Table 1.

A table displaying the definitions of phenotype, subphenotype, endotype, and treatable traits, as described by Lötvall et al. [1]

Term	Definition	Potential application to delirium
Phenotype	A set of clinical features in a group of patients who share a common syndrome or condition.	Altered cognition Inattention Altered awareness Disorientation
Subphenotype	A set of features in a group of patients who share a phenotype. Includes shared risk factors, traits, diagnostic features, expression markers, mortality risk, or treatment response—which distinguishes the group from other patients with the same phenotype.	Clinical Shared risk quantification Shared precipitants Specific symptoms, e.g. inattention, agitation Delirium duration Diagnostic features Defined by pathophysiology Prominent mechanism Inflammatory/non-inflammatory Melatonin levels Neurotransmitter presence Network connectivity extent Presence of oxidative stress
Endotype	A distinct biological mechanism of disease which is often associated with an anticipated clinical course, shared by a patient subgroup.	Associations between biological putative pathways of delirium and the clinical symptoms which occur as a result
Treatable traits	Subgroup characteristics which may be successfully targeted by an intervention.	Decisions and development of the best course of action for treatment- Treating symptoms Treating the mechanisms which express the symptoms A combination of both

The potential applications of these definitions to delirium are listed, where the phenotype describes the most common clinical domains. Potential subphenotyping methods may be divided by clinical features and by pathophysiological hypotheses, and the endotype is a hybrid between these. Future treatable traits will be decided once the most effective methods are determined. It is important to note that this is a suggested framework for categorisation