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Approximately half of drug-related (re)admissions are potentially preventable, and are therefore a target for healthcare interventions. Several studies have investigated the effects of in-hospital medication reviews on clinically relevant outcome measures, such as drug-related readmissions (DRAs). The identified factors for success of the intervention were multicomponent interventions, multidisciplinary approaches, attention to transitional care and the selection of high-risk patients. In the present study, the impact of transitional multidisciplinary pharmacotherapeutic care (TMPC) on DRAs in a high-risk population is assessed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Less Is More: Optimized pharmacotherapy with improved coNtinuity of CarE in hospitaLized oLder peOple (LIMONCELLO) is a cluster randomized controlled trial. A cluster is defined at the hospital level, and each cluster is randomly allocated (1:1) to the intervention or control group stratified by university or general hospitals. Patients aged 70\u00a0years and older with polypharmacy, a current non-elective hospital admission, completed medication reconciliation, and an increased risk of a DRA, as determined by the use of a DRA prediction model, are selected. TMPC consists of four elements: a pharmacotherapeutic analysis, a transitional multidisciplinary discussion, a pharmacotherapeutic care interview including shared decision-making with the patient, and a discharge letter with the pharmacotherapeutic plan sent to the general practitioner and community pharmacist. The comparator is usual care provided in the participating control hospitals. The primary outcome is the proportion of patients with DRA in the first 30\u00a0days after discharge. The secondary outcomes include cost-effectiveness, quality of life, and mortality.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>The novelty of this study lies in the selection of a patient group expected to be at high risk for DRAs, on the basis of an evidence-based prediction model, as well as in the combination of components used in the intervention. By selecting high-risk patients and applying a multicomponent approach, this study is expected to increase current knowledge on the effects of TMPC on clinically relevant outcomes and cost-effectiveness in hospitalized older patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>Clinicaltrials.gov: NCT05899114, prospective submission, registration June 02 2023 (first inclusion June 5 2023).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12877-025-06533-0","type":"journal-article","created":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T10:02:15Z","timestamp":1766570535000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Less Is More: Optimized pharmacotherapy with improved coNtinuity of CarE in hospitaLized oLder peOple (LIMONCELLO): study protocol of a cluster randomized controlled trial"],"prefix":"10.1186","volume":"25","author":[{"given":"Sjacky","family":"Cooijmans","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eline M. 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