BMC Public Health. 2023 May 19;23(1):910. doi: 10.1186/s12889-023-15654-3.

ABSTRACT

BACKGROUND: Work participation is a crucial aspect of health outcome and an important part of life for most people with rare genetic diseases. Despite that work participation is a social determinant of health and seems necessary for understanding health behaviours and quality of life, it is an under-researched and under-recognized aspect in many rare diseases. The objectives of this study was to map and describe existing research on work participation, identify research gaps, and point to research agendas in a selection of rare genetic diseases.

METHODS: A scoping review was performed by searching relevant literature in bibliographic databases and other sources. Studies addressing work participation in people with rare genetic diseases published in peer reviewed journals were assessed using EndNote and Rayyan. Data were mapped and extracted based on the research questions concerning the characteristics of the research.

RESULTS: Of 19,867 search results, 571 articles were read in full text, and 141 satisfied the eligibility criteria covering 33 different rare genetic diseases; 7 were reviews and 134 primary research articles. In 21% of the articles the primary aim was to investigate work participation. The extent of studies varied between the different diseases. Two diseases had more than 20 articles, but most had only one or two articles. Cross-sectional quantitative studies were predominant, with few utilizing prospective or qualitative design. Nearly all articles (96%) reported information about work participation rate, and 45% also included information about factors associated with work participation and work disability. Due to differences in methodologies, cultures and respondents, comparison between and within diseases are difficult. Nevertheless, studies indicated that many people with different rare genetic diseases experience challenges related to work, closely associated to the symptoms of the disease.

CONCLUSION: While studies indicate high prevalence of work disability in many patients with rare diseases, the research is scarce and fragmented. More research is warranted. Information about the unique challenges of living with different rare diseases is crucial for health and welfare systems to better facilitate work participation. In addition, the changing nature of work in the digital age, may also open up new possibilities for people with rare genetic diseases and should be explored.

PMID:37208707 | PMC:PMC10197424 | DOI:10.1186/s12889-023-15654-3

Stud Health Technol Inform. 2023 May 18;302:607-608. doi: 10.3233/SHTI230216.

ABSTRACT

The common occurrence of characteristic symptoms can be used to infer diagnoses. The aim of this study is to show how syndrome similarity analysis using given phenotypic profiles can help in the diagnosis of rare diseases. HPO was used to map syndromes and phenotypic profiles. The system architecture described is planned to be implemented in a clinical decision support system for unclear diseases.

PMID:37203759 | DOI:10.3233/SHTI230216

Stud Health Technol Inform. 2023 May 18;302:358-359. doi: 10.3233/SHTI230139.

ABSTRACT

Rare diseases are commonly defined by an incidence of less than 5/10000 inhabitants. There are some 8000 different rare diseases known. So even if a single rare disease is seldom, together they pose a relevant problem for diagnosis and treatment. This is especially true if a patient is treated for another common disease. University hospital of Gießen is part of the CORD-MI Project on rare diseases within the German Medical Informatics Initiative (MII) and a member of the MIRACUM consortium within the MII. As part of the ongoing Development for a clinical research study monitor within the use case 1 of MIRACUM, the study monitor has been configured to detect patients with rare diseases during their routine clinical encounters. The goal was to send a documentation request to the corresponding patient chart within the patient data management system for extended disease documentation to enhance clinical awareness for the patients' potential problems. The project was started in late 2022 and has so far been successfully tuned to detect patients with Mucoviscidosis and place notifications within the patient chart of the patient data management system (PDMS) on intensive care units.

PMID:37203683 | DOI:10.3233/SHTI230139

Stud Health Technol Inform. 2023 May 18;302:292-296. doi: 10.3233/SHTI230121.

