bioRxiv [Preprint]. 2024 Sep 27:2024.09.25.612672. doi: 10.1101/2024.09.25.612672.

ABSTRACT

In the first postnatal month, the developing mouse intestine shifts from an immature to a mature intestine that will sustain the organism throughout the lifespan. Here, we surveyed the mouse intestine in C57Bl/6 mice by RNA-Seq to evaluate the changes in gene expression over time from the day of birth through 1 month of age in both the duodenum and ileum. We analyzed gene expression for changes in gene families that correlated with the periods of NEC susceptibility or resistance. We highlight that increased expression of DNA processing genes and vacuolar structure genes, tissue development and morphogenesis genes, and cell migration genes all correlated with NEC susceptibility, while increases in immunity gene sets, intracellular transport genes, ATP production, and intracellular metabolism genes correlated with NEC resistance. Using trends identified in the RNA analyses, we further evaluated expression of cellular markers and epithelial regulators, immune cell markers, and adenosine metabolism components. We confirmed key changes with qRT-PCR and immunofluorescence. In addition, we compared some findings to humans using human intestinal biopsies and organoids. This dataset can serve as a reference for other groups considering the role of single molecules or molecular families in early intestinal and postnatal development.

PMID:39386454 | PMC:PMC11463582 | DOI:10.1101/2024.09.25.612672

Science. 2024 Oct 11;386(6718):217-224. doi: 10.1126/science.adq1456. Epub 2024 Oct 10.

ABSTRACT

Germline mutations modulate the risk of developing schizophrenia (SCZ). Much less is known about the role of mosaic somatic mutations in the context of SCZ. Deep (239×) whole-genome sequencing (WGS) of brain neurons from 61 SCZ cases and 25 controls postmortem identified mutations occurring during prenatal neurogenesis. SCZ cases showed increased somatic variants in open chromatin, with increased mosaic CpG transversions (CpG>GpG) and T>G mutations at transcription factor binding sites (TFBSs) overlapping open chromatin, a result not seen in controls. Some of these variants alter gene expression, including SCZ risk genes and genes involved in neurodevelopment. Although these mutational processes can reflect a difference in factors indirectly involved in disease, increased somatic mutations at developmental TFBSs could also potentially contribute to SCZ.

PMID:39388546 | DOI:10.1126/science.adq1456

Int J Public Health. 2024 Sep 25;69:1607548. doi: 10.3389/ijph.2024.1607548. eCollection 2024.

ABSTRACT

OBJECTIVES: This study aims to determine clusters of access to healthcare among adults with rare diseases in Switzerland, identify associated individual characteristics of access, and impact on health-related quality of life (HRQoL).

METHODS: Swiss adults (N = 341) diagnosed with a rare disease completed an online survey including the Perception of Access to Healthcare Questionnaire (PAHQ) and Short Form Health Survey (SF-12). We employed partition around medoids algorithm to identify patient clusters based on the PAHQ. Various sociodemographic/disease-related factors and HRQoL were assessed.

RESULTS: We identified two patient clusters: higher (n = 227) and lower access (n = 114). Significantly associated with lower access were an unstable disease course (p < 0.05), increased number of misdiagnoses (p < 0.05), and diseases affecting the nervous system (p < 0.01). Membership in the lower access cluster was significantly associated with worse HRQoL (p < 0.05).

CONCLUSION: Findings highlight the need for comprehensive assessment of healthcare access in adults with rare diseases and identifies potential targets for tailored interventions.

PMID:39386998 | PMC:PMC11461209 | DOI:10.3389/ijph.2024.1607548

Adv Rheumatol. 2024 Oct 9;64(1):79. doi: 10.1186/s42358-024-00421-8.

ABSTRACT

Systemic vasculitis is a group of rare diseases that share an essential characteristic: inflammation of blood vessel walls. This injury occurs during the disease course, but specific features vary for each entity. In this paper, we will address relevant aspects of the newest monogenic mutation vasculitis, such as deficiency of adenosine deaminase 2 (ADA2) and VEXAS syndrome (UBA1), and other relevant vasculitis, such as Cogan syndrome and Susac syndrome that may share some similarities with them.

PMID:39385260 | DOI:10.1186/s42358-024-00421-8

Orphanet J Rare Dis. 2024 Oct 8;19(1):371. doi: 10.1186/s13023-024-03367-8.

