Precision medicine : Its application in clinical investigation and practice innovation

His research focuses on personalised medicine in order to optimise drug efficacy and minimise toxicity,move discoveries from the lab to the clinic, and from clinic to appication.Universidad de Málaga. Campus de Excelencia Internacional Andalucia Tech

Direct oral anticoagulants versus warfarin: is new always better than the old?

About 1.4 British million people are at risk of strokes due to non-valvular atrial fibrillation (AF) necessitating long-term anticoagulation. The vitamin K antagonist, warfarin, has a long half-life and narrow therapeutic range necessitating regular monitoring and is a common cause of iatrogenic hospital admission. Direct-acting oral anticoagulants (DOACs), dabigatran, rivaroxaban, apixaban and edoxaban are not required to have monitoring but are sensitive to changes in renal function and are associated with poorer adherence. There are good grounds to believe that DOACs are not always superior to warfarin in routine practice particularly with an older population. Much higher levels of therapeutic effectiveness can be achieved using a simple genotype guidance to identify those who are highly sensitive and by adoption of home monitoring. These adjustments could make warfarin the preferred drug for most people and would reduce the dramatic rise in health service expenditure

Warfarin: The End or the End of One Size Fits All Therapy?

Oral anticoagulants are required for both treatment and prophylaxis in many different diseases. Clinicians and patients now have a choice of oral anticoagulants, including the vitamin K antagonists (of which warfarin is the most widely used and is used as the exemplar in this paper), and direct oral anticoagulants (DOACs: dabigatran, apixaban, rivaroxaban, and edoxaban). This paper explores the recent advances and controversies in oral anticoagulation. While some commentators may favour a complete switchover to DOACs, this paper argues that warfarin still has a place in therapy, and a stratified approach that enables the correct choice of both drug and dose would improve both patient outcomes and affordability

Cost effectiveness analysis of HLA-B*58:01 genotyping prior to initiation of allopurinol for gout

Objective. To determine whether prospective testing forHLA-B*58:01, as a strategy to prevent seriousadverse reactions to allopurinol in patients with gout, is cost-effective from the perspective of the NationalHealth Service in the UK. Methods. A systematic review and meta-analysis for the association ofHLA-B*58:01with cutaneous andhypersensitivity adverse drug reactions informed a decision analytic and Markov model to estimate lifetimecosts and outcomes associated with testingvsstandard care (with febuxostat prescribed for patients whotest positive). Scenario analyses assessed alternative treatment assumptions and patient populations. Results. The number of patients needed to test to prevent one case of adverse drug reaction was 11 286(95% central range (CR): 2573, 53 594). Cost and quality-adjusted life-year (QALY) gains were small, £103(95% CR: £98, £106) and 0.0023 (95% CR: 0.0006, 0.0055), respectively, resulting in an incrementalcost-effectiveness ratio (ICER) of £44 954 per QALY gained. The probability of testing being cost-effectiveat a threshold of £30 000 per QALY was 0.25. Reduced costs of testing or febuxostat resulted in an ICERbelow £30 000 per QALY gained. The ICER for patients with chronic renal insufficiency was £38 478 perQALY gained. Conclusion. Routine testing forHLA-B*58:01in order to reduce the incidence of adverse drug reactions inpatients being prescribed allopurinol for gout is unlikely to be cost-effective in the UK; however testing isexpected to become cost-effective with reductions in the cost of genotyping, and with the future avail-ability of cheaper, generic febuxosta

Associations between occupation and heavy alcohol consumption in UK adults aged 40-69 years: a cross-sectional study using the UK Biobank

BACKGROUND: Understanding the relationship between occupation and alcohol use offers opportunities to provide health promotion programmes based on evidence of need. We aimed to determine associations between occupation and heavy alcohol consumption in working individuals aged 40-69 years. METHODS: A cross-sectional study was conducted using 100,817 people from the UK Biobank: 17,907 participants categorised as heavy drinkers, defined as > 35 units/week for women and > 50 units/week for men, and 82,910 drinking controls. Prevalence ratios (PRs) and 95% CIs were calculated for gender-specific heavy drinking in 353 occupations using Standard Occupational Classification, V.2000. RESULTS: Seventy-seven occupations were associated with level of alcohol consumption in drinkers. The largest ratios for heavy drinkers were observed for publicans and managers of licenced premises (PR = 2.81, 95%CI 2.52-3.14); industrial cleaning process occupations (PR = 2.09, 1.33-3.28); and plasterers (PR = 2.07, 1.66-2.59). Clergy (PR = 0.20, 0.13-0.32); physicists, geologists and meteorologists (PR = 0.40, 0.25-0.65); and medical practitioners (PR = 0.40, 0.32-0.50) were least likely to be heavy drinkers. There was evidence of gender-specific outcomes with the proportion of jobs associated with heavy drinking accounted for by skilled trade occupations being 0.44 for males and 0.05 for females, and 0.10 for males and 0.40 for females when considering managers and senior officials. CONCLUSIONS: In the largest study of its kind, we found evidence for associations between a wider variety of occupations and the risk of heavy alcohol consumption than identified previously, particularly in females, although causality cannot be assumed. These results help determine which jobs and broader employment sectors may benefit most from prevention programmes

Repurposing Statins for Renal Protection: Is It a Class Effect?

There has been a great deal of excitement regarding the potential benefits of statins beyond their lipid-lowering effect, and repurposing them for other indications. In this commentary, we evaluate the role of statins in protecting the kidneys, with a focus on three areas: cardiac surgery, contrast-induced nephropathy, and aminoglycoside-induced nephrotoxicity

Evidence to support inclusion of pharmacogenetic biomarkers in randomised controlled trials

Pharmacogenetics and biomarkers are becoming normalised as important technologies to improve drug efficacy rates, reduce the incidence of adverse drug reactions, and make informed choices for targeted therapies. However, their wider clinical implementation has been limited by a lack of robust evidence. Suitable evidence is required before a biomarker’s clinical use, and also before its use in a clinical trial. We have undertaken a review of five pharmacogenetic biomarker-guided randomised controlled trials (RCTs) and evaluated the evidence used by these trials to justify biomarker inclusion. We assessed and quantified the evidence cited in published rationale papers, or where these were not available, obtained protocols from trial authors. Very different levels of evidence were provided by the trials. We used these observations to write recommendations for future justifications of biomarker use in RCTs and encourage regulatory authorities to write clear guidelines