The Association Between Physical Distancing Behaviors to Avoid COVID-19 and Health-Related Quality of Life in Immunocompromised and Nonimmunocompromised Individuals: Patient-Informed Protocol for the Observational, Cross-Sectional EAGLE Study.

BACKGROUND: Immunocompromised individuals are known to respond inadequately to SARS-CoV-2 vaccines, placing them at high risk of severe or fatal COVID-19. Thus, immunocompromised individuals and their caregivers may still practice varying degrees of social or physical distancing to avoid COVID-19. However, the association between physical distancing to avoid COVID-19 and quality of life has not been comprehensively evaluated in any study. OBJECTIVE: We aim to measure physical distancing behaviors among immunocompromised individuals and the association between those behaviors and person-centric outcomes, including health-related quality of life (HRQoL) measures, health state utilities, anxiety and depression, and work and school productivity impairment. METHODS: A patient-informed protocol was developed to conduct the EAGLE Study, a large cross-sectional, observational study, and this paper describes that protocol. EAGLE is designed to measure distancing behaviors and outcomes in immunocompromised individuals, including children (aged ≥6 mo) and their caregivers, and nonimmunocompromised adults in the United States and United Kingdom who report no receipt of passive immunization against COVID-19. We previously developed a novel self- and observer-reported instrument, the Physical Distancing Scale for COVID-19 Avoidance (PDS-C19), to measure physical distancing behavior levels cross-sectionally and retrospectively. Using an interim or a randomly selected subset of the study population, the PDS-C19 psychometric properties will be assessed, including structural validity, internal consistency, known-group validity, and convergent validity. Associations (correlations) will be assessed between the PDS-C19 and validated HRQoL-related measures and utilities. Structural equation modeling and regression will be used to assess these associations, adjusting for potential confounders. Participant recruitment and data collection took place from December 2022 to June 2023 using direct-to-patient channels, including panels, clinician referral, patient advocacy groups, and social media, with immunocompromising diagnosis confirmation collected and assessed for a randomly selected 25% of immunocompromised participants. The planned total sample size is 3718 participants and participant-caregiver pairs. Results will be reported by immunocompromised status, immunocompromising condition category, country, age group, and other subgroups. RESULTS: All data analyses and reporting were planned to be completed by December 2023. Results are planned to be submitted for publication in peer-reviewed journals in 2024-2025. CONCLUSIONS: This study will quantify immunocompromised individuals' physical distancing behaviors to avoid COVID-19 and their association with HRQoL as well as health state utilities. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/52643.

Heart disease symptoms and health-related quality of life in pediatric heart transplant recipients: A serial multiple mediator analysis.

BACKGROUND: A serial multiple mediator analysis was conducted to test the predictive effects of heart disease symptoms on pediatric heart transplant recipients health-related quality of life (HRQOL) from their perspective with patient-perceived cognitive problems, patient health communication, and treatment anxiety as hypothesized mediators. METHODS: One hundred and nineteen pediatric heart transplant recipients aged 8-18 completed the Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Core Scales and the PedsQL Cardiac Module Heart Disease Symptoms Scale, Cognitive Problems Scale, Communication Scale and Treatment Anxiety Scale. The serial multiple mediator analysis tested the hypothesized sequential mediation of the cross-sectional association between patient-perceived heart disease symptoms and their perceived HRQOL. RESULTS: Heart disease symptoms indirect effects on HRQOL were sequentially mediated through cognitive problems, with cognitive problems' indirect effects mediated through patient health communication and treatment anxiety. A predictive analytics analysis consisting of age, gender, and time since transplant demographic covariates, demonstrated that heart disease symptoms, cognitive problems, patient health communication, and treatment anxiety accounted for 66 percent of the variance in patient-perceived HRQOL (p < .001), representing a large effect size. CONCLUSIONS: Patient-perceived heart disease symptoms indirect effects on HRQOL in pediatric heart transplant recipients was explained by patient-perceived cognitive problems, patient health communication, and treatment anxiety. Delineating heart disease symptoms indirect effects on HRQOL from the perspective of pediatric patients may inform targeted clinical interventions to improve daily functioning in pediatric heart transplant recipients.

Bladder and bowel function effects on emotional functioning in youth with spinal cord injury: a serial multiple mediator analysis.

