Effect of carrier materials on the properties of the andrographolide solid dispersion

Abstract In the work the andrographolide (AG)-solid dispersions (SDs) were prepared by the spray-drying method, using polyethylene glycol 8000 (PEG8000), Poloxamer188, polyvinylpyrrolidone K30 (PVPK30), Soluplus® as carrier materials. The effect of different polymers as carrier materials on the properties of the AG-SDs were studied. The results showed obvious differences in intermolecular interaction, thermal stability, drug state, powder properties, dissolution behavior, and so on of AG-SDs prepared using different polymers as carrier materials. AG-PEG8000-SD was a partial-crystalline and partial-amorphous powder with smaller surface area and pore volume, but it was easy to wetting and did not swell in contact with dissolved medium. AG-Soluplus®-SD was completely amorphous powder with larger specific surface area and pore volume, but it swelled in contact with water. Therefore, the dissolution profile of AG in AG-PEG8000-SD was similar to that in AG-Soluplus®-SD. Soluplus® and PEG8000 were suitable polymers to design AG-SDs, considering both physicochemical properties and dissolution behaviors. The results of this reseach showed that when selecting carrier materials for SD, we should not only consider the state of drugs in SD and the powder properties of SD, but also consider whether there is swelling when the carrier materials are in contact with the dissolution medium.

Influencing factors for the quality of bowel preparation with polyethylene glycol electrolyte powder combined with diet control before colonoscopy in children / 中国当代儿科杂志

OBJECTIVES@#To investigate the influencing factors for the quality of bowel preparation before colonoscopy in children and the association of the interval from the last administration of laxative to the start of colonoscopy (shortly referred to as waiting time) with the quality of bowel preparation.@*METHODS@#A retrospective analysis was performed for the children who were admitted to the Department of Gastroenterology, Children's Hospital of Nanjing Medical University, from January to November 2020, and received bowel preparation with polyethylene glycol electrolyte powder combined with diet control before colonoscopy. According to the score of Boston bowel preparation scale, they were divided into two groups: adequate bowel preparation group (n=337) and inadequate bowel preparation group (n=30). Related data were collected from the children in both groups, including general information, possible influencing factors for the quality of bowel preparation, adverse reactions associated with bowel preparation, duration of colonoscopy, and postoperative diagnosis. Univariate and multivariate analyses were used to explore the influencing factors for the quality of bowel preparation.@*RESULTS@#The univariate analysis showed that age, body weight, and waiting time were associated with inadequate bowel preparation (P<0.05). The multivariate analysis showed that older age (OR=2.155, 95%CI: 1.087-4.273, P=0.028) and longer waiting time (OR=1.559, 95% CI: 1.191-2.041, P=0.001) were independent risk factors for inadequate bowel preparation. The receiver operating characteristic (ROC) curve analysis showed that the cut-off value of waiting time was 5.5 hours in determining whether bowel preparation was adequate or not, with a sensitivity of 90.0%, a specificity of 50.7%, and an area under the ROC curve of 0.708. After grouping based on waiting time, it was found that the incidence rate of inadequate bowel preparation in the ≥5.5 hours group was significantly higher than that in the <5.5 hours group [14.0% (27/193) vs 1.7% (3/174), P<0.001].@*CONCLUSIONS@#For children who use polyethylene glycol electrolyte powder combined with diet control for bowel preparation, older age is an independent risk factor for inadequate bowel preparation before colonoscopy, which may be associated with an insufficient dose of polyethylene glycol in older children. Longer waiting time is also an independent risk factor for inadequate bowel preparation, and it is recommended that the waiting time should not exceed 5.5 hours.

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.

PEGylation strategy to the development of analytical and therapeutic proteins / Potencial da PEGuilação para o desenvolvimento de proteínas para fins terapêuticos e analíticos

