Evolution of Clinical Fragility and Medication Burden in Children with Medical Complexity: A Longitudinal Cohort Study.

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 ≤23 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 > 50 (57% vs. 66%, p = 0.012) significantly increased on the second assessment. Also, the number of total daily administrations (5 [3-12] vs. 6 [3-14], p = 0.019) and the number of medications (4 [2-7] vs. 5 [3-8], 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 < 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.