Pricing of in-patent pharmaceuticals in the Middle East and North Africa: is external reference pricing implemented optimally?

In this paper we outline and compare pharmaceutical pricing policies for in-patent prescription pharma- ceuticals with emphasis on external reference pricing (ERP) in eleven countries across the Middle East and North Africa (MENA) region and explore possible improvements in their pricing systems. Primary and secondary evidence was used to inform our analysis. Comparative analysis of ERP systems across countries followed an analytical framework distilling ERP into twelve salient features, while ERP system performance was benchmarked against a framework of best practice principles across (a) objectives and scope, (b) administration and operations, (c) methods used, and (d) implementation. Results suggest that ERP is the dominant pricing method for in-patent pharmaceuticals. Although several good practice cases were identified, none of the eleven countries satisfy all best practice principles. ERP basket sizes vary sig- nificantly and are commonly composed using geographical proximity and low-price countries as criteria. Nine countries do not use the mean or median prices, but resort to using the lowest. Exchange rate fluc- tuations are routinely used to arrive at price reductions in local currency. Significant opportunities exist for MENA countries to develop their ERP regimes to achieve greater compliance with best practice princi- ples. Over the short-term, incremental changes could be implemented to several ERP salient features and can be achieved relatively easily, thereby enhancing the functionality and performance of national ERP systems. Countries in the region can also focus on the development of explicit value assessment systems, and minimize their dependence on ERP over the longer-term

Visual translations of ancient heritage – re-contextualising ancient European script through contemporary visual communication methods and media

The purpose of this practice led research project was to apply a design anthropology approach to the visual re-contexualisation of ancient European script, using contemporary visual communication practices and media strategies in order to explore opportunities for creative engagement with archaeological knowledge. Archaeology can grant us access to our history by allowing us encounters with remnants of the past, but how these remnants are translated for us, read by us and what we believe that they tell us is intimately tied up with the context of our own contemporary culture. What role can contemporary visual communication practices play in communicating archaeological knowledge to young audiences by overcoming potential aesthetic or media based barriers. Like visual design, ancient script deals with visual presentation of meaning and is directly relevant in relation to Frutiger’s interest in archetypes and Neurath’s Isotype collection. Under the guidance of a specialist Archaeologist advisor and two Design researchers, a team of visual communication designers used their individual creative practices to visually re-contextualise the oldest deciphered and un-deciphered European scripts of Linear A and Linear B, with the goal of engaging a teenage audience. The aim was to explore how visual communication can facilitate archaeological heritage experiences that explore a multi-layered narrative through co-creative and democratised strategies of engagement. This investigation raises not only the question of the overall relevance of creative re-contextualisation of archaeological heritage in engaging new audiences, but also to what extent this re-contextualisation can be allowed to undermine the ‘authenticity’ of the source material

Analysis of Death Receptor 5 and Caspase-8 Expression in Primary and Metastatic Head and Neck Squamous Cell Carcinoma and Their Prognostic Impact

Death receptor 5 (DR5) and caspase-8 are major components in the extrinsic apoptotic pathway. The alterations of the expression of these proteins during the metastasis of head and neck squamous cell carcinoma (HNSCC) and their prognostic impact have not been reported. The present study analyzes the expression of DR5 and caspase-8 by immunohistochemistry (IHC) in primary and metastatic HNSCCs and their impact on patient survival. Tumor samples in this study included 100 primary HNSCC with no evidence of metastasis, 100 primary HNSCC with lymph node metastasis (LNM) and 100 matching LNM. IHC analysis revealed a significant loss or downregulation of DR5 expression in primary tumors with metastasis and their matching LNM compared to primary tumors with no evidence of metastasis. A similar trend was observed in caspase-8 expression although it was not statistically significant. Downregulation of caspase-8 and DR5 expression was significantly correlated with poorly differentiated tumors compared to moderately and well differentiated tumors. Univariate analysis indicates that, in HNSCC with no metastasis, higher expression of caspase-8 significantly correlated with better disease-free survival and overall survival. However, in HNSCC with LNM, higher caspase-8 expression significantly correlated with poorer disease-free survival and overall survival. Similar results were also generated when we combined both DR5 and caspase-8. Taken together, we suggest that both DR5 and caspase-8 are involved in regulation of HNSCC metastasis. Our findings warrant further investigation on the dual role of caspase-8 in cancer development

Evaluation of Candidate Stromal Epithelial Cross-Talk Genes Identifies Association between Risk of Serous Ovarian Cancer and TERT, a Cancer Susceptibility “Hot-Spot”

We hypothesized that variants in genes expressed as a consequence of interactions between ovarian cancer cells and the host micro-environment could contribute to cancer susceptibility. We therefore used a two-stage approach to evaluate common single nucleotide polymorphisms (SNPs) in 173 genes involved in stromal epithelial interactions in the Ovarian Cancer Association Consortium (OCAC). In the discovery stage, cases with epithelial ovarian cancer (n = 675) and controls (n = 1,162) were genotyped at 1,536 SNPs using an Illumina GoldenGate assay. Based on Positive Predictive Value estimates, three SNPs—PODXL rs1013368, ITGA6 rs13027811, and MMP3 rs522616—were selected for replication using TaqMan genotyping in up to 3,059 serous invasive cases and 8,905 controls from 16 OCAC case-control studies. An additional 18 SNPs with Pper-allele<0.05 in the discovery stage were selected for replication in a subset of five OCAC studies (n = 1,233 serous invasive cases; n = 3,364 controls). The discovery stage associations in PODXL, ITGA6, and MMP3 were attenuated in the larger replication set (adj. Pper-allele≥0.5). However genotypes at TERT rs7726159 were associated with ovarian cancer risk in the smaller, five-study replication study (Pper-allele = 0.03). Combined analysis of the discovery and replication sets for this TERT SNP showed an increased risk of serous ovarian cancer among non-Hispanic whites [adj. ORper-allele 1.14 (1.04–1.24) p = 0.003]. Our study adds to the growing evidence that, like the 8q24 locus, the telomerase reverse transcriptase locus at 5p15.33, is a general cancer susceptibility locus

Computational analysis of antibody dynamics identifies recent HIV-1 infection.

