Episodic replacement of clotting factor concentrates does not prevent bleeding or musculoskeletal damage - the MUSFIH study.

PATIENTS AND METHODS: A longitudinal study was carried out in 255 children from 10 centres in nine developing countries over 5 years to assess the musculoskeletal outcome of children on episodic factor replacement. Outcome was documented by assessment of the annual joint bleeding rate (AJBR), WFH clinical and Pettersson radiological joint scores as well as the FISH score for activities. Of the 203 patients for whom data was available at the end of 5 years, 164 who had received only episodic treatment are included in this report. RESULTS: The median age at the beginning of the study was 10 years (IQR 7-12). The median clotting factor concentrate (CFC) usage was 662 IU kg-1 year-1 (IQ range: 280-1437). The median AJBR was 10 (IQ range: 5-17). The median AJBR was higher in the older children with the median being 5 for the 5 year old child, while it was 9 for the 10 year old and 11 for children older than 15. Given the episodic nature of the replacement therapy, those with a higher AJBR used significantly greater annual CFC doses (P < 0.001); The median change in WFH clinical score and Pettersson radiological score over the 5 years was 0.4/year for each, while the FISH deteriorated at a rate of 0.2/year with poor correlation of these changes with CFC dose. WFH and FISH scores were significantly worse in those with an AJBR of >3 per year (P = 0.001). The change in the Pettersson score was significantly more in those with an AJBR of >5 per year (P = 0.020). Significant changes in FISH scores were only noted after 10 years of age. CONCLUSION: Episodic CFC replacement over a large range of doses does not alter the natural course of bleeding in haemophilia or the musculoskeletal deterioration and should not be recommended as a long term option for treatment. Prophylaxis is the only way to preserve musculoskeletal function in haemophilia.

Comparing the burden of illness of haemophilia between resource-constrained and unconstrained countries: the São Paulo-Toronto Hemophilia Study.

INTRODUCTION: Although the regular replacement of clotting factor concentrates (prophylaxis) has been well established as the standard of care for severe haemophilia, the high cost of factor concentrates has limited access to prophylaxis in countries with under-developed or developing economies. AIMS: We studied the health gap that could be addressed by providing unlimited access to clotting factor concentrates with implementation of long-term prophylaxis initiated from an early age in life. METHODS: We performed a cross-sectional study of a random, representative sample of boys with moderate and severe haemophilia at three haemophilia treatment centres in Sao Paulo, Brazil, and one centre in Toronto, Canada. RESULTS: Canadian subjects were more often treated with prophylaxis, and began treatment at an earlier age. Fewer Canadian subjects had bleeds within the preceding 6 months (19 vs. 34, P = 0.003). Canadian subjects had lower (better) Pettersson radiographic scores (1.5 vs. 6.0, P = 0.0016), lower (better) Hemophilia Joint Health Scores (5.5 vs. 10.5, P = 0.0038), higher (better) Activity Scale for Kids scores (96.6 vs. 92.0, P = 0.033), more time spent in vigorous activity, and higher (better) social participation scores. CONCLUSIONS: Our findings suggest that increasing access to clotting factor concentrates for young boys with severe haemophilia is a global imperative.

Joint lavage followed by viscosupplementation and triamcinolone in patients with severe haemophilic arthropathy: objective functional results.

INTRODUCTION: Viscosupplementation can improve function in haemophilia patients. Viscosupplementation results can be improved by prior joint lavage and triamcinolone administration. AIM: To objectively assess whether viscosupplementation and associated triamcinolone use in patients with severe haemophilic arthropathy following joint lavage improves force and balance and reduces bleeding events. METHODS: Fourteen patients with haemophilic knee arthritis with and without the involvement of other joints underwent joint lavage and subsequent injections of Hylan G-F20 and triamcinolone into all affected joints. Patients were evaluated with NeuroCom® force and balance platforms using the step-up-and-over task (STP), sit-to-stand test (STS), one-leg stance (UNI) and weight-bearing squat (WBS) at baseline and at 1, 3, 6 and 12 months after the procedure. Bleeding events in the year prior to and the year after the procedure were analysed. RESULTS: Sixteen knees, 15 ankles, eight elbows and one shoulder were treated. The STP results indicated improvements in the lift-up indices (right leg) at all time points evaluated (P = 0.03). The STS results revealed coupled improvement in weight transfer and the rising index for up to a year (P = 0.02). Balance (UNI) with eyes open or closed improved in all evaluations. The WBS results revealed improvements at all degrees of flexion (0, P = 0.003; 30°, P = 0.001; 60°, P < 0.001 and 90°, P < 0.001). The numbers of total and traumatic bleeding events were reduced (P = 0.04). CONCLUSION: Joint lavage followed by injections of triamcinolone and Hylan G-F20 improved balance, function and bleeding events in severe haemophilic arthropathy patients.

