Cognitive functioning and pain interference mediate pain predictive effects on health-related quality of life in pediatric patients with Neurofibromatosis Type 1.

OBJECTIVES: The objective was to investigate the serial mediating effects of perceived cognitive functioning and pain interference in daily living in the relationship between perceived pain and overall generic health-related quality of life (HRQOL) in children, adolescents, and young adults with Neurofibromatosis Type 1 (NF1). METHODS: The Pain, Cognitive Functioning, and Pain Impact Scales from the PedsQL Neurofibromatosis Type 1 Module and the PedsQL 4.0 Generic Core Scales were completed in a multi-site national study by 323 patients ages 5-25 and 335 parents. A serial multiple mediator model analysis was conducted to test the hypothesized sequential mediating effects of cognitive functioning and pain interference as intervening variables in the association between pain as a predictor variable and overall generic HRQOL. RESULTS: Pain predictive effects on overall generic HRQOL were serially mediated by cognitive functioning and pain interference. In predictive analytics models utilizing hierarchical multiple regression analyses with age and gender demographic covariates, pain, cognitive functioning and pain interference accounted for 66% of the variance in patient-reported generic HRQOL and 57% of the variance in parent proxy-reported generic HRQOL (P < 0.001), reflecting large effect sizes. CONCLUSIONS: Cognitive functioning and pain interference explain in part the mechanism of pain predictive effects on overall generic HRQOL in pediatric patients with NF1. Identifying NF1-specific pain, cognitive functioning, and pain interference as salient predictors of overall generic HRQOL from the patient and parent perspective facilitates a family-centered orientation to the comprehensive care of children, adolescents, and young adults with NF1.

Cognitive functioning, patient health communication, and worry mediate pain predictive effects on health-related quality of life in youth with sickle cell disease.

OBJECTIVES: The objective was to investigate the serial mediating effects of perceived cognitive functioning, patient health communication, and disease-specific worry in the relationship between pain and overall generic health-related quality of life (HRQOL) in youth with sickle cell disease (SCD) from the patient perspective. METHODS: The pain, cognitive functioning, communication and worry scales from the Pediatric Quality of Life Inventory (PedsQL) Sickle Cell Disease Module and the PedsQL Multidimensional Fatigue Scale, and the PedsQL 4.0 Generic Core Scales were completed in a multisite national study by 233 youth with SCD of ages 5-18. Hierarchical multiple regression and serial multiple mediator model analyses were conducted to test the mediating effects of perceived cognitive functioning, health communication, and disease-specific worry as intervening variables in the association between the pain predictor variable and overall generic HRQOL. RESULTS: Pain predictive effects on overall generic HRQOL were serially mediated by cognitive functioning, health communication, and disease-specific worry. In predictive analytics models utilizing hierarchical multiple regression analyses with age and gender demographic covariates, pain, cognitive functioning, health communication, and worry accounted for 65% of the variance in patient-reported overall generic HRQOL (P < .001), representing a large effect size. CONCLUSIONS: Perceived cognitive functioning, patient health communication, and disease-specific worry explain in part the mechanism of pain predictive effects on overall generic HRQOL in youth with SCD. Identifying SCD-specific pain, perceived cognitive functioning, health communication, and disease-specific worry as predictor variables of overall generic HRQOL from the patient perspective may inform clinical interventions and future patient-centered clinical research.

Severe Acute Kidney Injury Is Associated With Increased Risk of Death and New Morbidity After Pediatric Septic Shock.

