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Contains fulltext : 296203.pdf (Publisher’s version ) (Open Access), INTRODUCTION: Clinical practice guidelines (CPGs) are a powerful instrument to ensure evidence-based practice in clinical diagnostics and disease management. As knowledge about the impact of sex and gender on health and disease is emerging, the need for its transfer into clinical practice is becoming more urgent. However, a systematic evaluation of the incorporation of sex-related and gender-related knowledge into CPGs in Europe is currently not available. This systematic review will fill this gap. We will analyse the operationalisation of sex and gender in internal medicine CPGs in Europe and the translation of this information into tailored recommendations. The results will offer a baseline assessment to inform prospective sex-sensitive and gender-sensitive guideline development. METHODS AND ANALYSIS: CPGs published by European internal medicine guidelines will be analysed according to a pre-established analysis framework. CPGs will be identified by a two-step approach, that is, through direct contact with the organisations and by a PubMed search, to ensure capture of all relevant guidelines. Prespecified keywords will be employed to identify the representation of sex-related and gender-related content throughout the CPGs. Structured data will be collected through machine-assisted text mining. Identified texts will then be manually reviewed by two independent coders using a specifically developed checklist. ETHICS AND DISSEMINATION: This study does not require approval by an ethics board. It will provide an overview of sex and gender considerations in European CPGs in the field of internal medicine regarding the time frame 2012-2022.

Item does not contain fulltext, Sex and gender play a pivotal role in health and disease. Differences can be identified in symptoms, biomarkers, lifetime experiences of diseases, incidence, prevalence, therapeutic options, health-related behavior, and resiliency. However, awareness of sex and gender differences in medicine is still limited. Systematic implementation of sex and gender-sensitive research is not yet the norm, resulting in gaps in evidence especially in the diagnosis and treatment of diseases in women. For decades research has predominantly included male persons and animals, leading to a lack of information about symptoms in female individuals or the classification of their symptoms as "atypical". Currently, the inclusion of female participants in clinical marketing access trials is mandatory. However, this does not automatically translate into sex-disaggregated analyses potentially limiting the discovery of sex-specific targeted therapeutic schemes. Consistent consideration of sex and gender in planning, conducting, analyzing, and dissemination of pharmacological research projects is an important prerequisite for closing the gender data gap. Targeted implementation strategies might help to include sex and gender aspects in different parts of the health system and thereby support the improvement of health care for all patients. Health economic aspects could be a further drive for the implementation of sex- and gender-sensitive medicine.The current chapter focuses on the role of sex and gender in biomedical research and, consequently, their potential role in pharmacology. We will explore the commonly used terminology in the field, the historical development of sex and gender-sensitive medicine (SGSM), the relevance of sex and gender to research and clinical practice and conclude with an outlook on future developments in the field.

Item does not contain fulltext, Sex- and gender-sensitive medicine has evolved from a feminist approach into an innovative cross-cutting approach to doing medicine. In the present chapter we define what sex and gender are in the context of biomedical research and describe the history of the development of this scientific approach. Looking back at crucial events in the U.S.A., Canada and Europe, we will outline how a structural framework has been established, ready to be filled with clinical and applied knowledge and to change the practice of medicine for decades to come.

