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Introduction: Evaluating treatment success in patients with haemophilia A (HA) remains a vigorous debate, especially concerning the interpretation of results from clinical and observational research. The benefits of short‐term prophylaxis are well established, but long‐term outcomes, particularly related to humanistic and economic burden, are not as well understood. Aim: We conducted a systematic literature review to evaluate the association of episodic or prophylactic bleed control with long‐term clinical, humanistic and economic outcomes. Methods: Studies published in English between 1 January 2006 and 15 December 2016 were included. Participants had HA (with or without inhibitors), received prophylactic or episodic treatment and had at least 4 years of treatment or follow‐up. Results were analysed qualitatively with descriptive findings. Results: A total of 2091 records were screened, resulting in 19 studies from 20 publications for inclusion. Most studies included children (84%), were limited to patients with severe disease (74%) and were conducted in Europe or North America (89%). Ten studies (53%) included patients with inhibitors. Median study follow‐up ranged from 5 to 19 years. Long‐term bleeding and haemarthrosis outcomes were consistently better for patients receiving prophylaxis, who also required fewer hospitalizations or surgeries. Health‐related quality of life, functionality and productivity were generally more favourable in patients receiving prophylaxis. Quantitative comparisons were not feasible due to the lack of consistency in endpoint collection and reporting among studies. Conclusion: This systematic review confirmed that the benefits of prophylactic treatment on short‐term outcomes translate to broader long‐term clinical, humanistic and economic benefits. Better harmonization of data collection and outcome assessments across both registries and clinical studies is needed to allow for effective comparisons across studies and across data sources. [ABSTRACT FROM AUTHOR]

Background Lifelong prophylactic replacement therapy with clotting factor concentrates is recommended for severe haemophilia. The prophylactic dose determines both clinical outcome and treatment cost. In the absence of clinical studies, computer simulation was used to explore lifelong effects and clotting factor consumption for various prophylactic dose levels, and optimize strategies for switching between prophylactic and on-demand treatment. Design and Methods Individual patients' lifetime joint bleeds, radiological arthropathy (Pettersson score, 0-78) and consumption were simulated for each treatment strategy. Treatment effectiveness (expressed as % of patients maintaining a lifetime Pettersson score ≤14) and clotting factor consumption were modelled for lifelong prophylaxis at dose levels 1000-4500 IU kg−1 year−1, for on-demand treatment and for switching strategies. Treatment efficiency (consumption per unit of effectiveness) was used to compare strategies. Results Compared to lifelong on-demand treatment, lifelong prophylaxis at 1000 IU kg−1 year−1 increased effectiveness from 21 to 36%, at an additional consumption of 0.9 × 106 IU kg−1. For lifelong prophylaxis, each additional 1000 IU kg−1 year−1 resulted in a proportional increase in consumption by ±5 × 106 IU kg−1 but a less than proportional reduction in arthropathy by ±50%; consequently, increasing consumption progressively diminished treatment efficiency. Switching strategies slightly reduce effectiveness and consumption. Optimum switching criteria were similar across prophylactic dose levels. Conclusion According to the simulation model, low-dose prophylaxis (1000 IU kg−1 year−1) improved outcome at a limited increase in consumption compared to on-demand treatment. Increasing prophylactic dose further improved health outcomes, but at decreasing efficiency. Optimal prophylactic dose should therefore be selected balancing acceptable health impact and available budget. [ABSTRACT FROM AUTHOR]

Introduction Coagulation products have allowed patients with severe haemophilia to lead a normal life. This is, however, only true for patients who received an early diagnosis and could start with primary prophylaxis. The absence of a positive family history for haemophilia, in the majority of children with severe haemophilia, postpones the age that treatment can be started. This makes general awareness of the clinical presentation important and a proper diagnosis a prerequisite for progress. The long delay between joint bleeding and overt arthropathy has been an important factor in the delay of implementation of primary prophylaxis. After the development of guidelines on 'how to treat', implementation of the advised practice is needed. Data collection of current treatment regimens in haemophilia centres will support the further optimization of the care for persons with haemophilia and further optimize treatment guidelines. Episodic ('on demand') therapy as a treatment strategy for severe haemophilia needs reconsideration. Conclusion In an era where clotting factor concentrates are abundant and gene therapy a reality, all patients with severe haemophilia should be offered a strategy of bleeding prevention. [ABSTRACT FROM AUTHOR]

Introduction Current factor prophylaxis strategy practised in developed countries is not feasible in resource constraint developing countries like India. Aim The aim of this study was to investigate the efficacy and safety of very low-dose factor prophylaxis in India. Methods Children of 1-10 years of age with severe haemophilia were randomized to Prophylaxis group and Episodic (On demand) group. Children in prophylaxis group received very low-dose factor VIII (FVIII) concentrate, i.e. 10 units kg−1 body weights on 2 days a week. Episodic group received factor concentrate in standard recommended doses. The study period was 11.5 months. Results In total 21 children were enrolled in this study, 11 assigned to prophylaxis and 10 to episodic group. Children on prophylaxis had 11 joint bleeds in comparison to 57 joint bleeds in episodic group. Mean number of haemarthrosis per patient per month were 0.08 (0.08 ± 0.13) in prophylaxis group compared to 0.48 (0.48 ± 0.34) in episodic group ( P < 0.05). Total FVIII consumption was 87.51 and 56.32 units kg−1 month−1 in prophylaxis and episodic group respectively ( P = ns). Overall median hospital emergency visits were 1 day in prophylaxis group and 9 days in episodic group ( P ≤ 0.05). Median days of absenteeism from school were 25 days in episodic group and 3 days in prophylaxis group ( P < 0.05). No significant complications were noted in prophylaxis group and compliance was 98%. Conclusion To conclude, low-dose FVIII prophylaxis is cost effective, efficacious and a safe method of preventing joint bleeds and consequent joint damages. [ABSTRACT FROM AUTHOR]