OBJECTIVES: Acute kidney injury is common in critically ill children; however, the frequency of septic shock-associated acute kidney injury and impact on functional status are unknown. We evaluated functional outcomes of children with septic shock-associated acute kidney injury. DESIGN: Secondary analysis of patients with septic shock from the prospective Life after Pediatric Sepsis Evaluation study. We defined acute kidney injury using Kidney Disease Improving Global Outcomes criteria, comparing patients with absent/Stage 1 acute kidney injury to those with Stage 2/3 acute kidney injury (severe acute kidney injury). Our primary outcome was a composite of mortality or new functional morbidity at day 28 of hospitalization or discharge. We also assessed poor long-term outcome, defined as mortality or a persistent, serious deterioration in health-related quality of life at 3 months. SETTING: Twelve academic PICUs in the United States. PATIENTS: Critically ill children, 1 month to 18 years, with community-acquired septic shock requiring vasoactive-inotropic support. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: More than 50% of patients (176/348) developed severe acute kidney injury; of those, 21.6% (38/176) required renal replacement therapy. Twice as many patients with severe acute kidney injury died or developed new substantive functional morbidity (38.6 vs 16.3%; p < 0.001). After adjustment for age, malignancy, and initial illness severity, severe acute kidney injury was independently associated with mortality or new substantive morbidity (adjusted odds ratio, 2.78; 95% CI, 1.63-4.81; p < 0.001). Children with severe acute kidney injury had poorer health-related quality of life at 3 months (adjusted effect size 2.46; 95% CI, 1.44-4.20; p = 0.002). Children with severe acute kidney injury required longer duration of mechanical ventilation (11.0 vs 7.0 d; p < 0.001) and PICU stay (11.7 vs 7.1 d; p < 0.001). CONCLUSIONS: Among children with septic shock, severe acute kidney injury was independently associated with increased risk of death or new substantive functional morbidity. Survivors of sepsis with severe acute kidney injury were more likely to have persistent, serious health-related quality of life deterioration at 3 months.

Speech difficulties and patient health communication mediating effects on worry and health-related quality of life in children, adolescents, and young adults with Neurofibromatosis Type 1.

The objective was to investigate the serial mediating effects of speech difficulties, patient health communication, and disease-specific worry in the relationship between neurofibromatosis (NF) symptoms (pain and skin symptoms) and total generic health-related quality of life (HRQOL) in children, adolescents, and young adults with NF Type 1 (NF1) from the patient perspective. The Speech, Communication, Worry, Pain, Skin Itch Bother, and Skin Sensations Scales from the Pediatric Quality of Life Inventory (PedsQL) NF1 Module and the PedsQL 4.0 Generic Core Scales were completed in a multi-site national study by 305 patients ages 5-25 years. A serial multiple mediator model analysis was conducted to test the hypothesized sequential mediating effects of speech difficulties, health communication, and worry as intervening variables in the association between NF1 symptoms and HRQOL. Symptoms predictive effects on total generic HRQOL were serially mediated by speech difficulties, patient health communication, and worry. In predictive analytics models utilizing hierarchical multiple regression analyses with age and gender demographic covariates, the pain, skin itch bother, and skin sensations multiple mediator models accounted for 61%, 59%, and 56% of the variance in generic HRQOL (p < .001), reflecting large effect sizes. Speech difficulties, patient health communication, and disease-specific worry explain in part the mechanism of symptoms predictive effects on total generic HRQOL in pediatric patients with NF1. Identifying NF1-specific predictors and serial mediators of total generic HRQOL in pediatric patients with NF1 from the patient perspective enables a patient-centered comprehensive care approach for children, adolescents, and young adults with NF1.

Higher Risks of Toxicity and Incomplete Recovery in 13- to 17-Year-Old Females after Marrow Donation: RDSafe Peds Results.

Although donation of bone marrow (BM) or peripheral blood stem cells (PBSCs) from children to family members undergoing allogeneic transplantation are well-established procedures, studies detailing levels of pain, symptoms, and long-term recovery are lacking. To address this lack, we prospectively enrolled 294 donors age <18 years at 25 pediatric transplantation centers in North America, assessing them predonation, peridonation, and at 1 month, 6 months, and 1 year postdonation. We noted that 71% of children reported pain and 59% reported other symptoms peridonation, with resolution to 14% and 12% at 1 month postdonation. Both older age (age 13 to 17 years versus younger) and female sex were associated with higher levels of pain peridonation, with the highest rates in older females (57% with grade 2-4 pain and 17% with grade 3-4 pain). Multivariate analyses showed a 4-fold increase in risk for older females compared with males age <13 years (P <.001). At 1 year, 11% of 13- to 17-year-old females reported grade 2-4 pain, compared with 3% of males age 13 to 17 years, 0% of females age <13 years, and 1% of males age <13 years (P = .01). Males and females age 13 to 17 years failed to return to predonation pain levels at 1 year 22% and 23% of the time, respectively, compared with 3% and 10% in males and females age <13 years (P = .002). Our data show that females age 13 to 17 years are at increased risk of grade 2-4 pain at 1 year and >20% of females and males age 13 to 17 years do not return to baseline pain levels by 1 year after BM donation. Studies aimed at decreasing symptoms and improving recovery in older children are warranted.

