Orphanet J Rare Dis. 2024 Jan 27;19(1):28. doi: 10.1186/s13023-024-03030-2.

ABSTRACT

BACKGROUND: In European Union countries, any disease affecting less than 5 people in 10,000 is considered rare. As expertise is scarce and rare diseases (RD) are complex, RD patients can remain undiagnosed for many years. The period of searching for a diagnosis, called diagnostic delay, sometimes leads to a diagnostic dead end when the patient's disease is impossible to diagnose after undergoing all available investigations. In recent years, extensive efforts have been made to support the implementation of ORPHA nomenclature in health information systems (HIS) so as to allow RD coding. Until recently, the nomenclature only encompassed codes for specific RD. Persons suffering from a suspected RD who could not be diagnosed even after full investigation, could not be coded with ORPHAcodes. The recognition of the RD status is necessary for patients, even if they do not have a precise diagnosis. It can facilitate reimbursement of care, be socially and psychologically empowering, and grant them access to scientific advances.

RESULTS: The RD-CODE project aimed at making those patients identifiable in HIS in order to produce crucial epidemiological data. Undiagnosed patients were defined as patients for whom no clinically-known disorder could be confirmed by an expert center after all reasonable efforts to obtain a diagnosis according to the state-of-the-art and diagnostic capabilities available. Three recommendations for the coding of undiagnosed RD patients were produced by a multi-stakeholder panel of experts: 1/ Capture the diagnostic ascertainment for all rare disease cases; 2/ Use the newly created ORPHAcode (ORPHA:616874 "Rare disorder without a determined diagnosis after full investigation"), available in the Orphanet nomenclature: as the code is new, guidelines are essential to ensure its correct and homogeneous use for undiagnosed patients' identification in Europe and beyond; 3/ Use additional descriptors in registries.

CONCLUSIONS: The recommendations can now be implemented in HIS (electronic health records and/or registries) and could be a game-changer for patients, clinicians and researchers in the field, enabling assessment of the RD population, including undiagnosed patients, adaptation of policy measures including financing for care and research programs, and to improved access of undiagnosed patients to research programs.

PMID:38280999 | PMC:PMC10822150 | DOI:10.1186/s13023-024-03030-2

Lancet. 2024 Feb 17;403(10427):592-593. doi: 10.1016/S0140-6736(23)02652-1. Epub 2024 Jan 23.

NO ABSTRACT

PMID:38278169 | DOI:10.1016/S0140-6736(23)02652-1

JCI Insight. 2024 Feb 22;9(4):e174097. doi: 10.1172/jci.insight.174097.

ABSTRACT

A distinct adipose tissue distribution pattern was observed in patients with methylmalonyl-CoA mutase deficiency, an inborn error of branched-chain amino acid (BCAA) metabolism, characterized by centripetal obesity with proximal upper and lower extremity fat deposition and paucity of visceral fat, that resembles familial multiple lipomatosis syndrome. To explore brown and white fat physiology in methylmalonic acidemia (MMA), body composition, adipokines, and inflammatory markers were assessed in 46 patients with MMA and 99 matched controls. Fibroblast growth factor 21 levels were associated with acyl-CoA accretion, aberrant methylmalonylation in adipose tissue, and an attenuated inflammatory cytokine profile. In parallel, brown and white fat were examined in a liver-specific transgenic MMA mouse model (Mmut-/- TgINS-Alb-Mmut). The MMA mice exhibited abnormal nonshivering thermogenesis with whitened brown fat and had an ineffective transcriptional response to cold stress. Treatment of the MMA mice with bezafibrates led to clinical improvement with beiging of subcutaneous fat depots, which resembled the distribution seen in the patients. These studies defined what we believe to be a novel lipodystrophy phenotype in patients with defects in the terminal steps of BCAA oxidation and demonstrated that beiging of subcutaneous adipose tissue in MMA could readily be induced with small molecules.

PMID:38271099 | DOI:10.1172/jci.insight.174097

Orphanet J Rare Dis. 2024 Jan 25;19(1):25. doi: 10.1186/s13023-024-03047-7.

ABSTRACT

BACKGROUND: The delay in diagnosis for rare disease (RD) patients is often longer than for patients with common diseases. Machine learning (ML) technologies have the potential to speed up and increase the precision of diagnosis in this population group. We aim to explore the expectations and experiences of the members of the European Reference Networks (ERNs) for RDs with those technologies and their potential for application.

