Child Health Ratings Inventories Research Articles

Longitudinal Differences By Treatment Arm in Health-Related Quality of Life Among High Risk Pediatric Hodgkin's Lymphoma Patients Treated on the Children's Oncology Group Ahod 1331 Study

Introduction: Brentuximab vendotin (BV) with AVE-PC demonstrated superior efficacy to ABVE-PC for pediatric patients with high-risk HL in the AHOD 1331 trial. However, there are no data regarding the impact on health-related quality of life (HRQoL) with the addition of BV into the treatment of pediatric HL. Methods: Eligibility for AHOD 1331 (NCT 02166463) included previously untreated HL with high risk disease, defined as stage IIB +bulk, IIIB, IVA, or IVB classic HL. Participants were randomized to either BV-AVE-PC (“BV” arm) or ABVE-PC (standard arm). Among the first 309 participants enrolled in a prespecified longitudinal patient-reported outcomes sub study, 280 were age 11+ years and eligible to self-report HRQoL using the seven-item Child Health Ratings Inventories (CHRIs)-Global scale. HRQoL was assessed prior to treatment (T1), at cycle 2 (T2), at cycle 5 (T3), and at the end of treatment (T4). A clinically meaningful increase in HRQoL was considered a change of 7 points in the CHRIs-Global score (CHRIs), translating to a 1/3 standard deviation. Multivariable linear regression estimated the association between demographic/clinical variables and HRQoL at T1. Linear mixed models estimated the change in HRQoL relative to T1 with a time*treatment arm interaction to estimate differences in the change in HRQoL across treatment arm. This model was adjusted for age, sex, race/ethnicity, stage, large mediastinal adenopathy (LMA), B-symptoms at diagnosis, and a time-varying covariate for involved site radiation prior to T4. Results: Participant and disease characteristics were balanced by treatment arm; mean age at enrollment was 15.6 years (SD= 1.9), 52% were female, 60.4% had LMA, and 58% were stage IV. 93% of participants completed the CHRIs at T1, 92% at T2, 89% at T3, and 74% at T4. At T1, female sex (mean (SD) 64.1 (20.2) vs 71.3 (23.3) p=0.004) and fever (60.8 (23.0) vs. 71.9 (20.4) p=0.024) were associated with worse HRQoL. At each time point after pre-treatment (T1), HRQoL was higher, on average, in the BV arm compared to the standard arm (Figure 1). By T2, participants in the BV arm experienced a statistically and clinically significant increase in HRQoL compared to pre-treatment (T1) (Table 1; β=7.3 95%CI 3.2, 11.4; p≤0.001), which was greater than the change experienced in the standard arm (difference in change β=5.1 95%CI -0.2, 10.3; p=0.057). At T3 and T4 the BV arm continued to experience statistically significant improvements in HRQoL relative to T1 (T3 β=5.3 95%CI 0.8, 9.9; p=0.022; T4 β=14.6 95%CI 10.3, 18.9; p≤0.001). The standard arm did not experience a statistically or clinically significant increase in HRQoL from T1 until T4 (β=9.3 95%CI 4.7, 11.5; p<0.001). Conclusion: Patients with high-risk pediatric HL treated with BV-AVE-PC experienced more rapid and sustained improvement in HRQoL compared to patients treated with ABVE-PC. These data also demonstrate the feasibility and importance of incorporating HRQoL assessments into pediatric clinical trials.

Promising Results at 1 Year Follow-up Following Familial Haploidentical (FHI) T-Cell Depleted (TCD) with CD34 Enrichment and T-Cell (CD3) Addback Allogeneic Stem Cell Transplantation in Patients with High-Risk Sickle Cell Disease (SCD) (IND 14359)

