Fighting to Breathe and Fighting for Health-Related Quality of Life: Measuring the Impact of Being Dependent on Technology for Breathing on the Child and Their Caregiver.

BACKGROUND AND OBJECTIVE: Medical advancement has enabled children to survive congenital airway anomalies, rare diseases and critical illnesses with medical technology including tracheostomies and long-term ventilation to support breathing. This study aimed to assess (1) the validity of the EQ-TIPS and EQ-5D-Y-3L in children dependent on technology and (2) the impact of caring for these children on the EQ-5D-5L and CarerQoL. METHODS: Caregivers of children aged 1 month to 18 years completed the EQ-TIPS or EQ-5D-Y-3L, Pediatric Quality of Life Inventory (PedsQL) and Paediatric Tracheostomy Health Status Instrument (PTHSI) to reflect the child's health. In addition, caregivers self-completed the EQ-5D-5L and CarerQoL. Reports of problems on EQ dimensions were compared across age groups with the Fisher's exact test. Spearman and Pearson's correlation coefficients and Kruskal-Wallis H-test were used to explore the association between caregiver and child scores, concurrent validity, and known-group validity of the EQ-TIPS and EQ-5D-Y-3L. RESULTS: Responses from 144 caregivers were collected, 66 for children aged 1 month to 4 years completing EQ-TIPS and 78 for children aged 5-18 years completing EQ-5D-Y-3L. The EQ-TIPS showed a higher report of no problems for social interaction for children aged 1-12 months (p = 0.040) than the older age groups, there were however no differences in the level sum score (LSS) or EQ Visual Analogue Scale scores between the age groups. The EQ-5D-Y-3L showed a significantly less report of problems for mobility (p = 0.013) and usual activities (p = 0.006) for children aged 5-7 years compared with children aged 8-12 and children aged 13-18 years. Similarly, the 5-7 years of age group had a significantly lower EQ-5D-Y-3L LSS compared with the older groups (H = 12.08, p = 0.002). The EQ-TIPS and EQ-5D-Y-3L showed moderate-to-strong associations with the PedsQL. EQ-TIPS median LSS was able to differentiate between groups on the clinical prognosis with a better health-related quality of life (HRQoL) in those where weaning from technology is possible compared with those where weaning is not possible (H = 18.98, p = 0.011). The EQ-5D-Y-3L can discriminate between breathing technology, where those with only a tracheostomy reported better HRQoL (H = 8.92, p = 0.012), and between mild and moderate clinical severity (H = 19.42, p < 0.001). Neither the PedsQL nor the PTHSI was able to discriminate between these groups across the age range. Caregiver and child HRQoL scores showed moderate-to-strong associations. CONCLUSIONS: The EQ-TIPS and EQ-5D-Y-3L showed good validity in children dependent on the technology for breathing. The EQ-TIPS and EQ-5D-Y-3L LSS were all able to differentiate between children with known clinical variables and outperformed both the PedsQL and PTHSI, making them preferable for intervention research. The caregiver scores are associated with the child HRQoL scores and thus a spill-over should be accounted for in any interventions targeting this cohort. It is recommended that future studies investigate the reliability and responsiveness of these measures in children dependent on technology for breathing.

Global disparities in cystic fibrosis outcomes prior to CFTR modulators: A CF registries cohort study in South Africa and Canada.

BACKGROUND: Outcomes of cystic fibrosis (CF) differ between low-middle income and high-income countries, but comparative data are lacking. We compared South African (SA) and Canadian CF outcomes to explore what disparities existed prior to access of CFTR modulators in Canada. METHODS: A cross-sectional study of SA and Canadian CF registries data for period 1 January to 31 December 2018. CF registry data were harmonised between countries to compare lung function and nutrition outcomes. Poor nutrition was defined as BMIz-score < -1 in children and < 18.5 kg/m2 in adults. Standardised mean difference (SMD) >10 was considered significant. RESULTS: After excluding Canadians on CFTR modulators and lung transplant recipients, data on 4049 Canadian and 446 SA people was analysed. Compared to Canada, people in SA were younger (median age 15.8 years vs. 24.1 years: SMD 52) with fewer males (47.8% vs 54.2%; SMD 12.5) and White (70.9% vs. 93.3%; SMD 61.3). Class I-III CFTR mutation frequency was similar in SA (n = 384, 86.1%) and Canada (n = 3426, 84.9%). After adjusting for age, gender, diagnosis age, genotype, P.aeruginosa infection and pulmonary treatments, FEV1pp was 8.9% lower (95% CI 6.3% to 11.4%) and poor nutrition 1.7-fold more common (OR 1.70; 95% CI 1.19-2.41) in SA compared to Canada. CONCLUSION: Lung function and nutrition was significantly lower in SA compared to Canada. Global disparities in CF outcomes between high and low-middle income countries are likely to widen as CFTR modulators are rapidly scaled up in only high-income countries.

