{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T11:01:44Z","timestamp":1789124504179,"version":"build-2803163510"},"reference-count":49,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,7,4]],"date-time":"2024-07-04T00:00:00Z","timestamp":1720051200000},"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: Children with medical complexity (CMC) often require multiple medications, leading to polypharmacy, which seems to be linked to adverse effects, administration errors, and increased caregiver burden. This study aimed to describe the prevalence of polypharmacy, medication burden, off-label drug use, and associated costs. Methods: Conducted at the Pediatric Palliative Care Center of Padua, Italy, from August to October 2021, this cross-sectional observational study included patients up to 23 years old with at least one prescribed drug. Data were collected from medical records and caregiver interviews. Drug costs were collected from the Italian Medicine Agency. Descriptive statistical analysis was performed. For comparisons among categorical variables, the Chi-square test was used, and for those among continuous variables, the ANOVA test was used. Results: This study analyzed treatment regimens of 169 patients with a median age of 12.5 years (0.3\u201323). Polypharmacy was present in 52.7% of patients, and medication burden was observed in 44.4%, both varying significantly by primary diagnosis (p &lt; 0.001). The median daily cost per patient was EUR 2.2 (IQR 0.9\u20137.1), with significant variation among subgroups. Only 34.6% of prescriptions were off-label. Conclusions: polypharmacy and medication burden are frequent among our CMC population, with some differences according to primary diagnosis.<\/jats:p>","DOI":"10.3390\/children11070821","type":"journal-article","created":{"date-parts":[[2024,7,4]],"date-time":"2024-07-04T09:50:32Z","timestamp":1720086632000},"page":"821","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Polypharmacy in Children with Medical Complexity: A Cross-Sectional Study in a Pediatric Palliative Care Center"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4210-8509","authenticated-orcid":false,"given":"Anna","family":"Zanin","sequence":"first","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"}]},{"given":"Fernando","family":"Baratiri","sequence":"additional","affiliation":[{"name":"Department of Women\u2019s and Children\u2019s Health, 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":"Lisa","family":"Pivato","sequence":"additional","affiliation":[{"name":"Hospital Pharmacy Department, Padua University Hospital, 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Avagnina","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"}]},{"given":"Irene","family":"Maghini","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"}]},{"given":"Antuan","family":"Divisic","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"}]},{"given":"Francesca","family":"Rusalen","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\/0000-0003-0584-8871","authenticated-orcid":false,"given":"Caterina","family":"Agosto","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\/0000-0003-0396-4377","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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8312-6976","authenticated-orcid":false,"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":[[2024,7,4]]},"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. J. Pediatr."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1093\/pch\/18.10.518","article-title":"Children with medical complexity in Canada","volume":"18","author":"Dewan","year":"2013","journal-title":"Paediatr. Child Health"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.jpeds.2022.10.012","article-title":"Making Polypharmacy Safer for Children with Medical Complexity","volume":"254","author":"Feinstein","year":"2023","journal-title":"J. Pediatr."},{"key":"ref_4","unstructured":"(2024, June 03). Definition of Polypharmacy. Available online: https:\/\/www.merriam-webster.com\/dictionary\/polypharmacy."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Ahmed, B., Nanji, K., Mujeeb, R., and Patel, M.J. (2014). Effects of polypharmacy on adverse drug reactions among geriatric outpatients at a tertiary care hospital in Karachi: A prospective cohort study. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0112133"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1016\/j.jclinepi.2012.02.018","article-title":"Polypharmacy cutoff and outcomes: Five or more medicines were used to identify community-dwelling older men at risk of different ad-verse outcomes","volume":"65","author":"Gnjidic","year":"2012","journal-title":"J. Clin. Epidemiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1046\/j.1528-1157.2001.30800.x","article-title":"Monotherapy versus polytherapy for epilepsy: A multicenter double-blind randomized study","volume":"42","author":"Deckers","year":"2001","journal-title":"Epilepsia"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Masnoon, N., Shakib, S., Kalisch-Ellett, L., and Caughey, G.E. (2017). What is polypharmacy? A systematic review of definitions. BMC Geriatr., 17.","DOI":"10.1186\/s12877-017-0621-2"},{"key":"ref_9","first-page":"48","article-title":"Predictors of Poor Seizure Control in Children Managed at a Tertiary Care Hospital of Eastern Nepal","volume":"10","author":"Poudel","year":"2016","journal-title":"Iran. J. Child Neurol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"515","DOI":"10.2147\/CEOR.S67424","article-title":"Level, pattern, and determinants of polypharmacy and inappropriate