AlloSCT from HLA-matched MSD has been successful for high-risk SCD, and is the only known curative therapy (Talano/Cairo et al EJH, 2014). We have recently demonstrated 100% EFS and absence of sickle cell symptoms following reduced toxicity conditioning in HLA matched sibling donor (MSD) or cord blood AlloSCT (Bhatia/Cairo et al BMT, 2014). However, 5 out of 6 children lack an HLA MSD without SCD. Only 19% of recipients of African descent will identify a well-matched unrelated donor (MUD) and results after unrelated UCBT are poor (Radhakrishnan/Cairo et al BBMT, 2013). Recent results utilizing matched unrelated donors in a multi-center trial showed unacceptable rates of cGVHD at 62% (95% CI 41-77) (Shenoy et al Blood, 2016). We demonstrated CD34+ selection followed by T-cell addback from MUD in pediatric recipients led to 100% engraftment with minimal aGVHD (Geyer/Cairo et al BJH, 2011). Limitations in the past of various T-cell depletion methods have included a higher incidence of graft failure, delayed immune reconstitution, opportunistic fungal infection and higher incidence of cGVHD. FHI TCD AlloSCT utilizing the approach of CD34+ enrichment and T-cell addback could expand the donor pool and improve outcomes for patients with high risk SCD and have similar outcomes to AlloSCT from HLA MSD.This SCD consortium trial (www.sicklecelltransplantconsortium.org) (NCT01461837) is investigating the safety, feasibility, EFS, donor chimerism, graft failure, aGVHD and cGVHD after FHI TCD AlloSCT in high-risk SCD patients.High risk included: ≥1 CVA, ≥2 ACS, ≥3 VOC in past 2 years, or 2 abnormal TCDs. Patients (2-<21 yrs) who have ≥1 high-risk SCD features were eligible. Patients received hydroxyurea and azathioprine, day -59 - day -11, fludarabine (150mg/m2), busulfan (12.8mg/kg) (targeted trough Css of 600-900), thiotepa (10 mg/kg), cyclophosphamide (200mg/kg), R-ATG (8mg/kg), and TLI (500cGy) followed by FHI T-cell depleted AlloSCT. AGVHD prophylaxis: tacrolimus. We utilized the CliniMACS to enrich for peripheral blood HPC's; target dose of 10 x 106 CD34+ cells/kg with a fixed dose of 2 x 105 CD3+ T cells/kg. The Child Health Rating Inventories (CHRIs) was used to serially collect parent proxy-rated health-related quality of life (HRQL).Twenty-one patients have been enrolled. Nineteen patients have received AlloSCT to date. Fifteen patients utilized maternal donors and 4 patients utilized paternal donors. Two donors encountered thrombocytopenia that resolved spontaneously. The mean ± SD CD34+ enrichment prior to cryopreservation was 12.66 ± 3.3 x 106/kg and log T-cell depletion was 4.8 ± 0.58. Evaluable pts had early neutrophil engraftment (median day +9), and ≥95% whole blood and RBC (CD71) donor chimerism at 1yr. Probability of aGVHD n=17, 7.1% (CI95: 0-70.0); cGVHD n=17, 20% (CI95: 0.7-59.6) (Figure 1A and 1B). Probability of 1-Year Overall Survival (OS) n=17; 88.2% (CI95: 60.6-96.9) (Figure 1C). Immune reconstitution was robust with 1 yr NK, CD3, CD4 and CD8 204±37 cells/μL, 795±168 cells/μL, 408±102 cells/μL and 375±90 cells/μL, respectively. Two-yr PFT results were also robust with % predicted FVC, FEV1, TLC and DLCO of 89%, 84%, 82%, and 68%, respectively. All survivors are free of SCD symptoms and without signs of progression of multi-organ toxicity. One patient developed late hepatic SOS and died at day +59; one patient died at day +390 due to complications of CGVHD, and one patient died at day +141 of steroid refractory aGVHD, the remainder are alive and free of SCD symptoms with a median follow-up of +711 days (range, +231 to +1684 days). Most importantly, mean + SD HRQL score (0-100) reported at 1 yr for emotional, physical functioning, role, and global scores were 82.9±9.7 points, 82.8±15.8 points, 89.6±13.3 points, and 86±8.2 points, respectively.Early results indicate promising results in 1 yr OS, stable donor chimerism, and low incidence of acute and/or cGVHD after FHI HCT utilizing CD34 enrichment and CD3/MNC addback in high-risk SCD patients who lack a MSD or URD. A longer term follow-up is needed to assess long-term safety and outcomes. This research was supported by RO1FD004090-01A1. [Display omitted] DisclosuresWalters:AllCells, Inc: Other: Medical Director; bluebird bio: Research Funding; Sangamo Therapeutics: Consultancy; ViaCord Processing Lab: Other: Medical Director. Cairo:Jazz Pharmaceuticals: Speakers Bureau.

Development and initial validation of self-report measures of general health, preoperative anxiety, and postoperative pain in young children using computer-administered animation.

For young children, existing measures of children's health-related quality of life must be parent-reported or interviewer-administered for those who cannot read or complete measures independently. Parents' and childrens' reports about the child's health have been shown to disagree. (a) To test the reliability and validity of an animated, computer-administered Child Health Rating Inventories (CHRIS2.0) among children aged 4-12 undergoing surgery; and (b) to develop and test two CHRIS measures of preoperative anxiety and postoperative pain management. We conducted a longitudinal cohort study of a diverse group of 542 children aged 4-12 undergoing surgery. We compared the CHRIS measures to Pediatric Quality of Life Inventory (PedsQL), the Functional Disabilities Inventory (FDI), State-Trait Anxiety Inventory for children (STAI-CH), and the Parent Postoperative Pain Measure (PPPM). Factor analyses supported the construct validity of the 12-item general physical health and the 8-item mental health CHRIS scales, as well as a composite 20-item scale, and the CHRIS preoperative anxiety and postoperative pain scales. Internal consistency reliability for all CHRIS scales exceeded the standard for group comparisons (Cronbach's α ≥0.70). The CHRIS general health composite was significantly correlated with composite PedsQL and FDI (r=0.28, P<.001 and r=0.43, P<.001, respectively). The CHRIS peri-operative anxiety measure was significantly correlated with the STAI-CH (r=0.44, P<.001), as was the CHRIS postoperative pain scale with the PPPM (r=0.52, P<.001). The CHRIS measures were reliable and valid in this diverse sample of young children (4-12). Because CHRIS measures are self-administered, scored in real time, and run on multiple different platforms, this approach provides a feasible method for the collection of health-related quality of life in young children and those with limited literacy. Our data indicate that this approach is psychometrically sound and has the potential for adding the child's voice to pediatric outcomes.