Protein PEGylation is the covalent bonding of polyethylene glycol (PEG) polymers to amino acid residues of the protein and it is one of the most promising techniques for improving the therapeutic effect of biopharmaceuticals and long-term stability of protein-based biosensors. This chemical modification brings advantages to biopharmaceuticals, such as an increased half-life, enhanced stability, and reduced immunogenicity. Moreover, in the analytical field, PEGylation improves the multiple properties of protein-based biosensors including biocompatibility, thermal and long-term stability, and solubility in organic solvents. However, the use of PEGylated conjugates in the analytical and therapeutic fields has not been widely explored. The limited industrial application of PEGylated bioconjugates can be attributed to the fact that the reaction and separation steps are currently a challenge. The correct selection of the PEGylation reaction design and the purification process are important challenges in the field of bioconjugation. In this sense, the design and optimization of site-specific PEGylation reactions and application of aqueous biphasic systems (ABS) as purification platforms for PEGylated conjugates are the two main objectives of this thesis. Regarding the purification step, the efficient fractionation (i) of the PEGylated conjugates from the native protein and (ii) of the PEGylated conjugates based on their degree of PEGylation was studied. Centrifugal partition chromatography (CPC) was applied as a continuous regime platform based on ABS technology to efficiently purify the PEGylated proteins. The two proteins under study are L-asparaginase, an important biopharmaceutical applied in the treatment of acute lymphoblastic leukemia and cytochrome c, a promising biosensor. The current work developed in this thesis demonstrates the great potential of ABS in the fractionation of PEGylated proteins, under batch and continuous regime. In addition, in situ recovery of the PEGylated products through one-pot bioconjugation and ABS purification was successfully demonstrated for both enzymes studied. Although further research on scale-up is still required, the results presented show the relevance of ABS platforms for the development of separation processes of PEGylated proteins

A PEGuilação de proteínas é a ligação covalente de polímeros de polietilenoglicol (PEG) a resíduos de aminoácidos da proteína e é uma das técnicas mais promissoras para melhorar o efeito terapêutico dos biofármacos e a estabilidade a longo prazo de biossensores proteícos. Esta modificação química traz vantagens aos produtos biofarmacêuticos, como um aumento da meia-vida, maior estabilidade e imunogenicidade reduzida. Além disso, no campo analítico, a PEGuilação melhora as múltiplas propriedades dos biossensores baseados em proteínas, incluindo biocompatibilidade, estabilidade térmica e a longo prazo, e solubilidade em solventes orgânicos. No entanto, o uso de conjugados PEGuilados em campos analíticos e terapêuticos não tem sido amplamente explorado. A aplicação industrial limitada dos bioconjugados PEGuilados pode ser atribuída ao facto de as etapas de reacção e separação serem atualmente um desafio. A seleção correcta do design da reacção de PEGuilação e do processo de purificação são importantes desafios no campo da bioconjugação. Neste sentido, a concepção e otimização de reações de PEGuilação sítio-específicas e aplicação de sistemas aquosos bifásicos (ABS) como plataformas de purificação de conjugados PEGuilados são os dois principais objetivos desta tese. No que concerne à etapa de purificação foi estudado o eficiente fracionamento (i) dos conjugados PEGuilados, da proteína nativa e (ii) dos conjugados PEGuilados baseados no seu grau de PEGuilação. A cromatografia por partição centrífuga (CPC) foi aplicada como uma plataforma de regime contínuo baseada na tecnologia de ABS para purificar eficientemente as proteínas PEGuiladas. As duas proteínas em estudo são a L-asparaginase, importante biofármaco aplicado no tratamento da leucemia linfoblástica aguda e o citocromo c, um potencial biossensor. A partir dos trabalhos desenvolvidos, é possível confirmar o grande potencial dos ABS no fracionamento de proteínas PEGuiladas, em regime contínuo e descontínuo. Além disso, a recuperação in situ dos produtos PEGuilados através da integração em uma única etapa de bioconjugação e purificação por ABS foi comprovada com sucesso para ambas as enzimas estudadas. Embora ainda sejam necessários estudos adicionais sobre a viabilidade destes sistemas em larga escala, os resultados aqui apresentados demonstram a relevância dos ABS para o desenvolvimento de processos de separação de proteínas PEGuiladas

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.

Tolerancia, seguridad y eficacia de la preparación intestinal con un día de PEG3350 + bisacodilo en comparación con 2 días de PEG3350 + bisacodilo en pacientes pediátricos / Tolerance, safety and efficacy of the one-day preparation of PEG3350 + bisacodyl compared to 2 days of PEG3350 + bisacodyl in pediatric patients

