Estimating the impact of improved management of haemophilia a on clinical outcomes and healthcare utilisation and costs.

OBJECTIVE: Haemophilia A (HA) is associated with high clinical and healthcare burden. We developed an Excel-based model comparing current practice to improved management in severe HA patients currently managed on demand (OD). Outcomes included short- and long-term bleed events. Expected annual bleeds were estimated based on locally-derived OD annualised bleed rate (ABR), adjusted by relative prophylaxis-related ABRs (published literature). The objective of our study was to explore the impact of improving HA prophylaxis in target countries with limited published data (Algeria, Argentina, Chile, India, Malaysia, Mexico, Taiwan and Thailand). Bleed-related healthcare resource use (HCRU) and costs were estimated as a function of bleed type, with inputs obtained from local expert estimates. Clotting factor concentrates (CFC) consumption related to treatment and prophylaxis was estimated based on locally relevant dosing. CFC costs were not included. RESULTS: When 20% of OD patients were switched to prophylaxis, projected reduction in bleeds was estimated between 3% (Taiwan) through 14% (Algeria and India); projected reductions in hospitalisations ranged from 3% (Taiwan) through 15% (India). Projected HCRU-related annual cost savings were estimated at USD 0.45 m (Algeria), 0.77 m (Argentina), 0.28 m (Chile), 0.13 m (India), 0.29 m (Malaysia), 2.79 m (Mexico), 0.15 m (Taiwan) and 0.78 m (Thailand). Net change in annual CFC consumption ranged from a 0.05% reduction (Thailand) to an overall 5.4% increase (Algeria). Our model provides a flexible framework to estimate the clinical and cost offsets of improved prophylaxis. Modest increase in CFC consumption may be an acceptable offset for improvements in health and healthcare capacity in resource constrained economies.

Breakthrough Bleeding Episodes at Minimum and Improvement in Quality of Life in a Child with Severe Hemophilia A with Inhibitors Treated with Emicizumab: A Case Report from Chile.

BACKGROUND People with hemophilia A have shown osteomuscular complications that have a significant impact on their quality of life (QoL) and on health care costs. Patients with hemophilia A with inhibitors living in developing countries such as Chile face a high disease and treatment burden. Emicizumab, a humanized bispecific monoclonal antibody, is associated with improvements in QoL and reduction in the financial impact of the disease related to treatment. This case report describes the impact of emicizumab on a patient with severe hemophilia A with inhibitors in terms of breakthrough bleeding control, improvements in QoL, and reduced financial impact after a year of treatment, in a country where this medication is not routinely available. CASE REPORT A 10-year-old child with severe hemophilia A with inhibitors had several restrictions in his daily life due to multiple incidences of breakthrough bleeding. He was on episodic treatment with bypassing agents, and in the year prior to treatment with emicizumab he had 18 bleeding episodes. After 1 year on prophylaxis treatment with emicizumab, the patient had only 1 bleeding episode (94.4% of reduction), improved pain control (5-point reduction on the visual analogue scale), a decrease in the Hemophilia Joint Health Score from 39 to 19, the QoL perception increased by 86% on the standardized Haemo-QoL-kids, and a 70% reduction in treatment costs versus the costs of episodic treatment with bypassing agents. CONCLUSIONS After 1 year of treatment with emicizumab, this patient had substantial improvements in the evaluated parameters. Further investigations with emicizumab are needed to assess its possible effects on public health policies.

Impact of Visual Biofeedback of Trunk Sway Smoothness on Motor Learning during Unipedal Stance.

The assessment of trunk sway smoothness using an accelerometer sensor embedded in a smartphone could be a biomarker for tracking motor learning. This study aimed to determine the reliability of trunk sway smoothness and the effect of visual biofeedback of sway smoothness on motor learning in healthy people during unipedal stance training using an iPhone 5 measurement system. In the first experiment, trunk sway smoothness in the reliability group (n = 11) was assessed on two days, separated by one week. In the second, the biofeedback group (n = 12) and no-biofeedback group (n = 12) were compared during 7 days of unipedal stance test training and one more day of retention (without biofeedback). The intraclass correlation coefficient score 0.98 (0.93-0.99) showed that this method has excellent test-retest reliability. Based on the power law of practice, the biofeedback group showed greater improvement during training days (p = 0.003). Two-way mixed analysis of variance indicates a significant difference between groups (p < 0.001) and between days (p < 0.001), as well as significant interaction (p < 0.001). Post hoc analysis shows better performance in the biofeedback group from training days 2 and 7, as well as on the retention day (p < 0.001). Motor learning objectification through visual biofeedback of trunk sway smoothness enhances postural control learning and is useful and reliable for assessing motor learning.

Knee haemophilic arthropathy care in Chile: Midterm outcomes and complications after total knee arthroplasty.

