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This systematic review provides insight into the costs of multimorbidity through addressing the following primary and secondary research questions: What evidence exists on the costs of multimorbidity? How do costs of specific disease combinations vary across countries? How do multimorbidity costs vary across disease combinations? What \u201ccost ingredients\u201d are most commonly included in these multimorbidity studies?<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a systematic review (PROSPERO: CRD42020204871) of studies published from January 2010 to January 2022, which reported on costs associated with combinations of at least two specified conditions. Systematic string-based searches were conducted in MEDLINE, The Cochrane Library, SCOPUS, Global Health, Web of Science, and Business Source Complete. We explored the association between costs of multimorbidity and country Gross Domestic Product (GDP) per capita using a linear mixed model with random intercept. Annual mean direct medical costs per capita were pooled in fixed-effects meta-analyses for each of the frequently reported dyads. Costs are reported in 2021 International Dollars (I$).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Fifty-nine studies were included in the review, the majority of which were from high-income countries, particularly the United States. (1) Reported annual costs of multimorbidity per person ranged from I$800 to I$150,000, depending on disease combination, country, cost ingredients, and other study characteristics. (2) Our results further demonstrated that increased country GDP per capita was associated with higher costs of multimorbidity. (3) Meta-analyses of 15 studies showed that on average, dyads which featured Hypertension were among the least expensive to manage, with the most expensive dyads being Respiratory and Mental Health condition (I$36,840), Diabetes and Heart\/vascular condition (I$37,090), and Cancer and Mental Health condition in the first year after cancer diagnosis (I$85,820). (4) Most studies reported only direct medical costs, such as costs of hospitalization, outpatient care, emergency care, and drugs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Multimorbidity imposes a large economic burden on both the health system and society, most notably for patients with cancer and mental health condition in the first year after cancer diagnosis. Whether the cost of a disease combination is more or less than the additive costs of the component diseases needs to be further explored. Multimorbidity costing\u00a0studies typically consider only a limited number of disease combinations, and few have been conducted in low- and middle-income countries and Europe. Rigorous and standardized methods of data collection and costing for multimorbidity should be developed to provide more comprehensive and comparable evidence for the costs of multimorbidity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12916-022-02427-9","type":"journal-article","created":{"date-parts":[[2022,7,18]],"date-time":"2022-07-18T20:02:36Z","timestamp":1658174556000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":191,"title":["Costs of multimorbidity: a systematic review and meta-analyses"],"prefix":"10.1186","volume":"20","author":[{"given":"Phuong Bich","family":"Tran","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Kazibwe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgios F.","family":"Nikolaidis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ismo","family":"Linnosmaa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mieke","family":"Rijken","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josefien","family":"van Olmen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,7,19]]},"reference":[{"key":"2427_CR1","unstructured":"Volksgezondheidenzorg. 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