Evaluation of a successful intervention for sustainability and effects in post research phase.

INTRODUCTION: Promoting appropriate use of drugs is an essential element in achieving quality of health and medical cares for patients and the community, and also to minimize financial burden. OBJECTIVE: The objective of this paper is to assess the successful intervention for sustainability and effects in post research phase. To address these problems, a variety of educational, managerial and regulatory strategies to improve prescribing have been tried in Nepal. When training is combined with a managerial intervention i.e. peer-group discussion, it results into improved changes in prescribing practices of paramedics in several practices. METHODOLOGY: A prospective, three-way design study consisting of small group training, small group training followed by peer-group discussion and control was conducted in three regions of Nepal including one hill and two terai (plains) districts from each region. The study included all health post from the sampled districts, making 80 health posts the study population. RESULTS: The study revealed the effectiveness of the peer-group discussion approach in improving the prescribing practices. An assessment to identify the sustainability of the strategy and its effect within the district healthcare system after the completion of the research phase was undertaken. The study found that peer-group discussion was discontinued in all targeted districts and the improved practices were not sustained after the completion of the research. Various reasons have been found for not continuing the effective intervention.     

Two year audit of perinatal mortality at Kathmandu Medical College Teaching Hospital.

Introduction: Perinatal mortality rate is a sensitive indicator of quality of care provided to women in pregnancy, at and after child birth and to the newborns in the first week of life. Regular perinatal audit would help in identifying all the factors that play a role in causing perinatal deaths and thus help in appropriate interventions to reduce avoidable perinatal deaths. Aims and objectives: This study was carried out to determine perinatal mortality rate (PMR) and the factors responsible for perinatal deaths at KMCTH in the two year period from November 2003 to October 2005 (Kartik 2060 B.S. to Ashoj 2062). Methodology: This is a prospective study of all the still births and early neonatal deaths in KMCTH during the two year period from November 2003 to October 2005. Details of each perinatal death were filled in the standard perinatal death audit forms of the Department of Pediatrics, KMCTH. Perinatal deaths were analyzed according to maternal characteristics like maternal age, parity, type of delivery and fetal characteristics like sex, birth weight and gestational age and classify neonatal deaths according to Wigglesworth's classification and comparison made with earlier similar study. Results: Out of the 1517 total births in the two year period, 22 were still births (SB) and 10 were early neonatal deaths (ENND). Out of the 22 SB, two were of < 1 kg in weight and out of 10 ENND, one was of <1 kg. Thus, perinatal mortality rate during the study period was 19.1 and extended perinatal mortality rate was 21.1 per 1000 births. The important causes of perinatal deaths were extreme prematurity, birth asphyxia, congenital anomalies and associated maternal factors like antepartum hemorrhage and most babies were of very low birth weight. According to Wigglesworth's classification, 43.8% of perinatal deaths were in Group I, 12.5% in Group II, 28.1% in Group III, 12.5% in Group IV and 12.5% in Group V. Discussion: The perinatal death audit done in KMCTH for 1 year period from September 2002 to August 2003 showed perinatal mortality rate of 30.7 and extended perinatal mortality rate of 47.9 per 1000 births. There has been a significant reduction in the perinatal mortality rate in the last 2 years at KMCTH. Main reasons for improvement in perinatal mortality rate were improvement in care of both the mothers and the newborns and the number of births have also increased significantly in the last 2 years without appropriate increase in perinatal deaths. Conclusion: Good and regular antenatal care, good care at the time of birth including appropriate and timely intervention and proper care of the sick neonates are important in reducing perinatal deaths. Prevention of preterm births, better care and monitoring during the intranatal period and intensive care of low birth weight babies would help in further reducing perinatal deaths. Key words: Perinatal mortality rate (PMR), still births, early neonatal death (ENND), Total perinatal death (PND).     

The ALK inhibitor ASP3026 eradicates NPM-ALK+ T-cell anaplastic large-cell lymphoma in vitro and in a systemic xenograft lymphoma model

NPM-ALK⁺ T-cell anaplastic large-cell lymphoma (ALCL) is an aggressive type of cancer. Standard treatment of NPM-ALK⁺ ALCL is CHOP polychemotherapy. Although patients initially respond favorably to CHOP, resistance, relapse, and death frequently occur. Recently, selective targeting of ALK has emerged as an alternative therapeutic strategy. ASP3026 is a second-generation ALK inhibitor that can overcome crizotinib resistance in non-small cell lung cancer, and is currently being evaluated in clinical trials of patients with ALK⁺ solid tumors. However, NPM-ALK⁺ ALCL patients are not included in these trials. We studied the effects of ASP3026 on NPM-ALK⁺ ALCL cell lines in vitro and on systemic lymphoma growth in vivo. ASP3026 decreased the viability, proliferation, and colony formation, as well as induced apoptotic cell death of NPM-ALK⁺ ALCL cells. In addition, ASP3026 significantly reduced the proliferation of 293T cells transfected with NPM-ALK mutants that are resistant to crizotinib and downregulated tyrosine phosphorylation of these mutants. Moreover, ASP3026 abrogated systemic NPM-ALK⁺ ALCL growth in mice. Importantly, the survival of ASP3026-treated mice was superior to that of control and CHOP-treated mice. Our data suggest that ASP3026 is an effective treatment for NPM-ALK⁺ ALCL, and support the enrollment of patients with this lymphoma in the ongoing clinical trials.     

Investigation of Solid Dosage Form Components Interaction Using Orthogonal Techniques- Discovery of New Forms of Sodium Stearyl Fumarate

Physical or chemical interactions between drug product (DP) components can occur during manufacturing and/or upon storage; and may alter DP shelf life and performance. In this work a new Powder X-ray Diffraction (PXRD) peak was observed in DP under accelerated storage conditions. Due to the complex drug product matrix (including API, polymer, fillers, super disintegrant and lubricant), it was challenging to pinpoint the component(s) responsible for the new peak. In addition to PXRD, other orthogonal techniques including Differential Scanning Calorimetry (DSC), thermogravimetric analysis (TGA), dynamic vapor sorption (DVS), Solid State Nuclear Magnetic Resonance (SSNMR) and Infrared (IR) spectroscopy were employed in this investigation to understand the root cause mechanistically. Specifically, multi nuclei SSNMR (¹H, ²³Na, ¹³C) was instrumental in delineating the components of the matrix. We identified the root cause to be an acid base reaction occurring in the DP, whereby sodium ion in sodium stearyl fumarate (SSF) is replaced by proton leading to SSF form conversion. We also identified commercially available SSF to be a hydrate that can dehydrate to an anhydrous form upon heating. In general, the same techniques can be used to investigate interactions of any multi component solid dosage forms.