Real Time-PCR HBV-DNA Analysis: Significance and First Experience in Armed Forces

Background

HBV DNA quantitation is used extensively world wide for the diagnosis and monitoring of treatment of Hepatitis B virus (HBV) infection. However, it has still to be popular in India. The aim of this study was to quantitate HBV – DNA by Real time – PCR method in Hepatitis B and in immuno-compromised patients, to compare the results with HBeAg detection and to monitor the response to therapy of chronic Hepatitis B patients to antivirals.

Methods

Ninety one serum samples of Hepatitis group of patients (all HBsAg positive), 41 samples from immuno-compromised patients (all HBsAg negative) and 49 patients of Chronic Hepatitis B group (all HBsAg positive) were the subjects of this first ever study in Armed Forces. Twenty serum samples from healthy volunteers and non-hepatitis B patients served as negative controls. The amplification detection was carried out in a Rotor-Gene 2000-sequence detector

Results

Amongst Hepatitis B group, 33% (30/91) of the samples were positive for HBV-DNA and 26% (24/91) of samples were positive for HBeAg. In the immuno-compromised group of patients 14.6% (6/11) of samples were positive for HIV-DNA and 9.7% (4/41) were positive for HBeAg. Of the Chronic Hepatitis B patients on treatment, all (100%) were positive by HBV-DNA, whereas 29/49 (59.2%) were positive by HBeAg before treatment. After treatment with antivirals, 06/49 (12.2%) were positive by both tests and 11/49 (22.5%) were positive only by HBV-DNA. 32/49 (65.3%) patients became negative serologically after therapy.

Conclusion

HBeAg status did not necessarily reflect HBV-DNA level in the serum, as 10/91 (11%) in the Hepatitis B group, 2/41 (4.9%) in the immuno compromised group and 20/49 (40.8%) patients in the Chronic Hepatitis B group were positive for HBV-DNA but negative for HBeAg. HBV-DNA was not found to be positive amongst any of the negative controls. Real time – PCR is a sensitive and reproducible assay for HBV-DNA quantitation and may be started in Armed Forces referral centers in the near future.Key Words: Real time – PCR, Chronic Hepatitis B, HBV – DNA, Antivirals     

Maladjusted children and the school health services. Development of a screening test for routine use.

Maladjustment, with social and mental dysfunction, is one of the most prevalent health problems threatening children in many countries. A method for the early identificantion of maladjusted schoolchildren is described and evaluated. The method involves the completion of a questionnaire for each child by the teacher and the calculation of a test score based on a set of weighting factors assigned to each question. The factors are determined by discriminant analysis. For a proper evaluation of the method an independent clinical assessment of maladjustment among 524 school children was performed, making calculations of specificity and sensitivity possible.     

Risk factors for unexplained antepartum fetal death in Norway 1967-1998

OBJECTIVE: To relate unexplained antepartum fetal death with maternal and fetal characteristics in order to identify risk factors. DESIGN: Population-based study based on records of 1,676,160 singleton births with gestational age > or =28 weeks. Unexplained antepartum fetal death was defined as fetal death before labour without known fetal, placental, or maternal pathology. RESULTS: Although unexplained fetal mortality in general declined from 2.4 per 1000 births in 1967-1976 to 1.6 in 1977-1998, the proportion among all fetal deaths increased from 30% to 43% during the same period of observation. Unexplained fetal death occurred later in gestation than explained. From 39 weeks of gestation, the risk increased progressively to 50/10,000 in women aged > or =35 years and <10/10,000 in women <25 years. In birth order > or =5, the risk was particularly high after 39 weeks of gestation. For birth weight percentile 2.5-9.9 and > or =97.5, unexplained fetal death was four and three times more likely to occur, respectively. We found an additive effect of maternal age and birth weight percentile 2.5-9.9. Women with less than 10 years education had higher risk than women with 13 years or more (OR=1.6). Weaker associations were observed with female gender, unmarried mothers, and winter season. CONCLUSIONS: Unexplained antepartum fetal death occurred later in gestation than explained and was associated with high maternal age, multiparity, low education, and moderately low and high birth weight percentile. The increased risk in post-term pregnancies and the additive effect of maternal age and birth weight percentile 2.5-9.9 suggests that older women would benefit from monitoring of fetal growth.     

Vitamin A and sudden infant death syndrome in Scandinavia 1992-1995

Aim: To assess the effect of vitamin supplementation on the risk of sudden infant death syndrome (SIDS). Methods: The analyses are based on data from the Nordic Epidemiological SIDS Study, a case-control study in which parents of SIDS victims in the Scandinavian countries were invited to participate together with parents of four matched controls between 1 September 1992 and 31 August 1995. The odds ratios presented are computed by conditional logistic regression analysis. Results: The crude odds ratio in Scandinavia for not giving vitamin substitution was 2.8 (95% CI (1.9, 4.3)). This effect was statistically significant in Norway and Sweden, which use A and D vitamin supplementation, but not in Denmark, where only vitamin D supplementation is given. The odds ratios remained significant in Sweden when an adjustment was made for confounding factors (OR 28.4, 95% CI (4.7, 171.3)). Conclusion: We found an association between increased risk of sudden infant death syndrome and infants not being given vitamin supplementation during their first year of life. This was highly significant in Sweden, and the effect is possibly connected with vitamin A deficiency. This effect persisted when an adjustment was made for potential confounders, including socioeconomic factors.     