Effect of Aging and Predonation Comorbidities on the Related Peripheral Blood Stem Cell Donor Experience: Report from the Related Donor Safety Study.

The development of reduced-intensity approaches for allogeneic hematopoietic cell transplantation has resulted in growing numbers of older related donors (RDs) of peripheral blood stem cells (PBSCs). The effects of age on donation efficacy, toxicity, and long-term recovery in RDs are poorly understood. To address this we analyzed hematologic variables, pain, donation-related symptoms, and recovery in 1211 PBSC RDs aged 18 to 79 enrolled in the Related Donor Safety Study. RDs aged > 60 had a lower median CD34+ level before apheresis compared with younger RDs (age > 60, 59 × 106/L; age 41 to 60, 81 × 106/L; age 18 to 40, 121 × 106/L; P < .001). This resulted in older donors undergoing more apheresis procedures (49% versus 30% ≥ 2 collections, P < .001) and higher collection volumes (52% versus 32% > 24 L, P < .001), leading to high percentages of donors aged > 60 with postcollection thrombocytopenia <50 × 109/L (26% and 57% after 2 and 3days of collection, respectively). RDs aged 18 to 40 had a higher risk of grades 2 to 4 pain and symptoms pericollection, but donors over age 40 had more persistent pain at 1, 6, and 12 months (odds ratio [OR], 1.7; P = 0.02) and a higher rate of nonrecovery to predonation levels (OR, 1.7; P = .01). Donors reporting comorbidities increased significantly with age, and those with comorbidities that would have led to deferral by National Marrow Donor Program unrelated donor standards had an increased risk for persistent grades 2 to 4 pain (OR, 2.41; P < .001) and failure to recover to predonation baseline for other symptoms (OR, 2.34; P = .004). This information should be used in counseling RDs regarding risk and can assist in developing practice approaches aimed at improving the RD experience for high-risk individuals.

Pain, skin sensations symptoms, and cognitive functioning predictors of health-related quality of life in pediatric patients with Neurofibromatosis Type 1.

OBJECTIVES: The aim was to investigate pain, skin sensations symptoms and patient self-reported, and parent proxy-reported cognitive functioning as predictors of generic health-related quality of life (HRQOL) in pediatric patients with Neurofibromatosis Type 1 (NF1) from the perspectives of patients and parents. METHODS: The Pain, Skin Itch Bother, Skin Sensations, and Cognitive Functioning Scales from the PedsQL™ Neurofibromatosis Type 1 Module and the PedsQL™ Generic Core Scales were completed in a multi-site national study by 323 patients and 335 parents. Patients were 5-25 years of age. Pain and skin symptoms and cognitive functioning were tested for bivariate and multivariate linear associations with generic HRQOL. RESULTS: Pain, skin itch bother, skin sensations, and cognitive functioning were associated with decreased HRQOL in bivariate analyses (Ps < 0.001). In predictive analytics models, utilizing hierarchical multiple regression analyses controlling for demographic covariates, pain, skin itch bother, skin sensations, and cognitive functioning as a group accounted for 61 percent of the variance in patient-reported generic HRQOL (P < 0.001), reflecting a large effect size. For parent proxy-report, the predictor variables as a group accounted for 53% of the variance in generic HRQOL. CONCLUSIONS: Pain, skin symptoms, and patient self-reported and parent proxy-reported cognitive functioning are key predictors of generic HRQOL in pediatric patients with NF1. Delineating NF1-specific symptoms and cognitive functioning as high-priority predictors from the patient and parents perspective enhances a family-centered approach in clinical research, clinical trials, and clinical practice intended to improve the global generic HRQOL of pediatric patients with NF1.