STUDY DESIGN: Preliminary explanatory or mechanistic cross-sectional study. OBJECTIVES: This preliminary cross-sectional study investigates the hypothesized serial mediating effects of bladder/bowel worry, social worry, and social participation in the relationship between bladder function or bowel function and emotional functioning in youth with spinal cord injury (SCI) from their perspective. METHODS: The Bladder Function, Bowel Function, Worry Bladder Bowel, Worry Social, and Social Participation Scales from the PedsQL™ Spinal Cord Injury Module and the Emotional Functioning Scale from the PedsQL™ 4.0 Generic Core Scales Short Form SF15 were completed by 127 youth with SCI ages 8-24. Serial multiple mediator model analyses were conducted to test the hypothesized sequential mediating effects of bladder/bowel worry, social worry, and social participation as intervening variables separately for the cross-sectional association between bladder function or bowel function and emotional functioning. RESULTS: The separate cross-sectional negative association of bladder function and bowel function with emotional functioning were serially mediated by bladder/bowel worry, social worry and social participation, accounting for 28% and 31%, respectively, of the variance in youth-reported emotional functioning (p < 0.001), representing large effect sizes. CONCLUSIONS: In this preliminary study, bladder/bowel worry, social worry, and social participation explain in part the cross-sectional negative association of bladder function and bowel function with emotional functioning in youth with SCI from the youth perspective. Identifying the hypothesized associations of bladder function and bowel function, bladder/bowel worry, social worry, and social participation with emotional functioning may help inform future clinical research and practice for youth with SCI.

Pain and health-related quality of life in Duchenne muscular dystrophy: A multiple mediator analysis.

OBJECTIVES: The objective was to investigate the serial mediating effects of daily activities, patient health communication, and disease-specific worry in the relationship between pain intensity and overall generic health-related quality of life (HRQOL) in pediatric patients with Duchenne muscular dystrophy from the patient perspective. METHODS: Pain Intensity Item, Daily Activities Scale, Communication Scale and Worry Scale from Pediatric Quality of Life Inventory (PedsQL) Duchenne Muscular Dystrophy Module and PedsQL 4.0 Generic Core Scales were completed by 110 pediatric patients with Duchenne muscular dystrophy ages 8-17. A serial multiple mediator model analysis was conducted to test the hypothesized sequential mediating effects of daily activities, patient health communication, disease-specific worry as intervening variables in the association between the pain intensity predictor variable and overall generic HRQOL. RESULTS: Pain predictive effects on overall generic HRQOL were serially mediated by daily activities, patient health communication, and disease-specific worry. In a predictive analytics model utilizing hierarchical multiple regression analysis with age demographic covariate, patient-reported pain intensity, daily activities, patient health communication, and disease-specific worry accounted for 47% of the variance in overall generic HRQOL (P < 0.001), representing a large effect size. CONCLUSIONS: Pain intensity, daily activities, patient health communication, and disease-specific worry explain in part the mechanism of pain predictive effects on overall generic HRQOL in pediatric patients with Duchenne muscular dystrophy. Identifying the mediators of pain intensity on overall generic HRQOL from the patient perspective may inform targeted clinical interventions and future patient-centered clinical research to improve overall daily functioning.

Gastrointestinal Symptoms Profile in Gastroparesis Compared to Other Functional and Organic Gastrointestinal Diseases.

