Assessment of tolerance and acceptability between mannitol solution and polyethylene glycol as bowel preparation for colonoscopy: a three-center study / Evaluación de tolerancia y aceptabilidad entre la solución de manitol y el polietilenglicol como preparación intestinal para la colonoscopía: un estudio de tres centros

ABSTRACT Introduction: Adequate bowel preparation is one of the most important factors related to the yield of colonoscopy. Low quality bowel preparation has been associated with lower adenoma detection rates and increased healthcare expenses. Bowel preparation is a major impediment to undergo colonoscopy since it is perceived as an unpleasant experience by patients. Objective: This study was aimed to assess tolerance and acceptability of the bowel preparation using either polyethylene glycol (PEG) or mannitol solution. Materials and methods: We enrolled 140 patients with indications of screening for colorectal cancer or with suspected large bowel diseases. They received either mannitol solution or PEG as bowel preparation. Patients were asked to fill a questionnaire about the bowel preparation experience. Results: Patients perceived more burdensome the preparation with PEG than mannitol for the variables nausea overall experience, post-procedure discomfort, disagreeable flavor, volume ingested and cost (p<0.05). A similar tolerance was reported for abdominal pain, bloating and anal irritation (p>0.05). The acceptability was 82.9% and 71.4% in the Mannitol group and in the PEG group, respectively (p=0.10). Conclusion: Acceptance of the bowel preparation between mannitol solution and PEG was comparable. However, mannitol was better tolerated by the patients in regard to most of the evaluated items.

RESUMEN Introducción: La preparación intestinal adecuada es uno de los factores más importantes relacionados con el rendimiento de la colonoscopía. La preparación intestinal de baja calidad se ha asociado con tasas de detección de adenoma más bajas y mayores gastos de atención sanitaria. La preparación intestinal es un impedimento importante para someterse a una colonoscopía, ya que los pacientes la perciben como una experiencia desagradable. Objetivo: Este estudio tuvo como objetivo evaluar la tolerancia y la aceptabilidad de la preparación intestinal utilizando polietilenglicol (PEG) o solución de manitol. Materiales y métodos: Fueron incluidos 140 pacientes con indicación de pesquisa de cáncer colorrectal o con sospecha de enfermedades del intestino grueso. Los pacientes recibieron solución de manitol o PEG como preparación intestinal. Se pidió a los pacientes que completaran un cuestionario sobre la experiencia de preparación intestinal. Resultados: Los pacientes percibieron más agobiante la preparación con PEG que el manitol para las variables náuseas, experiencia general, molestias posteriores al procedimiento, sabor desagradable, volumen ingerido y costo (p<0,05). Se informó una tolerancia similar para el dolor abdominal, distensión abdominal e irritación anal (p>0,05). La aceptabilidad fue de 82,9% y 71,4% en el grupo de manitol y en el grupo de PEG, respectivamente (p=0,10). Conclusión: La aceptación de la preparación intestinal entre la solución de manitol y el PEG fue comparable. Sin embargo, el manitol fue mejor tolerado por los pacientes con respecto a la mayoría de las variables evaluadas.

First-wave protease inhibitors for hepatitis C genotype 1 treatment: a real-life experience in Brazilian patients

Abstract INTRODUCTION: Licensed for chronic hepatitis C treatment in 2011, the protease inhibitors (PIs) telaprevir (TVR) and boceprevir (BOC), which have high sustained viral responses (SVR), ushered a new era characterized by the development of direct-action drugs against the hepatitis C virus (HCV). The aim of this study was to analyze the effectiveness and safety of BOC and TVR administered with pegylated interferon and ribavirin and to share the experience of a Brazilian reference center. METHODS: A retrospective descriptive study was conducted in patients with HCV genotype 1 infection who started treatment between July 2013 and December 2015. Data were collected using a computerized system. RESULTS: A total of 115 subjects were included, of which 58 (50.4 %) had liver cirrhosis and 103 (89.6 %) used TVR. The overall SVR rate was 61.7 % (62.1 % for TVR and 58.3 % for BOC). The presence of cirrhosis was associated with a lower SVR rate, whereas patients who relapsed after prior therapy had a greater chance of showing SVR than did non-responders. The incidence of adverse drug reactions (ADRs) was high. Almost all patients (~100 %) presented with hematologic events. Furthermore, treatment had to be discontinued in 15 subjects (13 %) due to severe ADRs. CONCLUSIONS: In conclusion, the SVR rates in our study were lower than those reported in pre-marketing studies but were comparable to real-life data. ADRs, particularly hematological ADRs, were more common compared to those in previous studies and resulted in a high rate of treatment discontinuity.

