Search

Background and Purpose: Miridesap, a depleter of serum amyloid P component (SAP), forms an essential component of a novel approach to remove systemic amyloid deposits; low oral bioavailability necessitates that it is given parenterally. We sought to identify and clinically characterise a pro-drug that preserves the pharmacological properties of miridesap while having adequate oral bioavailability and physical stability., Experimental Approach: We utilised a preclinical screening cascade focused on appropriate physicochemical properties, physical and gut stability, and conversion to miridesap in liver microsomes and blood. GSK3039294 (GSK294) had the desired in vitro profile and progressed to preclinical in vivo pharmacokinetic and safety assessments. Based on a favourable profile, it was tested in healthy participants after single and repeat dosing., Key Results: GSK294 was highly soluble and stable in simulated gastric and intestinal fluids, stable in intestinal microsomes, and permeable in Madine Darby Canine Kidney type II cells. GSK294 was rapidly hydrolysed to miridesap and its mono pro-drug ester in blood and liver microsomes. GSK294 showed good oral bioavailability of miridesap in rats and dogs. Following administration of GSK294 600 mg QD for 7 days in humans, pharmacodynamically active concentrations of miridesap were achieved with substantial and sustained depletion of plasma SAP. The study was terminated due to observations of arrhythmia, the relation of which to GSK294 remains unclear., Conclusion and Implications: Using a preclinical screening cascade, we identified a pro-drug for a palindromic molecule with unique pharmacology (miridesap). The pro-drug depleted circulating SAP with a time course and extent similar to that of parenterally administered miridesap., (© 2019 The British Pharmacological Society.)

Indonesia has reported highest number of fatal human cases of highly pathogenic avian influenza (HPAI) A (H5N1) virus infection worldwide since 2005. There are limited data available on seasonal and pandemic influenza in Indonesia. During 2012, we conducted a survey of clinicians in two districts in western Java, Indonesia, to assess knowledge, attitudes, and practices (KAP) of clinical diagnosis, testing, and treatment of patients with seasonal influenza, pandemic influenza, or HPAI H5N1 virus infections. Overall, a very low percentage of physician participants reported ever diagnosing hospitalized patients with seasonal, pandemic, or HPAI H5N1 influenza. Use of influenza testing was low in outpatients and hospitalized patients, and use of antiviral treatment was very low for clinically diagnosed influenza patients. Further research is needed to explore health system barriers for influenza diagnostic testing and availability of antivirals for treatment of influenza in Indonesia., (© 2016 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.)

The Iraq conflict resulted in the largest displacement in the Middle East since the Palestinian crisis, and provision of health services to the displaced population presents a critical challenge. The study aimed to provide information on chronic medical conditions and disability to inform humanitarian assistance planning. Nationally representative cross-sectional surveys of Iraqi populations displaced in Jordan and Syria were conducted in late 2008 and early 2009. Clusters of 10 household were randomly selected using probability-based sampling; a total of 1200 and 813 Iraqi households in Jordan and Syria, respectively, were interviewed. The majority of respondents in both countries perceived healthcare as unaffordable but accessible; cost was an important barrier to care. In Jordan, most routine health expenditures were for medications where in Syria, expenses were divided between medical consultations and medication. Chronic disease prevalence among adults was 51.5% (confidence interval (CI): 49.4-53.5) in Syria and 41.0% (CI: 39.4-42.7) in Jordan, most common were hypertension and musculoskeletal problems. Overall disability rates were 7.1% (CI: 6.3-8.0) in Syria and 3.4% (CI: 3.0-3.9) in Jordan. In both countries, the majority of disability was attributed to conflict, prevalence was higher in men than women, and depression was the leading cause of mental health disability. Chronic illnesses, disabilities and psychological health are key challenges for the Iraqi population and the health systems in Jordan and Syria. Continued attention to the development of systems to manage conditions that require secondary and tertiary care is essential, particularly given reported difficulties in accessing care and the anticipated prolonged displacement., (Copyright © 2012 John Wiley & Sons, Ltd.)