National Hemophilia Foundation

Abstract Sulfur stable isotope ratios (δ 34 S) have become increasingly common in archaeology for studying paleodiet, especially in occasions where there is a need to identify aquatic resource consumption more accurately. This is particularly relevant in the Baltic Sea region, where brackish conditions tend to mask “typical” marine carbon isotopic signals. Here we report new δ 34 S values for 126 human bone collagen samples which will be analyzed together with previously published data to investigate the potential of sulfur isotopes as an alternative proxy for aquatic resource consumption in historic period Estonia (ca. AD 1100‒1800). Bayesian statistical programming was used to provide quantitative dietary estimates, suggesting that the diet of the general population was predominantly terrestrial. The inclusion of δ 34 S as an additional dietary proxy produced generally comparable model results to the scenario that excluded δ 34 S. A sub-selection of samples was also radiocarbon dated and calibrated to take into account potential reservoir effects. For burials of commoners, the average contribution of 10% fish to dietary carbon does not significantly alter calibrated date ranges, even in the occasion where data on local reservoir effects is insufficient. This study has demonstrated both the potential and the pitfalls of using δ 34 S in this temporo-spatial context, and the new stable isotope and 14 C data have shed light onto individual site-histories but also to broader cultural processes and changes that occurred during these turbulent times in this region.

The healthcare systems in Asia vary greatly due to the socio-economic and cultural diversities which impact haemophilia management. An advisory board meeting was conducted with experts in haemophilia care from Asia to understand the heterogeneity in clinical practices and care provision in the region. The overall prevalence of haemophilia in Asia ranges between 3 and 8.58/100,000 patients. Haemophilia A was more prevalent as compared to haemophilia B with a ratio of around 5:1. There is under-diagnosis in the region due to lack of diagnosis, registries and/or lack of appropriate facilities in suburban areas. Most patients are referred to the haematologists by their families or primary care physicians, while some are identified during bleeding episodes. Genetic testing faces obstacles like resource constraints, services available at limited centres and unwillingness of patients to participate. Prophylaxis is offered for people with haemophilia (PWH) with a severe bleeding phenotype. Recombinant factors are approved in most countries across the region and are the preferred therapy. The challenges highlighted for not receiving a high standard of care include patients' reluctance to use an intravenous treatment, poor patient compliance due to frequency of infusions, budget constraints and lack of funding, insurance, availability and accessibility of factor concentrates. Prevalence of neutralizing antibodies ranged from 5% to 20% in the region. Use of immune tolerance induction and bypassing agents to treat inhibitors depends on their cost and availability. Haemophilia care in Asia has evolved to a great extent. However, some challenges remain for which a strategic approach along with multi-stakeholder involvement are needed.

Abstract A specialist nurse for over 20 years, Sandra reflects on her experience of finding ways to deliver effective care for a young girl with a very rare clotting disorder. Symptoms of the girl’s disorder were evident from birth and through an emergency use request Sandra and the care team enabled her family to access a treatment that at the time was in clinical trial. Poor venous access meant there was a need to adapt how treatment was administered and she worked with the girl’s parents to ensure that she was treated effectively. Alongside educating the parents, Sandra highlights the importance of her role in educating co-workers and other hospital staff likely to come into contact with the girl, to ensure that she always had access to timely and appropriate care. She also reflects on other instances where thinking creatively enabled patients in her care access to treatments that may not otherwise have been accessible. Now retired, Sandra continues to be involved in advocacy for people with bleeding disorders.

ABSTRACT Background Decades of research have transformed hemophilia from severely limiting children’s lives to a manageable disorder compatible with a full, active life, for many in high-income countries. The direction of future research will determine whether exciting developments truly advance health equity for all people with hemophilia (PWH). National Hemophilia Foundation (NHF) and American Thrombosis and Hemostasis Network conducted extensive inclusive all-stakeholder consultations to identify the priorities of people with inherited bleeding disorders and those who care for them. Research design and methods Working group (WG) 1 of the NHF State of the Science Research Summit distilled the community-identified priorities for hemophilia A and B into concrete research questions and scored their feasibility, impact, and risk. Results WG1 defined 63 top priority research questions concerning arthropathy/pain/bone health, inhibitors, diagnostics, gene therapy, the pediatric to adult transition of care, disparities faced by the community, and cardiovascular disease. This research has the potential to empower PWH to thrive despite lifelong comorbidities and achieve new standards of wellbeing, including psychosocial. Conclusions Collaborative research and care delivery will be key to capitalizing on current and horizon treatments and harnessing technical advances to improve diagnostics and testing, to advance health equity for all PWH.

ABSTRACT Background The National Hemophilia Foundation (NHF) conducted extensive, inclusive community consultations to guide prioritization of research in coming decades in alignment with its mission to find cures and address and prevent complications enabling people and families with blood disorders to thrive. Research Design and Methods With the American Thrombosis and Hemostasis Network, NHF recruited multidisciplinary expert working groups (WG) to distill the community-identified priorities into concrete research questions and score their feasibility, impact, and risk. WG6 was charged with identifying the infrastructure, workforce development, and funding and resources to facilitate the prioritized research. Community input on conclusions was gathered at the NHF State of the Science Research Summit. Results WG6 detailed a minimal research capacity infrastructure threshold, and opportunities to enable its attainment, for bleeding disorders centers to participate in prospective, multicenter national registries. They identified challenges and opportunities to recruit, retain, and train the diverse multidisciplinary care and research workforce required into the future. Innovative collaborative approaches to trial design, resource networking, and funding to surmount obstacles facing research in rare disorders were elucidated. Conclusions The innovations in infrastructure, workforce development, and resources and funding proposed herein may contribute to facilitating a National Research Blueprint for Inherited Bleeding Disorders.

