Cindy Wakefield

Development of a health-related quality of life measure for boys with haemophilia: the Canadian Haemophilia Outcomes--Kids Life Assessment Tool (CHO-KLAT).

Summary.  Several measures of quality of life (QoL) are available for children with haemophilia. However, most are not disease‐specific and few focus on childrens perspectives. The purpose of this study was to develop a psychometrically sound measure of QoL that included the perspectives of boys with haemophilia. A list of potential items was developed from the literature, other measures, and input from five discussion sessions with adults with haemophilia, children with haemophilia and their parents and haemophilia nurses. The list was augmented with items generated by three focus groups with children and three focus groups with parents. These groups also prioritized items and recommended a domain structure. Supplemental information was gathered by surveying haematologists. Data from all sources were analysed to reduce the number of items using a two‐step approach, based on rules that weighted the childrens priorities most heavily. The remaining items were compiled into a questionnaire that was pilot tested with 10 children and their parents. The total item pool contained 228 potential items. Of these, 33 were removed based on three focus groups and survey responses, 72 were removed after the completion of all focus groups and 46 were removed due to redundancy. This resulted in a 77‐item version of the CHO‐KLAT. Pilot testing identified the need to subdivide two items, resulting in a 79‐item CHO‐KLAT. The CHO‐KLAT is a promising disease‐specific measure of QoL that reflects childrens unique perspectives. This child‐centric focus distinguishes the CHO‐KLAT from alternative measures of QoL. Further research will assess the measurement properties of the CHO‐KLAT.

Fcγ receptor IIa and IIIa polymorphisms in childhood immune thrombocytopenic purpura

Summary. Fcγ receptor‐mediated destruction of autoantibody‐sensitized platelets is central to the immune pathophysiology of childhood immune thrombocytopenic purpura (ITP). Allelic variants exist among the random population for some Fcγ receptors. The variants represent single nucleotide polymorphisms, leading to functional differences in the ability to bind immunoglobulin (Ig)G or IgG subclasses. The genotypic frequencies for two Fcγ receptor single nucleotide polymorphisms, FcγRIIa‐131 arginine (R) versus histidine (H) and FcγRIIIa‐158 valine (V) versus phenylalanine (F) were examined in 98 children diagnosed with childhood ITP. The genotype frequencies were compared with those of 130 healthy control subjects. Chi‐square analysis was used to determine whether the allelic frequencies of the high‐affinity receptor variants were associated with childhood ITP. Both the FcγRIIa‐131H and the FcγRIIIa‐158V were significantly over‐represented in children with ITP versus the control subjects (P‐values 0·03). The same statistical difference was noted with the combined FcγRIIa‐131H and FcγRIIIa‐158V allelic gene frequencies. There was no statistical difference between children who later developed chronic ITP compared with children with acute ITP, suggesting that additional factors are responsible for the development of the chronic form of the disease. These observations underscore the importance of Fcγ receptor‐mediated cell clearance in childhood ITP.

How well does the Canadian haemophilia Outcomes-Kids' Life Assessment Tool (CHO-KLAT) measure the quality of life of boys with haemophilia?

It is important to measure the quality of life (QoL) of boys with haemophilia, because the diagnosis has a significant impact on their lives and this impact fluctuates over time. A disease‐specific measure of QoL is required because the aspects of life that are affected by haemophilia may differ from those assessed by generic QoL measures. This paper describes the final phase of development of a disease‐specific measure of QoL for boys with haemophilia: the Canadian Haemophilia Outcomes‐Kids Life Assessment Tool (CHO‐KLAT).

Assessment of thrombocytopenic disorders using the Platelet Function Analyzer (PFA-100).

Summary.  The Platelet Function Analyzer (PFA‐100®) was used to measure platelet function in paediatric patients with destructive versus underproduction thrombocytopenia. Closure time (CT) and total volume (TV) measurements with standard 150 μm apertures discriminated between patients with similar platelet counts from 30 to 150 × 109/l. However, at platelet counts < 30 × 109/l, a 100‐μm aperture (experimental) gave the best assessment of platelet function. TV results could be analysed even when CTs were indeterminate. Further investigations are warranted to more fully understand the relationships among platelet function as measured by the PFA‐100® in standard/experimental modes, bleeding and transfusion outcome in thrombocytopenia.

Comparing two measures of quality of life for children with haemophilia: the CHO-KLAT and the Haemo-QoL

Summary.  Disease‐specific measures of quality of life (QoL) for children with haemophilia are now available for use in clinical studies [Haemophilia, 10, 2004, 9–16]. One of these measures, the Canadian Haemophilia Outcomes – Kids’ Life Assessment Tool (CHO‐KLAT), was developed in Canada with emphasis on the perspectives of children [Pediatr Blood Cancer, 47, 2006, 305–11; Haemophilia, 10, 2004, 34–43]. Another, the Haemo‐QoL, was developed in Europe, with emphasis on the perspectives of clinicians [Haemophilia, 8, 2002, 47–54; Haemophilia, 10, 2004, 17–25]. While these two measures are unique and independent, researchers from both studies were collaboratively linked throughout development and testing. This study presents the results of a joint assessment of the two measures with respect to their strengths, limitations and unique contributions.

