Cluster of hepatitis C in a family: a twenty-year follow-up.

OBJECTIVE: We described an impressive cluster of hepatitis C in a single family. Of nine members of the family, six - the mother and five daughters - were affected by chronic hepatitis, hepatitis C virus (HCV) genotype 1b, of which two were co-infected with hepatitis B virus (HBV). Sharing a non-disposable injection equipment for intramuscular medical care was the most likely route of contagion. Twenty years after the first observation, we performed a follow up of this family. METHODS: The clinical history was updated, and the members of the family underwent a clinical evaluation, extensive liver laboratory tests, and whole serology for hepatitis C and B. Protein chain reaction for HCV RNA was performed when indicated. The eight spouses of the offspring and their eight children underwent the same evaluation. RESULTS: The main findings of this study are the favourable outcome of the two members of the family mono-infected by HCV, treated with peginterferon and ribavirin (sustained response and free of liver disease), in contrast with the ominous outcome of the two members co-infected with HCV and HBV, who evolved to decompensated cirrhosis, with hepatocellular carcinoma in one case, ultimately leading to death. A further feature is the absence of transmission of HCV to the spouses and to the third generation of children of this family, consistent with the assumption that sexual and vertical transmission is unlikely. CONCLUSIONS: A thorough epidemiological investigation of the two first generations of this family, the study of their spouses and children, and the twenty years of follow up provided a strong presumption that the infection with HCV had occurred within this family through the promiscuous use of the same inadequately sterilized glass syringe for intramuscular therapies, as was a common practice during the fifties and sixties worldwide and still is in some part of the world.

Functioning and disability in the vegetative state: results from a pilot study in Italy.

PURPOSE: To describe functioning and disability of patients in vegetative state (VS) according to the biopsychosocial model of the International Classification of Functioning, Disability and Health (ICF). METHOD: Patients in VS admitted to long-stay hospitals were consecutively enrolled, and the ICF checklist was completed by trained professionals. ICF categories utilisation is described. RESULTS: Twenty-one patients (15 males) were enrolled, mean age was 51.9 and mean duration of VS was 22 months. The majority of body functions and structures categories are reported as problems in less than 20% of patients. In the activity and participation domain, majority of ICF categories were not applicable and, among opened categories, performance was usually better than capacity. Among environmental factors, categories are mostly described as facilitators. CONCLUSIONS: This is the first pilot study in which the applicability of the ICF checklist to patients in VS was tested, showing the applicability of ICF categories within A&P domain, and the presence of few but very strong facilitating environmental factors. This study also sets the premises for a study on people in VS and in minimal conscious state both at a national and international level.

Multivariate meta-analysis helps examine the impact of outcome reporting bias in Cochrane rheumatoid arthritis reviews.

OBJECTIVES: Outcome reporting bias (ORB) is a threat to validity of systematic reviews. Multivariate meta-analysis (MVMA) can potentially reduce the impact of ORB when outcomes are correlated. The aim of this study was to assess ORB in Cochrane systematic reviews of rheumatoid arthritis and to demonstrate how MVMA may examine its impact. STUDY DESIGN AND SETTING: Reviews were assessed for ORB in relation to eight outcomes for rheumatoid arthritis using a nine-point classification system. Impact of ORB was assessed by comparing estimates from univariate meta-analysis and MVMA models. RESULTS: ORB assessment was applied in 21 included reviews, and all contained missing data on at least one of the eight outcomes. ORB was highly suspected in 247 (22%) of the 1,118 evaluable outcomes from 155 assessable trials. MVMA and univariate results sometimes differed importantly. The maximum change in treatment effect estimate between MVMA and univariate meta-analysis approach was found to be 176% for one of the outcome considered. CONCLUSION: ORB has the potential to affect the conclusions in meta-analyses. This could be avoided if trialists reported on all measured outcomes in full. If missing outcome data are unobtainable, MVMA is useful to examine the impact of missing outcomes and ORB on conclusions.

Bactericidal antibody against a representative epidemiological meningococcal serogroup B panel confirms that MATS underestimates 4CMenB vaccine strain coverage.

BACKGROUND: 4CMenB (Bexsero), a vaccine developed against invasive meningococcal disease caused by capsular group B strains (MenB), was recently licensed for use by the European Medicines Agency. Assessment of 4CMenB strain coverage in specific epidemiologic settings is of primary importance to predict vaccination impact on the burden of disease. The Meningococcal Antigen Typing System (MATS) was developed to predict 4CMenB strain coverage, using serum bactericidal antibody assay with human complement (hSBA) data from a diverse panel of strains not representative of any specific epidemiology. OBJECTIVE: To experimentally validate the accuracy of MATS-based predictions against strains representative of a specific epidemiologic setting. METHODS AND RESULTS: We used a stratified sampling method to identify a representative sample from all MenB disease isolates collected from England and Wales in 2007-2008, tested the strains in the hSBA assay with pooled sera from infant and adolescent vaccinees, and compared these results with MATS. MATS predictions and hSBA results were significantly associated (P=0.022). MATS predicted coverage of 70% (95% CI, 55-85%) was largely confirmed by 88% killing in the hSBA (95% CI, 72-95%). MATS had 78% accuracy and 96% positive predictive value against hSBA. CONCLUSION: MATS is a conservative predictor of strain coverage by the 4CMenB vaccine in infants and adolescents.

Predicted strain coverage of a meningococcal multicomponent vaccine (4CMenB) in Europe: a qualitative and quantitative assessment.

BACKGROUND: A novel multicomponent vaccine against meningococcal capsular group B (MenB) disease contains four major components: factor-H-binding protein, neisserial heparin binding antigen, neisserial adhesin A, and outer-membrane vesicles derived from the strain NZ98/254. Because the public health effect of the vaccine, 4CMenB (Novartis Vaccines and Diagnostics, Siena, Italy), is unclear, we assessed the predicted strain coverage in Europe. METHODS: We assessed invasive MenB strains isolated mainly in the most recent full epidemiological year in England and Wales, France, Germany, Italy, and Norway. Meningococcal antigen typing system (MATS) results were linked to multilocus sequence typing and antigen sequence data. To investigate whether generalisation of coverage applied to the rest of Europe, we also assessed isolates from the Czech Republic and Spain. FINDINGS: 1052 strains collected from July, 2007, to June, 2008, were assessed from England and Wales, France, Germany, Italy, and Norway. All MenB strains contained at least one gene encoding a major antigen in the vaccine. MATS predicted that 78% of all MenB strains would be killed by postvaccination sera (95% CI 63-90, range of point estimates 73-87% in individual country panels). Half of all strains and 64% of covered strains could be targeted by bactericidal antibodies against more than one vaccine antigen. Results for the 108 isolates from the Czech Republic and 300 from Spain were consistent with those for the other countries. INTERPRETATION: MATS analysis showed that a multicomponent vaccine could protect against a substantial proportion of invasive MenB strains isolated in Europe. Monitoring of antigen expression, however, will be needed in the future. FUNDING: Novartis Vaccines and Diagnostics.