Health-Related Quality of Life (HRQL) Trajectories during Treatment for Advanced Stage Pediatric Hodgkin Lymphoma (HL)

Introduction: The treatment of advanced stage HL typically includes dose-dense chemotherapy with or without involved field radiation. However, little is known about the HRQL of pediatric patients during initial treatment. We describe the HRQL trajectory over time by child and parent-proxy rater and examine baseline patient characteristics associated with the trajectory.Methods: Children and adolescents, ages 5-17.9 years newly diagnosed with advanced stage HL and enrolled in Children's Oncology Group AHOD 1331, and their parents were co-enrolled in an embedded study to assess HRQL (n=310). Children (age ≥11 years) and parent proxies (of children 5-17.9 years) reported on the child's global HRQL using the Child Health Rating Inventories (CHRIs) at four times: (1) baseline, (2) cycle 2, (3) cycle 5, and (4) end of therapy, approximately 6-7 months following initial diagnosis. The 7-item CHRIs-Global yields scores that range from 0-100, with higher scores indicating better HRQL. A repeated measures linear regression model was fit with categorical time (reference, baseline), rater, child race, ethnicity, and continuous age. An interaction of rater and time was tested and predicted means were plotted.Results: 97% of age-eligible patients and parents completed baseline HRQL assessments with 93% completing planned follow-ups. Median child age was 15.5 years (q1=5.4, q3=18.9) and 50.3% were female. Most children were white (76.1%) and non-Hispanic (82.6%). There was no significant interaction between rater and time (Figure), so this was subsequently excluded from the model. Scores improved slightly at time 2 (β=2.5, 95%CI=0.3, 4.6) and 3 (β=2.8, 95%CI=0.3, 5.3) compared to baseline; larger improvements were seen by time 4 (β=10.6, 95%CI=7.9, 13.3) after completion of therapy. Children reported higher HRQL than their parent proxies (β=5.6, 95%CI=3.9, 7.2), males had higher HRQL than females (β=4.6, 95%CI=1.0, 8.3), and older age was associated with lower HRQL (β=-0.8, 95%CI=-1.5, -0.1). There was no significant effect of race or ethnicity.Conclusions: Completion rates of HRQL were high across all time periods and for both raters. HRQL, impaired at baseline, likely from the disease process, improved slightly during treatment, with larger improvements by the end of initial therapy. Future research will examine how clinical and treatment factors impact the HRQL trajectory. [Display omitted] DisclosuresParsons:Seattle Genetics: Research Funding. Rodday:Seattle Genetics: Research Funding. Henderson:Seattle Genetics: Research Funding.

Productivity Loss Among Parent Caregivers Is Associated with Poor Health-Related Quality of Life (HRQL) at the Intial Diagnosis of Pediatric Advanced Stage Hodgkin Lymphoma (HL)

