RESUMO
BACKGROUND: The ANRS COV1-COHVAC cohort was a long-term safety cohort of healthy volunteers who received preventive HIV-vaccine candidates in 17 phase I/II clinical trials. METHODS: Data collected from the first vaccine candidate administration and annually after inclusion in the cohort included grade 3/4 adverse events and all grade adverse events suggestive of neurological, ophthalmological and immune disorders, self-administered questionnaires on behaviors and HIV ELISA results. Age-and-sex-standardized mortality ratios (SMRs) were calculated with respect to the French population. The cohort was early terminated in 2016 due to the absence of safety signal. RESULTS: Of 496 volunteers, 488 were included: 355 in the 7-year prospective follow-up and 133 in the retrospective data collection only. The total follow-up after the first vaccination was 4934 person-years (median: 10 years) and 270 (76%) volunteers completed their follow-up. No relevant adverse event possibly related to the vaccine was reported. Breast cancer incidence and woman mortality did not differ from those of the French general population (standardized incidence ratioâ=â1.47, Pâ=â0.45 and SMRâ=â0.65, Pâ=â0.28, respectively) while man mortality was significantly lower (SMRâ=â0.26, Pâ=â0.0003). At the last visit, 21/29 (72%) volunteers who received the recombinant HIV gp160 protein still showed vaccine-induced seropositivity after a median follow-up of 23 years. Only a few volunteers reported risky sexual practices (men: 20/192, women: 2/162). CONCLUSION: Volunteers showed a sustained high commitment. No long-term safety alert was identified during the postvaccine follow-up. Participating in vaccine trials did not increase risky behaviors for HIV infection. Vaccine-induced seropositivity may persist for more than 23 years after receiving rgp160.
Assuntos
Vacinas contra a AIDS/imunologia , Anticorpos Anti-HIV/sangue , Infecções por HIV/imunologia , Infecções por HIV/prevenção & controle , Vacinas contra a AIDS/efeitos adversos , Adulto , Ensaios Clínicos como Assunto , Ensaios Clínicos Fase I como Assunto , Ensaios Clínicos Fase II como Assunto , Feminino , França , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Comportamento Sexual , Comportamento Social , Inquéritos e Questionários , TempoRESUMO
BACKGROUND AND AIMS: In this French multicentre, open-label study, we analyzed the efficacy, safety and patient-reported outcomes of a boceprevir-based triple therapy in HCV genotype 1 cirrhotic patients awaiting liver transplantation (LT). METHODS: Patients received PEG-IFN/ribavirin (RBV) for 48 weeks (W) and boceprevir from W4 to W48 or until LT. RESULTS: Fifty-one patients (80% males, median age: 56 years) were included. Fifty-seven percent had hepatocellular carcinoma and 43% end-stage liver disease. At enrolment, the median MELD score was 9 (range: 6-18); the Child-Pugh score was A in 65%, B in 35% and C in 2%. Therapy was discontinued because of severe adverse events (SAEs) in 39% of cases and virological inefficacy in 24%. 16% of patients had undetectable HCV RNA 24 weeks after the end of treatment (SVR24). LT was performed in 18 patients (35%). HCV RNA was undetectable in 16.6% at LT. Seven patients (14%) died and three deaths were attributed to treatment. SAEs (n=129) were observed in 84% of patients. Twenty-four percent of patients developed severe infections. Albumin<35g/L was independently associated with severe infection. Compared with baseline values, a significant decrease (P=0.02) of the physical dimension of health-related quality of life was observed between W4 and W24. The mean (95% CI) number of self-reported symptoms doubled during treatment (from 6.3 [4.8-7.7] to 11.8 [9.3-14.3]; P<0.001). CONCLUSIONS: The safety of the PEG-IFN/RBV/boceprevir combination is poor in patients awaiting LT, with a high risk of severe infection. Moreover, the limited efficacy confirms the indication for IFN-free combinations in these patients.
Assuntos
Antivirais/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Hepatite C Crônica/tratamento farmacológico , Cirrose Hepática/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Transplante de Fígado , Prolina/análogos & derivados , Adolescente , Adulto , Idoso , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/mortalidade , Quimioterapia Combinada , Feminino , França , Hepatite C Crônica/complicações , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/mortalidade , Humanos , Interferon-alfa/uso terapêutico , Cirrose Hepática/diagnóstico , Cirrose Hepática/mortalidade , Cirrose Hepática/virologia , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Prolina/uso terapêutico , Qualidade de Vida , Estudos Retrospectivos , Ribavirina/uso terapêutico , Resultado do TratamentoRESUMO
OBJECTIVE: The aim of our study was to describe the MR imaging findings in patients with rapidly destructive osteoarthritis of the hip. CONCLUSION: The key MR imaging features of rapidly destructive hip osteoarthritis include joint effusion (100%), bone marrow edemalike pattern in the femoral head and neck (100%) or acetabulum (83%) or both, femoral head flattening (92%), and cystlike subchondral defects (83%). Additional findings are low-signal-intensity lines (33%) in the femoral epiphysis, bandlike areas of low signal intensity in the upper pole of the femoral head (8%), and focal signal abnormalities in the adjacent soft tissues (33%) on short tau inversion recovery MR images, fat-suppressed T2-weighted MR images, and fat-suppressed gadolinium-enhanced T1-weighted MR images.