Brian Custer

Global epidemiology of hepatitis B virus.

The burden of hepatitis B virus (HBV) disease and efforts to control infection will determine the future size of the population requiring treatment of HBV infection. To quantify the current prevalence of HBV infection and to reexamine the epidemiology of HBV infection, a structured review was conducted that focused on available primary literature for over 30 countries worldwide. The prevalence of chronic HBV infection continues to be highly variable, ranging over 10% in some Asian and Western Pacific countries to under 0.5% in the United States and northern European countries. The current global estimate of the number of HBV infected individuals is 350 million. Routes of transmission include vertical (mother to child or generation to generation through close contact and sanitary habits), early life horizontal transmission (through bites, lesions, and sanitary habits), and adult horizontal transmission (through sexual contact, intravenous drug use, and medical procedure exposure) and are evident to varying degrees in every country. Younger age at acquisition of infection continues to be the most important predictor of chronic carriage. However, the choice of serologic markers, temporal influences, and representativeness of the study population limit comparability of HBV seroprevalence results. HBV vaccination programs will decrease the future global burden of HBV infection and evidence of reduced burden is mounting in country-specific populations, but vaccination programs have still not been implemented in all countries, thereby maintaining reservoirs of infection and continued HBV transmission. Regardless of vaccination, large numbers of persons are infected with HBVor will become infected. Preventing the most severe HBV disease consequences in infected individuals, such as cirrhosis and hepatocellular carcinoma, will require appropriate therapeutic agents.

Tregs control the development of symptomatic West Nile virus infection in humans and mice

West Nile virus (WNV) causes asymptomatic infection in most humans, but for undefined reasons, approximately 20% of immunocompetent individuals develop West Nile fever, a potentially debilitating febrile illness, and approximately 1% develop neuroinvasive disease syndromes. Notably, since its emergence in 1999, WNV has become the leading cause of epidemic viral encephalitis in North America. We hypothesized that CD4+ Tregs might be differentially regulated in subjects with symptomatic compared with those with asymptomatic WNV infection. Here, we show that in 32 blood donors with acute WNV infection, Tregs expanded significantly in the 3 months after index (RNA+) donations in all subjects. Symptomatic donors exhibited lower Treg frequencies from 2 weeks through 1 year after index donation yet did not show differences in systemic T cell or generalized inflammatory responses. In parallel prospective experimental studies, symptomatic WNV-infected mice also developed lower Treg frequencies compared with asymptomatic mice at 2 weeks after infection. Moreover, Treg-deficient mice developed lethal WNV infection at a higher rate than controls. Together, these results suggest that higher levels of peripheral Tregs after infection protect against severe WNV disease in immunocompetent animals and humans.

Duration of red blood cell storage and survival of transfused patients (CME)

BACKGROUND: Disquieting reports of increased complication and death rates after transfusions of red blood cells (RBCs) stored for more than 14 days prompted us to perform an observational retrospective cohort study of mortality in relation to storage time.

The consequences of temporary deferral on future whole blood donation

BACKGROUND: The consequences of temporary deferral are not well understood. This study sought to investigate blood donor return after deferral expiration.

Dental X-rays and the risk of intracranial meningioma: a population-based case-control study.

Ionizing radiation is a likely cause of intracranial meningioma. The authors determined whether the risk of intracranial meningioma was associated with past dental X‐rays—specifically, posterior bitewings, full‐mouth series, and lateral cephalometric and panoramic radiographs.

West Nile Virus Infections Projected from Blood Donor Screening Data, United States, 2003

Routine donor nucleic acid amplification testing is a valuable surveillance screening tool.

Faint and prefaint reactions in whole-blood donors: an analysis of predonation measurements and their predictive value.

BACKGROUND: A small proportion of blood donors have adverse reactions. The purpose of this study was to determine predictors of faint and significant hypotensive reactions that could serve as targets for interventions to reduce reactions, thus improving the blood donation experience for those at higher risk of reactions and reducing the risk of serious adverse events.