ABSTRACT

The project "Collaboration on Rare Diseases" CORD-MI connects various university hospitals in Germany to collect sufficient harmonized electronic health record (EHR) data for supporting clinical research in the field of rare diseases (RDs). However, the integration and transformation of heterogeneous data into an interoperable standard through Extract-Transform-Load (ETL) processes is a complex task that may influence the data quality (DQ). Local DQ assessments and control processes are needed to ensure and improve the quality of RD data. We therefore aim to investigate the impact of ETL processes on the quality of transformed RD data. Seven DQ indicators for three independent DQ dimensions were evaluated. The resulting reports show the correctness of calculated DQ metrics and detected DQ issues. Our study provides the first comparison results between the DQ of RD data before and after ETL processes. We found that ETL processes are challenging tasks that influence the quality of RD data. We have demonstrated that our methodology is useful and capable of evaluating the quality of real-world data stored in different formats and structures. Our methodology can therefore be used to improve the quality of RD documentation and to support clinical research.

PMID:37203665 | DOI:10.3233/SHTI230121

Stud Health Technol Inform. 2023 May 18;302:1037-1041. doi: 10.3233/SHTI230342.

ABSTRACT

In the context of medical concept extraction, it is critical to determine if clinical signs or symptoms mentioned in the text were present or absent, experienced by the patient or their relatives. Previous studies have focused on the NLP aspect but not on how to leverage this supplemental information for clinical applications. In this paper, we aim to use the patient similarity networks framework to aggregate different phenotyping modalities. NLP techniques were applied to extract phenotypes and predict their modalities from 5470 narrative reports of 148 patients with ciliopathies (a group of rare diseases). Patient similarities were computed using each modality separately for aggregation and clustering. We found that aggregating negated phenotypes improved patient similarity, but further aggregating relatives' phenotypes worsened the result. We suggest that different modalities of phenotypes can contribute to patient similarity, but they should be aggregated carefully and with appropriate similarity metrics and aggregation models.

PMID:37203576 | DOI:10.3233/SHTI230342

Int J Equity Health. 2023 May 17;22(1):93. doi: 10.1186/s12939-023-01903-9.

ABSTRACT

BACKGROUND: Rare diseases (RDs) are difficult to diagnose and expensive to treat. Thus, the South Korean government has implemented several policies to help RD patients, including the Medical Expense Support Project, supporting low- to middle-income RD patients. However, no study in Korea has yet addressed health inequity in RD patients. This study assessed inequity trends in the medical utilization and expenditures of RD patients.

METHODS: This study measured the horizontal inequity index (HI) of RD patients and an age- and sex-matched control group using the National Health Insurance Service data from 2006 to 2018. Sex, age, number of chronic diseases, and disability variables were used to model expected medical needs and adjust the concentration index (CI) for medical utilization and expenditures.

RESULTS: The HI index of healthcare utilization in RD patients and the control group ranged from -0.0129 to 0.0145, increasing until 2012 and fluctuating since then. This increasing trend was more apparent for inpatient utilization in the RD patient group than in the outpatient group. The same index in the control group ranged from -0.0112 to -0.0040 without a significant trend. The healthcare expenditure HI in RD patients rose from -0.0640 to -0.0038, showing pro-poor values but moving toward a pro-rich state. In the control group, the HI for healthcare expenditures remained between 0.0029 and 0.0085.

CONCLUSIONS: The HI of inpatient utilization and inpatient expenditures increased in a pro-rich state. The study results showed that implementing a policy that supports inpatient service utilization could help achieve health equity for RD patients.

PMID:37198638 | DOI:10.1186/s12939-023-01903-9

Nat Rev Drug Discov. 2023 Jun;22(6):440-441. doi: 10.1038/d41573-023-00082-0.

NO ABSTRACT

PMID:37193741 | DOI:10.1038/d41573-023-00082-0

Biomedicines. 2023 Apr 20;11(4):1226. doi: 10.3390/biomedicines11041226.

ABSTRACT

Asthma affects 10% of the worldwide population; about 5% of cases are severe with the need for target therapies such as biologics. All the biologics approved for asthma hit the T2 pathway of inflammation. T2-high asthma is classified as allergic and non-allergic, whereas T2-low asthma can be further defined as paucigranulocytic asthma, Type 1 and Type-17 inflammation and the neutrophilic form that accounts for 20-30% of all patients with asthma. Neutrophilic asthma's prevalence is even higher in patients with severe or refractory asthma. We searched Medline and PubMed archives from the past ten years for articles with the subsequent titles: "neutrophilic asthma", "non-type 2 asthma" and "paucigranulocytic asthma". We identified 177 articles; 49 were considered relevant by the title and 33 by the reading of the abstract. Most of these articles are reviews (n = 19); only 6 are clinical trials. No study identified an effective treatment. We used the literature reported by these articles to search for further biologic treatments that target pathways different from T2. We identified 177 articles, 93 of which were considered relevant for the review and included in the present article. In conclusion, T2-low asthma remains poorly investigated in terms of biomarkers, especially as a therapeutic orphan disease.

