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Introduction: The UK National Haemophilia Database (NHD) collects data from all UK persons with haemophilia A with inhibitors (PwHA‐I). It is well‐placed to investigate patient selection, clinical outcomes, drug safety and other issues not addressed in clinical trials of emicizumab. Aims: To determine safety, bleeding outcomes and early effects on joint health of emicizumab prophylaxis in a large, unselected cohort using national registry and patient reported Haemtrack (HT) data between 01 January 2018 and 30 September 2021. Methods: Prospectively collected bleeding outcomes were analysed in people with ≥6 months emicizumab HT data and compared with previous treatment if available. Change in paired Haemophilia Joint Health Scores (HJHS) were analysed in a subgroup. Adverse events (AEs) reports were collected and adjudicated centrally. Results: This analysis includes 117 PwHA‐I. Mean annualised bleeding rate (ABR) was.32 (95% CI,.18;.39) over a median 42 months treatment with emicizumab. Within‐person comparison (n = 74) demonstrated an 89% reduction in ABR after switching to emicizumab and an increase in zero treated bleed rate from 45 to 88% (p <.01). In a subgroup of 37 people, total HJHS improved in 36%, remained stable in 46% and deteriorated in 18%, with a median (IQR) within‐person change of −2.0 (−9, 1.5) (p =.04). Three arterial thrombotic events were reported, two possibly drug related. Other AEs were generally non‐severe and usually limited to early treatment, included cutaneous reactions (3.6%), headaches (1.4%), nausea (2.8%) and arthralgia (1.4%). Conclusions: Emicizumab prophylaxis is associated with sustained low bleeding rates and was generally well‐tolerated in people with haemophilia A and inhibitors. [ABSTRACT FROM AUTHOR]

Background: Practising compassion has shown to increase well-being and reduce distress in people across cultures. However, very little research has explored cultural differences in different facets of compassion with a dearth of research evident especially in the Asian context. Several inhibitors and facilitators of compassion have been identified although the nuances of cultural differences of these remain unexploited. This study aimed to discover cross-cultural similarities and differences of the levels of compassion, facilitators and inhibitors of compassion between Sri Lankan and UK people. Methods: A cross-sectional, questionnaire-based quantitative research was conducted among 149 Sri Lankan and 300 UK participants. Individual predictors (such as fears of compassion, self-reassurance, external shame, social safeness and pleasure, depression and anxiety) were also explored in relation to compassion, compassion to others, and compassion from others in each group. Results: The results indicated that Sri Lankan participants were more self-reassured and self-compassionate and self-identifying as a Buddhist predicted higher self-compassion, when compared to UK participants. However, Sri Lankan participants reported higher levels of external shame and fear of compassion not just towards themselves, but also towards and from others, indicating difficulty in engaging compassionately with others. In contrast, UK participants reported higher social safeness, indicating that they were more likely to feel safe and soothed by the society than the Sri Lankan participants. Conclusions: Society plays a pivotal role in shaping one's experiences of compassion. This study suggests that specific cultural and social factors should be considered when implementing Western compassionate approaches to non-Western settings. [ABSTRACT FROM AUTHOR]

Organisations face ever increasing pressure to deliver triple-bottom-line performance results in their supply chains. Yet despite the importance and complexity associated with environmental supply chain performance measurement (ESCPM), organisations struggle to achieve this. The purpose of this paper is to identify the important enablers, inhibitors and benefits to implementing ESCPM as a practice in firms. Data were collected from three focus groups and an industry survey of 388 UK supply chain professionals in a three-phase empirical study. Eighteen enablers, seventeen inhibitors and eleven benefits were identified and ranked in importance. A supply chain practice-based view was utilised as an overarching theoretical lens to conceptualise the study's findings and propose nineteen antecedents, arranged in a hierarchical framework, to enable practitioners to make effective ESCPM decisions. This paper provides an up-to-date review of the factors which influence ESCPM practice, addressing the need for additional research in this area. [ABSTRACT FROM AUTHOR]

Introduction: Emicizumab (Hemlibra: Roche Switzerland) is a, humanized, bi‐specific monoclonal modified immunoglobulin G4 (IgG4) which binds human FX, FIX and activated FIX (FIXa) to mimic activated FVIII activity. Aim: Evaluate the effects of emicizumab on the APTT, surrogate FVIII activity and FVIII inhibitor results. Methods: Two samples were provided, one obtained from an emicizumab treated severe haemophilia A patient with FVIII inhibitors and one constructed by in vitro addition of emicizumab using plasma from a severe haemophilia A patient without FVIII inhibitors. An APTT screen, surrogate FVIII and FVIII inhibitor tests were performed on both samples by participating centres. Results: APTT results were below the lower limit of normal range. Chromogenic FVIII assay results with the Hyphen/Biophen human component‐based assay gave higher than expected coefficient of variation (CV) results, 38%–40%. The modified one‐stage FVIII assay with emicizumab calibrators showed similar results regardless of the APTT reagent. Inhibitor assay median results for sample S18:23 = 1.43 BU (range 0.9‐3.0 BU/ml, CV 38%). S18:24 was classified as below the lower limit of detection. Conclusion: APTT screens showed a consistent shortening. Unmodified one‐stage Factor VIII assay results were remarkably high. APTT‐based assays are unsuitable for measurement of coagulation factors or inhibitors in patients treated with emicizumab. Bovine origin chromogenic assays are insensitive to emicizumab and should be used to monitor FVIII levels/FVIII inhibitors in emicizumab treated patients. Product‐specific calibrators should be implemented to reduce result variability. [ABSTRACT FROM AUTHOR]

