An Approach for Widening the Bioequivalence Acceptance Limits in the Case of Highly Variable Drugs

Purpose. Highly variable drugs pose a problem in bioequivalence assessment because they often fail to meet current regulatory acceptance criteria for average bioequivalence (80–125%). This paper examines alternative approaches to establishing bioequivalence. Methods. Suggested solutions have included alternate study designs, e.g., replicate and multiple dose studies, reducing the level of the confidence interval, and widening the acceptance limits. We focus on the latter approach. Results. A rationale is presented for defining wider acceptance limits for highly variable drugs. Two previously described methods are evaluated, and a new method having more desirable properties is proposed. Conclusions. We challenge the one size fits all current definition of bioequivalence acceptance limits for highly variable drugs, proposing alternative limits or goal posts which vary in accordance with the intrasubject variability of the reference product.     

Peripheral nerve repair and grafting techniques: a review

In this review, various conventional nerve repair techniques including direct epineurial repair, grouped fascicular repair, fascicular repair, and nerve grafting are described. The indications for use, as well as the relative advantage and disadvantage, of each technique are discussed. The experimental and clinical evidence from a review of the pertinent literature does not demonstrate a significant difference in outcome of one method over the others. Surgical decisions should be made by a thorough evaluation of all aspects of the nerve injury and surgical methods. All nerve injuries cannot be repaired using only one type of nerve repair method. The surgeon should be familiar with all the techniques described and be prepared to use them under appropriate circumstances.     

Imaging spectrum in disseminated histoplasmosis: Case report and brief review

The clinical manifestations of chronic disseminated histoplasmosis are non-specific and resemble those of other chronic infections and malignancies. We report the radiographic, sonographic and contrast-enhanced CT appearances of histoplasmosis in an adult male with non-insulin dependent diabetes mellitus, who was HIV negative and presented with weight loss and pyrexia. Imaging studies simulated tuberculosis with mediastinal lymphadenopathy, bilateral fibrotic lung lesions, hepatomegaly and bilateral hypoattenuating adrenal enlargement, without clinical or laboratory evidence of hypoadrenalism. Computed tomography-guided fine-needle aspiration biopsy of adrenal glands revealed Histoplasma capsulatum. We report our experience to increase awareness of the imaging spectrum of disseminated histoplasmosis and its similarity to tuberculosis as, with increasing incidence of AIDS, the chances of these infections are likely to increase. Moreover, awareness of this entity is important because it is known that untreated disseminated histoplasmosis is fatal.     

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.     

Prevalence of hepatitis C virus in a selected geographical area of northern India: a population based survey

Background and Aim

Epidemiological data on hepatitis C virus (HCV) infection from India are scanty. We conducted a population-based seroepidemiologic survey to estimate the prevalence of hepatitis C in Punjab state of northern India.

Methods

A house-to-house survey was conducted in a defined population of 26,273 subjects. Information was gathered according to a predesigned questionnaire with socio-demographic characteristics (age, gender and substance abuse), family history of HCV infection, general health status, associated co-infection, immunization history and potential risk factors for HCV transmission. At the time of clinical evaluation, blood was tested for anti-HCV and those found positive were tested for HCV RNA.

Results

Among 5,258 subjects screened, 272 were found to be anti-HCV positive (prevalence rate of 5.2?%); highest prevalence being noticed in 41?C60?years age group. Anti-HCV positive rate were not different among males and females. Sixty-seven subjects (1.3?%) were found to be HBsAg positive; four of these being co-infected (5.9?%). Various risk factors for acquiring HCV infection identified were history of surgery, dental treatment and unprotected sex. Other associations were strong family history of HCV positivity, alcohol consumption and diabetes mellitus.

Conclusion

Chronic HCV infection is a major health problem in Punjab; it appears to be more common than HBV infection. Exercising safe health care related procedures should be emphasized in our country as main modes of transmission of infection identified were related to these.