Orphanet Journal of Rare Diseases最新文献

{"title":"Addressing cancer survivors' information needs and satisfaction: a systematic review of potential intervention components for survivors with a rare cancer type.","authors":"Tamsin Farrugia, Saskia F A Duijts, Carlene Wilson, Laura Hemming, Christine Cockburn, Evelien Spelten","doi":"10.1186/s13023-024-03403-7","DOIUrl":"10.1186/s13023-024-03403-7","url":null,"abstract":"<p><strong>Objective: </strong>Providing current, evidence-based information to cancer survivors is critical for informed decision making. People diagnosed with a rare cancer report higher unmet information needs compared to common cancer survivors. However, interventions providing informational support for rare cancers are limited. Therefore, the aims of this systematic review were to identify and synthesise interventions decreasing survivors' information needs and/or improving satisfaction with information, and to explore potential components to be included in an intervention for rare cancer survivors.</p><p><strong>Methods: </strong>Searches were conducted in PubMed, CINAHL, Embase, PsycINFO and the Cochrane Library. Studies reporting an intervention targeting information needs and/or patient satisfaction with information in survivors of any cancer type were included. Data were extracted, a quality assessment performed and findings were synthesised.</p><p><strong>Results: </strong>A total of 7012 studies were identified and 34 were included in the review. Five studies targeted patients with a rare cancer type; the remaining studies included common cancer survivors. Interventions varied in relation to the mode of information provision, timing of intervention delivery, and the intervention provider. The most promising interventions included face-to-face communication and written material and were delivered by a nurse. All rare cancer studies were designed around a web-based program, but none of them improved outcomes.</p><p><strong>Conclusions: </strong>Interventions targeting information needs and/or patient satisfaction with information in rare cancer survivors are lacking. Future studies should focus on this underserved group, and successful aspects of interventions for common cancer survivors should be considered for inclusion when designing an intervention for rare cancer survivors.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11488126/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142471808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An estimation of global genetic prevalence of PLA2G6-associated neurodegeneration.","authors":"Amina Kurtovic-Kozaric, Moriel Singer-Berk, Jordan Wood, Emily Evangelista, Leena Panwala, Amanda Hope, Stefanie M Heinrich, Samantha Baxter, Mark J Kiel","doi":"10.1186/s13023-024-03275-x","DOIUrl":"10.1186/s13023-024-03275-x","url":null,"abstract":"<p><strong>Background: </strong>PLA2G6-associated neurodegeneration (PLAN) comprises three diseases with overlapping features: infantile neuroaxonal dystrophy (INAD), atypical neuroaxonal dystrophy (atypical NAD), and PLA2G6-related dystonia-parkinsonism. INAD is an early onset disease characterized by progressive loss of vision, muscular control, and mental skills. The prevalence of PLA2G6-associated diseases has not been previously calculated.</p><p><strong>Methods: </strong>To provide the most accurate prevalence estimate, we utilized two independent approaches: database-based approach which included collecting variants from ClinVar, Human Gene Mutation Database (HGMD) and high confidence predicted loss-of-function (pLoF) from gnomAD (Rare Genomes Project Genetic Prevalence Estimator; GeniE), and literature-based approach which gathered variants through Mastermind Genomic Search Engine (Genomenon, Inc). Genetic prevalence of PLAN was calculated based on allele frequencies from gnomAD, assuming Hardy-Weinberg equilibrium.</p><p><strong>Results: </strong>In the PLA2G6 gene, our analysis found 122 pathogenic, 82 VUS, and 15 variants with conflicting interpretations (pathogenic vs VUS) between two approaches. Allele frequency was available for 58 pathogenic, 42 VUS, and 15 conflicting variants in gnomAD database. If pathogenic and/or conflicting variants are included, the overall genetic prevalence was estimated to be between 1 in 987,267 to 1 in 1,570,079 pregnancies, with the highest genetic prevalence in African/African-American (1 in 421,960 to 1 in 365,197) and East-Asian (1 in 683,978 to 1 in 190,771) populations.</p><p><strong>Conclusion: </strong>Our estimates highlight the significant underdiagnosis of PLA2G6-associated neurodegeneration and underscores the need for increased awareness and diagnostic efforts. Furthermore, our study revealed a higher carrier frequency of PLA2G6 variants in African and Asian populations, stressing the importance of expanded genetic sequencing in non-European populations to ensure accurate and comprehensive diagnosis. Future research should focus on confirming our findings and implementing expanded sequencing strategies to facilitate maximal and accurate diagnosis, particularly in non-European populations.