▪Background: Financial hardship is the combined effect of medical expenditures, out of pocket expenses, and the impact of a cancer diagnosis and treatment on work. Productivity loss is a measure of work engagement, specifically missed time and/or altered performance, experienced by parent caregivers of children with cancer in the form of missed time from work and/or altered performance at work. Health-related quality of life (HRQL) is an important indicator of the disease process and its functional consequences among children at the time of initial diagnosis with cancer. The association of parental productivity loss with the child's HRQL is unknown.Methods: Two hundred ninety-one parent caregivers of children and adolescents, ages 5-17.9 years with newly diagnosed advanced stage Hodgkin Lymphoma (HL) were invited to participate in a study to assess costs of care as part of a larger Children's Oncology Group Phase III trial. Consenting parents completed the Caregiver Work Limitations Questionnaire (CG WLQ) and the Child Health Ratings Inventories (CHRIs)-Global Health measure prior to start of therapy. The CG WLQ is a validated 23-item measure, which quantifies the percent of time respondents had difficulty performing four key dimensions of work because of caregiving: physical tasks, mental-interpersonal tasks, output tasks, and time management. Mean scale scores (SD), ranging from 0-100, indicate the percentage of time the respondent reported work limitations by dimension in the month prior to diagnosis. The estimated productivity loss score, expressed as a percentage of time, is calculated from the weighted sum of the four scale scores, using an established algorithm validated in the generic WLQ. This is then monetized by multiplying the productivity loss score by the national average wage index of $50,000. The 10-item CHRIs-Global is a parent-proxy report of child HRQL and yields scores that range from 0-100, with higher scores indicating better HRQL. To describe how CG WLQ varied by child global HRQL, CG WLQ scores were reported separately for the lowest quartile of HRQL scores (Q1) and quartiles 2-4 combined (Q2-4). Mean (SD) productivity loss scores were compared using the two-sample t-test.Results: Two hundred eighty-two parents of trial participants (282/291, 97%) completed any baseline measures. Of the 242 parents who initiated the CG WLQ, 159 (66%) reported working at a paying job and were eligible to complete the remainder of the measure. The average age (SD) of caregiver respondents was 43.8 (6.9) years with 75.3% female, 74.7% White and 63.7% with at least some college education. The average age of the child with HL was 15 (2.8) years and 55% were male. The mean HRQL score was 65.2 (21.9). On average CG WLQ scores indicated that the caregiving role resulted in disrupted work tasks at least 31.4% (27.6) of the time (Table). The average percent of time that caregiving disrupted mental-interpersonal tasks, output tasks, and time management was higher in working caregivers of children with HRQL scores in the lowest quartile compared to higher quartiles. The productivity loss score was higher for caregivers whose children had lower HRQL, resulting in larger annual productivity costs.Conclusions: Family caregivers of child and adolescent HL patients are vulnerable to productivity loss, which is costly to the families, employers and the nation. High productivity losses noted at initial diagnosis indicate that financial hardship begins prior to the start of cancer treatment. Provider understanding of the association of the child's HRQL on the caregiver's work will inform strategies to maximize adherence to intensive chemotherapy and improve patients' HRQL. DisclosuresParsons:Seattle Genetics: Research Funding. Henderson:Seattle Genetics: Research Funding.

Leveraging pediatric PROMIS item banks to assess physical functioning in children at risk for severe functional loss

BackgroundPediatric neuromuscular illnesses often result in decreased health-related quality of life (HRQL), notably in physical functioning. Generic HRQL measures have been developed for use in general populations, but may not adequately assess patients with severe functional loss. To address this measurement gap, we created two custom parent-proxy physical functioning short forms for use among children at risk for low levels of functioning, using pediatric Patient Reported Outcomes Measurement Information System (PROMIS) item banks for Upper Extremity and Mobility.MethodsTwo custom short forms from PROMIS Upper Extremity (13 items) and Mobility (13 items) parent-proxy item banks were created and administered to parents of children (ages 5 – 22 years) enrolled in an integrated care program for management of chronic respiratory insufficiency, largely due to neuromuscular illnesses. Standardized PROMIS T-scores have a mean of 50 (SD = 10); higher scores indicate better functioning. Physicians rated clinical severity. Single proxy-rated items on mental and physical health from the Child Health Rating Inventories (CHRIs) global health scale were completed by parents. Psychometric properties, including known groups comparisons, were explored.ResultsFifty-seven parents completed the parent-proxy custom PROMIS short forms. The mean Upper Extremity T-score was 21 (SD = 13); the mean Mobility T-score was 22 (SD = 11). Some participants scored at the measurement floor; two items on assistive devices did not perform well in this sample and were excluded from the Mobility T-score. Known groups comparisons showed that those with lower clinical severity had better median Upper Extremity (22 vs. 14, p < 0.001) and Mobility (28 vs. 16, p = 0.004) function than those with worse clinical severity. Both Upper Extremity and Mobility T-scores were higher in the subgroups defined by better physical and mental health, as measured by the CHRIs.ConclusionsUpper Extremity and Mobility T-scores were nearly three standard deviations below the PROMIS pediatric calibration population mean. Preliminary psychometrics demonstrated the potential to more accurately measure lower physical functioning using items from PROMIS item banks. However, some participants scored at the measurement floor despite targeting items at the lower end of the scale. Further short form refinement, enrichment of the item banks, and larger-scale field testing are needed.

Derivation and Validation of a Risk Model for Emergency Department Palliative Care Needs Assessment Using the Screen for Palliative and End-of-Life Care Needs in the Emergency Department (SPEED) (TH347-A)

using data from two longitudinal health-related quality of life (HRQL) studies. Methods. Parents of children undergoing HSCT (n1⁄4363) at eight US transplant centers completed the Child Health Ratings Inventories (CHRIs) measuring parent and child general health and HRQL at baseline (BL) through 12 months post HSCT. Main outcomes were responses to two CHRIs items developed to assess parent outlook regarding potential child outcomes, ‘‘might die’’ and ‘‘future health worse,’’ rated on a 5-point Likert scale ranging from worrying about the outcome none to all of the time, and transformed to 0-100 (higher, more worry). Analyses focus on BL to day +45 when improvement in parent outlook was pronounced. Clinical data were abstracted from charts. Personal, clinical, and HSCT course characteristics with p<0.2 on univariate analysis were entered into adjusted multivariable models, then eliminated by backward selection (p<0.1). Results. Parents were 83% female, 77% white, mean age 38.6 years (SD1⁄47.5). Child mean age was 9.6 years (SD1⁄45.1). Most (72%) had cancer; 78% underwent allogeneic HSCT. By day +45, 33% had systemic infection, 33% acute graft versus host disease, and 20% intermediate/poor Bearman toxicity score. Mean parent ‘‘might die’’ worry decreased from BL (41.9, SD1⁄48.3) to day +45 (26.6, SD1⁄424.6, p<0.001). ‘‘Health worse’’ worry similarly decreased. For both outcomes, identified risk factors for ongoing parent worry at day +45 include younger child age (p1⁄40.03) and malignancy (p<0.001) but not actual clinical outcomes. Conclusions. Some parents remain at risk for unmitigated worry about their child’s health, largely irrespective of the HSCT course. Implications for Research, Policy, or Practice. Enhanced clinician awareness of parent outlook and augmented support may benefit parents during HSCT.