The International Tamoxifen Pharmacogenomics Consortium was established to address the controversy regarding cytochrome P450 2D6 (CYP2D6) status and clinical outcomes in tamoxifen therapy. We performed a meta-analysis on data from 4,973 tamoxifen-treated patients (12 globally distributed sites). Using strict eligibility requirements (postmenopausal women with estrogen receptor-positive breast cancer, receiving 20 mg/day tamoxifen for 5 years, criterion 1), CYP2D6 poor metabolizer status was associated with poorer invasive disease-free survival (IDFS: hazard ratio = 1.25; 95% confidence interval = 1.06, 1.47; P = 0.009). However, CYP2D6 status was not statistically significant when tamoxifen duration, menopausal status, and annual follow-up were not specified (criterion 2, n = 2,443; P = 0.25) or when no exclusions were applied (criterion 3, n = 4,935; P = 0.38). Although CYP2D6 is a strong predictor of IDFS using strict inclusion criteria, because the results are not robust to inclusion criteria (these were not defined a priori), prospective studies are necessary to fully establish the value of CYP2D6 genotyping in tamoxifen therapy., Funding Agencies:National Institutes of Health (National Institute of General Medical Sciences)National Institutes of Health (National Cancer Institute)National Institutes of Health (National Institute of Child Health and Human Development)Breast Cancer Research (Scotland) Tayside Tissue Bank California Breast Cancer Research Program Cancer Research UK Deutsches Krebsforschungszentrum, Heidelberg, Germany Robert Bosch Foundation, Stuttgart, Germany Marie Curie Initial Training Network "FightingDrugFailure" GrantStichting Emmanuel van der Schueren (scientific partner of the Vlaamse Liga tegen Kanker) National Project for Personalized Genomic Medicine, Ministry for Health & Welfare, Republic of Korea Deutsche Forschungsgemeinschaft, Germany

1 december 2011, Item does not contain fulltext, Massively parallel pyrosequencing allows sensitive deep sequencing to detect molecular aberrations. Thus far, data are limited on the technical performance in a clinical diagnostic setting. Here, we investigated as an international consortium the robustness, precision and reproducibility of amplicon next-generation deep sequencing across 10 laboratories in eight countries. In a cohort of 18 chronic myelomonocytic leukemia patients, mutational analyses were performed on TET2, a frequently mutated gene in myeloproliferative neoplasms. Additionally, hotspot regions of CBL and KRAS were investigated. The study was executed using GS FLX sequencing instruments and the small volume 454 Life Sciences Titanium emulsion PCR setup. We report a high concordance in mutation detection across all laboratories, including a robust detection of novel variants, which were undetected by standard Sanger sequencing. The sensitivity to detect low-level variants present with as low as 1-2% frequency, compared with the 20% threshold for Sanger-based sequencing is increased. Together with the output of high-quality long reads and fast run time, we demonstrate the utility of deep sequencing in clinical applications. In conclusion, this multicenter analysis demonstrated that amplicon-based deep sequencing is technically feasible, achieves high concordance across multiple laboratories and allows a broad and in-depth molecular characterization of cancer specimens with high diagnostic sensitivity.

The narrow therapeutic range and wide interpatient variability in dose requirement make anticoagulation response to coumarin derivatives unpredictable. As a result, patients require frequent monitoring to avert adverse effects and maintain therapeutic efficacy. Polymorphisms in VKORC1 and CYP2C9 jointly account for about 40% of the interindividual

Introduction. The medical literature contains several definitions of premature ejaculation (PE). The most commonly quoted definition, the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition-Text Revision, and other definitions of PE are all authority based rather than evidence based, and have no support from controlled clinical and/or epidemiological studies. Aim. The aim of this article is to develop a contemporary, evidence-based definition of PE. Methods. In August 2007, the International Society for Sexual Medicine (ISSM) appointed several international experts in PE to an Ad Hoc Committee for the Definition of Premature Ejaculation. The committee met in Amsterdam in October 2007 to evaluate the strengths and weaknesses of current definitions of PE, to critique the evidence in support of the constructs of ejaculatory latency, ejaculatory control, sexual satisfaction, and personal/interpersonal distress, and to propose a new evidence-based definition of PE. Results. The committee unanimously agreed that the constructs that are necessary to define PE are rapidity of ejaculation, perceived self-efficacy and control, and negative personal consequences from PE. The committee proposed that lifelong PE be defined as "... a male sexual dysfunction characterized by ejaculation which always or nearly always occurs prior to or within about one minute of vaginal penetration, and the inability to delay ejaculation on all or nearly all vaginal penetrations, and negative personal consequences, such as distress, bother frustration and/or the avoidance of sexual intimacy." This definition is limited to men with lifelong PE who engage in vaginal intercourse. The panel concluded that there are insufficient published objective data to propose an evidence-based definition of acquired PE. Conclusion. The ISSM definition of lifelong PE represents the first evidence-based definition of PE. This definition will hopefully lead to the de