The effect of dyad versus individual simulation-based ultrasound training on skills transfer

CONTEXT: Dyad practice may be as effective as individual practice during clinical skills training, improve students’ confidence, and reduce costs of training. However, there is little evidence that dyad training is non‐inferior to single‐student practice in terms of skills transfer. OBJECTIVES: This study was conducted to compare the effectiveness of simulation‐based ultrasound training in pairs (dyad practice) with that of training alone (single‐student practice) on skills transfer. METHODS: In a non‐inferiority trial, 30 ultrasound novices were randomised to dyad (n = 16) or single‐student (n = 14) practice. All participants completed a 2‐hour training programme on a transvaginal ultrasound simulator. Participants in the dyad group practised together and took turns as the active practitioner, whereas participants in the single group practised alone. Performance improvements were evaluated through pre‐, post‐ and transfer tests. The transfer test involved the assessment of a transvaginal ultrasound scan by one of two clinicians using the Objective Structured Assessment of Ultrasound Skills (OSAUS). RESULTS: Thirty participants completed the simulation‐based training and 24 of these completed the transfer test. Dyad training was found to be non‐inferior to single‐student training: transfer test OSAUS scores were significantly higher than the pre‐specified non‐inferiority margin (delta score 7.8%, 95% confidence interval −3.8–19.6%; p = 0.04). More dyad (71.4%) than single (30.0%) trainees achieved OSAUS scores above a pre‐established pass/fail level in the transfer test (p = 0.05). There were significant differences in performance scores before and after training in both groups (pre‐ versus post‐test, p < 0.01) with large effect sizes (Cohen's d = 3.85) and no significant interactions between training type and performance (p = 0.59). The dyad group demonstrated higher training efficiency in terms of simulator score per number of attempts compared with the single‐student group (p = 0.03). CONCLUSION: Dyad practice improves the efficiency of simulation‐based training and is non‐inferior to individual practice in terms of skills transfer

The relationship of body mass index with quality of life among endometrial cancer survivors: A study from the population-based PROFILES registry

Item does not contain fulltextOBJECTIVE: The aim of the study was to assess the association of body mass index (BMI) and Health-Related Quality of Life (HRQoL), and the relative importance of BMI in explaining variation in QoL among stage I or II endometrial cancer (EC), independent of comorbidities, socio-demographic and clinical characteristics. METHODS: A population-based, cross-sectional survey was conducted in 2008 among endometrial cancer survivors diagnosed between 1999 and 2007 sampled from the Eindhoven Cancer Registry. The HRQoL (SF-36), EC specific HRQoL (EORTC-QLQ-EN24), comorbidities (SCQ) and fatigue (FAS) questionnaire were completed by 666 endometrioid EC survivors. Multivariate regression analyses were used to assess the associations of HRQoL with BMI reported at time of questionnaire completion and to assess the percentage of variance in HRQoL outcomes explained by BMI (R(2)), (controlled for socio-demographic and clinical characteristics and comorbidity). RESULTS: Of all women, 432 (67.6%) were pre-obese (BMI 25-30) or obese (BMI >30). Increased BMI was associated with decreased physical function, decreased vitality, more lymphoedema symptoms, decreased sexual/vaginal problems, less taste change and more fatigue symptoms. BMI added significantly to the explained variance of physical function (4.3%), physical limitations in daily life (role physical; 0.7%), bodily pain (1.5%), vitality (1.6%), emotional limitations in daily life (role emotional; 0.9%), lymphoedema symptoms (5.2%), sexual/vaginal problems (3.2%), urologic problems (0.7%), and fatigue (1.4%). CONCLUSION: BMI was related to several HRQoL outcomes. Therefore BMI needs to be taken into account in HRQoL studies. Moreover, future research should assess if interventions to decrease BMI in obese EC survivors might improve HRQoL

Variant Location Is a Novel Risk Factor for Individuals With Arrhythmogenic Cardiomyopathy Due to a Desmoplakin ( DSP) Truncating Variant.

BACKGROUND: Truncating variants in desmoplakin ( DSPtv) are an important cause of arrhythmogenic cardiomyopathy; however the genetic architecture and genotype-specific risk factors are incompletely understood. We evaluated phenotype, risk factors for ventricular arrhythmias, and underlying genetics of DSPtv cardiomyopathy. METHODS: Individuals with DSPtv and any cardiac phenotype, and their gene-positive family members were included from multiple international centers. Clinical data and family history information were collected. Event-free survival from ventricular arrhythmia was assessed. Variant location was compared between cases and controls, and literature review of reported DSPtv performed. RESULTS: There were 98 probands and 72 family members (mean age at diagnosis 43±8 years, 59% women) with a DSPtv, of which 146 were considered clinically affected. Ventricular arrhythmia (sudden cardiac arrest, sustained ventricular tachycardia, appropriate implantable cardioverter defibrillator therapy) occurred in 56 (33%) individuals. DSPtv location and proband status were independent risk factors for ventricular arrhythmia. Further, gene region was important with variants in cases (cohort n=98; Clinvar n=167) more likely to occur in the regions, resulting in nonsense mediated decay of both major DSP isoforms, compared with n=124 gnomAD control variants (148 [83.6%] versus 29 [16.4%]; P<0.0001). CONCLUSIONS: In the largest series of individuals with DSPtv, we demonstrate that variant location is a novel risk factor for ventricular arrhythmia, can inform variant interpretation, and provide critical insights to allow for precision-based clinical management

