RESUMO
BACKGROUND: Pain after major head and neck cancer surgery is underestimated and has both nociceptive and neuropathic characteristics. Extended resection, flap coverage, nerve lesions, inflammation, and high-dose opioid administration can also lead to hyperalgesia and chronic postoperative pain. Opioids are frequently associated with adverse events such as dizziness, drowsiness, nausea and vomiting, or constipation disturbing postoperative recovery and extending the length of hospital stay. Patients eligible for major head and neck cancer surgery cannot benefit from full multimodal pain management with locoregional anesthesia. Intravenous lidocaine, investigated in several studies, has been found to decrease acute pain and morphine consumption. Some data suggest also that it can prevent chronic postsurgical pain. Evidence supporting its use varies between surgical procedures, and there is no published study regarding systemic lidocaine administration in major head and neck cancer surgery. We hypothesized that intravenous lidocaine infused in the perioperative period would lead to opioid sparing and chronic postsurgical pain reduction. METHODS/DESIGN: A total of 128 patients undergoing major head and neck surgery will be included in this prospective two-center, double-blind, randomized controlled trial. Patients will be randomly assigned to lidocaine or placebo treatment. After induction of general anesthesia, an intravenous lidocaine bolus will be administered (1.5 mg.kg- 1), followed by a continuous infusion (2 mg.kg- 1.h- 1) which will be reduced in the postanesthesia care unit (1 mg.kg- 1.h- 1). The primary outcome measure is morphine consumption 48 h after surgery. The secondary outcomes include intraoperative remifentanil consumption, morphine consumption 24 h after surgery, and chronic postsurgical pain that will be assessed 3-6 months after surgery. DISCUSSION: Recent evidence suggests that intravenous lidocaine can lead to opioid sparing and chronic postsurgical pain reduction for certain types of surgery. This is the first trial to prospectively investigate the efficacy and safety of intravenous lidocaine in major head and neck cancer surgery. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02894710 . Registered on 11 August 2016.
Assuntos
Anestésicos Locais/administração & dosagem , Neoplasias de Cabeça e Pescoço/cirurgia , Lidocaína/administração & dosagem , Dor Pós-Operatória/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto , Interpretação Estatística de Dados , Método Duplo-Cego , Humanos , Infusões Intravenosas , Lidocaína/efeitos adversos , Avaliação de Resultados em Cuidados de Saúde , Estudos ProspectivosRESUMO
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
BACKGROUND & AIMS: In hepatitis B e antigen (HBeAg) positive-HIV co-infected patients treated with combined antiretroviral therapy (cART), including tenofovir disoproxil fumarate (TDF), the rate of HBe seroconversion remains low. Whether adding pegylated interferon alfa (PegIFN) could increase the likelihood of HBeAg loss and HBe seroconversion has not been assessed. METHODS: A 48-week PegIFN therapy was added to HBeAg positive-HIV co-infected patients on TDF and emtricitabine, or lamivudine for at least 6 months. The primary endpoint was HBV sustained response: HBe seroconversion with undetectable HBV DNA levels 24 weeks after completing PegIFN therapy (W72). RESULTS: Fifty-one patients (49 men, median age 46 years, range: 32-65), were included. Median duration of HIV, HBV infections and TDF therapy was 10.3 (0.6-22), 9.8 (0.5-16), and 3.3 (0.5-6.8)years, respectively. Median baseline CD4 count was 506 (175-1316)/mm(3). HIV viral load was <50 copies/ml in 49 (96%) patients. Nine (18%) patients stopped PegIFN prematurely. Ten (20%) patients experienced HBeAg loss at W72 and four (8%) patients had a HBV sustained response. No HBs seroconversion was observed. Only patients with more than 350 CD4/mm(3) at baseline achieved HBe loss. HBeAg level >10 PEIU/ml at W12 or a quantitative HBsAg decline <0.5 log IU/ml at W24 had 100% and 84% negative predictive values for response, respectively. CONCLUSIONS: 48-week PegIFN additional therapy to cART including TDF did not significantly increase the HBe seroconversion rate, despite an HBeAg loss in 20% of the patients. HBe and HBs kinetics may nevertheless be of help in tailoring and optimising this strategy.
Assuntos
Adenina/análogos & derivados , Desoxicitidina/análogos & derivados , Infecções por HIV , Antígenos E da Hepatite B/sangue , Hepatite B Crônica , Lamivudina/administração & dosagem , Organofosfonatos/administração & dosagem , Adenina/administração & dosagem , Adulto , Terapia Antirretroviral de Alta Atividade/métodos , Antivirais/administração & dosagem , Contagem de Linfócito CD4 , Coinfecção/tratamento farmacológico , Coinfecção/imunologia , Desoxicitidina/administração & dosagem , Portadores de Fármacos , Emtricitabina , Feminino , HIV/efeitos dos fármacos , HIV/imunologia , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Hepatite B Crônica/complicações , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/imunologia , Humanos , Interferon-alfa/administração & dosagem , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/administração & dosagem , Proteínas Recombinantes/administração & dosagem , Tenofovir , Resultado do Tratamento , Carga ViralRESUMO
In this study, we have analyzed the evolution of serum HBsAg levels in 16 patients with chronic hepatitis B who showed an HBsAg seroconversion following antiviral therapy. The data showed that the clearance of serum HBsAg is slower than that of serum HBV DNA, which may reflect a slow kinetics of clearance of infected hepatocytes. Interestingly, HBsAg was detectable for a longer time using the Architect assay than with the Bio-Rad assay. As viremia suppression is achieved in most patients under therapy with the new generation of nucleoside analogs, these data suggest that the quantitative monitoring of serum HBsAg may represent a novel tool for the assessment of antiviral therapy efficacy.