Rev Med Liege. 2023 Nov;78(11):626-633.

ABSTRACT

The Ehlers Danlos syndromes (EDS) are a heterogenous group of inherited connective tissue disorders characterized by generalized joint hypermobility and instability, tissue fragility and multiple functional disorders. The EDS hypermobility type (hEDS) is the most common but the mildest subtype of EDS and is defined by joint involvement. hSED diagnosis is based on clinical criteria because no genetic factors nor molecular basis have yet been identified. Since chronic pain constitutes one of hESD main symptoms, the diagnosis is frequently suspected although the syndrome is rare, with a prevalence estimated to be 1/10.000. An expert clinical evaluation is therefore necessary in order to establish an accurate diagnosis. This allows the implementation of physical therapy which is the only treatment that has proven efficacious in reducing joint instability, generalized pain and secondary osteoarthritis.

PMID:37955292

Med Clin North Am. 2024 Jan;108(1):xv-xvi. doi: 10.1016/j.mcna.2023.09.001. Epub 2023 Sep 19.

NO ABSTRACT

PMID:37951659 | DOI:10.1016/j.mcna.2023.09.001

Med Clin North Am. 2024 Jan;108(1):xvii-xviii. doi: 10.1016/j.mcna.2023.06.019. Epub 2023 Jul 19.

NO ABSTRACT

PMID:37951660 | DOI:10.1016/j.mcna.2023.06.019

Med Clin North Am. 2024 Jan;108(1):1-14. doi: 10.1016/j.mcna.2023.06.013. Epub 2023 Jul 26.

ABSTRACT

Patients with rare or otherwise undiagnosed disorders frequently find themselves on a diagnostic odyssey, the often-prolonged journey toward diagnosis that can be characterized by significant physical, emotional, and financial hardship, as well as by diagnostic errors and delays. The wider availability of clinical exome sequencing has helped end many diagnostic odysseys, though diagnostic success rates of around 35% for exome sequencing leave many patients undiagnosed. Diagnostic yields can be improved via the implementation of advanced genetic testing modalities, though both these modalities and exome sequencing perform significantly better when paired with high-quality phenotypic data. Diagnostic centers of excellence can improve outcomes for patients on a diagnostic odyssey by providing a process and environment that address shortfalls in diagnostic access while providing high-quality phenotyping. Features of successful undiagnosed and rare disease evaluation teams are discussed and an illustrative case is provided.

PMID:37951644 | DOI:10.1016/j.mcna.2023.06.013

Orphanet J Rare Dis. 2023 Nov 10;18(1):352. doi: 10.1186/s13023-023-02964-3.

ABSTRACT

BACKGROUND: Hereditary transthyretin amyloidosis (ATTRv) is a rare genetic disease that negatively affects patients' quality of life through the involvement of various organs and tissues. Despite a large amount of research on medical and psychosocial interventions, the impact of occupational therapy (OT) on patients with ATTRv is not well understood.

OBJECTIVE: The aim of this study was to develop an OT programme to improve the daily functioning and quality of life of patients with ATTRv.

METHODS: Fourteen patients with ATTRv were interviewed. Together they developed short- and medium-term occupational goals. Patients received the OT intervention for six months. Outcomes were measured using scores for activities of daily living and psychological well-being.

RESULTS: The study found that OT can have a positive impact as a complementary intervention to medical and other psychosocial treatments. Of the 14 patients, 12 maintained the same scores in activities of daily living. Two deteriorated and eight improved their psychological scores.

CONCLUSION: This study highlights the need for further research in this area and the importance of OT in the management of patients with ATTRv. Early intervention is of paramount importance and further research is needed to evaluate the long-term effects of OT interventions in patients with ATTRv.

PMID:37950297 | PMC:PMC10636990 | DOI:10.1186/s13023-023-02964-3

Comput Methods Programs Biomed. 2024 Jan;243:107917. doi: 10.1016/j.cmpb.2023.107917. Epub 2023 Nov 7.