Resumen: Introducción: Múltiples preparaciones intestinales se han utilizado en niños sometidos a una colonoscopia, con limitación variable debido a la aceptación, tolerancia y la limpieza adecuada. El objetivo del estudio fue comparar la tolerancia seguridad y eficacia de la preparación intestinal para colonoscopia de 1 día con PEG 3350 (polietilenglicol) (4 g/kg/día) + bisacodilo y el tratamiento con 2 días de preparación con PEG 3350 (2 g/kg/día) + bisacodilo en pacientes pediátricos. Métodos: Se realizó un ensayo clínico, aleatorizado y ciego. Se incluyeron pacientes de 2 a 18 años, que ameritaron colonoscopia en forma programada. Los pacientes se asignaron de manera aleatoria en dos grupos: 1 día de preparación con PEG 3350 4 g/kg/día + bisacodilo y 2 días de preparación con PEG 3350 2 g/kg/día + bisacodilo. Por medio de un cuestionario, exploración física y valoración endoscópica (escala de Boston), se determinó la tolerancia, seguridad y eficacia de las 2 preparaciones a evaluar. Se realizó una prueba t de Student para variables cuantitativas y χ2 para variables cualitativas. Resultados: No hubo diferencias significativas en las tasas de cumplimiento, los efectos adversos y la extensión de la evaluación colonoscópica. Conclusiones: La tolerancia y seguridad entre la preparación intestinal para colonoscopia de 1 día con PEG 3350 (polietilenglicol) (4 g/kg/día) + bisacodilo y la preparación de 2 días con PEG 3350 (2 g/kg/día) + bisacodilo fue semejante. La calidad de la limpieza fue buena en ambos grupos, siendo parcialmente más eficaz en el grupo de 1 día con PEG 3350 (polietilenglicol) (4 g/kg/día).

Abstract: Background: Multiple intestinal preparations have been used in children undergoing colonoscopy, with variable limitation due to acceptance, tolerance, and proper cleaning. The objective of this study was to compare the tolerability, safety and efficacy of the colonoscopy preparation with 1 day with PEG 3350 (poliethylenglycol) (4 g/kg/day) + bisacodyl compared to 2 days of preparation with PEG 3350 (2 g/kg/day) + bisacodyl in pediatric patients. Methods: A clinical, randomized, and blind trial was performed. Patients aged 2 to 18 years scheduled for colonoscopy were included. Patients were randomized into two groups: 1 day of preparation with PEG 3350 4 g/kg/day + bisacodyl and 2 days of preparation with PEG 3350 2 g/kg/day + bisacodyl. Through a questionnaire, physical examination and endoscopic evaluation (Boston scale), the tolerance, safety and efficacy of the 2 preparations to be evaluated were determined. Student's t test was performed for quantitative variables and χ2 for qualitative variables. Results: There were no significant differences in compliance rates, adverse effects, and extent of colonoscopic evaluation. Conclusions: Tolerance and safety between the intestinal preparation for 1-day colonoscopy with PEG 3350 (4 g/kg/day) + bisacodyl and the 2-day preparation with PEG 3350 (2 g/kg/day) + bisacodyl were similar. The quality of cleanliness was good in both groups, being partially more effective in the 1-day group with PEG 3350 (4 g/kg/day).

PEG-asparaginase induced severe hypertriglyceridemia

Asparaginase (ASP) is an effective chemotherapy agent extensively used in children with acute lymphocytic leukemia (ALL). There has been a recent interest in using ASP in adults with ALL, particularly the less toxic pegylated (PEG) formulation. Hypertriglyceridemia (HTG) is a rare complication of PEG-ASP therapy. We report two cases of obese patients who developed severe HTG after receiving PEG for ALL. Both patients were incidentally found to have severe HTG (TG of 4,330 and 4,420 mg/dL). In both patients, there was no personal or family history of dyslipidemia or hypothyroidism. There was no evidence of pancreatitis or skin manifestations of HTG. Both patients were treated with PEG cessation, low-fat diet and pharmacotherapy. Both patients were re-challenged with PEG, with subsequent increase in TG but no associated complications. TG returned to baseline after discontinuing PEG and while on therapy for HTG. A literature review of PEG-induced HTG in adults demonstrated similar results: asymptomatic presentation despite very severe HTG. HTG is a rare but clinically important adverse effect of PEG. Underlying obesity and/or diabetes may represent risk factors. Clinicians should monitor TG levels during PEG therapy to avoid TG-induced pancreatitis.

Depressive episode incidence in patients with chronic hepatitis c treated with pegylated interferon and ribavirin

