Addressing Thalassaemia Management from Patients' Perspectives: An International Collaborative Assessment.

Background and Objectives: The effective management of chronic diseases, particularly hereditary and rare diseases and thalassaemia, is an important indicator of the quality of healthcare systems. We aimed to assess healthcare services in different countries for thalassaemia patients by using publicly available health indicators and by surveying thalassaemia patients and their caregivers. Materials and Methods: We reviewed official worldwide databases from the WHO, World Bank, and scientific resources, and we used a structured patient-tailored self-completed questionnaire to survey thalassaemia patients and their caregivers in 2023. Results: A total of 2082 participants were surveyed (mean age, 27 years; males, 42%). About 1 in 4 respondents did not complete high-school education, while 24% had a bachelor's degree. About a third of respondents were married and were in either full- or part-time employment. The vast majority (~80%) had initiated transfusion therapy between 1 and 4 years of age. Only 42% reported no delays in receiving blood transfusion, while 47% reported occasional delays and 8% serious delays. About half of patients reported being very satisfied (11%) or satisfied (38%) with the quality of services provided, while 1 in 3 patients reported being unsatisfied or very unsatisfied, and that their access to treatment was difficult or very difficult due to traveling expenses and the high cost of treatment. Conclusions: Important improvements in the care of thalassaemia patients have been documented during the past few decades. Nevertheless, additional focus is required through national healthcare systems to effectively address the many unmet needs revealed by our recent survey, as well as to achieve satisfactory patient outcomes.

The Need for Translational Epidemiology in Beta Thalassemia Syndromes: A Thalassemia International Federation Perspective.

Epidemiology is the practical tool to provide information on which policy makers should base planning of services. Epidemiological data for thalassemia is based on inaccurate and often conflicting measurements. This study attempts to demonstrate with examples the sources of inaccuracy and confusion. The Thalassemia International Foundation (TIF) suggests that congenital disorders, for which increasing complications and premature death are avoidable through appropriate treatment and follow-up, should be given priority based on accurate data and patient registries. Moreover, only accurate information about this issue, especially for developing countries, will move national health resources in the right direction.

2021 Thalassaemia International Federation Guidelines for the Management of Transfusion-dependent Thalassemia.

Beta-thalassemia and particularly its transfusion-dependent form (TDT) is a demanding clinical condition, requiring life-long care and follow-up, ideally in specialized centers and by multidisciplinary teams of experts. Despite the significant progress in TDT diagnosis and treatment over the past decades that has dramatically improved patients' prognosis, its management remains challenging. On one hand, diagnostic and therapeutic advances are not equally applied to all patients across the world, particularly in several high-prevalence eastern regions. On the other, healthcare systems in low-prevalence western countries that have recently received large numbers of migrant thalassemia patients, were not ready to address patients' special needs. Thalassaemia International Federation (TIF), a global patient-driven umbrella federation with 232 member-associations in 62 countries, strives for equal access to quality care for all patients suffering from thalassemia or other hemoglobinopathies in every part of the world by promoting education, research, awareness, and advocacy. One of TIF's main actions is the development and dissemination of clinical practice guidelines for the management of these patients. In 2021, the fourth edition of TIF's guidelines for the management of TDT was published. The full text provides detailed information on the management of TDT patients and the clinical presentation, pathophysiology, diagnostic approach, and treatment of disease complications or other clinical entities that may occur in these patients, while also covering relevant psychosocial and organizational issues. The present document is a summary of the 2021 TIF guidelines for TDT that focuses mainly on clinical practice issues and recommendations.

Thalassaemia Registries: A Call for Action. A Position Statement from the Thalassaemia International Federation.

Disease registries can be extremely powerful evidence generating tools while providing a central meeting point for all implicated stakeholders, facilitating their networking and interaction. Registries can play a major role in addressing the challenges that the care of thalassemia patients is currently facing. By collecting updated and representative data on disease burden, features, management and outcomes at local, national, regional and global level, thalassemia registries can allow the evaluation and bench marking of provided healthcare services, the detection of unmet clinical needs and the identification of inequalities in healthcare delivery. A total of 17 thalassemia registries has been in place since 1984, being characterized by heterogeneity and incomplete geographic coverage. Representativeness, interoperability, harmonization, quality assurance and sustainability are important features that thalassemia registries should pursue. The Thalassaemia International Federation (TIF) aims at promoting the coordination and collaboration in existing thalassemia registries and the establishment of new ones, with a particular focus on areas of emerging economies. In this regard, TIF has undertaken the design, development and implementation of a web-based platform to host a global thalassemia registry.

