BACKGROUND: Children with medical complexity (CMC) often rely upon the use of multiple medications to sustain quality of life and control substantial symptom burden. Pediatric polypharmacy (≥ 5 concurrent medications) is prevalent and increases the risk of medication-related problems (MRPs). Although MRPs are associated with pediatric morbidity and healthcare utilization, polypharmacy is infrequently assessed during routine clinical care for CMC. The aim of this randomized controlled trial is to determine if a structured pharmacist-led Pediatric Medication Therapy Management (pMTM) intervention reduces MRP counts, as well as the secondary outcomes of symptom burden and acute healthcare utilization.

METHODS: This is a hybrid type 2 randomized controlled trial assessing the effectiveness of pMTM compared to usual care in a large, patient-centered medical home for CMC. Eligible patients include all children ages 2-18 years old, with ≥ 1 complex chronic condition, and with ≥ 5 active medications, as well as their English-speaking primary caregivers. Child participants and their primary parental caregivers will be randomized to pMTM or usual care before a non-acute primary care visit and followed for 90 days. Using generalized linear models, the overall effectiveness of the intervention will be evaluated using total MRP counts at 90 days following pMTM intervention or usual care visit. Following attrition, a total of 296 CMC will contribute measurements at 90 days, which provides > 90% power to detect a clinically significant 1.0 reduction in total MRPs with an alpha level of 0.05. Secondary outcomes include Parent-Reported Outcomes of Symptoms (PRO-Sx) symptom burden scores and acute healthcare visit counts. Program replication costs will be assessed using time-driven activity-based scoring.

DISCUSSION: This pMTM trial aims to test hypotheses that a patient-centered medication optimization intervention delivered by pediatric pharmacists will result in lower MRP counts, stable or improved symptom burdens, and fewer cumulative acute healthcare encounters at 90 days following pMTM compared to usual care. The results of this trial will be used to quantify medication-related outcomes, safety, and value for a high-utilization group of CMC, and outcomes may elucidate the role of integrated pharmacist services as a key component of outpatient complex care programs for this priority pediatric population.

TRIAL REGISTRATION: This trial was prospectively registered at clinicaltrials.gov (NCT05761847) on Feb 25, 2023.

<p><strong>Importance: </strong>Parents of children with severe neurological impairment (SNI) manage complex medication regimens (CMRs) at home, and clinicians can help support parents and simplify CMRs.</p>

<p><strong>Objective: </strong>To measure the complexity and potentially modifiable aspects of CMRs using the Medication Regimen Complexity Index (MRCI) and to examine the association between MRCI scores and subsequent acute visits.</p>

<p><strong>Design, Setting, and Participants: </strong>This cross-sectional study was conducted between April 1, 2019, and December 31, 2020, at a single-center, large, hospital-based, complex care clinic. Participants were children with SNI aged 1 to 18 years and 5 or more prescribed medications.</p>

<p><strong>Exposure: </strong>Home medication regimen complexity was assessed using MRCI scores. The total MRCI score is composed of 3 subscores (dosage form, dose frequency, and specialized instructions).</p>

<p><strong>Main Outcomes and Measures: </strong>Patient-level counts of subscore characteristics and additional safety variables (total doses per day, high-alert medications, and potential drug-drug interactions) were analyzed by MRCI score groups (low, medium, and high score tertiles). Associations between MRCI score groups and acute visits were tested using Poisson regression, adjusted for age, complex chronic conditions, and recent health care use.</p>

<p><strong>Results: </strong>Of 123 patients, 73 (59.3%) were male with a median (interquartile range [IQR]) age of 9 (5-13) years. The median (IQR) MRCI scores were 46 (35-61 [range, 8-139]) overall, 29 (24-35) for the low MRCI group, 46 (42-50) for the medium MRCI group, and 69 (61-78) for the high MRCI group. The median (IQR) counts for the subscores were 6 (4-7) dosage forms per patient, 7 (5-9) dose frequencies per patient, and 5 (4-8) instructions per patient, with counts increasing significantly across higher MRCI groups. Similar trends occurred for total daily doses (median [IQR], 31 [20-45] doses), high-alert medications (median [IQR], 3 [1-5] medications), and potential drug-drug interactions (median [IQR], 3 [0-6] interactions). Incidence rate ratios of 30-day acute visits were 1.26 times greater (95% CI, 0.57-2.78) in the medium MRCI group vs the low MRCI group and 2.42 times greater (95% CI, 1.10-5.35) in the high MRCI group vs the low MRCI group.</p>

<p><strong>Conclusions and Relevance: </strong>Higher MRCI scores were associated with multiple dose frequencies, complicated by different dosage forms and instructions, and associated with subsequent acute visits. These findings suggest that clinical interventions to manage CMRs could target various aspects of these regimens, such as the simplification of dosing schedules.</p>

<p><strong>Importance: </strong>Children with severe neurological impairment (SNI) often take multiple medications to treat problematic symptoms. However, for children who cannot self-report symptoms, no system exists to assess multiple symptoms and their association with medication use.</p>

<p><strong>Objectives: </strong>To assess the prevalence of 28 distinct symptoms, test whether higher global symptom scores (GSS) were associated with use of more medications, and assess the associations between specific symptoms and medications.</p>

