Understanding bias when estimating life expectancy from age at death: a simulation approach applied to Morquio syndrome A

Objective Life expectancy can be estimated accurately from a cohort of individuals born in the same year and followed from birth to death. However, due to the resource-consuming nature of following a cohort prospectively, life expectancy is often assessed based upon retrospective death record reviews. This conventional approach may lead to potentially biased estimates, in particular when estimating life expectancy of rare diseases such as Morquio syndrome A. We investigated the accuracy of life expectancy estimation using death records by simulating the survival of individuals with Morquio syndrome A under four different scenarios. Results When life expectancy was constant during the entire period, using death data did not result in a biased estimate. However, when life expectancy increased over time, as is often expected to be the case in rare diseases, using only death data led to a substantial underestimation of life expectancy. We emphasize that it is therefore crucial to understand how estimates of life expectancy are obtained, to interpret them in an appropriate context, and to assess estimation methods within a sensitivity analysis framework, similar to the simulations performed herein.

Anti-Neuronal IgG4 Autoimmune Diseases and IgG4-Related Diseases May Not Be Part of the Same Spectrum: A Comparative Study

BackgroundIgG4 is associated with two emerging groups of rare diseases: 1) IgG4 autoimmune diseases (IgG4-AID) and 2) IgG4-related diseases (IgG4-RLD). Anti-neuronal IgG4-AID include MuSK myasthenia gravis, LGI1- and Caspr2-encephalitis and autoimmune nodo-/paranodopathies (CNTN1/Caspr1 or NF155 antibodies). IgG4-RLD is a multiorgan disease hallmarked by tissue-destructive fibrotic lesions with lymphocyte and IgG4 plasma cell infiltrates and increased serum IgG4 concentrations. It is unclear whether IgG4-AID and IgG4-RLD share relevant clinical and immunopathological features.MethodsWe collected and analyzed clinical, serological, and histopathological data in 50 patients with anti-neuronal IgG4-AID and 19 patients with IgG4-RLD.ResultsA significantly higher proportion of IgG4-RLD patients had serum IgG4 elevation when compared to IgG4-AID patients (52.63% vs. 16%, p = .004). Moreover, those IgG4-AID patients with elevated IgG4 did not meet the diagnostic criteria of IgG4-RLD, and their autoantibody titers did not correlate with their serum IgG4 concentrations. In addition, patients with IgG4-RLD were negative for anti-neuronal/neuromuscular autoantibodies and among these patients, men showed a significantly higher propensity for IgG4 elevation, when compared to women (p = .005). Last, a kidney biopsy from a patient with autoimmune paranodopathy due to CNTN1/Caspr1-complex IgG4 autoantibodies and concomitant nephrotic syndrome did not show fibrosis or IgG4+ plasma cells, which are diagnostic hallmarks of IgG4-RLD.ConclusionOur observations suggest that anti-neuronal IgG4-AID and IgG4-RLD are most likely distinct disease entities.

Experienced fatigue in people with rare disorders: a scoping review on characteristics of existing research

Background Experienced fatigue is an under-recognized and under-researched feature in persons with many different rare diseases. A better overview of the characteristics of existing research on experienced fatigue in children and adults with rare diseases is needed. The purpose of this review was to map and describe characteristics of existing research on experienced fatigue in a selection of rare diseases in rare developmental defects or anomalies during embryogenesis and rare genetic diseases. Furthermore, to identify research gaps and point to research agendas. Methods We applied a scoping review methodology, and performed a systematic search in March 2020 in bibliographic databases. References were sorted and evaluated for inclusion using EndNote and Rayyan. Data were extracted on the main research questions concerning characteristics of research on experienced fatigue (definition and focus on fatigue, study populations, research questions investigated and methods used). Results This review included 215 articles on ten different rare developmental defects/anomalies during embryogenesis and 35 rare genetic diseases. Of the 215 articles, 82 had investigation of experienced fatigue as primary aim or outcome. Included were 9 secondary research articles (reviews) and 206 primary research articles. A minority of articles included children. There were large differences in the number of studies in different diseases. Only 29 of 215 articles gave a description of how they defined the concept of experienced fatigue. The most common research-question reported on was prevalence and/ -or associations to fatigue. The least common was diagnostics (development or validation of fatigue assessment methods for a specific patient group). A large variety of methods were used to investigate experienced fatigue, impeding comparisons both within and across diagnoses. Conclusion This scoping review on the characteristics of fatigue research in rare diseases found a large variety of research on experienced fatigue. However, the minority of studies had investigation of experienced fatigue as a primary aim. There was large variation in how experienced fatigue was defined and also in how it was measured, both within and across diagnoses. More research on experienced fatigue is needed, both in children and adults with rare diseases. This review offers a basis for further research.

