Personal Genomes in Practice:Exploring Citizen and Healthcare Professionals’ Perspectives on Personalized Genomic Medicine and Personal Health Data Spaces Using a Mixed-Methods Design

Ongoing health challenges, such as the increased global burden of chronic disease, are increasingly answered by calls for personalized approaches to healthcare. Genomic medicine, a vital component of these personalization strategies, is applied in risk assessment, prevention, prognostication, and therapeutic targeting. However, several practical, ethical, and technological challenges remain. Across Europe, Personal Health Data Space (PHDS) projects are under development aiming to establish patient-centered, interoperable data ecosystems balancing data access, control, and use for individual citizens to complement the research and commercial focus of the European Health Data Space provisions. The current study explores healthcare users’ and health care professionals’ perspectives on personalized genomic medicine and PHDS solutions, in casu the Personal Genetic Locker (PGL). A mixed-methods design was used, including surveys, interviews, and focus groups. Several meta-themes were generated from the data: (i) participants were interested in genomic information; (ii) participants valued data control, robust infrastructure, and sharing data with non-commercial stakeholders; (iii) autonomy was a central concern for all participants; (iv) institutional and interpersonal trust were highly significant for genomic medicine; and (v) participants encouraged the implementation of PHDSs since PHDSs were thought to promote the use of genomic data and enhance patients’ control over their data. To conclude, we formulated several facilitators to implement genomic medicine in healthcare based on the perspectives of a diverse set of stakeholders.</p

Correction:Dutch Pharmacogenetics Working Group (DPWG) guideline for the gene–drug interaction between CYP2D6 and opioids (codeine, tramadol and oxycodone) (European Journal of Human Genetics, (2021), 10.1038/s41431-021-00920-y)

The Data statement was partly wrong and should have read as below. DATA AVAILABILITY All data and material are either included in the Supplementary information or publicly available (i.e., the published articles, PubMed). The guidelines and background information are available on the website of the Royal Dutch Pharmacists Association (KNMP) (Pharmacogenetic Recommendations. Available from: https://www.knmp.nl/). The guidelines and background information will be available on PharmGKB.org

SERIES: eHealth in primary care. Part 1: Concepts, conditions and challenges.

Primary care is challenged to provide high quality, accessible and affordable care for an increasingly ageing, complex, and multimorbid population. To counter these challenges, primary care professionals need to take up new and innovative practices, including eHealth. eHealth applications hold the promise to overcome some difficulties encountered in the care of people with complex medical and social needs in primary care. However, many unanswered questions regarding (cost) effectiveness, integration with healthcare, and acceptability to patients, caregivers, and professionals remain to be elucidated. What conditions need to be met? What challenges need to be overcome? What downsides must be dealt with? This first paper in a series on eHealth in primary care introduces basic concepts and examines opportunities for the uptake of eHealth in primary care. We illustrate that although the potential of eHealth in primary care is high, several conditions need to be met to ensure that safe and high-quality eHealth is developed for and implemented in primary care. eHealth research needs to be optimized; ensuring evidence-based eHealth is available. Blended care, i.e. combining face-to-face care with remote options, personalized to the individual patient should be considered. Stakeholders need to be involved in the development and implementation of eHealth via co-creation processes, and design should be mindful of vulnerable groups and eHealth illiteracy. Furthermore, a global perspective on eHealth should be adopted, and eHealth ethics, patients' safety and privacy considered.Published versio

Dutch Pharmacogenetics Working Group (DPWG) guideline for the gene-drug interaction of DPYD and fluoropyrimidines

Despite advances in the field of pharmacogenetics (PGx), clinical acceptance has remained limited. The Dutch Pharmacogenetics Working Group (DPWG) aims to facilitate PGx implementation by developing evidence-based pharmacogenetics guidelines to optimize pharmacotherapy. This guideline describes the starting dose optimization of three anti-cancer drugs (fluoropyrimidines: 5-fluorouracil, capecitabine and tegafur) to decrease the risk of severe, potentially fatal, toxicity (such as diarrhoea, hand-foot syndrome, mucositis or myelosuppression). Dihydropyrimidine dehydrogenase (DPD, encoded by the DPYD gene) enzyme deficiency increases risk of fluoropyrimidine-induced toxicity. The DPYD-gene activity score, determined by four DPYD variants, predicts DPD activity and can be used to optimize an individual's starting dose. The gene activity score ranges from 0 (no DPD activity) to 2 (normal DPD activity). In case it is not possible to calculate the gene activity score based on DPYD genotype, we recommend to determine the DPD activity and adjust the initial dose based on available data. For patients initiating 5-fluorouracil or capecitabine: subjects with a gene activity score of 0 are recommended to avoid systemic and cutaneous 5-fluorouracil or capecitabine; subjects with a gene activity score of 1 or 1.5 are recommended to initiate therapy with 50% the standard dose of 5-fluorouracil or capecitabine. For subjects initiating tegafur: subjects with a gene activity score of 0, 1 or 1.5 are recommended to avoid tegafur. Subjects with a gene activity score of 2 (reference) should receive a standard dose. Based on the DPWG clinical implication score, DPYD genotyping is considered "essential", therefore directing DPYD testing prior to initiating fluoropyrimidines

