Impact of pharmaceutical price controls on the cost of cardiovascular drugs: does essentiality matter?

ABSTRACT

Background

With the goal of improving the affordability of medicines, governments across the globe have instituted various forms of price controls. Since 2013, India has been regulating the prices of drugs included in its national list of essential medicines (NLEM). Here we evaluate the cost variations among available cardiovascular drugs and perform cost-analysis comparing essential and non-essential drugs.     

Nutritional and Functional Properties of Defatted,Debittered and Off-Flavour Free High Protein Guar (Cyamopsis tetragonoloba) Meal Flour

Proceedings of the National Academy of Sciences, India Section B: Biological Sciences - A process for the preparation of defatted, debittered and off-flavour free guar meal flour (GMF) with high...     

Molecular characterisation of TP53 mutated squamous cell carcinomas of the lung to identify putative targets for therapy

Personalised cancer treatment depends on identification of therapeutically relevant biological subgroups of patients for assessing effect of treatment and to discover new therapeutic options. By analyses in heterogeneous patient populations, the effects may be lost in noise. Squamous cell carcinoma of the lung is a major killer worldwide. Despite recent advances, mortality is high and response to therapies varies greatly from patient to patient. Target search in biologically relevant subgroups may identify treatment options not so far discovered. A total of 198 patients undergoing surgery for squamous cell carcinomas of the lung were included in the study. The tumours were analysed for copy number alterations (n = 152) and gene expression from tumour (n = 188) and normal lung (n = 21), with both data levels present in 140 patients. We studied alterations in tumours harbouring mutations in TP53 and in previously published gene expression subtypes. Genes with consistent alterations in both genomic levels were identified as putative biomarkers. Results were validated in TCGA. The most convincing biomarker in TP53 mutated squamous cell carcinomas of the lung was BIRC5 with amplification in 36% of mutated samples, 5% in wild-type samples and a 17%-fold change of expression between TP53 mutated tumours and normal lung tissue. BIRC5 was significantly altered in the classical and primitive subtypes. We suggest BIRC5 as a putative predictive biomarker and putative druggable target in squamous cell lung carcinomas harbouring TP53 mutation or classified as classical and primitive subtypes.     

Assessment of health systems guidance using the Appraisal of Guidelines for Research and Evaluation – Health Systems (AGREE-HS) instrument

Health systems guidance (HSG) documents contain systematically developed statements or recommendations intended to address a health system challenge. The concept of HSG is fairly new and considerable effort has been undertaken to build tools to support the contextualization of recommendations. One example is the Appraisal of Guidelines for REsearch and Evaluation - Health Systems (AGREE-HS), created by international stakeholders and researchers, to assist in the development, reporting and evaluation of HSG. Here, we present the quality appraisal of 85 HSG documents published from 2012 to 2017 using the AGREE-HS. The AGREE-HS consists of five items (Topic, Participants, Methods, Recommendations, and Implementability), which are scored on a 7-point response scale (1=lowest quality; 7=highest quality). Overall, AGREE-HS item scores were highest for the 'Topic' and 'Recommendations' items (means above the mid-point of 4), while the 'Participants', 'Methods', and 'Implementability' items received lower scores. Documents without a specific health focus and those authored by the National Institute for Health and Care Excellence group, achieved higher AGREE-HS overall scores than their comparators. No statistically significant changes in overall scores were observed over time. This is the first time that the AGREE-HS has been applied, providing a current quality status report of HSG and identifying where improvements in HSG development and reporting can be made.     

Outcomes of Patients with Recurrent and Refractory Lymphoma Undergoing Allogeneic Hematopoietic Cell Transplantation with BEAM Conditioning and Sirolimus- and Tacrolimus-Based GVHD Prophylaxis

The current standard of care for patients with Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) is high-dose conditioning followed by autologous stem cell transplantation (ASCT). For some patients (ie, those with highest-risk disease, insufficient stem cell numbers after mobilization, or bone marrow involvement) allogeneic hematopoietic cell transplantation (alloHCT) offers the potential for cure. However, the majority of patients undergoing alloHCT receive reduced-intensity conditioning as a preparative regimen, and studies assessing outcomes of patients after alloHCT with myeloablative conditioning are limited. In this retrospective study, we reviewed outcomes of 22 patients with recurrent and refractory NHL who underwent alloHCT with myeloablative BEAM conditioning and received tacrolimus/sirolimus as graft-versus-host disease (GVHD) prophylaxis at City of Hope between 2005 and 2018. With a median follow-up of 2.6 years (range, 1.0 to 11.2 years), the probabilities of 2-year overall survival and event-free survival were 58.3% (95% confidence interval [CI], 35.0% to 75.8%) and 45.5% (95% CI, 24.4% to 64.3%), respectively. The cumulative incidence of grade II to IV acute GVHD was 45.5% (95% CI, 23.8% to 64.9%), with only 1 patient developing grade IV acute GVHD. However, chronic GVHD was seen in 55% of the patients (n?=?12). Of the 22 eligible patients, 2 had undergone previous ASCT and 2 had undergone previous alloHCT. Both patients with previous ASCT developed severe regimen-related toxicity. Patients who underwent alloHCT with chemorefractory disease had lower survival rates, with 1-year OS and EFS of 44.4% and 33.0%, respectively. In conclusion, alloHCT with a BEAM preparative regimen and tacrolimus/sirolimus-based GVHD should be considered as an alternative option for patients with highest-risk lymphoma whose outcomes are expectedly poor after ASCT.