Osler Centenary Papers: Osler as medical leader.

The Canadian physician Sir William Osler is a key figure in the history of modern medicine. He encouraged lifelong learning for doctors, starting with bedside teaching. Contemporary with Old World figures such as Pasteur in Paris and Virchow in Berlin, he played a major role in raising awareness among clinicians of the importance of the scientific basis for the practice of medicine. He championed a rational approach to treatment and did much to encourage avoidance of 'unnecessary drugging' by prescribers. He is credited with playing a key role in improving education of medical students and postgraduate education of doctors, with important benefits for the care of hospital patients. He also had a major influence on his medical colleagues through founding and leading medical societies. A century on from his death in December 1919, his specific contributions and how he achieved them are not well known. The aim of this article is to consider the evidence that Osler was an influential medical leader and to reflect on the extent to which the achievements which resulted from his leadership are relevant to modern clinical medicine. Questions of interest include his leadership style, what made for his success as a leader, his medical achievements both in North America and in England, his own insight into leadership and how he was viewed by his peers.

Barriers to reporting of adverse drugs reactions: a cross sectional study among community pharmacists in United Kingdom

Background: Adverse Drug Reactions (ADRs) are a major public health problem. Prompt reporting of suspected ADRs is fundamental in the post-marketing surveillance of medicines and helps in ensuring medicine safety. However, fewer ADRs are reported in general and in particular by community pharmacists. There is limited knowledge about the factors which are preventing community pharmacists in the UK from reporting an ADR. Objectives: To identify the barriers to ADR reporting among community pharmacists practicing in the UK. Methods: A cross sectional study using a 25-items questionnaire (both online and paper based) including 10 barriers to ADR reporting was conducted from 1st April 2012 to September 2012. Community pharmacists practicing in the West Midlands, UK, were approached for the participation in this study. Chi-Square and regression were applied to identify covariates for the barriers to ADR reporting. A significant value of 0.05 was assigned for analysis. Results: Of the 230 invited community pharmacists, 138 pharmacists responded (response rate 60%). The median age of respondents was 31 years. All pharmacists reported that they would report both serious and mild ADRs from drugs with black triangle among children as well as adults. About 95% (n=131) of the pharmacists were familiar with the paper based ADR reporting system. Store-based pharmacists were more likely to be more confident about which ADRs to report [0.680, 95% Confidence Interval 0.43-3.59]. Lack of time 46.4% (n=64), and pharmacists perception that ADR is not serious enough to report (65.2%; n=90) were identified as barriers to ADR reporting. Majority 63.0% (n=87) of the pharmacists identified training and information about what to report and access to Information Technology (IT) (For example access to internet connection) 61.6% (n=85) as facilitators to ADR reporting process. Conclusion: Lack of time and ADRs considered not serious enough by pharmacists to report were barriers to ADR reporting. Further training and education about the types of ADRs to be reported can help to improve the reporting of ADRs (AU)

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Influx transporter variants as predictors of cancer chemotherapy-induced toxicity: systematic review and meta-analysis.

AIM: Chemotherapeutic agents have been shown to increase lung patient survival, however their use may be limited by their serious adverse effects. We aimed to assess int impact of pharmacogenetic variation of influx transporters on inter-individual patient variation in adverse drug reactions. PATIENTS & METHODS: We conducted a meta-analysis and systemic review and identified 16 publications, totaling 1510 patients, to be eligible for review. RESULTS: Meta-analysis showed east-Asian patients expressing SLCO1B1 521T>C or 1118G>A to have a two- to fourfold increased risk of irinotecan-induced neutropenia but not diarrhea. American patients, expressing SLC19A1 IVS2(4935) G>A, were further associated with pemetrexed/gemcitabine-induced grade 3+ leukopenia. CONCLUSION: Future studies should look to robust validation of SLCO1B1 and SLC19A1 as prognostic markers in the management of lung cancer patients.

Efflux transporter variants as predictors of drug toxicity in lung cancer patients: systematic review and meta-analysis.

UNLABELLED: Chemotherapeutic drugs are underutilized in lung cancer management due in part to serious adverse drug reactions (ADRs). AIM: With studies revealing an association between interindividual patient ADR variation and efflux transporter variants, we carried out a meta-analysis and systemic review, in order to highlight current knowledge regarding the strength of association between efflux transporter SNPs variants and chemotherapeutic-drug induced ADRs. MATERIALS & METHODS: Papers were sourced from MEDLINE, Cochrane Library, CINHL, EMBASE, Web of Knowledge, Scopus. The Cochrane Collaboration Risk of Bias Tool v13 was used to evaluate six types of bias domains for each of the publications reviewed. RESULTS: Twenty-five publications comprising three randomised control trials, two retrospective case-controls and 20 clinical observation studies, totalling 3578 patients, were deemed eligible for review. Of the known efflux drug transporters, we report findings on the ABC members ABCB1, ABCC1, ABCC2, ABCG2, ABCA1, ABCC4 and ABCC5. Meta-analysis showed an decreased risk of irinotecan-induced neutropenia in patients expressing ABCB1 2677G>T/G (odds ratio [OR]: 0.24; 95% CI: 0.1-0.59; p = 0.002) but increased risk for ABCC2 3972T>T (OR: 1.67; 95% CI: 1.01-2.74; p = 0.04). ABCG2 34G>A was associated with a threefold increased risk of irinotecan-induced diarrhea (95% CI: 1.00-6.24; p = 0.05). CONCLUSION: The majority of studies have identified a role for variants in effluxdrug transporters in contributing to lung cancer treatment-associated ADRs. However, for implementation of use of these transporter genetic variants as prognostic markers for ADR risk, future studies must incorporate larger patient numbers.

Using companion and coupled diagnostics within strategy to personalize targeted medicines.

Regulatory authorities expect the pharmaceutical and biotechnology industries to accelerate their development of companion diagnostics and companion therapeutics towards the goal of personalized medicine, and expect health services to fund, prescribers to adopt and patients to accept these new therapeutic technologies. Expected benefits from more systematic development of combination products (companion diagnostic and its companion therapeutic) are expected to include safer and improved clinical and cost-effective use of medicines, more efficient patient selection for clinical trials, more cost-effective treatment pathways for health services, and a more profitable approach for drug developers. This review discusses challenges to timely development of companion diagnostics and provides case studies of single and multiple protein and genetic biomarkers of clinical response and risk of adverse drug effects.