METHODS: We used a mixed-methods approach with an online survey followed by a focus group discussion. Our study targeted primarily medical professionals but also other individuals affiliated with any of the 24 ERNs.

RESULTS: The online survey yielded 423 responses from ERN members. Participants reported a limited degree of knowledge of and experience with ML technologies. They considered improved diagnostic accuracy the most important potential benefit, closely followed by the synthesis of clinical information, and indicated the lack of training in these new technologies, which hinders adoption and implementation in routine care. Most respondents supported the option that ML should be an optional but recommended part of the diagnostic process for RDs. Most ERN members saw the use of ML limited to specialised units only in the next 5 years, where those technologies should be funded by public sources. Focus group discussions concluded that the potential of ML technologies is substantial and confirmed that the technologies will have an important impact on healthcare and RDs in particular. As ML technologies are not the core competency of health care professionals, participants deemed a close collaboration with developers necessary to ensure that results are valid and reliable. However, based on our results, we call for more research to understand other stakeholders' opinions and expectations, including the views of patient organisations.

CONCLUSIONS: We found enthusiasm to implement and apply ML technologies, especially diagnostic tools in the field of RDs, despite the perceived lack of experience. Early dialogue and collaboration between health care professionals, developers, industry, policymakers, and patient associations seem to be crucial to building trust, improving performance, and ultimately increasing the willingness to accept diagnostics based on ML technologies.

PMID:38273306 | PMC:PMC10809751 | DOI:10.1186/s13023-024-03047-7

Traffic. 2024 Jan;25(1):e12927. doi: 10.1111/tra.12927.

ABSTRACT

Endoplasmic reticulum (ER) retention of misfolded glycoproteins is mediated by the ER-localized eukaryotic glycoprotein secretion checkpoint, UDP-glucose glycoprotein glucosyl-transferase (UGGT). The enzyme recognizes a misfolded glycoprotein and flags it for ER retention by re-glucosylating one of its N-linked glycans. In the background of a congenital mutation in a secreted glycoprotein gene, UGGT-mediated ER retention can cause rare disease, even if the mutant glycoprotein retains activity ("responsive mutant"). Using confocal laser scanning microscopy, we investigated here the subcellular localization of the human Trop-2-Q118E, E227K and L186P mutants, which cause gelatinous drop-like corneal dystrophy (GDLD). Compared with the wild-type Trop-2, which is correctly localized at the plasma membrane, these Trop-2 mutants are retained in the ER. We studied fluorescent chimeras of the Trop-2 Q118E, E227K and L186P mutants in mammalian cells harboring CRISPR/Cas9-mediated inhibition of the UGGT1 and/or UGGT2 genes. The membrane localization of the Trop-2 Q118E, E227K and L186P mutants was successfully rescued in UGGT1-/- cells. UGGT1 also efficiently reglucosylated Trop-2-Q118E-EYFP in cellula. The study supports the hypothesis that UGGT1 modulation would constitute a novel therapeutic strategy for the treatment of pathological conditions associated to misfolded membrane glycoproteins (whenever the mutation impairs but does not abrogate function), and it encourages the testing of modulators of ER glycoprotein folding quality control as broad-spectrum rescue-of-secretion drugs in rare diseases caused by responsive secreted glycoprotein mutants.

PMID:38272446 | PMC:PMC10832616 | DOI:10.1111/tra.12927

Brief Bioinform. 2024 Jan 22;25(2):bbad508. doi: 10.1093/bib/bbad508.

ABSTRACT

Next-generation sequencing (NGS) has revolutionized the field of rare disease diagnostics. Whole exome and whole genome sequencing are now routinely used for diagnostic purposes; however, the overall diagnosis rate remains lower than expected. In this work, we review current approaches used for calling and interpretation of germline genetic variants in the human genome, and discuss the most important challenges that persist in the bioinformatic analysis of NGS data in medical genetics. We describe and attempt to quantitatively assess the remaining problems, such as the quality of the reference genome sequence, reproducible coverage biases, or variant calling accuracy in complex regions of the genome. We also discuss the prospects of switching to the complete human genome assembly or the human pan-genome and important caveats associated with such a switch. We touch on arguably the hardest problem of NGS data analysis for medical genomics, namely, the annotation of genetic variants and their subsequent interpretation. We highlight the most challenging aspects of annotation and prioritization of both coding and non-coding variants. Finally, we demonstrate the persistent prevalence of pathogenic variants in the coding genome, and outline research directions that may enhance the efficiency of NGS-based disease diagnostics.

