Randomized double-blind clinical trial of a new human epoetin versus a commercially available formula for anemia control in patients on hemodialysis

OBJECTIVES: Anemia is a common complication among chronic kidney disease patients on hemodialysis, occurring mostly due to erythropoietin deficiency. This randomized noninferiority trial sought to compare the efficacy and safety of a new epoetin formulation developed by Bio-Manguinhos, a biologics manufacturer affiliated with the Brazilian government, with those of a commercially available product currently used in Brazil (a biosimilar epoetin formulation). METHODS: The sample size needed to enable demonstration of noninferiority with a statistical power of 85% for a between-group difference in hemoglobin levels of no more than 1.5 g/dL was calculated. In total, 74 patients were randomly assigned to receive the epoetin formulation from Bio-Manguinhos (n = 36) or the biosimilar epoetin formulation (n = 38) in a double-blind fashion. The inclusion criteria were current epoetin therapy and stable hemoglobin levels for at least 3 months prior to the study. The primary and secondary outcomes were mean monthly hemoglobin levels and safety, respectively. The dose was calculated according to international criteria and adjusted monthly in both groups according to hemoglobin levels and at the assistant physicians' discretion. Iron storage was estimated at baseline and once monthly. Clinicaltrials.gov: NCT01184495. RESULTS: The study was conducted for 6 months after randomization. The mean baseline hemoglobin levels were 10.9±1.2 and 10.96±1.2 g/dL (p = 0.89) in the Bio-Manguinhos epoetin and biosimilar epoetin groups, respectively. During the study period, there was no significant change in hemoglobin levels in either group (p = 0.055, ANOVA). The epoetin from Bio-Manguinhos was slightly superior in the last 3 months of follow-up. The adverse event profiles of the two formulations were also similar. CONCLUSIONS: The epoetin formulations tested in this study are equivalent in efficacy and safety

Vasoconstrictors in hepatorenal syndrome – A critical review

Hepatorenal syndrome has the worst prognosis among causes of acute kidney injury in cirrhotic patients. Its definitive treatment is liver transplantation. Nevertheless, considering its high short-term mortality rate and the shortage of liver grafts, a pharmacological treatment is of utmost importance, serving as a bridge to liver transplant. The clinical management of hepatorenal syndrome is currently based on the use of a vasoconstrictor in association with albumin. Terlipressin, noradrenaline and the combination of midodrine and octreotide could be used to treat hepatorenal syndrome. Among these options, terlipressin seems to gather the strongest body of evidence regarding efficacy and should be considered the first line of treatment whenever available and in the absence of contraindications. Treatment with a vasoconstrictor and albumin should be promptly initiated after the diagnosis of hepatorenal syndrome in order for patients to have higher chances of recovery

Screening for esophageal varices in cirrhotic patients – Non-invasive methods

Variceal bleeding is a dramatic complication of cirrhosis. Primary prophylaxis against variceal bleeding is indicated for patients with high-risk varices. In order for these patients to be identified, endoscopic screening for esophageal varices has been traditionally recommended at the time of the diagnosis of cirrhosis. Considering that many patients do not have esophageal varices in the early stages of cirrhosis and, therefore, are submitted to endoscopy unnecessarily, non-invasive methods for variceal screening have been studied. Among these non-invasive methods, the most extensively studied probably are platelet count/spleen diameter ratio, liver stiffness, spleen stiffness and an association between liver stiffness and platelet count, referred to as the Baveno VI criteria. The Baveno VI criteria has recently been recommended by different medical associations for variceal screening. This is a critical review on the non-invasive methods for variceal screening, in which the performances of the different methods are presented and the limitations of the existing evidence is discussed. Despite reasonable performances of some of these methods, especially platelet count/spleen diameter ratio and the association between liver stiffness and platelet count, we understand that the available evidence still has relevant limitations and that physicians should decide on screening cirrhotic patients for esophageal varices with endoscopy or non-invasive methods on a case-by-case basis

Randomized double-blind clinical trial of a new human epoetin versus a commercially available formula for anemia control in patients on hemodialysis

OBJECTIVES: Anemia is a common complication among chronic kidney disease patients on hemodialysis, occurring mostly due to erythropoietin deficiency. This randomized noninferiority trial sought to compare the efficacy and safety of a new epoetin formulation developed by Bio-Manguinhos, a biologics manufacturer affiliated with the Brazilian government, with those of a commercially available product currently used in Brazil (a biosimilar epoetin formulation). METHODS: The sample size needed to enable demonstration of noninferiority with a statistical power of 85% for a between-group difference in hemoglobin levels of no more than 1.5 g/dL was calculated. In total, 74 patients were randomly assigned to receive the epoetin formulation from Bio-Manguinhos (n = 36) or the biosimilar epoetin formulation (n = 38) in a double-blind fashion. The inclusion criteria were current epoetin therapy and stable hemoglobin levels for at least 3 months prior to the study. The primary and secondary outcomes were mean monthly hemoglobin levels and safety, respectively. The dose was calculated according to international criteria and adjusted monthly in both groups according to hemoglobin levels and at the assistant physicians' discretion. Iron storage was estimated at baseline and once monthly. Clinicaltrials.gov: NCT01184495. RESULTS: The study was conducted for 6 months after randomization. The mean baseline hemoglobin levels were 10.9±1.2 and 10.96±1.2 g/dL (p = 0.89) in the Bio-Manguinhos epoetin and biosimilar epoetin groups, respectively. During the study period, there was no significant change in hemoglobin levels in either group (p = 0.055, ANOVA). The epoetin from Bio-Manguinhos was slightly superior in the last 3 months of follow-up. The adverse event profiles of the two formulations were also similar. CONCLUSIONS: The epoetin formulations tested in this study are equivalent in efficacy and safety

High Prevalence of Multidrug Resistant Bacteria in Cirrhotic Patients with Spontaneous Bacterial Peritonitis: Is It Time to Change the Standard Antimicrobial Approach?

Introduction. Spontaneous bacterial peritonitis (SBP) has a deleterious clinical impact in end-stage liver disease, and multidrug resistance has increased, raising concern about effectiveness of traditional antibiotic regimens. Patients and Methods. Single-center retrospective study of ascitic fluid infections in cirrhotic patients. Results. We analyzed medical records related to 2129 culture-positive ascitic fluid and found 183 samples from cirrhotic patients. There were 113 monobacterial SBP cases from 97 cirrhotic patients; 57% of patients were male; hepatitis C and alcohol were the main etiologies for cirrhosis. Multidrug resistant bacteria were isolated in 46.9% of SBP samples, and third-generation cephalosporin and quinolone resistant reached 38.9% and 25.7% of SBP cases. Conclusion. SBP due to multidrug resistant bacteria is a growing problem, and one should consider reported resistance profiles for the decision-making process of empirical first-line treatment prescription

Holographic Sensors: Three-Dimensional Analyte-Sensitive Nanostructures and Their Applications

Holographic sensors are analytical devices that systematically diffract narrow-band light in the ultraviolet to near-infrared range for application in the detection and quantification of analytes and/or physical parameters. They can be functionalized with analyte-responsive materials to construct highly sensitive optical sensors for use in testing, where a visual readout, fast turnaround time, and reversibility are needed. Holography allows fabrication of disposable sensors that are lightweight for miniaturization and multiplexing purposes.3 Holographic sensors offer three capabilities on a single analytical device: (i) label-free analyte-responsive polymer, (ii) real-time, reversible quantification of the external stimuli, and (iii) three-dimensional visual image display