Faculty Bibliography

BACKGROUND: Outbreaks of hepatitis C virus (HCV) infection have been reported in HIV-positive men who have sex with men (MSM) in North America, Europe and Asia. Transmission is believed to be the result of exposure to blood during sexual contact. In those infected with HIV, acute HCV infection is more likely to become chronic, treatment for both HIV and HCV is more complicated and HCV disease progression may be accelerated. There is a need for systematic reviews and meta-analyses to synthesize the epidemiology, prevention and methods to control HCV infection in this population. METHODS/DESIGN: Eligible studies will include quantitative empirical data related to sexual transmission of HCV in HIV-positive MSM, including data describing incidence or prevalence, and associations between risk factors or interventions and the occurrence or progression of HCV disease. Care will be taken to ensure that HCV transmission related to injection drug use is excluded from the incidence estimates. Scientific databases will be searched using a comprehensive search strategy. Proceedings of scientific conferences, reference lists and personal files will also be searched. Quality ratings will be assigned to each eligible report using the Newcastle-Ottawa scale. Pooled estimates of incidence rates and measures of association will be calculated using random effects models. Heterogeneity will be assessed at each stage of data synthesis. DISCUSSION: HIV-positive MSM are a key HCV-affected population in the US and other high-income countries. This review seeks to identify modifiable risk factors and settings that will be the target of interventions, and will consider how to constitute a portfolio of interventions to deliver the greatest health benefit. This question must be considered in relation to the magnitude of HCV infection and its consequences in other key affected populations, namely, young prescription opioid users who have transitioned to illicit opiate injection, and older injection drug users among whom HCV prevalence and incidence are extremely high. This review is part of a series of systematic reviews and meta-analyses that will synthesize the evidence across all these population groups and develop recommendations and decision tools to guide public health resource allocation. TRIAL REGISTRATION: PROSPERO registration number: CRD42013006462.

This pilot study explores the feasibility and preliminary efficacy of the Staying Safe Intervention, an innovative, strengths-based program to facilitate prevention of infection with the human immunodeficiency virus and with the hepatitis C virus among people who inject drugs (PWID). The authors explored changes in the intervention's two primary endpoints: (a) frequency and amount of drug intake, and (b) frequency of risky injection practices. We also explored changes in hypothesized mediators of intervention efficacy: planning skills, motivation/self-efficacy to inject safely, skills to avoid PWID-associated stigma, social support, drug-related withdrawal symptoms, and injection network size and risk norms. A 1-week, fivesession intervention (10 hours total) was evaluated using a pre- versus 3-month posttest design. Fifty-one participants completed pre- and posttest assessments. Participants reported significant reductions in drug intake and injection-related risk behavior. Participants also reported significant increases in planning skills, motivation/self-efficacy, and stigma management strategies, while reducing their exposure to drug withdrawal episodes and risky injection networks.

Publisher: Abstract available from the publisher. OABL- FRE

OBJECTIVES: To determine the effectiveness of a novel sonic toothbrush in reducing plaque and in maintenance of gingival health when compared to a standard manual brush. METHODS: This study was a block-randomized, examiner-blind, two-treatment, parallel group, single centre clinical investigation. A total of 84 subjects were enrolled and randomly assigned to receive either the Panasonic EW-DL90 or an American Dental Association-endorsed manual toothbrush. Subjects were instructed to follow a twice-daily brushing regimen without flossing. Plaque levels and gingival health were assessed at baseline and after 1 and 3 weeks of treatment using the Turesky Modification of the Quigley-Hein Plaque Index and the Papillary Bleeding Score. RESULTS: Subjects assigned to the EW-DL90 group had significantly lower plaque levels after 1 and 3 weeks of treatment than those in the manual group (P = 0.003 and 0.0035, respectively). Both groups showed a reduction in plaque levels at Week 3 relative to baseline. The EW-DL90 group had significantly lower gingival inflammation scores after 1 week of treatment (P = 0.0293), but there was no difference between groups after 3 weeks of treatment. CONCLUSION: The EW-DL90 toothbrush safely and effectively removes more plaque than a standard manual toothbrush. Improvement in gingival inflammation was observed after 1 week of treatment. There was no difference in Papillary Bleeding Score between the two groups after 3 weeks of treatment. CLINICAL SIGNIFICANCE: The newly developed sonic brush (Panasonic EW-DL90) tested in this study was found to be more effective than a manual toothbrush at plaque removal. The papillary bleeding scores were significantly lower in the sonic brush group after 1 week of product use. After 3 weeks of product use, both treatment groups had similar papillary bleeding scores almost returning to baseline values.