OBJECTIVES: The primary objective was to compare the patient-reported gastrointestinal symptoms profiles of pediatric patients with gastroparesis to pediatric patients with 1 of 7 other functional gastrointestinal disorders and organic gastrointestinal diseases using the Pediatric Quality of Life Inventory (PedsQL) Gastrointestinal Symptoms Scales. METHODS: The gastrointestinal symptoms profiles of 64 pediatric patients with gastroparesis who manifested abnormal gastric retention based on gastric emptying scintigraphy testing were compared to 582 pediatric patients with 1 of 7 physician-diagnosed gastrointestinal disorders (functional abdominal pain, irritable bowel syndrome, functional dyspepsia, gastroesophageal reflux disease, functional constipation, Crohn disease, ulcerative colitis). The PedsQL Gastrointestinal Symptoms Scales encompass 10 individual multi-item scales which measure stomach pain, stomach discomfort when eating, food and drink limits, trouble swallowing, heartburn and reflux, nausea and vomiting, gas and bloating, constipation, blood in poop, and diarrhea/fecal incontinence, with an overall total gastrointestinal symptoms score. RESULTS: The gastrointestinal symptoms profile analysis identified significantly worse overall total gastrointestinal symptoms scores between pediatric patients with gastroparesis compared to all other gastrointestinal groups except for irritable bowel syndrome (most P s < 0.001), with significant differences for stomach discomfort when eating compared to all 7 other gastrointestinal groups (most P s < 0.001). Nausea and vomiting were significantly worse for gastroparesis compared to all other gastrointestinal groups except for functional dyspepsia (all P s < 0.001). CONCLUSIONS: Pediatric patients with gastroparesis self-reported significantly worse overall total gastrointestinal symptoms compared to all other gastrointestinal diagnostic groups except for irritable bowel syndrome, with stomach discomfort when eating and nausea and vomiting symptoms exhibiting the greatest differences compared to most gastrointestinal diagnostic groups.

Prevalence of Gastrointestinal Symptoms and Impact on Quality of Life at 1-Year Follow-Up of Initial Attack of Acute Pancreatitis.

OBJECTIVES: This study aims to describe the prevalence of gastrointestinal (GI) symptoms following the first time occurrence of acute pancreatitis (AP) and to measure the impact of the episode on patient health-related quality of life (HRQOL) from the perspectives of patients and parents. METHODS: Questionnaires regarding GI symptoms 1 year following the initial occurrence of AP were obtained from 74 pediatric patients. Thirty of these patients completed both the Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Core Scales and the PedsQL Gastrointestinal Symptoms and Worry Scales. These data were compared to legacy-matched healthy controls. RESULTS: Children with a standalone occurrence of AP experienced a similar rate of GI symptoms compared to those who progressed to acute recurrent pancreatitis (ARP) within 1 year. PedsQL 4.0 Generic Core Scales scores were significantly lower for children self-report and parent proxy-report for patients that experienced AP compared to healthy controls. AP patients also demonstrated significantly more symptoms than healthy controls in the Gastrointestinal Symptoms and Worry Scales across multiple domains. CONCLUSIONS: Gastrointestinal symptoms affect many children who experience a single AP event even without recurrent attacks. The burden of symptoms is not significantly different from those who develop ARP. This is a novel study that evaluates patient-reported outcomes in children following an AP attack and demonstrates there is a significant impact on HRQOL in children and family experiences post AP. More data are needed to study the progression of disease and the extended impact of AP following an initial AP attack in pediatric patients.

Heart disease symptoms, cognitive functioning, health communication, treatment anxiety, and health-related quality of life in paediatric heart disease: a multiple mediator analysis.

OBJECTIVES: The objective was to investigate the serial mediating effects of perceived cognitive functioning, patient health communication, and treatment anxiety in the relationship between heart disease symptoms and overall generic health-related quality of life in children with heart disease from the patient perspective. METHODS: Heart Disease Symptoms, Cognitive Problems, Communication and Treatment Anxiety Scales from Pediatric Quality of Life Inventory™ (PedsQL™) Cardiac Module and PedsQL™ 4.0 Generic Core Scales were completed by 278 children with CHD ages 8-18. A serial multiple mediator model analysis was conducted to test the sequential mediating effects of perceived cognitive functioning, patient health communication, and treatment anxiety as intervening variables in the relationship between the heart disease symptoms predictor variable and overall generic health-related quality of life. RESULTS: Heart disease symptoms predictive effects on overall generic health-related quality of life were serially mediated in part by cognitive functioning, patient health communication, and treatment anxiety. In a predictive analytics model with age and gender demographic covariates, heart disease symptoms, perceived cognitive functioning, patient health communication, and treatment anxiety accounted for 67% of the variance in patient-reported overall generic health-related quality of life (p < 0.001), representing a large effect size. CONCLUSIONS: Perceived cognitive functioning, patient health communication, and treatment anxiety explain in part the mechanism of heart disease symptoms predictive effects on overall generic health-related quality of life in paediatric heart disease. Identifying the mediators of heart disease symptoms on overall generic health-related quality of life from the patient perspective may inform targeted clinical interventions and future patient-centred clinical research to improve overall daily functioning.

