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Background: Thrombocytopenia has been shown to be the single most useful laboratory investigation for identifying subclinical cirrhosis of varying etiologies. However, alcohol per se can result in thrombocytopenia, and hence it is unclear whether platelet count can identify cirrhosis in patients who are alcoholic., Objectives: To characterize the utility of clinical predictors, especially platelet count, for identifying the presence of cirrhosis in alcoholics. To develop a simple, objective model for identifying cirrhosis in alcoholics., Design: Retrospective cohort study., Participants: A total of 2,471 consecutive hospitalized patients with abnormal liver enzyme levels were screened, from which 272 patients with a history of recent and ongoing alcohol intake, negative diagnostic studies for alternative etiologies of chronic liver disease, and recent liver imaging with ultrasound or CT scan were included., Main Measures: Results of liver imaging and admission laboratory studies including liver enzymes, coagulation studies, and blood counts., Key Results: One hundred twenty-nine patients (47%) had cirrhosis based on imaging; 143 patients (53%) had no cirrhosis. A pre-sobriety platelet count (during ongoing alcohol intake) of less than 70*10(3) cells/mm(3) was effective for ruling in cirrhosis (positive likelihood ratio [LR] 6.8, 95% CI: 3.4, 14); platelet count greater than 200*10(3) was useful for ruling out cirrhosis in alcoholics (negative LR 0.18, 95% CI: 0.10, 0.35). Multivariate logistic regression analysis identified international normalized ratio (INR) (p < 0.01) and pre-sobriety platelet count (p < 0.01) as independent predictors of cirrhosis. A Model for identifying Cirrhosis in Alcoholic Liver Disease (MCALD) was developed using the INR and pre-sobriety platelet count; it had an area under the receiver operating characteristic curve of 0.89 and Hosmer-Lemeshow goodness of fit chi(2) (p value) of 8.9 (0.35) for predicting cirrhosis in alcoholics. A MCALD score > 5.5 corresponded to an increased likelihood of cirrhosis (LR: 6.5, 95% CI: 4.3, 11.0) and a MCALD score < 5.5 corresponded to decreased likelihood of cirrhosis in alcoholics (LR: 0.25, 95% CI: 0.19, 0.36). Sobriety platelet count (after alcohol abstinence) at a cutoff of 160*10(3) had positive LR of 7.9 (95% CI: 4.4, 14) and negative LR of 0.42 (95% CI: 0.34, 0.52) for predicting cirrhosis in alcoholics., Conclusions: A simple model of platelet count and INR has good diagnostic accuracy for identifying cirrhosis in alcoholics.

The purpose of the present study was to explore the passive and electrically assisted transdermal transport of diphenhydramine hydrochloride (DPH) by iontophoresis. For better bioavailability, better patient compliance, and enhanced delivery of DPH, an iontophoretic drug delivery system of a thermosensitive DPH gel was formulated using Lutrol F-127. The study was conducted using silver-silver chloride electrodes across hairless pig skin. The effects of pH, polymer concentration, electrode design, and pulse rate on the DPH permeation were investigated. The relationship between temperature, viscosity, and conductance of DPH was correlated using conductometry. Iontophoretic transport of DPH was found to increase with a decrease in the pH of the medium and an increase in the surface area of the electrode. Viscosity measurements and flux calculations indicated the suitability of the Lutrol gel for transdermal iontophoretic delivery of DPH. Anodal pulsed iontophoresis with disc electrode significantly increased the DPH skin permeation as compared with the passive controls.

The purpose of the present study was to develop and characterize an oral controlled release drug delivery system for concomitant administration of diclofenac sodium (DS) and chondroitin sulfate (CS). A hydrophilic matrix-based tablet using different concentrations of hydroxypropylmethylcellulose (HPMC) was developed using wet granulation technique to contain 100 mg of DS and 400 mg of CS. Formulations prepared were evaluated for the release of DS and CS over a period of 9 hours in pH 6.8 phosphate buffer using United States Pharmacopeia (USP) type II dissolution apparatus. Along with usual physical properties, the dynamics of water uptake and erosion degree of tablet were also investigated. The in vitro drug release study revealed that HPMC K100CR at a concentration of 40% of the dosage form weight was able to control the simultaneous release of both DS and CS for 9 hours. The release of DS matched with the marketed CR tablet of DS with similarity factor (f(2)) above 50. Water uptake and erosion study of tablets indicated that swelling followed by erosion could be the mechanism of drug release. The in vitro release data of CS and DS followed Korsmeyer-Peppas and zero-order kinetics, respectively. In conclusion, the in vitro release profile and the mathematical models indicate that release of CS and DS can be effectively controlled from a single tablet using HPMC matrix system.