PMID:38271481 | PMC:PMC10810331 | DOI:10.1093/bib/bbad508

G Ital Cardiol (Rome). 2024 Feb;25(2):98-105. doi: 10.1714/4187.41758.

ABSTRACT

Left ventricular non-compaction (LVNC) is a myocardial disease characterized by a two-layered structure typically seen at the apical and lateral left portions of the ventricular myocardium, distal to the papillary muscles. While considered a rare disease, its prevalence in children is increasing due to the increased awareness of this condition and improved resolution of imaging techniques. The etiology is heterogeneous, ranging from inherited conditions to acquired diseases. Although many patients are asymptomatic, some patients may experience adverse events, including heart failure, arrhythmias, or thromboembolic events. Several echocardiographic or cardiac magnetic resonance imaging diagnostic criteria have been proposed for diagnosing LVNC. However, their application in children is significantly limited. This review aims to describe the clinical and genetic characteristics of children with LVNC and discuss the role of the proposed diagnostic criteria.

PMID:38270365 | DOI:10.1714/4187.41758

Dis Model Mech. 2024 Jun 1;17(6):dmm050672. doi: 10.1242/dmm.050672. Epub 2024 Jan 25.

NO ABSTRACT

PMID:38270284 | PMC:PMC10846506 | DOI:10.1242/dmm.050672

Stud Health Technol Inform. 2024 Jan 25;310:1151-1155. doi: 10.3233/SHTI231145.

ABSTRACT

SelEe is a German citizen science project aiming to develop a smartphone app for a patient-managed record. The goal is to study rare diseases with the support of interested citizens and people affected by rare diseases. We established a core research team, including professional researchers (leading the project) and citizens. Citizens have the opportunity to discuss the progress, make suggestions regarding the app's design and data entry and contribute to the dissemination of the project. To gather feedback and experiences from the core research team, we performed an online questionnaire regarding the topics "influence and communication", "improvements and learning effect", and "satisfaction". Finally, 9 citizens of the core research team participated. The results show that the citizens are very satisfied with the design of the app, their participation opportunities and the communication in the project.

PMID:38269995 | DOI:10.3233/SHTI231145

Stud Health Technol Inform. 2024 Jan 25;310:94-98. doi: 10.3233/SHTI230934.

ABSTRACT

Drug development in rare diseases is challenging due to the limited availability of subjects with the diseases and recruiting from a small patient population. The high cost and low success rate of clinical trials motivate deliberate analysis of existing clinical trials to understand status of clinical development of orphan drugs and discover new insight for new trial. In this project, we aim to develop a user centered Rare disease based Clinical Trial Knowledge Graph (RCTKG) to integrate publicly available clinical trial data with rare diseases from the Genetic and Rare Disease (GARD) program in a semantic and standardized form for public use. To better serve and represent the interests of rare disease users, user stories were defined for three types of users, patients, healthcare providers and informaticians, to guide the RCTKG design in supporting the GARD program at NCATS/NIH and the broad clinical/research community in rare diseases.

PMID:38269772 | DOI:10.3233/SHTI230934

BMJ Case Rep. 2024 Jan 23;17(1):e257130. doi: 10.1136/bcr-2023-257130.

ABSTRACT

Malakoplakia is a rare granulomatous disease. Its aetiology is unclear but possible theories include infection with microorganisms (especially Escherichia coli), immunosuppression and impaired lysosomal function. It has been commonly documented to affect the genitourinary tract but can affect any organ, with the gastrointestinal system being the next most affected. We present a woman in her 70s, with a 2-week history of right-sided abdominal pain, 13 years following her renal transplant. She was admitted for treatment of an E. coli bacteraemia. CT scan had shown a caecal pole mass, highly suspicious for malignancy. It was surgically resected, and histology revealed findings of malakoplakia within the colon. Surgical intervention was combined with a prolonged course of antibiotics for successful treatment. We highlight the ability of malakoplakia to mimic malignancy and should be considered in the differentials in the context of an immunosuppressed patient with radiological findings of a colonic mass.

PMID:38262716 | PMC:PMC10826489 | DOI:10.1136/bcr-2023-257130

Int J Mol Sci. 2024 Jan 13;25(2):1014. doi: 10.3390/ijms25021014.