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 CD4+ 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 CD4+ T 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.

Cross-Cultural Adaptation and Validation of the EuroQoL Toddler and Infant Populations Instrument Into Afrikaans for South Africa.

OBJECTIVES: The EuroQol Group is exploring the development of a health-related quality of life measure for toddlers and infant populations (EuroQoL Toddler and Infant Populations [EQ-TIPS]) aged 0 to 36 months. This study aimed to report on the cross-cultural adaptation and validity of the South African Afrikaans EQ-TIPS. METHODS: The development of the Afrikaans EQ-TIPS followed the EuroQol guidelines including forward-backward translation and cognitive interviews with 10 caregivers of children aged 0 to 36 months. Thereafter, 162 caregivers of children 0 to 36 months of age were recruited from a pediatric hospital inpatient and outpatient facility. The EQ-TIPS; Ages and Stages Questionnaire; face, legs, activity, cry, and consolability; and dietary information were completed by all caregivers. The distribution of dimension scores, Spearman's correlation, analysis of variance, and regression analysis were used to explore the validity of the EQ-TIPS. RESULTS: The descriptive system of the EQ-TIPS was generally well understood and accepted by caregivers. The correlation coefficients for concurrent validity were significant and moderate for pain and weak and significant for the other dimensions hypothesized to correlate. Known groups were compared and inpatients had a significantly higher report of pain (χ2 = 7.47, P = .024) and more problems reported across all EQ-TIPS dimensions (recorded on the level sum score) (Kruskal Wallis H = 3.809, P = .05) and reported significantly worse health on the visual analog scale (Kruskal Wallis H = 15.387, P < .001). There were no age-related differences except for a lower report of problems with movement in the 0- to 12-month group (χ2 = 10.57, P = .032). CONCLUSION: The Afrikaans version of the EQ-TIPS is well understood and accepted by caregivers and valid for use with children aged 0 to 36 months in South Africa.

Psychometric performance of the Chichewa versions of the EQ-5D-Y-3L and EQ-5D-Y-5L among healthy and sick children and adolescents in Malawi.

OBJECTIVES: The EuroQol Group has developed an extended version of the EQ-5D-Y-3L with five response levels for each of its five dimensions (EQ-5D-Y-5L). The psychometric performance has been reported in several studies for the EQ-5D-Y-3L but not for the EQ-5D-Y-5L. This study aimed to psychometrically evaluate the EQ-5D-Y-3L and EQ-5D-Y-5L Chichewa (Malawi) versions. METHODS: The EQ-5D-Y-3L, EQ-5D-Y-5L and PedsQL™ 4.0 Chichewa versions were administered to children and adolescents aged 8-17 years in Blantyre, Malawi. Both of the EQ-5D-Y versions were evaluated for missing data, floor/ceiling effects, and validity (convergent, discriminant, known-group and empirical). RESULTS: A total of 289 participants (95 healthy, and 194 chronic and acute) self-completed the questionnaires. There was little problem with missing data (< 5%) except in children aged 8-12 years particularly for the EQ-5D-Y-5L. Ceiling effects was generally reduced in moving from the EQ-5D-Y-3L to the EQ-5D-Y-5L. For both EQ-5D-Y-3L and EQ-5D-Y-5L, convergent validity tested with PedsQL™ 4.0 was found to be satisfactory (correlation ≥ 0.4) at scale level but mixed at dimension /sub-scale level. There was evidence of discriminant validity (p > 0.05) with respect to gender and age, but not for school grade (p < 0.05). For empirical validity, the EQ-5D-Y-5L was 31-91% less efficient than the EQ-5D-Y-3L at detecting differences in health status using external measures. CONCLUSIONS: Both versions of the EQ-5D-Y-3L and EQ-5D-Y-5L had issues with missing data in younger children. Convergent validity, discriminant validity with respect to gender and age, and known-group validity of either measures were also met for use among children and adolescents in this population, although with some limitations (discriminant validity by grade and empirical validity). The EQ-5D-Y-3L seems particularly suited for use in younger children (8-12 years) and the EQ-5D-Y-5L in adolescents (13-17 years). However, further psychometric testing is required for test re-test reliability and responsiveness that could not be carried out in this study due to COVID-19 restrictions.

