Organoid models: the future companions of personalized drug development.

High failure rates of the current drug development process are driving exemplary changes toward methodologies centered on human disease in-vitro modeling. Organoids are self-organized tissue sub-units resembling their organ of origin and are widely acknowledged for their unique potential in recapitulating human physio-pathological mechanisms. They are transformative for human health by becoming the platform of choice to probe disease mechanisms and advance new therapies. Furthermore, the compounds' validation as therapeutics represents another point of the drug development pipeline where organoids may provide key understandings and help pharma organizations replace or reduce animal research. In this review, we focus on gastrointestinal organoid models, which are currently the most advanced organoid models in drug development. We focus on experimental validations of their value, and we propose avenues to enhance their use in drug discovery and development, as well as precision medicine and diagnostics.

[Study of cardiovascular drugs usage, among elderly subjects admitted to the emergency department for syncopal falls in Rhône-Alpes region]. / Étude de l'exposition médicamenteuse aux cardiotropes des sujets âgés consultant aux urgences pour chute avec malaise en Rhône-Alpes.

Study of cardiovascular drugs usage, among elderly subjects admitted to the emergency department for syncopal falls in Rhône-Alpes region. Polypharmacy and cardiovascular medication usage are risk factors for falls in the elderly. This study included subjects aged 75 and over, admitted in the emergency department for falls, based on evaluation data of professional practices carried out in the Nord Alpine region by the French Network of North-Alps Emergency Departments (Réseau Nord Alpin des Urgences, RENAU). The patients included were divided into 4 groups: "syncope", "accidental falls", "repeated falls" and "other types of fall". From the emergency room admission prescriptions, we studied the consumption of cardiovascular drugs in number and quality in the "syncope" group compared to other types of falls. The main objective in this study was to highlight higher cardiovascular drug usage among the elderly patients admitted to the emergency department for syncopal falls, in comparison with other types of falls. We included 1,476 patients among whom 262 patients came for "syncopal falls". We found superior usage of cardiovascular medication among syncopal falls compared to other type of falls (p < 0,01). However, there is no statistically significant association between inappropriate cardiovascular drug prescriptions, and the type of falls. The "standardized" fall assessment whose orthostatic hypotension investigation, is not always exhaustive in the emergency room. Orthostatic hypotension diagnostic is insufficiently sought in the emergency room. This study highlights a significantly higher usage of diuretic medication within the syncope group, in comparison to the other groups, and especially loop diuretic. Antihypertensive drugs (angiotensin-converting enzyme inhibitor, angiotensin II receptor blockers, calcium inhibitor) are also recurrent within the syncope group compared to the others. A careful supervising of these prescriptions among elderly patients seems required. These data prompt to revise prescriptions during fall related hospitalizations, and then with the primary-care physician, or with the cardiologist.

The Roadmap for Implementing Value-Based Healthcare in European University Hospitals-Consensus Report and Recommendations.

OBJECTIVES: Value-based healthcare (VBHC) aims at improving patient outcomes while optimizing the use of hospitals' resources among medical personnel, administrations, and support services through an evidence-based, collaborative approach. In this article, we present a blueprint for the implementation of VBHC in hospitals, based on our experience as members of the European University Hospital Alliance. METHODS: The European University Hospital Alliance is a consortium of 9 large hospitals in Europe and aims at increasing the quality and efficiency of care to ultimately drive better outcomes for patients. RESULTS: The blueprint describes how to prepare hospitals for VBHC implementation; analyzes gaps, barriers, and facilitators; and explores the most effective ways to turn patient pathways into a process that results in high-value care. Using a patient-centric approach, we identified 4 core minimum components that must be established as cornerstones and 7 organizational enablers to waive the barriers to implementation and ensure sustainability. CONCLUSION: The blueprint guides through pathway implementation and establishment of key performance indicators in 6 phases, which hospitals can tailor to their current status on their way to implement VBHC.

Satisfaction survey of general practitioners calling upon an external mobile geriatric team.

The external mobile geriatric team (équipe mobile de gériatrie extrahospitalière [EMGEH]) at the University Hospital of Grenoble-Alps intervenes with elderly subjects in complex medical and social situations at home at the request of general practitioners (GPs). To evaluate the satisfaction of GPs after EMGEH intervention. The secondary outcomes were the follow-up of recommendations and training requests from community care partners. Retrospective monocentric satisfaction survey of the 124 GPs who used the EMGEH between January 2015 and December 2018. Participation rate of 44%, representative of independent GPs in urban or semi-rural practices. Participants were "satisfied" or "very satisfied" (84.2%) with the responsiveness of the EMGEH, and 85.5% responded favourably to the content of the evaluation. The EMGEH was described as playing an expert and supportive role for GPs. The recommendations were followed by more than 89% of respondents. As many as 83.6% of participants wanted the EMGEH to conduct training sessions, mainly for the management of "behavioural disorders". Following this survey, five recommendations were formulated: decrease the response time by recruiting trained staff, systematically send an e-mail following the report to the requesting doctor, use a platform to exchange information, develop partnerships with the psychiatry team, and create an online resource space. This study contributed towards improving the relationship between the community and the hospital by strengthening links between the GPs within the CHUGA health region and the EMGEH.

