Orphanet J Rare Dis. 2023 Apr 28;18(1):97. doi: 10.1186/s13023-023-02672-y.

ABSTRACT

BACKGROUND: Rare diseases are a particular field of public health that is characterized by scattered, often insufficient knowledge and infrastructure. The scarcity of specialized knowledge often forces clinicians and patients to an incomplete picture of the diseases and their associated risks. Effective person-centred networks appear promising for solving such real world and life-defining problems by purposely sourcing expert knowledge that is geographically-dispersed. The design and implementation of the RARE-e-CONNECT network technology is described. The project was funded to create collaborative spaces for the development of international partnerships in Cyprus' healthcare, promoting the dissemination of expert knowledge on rare diseases while saving resources through teleconsultation. Parameters that matter for patients, providers and policy-makers through the RARE-e-CONNECT experience were evaluated through a participatory mixed-method approach, consisting of (1) a needs assessment survey with 27 patients/families and 26 healthcare professionals at the two referral hospitals for the diagnosis and management of rare diseases in Cyprus; (2) interviews with 40 patients, families and patient representatives, as well as 37 clinicians and laboratory scientists, including national ERN coordinators/members; (3) activity metrics from 210 healthcare professionals and 251 patients/families/patient representatives who participated on the platform at the time of the research.

RESULTS: Our results indicate usage and intention by both healthcare professionals and patients/families to openly provide decentralized specialized information for raising suspicion amongst clinicians to facilitate the necessary referrals, as well as peer to peer psychosocial support to help cope with the everyday challenges of living with the disease. User behavior was largely affected by the prevailing social norm favoring individual practice, as well as missing policies for telemedicine and shared care. This article discusses how telehealth is inextricably linked to social, cultural, organizational, technological and policy factors affecting uptake.

CONCLUSIONS: We argue that collective intelligence tools need to be formally considered and work hand in hand with national and European policies/regulatory frameworks to promote proactiveness amongst the healthcare community with regard to the timely diagnosis of rare diseases and the facilitation of patients' pathway to specialists. Collaborative channels between countries need to be established to source collective intelligence on complex cases and save resources through teleconsultation/telementoring.

PMID:37118739 | PMC:PMC10142407 | DOI:10.1186/s13023-023-02672-y

Viruses. 2023 Apr 18;15(4):995. doi: 10.3390/v15040995.

ABSTRACT

Mpox (previously known as monkeypox) is an infectious viral illness caused by the mpox virus (MPXV), an orthopoxvirus that belongs to the family Poxviridae. The symptoms of mpox in humans are similar to those of smallpox, although the mortality rate is lower. In recent years, the concern over a potential global pandemic has increased due to reports of mpox spreading across Africa and other parts of the world. Prior to this discovery, mpox was a rare zoonotic disease restricted to endemic regions of Western and Central Africa. The sudden emergence of MPXV cases in multiple regions has raised concerns about its natural evolution. This review aims to provide an overview of previously available information about MPXV, including its genome, morphology, hosts and reservoirs, and virus-host interaction and immunology, as well as to perform phylogenetic analysis on available MPXV genomes, with an emphasis on the evolution of the genome in humans as new cases emerge.

PMID:37112975 | PMC:PMC10142743 | DOI:10.3390/v15040995

Int J Mol Sci. 2023 Apr 21;24(8):7666. doi: 10.3390/ijms24087666.

ABSTRACT

Kimura's disease (KD) is a rare lymphoproliferative fibroinflammatory disorder that commonly affects the subcutaneous tissue and lymph nodes of the head and neck. The condition is a reactive process involving T helper type 2 cytokines. Concurrent malignancies have not been described. Differential diagnosis with lymphoma can be challenging without tissue biopsy. Here, we present the first reported case of coexisting KD and eosinophilic nodular sclerosis Hodgkin lymphoma of the right cervical lymphatics in a 72-year-old Taiwanese man.

PMID:37108825 | PMC:PMC10146151 | DOI:10.3390/ijms24087666

Int J Mol Sci. 2023 Apr 14;24(8):7275. doi: 10.3390/ijms24087275.

