Relevance of pharmacogenomics for developing countries in Europe : implementation in the Maltese population

Pharmacogenomics is a promising new discipline that can realize personalized treatment for patients suffering from many common diseases, particularly those with multiple treatment modalities. Recent advances in the deciphering of the human genome sequence and high throughput genotyping technology have led to the reduction of the overall genotyping costs and enabled the inclusion of genotype-related dosing recommendations into drug package inserts, hence allowing the integration of pharmacogenomics into clinical practice. Although, pharmacogenomics gradually assumes an integral part in mainstream medical practice in developed countries, many countries, particularly from the developing world, still do not have access either to the knowledge or the resources to individualize drug treatment. The PharmacoGenetics for Every Nation Initiative (PGENI) aims to fill in this gap, by making pharmacogenomics globally applicable, not only by defining population-specific pharmacogenomic marker frequency profiles and formulating country-specific recommendations for drug efficacy and safety but also by increasing general public and healthcare professionals’ awareness over pharmacogenomics and genomic medicine. This article highlights the PGENI activities in Europe and its implementation in the Maltese population, in an effort to make pharmacogenomics readily applicable in European healthcare systems.peer-reviewe

Delayed Intraventricular Hemorrhage following a Ventriculoperitoneal Shunt Placement: Exploring the Surgical Anatomy of a Rare Complication

Ventriculoperitoneal shunt (VPS) placement is one of the commoner neurosurgical procedures worldwide. The purpose of this article is to report a case of delayed intraventricular hemorrhage (IVH) following a VPS and to review the literature regarding anatomic factors that could potentially explain this rare complication. A 78-year-old man with normal pressure hydrocephalus, who underwent an uneventful right VPS placement, suffered from a catastrophic isolated IVH five days later. The reported cases of delayed intracerebral hemorrhage (ICH) following VPS are rare and those with IVH are even rarer. Potential factors of surgical anatomy that could cause delayed ICH/IVH following a VPS procedure include erosion of vasculature by catheter cannulation, multiple attempts at perforation, puncture of the choroid plexus, improper placement of the tubing within the brain parenchyma, VPS system revision, venous infarction, vascular malformations, head trauma, and brain tumors. Other causes include generalized convulsion, VPS system malfunction, increased intracranial or blood pressure, sudden intracranial hypotension, and bleeding disorders. According to the current literature, our case is the first reported delayed isolated IVH after a VPS placement so far. Neurosurgeons should be aware of the delayed ICH/IVH as a rare, potentially fatal complication of VPS, as well as of its risk factors

A(1)ATVar: A Relational Database of Human SERPINA1 Gene Variants Leading to alpha(1)-Antitrypsin Deficiency and Application of the VariVis Software

We have developed a relational database of human SERPINA1 gene mutations, leading to a,antitrypsin (AAT) deficiency, called A(1)ATVar, which can be accessed over the World Wide Web at www.goldenhelix.org/A1ATVar. Extensive information has been extracted from the literature and converted into a searchable database, including genotype information, clinical phenotype, allelic frequencies for the commonest AAT variant alleles, methods of detection, and references. Mutation summaries are automatically displayed and user-generated queries can be formulated based on fields in the database. A separate module, linked to the FINDbase database for frequencies of inherited disorders allows the user to access allele frequency information for the three most frequent AAT alleles, namely PiM, PiS, and PiZ. The available experimental protocols to detect AAT variant alleles at the protein and DNA levels have been archived in a searchable format. A visualization tool, called VariVis, has been implemented to combine A(1)ATVar variant information with SERPINA1 sequence and annotation data. A direct data submission tool allows registered users to submit data on novel AAT variant alleles as well as experimental protocols to explore SERPINA1 genetic heterogeneity, via a password-protected interface. Database access is free of charge and there are no registration requirements for querying the data. The A(1)ATVar database is the only integrated database on the Internet offering summarized information on AAT allelic variants and could be useful not only for clinical diagnosis and research on AAT deficiency and the SERPINA1 gene, but could also serve as an example for an all-in-one solution for locus-specific database (LSDB) development and curation. Hum Mutat 30, 308-313, 2009

Genomic medicine without borders: which strategies should developing countries employ to invest in precision medicine? A new "fast-second winner" strategy

Genomic medicine has greatly matured in terms of its technical capabilities, but the diffusion of genomic innovations worldwide faces significant barriers beyond mere access to technology. New global development strategies are sorely needed for biotechnologies such as genomics and their applications toward precision medicine without borders. Moreover, diffusion of genomic medicine globally cannot adhere to a “one-size-fits-all-countries” development strategy, in the same way that drug treatments should be customized. This begs a timely, difficult but crucial question: How should developing countries, and the resource-limited regions of developed countries, invest in genomic medicine? Although a full-scale investment in infrastructure from discovery to the translational implementation of genomic science is ideal, this may not always be feasible in all countries at all times. A simple “transplantation of genomics” from developed to developing countries is unlikely to be feasible. Nor should developing countries be seen as simple recipients and beneficiaries of genomic medicine developed elsewhere because important advances in genomic medicine have materialized in developing countries as well. There are several noteworthy examples of genomic medicine success stories involving resource-limited settings that are contextualized and described in this global genomic medicine innovation analysis. In addition, we outline here a new long-term development strategy for global genomic medicine in a way that recognizes the individual country's pressing public health priorities and disease burdens. We term this approach the “Fast-Second Winner” model of innovation that supports innovation commencing not only “upstream” of discovery science but also “mid-stream,” building on emerging highly promising biomarker and diagnostic candidates from the global science discovery pipeline, based on the unique needs of each country. A mid-stream entry into innovation can enhance collective learning from other innovators' mistakes upstream in discovery science and boost the probability of success for translation and implementation when resources are limited. This à la carte model of global innovation and development strategy offers multiple entry points into the global genomics innovation ecosystem for developing countries, whether or not extensive and expensive discovery infrastructures are already in place. Ultimately, broadening our thinking beyond the linear model of innovation will help us to enable the vision and practice of genomics without borders in both developed and resource-limited settings