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11489993/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142471809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cone dysfunction in ARR3-mutation-associated early-onset high myopia: an electrophysiological study.","authors":"Tamás Fehér, Noémi Széll, István Nagy, Zoltán Maróti, Tibor Kalmár, Zoltán Sohajda, Mirella T S Barboni","doi":"10.1186/s13023-024-03390-9","DOIUrl":"https://doi.org/10.1186/s13023-024-03390-9","url":null,"abstract":"<p><strong>Background: </strong>Myopia-26, a Mendelian form of early-onset high-myopia (eoHM) caused by mutations in the X-chromosomal ARR3 gene and predominantly affecting females, curiously, may provide an alternative route of investigation to unveil retinal mechanisms underlying pathological eye growth. We conducted a case-control cross-sectional prospective electrophysiological study in genetically characterized Myopia-26 patients (ARR3 heterozygous symptomatic females) compared with high myopes harboring intact ARR3 alleles and one carrier hemizygous male.</p><p><strong>Results: </strong>Participants were 26 volunteers: 10 healthy control females (E-CTRL, mean age = 31.5 ± 8.8 years), one healthy control male, one carrier male of the mutant ARR3 allele and 14 female eoHM patients (mean age = 27.0 ± 13.1 years) divided in two groups: seven without (M-CTRL) and seven with (MYP-26) genetic alteration in the ARR3 gene. The clinical evaluation included complete eye screening and full-field electroretinograms (ERGs) recorded from both eyes under mydriasis. Spherical equivalent was comparable (mean=-9.55 ± 2.46 and - 10.25 ± 3.22 for M-CTRL and MYP-26, respectively) and best corrected visual acuity (BCVA) was significantly different between M-CTRL and MYP-26 (1.0 vs. 0.406 ± 0.253, respectively). E-CTRL and M-CTRL showed similar light-adapted flash and flicker ERG amplitudes; however, the prior values were reduced by ~ 35% (a- and b-waves alike), the latter by ~ 55% in the MYP-26 group (F_{(2, 45)} > 21.821, p < 0.00001). Dark-adapted a-wave amplitudes were slightly reduced (by ~ 20%) in all myopic patients compared to E-CTRL, irrespective of the ARR3 genotype (E-CTRL vs. eoHM, p = 0.038).</p><p><strong>Conclusions: </strong>The cone dysfunction observed in Myopia-26 patients is specifically linked to the mutation of ARR3, and is not the consequence of eoHM, i.e. elongation of the eye. It may play a role in myopic refractive error development through a yet unconfirmed pathomechanism.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11488070/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142471810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Morphometric measurements of intraoral anatomy in children with Beckwith-Wiedemann syndrome: a novel approach.","authors":"Dominic J Romeo, Andrew M George, Jonathan H Sussman, Manisha Banala, Andrew Wiemken, Meagan Wu, Jinggang J Ng, Jesse A Taylor, Richard J Schwab, Christopher M Cielo, Jennifer M Kalish","doi":"10.1186/s13023-024-03350-3","DOIUrl":"https://doi.org/10.1186/s13023-024-03350-3","url":null,"abstract":"<p><strong>Background: </strong>An easy-to-use tool to objectively measure intraoral anatomy with meaningful clinical correlations may improve care for patients with Beckwith-Wiedemann syndrome (BWS), who commonly have symptomatic macroglossia.</p><p><strong>Methods: </strong>Children aged 2-17 years with BWS were enrolled between 12/2021 and 01/2024. Digital intraoral photographs with a laser ruler were taken, and morphometric measurements were made using ImageJ software. Relationships between morphometrics and outcomes including BWS clinical score, percentage mosaicism, and incidence of tongue reduction surgery were examined using t-tests and multivariate linear models.</p><p><strong>Results: </strong>Pharyngeal morphometric measurements were obtained in 49 patients with BWS. Mouth area, width, and height differed significantly across BWS molecular subtypes. Right-to-left tongue width and mouth width were larger in those with loss of methylation at imprinting control region 2 (IC2 LOM) than other BWS variants. Patients with paternal uniparental isodisomy of chromosome 11p15 (pUPD11) had narrower mouths than others. Those with tongue reduction surgery had more tongue ridging than those without surgery. There were correlations between mouth area and BWS clinical score, tongue width and BWS clinical score, and tongue length and percentage mosaicism.