Ridruejo E.,Hospital Universitario Austral |
Silva M.O.,Hospital Universitario Austral
Expert Opinion on Drug Safety | Year: 2012
Currently, five nucleos(t)ide analogs (NAs) are approved for the treatment of chronic hepatitis B (CHB) infection. They are lamivudine, adefovir dipivoxil, telbivudine, entecavir (ETV) and tenofovir disoproxil fumarate (TDF). Two of them, ETV and TDF, are recommended as first-line treatment options. Their main advantages include excellent tolerability, antiviral potency and a high genetic barrier to resistance within medium duration treatment periods (2 6 years). In most patients, NAs need to be administered on a long-term basis. Several studies suggest that NAs long-term administration have been associated with low rates of serious adverse events (AEs), including lactic acidosis, renal function impairment, osteopenia and osteoporosis. Discontinuations due to AEs tended to be low in published randomized clinical trial and in the experience in clinical practice. NAs long-term use appears to be safe and effective; and in patients with advanced liver disease, despite preliminary concerning reports, their short-term use also appears to be safe and effective. Although major AEs are infrequent, they can be initially clinically silent yet lead to serious medical problems, therefore, a proactive surveillance and their prompt management is recommended. © 2012 Informa UK, Ltd.
Ridruejo E.,Hospital Universitario Austral
World Journal of Hepatology | Year: 2015
Chronic hepatitis B infection is frequent in renal transplant patients. It negatively impacts long term outcomes reducing graft and patient survival. Current guidelines clearly define who needs treatment, when to start, what is the first line therapy, how to monitor treatment response, when to stop, and how patients must be controlled for its safety. There is some data showing a favorable safety and efficacy profile of nucleos(t)ide analogue (NUC) treatment in the renal transplant setting. Entecavir, a drug without major signs of nephrotoxicity, appears to be the first option for NUC naïve patients and tenofovir remains the preferred choice for patients with previous resistance to lamivudine or any other NUC. Renal transplant recipients under antiHBV therapy should be monitored for its efficacy against HBV but also for its safety with a close renal monitoring. Studies including a large number of patients with long term treatment and follow up are still needed to better demonstrate the safety and efficacy of newer NUCs in this population. © The Author(s) 2015.
Ridruejo E.,Hospital Universitario Austral
World Journal of Gastroenterology | Year: 2014
Results from phase III clinical trials clearly demonstrate the efficacy and safety of entecavir and tenofovir in the controlled environment of randomized clinical studies. There are several studies with both drugs performed in clinical practice (also called "real life studies"). Despite the pros and cons, studies performed in real life conditions represent everyday practice and add important information about long term treatment effectiveness and safety in this clinical setting. This review shows that patients treated with first line nucleos(t)ide analogs at referral centres, with good clinical follow-up and adherence to international guidelines, can achieve high treatment response rates with a very low rate of adverse events. © 2014 Baishideng Publishing Group Inc. All rights reserved.
Ridruejo E.,Hospital Universitario Austral
Expert Opinion on Drug Safety | Year: 2014
Introduction: Combination therapy with pegylated interferon, ribavirin and the two first-generation NS3/4A protease inhibitors (PIs), telaprevir (TVR) and boceprevir (BOC), is the new standard-of-care therapy for patients who are chronically infected with genotype 1 hepatitis C virus. These combinations significantly increase sustained virological response (SVR) rates, but they also increase the rates of adverse events (AEs). Appearance of significant AEs may necessitate dose reduction or discontinuation of treatment, and may impact on virological response. Areas covered: In registration trials, IFN-related AEs were a dominant feature in both types of therapy. Some events were more frequent with PI-containing regimens, like anemia and dysgeusia with BOC and anemia, pruritus, rash and anorectal symptoms with TVR. This review addresses the early identification and management of AEs to improve tolerance, and to avoid reduction in SVR rates. Expert opinion: Every patient will experience adverse effects to differing degrees; a systematic approach to their management can be very helpful. Early recognition and intervention can help clinicians ensure that patients are able to complete therapy where possible and achieve the goal of viral eradication. Treatment with the next generation of antivirals will improve safety and efficacy. © 2014 Informa UK, Ltd.
Ridruejo E.,Hospital Universitario Austral
Expert Opinion on Drug Safety | Year: 2015
Introduction: Liver cancer is one of the most common cancers. Hepatocellular carcinoma (HCC) represents > 90% of primary liver cancers and is a major global health problem today. Chronic hepatitis B virus (HBV) infection is associated with more than half of HCCs.Areas covered: Long-term therapy with nucleos(t)ide analogues (NUCs) improves outcomes in HBV-infected patients by slowing the progression of liver disease. It is associated with improvements in histological and clinical outcomes, improved patient survival, reduced need for liver transplantation and improved liver function in patients with decompensated liver disease. This review highlights the results of previous studies conducted on HCC prevention with long-term NUC therapy. Studies include the use of all available drugs in different clinical scenarios, and the comparison between treated and untreated patients.Expert opinion: NUCs have been studied extensively in HCC prevention. A comprehensive review of the literature has shown that they can be safely and effectively used for this purpose. Despite some discrepancies between studies, most of the evidence favors using NUC therapy for HCC prevention. © 2014 Informa UK, Ltd.
