Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Translation and cross-cultural adaptation of a survey on skin tears among nurses in French-speaking Switzerland

Background: There is a paucity of research investigating the experiences of nurses using a standardised skin tears programme and the influence that such a programme has on their clinical practice. The available literature is primarily in English, and there is a lack of validated instruments for use in other languages, including French. Aim : The aim of this study is to translate and cross-culturally adapt an original English language survey conducted among Australian nurses into Swiss French. Method/results : A structured methodological approach was used to translate, adapt and validate the survey based on Sousa and Rojjanasrirat’s translating process: (1) two independent bilingual experts were involved in the translation from English to Swiss French, and a synthesis version from both translations in Swiss French was obtained; (2) a blind back-translation of the synthesis version in English by two experts was completed, and consensus attained by a committee, to generate a pre-final version of the survey in Swiss French; (3) validation of the translated version was provided by postgraduate wound care students. Conclusion : The translated Swiss French 2020 survey is now ready to be used to assess the clinical reasoning of wound care specialists on the prevention

Prevention and management of skin tears ::a survey of nurses in French-speaking Switzerland

Background : Skin tears are common in many care settings. Clinicians’ practices show a lack of knowledge on skin tear classification, prevention and treatment; documentation problems; and a lack of uniform language. Aim: The aim of this study is to investigate nurses’ perceptions, opinions, knowledge and practices on the prevention and management of skin tears in Frenchspeaking Switzerland. Method : A survey was conducted among nurses and wound care specialists in Western Switzerland. Data were collected between 17 November and 14 December 2020 and analysed using descriptive statistical and thematic analyses. Result : A total of 117 nurses and wound care specialists participated in this survey; 89% described skin tears as common. Skin tear definitions (18%, n=15), classification systems (7%, n=6) and risk factors were not well known. Prevention measures were often non-existent (87%, n=82). A standard of care was infrequent (5%, n=6). Pain (76%, n=70), delayed healing (75%, n=70) and frequent dressing changes (72%, n=67) were common issues and complications. Education on dressing choices (89%, n=80); prevention measures (88%, n=79); and aged skin issues (86%, n=77), were identified as important teaching topics. Conclusion: The results contribute to our understanding of wound care specialists’ clinical judgment on preventing and managing skin tears in French-speaking Switzerland and highlight the importance of wound care education. Implication for clinical practice : To enhance nurses’ knowledge of wound care and ensure evidence-based practices, we recommend implementing standard, unified wound curricula for nurses at the undergraduate and post-graduate levels, based on the existing European curricula

E-learning and blended-learning program in wound care for undergraduate nursing students

Background: Due to an increasing number of undergraduate students in a Bachelor of Nursing Science program, the existing teaching modalities in wound care were shifted into blended- and e-learning units. The aim is to present the development and implementation of a blended- and e-learning wound care curriculum in an actual nursing program. Method: The development of the blended- and e-learning units is based on literature reviews and expert discussions. The process was guided by the learning outcomes defined by the European Wound Management Association. The implementation was planned for 3 years. Results: All 14 learning units were developed and implemented using 12 blended and two e-learning units. Flipped classrooms using asynchronous e-learnings and workshops with clinical wound care specialists were used for blended learning. Conclusion: Blended and e-learning are valuable modalities to provide flexibility and deliver learning units based on the latest evidence. The effectiveness of this curriculum needs to be investigated

Bachelor nursing students' perceptions of a blended-learning unit on leg ulcers during the COVID-19 pandemic