ABSTRACT

The expression "rare disease" describes a group of diseases whose individual prevalence is low (between 3.9 and 6.6 in 10,000 subjects depending on the country) but which in total affect up to the 3-6% of the worldwide population [...].

PMID:37108436 | PMC:PMC10139002 | DOI:10.3390/ijms24087275

Ann Med Surg (Lond). 2023 Apr 10;85(4):1231-1234. doi: 10.1097/MS9.0000000000000473. eCollection 2023 Apr.

ABSTRACT

Alagille syndrome has been described as a multisystemic clinical spectrum caused by an autosomal dominant genetic disorder. Although it is estimated that there is 1 case per 100 000 live births, the prognosis for survival and quality of life for these patients is varied but tends to be negative. In Colombia, this condition is considered an orphan disease with difficult management due to the lack of specialized centers that have all the medical specialties and subspecialties. Some reports state that no more than 30 cases have been published in this country.

MATERIALS AND METHODS: The authors report a case of a male baby who, at 8 days old, he was taken to the general practitioner's outpatient clinic for persistent jaundice. At 3 months of age, he was reviewed by the pediatric gastroenterology department, which requested liver and biliary tract scintigraphy, showing atresia of the biliary tract, hepatomegaly, and the absence of a gallbladder.

RESULTS: Liver transplantation is the definitive solution. However, in low- and middle-income countries, where there are no well-established organ transplantation programs, the prognosis for these patients is presumed to be worse.

CONCLUSION: Alagille syndrome is a rare disease that requires an accurate and early diagnosis and timely multidisciplinary management to reduce the impact of multisystemic complications. It is necessary to advance in transplant programs in low- and middle-income countries, to provide a solution to cases where there are no other therapeutic alternatives, and to contribute to the quality of life of the affected patient.

PMID:37113962 | PMC:PMC10129178 | DOI:10.1097/MS9.0000000000000473

Medicina (Kaunas). 2023 Apr 11;59(4):745. doi: 10.3390/medicina59040745.

ABSTRACT

Background and objectives: Bullous pemphigoid (BP), the most common subepidermal autoimmune skin blistering disease (AIBD) has an estimated annual incidence of 2.4 to 42.8 new cases per million in different populations, designating it an orphan disease. Characterized by disruption of the skin barrier combined with therapy-induced immunosuppression, BP could pose a risk for skin and soft tissue infections (SSTI). Necrotizing fasciitis (NF) is a rare necrotizing skin and soft tissue infection, with a prevalence of 0.40 cases per 100,000 to 15.5 cases per 100,000 population, often associated with immunosuppression. Low incidences of NF and BP classify them both as rare diseases, possibly contributing to the false inability of making a significant correlation between the two. Here, we present a systematic review of the existing literature related to the ways these two diseases correlate. Materials and methods: This systematic review was conducted according to the PRISMA guidelines. The literature review was conducted using PubMed (MEDLINE), Google Scholar, and SCOPUS databases. The primary outcome was prevalence of NF in BP patients, while the secondary outcome was prevalence and mortality of SSTI in BP patients. Due to the scarcity of data, case reports were also included. Results: A total of 13 studies were included, six case reports of BP complicated by NF with six retrospective studies and one randomized multicenter trial of SSTIs in BP patients. Conclusions: Loss of skin integrity, immunosuppressive therapy, and comorbidities commonly related to BP patients are risk factors for necrotizing fasciitis. Evidence of their significant correlation is emerging, and further studies are deemed necessary for the development of BP-specific diagnostic and treatment protocols.

PMID:37109703 | DOI:10.3390/medicina59040745

Genes (Basel). 2023 Mar 23;14(4):779. doi: 10.3390/genes14040779.

ABSTRACT

BACKGROUND: Children and adolescents with early-onset psychosis (EOP) have more rare genetic variants than individuals with adult-onset forms of the illness, implying that fewer EOP participants are needed for genetic discovery. The Schizophrenia Exome Sequencing Meta-analysis (SCHEMA) study predicted that 10 genes with ultra-rare variation were linked to adult-onset schizophrenia. We hypothesized that rare variants predicted "High" and "Moderate" by the Variant Effect Predictor Algorithm (abbreviated as VEPHMI) in these 10 genes would be enriched in our EOP cohort.

