Tailored frequency-escalated primary prophylaxis for severe haemophilia A: results of the 16-year Canadian Hemophilia Prophylaxis Study longitudinal cohort.

BACKGROUND: Severe haemophilia A has high morbidity, and treatment, while effective, is very expensive. We report the 16-year follow-up of the Canadian Hemophilia Prophylaxis Study, which examined the effectiveness of tailored frequency-escalated primary prophylaxis with a focus on health outcomes within the domains of body structures and functions, and activities and participation (according to the WHO International Classification of Functioning, Disability and Health [WHO-ICF] framework) and a view to reducing consumption of costly clotting factor, which accounts for more than 90% of the cost of care of severe haemophilia. METHODS: In this longitudinal study, boys with severe haemophilia A from 12 Canadian centres were enrolled at age 1·0-2·5 years. They were treated with standard half-life recombinant factor VIII (SHL-rFVIII), beginning as once-weekly prophylaxis with 50 IU/kg and escalating in frequency (with accompanying dose adjustments) in response to breakthrough bleeding as determined by the protocol. The primary endpoint for this analysis was joint health, as measured by the modified Colorado Child Physical Examination Scores (CCPES) at study end. All analyses were done by intention to treat. The trial is complete, and is registered with ClinicalTrials.gov, number NCT01085344. FINDINGS: Between June 26, 1997, and Jan 30, 2007, 56 boys were enrolled. They were followed for a median of 10·2 years (to a maximum of 16·1 years). Median rFVIII usage was about 3600 IU/kg per year. The median end-of-study CCPES physical examination score was 1 (IQR 1-3; range 0-12) for the left ankle and 1 (1-2; 0-12) for the right ankle, with all other joints having a median score of 0. No treatment-related safety events occurred over the duration of the study, including central venous catheter infections. The median annualised index joint bleeding rate was 0·95 per year (IQR 0·44-1·35; range 0·00-13·43), but 17 (30%) patients had protocol-defined unacceptable breakthrough bleeding at some point during the study. INTERPRETATION: Tailored frequency-escalated prophylaxis leads to very little arthropathy and very good health outcomes within the WHO-ICF domains, and only uses a moderate amount of expensive clotting factor as compared with standard prophylaxis protocols. Some sequelae of bleeding were observed in our cohort, and future studies should consider a more stringent protocol of escalation. FUNDING: This study was initially funded by grants from the Medical Research Council of Canada/Pharmaceutical Manufacturers Association of Canada Partnership Fund and the Bayer/Canadian Blood Services/Hema-Quebec Partnership Fund. Subsequent renewals were funded by Bayer.

A randomised comparison of melphalan with prednisone or dexamethasone as induction therapy and dexamethasone or observation as maintenance therapy in multiple myeloma: NCIC CTG MY.7.

The effectiveness of melphalan plus dexamethasone (M-Dex) with melphalan plus prednisone (MP) as induction therapy and dexamethasone with observation as maintenance therapy was compared in 585 older patients with multiple myeloma. Randomization to the M-Dex arm was stopped as a result of an analysis performed which met a predetermined event-related criterion. Of 466 patients randomised to MP or M-Dex, no differences were detected in the respective median progression-free survivals (PFS) [1.8 vs. 1.9 years; Hazard Ratio (HR) = 0.88, 95% CI 0.72-1.07; P = 0.2] or overall survivals (OS) (2.5 vs. 2.7 years; HR = 0.91, 95% CI 0.74-1.11; P = 0.3). Of the initial 585 patients, 292 remained evaluable for maintenance therapy. Patients randomised to maintenance dexamethasone had a superior median PFS (2.8 years vs. 2.1 years; HR = 0.61, 95% CI 0.47-0.79; P = 0.0002). No difference in median OS was detected (4.1 years vs. 3.8 years; HR = 0.88, 95% CI 0.65-1.18; P = 0.4). The maintenance therapy results were robust when analysed by using two additional methodologies. Dexamethasone did not improve clinical outcome when combined with melphalan during induction; maintenance dexamethasone improved PFS, but this did not translate into a detectable survival advantage.