The validity and reliability of the interviewer-administered EQ-5D-Y-3L version in young children.

OBJECTIVES: The aim of this study was to determine the validity and reliability of the EQ-5D-Y-3L interviewer-administered (IA) version in South African children aged 5-7-years compared to 8-10-years. METHODS: Children aged 5-10-years (n = 388) were recruited from healthcare facilities, schools for learners with special educational needs and mainstream schools across four known condition groups: chronic respiratory illnesses, functional disabilities, orthopaedic conditions and the general population. All children completed the EQ-5D-Y-3L IA, Moods and Feelings Questionnaire (MFQ), Faces Pain Scale-Revised (FPS-R) and a functional independence measure (WeeFIM) was completed by the researcher. Cognitive debriefing was done after the EQ-5D-Y-3L IA to determine comprehensibility. Test-retest of the EQ-5D-Y-3L IA was done 48 h later and assessed using Cohen's kappa (k). RESULTS: Results from children aged 5-7-years (n = 177) and 8-10-years (n = 211) were included. There were significantly higher reports of problems in the Looking After Myself dimension in the 5-7-year-olds (55%) compared to the 8-10-year-olds (28%) (x2 = 31.021; p = 0.000). The younger children took significantly longer to complete the measure (Mann-Whitney U = 8389.5, p < 0.001). Known-group validity was found at dimension level with children receiving orthopaedic management reporting more problems on physical dimensions across both age-groups. Convergent validity between Looking After Myself and WeeFIM items of self-care showed moderate to high correlations for both age-groups with a significantly higher correlation in the 8-10-year-olds for dressing upper (z = 2.24; p = 0.013) and lower body (z = 2.78; p = 0.003) and self-care total (z = 2.01; p = 0.022). There were fair to moderate levels of test-retest reliability across age-groups. CONCLUSION: The EQ-5D-Y-3L IA showed acceptable convergent validity and test-retest reliability for measuring health in children aged 5-7-years. There was more report of problems with the dimension of Looking After Myself in the 5-7-year group due to younger children requiring help with dressing, including buttons and shoelaces due to their developmental age, rather than their physical capabilities. Therefore, it may be useful to include examples of age-appropriate dressing tasks. There was further some reported difficulty with thinking about the dimensions in the younger age-group, most notably for Usual Activities which includes a large number of examples. By decreasing the number of examples it may reduce the burden of recall for the younger age-group.

ß-adrenergic sweat test in children with inconclusive cystic fibrosis diagnosis: Do we need new reference ranges?

BACKGROUND: Investigating inconclusive cystic fibrosis (CF) diagnosis in children is difficult without advanced cystic fibrosis transmembrane conductance regulator (CFTR) function tests. This study investigated the utility of beta (ß)-adrenergic sweat test to exclude CF in participants with inconclusive diagnosis (CF suspects) in South Africa. METHODS: ß-adrenergic sweat test and sweat chloride tests (SCT) were performed simultaneously in CF suspects and adult controls (healthy, CFTR heterozygotes and CF). Cholinergic and ß-adrenergic induced sweat rate was measured by evaporimetry (transepithelial water loss [TEWL]: g H2 O/m2 /h) following intradermal injections. Next-generation sequencing of CFTR was performed in CF suspects. CF diagnosis was defined by genotype. RESULTS: Thirty-seven controls (10 healthy, 14 CF, 13 CFTR heterozygotes) and 32 CF suspects (26 children; 6 adults) were enrolled. Six were excluded from formal analyses due to ß-adrenergic sweat test failure. In adults, evaporimetry was superior to SCT for diagnosis of CF with ß-adrenergic:cholinergic ratio TEWL ≤ 0.05 achieving 100% sensitivity and specificity. Twenty-two CF suspect children (age range: 3.4-15.6 years) completed ß-adrenergic sweat testing of which none had CF confirmed by genotyping: ß-adrenergic:cholinergic ratio > 0.05 successfully excluded CF in all but one child who was CFTR heterozygous. Median peak ß-adrenergic TEWL and ß-adrenergic:cholinergic ratio in CFTR negative and CFTR heterozygous children was significantly lower than adult controls. CONCLUSION: ß-adrenergic sweat test is more accurate than SCT for excluding CF in children with inconclusive diagnosis. Established reference ranges for ß-adrenergic sweat test may not be suitable for children due to lower ß-adrenergic sweat secretion compared to adults.