Variant Location Is a Novel Risk Factor for Individuals With Arrhythmogenic Cardiomyopathy Due to a Desmoplakin (DSP) Truncating Variant

BACKGROUND: Truncating variants in desmoplakin (DSPtv) are an important cause of arrhythmogenic cardiomyopathy; however the genetic architecture and genotype-specific risk factors are incompletely understood. We evaluated phenotype, risk factors for ventricular arrhythmias, and underlying genetics of DSPtv cardiomyopathy. METHODS: Individuals with DSPtv and any cardiac phenotype, and their gene-positive family members were included from multiple international centers. Clinical data and family history information were collected. Event-free survival from ventricular arrhythmia was assessed. Variant location was compared between cases and controls, and literature review of reported DSPtv performed. RESULTS: There were 98 probands and 72 family members (mean age at diagnosis 43±8 years, 59% women) with a DSPtv, of which 146 were considered clinically affected. Ventricular arrhythmia (sudden cardiac arrest, sustained ventricular tachycardia, appropriate implantable cardioverter defibrillator therapy) occurred in 56 (33%) individuals. DSPtv location and proband status were independent risk factors for ventricular arrhythmia. Further, gene region was important with variants in cases (cohort n=98; Clinvar n=167) more likely to occur in the regions, resulting in nonsense mediated decay of both major DSP isoforms, compared with n=124 gnomAD control variants (148 [83.6%] versus 29 [16.4%]; P<0.0001). CONCLUSIONS: In the largest series of individuals with DSPtv, we demonstrate that variant location is a novel risk factor for ventricular arrhythmia, can inform variant interpretation, and provide critical insights to allow for precision-based clinical management

Confirmation of 5p12 as a susceptibility locus for progesterone-receptor-positive, lower grade breast cancer.

BACKGROUND: The single-nucleotide polymorphism (SNP) 5p12-rs10941679 has been found to be associated with risk of breast cancer, particularly estrogen receptor (ER)-positive disease. We aimed to further explore this association overall, and by tumor histopathology, in the Breast Cancer Association Consortium. METHODS: Data were combined from 37 studies, including 40,972 invasive cases, 1,398 cases of ductal carcinoma in situ (DCIS), and 46,334 controls, all of white European ancestry, as well as 3,007 invasive cases and 2,337 controls of Asian ancestry. Associations overall and by tumor invasiveness and histopathology were assessed using logistic regression. RESULTS: For white Europeans, the per-allele OR associated with 5p12-rs10941679 was 1.11 (95% CI = 1.08-1.14, P = 7 × 10(-18)) for invasive breast cancer and 1.10 (95% CI = 1.01-1.21, P = 0.03) for DCIS. For Asian women, the estimated OR for invasive disease was similar (OR = 1.07, 95%CI = 0.99-1.15, P = 0.09). Further analyses suggested that the association in white Europeans was largely limited to progesterone receptor (PR)-positive disease (per-allele OR = 1.16, 95% CI = 1.12-1.20, P = 1 × 10(-18) vs. OR = 1.03, 95% CI = 0.99-1.07, P = 0.2 for PR-negative disease; P(heterogeneity) = 2 × 10(-7)); heterogeneity by ER status was not observed (P = 0.2) once PR status was accounted for. The association was also stronger for lower grade tumors [per-allele OR (95% CI) = 1.20 (1.14-1.25), 1.13 (1.09-1.16), and 1.04 (0.99-1.08) for grade 1, 2, and 3/4, respectively; P(trend) = 5 × 10(-7)]. CONCLUSION: 5p12 is a breast cancer susceptibility locus for PR-positive, lower grade breast cancer. IMPACT: Multicenter fine-mapping studies of this region are needed as a first step to identifying the causal variant or variants

Current state-of-the-art and gaps in platform trials: 10 things you should know, insights from EU-PEARL

Summary: Platform trials bring the promise of making clinical research more efficient and more patient centric. While their use has become more widespread, including their prominent role during the COVID-19 pandemic response, broader adoption of platform trials has been limited by the lack of experience and tools to navigate the critical upfront planning required to launch such collaborative studies. The European Union-Patient-cEntric clinicAl tRial pLatform (EU-PEARL) initiative has produced new methodologies to expand the use of platform trials with an overarching infrastructure and services embedded into Integrated Research Platforms (IRPs), in collaboration with patient representatives and through consultation with U.S. Food and Drug Administration and European Medicines Agency stakeholders. In this narrative review, we discuss the outlook for platform trials in Europe, including challenges related to infrastructure, design, adaptations, data sharing and regulation. Documents derived from the EU-PEARL project, alongside a literature search including PubMed and relevant grey literature (e.g., guidance from regulatory agencies and health technology agencies) were used as sources for a multi-stage collaborative process through which the 10 more important points based on lessons drawn from the EU-PEARL project were developed and summarised as guidance for the setup of platform trials. We conclude that early involvement of critical stakeholder such as regulatory agencies or patients are critical steps in the implementation and later acceptance of platform trials. Addressing these gaps will be critical for attaining the full potential of platform trials for patients. Funding: Innovative Medicines Initiative 2 Joint Undertaking with support from the European Union’s Horizon 2020 research and innovation programme and EFPIA