In Vitro and In Vivo Antiviral Activity and Resistance Profile of the Hepatitis C Virus NS3/4A Protease Inhibitor ABT-450

The development of direct-acting antiviral agents is a promising therapeutic advance in the treatment of hepatitis C virus (HCV) infection. However, rapid emergence of drug resistance can limit efficacy and lead to cross-resistance among members of the same drug class. ABT-450 is an efficacious inhibitor of HCV NS3/4A protease, with 50% effective concentration values of 1.0, 0.21, 5.3, 19, 0.09, and 0.69 nM against stable HCV replicons with NS3 protease from genotypes 1a, 1b, 2a, 3a, 4a, and 6a, respectively. In vitro, the most common amino acid variants selected by ABT-450 in genotype 1 were located in NS3 at positions 155, 156, and 168, with the D168Y variant conferring the highest level of resistance to ABT-450 in both genotype 1a and 1b replicons (219- and 337-fold, respectively). In a 3-day monotherapy study with HCV genotype 1-infected patients, ABT-450 was coadministered with ritonavir, a cytochrome P450 3A4 inhibitor shown previously to markedly increase peak, trough, and overall drug exposures of ABT-450. A mean maximum HCV RNA decline of 4.02 log₁₀ was observed at the end of the 3-day dosing period across all doses. The most common variants selected in these patients were R155K and D168V in genotype 1a and D168V in genotype 1b. However, selection of resistant variants was significantly reduced at the highest ABT-450 dose compared to lower doses. These findings were informative for the subsequent evaluation of ABT-450 in combination with additional drug classes in clinical trials in HCV-infected patients. (Study M11-602 is registered at ClinicalTrials.gov under registration no. {"type":"clinical-trial","attrs":{"text":"NCT01074008","term_id":"NCT01074008"}}NCT01074008.)     

Predictors of mortality in children due to severe and very severe pneumonia

Background:

Mortality due to pneumonia in children is more than any other illness. Limited data is available to predict mortality in children with pneumonia from central India.

Aim:

To study predictors of mortality in children aged 1-59 months hospitalised with severe and very severe pneumonia.

Materials and Methods:

Present study was observational longitudinal study that was done in a tertiary care hospital of central India. Two hundred and ninety children, aged 1-59 months, presented with severe and very severe pneumonia were enrolled in this study. Outcome and predictors of mortality were studied. Data was analysed with Chi-square test, univariate and multivariate regression analysis.

Results:

Out of 270 enrolled study subjects, maximum (108, 37.24%) were belonged to 1-6-months age group. Proportion of mortality was maximum (16, 64.00%) in that age group. Overall case fatality rate was 8.62%. Among significant variables, delayed hospital referral [adjusted odds ratio (OR)-52.09, 95% confidence interval (CI)- 6.74-402.39], incomplete immunisation (OR-12.28, 95% CI-2.15-69.93), severe malnutrition (Z score < −3) (OR-15.51, 95% CI- 2.04-117.83), refusal to feed (OR- 30.57, 95% CI- 2.47-378.26), and hypoglycaemia (OR- 6.98, 95% CI- 1.05-46.30) were found significant independently on multivariate regression analysis. Conclusion: Delayed hospital referral, incomplete immunisation, severe malnutrition, refusal to feed, and hypoglycaemia were independent predictors of mortality in children with severe and very severe pneumonia.     

National Trends and Outcomes in Dialysis-Requiring Acute Kidney Injury in Heart Failure: 2002–2013

Background

Dialysis-requiring acute kidney injury (D-AKI) is a serious complication in hospitalized heart failure (HF) patients. However, data on national trends are lacking after 2002.

Hepatitis C Virus Genotype 4 Resistance and Subtype Demographic Characterization of Patients Treated with Ombitasvir plus Paritaprevir/Ritonavir

Hepatitis C virus (HCV) genotype 4 (GT4) is genetically diverse, with 17 confirmed subtypes, and comprises approximately 13% of infections worldwide. In this study, we identified GT4 subtypes by phylogenetic analysis, assessed differences in patient demographics across GT4 subtypes, examined baseline sequence variability among subtypes and the potential impact on treatment outcome, and analyzed the development of viral resistance in patients who received a regimen of ombitasvir (nonstructural protein 5A [NS5A] inhibitor) plus ritonavir-boosted paritaprevir (NS3/4A inhibitor) with or without ribavirin (RBV) for the treatment of HCV GT4 infection. Phylogenetic analysis of HCV NS3/4A, NS5A, and NS5B nucleotide sequences identified 7 subtypes (4a, 4b, 4c, 4d, 4f, 4g/4k, and 4o) among 132 patient samples. Subtype prevalence varied by country, and the distributions of patient birth cohort and race were significantly different across GT4 subtypes 4a, 4d, and non-4a/4d. Baseline amino acid variability was detected in NS5A across GT4 subtypes but had no impact on treatment outcome. Three patients experienced virologic failure and were infected with subtype 4d, and the predominant resistance-associated variants at the time of failure were D168V in NS3 and L28V in NS5A. Overall, high response rates were observed among patients infected with 7 HCV GT4 subtypes, with no impact of baseline variants on treatment outcome. GT4 subtype distribution in this study differed based on patient demographics and geography.     

Vertical and horizontal proportions of the face and their correlation to phi among Indians in Moradabad population: A survey

Purpose:

The purpose was to examine the existence of divine proportions among the Indian faces in Moradabad population.

Materials and Methods:

Totally, 100 patients (50 males; 50 females) aged 25-45 years were selected for the study. All facial photographs were analyzed based on the method of Ricketts assessing the divine proportions in vertical and transverse facial planes. Six horizontal and seven vertical ratios were determined, which were then compared with the phi ratio.

Results:

The horizontal ratio results showed that three male and female ratios were not significantly different from each other (P > 0.05), and interchilion/nose width ratio was highly significant (P < 0.001). The horizontal mean ratios for females as well as males were highly significant from the phi ratio (P < 0.001) except for interchilion/interdacryon ratio, which was significant (P < 0.05) for females and not significant (P > 0.05) for males. The vertical ratio results showed that there was a highly significant difference (P < 0.001) for forehead height/stomion-soft menton ratio and no significant difference for two ratios between the mean ratios of males and females. All the vertical mean ratios for both the groups were highly significant (P < 0.001), except for the intereye-soft menton/intereye-stomion ratio, which was significant (P < 0.05) for female group and not significant (P > 0.05) for the male group.

Conclusion:

Although, the golden proportion is a prominent and recurring theme in esthetics, it should not be embraced as the only method by which human beauty is measured to the exclusion of others factors.     

Ophthalmic Complication Following Posterior Superior Alveolar Nerve Block for Tooth Extraction! A Rare Occurrence

One of the most commonly asked question by a patient who comes for extraction especially in the rural areas is whether the procedure will cause problems to the eye!! In reality however, ophthalmic complications following routine maxillary molar extractions are practically unheard of. When they occur they can be extremely unnerving not just to the patient but also to the surgeon. Patients generally panic which makes it tougher for the clinician to assess the situation. We present a case of a 26 year old female patient developing ophthalmic complication following local anesthesia administration during extraction of upper left maxillary third molar. In this article, ophthalmic complications arising from posterior superior alveolar nerve block are discussed and management guidelines are highlighted.