Perceived medication adherence barriers mediating effects between gastrointestinal symptoms and health-related quality of life in pediatric inflammatory bowel disease.

OBJECTIVES: The primary objective was to investigate the mediating effects of patient-perceived medication adherence barriers in the relationship between gastrointestinal symptoms and generic health-related quality of life (HRQOL) in adolescents with inflammatory bowel disease (IBD). The secondary objective explored patient health communication and gastrointestinal worry as additional mediators with medication adherence barriers in a serial multiple mediator model. METHODS: The Pediatric Quality of Life Inventory™ Gastrointestinal Symptoms, Medicines, Communication, Gastrointestinal Worry, and Generic Core Scales were completed in a 9-site study by 172 adolescents with IBD. Gastrointestinal Symptoms Scales measuring stomach pain, constipation, or diarrhea and perceived medication adherence barriers were tested for bivariate and multivariate linear associations with HRQOL. Mediational analyses were conducted to test the hypothesized mediating effects of perceived medication adherence barriers as an intervening variable between gastrointestinal symptoms and HRQOL. RESULTS: The predictive effects of gastrointestinal symptoms on HRQOL were mediated in part by perceived medication adherence barriers. Patient health communication was a significant additional mediator. In predictive analytics models utilizing multiple regression analyses, demographic variables, gastrointestinal symptoms (stomach pain, constipation, or diarrhea), and perceived medication adherence barriers significantly accounted for 45, 38, and 29 percent of the variance in HRQOL (all Ps < 0.001), respectively, demonstrating large effect sizes. CONCLUSIONS: Perceived medication adherence barriers explain in part the effects of gastrointestinal symptoms on HRQOL in adolescents with IBD. Patient health communication to healthcare providers and significant others further explain the mechanism in the relationship between gastrointestinal symptoms, perceived medication adherence barriers, and HRQOL.

PedsQL Neurofibromatosis Type 1 Module for children, adolescents and young adults: feasibility, reliability, and validity.

The objective of the present study was to report on the measurement properties of the Pediatric Quality of Life Inventory (PedsQL) Neurofibromatosis Type 1 Module for pediatric patients ages 5-25 from the perspectives of patients and parents. The 104-item PedsQL NF1 Module and 23-item PedsQL Generic Core Scales were completed in a multi-site national study by 323 patients and 335 parents (343 families). Patients were diagnosed with NF1 using the National Institutes of Health diagnostic criteria. In addition to a Total Scale Score, 18 unidimensional scales were derived measuring skin itch bother, skin sensations, pain, pain impact, pain management, cognitive functioning, speech, fine motor, balance, vision, perceived physical appearance, communication, worry, treatment anxiety, medicines, stomach discomfort, constipation, and diarrhea. The PedsQL NF1 Module Scales evidenced excellent feasibility, excellent reliability for the Total Scale Scores (patient self-report α = 0.98; parent proxy-report α = 0.98), and good to excellent reliability for the 18 individual scales (patient self-report α = 0.71-0.96; parent proxy-report α = 0.73-0.98). Intercorrelations with the Generic Core Scales supported construct validity. Factor analysis supported the unidimensionality of the 18 individual scales. The PedsQL NF1 Module Scales demonstrated acceptable to excellent measurement properties, and may be utilized as standardized metrics to assess NF1-specific symptoms and problems in clinical research and practice in children, adolescents, and young adults.

The health-related quality of life of children, adolescents, and young adults with neurofibromatosis type 1 and their families: Analysis of narratives.

PURPOSE: Provide an in-depth description of the health-related quality of life (HRQoL) in youth diagnosed with neurofibromatosis type 1 (NF1) and their families. DESIGN AND METHODS: Data were drawn from qualitative interviews conducted for a larger study aimed at developing the Pediatric Quality of Life Inventory™ (PedsQL™) NF1 module. RESULTS: Youth with NF1 and their families experience a wide range of concerns related to HRQoL due to the varied symptom expression and uncertain trajectory of the disorder. PRACTICE IMPLICATIONS: Pediatric nurses should routinely assess for HRQoL in this population and develop strategies tailored to those concerns that require intervention.