use of medications by village doctors in a rural area of Bangladesh","volume":"6","author":"Rasu","year":"2014","journal-title":"Clin. Outcomes Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1111\/j.1365-2125.2006.02744.x","article-title":"Polypharmacy as commonly defined is an indicator of limited value in the assessment of drug-related problems","volume":"63","author":"Viktil","year":"2007","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1007\/s40272-019-00372-4","article-title":"A scoping review of medications studied in pediatric polypharmacy research","volume":"22","author":"Horace","year":"2020","journal-title":"Pediatr. Drugs"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.jpainsymman.2022.05.020","article-title":"Polypharmacy in Children and Young People With Life-limiting Conditions From 2000 to 2015: A Repeated Cross-sectional Study in England","volume":"64","author":"Fraser","year":"2022","journal-title":"J. Pain Symptom Manag."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1002\/pds.3843","article-title":"The depth, duration, and degree of outpatient pediatric polypharmacy in Colorado fee-for-service Medicaid patients","volume":"24","author":"Feinstein","year":"2015","journal-title":"Pharmacoepidemiol. Drug Saf."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e2029082","DOI":"10.1001\/jamanetworkopen.2020.29082","article-title":"Parent-Reported Symptoms and Medications Used Among Children With Severe Neurological Impairment","volume":"3","author":"Feinstein","year":"2020","journal-title":"JAMA Netw. Open"},{"key":"ref_16","first-page":"113","article-title":"Polypharmacy in pediatric patients and opportunities for pharmacists\u2019 involvement","volume":"4","author":"Horace","year":"2015","journal-title":"Integr. Pharm. Res. Pract."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1007\/s40267-019-00650-8","article-title":"Outcome measures in pediatric polypharmacy research: A scoping review","volume":"35","author":"Golchin","year":"2019","journal-title":"Drugs Ther. Perspect."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Nelson, K.E., Feinstein, J.A., Gerhardt, C.A., Rosenberg, A.R., Widger, K., Faerber, J.A., and Feudtner, C. (2018). Emerging Methodologies in Pediatric Palliative Care Research: Six Case Studies. Children, 5.","DOI":"10.3390\/children5030032"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1186\/s13052-018-0584-8","article-title":"Off-label drugs use in pediatric palliative care","volume":"44","author":"Marchetti","year":"2018","journal-title":"Ital. J. Pediatr."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1046\/j.1365-2125.2000.00125.x","article-title":"Drug trials in children: Problems and the way forward","volume":"49","author":"Conroy","year":"2000","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1016\/j.jpainsymman.2020.06.014","article-title":"Off-Label and Unlicensed Drugs in Pediatric Palliative Care: A Prospective Observational Study","volume":"60","year":"2020","journal-title":"J. Pain Symptom Manag."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"18","DOI":"10.2174\/1574884712666170317161935","article-title":"Pediatric Off-Label and Unlicensed Drug Use and Its Implications","volume":"12","author":"Gore","year":"2017","journal-title":"Curr. Clin. Pharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1517\/14740338.5.5.703","article-title":"Off-label and unlicensed prescribing for newborns and children in different settings: A review of the literature and a consideration about drug safety","volume":"5","author":"Cuzzolin","year":"2006","journal-title":"Expert Opin. Drug Saf."},{"key":"ref_24","first-page":"28","article-title":"Off-label and unlicensed drug use: Results from a pilot study in a pediatric intensive care unit","volume":"86","year":"2017","journal-title":"An. Pediatr\u00eda"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1007\/s12519-021-00430-3","article-title":"Extent, reasons and consequences of off-labeled and unlicensed drug prescription in hospitalized children: A narrative review","volume":"17","author":"Shuib","year":"2021","journal-title":"World J. Pediatr. WJP"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e218","DOI":"10.1097\/PCC.0000000000000684","article-title":"Epidemiology of Polypharmacy and Potential Drug-Drug Interactions among Pediatric Patients in ICUs of U.S. Children\u2019s Hospitals","volume":"17","author":"Dai","year":"2016","journal-title":"Pediatr. Crit. Care Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e99","DOI":"10.1542\/peds.2014-2015","article-title":"Potential drug-drug interactions in infant, child, and adolescent patients in children\u2019s hospitals","volume":"135","author":"Feinstein","year":"2015","journal-title":"Pediatrics"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1612","DOI":"10.1097\/CCM.0000000000001022","article-title":"A Multicenter Evaluation of Off-Label Medication Use and Associated Adverse Drug Reactions in Adult Medical ICUs","volume":"43","author":"Smithburger","year":"2015","journal-title":"Crit. Care Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1001\/jamainternmed.2015.6058","article-title":"Association of Off-label Drug Use and Adverse Drug Events in an Adult Population","volume":"176","author":"Eguale","year":"2016","journal-title":"JAMA Intern. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.jpainsymman.2017.03.014","article-title":"Off-Label Medication Use in the Inpatient Palliative Care Unit","volume":"54","author":"Kwon","year":"2017","journal-title":"J. Pain Symptom Manag."