ABSTRACT Background The effectiveness of antiviral therapy with pegylated interferon and ribavirin for chronic hepatitis C is far from ideal and presents several adverse events. Among such events, there is the depressive episode that can even lead to treatment discontinuity Objective Analyze the incidence of depressive episodes in patients with chronic hepatitis C treated with pegylated interferon (IFN-PEG) and ribavirin, as well as the possible factors associated with its occurrence and its impact on patients' sustained virological response. Methods People with chronic hepatitis C undergoing antiviral therapy were interviewed at the baseline, at the 4th, 12th, 24th and 48th treatment weeks and 4 weeks after the end of it, using the HADS scale for tracking the depressive episode. Patients with HADS ≥9 were subjected to Beck Depression Inventory (BDI-II) to grade the episode. Clinical, sociodemographic, laboratorial and histological variables were obtained to identify factors related to the onset of depression. The sustained virological response rate (negative HCV-RNA 6 months after end of therapy) was compared among patients with and without depressive symptoms. Results The study comprised 32 patients, most men (59%) with mean age of 54±11.13 years old. Genotype non-1 was prevalent (56%) and 81% of the patients were non-cirrhotic. The depressive episode was diagnosed in 25% of the patients and the peak incidence was found in the 12th treatment week. The depressive episode was moderate in 87% of the patients and only one patient abandoned the treatment. None of the analyzed factors was associated with depressive episode onset. A trend was observed in female patients ( P=0.08). The sustained virological response rate was of 75% and 67% in patients with and without depressive episode, respectively (P =0.66). Conclusion The incidence of depressive episodes in patients with chronic hepatitis C undergoing antiviral therapy was of 25% and the 12th treatment week was the most critical one. The presence of depressive episode did not affect the sustained virological response rate.

RESUMO Contexto A terapia antiviral para a hepatite C crônica com interferon peguilado e ribavirina tem eficácia longe do ideal e é repleta de eventos adversos. Entre estes, destaca-se o transtorno depressivo que pode inclusive levar a interrupção do tratamento. Objetivos Em pacientes com hepatite C crônica tratados com interferon peguilado (IFN-PEG) e ribavirina, verificar a incidência de episódio depressivo, os possíveis fatores associados ao seu surgimento e o impacto deste sobre a resposta virológica sustentada. Métodos Portadores de hepatite C crônica submetidos à terapia antiviral foram entrevistados no Baseline, nas semanas 4, 12, 24, 48 de tratamento e quatro semanas após o término do mesmo utilizando a escala HADS para rastreamento do episódio depressivo e naqueles com HADS ≥9 o Inventário de Depressão de Beck (BDI-II) para graduação do episódio. Variáveis clínicas, sociodemográficas, laboratoriais e histológicas foram obtidas com o objetivo de identificar os fatores relacionados ao surgimento da depressão. A taxa de resposta virológica sustentada (HCV-RNA negativo seis meses após a interrupção da terapia) foi comparada entre os pacientes com e sem sintomas depressivos. Resultados Foram incluídos 32 pacientes, a maioria do sexo masculino (59%) e com média de idade de 54±11,13 anos. Prevaleceu o genótipo não 1 (56%) e 81% dos pacientes foram não cirróticos. Episódio depressivo foi diagnosticado em 25% dos pacientes sendo o pico de incidência observado na semana 12 de tratamento. O episódio depressivo foi moderado em 87% dos pacientes e motivou a interrupção em somente 1 deles. Nenhum dos fatores analisados foi associado ao surgimento de episódio depressivo observando-se uma tendência com relação ao sexo feminino ( P =0,08). A taxa de resposta virológica sustentada foi 75% e 67% nos pacientes com e sem episódio depressivo, respectivamente ( P =0,66). Conclusão A incidência de episódio depressivo em pacientes com hepatite C crônica submetidos à terapia antiviral foi de 25% e a semana 12 é a mais crítica. A presença de episódio depressivo não interferiu na taxa de resposta virológica sustentada.

Acute pancreatitis associated with pegylated interferon-alpha-2a therapy in chronic hepatitis C

Chronic hepatitis C virus (HCV) infection is a major cause of liver cirrhosis and hepatocellular carcinoma. Combination therapy of pegylated interferon-alpha (PEG-IFN-α) and ribavirin (RBV) is a current standard treatment for chronic HCV infection in Korea, which has considerable adverse effects. Acute pancreatitis is a rare complication of PEG-IFN-α administration. We report a case of a 62-year-old female who experienced acute pancreatitis after 4 weeks of PEG-IFN-α-2a and RBV combination therapy for chronic HCV infection. The main cause of the acute pancreatitis in this case was probably PEG-IFN-α rather than RBV for several reasons. A few cases have been reported in which acute pancreatitis occurred during treatment with PEG-IFN-α-2b. This is the first report of acute pancreatitis associated with PEG-IFN-α-2a in Korea.

