The development of an English Health-Related Quality of Life (HRQoL) measure for very young children, to be completed by proxy

Background and Aims: There is an increasing awareness that, in order to monitor health outcomes both mortality and morbidity need to be assessed. A common metric used to measure morbidity and functional limitation is the quality adjusted life year or QALY, which incorporates time spent in a health condition and Health-Related Quality of Life (HRQoL) into the measure. This is of increasing importance in Low Income Countries (LIC) where programmes have been adopted and implemented to address the high burden of child mortality. The ‘first 1000 days’ is one such initiative which has been adopted by the WHO to improve nutritional support, health care and social support for both the mother and child. One of the aims is to improve quality of life during this vulnerable period. As there is currently no appropriate measure of HRQoL in this age group, we set out to develop a valid and reliable, HRQoL instrument for children from 1 month to 3 years old, amenable to the elicitation of preference weights. Methods: The new HRQoL instrument, HRQoL-6D-IT, was based firstly on a mapping review of HRQoL measures for children. The next stage involved eliciting options through cognitive review from caregivers of very young children regarding HRQoL dimensions included in the EQ-5D-Y an existing validated HRQoL measure for older children. The care-givers were requested to identify items to be considered for inclusion, the wording and layout of the new measure. The item pool generated from the literature reviews and cognitive interviews were then assessed through a Delphi study with experts in the field. These items were further reduced through subsequent testing of items and retesting of a preliminary measure. The final items on the HRQoL-6D-IT included: movement, play, pain, relationships, communication and eating and, apart from pain, the descriptors referenced the behaviour of the child to age appropriate behaviour. The HRQoL-6D-IT was then tested for validity and reliability in a group of acutely-ill (AI), chronically-ill (CI) and typically developing (TD) children in two provinces in South Africa: Western and Eastern Cape. Results: The methodology used to identify candidate items was rigorous and yielded items which were developed to be observable with dimension descriptors referring to ‘age appropriate behaviour’. Caregivers were able to reliably report on HRQoL of their very young children from age 1-36 months. The content validity had been established during the development of the instrument. Concurrent validity of the different items (dimensions) was tested between the HRQoL-6D-IT and relevant items from the ASQ, FLACC and NIPS pain scale and Diet History

Performance of the EQ-5D-Y Interviewer Administered Version in Young Children

(1) Background: An estimated 78% of South African children aged 9–10 years have not mastered basic reading, therefore potentially excluding them from self-reporting on health-related outcome measures. Thus, the aim of this study was to compare the performance of the EQ-5D-Y-3L self-complete to the newly developed interviewer-administered version in children 8–10 years. (2) Methods: Children (n = 207) with chronic respiratory illnesses, functional disabilities, orthopaedic conditions and from the general population completed the EQ-5D-Y-3L self-complete and interviewer-administered versions, Moods and Feelings Questionnaire (MFQ) and Faces Pain Scale-Revised (FPS-R). A functional independence measure (WeeFIM) was completed by the researcher. (3) Results: The 8-year-olds had significantly higher missing responses (x2 = 14.23, p < 0.001) on the self-complete version. Known-group and concurrent validity were comparable across dimensions, utility and VAS scores for the two versions. The dimensions showed low to moderate convergent validity with similar items on the MFQ, FPS-R and WeeFIM with significantly higher correlations between the interviewer-administered dimensions of Mobility and WeeFIM mobility total (z = 1.91, p = 0.028) and Looking After Myself and WeeFIM self-care total (z = 3.24, p = 0.001). Children preferred the interviewer-administered version (60%) (x2 = 21.87, p < 0.001) with 22% of the reasons attributed to literacy level. (4) Conclusions: The EQ-5D-Y-3L interviewer-administered version is valid and reliable in children aged 8–10 years. The results were comparable to the self-complete version indicating that versions can be used interchangeably

Item generation for a proxy health related quality of life measure in very young children

Abstract Background and aims Very young children have a relatively high prevalence of morbidity and mortality. Health care and supportive technology has improved but may require difficult choices and decisions regarding the allocation of these resources in this age group. Cost-effective analysis (CEA) can inform these decisions and thus measurement of Health-Related Quality of Life (HRQoL) is becoming increasingly important. However, the components of HRQoL are likely to be specific to infants and young children. This study aimed to develop a bank of items to inform the possible development of a new proxy report instrument. Methods A review of the literature was done to define the concepts, generate items and identify measures that might be an appropriate starting point of reference. The items generated from the cognitive interviews and systematic review were subsequently pruned by experts in the field of HRQoL and paediatrics over two rounds of a Delphi study. Results Based on the input from the different sources, the greatest need for a new HRQoL measure was in the 0–3-year age group. The item pool identified from the literature consisted of 36 items which was increased to 53 items after the cognitive interviews. The ranking of items from the first round of the Delphi study pruned this pool to 28 items for consideration. The experts further reduced this pool to 15 items for consideration in the second round. The experts also recommended that items could be merged due to their similar nature or construct. This process allowed for further reduction of items to 11 items which showed content validity and no redundancy. Conclusion The need for an instrument to measure appropriate aspects of HRQoL in infants and young children became apparent as items included in existing measures did not cover the required spectrum. The identification of the final items was based on a sound conceptual model, acceptability to stakeholders and consideration of the observability of the item selected. The pruned item bank of 11 items needs to be subject to further testing with the target population to ensure validity and reliability before a new measure can be developed