ABSTRACT

BACKGROUND: Rare disease diagnoses are often delayed by years, including multiple doctor visits, and potential imprecise or incorrect diagnoses before receiving the correct one. Machine learning could solve this problem by flagging potential patients that doctors should examine more closely.

METHODS: Making the prediction situation as close as possible to real situation, we tested different masking sizes. In the masking phase, data was removed, and it was applied to all data points following the first rare disease diagnosis, including the day when the diagnosis was received, and in addition applied to selected number of days before initial diagnosis. Performance of machine learning models were compared with positive predictive value (PPV), negative predictive value (NPV), prevalence PPV (pPPV), prevalence NPV (pNPV), accuracy (ACC) and area under the receiver operation characteristics curve (AUC).

RESULTS: XGBoost had PPVs over 90 % in all masking settings, and InceptionVasGloMyotides had most of the PPVs over 90 %, but not as consistently. When the prevalence of the diseases was considered XGBoost achieved highest value of 8.8 % in binary classification with 30 days masking and InceptionVasGloMyotides achieved the best value of 6 % in the binary classification as well, but with 2160 days and 4320 days masking. ACC were varying between 89 % and 98 % with XGBoost and InceptionVasGloMyotides having variation between 79 % and 94 %. AUC on the other hand varied between 72.6 % and 94.5 % with InceptionVasGloMyotides and for XGBoost it varied between 69.9 % and 96.4 %.

CONCLUSIONS: XGBoost and InceptionVasGloMyotides could successfully predict rare diseases for patients at least 30 days prior to initial rare disease diagnose. In addition, we managed to build performative custom deep learning model.

PMID:37948909 | DOI:10.1016/j.cmpb.2023.107917

Anaesthesiologie. 2023 Dec;72(12):907-918. doi: 10.1007/s00101-023-01353-6. Epub 2023 Nov 10.

ABSTRACT

Due to refined and new diagnostic possibilities and improved medical care, in the future anesthesiologists will be more frequently confronted with patients suffering from rare diseases. As the physicians providing perioperative care often have little or no experience with the diseases of such patients, the access to high-quality specific literature is essential. In this respect they must be able to assess and classify the quality of the information which is predominantly available online, especially as when evidence-based knowledge is available, it is only available to a very limited extent. Patients with rare diseases mostly present with recurring problem constellations. A systematic assignment to the most important problem areas (airway, circulation, metabolism, etc.) as well as a structured and interdisciplinary approach are decisive for a successful perioperative treatment of these patients. Due to low prevalence, lack of personal experience and lack of evidence-based data, anesthesia in patients with SE is an absolute challenge, especially in time-critical situations.

PMID:37947803 | DOI:10.1007/s00101-023-01353-6

Genome Med. 2023 Nov 9;15(1):94. doi: 10.1186/s13073-023-01240-0.

ABSTRACT

BACKGROUND: Whole genome sequencing is increasingly being used for the diagnosis of patients with rare diseases. However, the diagnostic yields of many studies, particularly those conducted in a healthcare setting, are often disappointingly low, at 25-30%. This is in part because although entire genomes are sequenced, analysis is often confined to in silico gene panels or coding regions of the genome.

METHODS: We undertook WGS on a cohort of 122 unrelated rare disease patients and their relatives (300 genomes) who had been pre-screened by gene panels or arrays. Patients were recruited from a broad spectrum of clinical specialties. We applied a bioinformatics pipeline that would allow comprehensive analysis of all variant types. We combined established bioinformatics tools for phenotypic and genomic analysis with our novel algorithms (SVRare, ALTSPLICE and GREEN-DB) to detect and annotate structural, splice site and non-coding variants.

