[Efficacy of antenatal screening for hepatitis B among pregnant women in Denmark].
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Biomedical subjects
Publications and source records attributed to Kim Krogsgaard.
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OBJECTIVE: This study was designed to assess the effects of a perioperative dosing regimen of amiodarone administration, high thoracic epidural anesthesia (TEA), or a combination of the 2 regimens on atrial fibrillation (AF) after coronary artery bypass grafting (CABG). DESIGN AND SETTING: The study was prospective, controlled, and randomized and was performed in a tertiary health care center associated with a university. PARTICIPANTS: One hundred sixty-three patients scheduled for coronary artery bypass graft surgery. INTERVENTIONS: In this 2 x 2 factorial-designed study the patients were randomized to 1 of 4 regimens in which group E had perioperative TEA, group E+A had TEA and amiodarone, group A had amiodarone, and group C served as control. The epidural catheter was inserted at T1-3 the day before surgery. TEA groups received TEA for 96 hours. The amiodarone regimen consisted of a single loading dose of 1,800 mg of amiodarone orally. Intravenous infusion of amiodarone was started after induction of anesthesia and was administered at 900 mg over 24 hours for the subsequent 3 days. MEASUREMENTS AND MAIN RESULTS: AF was documented using Holter monitoring. In group E 22 of 44 (50%), in group E+A 10 of 35 (28.6%), in group A 10 of 36 (27.8%), and in the control group 20 of 48 (41.7%) patients developed AF (odds ratio amiodarone/nonamiodarone 0.47 [0.24-0.90]; P = 0.02). CONCLUSIONS: The perioperative amiodarone regimen used in this study was effective in reducing the incidence of AF after CABG while TEA was not.
OBJECTIVE: To investigate the effect of an antiviral compound, valacyclovir, on pain and tenderness in patients with the fibromyalgia (FM) syndrome. METHODS: Sixty patients were randomized into a double blind, placebo controlled 6 week trial. Primary outcome was pain intensity change (on visual analog scale). Secondary outcome measures were tender points (myalgic score) and Fibromyalgia Impact Questionnaire (FIQ). RESULTS: Fifty-two patients completed the study. The numbers of dropouts due to adverse events were equal in valacyclovir (2) and placebo (2) groups. The effect of valacyclovir on pain and tenderness and FIQ did not differ from placebo. CONCLUSION: Valacyclovir cannot be recommended as a therapy for FM at this point.
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The paper describes the current organisation of clinical trials in Danish hospitals, with particular emphasis on the relationship between hospitals and the pharmaceutical industry. Legal responsibilities as well as mutual agreements on collaboration and organisation are described and discussed.
According to a new EU Directive investigator initiated drug trials are to comply with the guidelines for Good Clinical Practice (GCP) as of May 2004. This implies that trials should be conducted according to a set of Standard Operating Procedures (SOPs) and be subject to monitoring and auditing. In 2001, investigators in Denmark initiated 73 drug trials. In order to provide GCP services and guidance to the investigators it is proposed to establish 3-4 regional GCP units at the three university hospitals. The estimated annual cost for the 3-4 GCP units will be between DDK 7.5 and 10 million.
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The prevalence of hepatitis B virus (HBV) carriage in Denmark is unknown, but expected to be low (0.1%). This study aimed to evaluate the efficacy of selective antenatal screening for HBV infection and the epidemiology of HBV and hepatitis C virus (HCV) among pregnant women. 4098 women were included in the study. Blood tests were examined for hepatitis B surface antigen (HBsAg), anti-hepatitis B core antigen (HBc) and anti-HCV. Case records were studied to evaluate whether patients at risk for HBV infection had been tested. Among the 4098 women, 18 10.4%, 95% confidence interval (95% CI) 0.3-0.71 were HBsAg positive. All had a risk factor for HBV infection. Only 13 (72%) were identified as HBsAg positive in the selective screening programme. 115 women (2.8%, 95% CI 2.3-3.4) were anti-HBc positive only. 95 (83%) were at risk for HBV. Only 72 of these (63%) were tested for HBsAg. The screening programme in this area of Denmark did not pick up one-third of pregnant women at risk of HBV.
OBJECTIVES: To determine the prevalence of TT virus (TTV) in a population of Danish hemodialysis patients and evaluate possible relations between TTV infection and elevated levels of C-reactive protein (CRP) and hypo-response to treatment with erythropoietin (EPO). MATERIAL AND METHODS: Patients on maintenance hemodialysis at a single center were invited to participate. Demographic and clinical data were registered. Blood samples for virological and routine biochemical tests were drawn simultaneously. TTV DNA was detected using polymerase chain reaction (PCR). TTV viral load was estimated by means of semi-quantitative PCR. All patients were tested for hepatitis B, hepatitis C and GB virus C. RESULTS: Of 252 patients, 204 (80.9%) gave their written informed consent to participate in the study. The prevalence of TTV was 68% and 50% of TTV-positive patients had a high TTV viral load. TTV-positive patients were significantly older than TTV-negative patients (p = 0.011). No relations were found between TTV infection and elevated levels of alanine aminotransferase (ALT) or CRP or hypo-response to EPO treatment. The mean hemoglobin concentration was 11.24 +/- 1.48 g/dl. Patients with a high TTV viral load had a lower level of hemoglobin (10.86 +/- 1.47 g/dl) than the others (p = 0.01). This trend suggested a positive relation between TTV infection and the number of blood transfusions. A restriction fragment length polymorphism assay suggested that patients were infected with different TTV strains. CONCLUSIONS: TTV is common in patients on maintenance hemodialysis. The presence of TTV is associated with increasing age. Patients with a high TTV viral load had lower levels of hemoglobin than the others. TTV infection is not related to elevated levels of ALT or CRP or to hypo-response to EPO treatment.