Pain, pain interference, social and school/work functioning in youth with spinal cord injury: A mediation analysis.

Context/Objective: The objective of the present study was to investigate the effects of pain severity, pain interference and social functioning in a serial multiple mediator model predicting school/work functioning in youth with spinal cord injury (SCI) from their perspective.Design: Explanatory or mechanistic study.Setting: Pediatric specialty hospital.Participants: 125 youth with SCI ages 8-24.Outcome Measures: The Pain Severity Item and Pain Interference Scale from the PedsQL™ Spinal Cord Injury Module, and the Social Functioning and School/Work Functioning Scales from the PedsQL™ 4.0 Generic Core Scales Short Form SF15 were completed.Results: Hierarchical multiple regression and serial multiple mediator model analyses were conducted to test the percent variability accounted for and the mediating effects of pain interference and social functioning in the association between pain severity and school/work functioning. Pain predictive effects on school/work functioning were serially mediated by pain interference and social functioning. In a predictive analytics model conducted with hierarchical multiple regression analysis, age, sex, pain, pain interference and social functioning accounted for 45% of the variance in youth-reported school/work functioning (P < 0.001), demonstrating a large effect size.Conclusion: The mechanisms of the predictive effects of pain severity on school/work functioning in youth with SCI are explained in part by the serial multiple mediator effects of pain interference and social functioning. Identifying the multiple mediators of SCI pain on school/work functioning from the perspective of youth with SCI may facilitate future clinical research and practice to ameliorate impaired daily functioning and improve overall well-being.

Association of Pathogen Type With Outcomes of Children Encountering Community-Acquired Pediatric Septic Shock.

OBJECTIVES: To determine the association of pathogen type with mortality, functional status, and health-related quality of life (HRQL) among children at hospital discharge/1 month following hospitalization for septic shock. DESIGN: Secondary database analysis of a prospective, descriptive cohort investigation. SETTING: Twelve academic PICUs in the United States. PATIENTS: Critically ill children, 1 month to 18 years old, enrolled from 2013 to 2017. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Association of clinical outcomes with pathogen type was assessed for all patients and separately for surviving patients enrolled in the primary Life After Pediatric Sepsis Evaluation (LAPSE) investigation. For this secondary analysis, we predicted that age would be associated with pathogen type and outcomes, and accordingly, it was incorporated as a confounding variable in primary analyses. Among 389 children enrolled with septic shock, at 1 month/hospital discharge, we observed no statistically significant differences in relation to pathogen types for the composite outcome mortality or substantial new functional morbidity: no causative organism identified (27% [28/103]), pure viral infections (26% [24/91]), pure bacterial/fungal infections (25% [31/125]), and bacterial/fungal+viral coinfections (33% [23/70]). Similarly, we observed no statistically significant differences in relation to pathogen types for the composite outcome, mortality, or persistent serious deterioration of HRQL: no causative organism identified (43% [44/103]), pure viral infections (33% [30/91]), pure bacterial/fungal infections (46% [57/125]), and bacterial/fungal+viral coinfections (43% [30/70]). However, we did identify statistically significant associations between pathogen type and the outcome ventilator-free days ( p = 0.0083) and PICU-free days (0.0238). CONCLUSIONS: This secondary analysis of the LAPSE database identified no statistically significant association of pathogen type with composite mortality and morbidity outcomes. However, pathogen type may be associated with PICU resources employed to treat sepsis organ dysfunction. Ultimately, pediatric septic shock was frequently associated with adverse patient-centered, clinically meaningful outcomes regardless of infectious disease pathogen type.

Gastrointestinal Symptoms Profile in Pediatric Patients With Gastroparesis Compared to Healthy Controls.

