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.

BACKGROUND: Despite the widespread implementation of Tall Man lettering, little evidence exists regarding whether this technique has reduced drug errors due to look-alike sound-alike (LA-SA) drug names. This study evaluated rates of potential LA-SA drug errors in the drug management process through to the point of dispensing before and after implementation of Tall Man lettering in 2007.

METHODS: We used detailed pharmacy data for paediatric inpatients (<21 years old) from 42 children's hospitals in 2004-2012. After prespecifying a set of 8 potential LA-SA drug error patterns we searched within each hospitalisation for the occurrence of one of these patterns for a total of 12 LA-SA drug pairs deemed highly relevant to paediatric inpatients. To assess for potential change of error rates before and after Tall Man lettering implementation, we performed segmented regression analyses for each of 11 LA-SA drug pairs (because 1 pair had no detected potential errors) and for the overall total errors of all 11 LA-SA drug pairs.

RESULTS: Among 1 676 700 hospitalisations, no statistically significant change was detected for either the intercept or the slope of LA-SA error rate for each of the 11 drug pairs or for the combined error rate. In a sensitivity analysis of the moving average of the potential error rate over the entire study period, no downward trend in potential LA-SA drug error rates was evident over any time period 2004 onwards.

CONCLUSIONS: Implementation of Tall Man lettering in 2007 was not associated with a reduction in the potential LA-SA error rate. Whether Tall Man lettering is effective in clinical practice warrants further study.

<p>Healthcare and outcomes for children with medical complexity (CMC) and their families can be improved by conducting well-conceived, designed, implemented, and analyzed research studies of clinical interventions. This article presents a framework for how to approach the study of clinical interventions for CMC, including 7 key questions and example answers to each: (1) What intervention questions should be our focus? (2) What barriers to intervention research exist? (3) How do we design and optimize interventions? (4) How do we characterize and select patients to enroll? (5) How can we enhance data collection and integration? (6) How can we improve enrollment and participation? And (7) which intervention experimental designs should we choose? By exploring each of these key aspects of intervention-based research, we hope to expand thinking about and spark ideas for specific research projects focused on clinical interventions for CMC.</p>

<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>OBJECTIVE: </strong>To assess the performance of previously published high-intensity neurologic impairment (NI) diagnosis codes in identification of hospitalized children with clinical NI.</p>

<p><strong>METHODS: </strong>Retrospective study of 500 randomly selected discharges in 2019 from a freestanding children's hospital. All charts were reviewed for 1) NI discharge diagnosis codes and 2) documentation of clinical NI (a neurologic diagnosis and indication of functional impairment like medical technology). Test statistics of clinical NI were calculated for discharges with and without an NI diagnosis code. A sensitivity analysis varied the threshold for "substantial functional impairment." Secondary analyses evaluated misclassified discharges and a more stringent definition for NI.</p>

<p><strong>RESULTS: </strong>Diagnosis codes identified clinically documented NI with 88.1% (95% CI: 84.7, 91) specificity, and 79.4% (95% CI: 67.3, 88.5) sensitivity; NPV was 96.7% (95% CI: 94.8, 98.0), and PPV was 49% (95% CI: 42, 56.1). Including children with milder functional impairment (lower threshold) resulted in NPV of 95.7% and PPV of 77.5%. Restricting to children with more severe functional impairment (higher threshold) resulted in NPV of 98.2% and PPV of 44.1%. Misclassification was primarily due to inclusion of children without functional impairments. A more stringent NI definition including diagnosis codes for NI and feeding tubes had a specificity of 98.4% (95% CI: 96.7-99.3) and sensitivity of 28.6% (19.4-41.3).</p>

<p><strong>CONCLUSIONS: </strong>All scenarios evaluated demonstrated high NPV and low-to-moderate PPV of the diagnostic code list. To maximize clinical utility, NI diagnosis codes should be used with strategies to mitigate the risk of misclassification.</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>Although potentially dangerous, little is known about outpatient opioid exposure (OE) in children and youth with special health care needs (CYSHCN). We assessed the prevalence and types of OE and the diagnoses and health care encounters proximal to OE in CYSHCN.</p>

<p><strong>METHODS: </strong>This is a retrospective cohort study of 2 597 987 CYSHCN aged 0-to-18 years from 11 states, continuously enrolled in Medicaid in 2016, with ≥1 chronic condition. OE included any filled prescription (single or multiple) for opioids. Health care encounters were assessed within 7 days before and 7 and 30 days after OE.</p>

<p><strong>RESULTS: </strong>Among CYSHCN, 7.4% had OE. CYSHCN with OE versus without OE were older (ages 10-18 years: 69.4% vs 47.7%), had more chronic conditions (≥3 conditions: 49.1% vs 30.6%), and had more polypharmacy (≥5 other medication classes: 54.7% vs 31.2%), &lt; .001 for all. Most (76.7%) OEs were single fills with a median duration of 4 days (interquartile range: 3-6). The most common OEs were acetaminophen-hydrocodone (47.5%), acetaminophen-codeine (21.5%), and oxycodone (9.5%). Emergency department visits preceded 28.8% of OEs, followed by outpatient surgery (28.8%) and outpatient specialty care (19.1%). Most OEs were preceded by a diagnosis of infection (25.9%) or injury (22.3%). Only 35.1% and 62.2% of OEs were associated with follow-up visits within 7 and 30 days, respectively.</p>

<p><strong>CONCLUSIONS: </strong>OE in CYSHCN is common, especially with multiple chronic conditions and polypharmacy. In subsequent studies, researchers should examine the appropriateness of opioid prescribing, particularly in emergency departments, as well as assess for drug interactions with chronic medications and reasons for insufficient follow-up.</p>

<p>Identification of children with complex chronic conditions (CCCs) is necessary to improve health care delivery and perform clinical research, because this patient population uses significant inpatient and outpatient medical resources. The original CCC classification was published in 2000. A second version was published in 2014 to reflect additions to the International Classification of Diseases system and the US adoption of the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision. The CCC classification is widely used in research (currently cited in more than 100 peer-reviewed journal publications). However, the current approach to assigning the CCC categories in health care–related data sets is limited by proprietary software and computational inefficiency. SAS and Stata software to assign CCC categories were published as appendices to the 2014 update, but not all investigators have access to these statistical packages. In addition, increasingly large data sets are available to investigators. Although the data processing capability of individual computers continues to improve, the SAS and Stata software can take significant time to run on data sets with millions of observations. The objective of this project was to develop computationally efficient software to generate the CCC categories using R, a free, open-source statistical environment. We then compared the SAS, Stata, and R software with respect to accuracy and speed of classification on a typical desktop system.</p>

<p>Given the broad focus of pediatric palliative care (PPC) on the physical, emotional, and spiritual needs of children with potentially life-limiting illnesses and their families, PPC research requires creative methodological approaches. This manuscript, written by experienced PPC researchers, describes issues encountered in our own areas of research and the novel methods we have identified to target them. Specifically, we discuss potential approaches to: assessing symptoms among nonverbal children, evaluating medical interventions, identifying and treating problems related to polypharmacy, addressing missing data in longitudinal studies, evaluating longer-term efficacy of PPC interventions, and monitoring for inequities in PPC service delivery.</p>