Development of the pediatric quality of life inventory neurofibromatosis type 1 module items for children, adolescents and young adults: qualitative methods.

Health-related quality of life (HRQOL) is arguably one of the most important measures in evaluating effectiveness of clinical treatments. At present, there is no disease-specific outcome measure to assess the HRQOL of children, adolescents and young adults with Neurofibromatosis Type 1 (NF1). This study aimed to develop the items and support the content validity for the Pediatric Quality of Life Inventory™ (PedsQL™) NF1 Module for children, adolescents and young adults. The iterative process included multiphase qualitative methods including a literature review, survey of expert opinions, semi-structured interviews, cognitive interviews and pilot testing. Fifteen domains were derived from the qualitative methods, with content saturation achieved, resulting in 115 items. The domains include skin, pain, pain impact, pain management, cognitive functioning, speech, fine motor, balance, vision, perceived physical appearance, communication, worry, treatment, medicines and gastrointestinal symptoms. This study is limited because all participants are recruited from a single-site. Qualitative methods support the content validity for the PedsQL™ NF1 Module for children, adolescents and young adults. The PedsQL™ NF1 Module is now undergoing national multisite field testing for the psychometric validation of the instrument development.

Gastrointestinal Symptoms Predictors of Health-Related Quality of Life in Patients With Inflammatory Bowel Disease.

OBJECTIVES: The aim of the study was to investigate the multidimensional gastrointestinal symptoms predictors of generic health-related quality of life (HRQOL) in pediatric patients with inflammatory bowel disease from the perspectives of pediatric patients and parents. METHODS: The Pediatric Quality of Life Inventory Gastrointestinal Symptoms Scales and Pediatric Quality of Life Inventory 4.0 Generic Core Scales were completed in a 9-site study by 260 families of patients with inflammatory bowel disease. Gastrointestinal Symptoms Scales measuring stomach pain, food and drink limits, gas and bloating, constipation, blood in stool, and diarrhea were identified as clinically important symptom differentiators from healthy controls based on prior findings, and subsequently tested for bivariate and multivariate linear associations with overall HRQOL (Generic Core Scales). RESULTS: Stomach pain, food and drink limits, gas and bloating, constipation, blood in stool, and diarrhea were significantly associated with decreased HRQOL in bivariate analyses (P < 0.001). In predictive models utilizing hierarchical multiple regression analyses controlling for age, sex, and race/ethnicity, gastrointestinal symptoms accounted for an additional 40% of the variance in patient self-reported HRQOL (P < 0.001) and 37% of the variance in parent proxy-reported HRQOL (P < 0.001), reflecting large effect sizes. Stomach pain, food and drink limits, and constipation were significant individual patient-reported predictors after controlling for the other gastrointestinal symptoms in the predictive models. CONCLUSIONS: Patient-reported gastrointestinal symptoms differentially predicted HRQOL. Identifying the specific gastrointestinal symptoms from a standardized multidimensional gastrointestinal symptoms profile that are the most important predictors from the patient perspective facilitates a patient-centered approach for interventions designed to ameliorate impaired HRQOL.

Health-Related Quality of Life among Pediatric Hematopoietic Stem Cell Donors.

OBJECTIVES: To examine health-related quality of life (HRQoL) among sibling pediatric hematopoietic stem cell donors from predonation through 1 year postdonation, to compare donor-reported HRQoL scores with proxy-reports by parents/guardians and those of healthy norms, and to identify predonation factors (including donor age) potentially associated with postdonation HRQoL, to better understand the physical and psychosocial effects of pediatric hematopoietic stem cell donation. STUDY DESIGN: A random sample of 105 pediatric donors from US centers and a parent/guardian were interviewed by telephone predonation and 4 weeks and 1 year postdonation. The interview included sociodemographic, psychosocial, and HRQoL items. A sample of healthy controls matched to donors by age, gender, and race/ethnicity was generated. RESULTS: Key findings included (1) approximately 20% of donors at each time point had very poor HRQoL; (2) child self-reported HRQoL was significantly lower than parent proxy-reported HRQoL at all 3 time points and significantly lower than that of norms at predonation and 4 weeks postdonation; and (3) younger children were at particular risk of poor HRQoL. CONCLUSIONS: Additional research to identify the specific sources of poorer HRQoL among at-risk donors (eg, the donation experience vs having a chronically ill sibling) and the reasons that parents may be overestimating HRQoL in their donor children is critical and should lead to interventions and policy changes that ensure positive experiences for these minor donors.

