Variation in Human Papillomavirus Vaccine Uptake and Acceptability Between Female and Male Adolescents and Their Caregivers.

HPV vaccination coverage is suboptimal. Previous research largely focused on vaccinating girls. This study aimed to identify factors associated with HPV vaccination among male and female adolescents. We conducted secondary analyses using the National Immunization Survey-Teen. We specified parallel logistic models to examine associations of adolescent, caregiver, and provider characteristics with vaccination status among boys and girls. The primary outcome was HPV vaccination status defined as unvaccinated, initiated, or completed. Additionally, we analyzed caregivers' intent to initiate or complete the three-dose series. The vaccination completion rate was 26 %. Among teens aged 13-17 years, 19 % initiated, but did not complete the vaccine. Additionally, 14 % of males completed the 3-dose series as compared to 38 % of females. Vaccination rates were higher among teens receiving a provider recommendation [girls: adjusted odds ratio (AOR) = 3.33, 95 % confidence interval (CI) (2.44, 4.55); boys: AOR = 10.0, 95 % CI (7.69, 12.5)]. Moreover, provider recommendation was associated with caregivers' intent to initiate vaccination [girls: AOR = 2.32, 95 % CI (1.77, 3.02); boys: AOR = 2.76, 95 % CI (2.22, 3.43)]. Other associations differed by gender. Higher vaccine initiation rates were associated with younger age and residing in the mid-west for girls and racial/ethnic minority and eligibility for the "Vaccine for Children" program for boys. Provider recommendation for vaccination was the strongest predictor for both genders; however, it is insufficient to achieve high coverage rates, especially among boys. Factors associated with HPV vaccination were different for males and females. These findings suggest providers should consider gender bias with regard to HPV vaccination.

Efficacy of a clinical decision-support system in an HIV practice: a randomized trial.

BACKGROUND: Data to support improved patient outcomes from clinical decision-support systems (CDSSs) are lacking in HIV care. OBJECTIVE: To test the efficacy of a CDSS in improving HIV outcomes in an outpatient clinic. DESIGN: Randomized, controlled trial. (ClinicalTrials.gov registration number: NCT00678600) SETTING: Massachusetts General Hospital HIV Clinic. PARTICIPANTS: HIV care providers and their patients. INTERVENTION: Computer alerts were generated for virologic failure (HIV RNA level >400 copies/mL after a previous HIV RNA level ≤400 copies/mL), evidence of suboptimal follow-up, and 11 abnormal laboratory test results. Providers received interactive computer alerts, facilitating appointment rescheduling and repeated laboratory testing, for half of their patients and static alerts for the other half. MEASUREMENTS: The primary end point was change in CD4 cell count. Other end points included time to clinical event, 6-month suboptimal follow-up, and severe laboratory toxicity. RESULTS: Thirty-three HIV care providers followed 1011 patients with HIV. In the intervention group, the mean increase in CD4 cell count was greater (0.0053 vs. 0.0032 × 109 cells/L per month; difference, 0.0021 × 109 cells/L per month [95% CI, 0.0001 to 0.004]; P = 0.040) and the rate of 6-month suboptimal follow-up was lower (20.6 vs. 30.1 events per 100 patient-years; P = 0.022) than those in the control group. Median time to next scheduled appointment was shorter in the intervention group than in the control group after a suboptimal follow-up alert (1.71 vs. 3.48 months; P < 0.001) and after a toxicity alert (2.79 vs. >6 months; P = 0.072). More than 90% of providers supported adopting the CDSS as part of standard care. LIMITATION: This was a 1-year informatics study conducted at a single hospital subspecialty clinic. CONCLUSION: A CDSS using interactive provider alerts improved CD4 cell counts and clinic follow-up for patients with HIV. Wider implementation of such systems can provide important clinical benefits. PRIMARY FUNDING SOURCE: National Institute of Allergy and Infectious Diseases.

Spontaneous control of HCV is associated with expression of HLA-B 57 and preservation of targeted epitopes.

BACKGROUND & AIMS: HLA class I alleles are linked to spontaneous control of hepatitis C virus (HCV) and human immunodeficiency virus-1, but for HCV the roles of particular alleles and corresponding CD8(+) T-cell responses remain incompletely defined. We aimed to determine the correlations between these alleles and natural outcomes of HCV and determine associated key T-cell responses. METHODS: In a cohort of HCV individuals, we determined HLA class I alleles, HCV outcomes, T-cell responses, and examined sequence data for mutational changes within key epitopes. RESULTS: Carriage of HLA-B 57 was associated with a higher rate of viral clearance (risk ratio = 2.0; 95% confidence interval: 1.2-3.4), while HLA-B 08 was associated with a lower rate (risk ratio = 0.34; 95% confidence interval: 0.1-0.9]. Two HLA-B 57-restricted T-cell epitopes were targeted in spontaneous clearance; subjects with chronic viremia expressing HLA-B 57 harbored HCV strains with a high frequency of mutations in key residues. HLA-B 57-mediated escape was supported by diminished immune recognition of these variants and acute HCV infection revealing viral evolution toward less recognized variants. Analysis of a genotype 1b strain from a single-source HCV outbreak in which HLA-B 57 was not protective revealed sequence variations that interfere with immunogenicity, thereby preventing HLA-B 57-mediated immune pressure. CONCLUSIONS: Our data indicate a role of HLA-B 57-restricted CD8(+) T-cell responses in mediating spontaneous clearance and evolution in HCV infection, and viral strains containing epitope variants that are less recognized abrogate the protective effects of HLA-B 57. The finding that HLA-B 57-mediated antiviral immunity is associated with control of both human immunodeficiency virus-1 and HCV suggests a common shared mechanism of a successful immune response against persistent viruses.