[Satisfaction survey about general practitioners who used an External Mobile Geriatric Team]. / Enquête de satisfaction auprès des médecins généralistes ayant eu recours à une équipe mobile de gériatrie extrahospitalière.

CONTEXT: The External Mobile Geriatric Team (EMGT) of the University Hospital of Grenoble-Alps (UHGA) intervenes with elderly subjects in a complex medicosocial situation at home at the request of the general practitioner (GPs). OBJECTIVE: To evaluate the satisfaction of GPs after EMGT intervention. The secondary outcomes were the follow-up of recommendations and the training request of community partners. METHOD: Retrospective monocentric satisfaction survey of the 124 GPs who used EMGT from January 2015 to December 2018. RESULTS: Participation rate of 44 %, representative of GPs liberal urban or semi-rural. Participants were "satisfied" or "very satisfied" with the responsiveness of EMGT to 84,2 % and 85,5 % respond favorably to the content of the evaluation. EMGT was described as having an expert and supportive role for GPs. The recommendations were followed more than 89 %. The participants wanted to 83,6 % that the EMGT conducts training sessions, mainly for "behavioral disorders management". Following this survey, five improvement proposals were formulated: decrease the response time by recruiting trained staff, systematically send an e-mail post-analysis of the report to the doctor-applicant, use a platform of exchange, develop the partnership with the psychiatry team, and create a dematerialized resource space. CONCLUSION: This study contributed to the improvement of the city-hospital relationship by strengthening the links between the GPs of the CHUGA sanitary territory and the EMGT.

Management of preoperative pain in elderly patients with moderate to severe cognitive deficits and hip fracture: a retrospective, monocentric study in an orthogeriatric unit.

BACKGROUND: Patients with cognitive deficits are 3 times more likely to suffer a hip fracture than geriatric patients of the same age group without cognitive deficits. The persistence of perioperative pain following hip fracture is a risk factor for the occurrence of delirium, poor functional prognosis, and the development of secondary chronic pain. Patients with cognitive deficits receive 20 to 60% less analgesics than those without cognitive deficits. Our retrospective descriptive monocentric study was performed in an orthogeriatric unit on a cohort of elderly patients hospitalized for hip fracture. The aim of the study was to compare the quantity of strong opioids delivered in a morphine sulfate equivalent daily during the preoperative period after a hip fracture between cognitively intact patients and those with cognitive deficits. RESULTS: Our total population of 69 patients had a median age of 90 years old, and 46% of these patients had moderate or severe cognitive deficits. During the preoperative period, the same quantity of strong opioids was administered to both groups of patients (13.1 mg/d versus 10.8 mg/d (p = 0.38)). Patients with moderate to severe cognitive deficits more often experienced delirium during their hospitalization (p < 0.01) and received more psychotropic drugs in the first 3 postoperative days (p = 0.025). CONCLUSIONS: We reported that with standardized pain management in an orthogeriatric unit, patients aged 75 years and older received the same daily average quantity of strong opioids during the preoperative period regardless of the presence of cognitive deficits.

[A TPE programme for patients with neurodegenerative diseases and their carers]. / Un programme d'ETP pour les patients porteurs d'une maladie neurodégénérative et leurs aidants.

The team of the geriatric department of the Grenoble-Alpes (38) University Hospital Center has created the Accompagner therapeutic education program to meet the needs of patients suffering from neurocognitive disorders in the context of a neurodegenerative disease and their families. Presentation and current organization of the workshops.

Interface quality of endothelial keratoplasty buttons obtained with optimised femtosecond laser settings.

AIM: To optimise interfaces of endothelial buttons created with femtosecond (FS) lasers. SETTING: Department of Ophthalmology, Hôtel-Dieu Hospital, Paris, France. METHODS: Forty-two corneas were divided into five groups of various cutting patterns and a control group of 100 µm laser in situ keratomileusis flap creation. A single path full lamellar cut (500 µm) was applied to groups 1 and 2. The same full lamellar cut was applied twice to groups 3 and 4. Two successive lamellar cuts were performed in group 5 (350 and 150 µm). 60 kHz and 150 kHz were used respectively in groups 1, 3, 5, 6 and 2, 4. In each group, different laser settings were tested to obtain the best interface quality while delivering minimal energy to the stroma. The quality of stromal interfaces from created endothelial lenticules was observed using a scanning electron microscope. RESULTS: Stromal adherences persisted after both the single- and double-path procedure, creating central irregularities on the endothelial lenticule. Among all groups and settings tested, the double-layer pattern (group 5) with FS full lamellar cut parameters set for diameter (mm), depth (µm), energy (µJ) and spot size/step (µm) respectively on 9.0 mm, 350 µm, 2.1 µJ, 4:4 µm and 8.3 mm, 150 µm, 0.9 µJ, 4:4 µm created the smoothest interfaces with the best reproducibility. CONCLUSIONS: Buttons for endothelial keratoplasty can be created with FS laser with a stromal interface quality comparable with that of refractive surgery.