Introduction: Intracranial haemorrhage in children with inherited bleeding disorders is a potentially life‐threatening complication and presents a significant therapeutic challenge. Aim: To define the characteristics, management and outcomes of intracranial haemorrhage presenting in UK children ≤16 years of age with inherited bleeding disorders from 2003 to 2015. Method: Retrospective analysis of children treated at UK haemophilia centres. Results: Of 66 children presenting with Intracranial haemorrhage (ICH), 82% had haemophilia A or B, 3% VWD and 15% a rare IBD. The IBD was a severe phenotype in 91%. The rates of ICH were 6.4 and 4.2 per 1000 patient years for haemophilia A and B, respectively. Median age at presentation was 4 months (33% neonates; 91% children <2 years of age). In neonates, delivery was spontaneous vaginal (SV) in 11, instrumental in 6, caesarean in 4 and unknown in 1. In children with haemophilia, the risk of ICH after instrumental delivery was 10.6 times greater than after SV delivery. Trauma was more common in children >2 years (67%) than in children 1 month to 2 years (18%; P = .027). Prior to ICH, only 4.5% of children were on prophylaxis. 6% of haemophiliacs had an inhibitor. The median duration of initial replacement therapy was 15 days. Mortality was 13.5%. Neurological sequelae occurred in 39% of survivors, being more common following intracerebral bleeding. In haemophilia survivors, 52% subsequently developed a FVIII inhibitor. Conclusion: Intracranial haemorrhage occurs most frequently in children with severe IBDs, during the first 2 years of life and in children not receiving prophylaxis. Intracranial haemorrhage often occurs without documented trauma. [ABSTRACT FROM AUTHOR]

Haemophilia A and B are inherited bleeding disorders whose diagnosis and management is generally well established and best provided by specialists in a comprehensive care setting. Patients may be put at unnecessary risk if appropriate expertise is not sought for the management of accidents and surgery. The delivery of a high quality comprehensive service to patients with bleeding disorders depends upon defined standards and a network of haemophilia centres in the UK with similar models in other countries. In developing countries, despite a shortage or absence of treatment products, development of local expertise results in an improved outlook and reduction in mortality. Optimal care for severe haemophilia includes accurate diagnosis, early and adequate factor replacement for bleeding episodes and the provision of prophylaxis from an early age to prevent joint bleeding and the consequent arthropathy. Haemophilia treatment is expensive resulting in considerable inequity in provision of care across the world. Despite decades of experience, optimal treatment levels are not robustly defined. Transfusion-transmitted infections continue to have a significant impact on patient management. The development of inhibitory antibodies seriously complicates the management both in morbidity and cost. While gene therapy has not yet produced the hoped-for cure, new technologies will produce improved products. [ABSTRACT FROM AUTHOR]

Introduction: Factor VIII inhibitor development is currently the most serious complication of the treatment of haemophilia A. Differences in manufacturing and the molecular structure of brands of recombinant factor VIII have led to speculation that concentrates may differ in immunogenicity. This has led to a regulatory focus on the immunogenicity of factor VIII concentrates both before and after licensure., Aim: To investigate the immunogenicity of ReFacto AF post licensure in a real-world setting in previously untreated patients (PUPs) treated exclusively with this product until at least 50 exposure days (EDs)., Methods: The United Kingdom Haemophilia Centre Doctors' Organisation (UKHCDO) National Haemophilia Database (NHD) identified a consecutive cohort of patients with severe haemophilia A (<0.01 IU/L) whose first treatment was with ReFacto AF, monitored time to inhibitor development and described associated risk factors., Results: One hundred and three boys reached 50 EDs within the study period, of whom 35 developed an inhibitor (P(t ≤ 50) = 0.33, [95% CI: 0.25-0.43]), of which 15 (P(t ≤ 50) = 0.16, [95% CI: 0.10-0.25]) were high titre. Inhibitors arose after a median (interquartile range) 11 (7-16) EDs. Inhibitors were significantly associated with high-risk mutations and non-significantly associated with non-white ethnicity. Inhibitors were negatively associated with a family history of haemophilia A. High-titre inhibitors were significantly associated with a family history of inhibitors., Conclusion: Inhibitor incidence in a single country population of ReFacto AF PUPs was similar to that previously described. Low- and high-titre inhibitors were detected after a similar number of EDs, contrasting with previous data, probably reflecting standardized inhibitor monitoring within the United Kingdom., (© 2018 John Wiley & Sons Ltd.)