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Eva Herrmann

Publications and source records attributed to Eva Herrmann.

28 records · Page 2Linked to original sources
PubMed2003

Prediction of treatment outcome in patients with chronic hepatitis C: significance of baseline parameters and viral dynamics during therapy.

In patients with chronic hepatitis C virus (HCV) infection scheduled for a 48-week treatment period, premature discontinuation of treatment was previously recommended if HCV-RNA levels remained detectable at week 24 of therapy. Considering the number of side effects and treatment costs, measurement of initial viral decline during therapy may identify virologic nonresponse earlier than 24 weeks. We retrospectively analyzed 260 European patients treated with standard or pegylated interferon alfa (IFN-alpha) and ribavirin for 24 to 48 weeks. Early prediction of virologic response by HCV-RNA decline at weeks 4 and 12 (Versant Quantitative [branched DNA (bDNA) 3.0]; Bayer Diagnostics, Emeryville, CA; and Qualitative [transcription-mediated amplification (TMA)] HCV RNA assay; Bayer Diagnostics) as well as clinical, biochemical, virologic, and histologic baseline parameters were analyzed by logistic regression and receiver operating characteristic (ROC) curves. A viral load at treatment week 4 above 450,000 IU/mL and at week 12 above 30,000 IU/mL was 100% predictive for virologic nonresponse in all patients. From multivariate logistic regression analysis of all patients, independent predictors for sustained virologic response were: genotypes 2 and 3 (P <.0001), a low baseline gamma-glutamyltransferase (GGT) level (P <.0001), a high baseline alanine aminotransferase level (P =.002), and a low baseline viral load (P =.04). None of the latter 3 factors were predictive for sustained virologic response when analysis was restricted to the subgroup of genotypes 2- and 3-infected patients. In conclusion, virologic nonresponse can be predicted early at week 12 of treatment independent from the applied therapeutic regimen based on a cutoff level for HCV RNA of 30,000 IU/mL. This algorithm recognizes 53.7% of nonresponders previously identified at week 24 of treatment.

Adult↗
PubMed2003

Effect of ribavirin on hepatitis C viral kinetics in patients treated with pegylated interferon.

A dynamic equilibrium between viral production and clearance characterizes untreated chronic hepatitis C viral infection. After initiating antiviral treatment, a typical multiphasic decay of viremia can be observed and analyzed using mathematical models. To elucidate the antiviral mechanism of ribavirin when used in combination with (pegylated) interferon alfa, we investigated kinetic parameters in patients with chronic hepatitis C treated with either peginterferon alpha-2a with or without ribavirin and standard interferon alpha-2b plus ribavirin for 48 weeks. Serum HCV RNA was measured frequently before, during, and at the end-of-treatment and the follow-up period. By using an appropriate model for viral dynamics, kinetic parameters were derived from nonlinear, least square fitting of serum HCV RNA quantifications. The first phase of viral decay (day 1) and the second phase of viral decay (days 2 to 21) were similar for all treatment groups. After about 7 to 28 days, a third phase of viral decay was seen in several patients, and this phase of decay was significantly faster in patients treated with peginterferon alpha-2a plus ribavirin compared with those treated with peginterferon alpha-2a alone. The decay of this third phase was associated with the virologic end-of-treatment response and sustained virologic response. In conclusion, the third-phase decay of initial viral kinetics, which may represent a treatment-enhanced degradation of infected cells, was more pronounced in patients treated with peginterferon alpha-2a plus ribavirin. This finding suggests that combination treatment leads to a better restoration of the patient's immune response.

Adult↗
PubMed2003

Triple therapy with amantadine in treatment-naive patients with chronic hepatitis C: a placebo-controlled trial.

The antiviral efficacy of amantadine in patients with chronic hepatitis C is controversial. In this randomized, prospective, placebo-controlled, multicenter trial, triple therapy with interferon alfa (IFN-alpha)-2a plus ribavirin and amantadine (amantadine group) was compared with combination therapy IFN-alpha plus ribavirin (control group). Four hundred previously untreated patients with histologically proven chronic hepatitis C were randomly allocated to treatment with amantadine sulphate (100 mg twice daily orally) or a matched placebo together with IFN-alpha induction plus ribavirin (1,000-1,200 mg/day orally) for 48 weeks. The primary end point was sustained virologic response (SVR) defined as undetectable serum hepatitis C virus (HCV) RNA (<100 copies/mL) 24 weeks after the end of treatment. SVR was observed in 52% of the amantadine group and in 43.5% of the control group (P =.11). Among patients with HCV genotype 1 infection, the corresponding SVR rates were 39% and 31%, respectively. The virologic on-treatment response rate in week 24 was significantly higher in the amantadine group as compared with the control group (70% vs. 59%, respectively, P =.016). This beneficial effect was mainly related to HCV type 1-infected patients (63% vs. 47%, respectively, P =.012). Independent factors associated with SVR, according to multiple logistic regression analysis, were amantadine treatment, low baseline HCV RNA, platelet counts (>/=250/nL), pretreatment ALT quotient >/=3, and GGT level (<28 U/L) as well as HCV genotypes other than 1. In conclusion, although we could not demonstrate a significant advantage of the triple regimen in univariate analysis, multivariate analysis offers arguments that amantadine should be considered as a potential anti-HCV drug in future studies.

Adult↗
PubMed2003

Pharmacokinetics of peginterferons.

