{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:15:43Z","timestamp":1785402943992,"version":"3.56.0"},"reference-count":25,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:00:00Z","timestamp":1785369600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>Background\/Objectives: Children with medical complexity (CMC) often suffer from chronic or evolving conditions that require increasingly complex treatment regimens over time, resulting in increased therapeutic and care burdens, costs, and the risk of adverse effects and medication errors. The study aimed to describe the variation in healthcare needs, medication regimens and medication burden over time and to describe the relationship between the number of drugs and healthcare needs. Methods: In this cohort study, conducted at the Pediatric Palliative Care Center of Padua, Italy, two repeated assessments were performed, respectively, in October 2021 (t0) and in February 2023 (t1). A total of 169 patients aged \u226423 years receiving at least one prescribed medication were enrolled. Longitudinal analyses were performed in the 147 patients with complete assessments at both time points. Data were collected from medical records and caregiver interviews. Drug costs were collected from the Italian Medicines Agency. Changes between baseline and follow-up were assessed using paired statistical tests (Wilcoxon signed-rank test for continuous variables and McNemar test for categorical variables). The associations between the number of drugs and the ACCAPED scale (Accertamento dei Bisogni Clinico Assistenziali Complessi in Cure Palliative Pediatriche) were assessed using linear regression models. Results: The study analyzed treatment regimens of 147 patients with a median age of 12.1 years at t0 and 14.1 at t1. The prevalence of patients with medication burden (42% vs. 50%, p = 0.022), do-not-resuscitate order (20% vs. 27%, p = 0.027) and an ACCAPED score &gt; 50 (57% vs. 66%, p = 0.012) significantly increased on the second assessment. Also, the number of total daily administrations (5 [3\u201312] vs. 6 [3\u201314], p = 0.019) and the number of medications (4 [2\u20137] vs. 5 [3\u20138], p = 0.013) significantly increased. However, polypharmacy and the median daily cost per patient did not significantly increase between t0 and t1. The association between the number of drugs and the ACCAPED score showed that each additional prescribed drug is associated with an average increase of 3.2 points in the ACCAPED score (95% CI: 2.6, 3.9; p &lt; 0.001). Conclusions: Over time, the degree of complexity in our population increased significantly, as evidenced by the increased healthcare needs, treatment regimens and burden on families. The number of prescribed drugs showed a strong and statistically significant relationship with patient care complexity. Treatment regimen characteristics were strongly associated with patient care complexity. Future studies should evaluate whether these pharmacological variables may have a role in supporting clinical assessment.<\/jats:p>","DOI":"10.3390\/children13081012","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T08:09:42Z","timestamp":1785398982000},"page":"1012","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Evolution of Clinical Fragility and Medication Burden in Children with Medical Complexity: A Longitudinal Cohort Study"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4210-8509","authenticated-orcid":false,"given":"Anna","family":"Zanin","sequence":"first","affiliation":[{"name":"Centre de Coordination Interdisciplinaire et de Soins des Maladies Rares et Complexes de l\u2019Enfant et de l\u2019Adolescent, D\u00e9partement de la Femme, de l\u2019Enfant et de l\u2019Adolescent, Service de P\u00e9diatrie G\u00e9n\u00e9rale, H\u00f4pital des Enfants, 1211 Geneva, Switzerland"},{"name":"Palliative Care and Pain Service, Department of Women\u2019s and Children\u2019s Health, University of Padua, 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Baratiri","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Azienda Ulss3 Serenissima, Ospedale Dell\u2019Angelo, Mestre-Venezia, 30174 Venice, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7274-4373","authenticated-orcid":false,"given":"Gloria","family":"Brigiari","sequence":"additional","affiliation":[{"name":"Unit of Biostatistics, Epidemiology and Public Health, Department of Cardiac, Vascular Sciences and Public Health, University of Padova, 35128 Padua, Italy"},{"name":"BIOSTAT-X Biostatistics & AI for Biomedical Discovery, Pediatric Research Institute (IRP) \u201cCitt\u00e0 della Speranza\u201d, 35127 Padova, Italy"},{"name":"PhD Program in Translation Specialistic Medicine \u201cG.B. Morgagni\u201d, Curriculum \u201cBiostatistics and Clinical Epidemiology\u201d, University of Padua, 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Roverato","sequence":"additional","affiliation":[{"name":"Palliative Care and Pain Service, Department of Women\u2019s and Children\u2019s Health, University of Padua, 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1374-1505","authenticated-orcid":false,"given":"Daniele","family":"Mengato","sequence":"additional","affiliation":[{"name":"Hospital Pharmacy Department, Padua University Hospital, 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Camuffo","sequence":"additional","affiliation":[{"name":"Hospital Pharmacy Department, Padua University Hospital, 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7906-0580","authenticated-orcid":false,"given":"Dario","family":"Gregori","sequence":"additional","affiliation":[{"name":"Unit of Biostatistics, Epidemiology and Public Health, Department of Cardiac, Vascular Sciences and Public Health, University of Padova, 35128 Padua, Italy"},{"name":"BIOSTAT-X Biostatistics & AI for Biomedical Discovery, Pediatric Research Institute (IRP) \u201cCitt\u00e0 della Speranza\u201d, 35127 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0396-4377","authenticated-orcid":false,"given":"Francesca","family":"Venturini","sequence":"additional","affiliation":[{"name":"Hospital Pharmacy Department, Padua University Hospital, 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franca","family":"Benini","sequence":"additional","affiliation":[{"name":"Palliative Care and Pain Service, Department of Women\u2019s and Children\u2019s Health, University of Padua, 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13052-020-00935-z","article-title":"The Child with Medical Complexity","volume":"47","author":"Gallo","year":"2021","journal-title":"Ital. 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Protoc."}],"container-title":["Children"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2227-9067\/13\/8\/1012\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T08:45:43Z","timestamp":1785401143000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2227-9067\/13\/8\/1012"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,30]]},"references-count":25,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["children13081012"],"URL":"https:\/\/doi.org\/10.3390\/children13081012","relation":{},"ISSN":["2227-9067"],"issn-type":[{"value":"2227-9067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,30]]}}}