Estimating the Cost of Thalassemia Care across the World: A Thalassemia International Federation Model.

Estimating the cost of thalassemia care is important for the optimization of care planning, resource allocation and the empowerment of patient advocacy. However, available evidence is heterogeneous, reflecting diverse healthcare systems and cost estimation methods. We sought to build a globally applicable cost model for thalassemia care. We followed a three-step approach, including (i) a targeted literature review to identify previous cost-of-illness studies on thalassemia; (ii) a generic model development based on the main determinants of cost in different countries emerged from a literature review and validated by a team of medical experts; (iii) a piloting of the model using data from two diverse countries. The literature review revealed studies focusing on the total costs of thalassemia care or the cost or cost-effectiveness of specific treatment or prevention modalities in high- and low-prevalence countries across the world. The resulting evidence was used to build a model that calculates total annual therapy cost based on entry of country-level and patient-level data, and data on healthcare modalities, indirect costs and prevention. Testing the model using published data from the UK, Iran, India and Malaysia, revealed an annual cost per patient of £81,796.00 for the UK, Iranian rial (IRR) 13,757.00 for Iran, Indian rupee (INR) 166,750.00 for India and Malyasian ringgit (or dollar) (MYR) 111,372.00 for Malaysia. A globally applicable model that calculates total annual cost of thalassemia care was built based on existing evidence. The model successfully predicted the annual cost of thalassemia care in the UK, Iran, India and Malaysia.

COVID-19 pandemic and the great impulse to telemedicine: the basis of the WONCA Europe Statement on Telemedicine at the WHO Europe 70th Regional Meeting September 2020.

Telemedicine is the use of telecommunication and information technologies to support the delivery of healthcare at a distance, guaranteeing patients healthcare by facilitating access where barriers exist; the COVID-19 pandemic has attracted worldwide interest in this field.The purpose of this paper is to highlight the main pros and cons of telemedicine, which serve as the basis of the WONCA Europe Statement at the WHO Europe 70th Regional Meeting on 14 September 2020.Pros of telemedicine include virtual healthcare at home, where patients receive support in certain conditions without leaving their houses. During a pandemic, it can be adopted to limit physical human interaction. Unfortunately, it can negatively affect the quality of the doctor-patient relationship, the quality of the physical examination, and the quality of care. Telemedicine requires effective infrastructure and robust investments to be feasible and effective.

The Prevention of Thalassemia Revisited: A Historical and Ethical Perspective by the Thalassemia International Federation.

Hemoglobinopathies are the most common monogenic disorders in humans; among them, thalassemia constitutes a serious medical and public health problem in high prevalence regions, in a geographical zone ranging from the Mediterranean Basin to China. In addition, migrations over the years have introduced thalassemia to many parts of the world. Although disease-specific programs are in place and accessible to most patients in prosperous countries, this is not the case in developing economies, where more than 75.0% of the patient population is born and lives; this concerns both prevention and treatment programs. In view of the significant improvements in public health and healthcare systems over the past few years, the Thalassemia International Federation has revisited the thalassemia prevention programs, initiatives and policies in some of its member countries, discussing their effectiveness and whether any changes in policy or public attitudes to thalassemia prevention have occurred through the recent years.

COVID-19 and thalassaemia: A position statement of the Thalassaemia International Federation.