PMID:37189844 | DOI:10.3390/biomedicines11041226

Taiwan J Obstet Gynecol. 2023 May;62(3):440-443. doi: 10.1016/j.tjog.2022.12.011.

ABSTRACT

OBJECTIVE: Wolfram Syndrome (WS) is a rare autosomal recessive neurodegenerative disorder caused by mutations in WFS1 or CISD2 (WFS2). We present a rare case report of pregnancy with WFS1 spectrum disorder (WFS1-SD) in our hospital and reviewed literature to provide the management of pregnancy in these patients through multi-disciplinary cooperation.

CASE REPORT: A 31-year-old (gravida 6, para 1) woman with WFS1-SD conceived naturally. During the pregnancy, she adjusted insulin intermittently to control blood glucose and monitored intraocular pressure changes under the guidance of doctors without any complications. Cesarean section was delivered at 37+4 weeks of gestation due to breech position and uterine scar and the neonatal weight was 3200 g. Apgar score 10 at 1 min, 10 at 5-min and 10 at 10 min, respectively. This rare case had a good maternal and infant outcome under multidisciplinary management.

CONCLUSION: WS is an extremely rare disease. Limited information is available on the impact and management of WS on maternal physiologic adaptation and fetal outcome. This case provide a guide for clinicians to raise awareness of this rare disease and strengthen the management of pregnancy in these patients.

PMID:37188450 | DOI:10.1016/j.tjog.2022.12.011

Khirurgiia (Mosk). 2023;(5):101-104. doi: 10.17116/hirurgia2023051101.

ABSTRACT

We report a patient with combination of esophageal atresia, proximal tracheoesophageal fistula and meconium peritonitis. These two rare disorders have different etiology, pathogenetic mechanisms and require different diagnostic manipulations and surgical treatments. The authors discuss the features of diagnosis and surgical treatment of this disease.

PMID:37186657 | DOI:10.17116/hirurgia2023051101

Ann Ig. 2023 Jul-Aug;35(4):379-402. doi: 10.7416/ai.2023.2555. Epub 2023 Feb 3.

ABSTRACT

INTRODUCTION: Communication has a crucial role in public health, because it becomes an essential component of prevention; it is also a proactive tool in health promotion. From a planning perspective, it is appropriate to use communication means that can help the bidirectional communication process, such as face-to-face communication and telephone communication.

MATERIALS AND METHODS: In relation to this, the Italian National Institute of Health has developed the "Modello Operativo Comunicativo-Relazionale" (the "Communicative-Relational Operating Model"). It is based on the fundamental skills of the counselling, this gives a protocol to the health professionals that is replicable and organized and it allows health professionals to carry out a telephone communication that is efficient with the user through technical-scientific and communication-relational skills. The goal is to answer in a customized way to the various users' health needs. The Operating Model was created by experts of the National AIDS and Sexually Transmitted Infections Helpline of the Operational Unit of Psycho-Socio-Behavioural Research, Communication, Training, of the Infectious Diseases Department. Later, the Operating Model was proposed to the experts of the Helplines in the National Centre on Addictions and Doping and the National Helpline of the National Centre for Rare Diseases in the National Institute of Health that integrated this method into their telephone approach.

RESULTS: The Operating Model illustrated above was applied to several helplines of the National Institute of Health as an example of correct scientific information, updated and customized on sexual transmitted infections, addictions and rare diseases.

CONCLUSIONS: This article aims to illustrate the Operating Model, the theoretical prerequisites that subtend it and its possible application in the different public health structures that use the telephone for a profes-sional relationship with their users.

PMID:37184351 | DOI:10.7416/ai.2023.2555

Hepatology. 2023 May 16. doi: 10.1097/HEP.0000000000000458. Online ahead of print.