</p><p><strong>Conclusion: </strong>Intraoral morphometric measurements are associated with phenotypic burden in BWS. Tongue morphology varies across the BWS spectrum, with IC2 LOM having wider tongues and mouths, and pUPD11 having narrower mouths. Tongue ridging is more common in those selected for surgery. Intraoral morphometric measurements may be safely obtained at low costs across centers caring for children with BWS or others at risk of upper airway obstruction.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11483972/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142471815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of global and regional myocardial work by echocardiography in patients with Fabry disease.","authors":"Han Wang, Ying Yang, Lin Liu, Yawen Zhao, Yang Li, Wei Zhang, Wei Ma","doi":"10.1186/s13023-024-03396-3","DOIUrl":"https://doi.org/10.1186/s13023-024-03396-3","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to quantitatively evaluate the left ventricular global and regional myocardial work of patients in Fabry disease (FD) by echocardiographic pressure-strain loop (PSL) analysis.</p><p><strong>Results: </strong>The study included 48 patients with FD and 48 healthy controls matched for age and sex. According to the presence/absence of left ventricular hypertrophy (LVH), the patients with FD were divided into an LVH + group and an LVH- group. Left ventricular blood pressure was estimated noninvasively according to echocardiographic valvular events and systolic pressure in the brachial artery. Left ventricular myocardial work parameters were acquired by echocardiographic pressure-strain loop analysis. The FD groups had a significantly lower global longitudinal strain (GLS), global work index, global work efficiency (GWE), global constructive work and higher global waste work than the control group (P < .05). Regional analysis showed that all segmental myocardial waste work increased and myocardial work efficiency decreased in the LVH + group than in the LVH- group (P < .05). Segmental longitudinal strain, myocardial work index, and myocardial constructive work were markedly lower in the basal and middle segments (P < .05) and preserved in the apical segments. Multivariate analysis revealed that GWE and GLS were significant related to LVH.</p><p><strong>Conclusions: </strong>Myocardial work analysis can be used to assess global and regional myocardial work in patients with FD. In this study, GLS and GWE were reduced in patients with FD and associated with the presence of LVH. Basal and middle myocardial work decreased in relation to the LVH, while apical myocardial work remained, which added value to explore the distribution of myocardial impairment.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11484302/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142471812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A series of cases of transthyretin amyloid cardiomyopathy with negative bone scintigraphy but a confirmed positive endomyocardial biopsy.","authors":"Antoine Fraix, Emmanuel Itti, Amira Zaroui, Mounira Kharoubi, Elsa Poullot, Lionel Lerman, Soulef Guendouz, Olivier Huttin, Thibaud Damy, Arnault Galat","doi":"10.1186/s13023-024-03401-9","DOIUrl":"https://doi.org/10.1186/s13023-024-03401-9","url":null,"abstract":"<p><strong>Background: </strong>Bone scintigraphy (BS) is established as an accurate, non-invasive method for the diagnosis of transthyretin amyloid cardiomyopathy (ATTR-CM). In a real-life setting, however, some patients with no cardiac uptake on BS turn out to have cardiac-biopsy-confirmed ATTR-CM. We retrospectively included all patients diagnosed at the French Referral Center for ATTR-CM and who had data for BS and a cardiac biopsy.</p><p><strong>Results: </strong>Of 271 patients with positive cardiac biopsy, 14 (5%) had no cardiac uptake on ^99mTc-hydroxymethylene diphosphonate BS. Cardiac uptake was found in four of the seven patients who had a second BS assessment with ^99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD). A retrospective review of the BS data found low cardiac uptake in four patients (two with HMDP and two with both radiotracers). Ultimately, six of the 14 patients with a biopsy-confirmed diagnosis of ATTR-CM did not show any cardiac radiotracer uptake.</p><p><strong>Conclusions: </strong>An endomyocardial biopsy may be necessary for confirming the diagnosis of ATTR-CM in patients with clinical and imaging signs of cardiac amyloidosis but no cardiac radiotracer uptake in BS.