Peginterferon plus ribavirin and sustained virological response rate in HCV-related advanced fibrosis: a real life study

Background: Tolerance and response to antiviral HCV treatment is poor in advanced fibrosis. The aim of this study was to assess SVR rate and its predictive factors in HCV advanced fibrosis patients treated in real life with full dose PEG-IFN plus RBV and to evaluate the adverse events related to treatment. Methods: A multicentric, retrospective study was conducted at six university hospitals. METAVIR F3 and F4 HCV monoinfected patients who were treated with PEG-IFN and RBV had their data analyzed. A stepwise logistic regression analysis was performed to identify the variables independently related to SVR. Adverse events were recorded during treatment. Results: 308 patients were included, 75% genotype 1 and 23% genotype 3. METAVIR F3 was present in 39% and F4 in 61% of patients. The median Child Pugh score for F4 patients was 5 (5–9). The global SVR rate was 34%, 11% were relapsers and 55% were nonresponders. SVR rates were similar between patients treated with PEG-IFN alfa 2a or alfa 2b (p = 0.24). SVR rates according to Child–Pugh score were 26% (Child A) and 18% (Child B). The independent factors related to SVR in F4 patients were genotype 3, RVR and fewer Child Pugh score points. Treatment interruption occurred in 31% patients and death occurred in 1.9%, all with liver cirrhosis. Conclusion: Treatment of HCV in patients with advanced fibrosis should not be postponed. However, a very careful evaluation of cirrhotic patients must be performed before treatment is indicated and careful monitoring is required during treatment. .

Gender influence on treatment of chronic hepatitis C genotype 1 / Influência do gênero no tratamento da hepatite C crônica genótipo 1

INTRODUCTION: Although various studies have been published regarding the treatment of chronic hepatitis C (CHC) with peginterferon (Peg-IFN) and ribavirin, little is known regarding the real impact of gender on the characteristics that influence the effectiveness and safety of antiviral treatment for CHC patients. The objective of this study was to evaluate the influence of gender on HCV treatment outcomes. METHODS: A retrospective analytical study was conducted among selected carriers of CHC genotype 1, who were treated with Peg-IFN α-2b at a dose of 1.5 μg/kg or Peg-IFN α-2a at a dose of 180 μg/week plus a ribavirin dose of 1,000-1,250 mg/day, according to weight, between 2001 and 2007. RESULTS: Among 181 patients undergoing treatment, the mean age was 46.4 ± 11.0 years and 46 percent were women. At baseline, 32 percent of the patients had advanced fibrosis (F3-F4 Scheuer), and 83 percent of the subjects had viral load > 400,000 IU/ml, without significant difference between the genders (p = 0.428 and p = 0.452, respectively). When compared with men, women had higher incidence of many adverse events such as anemia (p < 0.001) and higher need for dose reduction, for both Peg-IFN (p = 0.004) and ribavirin (p = 0.006). However, the rate of sustained virological response (SVR) did not differ between the genders: 45 percent (female) vs 41 percent (male); p=0.464. CONCLUSIONS: This study suggests that women and men react differently to combined therapy, especially in relation to the incidence of adverse events and the need for dose modification. Nevertheless, these differences do not influence the SVR rate.

