2,553 research outputs found
Antiviral treatment for chronic hepatitis B virus infection--immune modulation or viral suppression?
The availability of nucleoside analogues has broadened treatment options
for chronic hepatitis B virus (HBV ) infection. Registered treatment for
chronic hepatitis B currently consists of (pegylated) interferon,
lamivudine and adefovir, while entecavir is expected to be licensed in the
short term. Treatment is generally recommended for patients with high
serum HBV DNA and elevated ALAT, indicating the host's immune response
against HBV. Induction of an HBV -specific immune response seems crucial
for persistent control of HBV infection. Currently available treatment
strategies can be differentiated into those that provide sustained
off-treatment response and those that provide therapy maintained response.
A finite treatment course with immunomodulatory agents (interferon-based
therapy) results in sustained response in about one third of patients,
while nucleoside analogue treatment generally requires indefinite therapy
without a clear stopping point. Since nucleoside analogues are well
tolerated, prolonged therapy is feasible, but a major drawback is the
considerable risk of developing antiviral resistance, which occurs most
frequently in lamivudine treated patients and to a lesser extent during
adefovir or entecavir therapy. In our opinion, treatment with
peginterferon should therefore be considered first-line therapy in
eligible patients with a high likelihood of response based on serum HBV
DNA, ALAT and HBV genotype. Patients not responding to PEG-IF N therapy or
not eligible for peginterferon therapy should be treated with
nucleos(t)ide analogues
New approaches in the management of chronic hepatitis B: role of tenofovir
In the field of HIV management, tenofovir disoproxil fumarate (TDF) plays a pivotal role and has been demonstrated to be a safe and well-tolerated antiviral agent. Recent data showed the efficacy of TDF in the treatment of chronically hepatitis B virus (HBV)-infected patients. TDF was superior to adefovir dipivoxil (ADV) in both nucleos(t)ide-naïve HBeAg-positive and HBeAg-negative HBV patients, and appeared to be one of the most potent antiviral agents so far. In addition, several reports showed that TDF was also effective in the nucleos(t)ide-experienced population, although conflicting results have been presented concerning patients with genotypic resistance to ADV. TDF seems to have a good resistance profile as well. The rtA194T mutation in association with lamivudine resistance may confer resistance to TDF, although both in vivo and in vitro studies regarding this mutation demonstrate conflicting results. As treatment with TDF may be associated with nephrotoxicity, all TDF-treated patients should be monitored for renal function at baseline and periodically thereafter. While the relative roles of interferon vs nucleos(t)ide analogues (NA) as initial anti-HBV therapy remains unclear, TDF will probably become one of the key factors in HBV management both as first-choice NA for nucleos(t)ide-naïve patients and as rescue therapy for nucleos(t)ide-experienced patients
Clinical and virological studies on α-interferon treatment of chronic hepatitis type B
The positive results of a-interferon (IFN) therapy have generated an important change in
the therapeutic approach of chronic hepatitis B patients. The studies presented in this
thesis are directed to the question how the efficacy of a-IFN therapy for chronic hepatitis
B could be improved (chapter 1). In particular we investigated whether patient selection,
modification of the treatment schedule and new virological assessments could contribute to
answer this question.
For optimal management of the HBV-infected patients it is important to defme indications
for new treatment modalities as a-IFN and liver transplantation. We followed a cohort of
98 patients with HBsAg-positive cirrhosis and determined which variables influenced the
survival (chapter 2). High age, the presence of ascites and a high serum bilirubin level
were indepently associated with a short duration survival. For the group with a
compensated cirrhosis HBeAg-negative patients exhibited a significantly better prognosis
than HBeAg-positive patients. In contrast we could not fmd a difference in survival in
decompensated patients with a different HBeAg status. These fmdings suggest that there is
an indication for antiviral therapy for patients with a compensated hepatitis B cirrhosis and
active viral replication (HBeAg positive) whereas liver transplantation appears the major
therapeutic option for patients with a decompensated chronic hepatitis B infection.
