Hepatitis B and pregnancy

Chronic hepatitis B virus (HBV) infection remains an important cause of chronic liver disease worldwide and affects a disproportionate number of individuals from areas of high endemicity, where perinatal transmission is the predominant mode of infection. Introduction of a safe and effective hepatitis B vaccine has led to universal infant vaccination and resulted in a reduced rate of perinatal HBV transmission from infected mothers. With appropriate hepatitis B vaccination and passive immunoprophylaxis using hepatitis B immune globulin (HBIG), infants born to mothers with HBV infection have perinatal transmission rates between 5% and 10%. Management of pregnant women with chronic HBV infection is aimed primarily at counseling regarding maternal risk of infection, rates of vertical transmission, and preparation for neonatal vaccination. Limited data suggest that intrauterine infection may occur at higher rates in mothers with high serum HBV DNA levels, leading to failure of standard passive-active immunoprophylaxis with HBIG and vaccine. Thus, treatment with an oral HBV antiviral agent in the third trimester may be considered after discussing the risks and benefits of therapy with the mother.     

Clinical Advances in Hemoglobin A1c Measurement: Influence of Variables on Hemoglobin A1c Values and Nonheterogeneity of Hemoglobin A1c Reference Ranges

Introduction

Hemoglobin A1c (HbA1c) values are influenced by analytical interferences such as HbF and hemoglobin variants and clinical factors such as increased red cell turnover. Although less well-known, demographic factors such as race, age, and sex also influence HbA1c values.The HbA1c reference range should be homogenous in the United States based on the use of National Glycohemoglobin Standardization Program certified methods and the recommendations in the National Academy of Clinical Biochemistry guidelines.

Methods

Data on age, race, sex, HbA1c, and glucose values were extracted from the National Health and Nutrition Examination study for a 3 year period. A search for reference range data for laboratories in the United States was performed using the Google search engine.

Results

Extracted data agree with published data on the influence of age, sex, and smoking status on HbA1c values. There is substantial heterogeneity in HbA1c reference ranges in laboratories in the United States.

Conclusion

Age, sex, and smoking status influence HbA1c values. Despite standardization of HbA1c methods and published recommendations, there is wide heterogeneity in HbA1c reference ranges in the United States.     

Re-engineering primary epithelial cells from rhesus monkey parotid glands for use in developing an artificial salivary gland

There is no satisfactory conventional treatment for patients who experience irreversible salivary gland damage after therapeutic radiation for head and neck cancer or because of Sj?gren's syndrome. Additionally, if most parenchyma is lost, these patients also are not candidates for evolving gene transfer strategies. To help such patients, several years ago we began to develop an artificial salivary gland. In the present study, we used a non-human primate tissue source, parotid glands from rhesus monkeys, to obtain potential autologous graft cells for development of a prototype device for in situ testing. Herein, we present 3 major findings. First, we show that primary cultures of rhesus parotid gland (RPG) cells are capable of attaining a polarized orientation, with Na(+)/K(+)-adenosine triphosphatase, zonula occludens-1, and claudin-1 distributed in specific domains appropriate for epithelial cells. Second, we show that RPG cells exhibit 2 essential epithelial functions required for graft cells in an artificial salivary gland device (i.e., an effective barrier to paracellular water flow and the generation of a moderate transepithelial electrical resistance). Third, we show that RPG cells can express functional water channels, capable of mediating directional fluid movement, after transduction by adenoviral and adeno-associated virus type 2 vectors. Together these results demonstrate that it is feasible to individually prepare RPG cells for eventual use in a prototype artificial salivary gland.     

Rapid degradation of oseltamivir phosphate in clinical samples by plasma esterases

The anti-influenza drug oseltamivir is an ester prodrug activated by hepatic carboxylesterases. Plasma esterases also convert up to 31.8% of the parent compound to the active metabolite after 4 h ex vivo, with wide interindividual variation. This source of error is removed by adding the esterase inhibitor dichlorvos to blood collection tubes.     