The reliability and validity of the isixhosa version of the euroqol toddler and infant populations (EQ-TIPS) health related quality of life instrument.

Background: Considering the high burden of disease in young children measurement of Health-Related Quality of Life is needed to evaluate the burden of morbidity. This study aims to report on the validity and reliability of the isiXhosa EuroQol Toddler and Infant Populations (EQ-TIPS) measure for South Africa. Methods: A sample of 181 caregivers of children 0-36 months were recruited from a hospital in-patient (inpt) and outpatient (outpt) facility and crèches. The EQ-TIPS, Ages and Stages Questionnaire (ASQ), Faces, Leg, Activity, Cry, Consolability (FLACC) and dietary information were administered at baseline. EQ-TIPS was administered one week later in crèche children for test-retest reliability. Results: Known groups showed significant differences for pain (X2=37.21, p<0.001), and EQ-TIPS level sum score (KWH=25.9, p<0.001) between health groups. The Visual Analogue Scale was unable to discriminate general health between groups (KW-H=3.92, p=0.141). Concurrent validity was weak to moderate and significant for all dimensions hypothesised to correlate. There was significant fair to moderate test-retest reliability for EQ-TIPS dimensions of movement, play, pain and eating. Conclusion: The isiXhosa EQ-TIPS is valid and reliable for very young children in South Africa and we suggest that it be included in the assessment of children with health conditions within this context.

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.

Comparing Measurement Properties of the English EQ-5D-Y 3-Level Version With the 5-Level Version in South Africa.

OBJECTIVES: This study aimed to compare the performance of the EQ-5D-Y 3-level version (Y-3L) and the expanded 5-level version, the EQ-5D-Y 5-level version (Y-5L). METHODS: Children or adolescents with an acute or chronic health condition and from the general population completed the Y-5L and Y-3L self-report questionnaires. The performance of the Y-5L and Y-3L was determined by comparing feasibility, redistribution of dimension responses, discriminatory power, validity, and test-retest reliability. RESULTS: A total of 550 children/adolescents completed baseline measures and 173 completed repeat measures. The ceiling effect decreased by 15% from the Y-3L to Y-5L. Informativity of dimensions improved by 0.094 on the Y-5L. There was a range of 4% to 9% inconsistent responses moving from the Y-3L to Y-5L. Convergent validity of the visual analog scale and Y-3L and Y-5L dimensions was similar and weak to moderate (rs range 0.18-0.38) but similar and strong on paired Y-3L and Y-5L dimensions: Kendall tau B (range 0.69-0.80) and gamma (range 0.92-0.98). The Y-5L and Y-3L showed moderate to substantial agreement for test-retest reliability across dimensions and visual analog scale scores in stable chronic health conditions and fair agreement for the general population. CONCLUSION: The Y-5L is a valid, reliable extension of the Y-3L for children or adolescents across health conditions and healthy children/adolescents. The expanded levels reduced the ceiling effect. The relative informativity of report across dimensions increased on the Y-5L compared with the Y-3L with retention of the evenness of reporting. The convergent validity and test-retest reliability of the Y-5L was comparable with the Y-3L.

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.

Why Do Adults Value EQ-5D-Y-3L Health States Differently for Themselves Than for Children and Adolescents: A Think-Aloud Study.

