PROFILEing Idiopathic Pulmonary Fibrosis: Rethinking Biomarker Discovery.

PROFILEing idiopathic pulmonary fibrosis: rethinking biomarker discovery.

Eur Respir Rev. 2013 Jun 1; 22(128): 148-152
Maher TM

Despite major advances in the understanding of the pathogenesis of idiopathic pulmonary fibrosis (IPF), diagnosis and management of the condition continue to pose significant challenges. Clinical management of IPF remains unsatisfactory due to limited availability of effective drug therapies, a lack of accurate indicators of disease progression, and an absence of simple short-term measures of therapeutic response. The identification of more accurate predictors of prognosis and survival in IPF would facilitate counseling of patients and their families, aid communication among clinicians, and would guide optimal timing of referral for transplantation. Improvements in molecular techniques have led to the identification of new disease pathways and a more targeted approach to the development of novel anti-fibrotic agents. However, despite an increased interest in biomarkers of IPF disease progression there are a lack of measures that can be used in early phase clinical trials. Careful longitudinal phenotyping of individuals with IPF together with the application of novel omics-based technology should provide important insights into disease pathogenesis and should address some of the major issues holding back drug development in IPF. The PROFILE (Prospective Observation of Fibrosis in the Lung Clinical Endpoints) study is a currently enrolling, prospective cohort study designed to tackle these issues. HubMed – drug


Small airways diseases, excluding asthma and COPD: an overview.

Eur Respir Rev. 2013 Jun 1; 22(128): 131-147
Burgel PR, Bergeron A, de Blic J, Bonniaud P, Bourdin A, Chanez P, Chinet T, Dalphin JC, Devillier P, Deschildre A, Didier A, Kambouchner M, Knoop C, Laurent F, Nunes H, Perez T, Roche N, Tillie-Leblond I, Dusser D

This review is the summary of a workshop on small airways disease, which took place in Porquerolles, France in November 2011. The purpose of this workshop was to review the evidence on small airways (bronchiolar) involvement under various pathophysiological circumstances, excluding asthma and chronic obstructive pulmonary disease. Histopathological patterns associated with small airways disease were reviewed, including cellular and obliterative bronchiolitis. Many pathophysiological conditions have been associated with small airways disease including airway infections, connective tissue diseases and inflammatory bowel diseases, bone marrow and lung transplantation, common variable immunodeficiency disorders, diffuse panbronchiolitis, and diseases related to environmental exposures to pollutants, allergens and drugs. Pathogenesis, clinical presentation, a computed tomography scan and pulmonary function test findings are reviewed, and therapeutic options are described with the objective of providing an integrative approach to these disorders. HubMed – drug


Population pharmacokinetics of carvedilol in patients with congestive heart failure.

J Pharm Sci. 2013 May 31;
Nikolic VN, Jankovic SM, Velickovic-Radovanovi? R, Apostolovi? S, Stanojevic D, Zivanovic S, Stefanovic N, Pesic S, Jevtovic-Stoimenov T, Djuric J, Markovic V, Milovanovic JR

The aim of this study was to derive population pharmacokinetic (PK) model for clearance (CL) of carvedilol in adult patients with chronic heart failure (CHF). Medication and demographic data were obtained from 52 Caucasian patients with CHF taking carvedilol. Population PK analysis was performed by nonlinear mixed-effects modeling (NONMEM) to estimate and identify different factors that could affect carvedilol CL. A total of 55 plasma concentrations were collected from 52 patients with mean age of 63.02?± 11.95 years and total body weight (TBW) of 77.96?± 13.46 kg. Total daily doses of carvedilol in the target population had wide range of variability (6.25-50 mg), followed by high variability of drug plasma concentrations (1-59.07 ng/mL). The typical mean value for carvedilol CL, estimated by the base model, in the target population was 43.8 L/h. The TBW, concomitant therapy with digoxin, and tobacco using were determinants of a derived population model. The final regression model for the CL of carvedilol is: [Formula: see text] Our results suggest that the TBW, concomitant therapy with digoxin, and tobacco using are the main subjects of carvedilol PK variability. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci. HubMed – drug


Clinical Outcomes, Health Resource Use, and Cost in Patients with Early versus Late Dual or Triple Anti-Platelet Treatment for Acute Coronary Syndrome.

Am J Cardiovasc Drugs. 2013 Jun 1;
Friedman H, Mollon P, Lian J, Navaratnam P

BACKGROUND: Acute coronary syndrome (ACS) guidelines recommend early dual anti-platelet therapy (thienopyridines + acetylsalicylic acid [aspirin]). However, triple therapy (thienopyridines + aspirin + glycoprotein IIb/IIIa receptor inhibitors [GRIs]) has shown benefit in clinical trials. OBJECTIVE: This study assessed real-world ACS treatment patterns and outcomes in the acute care setting. STUDY DESIGN: A retrospective analysis of patients admitted to hospital with ACS (index event) from January 2007 to December 2009 was conducted (Thomson’s MarketScan Hospital Drug Database). PATIENTS: Eligible patients were ?18 years of age, of either sex, and had primary admission and discharge diagnoses of ACS. OUTCOME MEASURES: Cohorts were defined by anti-platelet treatment and then by the timing of treatment initiation (early initiation: within ?2 days of admission; late initiation: ?2 days post-admission). Patient characteristics, clinical outcomes, resource utilization, and costs were assessed using descriptive statistics. RESULTS: A total of 249,907 eligible patients were placed into four treatment cohorts (aspirin assumed for all patients): aspirin only; clopidogrel only (dual therapy); GRI only (dual therapy); and clopidogrel + GRI (triple therapy). Patients in the ‘clopidogrel-only’ cohort were more likely to be older, female, and have more co-morbidities than those in other cohorts; stroke (6.2 %) and re-hospitalization (15.4 %) rates were higher than in the ‘GRI-only’ and ‘triple therapy’ cohorts. The GRI-only cohort had higher major bleeding rates (3.3 %), mortality (7.6 %), and costs ($ US21,975 2020) than the clopidogrel-only and triple-therapy cohorts. Late initiation cohorts were more likely to be older, female, and have more co-morbidities than early initiation cohorts. Major bleeding was more likely with GRI-only patients (regardless of initiation timing) than with other cohorts. Late-treated clopidogrel-only patients had higher rates of stroke (6.9 %), ACS-related re-admissions (6.1 %), and all-cause re-admissions (15.9 %) than other cohorts. Late treatment was associated with longer length of stay and significantly higher costs. CONCLUSIONS: Real-world anti-platelet treatment patterns are consistent with ACS guidelines recommending early initiation and selective GRI use. In contrast to recommendations, some outcomes were improved with triple therapy compared with dual therapy. HubMed – drug