ABSTRACT

Organoids are self-organized, three-dimensional structures derived from stem cells that can mimic the structure and physiology of human organs. Patient-specific induced pluripotent stem cells (iPSCs) and 3D organoid model systems allow cells to be analyzed in a controlled environment to simulate the characteristics of a given disease by modeling the underlying pathophysiology. The recent development of 3D cell models has offered the scientific community an exceptionally valuable tool in the study of rare diseases, overcoming the limited availability of biological samples and the limitations of animal models. This review provides an overview of iPSC models and genetic engineering techniques used to develop organoids. In particular, some of the models applied to the study of rare neuronal, muscular and skeletal diseases are described. Furthermore, the limitations and potential of developing new therapeutic approaches are discussed.

PMID:38256087 | PMC:PMC10815694 | DOI:10.3390/ijms25021014

BMC Med Genomics. 2024 Jan 22;17(1):29. doi: 10.1186/s12920-024-01801-1.

ABSTRACT

BACKGROUND: X-linked nephrogenic diabetes insipidus (NDI) is a rare genetic renal disease caused by pathogenic variants in the AVPR2 gene. Single nucleotide variants and small insertions/deletions in AVPR2 are reliably detected by routine clinical sequencing. Nevertheless, structural variants involving AVPR2 are challenging to identify accurately by conventional genetic testing. Here, we report a novel deletion of AVPR2 in a Czech family identified for the first time by targeted long-read sequencing (T-LRS).

METHODS: A male proband with X-linked NDI underwent clinical sequencing of the AVPR2 gene that failed and thus indicated possible whole-gene deletion. Therefore, PCR mapping and subsequent targeted long-read sequencing (T-LRS) using a Pacific Biosciences sequencer were applied to search for the suspected deletion. To validate the deletion breakpoints and prove variant segregation in the family with X-linked NDI, Sanger sequencing of the deletion junction was performed. Quantitative real-time PCR was further carried out to confirm the carrier status of heterozygous females.

RESULTS: By T-LRS, a novel 7.5 kb deletion of AVPR2 causing X-linked NDI in the proband was precisely identified. Sanger sequencing of the deletion junction confirmed the variant breakpoints and detected the deletion in the probands´ mother, maternal aunt, and maternal cousin with X-linked NDI. The carrier status in heterozygous females was further validated by quantitative real-time PCR.

CONCLUSIONS: Identifying the 7.5 kb deletion gave a precise molecular diagnosis for the proband, enabled genetic counselling and genetic testing for the family, and further expanded the spectrum of structural variants causing X-linked NDI. Our results also show that T-LRS has significant potential for accurately identifying putative structural variants.

PMID:38254165 | PMC:PMC10804598 | DOI:10.1186/s12920-024-01801-1

Orphanet J Rare Dis. 2024 Jan 22;19(1):23. doi: 10.1186/s13023-023-02986-x.

ABSTRACT

BACKGROUND: Research priorities are best defined through engagement with communities who will be impacted by the research and have lived experience of the topics to be studied. We aimed to establish a pediatric rare disease community stakeholder group and empower them in (1) eliciting perspectives from affected families in the wider region and (2) synthesizing collective ideas into a research agenda focused on shared ethical, legal, and social implications (ELSI) across rare disease.

METHODS: This two-year project utilized a community-centered approach to engage rare disease community members as equal partners in developing a research agenda for ELSI in rare disease. We established "Rare Voices" (RV), a 22-member stakeholder group of patients, parents, clinicians and researchers. Following capacity-building trainings, RV designed and conducted listening sessions with teen patients and parents of children with rare diseases to explore challenges, positive experiences, and ethical concerns. Listening session findings were synthesized and contextualized into research topics, which RV members further refined and prioritized. We used established measures to assess RV member engagement and satisfaction.

RESULTS: From 14 listening sessions with parents (n = 52) and teen patients (n = 13), RV identified eight core research topics as most important for future rare disease research: coordinating care, communication, accessing resources and care, impact on family unit, community and support in society, mental health and identity, ethical aspects of care, and uncertainty. RV members were highly engaged throughout the two-year project and reported high levels of satisfaction with the experience and research agenda.

CONCLUSIONS: Through capacity-building and authentic engagement, this project resulted in a community-led rare disease research agenda to guide future rare disease ELSI research that aligns with patients' and families' priorities. An environment of equal partnership and respect created a space for mutual learning where community members were empowered to shape the research agenda based on their collective experiences. The agenda recognizes the shared psychosocial and healthcare experiences of rare disease and offers practical areas of research to address patient and family needs.

PMID:38254122 | PMC:PMC10801933 | DOI:10.1186/s13023-023-02986-x

Nat Commun. 2024 Jan 22;15(1):657. doi: 10.1038/s41467-024-44980-2.

