A retrospective cohort study on European Reference Network for Rare Vascular Diseases 5 outcome measures for Hereditary Haemorrhagic Telangiectasia in Denmark

Background Hereditary Haemorrhagic Telangiectasia (HHT) is an autosomal dominant disorder characterized by several clinical symptoms including epistaxis, arteriovenous malformations (AVM), and telangiectasia. In 2018, European Reference Network for Rare Vascular Diseases (VASCERN) recommended five outcome measures for HHT-patients to guide health care providers, some with limited experience in treating HHT, and thereby maximizing the number of HHT-patients receiving good care. The outcome measures cover the following aspects: (1) 90% of the patients should receive a pulmonary AVM (PAVM) screening; (2) 90% of the patients should receive written advice on nosebleed; (3) 70% should be assessed for iron deficiency; (4) 100% of the patients should receive written advice on antibiotic (AB) prophylaxis prior to dental and surgical procedures, and (5) 100% of relevant patients should receive written advice on pregnancy. We have introduced the outcome measures as Benchmarks in our HHT-centre and wanted to evaluate the extend of implementation we have achieved. We constantly struggle to secure the best possible treatment of our HHT-patients. Methods The study was a non-interventional retrospective study. Data was collected manually from patient records and from the Danish HHT-database. Results A total of 180 HHT-patients were included, all diagnosed in the period from January 1st, 2016, to December 31st, 2020. All patients were screened for PAVM. We could confirm that 66% of patients who had epistaxis received thoroughly advice. Assessment for iron deficiency was performed in 80% of the adult patients. Thoroughly advice on AB prophylaxis was documented in 75%. Thoroughly advice on pregnancy was documented in 80% of female patients 15–45 years of age. There were no significant differences over time for any of the outcome measures. Conclusions The Danish HHT-centre reached the target threshold for outcome measures 1 and 3. It could not be documented that the target thresholds for outcome measures 2, 4, and 5 were achieved. As information and education are a very important part of HHT care, focus on and documentation that all patients receive the relevant advice must be a priority in order to ensure best care.

A complex unit for a complex disease: the HCM-Family Unit

Hypertrophic cardiomyopathy (HCM) is a group of heterogeneous disorders that are most commonly passed on in a heritable manner. It is a relatively rare disease around the globe, but due to increased rates of consanguinity within the Kingdom of Saudi Arabia, we speculate a high incidence of undiagnosed cases. The aim of this paper is to elucidate a systematic approach in dealing with HCM patients and since HCM has variable presentation, we have summarized differentials for diagnosis and how different subtypes and genes can have an impact on the clinical picture, management and prognosis. Moreover, we propose a referral multi-disciplinary team HCM-Family Unit in Saudi Arabia and an integrated role in a network between King Faisal Hospital and Inherited and Rare Cardiovascular Disease Unit-Monaldi Hospital, Italy (among the 24 excellence centers of the European Reference Network (ERN) GUARD-Heart). Graphical Abstract

Current Clinical Practice for Thromboprophylaxis Management in Patients With Cushing’s Syndrome Across Reference Centers of the European Reference Network on Rare Endocrine Conditions (Endo-ERN)

Background: Cushing’s syndrome (CS) is associated with an hypercoagulable state and an increased risk of venous thromboembolism (VTE). Evidence-based guidelines on thromboprophylaxis strategies in patients with CS are currently lacking. We aimed to map the current clinical practice for thromboprophylaxis management in patients with CS across reference centers (RCs) of the European Reference Network on Rare Endocrine Conditions (Endo-ERN), which are endorsed specifically for the diagnosis and treatment of CS. Using the EU survey tool, a primary screening survey, and subsequently a secondary, more in-depth survey were developed. Results: The majority of the RCs provided thromboprophylaxis to patients with CS (n=23/25), although only one center had a standardized thromboprophylaxis protocol (n=1/23). RCs most frequently started thromboprophylaxis from CS diagnosis onwards (n=11/23), and the majority stopped thromboprophylaxis based on individual patient characteristics, rather than standardized treatment duration (n=15/23). Factors influencing the initiation of thromboprophylaxis were ‘medical history of VTE’ (n=15/23) and ‘severity of hypercortisolism’ (n=15/23). Low-Molecular-Weight-Heparin was selected as the first-choice anticoagulant drug for thromboprophylaxis by all RCs (n=23/23). Postoperatively, the majority of RCs reported ‘severe immobilization’ as an indication to start thromboprophylaxis in patients with CS (n=15/25). Most RCs (n=19/25) did not provide standardized testing for variables of hemostasis in the postoperative care of CS. Furthermore, the majority of the RCs provided preoperative medical treatment to patients with CS (n=23/25). About half of these RCs (n=12/23) took a previous VTE into account when starting preoperative medical treatment, and about two-thirds (n=15/23) included ‘reduction of VTE risk’ as a goal of treatment. Conclusions: There is a large practice variation regarding thromboprophylaxis management and perioperative medical treatment in patients with CS, even in Endo-ERN RCs. Randomized controlled trials are needed to establish the optimal prophylactic anticoagulant regimen, carefully balancing the increased risk of (perioperative) bleeding, and the presence of additional risk factors for thrombosis.