Comparative Study on Bowel Preparation Efficacy of Ascorbic Acid Containing Polyethylene Glycol by Adding Either Simethicone or 1 L of Water in Health Medical Examination Patients: A Prospective Randomized Controlled Study / 대한소화기학회지

BACKGROUND/AIMS: There are no studies that looked into the bubble eliminating efficacy of polyethylene glycol with ascorbic acid (PEGA), which has been one of the shortcomings of polyethylene glycol (PEG). In this study, we compared newly introduced PEGA regimen by adding either simethicone or 1 L of water. METHODS: A prospective randomized controlled study was carried out at Dongguk Universtiy Gyeongju Hospital from July 2014 to September 2014. A total of 90 patients were randomly assigned to 3 groups; PEGA group (n=30) which served as control, simethicone addition group (n=30) to which simethicone 400 mg was additionally prescribed, and water addition group (n=30) to whom additional 1 L of water was given. Cleansing effectiveness, gas elimination efficacy, side effects, and patient satisfaction were compared between the groups. RESULTS: PEGA group demonstrated the highest cleansing effectiveness, but there was no statistically significant difference among the groups. Simethicone addition group showed significantly lesser amount of bubbles than the other groups (2.57±2.05 vs. 1.10±1.83 vs. 2.60±2.84, p=0.017). The rates of side effects in each group were 20.00% vs. 16.77% vs. 53.33%. Water addition group had significantly more side effects than the PEGA group and the simethicone addition group (p=0.003). The patient satisfaction score of each group was 3.37±0.85 vs. 3.73±0.74 vs. 3.20±0.66 with simethicone addition group showing significantly higher satisfaction than water addition group (p=0.020). CONCLUSIONS: PEGA bowel preparation agent showed satisfactory bowel cleansing despite the decrease in dosage, and addition of simethicone resulted in better bubble elimination.

Serious stomatitis and esophagitis: a peculiar mucous reaction induced by pegylated liposomal doxorubicin

Pegylated liposomal doxorubicin is an important antineoplastic agent with activity in a variety of solid tumors. It has a totally different profile of pharmacokinetics and toxicity compared with doxorubicin. It rarely causes side-effects like cardiotoxicity or hair loss, but frequently results in many kinds of mucocutaneous reactions, including palmar-plantar erythrodysesthesia, diffuse follicular rash, intertrigo-like eruption, new formation of melanotic macules, stomatitis and radiation recall dermatitis. We present a rare case of multiple myeloma who immediately developed serious stomatitis and esophatitis associated with minor palmar-plantar erythrodysesthesia after a single course of pegylated liposomal doxorubicin.

The clinical effectiveness of pegylated interferon and ribavirin for the treatment of chronic hepatitis C in HIV-infected patients in Brazil: a multicentric study

Introduction: in Brazil, chronic hepatitis C in patients coinfected with the human immunodeficiency virus (HIV) is treated with pegylated interferon (Peg-IFN) and ribavirin (RBV). However, few studies have evaluated the effectiveness of this treatment in this particular population. The identification of the factors that predict sustained virological response (SVR) under current clinical practice would enable clinicians to more accurately estimate the probability of achieving an SVR and therefore utilize the appropriate therapeutics, especially in the era of direct-acting antiviral (DAA) agents. Aims: the primary aim of our study was to determine the SVR rate under current clinical practice. The secondary aims were as follows: (1) to determine the factors before and during treatment that predict SVR; and (2) to identify the causes of treatment interruption. Methods: within a cohort of HIV/hepatitis C virus (HCV)-coinfected patients in Brazil, we performed a retrospective analysis of those individuals treated with Peg-IFN and RBV. Results: among the 382 analyzed patients, SVR was observed in 118 [30.9% (95% confidence interval (CI): 26.3-35.8)], which included 25.9% (75/289) of the patients with genotypes 1 and 4 and 48.2% (41/85) of those with genotypes 2 and 3. After multivariate analyses the independent positive predictors for SVR after treatment for chronic hepatitis C with PegIFN and RBV were: absence of an AIDS-defining illness (p = 0.001), HCV viral load lower than 600,000 IU/mL at the onset of treatment (p = 0.003), higher liver enzyme levels (p = 0.039) at baseline, infection with genotypes 2 or 3 (p = 0.003), and no transient treatment interruption (p = 0.001). The treatment was interrupted in 25.6% (98/382) of the patients because of adverse events (11.3%, 43/382), virologic failure (7.8%, 30/382), and dropout (6.5%, 43/382). The main adverse events were cytopenia and psychiatric disorders. Conclusions: ...