ABSTRACT

Acute liver failure (ALF) describes a clinical syndrome of rapid hepatocyte injury leading to liver failure manifested by coagulopathy and encephalopathy in the absence of pre-existing cirrhosis. The hallmark diagnostic features are a prolonged prothrombin time (i.e., an international normalized ratio of prothrombin time (INR) of ≥ 1.5) and any degree of mental status alteration (hepatic encephalopathy, HE). As a rare, orphan disease, it seemed an obvious target for a multi-center network. The Acute Liver Failure Study Group (ALFSG) began in 1997 to more thoroughly study and understand the causes, natural history, and management of ALF. Over the course of 22 years, 3,364 adult patients were enrolled in the study registry (2,614 ALF and 857 acute liver injury-INR 2.0 but no encephalopathy--ALI) and more than 150,000 bio-samples collected, including serum, plasma, urine, DNA, and liver tissue. Within the Registry study sites, four prospective substudies were conducted and published, two interventional (N-acetylcysteine (NAC) and ornithine phenylacetate (OPA)), one prognostic (13C-methacetin breath test (MBT)), and one mechanistic (rotational thromboelastometry (ROTEM)). To review ALFSG's accomplishments and consider next steps, a two-day in-person conference was held at UT Southwestern Medical Center, Dallas, Texas, entitled "Acute Liver Failure: Science and Practice," in May 2022. To summarize the important findings in the field, this review highlights the current state of understanding of ALF and, more importantly, asks what further studies are needed to improve our understanding of the pathogenesis, natural history, and management of this unique and dramatic condition.

PMID:37183883 | DOI:10.1097/HEP.0000000000000458

Expert Opin Drug Discov. 2023 May 15:1-13. doi: 10.1080/17460441.2023.2211802. Online ahead of print.

ABSTRACT

INTRODUCTION: Zebrafish larvae are one of the few vertebrates amenable to large-scale drug discovery screens. Larval swimming behavior is often used as an outcome variable and many fields of study have developed assays for evaluating swimming performance. An unintended consequence of this wide interest is that details related to assay methodology and interpretation become scattered across the literature. The aim of this review is to consolidate this information, particularly as it relates to high-throughput approaches.

AREAS COVERED: The authors describe larval swimming behaviors as this forms the basis for understanding their experimentally evoked swimming or spontaneous activity. Next, they detail how swimming activity can serve as an outcome variable, particularly in the multi-well formats used in large-scale screening studies. They also highlight biological and technical factors that can impact the sensitivity and variability of these measurements.

EXPERT OPINION: Careful attention to animal husbandry, experimental design, data acquisition, and interpretation of results can improve screen outcomes by maximizing swimming activity while minimizing intra- and inter-larval variability. The development of more sensitive, quantitative methods of assessing swimming performance that can be incorporated into high-throughput workflows will be important in order to take full advantage of the zebrafish model.

PMID:37183669 | DOI:10.1080/17460441.2023.2211802

Am J Med Genet A. 2023 May 14. doi: 10.1002/ajmg.a.63226. Online ahead of print.

ABSTRACT

Jansen-de Vries syndrome (JdVS) is a neurodevelopmental condition attributed to pathogenic variants in Exons 5 and 6 of PPM1D. As the full phenotypic spectrum and natural history remain to be defined, we describe a large cohort of children and adults with JdVS. This is a retrospective cohort study of 37 individuals from 34 families with disease-causing variants in PPM1D leading to JdVS. Clinical data were provided by treating physicians and/or families. Of the 37 individuals, 27 were male and 10 female, with median age 8.75 years (range 8 months to 62 years). Four families document autosomal dominant transmission, and 32/34 probands were diagnosed via exome sequencing. The facial gestalt, including a broad forehead and broad mouth with a thin and tented upper lip, was most recognizable between 18 and 48 months of age. Common manifestations included global developmental delay (35/36, 97%), hypotonia (25/34, 74%), short stature (14/33, 42%), constipation (22/31, 71%), and cyclic vomiting (6/35, 17%). Distinctive personality traits include a hypersocial affect (21/31, 68%) and moderate-to-severe anxiety (18/28, 64%). In conclusion, JdVS is a clinically recognizable neurodevelopmental syndrome with a characteristic personality and distinctive facial features. The association of pathogenic variants in PPM1D with cyclic vomiting bears not only medical attention but also further pathogenic and mechanistic evaluation.

