[Healthy aging in Geneva : the innovative approach of the VieSA project]. / Vieillir en santé à Genève : l'approche novatrice du projet VieSA.

With Switzerland's population ageing, promoting healthy ageing remains a public health issue. This represents a challenge for the healthcare system, which is still mainly focused on curative or palliative care. It has been clearly established that it is possible to maintain the functional capacity of older people by taking early action on health-related behaviors. The VieSA (Vieillissement en Santé) project in the canton of Geneva, inspired by the WHO's ICOPE programme, offers innovative ways of promoting healthy ageing for and by seniors, by focusing on maintaining seniors' resources rather than targeting any deficits.

Face au vieillissement de la population en Suisse, la promotion du vieillissement en santé reste un enjeu de santé publique. Cela représente un défi pour le système de soins encore principalement orienté vers les soins curatifs ou palliatifs. Il est clairement établi qu'il est possible de maintenir les capacités fonctionnelles des seniors en agissant précocement sur les comportements liés à la santé. Le projet VieSA (Vieillissement en santé), mené dans le canton de Genève, s'inspire du programme ICOPE de l'OMS et offre des perspectives novatrices pour promouvoir le vieillissement en santé pour et par les seniors, en s'appuyant sur le maintien des ressources des seniors plutôt qu'en ciblant les déficits éventuels.

Delirium in Older Patients With COVID-19: Prevalence, Risk Factors, and Clinical Relevance.

BACKGROUND: Delirium prevalence increases with age and is associated with poor outcomes. We aimed to investigate the prevalence and risk factors for delirium in older patients hospitalized with COVID-19, as well as its association with length of stay and mortality. METHOD: This was a retrospective study of patients aged 65 years and older hospitalized with COVID-19. Data were collected from computerized medical records and all patients had delirium assessment at admission. Risk factors for delirium as well as the outcomes mentioned above were studied by 2-group comparison, logistic regression, and Cox proportional hazard models. RESULTS: Of a total of 235 Caucasian patients, 48 (20.4%) presented with delirium, which was hypoactive in 41.6% of cases, and hyperactive and mixed in 35.4% and 23.0%, respectively. Patients with cognitive impairment had a nearly 4 times higher risk of developing delirium compared to patients who were cognitively normal before SARS-CoV-2 infection (odds ratio 3.7; 95% CI: 1.7-7.9, p = .001). The presence of delirium did not modify the time from symptoms' onset to hospitalization or the length of stay in acute care, but it was associated with an increased risk of dying (hazard ratio 2.1; 95% CI: 1.2-3.7, p = .0113). CONCLUSION: Delirium was a prevalent condition in older people admitted with COVID-19 and preexisting cognitive impairment was its main risk factor. Delirium was associated with higher in-hospital mortality. These results highlight the importance of early recognition of delirium especially when premorbid cognitive comorbidities are present.

Identification of pathway-biased and deleterious melatonin receptor mutants in autism spectrum disorders and in the general population.

Melatonin is a powerful antioxidant and a synchronizer of many physiological processes. Alteration of the melatonin pathway has been reported in circadian disorders, diabetes and autism spectrum disorders (ASD). However, very little is known about the genetic variability of melatonin receptors in humans. Here, we sequenced the melatonin receptor MTNR1A and MTNR1B, genes coding for MT1 and MT2 receptors, respectively, in a large panel of 941 individuals including 295 patients with ASD, 362 controls and 284 individuals from different ethnic backgrounds. We also sequenced GPR50, coding for the orphan melatonin-related receptor GPR50 in patients and controls. We identified six non-synonymous mutations for MTNR1A and ten for MTNR1B. The majority of these variations altered receptor function. Particularly interesting mutants are MT1-I49N, which is devoid of any melatonin binding and cell surface expression, and MT1-G166E and MT1-I212T, which showed severely impaired cell surface expression. Of note, several mutants possessed pathway-selective signaling properties, some preferentially inhibiting the adenylyl cyclase pathway, others preferentially activating the MAPK pathway. The prevalence of these deleterious mutations in cases and controls indicates that they do not represent major risk factor for ASD (MTNR1A case 3.6% vs controls 4.4%; MTNR1B case 4.7% vs 3% controls). Concerning GPR50, we detected a significant association between ASD and two variations, Delta502-505 and T532A, in affected males, but it did not hold up after Bonferonni correction for multiple testing. Our results represent the first functional ascertainment of melatonin receptors in humans and constitute a basis for future structure-function studies and for interpreting genetic data on the melatonin pathway in patients.