios [PRs]) with inmate characteristics. Of 871 tested, 11.8% were unknowingly tested and 10.8% had unwanted tests. Not attending an educational HIV course (PR=2.34, 95% CI 1.47–3.74), lower HIV knowledge (PR=0.95, 95% CI 0.91–0.98), and thinking testing is not mandatory (PR=9.84, 95% CI 4.93–19.67) were associated with unawareness of testing. No prior incarcerations (PR=1.59, 95% CI 1.03–2.46) and not using crack/cocaine recently (PR=2.37, 95% CI 1.21–4.64) were associated with unwanted testing. Residence at specific facilities was associated with both outcomes. Increased assessment of inmate understanding and enhanced implementation are needed to ensure inmates receive full benefits of opt-out testing: being informed and tested according to their wishes

An Evaluation of HIV Testing Among Inmates in the North Carolina Prison System

We examined the use of voluntary HIV testing among state prisoners in the North Carolina prison system

Opt-out HIV testing in prison: informed and voluntary?

HIV testing in prison settings has been identified as an important mechanism to detect cases among high-risk, underserved populations. Several public health organizations recommend that testing across healthcare settings, including prisons, be delivered in an opt-out manner. However, implementation of opt-out testing within prisons may pose challenges in delivering testing that is informed and understood to be voluntary. In a large state prison system with a policy of voluntary opt-out HIV testing, we randomly sampled adult prisoners in each of seven intake prisons within two weeks after their opportunity to be HIV tested. We surveyed prisoners’ perception of HIV testing as voluntary or mandatory and used multivariable statistical models to identify factors associated with their perception. We also linked survey responses to lab records to determine if prisoners’ test status (tested or not) matched their desired and perceived test status. Thirty eight percent (359/936) perceived testing as voluntary. The perception that testing was mandatory was positively associated with age less than 25 years (adjusted relative risk [aRR]: 1.45, 95% CI: 1.24, 1.71) and preference that testing be mandatory (aRR: 1.81, 95% CI: 1.41, 2.31), but negatively associated with entry into one of the intake prisons (aRR: 0.41 95% CI: 0.27, 0.63). Eighty-nine percent of prisoners wanted to be tested, 85% were tested according to their wishes, and 82% correctly understood whether or not they were tested. Most prisoners wanted to be HIV tested and were aware that they had been tested, but less than 40% understood testing to be voluntary. Prisoners’ understanding of the voluntary nature of testing varied by intake prison and by a few individual-level factors. Testing procedures should ensure that opt-out testing is informed and understood to be voluntary by prisoners and other vulnerable populations

PPAR? Downregulation by TGF in Fibroblast and Impaired Expression and Function in Systemic Sclerosis: A Novel Mechanism for Progressive Fibrogenesis

The nuclear orphan receptor peroxisome proliferator-activated receptor-gamma (PPAR-γ) is expressed in multiple cell types in addition to adipocytes. Upon its activation by natural ligands such as fatty acids and eicosanoids, or by synthetic agonists such as rosiglitazone, PPAR-γ regulates adipogenesis, glucose uptake and inflammatory responses. Recent studies establish a novel role for PPAR-γ signaling as an endogenous mechanism for regulating transforming growth factor-ß (TGF-ß)- dependent fibrogenesis. Here, we sought to characterize PPAR-γ function in the prototypic fibrosing disorder systemic sclerosis (SSc), and delineate the factors governing PPAR-γ expression. We report that PPAR-γ levels were markedly diminished in skin and lung biopsies from patients with SSc, and in fibroblasts explanted from the lesional skin. In normal fibroblasts, treatment with TGF-ß resulted in a time- and dose-dependent down-regulation of PPAR-γ expression. Inhibition occurred at the transcriptional level and was mediated via canonical Smad signal transduction. Genome-wide expression profiling of SSc skin biopsies revealed a marked attenuation of PPAR-γ levels and transcriptional activity in a subset of patients with diffuse cutaneous SSc, which was correlated with the presence of a ''TGF-ß responsive gene signature'' in these biopsies. Together, these results demonstrate that the expression and function of PPAR-γ are impaired in SSc, and reveal the existence of a reciprocal inhibitory cross-talk between TGF-ß activation and PPAR-γ signaling in the context of fibrogenesis. In light of the potent anti-fibrotic effects attributed to PPAR-γ, these observations lead us to propose that excessive TGF-ß activity in SSc accounts for impaired PPAR-γ function, which in turn contributes to unchecked fibroblast activation and progressive fibrosis. © 2010 Wei et al