Grazoprevir plus elbasvir in treatment-naive and treatment-experienced patients with hepatitis C virus genotype 1 infection and stage 4-5 chronic kidney disease (the C-SURFER study): A combination phase 3 study
Roth D.,University of Miami |
Nelson D.R.,Clinical Translational Science Institute |
Bruchfeld A.,Karolinska University Hospital |
Liapakis A.,Yale University |
And 15 more authors.
The Lancet | Year: 2015
Summary Background Chronic hepatitis C virus (HCV) infection in patients with stage 4-5 chronic kidney disease increases the risk of death and renal graft failure, yet patients with hepatitis C and chronic kidney disease have few treatment options. This study assesses an all-oral, ribavirin-free regimen in patients with HCV genotype 1 infection and stage 4-5 chronic kidney disease. Methods In this phase 3 randomised study of safety and observational study of efficacy, patients with HCV genotype 1 infection and chronic kidney disease (stage 4-5 with or without haemodialysis dependence) were randomly assigned to receive grazoprevir (100 mg, NS3/4A protease inhibitor) and elbasvir (50 mg, NS5A inhibitor; immediate treatment group) or placebo (deferred treatment group) once daily for 12 weeks. Randomisation was done centrally with an interactive voice response system. An additional cohort of patients who were not randomised received the same regimen open-label and underwent intensive pharmacokinetic sampling. The primary efficacy outcome was a non-randomised comparison of sustained virological response at 12 weeks (SVR12) after the end of therapy for the combined immediate treatment group and the pharmacokinetic population with a historical control. The primary safety outcome was a randomised comparison between the immediate treatment group and the deferred treatment group. After 4 weeks of follow-up (study week 16), unmasking occurred and patients in the deferred treatment group received grazoprevir and elbasvir. The primary efficacy hypothesis was tested at a two-sided significance level (type I error) of 0·05 using an exact test for a binomial proportion. Safety event rates were compared between immediate treatment and deferred treatment groups using the stratified Miettinen and Nurminen method with baseline dialysis status as the strata. The study is registered at ClinicalTrials.gov, number NCT02092350. Findings 224 patients were randomly assigned to the immediate treatment group with grazoprevir and elbasvir (n=111) or the deferred treatment group (n=113), and 11 were assigned to the intensive pharmacokinetic population. Overall, 179 (76%) were haemodialysis-dependent, 122 (52%) had HCV genotype 1a infection, 189 (80%) were HCV treatment-naive, 14 (6%) were cirrhotic, and 108 (46%) were African American. Of the 122 patients receiving grazoprevir and elbasvir, six were excluded from the primary efficacy analysis for non-virological reasons (death, lost-to-follow-up [n=2], non-compliance, patient withdrawal, and withdrawal by physician for violent behaviour). No patients in the combined immediate treatment group and intensive pharmacokinetic population and five (4%) in the deferred treatment group discontinued because of an adverse event. Most common adverse events were headache, nausea, and fatigue, occurring at similar frequencies in patients receiving active and placebo drugs. SVR12 in the combined immediate treatment group and intensive pharmacokinetic population was 99% (95% CI 95·3-100·0; 115/116), with one relapse 12 weeks after end of treatment when compared with a historical control of 45%, based on meta-analyses of interferon-based regimens used in clinical trials of patients infected with HCV who are on haemodialysis. Interpretation Once-daily grazoprevir and elbasvir for 12 weeks had a low rate of adverse events and was effective in patients infected with HCV genotype 1 and stage 4-5 chronic kidney disease. Funding Merck Sharp & Dohme Corp. © 2015 Elsevier Ltd.
Margaride L.A.,Hospital Universitario Austral |
Breuer J.,University of Buenos Aires
Journal of Craniofacial Surgery | Year: 2012
Midfacial retrusion and class III malocclusion in maxillary hypoplasia are frequent sequelae in patients with cleft lip and palate. Similar deformities are seen in craniofacial dysostosis surgically treated in infancy. Recurrences after orthognathic surgery are unpredictable even using rigid fixations. Distraction osteogenesis, using Le Fort I osteotomies with external distractors, is uncomfortable for the patient, and internal distractors require a second procedure for removing the retractor. A new model of distraction osteogenesis is presented. Transmaxillary osteogenic distraction, using tooth-borne devices, is a simple method and allows ambulatory retraction of distractors. Osteogenesis between molars and premolars at the alveolar level is stable and allows orthodontic mobilization and dental implants. Anchorage in molars and maxillary tuberosities avoids velopharyngeal incompetence. Transmaxillary osteogenic distraction techniques are described, as well as results after 7 years of experience in 45 patients with maxillary hypoplasia. Results are satisfactory and stable, surgery is simple, and custom-made intraoral devices are easy to handle with minimal discomfort for the patients. Copyright © 2012 by Mutaz B. Habal, MD.