OBJECTIVES: The primary objective was to compare the patient-reported gastrointestinal symptoms profiles of pediatric patients with gastroparesis to matched healthy controls using the Pediatric Quality of Life Inventory™ (PedsQL™) Gastrointestinal Symptoms Scales. The secondary objectives were to compare pediatric patients with gastroparesis to pediatric patients with gastroparesis-like symptoms and normal gastric emptying and to compare pediatric patients with gastroparesis-like symptoms and normal gastric emptying to matched healthy controls. METHODS: The PedsQL™ Gastrointestinal Symptoms Scales were completed by 64 pediatric patients with gastroparesis, 59 pediatric patients with gastroparesis-like symptoms and normal gastric emptying, and 200 age, gender, and race/ethnicity matched healthy controls. The PedsQL™ Gastrointestinal Symptoms Scales encompass 10 individual multi-item scales which measure stomach pain, stomach discomfort when eating, food and drink limits, trouble swallowing, heartburn and reflux, nausea and vomiting, gas and bloating, constipation, blood in poop, and diarrhea/fecal incontinence. Based on gastric emptying scintigraphy testing, those with abnormal gastric retention were classified as having gastroparesis. RESULTS: The gastrointestinal symptoms profile analysis identified large differences between those with gastroparesis compared to healthy controls (most P <0.001), with the largest effect sizes for upper gastrointestinal symptoms including stomach pain, stomach discomfort when eating, food and drink limits, nausea, and vomiting. Those with gastroparesis self-reported similar gastrointestinal symptoms to those with normal gastric emptying, except for increased constipation. CONCLUSIONS: Pediatric patients with gastroparesis self-reported broad multidimensional gastrointestinal symptoms profiles in comparison to healthy controls with large differences, indicating the critical need for more highly efficacious interventions to bring patient functioning within the normal range of healthy functioning.

The Association of Early Corticosteroid Therapy With Clinical and Health-Related Quality of Life Outcomes in Children With Septic Shock.

OBJECTIVES: Corticosteroids are commonly used in the treatment of pediatric septic shock without clear evidence of the potential benefits or risks. This study examined the association of early corticosteroid therapy with patient-centered clinically meaningful outcomes. DESIGN: Subsequent cohort analysis of data derived from the prospective Life After Pediatric Sepsis Evaluation (LAPSE) investigation. Outcomes among patients receiving hydrocortisone or methylprednisolone on study day 0 or 1 were compared with those who did not use a propensity score-weighted analysis that controlled for age, sex, study site, and measures of first-day illness severity. SETTING: Twelve academic PICUs in the United States. PATIENTS: Children with community-acquired septic shock 1 month to 18 years old enrolled in LAPSE, 2013-2017. Exclusion criteria included a history of chronic corticosteroid administration. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among children enrolled in LAPSE, 352 of 392 met analysis inclusion criteria, and 155 of 352 (44%) received early corticosteroid therapy. After weighting corticosteroid therapy administration propensity across potentially confounding baseline characteristics, differences in outcomes associated with treatment were not statistically significant (adjusted effect or odds ratio [95% CI]): vasoactive-inotropic support duration (-0.37 d [-1.47 to 0.72]; p = 0.503), short-term survival without new morbidity (1.37 [0.83-2.28]; p = 0.218), new morbidity among month-1 survivors (0.70 [0.39-1.23]; p = 0.218), and persistent severe deterioration of health-related quality of life or mortality at month 1 (0.70 [0.40-1.23]; p = 0.212). CONCLUSIONS: This study examined the association of early corticosteroid therapy with mortality and morbidity among children encountering septic shock. After adjusting for variables with the potential to confound the relationship between early corticosteroid administration and clinically meaningful end points, there was no improvement in outcomes associated with this therapy. Results from this propensity analysis provide additional justification for equipoise regarding corticosteroid therapy for pediatric septic shock and ascertain the need for a well-designed clinical trial to examine benefit/risk for this intervention.

PedsQL™ Spinal Cord Injury Module: Reliability and Validity.