METHODS: We compared rare VEPHMI variants in individuals with EOP (N = 34) with race- and sex-matched controls (N = 34) using the sequence kernel association test (SKAT).

RESULTS: GRIN2A variants were significantly increased in the EOP cohort (p = 0.004), with seven individuals (20% of the EOP cohort) carrying a rare VEPHMI variant. The EOP cohort was then compared to three additional control cohorts. GRIN2A variants were significantly increased in the EOP cohort for two of the additional control sets (p = 0.02 and p = 0.02), and trending towards significance for the third (p = 0.06).

CONCLUSION: Despite a small sample size, GRIN2A VEPHMI variant burden was increased in a cohort of individuals with EOP in comparison to controls. GRIN2A variants have been associated with a range of neuropsychiatric disorders including adult-onset psychotic spectrum disorder and childhood-onset schizophrenia. This study supports the role of GRIN2A in EOP and emphasizes its role in neuropsychiatric disorders.

PMID:37107537 | DOI:10.3390/genes14040779

Sci Rep. 2023 Apr 27;13(1):6869. doi: 10.1038/s41598-023-33374-x.

ABSTRACT

Up to 40% of rare disorders (RD) present facial dysmorphologies, and visual assessment is commonly used for clinical diagnosis. Quantitative approaches are more objective, but mostly rely on European descent populations, disregarding diverse population ancestry. Here, we assessed the facial phenotypes of Down (DS), Morquio (MS), Noonan (NS) and Neurofibromatosis type 1 (NF1) syndromes in a Latino-American population, recording the coordinates of 18 landmarks in 2D images from 79 controls and 51 patients. We quantified facial differences using Euclidean Distance Matrix Analysis, and assessed the diagnostic accuracy of Face2Gene, an automatic deep-learning algorithm. Individuals diagnosed with DS and MS presented severe phenotypes, with 58.2% and 65.4% of significantly different facial traits. The phenotype was milder in NS (47.7%) and non-significant in NF1 (11.4%). Each syndrome presented a characteristic dysmorphology pattern, supporting the diagnostic potential of facial biomarkers. However, population-specific traits were detected in the Colombian population. Diagnostic accuracy was 100% in DS, moderate in NS (66.7%) but lower in comparison to a European population (100%), and below 10% in MS and NF1. Moreover, admixed individuals showed lower facial gestalt similarities. Our results underscore that incorporating populations with Amerindian, African and European ancestry is crucial to improve diagnostic methods of rare disorders.

PMID:37106005 | PMC:PMC10140286 | DOI:10.1038/s41598-023-33374-x

Orphanet J Rare Dis. 2023 Apr 25;18(1):93. doi: 10.1186/s13023-023-02698-2.

ABSTRACT

PURPOSE: The transition process from paediatric/adolescent to adult medical care settings is of utmost importance for the future health of adolescents with chronic diseases and poses even more difficulties in the context of rare diseases (RDs). Paediatric care teams are challenged to deliver adolescent-appropriate information and structures. Here we present a structured transition pathway which is patient-focused and adoptable for different RDs.

METHODS: The transition pathway for adolescents 16 years and older was developed and implemented as part of a multi-centre study in 10 university hospitals in Germany. Key elements of the pathway included: assessment of patients' disease-related knowledge and needs, training/educational and counselling sessions, a structured epicrisis and a transfer appointment jointly with the paediatric and adult specialist. Specific care coordinators from the participating university hospitals were in charge of organization and coordination of the transition process.

RESULTS: Of a total of 292 patients, 286 completed the pathway. Deficits in disease-specific knowledge were present in more than 90% of participants. A need for genetic or socio-legal counselling was indicated by > 60%. A mean of 2.1 training sessions per patient were provided over a period of almost 1 year, followed by the transfer to adult care in 267 cases. Twelve patients remained in paediatric care as no adult health care specialist could be identified. Targeted training and counselling resulted in improved disease-specific knowledge and contributed to empowering of patients.

CONCLUSION: The described transition pathway succeeds to improve health literacy in adolescents with RDs and can be implemented by paediatric care teams in any RD specialty. Patient empowerment was mainly achieved by individualized training and counselling.