RESULTS: Our diagnostic yield was 43/122 cases (35%), although 47/122 cases (39%) were considered solved when considering novel candidate genes with supporting functional data into account. Structural, splice site and deep intronic variants contributed to 20/47 (43%) of our solved cases. Five genes that are novel, or were novel at the time of discovery, were identified, whilst a further three genes are putative novel disease genes with evidence of causality. We identified variants of uncertain significance in a further fourteen candidate genes. The phenotypic spectrum associated with RMND1 was expanded to include polymicrogyria. Two patients with secondary findings in FBN1 and KCNQ1 were confirmed to have previously unidentified Marfan and long QT syndromes, respectively, and were referred for further clinical interventions. Clinical diagnoses were changed in six patients and treatment adjustments made for eight individuals, which for five patients was considered life-saving.

CONCLUSIONS: Genome sequencing is increasingly being considered as a first-line genetic test in routine clinical settings and can make a substantial contribution to rapidly identifying a causal aetiology for many patients, shortening their diagnostic odyssey. We have demonstrated that structural, splice site and intronic variants make a significant contribution to diagnostic yield and that comprehensive analysis of the entire genome is essential to maximise the value of clinical genome sequencing.

PMID:37946251 | PMC:PMC10636885 | DOI:10.1186/s13073-023-01240-0

Orphanet J Rare Dis. 2023 Nov 9;18(1):348. doi: 10.1186/s13023-023-02966-1.

ABSTRACT

Over the last 15 years, Undiagnosed Diseases Programs have emerged to address the significant number of individuals with suspected but undiagnosed rare genetic diseases, integrating research and clinical care to optimize diagnostic outcomes. This narrative review summarizes the published literature surrounding Undiagnosed Diseases Programs worldwide, including thirteen studies that evaluate outcomes and two commentary papers. Commonalities in the diagnostic and research process of Undiagnosed Diseases Programs are explored through an appraisal of available literature. This exploration allowed for an assessment of the strengths and limitations of each of the six common steps, namely enrollment, comprehensive clinical phenotyping, research diagnostics, data sharing and matchmaking, results, and follow-up. Current literature highlights the potential utility of Undiagnosed Diseases Programs in research diagnostics. Since participants have often had extensive previous genetic studies, research pipelines allow for diagnostic approaches beyond exome or whole genome sequencing, through reanalysis using research-grade bioinformatics tools and multi-omics technologies. The overall diagnostic yield is presented by study, since different selection criteria at enrollment and reporting processes make comparisons challenging and not particularly informative. Nonetheless, diagnostic yield in an undiagnosed cohort reflects the potential of an Undiagnosed Diseases Program. Further comparisons and exploration of the outcomes of Undiagnosed Diseases Programs worldwide will allow for the development and improvement of the diagnostic and research process and in turn improve the value and utility of an Undiagnosed Diseases Program.

PMID:37946247 | PMC:PMC10633944 | DOI:10.1186/s13023-023-02966-1

Science. 2023 Nov 10;382(6671):657. doi: 10.1126/science.adk8633. Epub 2023 Nov 9.

ABSTRACT

Mathematical models hold the key to equitable patient care.

PMID:37943923 | DOI:10.1126/science.adk8633

J Patient Rep Outcomes. 2023 Nov 9;7(1):112. doi: 10.1186/s41687-023-00650-3.

ABSTRACT

BACKGROUND: Pyruvate kinase (PK) deficiency is a rare hereditary disorder characterized by chronic hemolytic anemia and serious sequalae which negatively affect patient quality of life. This study aimed to psychometrically validate the first disease-specific patient-reported outcome (PRO) instruments: the 7-item PK Deficiency Diary (PKDD) and 12-item PK Deficiency Impact Assessment (PKDIA), designed to assess signs, symptoms, and impacts of PK deficiency in patients enrolled in the ACTIVATE global phase 3 study of mitapivat versus placebo (NCT03548220).