Oncogenetics

Determining whether a hereditary cancer predisposition is present, is important for both the cancer patient and his family. It is relevant for surveillance and prevention or early detection of new tumours, treatment options and issues surrounding the desire to have children. For this reason, it must be ensured that for every patient with cancer (now or in the past) referral for genetic testing is considered. In this article we indicate how to take a family history and where to find and how to apply referral criteria if such a question arises in clinical practice. The consequences of a genetic diagnosis are illustrated by a breast cancer case

Effectiveness of oncogenetics training on general practitioners' consultation skills: a randomized controlled trial

Contains fulltext : 137892.pdf (publisher's version ) (Open Access)PURPOSE: General practitioners are increasingly called upon to deliver genetic services and could play a key role in translating potentially life-saving advancements in oncogenetic technologies to patient care. If general practitioners are to make an effective contribution in this area, their genetics competencies need to be upgraded. The aim of this study was to investigate whether oncogenetics training for general practitioners improves their genetic consultation skills. METHODS: In this pragmatic, blinded, randomized controlled trial, the intervention consisted of a 4-h training (December 2011 and April 2012), covering oncogenetic consultation skills (family history, familial risk assessment, and efficient referral), attitude (medical ethical issues), and clinical knowledge required in primary-care consultations. Outcomes were measured using observation checklists by unannounced standardized patients and self-reported questionnaires. RESULTS: Of 88 randomized general practitioners who initially agreed to participate, 56 completed all measurements. Key consultation skills significantly and substantially improved; regression coefficients after intervention were equivalent to 0.34 and 0.28 at 3-month follow-up, indicating a moderate effect size. Satisfaction and perceived applicability of newly learned skills were highly scored. CONCLUSION: The general practitioner-specific training proved to be a feasible, satisfactory, and clinically applicable method to improve oncogenetics consultation skills and could be used as an educational framework to inform future training activities with the ultimate aim of improving medical care

Dutch Pharmacogenetics Working Group (DPWG) guideline for the gene–drug interaction between CYP2D6 and opioids (codeine, tramadol and oxycodone)

The current Dutch Pharmacogenetics Working Group (DPWG) guideline, describes the gene–drug interaction between CYP2D6 and the opioids codeine, tramadol and oxycodone. CYP2D6 genotype is translated into normal metaboliser (NM), intermediate metaboliser (IM), poor metaboliser (PM) or ultra-rapid metaboliser (UM). Codeine is contraindicated in UM adults if doses >20 mg every 6 h (q6h), in children ≥12 years if doses >10 mg q6h, or with additional risk factors. In PMs, an alternative analgesic should be given which is not or to a lesser extent metabolised by CYP2D6 (not tramadol). In IMs with insufficient analgesia, a higher dose or alternative analgesic should be given. For tramadol, the recommendations for IMs and PMs are the same as the recommendation for codeine and IMs. UMs should receive an alternative drug not or to a lesser extent metabolised by CYP2D6 or the dose should be decreased to 40% of the commonly prescribed dose. Due to the absence of effect on clinical outcomes of oxycodone in PMs, IMs and UMs no action is required. DPWG classifies CYP2D6 genotyping for codeine “beneficial” and recommends testing prior to, or shortly after initiation of treatment in case of higher doses or additional risk factors. CYP2D6 genotyping is classified as “potentially beneficial” for tramadol and can be considered on an individual patient basis

Dutch Pharmacogenetics Working Group (DPWG) guideline for the gene-drug interaction between CYP2C19 and CYP2D6 and SSRIs

The Dutch Pharmacogenetics Working Group (DPWG) guideline presented here, presents the gene-drug interaction between the genes CYP2C19 and CYP2D6 and antidepressants of the selective serotonin reuptake inhibitor type (SSRIs). Both genes’ genotypes are translated into predicted normal metabolizer (NM), intermediate metabolizer (IM), poor metabolizer (PM), or ultra-rapid metabolizer (UM). Evidence-based dose recommendations were obtained, based on a structured analysis of published literature. In CYP2C19 PM patients, escitalopram dose should not exceed 50% of the normal maximum dose. In CYP2C19 IM patients, this is 75% of the normal maximum dose. Escitalopram should be avoided in UM patients. In CYP2C19 PM patients, citalopram dose should not exceed 50% of the normal maximum dose. In CYP2C19 IM patients, this is 70% (65–75%) of the normal maximum dose. In contrast to escitalopram, no action is needed for CYP2C19 UM patients. In CYP2C19 PM patients, sertraline dose should not exceed 37.5% of the normal maximum dose. No action is needed for CYP2C19 IM and UM patients. In CYP2D6 UM patients, paroxetine should be avoided. No action is needed for CYP2D6 PM and IM patients. In addition, no action is needed for the other gene-drug combinations. Clinical effects (increase in adverse events or decrease in efficacy) were lacking for these other gene-drug combinations. DPWG classifies CYP2C19 genotyping before the start of escitalopram, citalopram, and sertraline, and CYP2D6 genotyping before the start of paroxetine as “potentially beneficial” for toxicity/effectivity predictions. This indicates that genotyping prior to treatment can be considered on an individual patient basis