Recent whole genome melanoma sequencing studies have identified recurrent mutations in the gene encoding the catalytic subunit of serine/threonine phosphatase 6 (PPP6C/PP6C). However, the biochemical, functional, and clinical ramifications of these mutations are unknown. Sequencing PP6C from patients with melanoma (233 primary and 77 metastatic specimens) with extended prospective clinical outcome revealed a large number of hotspot mutations in patients with both primary and metastatic melanoma. Despite minimal association between stage and presence of PP6C mutations in patients with primary melanoma, a subpopulation of cells within each tumor did contain PP6C mutations, suggesting PP6C mutation is an early, but non-tumor-initiating event in melanoma. Among patients with primary melanoma with PP6C mutations, patients with stop mutations had significantly shorter recurrence-free survival compared with patients without stop mutations. In addition, PP6C mutations were independent of commonly observed BRAF and NRAS mutations. Biochemically, PP6C mutations could be classified as those that interact with PP6C regulatory subunits and those that do not. Mutations that did not bind to PP6C regulatory subunits were associated with increased phosphorylation of Aurora kinase, a PP6C substrate, and mitotic defects. However, both classes of PP6C mutations led to increased sensitivity to Aurora kinase inhibition. Together, these data support for the first time that PP6C mutations are molecularly, biochemically, and clinically heterogeneous. Implications: PP6C mutations have distinct functional and clinical consequences in melanoma, and confer sensitivity to Aurora A kinase inhibitors. Mol Cancer Res; 12(3); 433-9. (c)2013 AACR.

BACKGROUND: This study was designed to examine the characteristics of pedestrian and bicyclist collisions with motor vehicles within New York City's high-density hub. The primary objectives were to map crash locations and to identify hot spots within these injury clusters. The secondary objective was to quantify differences in injury severity based on road type and user behaviors. METHODS: Between December 2008 and June 2011, data were prospectively collected from pedestrians and bicyclists struck by motor vehicles and brought to Bellevue Hospital, a Level 1 trauma center in New York City. Behaviors by cohort (i.e., crossing patterns for pedestrians, riding patterns for bicyclists), Injury Severity Score (ISS), and collision locations were extracted from the database. Analyses of mean ISS were performed using a Student's t test with a p < 0.05 considered significant. Geomaps were created to identify clusters or "hot spots," where higher volumes of crashes occurred over time. Spatial analysis was performed to demonstrate whether these were random events. RESULTS: A total of 1,457 patients (1,075 pedestrians and 382 bicyclists) were enrolled. Collision locations were known for 97.5%. Of the injured pedestrians, those crossing avenues (n = 277) had higher ISSs than those crossing streets (n = 522) (p = 0.01) and were more likely to die (p = 0.002). Pedestrians crossing midblock (n = 185) had higher mean ISSs than those crossing with the signal in the crosswalk (n = 320) (8.12 vs. 5.01, p < 0.001). Based on density mapping, hot spots of pedestrian collisions were detected in midtown Manhattan, while hot spots for bicyclists were detected at bridge and tunnel portals. Spatial analysis indicates that these are not random events (p < 0.05). CONCLUSION: Pedestrians injured on avenues sustained more serious injuries than those injured on narrower streets. A better understanding of collision locations and features may allow for tailored injury prevention strategies. Trauma centers serve an important role in public health surveillance within their local communities. LEVEL OF EVIDENCE: Epidemiologic study, level III.

