Implementation of pharmacogenetic testing in pediatric oncology: barriers and facilitators assessment at eight Canadian academic health centres
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Understanding general practitioner and pharmacist preferences for pharmacogenetic testing in primary care: a discrete choice experiment
Pharmacogenetic testing in the United Kingdom’s National Health Service (NHS) has historically been reactive in nature, undertaken in the context of single gene-drug relationships in specialist settings. Using a discrete choice experiment we aimed to identify healthcare professional preferences for development of a pharmacogenetic testing service in primary care in the NHS. Respondents, representing two professions groups (general practitioners or pharmacists), completed one of two survey versions, asking them to select their preferred pharmacogenetic testing service in the context of a presentation of low mood or joint pain. Responses from 235 individuals were included. All respondents preferred pharmacogenetic testing over no testing, though preference heterogeneity was identified. Both professional groups, but especially GPs, were highly sensitive to service design, with uptake varying depending on the service offered. This study demonstrates uptake of a pharmacogenetic testing service is impacted by service design and highlights key areas which should be prioritised within future initiatives.
Assessing competence of primary care respiratory healthcare professionals to deliver a psychologically-based intervention for people with COPD: results from the TANDEM study
Management of long-term conditions is a significant challenge in contemporary health care as people often require support for both physical and psychological symptoms. Assessing the competence of healthcare professionals delivering psychologically informed interventions informs decisions about future implementation. This is a comprehensive intervention fidelity assessment nested within a randomised controlled trial. We developed a bespoke intervention fidelity assessment framework to assess the competence of primary care respiratory nurses, physiotherapists and occupational therapists delivering a cognitive behavioural intervention for people with COPD. A total of 180 (representing 15% of trial cases) intervention audio files, from 36 intervention arm participants, were coded. The intervention was delivered with acceptable adherence for most components. Therapeutic competency was achieved and comparable with previous research studies. Interpersonal skills and focus had higher competency whilst guided discovery and application of appropriate change techniques was lower but still adequate. Skills improved over time and with an increased number of clients. With proper training and supervision, primary care respiratory nurses, physiotherapists and occupational therapists can deliver cognitive behavioural interventions with acceptable therapeutic competency but questioning and change techniques may need particular focus in training and greater practice.
Personalized prediction of anticancer potential of non-oncology drugs through learning from genome derived molecular pathways
Advances in cancer genomics have significantly expanded our understanding of cancer biology. However, the high cost of drug development limits our ability to translate this knowledge into precise treatments. Approved non-oncology drugs, comprising a large repository of chemical entities, offer a promising avenue for repurposing in cancer therapy. Herein we present CHANCE, a supervised machine learning model designed to predict the anticancer activities of non-oncology drugs for specific patients by simultaneously considering personalized coding and non-coding mutations. Utilizing protein–protein interaction networks, CHANCE harmonizes multilevel mutation annotations and integrates pharmacological information across different drugs into a single model. We systematically benchmarked the performance of CHANCE and show its predictions are better than previous model and highly interpretable. Applying CHANCE to approximately 5000 cancer samples indicated that >30% might respond to at least one non-oncology drug, with 11% non-oncology drugs predicted to have anticancer activities. Moreover, CHANCE predictions suggested an association between SMAD7 mutations and aspirin treatment response. Experimental validation using tumor cells derived from seven patients with pancreatic or esophageal cancer confirmed the potential anticancer activity of at least one non-oncology drug for five of these patients. To summarize, CHANCE offers a personalized and interpretable approach, serving as a valuable tool for mining non-oncology drugs in the precision oncology era.
The interplay between positive lifestyle habits and academic excellence in higher education
Systematically examining the correlation between the lifestyle habits of undergraduate students and their academic performance holds significant practical implications in advancing higher education. This study adopts an integrated perspective and analyzes a substantial dataset (3,123,840 data points) of 3499 undergraduates at a Chinese university. This study employs a Long short-term memory neural network to identify eating behavior indicators and develops a comprehensive model to evaluate the relationship between students’ lifestyle habits and academic performance; the lifestyle habits cover eating, hygiene, and studying habits. The findings challenge conventional wisdom by revealing that stringent eating schedules do not consistently correlate with superior academic performance. Instead, a higher degree of inertia in eating behavior (e.g., waking up early) correlates with better academic outcomes. Positive correlations also exist between students’ hygiene and studying habits and their academic performance. These results provide valuable insights into the relationship between students’ behavior and academic performance. This work carries implications for promoting the digitalization of higher education and enhancing education management for undergraduate students.
Polygenic scores for cardiovascular risk factors improve estimation of clinical outcomes in CCB treatment compared to pharmacogenetic variants alone
Pharmacogenetic variants are associated with clinical outcomes during Calcium Channel Blocker (CCB) treatment, yet whether the effects are modified by genetically predicted clinical risk factors is unknown. We analyzed 32,000 UK Biobank participants treated with dihydropiridine CCBs (mean 5.9 years), including 23 pharmacogenetic variants, and calculated polygenic scores for systolic and diastolic blood pressures, body fat mass, and other patient characteristics. Outcomes included treatment discontinuation and heart failure. Pharmacogenetic variant rs10898815-A (NUMA1) increased discontinuation rates, highest in those with high polygenic scores for fat mass. The RYR3 variant rs877087 T-allele alone modestly increased heart failure risks versus non-carriers (HR:1.13, p = 0.02); in patients with high polygenic scores for fat mass, lean mass, and lipoprotein A, risks were substantially elevated (HR:1.55, p = 4 × 10−5). Incorporating polygenic scores for adiposity and lipoprotein A may improve risk estimates of key clinical outcomes in CCB treatment such as treatment discontinuation and heart failure, compared to pharmacogenetic variants alone.
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