Pediatric Eosinophilic Esophagitis Symptom Scores (PEESS v2.0) identify histologic and molecular correlates of the key clinical features of disease.

BACKGROUND: The Pediatric Eosinophilic Esophagitis Symptom Score (PEESS v2.0) measures patient-relevant outcomes. However, whether patient-identified domains (dysphagia, gastroesophageal reflux disease [GERD], nausea/vomiting, and pain) align with clinical symptomology and histopathologic and molecular features of eosinophilic esophagitis (EoE) is unclear. OBJECTIVE: The purpose of this study was to determine whether clinical features of EoE, measured through PEESS v2.0, associate with histopathologic and molecular features of EoE. This represents a novel approach for analysis of allergic diseases, given the availability of allergic tissue biopsy specimens. METHODS: We systematically recruited treated and untreated pediatric patients with EoE (aged 2-18 years) and examined parent proxy-reported symptoms using the PEESS v2.0. Clinical symptomology was collected by questionnaire. Esophageal biopsy samples were quantified for levels of eosinophils, eosinophil peroxidase (EPX) immunohistochemical staining, and mast cells. Molecular features were assessed by using the EoE Diagnostic Panel (94 EoE-related gene transcripts). Associations between domain scores and clinical symptoms and biological features were analyzed with Wilcoxon rank sum and Spearman correlation. RESULTS: The PEESS v2.0 domains correlated to specific parent-reported symptoms: dysphagia (P = .0012), GERD (P = .0001), and nausea/vomiting (P < .0001). Pain correlated with multiple symptoms (P < .0005). Dysphagia correlated most strongly with overall histopathology, particularly in the proximal esophagus (P ≤ .0049). Markers of esophageal activity (EPX) were significantly associated with dysphagia (strongest r = 0.37, P = .02). Eosinophil levels were more associated with pain (r = 0.27, P = .06) than dysphagia (r = 0.24, P = .13). The dysphagia domain correlated most with esophageal gene transcript levels, predominantly with mast cell-specific genes. CONCLUSION: We have (1) established a validated, parent proxy-reported measure for pediatric EoE, the PEESS v2.0; (2) verified that the parent proxy effectively captures symptoms; (3) determined that the dysphagia domain most closely aligns with symptoms and tissue-based molecular biomarkers; (4) established that symptoms correlate with EPX staining; and (5) observed association between mast cells and dysphagia.

PROMIS(®) pediatric self-report scales distinguish subgroups of children within and across six common pediatric chronic health conditions.

PURPOSE: To conduct a comparative analysis of eight pediatric self-report scales for ages 8-17 years from the National Institutes of Health (NIH) Patient Reported Outcomes Measurement Information System (PROMIS(®)) in six pediatric chronic health conditions, using indicators of disease severity. METHODS: Pediatric patients (N = 1454) with asthma, cancer, chronic kidney disease, obesity, rheumatic disease, and sickle cell disease completed items from the PROMIS pediatric mobility, upper extremity functioning, depressive symptoms, anxiety, anger, peer relationships, pain interference, and fatigue self-report scales. Comparisons within the six pediatric chronic health conditions were conducted by examining differences in groups based on the disease severity using markers of severity that were specific to characteristics of each disease. A comparison was also made across diseases between children who had been recently hospitalized and those who had not. RESULTS: In general, there were differences in self-reported health outcomes within each chronic health condition, with patients who had higher disease severity showing worse outcomes. Across health conditions, when children with recent hospitalizations were compared with those who had not been hospitalized in the past 6 months, we found significant differences in the expected directions for all PROMIS domains, except anger. CONCLUSIONS: PROMIS measures discriminate between different clinically meaningful subgroups within several chronic illnesses. Further research is needed to determine the responsiveness of the PROMIS pediatric scales to change over time.

