Health-related quality of life assessment in haemophilia patients on prophylaxis therapy: a systematic review of results from prospective clinical trials.

INTRODUCTION: Prophylaxis is effective in reducing the number of bleeding episodes in patients with severe or moderately severe haemophilia A and B, including those with inhibitors. However, data, predominantly from observational studies, suggest more equivocal effects on health-related quality of life (HRQoL). AIM: To examine the impact of prophylaxis on HRQoL from prospective clinical trials. METHODS: We performed a systematic literature review of clinical trials evaluating the efficacy of prophylaxis with factor VIII, FIX or bypassing agents. Trials assessing HRQoL via validated instruments were selected and summarized. RESULTS: Thirteen trials (haemophilia A [n = 8]; haemophilia B [n = 2]; inhibitors [n = 3]) met all inclusion criteria. HRQoL instruments included the EQ-5D, SF-36, Haem-QoL-A, Haem-A-QoL, Haemo-QoL and CHO-KLAT. Improvements in HRQoL following prophylaxis were observed with the EQ-VAS, SF-36 and haemophilia-specific instruments in adult patients and were associated with reduced pain, fewer restrictions in physical activities and better general health. Prophylaxis led to statistically significant or clinically meaningful HRQoL improvement in six trials and non-significant improvement in four trials; two trials found no improvement and one reported no data. Despite study differences, consistent trends suggested that patients previously treated solely on-demand and those who experienced marked reductions in the frequency of bleeding with prophylaxis had a greater improvement in HRQoL. CONCLUSION: Contrary to findings of observational studies, the results from the majority of prospective trials using validated instruments showed positive trends for improved HRQoL with prophylaxis in adults.

Applicability of 3T body MRI in assessment of nonfocal bone marrow involvement of hematopoietic neoplasia in dogs.

BACKGROUND: The utility of whole body magnetic resonance imaging (MRI) in detecting bone marrow infiltration in dogs with cancer has not been investigated. OBJECTIVES: To assess the feasibility of 3T body MRI for bone marrow assessment in dogs with hematopoietic neoplasia. ANIMALS: Seven dogs with B-cell lymphoma, 3 dogs with myelodysplastic syndrome (MDS), and 2 clinically normal dogs. METHODS: A prospective study of dogs with hematopoetic cancer was conducted using T1W, T2W, In-Phase, Out-of-Phase and STIR pulse sequences of the body excluding the head prior to bone marrow sampling. The relative signal intensity of a midlumbar vertebral body and a midshaft femoral bone marrow was compared by visual and point region of interest analysis to regional skeletal muscle. RESULTS: Similarity of femoral diaphyseal and vertebral body marrow signal intensity to that of skeletal muscle on the Out-of-Phase sequence was useful in distinguishing the 3 dogs with hypercellular marrow because of MDS from the 7 dogs with B-cell lymphoma and from the 2 clinically normal dogs. 1/7 dogs with lymphoma had proven bone marrow involvement but normal cellularity and less than 5% abnormal cells. Unaffected midfemoral marrow had greater signal intensity than skeletal muscle and unaffected vertebral marrow had less signal intensity than skeletal muscle on the Out-of-Phase sequence. CONCLUSIONS AND CLINICAL IMPORTANCE: 3T, Out-of-Phase MR pulse sequence was useful in distinguishing diffuse bone marrow infiltrate (MDS) from minimally or unaffected marrow using skeletal muscle for signal intensity comparison on whole body MRI.

Clinical canine spinal cord injury provides an opportunity to examine the issues in translating laboratory techniques into practical therapy.

STUDY DESIGN: Review. OBJECTIVES: To highlight the value of investigating the effects of putative therapeutic interventions in clinical spinal cord injury (SCI) in domestic dogs. SETTING: England, UK. METHODS: Many experimental interventions in laboratory rodents have been shown to ameliorate the functional deficits caused by SCI; the challenge now is to determine whether they can be translated into useful clinical techniques. Important differences between clinical SCI in human patients and that in laboratory rodents are in the size of the spinal cord and heterogeneity of injury severity. A further key issue is whether the statistical difference in outcome in the laboratory will translate into a useful difference in clinical outcome. Here, we stress the value of investigating the effects of putative therapies in clinical SCI in domestic dogs. The causes of injury, ability to categorise the severity and methods available to measure outcome are very similar between canine and human patients. Furthermore, postmortem tissue more rapidly becomes available from dogs because of their short lifespan than from human patients. RESULTS: The role that investigation of canine SCI might play is illustrated by our preliminary trials on intraspinal transplantation of olfactory glial cells for severe SCI. CONCLUSIONS: This canine translational model provides a means of 'filtering' putative treatments before human application.