Parent distress related to child health outcomes during hematopoietic stem cell transplant (HSCT).

31 Background: HSCT offers possible cure yet remains intensive and high risk. Parent distress related to potential child outcomes during HSCT is unexplored. Methods: Parents of children undergoing HSCT (n=363) at 8 US transplant centers completed the Child Health Ratings Inventories (CHRIs) measuring parent and child general health and QOL at baseline (BL) through 12 mos post HSCT. Main outcomes: responses to 2 CHRIs items regarding parent worry about child "health worse" and "might die," rated on a 5-point Likert scale ranging from none to all of the time, and transformed to 1-100 (higher, more worry). Analyses focus on BL to D45 when parent worry decrease was pronounced. Clinical data were abstracted from charts. BL personal, clinical and HSCT course characteristics with p&lt;0.2 on univariate analysis were entered into multivariable models adjusting for transplant center, then eliminated by backward selection (p&lt;0.1). Results: Parents were 83% female, 77% White, median age 38.7 yr (IQR 33-44). Child median age was 9.6 yr (IQR 6-14). Most (72%) had cancer; 78% underwent allogeneic HSCT. By D45, 33% had systemic infection, 33% acute graft versus host disease (aGVHD) and 20% intermediate/poor Bearman toxicity score. Mean parent "might die" worry decreased from BL (41.9, SD 8.3) to D45 (26.6, SD 24.6) (p&lt;0.001). "Health worse" worry similarly decreased. Despite this, ongoing worry risk factors exist including younger child age, solid tumor and hematologic malignancy but not HSCT course characteristics (Table). Conclusions: Some parents remain at risk for unmitigated distress about child health, largely irrespective of the HSCT course. Enhanced supports such as palliative care consultation may be of benefit. [Table: see text]

Joint models for predicting transplant-related mortality from quality of life data

To test whether longitudinally measured health-related quality of life (HRQL) predicts transplant-related mortality (TRM) in pediatric hematopoietic stem cell transplant (HSCT). The predictors of interest were emotional functioning, physical functioning, role functioning, and global HRQL, as rated by the parent about the child up to 6 times over 12 months of follow-up and measured by the Child Health Ratings Inventories. We used joint models, specifically shared parameter models, with time to TRM as the outcome of interest and other causes of mortality as a competing risk, via the JM software package in R. Choosing shared parameter models instead of standard survival models, such as Cox models with time-dependent covariates, enabled us to address measurement error in the HRQL trajectories and appropriately handle missing data. The nonlinear trajectories for each HRQL domain were modeled by random spline functions. The survival submodels were adjusted for baseline patient, family, and transplant characteristics. Hazard ratios per one-half standard deviation difference in emotional, physical, and role functioning, and global HRQL were 0.61 (95 % CI 0.46-0.81; p < 0.001), 0.70 (0.51-0.96; p = 0.03), 0.54 (0.34-0.85; p = 0.007), and 0.57 (0.41-0.79; p < 0.001), respectively. HRQL trajectories were predictive of TRM in pediatric HSCT, even after adjusting the survival outcome for baseline characteristics.

Family-Centered Assessment and Function for Children With Chronic Mechanical Respiratory Support

IntroductionThe purpose of this study was to assess health-related quality of life (HRQL) when managing severe, chronic respiratory insufficiency (CRI) at home. MethodsFamilies enrolled in a comprehensive program for CRI completed the Child Health Ratings Inventories with (a) parent-proxy ratings of the child's HRQL and (b) the parent's own HRQL. Psychometrics and known groups comparisons were reported. Linear regressions models assessed the effect of the parent's HRQL on proxy ratings. ResultsEighty-six parents (67%) completed the measures. The child global HRQL score was low (63.1, SD = 24.9), although ratings of “family life” were higher (73.8, SD = 26.5). The parent global HRQL and emotional functioning (EF) scores were low, despite preserved physical and role function. Having a child with a congenital versus an acquired disability was associated with higher parental EF (p = .004). Higher parental EF correlated with a higher global child HRQL (p < .001). DiscussionFamilies of children with CRI experience reduced HRQL. The Child Health Ratings Inventories is a valid tool for this assessment, identifying emotional distress and potential gaps in support.

