Paula Ribeiro Villaça

A cost evaluation of treatment alternatives for mild‐to‐moderate bleeding episodes in patients with haemophilia and inhibitors in Brazil

Summary.  The first‐line treatment for mild‐to‐moderate bleeding episodes in patients with haemophilia and inhibitors in Brazil is currently activated prothrombin complex concentrate (aPCC), with recombinant activated factor VII (rFVIIa) used as second‐line therapy or as a last resort. The aim of this study was to determine the cost and effectiveness of these treatments from the perspective of the Brazilian National Health Service. A decision analysis model was constructed to assess total direct medical costs (including drug costs, costs of outpatient or inpatient care, ambulance transportation and cost of concomitant medications) of first‐line treatment with aPCC or rFVIIa. Clinical outcome and resource utilization data were obtained both retrospectively and prospectively and validated by the consensus of an expert panel of Brazilian haematologists. A total of 103 bleeds in 25 patients were included in the analysis. rFVIIa resolved bleeds more quickly (4.4 h) than aPCC (62.6 h) and was more effective (100% vs. 56.7% respectively). Mean total direct medical costs (from initiation to cessation of bleed) were estimated to be US

Ethnic Differences in Cerebral Venous Thrombosis

13 500 (aPCC) and US

Postural adjustment after an unexpected perturbation in children with haemophilia

7590 (rFVIIa). Extensive sensitivity analyses confirmed the cost‐effectiveness of rFVIIa. Compared with aPCC, rFVIIa was more effective and less expensive when used as first‐line treatment for mild‐to‐moderate bleeding episodes in patients with haemophilia and inhibitors in Brazil. rFVIIa should be considered a first‐line treatment for the management of these patients.

The effects of repetitive haemarthrosis on postural balance in children with haemophilia.

Background: Cerebral venous thromboses (CVT) with distinct clinical presentations have been shown worldwide. However, there is little information regarding race-ethnic differences in this disease. Methods: We prospectively studied 50 CVT patients from Brazil, comparing clinical and laboratory data among white (W) and African-Brazilian (AB) patients. Results: Seventy percent of the patients were female, 26 W and 23 AB, mean age 34.7 years. Multiple sinus CVT, deep CVT and worse outcome were significantly more frequent in AB than in W patients. There was a trend towards a higher frequency of factor V Leiden and prothrombin mutation in W than in AB, and of protein C deficiency in AB. Conclusions: CVT was more severe in AB patients than in W patients. Race-ethnic differences may account for the heterogeneous distribution of inherited thrombophilia in this series.

Musculoskeletal evaluation in severe haemophilia A patients from Latin America

Summary.  Children with haemophilia often bleed inside joints and muscles, which may impair postural adjustments. These postural adjustments are necessary to control postural balance during daily activities. The inability to quickly recover postural balance could elevate the risk of bleeding. To determine whether children with haemophilia have impaired postural adjustment after an unexpected perturbation compared with healthy children. Twenty children with haemophilia comprised the haemophilic group (HG), and 20 healthy, age‐paired children comprised the control group (CG). Subjects stood on a force plate, and 4% of the subjects’ body weight was applied via a pulley system to a belt around the subjects’ trunks. The centre of pressure (COP) displacement was measured after the weight was unexpectedly released to produce a controlled postural perturbation followed by postural adjustment to recover balance. The subjects’ postural adjustments in eight subsequent intervals of 1 s (t1–t8), beginning with the moment of weight removal, were compared among intervals and between groups. The applied perturbation magnitudes were the same for both groups, and no difference was observed between the groups in t1. However, the COP displacement in t2 in the HG was significantly higher than in the CG. No differences were observed between the groups in the other intervals. Within‐group analysis showed that the COP was higher in t2 than in t4 (P = 0.016), t5 (P = 0.001) and t8 (P = 0.050) in the HG. No differences were observed among intervals in the CG. Children with haemophilia demonstrated differences in postural adjustment while undergoing unexpected balance perturbations when compared with healthily children.

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

Sensory information from visual, vestibular and proprioceptive systems is necessary to control posture and balance. Impairment in proprioception due to repetitive joints bleeding may lead to a deficit in postural balance which, in turn, leads to high joint stress and risk of bleeding recurrence. Despite the increase in attention in this field during the past few years, the data concerning to how bleeds can affect postural control in children with haemophilia (CWH) remain scarce. This study aimed to evaluate the postural balance in CWH. Twenty CWH Haemophilia Group (HG) and 20 age‐matched children Control Group (CG) were recruited to this study. A force plate was used to record centre of pressure (COP) displacement under four different postural conditions during quiet standing: eyes open on firm surface, eyes open on foam surface, eyes closed on firm surface and eyes closed on a foam surface. Variables of COP as sway area and mean velocity and in anterior–posterior (y) medio‐lateral (x) direction were processed and for each variable sensory, quotients were calculated and compared between groups. No differences were found in visual and vestibular quotients variables between groups. A higher value was found in sway area variable on proprioception quotient in the HG when compared with CG (P = 0.042). CWH with repetitive joint bleed on lower limbs showed differences in postural balance when compared with non‐haemophiliac children. The identification of early balance impairments in CWH can help us understand better the effects of bleeds inside joints on postural control and plan a more effective preventive and rehabilitative treatment.

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

There is a paucity of literature on haemophilia treatment in Latin American countries, a region characterized by rapidly improving systems of care, but with substantial disparities in treatment between countries. The aim of this study was to evaluate the musculoskeletal status of haemophilia patients from Latin America and to examine the relationship between musculoskeletal status and treatment practices across countries. The Committee of Latin America on the Therapeutics of Inhibitor Groups conducted a survey of its member country representatives on key aspects of haemophilia treatment in 10 countries. Musculoskeletal status of patients was obtained during routine comprehensive evaluations between March 2009 and March 2011. Eligible patients had severe haemophilia A (factor VIII <1%) without inhibitors (<0.6 BU mL−1) and were ≥5 years of age. Musculoskeletal status was compared between three groups of countries, based primarily on differences in the availability of long‐term prophylaxis. Overall, 143 patients (5–66 years of age) were enrolled from nine countries. In countries where long‐term prophylaxis had been available for at least 10 years (Group A), patients aged 5–10 years had significantly better mean World Federation of Hemophilia clinical scores, fewer target joints and fewer affected joints than patients from countries where long‐term prophylaxis has been available for about 5 years (Group B) or was not available (Group C). In Latin America, the musculoskeletal status of patients with severe haemophilia without inhibitors has improved significantly in association with the provision of long‐term prophylaxis. As more countries in Latin America institute this practice, further improvements are anticipated.

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

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‐KLAT2.0 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‐KLAT2.0 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‐KLAT2.0 is well understood by Sao Paulo boys/parents. The next step will be to test its validity and reliability locally.

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

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.

Validity of the Portuguese CHO-KLAT in Brazil

Viscosupplementation can improve function in haemophilia patients. Viscosupplementation results can be improved by prior joint lavage and triamcinolone administration.