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11481466/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142471807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oral functions in adult persons with spinal muscular atrophy compared to a healthy control group: a prospective cross-sectional study with a multimodal approach.","authors":"Teresa Kruse, Diana Leflerovà, Annette Cap, Sara Portegys, Brunhilde Wirth, Raoul Heller, Svenja Brakemeier, Tim Hagenacker, Bert Braumann, Gilbert Wunderlich","doi":"10.1186/s13023-024-03405-5","DOIUrl":"https://doi.org/10.1186/s13023-024-03405-5","url":null,"abstract":"<p><strong>Background: </strong>Oral function tests have been shown to reliably detect impaired bulbar function in adults with spinal muscular atrophy (SMA). Although not routinely recorded, it is known that persons with SMA are affected to varying degrees. Detecting differences in bite and tongue force, endurance, and maximum mouth opening has become particularly promising since the introduction of causal therapy for SMA. This study aimed to compare oral function among adult persons with SMA with different SMA types, walking abilities, and treatment status to a healthy control group.</p><p><strong>Methods: </strong>Data from oral function tests conducted on 58 persons with SMA and 45 healthy individuals were analyzed. Differences in oral function between SMA subgroups were pairwise tested and compared to the healthy control group using Wilcoxon rank sum tests.</p><p><strong>Results: </strong>In an overall comparison, three out of five oral function tests revealed lower values for the SMA group compared to the control group. Subgroup analyses indicated lower scores for most oral function tests in non-ambulatory, untreated patients with SMA type 2 compared to controls. Ambulatory, treated patients with SMA type 3 achieved strength and endurance values comparable to those of healthy individuals.</p><p><strong>Conclusions: </strong>The impairment of oral function varies across persons with SMA. Routine measurement of oral function is warranted to determine individual bulbar involvement stages. Further evaluation should be scheduled if indicators such as restricted maximum mouth opening arise. Trial registration DRKS, DRKS00015842. Registered 30 July 2019, https://drks.de/register/de/trial/DRKS00015842/preview .</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11481369/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142471716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of circRNA CDR1as/miR-214-3p regulatory axis in Legg-Calvé-Perthes disease.","authors":"Xia Lan, Ronghui Yu, Jianyun Xu","doi":"10.1186/s13023-024-03394-5","DOIUrl":"https://doi.org/10.1186/s13023-024-03394-5","url":null,"abstract":"<p><strong>Background: </strong>Legg-Calvé-Perthes disease (LCPD) commonly occurs among adolescents, threatening their health. However, the potential mechanism underlying LCPD remains unclear. miR-214-3p is shown as a critical role in LCPD development with unspecified upstream regulators.</p><p><strong>Methods: </strong>Levels of miR-214-3p and circCDR1as in healthy controls and LCPD patients were determined by qRT-PCR. The role of circCDR1as/miR-214-3p axis in LCPD was determined by testing the cell viability and apoptosis in TC28 cells and primary chondrocytes. Regulation between circCDR1as and miR-214-3p was examined by RIP and ChIP assays. The inflammatory response and angiogenesis were evaluated by M2 macrophage polarization and HUVECs tumor formation.</p><p><strong>Results: </strong>circCDR1as was overexpressed in LCPD patients with a negative correlation with miR-214-3p. Inhibition of circCDR1as alleviated the cell viability and apoptosis of DEX-treated chondrocytes, stimulated M2 macrophage polarization and angiogenesis. miR-214-3p was proved as a downstream effector to participate in circCDR1as mediated actions. circCDR1as recruited PRC2 complex to epigenetically suppress miR-214-3p.</p><p><strong>Conclusion: </strong>Our study illustrated the role and mechanism of circCDR1as in LCPD development by targeting miR-214-3p, highlighting its potential in the therapy for LCPD.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11481470/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142471813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Incidence and predictors of in-stent restenosis following intervention for pulmonary vein stenosis due to fibrosing mediastinitis.","authors":"Mengfei Jia, Hongling Su, Kaiyu Jiang, Aqian Wang, Zhaoxia Guo, Hai Zhu, Fu Zhang, Xuechun Sun, Yiwei Shi, Xin Pan, Yunshan Cao","doi":"10.1186/s13023-024-03391-8","DOIUrl":"https://doi.org/10.1186/s13023-024-03391-8","url":null,"abstract":"<p><strong>Background: </strong>Fibrosing mediastinitis (FM) is a rare yet fatal condition, caused by different triggers and frequently culminating in the obstruction of the pulmonary vasculature and airways, often leading to pulmonary hypertension and right heart failure. Percutaneous transluminal pulmonary venoplasty (PTPV) is an emerging treatment for pulmonary vein stenosis (PVS) caused by FM. Our previous study showed as high as 24% of in-stent restenosis (ISR) in FM. However, the predictors of ISR are elusive.