Lamivudine Treatment for Chronic Hepatitis B

The hepatitis B virus (HBV) is one of the smallest human viruses known and belongs to the family of Hepadnaviridae; it was the first human hepatitis virus that could be characterized. Before the discovery of the virus two types of transmission of infectious hepatitis were distinguished on the basis of epidemiological observations: the classical hepatitis (type A) was transmitted by the faecal-oral route, while type B was transmitted parentally.' In 1963, B8 Blumberg discovered a previously unknown antigen in the blood of an Australian aboriginal (Australia antigen) and within a few years this was found to be related to the parentally transmitted type B hepatitis.' In the early seventies the virus was seen by electron microscopy3 and the genome was found to be a small, circular DNA that was partially double-stranded (figure I). The nucleotide sequence of the virus contains only 3200 nucleotides (3.2 kb) and revealed 4 overlapping genes for the production of seven viral proteins

p53 and P-glycoprotein are often co-expressed and are associated with poor prognosis in breast cancer.

Expression of both P-glycoprotein (P-gp) and mutant p53 have recently been reported to be associated with poor prognosis of breast cancer. The expression of P-gp is associated in vitro and in vivo with cross-resistance to several anti-cancer drugs. p53 plays a regulatory role in apoptosis, and mutant p53 has been suggested to be involved in drug resistance. Interestingly, in vitro experiments have shown that mutant p53 can activate the promoter of the MDR1 gene, which encodes P-gp. We investigated whether p53 and P-gp are simultaneously expressed in primary breast cancer cells and analysed the impact of the co-expression on patients prognosis. Immunohistochemistry was used to investigate P-gp expression (JSB-1, C219) and nuclear p53 accumulation (DO-7) in 20 operable chemotherapy untreated and 30 locally advanced breast cancers undergoing neoadjuvant chemotherapy with doxorubicin and cyclophosphamide. Double immunostaining showed that P-gp expression and nuclear p53 accumulation often occur concomitantly in the same tumour cells. A correlation between p53 and P-gp expression was found in all 50 breast cancers (P = 0.003; Fisher's exact test). P-gp expression, nuclear p53 accumulation, and co-expression of p53 and P-gp were more frequently observed in locally advanced breast cancers than in operable breast cancers (P = 0.0004, P = 0.048; P = 0.002 respectively. Fisher's exact test). Co-expression of p53 and P-gp was the strongest prognostic factor for shorter survival by multivariate analysis (P = 0.004) in the group of locally advanced breast cancers (univariate analysis: P = 0.0007). Only 3 out of 13 samples sequentially taken before and after chemotherapy displayed a change in P-gp or p53 staining. In conclusion, nuclear p53 accumulation is often associated with P-gp expression in primary breast cancer, and simultaneous expression of p53 and P-gp is associated with shorter survival in locally advanced breast cancer patients. Co-expression of P-gp and mutant p53 belong to a series of molecular events resulting in a more aggressive phenotype, drug resistance and poor prognosis

InternationaL cross-sectIonAl and longItudinal assessment on aSthma cONtrol in European adult patients : the LIAISON study protocol

The study is funded by Chiesi Farmaceutici S.p.A., Parma, ItalyPeer reviewedPublisher PD

Efficacy and safety of an intravenous monoclonal anti-HBs in chronic hepatitis B patients

Background Aims: In this study the safety and efficacy of a monoclonal anti-HBs, Tuvirumab (Mab), were investigated. Tuvirumab is a human monoclonal antibody recognizing the stable 'a'-determinant of the HBsAg. Methods: We included ten chronic hepatitis B patients: four received monotherapy, and six combination therapy with interferon alpha 2b. Results: Because the development of insoluble [HBsAg-HBsAb] complexes led to adverse events, the Mab dose had to be reduced in seven patients. In nine patients treatment was stopped prematurely because of lack of efficacy, i.e. neutralization of HBsAg in serum. However, temporary HBsAg levels were reduced by at least 50% in all patients; in three patients receiving combination therapy, background levels of HBsAg in serum were reached. A loss of serum HBV-DNA was seen in three patients in the combination group, followed by HBeAg seroconversion in two patients. Conclusions: We conclude that Mab was not effective in achieving primary efficacy as assessed by neutralization of circulating HBsAg. Whether a combination of Mab with an antiviral agent that reduces the HBsAg load - and therefore minimizes the risk of adverse events - may result in clinical efficacy should be investigated

SERIES: eHealth in primary care. Part 5: a critical appraisal of five widely used eHealth applications for primary care - opportunities and challenges

Background Given the pressure on modern healthcare systems, eHealth can offer valuable opportunities. However, understanding the potential and challenges of eHealth in daily practice can be challenging for many general practitioners (GPs) and their staff. Objectives To critically appraise five widely used eHealth applications, in relation to safe, evidence-based and high-quality eHealth. Using these applications as examples, we aim to increase understanding of eHealth among GPs and highlight the opportunities and challenges presented by eHealth. Discussion eHealth applications can support patients while increasing efficiency for GPs. A three-way division (inform, monitor, track; interaction; data utilisation) characterises many eHealth applications, with an increasing degree of complexity depending on the domain. All applications provide information and some have extra functionalities that promote interaction, while data analysis and artificial intelligence may be applied to support or (fully) automate care processes. Applications in the inform domain are relatively easy to use and implement but their impact on clinical outcomes may be limited. More demanding applications, in terms of privacy and ethical aspects, are found in the data utilisation domain and may potentially have a more significant impact on care processes and patient outcomes. When selecting and implementing eHealth applications, we recommend that GPs remain critical regarding preconditions on safe, evidence-based and high-quality eHealth, particularly in the case of more complex applications in the data utilisation domain.Prevention, Population and Disease management (PrePoD)Public Health and primary car

Interferon alfa for chronic hepatitis B infection: Increased efficacy of prolonged treatment

Interferon alfa (IFN-a) is the primary treatment for chronic hepatitis B. The standard duration of IFN-a therapy is considered 16 weeks; however, the optimal treatment length is still poorly defined. We evaluated the efficacy and acceptability of prolonged IFN-a treatment in patients with chronic hepatitis B. To investigate whether treatment prolongation could enhance the rate of hepatitis B e antigen (HBeAg) seroconversion, we conducted a prospective, controlled, multicenter trial in wh