ABSTRACT

Phenotypes play a fundamental role in medical genetics, serving as external manifestations of underlying genotypes. Deep phenotyping, a cornerstone of precision medicine, involves precise multi-system phenotype assessments, facilitating disease subtyping and genetic understanding. Despite their significance, the field lacks standardized protocols for accurate phenotype evaluation, hindering clinical comprehension and research comparability. We present a comprehensive workflow of deep phenotyping for rare bone diseases from the Genetics Clinic of Skeletal Deformity at Peking Union Medical College Hospital. Our workflow integrates referral, informed consent, and detailed phenotype evaluation through HPO standards, capturing nuanced phenotypic characteristics using clinical examinations, questionnaires, and multimedia documentation. Genetic testing and counseling follow, based on deep phenotyping results, ensuring personalized interventions. Multidisciplinary team consultations facilitate comprehensive patient care and clinical guideline development. Regular follow-up visits emphasize dynamic phenotype reassessment, ensuring treatment strategies remain responsive to evolving patient needs. In conclusion, this study highlights the importance of deep phenotyping in rare bone diseases, offering a standardized framework for phenotype evaluation, genetic analysis, and multidisciplinary intervention. By enhancing clinical care and research outcomes, this approach contributes to the advancement of precision medicine in the field of medical genetics.

PMID:39380097 | PMC:PMC11462960 | DOI:10.1186/s13023-024-03367-8

BMC Med Inform Decis Mak. 2024 Oct 8;24(1):289. doi: 10.1186/s12911-024-02698-7.

ABSTRACT

PURPOSE: Rare diseases pose significant challenges in diagnosis and treatment due to their low prevalence and heterogeneous clinical presentations. Unstructured clinical notes contain valuable information for identifying rare diseases, but manual curation is time-consuming and prone to subjectivity. This study aims to develop a hybrid approach combining dictionary-based natural language processing (NLP) tools with large language models (LLMs) to improve rare disease identification from unstructured clinical reports.

METHODS: We propose a novel hybrid framework that integrates the Orphanet Rare Disease Ontology (ORDO) and the Unified Medical Language System (UMLS) to create a comprehensive rare disease vocabulary. SemEHR, a dictionary-based NLP tool, is employed to extract rare disease mentions from clinical notes. To refine the results and improve accuracy, we leverage various LLMs, including LLaMA3, Phi3-mini, and domain-specific models like OpenBioLLM and BioMistral. Different prompting strategies, such as zero-shot, few-shot, and knowledge-augmented generation, are explored to optimize the LLMs' performance.

RESULTS: The proposed hybrid approach demonstrates superior performance compared to traditional NLP systems and standalone LLMs. LLaMA3 and Phi3-mini achieve the highest F1 scores in rare disease identification. Few-shot prompting with 1-3 examples yields the best results, while knowledge-augmented generation shows limited improvement. Notably, the approach uncovers a significant number of potential rare disease cases not documented in structured diagnostic records, highlighting its ability to identify previously unrecognized patients.

CONCLUSION: The hybrid approach combining dictionary-based NLP tools with LLMs shows great promise for improving rare disease identification from unstructured clinical reports. By leveraging the strengths of both techniques, the method demonstrates superior performance and the potential to uncover hidden rare disease cases. Further research is needed to address limitations related to ontology mapping and overlapping case identification, and to integrate the approach into clinical practice for early diagnosis and improved patient outcomes.

PMID:39375687 | PMC:PMC11460004 | DOI:10.1186/s12911-024-02698-7

Proc Natl Acad Sci U S A. 2024 Oct 15;121(42):e2400709121. doi: 10.1073/pnas.2400709121. Epub 2024 Oct 7.

ABSTRACT

Developmental and epileptic encephalopathies (DEE) are rare but devastating and largely intractable childhood epilepsies. Genetic variants in ARHGEF9, encoding a scaffolding protein important for the organization of the postsynaptic density of inhibitory synapses, are associated with DEE accompanied by complex neurological phenotypes. In a mouse model carrying a patient-derived ARHGEF9 variant associated with severe disease, we observed aggregation of postsynaptic proteins and loss of functional inhibitory synapses at the axon initial segment (AIS), altered axo-axonic synaptic inhibition, disrupted action potential generation, and complex seizure phenotypes consistent with clinical observations. These results illustrate diverse roles of ARHGEF9 that converge on regulation of the structure and function of the AIS, thus revealing a pathological mechanism for ARHGEF9-associated DEE. This unique example of a neuropathological condition associated with multiple AIS dysfunctions may inform strategies for treating neurodevelopmental diseases.