Highly effective peginterferon alpha-2a plus ribavirin combination therapy for chronic hepatitis C in hemophilia in Korea

BACKGROUND/AIMS: Chronic hepatitis C (CHC) is a major comorbidity in patients with hemophilia. However, there are no published data on the efficacy of antiviral therapy in Korea. We assessed the safety and efficacy of combination therapy with peginterferon alpha-2a plus ribavirin for CHC in hemophilia. METHODS: Patients (n=115) were enrolled between March 2007 and December 2008. Seventy-seven patients were genotype 1 or 6, and 38 patients were genotype 2 or 3. We evaluated rapid virologic responses (RVRs), early virologic response (EVRs), end-of-treatment response (ETRs), sustained virologic response (SVRs), and relapses. Safety evaluations included adverse events and laboratory tests. RESULTS: Eleven patients were excluded from the study because they had been treated previously. Among the remaining 104 treatment-naive patients, RVR was achieved in 64 (60.6%), ETR was achieved in 95 (91.3%), and SVR was achieved in 89 (85.6%). Relapse occurred in eight patients (8.9%). Common adverse events were hair loss (56.7%) and headache (51.0%). Common hematologic adverse events were neutropenia (22.1%), anemia (27.9%), and thrombocytopenia (3.8%). However, there were no serious adverse events such as bleeding. RVR was the only predictor of SVR in multivariate analysis. CONCLUSIONS: Peginterferon alpha-2a plus ribavirin combination treatment produced a favorable response rate in CHC patients with hemophilia without serious adverse events.

Incidence of and risk factors for thyroid dysfunction during peginterferon alpha and ribavirin treatment in patients with chronic hepatitis C

BACKGROUND/AIMS: Thyroid dysfunction (TD) is more likely to occur in patients with chronic hepatitis C (CHC) and is particularly associated with interferon (IFN) treatment. The purpose of this study was to investigate the incidence, outcomes, and risk factors for TD during pegylated interferon (PEG-IFN) and ribavirin (RBV) combined therapy in patients with CHC. METHODS: A total of 242 euthyroid patients with CHC treated with PEG-IFN/RBV were included. Thyroid function and autoantibodies were measured at baseline, and virologic response and thyroid function were assessed every 3 months during therapy. RESULTS: TD developed in 67 patients (27.7%) during the PEG-IFN/RBV treatment. The types of TD were subclinical hypothyroidism (50.7%), hypothyroidism (14.9%), thyroiditis (11.9%), subclinical hyperthyroidism (10.4%), and hyperthyroidism (10.4%). Most of the patients with TD recovered spontaneously; however, seven patients (10.4%) needed thyroid treatment. The sustained virological response rate was higher in patients with TD than those without (65.7% vs. 49.1%, p = 0.02). Baseline thyroid stimulating hormone (TSH) concentrations (odds ratio [OR], 2.09; 95% confidence interval [CI], 1.96 to 8.77; p < 0.001), presence of the thyroid peroxidase antibody (OR, 8.81; 95% CI, 1.74 to 44.6; p = 0.009), and PEG-IFNalpha-2b (OR, 3.01; 95% CI, 1.43 to 6.39; p = 0.004) were independent risk factors for the development of TD. CONCLUSIONS: TD developed in 27.7% of patients with CHC during PEG-IFN/RBV treatment, and 10.4% of these patients needed thyroid treatment. TD is associated with a favorable virologic response to PEG-IFN/RBV. Assessment of TSH and thyroid autoantibodies at baseline and close monitoring of thyroid function during PEG-IFN/RBV therapy are necessary for early detection and management of IFN-induced TD.

Acute exposure to silica nanoparticles aggravate airway inflammation: different effects according to surface characteristics

Silica nanoparticles (SNPs) are widely used in many scientific and industrial fields despite the lack of proper evaluation of their potential toxicity. This study examined the effects of acute exposure to SNPs, either alone or in conjunction with ovalbumin (OVA), by studying the respiratory systems in exposed mouse models. Three types of SNPs were used: spherical SNPs (S-SNPs), mesoporous SNPs (M-SNPs), and PEGylated SNPs (P-SNPs). In the acute SNP exposure model performed, 6-week-old BALB/c female mice were intranasally inoculated with SNPs for 3 consecutive days. In the OVA/SNPs asthma model, the mice were sensitized two times via the peritoneal route with OVA. Additionally, the mice endured OVA with or without SNP challenges intranasally. Acute SNP exposure induced significant airway inflammation and airway hyper-responsiveness, particularly in the S-SNP group. In OVA/SNPs asthma models, OVA with SNP-treated group showed significant airway inflammation, more than those treated with only OVA and without SNPs. In these models, the P-SNP group induced lower levels of inflammation on airways than both the S-SNP or M-SNP groups. Interleukin (IL)-5, IL-13, IL-1beta and interferon-gamma levels correlated with airway inflammation in the tested models, without statistical significance. In the mouse models studied, increased airway inflammation was associated with acute SNPs exposure, whether exposed solely to SNPs or SNPs in conjunction with OVA. P-SNPs appear to be relatively safer for clinical use than S-SNPs and M-SNPs, as determined by lower observed toxicity and airway system inflammation.