The standard course of a-IFN therapy for chronic hepatitis B lasts 16 weeks and leads in
about one third of the patients to cessation of virus replication. Intermittent a-IFN therapy
of 24 weeks duration and prolongation of treatment in patients who already exhibited a
partial response (HBV-DNA negative) could enhance the HBeAg serocvonversion rate
(chapter 3). Another modification of the standard a-IFN treatment is combination therapy
with zidovudine. In a randomized controlled study (chapter 4) we found that this
combination was not more effective than a-IFN monotherapy. In patients treated with the
combination of a-IFN and zidovudine side effects, in particular anemia and leucopenia,
were more prominent than in those treated with a-IFN and placebo. In chapter 5 the
benefit of a-IFN retreatment in chronic hepatitis B patients who previously failed to
respond was evaluated. A response (HBeAg seroconversion) to therapy occurred in 2 of
the 18 (11 %) investigated patients. This response rate may be comparable to the
spontaneous HBeAg seroconversion incidence and therefore the efficacy of a-IFN
retreatment in chronic hepatitis B appears limited. Variables with a known predictive
value towards response for initial a-IFN courses (e.g. the level of inflammatory acitvity)
did not influence the result of the retreatment
Business Architectures in the Public Sector: Experiences from Practice
Government agencies need to transform the way in which they are organized in order to be able to provide better services to their constituents and adapt to changes in legislation. Whereas much e-government research has a technology focus, our goal is to investigate whether business architectures can help governments to recreate agencies to make them robust in dealing with political preferences, and further, whether their adoption can guide the realization of IT-oriented enterprise architectures. In this article the concept of business architecture and its implications are analyzed by investigating the case study of the Dutch Immigration and Naturalization Services. The case demonstrates the mediating role business architectures can play between policy and strategy on the one hand, and enterprise IT architecture on the other. Business architectures help: (1) to define business domains and the events connecting them, and (2) to use principles to integrate the domains and ensure synergies. Business domains can be designed and operated independently, which enable higher levels of adaptability. Our case analyses show that the pluriformity of the political visions, public values, and actors involved and the division of responsibilities complicate the creation of a business architecture
Editorial: only steps away from primetime?:Hepatitis B virus RNA as a routine marker to guide HBV treatment decisions—authors' reply
Baseline anti-NS4a antibodies in combination with on-treatment quantitative HCV-RNA reliably identifies nonresponders to pegylated interferon-ribavirin combination therapy after 4 weeks of treatment
Background Early detection of nonresponders to hepatitis C therapy limits unnecessary exposure to treatment and its side-effects. A recent algorithm combining baseline anti-NS4a antibodies and on-treatment quantitative PCR identified nonresponders to a combination of interferon and ribavirin after 1 week of treatment. Aim To validate a stopping rule based on baseline anti-NS4a antibody levels and early on-treatment virological response in treatment-naive genotype 1 chronic hepatitis C patients treated with the current standard pegylated interferon and ribavirin combination therapy. Methods Eighty-nine genotype 1 patients from the Dynamically Individualized Treatment of hepatitis C Infection and Correlates of Viral/Host dynamics Study treated for 48 weeks with standard 180 mu g pegylated interferon (PEG-IFN)-alpha-2a (weekly) and ribavirin 1000-1200mg (daily) were analysed. Baseline anti-NS4a antibody enzyme-linked immunosorbent assay (NS4a AA 1687-1718) was performed on pretreatment serum. Hepatitis C virus-RNA was assessed at days 0, 1, 4, 7, 8, 15, 22, 29, weeks 6, 7, 8, 10, 12 and 6 weekly thereafter until end of treatment. Multiple regression logistic analysis was performed. Results Overall 54 of 89 (61%) patients achieved sustained virological response. A baseline anti-NS4a antibody titre less than 1/1250 correlated with absence of favourable initial viral decline according to variable response types (P=0.015). The optimal algorithm was developed using the combination of the absence of anti-NS4a Ab (= 100.000 IU/ml at week 4. This algorithm has a specificity of 43% and negative predictive value of 100% to detect nonresponse to standard PEG-IFN-alpha-2a and ribavirin therapy at fourth week of therapy (intention-to-treat analysis). Conclusion The decision to stop the therapy in genotype 1 chronic hepatitis C patients treated with PEG-IFN-alpha-2a and ribavirin can be confidently made after 4 weeks of treatment based on the absence of baseline anti-NS4a Ab and a week-4 hepatitis C virus-RNA above 100.000 IU/ml. Eur J Gastroenterol Hepatol 22:1443-1448 (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins
A Nation-wide ePortfolio:Reflections on Ambitions and Experiences in the Netherlands
Janssen, J., Brouns, F., Vaessen, H., Weijnen, G., Huveneers, E., & Hodzelmans, R. (2011). A Nation-wide ePortfolio: Reflections on Ambitions and Experiences in the Netherlands. In Proceedings of the ePortfolio and Identity Conference (ePIC) 2011 (pp. 191-196). July, 10-12, 2011, London, UK. For the presentation, please see also: http://hdl.handle.net/1820/3436In the Netherlands 2008 stands out as a year of significant boosts for nation wide adoption of e-portfolios. In that year the Netherlands Institute for Normalisation (NEN) published the first version of a National Technical Agreement (NTA 2035) for the exchange of e-portfolios using an application profile based on (among others) the IMS ePortfolio specification. In that same year two important government advisory committees on employment and the labour market recommended nationwide adoption of e-portfolios as an instrument to assess and stimulate personal professional development and to increase mobility. In this paper we reflect on the current state of affairs from three different perspectives: a recent study investigating means to accelerate adoption of the NTA 2035, the Service Centre for Lifelong Learning Limburg project which aims to deploy the NTA, and current provision of software supporting the NTA.Service Center Leven Lang Leren Limbur
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