Genomics knowledge and attitudes among European public health professionals. Results of a cross-sectional survey

Background The international public health (PH) community is debating the opportunity to incorporate genomic technologies into PH practice. A survey was conducted to assess attitudes of the European Public Health Association (EUPHA) members towards their role in the implementation of public health genomics (PHG), and their knowledge and attitudes towards genetic testing and the delivery of genetic services. Methods EUPHA members were invited via monthly newsletter and e-mail to take part in an online survey from February 2017 to January 2018. A descriptive analysis of knowledge and attitudes was conducted, along with a univariate and multivariate analysis of their determinants. Results Five hundred and two people completed the questionnaire, 17.9% were involved in PHG activities. Only 28.9% correctly identified all medical conditions for which there is (or not) evidence for implementing genetic testing; over 60% thought that investing in genomics may divert economic resources from social and environmental determinants of health. The majority agreed that PH professionals may play different roles in incorporating genomics into their activities. Better knowledge was associated with positive attitudes towards the use of genetic testing and the delivery of genetic services in PH (OR = 1.48; 95% CI 1.01–2.18). Conclusions Our study revealed quite positive attitudes, but also a need to increase awareness on genomics among European PH professionals. Those directly involved in PHG activities tend to have a more positive attitude and better knowledge; however, gaps are also evident in this group, suggesting the need to harmonize practice and encourage greater exchange of knowledge among professionals

The provision of genetic testing and related services in Quebec, Canada

Background: Research in the field of genomics and genetics has evolved in recent years and so has the demand of consumers who are increasingly interested in genomic prediction of diseases and various traits. The aim of this study is to identify genetic service delivery models, policies governing the use of genomics medicine, and measures to evaluate genetic services in the province of Quebec, Canada. Methods: An ad hoc questionnaire was designed and administered online in 2017 to healthcare workers with good knowledge or experience in the provision of BReast CAncer genes 1 and 2 (BRCA1/2), Lynch syndrome, familial hypercholesterolemia, inherited thrombophilia genetic tests, engaged in policy planning or evaluation of genetic services. A quali-quantitative analysis of the survey results was performed. Results: Thirty professionals participated in the study. The delivery models are classified in five categories according to the leading role of healthcare professionals in patient care pathways: i) the geneticist model; ii) the primary care model; iii) the medical specialist model; iv) the population screening program model; and v) the direct-to-consumer model. Barriers to genetic services are the coverage of genetic tests by the publicly funded healthcare system, the availability of qualified personnel, and the number of genetic centers. Regulatory oversight concerning the provision of genetic services appears to be insufficient. Conclusions: Integration between genetics and the overall healthcare system in Quebec is in an early phase. Current models of genetic services require good level of genetic knowledge by all medical specialists, collaboration among different healthcare personnel, and work redistribution. The proper implementation of genomics into healthcare can be achieved through education and training, proper regulatory oversight, genomic policies, and public awareness

Sex-dependent differences in left ventricular function and structure in chronic pressure overload

To evaluate gender-related differences in left ventricular (LV) structure and function in aortic stenosis, LV biplane cineangiography, micromanometry and endomyocardial biopsies were carried out in 56 patients with aortic stenosis and normal coronary arteries. Patients were divided into males (M: n= θ35), and females (F: n= θ21). Sixteen normal subjects 8 M, 8 F) served as haemodynamic controls. Control biopsy data were obtained from six pre-transplantation donor hearts (3 M and 3 F). LV systolic function was evaluated by ejection fraction and its relationship to mean systolic circumferential wall stress, diastolic function by the time constant of LV pressure decay, peak filling rates and passive myocardial stiffness constant. Biopsy samples were evaluated for interstitial fibrosis, muscle fibre diameter and volume fraction of myofibrils. In a subset of 27 consecutive patients, biopsy samples were evaluated with a morphometric-morphological method, for total collagen volume fraction, endocardial fibrosis and the extension and thickness of orthogonal collagen fibres (cross-hatching). In patients with aortic stenosis, aortic valve area, aortic valve resistance and mean aortic pressure gradient were comparable in males and females, whereas end-systolic and end-diastolic volumes were larger in males than females. Ejection fraction was lower (56%) in males than females (64%) (P 1.5 grade) was present in 11 males and four females with aortic stenosis (P<0.0I). An abnormal collagen architecture was present in 13114 males and 5113 females (V<0.002). In aortic stenosis, males have a depressed systolic function and abnormal passive elastic properties when compared to females with valve lesions of similar severity. Changes in collagen architecture may account, at least in part, for these difference

Cost-effectiveness of RAS genetic testing strategies in patients with metastatic colorectal cancer. A systematic review

