Risk of invasive meningococcal disease in children and adults with HIV in England: a population-based cohort study.

BACKGROUND: Recent studies have identified HIV infection as a potential risk factor for invasive meningococcal disease (IMD), suggesting that HIV-infected individuals could benefit from meningococcal vaccination to reduce their risk of this rare, but severe and potentially fatal infection. In the United Kingdom, as in most industrialised countries, HIV is not considered a risk factor for IMD. METHODS: IMD incidence and relative risk by age group and meningococcal capsular group in HIV-positive compared with HIV-uninfected individuals was estimated through data linkage of national datasets in England between 2011 and 2013. RESULTS: IMD incidence among persons diagnosed with HIV was 6.6 per 100,000 compared to 1.5 per 100,000 among HIV-negative individuals, with a relative risk of 4.5 (95 % CI, 2.7-7.5). All but one case occurred in adults aged 16-64 years, who had a 22.7-fold (95 % CI, 12.4-41.6; P <0.001) increased risk compared with the HIV-negative adults. IMD risk by capsular group varied with age. HIV-positive children and adolescents had a higher risk of meningococcal group B disease, while adults were at increased risk of groups C, W and Y disease. Most HIV-positive individuals had been born in Africa, had acquired HIV through heterosexual contact, and were known to be HIV-positive and receiving antiretroviral treatment at IMD diagnosis. The most common clinical presentation was septicemia and, although intensive care admission was common, none died of IMD. CONCLUSIONS: HIV-positive children and adults are at significantly increased risk of IMD, providing an evidence base for policy makers to consider HIV as a risk factor for meningococcal vaccination.

Blood donors in England and North Wales: demography and patterns of donation.

BACKGROUND: As populations in the developed world shift toward an older and more ethnically diverse population, the challenges of recruiting and retaining sufficient donors to secure an adequate, safe supply of blood in the future will increase. STUDY DESIGN AND METHODS: The study population included all first-time (n = 348,740) and repeat (n = 1,805,255) blood donors and their donations (n = 3,854,460) received by NHS Blood and Transplant during 2010 and 2011. Rates of new and repeat donors per 1000 population were estimated using Office for National Statistics 2011 population estimates. Factors associated with new blood donors returning within 6 months were analyzed using multivariate logistic regression. RESULTS: The majority (87.9%) of donors were white British; 5.5% were unknown; 3.4% white Irish or white other; and 3.2% composed of all other ethnic groups. The median ages of new and repeat donors in 2010 were 28.0 and 45.0 years, respectively, compared to 29.0 and 47.0 years in 2011. Rates of donation varied by ethnicity, ranging from 1.59 per 1000 among Asian Bangladeshi origin, compared to 22.1 per 1000 among white British origin. Approximately two in five (38.4%) new blood donors returned within 6 months and were more likely to be male and of white ethnicity. CONCLUSIONS: Blood supply is impacted by numerous factors, including an aging population and an increasing population of migrant communities with lower donation rates. It is therefore critical that changes within the blood donor and wider population are monitored to inform donor recruitment and retention strategies.

Circumcision among men who have sex with men in London, United Kingdom: an unlikely strategy for HIV prevention.

OBJECTIVES: To explore attitudes toward circumcision among men who have sex with men (MSM) in London and the feasibility of conducting research into circumcision and HIV prevention in this population. METHODS: A convenience sample of MSM visiting central London gyms completed a confidential, self-administered questionnaire between May and June 2008. Information was collected on participants' demographic characteristics, self-reported HIV status, sexual behavior, circumcision status, attitudes toward circumcision, and willingness to participate in research on circumcision and HIV prevention. RESULTS: Of 653 MSM, 29.0% reported that they were circumcised. Overall, HIV prevalence was 23.3%; this did not differ significantly between circumcised and uncircumcised men (18.6% vs. 25.2%, respectively; adjusted odds ratio 0.79, 95% confidence interval: 0.50-1.26). A similar proportion of circumcised and uncircumcised men reported unprotected anal intercourse in the previous 3 months (38.8% vs. 36.7%, adjusted odds ratio 1.06, 95% confidence interval: 0.72-1.55). Uncircumcised men were less likely to think that there were benefits of circumcision than circumcised men (31.2% vs. 65.4, P < 0.001). Only 10.3% of uncircumcised men said that they would be willing to participate in research on circumcision as an HIV prevention strategy. CONCLUSIONS: Most uncircumcised MSM in this London survey were unwilling to participate in research on circumcision and HIV prevention. Only a minority of uncircumcised men thought that there were benefits of circumcision. It is unlikely that circumcision would be a feasible strategy for HIV prevention among MSM in London.