OBJECTIVES: Following protocol, adults value EQ-5D-Y-3L health states from the perspective of a 10-year-old child. It remains unclear why adults value health states differently for themselves than for a 10-year-old child and whether the latter perspective is representative of adults' preferences for the 8 to 15 years age range of the EQ-5D-Y-3L. This study examines the reasons underlying (potential) differences in adults' health-state preferences for themselves, a 10-year-old child, and 15-year-old adolescent. METHODS: We conducted semistructured interviews using a think-aloud protocol with 25 participants who performed valuation tasks in July 2020 to August 2020. Using the Framework Method, we developed 28 categories grouped under 5 themes that illustrated the differences emerging from the interviews. RESULTS: Participants (A) deemed it more straining to perform valuation tasks for a 10-year-old child and 15-year-old adolescent than for themselves, (B) had a stable self-image, but varied in whom they imagined as 10-year-old child and 15-year-old adolescent, (C) focused on different dimensions and levels for a 15-year-old adolescent than for a 10-year-old child and themselves, (D) had various thoughts about nonhealth-related factors that influenced their preferences, and (E) gave up relatively few life-years for a 10-year-old child and 15-year-old adolescent, also to avoid others bearing a grudge against them. CONCLUSIONS: Our results indicate that differences in adults' health-state preferences for themselves and a 10-year-old child largely result from differences in thoughts about nonhealth-related factors. They further indicate that health-state preferences for a 10-year-old child may not be representative of such preferences for the full EQ-5D-Y-3L age range.

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.

Trends in cystic fibrosis survival over 40 years in South Africa: An observational cohort study.

INTRODUCTION: Temporal trends in cystic fibrosis (CF) survival from low-middle-income settings is poorly reported. We describe changes in CF survival after diagnosis over 40 years from a South African (SA) CF center. METHODS: An observational cohort study of people diagnosed with CF from 1974 to 2019. Changes in age-specific mortality rates from 2000 (vs. before 2000) were estimated using multivariable Poisson regression. Data were stratified by current age < or ≥10 years and models controlled for diagnosis age, sex, ethnicity, genotype, and Pseudomonas aeruginosa (PA) infection. A second analysis explored the association of mortality with weight and forced expiratory volume in 1 s reported as z-scores (FEV1z-scores) at age 5-8 years. RESULTS: A total of 288 people (52% male; 57% Caucasian; 44% p.Phe508del homozygous) were included (median diagnosis age 0.5 years: Q1, Q3: 0.2, 2.5); 100 (35%) died and 30 (10%) lost to follow-up. Among age >10 years, age-specific mortality from 2000 was significantly lower (adjusted hazard ratio [aHR]: 0.14; 95% confidence interval [CI]: 0.06, 0.29; p < 0.001), but not among age <10 years (aHR: 0.67; 95% CI: 0.28, 1.64; p = 0.383). In children <10 years, Caucasian ethnicity was associated with lower mortality (aHR 0.17; 95% CI: 0.05, 0.63), and longer times since first PA infection with higher mortality (aHR: 1.31; 95% CI: 1.01, 1.68). Mortality was sevenfold higher if FEV1z was <-2.0 at age 5-8 years (aHR: 7.64; 95% CI: 2.58, 22.59). CONCLUSION: Overall, CF survival has significantly improved in SA from 2000 in people older than 10 years. However, increased risk of mortality persists in young non-Caucasian children, and with FEV1z <-2.0 at age 5-8 years.

The performance of the EQ-5D-Y-5L compared to the EQ-5D-Y-3L in children and adolescents with cerebral palsy (CP).

Objectives: The aim of this study is to compare the performance and validity of the EQ-5D-Y-3L (Y-3L) and EQ-5D-Y-5L (Y-5L) in South African children and adolescents with cerebral palsy (CP). Methods: Children/adolescents with CP and those from the general population completed the Y-5L, Y-3L, and PedsQL. Physiotherapists at the school classified participants' functional ability on the Gross Motor Functioning Classification System (GMFCS). Results: Fifty-one children/adolescents completed the measures. The ceiling effect had a 44% relative reduction for Mobility and floor effects decreased across all dimensions except for Looking After Myself when moving from the Y-3L to Y-5L. Informativity of dimensions improved on average by 0.27 on the Y-5L with similar evenness. There was a range of 6-16% inconsistent responses when moving from the Y-3L to the Y-5L. Convergent validity was strong on paired Y-3L and Y-5L dimensions: Kendall's Tau B (range 0.53 - 0.85) and Gamma (range 0.79 - 0.99). There was significant moderate association between Y-3L and Y-5L with similar items on the PedsQL. The physical dimensions of Mobility, Looking After Myself and Usual Activities were significantly associated with GMFCS with those having less independent mobility reporting more severe problems on dimension scores. Conclusion: The Y-5L showed a notable reduction in ceiling and floor effects, improved discriminatory power, higher criterion validity with the GMFCS and similar concurrent validity with the PedsQL as the Y-3L. It is recommended that the Y-5L is further tested for reliability and responsiveness in this population group so that its utility for detecting change in clinical trials or as a routine outcome measure can be determined.

