Efficacy and safety of pegylated IFN alfa 2b alone or in combination with ribavirin in thalassemia major with chronic hepatitis C

Background  

Treatment of HCV infection in patients with thalassemia major (TM) is limited by the lack of large clinical trials and concerns about ribavirin-induced hemolysis.     

Conference report: Bio-International 2005

This is a summary report of the International Pharmaceutical Federation/Board of Pharmaceutical Sciences (FIP/BPS) international conference, Bio-International 2005, which was held October 24-26, 2005 at the Royal Pharmaceutical Society, in London, UK. Bioequivalence (BE) issues related to multisource locally delivered topical dosage forms, oral inhalation drug products, highly variable drug products (HVDP), and endogenously occurring drugs were discussed. The conference also focused on alternate approaches to assess BE for some of these drug products. Pharmacokinetic (PK) approaches like, dermatopharmacokinetics (DPK) for dermatological topical dosage forms, scaled average BE (s-ABE) where within-subject variability is considered for estimation of 90% confidence intervals to document BE for highly variable drugs (HVD) were recommended. In addition, issues and difficulties related to the BE assessment of oral inhalation products, role, and appropriateness of metabolites in BE assessment, importance of base line correction in BE assessment of endogenously occurring drugs, and waiver of BE study requirements for certain drugs based on a Biopharmaceutics Classification System (BCS), were also discussed.     

Behavioural and anatomical analysis of selective tibial nerve branch transfer to the deep peroneal nerve in the rat

Nerve transfer procedures involving the repair of a distal denervated nerve element with that of a foreign proximal nerve have become increasingly popular for clinical nerve repair as a surgical alternative to autologous nerve grafting. However, the functional outcomes and the central plasticity for these procedures remain poorly defined, particularly for a clinically relevant rodent model of hindlimb nerve transfer. We therefore evaluated the effect of selective tibial branch nerve transfer on behavioural recovery in animals following acute transection of the deep peroneal nerve. The results indicate that not only can hindlimb nerve transfers be successfully accomplished in a rat model but that these animals display a return of skilled locomotor function on a par with animals that underwent direct deep peroneal nerve repair (the current gold standard). At 2 months, ground reaction force analysis demonstrated that partial restoration of braking forces occurred in the nerve transfer group, whereas the direct repair group had fully restored these forces to similar to baseline levels. Ankle kinematic analysis revealed that only animals in the direct repair group significantly recovered flexion during the step cycle, indicating a recovery of surgically induced foot drop. Terminal electrophysiological and myological assessments demonstrated similar levels of reinnervation, whereas retrograde labelling studies confirmed that the peroneal nerve‐innervated muscles were innervated by neurons from the tibial nerve pool in the nerve transfer group. Our results demonstrate a task‐dependent recovery process, where skilled locomotor recovery is similar between nerve transfer and direct repair animals, whereas flat surface locomotion is significantly better in direct repair animals.     

Comparison of the EUCAST and CLSI Broth Microdilution Methods for Testing Isavuconazole,Posaconazole, and Amphotericin B against Molecularly Identified Mucorales Species

We compared EUCAST and CLSI antifungal susceptibility testing (AFST) methods for triazoles and amphotericin B against 124 clinical Mucorales isolates. The EUCAST method yielded MIC values 1- to 3-fold dilutions higher than those of the CLSI method for amphotericin B. The essential agreements between the two methods for triazoles were high, i.e., 99.1% (voriconazole), 98.3% (isavuconazole), and 87% (posaconazole), whereas it was significantly lower for amphotericin B (66.1%). Strategies for harmonization of the two methods for Mucorales AFST are warranted.     

A case of allergic fungal rhinosinusitis due to Ceratocystis adiposa

Ceratocystis adiposa known as phytopathogen of conifers has not been recognized so far as a human pathogen. Herein, we report for the first time a case of allergic fungal rhinosinusitis due to C. adiposa. The fungus was identified by sequencing internal transcribed spacer of rDNA and D1/D2 of larger subunit region.     

Cause and effect relationship of malnutrition with idiopathic chronic pancreatitis: prospective case-control study

Background and Aim:  Patients with chronic pancreatitis are often malnourished. The role of malnutrition in the pathogenesis of chronic pancreatitis is unclear. The aim of the present article was to study prospectively the cause and effect relationship of malnutrition with idiopathic chronic pancreatitis in a case–control study.
Methods:  Consecutive patients with chronic pancreatitis underwent anthropometry, nutritional and dietary assessments. For dietary assessment, food frequency questionnaire and 24-hour dietary recall methods were used. Primary outcome measure was cause and effect relationship of malnutrition with idiopathic chronic pancreatitis.
Results:  Of 201 patients with chronic pancreatitis, 120 had idiopathic chronic pancreatitis (mean age 29.60 years, 74 males) who formed the study group. None of the patients consumed cassava. The nutritional status and dietary intake of the patients before the onset of chronic pancreatitis were comparable with those of controls with 20.6% of patients and 22.5% of controls being malnourished (body mass index [BMI] < 18.5). After the onset of chronic pancreatitis, 56.5% of patients lost weight and significantly more patients became malnourished compared with controls (45.8% vs 22.5%; P  < 0.001). The causes of weight loss were diabetes, higher calories from proteins, and pseudocyst.
Conclusion:  Malnutrition was not a cause of idiopathic chronic pancreatitis and weight loss occurred as an effect of chronic pancreatitis. Cassava was not found to be a cause of idiopathic chronic pancreatitis.     

Comparison of low-dose pegylated interferon versus standard high-dose pegylated interferon in combination with ribavirin in patients with chronic hepatitis C with genotype 3: an Indian experience

Background and Aims: In chronic hepatitis C virus (HCV) infection with genotype 3, therapy with pegylated interferon (peg‐IFN) alfa‐2b in a dose of 1.5 μg/kg/week and ribavirin (800–1000 mg/day) is recommended for 24 weeks. Reduced doses of peg‐IFN may increase compliance and decrease cost and adverse events. This study aimed to assess the safety and efficacy of two different regimens of peg‐IFN alfa‐2b, in combination with ribavirin, in genotype 3 patients. Methods: A total of 103 liver biopsy–proven chronic HCV patients with genotype 3, having alanine aminotransferase levels >1.2 × ULN and positive HCV‐RNA were randomized into two groups: group I (n = 76; age, 43.1 ± 11.4 years; male/female, 67/9) received peg‐IFN 1.0 μg/kg/week + ribavirin 10.6 mg/kg/day, while group II (n = 27; age, 37.3 ± 11.6 years; male/female, 21/6) received peg‐IFN 1.5 μg/kg/week + ribavirin 10.6 mg/kg/day. Patients in both groups were treated for 24 weeks. End of treatment viral response (ETVR) and sustained viral response (SVR) after a 6‐month follow‐up period were assessed. Results: In both groups I and II, one patient was lost to follow‐up, while one patient in group II withdrew due to side‐effects. ETVR was seen in 72/76 (94.7%) of patients in the low dose group and 24/27 (88.9%) of patients in the high dose group (P = 0.375). SVR was seen in 60/76 (78.9%) of patients in the low dose group and 25/27 (92.6%) of patients in the high dose group (P = 0.145). Age (Pearson correlation coefficient = 0.263; P = 0.008) and fibrosis (correlation coefficient, 0.263; P = 0.008) showed a significant correlation with the SVR. Conclusion: In patients with genotype 3, peg‐IFN at 1.0 μg/kg/week with ribavirin is as effective as peg‐IFN at 1.5 μg/kg/week with ribavirin.