EPO markets have proven to be highly country-specific. EPO market sizes, EPO retail/hospital distribution mixes and BIOSIM-EPO/REF price differences may not be determining factors of BIOSIM-EPO uptakes. Prescription and substitution incentives to use BIOSIM-EPO appear to be determining factors in Germany. The heterogeneity of national EPO markets makes it impossible to outline country profile types with significant BIOSIM-EPO penetrations.

The competition with G-CSF biosimilars varies significantly between EU-5 countries, probably because of G-CSF distribution channel differences. Currently, this competition is not mainly based on prices, but on local political options to stimulate tendering between them and recently branded second- or third-generation products.

In many instances, the ATU programme responds to a public health need by accelerating the availability of new drugs even though this study suggests an impact of the programme on the market access of these drugs for which the standard administrative path is longer than usual. In addition, pharmaceutical companies seem to market compassionate-use drugs with a presumed benefit/risk ratio at a price that guarantees a margin for future negotiation.

Spontaneous bacterial peritonitis (SBP) is a severe complication in patients with cirrhosis and ascites. It is predominantly caused by Escherichia coli. The phylogenetic group and virulence genotype of E. coli isolates causing SBP were investigated, and the association of these characteristics with host factors and prognosis was examined. Seventy-six episodes of E. coli SBP that occurred over a 9-year period were studied. The phylogenetic group of the isolates and the presence of 36 virulence factor genes were investigated. The influence of bacterial and host factors on in-hospital mortality was assessed by multiple logistic regression. Phylogenetic groups A, B1, B2 and D were found in 26%, 4%, 46% and 24% of the isolates, respectively. Virulence factor genes were more frequent in B2 isolates than in non-B2 isolates (mean virulence score 15.4 vs. 7.3, p <10(-4)). Ciprofloxacin resistance was significantly associated with non-B2 groups and a low virulence score. Host factors independently associated with a shift from B2 to non-B2 isolates were norfloxacin prophylaxis (OR 13.01, p 0.0213) and prothrombin ratio (OR 1.04 for a 10% decrease, p 0.0211). The model for end-stage liver disease (MELD) score (OR 1.83, p 0.0007) and hospital-acquired SBP (OR 4.13, p 0.0247) were independent predictors of in-hospital mortality. In contrast, outcome was not influenced by the phylogenetic group or the virulence profile. These findings indicate that the characteristics of E. coli isolates causing SBP vary with the severity of liver disease and with fluoroquinolone prophylaxis. Host factors are more important than bacterial factors in predicting in-hospital mortality.

Treatment of patients with chronic hepatitis C has had limited success because of relapses and nonresponse to interferon alfa therapy (currently the only established therapeutic agent). A retrospective study was done to determine the efficacy of re-treatment with interferon and the predictors of response in patients who failed to achieve sustained response after one standard course of interferon therapy (3 million units three times a week for 24 weeks). One hundred and eleven patients (47 relapsers and 64 nonresponders), mean age 45 years, were included in the study. Eighteen relapsers and 13 nonresponders received a higher dose (5 MU), and 11 relapsers and 6 nonresponders received a longer duration (48 weeks) of interferon therapy. The remaining patients received the same regimen as the first treatment. Eighty-one percent and 23% of relapsers and nonresponders, respectively, had an end-of-treatment response, and 19% and 3% of the corresponding patient groups had a sustained response to re-treatment. Two patients with breakthrough during their first treatment were the only nonresponders with sustained response after re-treatment. Sustained response was observed only in patients who received an increased dose or duration of interferon therapy. No predictor of sustained response was found. In conclusion, sustained response to re-treatment with interferon was only observed with augmentation of dose or duration of therapy in some relapsers and patients who had breakthrough. Established predictors of response to interferon in naive patients, in particular serum hepatitis C virus RNA and genotype, were not associated with sustained response to re-treatment. (HEPATOLOGY 1998;27: 1144-1148.)To date, interferon remains the only established therapeutic agent for the treatment of chronic hepatitis C. Administration of 3 MU of interferon alfa three times a week for 6 months produces a sustained response rate of less than 20%. [1][2][3][4][5][6] Various workers have attempted to re-treat with interferon patients who failed to achieve sustained response after one course of interferon treatment. Discordant results have been reported, with sustained response rates ranging from 0% to 53% in relapsers and nonresponders. 7-10 Most of these studies were of small sample size, and heterogeneous treatment regimens complicate interpretation of results. Others have tried to re-treat with ribavirin, either alone 11,12 or in combination with interferon, 13,14 with variable success. However, these were again small series and their results need to be confirmed with larger randomized trials. Iron reduction, alone 15 or in combination with interferon therapy, 16 has been attempted by others, but no sustained responses were reported in these series. In summary, the appropriate retreatment regimen for relapsers and nonresponders after one course of interferon therapy is yet to be established.It has been shown that virological factors such as viral load and genotype are predictors of sustained response to the first course of interferon treatment...