Validity of the Portuguese CHO-KLAT in Brazil.

INTRODUCTION: It is essential to assess the health-related quality of life outcomes of boys with haemophilia in Brazil. The Canadian Haemophilia Outcomes-Kids Life Assessment Tool (CHO-KLAT) was recently adapted for this population. AIM: To test the construct validity of the Portuguese version of the CHO-KLAT. METHODS: We recruited 50 boys, with moderate [factor VIII (FVIII) level 1-5%] or severe (FVIII level <1%) haemophilia, to participate in a descriptive study to establish a baseline understanding of the current status of boys with haemophilia in Brazil. All boys were required to complete the Brazilian CHO-KLAT and Brazilian Pediatric Quality of Life Inventory (PedsQL) by self-report. We examined the correlation between the CHO-KLAT and PedsQL scores to establish the construct validity of the Brazilian version of the CHO-KLAT. RESULTS: We obtained CHO-KLAT and PedsQL data from 35 boys with severe haemophilia and 15 with moderate haemophilia. They ranged in age from 7.3 to 18.0 years, with a mean of 13.0 years. They reported a mean CHO-KLAT score of 72.3 (range = 44.1-93.9). The mean PedsQL score was 79.9 (range = 45.7-96.7), with physical health (mean of 83.9) being better than psychosocial health (77.8). The Pearson's correlation between CHO-KLAT and PedsQL was 0.47 respectively (P < 0.001). The CHO-KLAT had a moderate and inverse relationship with the degree to which they were bothered by their haemophilia (ρ = -0.53), while the PedsQL had a weaker relationship (ρ = -0.27). CONCLUSION: The results confirm the validity of the Portuguese version of the CHO-KLAT. This measure is now available for clinical trials in boys with haemophilia in Brazil.

Process and experience of cross-cultural adaptation of a quality of life measure (CHO-KLAT) for boys with haemophilia in Brazil.

Health-related quality of life (HRQoL) is an important outcome from the perspective of boys with haemophilia and their parents. Few studies have captured the HRQoL of boys with haemophilia in developing countries. This article reports on the cross-cultural adaptation of the Canadian Haemophilia Outcomes - Kids Life Assessment Tool (CHO-KLAT) for use in São Paulo, Brazil. The CHO-KLAT(2.0) was translated into Portuguese, and then translated back into English. The original English and back-translation versions were compared by a group of three clinicians, whose first language was Portuguese. The resulting Portuguese version was assessed through a series of cognitive debriefing interviews with children and their parents. This process identified concepts that were not clear and revised items to ensure appropriate understanding through an iterative process. The initial back-translation was not discrepant from the original English version. We made changes to 66% of the CHO-KLAT(2.0) items based on clinical expert review and 26% of the items based on cognitive debriefings. In addition, two new items were added to the final Portuguese version to reflect the local cultural context. The final result had good face validity. This process was found to be extremely valuable in ensuring the items were accurately interpreted by the boys/parents in São Paulo Brazil. The results suggest that professional translators, clinical experts and cognitive debriefing are all required to achieve a culturally appropriate instrument. The Portuguese CHO-KLAT(2.0) is well understood by Sao Paulo boys/parents. The next step will be to test its validity and reliability locally.

Importance of literacy for self-reported health-related quality of life: a study of boys with haemophilia in Brazil.

Psychosocial outcomes are important in the perspective of boys with haemophilia. However, health-related quality of life (HRQoL) is based on self-report, and assumes adequate literacy. Yet, literacy is rarely assessed prior to data collection. This study sought to identify criteria that might indicate the level of literacy of children being recruited for clinical trials and to develop a simple method to prescreen those whose literacy was uncertain. We developed a brief screening tool in the form of two stories, at a grade 3 reading level, followed by comprehension questions. We applied the screening test to a sample of haemophilic boys between the ages of 7 and 13 years to assess their literacy. The data were analysed to determine the best criteria to use in identifying the ability to independently self-report for HRQoL studies. Twenty-four Brazilian boys (7.9-12.8) completed the testing. The results showed that 17 (70.8%) were literate (were able to both read and comprehend), and could complete a questionnaire without assistance. All boys over 11.0 years of age were sufficiently literate. Grade level was not found to be a helpful criterion. We recommend that all children under the age of 11.0 years be prescreened before providing self-reported HRQoL data. Those with limited literacy should be provided assistance to ensure comprehension of the questions. This is important to ensure high-quality data on HRQoL for future clinical trials.