Profile of amblyopia in a hospital referral practice.

OBJECTIVE: Evaluation of the clinical profile and distribution of different sub-types of amblyopia in a referral eye hospital in India. METHODS: This was a prospective hospital-based observational study, evaluating the clinical profile of patients with amblyopia presenting to a referral strabismology practice. The examination included assessment of the visual acuity, the refractive status, the fixation pattern, the grade of binocularity, and evaluation of the associated strabismus, if any before treatment was started. RESULTS: The average age of the patients at presentation was 7.97?6.18 years with 81 out of 683 patients (11.8%) presenting above the age of 20 years. The best-corrected visual acuity (BCVA) was less than 6/60 in the amblyopic eye in 121 out of 733 eyes (16.5%). Strabismic amblyopia was the most common sub-type of amblyopia seen (274/733 eyes, 37.38%). Though patients with anisometropic amblyopia presented at a later age (average of 10.03+/-6.92 years), they had better visual acuity, binocular functions, and centricity of fixation at all ages, relative to other sub-types of amblyopia. The BCVA did not show any co-relation with the age of presentation [co-relation co-efficient (CF) of 0.074], refractive status of the amblyopic eye (CF of 0.078), the type of amblyopia (CF of 0.196), or the type of strabismus present (CF of 0.079). However, a very significant co-relation was seen between the BCVA and the fixation pattern of the amblyopic eye (CF of 0.817). CONCLUSIONS: Lack of knowledge and awareness about amblyopia and its appropriate timely management has been the main cause for the late presentations and significant visual impairment associated with the condition.

Factors influencing visual rehabilitation after occlusion therapy in unilateral amblyopia in children.

BACKGROUND & OBJECTIVE: Amblyopia is one of the most common causes of visual impairment in adults and children, and visual loss may be permanent if not treated in time. Though many studies have been done on occlusion therapy which is the mainstay in the treatment of unilateral amblyopia, discrepancies exist in literature about quantification of treatment and follow up measures. The present study was undertaken to evaluate the factors responsible for the successful outcome of treatment and the optimum time required for the same in children with unilateral amblyopia. METHODS: Baseline characteristics of 63 verbal patients with unilateral amblyopia (strabismic, anisometropic, mixed) referred to the Strabismus and Amblyopia Clinic at the Dr Rajendra Prasad Centre for Ophthalmic Sciences, New Delhi between September 2001 to December 2002 who improved to the desired level of visual acuity after treatment for amblyopia in the mentioned time period, were analyzed to assess for factors that directly or indirectly influenced the optimum visual rehabilitation and the average duration of therapy required for the same. The evaluation included assessment of the baseline best-corrected visual acuity (BCVA) and refractive status in both eyes, the age at presentation, the type of amblyopia present, fixation pattern in the amblyopic eye, inter-eye visual acuity difference, and evaluation of compliance through a parental diary system. RESULTS: Baseline BCVA in the amblyopic eye was similar in all the three groups. Patients with anisometropic amblyopia showed a quicker response to therapy. Compliance to treatment was the major factor affecting the overall time required for a successful outcome in most cases. The overall time required for the treatment to be successful (including the period of maintenance) was about 1,089 h. INTERPRETATION & CONCLUSION: This hospital-based study showed that the average duration of occlusion therapy to achieve stable isoacuity was 7.2 months with an average occlusion of 6-7 h/day. Compliance to therapy was the most important factor affecting the duration of therapy. With increasing emphasis on paediatric eye diseases, amblyopia is at last getting its due importance as a cause of treatable correctable paediatric visual impairment which can have lifelong repercussions, both in terms of individual disability and financial burden to the society if not treated in time. As the therapy is simple and effective if started early, mass awareness, visual screening, and counselling would go a long way in treating the patients, thus decreasing the prevalence of amblyopia in the country.