PMID:37183572 | DOI:10.1002/ajmg.a.63226

Ther Adv Rare Dis. 2020 Oct 22;1:2633004020959349. doi: 10.1177/2633004020959349. eCollection 2020 Jan-Dec.

ABSTRACT

Paroxysmal nocturnal haemoglobinuria (PNH) is an ultra-orphan disease, which until 15 years ago had limited treatment options. Eculizumab, a monoclonal antibody that inhibits C5 in the terminal complement cascade, has revolutionised treatment for this disease, near normalising life expectancy and improving quality of life for patients. The treatment landscape of PNH is now evolving, with ravulizumab a second longer acting intravenous C5 inhibitor now licenced by the FDA and EMA. With different therapeutic targets in the complement cascade and difference modalities of treatment, including subcutaneous, oral and intravenous therapies being developed, increasing independence for patients and reducing healthcare requirements. This review discusses the current and future therapies for PNH.

LAY SUMMARY: Review of current and future treatments for patients with Paroxysmal Nocturnal Haemoglobinuria What is Paroxysmal Nocturnal Haemoglobinuria? Paroxysmal nocturnal haemoglobinuria (PNH) is a very rare disease. It arises from PNH stem cells in the bone marrow. In a normal bone marrow these are inactive; however, if there has been a problem in the bone marrow, the PNH stem cells can expand and make PNH red blood cells, white blood cells and platelets. The problem with these cells is that they lack the cell surface markers that usually protect them. Red blood cells are broken down in the circulation rather than the spleen, which gives rise to PNH symptoms such as abdominal pain, difficulty swallowing, erectile dysfunction and red or black urine (known as haemoglobinuria). The white blood cells and platelets are 'stickier' increasing the risk of blood clots. Previously life expectancy was reduced as there were limited treatment options available. What was the aim of this review? To provide an overview of current and future treatment options for PNH Which treatments are available? • Eculizumab is an treatment given through a vein (intravenous) every week for 5 weeks then every 2 weeks after this, and has been available for 13 years, improving life expectancy to near normal.• Ravulizumab is a newer intravenous treatment similar to eculizumab but is given every 8 weeks instead of every 2 weeks. In clinical studies it was comparable with eculizumab.• Future Treatments - There is new research looking at different methods of treatment delivery, including injections under the skin (subcutaneous) that patients can give themselves, treatments taken by mouth (oral) or a combination of an intravenous and oral treatment for those patients who are not optimally controlled on eculizumab or ravulizumab. What does this mean? PNH is now treatable. For years, the only drug available was eculizumab, but now different targets and drug trials are available. Ravulizumab is currently the only second licenced product available, in USA and Europe, there are other medications active in clinical trials. Why is this important? The benefit for patients, from treatment every 2 weeks to every 8 weeks is likely to be improved further with the development of these new treatments, providing patients with improved disease control and independence.As we move into an era of more patient-friendly treatment options, the PNH community both physicians and patients look forward to new developments as discussed in this article.

PMID:37180495 | PMC:PMC10032435 | DOI:10.1177/2633004020959349

Int J Mol Sci. 2023 Apr 26;24(9):7880. doi: 10.3390/ijms24097880.

ABSTRACT

Drug-Induced Enterocolitis Syndrome (DIES) is a drug-induced hypersensitivity reaction non-IgE mediated involving the gastrointestinal system that occurs 2 to 4 h after drug administration. Antibiotics, specifically amoxicillin or amoxicillin/clavulanate, represent the most frequent drugs involved. Symptoms include nausea, vomiting, abdominal pain, diarrhea, pallor, lethargy, and dehydration, which can be severe and result in hypovolemic shock. The main laboratory finding is neutrophilic leukocytosis. To the best of our knowledge, 12 cases of DIES (9 children-onset and 3 adult-onset cases) were described in the literature. DIES is a rare clinically well-described allergic disease; however, the pathogenetic mechanism is still unclear. It requires to be recognized early and correctly treated by physicians.