METHODS: All validation analyses for the PKDD and PKDIA were performed on blinded data, with analyses on item integrity, scoring, reliability, and validity conducted on data from screening and baseline. Completion rates and baseline response distributions were characterized using descriptive statistics. Item response modelling was used to inform a weighted scoring system. Reliability was assessed by internal consistency and test-retest reliability; and validity by convergent and known-groups analyses.

RESULTS: Of the 80 adults enrolled, baseline data were available for 77 (96.3%) and 78 (97.5%) patients for the PKDD and PKDIA, respectively. Item responses skewed right, indicating that mean values exceeded median values, especially for items utilizing a 0-10 numeric scale, which were subsequently recoded to a 0-4 scale; 4 items were removed from the PKDIA due to redundancy or low relevance to the trial population. Both the PKDD and PKDIA demonstrated high internal consistency (McDonald's coefficient ω = 0.86 and 0.90, respectively), test-retest reliability (intra-class coefficients of 0.94 and 0.87, respectively), and convergent validity with other PROs (linear correlation coefficients [|r|] between 0.30-0.73 and 0.50-0.82, respectively).

CONCLUSIONS: The findings provide evidence of validity and reliability for the PKDD and PKDIA, the first disease-specific PRO measures for PK deficiency, and can therefore increase understanding of, and more accurately capture, the wider impact of PK deficiency on health-related quality of life. Trial registration ClinicalTrials.gov, NCT03548220. Registered June 07, 2018; https://www.

CLINICALTRIALS: gov/ct2/show/NCT03548220 .

PMID:37943362 | DOI:10.1186/s41687-023-00650-3

Blood Coagul Fibrinolysis. 2023 Dec 1;34(8):545-548. doi: 10.1097/MBC.0000000000001249. Epub 2023 Oct 20.

ABSTRACT

Glanzmann's Thrombasthenia (GT) is a rare hemorrhagic condition caused by a platelet surface receptor disorder of the glycoprotein (GP) IIb/IIIa. Symptoms of GT are various forms of hemorrhages, such as purpura, epistaxis and menorrhagia. Gastrointestinal bleeding (GIB) is a rare expression of the condition and may occur due to traumas in the GI tract or as a consequence of gastrointestinal angiodysplasia (GIADs). In this case report, we present a middle-aged woman with recurrent GIB consequent to GIADs with persistent melena and iron deficiency anemia. After several unsuccessful therapeutic interventions, the patient was studied by the hereditary hemorrhagic telangiectasia's (HHT - Osler-Weber-Rendu disease) unit, where she received bevacizumab, showing a complete improvement in symptoms as well as a reduction in her GIADs. This case shows that bevacizumab could be a possible line of treatment for patients with coagulation disorders with GIADs.

PMID:37942747 | DOI:10.1097/MBC.0000000000001249

BMC Oral Health. 2023 Nov 8;23(1):843. doi: 10.1186/s12903-023-03586-8.

ABSTRACT

BACKGROUND: Plasminogen serves as the precursor to plasmin, an essential element in the fibrinolytic process, and is synthesized primarily in the liver. Plasminogen activation occurs through the action of plasminogen activator, converting it into plasmin. This conversion greatly enhances the fibrinolytic system within tissues and blood vessels, facilitating the dissolution of fibrin clots. Consequently, congenital deficiency of plasminogen results in impaired fibrin degradation. Patients with plasminogen deficiency typically exhibit fibrin deposits in various mucosal sites throughout the body, including the oral cavity, eyes, vagina, and digestive organs. Behcet's disease is a chronic recurrent systemic inflammatory disease with four main symptoms: aphthous ulcers of the oral mucosa, vulvar ulcers, skin symptoms, and eye symptoms, and has been reported worldwide. This disease is highly prevalent around the Silk Road from the Mediterranean to East Asia. We report a case of periodontitis in a patient with these two rare diseases that worsened quickly, leading to alveolar bone destruction. Genetic testing revealed a novel variant characterized by a stop-gain mutation, which may be a previously unidentified etiologic gene associated with decreased plasminogen activity.