Clinically meaningful interpretation of pediatric health-related quality of life in sickle cell disease.

Health-related quality of life (HRQL) measures provide information about disease assessment; however, health care providers may be reluctant to use HRQL assessments as scores can be difficult to interpret. We sought to identify levels for impaired pain-related HRQL in children with sickle cell disease (SCD). Children (n=251) completed the Pediatric Quality of Life Inventory (PedsQL) Generic Core Scales and PedsQL SCD Module in a multisite study. Using children's item scores on the Pain and Hurt and Pain Impact scales of the PedsQL SCD Module, High, Intermediate, and Low Functioning groups were created. We compared functioning groups with the Pain and Hurt and Pain Impact scale scores to determine levels representing high and low HRQL. These scores were compared with disease severity and the PedsQL Generic Core Scales. Scores of ≤60 on the PedsQL SCD Pain and Hurt and Pain Impact scales were associated with severe disease and met requirements for impaired functioning on the PedsQL Generic Core Scales. Scores of ≥81 on the Pain and Hurt and the Pain Impact scales can be considered consistent with good HRQL in those domains in SCD. Alternately, scores of ≤60 are cause for concern and suggest areas of HRQL impairment in SCD.

Using item response theory to enrich and expand the PROMIS® pediatric self report banks.

BACKGROUND: The primary objective was to enhance the content coverage of some of the pediatric self-report item banks for ages 8-17 years from the National Institutes of Health (NIH) Patient Reported Outcomes Measurement Information System (PROMIS®), and extend the range of precise measurement to higher levels of physical functioning. METHODS: Data from 1,419 pediatric patients with cancer, chronic kidney disease, obesity, rehabilitation needs, rheumatic disease, and sickle cell disease were combined with item responses from the original standardization sample of 3,048 children to calibrate new items for the pediatric PROMIS Anger, Anxiety, Depressive Symptoms, Pain Interference, Fatigue, and physical functioning Upper Extremity and Mobility scales. Simultaneous or concurrent calibration using the graded item response theory model placed all of the items on the same scale. RESULTS: Twenty-two of 28 potential new items were added across the seven scales. A recommended short form was proposed for the Anger scale, and the recommended short forms for the Anxiety and Depressive Symptoms scales were revised. Unfortunately, we were not particularly successful at extending the range of measurement for the physical functioning banks. CONCLUSIONS: The present study expanded PROMIS pediatric item banks to add new content and to increase the range of measurement. Using item response theory, the banks were revised and expanded without changing the underlying scale of measurement. For Anger, Anxiety, and Depressive Symptoms, we successfully added new content that may render those banks more robust and flexible.

PedsQL™ Multidimensional Fatigue Scale in sickle cell disease: feasibility, reliability, and validity.

BACKGROUND: Sickle cell disease (SCD) is an inherited blood disorder characterized by a chronic hemolytic anemia that can contribute to fatigue and global cognitive impairment in patients. The study objective was to report on the feasibility, reliability, and validity of the PedsQL™ Multidimensional Fatigue Scale in SCD for pediatric patient self-report ages 5-18 years and parent proxy-report for ages 2-18 years. PROCEDURE: This was a cross-sectional multi-site study whereby 240 pediatric patients with SCD and 303 parents completed the 18-item PedsQL™ Multidimensional Fatigue Scale. Participants also completed the PedsQL™ 4.0 Generic Core Scales. RESULTS: The PedsQL™ Multidimensional Fatigue Scale evidenced excellent feasibility, excellent reliability for the Total Scale Scores (patient self-report α = 0.90; parent proxy-report α = 0.95), and acceptable reliability for the three individual scales (patient self-report α = 0.77-0.84; parent proxy-report α = 0.90-0.97). Intercorrelations of the PedsQL™ Multidimensional Fatigue Scale with the PedsQL™ Generic Core Scales were predominantly in the large (≥0.50) range, supporting construct validity. PedsQL™ Multidimensional Fatigue Scale Scores were significantly worse with large effects sizes (≥0.80) for patients with SCD than for a comparison sample of healthy children, supporting known-groups discriminant validity. Confirmatory factor analysis demonstrated an acceptable to excellent model fit in SCD. CONCLUSIONS: The PedsQL™ Multidimensional Fatigue Scale demonstrated acceptable to excellent measurement properties in SCD. The results demonstrate the relative severity of fatigue symptoms in pediatric patients with SCD, indicating the potential clinical utility of multidimensional assessment of fatigue in patients with SCD in clinical research and practice.

