The COVID-19 pandemic impact on continuity of care provision on rare brain diseases and on ataxias, dystonia and PKU. A scoping review.

One of the most relevant challenges for healthcare providers during the COVID- 19 pandemic has been assuring the continuity of care to patients with complex health needs such as people living with rare diseases (RDs). The COVID-19 pandemic accelerated the healthcare sector's digital transformation agenda. The delivery of telemedicine services instead of many face-to-face procedures has been expanded and, many healthcare services not directly related to COVID-19 treatments shifted online remotely. Many hospitals, specialist centres, patients and families started to use telemedicine because they were forced to. This trend could directly represent a good practice on how care services could be organized and continuity of care could be ensured for patients. If done properly, it could boast improved patient outcomes and become a post COVID-19 major shift in the care paradigm. There is a fragmented stakeholders spectrum, as many questions arise on: how is e-health interacting with 'traditional' healthcare providers; about the role of the European Reference Networks (ERNs); if remote care can retain a human touch and stay patient centric. The manuscript is one of the results of the European Brain Council (EBC) Value of Treatment research project on rare brain disorders focusing on progressive ataxias, dystonia and phenylketonuria with the support of Academic Partners and in collaboration with European Reference Networks (ERNs) experts, applying empirical evidence from different European countries. The main purpose of this work is to investigate the impact of the COVID-19 pandemic on the continuity of care for ataxias, dystonia and phenylketonuria (PKU) in Europe. The analysis carried out makes it possible to highlight the critical points encountered and to learn from the best experiences. Here, we propose a scoping review that investigates this topic, focusing on continuity of care and novel methods (e.g., digital approaches) used to reduce the care disruption. This scoping review was designed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews (PRISMA-ScR) standards. This work showed that the implementation of telemedicine services was the main measure that healthcare providers (HCPs) put in place and adopted for mitigating the effects of disruption or discontinuity of the healthcare services of people with rare neurological diseases and with neurometabolic disorders in Europe.

Long-term outcomes of COVID-19 vaccination in patients with rare and complex connective tissue diseases: The ERN-ReCONNET VACCINATE study.

Background: Vaccination is one of the most important measures to contain the COVID-19 pandemic, especially for frail patients. VACCINATE is a multicentre prospective observational study promoted by the European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases (ERN ReCONNET) aimed at assessing the long-term outcomes of COVID-19 vaccination in patients with rare and complex connective tissue diseases (rcCTDs) in terms of efficacy and safety. Methods: Adult rcCTDs patients were eligible for recruitment. Demographic, clinical and vaccination data were collected at enrolment. Follow-up visits were scheduled 4, 12, 24, 36 and 48 weeks after completion of the first vaccination cycle; data on adverse events, disease exacerbations and the occurrence of new SARS-CoV-2 infections were collected at these time-points. Findings: 365 rcCTDs patients (87 % female, mean age 51.8 ± 14.6 years) were recruited. Overall, 200 patients (54.8 %) experienced at least one adverse event, generally mild and in most cases occurring early after the vaccination. During follow-up, 55 disease exacerbations were recorded in 39 patients (10.7 %), distributed over the entire observation period, although most frequently within 4 weeks after completion of the vaccination cycle. The incidence of new SARS-CoV-2 infections was 8.9 per 1000 person-months, with no cases within 12 weeks from vaccine administration and an increasing trend of infections moving away from the primary vaccination cycle. Only one case of severe COVID-19 was reported during the study period. Interpretation: COVID-19 vaccination seems effective and safe in rcCTDs patients. The rate of new infections was rather low and serious infections were uncommon in our cohort. No increased risk of disease flares was observed compared to previous disease history; however, such exacerbations may be potentially severe, emphasising the need for close monitoring of our patients.

State of the art and future directions in assessing the quality of life in rare and complex connective tissue and musculoskeletal diseases.