ABSTRACT

Rare DNA alterations that cause heritable diseases are only partially resolvable by clinical next-generation sequencing due to the difficulty of detecting structural variation (SV) in all genomic contexts. Long-read, high fidelity genome sequencing (HiFi-GS) detects SVs with increased sensitivity and enables assembling personal and graph genomes. We leverage standard reference genomes, public assemblies (n = 94) and a large collection of HiFi-GS data from a rare disease program (Genomic Answers for Kids, GA4K, n = 574 assemblies) to build a graph genome representing a unified SV callset in GA4K, identify common variation and prioritize SVs that are more likely to cause genetic disease (MAF < 0.01). Using graphs, we obtain a higher level of reproducibility than the standard reference approach. We observe over 200,000 SV alleles unique to GA4K, including nearly 1000 rare variants that impact coding sequence. With improved specificity for rare SVs, we isolate 30 candidate SVs in phenotypically prioritized genes, including known disease SVs. We isolate a novel diagnostic SV in KMT2E, demonstrating use of personal assemblies coupled with pangenome graphs for rare disease genomics. The community may interrogate our pangenome with additional assemblies to discover new SVs within the allele frequency spectrum relevant to genetic diseases.

PMID:38253606 | PMC:PMC10803329 | DOI:10.1038/s41467-024-44980-2

Rev Esp Patol. 2024 Jan-Mar;57(1):64-66. doi: 10.1016/j.patol.2023.07.002. Epub 2023 Oct 14.

ABSTRACT

Fraser syndrome or cryptophthalmos-syndactyly syndrome is a rare genetic disease, the diagnosis of which is based on a series of major and minor clinical criteria and that can be supported by genetic tests. This article presents the case of a fetal autopsy at 37 weeks of gestation with suspicion of CHAOS syndrome (congenital obstructive syndrome of the upper airways).

PMID:38246713 | DOI:10.1016/j.patol.2023.07.002

Rev Esp Patol. 2024 Jan-Mar;57(1):53-58. doi: 10.1016/j.patol.2023.04.003. Epub 2023 Jul 5.

ABSTRACT

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare disease with a poor prognosis. It frequently affects the skin; indeed, dermal lesions may be the first clinical manifestation. We report three cases of BPDCN where the patients presented with skin lesions and describe the clinical, histopathological and immunohistochemical findings, its molecular characteristics and metastatic work-up. One of the patients remains in a clinical trial with IMGN632, a molecule directed against CD123, while the other two patients died after different therapeutic regimens. BPDCN is a complex diagnostic challenge which, together with its poor prognosis, requires close clinical-pathological cooperation in order to accelerate its diagnosis and offer early therapeutic alternatives with drugs directed against specific molecular targets.

PMID:38246711 | DOI:10.1016/j.patol.2023.04.003

Medicine (Baltimore). 2024 Jan 19;103(3):e37005. doi: 10.1097/MD.0000000000037005.

ABSTRACT

RATIONALE: A huge hypertrophic scar formation secondary to chronic ingrown toe nail mimicking tumor is a rare disease. It is not only causing concerns cosmetically, but also hindering normal daily activities physically and socially. In this paper, we present an unusual case of bilateral ingrown nails with different phases. One resulted in a large hypertrophic scar caused by stimulation from secondary to chronic ingrown nail.

PATIENT CONCERNS AND DIAGNOSIS: A 44-year-old man with a huge mass (7 × 4 × 8.5 cm) in his right great toe and inflamed ingrown nail in his left great toe visited the clinic. The mass in the right toe showed an irregular and bizarre shape with a stellate ulcer (2 × 2 cm) at the distal end. After removing an ingrown nail 3 years ago with minor repetitive trauma, self-managed wound has grown into a tumor-like mass, resulting in intolerable discomfort. In gross appearance, a stalk appeared to originate from the lateral side of the nail bed with the ingrown nail in the great toe showing inflamed medial and lateral gutter and causing redness and tenderness. Huge hypertrophic scar formation secondary to chronic ingrown toe nail mimicking tumor is a rare disease that is not only causing a cosmetic concern, but also hindering normal daily activities physically and socially.

INTERVENTION AND OUTCOMES: Excisional biopsy was performed for both great toes. Biopsy confirmed chronic ulcerative inflammation with a hypertrophic scar. The resection site healed and persisted well at 12 months after surgery.