OBJECTIVES: The objective was to report on the initial measurement properties of the Pediatric Quality of Life Inventory™ (PedsQL™) Spinal Cord Injury (SCI) Module in youth with SCI from the youth and parent perspectives. METHODS: PedsQL™ SCI Module and PedsQL™ 4.0 Generic Core Scales SF15 were completed in a multisite national study by 166 youth ages 8 to 25 years and 128 parents of youth ages 5 to 23 years. Data from the PedsQL™ Generic Core Scales were compared with an age- and sex-matched healthy control sample. Factor analysis was conducted to determine the factor structure of the items. RESULTS: In addition to a Total Scale Score, nine unidimensional scales were derived measuring daily activities, mobility, bladder function, bowel function, pressure injury, pain interference, social participation, worry bladder bowel, and worry social. The PedsQL™ SCI Module evidenced excellent reliability for Total Scale Scores (youth self-report, α = 0.93; parent proxy-report, α = 0.93) and acceptable reliability for the nine individual scales (youth self-report, α = 0.71-0.83; parent proxy-report, α = 0.67-0.87). Intercorrelations with the Generic Core Scales supported construct validity with medium to large effect sizes (most ps < .001). Factor analysis supported the unidimensionality of the nine individual scales. PedsQL™ Generic Core Scales comparisons to healthy controls demonstrated significantly impaired generic health-related quality of life in youth with SCI with large effect sizes. CONCLUSION: The PedsQL™ SCI Module Scales demonstrated acceptable measurement properties and may be utilized as standardized scales to assess SCI-specific concerns and problems in clinical research and practice in youth with SCI.

PedsQL Multiple Sclerosis Module Domain and Item Development: Qualitative Methods.

BACKGROUND: The objective of this qualitative methods study was to develop the domains and items to support the content validity for the Pediatric Quality of Life Inventory (PedsQL) Multiple Sclerosis Module for youth with pediatric-onset multiple sclerosis. METHODS: A literature review of multiple sclerosis-specific questionnaires and clinical research was conducted to generate domains. An expert panel composed of 12 neurologists who were pediatric-onset multiple sclerosis specialists provided feedback on the conceptual framework. Focus interviews with 9 youth with pediatric-onset multiple sclerosis and 6 parents were conducted to develop the relevant domains and item content from the patient and parent perspective. In the cognitive interviews phase, 9 youth with pediatric-onset multiple sclerosis and 6 parents provided feedback on item content, relevance, importance, and understandability of the pediatric-onset multiple sclerosis-specific domains and items. The final interview phase with 5 youth with pediatric-onset multiple sclerosis and 5 parents comprised a pilot testing of the new PedsQL MS Module. RESULTS: Eighteen domains were derived from the qualitative methods with item content saturation achieved at 100 items based on 40 interviews with 23 youth with pediatric-onset multiple sclerosis aged 10-21 years and 17 parents. The domains derived include general fatigue, sleep/rest fatigue, cognitive functioning, tingling sensations, numbness sensations, physical weakness, pain, speech, balance, fine motor, vision, urination, constipation, bowel incontinence, worry, communication, treatment, and medicines. CONCLUSIONS: Qualitative methods involving 23 youth with pediatric-onset multiple sclerosis and 17 parents in the domain and item development process support the content validity for the new PedsQL MS Module. Future plans include a national field test of the PedsQL MS Module scales and items.

PedsQL™ Gastroparesis Symptoms Module Domain and Item Development: Qualitative Methods.

OBJECTIVES: Like adults, children suffer from gastroparesis; however, there are currently no validated instruments to determine the impact of gastroparesis in pediatric patients. The objective of this study was to develop the items and domains to support the content validity of the new Pediatric Quality of Life Inventory (PedsQL™) Gastroparesis Symptoms Module. METHODS: Patients were recruited from the National Institute of Diabetes and Digestive and Kidney Diseases Pediatric Gastroparesis Registry. The qualitative methods involved an iterative process comprising a literature review of existing questionnaires and gastroparesis clinical research, an expert review panel of pediatric gastroenterologists who provided feedback on the conceptual framework in developing the semi-structured interview, and in-depth focus interviews with six pediatric patients with gastroparesis and five of their parents (one did not participate) in developing relevant domains and item content. In the subsequent cognitive interviews phase, five additional patients with gastroparesis and their parents provided detailed feedback on item content, relevance, importance, and understandability of the domains and items. RESULTS: Ten domains/scales were derived from the qualitative methods, with item content saturation achieved at 67 items, with no further themes or content identified during the final cognitive interviews. The Module is comprised of 10 individual scales measuring nausea, stomach fullness when eating, vomiting, dry heaves, heartburn and reflux, stomach pain and hurt, food and drink limits, bloating, appetite, and worry. CONCLUSIONS: Our study supports the content validity of the new PedsQL Gastroparesis Symptoms Module. The Module field test study will be conducted in a multisite national study.