Background: As chronic conditions, rare and complex connective tissue and musculoskeletal diseases (rCTDs) significantly affect the quality of life generating an impact on the physical, psychological, social, and economic dimensions of the patients' lives, having implications on the family, changing the lifestyle and interpersonal relationships. Traditionally, generic and disease-specific measures for Quality of Life (QoL) provide valuable information to clinicians since QoL affects healthcare services utilization, predicts morbidities and mortalities, workability, etc. Moreover, the assessment of unmet clinical needs, satisfaction, the experience with the treatment and the care, the psychological dimensions, and the effects of the diseases, such as fatigue, could represent valuable dimensions to be considered in the QoL impact assessment. It is also necessary to measure the impact of rCTDs by considering the perspectives of family members/informal caregivers, for instance considering values, beliefs, experiences, life circumstances, psychological aspects, family relationships, economic issues, changes in social activities, etc. Objective: The aim of this scoping review is to better understand the status of QoL metrics used in clinical and economic research for the assessment of the individual's perspective on living with rCTDs. Research question: What are the main challenges in QoL measures (and/or) measurement/assessment in rCTDs? Materials and methods: Scoping review of the literature referring to QoL measures in rCTDs. Database: PUBMED, ISI-Web of Science; last date: 21/09/2021. Results: Anxiety and depression, body image satisfaction, daily activity, fatigue, illness perception, pain, personality, QoL, resilience, satisfaction with the relationship, self-management, sexual QoL, sleep quality, social support, stress, uncertainty, and work productivity are the observed dimensions covered by the included studies. However, "more shadows than lights" can summarize the review's outcome in terms of Patient Reported Outcome Measures (PROMs) domains covered for each of the rCTDs. Also, for those diseases characterized by a relatively high prevalence and incidence, such as Systemic Lupus Erythematosus, Sjögren's Syndrome, and Systemic Sclerosis, the analysis of patients' resilience, satisfaction with the quality of the relationship, personality, and stress are still missing dimensions. It has been observed how reducing items, increasing the number of domains, and disease-specific questionnaires characterize the "technological trajectory," such as the evolution of questionnaires' characteristics for assessing QoL and QoL-related dimensions and the burden of rCTDs. Conclusion: The scoping review presents an overview of studies focused on questionnaires used to evaluate the different dimensions of quality of life in terms of general instruments and disease-specific questionnaires. Future research should include the co-design with patients, caregivers, and patient representatives to create questionnaires focused on the unmet needs of people living with rCTDs.

An overlook on the current registries for rare and complex connective tissue diseases and the future scenario of TogethERN ReCONNET.

Background: Patient registries play a crucial role in supporting clinical practice, healthcare planning and medical research, offering a real-world picture on rare and complex connective tissue diseases (rCTDs). ERN ReCONNET launched the first European Registry Infrastructure with the aim to plan, upgrade and link registries for rCTDs, with the final goal to promote a harmonized data collection approach all over Europe for rCTDs. Methods: An online survey addressed to healthcare professionals and patients' representatives active in the field of rCTDs was integrated by an extensive database search in order to build a mapping of existing registries for rCTDs. Findings: A total of 140 registries were found, 38 of which include multiple diseases. No disease-specific registry was identified for relapsing polychondritis, mixed connective tissue disease and undifferentiated connective tissue disease. Discussion: This overview on the existing registries for rCTDs provides a useful starting point to identify the gaps and the strengths of registries on the coverage of rCTDs, and to develop a common data set and data collection approach for the establishment of the TogethERN ReCONNET Infrastructure.

The added value of a European Reference Network on rare and complex connective tissue and musculoskeletal diseases: insights after the first 5 years of the ERN ReCONNET.

In order to address the main challenges related to the rare diseases (RDs) the European Commission launched the European Reference Networks (ERNs), virtual networks involving healthcare providers (HCPs) across Europe. The mission of the ERNs is to tackle low prevalence and RDs that require highly specialised treatment and a concentration of knowledge and resources. In fact, ERNs offer the potential to give patients and healthcare professionals across the EU access to the best expertise and timely exchange of lifesaving knowledge, trying to make the knowledge travelling more than patients. For this reason, ERNs were established as concrete European infrastructures, and this is particularly crucial in the framework of rare and complex diseases in which no country alone has the whole knowledge and capacity to treat all types of patients.It has been five years since their kick-off launch in Vilnius in 2017. The 24 ERNs have been intensively working on different transversal areas, including patient management, education, clinical practice guidelines, patients' care pathways and many other fundamental topics. The present work is therefore aimed not only at reporting a summary of the main activities and milestones reached so far, but also at celebrating the first 5 years of the ERN on Rare and Complex Connective Tissue and Musculo-skeletal Diseases (ReCONNET), in which the members of the network built together one of the 24 infrastructures that are hopefully going to change the scenario of rare diseases across the EU.