PMID:37098531 | PMC:PMC10131406 | DOI:10.1186/s13023-023-02698-2

PLoS One. 2023 Apr 25;18(4):e0284084. doi: 10.1371/journal.pone.0284084. eCollection 2023.

ABSTRACT

Antithrombin resistance is a rare subtype of hereditary thrombophilia caused by prothrombin gene variants, leading to thrombotic disorders. Recently, the Prothrombin Belgrade variant has been reported as a specific variant that leads to antithrombin resistance in two Serbian families with thrombosis. However, due to clinical data scarcity and the inapplicability of traditional genome-wide association studies (GWAS), a broader perspective on molecular and phenotypic mechanisms associated with the Prothrombin Belgrade variant is yet to be uncovered. Here, we propose an integrative framework to address the lack of genomic samples and support the genomic signal from the full genome sequences of five heterozygous subjects by integrating it with subjects' phenotypes and the genes' molecular interactions. Our goal is to identify candidate thrombophilia-related genes for which our subjects possess germline variants by focusing on the resulting gene clusters of our integrative framework. We applied a Non-negative Matrix Tri-Factorization-based method to simultaneously integrate different data sources, taking into account the observed phenotypes. In other words, our data-integration framework reveals gene clusters involved with this rare disease by fusing different datasets. Our results are in concordance with the current literature about antithrombin resistance. We also found candidate disease-related genes that need to be further investigated. CD320, RTEL1, UCP2, APOA5 and PROZ participate in healthy-specific or disease-specific subnetworks involving thrombophilia-annotated genes and are related to general thrombophilia mechanisms according to the literature. Moreover, the ADRA2A and TBXA2R subnetworks analysis suggested that their variants may have a protective effect due to their connection with decreased platelet activation. The results show that our method can give insights into antithrombin resistance even if a small amount of genetic data is available. Our framework is also customizable, meaning that it applies to any other rare disease.

PMID:37098010 | PMC:PMC10128975 | DOI:10.1371/journal.pone.0284084

Medicina (B Aires). 2023;83(2):324-328.

ABSTRACT

Monkey pox is a rare zoonotic disease. It was first described in humans in Africa in 1970. On July 23, 2022, in view of the increasing number of cases reported in several countries and territories, the World Health Organization (WHO) concluded that the global outbreak constitutes a public health emergency of international concern. In our country, the first case was reported on May 22, 2022 and up to November 22 of this year, 895 patients were reported. We describe here the first case registered in Argentina requiring intensive care, according to the Epidemiological Bulletin, 46th epidemiological week, National Ministry of Health. The patient was a 44-year-old man with acquired immunodeficiency syndrome and severe Monkeypox, who presented obstructive ventilatory failure due to airway compromise and extensive generalized lesions of the integument, genitalia and fauces. In conclusion, the case presented alerts about potential complications that may require critical care and risk the patient's life.

PMID:37094206

Lancet. 2023 Apr 22;401(10385):1339-1340. doi: 10.1016/S0140-6736(23)00343-4.

NO ABSTRACT

PMID:37087169 | DOI:10.1016/S0140-6736(23)00343-4

Z Rheumatol. 2023 May;82(4):285-297. doi: 10.1007/s00393-023-01351-4. Epub 2023 Apr 20.

ABSTRACT

Inborn errors of immunity (IEI) are a heterogeneous group of nearly 500 diseases characterized by a congenital dysfunction of the immune system. The vast majority of IEIs are rare diseases but all IEIs share a cumulative prevalence of 1:1200-1:2000. In addition to a pathological susceptibility to infections, IEIs can also present with lymphoproliferative, autoimmune or autoinflammatory manifestations. There is often an overlap with classical rheumatic and inflammatory disease patterns. Therefore, a basic knowledge of the clinical presentation and the diagnostics of IEIs is also relevant for the practicing rheumatologist.

PMID:37079035 | DOI:10.1007/s00393-023-01351-4

J Med Internet Res. 2023 Apr 20;25:e45249. doi: 10.2196/45249.