Two polyethylene glycol (PEG)-modified interferons are approved for the treatment of chronic hepatitis C. The pharmocokinetic properties of the branched 40 kDa pegylated interferon alfa-2a differ from the linear 12 kDa pegylated interferon alfa-2b. The absorption half-life of standard interferon alfa is 2.3 hours, while absorption half-lives for peginterferon alfa-2a and alfa-2b are 50 hours and 4.6 hours, respectively. The volume of distribution for peginterferon alfa-2a is considerably restricted, while the volume of distribution for peginterferon alfa-2b is only approximately 30% lower than that for conventional interferon. Because of its large size, the 40 kD peginterferon alfa-2a has a more than 100-fold reduction in renal clearance compared with conventional interferon alfa. Clearance of peginterferon alfa-2b is about one-tenth that of unmodified interferon alfa. Although data are limited, both drugs appear to show differences in the initial viral decay pattern in patients with chronic hepatitis C. However, it remains unknown whether these differences in the initial viral decline predict differences in the primary clinical endpoint, sustained virological response.

Antiviral Agents↗
PubMed2002

[Attitudes of psychiatrists toward physician-assisted suicide].

BACKGROUND: Physician-assisted suicide (PAS) is an important subject of the public debate. So far, legal regulations exist in the Netherlands, Belgium and in Oregon (USA). This review reports results of nine empirical studies from Japan, the Netherlands, the United Kingdom and the U. S. which examine attitudes of psychiatrists toward PAS. RESULTS: The approval of PAS by psychiatrists varies between the four countries (40 - 69 %). Comparisons with the attitudes of other physicians show a greater agreement among the psychiatrists. A psychiatric examination in order to evaluate competence even in patients with severe somatic illness was advocated by the majority of psychiatrists. CONCLUSION: Psychiatrists' attitudes toward PAS vary and are compared with other medical specialties, as well as in different legal and cultural contexts. Therefore, and because of missing empirical studies, results can not be transferred into the context of German speaking countries easily. So far, no acknowledged criteria for the assessment of competence exist. Further empirical research is needed on German psychiatrists' attitudes towards PAS and on competence assessment at the end of life. It remains an open question how legal changes and future developments of palliative care will influence attitudes toward PAS.

Attitude of Health Personnel↗
PubMed2002

Hepatitis C virus nonstructural 5A protein and interferon resistance: a new model for testing the reliability of mutational analyses.

Presumably due to the capability of the hepatitis C virus (HCV) to evade the antiviral effects of alpha interferon, treatment is ineffective in more than half of chronically genotype HCV type 1 (HCV-1)-infected patients. Previous approaches to correlate the number of amino acid mutations within regions of HCV nonstructural (NS)-5A protein with virologic treatment response provided conflicting results. In the present study, we developed a new mathematical model to investigate NS5A sequences of HCV-1-infected patients. The mean number of all mutations within the complete NS5A protein was significantly higher in virologic responders compared to nonresponders (P = 0.008 and P = 0.0001 for amino acid residues predicted on the surface of the NS5A protein). Differences did not achieve statistical significance for NS5A regions that are currently assumed to be functionally relevant (e.g., the interferon sensitivity-determining region, the RNA-activated protein kinase-binding domain, etc.). Analyses of smoothed mutational frequencies showed that the number of mutations in other NS5A regions correlated with virologic response. Such a correlation was observed for both genuine and randomly generated NS5A sequences. The existence of local accumulations of mutations within genuine NS5A isolates that truly correlated with treatment response was defined by a refined test procedure. Upon considering the predicted residue accessibility, we identified the main focus of mutations correlating with treatment response to be the sequence from amino acids 2350 to 2370. Thus, evaluation of NS5A mutations in correlation with treatment response is improved by consideration of functional and predicted conformational amino acid properties. As shown by simulations with randomly generated sequences, multiple analyses of simple counts of local NS5A amino acid mutations and correlation with treatment response are insufficient. For improvement of mutational analysis, a refined specific functional data test procedure is proposed.

Adult↗
PubMedDate not supplied

Physician assisted suicide: knowledge and views of fifth-year medical students in Germany.

Suicide and assisted suicide are not criminal acts in Germany. However, attempting suicide may create a legal duty for physicians to try to save a patient's life. This study presents data on medical students' legal knowledge and ethical views regarding physician assisted suicide (PAS). The majority of 85 respondents held PAS to be illegal. More than a third of the students viewed PAS in certain situations to be ethically acceptable whereas a smaller proportion thought that it should be legal. Compared with German physicians the medical students taking part in this study were less opposed to PAS. The majority perceived the undergraduate training concerning ethical aspect of assisted death as deficient.

Attitude↗
PubMedDate not supplied

Dynamics of hepatitis C virus infection.

Viremia shows only minor fluctuations in untreated patients chronically infected with hepatitis C virus. The steady state situation of balanced viral production and clearance in untreated patients can be disturbed by active antiviral treatment. After initiating interferon- alpha therapy, a typical biphasic decline of viremia can be observed and analyzed. Evaluation of mathematical models of viral dynamics during the initial phase of antiviral treatment shows high turnover rates of pre-treatment viral production and clearance of about 10(11) -10(13) virions each day and in-vivo half-lives of a few hours for free hepatitis C virions. During the first 24 to 48 hours of therapy, a dose-dependent first phase of interferon-alpha induced viral kinetics is characterized by a rapid exponential decline of serum viral load. Then viral decline enters a second phase of a relatively slow exponential decay during the following weeks of therapy which mainly reflects the death rate of infected hepatocytes. This second phase decay is predictive for the virologic end-of-treatment and even more the sustained response. Non-responding patients typically show constant viremia or even a rebound during this second phase.

Antiviral Agents↗