ABSTRACT Introduction The National Hemophilia Foundation State of the Science Research Summit initiative sought to unify research efforts in the US inherited bleeding disorders (BDs) community around key topics of importance to people living with inherited BDs, the lived experience experts. Areas covered This community-led and -informed project focused on six broad areas – hemophilia A or B; von Willebrand Disease (VWD), platelet dysfunctions and other mucocutaneous inherited BDs; ultra-rare inherited BDs; the unique challenges of people with the potential to menstruate with inherited BDs; diversity, equity and inclusion, health services research, and implementation science; and facilitating research in the inherited BD community through designing an optimizied research infrastructure, enabling resources and funding, and furthering workforce capabilities required to execute the research priorities. Expert opinion The work summarized here, and in the accompanying supplement manuscripts , has implications not only for the US population but for people globally who have inherited BDs. The information is equally relevant to people living with hemophilia, VWD, the spectrum of inherited platelet disorders, ultra-rare factor deficiencies, and all other inherited BDs as it is to the health care providers and researchers focused on the care and treatment of inherited BDs in the US and globally.

Pharmacovigilance, the science and practice of monitoring the effects ofmedicinals and their safety, is the responsibility of all stakeholders involvedin the development, manufacture, regulation, distribution, prescription, and useof drugs and devices. The patient is the stakeholder most impacted by and thegreatest source of information on safety issues. It is rare, however, for thepatient to take a central role and exert leadership in the design and executionof pharmacovigilance. Patient organizations in the inherited bleeding disorderscommunity are among the most established and empowered, particularly in the raredisorders. In this review, two of the largest bleeding disorders patientorganizations, Hemophilia Federation of America (HFA) and National HemophiliaFoundation (NHF), offer insights into the priority actions required of allstakeholders to improve pharmacovigilance. The recent and ongoing increase inincidents raising safety concerns and a therapeutic landscape on the cusp ofunprecedented expansion heighten the urgency of a recommitment to the primacy ofpatient safety and well-being in drug development and distribution.Plain Language SummaryPatients at the center of product safetyEvery medical device and therapeutic product has potential benefits andharms. The pharmaceutical and biomedical companies that develop them mustdemonstrate that they are effective, and the safety risks are limited ormanageable, for regulators to approve them for use and sale. After theproduct has been approved and people are using it in their daily lives, itis important to continue to collect information about any negative sideeffects or adverse events; this is called pharmacovigilance. Regulators,like the United States (US) Food and Drug Administration, the companies thatsell and distribute the products, and healthcare professionals who prescribethem are all required to participate in collecting, reporting, analyzing,and communicating this information. The people with the most firsthandknowledge of the benefits and harms of the drug or device are the patientswho use them. They have an important responsibility to learn how torecognize adverse events, how to report them, and to stay informed of anynews about the product from the other partners in the pharmacovigilancenetwork. Those partners have a crucial responsibility to provide clear,easy-to-understand information to patients about any new safety concernsthat come to light. The community of people with inherited bleedingdisorders has recently encountered problems with poor communication ofproduct safety issues, prompting two large US patient organizations,National Hemophilia Foundation and Hemophilia Federation of America, to holda Safety Summit with all the pharmacovigilance network partners. Togetherthey developed recommendations to improve the collection and communicationof information about product safety so that patients can make well-informed,timely decisions about their use of drugs and devices. This article presentsthese recommendations in the context of how pharmacovigilance is supposed towork and some of the challenges encountered by the community.

IntroductionDecades of inherited bleeding disorders (BD) research transformed severe haemophilia from a childhood killer to a disorder managed across a full lifespan for many in economically developed countries. Health equity, a life unimpaired by disease complications, however, remains unimaginable for most people with an inherited BD (PWIBD).AimThe National Hemophilia Foundation (NHF) and American Thrombosis and Hemostasis Network (ATHN) undertook the development of a community‐driven United States (US) National Blueprint for Inherited Bleeding Disorders Research to transform the experience of all PWIBD and those who care for them.MethodsExtensive community consultations were conducted to identify the issues most important to PWIBD and those who love and care for them. Expert multidisciplinary teams distilled these key areas of need into prioritised research questions, and identified the resources and infrastructure required to pursue them. A summit was held to gather feedback and inform the detailed blueprint.ResultsCommunity‐prioritised research areas fell into three broad categories: issues common across inherited BDs, those specific to individual disorders, and issues of infrastructure and capacity. NHF State of the Science Research Summit discussions of the research questions derived from the community priorities by six working groups provided important input for the drafting of the research blueprint for the coming decades.ConclusionThe inherited BD community came together to develop the US National Blueprint for Inherited Bleeding Disorders Research dedicated to transforming the lives of all PWIBD including innovating solutions for the rarest disorders and under‐represented populations.