OBJECTIVES: Many patients with haemoglobinopathies, including thalassaemia and sickle cell disease, are at increased risk of developing severe complications from the coronavirus disease 2019 (COVID-19). Although epidemiologic evidence concerning the novel coronavirus (SARS-CoV-2) infection in these patients is currently lacking, the COVID-19 pandemic represents a significant challenge for haemoglobinopathy patients, their families and their attending physicians. METHODS: The present statement summarizes the key challenges concerning the management of haemoglobinopathies, with particular focus on patients with either transfusion-dependent or non-transfusion-dependent thalassaemia, identifies the gaps in knowledge and suggests measures and strategies to deal with the pandemic, based on available evidence and expert opinions. Key areas covered include patients' risk level, adaptation of haemoglobinopathy care, safety of blood transfusions, blood supply challenges, and lifestyle and nutritional considerations. CONCLUSIONS: The proposed measures and strategies may be useful as a blueprint for other disorders which require regular hospital visits, as well as for the timely adaptation of patient care during similar future pandemics.

The changing epidemiology of the ageing thalassaemia populations: A position statement of the Thalassaemia International Federation.

Therapeutic advances in ß-thalassaemia have gradually lead to a significant improvement in prognosis over the past few decades. As a result, patients living in areas where disease-specific programmes offering access to modern therapy are in place experience a new era of prolonged survival that tends to reach that of the normal population. This ageing thalassaemia population, however, faces a new spectrum of comorbidities resulting from increasing age that may jeopardise the advances in prognosis provided by current therapy and thus poses new challenges in diagnosis, monitoring and treatment. In this position paper of the Thalassaemia International Federation, we review the changing epidemiology and clinical spectrum of patients with ß-thalassaemia and propose actions to be undertaken in order to address the emerging spectrum of comorbidities resulting from ageing.

EHA Research Roadmap on Hemoglobinopathies and Thalassemia: An Update.

The inherited disorders of hemoglobin, which include sickle cell disease and thalassemias, are the most common and widespread distributed monogenic disorders. Due to a selective advantage in malaria regions, these hemoglobin defects are particularly frequent in Africa, Asia, or in the Mediterranean areas, where malaria was endemic until the last century. In recent decades, the globalization of migration has contributed to generate multiethnic European societies. Due to migration from countries or regions with high hemoglobinopathy frequencies such as Africa, Middle East, or Asia, large numbers of patients with these disorders are living in almost every European country today. Furthermore, the numbers are increasing because of increasing refugee flows toward Europe. Additional requirements are the development of European recommendations and guidelines for diagnosis and effective therapeutic approaches. These, together with the advancement of clinical trials using new drugs and therapeutic procedures could ameliorate the quality of life of patients affected with these diseases and increase their life expectancy. Lastly, coordinated efforts should be made to develop diagnostic pathways for thalassemias and hemoglobinopathies, in order to plan interventions, including prenatal diagnosis and cure. For these reasons, the development of new tools to reliably diagnose anemias is urgently needed and fits well with the needs of personalized medicine. In the last 15 years, hematology research has made many big leaps forward. Our general aim will be to solve several hematologic problems using these new approaches. We expect that the development of such a diagnostic tool will improve timely diagnosis throughout Europe, especially in those countries where it is difficult to gain access to "classical" diagnostic tests.

Haemoglobinopathies in Europe: health & migration policy perspectives.

BACKGROUND: Major haemoglobinopathies (MH), such as thalassaemia syndromes (Thal) and sickle cell disorders (SCD), are genetic defects associated with chronic anaemia and other complications. In Europe, MH are rare diseases (RD) but their prevalence is significantly growing in many countries due to mobility and migration flows. This creates a growing health problem in the EU that has not yet been effectively addressed by Member States (MS) authorities. The present study has been conducted with the aim of: (i) providing an overview of policies for MH in 10 EU member states (MS) (ii) analysing the challenges linked to these RD due to growing requirements imposed by population, mobility and migration trends and (iii) identifying gaps, proposing improvements on existing policies, or developing new ones to fit the identified needs. METHODS: The study has been undertaken by a group of members of the European Network for Rare and Congenital Anaemias (ENERCA) and the Thalassaemia International Federation (TIF), in collaboration with the public affairs firm Burson-Marsteller Brussels. Data from 10 EU countries have been gathered using targeted desk research and one-to-one interviews with local stakeholders, including healthcare professionals, patients and public health officers/providers. RESULTS: 1. MH are the most common RD in all the 10 countries, 2. Data on prevalence, overall burden, trends, and clinical follow up costs are lacking in most countries. 3. Neonatal screening practices show a wide variation across and within countries. 4. Awareness on MH and their related complications is very low, exception made of Italy, Greece, Cyprus and UK, 5. No disaggregated data is available to understand the impact of mobility and migration on the prevalence of haemoglobinopathies, and how healthcare delivery systems should adapt to respond to this situation. 6. Targeted policy measures and/or actions are generally lacking and/or delayed. CONCLUSIONS: Ten policy recommendations have been drawn from this study, building on 2006 WHO recommendations for MH to include haemoglobinopathies in National Plans of Actions for Rare Diseases.

