Efficacy and Safety of Inhaled Dry Powder Mannitol in Treating Cystic Fibrosis: A Meta-Analysis and Systematic Review of Randomized Trials

Background: Inhaled dry powder mannitol is an osmotic agent with a potential to improve lung functions in Cystic Fibrosis (CF) patients and possibly act as a disease modifying agent. Aim: Primary outcomes are to evaluate the improvement of lung functions. Methods Study selection criteria: Randomized trials that evaluated the improvement of lung functions in CF patients with the use of inhaled dry powder mannitol. Data collection & extraction: Articles were searched in Medline, Pubmed, and Ovid journals. Statistical method: Pooled proportions were calculated using fixed and random effects model. Results: Initial search identified 387 reference articles, of which 31 articles were selected and reviewed. Data was extracted from 6 studies (N = 771) which met the inclusion criteria. After the treatment duration (median12 weeks), FEV1% increased by 7.23 (95% CI = 6.88 to 7.58) and 2.77 (95% CI = 2.57 to 2.97) in the pooled patients of treatment and control groups respectively. FEV1 (in ml) improved by 114.12 (95% CI = 108.96 to 119.29) and 6.80 (95% CI = 6.13 to 7.48) in treatment and control groups respectively. Odds ratio for pharyngeal pain, cough, hemoptysis and headache in treatment group compared to control group were 1.52 (95% CI = 0.91 to 2.52), 1.27 (95% CI = 0.85 to 1.90), 1.82 (95% CI = 0.97 to 3.39) and 0.80 (95% CI = 0.54 to 1.19) respectively. Conclusion: Inhaled mannitol may be used as a chronic disease modifying treatment in patients with pulmonary CF and possibly improve the overall outcomes

Universal Index for Cirrhosis (UIC index): The development and validation of a novel index to predict advanced liver disease

Zohair Ahmed,1 Jinma Ren,2 Adam Gonzalez,3 Umair Ahmed,4 Saqib Walayat,4 Daniel K Martin,5 Harsha Moole,4 Sherri Yong,6 Sean Koppe,7 Sonu Dhillon5 1Department of Gastroenterology and Hepatology, University of Illinois at Chicago, IL, USA; 2Department of Center for Outcomes Research, University of Illinois College of Medicine, Peoria, IL, USA; 3University of Illinois College of Medicine, Peoria, IL, USA; 4Department of Internal Medicine, University of Illinois College of Medicine, Peoria, IL, USA; 5Department of Gastroenterology and Hepatology, University of Illinois College of Medicine, Peoria, IL, USA; 6Department of Pathology, University of Illinois College of Medicine, Peoria, IL, USA; 7Department of Hepatology, University of Illinois at Chicago, IL, USA Aim: The purpose of this study was to create and validate a novel serological diagnostic index to predict cirrhosis of all etiologies.Methods: This was a retrospective observational study of 771 patients, age >18 years, who underwent a liver biopsy. The stage of fibrosis and routine laboratory values were recorded. The data were randomly separated into 2 datasets (training 50% and testing 50%). A stepwise logistic regression model was used to develop the novel index. The area under the curve of receiver operating characteristic (AUROC) was applied to compare the new index to existing ones (Fibro-Q, FIB4, APRI, AAR), which was also validated in the testing dataset.Results: Variables associated with the presence of cirrhosis were first assessed by univariate analysis then by multivariable analysis, which indicated serum glutamic-oxaloacetic acid transaminase, serum glutamic-pyruvic transaminase, international normalized ratio, albumin, blood urea nitrogen, glucose, platelet count, total protein, age, and race were the independent predictors of cirrhosis (P<0.05). Regression formula for prediction of cirrhosis was generated and a novel index was subsequently created. The diagnostic performance of the novel index for predicting cirrhosis was assessed using the receiver operating characteristic curve. The new index had significantly higher AUROC (0.83, 95% CI: 0.79–0.87) than Fibro-Q (0.80, 95% CI: 0.76–0.85), FIB4 (0.79, 95% CI: 0.74–0.83), APRI (0.74, 95% CI: 0.69–0.78), and AAR (0.72, 95% CI: 0.67–0.78).Conclusion: The novel index had the highest AUROC curve when compared with current indices and can be applied to all etiologies of chronic liver disease. Keywords: cirrhosis, liver, fibrosis, diagnosis, screening, NAFLD, HCV, alcoho