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Associations between Multimorbidity Clusters and All-Cause Mortality, Quality of Life and Physical Function: A
Joice Cunningham1, Claire M Buckley1, Patricia M Kearney1
1School of Public Health, University College Cork, Cork, County Cork, Ireland.
Background:
Multimorbidity, defined as the coexistence of two or more chronic health conditions in affected individuals, is recognised as a significant global public health concern. While previous research has identified common multimorbidity clusters, the relationships of these clusters with health outcomes is not well understood.
Aim:
To systematically retrieve, synthesise, and appraise the available evidence on the association between multimorbidity clusters and mortality, quality of life (QoL), and physical function.
Methods:
We will conduct a systematic search of PubMed, EMBASE, Web of Science, Ebsco APA PsyInfo and CINAHL from inception until April 2025. Eligible studies will include observational studies (e.g. cohort, cross-sectional or case control) investigating the association between multimorbidity clusters and all-cause mortality, QoL, or physical function in community- dwelling adult populations. Multimorbidity clustering will be defined as the non-random co-occurrence of chronic health conditions. Outcomes of interest include all-cause mortality, health-related quality of life (QoL) (i.e., self-perceived health status), and physical function (e.g., functional independence/physical performance)). Risk of bias will be evaluated using appropriate tools, e.g., the risk of bias in observational studies of exposures (ROBINS-E) tool. Findings will be synthesised narratively, and if feasible, a meta-analysis will be performed. Given the anticipated heterogeneity of multimorbidity clusters, a robust methodological framework, informed by existing multimorbidity literature and stakeholder engagement, will be applied to facilitate comparability across studies.
Conclusion:
This review will lay out and summarise current evidence on the association between different multimorbidity clusters and key health outcomes, including all-cause mortality, QoL, and physical function. It will address methodological approaches used to investigate the multimorbidity-health outcomes associations of interest and summarise current evidence. The findings will enhance our understanding of the unique burden imposed by different clusters of chronic conditions and may inform improvements in healthcare policy, the delivery of health services and patient care. Prospero Registration Number: CRD420251014288 (Date of Registration: 25 Jun 2025 13:08 UTC version 1.0 published).