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1089\/jpm.2020.0148","article-title":"A Tool for the Evaluation of Clinical Needs and Eligibility to Pediatric Palliative Care: The Validation of the ACCAPED Scale","volume":"24","author":"Lazzarin","year":"2021","journal-title":"J. Palliat. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e1575","DOI":"10.1542\/peds.2013-3060","article-title":"Adverse drug event-related emergency department visits associated with complex chronic conditions","volume":"133","author":"Feinstein","year":"2014","journal-title":"Pediatrics"},{"key":"ref_33","unstructured":"(2024, June 05). Early Access and Off-Label Use, Available online: https:\/\/aifa.gov.it\/accesso-precoce-uso-off-label."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1016\/j.mayocp.2012.04.017","article-title":"Ten common questions (and their answers) about off-label drug use","volume":"87","author":"Wittich","year":"2012","journal-title":"Mayo Clin. Proc."},{"key":"ref_35","unstructured":"LEGGE 23 Dicembre 1996, n. (2024, June 03). 648\u2014Normattiva. Available online: https:\/\/www.normattiva.it\/uri-res\/N2Ls?urn:nir:stato:legge:1996-12-23;648!vig=."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1017\/S1744133111000090","article-title":"Determinants of branded prescription medicine prices in OECD countries","volume":"6","author":"Kanavos","year":"2011","journal-title":"Health Econ. Policy Law"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2099","DOI":"10.1377\/hlthaff.2014.0832","article-title":"The rise in chronic conditions among infants, children, and youth can be met with continued health system innovations","volume":"33","author":"Perrin","year":"2014","journal-title":"Health Aff. Proj. Hope"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Bakaki, P.M., Horace, A., Dawson, N., Winterstein, A., Waldron, J., Staley, J., Knight, E.M.P., Meropol, S.B., Liu, R., and Johnson, H. (2018). Defining pediatric polypharmacy: A scoping review. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0208047"},{"key":"ref_39","first-page":"96","article-title":"Polypharmacy\u2013An Important Contributor to Health and Safety for Children with Medical Complexity: How Can We Improve Care for This Vulnerable Population?","volume":"29","author":"Grossberg","year":"2024","journal-title":"J. Pediatr. Pharmacol. Ther."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"797","DOI":"10.2147\/CIA.S248377","article-title":"Simplifying Medication Regimens for People Receiving Community-Based Home Care Services: Outcomes of a Non-Randomized Pilot and Feasibility Study","volume":"15","author":"Sluggett","year":"2020","journal-title":"Clin. Interv. Aging"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1093\/pch\/pxy188","article-title":"Choosing medications wisely: Is it time to address paediatric polypharmacy?","volume":"24","author":"Bogler","year":"2019","journal-title":"Paediatr. Child Health"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Tran, V.T., Barnes, C., Montori, V.M., Falissard, B., and Ravaud, P. (2015). Taxonomy of the burden of treatment: A multi-country web-based qualitative study of patients with chronic conditions. BMC Med., 13.","DOI":"10.1186\/s12916-015-0356-x"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"39","DOI":"10.2147\/PROM.S34681","article-title":"Building a measurement framework of burden of treatment in complex patients with chronic conditions: A qualitative study","volume":"3","author":"Eton","year":"2012","journal-title":"Patient Relat. Outcome Meas."},{"key":"ref_44","first-page":"665","article-title":"\u201cYou say treatment, I say hard work\u201d: Treatment burden among people with chronic illness and their carers in Australia","volume":"21","author":"Sav","year":"2013","journal-title":"Health Soc. Care Community"},{"key":"ref_45","unstructured":"(2023, January 23). Recommendations|Cystic Fibrosis: Diagnosis and Management|Guidance|NICE. Available online: https:\/\/www.nice.org.uk\/guidance\/ng78\/chapter\/Recommendations#other-monitoring-assessment-and-management."},{"key":"ref_46","first-page":"725","article-title":"Prevalence and nature of off-label anti-biotic prescribing for children in a tertiary setting: A descriptive study from Jordan","volume":"14","author":"Mukattash","year":"2016","journal-title":"Pharm. Pract."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1007\/s00228-010-0842-1","article-title":"Off-label antibiotic use in children in three European countries","volume":"66","author":"Porta","year":"2010","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_48","first-page":"43","article-title":"Off-label Use of Antibiotics in Pediatrics","volume":"4","author":"Unni","year":"2022","journal-title":"Pediatr. Infect. Dis."},{"key":"ref_49","unstructured":"(2024, June 03). Gazzetta Ufficiale Anno 159\u00b0\u2014Numero 281, Determina AIFA del 22 Novembre 2018. Available online: https:\/\/www.sicp.it\/wp-content\/uploads\/2020\/02\/GU-3-12-18-off-label-cure-palliative.pdf."}],"container-title":["Children"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2227-9067\/11\/7\/821\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:10:11Z","timestamp":1760109011000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2227-9067\/11\/7\/821"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,4]]},"references-count":49,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2024,7]]}},"alternative-id":["children11070821"],"URL":"https:\/\/doi.org\/10.3390\/children11070821","relation":{},"ISSN":["2227-9067"],"issn-type":[{"value":"2227-9067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,4]]}}}