Biomarkers for Estimating Risk of Hospital Mortality and Long-Term Quality-of-Life Morbidity After Surviving Pediatric Septic Shock: A Secondary Analysis of the Life After Pediatric Sepsis Evaluation Investigation.

OBJECTIVES: The Life After Pediatric Sepsis Evaluation investigation recently reported that one-third of children who survive sepsis experience significant health-related quality-of-life impairment compared with baseline at 1 year after hospitalization. Pediatric Sepsis Biomarker Risk Model is a multibiomarker tool for estimating baseline risk of mortality among children with septic shock. We determined if the Pediatric Sepsis Biomarker Risk Model biomarkers have predictive capacity for estimating the risk of hospital mortality and long-term health-related quality-of-life morbidity among children with community-acquired septic shock. DESIGN: Secondary analysis. SETTING: Twelve academic PICUs. PATIENTS: A subset of Life After Pediatric Sepsis Evaluation subjects (n = 173) with available blood samples. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Three predefined outcomes from the Life After Pediatric Sepsis Evaluation investigation were evaluated: all-cause hospital mortality (n = 173), and the composite outcome of mortality or persistent, serious deterioration of health-related quality of life (> 25% below baseline) among surviving children at 1 month (n = 125) or 3 months (n = 117). Pediatric Sepsis Biomarker Risk Model had an area under the receiver operating characteristic curve of 0.73 (95% CI, 0.59-0.87; p = 0.002) for estimating the risk of hospital mortality and was independently associated with increased odds of hospital mortality. In multivariable analyses, Pediatric Sepsis Biomarker Risk Model was not independently associated with increased odds of the composite outcome of mortality or deterioration of persistent, serious deterioration health-related quality of life greater than 25% below baseline. A new decision tree using the Pediatric Sepsis Biomarker Risk Model biomarkers had an area under the receiver operating characteristic curve of 0.87 (95% CI, 0.80-0.95) for estimating the risk of persistent, serious deterioration health-related quality of life at 3 months among children who survived septic shock. CONCLUSIONS: Pediatric Sepsis Biomarker Risk Model had modest performance for estimating hospital mortality in an external cohort of children with community-acquired septic shock. The Pediatric Sepsis Biomarker Risk Model biomarkers appear to have utility for estimating the risk of persistent, serious deterioration of health-related quality of life up to 3 months after surviving septic shock. These findings suggest an opportunity to develop a clinical tool for early assignment of risk for long-term health-related quality-of-life morbidity among children who survive septic shock.

Associations of Abdominal Pain and Psychosocial Distress Measures With Health-Related Quality-of-Life in Pediatric Healthy Controls and Irritable Bowel Syndrome.

BACKGROUND: Children with irritable bowel syndrome (IBS) have lower health-related quality-of-life (HRQOL) than healthy controls (HC). Abdominal pain and psychosocial distress are negatively associated with HRQOL, although their relative effect is unclear. AIM: The aim of this study was to compare the relative associations of abdominal pain and psychosocial distress with HRQOL in HC and IBS. STUDY: Baseline abdominal pain, psychosocial distress, and HRQOL measures were obtained from HC and IBS pediatric clinical trial participants. Regression assessed which measures were most strongly associated with Physical and Psychosocial HRQOL separately by group. Interaction analyses examined group differences in the associations of abdominal pain and psychosocial distress with HRQOL. RESULTS: Eight-five HC and 213 children with IBS participated. Somatization was most strongly associated with Physical HRQOL in HC, and functional disability was most strongly related in IBS. With respect to Psychosocial HRQOL, somatization was most strongly associated for both HC and IBS; depression was also significantly associated in HC. The strength of association between somatization and Physical HRQOL differed between groups; the negative association was less pronounced for IBS than HC. The association between functional disability and both Physical and Psychosocial HRQOL differed significantly between groups; the negative associations were more pronounced for IBS than HC. CONCLUSIONS: Multiple psychosocial distress measures, including somatization, were associated with HRQOL in children with IBS; HRQOL in HC was driven consistently by somatization, to the exclusion of other psychosocial concerns. The associations of somatization and functional disability with HRQOL are distinctly different between HC and IBS. This knowledge supports utilization of psychosocial interventions to improve overall well-being for children with IBS.

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.

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.

Trajectories and Risk Factors for Altered Physical and Psychosocial Health-Related Quality of Life After Pediatric Community-Acquired Septic Shock.

