Cortical spreading depolarisation (SD) is a pathological wave of depolarisation in the cortex. SDs occur frequently after severe acute brain injury, and SDs in clusters can contribute to secondary brain damage in patients with severe acute brain injury through hypoperfusion and upregulation of cerebral metabolism in vulnerable brain tissue. Ketamine appears to inhibit SDs both in vitro and in patient series of severe acute brain injury. The KETA-BID trial aims to examine the efficacy and safety of S-ketamine for SDs in severe acute brain injury, as well as the feasibility of the trial design.

This randomised, blinded feasibility and pilot trial includes adults (≥ 18 years) undergoing a supratentorial craniotomy or craniectomy for severe acute brain injury (ie, traumatic brain injury, aneurysmal subarachnoid haemorrhage or spontaneous intracerebral haemorrhage). During surgery, an electrocorticography (ECoG) strip is placed adjacent to injured brain tissue. Patients are continuously monitored throughout their stay at the neurointensive care unit and the neurosurgical step-down unit. In the case of an SD, physiological optimisation of intracranial pressure, brain tissue oxygen tension (PbtO₂), core temperature and blood glucose is initiated. Participants developing SD clusters are randomised for continuous infusion with S-ketamine or matching placebo in a 1:1 allocation with full blinding of the treatment allocation. Infusion rates (ie, dose) and duration of trial medication are adjusted following a dosing algorithm according to SD occurrence. Surviving participants are followed until 6 months after the injury with recording of functional outcome. The primary outcome is occurrence of SDs per hour of monitoring after randomisation.

The Scientific Ethics Committee of the Capital Region of Denmark (H-21056972), the Danish Medicines Agency (EudraCT 2021-003716-12), as well as the Clinical Trials Information System (CTIS 2024-515315-22-00) approved this trial. This trial will provide insight into both SD and the clinical effects of ketamine following severe acute brain injury, presenting a potential new treatment for these patients. The findings will be submitted for publication in peer-reviewed publications.

NCT05095857.

Mental health problems are important causes of disability and economic costs worldwide. Randomised clinical trials examining the treatment of mental health disorders measure heterogeneous outcomes, causing difficulties in data synthesis, interpretation and translation into clinical practice. The aim of the Patient Important Outcomes in Psychiatry (PIO-Psych) Initiative is to develop an overarching, transdiagnostic research-based and consensus-based core outcome set for adult mental health disorders.

The development of the PIO-Psych transdiagnostic core outcome set will include three phases: (1) a systematic scoping review of the literature to develop the initial list of outcomes for the Delphi study; (2) a Delphi study in three rounds including people with lived experience of mental health disorders and their relatives, clinicians, researchers and others (administrators, mental healthcare policymakers, philosophers); (3) a hybrid consensus meeting to agree on the final overarching, transdiagnostic core outcome set and corresponding time points of assessment of each outcome.

Ethical approval is not applicable to this study according to the Research Ethics Committee of the Capital Region of Denmark, as it is not an interventional study. All data will be reported anonymously, and it will not be possible to identify study participants. Results will be disseminated via stakeholder and research networks and peer-reviewed publications.

The PIO-Psych Initiative was pre-registered with COMET (Core Outcome Measures for Effectiveness Trials) on 17 May 2024 (https://www.comet-initiative.org/Studies/Details/3125).

Cardiovascular diseases remain the leading cause of mortality worldwide. Tirzepatide is approved for the treatment of type 2 diabetes mellitus and overweight and is increasingly used. The adverse effects with tirzepatide may not be disease-specific and have not been assessed previously.

We will conduct a systematic review and search major medical databases (Cochrane Central Register of Controlled Trials, Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica database (EMBASE), Latin American and Caribbean Health Sciences Literature (LILACS), Science Citation Index Expanded (SCI-EXPANDED), Conference Proceedings Citation Index—Science (CPCI-S)) and clinical trial registries from their inception and onwards to identify relevant randomised clinical trials. We expect to conduct the literature search in January 2025. Two review authors will independently extract data and perform risk of bias assessments. We will include randomised clinical trials comparing tirzepatide versus placebo or no intervention in all patient groups with an increased risk of cardiovascular events. Primary outcomes will be all-cause mortality and serious adverse events. Secondary outcomes will be myocardial infarction, stroke, all-cause hospitalisation and non-serious adverse events. Data will be synthesised by meta-analyses and Trial Sequential Analysis, risk of bias will be assessed with the Cochrane Risk of Bias tool—version 2. We will systematically assess if the thresholds for statistical and clinical significance are crossed, and the certainty of the evidence will be assessed by Grading of Recommendations, Assessment, Development and Evaluations.

This protocol does not present any results. Findings of this systematic review will be published in international peer-reviewed scientific journals.

CRD42024599035.