INTRODUÇÃO: Apesar dos vários estudos publicados a respeito do tratamento da hepatite C crônica (CHC) com Peg-Interferon (Peg-IFN) e ribavirina, se desconhece o real impacto do gênero sobre as características que influenciam a eficácia e a segurança da terapia antiviral em portadores de CHC. O objetivo deste estudo foi avaliar a influência do gênero no tratamento da CHC. MÉTODOS: Foi realizado um estudo analítico retrospectivo de portadores de CHC genótipo 1 tratados com Peg-IFN α-2b na dose de 1,5μg/kg ou Peg-IFN α-2a na dose de180μg/sem associado à ribavirina 1.000-1.250 mg/dia, de acordo com o peso, entre 2001 e 2007. RESULTADOS: Entre 181 pacientes submetidos ao tratamento, a média de idade foi de 46,4±11,0 anos e 46 por cento eram mulheres. No pré-tratamento, 32 por cento dos pacientes apresentavam fibrose avançada (F3-F4 Scheuer), e 83 por cento dos indivíduos apresentavam carga viral >400.000IU/mL, sem diferença significativa entre os gêneros (p=0,428 e p=0,452, respectivamente). Quando comparadas aos homens, as mulheres exibiram maior incidência de eventos adversos como anemia (p<0,001) e maior necessidade de redução de dose tanto do Peg-IFN (p=0,004) quanto da ribavirina (p=0,006). Entretanto, as taxas de resposta virológica sustentada (RVS) não diferiram entre os gêneros (45 por cento (mulheres) . vs 41 por cento (homens); p=0,464). CONCLUSÕES: Este estudo sugere que homens e mulheres reagem à terapia combinada de forma diferente, especialmente com relação aos eventos adversos e à necessidade de modificação de dose. No entanto, essas diferenças não influenciam as taxas de RVS.

The use of monoclonal antibody (Rituximab) in the treatment of type II mixed cryoglobulinemia

Anti-CD20 monoclonal antibody has been successfully used to treat several self-immune diseases. The authors report the case of a 71 year-old female patient under the use of pegylated form of interferon á associated with ribavirin for the treatment of hepatitis C, who, after concluding the therapeutic program - negative Polymerase Chain Reaction (PCR) - developed a severe cutaneous vasculitis, receiving the diagnostic of type II mixed cryoglobulinemia. Four sessions of plasmapheresis were prescribed along the period of 11 days, with no result. The choice made was to administer anti-CD 20 monoclonal antibody (rituximab), 375 mg/m², per week, during four consecutive weeks. One could observe fast recovery from the purpura, as well as total remission of urticaria.

Peginterferon alfa-2a (40KD) (PEGASYS®) plus ribavirin (COPEGUS®) in retreatment of chronic hepatitis C patients, nonresponders and relapsers to previous conventional interferon plus ribavirin therapy

Peginterferon alfa plus ribavirin is currently the treatment of choice for chronic hepatitis C. Peginterferon alfa-2a (40KD) plus ribavirin has given an overall sustained virological response of 18 percent in F3/F4 previous nonresponder US patients. We evaluated the effectiveness of peginterferon alfa-2a (40KD) plus ribavirin in Brazilian patients who were relapsers or nonresponders to previous interferon-based therapy. One-hundred-thirty-four patients with biopsy-proven chronic hepatitis C, HCV RNA positive, elevated ALT and who were either relapsers (n=37) or nonresponders (n=97) to at least 24 weeks of conventional interferon/ribavirin therapy were retreated with peginterferon alfa-2a (40KD) 180mg/qw and ribavirin 800mg bid for 48 weeks. Efficacy was assessed as virological response (defined as undetectable HCV RNA) at the end of treatment (EoT) and at the end of follow-up (SVR - Sustained Virological Response). Safety assessments consisted of clinical and laboratory evaluations. In the patient sample, 72 percent were genotype 1 and 34 percent were cirrhotic. In an intention-to-treat analysis, relapser patients showed 78 percent EoT response and 51 percent SVR. Nonresponders showed 57 percent EoT response and 26 percent SVR. Positive predictive factors of SVR were non-1 genotype and relapser state. Six percent of the patients interrupted treatment because of adverse events and 45 percent had dose reduction (mainly associated with leucopenia and anemia). Brazilian patient relapsers and nonresponders to conventional interferon and ribavirin treatment can achieve a sustained virological response when retreated with peginterferon alfa-2a (40KD) and ribavirin. The safety profile is similar to that of naive patients.