Multilevel challenges to engagement in HIV care after prison release: a theory-informed qualitative study comparing prisoners’ perspectives before and after community reentry

Abstract Background Although prison provides the opportunity for HIV diagnosis and access to in-prison care, following release, many HIV-infected inmates experience clinical setbacks, including nonadherence to antiretrovirals, elevations in viral load, and HIV disease progression. HIV-infected former inmates face numerous barriers to successful community reentry and to accessing healthcare. However, little is known about the outcome expectations of HIV-infected inmates for release, how their post-release lives align with pre-release expectations, and how these processes influence engagement in HIV care following release from prison. Methods We conducted semi-structured interviews (24 pre- and 13 post-release) with HIV-infected inmates enrolled in a randomized controlled trial of a case management intervention to enhance post-release linkage to care. Two researchers independently coded data using a common codebook. Intercoder reliability was strong (kappa = 0.86). We analyzed data using Grounded Theory methodology and Applied Thematic Analysis. We collected and compared baseline sociodemographic and behavioral characteristics of all cohort participants who did and did not participate in the qualitative interviews using Fisher’s Exact Tests for categorical measures and Wilcoxon rank-sum tests for continuous measures. Results Most participants were heterosexual, middle-aged, single, African American men and women with histories of substance use. Substudy participants were more likely to anticipate living with family/friends and needing income assistance post-release. Most were taking antiretrovirals prior to release and anticipated needing help securing health benefits and medications post-release. Before release, most participants felt confident they would be able to manage their HIV. However, upon release, many experienced intermittent or prolonged periods of antiretroviral nonadherence, largely due to substance use relapse or delays in care initiation. Substance use was precipitated by stressful life experiences, including stigma, and contact with drug-using social networks. As informed by the Social Cognitive Theory and HIV Stigma Framework, findings illustrate the reciprocal relationships among substance use, experiences of stigma, pre- and post-release environments, and skills needed to engage in HIV care. Conclusion These findings underscore the need for comprehensive evidence-based interventions to prepare inmates to transition from incarceration to freedom, particularly those that strengthen linkage to HIV care and focus on realities of reentry, including stigma, meeting basic needs, preventing substance abuse, and identifying community resources

Is there scope for cost savings and efficiency gains in HIV services? A systematic review of the evidence from low- and middle-income countries.

OBJECTIVE: To synthesize the data available--on costs, efficiency and economies of scale and scope--for the six basic programmes of the UNAIDS Strategic Investment Framework, to inform those planning the scale-up of human immunodeficiency virus (HIV) services in low- and middle-income countries. METHODS: The relevant peer-reviewed and "grey" literature from low- and middle-income countries was systematically reviewed. Search and analysis followed Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. FINDINGS: Of the 82 empirical costing and efficiency studies identified, nine provided data on economies of scale. Scale explained much of the variation in the costs of several HIV services, particularly those of targeted HIV prevention for key populations and HIV testing and treatment. There is some evidence of economies of scope from integrating HIV counselling and testing services with several other services. Cost efficiency may also be improved by reducing input prices, task shifting and improving client adherence. CONCLUSION: HIV programmes need to optimize the scale of service provision to achieve efficiency. Interventions that may enhance the potential for economies of scale include intensifying demand-creation activities, reducing the costs for service users, expanding existing programmes rather than creating new structures, and reducing attrition of existing service users. Models for integrated service delivery--which is, potentially, more efficient than the implementation of stand-alone services--should be investigated further. Further experimental evidence is required to understand how to best achieve efficiency gains in HIV programmes and assess the cost-effectiveness of each service-delivery model