PMID:39374387 | DOI:10.1073/pnas.2400709121

Elife. 2024 Oct 7;13:e102833. doi: 10.7554/eLife.102833.

ABSTRACT

Solitary fibrous tumors have gene expression signatures similar to those of neuroendocrine tumors.

PMID:39370970 | PMC:PMC11458173 | DOI:10.7554/eLife.102833

Gastroenterol Nurs. 2024 Sep-Oct 01;47(5):368-372. doi: 10.1097/SGA.0000000000000805. Epub 2024 Sep 27.

NO ABSTRACT

PMID:39356123 | DOI:10.1097/SGA.0000000000000805

Front Public Health. 2024 Sep 17;12:1373649. doi: 10.3389/fpubh.2024.1373649. eCollection 2024.

ABSTRACT

BACKGROUND: A definite diagnosis goes undiscovered for a percentage of children with undiagnosed disorders, with significant medical, psychological, and social effects. Other than specialized clinical centers, exceptional molecular studies, common procedures, and devoted activities at the national and international levels, children with complex undiagnosed disorders require innovative approaches.

METHODS: In March 2016, Children's hospital of Fudan university represented the Children's Undiagnosed Diseases Program (UDP). The purpose of this study is to describe the project findings and underline the critical significance of multidisciplinary teamwork in China's undiagnosed rare illnesses program. We investigated the 758 cases in our UDP system retrospectively. Demographic information, laboratory test results, and genetic information were gathered.

RESULTS: Between January 2017 and December 2021, 758 cases were examined. Males made up 436 (57.5%) of the total. Over half of the patients were children under the age of five. The average patient course time preceding admission to UDP was 6.0 months (95% CI 10.512.6). These patients visited an average of 1.8 clinics during their diagnostic journey. Except for 69 individuals (90.9%), all had more than one presenting symptom in various organs: 460 (60.7%) had neurology difficulties, 151 (19.9%) had endocrine problems, and 141 (18.6%) had immunology problems. UDP has a diagnosis rate of 61.3%. Genetic testing was performed on 469 of the 758 patients, for a genetic diagnosis rate of 15.8%. The UDP method has a sensitivity of 94.5%, a specificity of 86.4%, a positive predictive value of 92.8%, and an negative predictive value of 89.5%.

CONCLUSION: Our UDP targets an unmet need, namely the diagnosis of patients with complicated, multisystem illnesses. Using a multidisciplinary team model approach, this UDP pilot study achieved a reasonable diagnosis success rate, increasing the possibility of more diagnoses and new scientific discoveries of difficult and rare diseases.

PMID:39354993 | PMC:PMC11442281 | DOI:10.3389/fpubh.2024.1373649

Methodist Debakey Cardiovasc J. 2024 Sep 26;20(1):94-97. doi: 10.14797/mdcvj.1458. eCollection 2024.

ABSTRACT

Coronary arteries normally originate from two separate cusps from the aorta, and various anomalies can occur. One such anomaly is the single coronary artery (SCA), where the coronary arteries originate from a single ostium due to the absence of the contralateral ostia. In a rare case we encountered while evaluating a patient with atypical chest pain, computed tomography angiography revealed that the right ostia was absent, and the right coronary artery originated from the left circumflex artery. This subtype of SCA has been exceedingly rare, with only a few cases reported in the literature.

PMID:39346745 | PMC:PMC11428661 | DOI:10.14797/mdcvj.1458

BMC Public Health. 2024 Sep 30;24(1):2675. doi: 10.1186/s12889-024-19956-y.

ABSTRACT

BACKGROUND: Bronchiectasis, once considered an orphan disease, is receiving attention globally owing to its increasing prevalence, healthcare burden, and associated morbidity. However, the prevalence of bronchiectasis is unclear. This meta-analysis estimates the prevalence of bronchiectasis in adults, providing a valuable reference for future research.

METHODS: PubMed, Embase, Cochrane Library, and Web of Science databases were searched from inception to May 31, 2024 for studies reporting the prevalence of bronchiectasis. Study selection, data extraction, and overall analysis of risk of the retrieved studies were conducted independently by two authors. The tool for assessing the risk of bias in prevalence studies was used to evaluate overall risk. Stata software (version 15.1) was used to performed the meta-analysis. Subgroup and sensitivity analyses were conducted to identify the source of heterogeneity. Funnel plots combined with Egger's test were used to detect publication bias.