<p><strong>Design, Setting, and Participants: </strong>This cross-sectional study was conducted between April 1, 2019, and December 31, 2019, using structured parent-reported symptom data paired with clinical and pharmacy data, at a single-center, large, hospital-based special health care needs clinic. Participants included children aged 1 to 18 years with SNI and 5 or more prescribed medications. Data analysis was performed from April to June 2020.</p>

<p><strong>Exposure: </strong>During routine clinical visits, parent-reported symptoms were collected using the validated 28-symptom Memorial Symptom Assessment Scale (MSAS) and merged with clinical and pharmacy data.</p>

<p><strong>Main Outcomes and Measures: </strong>Symptom prevalence, counts, and GSS (scored 0-100, with 100 being the worst) were calculated, and the association of GSS with medications was examined. To evaluate associations between symptom-medication pairs, the proportion of patients with a symptom who used a medication class or specific medication was calculated.</p>

<p><strong>Results: </strong>Of 100 patients, 55.0% were boys, the median (interquartile range [IQR]) age was 9 (5-12) years, 62.0% had 3 or more complex chronic conditions, 76.0% took 10 or more medications, and none were able to complete the MSAS themselves. Parents reported a median (IQR) of 7 (4-10) concurrent active symptoms. The median (IQR) GSS was 12.1 (5.4-20.8) (range, 0.0-41.2) and the GSS was 9.8 points (95% CI, 5.5-14.1 points) higher for those with worse recent health than usual. Irritability (65.0%), insomnia (55.0%), and pain (54.0%) were the most prevalent symptoms. Each 10-point GSS increase was associated with 12% (95% CI, 4%-19%) higher medication counts, adjusted for age and complex chronic condition count. Among the 54.0% of children with reported pain, 61.0% were prescribed an analgesic.</p>

<p><strong>Conclusions and Relevance: </strong>These findings suggest that children with SNI reportedly experience substantial symptom burdens and that higher symptom scores are associated with increased medication use. Paired symptom-medication data may help clinicians identify targets for personalized symptom management, including underrecognized or undertreated symptoms.</p>

<p><strong>BACKGROUND AND OBJECTIVES: </strong>Outpatient adverse drug events (ADEs) can result in serious outcomes requiring emergency department (ED) visits and hospitalizations. The incidence and severity of ADEs in children with complex chronic conditions (CCCs), who often take multiple medications, is unknown. We sought to describe the characteristics of ADE-related ED visits, including association with CCC status; determine the implicated medications; and determine if CCC status increased the risk of ADE-related admission.</p>

<p><strong>METHODS: </strong>Retrospective cohort study of ED visits by patients aged 0 to 18 years using a national sample. ADEs were identified by external cause of injury codes; cases with overdose, wrongful administration, self-harm, or diagnosis of malignancy were excluded. Multivariable logistic regression was used to test outcomes of having an ADE-related ED visit and of subsequent admission. All statistics accounted for the complex survey design.</p>

<p><strong>RESULTS: </strong>Of 144 million ED visits, 0.5% were associated with ADEs. Adjusting for age, gender, insurance type, day of week, and location of hospital, ADEs were associated with the presence of a CCC (odds ratio 4.76; 95% confidence interval: 4.45-5.10). The implicated medications differed significantly by CCC status. Adjusting for the same variables, ADEs were associated with subsequent inpatient admission (odds ratio 2.18; 95% confidence interval: 2.04-2.32) for all children; an interaction between ADE and CCC status was not significant.</p>

<p><strong>CONCLUSIONS: </strong>ED visits associated with ADEs were more likely to occur for children with CCCs, and the implicated drugs differed, but ADE-related admissions were not differentially affected by CCC status.</p>

<p><b>BACKGROUND AND OBJECTIVES: </b>Outpatient pediatric polypharmacy is poorly characterized. Identification of at-risk populations has clinical implications for pharmacy case management programs. We described the degree of exposure to polypharmacy using parameters of depth (concurrent medication count) and duration, reported commonly dispensed medications and exposure to three example potential drug-drug interactions by different depths of polypharmacy, and determined patient characteristics associated with exposure to increased degrees (a function of depth and duration) of polypharmacy.</p><p><b>METHODS: </b>Retrospective cohort study of Colorado fee-for-service Medicaid patients aged <18 years with 12 months of continuous enrollment. We calculated depth of polypharmacy using daily concurrent medication counts and duration of polypharmacy using days exposed to a certain depth. Multinomial logistic regression was used to assess patient characteristics associated with different degrees of polypharmacy.</p><p><b>RESULTS: </b>Of 242 230 patients, 35% percent were exposed to any depth of polypharmacy, most commonly to anti-infective medications. Patients with higher depth polypharmacy were exposed to less common medications (psychotropic drugs, anticonvulsants, cardiovascular agents, and opioids) and to higher rates of exposure to potential drug-drug interactions. Of 47 972 patients exposed to ≥3 concurrent medications, 50% were exposed for <15 days, 25% for 15-38 days, 15% for 39-111 days, and 10% for 112-327 days. High-degree polypharmacy was associated with increasing age, male gender, and presence of a complex chronic condition.</p><p><b>CONCLUSIONS: </b>Outpatient pediatric polypharmacy occurs to a substantial degree for a small but vulnerable population of children, who may be candidates for pharmacy case management. We must determine whether increased exposure to high-degree polypharmacy causes harm. Copyright © 2015 John Wiley & Sons, Ltd.</p>