Adapting the Rx-Risk-V for mortality prediction in outpatient populations

OBJECTIVES: We sought to operationalize, test, and validate an outpatient pharmacy-based case-mix adjuster. METHODS: Outpatients from the Department of Veterans Affairs (VA) prescribed a nonsteroidal anti-inflammatory drug (NSAID) or cyclooxygenase-2 selective drug during 2002 were identified. We updated and extended the Rx-Risk-V by adding 26 additional disease categories and mapping them to VA drug-class codes; derived empirical weights for each from a logistic model of 1-year mortality; adjusted for age, race and sex; and scored the weights into 1 measure of comorbidity. We compared the weighted score to the Deyo diagnosis-based comorbidity index and validated it in a national cohort of 260,321 outpatients with chronic heart failure (CHF). RESULTS: One-year mortality among the 724,270-outpatient NSAID cohort was 1.6% (n = 11,766). Using a baseline model of age, race, and gender (c-index = 0.716), we found that the Deyo measure improved the prediction of mortality (c-index = 0.765), and the pharmacy comorbidity score further improved the prediction (c-index = 0.782), an increase of 25.8%. Using both, we found further improvement (c-index = 0.792). Among the CHF cohort, 9.7% (n = 25,251) died within 1 year. Performance of the baseline model controlling for age, race, and gender (c index = 0.620) improved with addition of the pharmacy comorbidity score (c index = 0.689), compared with the addition of the Deyo measure (c index = 0.651), an increase of 55.1%. Together, they slightly improved prediction in CHF patients (c index = 0.695). CONCLUSIONS: The updated and extended Rx-Risk-V is useful for case-mix adjustment of mortality in an outpatient population.     

Successful use of recombinant factor VII in massive hemoptysis due to community-acquired pneumonia

Recombinant activated factor VII (rFVIIa) is a powerful hemostatic agent developed for use in hemophilia. It has been used increasingly in life-threatening hemorrhage in a variety of other settings in which conventional medical or surgical therapy is unsuccessful. This report describes the successful use of rFVIIa for pulmonary hemorrhage due to a focal bleeding source in a regional hospital where bronchial artery embolization or surgery were not available. rFVIIa may be a useful temporizing measure in the unstable patient with pulmonary hemorrhage without coagulopathic bleeding when conventional treatment is not immediately available.     

Phosphoinositide 3-kinase regulatory subunit p85alpha suppresses insulin action via positive regulation of PTEN

The phosphoinositide 3-kinase (PI3K) pathway is central to the metabolic actions of insulin on liver. Here, we show that mice with a liver-specific deletion of the p85alpha regulatory subunit of PI3K (L-Pik3r1KO) exhibit a paradoxical improvement of hepatic and peripheral insulin sensitivity. Although PI3K enzymatic activity is diminished in L-Pik3r1KO livers because of a reduced level of regulatory and catalytic subunits of PI3K, insulin-stimulated Akt activity is actually increased. This increased Akt activity correlates with increased phosphatidylinositol (3,4,5)-trisphosphate levels which are due, at least in part, to diminished activity of the (3,4,5)-trisphosphate phosphatase PTEN. Thus, the regulatory subunit p85alpha is a critical modulator of insulin sensitivity in vivo not only because of its effects on PI3K activation, but also as a regulator of PTEN activity.     

Can stock rotation effectively mitigate EMS medication exposure to excessive heat and cold?

The United States Pharmacopeia recently published a general chapter specifically addressing on-ambulance storage of medications, including a suggestion for stock rotation. This study describes the effectiveness of a simple stock rotation strategy in mitigating EMS medication exposure to excessive heat and cold. Previously collected on-ambulance temperature data from 5 US cities were randomly resampled to generate model exposures of 2 days to 6 months duration. The temperature measurements for every other 24-hour period were then set at 20 degrees C to model the rotation of medications into a controlled environment. For each model, we then determined consistency with the official United States Pharmacopeia definition of controlled room temperature. Without stock rotation, excessive heat occurred in 39.9% of the model exposures. With stock rotation, exposures to excessive heat occurred in less than 1% of northern city models and in 2.9% of the central US models. Stock rotation did not reduce heat exposures in the models for southern cities.     

Status of cancer pain in Hanoi, Vietnam: A hospital-wide survey in a tertiary cancer treatment center

Little is known about the prevalence of cancer pain in many developing countries. We report a hospital-wide survey of pain in a tertiary cancer center in Hanoi, Vietnam. All inpatients and outpatients age 18 years or older were approached for participation in the study. Data were collected using the Brief Pain Inventory. Results showed a 70% response rate. Prevalence of moderate to severe pain was 50% (89/178), with 23% reporting severe ratings of pain at its "worst" and 33% reporting severe impairment in their ability to work due to pain. Only 1% and 40% reported total and partial pain relief from medications, respectively. This study is among the first to provide a representative view of pain in a tertiary cancer treatment center in Hanoi, Vietnam. The findings provide empirical support for the need for better programmatic efforts to improve relief of cancer pain in developing countries, including Vietnam.