The impact of migrations on the health services for rare diseases in Europe: the example of haemoglobin disorders.

Migration from different parts of the world to several European countries leads to the introduction of haemoglobinopathy genes into the population, which creates several demanding needs for prevention and treatment services for Hb disorders. In this paper we examined the degree to which European health services have responded to such challenges and in particular to health services necessary to address the needs of patients with thalassaemia and sickle cell disease (SCD). Information on available services was obtained from international organizations, collaborated European project, and the Thalassaemia International Federation (TIF) Databases, which include information from published surveys, registries, field trips, and delegation visits to countries and regions by expert advisors, local associations, and other collaborators' reports. Results show that countries with traditional strong prevention and treatment programs are well prepared to face the above challenges, while others are urgently needed to address these problems in a systematic way. The Thalassaemia International Federation (TIF) is committed to monitor the progress, raise awareness, and support the promotion of more immigrant-oriented health policies to ensure their integration in society and their access to appropriate, adequate, and timely health services.

Cross-talk between available guidelines for the management of patients with beta-thalassemia major.

Efforts to optimize the management of patients with ß-thalassemia major (TM) continue to expand. Evidence from biomedical research evaluating safe and careful processing measures of blood products, the efficacy and safety of oral iron chelators, and noninvasive techniques for the assessment of iron overload are translated into better patient outcomes. The construction of TM management guidelines facilitated the incorporation of such evidence into practice. However, as several aspects of the management of TM remain controversial or governed by resource availability, a concern regarding potential variations in recommendations made by the different guidelines becomes rational, especially for physicians treating TM patients outside countries where the guidelines were constructed. In this work, we overview currently available guidelines for the management of TM and explore apparent similarities and differences between them. The evaluated guidelines included the Thalassaemia International Federation, US, Canadian, UK, Italian and Australian guidelines. We noted a general consensus for most aspects of management, although some guidelines provided more comprehensive and contemporary recommendations than others. We did not identify differences warranting concern, although minor differences in iron overload assessment strategy and more notable variations in the recommendations for iron chelation therapy were observed.

Epidemiology of rare anaemias in Europe.

Registry and epidemiological data of Rare Anaemias (RA) in Europe is in general still incomplete and/or partially documented. One important issue is the increasing prevalence of haemoglobin disorders (HD) due to migrations from high prevalence areas. The size of the problem, particularly for sickle cell disease (SCD), is already having an impact on health services in many European countries. The best known cause of rare anaemias associated with congenital haemolytic anaemia (CHA) in Europe is Hereditary Spherocytosis (HS) a red blood cell (RBC) membrane defect with a prevalence of 1 to 5 cases per 10.000 individuals. Some other causes of CHA are extremely rare and only few individual cases have been described worldwide (i.e. some RBC enzymopathies). Congenital defects of erythropoiesis are less frequent Diamond-Blackfan Anaemia (DBA) and Fanconi Anaemia (FA) exhibit a very low prevalence ranging from 4 to 7 per million live births. Congenital Dyserythropoietic Anaemia (CDA), a genetically heterogenous group, is still less frequent and exhibits a large variability of frequency depending on the European region: 0.1-3.0 cases per million births In addition many cases are known from a large autosomal dominant family in Sweden. Although incidence of Paroxysmal Nocturnal Haemoglobinuria (PNH) in Europe is still unknown, data collection from different sources has given quotes of 1 case per 100,000 individuals to 5 cases per million births.