Background: Monoclonal antibodies against epidermal growth factor receptor (EGFR) have proved beneficial for the treatment of metastatic colorectal cancer (mCRC), particularly when combined with predictive biomarkers of response. International guidelines recommend anti-EGFR therapy only for RAS (NRAS, KRAS) wild-type tumors because tumors with RAS mutations are unlikely to benefit. Objectives: We aimed to review the cost-effectiveness of RAS testing in mCRC patients before anti-EGFR therapy and to assess how well economic evaluations adhere to guidelines. Methods: A systematic review of full economic evaluations comparing RAS testing with no testing was performed for articles published in English between 2000 and 2018. Study quality was assessed using the Quality of Health Economic Studies scale, and the British Medical Journal and the Philips checklists. Results: Six economic evaluations (2 cost-effectiveness analyses, 2 cost-utility analyses, and 2 combined cost-effectiveness and cost-utility analyses) were included. All studies were of good quality and adopted the perspective of the healthcare system/payer; accordingly, only direct medical costs were considered. Four studies presented testing strategies with a favorable incremental cost-effectiveness ratio under the National Institute for Clinical Excellence (£20 000-£30 000/QALY) and the US ($50 000-$100 000/QALY) thresholds. Conclusions: Testing mCRC patients for RAS status and administering EGFR inhibitors only to patients with RAS wild-type tumors is a more cost-effective strategy than treating all patients without testing. The treatment of mCRC is becoming more personalized, which is essential to avoid inappropriate therapy and unnecessarily high healthcare costs. Future economic assessments should take into account other parameters that reflect the real world (eg, NRAS mutation analysis, toxicity of biological agents, genetic test sensitivity and specificity)

Isotopic distribution of fission fragments in collisions between 238U beam and 9Be and 12C targets at 24 MeV/u

Inverse kinematics coupled to a high-resolution spectrometer is used to investigate the isotopic yields of fission fragments produced in reactions between a 238U beam at 24 MeV/u and 9Be and 12C targets. Mass, atomic number and isotopic distributions are reported for the two reactions. These informations give access to the neutron excess and the isotopic distribution widths, which together with the atomic-number and mass distributions are used to investigate the fusion-fission dynamics.Comment: Submitted to PR

Direct mass measurements of 19B, 22C, 29F, 31Ne, 34Na and other light exotic nuclei

We report on direct time-of-flight based mass measurements of 16 light neutron-rich nuclei. These include the first determination of the masses of the Borromean drip-line nuclei $^{19}$B, $^{22}$C and $^{29}$F as well as that of $^{34}$Na. In addition, the most precise determinations to date for $^{23}$N and $^{31}$Ne are reported. Coupled with recent interaction cross-section measurements, the present results support the occurrence of a two-neutron halo in $^{22}$C, with a dominant $\nu2s_{1/2}^2$ configuration, and a single-neutron halo in $^{31}$Ne with the valence neutron occupying predominantly the 2$p_{3/2}$ orbital. Despite a very low two-neutron separation energy the development of a halo in $^{19}$B is hindered by the 1$d_{5/2}^2$ character of the valence neutrons.Comment: 5 page

Force-frequency relationship during dobutamine stress echocardiography predicts exercise tolerance and BNP levels in patients with chronic congestive heart failure

Purpose: D obutamine stress echocardiography (DSE) is widely used to evaluate myocardial contractile reserve; it provides prognostic information in patients with chronic congestive heart failure (CHF). The force?frequency relationship (FFR) is a method for evaluate LV contractility during DSE . The aim of our study is to assess the relationship among FFR, BNP levels, and aerobic exercise capacity in CHF patients. Methods and materials: 37 CHF patients (age 67?8 years, 54% with an ischemic etiology), underwent high dose DSE (up to 40 m g/kg/min). FFR was determined as a ratio between systolic cuff pressure and end-systolic volume (biplane using a Simposon rule) assessed at baseline and peak DSE . BNP levels were determined on blood samples withdrawn at baseline. After a few hours, CHF patients underwent cardiopulmonary exercise test with expired gas measurement. Results: Mean ejection fraction was 32?7% and NHYA class 2.5?0.6. FFR was directly related to peak oxygen consumption (Figure Left), LV ejection fraction (r=0.398, p=0.015) and mitral annulus peak systolic velocity (r=0.428, p=0.013). FFR was inversely related to NYHA class (r=-0.43, p=0.013), LV end-diastolic diameter (r=-0.377, p=0.022), LV intraventricular dyssynchrony (r=-0.394, p=0.016), and BNP levels (Figure Right). At multiple regression analysis, FFR (B=0.502, p= 0.004) and E/Ea ratio (B=-0.336, p=0.044) were the best predictors of exercise tolerance. Conclusions: In patients with stable CHF, impaired myocardial contractility during DSE is related to higher BNP levels and poorer exercise tolerance