Ophthalmologic findings in hepatitis C patients treated with pegylated interferon α-2b and ribavirin / Achados oftalmológicos nos pacientes portadores de hepatite C em tratamento com interferon peguilado α-2b e ribavirina

Purpose: To identify the effect of pegylated interferon α-2b and ribavirin treatment in the ocular fundus examination, visual acuity, and visual field. Methods: Prospective observational study was performed at the Hepatology Clinic of São José Regional Hospital and at the Vitreoretinal Department at the Sadalla Amin Ghanem Eye Hospital in patients with chronic hepatitis C before and during treatment with pegylated interferon α-2b together with ribavirin. Results: Six (37.5%) of 16 patients developed retinopathy during the treatment, two of which (12.5%) presented retinal hemorrhage, and four patients (6 eyes) presented cotton-wool spots (25%) that regressed during the treatment. One patient (6.25%) presented transient decrease in visual acuity during the treatment and recovered spontaneously without specific therapy. Conclusion: Recommended treatment methods for hepatitis C may cause transient retinopathy, commonly without any damage to visual function in most patients. Although ocular involvement is rare, follow-up with an ophthalmologist is recommended during the course of the hepatitis C medication. .

Objetivo: Identificar possíveis mudanças no exame de fundo de olho após o início do tratamento, bem como alterações na acuidade visual e campo visual. Métodos: Estudo observacional prospectivo realizado na Clínica de Hepatologia do Hospital Regional de São José e no Departamento de Vítreo e Retina do Hospital de Olhos Sadalla Amin Ghanem, em pacientes com hepatite C crônica antes e durante o tratamento com interferon peguilado α-2b associado à ribavirina. Resultados: Six (37,5%) dos 16 participantes desenvolveram retinopatia durante o tratamento, dois dos quais (12,5%) apresentaram hemorragia retiniana unilateral, e quatro pacientes com exsudatos algodonosos (25%), seis olhos, que regrediu durante o tratamento. Um participante (6,25%) apresentou diminuição transitória da acuidade visual durante o tratamento com recuperação espontaneamente sem tratamento específico. Conclusão: O tratamento recomendado para a hepatite C pode estar associado com o desenvolvimento de retinopatia transitória, geralmente sem dano à função visual na maioria dos pacientes. Embora o envolvimento ocular seja raro, o acompanhamento com o médico oftalmologista é recomendado durante todo o uso da medicação. .

Double-blind prospective randomized study comparing polyethylene glycol to lactulose for bowel preparation in colonoscopy / Estudo prospectivo randomizado duplo-cego comparando polietilenoglicol com lactulose para preparo de colon em colonoscopia

Background: Colonoscopy is the most frequent exam used to evaluate colonic mucosa, allowing the diagnosis and treatment of many diseases. The appropriate bowel preparation is indispensable for the realization of colonoscopy. Therefore, it is necessary the use of laxative medications, preferentially by oral administration. Aim: To compare two medications used in bowel preparation in adult patients going to ambulatory colonoscopy and to analyze the patients' profile. Methods: A double-blind prospective study with 200 patients, randomized in two groups: one that received polyethilene glycol and another that received lactulose. The patients answered to questionnaires to data compilation, as tolerance, symptoms and complications related to preparation. Besides, it was also evaluated the prepare efficacy related to the presence of fecal residue. Results: Intestinal habit alterations and abdominal pain were the main reasons to realize the exams and hypertension was the most prevalent comorbidity. Ten percent of the ones who received lactulose didn't get to finish the preparation and 50% considered the taste "bad, but tolerable". The most common subjective symptom after the medication was nausea, especially after lactulose. During the exam, most of the patients who used lactulose had a "light discomfort" and the ones who used polyethilene glycol considered the discomfort as "tolerable". The quality of the preparation was good in 75%, undependable of the medication that was used. Conclusion : Polyethilene glycol was more tolerable when compared to lactulose, without difference on the quality of the preparation. .

