Publications

BACKGROUND

Individuals infected with both HIV and hepatitis C virus (HCV) have shown impaired performance on different neuropsychological (NP) tests; however, whether coinfected individuals with controlled HIV and minimal liver damage in the era of antiretroviral therapy have impairment is understudied.

METHODS

Nineteen HCV monoinfected, 17 HIV/HCV coinfected, and 17 control male participants were evaluated for depression, attention, executive function, information processing, fine motor speed, and verbal/visual learning/memory. Eleven controls and 14 HIV monoinfected participants with controlled viral load from a previous study were also included for comparison. At time of testing, participants were not using drugs or alcohol and did not have cirrhosis. A global deficit score (GDS) was calculated from 7 domains of NP tests and alterations in specific domains were determined.

RESULTS

HIV/HCV subjects had a higher depression score (11.1 ± 7.5) than controls (5.4 ± 4.1, P = 0.010) and a higher GDS score (0.77 ± 0.47) than HCV (0.46 ± 0.34, P = 0.036), HIV (0.45 ± 0.36, P = 0.008), and controls (0.30 ± 0.29, P = 0.001). Coinfection was associated with worse scores in attention working memory (P =0.007), executive function (P = 0.01), fine motor function (P = 0.011), verbal learning/memory (P < 0.001), and visual learning/memory (P < 0.001) compared to controls. Within the HCV group, viral load was associated with lower attention, executive function, and information processing speed and positively with GDS.

CONCLUSIONS

Coinfection significantly increased the risk of cognitive impairment in subjects with controlled HIV viral loads. In HCV monoinfected but not coinfected subjects, HCV viral load correlated with worsening GDS, suggesting different pathways for NP impairment.

BACKGROUND

Optimizing colorectal cancer (CRC) screening requires identification of unscreened individuals and tracking screening trends. A recent National Institutes of Health State of the Science Conference, "Enhancing Use and Quality of CRC Screening," cited a need for more population data sources for measurement of CRC screening, particularly for the medically underserved. Medical claims data (claims data) are created and maintained by many health systems to facilitate billing for services rendered and may be an efficient resource for identifying unscreened individuals. The aim of this study, conducted at a safety-net health system, was to determine whether CRC test use measured by claims data matches medical chart documentation.

METHODS

The authors randomly selected 400 patients from a universe of 20,000 patients previously included in an analysis of CRC test use based on claims data 2002-2006 in Tarrant Co, TX. Claims data were compared with medical chart documentation by estimation of agreement and examination of test use over/underdocumentation.

RESULTS

The authors found that agreement on test use was very good for fecal occult blood testing (κ = 0.83, 95% confidence interval: 0.75-0.90) and colonoscopy (κ = 0.91, 95% confidence interval: 0.85-0.96) and fair for sigmoidoscopy (κ = 0.39, 95% confidence interval: 0.28-0.49). Over- and underdocumentations of the 2 most commonly used CRC tests--colonoscopy and fecal occult blood testing--were rare.

CONCLUSIONS

Use of claims data by health systems to measure CRC test use is a promising alternative to measuring CRC test use with medical chart review and may be used to identify unscreened patients for screening interventions and track screening trends over time.

OBJECTIVE

We examine the extent to which ClinicalTrials.gov is meeting its goal of providing oversight and transparency of clinical trials with human subjects. We analyzed the ClinicalTrials.gov database contents as of June 2011, comparing interventions, medical conditions, and trial characteristics by sponsor type. We also conducted a detailed analysis of incomplete data.

RESULTS

Among trials with only government sponsorship (N=9252), 36% were observational and 64% interventional; in contrast, almost all (90%) industry-only sponsored trials were interventional. Industry-only sponsored interventional trials (N=30,036) were most likely to report a drug intervention (81%), followed by biologics (9%) and devices (8%). Government-only interventional trials (N=5886) were significantly more likely to test behavioral interventions (28%) and procedures (13%) than industry-only trials (p<0.001). Medical conditions most frequently studied in industry-only trials were cancer (19%), cardiovascular conditions (12%) and endocrine/metabolic disorders (11%). Government-only funded trials were more likely to study mental health (19% vs. 7% for industry, p<.001), and viral infections, including HIV (15% vs 7% for industry, p<.001). Government-funded studies are significantly more likely to be missing data about study design and intervention arms in the registry. For all studies, we report ambiguous and contradictory data entries.

CONCLUSIONS

Industry-sponsored studies differ systematically from government-sponsored studies in study type, choice of interventions, conditions studied, and completeness of submitted information. Imprecise study design information, incomplete coding of conditions, out-of-date or unspecified enrollment numbers, and other missing data continue to hinder robust analyses of trials registered in ClinicalTrials.gov.

OBJECTIVE

To describe the prevalence and location of new and acute HIV diagnoses in a large urban medical center. Secondary objectives were to evaluate rapid HIV test performance, the added yield of acute HIV screening, and linkage-to-care outcomes.

DESIGN

Cross-sectional study from November 1, 2008, to April 30, 2009.

METHODS

The hospital laboratory performed round-the-clock rapid HIV antibody testing on venipuncture specimens from patients undergoing HIV testing in hospital and community clinics, inpatient settings, and the emergency department (ED). For patients with negative results, a public health laboratory conducted pooled HIV RNA testing for acute HIV infection. The laboratories communicated positive results from the hospital campus to a linkage team. Linkage was defined as 1 outpatient HIV-related visit.