Aim : To face teaching challenges during COVID-19, a new three-step blended learning pedagogical scenario for leg ulcers was developed combining e-learning, theoretical seminars and workshops. The aim of this survey is to explore students’ perceptions of the three-step learning unit presented during the COVID-19 pandemic. Method : An online anonymous survey comprising five Likert scale questions and two open-ended questions was sent to the 151 participating nursing students. Quantitative data were analysed with descriptive statistics, and qualitative data were addressed using thematic analysis. Results : A total of 68 students participated in this survey. The students reported that the newly developed three-step unit promoted their learning. The allocated time for the e-learning was, for 20 (29%) students, insufficient. The qualitative data demonstrated the benefits of studying in small groups and using e-learning as well as following a structured learning program. Workshops led by clinical nurse specialists and the use of adapted wound care materials were reported as essential. Conclusion : Students appreciate this three-step blended-learning unit. Small groups led by clinical specialists promote a positive learning environment. Further research is needed to evaluate the effectiveness of this approach

Les soins des plaies évoluent grâce à la Haute école de santé genevoise

Le laboratoire spécialisé en cicatrisation et soins des plaies développe, mène et implémente des projets de recherche appliquée dont bénéficie en direct l'enseignement aux niveaux Bachelor et post-grade. Découvrez les activités de ce centre de compétences genevois

Prognostic accuracy of SOFA, qSOFA and SIRS criteria in hematological cancer patients: a retrospective multicenter study

Background With Sepsis-3, the increase in sequential organ failure assessment (SOFA) as a clinical score for the identification of patients with sepsis and quickSOFA (qSOFA) for the identification of patients at risk of sepsis outside the intensive care unit (ICU) were introduced in 2016. However, their validity has been questioned, and their applicability in different settings and subgroups, such as hematological cancer patients, remains unclear. We therefore assessed the validity of SOFA, qSOFA, and the systemic inflammatory response syndrome (SIRS) criteria regarding the diagnosis of sepsis and the prediction of in-hospital mortality in a multicenter cohort of hematological cancer patients treated on ICU and non-ICU settings. Methods We retrospectively calculated SIRS, SOFA, and qSOFA scores in our cohort and applied the definition of sepsis as life-threatening organ dysfunction caused by dysregulated host response to infection as reference. Discriminatory capacity was assessed using the area under the receiver operating characteristic curve (AUROC). Results Among 450 patients with hematological cancer (median age 58 years, 274 males [61%]), 180 (40%) had sepsis of which 101 (56%) were treated on ICU. For the diagnosis of sepsis, sensitivity was 86%, 64%, and 42% for SIRS, SOFA, and qSOFA, respectively. However, the AUROCs of SOFA and qSOFA indicated better discrimination for sepsis than SIRS (SOFA, 0.69 [95% CI, 0.64-0.73] p = 2, mortality was 49% compared to 33% for those with qSOFA = 2 had better prognostic accuracy for both diagnosis of sepsis and in-hospital mortality in this setting, and especially on ICU, we observed limited validity of SIRS criteria and qSOFA in identifying hematological patients with sepsis and at high risk of death

L'eau à découvert

Indispensable à la régulation du climat, au développement de la vie sur Terre, au maintien des écosystèmes, aux populations, au développement de l'agriculture, de l'industrie comme à la production d'énergie, l'eau est un élément vital. Il convient donc, dans un contexte de changement global, d'analyser dans toute sa diversité la place et le rôle de l'eau et de se donner ainsi les moyens de mieux la préserver. Autour de cet enjeu qui engage toute l'humanité, Agathe Euzen, Catherine Jeandel et Rémy Mosseri ont réuni près de cent cinquante contributions, visant à apporter un éclairage sur chacun des domaines et des approches que couvre cette thématique. Quelle est l'origine de l'eau ? Son rapport avec l'apparition de la vie ? Quel rôle a-t-elle joué dans l'histoire de la planète et dans le développement de la vie végétale, animale et humaine ? Quel est son cycle ? Quelles sont ses propriétés chimiques ? Comment les sociétés se sont-elles emparées de cet élément précieux ? Allons-nous manquer d'eau ? L'eau est-elle source de conflits ? Comment l'eau est-elle gérée ? Comment recycle-t-on une eau polluée ? Quels sont les risques pour la santé mondiale ? Quels sont les grands enjeux liés à l'eau au xxie siècle ? Comprendre et proposer des solutions à ces défis majeurs est l'intention de cet ouvrage