Measuring global health-related quality of life in children undergoing hematopoietic stem cell transplant: a longitudinal study.

BackgroundPediatric health-related quality of life (HRQL) measures explore multiple domains of HRQL. To ease administration, burden, and implementation, we created a 7-item unidimensional global HRQL scale for children. This paper evaluates the psychometric properties of the global HRQL scale in children undergoing hematopoietic stem cell transplant (HSCT) and describes the trajectory of global HRQL scores over the 12-month course following HSCT.MethodsAs part of two longitudinal HSCT studies, HRQL was collected on 312 parent–child dyads using the Child Health Ratings Inventories. Parents of children aged 5–18 completed the pediatric global HRQL scale about their child and 117 adolescents completed the scale themselves. Psychometric properties were compared across both raters. Two repeated measures models were built to describe trajectories of (1) global HRQL for all children based on parent proxy report and (2) global HRQL for adolescents based on adolescent self-report and parent proxy report.ResultsInternal consistency reliability was high for parent proxy report and adolescent self-report (Cronbach’s alpha 0.9, 0.8, respectively). Unidimensionality was verified using principal components analysis. Both models indicated decreased global HRQL in the presence of early complications related to HSCT and Model 1 further indicated decreased HRQL in the presence of later complications. Model 2 showed that parent proxies reported lower global HRQL scores than adolescent self-report.ConclusionsThis study has demonstrated the unidimensionality and strong psychometric properties of a 7-item global HRQL scale in a sample of children undergoing HSCT. Despite its brevity, scale scores vary in clinically meaningful ways. Future applications of this scale are encouraged.

Parental emotional functioning declines with occurrence of clinical complications in pediatric hematopoietic stem cell transplant

Parents' stress levels are high prior to their child's hematopoietic stem cell transplant (HSCT) and during transplant hospitalization, usually abating after discharge. Nevertheless, a subgroup of parents continues to experience frequent anxiety and mood disruption, the causes of which are not well understood. The purpose of this study was to assess whether clinical complications of HSCT could explain variation in parents' recovery of emotional functioning. Pediatric HSCT recipients (n = 165) aged 5-18 and their parents were followed over the first year post-transplant. Health-related quality of life assessments and medical chart reviews were performed at each time period (baseline, 45 days, 3, 6, and 12 months). We tested the association between clinical complications [acute and chronic graft versus host disease (aGVHD and cGVHD), organ toxicity, and infection] and longitudinally measured parental emotional functioning, as assessed by the Child Health-Ratings Inventories. The models used maximum likelihood estimation with repeated measures. In adjusted analyses covering the early time period (45 days and 3 months), aGVHD grade ≥2, intermediate or poor organ toxicity, and systemic infection were associated with decreases in mean parental emotional functioning of 5.2 (p = 0.086), 5.8 (p = 0.052), and 5.1 (p = 0.023) points, respectively. In the later time period (6 and 12 months), systemic infection was associated with a decrease of 20 points (p < 0.0001). cGVHD was not significantly associated. When children experience clinical complications after HSCT, parental emotional functioning can be impacted. Intervening at critical junctures could mitigate potential negative consequences for parents and their children.

Performance of the parent emotional functioning (PREMO) screener in parents of children undergoing hematopoietic stem cell transplantation

Parents of children undergoing hematopoietic stem cell transplantation (HSCT) may face emotional distress while managing intense treatments with uncertain outcomes. We evaluated a brief parental emotional functioning (PREMO) screener from a health-related quality of life instrument to identify parental emotional distress, as measured by the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID). As part of a longitudinal pediatric HSCT study, parents (N = 165) completed the Child Health Ratings Inventories, which contain the 7-item PREMO screener. Some parents (n = 117) also completed SCID modules for Anxiety, Mood, and Adjustment disorders at baseline and/or 12 months. A composite outcome was created for threshold or subthreshold levels of any of these disorders. Receiver operating characteristic (ROC) analysis assessed how the PREMO screener predicted emotional distress as measured by the SCID. A prediction model was then built. Fifty-two percent of parents completing the SCID had an Axis I disorder at baseline, while 41 % had an Axis I disorder at 12 months. The area under the ROC curve was 0.75 for the PREMO screener and 0.81 for the prediction model. The PREMO screener may identify parents with, or at risk for, emotional distress and facilitate further evaluation and intervention.