INTRODUCTION: Total knee arthroplasty (TKA) can improve knee function in the general population, but challenges arise for TKA use in haemophilic patients (HPs). AIM: This study aimed to evaluate the midterm clinical experience of a single medical centre in TKA in HPs. METHODS: We performed a case series of consecutive TKAs from 2007 to 2013 in HPs. All patients received coagulation factor supplementation according to the institutional protocol. Surgery was performed without a tourniquet by a standard midline medial parapatellar approach. We compared the range of motion (ROM) and flexion contracture before surgery and 1-year postoperative using paired Wilcoxon-non-parametric test (P < .05 was considered significant). The need for revision surgery was considered TKA survival failure. RESULTS: Forty-one HP/60 TKAs were reviewed (19 cases were bilateral). Preoperative median ROM and flexion contracture was 75° (range, 0°-95°) and 20° (range, 5°-80°), respectively. The postoperative median ROM increased to 83° (range, 45°-110°), and median flexion contracture decrease to 0° (range, 0°-40°) a statistically significant difference (P < .01). Postoperative median clinical Knee Society Score (KSS) and functional KSS were 88 (range, 59-97) and 100 (range, 30-100), respectively. Six patients required revision (6.66%) due to infection. TKA survival at 5 years was 92% (range, 82%-96%). CONCLUSION: This study supports that TKA improves function and ROM in haemophilic knee arthropathy. The protocol of coagulation factors used in this cohort is valid as no related complications were reported. A higher incidence of complications, especially infections, must be expected compared with a TKA in non-HPs.

Effects of performing dual tasks on postural sway and postural control complexity in people with haemophilic arthropathy.

INTRODUCTION: People with haemophilic arthropathy (PWHA) have impairments in postural control. However, little is known about the effects of demanding conditions, including the unipedal stance and dual tasks, on postural control in PWHA. AIM: Determine the effects of performing dual tasks while in the one-leg stance on postural sway and postural control complexity in PWHA vs. healthy active (HAG) and non-active (HNAG) groups of individuals. METHODS: Fifteen PWHA and 34 healthy subjects (18 active and 16 non-active) were recruited. Vertical (V), mediolateral (ML) and anteroposterior (AP) centre of mass signals were acquired using a 3-axis accelerometer placed at the L3/L4 vertebrae of subjects as they performed the one-leg stance under single and dual-task conditions. Sway balance and the complexity of postural control were studied via root mean square (RMS) acceleration and sample entropy, respectively. Increased complexity of postural sway was attributed to increased automatism of postural control. RESULTS: RMS values for PWHA were higher than HAG under both conditions for the V and ML axes, and higher than HNAG under the dual-task condition for the ML axis. Sample entropy was lower in PWHA than healthy individuals under the dual-task condition for V and ML axes, and the single-task condition for the ML axis (P < .05). CONCLUSION: PWHA had poorer postural sway and decreased postural control complexity when performing a one-leg stance than healthy people, especially when the dual-task condition was applied. These results may help to design new approaches to assess and improve postural control in PWHA.

A Randomized Trial of Factor VIII and Neutralizing Antibodies in Hemophilia A.

BACKGROUND: The development of neutralizing anti-factor VIII alloantibodies (inhibitors) in patients with severe hemophilia A may depend on the concentrate used for replacement therapy. METHODS: We conducted a randomized trial to assess the incidence of factor VIII inhibitors among patients treated with plasma-derived factor VIII containing von Willebrand factor or recombinant factor VIII. Patients who met the eligibility criteria (male sex, age <6 years, severe hemophilia A, and no previous treatment with any factor VIII concentrate or only minimal treatment with blood components) were included from 42 sites. RESULTS: Of 303 patients screened, 264 underwent randomization and 251 were analyzed. Inhibitors developed in 76 patients, 50 of whom had high-titer inhibitors (≥5 Bethesda units). Inhibitors developed in 29 of the 125 patients treated with plasma-derived factor VIII (20 patients had high-titer inhibitors) and in 47 of the 126 patients treated with recombinant factor VIII (30 patients had high-titer inhibitors). The cumulative incidence of all inhibitors was 26.8% (95% confidence interval [CI], 18.4 to 35.2) with plasma-derived factor VIII and 44.5% (95% CI, 34.7 to 54.3) with recombinant factor VIII; the cumulative incidence of high-titer inhibitors was 18.6% (95% CI, 11.2 to 26.0) and 28.4% (95% CI, 19.6 to 37.2), respectively. In Cox regression models for the primary end point of all inhibitors, recombinant factor VIII was associated with an 87% higher incidence than plasma-derived factor VIII (hazard ratio, 1.87; 95% CI, 1.17 to 2.96). This association did not change in multivariable analysis. For high-titer inhibitors, the hazard ratio was 1.69 (95% CI, 0.96 to 2.98). When the analysis was restricted to recombinant factor VIII products other than second-generation full-length recombinant factor VIII, effect estimates remained similar for all inhibitors (hazard ratio, 1.98; 95% CI, 0.99 to 3.97) and high-titer inhibitors (hazard ratio, 2.59; 95% CI, 1.11 to 6.00). CONCLUSIONS: Patients treated with plasma-derived factor VIII containing von Willebrand factor had a lower incidence of inhibitors than those treated with recombinant factor VIII. (Funded by the Angelo Bianchi Bonomi Foundation and others; ClinicalTrials.gov number, NCT01064284; EudraCT number, 2009-011186-88.).