IMPORTANCE Retrospective studies have demonstrated disparate outcomes following acute optic neuritis in individuals of African descent compared with individuals of white race/ethnicity. However, published analyses of the prospectively collected Optic Neuritis Treatment Trial (ONTT) data identified no association between worse visual outcomes and black race/ethnicity. OBJECTIVES To investigate the associations of age, sex, and race/ethnicity with visual outcomes following acute optic neuritis through application of longitudinal data analysis techniques to the ONTT data set. DESIGN Secondary analysis of the ONTT (a prospective randomized controlled trial) data set. Our models included effects of treatment (placebo, oral prednisone, or intravenous methylprednisolone), time, and treatment x time interaction, as well as demographic covariates of age, sex, and race/ethnicity. SETTING AND PARTICIPANTS The ONTT data were collected at multiple centers in the United States. Patients of black (n = 58) and white (n = 388) race/ethnicity with acute optic neuritis who enrolled in the ONTT within 8 days of symptom onset were included in analyses. MAIN OUTCOMES AND MEASURES The contrast sensitivity and visual acuity (logMAR) in the affected eye were modeled using 2-stage mixed-effects regression techniques. All available follow-up data from baseline to 15 to 18 years were included. RESULTS The data identified no relationship of age, sex, or treatment with contrast sensitivity or visual acuity outcomes. Race/ethnicity was significantly related to contrast sensitivity (P < .001) and visual acuity (P < .001) during a 15-year period following acute optic neuritis, with black race/ethnicity being associated with worse scores for both. CONCLUSIONS AND RELEVANCE Race/ethnicity seems to be associated with contrast sensitivity and visual acuity outcomes in affected eyes following acute optic neuritis. To our knowledge, this is the largest cohort of black race/ethnicity with acute optic neuritis to be studied and represents the first evidence from a prospectively collected data set to support a hypothesis of race/ethnicity-dependent visual outcomes of acute optic neuritis.

BACKGROUND: The 2013 American College of Cardiology Foundation/American Heart Association ST-segment elevation myocardial infarction (STEMI) guidelines have shifted focus from door-to-balloon (D2B) time to the time from first medical contact to device activation (contact-to-device time [C2D] ). HYPOTHESIS: This study investigates the impact of prehospital wireless electrocardiogram transmission (PHT) on reperfusion times to assess the impact of the new guidelines. METHODS: From January 2009 to December 2012, data were collected on STEMI patients who received percutaneous coronary interventions; 245 patients were included for analysis. The primary outcome was median C2D time in the PHT group and the secondary outcome was D2B time. RESULTS: Prehospital wireless electrocardiogram transmission was associated with reduced C2D times vs no PHT: 80 minutes (interquartile range [IQR], 64-94) vs 96 minutes (IQR, 79-118), respectively, P < 0.0001. The median D2B time was lower in the PHT group vs the no-PHT group: 45 minutes (IQR, 34-56) vs 63 minutes (IQR, 49-81), respectively, P < 0.0001. Multivariate analysis showed PHT to be the strongest predictor of a C2D time of <90 minutes (odds ratio: 3.73, 95% confidence interval: 1.65-8.39, P = 0.002). Female sex was negatively predictive of achieving a C2D time <90 minutes (odds ratio: 0.23, 95% confidence interval: 0.07-0.73, P = 0.01). CONCLUSIONS: In STEMI patients, PHT was associated with significantly reduced C2D and D2B times and was an independent predictor of achieving a target C2D time. As centers adapt to the new guidelines emphasizing C2D time, targeting a shorter D2B time (<50 minutes) is ideal to achieve a C2D time of <90 minutes.

OBJECTIVE: To investigate whether past-30 day illicit drug use among sexual minority youth was more common in neighborhoods with a greater prevalence of hate crimes targeting lesbian, gay, bisexual, and transgender (LGBT, or sexual minority) individuals. METHODS: We used a population-based survey of public school youth in Boston, Massachusetts, consisting of 1292 9th-12th grade students from the 2008 Boston Youth Survey Geospatial Dataset (sexual minority n=108). Data on LGBT hate crimes involving assaults or assaults and battery between 2005 and 2008 were obtained from the Boston Police Department and linked to youths' residential address. Youth reported past-30 day use of marijuana and other illicit drugs. Wilcoxon-Mann-Whitney tests and corresponding p-values were computed to assess differences in substance use by neighborhood-level LGBT assault hate crime rate among sexual minority youth (n=103). RESULTS: The LGBT assault hate crime rate in the neighborhoods of sexual minority youth who reported current marijuana use was 23.7 per 100,000, compared to 12.9 per 100,000 for sexual minority youth who reported no marijuana use (p=0.04). No associations between LGBT assault hate crimes and marijuana use among heterosexual youth (p>0.05) or between sexual minority marijuana use and overall neighborhood-level violent and property crimes (p>0.05) were detected, providing evidence for result specificity. CONCLUSIONS: We found a significantly greater prevalence of marijuana use among sexual minority youth in neighborhoods with a higher prevalence of LGBT assault hate crimes. These results suggest that neighborhood context (i.e., LGBT hate crimes) may contribute to sexual orientation disparities in marijuana use.