An Opportunity to Harmonise the Approach to Patients' Care Pathways for Rare and Complex Diseases: RarERN Path™.

As a matter of fact, organisation always matters when discussing about healthcare, since it is fundamental in order to ensure the delivery of the most appropriate care to patients in the most appropriate way. Unfortunately, the pandemic brought by the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) imposed a huge reorganisation of the healthcare systems, with several repercussions on the care of several chronic conditions, that were in many cases discontinued. This was the case of rare diseases (RDs), conditions that even under normal circumstances can experience diagnostic delays and difficulties in receiving appropriate care. The context of the European Reference Networks (ERNs) represents one of the most appropriate settings for the creation of organisational reference models for patient care pathways (PCP). As a matter of fact, the main mission of ERNs is to improve the care of patients with RDs in Europe through a patient-centred approach, thanks to real multistakeholder involvement. For this reason, in the last years, an extensive effort has been made towards the creation of a methodological approach aimed at providing organisational reference models for PCP in RDs across the different Member States. In fact, in order to develop the reference model, a structured methodology was created to enable the design of the PCP based on a deep sharing of expertise on high-quality care and characterised by a strong patient-centred approach: RarERN Path™. Among the different stakeholders that need to be involved in planning strategic actions to ensure care also during an emergency, patients' representatives, healthcare professionals, hospital managers, and experts in healthcare organisations play a crucial role.

Being a caregiver of a Behçet's syndrome patient: challenges and perspectives during a complex journey.

BACKGROUND: As often seen in many chronic diseases, the disease impact on patients also induces a significant impact on the quality of life (QoL) of caregivers. Caregivers are the ones who are really willing to offer care in the general approach of many aspects of the disease, including the awareness of the diseases itself, the daily management of therapy, and all the potential challenges that living with a chronic disease can include. The main objectives of the study were to explore the perspectives and views of caregivers of Behçet's syndrome (BS) patients, to study their level of awareness on the disease and the impact that BS may have on their lives by means of a survey co-designed with caregivers and patients with this purpose. A survey was entirely co-designed with a panel of caregivers of patients living with BS patients. RESULTS: Results show that BS caregivers organise their life according to the needs of the patient, that they (79%) considered themselves as helpful for the patient and 53% of them replied that they can freely express their emotions. Notably, 70% and 68% of the respondents reported they renounced with a variable frequency to sexual relationships due to concerns regarding the health of the partner or to the partner's illness, respectively. The majority (79%) of respondents indicated that they are familiar with the treatment taken by the patients and that 68% deal with the administration of some medicines. In terms of awareness, a good percentage (64%) of respondents reported to understand the illness and, in terms of education, 68% of participants are willing to take part in training programmes dedicated to BS. CONCLUSIONS: The results of this survey contribute to provide new information on BS caregivers and on their important role, and to identify areas in which new initiatives could provide BS caregivers (and therefore patients) with tools and knowledge that can empower them in reducing the burden of the disease on their lives, on families, and on the patient.

The impact of COVID-19 on rare and complex connective tissue diseases: the experience of ERN ReCONNET.

During the COVID-19 pandemic, the need to provide high-level care for a large number of patients with COVID-19 has affected resourcing for, and limited the routine care of, all other conditions. The impact of this health emergency is particularly relevant in the rare connective tissue diseases (rCTDs) communities, as discussed in this Perspective article by the multi-stakeholder European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases (ERN ReCONNET). The clinical, organizational and health economic challenges faced by health-care providers, institutions, patients and their families during the SARS-CoV-2 outbreak have demonstrated the importance of ensuring continuity of care in the management of rCTDs, including adequate diagnostics and monitoring protocols, and highlighted the need for a structured emergency strategy. The vulnerability of patients with rCTDs needs to be taken into account when planning future health policies, in preparation for not only the post-COVID era, but also any possible new health emergencies.