ABSTRACT

BACKGROUND: The COVID-19 pandemic disrupted the needs and concerns of the cystic fibrosis community. Patients with cystic fibrosis were particularly vulnerable during the pandemic due to overlapping symptoms in addition to the challenges patients with rare diseases face, such as the need for constant medical aid and limited information regarding their disease or treatments. Even before the pandemic, patients vocalized these concerns on social media platforms like Reddit and formed communities and networks to share insight and information. This data can be used as a quick and efficient source of information about the experiences and concerns of patients with cystic fibrosis in contrast to traditional survey- or clinical-based methods.

OBJECTIVE: This study applies topic modeling and time series analysis to identify the disruption caused by the COVID-19 pandemic and its impact on the cystic fibrosis community's experiences and concerns. This study illustrates the utility of social media data in gaining insight into the experiences and concerns of patients with rare diseases.

METHODS: We collected comments from the subreddit r/CysticFibrosis to represent the experiences and concerns of the cystic fibrosis community. The comments were preprocessed before being used to train the BERTopic model to assign each comment to a topic. The number of comments and active users for each data set was aggregated monthly per topic and then fitted with an autoregressive integrated moving average (ARIMA) model to study the trends in activity. To verify the disruption in trends during the COVID-19 pandemic, we assigned a dummy variable in the model where a value of "1" was assigned to months in 2020 and "0" otherwise and tested for its statistical significance.

RESULTS: A total of 120,738 comments from 5827 users were collected from March 24, 2011, until August 31, 2022. We found 22 topics representing the cystic fibrosis community's experiences and concerns. Our time series analysis showed that for 9 topics, the COVID-19 pandemic was a statistically significant event that disrupted the trends in user activity. Of the 9 topics, only 1 showed significantly increased activity during this period, while the other 8 showed decreased activity. This mixture of increased and decreased activity for these topics indicates a shift in attention or focus on discussion topics during this period.

CONCLUSIONS: There was a disruption in the experiences and concerns the cystic fibrosis community faced during the COVID-19 pandemic. By studying social media data, we were able to quickly and efficiently study the impact on the lived experiences and daily struggles of patients with cystic fibrosis. This study shows how social media data can be used as an alternative source of information to gain insight into the needs of patients with rare diseases and how external factors disrupt them.

PMID:37079359 | DOI:10.2196/45249

Arch Soc Esp Oftalmol (Engl Ed). 2023 May;98(5):254-258. doi: 10.1016/j.oftale.2023.04.007. Epub 2023 Apr 17.

ABSTRACT

OBJECTIVE: To analyse the impact of the COVID-19 pandemic on the diagnosis and management of uveal melanoma (a tumour included in the Orphanet catalogue of rare diseases) in a Spanish national reference unit for intraocular tumours during the first year of the pandemic.

METHOD: An observational retrospective study of patients with uveal melanoma in the National Reference Unit for Adult Intraocular Tumors of the Hospital Clínico Universitario de Valladolid (Spain) was performed, analysing the pre- and post-COVID-19 periods: from March 15, 2019 to March 15, 2020 and from March 16, 2020 to March 16, 2021. Demographic data, diagnostic delay, tumour size, extraocular extension, treatment and evolution were collected. A multivariable logistic regression model was used to identify factors that were associated with the variable: enucleation.

RESULTS: Eighty-two patients with uveal melanoma were included, of which 42 (51.21%) belonged to the pre-COVID-19 period and 40(40.78%) to the post-COVID-19 period. An increase in tumour size at diagnosis and in the number of enucleations was observed during the post-COVID-19 period (p < 0.05). Multivariable logistic regression demonstrated that both medium-large tumour size and patients diagnosed in the post-COVID-19 period were independently related to an increased risk of enucleation (OR 250, 95%CI, 27.69-2256.37; p < 0.01 and OR 10; 95%CI, 1.10-90.25; p = 0.04, respectively).

CONCLUSIONS: The increase in tumour size observed in uveal melanomas diagnosed during the first year of the COVID-19 pandemic may have favored the increase in the number of enucleations performed during that period.

PMID:37075839 | PMC:PMC10110274 | DOI:10.1016/j.oftale.2023.04.007

Orphanet J Rare Dis. 2023 Apr 19;18(1):89. doi: 10.1186/s13023-023-02702-9.