OBJECTIVES: To evaluate the physical and psychosocial domains of health-related quality of life among children during the first year following community-acquired septic shock, and explore factors associated with poor physical and psychosocial health-related quality of life outcomes. DESIGN: Secondary analysis of the Life After Pediatric Sepsis Evaluation. SETTING: Twelve academic PICUs in the United States. PATIENTS: Children greater than or equal to 1 month and less than 18 years old who were perceived to be without severe developmental disability by their family caregiver at baseline and who survived hospitalization for community-acquired septic shock. INTERVENTIONS: Family caregivers completed the Pediatric Quality of Life Inventory for children 2-18 years old or the Pediatric Quality of Life Inventory Infant Scales for children less than 2 years old at baseline (reflecting preadmission status), day 7, and months 1, 3, 6, and 12 following PICU admission. Higher Pediatric Quality of Life Inventory Physical and Psychosocial Health Summary Scores indicate better health-related quality of life. MEASUREMENTS AND MAIN RESULTS: Of 204 children, 58 (28.2%) had a complex chronic comorbid condition. Children with complex chronic comorbid conditions had lower baseline physical health-related quality of life (62.7 ± 22.6 vs 84.1 ± 19.7; p < 0.001) and psychosocial health-related quality of life (68.4 ± 14.1 vs 81.2 ± 15.3; p < 0.001) than reference norms, whereas children without such conditions had baseline scores similar to reference norms. Children with complex chronic comorbid conditions recovered to their baseline health-related quality of life, whereas children without such conditions did not (physical health-related quality of life 75.3 ± 23.7 vs 83.2 ± 20.1; p = 0.008 and psychosocial health-related quality of life 74.5 ± 18.7 vs 80.5 ± 17.9; p = 0.006). Age less than 2 years was independently associated with higher month 12 physical health-related quality of life, and abnormal neurologic examination and neurologic injury suspected by a healthcare provider during the PICU course were independently associated with lower month 12 physical health-related quality of life. Treatment of increased intracranial pressure and medical device use at month 1 were independently associated with lower month 12 psychosocial health-related quality of life. CONCLUSIONS: Physical and psychosocial health-related quality of life were reduced among children during the first year following community-acquired septic shock compared with reference norms, although many recovered to baseline. Risk factors for poor health-related quality of life included neurologic complications during the hospitalization and dependence on a medical device 1 month postadmission.

Longitudinal Trajectories of Caregiver Distress and Family Functioning After Community-Acquired Pediatric Septic Shock.

OBJECTIVES: To identify trajectories and correlates of caregiver distress and family functioning in families of children who survived community-acquired septic shock. We hypothesized that: 1) a substantial subset of families would demonstrate trajectories of persistent elevated caregiver distress and impaired family functioning 12 months after hospitalization and 2) sociodemographic and clinical risk factors would be associated with trajectories of persistent distress and family dysfunction. DESIGN: Prospective cohort. SETTING: Fourteen PICUs in the United States. PATIENTS: Caregivers of 260 children who survived community-acquired septic shock. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Caregivers completed ratings of distress on the Brief Symptom Inventory and of family functioning on the Family Assessment Device at baseline, 1, 3, 6, and 12 months after hospitalization. Results from group-based trajectory modeling indicated that 67% of the current sample was characterized by persistent low caregiver distress, 26% by persistent moderate to high distress that remained stable across 12 months (high-risk caregiver distress group), and 8% by initial high distress followed by gradual recovery. Forty percent of the sample was characterized by stable high family functioning, 15% by persistent high dysfunction across 12 months (high-risk family functioning group), 12% by gradually improving functioning, and 32% by deteriorating function over time. Independently of age, child race was associated with membership in the high-risk caregiver distress group (non-white/Hispanic; effect size, -0.12; p = 0.010). There were no significant sociodemographic or clinical correlates of the high-risk family functioning group in multivariable analyses. CONCLUSIONS: Although the majority of families whose children survived community-acquired septic shock were characterized by resilience, a subgroup demonstrated trajectories of persistently elevated distress and family dysfunction during the 12 months after hospitalization. Results suggest a need for family-based psychosocial screening after pediatric septic shock to identify and support at-risk families.