Quality of life in childhood immune thrombocytopenia: international validation of the kids' ITP tools.

The Kids ITP Tools (KIT) is a disease‐specific measure of health‐related quality of life for children with immune thrombocytopenia (ITP). To facilitate use in international trials it has been cross‐culturally adapted for France, Germany, the United Kingdom and Uruguay. This study assessed the validity and reliability of the translated KIT in comparison to generic quality of life measures.

International cross‐cultural validation study of the Canadian Haemophilia Outcomes: Kids’ Life Assessment Tool

Health‐related quality of life (HRQoL) assessment is recognized as an important outcome in the evaluation of different therapeutic regimens for persons with haemophilia. The Canadian Haemophilia Outcomes–Kids’ Life Assessment Tool (CHO‐KLAT) is a disease‐specific measure of HRQoL for 4 to 18‐year‐old boys with haemophilia. The purpose of this study was to extend this disease‐specific, child‐centric, outcome measure for use in international clinical trials.

Updating the Canadian Hemophilia Outcomes–Kids Life Assessment Tool (CHO-KLAT Version2.0)

OBJECTIVES Hemophilia is an X-chromosome-linked disorder associated with recurrent bleeding into muscles and joints, leading to pain and limitations in physical function that may diminish quality of life. The Canadian Hemophilia Outcomes-Kids Life Assessment Tool (CHO-KLAT) is a disease-specific measure of quality of life that was recently revised to facilitate cross-cultural adaptation. This study assessed the validity and reliability of version 2.0 of the CHO-KLAT (CHO-KLAT2.0). METHODS Content validity was assessed via detailed cognitive debriefing to confirm that Canadian boys understood the CHO-KLAT2.0. The measurement properties of the CHO-KLAT2.0 were assessed in comparison to those of the PedsQL, the Haemo-QoL, and two global ratings. Most children completed the CHO-KLAT2.0 a second time to assess test-retest reliability. RESULTS Cognitive debriefing was completed with 12 boys (age 8.6-17.8 years) and 9 of their parents and resulted in no substantive changes. Sixty boys (mean age 11.8 years) participated in the validation phase, which showed a mean CHO-KLAT2.0 score of 75.4±12.0, strong correlations with the PedsQL (r = 0.62, P<0.001) and Haemo-QoL (r = 0.64, P<0.001), and moderate correlations with global ratings of hemophilia bother (ρ =-0.39, P = 0.002) and health (ρ =-0.47, P = 0.0002). Test-retest concordance was better among parents (0.79) than among boys (0.63). CONCLUSIONS This study establishes the measurement properties of the CHO-KLAT2.0. The summary scores are very similar to those from the original development study, and thus, these have not been affected by the revisions. These results provide reference standards for comparing data from other countries to the Canadian experience and to estimate sample sizes for future clinical trials.

Returning the focus to the quality of life of boys with Haemophilia

To the Editor: We appreciate the opportunity to respond to the Letter to the Editor that addressed our paper entitled ‘‘Does the Canadian Haemophilia Outcomes—Kids’ Life Assessment Tool (CHO-KLAT) Measure the Quality of Life of Boys with Haemophilia?’’ The focus of the preceding Letter is on the ‘‘dismissal of the HUI’’ from our study. Our study was conducted by a group of clinician specialists and measurement experts from several Canadian institutions. We reviewed several generic quality of life measures for children and selected measures for this study based on our extensive experience with a wide variety of measures, information from pertinent web sites (e.g., www.pedsql.org and www.healthutilities.com) and the peer-reviewed literature. Based on the evidence, the Pediatric Quality of Life Inventory (PedsQL) was identified as the best generic measure for our purpose and population. The PedsQL is extremely well validated, permits comparison to other patient populations nationally and internationally, is exclusively focused on children, is accessible at reasonable cost, and the support from the PedsQL developers is excellent. We also included a newly developed disease-specific measure, the HaemoQoL (www. haemoqol.de). Barr et al. do not mention either the PedsQL or the HaemoQoL in their critique. We believe the relationships between the CHO-KLAT, the PedsQL and HaemoQoL reported in our paper support the validity of the CHO-KLAT. It is certainly time to return to the focus to the quality of life of boys with haemophilia. There is no gold standard for assessing children’s quality of life, but the CHO-KLAT is a valid method for assessing this construct for boys with haemophilia, and should be applied in studies that assess new interventions intended to improve the health of these boys.