Performance of the Toddler and Infant (TANDI) Health-Related Quality of Life Instrument in 3-4-Year-Old Children.

The Toddler and Infant (TANDI) dimensions of Health-Related Quality of Life assess 'age appropriate' behaviour and measurement could be extended to older children. A sample of 203 children 3-4 years of age was recruited, and their caregivers completed the TANDI, Pediatric Quality of Life Inventory (PedsQL) and EQ-5D-Y Proxy. Spearman and Pearson's correlation coefficients, and Kruskal-Wallis H-test were used to explore the feasibility, known-group validity, discriminate validity and concurrent validity of the TANDI. Children with a health condition (n = 142) had a lower ceiling effect (p = 0.010) and more unique health profiles (p < 0.001) than the healthy group (n = 61). The TANDI discriminated between those with and without a health condition. In children with a health condition, the TANDI discriminated between clinician rated severity of the health condition. The TANDI had moderate to strong correlations with similar PedsQL and EQ-5D-Y items and scores. The TANDI is valid for children aged 3-4 years and is recommended for children with a health condition, whereas the PedsQL may be better for healthy children. The TANDI is recommended for studies with young children whereas the EQ-5D-Y Proxy is recommended for a sample including older children or for longitudinal studies with preschoolers. Further work on the TANDI is recommended to establish test-retest reliability and responsiveness.

Cystic fibrosis in South Africa: spectrum of disease and determinants of outcome.

INTRODUCTION: Little is known about cystic fibrosis (CF) in low- to middle-income settings. This study aimed to describe the spectrum and outcomes of CF in South Africa (SA) from the recently established SA CF registry (SACFR). METHODS: Demographic, diagnosis and clinical data were extracted from the SACFR. Cross-sectional univariable and multivariable regression analysis of best forced expiratory volume in 1 s (FEV1; age≥6 years) and nutrition (all ages) in 2018 was conducted to investigate factors associated with severe lung disease (SLD; FEV1 ≤3.0 z-score) and undernutrition. RESULTS: By December 2018, ancestry of 447 individuals included in the SACFR was Caucasian (315; 70%), mixed (87; 19%) and black African (41; 9%). Median diagnosis age was 7.6 months (IQR 2.7-37.1). Genotype was p.Phe508del homozygous (220; 49%); p.Phe508del heterozygous (144; 32%) and neither p.Phe508del or unknown Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) variant in 83 (19%); the second most frequent CFTR variant was 3120+1G>A, common in black Africans. Median age of patients in 2018 was 14.7 years (IQR 7.4-24.4). SLD was independently associated with chronic methicillin-resistant Staphylococcus aureus (MRSA) (adjusted odds ratio( aOR) 16.75; 95% CI 1.74-161.50), undernutrition (aOR 5.20; 95% CI 2.23-12.13) and age (aOR 2.23 per 10 years; 95% CI 1.50-3.31). Undernutrition was associated in univariable analysis with low weight at diagnosis, non-Caucasian ancestry, chronic P. aeruginosa infection and lower socioeconomic status. CONCLUSION: Interventions targeting MRSA infection and nutrition are needed to improve CF outcomes in SA. Most people with CF in SA are eligible for highly effective CFTR modulator therapy.

Validity and reliability testing of the Toddler and Infant (TANDI) Health Related Quality of Life instrument for very young children.