Requirements for a reference or expert thalassemia center: the structure/model for centers dealing with chronic/hereditary blood disorders.

Chronic disorders, such as the hemoglobin disorders, have a multi-organ involvement and are subject to complications, requiring multidisciplinary care. Most convenient for the patient is the concentration of expertise under one roof and where routine care, such as blood transfusions, can be provided away from acutely ill patients with episodic infections and other conditions. These specialized centers already exist but as yet the standards, which should designate a center as an expert center or a reference center, have not yet been specified or applied. This article examines standards that have been described by two separate authorities in the United States and Europe and suggests the application of these standards to existing or proposed hemoglobinopathy centers.

An electronic infrastructure for research and treatment of the thalassemias and other hemoglobinopathies: the Euro-mediterranean ITHANET project.

Hemoglobin (Hb) disorders are common, potentially lethal monogenic diseases, posing a global health challenge. With worldwide migration and intermixing of carriers, demanding flexible health planning and patient care, hemoglobinopathies may serve as a paradigm for the use of electronic infrastructure tools in the collection of data, the dissemination of knowledge, the harmonization of treatment, and the coordination of research and preventive programs. ITHANET, a network covering thalassemias and other hemoglobinopathies, comprises 26 organizations from 16 countries, including non-European countries of origin for these diseases (Egypt, Israel, Lebanon, Tunisia and Turkey). Using electronic infrastructure tools, ITHANET aims to strengthen cross-border communication and data transfer, cooperative research and treatment of thalassemia, and to improve support and information of those affected by hemoglobinopathies. Moreover, the consortium has established the ITHANET Portal, a novel web-based instrument for the dissemination of information on hemoglobinopathies to researchers, clinicians and patients. The ITHANET Portal is a growing public resource, providing forums for discussion and research coordination, and giving access to courses and databases organized by ITHANET partners. Already a popular repository for diagnostic protocols and news related to hemoglobinopathies, the ITHANET Portal also provides a searchable, extendable database of thalassemia mutations and associated background information. The experience of ITHANET is exemplary for a consortium bringing together disparate organizations from heterogeneous partner countries to face a common health challenge. The ITHANET Portal as a web-based tool born out of this experience amends some of the problems encountered and facilitates education and international exchange of data and expertise for hemoglobinopathies.

Thalassaemic bone disease. An overview.

Thalassaemic bone disease is a composite entity in which structural damage to bone is brought about by several influences, each of which may affect the bone in a different way and to a variable degree, but which may co-exist in individual patients. Understanding these damaging factors in each patient should lead to an orthologistic approach to management. However there is currently no agreed investigational protocol for the elucidation of these factors and no evidence based protocol for management. In this article the role of each of the causative influences is reviewed according to current literature and a critical examination of investigation and management is made. The conclusion is that there is a lack of agreed guidelines for the investigation and monitoring of thalassaemia patients and a lack of evidence based protocol for management of patients whose bone disease starts at an early age and continues for the rest of their lives. The natural history of this complex osteopathy and the long term effects of therapy are not well documented.

The role of the Thalassaemia International Federation in health professionals' education.

The Thalassaemia International Federation (TIF) was established in 1986. The Federation has two important objectives: 1. To promote the continued control of thalassaemia major in countries with existing policies aimed at control, and 2. To support the establishment of policies of control in every affected country of the world. Over the years TIF has: - Held workshops and seminars attended by over 7,000 from 35 countries - Organized 11 International Conferences attended by 5,150 from 62 countries - Organized field trips/delegation visits in 42 countries - Prepared, published and distributed 70,000 books to 96 countries - Trained physicians and scientists from medical centres in the UK, US, Italy, Greece and Cyprus - Initiated and co-ordinated projects and clinical studies overseen by international experts in over 50 countries. - Established a vast network of scientific collaborators from every corner of the world, and - Has promoted close and productive collaborations with major health organizations. One of the most important projects that TIF has conducted was a multi-centre study on endocrine complications in the different affected regions of the world. It is hopeful that through the analysis of data already obtained and expected, other projects related to blood transfusion therapy, iron chelation and chronic hepatitis could be organized.