CASE PRESENTATION: This case report depicts a patient diagnosed with ligneous gingivitis during childhood, originating from plasminogen deficiency and progressing to periodontitis. Genetic testing revealed a suspected association with the PLG c.1468C > T (p.Arg490*) stop-gain mutation. The patient's periodontal condition remained stable with brief intervals of supportive periodontal therapy. However, the emergence of Behçet's disease induced acute systemic inflammation, necessitating hospitalization and treatment with steroids. During hospitalization, the dental approach focused on maintaining oral hygiene and alleviating contact-related pain. The patient's overall health improved with inpatient care and the periodontal tissues deteriorated.

CONCLUSIONS: Collaborative efforts between medical and dental professionals are paramount in comprehensively evaluating and treating patients with intricate complications from rare diseases. Furthermore, the PLG c.1468C > T (p.Arg490*) stop-gain mutation could contribute to the association between plasminogen deficiency and related conditions.

PMID:37940896 | PMC:PMC10633900 | DOI:10.1186/s12903-023-03586-8

Mol Psychiatry. 2023 Nov 8. doi: 10.1038/s41380-023-02313-7. Online ahead of print.

ABSTRACT

Neurodevelopmental changes and impaired stress resistance have been implicated in the pathogenesis of bipolar disorder (BD), but the underlying regulatory mechanisms are unresolved. Here we describe a human cerebral organoid model of BD that exhibits altered neural development, elevated neural network activity, and a major shift in the transcriptome. These phenotypic changes were reproduced in cerebral organoids generated from iPS cell lines derived in different laboratories. The BD cerebral organoid transcriptome showed highly significant enrichment for gene targets of the transcriptional repressor REST. This was associated with reduced nuclear REST and REST binding to target gene recognition sites. Reducing the oxygen concentration in organoid cultures to a physiological range ameliorated the developmental phenotype and restored REST expression. These effects were mimicked by treatment with lithium. Reduced nuclear REST and derepression of REST targets genes were also observed in the prefrontal cortex of BD patients. Thus, an impaired cellular stress response in BD cerebral organoids leads to altered neural development and transcriptional dysregulation associated with downregulation of REST. These findings provide a new model and conceptual framework for exploring the molecular basis of BD.

PMID:37938767 | DOI:10.1038/s41380-023-02313-7

J Med Genet. 2023 Nov 7:jmg-2023-109473. doi: 10.1136/jmg-2023-109473. Online ahead of print.

ABSTRACT

BACKGROUND: Titinopathies are caused by mutations in the titin gene (TTN). Titin is the largest known human protein; its gene has the longest coding phase with 364 exons. Titinopathies are very complex neuromuscular pathologies due to the variable age of onset of symptoms, the great diversity of pathological and muscular impairment patterns (cardiac, skeletal muscle or mixed) and both autosomal dominant and recessive modes of transmission. Until now, only few CNVs in TTN have been reported without clear genotype-phenotype associations.

METHODS: Our study includes eight families with dominant titinopathies. We performed next-generation sequencing or comparative genomic hybridisation array analyses and found CNVs in the TTN gene. We characterised these CNVs by RNA sequencing (RNAseq) analyses in six patients' muscles and performed genotype-phenotype inheritance association study by combining the clinical and biological data of these eight families.

RESULTS: Seven deletion-type CNVs in the TTN gene were identified among these families. Genotype and RNAseq results showed that five deletions do not alter the reading frame and one is out-of-reading frame. The main phenotype identified was distal myopathy associated with contractures. The analysis of morphological, clinical and genetic data and imaging let us draw new genotype-phenotype associations of titinopathies.

CONCLUSION: Identifying TTN CNVs will further increase diagnostic sensitivity in these complex neuromuscular pathologies. Our cohort of patients enabled us to identify new deletion-type CNVs in the TTN gene, with unexpected autosomal dominant transmission. This is valuable in establishing new genotype-phenotype associations of titinopathies, mainly distal myopathy in most of the patients.