Proteomic analysis of chronic pancreatitis and pancreatic adenocarcinoma.

BACKGROUND & AIMS: Markers to differentiate among pancreatic adenocarcinoma, chronic pancreatitis, and normal pancreas would be of significant clinical utility. This study was therefore designed to analyze the proteome of such specimens and identify new candidate proteins for differential diagnosis. METHODS: A PowerBlot analysis with more than 900 well-characterized antibodies was performed with tissue specimens from patients with chronic pancreatitis, pancreatic adenocarcinoma, and normal pancreas. Differential expression of selected proteins was confirmed on a larger scale by quantitative reverse transcription-polymerase chain reaction and immunohistochemistry using tissue arrays. RESULTS: A total of 30 and 102 proteins showed significant deregulation between normal pancreas when compared with chronic pancreatitis and pancreatic adenocarcinoma, respectively, and although a substantial proportion were found similarly dysregulated in both chronic pancreatitis and pancreatic adenocarcinoma, several proteins were identified as potential disease-specific markers. CONCLUSIONS: A large number of proteins are differentially expressed in chronic pancreatitis and pancreatic adenocarcinoma compared with normal pancreas. Among these, expression analysis of UHRF1, ATP7A, and aldehyde oxidase 1 in combination could potentially provide a useful additional diagnostic tool for fine-needle aspirated or cytological specimens obtained during endoscopic investigations.

Intrinsic chemoresistance to gemcitabine is associated with decreased expression of BNIP3 in pancreatic cancer.

PURPOSE: Although chemotherapy with gemcitabine is a common mode of treatment of pancreatic cancer, 75% of patients do not benefit from this therapy. It is likely that the sensitivity of cancer cells to gemcitabine is determined by a number of different factors. EXPERIMENTAL DESIGN: To identify genes that might contribute to resistance to gemcitabine, 15 pancreatic cancer cell lines were subjected to gemcitabine treatment. Simultaneously, gene expression profiling using a cDNA microarray to identify genes responsible for gemcitabine sensitivity was performed. RESULTS: The pancreatic cancer cell lines could be classified into three groups: a gemcitabine "sensitive," an "intermediate sensitive," and a "resistant" group. Microarray analysis identified 71 genes that show differential expression between gemcitabine-sensitive and -resistant cell lines including 27 genes relatively overexpressed in sensitive cell lines whereas 44 genes are relatively overexpressed in resistant cell lines. Among these genes, 7 genes are potentially involved in the phosphatidylinositol 3-kinase/Akt pathway. In addition to this major signaling pathway, Bcl2/adenovirus E1B 19 kDa protein interacting protein (BNIP3), a Bcl-2 family proapoptotic protein, was identified as being expressed at lower levels in drug-resistant pancreatic cancer cell lines. In an analysis of 21 pancreatic cancer tissue specimens, more than 90% showed down-regulated expression of BNIP3. When expression of BNIP3 was suppressed using small interfering RNA, gemcitabine-induced cytotoxicity in vitro was much reduced. CONCLUSIONS: These results suggest that BNIP3 and the phosphatidylinositol 3-kinase/Akt pathway may play an important role in the poor response to gemcitabine treatment in pancreatic cancer patients.