PMID:37175584 | PMC:PMC10178722 | DOI:10.3390/ijms24097880

Cancers (Basel). 2023 Apr 28;15(9):2527. doi: 10.3390/cancers15092527.

ABSTRACT

T-prolymphocytic leukemia (T-PLL) is a rare and mature T-cell malignancy with characteristic chemotherapy-refractory behavior and a poor prognosis. Molecular concepts of disease development have been restricted to protein-coding genes. Recent global microRNA (miR) expression profiles revealed miR-141-3p and miR-200c-3p (miR-141/200c) as two of the highest differentially expressed miRs in T-PLL cells versus healthy donor-derived T cells. Furthermore, miR-141/200c expression separates T-PLL cases into two subgroups with high and low expression, respectively. Evaluating the potential pro-oncogenic function of miR-141/200c deregulation, we discovered accelerated proliferation and reduced stress-induced cell death induction upon stable miR-141/200c overexpression in mature T-cell leukemia/lymphoma lines. We further characterized a miR-141/200c-specific transcriptome involving the altered expression of genes associated with enhanced cell cycle transition, impaired DNA damage responses, and augmented survival signaling pathways. Among those genes, we identified STAT4 as a potential miR-141/200c target. Low STAT4 expression (in the absence of miR-141/200c upregulation) was associated with an immature phenotype of primary T-PLL cells as well as with a shortened overall survival of T-PLL patients. Overall, we demonstrate an aberrant miR-141/200c-STAT4 axis, showing for the first time the potential pathogenetic implications of a miR cluster, as well as of STAT4, in the leukemogenesis of this orphan disease.

PMID:37173993 | DOI:10.3390/cancers15092527

Ugeskr Laeger. 2023 May 1;185(18):V01230060.

ABSTRACT

Cholesterol pericarditis is an extremely rare type of pericarditis characterized by a continuous pericardial effusion containing high amounts of cholesterol crystals. This case report of a 51-year-old male with syncopal episodes and a massive, cholesterol-rich pericardial effusion highlights the interdisciplinary approach and rationale in treating this rare condition of largely unknown pathogenesis.

PMID:37170745

Orphanet J Rare Dis. 2023 May 11;18(1):114. doi: 10.1186/s13023-023-02713-6.

ABSTRACT

BACKGROUND: Rare disease is a general term for a disease that affects a small number of people but recognized as a global public health priority. Governments worldwide are paying more and more attention to the academical research and drug investment of rare diseases. The conduct of rare disease clinical trials is still difficult, despite the promotion of government policies and the awakening of social consciousness. In this article, we outlined the characteristics and obstacles of clinical trials of rare diseases in China and expected to provide reference for subsequent clinical trials in this field.

RESULTS: In recent years, China has made some progress in clinical trials of rare diseases in the past 10 years. There were 481 clinical trials on rare diseases in total, covering more than 10 rare diseases with high incidence. Clinical trial applications on rare diseases for a total of 481 were submitted and with an average annual growth rate of 28.2% from 2013 to 2022. The number of clinical trial application for rare diseases in 2016 dramatically increased by 80% compared to 2015 due to the policy document issued by China for clinical research in rare diseases in 2015. Besides, about 70% of applications registering for clinical trials could recruit subjects as expected. Despite this, the number of clinical trials of rare diseases in China was less compared with the United States, Europe and Japan, and the types of infant drugs were limited to biological products and chemical drugs lacking other new treatments.

CONCLUSIONS: Efforts have been made in recent years to develop clinical research on rare diseases in China. The number of clinical trials for rare diseases in China was growing steadily every year, which was inseparable from the support of the country, society and rare disease patients. Still, there was a large gap between China and other developed countries in this field and this merit further investigation.

PMID:37170366 | PMC:PMC10173236 | DOI:10.1186/s13023-023-02713-6

An Sist Sanit Navar. 2023 Apr 29;46(1):e1038. doi: 10.23938/ASSN.1038.

NO ABSTRACT

PMID:37166237 | DOI:10.23938/ASSN.1038