PMID:37935568 | DOI:10.1136/jmg-2023-109473

Soins. 2023 Nov;68(880):30-32. doi: 10.1016/j.soin.2023.09.008. Epub 2023 Oct 20.

ABSTRACT

The transition from pediatrics to adult wards concerns all chronic diseases with a pediatric onset, but there are a number of specific features in the case of severe forms of hereditary epidermolysis bullosa: worsening wound surface and chronicity with age, appearance or increase in certain complications (carcinological, renal, nutritional, dental), sometimes difficult therapeutic choices, sometimes life-threatening prognosis. But one of the major problems limiting the patient's autonomy is the difficulty of finding a paramedic to take over skin care, often provided from birth by a parent who has become a caregiver through necessity.

PMID:37931994 | DOI:10.1016/j.soin.2023.09.008

BMJ Case Rep. 2023 Nov 6;16(11):e257108. doi: 10.1136/bcr-2023-257108.

ABSTRACT

A male patient in his early childhood presented to rheumatology with a hoarse voice and recurrent oral and cutaneous ulceration. Serological investigation revealed persistently elevated inflammatory markers. Despite compliance to treatment, flare-ups persisted, prompting the use of further treatment. An airway endoscopy revealed cystic changes to the left vocal cord. Referral to ophthalmology revealed multiple, waxy, skin-coloured, beaded papules on thickened, irregular eyelid margins with distichiasis, in keeping with moniliform blepharosis. Enrolment into the 100 000-genome project helped clinch the diagnosis of lipoid proteinosis. Although this case highlights the diagnostic power of genetics, it also sheds light on the importance of targeted clinical referral. When one considers the typical symptoms and signs of lipoid proteinosis, referral to a centre of rare diseases would have proven effective in not only avoiding polypharmacy but also reducing the psychological burden of several years of uncertainty must have had on our patient.

PMID:37931963 | DOI:10.1136/bcr-2023-257108

Orphanet J Rare Dis. 2023 Nov 1;18(1):342. doi: 10.1186/s13023-023-02956-3.

ABSTRACT

BACKGROUND: The Orphan Regulation ((EC) No 141/2000) has successfully redirected private and public investment towards previously neglected areas through incentives, regulatory obligations and rewards. However, the growth in the number of licensed orphan medicinal products (OMPs) has led to concerns about increased costs. The aims were to investigate the trend in the costs of OMPs to the National Health Service in Wales, to attribute costs of medicines within and outside periods of marketing exclusivity, and estimate the contribution of individual medicines to the overall costs of OMPs.

METHODS: Expenditure on OMPs in Wales was analysed between the 2014/15 and 2019/20 financial years using data on prescriptions dispensed in primary care, secondary care, and specialised commissioned services. OMP spend was calculated as a proportion of total medicines expenditure, whether it was incurred during, or outside the marketing exclusivity period (MEP), and by therapeutic area and medicine.

RESULTS: Overall spend on OMPs and all medicines increased from £32 m to £82 m, and from £1,030 m to £1,198 m, respectively, with the proportion of spend on OMPs more than doubling from 3.1% to 6.9% per annum. Average year-on-year growth in the costs of OMPs was 21%, compared to 2% for other medicines. Costs following MEP expiry contributed significantly to overall OMP costs, increasing from £8 m to £30 m, corresponding to an increase from 24% to 37%. Treatments for 'malignant disease and immunosuppression', 'nutrition and blood' and the 'respiratory system' accounted for 90% of all OMP spend. Half of total OMP annual expenditure was on just 4 medicines in 2014/15, increasing to 8 in 2019/20.

CONCLUSIONS: Both the number of OMPs and the amount spent on OMPs in Wales has increased over time, possibly as a consequence of favourable licensing conditions, permissive health technology assessment policies and dedicated funding.