RESULTS: The pooled prevalence of bronchiectasis in adults from 15 studies covering 437,851,478 individuals was 680 per 100,000 (95% CI: 634-727 per 100,000). Subgroup analysis showed that the prevalence of bronchiectasis in the United States, Korea, and China was 478 per 100,000 (95% CI: 367-588 per 100,000), 886 per 100,000 (95% CI: 778-993 per 100,000), and 759 per 100,000 (95% CI: 35-2399 per 100,000), respectively; 467 per 100,000 (95% CI: 416-518 per 100,000) in males and 535 per 100,000 (95% CI: 477-592 per 100,000) in females; 3958 per 100,000 (95% CI: 117-12637 per 100,000), 4677 per 100,000 (95% CI: 427-8928 per 100,000), and 3630 per 100,000 (95% CI: 158-7103 per 100,000) among never-smokers, ever-smokers, and current smokers, respectively; 430 per 100,000 (95% CI: 411-450 per 100,000), 380 per 100,000 (95% CI: 374-386 per 100,000), and 351 per 100,000 (95% CI: 342-360 per 100,000) among individuals with body mass index<18.5, 18.5-24.9, and ≥ 25, respectively. Sixteen comorbidities were evaluated in patients with bronchiectasis, revealing a high rate.

CONCLUSION: Bronchiectasis is not a rare disease and requires more attention from scientific researchers.

TRIAL REGISTRATION: The protocol for this review was registered with PROSPERO: CRD42023409216. Registered 26 June 2023.

PMID:39350110 | PMC:PMC11443950 | DOI:10.1186/s12889-024-19956-y

Health Policy. 2024 Nov;149:105176. doi: 10.1016/j.healthpol.2024.105176. Epub 2024 Sep 26.

ABSTRACT

Ageism in healthcare has received increased attention in recent years, but literature focusing on how it affects individuals living with rare diseases remains scant. The rare disease population already faces obstacles when navigating health systems, and ageism has the potential to exacerbate existing health inequities. We conducted a systematic review of peer-reviewed and gray literature on health inequities in rare disease populations, seeking to identify publications that reported primary or secondary data on the equitable or inequitable treatment of these populations, or that discussed related regulatory, moral, or philosophical issues. Our aims were to understand how health inequities in these populations arise, how they are justified from societal points of view, how they manifest themselves in laws and regulations, and what effects they have on health care access and health outcomes. We retrieved information from 63 publications, which we inductively synthesized into five categories: ethical discussions, societal preferences, regulations, access to care, and health outcomes. Integrating insights from these categories, we developed an Ethical Spectrum and Resource Allocation Framework, which explains the emergence of equity issues and how they are manifested in health systems. By providing a better understanding of the root causes of health inequities, particularly among older adults, the framework can inform health policymaking, improving access to care and health outcomes for rare disease patients.

PMID:39348734 | DOI:10.1016/j.healthpol.2024.105176

Nutrients. 2024 Sep 15;16(18):3114. doi: 10.3390/nu16183114.

ABSTRACT

Background/Objectives: Rare diseases are a wide and heterogeneous group of multisystem life-threatening or chronically debilitating clinical conditions with reduced life expectancy and a relevant mortality rate in childhood. Some of these disorders have typical neurological symptoms, presenting from birth to adulthood. Dietary patterns and nutritional compounds play key roles in the onset and progression of neurological disorders, and the impact of alimentary needs must be enlightened especially in rare neurological diseases. This work aims to collect the in vitro, in vivo, and clinical evidence on the effects of diet and of nutrient intake on some rare neurological disorders, including some genetic diseases, and rare brain tumors. Herein, those aspects are critically linked to the genetic, biological, biochemical, and pathophysiological hallmarks typical of each disorder. Methods: By searching the major web-based databases (PubMed, Web of Science Core Collection, DynaMed, and Clinicaltrials.gov), we try to sum up and improve our understanding of the emerging role of nutrition as both first-line therapy and risk factors in rare neurological diseases. Results: In line with the increasing number of consensus opinions suggesting that nutrients should receive the same attention as pharmacological treatments, the results of this work pointed out that a standard dietary recommendation in a specific rare disease is often limited by the heterogeneity of occurrent genetic mutations and by the variability of pathophysiological manifestation. Conclusions: In conclusion, we hope that the knowledge gaps identified here may inspire further research for a better evaluation of molecular mechanisms and long-term effects.

PMID:39339713 | PMC:PMC11435074 | DOI:10.3390/nu16183114

Int J Environ Res Public Health. 2024 Sep 20;21(9):1245. doi: 10.3390/ijerph21091245.