CONCLUSION: Our unusual case suggests that the natural course of an untreated ingrown toe nail may result in hypertrophic scar extending far to mimic tumorous conditions.

PMID:38241575 | PMC:PMC10798770 | DOI:10.1097/MD.0000000000037005

Medicine (Baltimore). 2024 Jan 19;103(3):e36920. doi: 10.1097/MD.0000000000036920.

ABSTRACT

RATIONALE: Pure white cell aplasia (PWCA) is a rare paraneoplastic syndrome that occurs in patients with thymomas. Currently, the pathogenesis and treatment of this disease remain in the exploratory stage.

PATIENT CONCERNS: We report a 68-year-old woman with thymoma experienced PWCA involvement as her first presentation. The patient had high fever and agranulocytosis at the onset of the disease. The white blood cell count in the complete blood count was 1.9 × 109/L with a neutrophil of 0.1 × 109/L. The bone marrow aspirates showed decreased granulocyte proliferation. Computed tomography showed a large mass in the anterior mediastinum.

DIAGNOSES: The final diagnosis of our patient was PWCA and thymoma.

INTERVENTIONS: She underwent a thymectomy and cyclosporine A administration during first remission.

OUTCOMES: Long-term remission was achieved following the readministration of cyclosporine A after the disease recurrence.

LESSONS: PWCA or agranulocytosis with thymoma has been confirmed to be an extremely rare disease. Thymomas with PWCA correlate with autoimmunity. From this case study and the literature review, we concluded that the pathogenesis of thymomas in PWCA is mainly related to the activation of autoreactive T cells. Thymectomy and the immunosuppressive drug, cyclosporine A, were chosen for treatment. The patient's granulocyte levels were unable to recover after surgery because of the inability to promptly clear activated T cells. After surgery, cyclosporine A continued to take for a long time. Thymectomy combined with prolonged cyclosporine A administration may be an effective method for treating this rare disease.

PMID:38241556 | PMC:PMC10798751 | DOI:10.1097/MD.0000000000036920

Orphanet J Rare Dis. 2024 Jan 18;19(1):18. doi: 10.1186/s13023-024-03018-y.

ABSTRACT

BACKGROUND: Vascular anomalies (VAs) are rare congenital disorders that can cause pain, disfigurement, coagulopathy, asymmetric growth, and disability. Patients with complex VAs experience multiple barriers to accessing expert care. It is imperative to understand which factors support these patients' ability to navigate the healthcare system.

RESULTS: We surveyed adult patients with VAs using previously validated measures, recruiting participants from five patient advocacy groups and multidisciplinary VA clinics. The primary outcome was self-reported ability to access needed medical care, using the "Navigating the Healthcare System" subscale of the Health Literacy Questionnaire. We evaluated factors associated with the ability to navigate the healthcare system using multivariate linear regression (n = 136). We also performed an exploratory model that included the primary care doctor's knowledge of VAs for the subset of participants with a primary care doctor (n = 114). Participants were predominantly women (n = 90, 66%), White and non-Hispanic (n = 109, 73%), and college-educated (n = 101, 73%). Most participants had PIK3CA-Related Overgrowth Spectrum (n = 107, 78%). Most participants reported that navigating the healthcare system was "sometimes" or "usually difficult" (mean score 16.4/30, standard deviation 5.6). In multivariate linear regression, ability to navigate the healthcare system was associated positively with quality of information exchange (β = 0.38, 95% Confidence Interval (CI) 0.22 to 0.55, p <.001) and whether patients had VA specialists (β = 2.31, 95% CI 0.35 to 4.28, p =.021), but not associated with patient self-advocacy, anxiety, education, age, race and ethnicity, gender, or having a primary care doctor. In exploratory analysis of participants with primary care doctors, ability to navigate the healthcare system was positively associated with quality of information exchange (β = 0.27, 95% CI 0.09 to 0.45, p =.004), having a VA specialist (β = 2.31, 95% CI 0.22 to 4.39, p =.031), and primary care doctors' VA knowledge (β = 0.27, 95% CI 0.04 to 0.50, p =.023).

CONCLUSION: Patients with VAs struggle to navigate the healthcare system. High-quality information from clinicians and more knowledgeable primary care doctors might help patients to access needed care. Relying on patient self-advocacy is insufficient. Future efforts should focus on patient-directed and clinician-directed educational interventions. Additionally, future work should assess the structural barriers that impede healthcare access for these patients.

PMID:38238812 | PMC:PMC10797881 | DOI:10.1186/s13023-024-03018-y