BACKGROUND: Despite the high burden of disease in younger children there are few tools specifically designed to estimate Health Related Quality of Life (HRQoL) in children younger than 3 years of age. A previous paper described the process of identifying a pool of items which might be suitable for measuring HRQoL of children aged 0-3 years. The current paper describes how the items were pruned and the final draft of the measure, Toddler and Infant (TANDI) Health Related Quality of Life, was tested for validity and reliability. METHODS: A sample of 187 caregivers of children 1-36 months of age were recruited which included children who were either acutely ill (AI), chronically ill (CI) or from the general school going population (GP). The TANDI, an experimental version of the EQ-5D-Y proxy, included six dimensions with three levels of report and general health measured on a Visual Analogue Scale (VAS) from 0 to 100. The content validity had been established during the development of the instrument. The TANDI, Ages and Stages Questionnaire (ASQ), Faces, Leg, Activity, Cry, Consolabilty (FLACC) or Neonatal Infant Pain Scale (NIPS) and a self-designed dietary information questionnaire were administered at baseline. The TANDI was administered 1 week later in GP children to establish test-retest reliability. The distribution of dimension scores, Cronbach's alpha, rotated varimax factor analysis, Spearman's Rho Correlation, the intraclass correlation coefficient, Pearson's correlation, analysis of variance and regression analysis were used to explore the reliability, and validity of the TANDI. RESULTS: Concurrent validity of the different dimensions was tested between the TANDI and other instruments. The Spearman's Rho coefficients were significant and moderate to strong for dimensions of activity and participation and significant and weak for items of body functions. Known groups were compared and children with acute illness had the lowest ranked VAS (median 60, range 0-100), indicating worse HRQoL. The six dimensions of the TANDI were tested for internal consistency and reliability and the Cronbach's α as 0.83. Test-retest results showed no variance for dimension scores of movement and play, and high agreement for pain (83%), relationships (87%), communication (83%) and eating (74%). The scores were highly correlated for the VAS (ICC = 0.76; p < 0.001). CONCLUSION: The TANDI was found to be valid and reliable for use with children aged 1-36 months in South Africa. It is recommended that the TANDI be included in future research to further investigate HRQoL and the impact of interventions in this vulnerable age group. It is further recommended that future testing be done to assess the feasibility, clinical utility, and cross-cultural validity of the measure and to include international input in further development.

How does the EQ-5D-Y Proxy version 1 perform in 3, 4 and 5-year-old children?

BACKGROUND: The EQ-5D-Y Proxy is currently recommended for Health Related Quality of Life (HRQoL) measurement in children aged 4-8 years of age. However, it has only been validated in children over six years of age. The aim of this study was to investigate the performance of the EQ-5D-Y proxy version 1 in children between the ages of 3-6 years. METHODS: A sample of 328 children between 3 and 6 years of age were recruited which included children who were either acutely-ill (AI), chronically-ill (CI) or from the general school going population (GP). The EQ-5D-Y Proxy Version 1 and the PedsQL questionnaires were administered at baseline. The EQ-5D-Y Proxy was administered telephonically 24 h later to children with chronic illnesses to establish test-retest reliability. The distribution of dimensions and summary scores, Cohen's kappa, the intraclass correlation coefficient, Pearson's correlation and Analysis of variance were used to explore the reliability, and validity of the EQ-5D-Y for each age group. A single index score was estimated using Latent scores and Adult EQ-5D-3 L values (Dolan). RESULTS: The groups included 3-year olds (n = 105), 4-year olds (n = 98) and 5-years olds (n = 118). The dimension Looking after Myself had the greatest variability between age groups and had the highest rate of problems reported. Worried, Sad or Unhappy and Pain or Discomfort were not stable across time in test-retest analysis. The Visual Analogue Scale (VAS), and single index scores estimated using the latent values and Dolan tariff had good test retest (except for the latent value scores in a small number of 4-year olds). EQ-5D-Y scores for all ages had small to moderate correlations with PedsQL total score. The EQ-5D-Y discriminated well between children with a health condition and the general population for all age groups. Caregivers reported difficulty completing the Looking after Myself dimension due to age-related difficulties with washing and dressing. CONCLUSION: The dimension of Looking after Myself is problematic for these young children but most notably so in the 3 year old group. If one considers the summary scores of the EQ-5D-Y Proxy version 1 it appears to work well. Known group validity was demonstrated. Concurrent validity was demonstrated on a composite level but not for individual dimensions of Usual Activities or Worried, Sad or Unhappy.. The observable dimensions demonstrated stability over time, with the inferred dimensions (Pain or Discomfort and Worried, Sad or Unhappy) less so, which is to be expected. Further work is needed in exploring either the adaptation of the dimensions in the younger age groups.