Racional - A colonoscopia é o exame mais utilizado atualmente para avaliação da mucosa colônica, permitindo diagnóstico e tratamento de diversas doenças. O preparo de cólon adequado é imprescindível para a realização do exame. Para tanto, é necessária a utilização de laxantes, cuja via preferencial de preparo é a oral. Objetivo - Comparar duas soluções para preparo de cólon nos pacientes adultos a serem submetidos à colonoscopia em regime ambulatorial e o perfil destes pacientes. Métodos - Estudo prospectivo duplo-cego com 200 pacientes distribuídos aleatoriamente em dois grupos: um que recebeu dose padrão de polietilenoglicol e o outro que recebeu dose padrão de lactulose. Os pacientes responderam a questionários para compilação de dados, como tolerância, sintomas e complicações relacionadas ao preparo. Além disso, foi avaliada também a eficácia do preparo com relação à presença de resíduos fecais. Resultados - Alteração do hábito intestinal e dor abdominal foram os principais motivos para o exame, sendo que hipertensão a comorbidade mais prevalente. Dez por cento dos que receberam lactulona não conseguiram completar o preparo e 50% consideraram o gosto do preparo "ruim, mas tolerável". O sintoma subjetivo mais comum após o preparo foi náusea, principalmente após a lactulona. Durante o exame, a maioria dos usuários da lactulona teve desconforto "leve", sendo que os que usaram polietilenoglicol consideraram o desconforto como "tolerável". A qualidade do preparo foi boa em 75%, independentemente do preparo utilizado. Conclusão - O polietilenoglicol apresentou melhor tolerância quando comparado à lactulona, não havendo diferença na qualidade do preparo. .

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. .

Interferon-induced depression in patients with hepatitis C: an epidemiologic study / Depressão induzida por interferon em pacientes com hepatite C: um estudo epidemiológico

Objective To assess the incidence rate and severity of depressive symptoms in different time points (12, 24 and 48 weeks) in Brazilian patients with HCV treated with PEG IFN plus ribavirin. Methods We conducted an observational prospective study using the Beck Depression Inventory (BDI) and the Center for Epidemiologic Studies Depression Scale (CES-D). Results Fifty patients were included. The assessments with either scale showed the highest score of depressive symptoms in the 24th week of treatment; the mean BDI score before treatment was 6.5 ± 5.3 and the mean CES-D was 10.9 ± 7.8. After 24 weeks, the mean BDI was 16.1 ± 10.2 and mean CES-D was 18.6 ± 13.0; 46% were diagnosed with depression according to combined BDI and CES-D scores. The somatic/psychomotor subscales were highly correlated with overall scale scores . Subjects with history of substance and alcohol abuse had higher risk for IFN-induced depression. Conclusion Treatment with PEG IFN was associated with a high incidence rate of depressive symptoms in this sample of Brazilian patients, as measured by CES-D and BDI. Alcohol and substance abuse increase the risk of PEG IFN-induced depression. .

Objetivo Avaliar a incidência e a gravidade de sintomas depressivos em diferentes intervalos (12, 24 e 48 semanas) em pacientes brasileiros com HCV tratados com PEG IFN mais ribavirina. Métodos Foi feito um estudo prospectivo observacional, usando o Inventário de Depressão de Beck (BDI) e a Escala de Rastreamento Populacional de Depressão (CES-D). Resultados Foram incluídos 50 pacientes. As avaliações com ambas as escalas mostraram os maiores escores de depressão na 24a semana de tratamento; o escore BDI médio antes do tratamento foi de 6,5 ± 5,3 e o CES-D foi 10,9 ± 7,8. Após 24 semanas, o BDI médio foi 16,1± 10,2 e o CES-D foi 18,6 ± 13,0; de acordo com os escores combinados BDI e CES-D, 46% receberam diagnóstico de depressão. As subescalas somática e psicomotora tiveram alta correlação. Indivíduos com história de abuso de substâncias e de álcool apresentaram maior risco de desenvolver depressão por PEG IFN. Conclusão O tratamento com PEG IFN associou-se a uma alta incidência de sintomas depressivos nessa população de pacientes brasileiros, de acordo com a BDI e CES-D. Abuso de álcool e substâncias aumentam o risco de depressão induzida por PEG IFN. .

Cryptococcal meningitis in a patient with chronic hepatitis C treated with pegylated-interferon and ribavirin

Various adverse events have been reported during combination therapy with pegylated (PEG)-interferon-alpha and ribavirin, although opportunistic infections, especially cryptococcal meningitis, are very rare. A 61-year-old woman complained of headaches and a fever during treatment of a chronic hepatitis C virus (HCV) infection. She had been treated for 7 months. Her headaches were refractory to analgesics, and she developed subtle nuchal rigidity. The cerebral spinal fluid (CSF) revealed a white blood cell count of 205/mm3, 51 mg/dL protein, 35 mg/dL glucose, and negative Cryptococcus antigen. The CSF culture resulted in no growth. Five days later, the CSF was positive for Cryptococcus antigen. We administered amphotericin B and flucytosine, followed by fluconazole. Approximately 2 months later, she was discharged. For the first time, we report a case of cryptococcal meningitis during the treatment of chronic HCV with PEG-interferon-alpha and ribavirin.