Hereditary haemorrhagic telangiectasia: development of a regional life-course collaborative clinical care pathway

Hereditary haemorrhagic telangiectasia is a rare, genetic disorder that can present at any age. It is characterised by epistaxis, mucocutaneous telangiectasia and visceral arteriovenous malformations, which can affect multiple organs. Early diagnosis and management reduces the morbidity and mortality associated with the disease. There is a well-established hereditary haemorrhagic telangiectasia clinic in London, and excellent links across Europe via the European Reference Network. However, local coordinated care for patients with hereditary haemorrhagic telangiectasia across the UK can be variable and often absent for children and young people. Some patients travel long distances to receive care in London, while others are referred to local clinicians or lost to follow up entirely. This article presents the experience to date from two regional UK centres (Liverpool and Dundee) where care for patients with hereditary haemorrhagic telangiectasia is being coordinated and streamlined. While there is still a lot to learn, this article highlights some of the successes and challenges identified so far, with suggestions for how these could be addressed. Collaborative regional networks such as these can facilitate the sharing of best practice and ensure that all patients with hereditary haemorrhagic telangiectasia are able to access safe, high-quality care.

Overview of the Clinical Features of Li-Fraumeni Syndrome and the Current European ERN GENTURIS Guideline

Patients with a tumour-risk syndrome have a significantly increased risk of developing cancer during their lifetime. A positive family history of tumour disease or an unusually early age of onset may be indicative of a tumour risk syndrome. With the diagnosis of a tumour risk syndrome it is possible to recommend a risk-adapted tumour surveillance programme for the patient and (asymptomatic) family members at risk. This facilitates early detection of possible tumours and thus often prevents advanced tumour stages. Li-Fraumeni syndrome is associated with a significantly increased risk of sarcoma and breast cancer in particular, but it is often not diagnosed clinically in those affected. This article reviews the clinical picture, genetic cause and special aspects in the diagnosis and care of patients with Li-Fraumeni syndrome. The initiative resulted from the European reference network GENTURIS, which has set itself the task of improving the identification and care of patients with tumour risk syndromes. A first step is the recent publication of a European guideline for Li-Fraumeni syndrome, which is summarised here and discussed in the context of existing recommendations.

Establishing and Boosting Communication in The European Reference Network For Rare Neurological Diseases (ERN-RND): The Impact of Offering Free Educational Webinars

Background: Since it first started operating in 2017, the European Reference Network for Rare Neurological Diseases (ERN-RND) implemented a multi-channel communication strategy to effectively reach its target audience: healthcare professionals, patients, researchers, industry representatives and the general public. It first created a website containing useful and up to date information followed by social media accounts. We compared the analytical data collected about the ERN-RND website and social media channels (Twitter, Facebook, YouTube) during two periods: October 2018 to September 2019 and the year after the ERN-RND free educational webinars were launched, from October 2019 to September 2020. This allowed us to quantify the impact of offering a tangible product (webinars) on the communication strategy. Results: The analytical data obtained from October 2018 to September 2019 and from October 2019 to September 2020 clearly shows a significant increase in traffic and followers since the launch of the ERN-RND webinars in November 2019. We also created a communication survey which was disseminated between February and June 2021. We collected responses from 61 people: 38 healthcare professionals, 11 scientists, 10 patients (advocates), 2 industry representatives, 1 patient association, 1 charity representative, 1 resident and 1 master student. Most respondents answered ”webinars” as the number one reason when asked about which content they look for on the ERN-RND website. Conclusions: Offering a tangible product - such as the webinars presented in this report - to a specific target group (healthcare professionals) supported our communication strategy by driving traffic to ERN-RND communication channels. It has also successfully tackled ERN-RND’s general aim: by enabling the flow of knowledge on rare neurological and movement disorders reach the medical community in hospitals treating patients with these rare and complex conditions, patients ultimately benefit from improved and faster diagnosis, care, and treatment. We aim to set up similar strategies to effectively reach other or the same target groups. For healthcare professionals, organising eConsultations via the Clinical Patient Management System (CPMS) or disseminating standards of care such as diagnostic and therapeutic algorithms as well as clinical practice guidelines might offer potential. For the patient community, organising customised and multilingual webinars could also work.