CAPRISA, 2017.Abstract available in pdf

Feline low-grade alimentary lymphoma: an emerging entity and a potential animal model for human disease

Background: Low-grade alimentary lymphoma (LGAL) is characterised by the infiltration of neoplastic T-lymphocytes, typically in the small intestine. The incidence of LGAL has increased over the last ten years and it is now the most frequent digestive neoplasia in cats and comprises 60 to 75% of gastrointestinal lymphoma cases. Given that LGAL shares common clinical, paraclinical and ultrasonographic features with inflammatory bowel diseases, establishing a diagnosis is challenging. A review was designed to summarise current knowledge of the pathogenesis, diagnosis, prognosis and treatment of feline LGAL. Electronic searches of PubMed and Science Direct were carried out without date or language restrictions. Results: A total of 176 peer-reviewed documents were identified and most of which were published in the last twenty years. 130 studies were found from the veterinary literature and 46 from the human medicine literature. Heterogeneity of study designs and outcome measures made meta-analysis inappropriate. The pathophysiology of feline LGAL still needs to be elucidated, not least the putative roles of infectious agents, environmental factors as well as genetic events. The most common therapeutic strategy is combination treatment with prednisolone and chlorambucil, and prolonged remission can often be achieved. Developments in immunohistochemical analysis and clonality testing have improved the confidence of clinicians in obtaining a correct diagnosis between LGAL and IBD. The condition shares similarities with some diseases in humans, especially human indolent T-cell lymphoproliferative disorder of the gastrointestinal tract. Conclusions: The pathophysiology of feline LGAL still needs to be elucidated and prospective studies as well as standardisation of therapeutic strategies are needed. A combination of conventional histopathology and immunohistochemistry remains the current gold-standard test, but clinicians should be cautious about reclassifying cats previously diagnosed with IBD to lymphoma on the basis of clonality testing. Importantly, feline LGAL could be considered to be a potential animal model for indolent digestive T-cell lymphoproliferative disorder, a rare condition in human medicine

Catechol metabolism and glutamate uptake in the prefrontal cortex of subjects with schizophrenia: implications for cognitive function

© 2019 Dr. Georgia May ParkinMy thesis comprises of two projects, the first which investigates catechol-O-methyltransferase (COMT) protein levels by genotype (chapter 1 and 2), and the second which investigates excitatory amino acid transporter (EAAT)1 and EAAT2 and metabotropic glutamate receptor 5 mRNA levels (chapter 3) in the prefrontal cortex of subjects with schizophrenia. Project 1. COMT genotype has previously been associated with cognitive function; I hypothesized that COMT genotype would also be associated with differing levels of cortical COMT protein. Using western blotting, I measured protein levels of the two COMT protein isoforms, membrane bound (MB-) COMT and soluble (S-) COMT, as well as beta-actin protein levels, in Brodmann’s area (BA) 9 of 199 individuals, 119 of whom had psychiatric disorders. I have shown that levels of S-COMT protein vary with genotype at rs4818 and rs4680, but not rs737865 and rs165599 (rs4818 genotype: CC0.05), suggesting that this variation in protein level by genotype occurs even in the presence of cortical dysfunction. Project 2. EAAT1 and EAAT2 mediate glutamatergic neurotransmission and prevent glutamate excitotoxicity, through the perisynaptic binding and transportation of glutamate into glia. An Affymetrix™ microarray analysis which preceded my PhD studies found a 36% increase in EAAT1 mRNA levels in BA9 of subjects with schizophrenia. The aim of this chapter was to determine whether changes in EAAT1 and EAAT2 mRNA levels occur in other cortical regions from subjects with schizophrenia. I used quantitative PCR to compare mRNA levels of EAAT1, EAAT2 and mGluR5 across post-mortem BA10, BA44 and BA46 of subjects with schizophrenia (n=20) and non-psychiatric controls (n=18). Reactions were measured in triplicate with results normalised to the geometric mean of two stably expressed reference genes – transcription factor B1, mitochondrial (TFB1M) and S-phase kinase-associated protein 1A (SKP1A). EAAT1 mRNA levels were significantly higher in BA10 (U=67, p=0.0006) and BA44 (U=68, p=0.0007), and EAAT2 mRNA levels w¬ere significantly higher in BA10 (U=85, p=0.0047), with mRNA levels of both transporters showing no change in BA46 (EAAT1: U=164, p=0.65; EAAT2: U=146, p=0.33), of subjects with schizophrenia compared to age and sex matched controls. My data suggests that region-specific increases in cortical EAAT1 and EAAT2 mRNA levels are involved in the pathophysiology of schizophrenia. These findings support a role for disrupted glutamate uptake in schizophrenia and may have important implications for treatment of the disorder