ABSTRACT

BACKGROUND: Randomized controlled trial (RCT) data have important implications in drug development. However, the feasibility and cost of conducting RCTs lower the motivation for drug development, especially for rare diseases. We investigated the potential factors associated with the need for RCTs in the clinical data package for new drug applications for rare diseases in the United States (US). This study focused on 233 drugs with orphan drug designations approved in the US between April 2001 and March 2021. Univariable and multivariable logistic regression analyses were conducted to investigate the association between the presence or absence of RCTs in the clinical data package for new drug applications.

RESULTS: Multivariable logistic regression analysis showed that the severity of the disease outcome (odds ratio [OR] 5.63, 95% confidence interval [CI] 2.64-12.00), type of drug usage (odds ratio [OR] 2.95, 95% confidence interval [CI] 1.80-18.57), and type of primary endpoint (OR 5.57, 95% CI 2.57-12.06) were associated with the presence or absence of RCTs.

CONCLUSIONS: Our results indicated that the presence or absence of RCT data in the clinical data package for successful new drug application in the US was associated with three factors: severity of disease outcome, type of drug usage, and type of primary endpoint. These results highlight the importance of selecting target diseases and potential efficacy variables to optimize orphan drug development.

PMID:37076897 | DOI:10.1186/s13023-023-02702-9

Nat Commun. 2023 Apr 19;14(1):2229. doi: 10.1038/s41467-023-37691-7.

ABSTRACT

Expression quantitative trait locus (eQTL) studies illuminate genomic variants that regulate specific genes and contribute to fine-mapped loci discovered via genome-wide association studies (GWAS). Efforts to maximize their accuracy are ongoing. Using 240 glomerular (GLOM) and 311 tubulointerstitial (TUBE) micro-dissected samples from human kidney biopsies, we discovered 5371 GLOM and 9787 TUBE genes with at least one variant significantly associated with expression (eGene) by incorporating kidney single-nucleus open chromatin data and transcription start site distance as an "integrative prior" for Bayesian statistical fine-mapping. The use of an integrative prior resulted in higher resolution eQTLs illustrated by (1) smaller numbers of variants in credible sets with greater confidence, (2) increased enrichment of partitioned heritability for GWAS of two kidney traits, (3) an increased number of variants colocalized with the GWAS loci, and (4) enrichment of computationally predicted functional regulatory variants. A subset of variants and genes were validated experimentally in vitro and using a Drosophila nephrocyte model. More broadly, this study demonstrates that tissue-specific eQTL maps informed by single-nucleus open chromatin data have enhanced utility for diverse downstream analyses.

PMID:37076491 | DOI:10.1038/s41467-023-37691-7

J Clin Res Pediatr Endocrinol. 2023 Apr 19. doi: 10.4274/jcrpe.galenos.2023.2023-1-23. Online ahead of print.

ABSTRACT

Pituitary stalk interruption syndrome (PSIS) is a rare congenital disease resulting in hypopituitarism of variable degree. Serious courses, due to severe combined pituitary insufficiency, are even rarer and associated with a very early manifestation immediately after birth. First clinical signs are elusive and lead to delayed diagnosis and treatment, often resulting in life-threatening complications. Objective of the current report is to point out early leading symptoms and key issues of neonatal manifested PSIS to increase the awareness, improve the clinical management and thereby enable an early diagnosis and treatment to prevent further complications. This report presents and compares the clinical course and management of two male newborns with manifested PSIS. Early leading symptoms were the same in both patients, including recurrent hypoglycaemia, hyponatraemia, jaundice, cholestasis, sucking weakness and genital abnormalities. Patient 1 developed an infection-induced adrenal crisis, persistent substitution-dependent thrombocytopenia and convulsions due to severe hypoglycaemia in delayed PSIS diagnosis. In patient 2, due to recognised above-mentioned symptoms, endocrine testing and a subsequent cerebral magnetic resonance imaging were performed early and he was diagnosed and treated before major complications occurred. Genetic testing was performed in both patients. GLI2 gene mutation (NM_005270.5:c.2537del; p.(Pro846Argfs*66)) heterozygous was detected in patient 1. No mutation was found in patient 2. Conclusively, the early diagnosis of neonatal PSIS is indispensable in the treatment and prevention of the possible severe clinical manifestation of this orphan disease. Therefore, increased awareness for early leading symptoms and proper clinical management are crucial.