Unexplained antepartum fetal death in Norway, 1985-97: diagnostic validation and some epidemiologic aspects

OBJECTIVE: To validate the diagnosis of an unexplained antepartum fetal death in the Medical Birth Registry of Norway against data obtained from hospital records, alone and combined with autopsy data. To compare epidemiologic characteristics of an unexplained fetal death based on cases recorded by the three data sources. METHODS: Data on unexplained fetal deaths in the Registry were compared with clinical and autopsy data from 108 457 singletons with a gestational age >or= 28 weeks or a birthweight >or= 1000 g delivered in 1985-97 at Haukeland Hospital in Bergen and Aker Hospital in Oslo. RESULTS: Compared with clinical data, the positive and negative predictive values of a Registry diagnosis of an unexplained fetal death were 88% and 86%, respectively, while the sensitivity and specificity were 76% and 93%, respectively. Compared with clinical and autopsy data combined, the positive and negative predictive values of a Registry diagnosis of an unexplained fetal death were 77% and 89%, respectively, while the sensitivity and specificity were 78% and 88%, respectively. High agreement was observed in comparisons between the data sources of risks according to various independent variables. CONCLUSIONS: The validity of a diagnosis of an unexplained antepartum fetal death based on the Medical Birth Registry of Norway is sufficiently high to justify future large-scale epidemiologic studies based on this database.     

The recurrence risk of adverse outcome in the second pregnancy in women with rheumatic disease1

OBJECTIVE: To study recurrence risks of adverse pregnancy outcome in the second pregnancy in women with rheumatic disease. METHODS: In a national population-based cohort study, women with rheumatic disease recorded from 1967 to 1995 in the Medical Birth Registry of Norway were compared with mothers without such diagnoses with regard to recurrence risks of adverse pregnancy outcomes in the second pregnancy. The odds ratios (ORs) of all outcomes were adjusted for maternal age, those of cesarean delivery for time period, and those of preeclampsia for interpregnancy interval. RESULTS: Women with rheumatic disease an dadverse pregnancy outcome in the first pregnancy had a statistically significant higher recurrence risk of the same event in the second pregnancy than women without rheumatic disease (preeclampsia: OR 2.22; 95% confidence interval [CI] 1.18, 4.19) (cesarean delivery: OR 1.52; 95% CI 1.05, 2.21) (preterm birth: OR 1.86; 95% CI 1.12, 3.11). In women with rheumatic disease diagnosed between the first and second births, a significantly increased recurrence risk of low birth weight occurred. Women with rheumatic disease also had a higher occurrence of markers for placental dysfunction (preeclampsia, preterm birth, or small for gestational age) in the second birth after any of these outcomes in the first birth (OR 1.35; 95% CI 1.02, 1.78) (35.1% versus 29.2%). CONCLUSION: The recurrence risk of an adverse outcome in the second pregnancy is increased in any woman, but was even higher in women with a rheumatic disease. These patients should be counseled accordingly, be closely monitored during pregnancy, and have access to appropriate subspecialists.     

Early prophylactic inhaled beclomethasone in infants less than 1250 g for the prevention of chronic lung disease

OBJECTIVE:

Inflammation plays an important role in the development of chronic lung disease (CLD), which has become a major cause of morbidity in surviving infants less than 1250 g at birth. The authors hypothesized that the progression of this inflammation and, therefore, the establishment of CLD would be decreased with the use of early prophylactic inhaled corticosteroids. Short, and long term respiratory and neurodevelopmental outcomes were also examined.

DESIGN:

A double-blind, randomized placebo controlled trial.

SETTING:

Level-III neonatal intensive care unit.

POPULATION STUDIED:

Sixty infants less than 1250 g at birth, diagnosed with respiratory distress syndrome and requiring ventilatory support at 72 h of age were enrolled in the study.

INTERVENTION:

Infants enrolled received either placebo or beclomethasone diproprionate by a metered dose inhaler, which was used in-line with the ventilator circuit while the infant was ventilated and then via a spacer until 28 days of age.

RESULTS:

Thirty infants were given beclomethasone and 30 were given placebo. There were two deaths in each group. Among the surviving infants, the frequency of moderate-to-severe CLD was 17% in each study group. Mean time to extubation was not different for beclomethasone compared with placebo at 16.4 and 12.5 days (P=0.12), respectively. The requirement for intravenous corticosteroids was lower in the beclomethasone-treated group (RR 0.67, 95% CI 0.43 to 1.04), although this difference was not statistically significant. The incidence of growth failure, infection and intraventricular hemmorhage did not differ between the two groups. Long term outcomes were not different with respect to the incidence of respiratory re-admissions, cerebral palsy, developmental delay, blindness or deafness.

CONCLUSIONS:

Early treatment with inhaled beclomethasone diproprionate did not reduce the incidence of CLD or decrease the duration of mechanical ventilation. The decrease in intravenous corticosteroid use was not statistically significant. Long term outcome was not affected.