Treating Rare Diseases in Africa: The Drugs Exist but the Need Is Unmet

Rare diseases (RD) pose serious challenges in terms of both diagnosis and treatment. Legislation was passed in the US (1983) and in EU (2000) aimed to reverse the previous neglect of RD, by providing incentives for development of “orphan drugs” (OD) for their management. Here we analyse the current situation in Africa with respect to (1) sickle cell disease (SCD), that qualifies as rare in the US and in EU, but is not at all rare in African countries (frequencies up to 1–2%); (2) paroxysmal nocturnal haemoglobinuria (PNH), that is ultra-rare in Africa as everywhere else (estimated <10 per million). SCD can be cured by bone marrow transplantation and recently by gene therapy, but very few African patients have access to these expensive procedures; on the other hand, the disease-ameliorating agent hydroxyurea is not expensive, but still the majority of patients in Africa are not receiving it. For PNH, currently most patients In high income countries are treated with a highly effective OD that costs about $400,000 per year per patient: this is not available in Africa. Thus, the impact of OD legislation has been practically nil in this continent. As members of the medical profession and of the human family, we must aim to remove barriers that are essentially financial: especially since countries with rich economies share a history of having exploited African countries. We call on the Global Fund to supply hydroxyurea for all SCD patients; and we call on companies who produce ODs to donate, for every patient who receives an expensive OD in a high income country, enough of the same drug, at a symbolic price, to treat one patient in Africa.

Education and Information Need for Emergency Physicians About Rare Diseases in China

Background: Rare diseases are serious and chronic disease that affect no more than 1 person in 2000. The patients suffering from RD may come to emergency department for life-threatening symptoms, such as acute aortic dissection, intracranial hemorrhage, and severe respiratory distress. Diagnostic delay of rare disease patients is common and often caused by low rare disease awareness among physicians. The main aim of this study was to investigate the Chinese emergency physicians’ basic knowledge, information access and educational needs regarding rare diseases. An online questionnaire was completed by Chinese emergency physicians during January and March 2021. Methods and Results: A total of 539 emergency physicians responded to the questionnaire-based study, including 200 females and 339 males. More than half of respondents were from Tertiary A hospital and had engaged in medical clinical work more than 10 years. Only 4.27% of respondents correctly estimated the prevalence of rare diseases. A few respondents knew the exact number of RD in the first official list of rare diseases in 2018. 98.5% of respondents rated their knowledge about rare diseases as rare or insufficient. Most of emergency physicians preferred to getting information by search engine instead of specialized websites of rare diseases. Lack of practice guidelines or consensus and were considered as the most important reason for diagnostic delay of RD. Practice guidelines or consensus and professional websites on rare diseases were urgently needed for emergency physicians.Conclusion: The investigation shows poor knowledge of emergency physicians regarding rare diseases. Practice guidelines and professional websites on rare diseases were the prominently urgent needs for emergency physicians. Specialized RD courses should also be added in medical education.

Psychosoziale Versorgung für Kinder mit seltenen Erkrankungen und ihren Eltern und Geschwistern im Verbund CARE-FAM-NET

ZusammenfassungSeltene Erkrankungen (SE) sind eine sehr heterogene Gruppe komplexer Krankheitsbilder, verlaufen meist chronisch, können die Lebenserwartung einschränken und manifestieren sich oft bereits im Kindesalter. Das Krankheitsmanagement erfordert meist einen hohen Grad an Unterstützung und Pflege durch Eltern und Geschwister und stellt hohe Anforderungen an die Familie. Die Betroffenen, ihre Geschwister und Eltern sind häufig körperlich und psychisch hochbelastet. Dennoch muss die Familie „funktionieren“ und die Pflege des erkrankten Kindes organisieren. Selbst bei großen Belastungen und psychischen Symptomen suchen viele Eltern keine herkömmliche psychosoziale Versorgung für sich oder ihr Kind auf, weil dies zusätzliche Ressourcen erfordern würde. „Children affected by rare diseases and their families–network“ (CARE-FAM-NET) bündelt renommierte, auf Kinder mit SE spezialisierte Partner und Zentren: vonseiten der Kinderkliniken, psychosozialen Medizin, Selbsthilfe, Gesundheitsökonomie, Biometrie und Qualitätssicherung, Jugendhilfe und Bundespolitik. Zentrale Ziele bestehen in Implementierung, Begleitevaluation und Transfer der neuen „Face-to-face“- (CARE-FAM) und Online-Intervention (WEP-CARE [Webbasiertes Elterprogramm-CARE]) für Kinder mit SE und ihre Familien an bundesweit 17 Standorten. Im Zentrum des Versorgungsmodells von CARE-FAM-NET steht eine psychosoziale Intervention, die individuell und passgenau auf die jeweilige Familie zugeschnitten ist und den genannten Anforderungen gerecht wird: sektorenübergreifend, bedarfs-, familienorientiert, interdisziplinär und fachübergreifend. Die Bedingungen für den Transfer der neuen Versorgungsformen in die Regelversorgung werden in CARE-FAM-NET geschaffen, geprüft und diese sollen nach positiver Evaluation in der Regelversorgung umgesetzt werden.

Representation of Patients With Rare Diseases in Spanish Media

There are more than 360 associations of patients with rare diseases in Spain that strive for visibility to obtain funding and encourage clinical pathologies. The Spanish Year of Rare Diseases has been a considerable effort to be part of media agenda since 2013 and a “collective voice” throughout the media has been encouraged with the international initiatives devoted to the cause. Over the past years, representation of patients with rare diseases in Spanish media has been very superficial, despite the renewed interest during the Spanish Year of Rare Diseases. Certain cases as “Paco Sanz” or “Los Padres de la Pequeña Nadia” have negatively affected this representation by using the disease to pursue economic benefit. This chapter reports on the representation of rare diseases through Spanish media and the way it evolved in the last 6 years. The findings highlight the effort that has been made by patient advocacy groups with rare diseases and their relatives and caregivers, who have been recognized and proactive to get the treatment and medication needed.