Influence of the child’s perceived general health on the primary caregiver’s health status

Background: In estimating the impact of an intervention, ignoring the effect of improving the health of one member of the caregiver/child dyad on the Health Related Quality of Life (HRQoL) of the other member may lead to an underestimation of the utility gained. This may be particularly true for infants/young children and their caregivers. The aim of this study was to quantify the interaction between the child’s perceived general health as assessed by the newly developed Toddler and Infant Questionnaire (TANDI) on the reporting of the caregiver’s own HRQoL as assessed by the EQ-5D-3 L. Methods: A sample of 187 caregivers participated. A total of 60 caregivers of acutely-ill (AI) and 60 caregivers of chronically-ill (CI) children were recruited from a children’s hospital. The 67 caregivers of general population (GP) children were recruited at a pre-school. Each caregiver completed the proxy rating of their child’s HRQoL on the TANDI (The TANDI is an experimental HRQoL instrument, modelled on the EQ-5D-Y proxy, for children aged 1-36 months), which comprises of six dimensions of health and a rating of general health on a Visual Analogue Scale (VAS). The caregiver completed the EQ-5D-3 L, a self-report measure of their own HRQoL. Forward stepwise regression models were developed with 1) the VAS score of the caregiver and 2) the VAS score of the child as dependent variables. The independent variables for the caregiver included dummy variables for the presence or absence of problems on the EQ-5D-3 L and the VAS score of the child. The independent variables for the child included dummy variables for each TANDI dimension and the VAS of the caregiver. Results: The TANDI results indicated that in five of the six dimensions AI children had more problems than the other two groups and the GP children were reported to have a significantly higher VAS than the other two groups. The child’s VAS was significantly correlated with the caregiver’s VAS in all groups, but most strongly in the AI group. The preference based scores (using the UK TTO tariff) were only correlated in the AI group. The inclusion of the child’s VAS increased the variance accounted for 11% of the VAS score of the caregiver. Anxiety and depression was the only dimension which accounted for more variance (18%). Similarly the perceived health state, VAS of the caregiver accounted for 14% of the variance in the child’s VAS, second only to problems with play (25%). Conclusion: There does indeed appear to be a strong relationship between the VAS scores of the children and their caregivers. The perceived general health of the child influences the caregivers reporting of their general health, more than their own report of experiencing pain or discomfort or problems with mobility. Thus, improving the HRQoL of the very young child may improve the caregiver’s HRQoL as well. Conversely, if the caregiver has a lower perceived HRQoL this may result in a decrement in the reported VAS of the child, independent of the presence or absence of problems in the different dimensions. This improvement is not currently captured by Cost Utility Analysis (CUA). It is recommended that future research investigates this effect with regards to CUA calculations

Measurement properties and responsiveness of the EQ-5D-Y-5L compared to the EQ-5D-Y-3L in children and adolescents receiving acute orthopaedic care

Objective The aim of this study is a head-to-head comparison of the instrument performance and responsiveness of the EQ-5D-Y-3L and the expanded English version of the EQ-5D-Y-5L in children/adolescents receiving acute orthopaedic management in South Africa. Methods Children/adolescents aged 8–15 years completed the EQ-5D-Y-5L, EQ-5D-Y-3L, self-rated health (SRH) question and PedsQL at baseline. The EQ-5D-Y-5L, EQ-5D-Y-3L and SRH question were repeated after 24 and 48 h. Performance of the EQ-5D-Y-5L and EQ-5D-Y-3L was determined by comparing feasibility (missing responses), redistribution of dimensions responses, discriminatory power, concurrent validity, and responsiveness. Results Eighty-three children/adolescents completed baseline measures and seventy-one at all three time-points. Reporting of 11111 decreased by 20% from the EQ-5D-Y-3L to the EQ-5D-Y-5L. Informativity of dimensions improved on average by 0.267 on the EQ-5D-Y-5L with similar evenness. There was a range of 11–27% inconsistent responses when moving from the EQ-5D-Y-3L to the EQ-5D-Y-5L. There was a low to moderate and significant association on the EQ-5D-Y-3L and EQ-5D-Y-5L to similar items on the PedsQL and SRH scores. Percentage change over time was greater for the EQ-5D-Y-5L (range 0–182%) than EQ-5D-Y-3L (range 0–100%) with the largest reduction for both measures between 0 and 48 h. For those who respondents who showed an improved SRH the EQ-5D-Y-5L and EQ-5D-Y-3L showed significant paired differences. Conclusion The English version of the EQ-5D-Y-5L appears to be a valid and responsive extension of the EQ-5D-Y-3L for children receiving acute orthopaedic management. The expanded levels notably reduce the ceiling effect and has greater discriminatory power. Concurrent validity of the EQ-5D-Y-3L and EQ-5D-Y-5L was low to moderate with similar PedsQL items and SRH. The EQ-5D-Y-5L generally showed greater change than the EQ-5D-Y-3L across all dimensions with the greatest change observed for 0–48 h. Responsiveness was comparable across the EQ-5D-Y-3L and EQ-5D-Y-5L for those with improved SRH. Greater sensitivity to change may be observed on comparison of utility scores, once preference-based value sets are available for the EQ-5D-Y-5L