Health‐related quality of life (HRQL) in children with sickle cell disease and thalassemia following hematopoietic stem cell transplant (HSCT)

Little is known regarding the health-related quality of life (HRQL) trajectory of children with sickle cell disease or thalassemia ("hemoglobinopathies") following hematopoietic stem cell transplantation (HSCT). We serially evaluated the HRQL of 13 children with hemoglobinopathies who received HSCT during two prospective multi-center studies using the Child Health Ratings Inventories (CHRIs). The HRQL scores among children with hemoglobinopathies, as reported separately by the children and their parents were compared using repeated measures models to scores of a comparison group of children receiving HSCT for malignancies or severe aplastic anemia. The sample included 13 children with hemoglobinopathies (median age: 8 years, range 5-18) and 268 children in the comparison group (median age: 11 years, range 5-18). There were similar rates of early infection, chronic graft versus host disease, and all-cause mortality between the two groups. There was no significant difference in recovery to baseline scores for physical, emotional, and role functioning by 3 months for either group. Children with hemoglobinopathies had higher HRQL scores for physical (beta = 12, se = 5.5, P = 0.01) and baseline emotional functioning (beta = 11.6, se = 5.5, P = 0.03) than the comparison group. For all domains for both groups, parent reports demonstrated a nadir at 45 days with recovery to baseline by 3 months following transplant. Children's ratings were higher than those of their parents in both diagnostic groups. Children with hemoglobinopathies had higher physical and emotional functioning scores prior to HSCT and experienced a similar pattern of recovery to their baseline functioning by 3 months post-HSCT when compared to children receiving HSCT for acquired conditions.

Impact on family of survivors of congenital diaphragmatic hernia repair: a pilot study

Background/Purpose We hypothesized that long-term impact on the family of survivors of congenital diaphragmatic hernia (CDH) would vary based on the child's current clinical problems and clinical severity, family income, insurance, and out-of-pocket expenses. Methods Parents of a retrospective cohort of 53 CDH survivors who underwent repair at Children's Hospital Boston in Massachusetts from 1991 through 1999 completed the Impact on Family Scale (IFS), the Child Health Ratings Inventories General Health Module Parent Report, a rating of their child's clinical severity, an inventory of current clinical problems, and family demographics. Statistical tests of the primary outcome, the IFS total score, were performed. Results Survivors of CDH had a median age of 8 years. Most families had private insurance (78%) and annual income levels higher than the federal poverty level (96%). The IFS total score was correlated with child's clinical severity ( r = 0.71, P < .001) and was worse among families of children with current clinical problems ( P = .01), families with public insurance ( P = .01), and those with out-of-pocket expenses of at least $500 ( P = .002). Regression analysis identified the independent effect of clinical severity on family impact ( P < .001). Conclusion Family impact is profound and long-standing at a median of 8 years after surgery for a subset of CDH survivors with more severe conditions and current clinical problems.

Long-term functional impact of congenital diaphragmatic hernia repair on children

Background/Purpose Congenital diaphragmatic hernia (CDH) is a malformation requiring neonatal surgical repair with in-hospital survival rates above 90%. We examined the long-term functional impact of CDH repair on a cross-sectional cohort of survivors. Methods A cohort of 53 CDH families participated in this study. Functional impact was evaluated with parent report of the Functional Status IIR and the Child Health Ratings Inventories General Health Module. Parents also provided a clinical severity score, the child's medical history, and family demographic information. The primary outcome was the effect of medical morbidity on the Functional Status IIR total score. Results Congenital diaphragmatic hernia survivors had a median age of 8 years; 50% were in third grade or above. Sixty-six percent had major medical issues at hospital discharge, whereas 48% had current clinical problems. Functional Status IIR total score was strongly correlated with child's clinical severity ( r = −0.65; P < .0001) and was lower among children with ongoing medical morbidity, denoting worse functioning ( P = .01). Child Health Ratings Inventories General Health Module scores followed a similar pattern. Conclusions A subset of long-term CDH survivors continues to have ongoing clinical problems a median of 8 years after surgery, translating to lower functional status. Affected children and their families may benefit from prospective identification and ongoing interventions.

Health-Related Quality of Life (HRQL) in Children with Severe, Chronic Immune Thrombocytopenia (cITP) Treated with Rituximab.