PMID:37915031 | PMC:PMC10621215 | DOI:10.1186/s13023-023-02956-3

ACR Open Rheumatol. 2023 Nov 2. doi: 10.1002/acr2.11627. Online ahead of print.

ABSTRACT

OBJECTIVE: Systemic sclerosis (SSc) is an orphan disease that can lead to severe involvement of the gastrointestinal tract with a significant impact on patients' quality of life (QoL). The Mediterranean diet (MD) was consistently demonstrated to have beneficial effects on chronic diseases based on biological bases. We aimed to evaluate the adherence to the MD of Italian patients with SSc to preliminarily assess its association with gastrointestinal symptoms and other disease features, mood, and QoL.

METHODS: In this cross-sectional study, adherence to the MD was measured in 387 patients from four SSc Italian referral centers through the 14-item Mediterranean Diet Adherence Screener (14-MEDAS) questionnaire. We also registered patients' reported outcomes related to the QoL and mood.

RESULTS: Overall, an optimal adherence to MD was observed in 14.7% of patients with SSc, a moderate adherence in 71.3%, and a low adherence in 14.0%. In univariate analysis, poor adherence to the MD was associated with a more prominent depressive mood, time missed at work, and perception of more severe Raynaud's phenomenon and digital ulcers, whereas the 14-MEDAS score inversely correlated with depression score and reflux.

CONCLUSION: In our cohort of patients with SSc, overall adherence to MD was moderate. Patients with lower adherence to MD also reported worse outcomes related to QoL and mood. Administration of the 14-MEDAS could be a reasonable choice to assess adherence to the MD in patients with SSc. Future initiatives to study the role of MD in the management of patients with SSc are warranted.

PMID:37916477 | DOI:10.1002/acr2.11627

BMC Health Serv Res. 2023 Oct 31;23(1):1187. doi: 10.1186/s12913-023-10049-x.

ABSTRACT

BACKGROUND: Rare disease registries (RDRs) facilitate monitoring of rare diseases by pooling small datasets to increase clinical and epidemiological knowledge of rare diseases and promote patient centred best practice. The aim of this study was to understand the current state of RDRs in Australia, data captured, impact on patient outcomes, funding models, and barriers and enablers regarding their establishment and maintenance.

METHODS: An exploratory sequential mixed methods study design was adopted. First, a list of Australian RDRs, primary contacts and data custodians was generated through online and consumer group (Rare Voices Australia (RVA)) contacts. A cross-sectional, anonymous online survey was distributed to registry custodians, managers, or principal investigators of 74 identified Australian RDRs, 88 RVA Partners, 17 pharmaceutical organizations and 12 RVA Scientific and Medical Advisory Committee members. Next, managers and coordinators of RDRs and databases who participated in the survey were invited to participate in semi-structured interviews. Quantitative and qualitative data were analysed using basic descriptive statistics and content analysis, respectively.

RESULTS: Forty RDRs responded to the survey; nine were national, five were based in Australia and New Zealand, and the remaining were global. Of the 40 survey respondents, eight were interviewed. Most of the RDRs captured similar information regarding patient characteristics, comorbidities and clinical features, diagnosis, family history, genetic testing, procedures or treatment types, response to treatments and complications of treatments. Better treatment outcomes, changes in process of care and changes in quality of care were the most frequently reported benefits of the RDRs. The main challenges proved to be cost/funding of data collection, data completeness, and patient consent. When asked, the participants identified opportunities and challenges regarding potential options to streamline RDRs in Australia in the future.

CONCLUSION: Findings from this study highlighted significant dataset heterogeneity based on the individual disease, and current lack of interoperability and coordination between different existing RDRs in Australia. Nevertheless, a nationally coordinated approach to RDRs should be investigated given the particular benefits RDRs offer, such as access to research and the monitoring of new disease-modifying treatments.

PMID:37907945 | PMC:PMC10619239 | DOI:10.1186/s12913-023-10049-x