Clinical and Experimental Determination of Protection Afforded by BCG Vaccination against Infection with Non-Tuberculous Mycobacteria: A Role in Cystic Fibrosis?

Mycobacterium abscessus is a nontuberculous mycobacterium (NTM) of particular concern in individuals with obstructive lung diseases such as cystic fibrosis (CF). Treatment requires multiple drugs and is characterised by high rates of relapse; thus, new strategies to limit infection are urgently required. This study sought to determine how Bacille Calmette-Guérin (BCG) vaccination may impact NTM infection, using a murine model of Mycobacterium abscessus infection and observational data from a non-BCG vaccinated CF cohort in Sydney, Australia and a BCG-vaccinated CF cohort in Cape Town, South Africa. In mice, BCG vaccination induced multifunctional antigen-specific CD up sup T cells circulating in the blood and was protective against dissemination of bacteria to the spleen. Prior infection with M. abscessus afforded the highest level of protection against M. abscessus challenge in the lung, and immunity was characterised by a greater frequency of pulmonary cytokine-secreting CD4 T cells compared to BCG vaccination. In the clinical CF cohorts, the overall rates of NTM sampling during a three-year period were equivalent; however, rates of NTM colonisation were significantly lower in the BCG-vaccinated (Cape Town) cohort, which was most apparent for M. abscessus. This study provides evidence that routine BCG vaccination may reduce M. abscessus colonisation in individuals with CF, which correlates with the ability of BCG to induce multifunctional CD4T cells recognising M. abscessus in a murine model. Further research is needed to determine the optimal strategies for limiting NTM infections in individuals with CF

Comparison of the EQ-5D-Y-5L, EQ-5D-Y-3L and PedsQL in children and adolescents

Background There is an increased use of Patient-Reported Outcome Measures (PROMs) in children and adolescents. The aim of this study was to compare the feasibility, concurrent validity and known-group validity of the EQ-5D-Y-3L (Y-3L), EQ-5D-Y-5L (Y-5L) and PedsQL self-report PROMs. Methods Five hundred and fifty children and adolescents, aged 8–15-years, with acute and chronic health conditions and a general population sample were recruited from schools and hospitals in Cape Town South Africa. All respondents self-completed the Y-5L, PedsQL, Self-Rated Health Question and Y-3L. Feasibility of the measures was determined by comparing the number of missing responses. Convergent validity was assessed by Spearman’s and Intra-class correlations on the corresponding items and summary scores respectively. Known-groups validity across health conditions was assessed across the summary scores of the measures with analysis of variance (ANOVA). Results The Y-3L and Y-5L had a total of 1% and 3.5% missing responses compared to 19% on the PedsQL. Similar items on the PedsQL and Y-3L/Y-5L showed high correlations (> 0.5) and related items showed moderate correlations (0.3). PedsQL total score was moderately and significantly associated with Y-3L and Y-5L level sum and VAS scores. The Y-3L and Y-5L level sum and VAS scores showed significant differences between known health groups whereas the PedsQL only showed differences between those with acute and chronic illness. Conclusion The results of this study show that the Y-3L and Y-5L showed comparable psychometric validity to the PedsQL. When considering the choice between the PedsQL, Y-5L and Y-3L these study results indicate that the EQ-5D-Y instruments (Y-3L and Y-5L) are recommended for studies assessing known-group validity or where missing data should be minimised. The PedsQL generic measure may be preferable in future studies including the general population where a ceiling effect is anticipated. When considering the choice between the Y-5L and the Y-3L there was no systematic difference in the validity between these instruments or between the Y-3L or Y-5L and the PedsQL. Thus, the selection of EQ-5D-Y measures to include in future studies should be guided by the characteristics of the population to be tested