The aim of this study is to determine if a geriatric co-management model, referred to as ‘The Geriatric Emergency Medicine (GEM)-team’ is associated with less admissions to hospital in older patients compared with the usual care without increasing the risk of mortality or 30-day emergency department (ED) readmissions.

This observational, controlled study used 18-month data prospectively collected from hospital records. Inverse probability weighting was used to account for baseline differences.

An ED at a suburban Dutch general hospital, receiving approximately 10 000 patients aged 70 or older per year.

All patients aged 70 or older were screened according to predefined criteria. When positively screened patients were presented at the ED on weekdays between 09:00–17:00, they received geriatric co-management. Outside these hours and when the capacity of the GEM team was reached, patients received care as usual.

Geriatric co-management at the ED involves a geriatric multidisciplinary team in collaboration with the primary ED physician who share management and responsibility for the provided medical treatment and nursing care starting directly at the primary assessment.

The primary outcome was hospital admission and secondary outcomes were the composite outcome of 30-day ED readmissions and mortality.

Patients receiving geriatric co-management (n=972) had lower odds for hospitalisation (OR: 0.77, 95% CI 0.65 to 0.91) compared with the control group (n=1355) while 30-day ED readmissions and mortality did not differ between groups (OR: 1.11, 95% CI 0.91 to 1.36).

Geriatric co-management at the ED is associated with decreased hospital admissions while 30-day ED readmissions or mortality was not impacted. These preliminary results contribute to the evidence that geriatric co-management may be an effective intervention for older patients with frailty at the ED.

Neonatal death and later disability remain common sequelae of hypoxic-ischaemic encephalopathy (HIE) despite the now standard use of therapeutic hypothermia (HT). New therapeutic approaches to brain protection are required. Melatonin is an indolamine hormone with free-radical scavenging, antiapoptotic, anti-inflammatory and gene regulatory neuroprotective properties, which has extensive preclinical evidence of safety and efficacy. Pharmacokinetic (PK) data suggest it is necessary to reach melatonin levels of 15–30 mg/L within 6–8 hours of hypoxia-ischaemia for brain protection. We developed a novel Good Manufacturing Practice (GMP) grade melatonin in ethanol 50 mg/mL solution for intravenous use. In preclinical studies, ethanol is an adjuvant excipient with additional neuroprotective benefit; optimised dosing protocols can achieve therapeutic melatonin levels while limiting blood alcohol concentrations (BACs).

The Acute High Dose Melatonin for Encephalopathy of the Newborn (ACUMEN) Study is a first-in-human, international, multicentre, phase 1 safety study of intravenous melatonin in babies with moderate/severe HIE receiving HT. Sixty babies will be studied over two phases: a dose escalation study including four dose levels to establish the recommended phase 2 dose (RP2D), followed by a 6-month cohort expansion study of RP2D to further characterise PKs and affirm safety. Participants will receive a 2-hour intravenous infusion of melatonin within 6 hours of birth, followed by five maintenance doses every 12 hours to cover the period of HT. Plasma melatonin and BACs will be monitored. The RP2D will be based on the attainment of therapeutic melatonin levels while limiting BACs and the frequency of dose-limiting events (DLEs). A Bayesian Escalation with Overdose Control approach will be used to estimate the risk of DLE per dose level, with a target level of

Approval has been given by the London Central National Health Service Health Research Authority Ethics Committee (25/LO/0170) and UK Clinical Trials Authorisation from the Medicines and Healthcare products Regulatory Agency. Separate approvals have been sought in Ireland and Australia. Dissemination will be via peer-reviewed journals, conference presentations, public registries and plain language summaries for parent/legal guardian(s), in accordance with national requirements.

ISRCTN61218504. EU CT: 2025-520538-49-00.

Publication based on the UK protocol V.3.0, 08 May 2025