RESULTS

Among 7927 patients, 8550 rapid tests resulted in 137 cases of HIV infection [1.7%, 95% confidence interval (CI): 1.5% to 2.0%], of whom 46 were new HIV diagnoses (0.58%, 95% CI: 0.43% to 0.77%). Pooled HIV RNA testing of 6704 specimens (78.4%) resulted in 3 cases of acute HIV infection (0.05%, 95% CI: 0.01% to 0.14%) and increased HIV case detection by 3.5%. Half of new HIV diagnoses and two thirds of acute infections were detected in the ED and urgent care clinic. Rapid test sensitivity was 98.9% (95% CI: 93.8% to 99.8%) and the specificity 99.9% (95% CI: 99.7% to 99.9%). More than 95% of newly diagnosed and out-of-care HIV-infected patients were linked to care.

CONCLUSIONS

Patients undergoing HIV testing in EDs and urgent care clinics may benefit from being simultaneously screened for acute HIV infection.

Caspase-14 is an enzyme that is expressed predominantly in cornifying epithelia and catalyses the degradation of profilaggrin. Additionally, caspase-14 plays an important role in the terminal differentiation of keratinocytes. However, how caspase-14 expression is regulated remains largely unknown. Here we demonstrate that ceramides (C(2) -Cer and C(6) -Cer), but not other sphingolipids (C(8) -glucosylceramides, sphinganine, sphingosine-1-phosphate or ceramide-1-phosphate), increase caspase-14 expression (mRNA and protein) in cultured human keratinocytes in a dose- and time-dependent manner. Inhibitors of glucosylceramide synthase and ceramidase increase endogenous ceramide levels and also increase caspase-14 expression, indicating an important regulatory role for ceramides and suggesting that the conversion of ceramides to other metabolites is not required. The increase in caspase-14 expression induced by ceramides is first seen at 16 h and requires new protein synthesis, suggesting that the ceramide-induced increase is likely an indirect effect. Furthermore, ceramides increase caspase-14 gene expression primarily by increasing transcription. Blocking de novo synthesis of ceramides does not affect caspase-14 expression, suggesting that basal expression is not dependent on ceramide levels. These studies show that ceramides, an important structural lipid, stimulate caspase-14 expression providing a mechanism for coordinately regulating the formation of lipid lamellar membranes with the formation of corneocytes.

The Institute of Medicine (2011) report Occupational Health Nurses and Respiratory Protection: Improving Education and Training outlined seven recommendations to improve the competency of occupational health nurses in respiratory protection. An advisory group was convened in December 2011, with stakeholder representation from the Centers for Disease Control and Prevention/National Institute for Occupational Safety and Health/National Personal Protective Technology Laboratory, American Association of Occupational Health Nurses, Inc., American Board for Occupational Health Nurses, Inc., Association of Occupational Health Professionals in Healthcare, American Nurses Association, and Institute of Medicine Standing Committee on Personal Protective Equipment for Workplace Safety and Health. The initial work of the advisory group included developing and administering a survey to assess current occupational health nurse roles and responsibilities relevant to respiratory protection. Development of the survey was led by a master's student and advisor who worked with the advisory group. The process of tool development and preliminary findings are presented in this article.

OBJECTIVE

Integrin αvβ5 has been identified as a regulator of vascular leak and endothelial permeability. We hypothesized that targeting αvβ5 could represent a viable treatment strategy for sepsis.

DESIGN

Integrin β5 subunit knockout and wild-type 129/svJae mice and wild-type mice treated with αvβ5 blocking or control antibodies were tested in models of intraperitoneal lipopolysaccharide and cecal ligation and puncture. Human umbilical vein endothelial cell and human lung microvascular endothelial cell monolayers were treated with αvβ5 antibodies to assess for effects on lipopolysaccharide-induced changes in transendothelial resistance and on patterns of cytoskeletal reorganization.

SETTING

Laboratory-based research.

SUBJECTS

Mice and endothelial cell monolayers.

INTERVENTIONS, MEASUREMENTS, AND MAIN RESULTS

Measurements taken after intraperitoneal lipopolysaccharide and/or cecal ligation and puncture included mortality, vascular leak, hematocrit, quantification of a panel of serum cytokines/chemokines, and assessment of thioglyccolate-induced leukocyte migration. β5 knockout mice had decreased mortality after intraperitoneal lipopolysaccharide and cecal ligation and puncture and decreased vascular leak, as measured by extravasation of an I-labeled intravascular tracer. Treating clinically ill mice with αvβ5 antibodies, up to 20 hrs after intraperitoneal lipopolysaccharide and cecal ligation and puncture, also resulted in decreased mortality. αvβ5 antibodies attenuated lipopolysaccharide-induced transendothelial resistance changes and cytoskeletal stress fiber formation in both human umbilical vein endothelial cell and human lung microvascular endothelial cell monolayers. αvβ5 antibodies had no effect on cytokine/chemokine serum levels after cecal ligation and puncture. β5 knockout mice and wild-type controls did not exhibit differences in thioglyccolate-induced leukocyte migration.

CONCLUSIONS

Our studies suggest that αvβ5 is an important regulator of the vascular endothelial leak response in sepsis and that αvβ5 blockade may provide a novel approach to treating this devastating disease syndrome.