A retrospective cohort study on European Reference Network for Rare Vascular Diseases 5 outcome measures for Hereditary Haemorrhagic Telangiectasia in Denmark

Background Hereditary Haemorrhagic Telangiectasia (HHT) is an autosomal dominant disorder characterized by several clinical symptoms including epistaxis, arteriovenous malformations (AVM), and telangiectasia. In 2018, European Reference Network for Rare Vascular Diseases (VASCERN) recommended five outcome measures for HHT-patients to guide health care providers, some with limited experience in treating HHT, and thereby maximizing the number of HHT-patients receiving good care. The outcome measures cover the following aspects: 1) 90% of the patients should receive a pulmonary AVM (PAVM) screening; 2) 90% of the patients should receive written advice on nosebleed; 3) 70% should be assessed for iron deficiency; 4) 100% of the patients should receive written advice on antibiotic (AB) prophylaxis prior to dental and surgical procedures, and; 5) 100% of relevant patients should receive written advice on pregnancy. We have introduced the outcome measures as Benchmarks in our HHT-centre and wanted to evaluate the extend of implementation we have achieved. We constantly struggle to secure the best possible treatment of our HHT-patients.Methods The study was a non-interventional retrospective study. All data was collected from medical journals and from the Danish HHT-database. Results A total of 180 HHT-patients were included, all diagnosed in the period from January 1st 2016 to December 31st 2020. All patients were screened for PAVM. We could confirm that 66% of patients who had epistaxis received thoroughly advice. Assessment for iron deficiency was performed in 80 % of the adult patients. Thoroughly advice on antibiotic prophylaxis was documented in 75%. Thoroughly advice on pregnancy was documented in 80% of female patients 15-45 years of age. There were no significant differences over time for any of the outcome measures. Conclusions The Danish HHT-centre reached the target threshold for outcome measures 1 and 3. We could not document reaching the target thresholds for outcome measures 2, 4, and 5. As information and education is a very important part of HHT care, we will focus on and document that all patients receive the relevant advice and as part of our care, we will in the near future implement an electronic solution with advice for HHT patients.

Efficacy of Sirolimus in Patients Requiring Tracheostomy for Life-Threatening Lymphatic Malformation of the Head and Neck: A Report From the European Reference Network

Extensive lymphatic malformations (LMs) of the head and neck region may require tracheostomy to secure the airway. Treatment of these life-threatening LMs is usually multimodal and includes sclerotherapy and surgery, among others. Recently, systemic therapy with sirolimus has been introduced as an effective treatment for venous and lymphatic malformations; its efficacy and safety profile in patients with extensive LM requiring tracheostomy are, however, as yet not fully known. We performed a retrospective, multicenter review and identified 13 patients with an extensive LM of the head and neck region, who previously underwent placement of tracheostomy and subsequently received sirolimus treatment with the aim to improve the local respiratory situation and remove the tracheostomy. Under sirolimus therapy, tracheostomy could be reversed in 8/13 (62%) patients, a further 2/13 (15%) patients improved markedly, and removal of the tracheostomy was planned at the time of writing, while 3/13 (23%) patients showed insufficient or absent response to sirolimus, rendering tracheostomy reversal not feasible. The median duration of sirolimus treatment until removal of tracheostomy was 18 months (range, 8 months to 5.6 years). Adverse events of sirolimus therapy were common [10/13 (77%) patients], yet the majority of these were mild [9/10 (90%) patients] and only one severe adverse event was recorded, with ulceration and necrosis at a catheter insertion site. In conclusion, sirolimus can be considered an effective and safe salvage treatment in patients with extensive LM even after placement of a tracheostomy, as closure of the latter was possible in the majority of patients (62%) of our retrospective cohort. A better understanding of when to start sirolimus therapy, of the duration of treatment, and of factors allowing the prediction of treatment response will require further investigation.