</p><p><strong>Objectives: </strong>We sought to identify the predictors of ISR in patients with PVS caused by extraluminal compression due to FM.</p><p><strong>Methods: </strong>We retrospectively enrolled patients with PVS-FM who underwent PTPV between July 1, 2018, and December 31, 2022. According to ISR status, patients were divided into two groups: the ISR group and the non-ISR group. Baseline characteristics (demographics and lesions) and procedure-related information were abstracted from patient records and analyzed. Univariate and multivariate analyses were performed to determine the predictors of ISR.</p><p><strong>Results: </strong>A total of 142 stents were implanted in 134 PVs of 65 patients with PVS-FM. Over a median follow-up of 6.6 (3.4-15.7) months, 61 of 134 PVs suffered from ISR. Multivariate analysis demonstrated a significantly lower risk of ISR in PVs with a larger reference vessel diameter (RVD) (odds ratio (OR): 0.79; 95% confidence interval [CI]: 0.64 to 0.98; P = 0.032), and stenosis of the corresponding pulmonary artery (Cor-PA) independently increased the risk of restenosis (OR: 3.41; 95% CI: 1.31 to 8.86; P = 0.012). The cumulative ISR was 6.3%, 21.4%, and 39.2% at the 3-, 6-, and 12-month follow-up, respectively.</p><p><strong>Conclusion: </strong>ISR is very high in PVS-FM, which is independently associated with RVD and Cor-PA stenosis.</p><p><strong>Trail registration: </strong>Chinese Clinical Trials Register; No.: ChiCTR2000033153. URL: http://www.chictr.org.cn .</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11472477/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142471814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A machine learning algorithm for the detection of paroxysmal nocturnal haemoglobinuria (PNH) in UK primary care electronic health records.","authors":"Amanda Worker, Hadley Mahon, Jack Sams, Freya Boardman-Pretty, Elena Marchini, Rand Dubis, Alan Warren, Jez Stockdale, Jyothika Kumar, Elizabeth Varones, Daniel Ollerenshaw, Calum Grant, Peter Fish, Richard J Kelly","doi":"10.1186/s13023-024-03406-4","DOIUrl":"https://doi.org/10.1186/s13023-024-03406-4","url":null,"abstract":"<p><strong>Background: </strong>Paroxysmal Nocturnal Haemoglobinuria (PNH) is an ultra-rare, acquired disorder that is challenging to diagnose due to varied symptoms, heterogeneous patient presentations, and lack of awareness among healthcare professionals. This leads to frequent misdiagnosis and delays in diagnosis. This study evaluated the feasibility of a machine learning model to identify undiagnosed PNH patients using structured electronic health records.</p><p><strong>Methods: </strong>The study used data from the Optimum Patient Care Research Database, which contains electronic health records from general practitioner (GP) practices across the United Kingdom. PNH patients were identified by the presence, and control patients by the absence of a PNH diagnosis code in their records. Clinical features (symptoms, diagnoses, healthcare utilisation) from 131 patients in the PNH group and 593,838 patients in the control group, were inputted to a tree-based XGBoost machine learning model to classify patients as either \"positive\" or \"negative\" for PNH suspicion. The algorithm was finalised after additional exclusions and inclusions applied. Performance was assessed using positive predictive value (PPV), recall and specificity. As the sample used to develop the algorithm was not representative of the true population prevalence, PPV was additionally adjusted to reflect performance in the wider population.</p><p><strong>Results: </strong>Of all the patients in the PNH group, 27% were classified as positive (recall). 99.99% of the control group were classified as negative (specificity). Of all the patients classified as positive, 60.4% had a diagnosis of PNH in their record (PPV). The PPV adjusted for the population prevalence of PNH was 19.59 suggesting nearly 1 in 5 patients flagged may warrant further PNH investigation. The key clinical features in the model were aplastic anaemia, pancytopenia, haemolytic anaemia, myelodysplastic syndrome, and Budd-Chiari syndrome.</p><p><strong>Conclusion: </strong>This is the first study to combine clinical understanding of PNH with machine learning, demonstrating the ability to discriminate between PNH and control patients in retrospective electronic health records. With further investigation and validation, this algorithm could be deployed on live health data, potentially leading to earlier diagnosis for patients who currently experience long diagnostic delays or remain undiagnosed.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11479535/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142471806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}