PMID:37074078 | DOI:10.4274/jcrpe.galenos.2023.2023-1-23

Orphanet J Rare Dis. 2023 Apr 17;18(1):84. doi: 10.1186/s13023-023-02682-w.

ABSTRACT

BACKGROUND: The diversity of patient experiences of orphan drug development has until recently been overlooked, with the existing literature reporting the experience of some patients and not others. The current evidence base (the best available current research) is dominated by quantitative surveys and patient reported outcome measures defined by researchers. Where research that uses qualitative methods of data collection and analysis has been conducted, patient experiences have been studied using content analysis and automatic textual analysis, rather than in-depth qualitative analytical methods. Systematic reviews of patient engagement in orphan drug development have also excluded qualitative studies. The aim of this paper is to review qualitative literature about how patients and other members of the public engage with orphan drug development.

METHODS: We conducted a systematic search of qualitative papers describing a range of patient engagement practices and experiences were identified and screened. Included papers were appraised using a validated tool (CASP), supplemented by reporting guidance (COREQ), by two independent researchers.

RESULTS: 262 papers were identified. Thirteen papers reported a range of methods of qualitative data collection. Many conflated patient and public involvement and engagement (PPIE) with qualitative research. Patients were typically recruited via their physician or patient organisations. We identified an absence of overarching philosophical or methodological frameworks, limited details of informed consent processes, and an absence of recognisable methods of data analysis. Our narrative synthesis suggests that patients and caregivers need to be involved in all aspects of trial design, including the selection of clinical endpoints that capture a wider range of outcomes, the identification of means to widen access to trial participation, the development of patient facing materials to optimise their decision making, and patients included in the dissemination of trial results.

CONCLUSIONS: This narrative qualitative synthesis identified the explicit need for methodological rigour in research with patients with rare diseases (e.g. appropriate and innovative use of qualitative methods or PPIE, rather than their conflation); strenuous efforts to capture the perspectives of under-served, under-researched or seldom listened to communities with experience of rare diseases (e.g. creative recruitment and wider adoption of post-colonial practices); and a re-alignment of the research agenda (e.g. the use of co-design to enable patients to set the agenda, rather than respond to what they are being offered).

PMID:37069597 | DOI:10.1186/s13023-023-02682-w

CNS Drugs. 2023 Apr 18. doi: 10.1007/s40263-023-00998-6. Online ahead of print.

ABSTRACT

Idiopathic hypersomnia is a chronic neurologic sleep disorder that manifests as excessive daytime sleepiness despite normal or prolonged sleep times for age. Frequently, idiopathic hypersomnia is clinically characterized by marked sleep inertia, long and unrefreshing naps, and a high sleep efficiency. Since the initial description, there has been an ongoing evolution of its nomenclature, approach to diagnosis, characterization of symptoms, and determination of the burden of disease. In addition, an increased attention to and study of its epidemiology, neurobiology, and potential therapeutic strategies has begun to contribute to a better approach to identifying and treating it. At present, idiopathic hypersomnia is considered an orphan disease with unknown frequency and the cause is unknown; however, there is evidence to suggest circadian and sleep structure differences, structural brain changes, and neurochemical changes may contribute to the development and expression of this disease. The approach to treatment can be challenging owing to a limited number of approved treatments (calcium, magnesium, potassium, and sodium oxybates) in idiopathic hypersomnia. However, consideration of therapies shown to improve excessive daytime sleepiness in other disorders is frequently employed. Future directions require a clear consensus on the defining characteristics of idiopathic hypersomnia to enhance the opportunity for improved recognition, diagnosis, and treatment strategies to be established. This article provides a historical review of the evolving diagnostic classification of idiopathic hypersomnia, potential insights to the underlying pathophysiology, and a summary of proposed approaches for diagnosis and therapeutic intervention.

PMID:37069414 | DOI:10.1007/s40263-023-00998-6