Predicting virologic failure in an HIV clinic.

BACKGROUND: We sought to use data captured in the electronic health record (EHR) to develop and validate a prediction rule for virologic failure among patients being treated for infection with human immunodeficiency virus (HIV). METHODS: We used EHRs at 2 Boston tertiary care hospitals, Massachusetts General Hospital and Brigham and Women's Hospital, to identify HIV-infected patients who were virologically suppressed (HIV RNA level < or = 400 copies/mL) on antiretroviral therapy (ART) during the period from 1 January 2005 through 31 December 2006. We used a multivariable logistic model with data from Massachusetts General Hospital to derive a 1-year virologic failure prediction rule. The model was validated using data from Brigham and Women's Hospital.We then simplified the scoring scheme to develop a clinical prediction rule. RESULTS: The 1-year virologic failure prediction model, using data from 712 patients from Massachusetts General Hospital, demonstrated good discrimination (C statistic, 0.78) and calibration (chi(2)= 6.6; P= .58). The validation model, based on 362 patients from Brigham and Women's Hospital, also showed good discrimination (C statistic, 0.79) and calibration (chi(2)= 1.9; P= .93). The clinical prediction rule included 7 predictors (suboptimal adherence, CD4 cell count < 100 cells/microL, drug and/or alcohol abuse, highly ART experienced, missed > or = 1 appointment, prior virologic failure, and suppressed < or = 12 months) and appropriately stratified patients in the validation data set into low-, medium-, and high-risk groups, with 1-year virologic failure rates of 3.0%, 13.0%, and 28.6%, respectively. CONCLUSIONS: A risk score based on 7 variables available in the EHR predicts HIV virologic failure at 1 year and could be used for targeted interventions to improve outcomes in HIV infection.

Human umbilical vein endothelial cells and human dermal microvascular endothelial cells offer new insights into the relationship between lipid metabolism and angiogenesis.

Human umbilical vein endothelial cells (HUVECs) have played a major role as a model system for the study of the regulation of endothelial cell function and the role of the endothelium in the response of the blood vessel wall to stretch, shear forces, and the development of atherosclerotic plaques and angiogenesis. Here, we use HUVECs and human microvascular endothelial cells to study the role of the HMG-CoA reductase inhibitor, simvastatin, and the small GTP-binding protein Rho in the regulation of angiogenesis. Simvastatin inhibited angiogenesis in response to FGF-2 in the corneal pocket assay of the mouse and in vascular endothelial growth factor (VEGF)-stimulated angiogenesis in the chick chorioallontoic membrane. Furthermore, simvastatin inhibited VEGF-stimulated tube formation by human dermal microvascular endothelial cells and the formation of honeycomb-like structures by HUVECs. The effect was dose-dependent and was not secondary to apoptosis. Geranylgeranyl-pyrophosphate (GGPP), a product of the cholesterol metabolic pathway that serves as a substrate for the posttranslational lipidation of RhoA, was required for membrane localization, but not farnesylpyrophosphate (FPP), the substrate for the lipidation of Ras. Furthermore, GGTI, a specific inhibitor of GGPP, mimicked the effect of simvastatin of tube formation and the formation of honeycombs whereas FTI, a specific inhibitor of the farnesylation of Ras, had no effect. Adenoviral expression of a DN-RhoA mutant mimicked the effect of simvastatin on tube formation and the formation of honeycombs, whereas a dominant activating mutant of RhoA reversed the effect of simvastatin on tube formation. Finally, simvastatin interfered with the membrane localization of RhoA with a dose-dependence similar to that for the inhibition of tube formation. Simvastatin also inhibited the VEGFstimulated phosphorylation of the VEGF receptor KDR, and the tyrosine kinase FAK, which plays a role in cell migration. These data demonstrate that simvastatin interfered with angiogenesis via the inhibition of RhoA. Data supporting a role for angiogenesis in the development and growth of atherosclerotic plaques suggest that this antiangiogenic effect of Statins might prevent the progression of atherosclerosis via the inhibition of plaque angiogenesis.