Increased All-Cause, Liver, and Cardiac Mortality among Hepatitis C Virus-seropositive Blood Donors

Hospital-based studies suggest that hepatitis C virus (HCV) infection causes frequent cirrhosis, hepatocellular carcinoma, and mortality, but epidemiologic studies have shown less morbidity and mortality. The authors performed a retrospective cohort study of 10,259 recombinant immunoblot assay-confirmed, HCV antibody-positive (HCV+), allogeneic blood donors from 1991 to 2002 and 10,259 HCV antibody-negative (HCV-) donors matched for year of donation, age, gender, and Zone Improvement Plan Code (ZIP Code). Vital status through 2003 was obtained from the US National Death Index, and hazard ratios with 95% confidence intervals were calculated by survival analysis. After a mean follow-up of 7.7 years, there were 601 (2.92%) deaths: 453 HCV+ and 148 HCV- (hazard ratio (HR) = 3.13, 95% confidence interval (CI): 2.60, 3.76). Excess mortality in the HCV+ group was greatest in liver-related (HR = 45.99, 95% CI: 11.32, 186.74), drug- or alcohol-related (HR = 10.81, 95% CI: 4.68, 24.96), and trauma/suicide (HR = 2.99, 95% CI: 2.05, 4.36) causes. There was also an unexpected increase in cardiovascular mortality among the HCV+ donors (HR = 2.21, 95% CI: 1.41, 3.46). HCV infection is associated with a significant, threefold increase in overall mortality among former blood donors, including significantly increased mortality from liver and cardiovascular causes. High rates of mortality from drug/alcohol and trauma/suicide causes are likely due to lifestyle factors and may be at least partially preventable.

The association between breast carcinoma and meningioma in women

Published case reports of a possible association between meningioma and breast carcinoma are not uncommon in the literature. Four published analytic studies have addressed this suggested association specifically. Three of these studies reported significant associations, with relative risk estimates mostly between 1.5 and 2.0. The other study reported relative risk point estimates near 1.5, but confidence intervals included 1.0. The current study was a population‐based, retrospective cohort analysis that evaluated the risk of subsequent breast carcinoma in women who were diagnosed with meningioma and the risk of subsequent meningioma in women who were diagnosed with breast carcinoma.

Hormonal exposures and the risk of intracranial meningioma in women: a population-based case-control study

BackgroundThe role of exogenous hormone exposures in the development of meningioma is unclear, but these exposures have been proposed as one hypothesis to explain the over-abundance of such tumors in women.MethodsThe association between oral contraception (OC) or hormone replacement therapy (HRT) and intracranial meningioma in women was investigated using a population-based, matched case-control study. Exposures for 143 cases and 286 controls matched on age within five years were obtained by interview. Diagnoses were confirmed histopathologically and estrogen and progesterone receptor assays conducted.ResultsAlthough risk of meningioma appeared modestly elevated in past OC users (OR = 1.5, 95% CI 0.8 – 2.7), and in current users (OR = 2.5, 95% CI 0.5 – 12.6), the confidence intervals were wide. No significant association between meningioma risk and duration of OC use was found. Likewise, risk of meningioma was only weakly associated with past use of HRT (OR = 0.7, 95% CI 0.4 – 1.3), and not at all with current use of HRT (OR = 1.0, 95% CI 0.5 – 2.2). Of 142 available specimens, 2 (1%) expressed estrogen receptors, whereas 130 (92%) expressed progesterone receptors (PR). OC use was associated with increased risk of a meningioma expressing less rather than more PR (OR = 3.2, 95% CI 1.3 – 8.0). Overall, in post menopausal women, HRT use appeared to confer a non-significant protective effect, and was not associated with low or high PR expressing meningiomas.ConclusionThis study found little evidence of associations between meningioma and exogenous hormone exposures in women but did suggest that some hormonal exposures may influence tumor biology in those women who develop meningioma.