PedsQL eosinophilic esophagitis module: feasibility, reliability, and validity.

OBJECTIVE: Eosinophilic esophagitis (EoE) is a chronic esophageal inflammatory condition with a paucity of information on health-related quality of life (HRQOL). The objective of the study was to report on the measurement properties of the PedsQL EoE Module. METHODS: The PedsQL EoE Module was completed in a multisite study by 196 pediatric patients with EoE and 262 parents of patients with EoE. RESULTS: The PedsQL EoE Module scales evidenced excellent feasibility (0.6%-3.1% missing), excellent group comparison reliability across total scale scores (patient α 0.93; parent proxy α 0.94), good reliability for the 7 individual scales (patient α 0.75-0.87; parent proxy α 0.81-0.92), excellent test-retest reliability (patient intraclass correlation coefficient 0.88; parent intraclass correlation coefficient 0.82), demonstrated no floor effects and low ceiling effects, and demonstrated a high percentage of scaling success for most scales. Intercorrelations with the PedsQL Generic Core Scales were in the medium (0.30) to large (0.50) range. PedsQL EoE Module scores were worse among patients with active histologic disease (≥ 5 eos/hpf) compared with those in remission (patient self-report: 63.3 vs 69.9 [P < 0.05]; parent proxy report: 65.1 vs 72.3 [P < 0.01]), and those treated with dietary restrictions compared with those with no restrictions (patient self-report: 61.6 vs 74.3 [P < 0.01]; parent proxy report: 65.5 vs 74.7 [P < 0.01]). CONCLUSIONS: The results demonstrate excellent measurement properties of the PedsQL EoE Module. Patients with active histologic disease and those treated with dietary restrictions demonstrated worse PedsQL scores. The PedsQL EoE Module may be used in the evaluation of pediatric EoE disease-specific HRQOL in clinical research and practice.

PedsQL™ sickle cell disease module: feasibility, reliability, and validity.

BACKGROUND: Sickle cell disease (SCD) is an inherited chronic disease that is characterized by complications such as recurrent painful vaso-occlusive events that require frequent hospitalizations and contribute to early mortality. The objective of the study was to report on the initial measurement properties of the new PedsQL™ SCD Module for pediatric patient self-report ages 5-18 years and parent proxy-report for ages 2-18 years. PROCEDURE: The 43-item PedsQL™ SCD Module was completed in a multisite study by 243 pediatric patients with SCD and 313 parents. Participants also completed the PedsQL™ 4.0 Generic Core Scales and PedsQL™ Multidimensional Fatigue Scale. RESULTS: The PedsQL™ SCD Module Scales evidenced excellent feasibility, excellent reliability for the Total Scale Scores (patient self-report α = 0.95; parent proxy-report α = 0.97), and good reliability for the nine individual scales (patient self-report α = 0.69-0.90; parent proxy-report α = 0.83-0.97). Intercorrelations with the PedsQL™ Generic Core Scales and PedsQL™ Multidimensional Fatigue Scales were medium (0.30) to large (0.50) range, supporting construct validity. PedsQL™ SCD Module Scale Scores were generally worse for patients with severe versus mild disease. Confirmatory factor analysis demonstrated an acceptable to excellent model fit. CONCLUSIONS: The PedsQL™ SCD Module demonstrated acceptable measurement properties. The PedsQL™ SCD Module may be utilized in the evaluation of SCD-specific health-related quality of life in clinical research and practice. In conjunction with the PedsQL™ Generic Core Scales and the PedsQL™ Multidimensional Fatigue Scale, the PedsQL™ SCD Module will facilitate the understanding of the health and well-being of children with SCD.