ABSTRACT

The caregivers of children suffering from rare diseases face numerous emotional, social, economic, organizational, and other difficulties, which can significantly impair their quality of life and mental health. Therefore, among other things, it is important to understand the factors which can influence psychosocial well-being. This research aimed to explore the association between healthcare satisfaction and social support and stress, depression, and life satisfaction in caregivers, with a moderating role of the ill child's dependence on their caregiver.

METHODS: A cross-sectional study was conducted among 185 female caregivers of children with rare diseases. The data were analysed by using hierarchical regression analysis to examine the moderating effect of the child's dependence.

RESULTS: Lower dependence of the child moderated the association between a higher level of healthcare satisfaction and reduced stress and a higher level of life satisfaction. Furthermore, lower child dependence moderated the association between a higher level of social support and a reduction in depression. In contrast, this association was absent in female caregivers with highly dependent children. On the other hand, the research confirmed that a higher level of social support led to stress reduction and increased life satisfaction in all respondents, regardless of the child's dependence. Furthermore, the research confirmed that higher levels of healthcare satisfaction are associated with a reduction in depression in caregivers, regardless of the child's dependence level.

CONCLUSION: This research highlights the importance of providing adequate social support and high-quality healthcare in order to improve the psychosocial well-being of caregivers of children with rare diseases. Interventions to increase this support can reduce stress and depression and increase caregivers' life satisfaction. Thus, future research should focus on the development and evaluation of specific interventions that support these factors.

PMID:39338128 | PMC:PMC11431563 | DOI:10.3390/ijerph21091245

Int J Environ Res Public Health. 2024 Sep 18;21(9):1227. doi: 10.3390/ijerph21091227.

ABSTRACT

The present study aimed to compare the prevalence of oral problems between individuals with rare genetic diseases that affect skeletal development and individuals without rare diseases. A cross-sectional study was conducted with 210 individuals between two and fifty-four years of age: 105 with rare genetic diseases (27 with mucopolysaccharidosis [MPS] and 78 with osteogenesis imperfecta [OI]) and 105 without rare diseases. The rare genetic disease group was recruited from hospital units that provide care for patients with MPS and OI in five states of Brazil, and the other group was recruited from the same location. The participants were examined with regards to malocclusion, dental anomalies, dental caries, and gingivitis. A questionnaire was administered addressing individual, sociodemographic, and behavioral characteristics as well as dental history. A descriptive analysis was performed, followed by unadjusted and adjusted binary logistic regression analyses. The mean age was 14.1 ± 12.2 years. Individuals with a rare disease were 12.9-fold more likely to have some type of oral problem (95% CI: 3.7-44.7) compared to the group without rare diseases. The prevalence of oral problems was higher among Brazilians with MPS and OI compared to normotypical individuals.

PMID:39338110 | PMC:PMC11431253 | DOI:10.3390/ijerph21091227

Genes (Basel). 2024 Sep 3;15(9):1162. doi: 10.3390/genes15091162.

ABSTRACT

In 2023, the genetics scientific community celebrated two special anniversaries: the discovery of the double helix structure of DNA was published in 1953 and in 2003 the Human Genome Project was declared completed and made publicly available. To this day, genetics and genomics research is continuing to evolve at high pace and is identifying a steadily increasing number of genes as causal for distinct genetic diseases. The success story of genetics and genomics would not be complete without taking due account of the role of patient advocacy organizations in this process. This paper is based on the personal narrative (oral history) of a father whose daughter was born with a rare genetic disease (RGD) in the 1960s. The first-hand experience of living as a family with an RGD in those days made him a leading pioneer not only in the foundation of patient organizations at national, pan-European, and international levels but also in the development of multi-stakeholder co-operation and networking. Today, patient advocacy organizations play an active role in shaping health and research policies at national, EU, and international levels to ensure that their needs in regard to advancing RGD diagnostics, care, and treatment are addressed.

PMID:39336753 | PMC:PMC11431757 | DOI:10.3390/genes15091162

Adv Rheumatol. 2024 Sep 27;64(1):74. doi: 10.1186/s42358-024-00407-6.