Szulman C.,Sanatorio Nuestra Senora del Rosario |
Gimenez M.,University of Buenos Aires |
Sierre S.,Hospital Universitario Austral
Journal of Vascular and Interventional Radiology | Year: 2011
Purpose: To report the authors' experience with percutaneous papillary balloon dilation for extrahepatic bile duct stone clearance to the duodenum in 300 patients. Materials and Methods: During a 16-year period, 300 patients with extrahepatic bile duct stones who underwent papillary balloon dilation were retrospectively evaluated. Two hundred eighty-six patients with retained extrahepatic bile duct stones were treated through a postoperative drain placed during cholecystectomy; 245 patients were treated through a T-tube route and 41 through a transcystic approach. In the remaining 14 patients, the procedure was performed through a newly created percutaneous transhepatic route. Success rates, technical features, reasons for failure, and complications were evaluated. Results: Biliary duct stone removal after papillary dilation was successful in 288 patients (96%). In 244 patients, the procedure was successfully completed on the first attempt. Forty-three patients needed two sessions, and in one patient it took three sessions. Stone diameters ranged from 4 mm to 18 mm (mean, 8 mm). Two hundred fourteen patients had four or fewer stones (mean, 2.3), and 86 patients had more than four (mean, 8.8; range, 5-25). Two patients required surgical intervention after loss of transcystic drainage, with subsequent development of peritonitis. During the follow-up period (mean, 26.6 months), no clinical or laboratory abnormalities were observed. Conclusions: Percutaneous antegrade papillary balloon dilation and stone clearance is a safe and effective tool in removing common bile duct stones. Some technical issues should be considered to achieve complete stone removal while minimizing the incidence of complications. © 2011 SIR.
Amartino H.,Hospital Universitario Austral
European Neurological Review | Year: 2015
Hunter syndrome (mucopolysaccharidosis II) is a rare X-linked lysosomal storage disease caused by deficiency of the enzyme iduronate-2- sulfatase. The condition is one of a group of disorders, the mucopolysaccharidoses, which all result in accumulation of glycosaminoglycans. Hunter syndrome is a chronic progressive disorder whose clinical manifestations vary widely in severity and involve multiple organs and tissues. In addition to developing somatic symptoms, patients having the neuronopathic form of the disease also display developmental delay and cognitive impairment in early childhood that progressively worsens and that is severely life-limiting. Patients are at risk of developing secondary neurological manifestations, including hydrocephalus, vision and hearing loss, carpal tunnel syndrome and spinal cord compression. Common findings from brain magnetic resonance imaging (MRI) scans and at autopsy include neurodegenerative changes in white matter, the corpus callosum and basal ganglia; enlargement of periventricular spaces; ventriculomegaly; closed cephaloceles; and tissue atrophy. Though at present there is no specific treatment for the neurodegenerative aspects of the disease, hydrocephalus, carpal tunnel syndrome and spinal cord compression can be managed surgically. Patients who have Hunter syndrome should receive coordinated care from a multidisciplinary team: in light of the extensive neurological symptoms of the disease, neurologists play an important role in the diagnosis and management of this condition. © 2015 Touch Briefings. All rights reserved.
Saravia M.,Hospital Universitario Austral
Medical Hypotheses | Year: 2011
Diabetic macular edema (DME) affects 10% of subjects with diabetes and is the major cause of visual loss. Metabolic control and focal laser can reverse edema in some patients. However, persistent and diffuse diabetic macular edema is usually resistant to these treatments.Since 1992, vitrectomy has been considered for the treatment of some forms of diabetic macular edema. Removal of internal limiting membrane (ILM) has been proposed as a procedure that contributes to improvement of outcomes. Though its efficacy has been debated in some publications, its results seem to be better than those reported with standard laser treatment. The reason of persistence of chronic edema and how this surgery could improve outcomes in these patients remain unknown.The significant role of the ILM in the pathogenesis of persistent diffuse DME might be explained by stressing the importance of colloid and protein accumulation and retention in the retinal interstitial space.A hypothesis is proposed supporting that the ILM has selective permeability by which macular edema is sustained over time. © 2011 Elsevier Ltd.