Identifying Important Clinical Symptoms in Children With Severe Neurological Impairment Using Parent-Reported Outcomes of Symptoms | Neurology | JAMA Pediatrics | JAMA Network
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Research Letter
October 12, 2020

Identifying Important Clinical Symptoms in Children With Severe Neurological Impairment Using Parent-Reported Outcomes of Symptoms

Author Affiliations
  • 1Adult and Child Consortium for Health Outcomes Research & Delivery Science (ACCORDS), University of Colorado, Children’s Hospital Colorado, Aurora
  • 2Division of General Pediatrics, Department of Pediatrics, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania
  • 3Skaggs School of Pharmacy & Pharmaceutical Sciences, University of Colorado, Aurora
  • 4Research Institute, Children’s Hospital Colorado, Aurora
  • 5Research Informatics, Analytics Resource Center, Children’s Hospital Colorado, Aurora
JAMA Pediatr. 2020;174(11):1114-1117. doi:10.1001/jamapediatrics.2020.2987

Children with severe neurological impairment (SNI) and limited communication abilities often receive numerous medications to treat their medical conditions and ameliorate symptoms.1 To our knowledge, no system currently exists to assess multiple symptoms in this vulnerable population of children who cannot self-report; consequently, the clinical identification and subsequent management of adverse symptoms may be impeded.2 Patient-reported outcomes using the Memorial Symptom Assessment Scale (MSAS) have helped guide symptom management in children with terminal cancers.3 We created the Parent-Reported Outcomes of Symptoms (PRO-Sx) system to collect structured clinical, medication, and symptom data using the MSAS for symptom assessment.4 We used PRO-Sx in a population of children with SNI to test the hypothesis that previsit PRO-Sx data would identify more symptoms than clinicians do at the time of visit and to assess concordance between PRO-Sx and clinician-collected symptom data.


Between April 1, 2019, and December 31, 2019, we obtained written parental consent to enroll participants aged 1 to 18 years with SNI5 who were cared for in a large, hospital-based special needs primary care clinic. This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guidelines for observational cross-sectional studies. This study was approved by the Colorado Multiple Institutional Review Board and registered with (NCT03849066). Before nonacute routine visits, PRO-Sx data were collected using a tablet-based pediatric-specific MSAS, which measures the frequency, severity, and associated distress in the past week for 28 distinct symptoms.3,4 After visit completion, clinician-identified symptoms were abstracted through blinded manual medical record review and text mining using WordStat version 8.0 (Provalis Research). We compared PRO-Sx and clinician-reported total symptom counts using paired t tests. We assessed concordance between PRO-Sx and clinician-noted symptoms using Cohen κ and directionality using the McNemar test. Analyses were conducted using Stata version 16.1, and significance was set at a 2-tailed P value less than .05.


Of 100 participants with SNI (Table), 55 (55.0%) were male, and the median (interquartile range; range) age was 9 (5-12; 1-18) years. There was a high prevalence of 3 or more complex chronic conditions (71 [71.0%]) and of 10 or more concurrent prescription medications (76 [76.0%]). Most (67 [67.0%]) were taking 1 or more central nervous system medications. Overall, parents identified significantly more symptoms (mean, 6.9 symptoms; 95.0% CI, 6.1-7.9) than clinicians did (mean, 4.0 symptoms; 95.0% CI, 3.6-4.4). Twenty-five of 28 possible symptoms were prevalent in 10.0% or more of the children. The most prevalent parent-reported symptoms were irritability (65 [65.0%]), insomnia (55 [55.0%]), and pain (54 [54.0%]) (Figure). One in 5 participants were reported to have itching and 1 in 7 had dry mouth. Overall mean concordance was low (κ = 0.35; 95.0% CI, 0.33-0.38) but was higher for certain important symptoms, like seizures (κ = 0.91; 95.0% CI, 0.71-1.00), headaches (κ = 0.71; 95.0% CI, 0.52-0.89), and dyspnea (κ = 0.67; 95.0% CI, 0.49-0.86) (Figure). Concordance was weaker to absent for most symptoms, including highly prevalent symptoms, like pain (κ = 0.33; 95.0% CI, 0.19-0.48), irritability (κ = 0.10; 95.0% CI, 0-0.19), and drowsiness (κ = 0.04; 95.0% CI, 0-0.09), and bothersome symptoms, like itching (κ = 0.16; 95.0% CI, 0.05-0.27) and dry mouth (κ = 0; 95.0% CI, 0-0). Parents noted each symptom at a higher proportion than clinicians did (Figure).

Table.  Demographic and Clinical Characteristics of 100 Children With Severe Neurological Impairment
Demographic and Clinical Characteristics of 100 Children With Severe Neurological Impairment
Figure.  Concordance Between Parent-Reported Outcomes of Symptoms (PRO-Sx) and Clinician-Noted Symptoms Among 100 Children With Severe Neurological Impairment
Concordance Between Parent-Reported Outcomes of Symptoms (PRO-Sx) and Clinician-Noted Symptoms Among 100 Children With Severe Neurological Impairment

This figure displays the Cohen κ value with 95% CI for each of the 28 symptoms. The parent-reported symptom prevalence is noted next to each symptom.

aThe McNemar test was significant for parents reporting the symptom at a higher proportion than what was documented in clinical notes.


In this study, parents reported nearly twice as many concomitant symptoms compared with clinicians during clinical visits. Although parents and clinicians jointly identified severe or life-threatening symptoms (eg, seizures), this occurred less frequently for less severe but still bothersome symptoms (eg, itching). For example, these patients’ polypharmacologic regimens often included central nervous system medications with a high propensity to cause anticholinergic symptoms,6 and parents reported that more than one-third of participants had anticholinergiclike symptoms, including drowsiness or dry mouth, but these symptoms were largely unaddressed in clinical documentation. Thus, for children with SNI, routine previsit PRO-Sx data collection may assist clinicians in identifying important clinical symptoms to prioritize and address during outpatient encounters. Monitoring changes over time in PRO-Sx data may enable personalized symptom management via initiating, modifying, or discontinuing different types of interventions to maximize symptom control while minimizing adverse symptoms.

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Article Information

Accepted for Publication: April 3, 2020.

Corresponding Author: James A. Feinstein, MD, MPH, Adult and Child Consortium for Health Outcomes Research & Delivery Science (ACCORDS), University of Colorado, Children’s Hospital Colorado, 11389 E Montview Ave, Ste 300, Room 312A, Aurora, CO 80045 (

Published Online: October 12, 2020. doi:10.1001/jamapediatrics.2020.2987

Author Contributions: Dr Feinstein had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Feinstein, Feudtner, Valuck, Kempe.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Feinstein, Fairclough.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Feinstein, Valuck, Fairclough.

Obtained funding: Feinstein.

Administrative, technical, or material support: Feinstein, Holstein, Samay.

Supervision: Feinstein, Kempe.

Conflict of Interest Disclosures: None reported.

Funding/Support: Dr Feinstein was supported by grant K23HD091295 from the Eunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institutes of Health.

Role of the Funder/Sponsor: The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Disclaimer: The content is solely the responsibility of the authors and does not represent the official views of the National Institutes of Health or the US government.

Additional Contributions: We acknowledge LiseAnne Gregoire, BS, who is a salaried professional research coordinator in the Research Institute at Children’s Hospital Colorado, Aurora, for her participation in data acquisition. Ms Gregoire did not receive additional compensation for her participation in this study.

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