ABSTRACT

Although the terms "rare diseases" (RD) and "orphan diseases" (OD) are often used interchangeably, specific nuances in definitions should be noted to avoid misconception. RD are characterized by a low prevalence within the population, whereas OD are those inadequately recognized or even neglected by the medical community and drug companies. Despite their rarity, as our ability on discovering novel clinical phenotypes and improving diagnostic tools expand, RD will continue posing a real challenge for rheumatologists. Over the last decade, there has been a growing interest on elucidating mechanisms of rare autoimmune and autoinflammatory rheumatic diseases, allowing a better understanding of the role played by immune dysregulation on granulomatous, histiocytic, and hypereosinophilic disorders, just to name a few. This initiative enabled the rise of innovative targeted therapies for rheumatic RD. In this review, we explore the state-of-the art of rare RD and the critical role played by rheumatologists in healthcare. We also describe the challenges rheumatologists may face in the coming decades.

PMID:39334496 | DOI:10.1186/s42358-024-00407-6

Orphanet J Rare Dis. 2024 Sep 27;19(1):357. doi: 10.1186/s13023-024-03361-0.

ABSTRACT

Genetic diagnosis plays a crucial role in rare diseases, particularly with the increasing availability of emerging and accessible treatments. The International Rare Diseases Research Consortium (IRDiRC) has set its primary goal as: "Ensuring that all patients who present with a suspected rare disease receive a diagnosis within one year if their disorder is documented in the medical literature". Despite significant advances in genomic sequencing technologies, more than half of the patients with suspected Mendelian disorders remain undiagnosed. In response, IRDiRC proposes the establishment of "a globally coordinated diagnostic and research pipeline". To help facilitate this, IRDiRC formed the Task Force on Integrating New Technologies for Rare Disease Diagnosis. This multi-stakeholder Task Force aims to provide an overview of the current state of innovative diagnostic technologies for clinicians and researchers, focusing on the patient's diagnostic journey. Herein, we provide an overview of a broad spectrum of emerging diagnostic technologies involving genomics, epigenomics and multi-omics, functional testing and model systems, data sharing, bioinformatics, and Artificial Intelligence (AI), highlighting their advantages, limitations, and the current state of clinical adaption. We provide expert recommendations outlining the stepwise application of these innovative technologies in the diagnostic pathways while considering global differences in accessibility. The importance of FAIR (Findability, Accessibility, Interoperability, and Reusability) and CARE (Collective benefit, Authority to control, Responsibility, and Ethics) data management is emphasized, along with the need for enhanced and continuing education in medical genomics. We provide a perspective on future technological developments in genome diagnostics and their integration into clinical practice. Lastly, we summarize the challenges related to genomic diversity and accessibility, highlighting the significance of innovative diagnostic technologies, global collaboration, and equitable access to diagnosis and treatment for people living with rare disease.

PMID:39334316 | PMC:PMC11438178 | DOI:10.1186/s13023-024-03361-0

BMC Health Serv Res. 2024 Sep 27;24(1):1123. doi: 10.1186/s12913-024-11632-6.

ABSTRACT

BACKGROUND: An increasing number of orphan medicinal products (OMPs) are being included in social health insurance schemes, significantly improving access to medicines for patients with rare diseases. However, high-priced OMPs are still not covered, primarily due to health equity controversies and inadequate data systems required for economic evaluation. The aim of this study was to estimate the burden of drug expenditures and the size of the reimbursement budget required for high-priced OMPs from the perspectives of society and healthcare payers.

METHODS: The study performed a budget impact analysis using data from multiple sources to estimate the reimbursement budget for high-priced OMPs in Chengdu, a densely populated metropolis in China. The budget analysis consisted of three main elements: the number of patients, the price of drugs, and the simulated policy scenario. By adjusting the combinations of these elements, the budget fluctuations for payers were estimated. Furthermore, the study predicted the budget trend for the next three years to validate its sustainability.

RESULTS: The analysis indicated that 98 rare disease patients in Chengdu required high-priced OMPs in 2019. This suggested a projected budget of CNY 179 million for these patients without reimbursement policies, from a societal perspective. Under six assumed policy scenarios, this budget ranged from CNY 32 million to CNY 156 million. Over the next three years, the annual budget was estimated to range from CNY 200 million to CNY 1.303 billion.

CONCLUSION: Integration of multi-source data helps to obtain more scientifically reliable results on budget impacts. The study found that the budgetary impacts of high-priced OMPs on society and payers are relatively limited. Health policymakers can choose appropriate reimbursement strategies based on financial affordability among a diverse mix of elements. The results of related studies provided insights for optimizing the allocation of health resources and improving patient access to medications.

PMID:39334210 | PMC:PMC11430509 | DOI:10.1186/s12913-024-11632-6