Cerebellar Integrity in the Amyotrophic Lateral Sclerosis - Frontotemporal Dementia Continuum

Amyotrophic lateral sclerosis (ALS) and behavioural variant frontotemporal dementia (bvFTD) are multisystem neurodegenerative disorders that manifest overlapping cognitive, neuropsychiatric and motor features. The cerebellum has long been known to be crucial for intact motor function although emerging evidence over the past decade has attributed cognitive and neuropsychiatric processes to this structure. The current study set out i) to establish the integrity of cerebellar subregions in the amyotrophic lateral sclerosis-behavioural variant frontotemporal dementia spectrum (ALS-bvFTD) and ii) determine whether specific cerebellar atrophy regions are associated with cognitive, neuropsychiatric and motor symptoms in the patients. Seventy-eight patients diagnosed with ALS, ALS-bvFTD, behavioural variant frontotemporal dementia (bvFTD), most without C9ORF72 gene abnormalities, and healthy controls were investigated. Participants underwent cognitive, neuropsychiatric and functional evaluation as well as structural imaging using voxel-based morphometry (VBM) to examine the grey matter subregions of the cerebellar lobules, vermis and crus. VBM analyses revealed: i) significant grey matter atrophy in the cerebellum across the whole ALS-bvFTD continuum; ii) atrophy predominantly of the superior cerebellum and crus in bvFTD patients, atrophy of the inferior cerebellum and vermis in ALS patients, while ALS-bvFTD patients had both patterns of atrophy. Post-hoc covariance analyses revealed that cognitive and neuropsychiatric symptoms were particularly associated with atrophy of the crus and superior lobule, while motor symptoms were more associated with atrophy of the inferior lobules. Taken together, these findings indicate an important role of the cerebellum in the ALS-bvFTD disease spectrum, with all three clinical phenotypes demonstrating specific patterns of subregional atrophy that associated with different symptomology

The HLA class II allele DRB1*1501 is over-represented in patients with idiopathic pulmonary fibrosis

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive and medically refractory lung disease with a grim prognosis. Although the etiology of IPF remains perplexing, abnormal adaptive immune responses are evident in many afflicted patients. We hypothesized that perturbations of human leukocyte antigen (HLA) allele frequencies, which are often seen among patients with immunologic diseases, may also be present in IPF patients. Methods/Principal Findings: HLA alleles were determined in subpopulations of IPF and normal subjects using molecular typing methods. HLA-DRB1*15 was over-represented in a discovery cohort of 79 Caucasian IPF subjects who had lung transplantations at the University of Pittsburgh (36.7%) compared to normal reference populations. These findings were prospectively replicated in a validation cohort of 196 additional IPF subjects from four other U.S. medical centers that included both ambulatory patients and lung transplantation recipients. High-resolution typing was used to further define specific HLA-DRB1*15 alleles. DRB1*1501 prevalence in IPF subjects was similar among the 143 ambulatory patients and 132 transplant recipients (31.5% and 34.8%, respectively, p = 0.55). The aggregate prevalence of DRB1*1501 in IPF patients was significantly greater than among 285 healthy controls (33.1% vs. 20.0%, respectively, OR 2.0; 95%CI 1.3-2.9, p = 0.0004). IPF patients with DRB1*1501 (n = 91) tended to have decreased diffusing capacities for carbon monoxide (DLCO) compared to the 184 disease subjects who lacked this allele (37.8±1.7% vs. 42.8±1.4%, p = 0.036). Conclusions/Significance: DRB1*1501 is more prevalent among IPF patients than normal subjects, and may be associated with greater impairment of gas exchange. These data are novel evidence that immunogenetic processes can play a role in the susceptibility to and/or manifestations of IPF. Findings here of a disease association at the HLA-DR locus have broad pathogenic implications, illustrate a specific chromosomal area for incremental, targeted genomic study, and may identify a distinct clinical phenotype among patients with this enigmatic, morbid lung disease