Background: A subset of children with cITP is at increased risk for severe bleeding and functional limitations. We evaluated the HRQL of children with cITP as part of a multicenter, open label Phase I/II clinical trial of four weekly doses of Rituximab, evaluated for response at 12 weeks. Responders had a ≥ 50,000/mm3 platelet count over weeks 9–12 without other supportive therapy.Methods: All participating parents were invited to complete the Child Health Ratings Inventories (CHRIs) at baseline and 12 wks. The CHRIs, a generic HRQL questionnaire, contains 20 items, forming four domains in the areas of physical, role, and emotional functioning, and school. Each item has a five-point Likert response scale. Domain scores range from 0–100, with higher scores connoting better functioning. Of the 36 study participants, 24 parents opted to participate in the HRQL evaluation; 22 of 24 (91%) completed both the baseline and 12-week assessments. The baseline clinical profile and 12-week Rituximab response rates of HRQL participants and non participants (n=12) were compared. Potential clinical covariates (e.g., duration of illness, worst bleeding score, platelet count, number of prior therapies) were examined in a univariate analysis (UVA) with baseline HRQL domain scores. Regression analyses (MVA) adjusting for age and gender were used to assess the effects of treatment response and clinical covariates on the mean change in scores between baseline and week 12.Results: While HRQL participants had more previous treatments and lower platelet counts than nonparticipants, their clinical profile was otherwise similar; Rituximab response rates did not differ. Mean HRQL domain scores (standard deviation) at baseline were as follows: physical-52.1 (36.2); role-78.6 (23.7); emotional-63.4 (18.3); school-64.1 (25.8). Lower platelet count and greater number of prior therapies were significantly associated with worse baseline HRQL scores on UVA. By week 12, 36% (8/22) responded to Rituximab. Clinically meaningful improvements in HRQL scores (≥ 0.5 standard deviation improvement) were observed in responders; no change was detected in non-responders. In MVA, responder status contributed the predominate effect on the HRQL change scores, with the greatest improvement noted in emotional functioning (p=.002). No other clinical variables emerged in this limited sample size.Conclusions: The pattern of parent-reported HRQL scores for these children with severe cITP mirrored scores from other severe, pediatric health conditions. Significant improvements in HRQL were observed among Rituximab responders over the 12-week period while non-responders had no change. Further overall characterization of HRQL in the cITP pediatric population is needed.

Maternal Perspectives on Children’s Health-Related Quality of Life During the First Year After Pediatric Hematopoietic Stem Cell Transplant

To assess the longitudinal health-related quality of life (HRQL) of children receiving hematopoietic stem cell transplantation (HSCT). Mothers (N = 160) of HSCT recipients aged 5-20 at six US transplant centers completed the Child Health Ratings Inventories (CHRIs), the Disease Impairment Inventory (DSII)-HSCT module, and the Short Form (SF)-36 at baseline, 3, 6, and 12 months. HRQL domain scores at baseline varied by recipient age and program site. Longitudinal data over the first year post-HSCT revealed lowest functioning at baseline and 3 months, with largest improvement in functioning between the 3 and 6-months assessments and continued improvement from 6 to 12 months. Recipients of unrelated donor transplants had steepest declines in functioning at 3 months and great HSCT-specific issues at 3 and 6 months. Among children who survived the first year, functioning at 12 months was similar across transplant types and surpassed baseline scores. Children who did not survive the first year exhibited deterioration in HRQL in the months before death and trajectories were strikingly different than for survivors. This study offers the first glimpse of the 12-month trajectory of HRQL following pediatric HSCT from mothers' perspectives. This study also highlights the importance of and approaches to addressing missing data in longitudinal research.

Health-related quality of life in pediatric bone marrow transplant survivors: according to whom?

Historically, health-related quality of life (HRQL) assessment in pediatrics, including the few validated instruments in pediatric oncology, has been based on proxy reporting, relying primarily on parental assessment. Children have been deemed incapable of providing consistent and reliable information about their level of functioning or state of well-being. Previous studies have been hampered by either limited or poor correlation among the proxy reporters, i.e., teachers, parents and physicians, and in comparisons to disease severity. Simply stated, proxy reporters have greater agreement about what the child can do vs. what the child thinks or feels. Comparisons among proxy reporters have been hindered also by a lack of parallel content in the instruments used, which may result in poorly congruent assessments simply because the instruments measure different constructs. In addition to the measurement issues, the emotional milieu of the parent, particularly the mother, has been shown to influence assessments of the child's functioning. Maternal distress, marital adjustment and health locus of control all co-vary with reports of the child's behavior. What, then, is the proxy reporter telling us about the child? We conducted a cross-sectional study of school-aged pediatric bone marrow transplant (BMT) patients at our institution to evaluate children's self-reported HRQL and functional status. We formally tested the Child Health Rating Inventories (CHRIs), a recently developed generic health-status measure, with its companion measure, the Disease Impairment Inventories-Bone Marrow Transplant (DSII-BMT). Separate questionnaires were administered to patients, parents and physicians at a scheduled outpatient visit after BMT. The questionnaires were designed to have parallel content. All responses were confidential. The psychometric properties of the CHRIs and DSII-BMT are reported elsewhere. In brief, the responses of all raters were reliable, based on measurements of internal consistency. The children's self-reported health status was correlated significantly with the physicians' disease severity rating (DSR) across all generic and disease-specific domains. In contrast, parental reports of child health status were not correlated significantly with the DSR for disease-specific problems or the child's pain. Parental ratings deviated most from the children's ratings within the dimensions of mental health and quality of life (p < 0.001). For the entire sample, parental ratings were significantly lower than the children's ratings. Within the subgroup "early after transplant (<6 months)", parental ratings were significantly lower than the children's self-reports in all categories. In the subgroup ">12 months after transplant", with the exception of mental health and quality of life, parental scores were the same as or higher than the children's ratings. Our results confirm previous studies that the parental reporting of children's health status is a complex construct and that valuable information can be elicited directly from the children. Further research is needed to substantiate these findings, particularly in longitudinal applications with adequate sample sizes.