Lithium for Alzheimer Disease-Pilot Study Sets the Stage for Larger Trials

# Lithium for Alzheimer Disease-Pilot Study Sets the Stage for Larger Trials *Published: 2026 Apr 14* Restrictive vs Liberal Physical Restraint Strategies in Critically Ill Patients: The R2D2-ICU Randomized Clinical Trial. Sonneville R(1)(2), Couffignal C(1)(3), Sigaud F(4), Thy M(1)(2), Godard V(3), Audibert J(5), Contou D(6), Celier A(7), Djibré M(8), Rambaud T(9), Jaquet P(10), Mekontso Dessap A(11), Bourel C(12), Belot R(3), Roy C(3), Nait Sidenas F(2), Essardy F(2), Timsit JF(1)(2), Cornic R(3), Bouadma L(1)(2); R2D2-ICU Investigator Study Group. Collaborators: Abgrall G, Arrestier R, Audibert J, Augy JL, Bagate F, Bay P, Begot E, Ben Salah A, Benelli B, Berti E, Bertier A, Beurton A, Billiet PA, Bouadma L, Bougnaud J, Bouilland AL, Boujelben M, Bureau C, Candille C, Cariou E, Carteaux G, Catano J, Cavaleiro P, Celier A, Chafiotte P, Cirillo G, Clerc S, Conia A, Cordier C, Coupry LM, DA Silva D, Dartevel A, DE Montmollin E, DE Montmollin N, DE Prost N, Decavele M, Deleris R, Desnos C, Dessajan J, Diemoz MC, DO Rego H, DO Vale J, Dres M, Dufranc E, Ejzenberg M, Elabbadi A, Floch PE, Fosse Q, Frapard T, Gaillet A, Galerneau LM, Gendreau S, Goncalves Cavaleiro P, Gontier O, Hamrouni M, Haudebourg AF, Haudebourg L, Jolly F, LE Marec J, Labedade P, Lavillegrand JR, Lecronier M, Lopinto J, Masi P, Mayaux J, Menat S, Moncomble E, Morawiec E, Nagle S, Nemlaghi S, Picard B, Pichon J, Plais H, Razazi K, Rigault G, Sigaud F, Sonneville R, Tchoubou T, Thy M, Timsit JF, Tuffet S, Turpin M, Vincent X, Voiriot G, Wicky PH, Windsor C. Author information: (1)Université Paris Cité, IAME, INSERM UMR 1137, Paris, France. (2)AP-HP.Nord, Department of Intensive Care Medicine, Bichat-Claude Bernard University Hospital, DMU INVICTUS, Paris, France. (3)AP-HP.Nord, Epidemiology, Biostatistics, and Clinical Research, Bichat-Claude Bernard University Hospital, DMU PRISME, Paris, France. (4)Medical Intensive Care Unit, Grenoble Alpes University Hospital, La Tronche, France. (5)Department of Intensive Care, Chartres Hospital, Chartres, France. (6)Department of Intensive Care Medicine, Victor Dupouy Hospital, Argenteuil, France. (7)APHP-Sorbonne Université, Pitié-Salpêtrière University Hospital, Department of Intensive Care Medicine R3S, Paris, France. (8)Medical Intensive Care Unit, Tenon Hospital, Assistance Publique-Hôpitaux de Paris, France. (9)Medical Intensive Care Unit, Avicenne Hospital, Assistance Publique-Hôpitaux de Paris, Bobigny, France. (10)Medical Intensive Care Unit, Delafontaine Hospital, Saint-Denis, France. (11)Medical Intensive Care Unit, Henri Mondor Hospital, Assistance Publique-Hôpitaux de Paris, Créteil, France. (12)Medical Intensive Care Unit, Lille University Hospital, Lille, France. Comment in JAMA. 2026 Apr 14;335(14):1215-1216. doi: 10.1001/jama.2026.2785. ## IMPORTANCE The effect of wrist-strap physical restraints on outcomes in patients receiving mechanical ventilation in the intensive care unit (ICU) remains uncertain. ## OBJECTIVE To investigate the effect of a low-use wrist-strap physical restraint strategy in critically ill patients receiving invasive mechanical ventilation. DESIGN, SETTING, AND PARTICIPANTS Open-label randomized clinical trial conducted across 10 ICUs in France. Between January 5, 2021, and January 2, 2024, 405 adult patients who had initiated invasive mechanical ventilation within the previous 6 hours and were expected to require ventilation for at least 48 hours were enrolled. Follow-up was completed on May 17, 2024. Statistical analysis was conducted from June 1, 2025, to December 15, 2025. ## INTERVENTIONS Patients were randomized to undergo either a restrictive, low-use physical restraint strategy (wrist straps avoided unless necessary because of severe agitation, defined as a Richmond Agitation-Sedation Scale score of ≥3 [on a scale from -5 (unresponsive) to 4 (combative)]; n = 201) or a liberal, high-use strategy (wrist straps applied systematically and reassessed daily; n = 204). Discontinuation of restraints was allowed in patients who were awake or extubated without delirium (measured via the Confusion Assessment Method for the ICU). MAIN OUTCOMES AND MEASURES The primary outcome was the number of days alive without coma or delirium during the first 14 days after randomization. Secondary outcomes included incidence of self-extubation and day-90 mortality. ## RESULTS Among 396 patients with available primary outcome data, the median (IQR) age was 65 (56-73) years, 245 (62%) were male, and the median (IQR) Sequential Organ Failure Assessment score was 7 (4-10). The mean days alive without coma or delirium were 6.67 days (95% CI, 5.69-7.65) in the low-use strategy group and 6.30 days (95% CI, 5.35-7.24) in the high-use strategy group (adjusted mean difference, 0.37 days [95% CI, -0.71 to 1.46]; P = .51). Self-extubation occurred in 18 patients (9.2%) in the low-use strategy group and 17 (8.5%) in the high-use strategy group, and day-90 mortality was 37.2% and 41.0%, respectively. CONCLUSIONS AND RELEVANCE In this randomized clinical trial, among adult patients receiving mechanical ventilation in the ICU, a low-use wrist-strap physical restraint strategy compared with a high-use strategy did not reduce days free of delirium or coma at 14 days. ## TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT04273360. DOI: 10.1001/jama.2026.2897 PMCID: PMC13080548 DOI: 10.1001/jama.2026.3046