Infection with hepatitis B virus may develop into a chronic carrier state, which may result in chronic hepatitis, cirrhosis and hepatocellular carcinoma, but the exact mechanism of the development of hepatocellular carcinoma is still not known. The question is whether it is hepatitis B virus itself or the cellular changes due to persistent hepatitis B virus infection that cause malignant changes? The purpose of this article was to describe the natural history of hepatitis B virus infection together with epidemiological, serological, and molecular data that show a connection between chronic hepatitis B virus infection and the development of hepatocellular carcinoma.
Little is known about coinfection among several hepatitis B virus (HBV) genotypes, although previous reports of recombination and genotype shifts indicate that this should occur. In the present study, we designed a method to identify mixtures of genotype A and another genotype, regardless of whether one of them predominates. Using this method, signs of genotypic coinfection were found in 20 (67%) of 30 hepatitis B e antigen-positive patients treated with interferon (IFN). In 8 of these patients, coinfection or genotype shifts were detectable by direct sequencing or standard preS genotyping. In most of these cases, genotype changes were detected after a >2-log decrease or increase of the HBV DNA level. The presence of genotype mixtures did not significantly influence IFN response. Because quasi-species selection may occur at or shortly after transmission, patients might acquire HBV infection from subjects who appear to be infected with a different genotype. This should be considered when tracing the source of HBV infection.
A 36-year-old man was diagnosed with polyarteritis nodosa (PAN). He presented with weight loss, hypertension, and mono-neuritis. Pneumoperitoneum and septicaemia developed and laparotomy revealed necrosis of a segment of the ileum. The patient was HBsAg/HBeAg and HBV DNA positive. Liver biopsy showed active cirrhosis. The PAN symptoms remitted upon treatment with prednisolone and lamivudine. Seroconversion from HBeAg to anti-HBe occurred six months later. One year after the end of treatment, the patient was still HBeAg and HBV DNA negative, with normal liver enzymes and no symptoms of PAN.
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Therapy for chronic hepatitis B with interferon-alpha (IFN) may result in viral clearance and hepatitis B e seroconversion in 30-40% of patients. It is still unclear whether viral genetic variability influences response rates. However, certain core promoter mutations were recently associated with a better response to IFN. In the present study, the entire X region, including the core promoter, of hepatitis B virus (HBV) from 26 HBeAg-positive patients treated with IFN for 12 weeks, was sequenced. Serum samples pre-treatment, at end-of-treatment, and at follow-up of 18 sustained and 8 nonsustained responders were analyzed. Most patients were of European origin and had moderate aminotransferase elevation (mean 2.4 x upper limit of normal) and genotype A infection. Before treatment, 16 patients had an X region identical to a consensus sequence of the corresponding genotype; in the remaining 10 patients, a median of 1.5 mutations were found. After treatment, 1-4 new mutations (mean 1.8) had emerged in 5 patients. There was no association between specific mutations, or the number of mutations, and response to IFN. The low frequency of mutations indicates that analysis of this region is of limited clinical value and that emerging mutations in this region are not major determinants of response to treatment with IFN-alpha.
PURPOSE: To investigate whether TT virus (TTV) viral load may be used as a surrogate marker for functional immune reconstitution in HIV-infected patients receiving highly active antiretroviral therapy (HAART). METHOD: Fifteen protease inhibitor-naïve HIV-infected patients were included in a longitudinal study. From each patient, three serum samples taken before HAART initiation and three samples taken during HAART were analyzed. TTV was detected by polymerase chain reaction (PCR) and was quantitated by competitive PCR. TTV viral heterogeneity was determined by restriction fragment length polymorphisms (RFLPs) and sequencing. RESULTS: All 15 HIV-infected patients were TTV positive. No significant change in HIV RNA or TTV viral load was observed at the three time points before HAART initiation. Even though HAART lead to an immediate and significant reduction in HIV RNA (p =.0001), a significant reduction in TTV viral load (p =.0002) was not observed until after 3-5 months of HAART. Four patients did not have an increase in CD4+ T cell count after 1 year of HAART; however, a decrease in TTV viral load was still observed, and three of these patients had a reduction in HIV RNA. RFLPs and sequencing revealed that TTV is represented as a heterogeneous population of virus in HIV-infected patients. CONCLUSION: This pilot study suggests that HAART leads to improved immunological responses, even in patients who do not have an increase in CD4+ T cell counts. We propose that the change in TTV viral load may be useful in the evaluation of cellular immune response at a functional level in HIV-infected patients who receive HAART.