This study prospectively compared the effect of secondary prophylaxis to episodic treatment on target joint ( TJ) range of motion ( ROM), number of joint haemorrhages and new TJ development in patients with moderate or severe haemophilia. Two-hundred and eighty-six males, 17% in prophylaxis, 83% in episodic treatment group, participating in the Centers for Disease Control and Prevention's Universal Data Collection project, fulfilled inclusion criteria: age >2 years at enrolment, free of TJs at enrolment, developed at least one TJ after enrolment, and received either prophylaxis or episodic treatment continuously for two follow-up visits after TJ development. The outcomes of interest - percentage change in TJ ROM, number of joint haemorrhages and new TJ development, were modelled using multivariate linear, Poisson and logistic regression techniques respectively. Individuals who received secondary prophylaxis in comparison to episodic treatment were younger at TJ development ( P < 0·01); there was no difference in the decrease in TJ ROM between the two groups ( P = 0·9). Factors significantly associated with a higher rate of haemarthroses included episodic treatment, severe haemophilia, age >5 years at TJ development, obesity and inhibitor negative status. Secondary prophylaxis significantly decreased haemarthroses but was not associated with a significant improvement in TJ ROM or with new TJ development. [ABSTRACT FROM AUTHOR]

Episodic treatment of bleeding disorders is defined as utilization of clotting factor concentrates in response to acute bleeding episodes to achieve haemostasis. Non-adherence to prescribed episodic regimens can limit treatment effectiveness and result in target joint formation, pain and disability. Evaluation of and interventions to promote adherence may improve health outcomes. The purpose of this study was to validate a new adherence scale developed for individuals with bleeding disorders treated on episodic infusion regimens, entitled VERITAS-PRN [Validated Hemophilia Reg imen Treatment Adherence Scale – PRN]. Participants were recruited from the Indiana Hemophilia and Thrombosis Center patient population. Participants completed the scale for psychometric development and analysis. Subjective ratings of adherence from participants and providers were used for validation. The study sample included 51 male and three female patients. Twenty-seven participants (50.0%) were diagnosed with FVIII deficiency, 21 (38.9%) with FIX deficiency and six (11.1%) with von Willebrand’s disease (VWD). Internal consistency reliability for the total VERITAS-PRN score and the majority of subscales was good-to-excellent, with the one exception being the ‘Plan’ subscale. Test-retest reliability correlations were good-to-excellent for the total scale and all subscales. The VERITAS-PRN total scale had moderate-to-strong and statistically significant correlations with validity measures. The VERITAS-PRN is a reliable and valid measure of adherence to episodic treatment regimens for bleeding disorders. This tool may be utilized as a standard measure of adherence to increase sensitivity to adherence problems and promote targeted interventions to enhance adherence and health outcomes [ABSTRACT FROM AUTHOR]

Aims To study the absorption kinetics of sotalol following administration of different formulations. A formulation which results in fast absorption might be useful in the episodic treatment of paroxysmal supraventricular tachycardia (SVT), atrial fibrillation (Afib) or atrial flutter (Afl). Methods In an open randomized crossover study seven healthy male volunteers were given an intravenous infusion of 20 mg sotalol, for assessing the absolute bioavailability, an oral solution containing 80 mg sotalol, an oral solution containing both 80 mg sotalol and 20 mg cisapride and an 80 mg sotalol tablet, which was taken sublingually. Results The addition of cisapride decreased the time at which maximum serum concentrations were reached (t max ) from 2.79 (1.85–4.34) h to 1.16 (0.68–2.30) h (P =0.009) [95% CI: -2.59, -0.55] and increased the absorption rate constant (k a ) from 0.49 (0.31–0.69) h-1 to 1.26 (0.52–5.61) h-1 (P =0.017). The absolute bioavailability of sotalol was reduced by cisapride from 1.00±0.15 to 0.70±0.26 (P =0.006), while maximum serum concentrations of both oral solutions were not significantly different. Compared with the sublingually administered tablet with a median t max of 2.12 (0.89–3.28) h, the sotalol/cisapride oral solution gave a smaller t max (p=0.009) [95% CI: -1.64, -0.36]. The k a of the sotalol/cisapride solution was significanty (P =0.010) larger than the k a of 0.56 (0.33–0.75) h-1 found after sublingual administration of the tablet. Conclusions The sotalol/cisapride oral solution might be suitable for the episodic treatment of SVT, Afib or Afl. [ABSTRACT FROM AUTHOR]