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Environmental factors amplified by climate change contribute significantly to the global burden of disease, disproportionately impacting vulnerable populations, such as individuals with rare diseases. Researchers require innovative, dynamic data linkage methods to enable the development of risk prediction models, particularly for diseases like vasculitis with unknown aetiology but potential environmental triggers. In response, we present the Semantic Environmental and Rare Disease Data Integration Framework (SERDIF). SERDIF was evaluated with researchers studying climate-related health hazards of vasculitis disease activity across European countries (NP1 = 10, NP2 = 17, NP3 = 23). Usability metrics consistently improved, indicating SERDIF's effectiveness in linking complex environmental and health datasets. Furthermore, SERDIF-enabled epidemiologists to study environmental factors in a pregnancy cohort in Lombardy, showcasing its versatility beyond rare diseases. This framework offers for the first time a user-friendly, FAIR-compliant design for environment-health data linkage with export capabilities enabling data analysis to mitigate health risks posed by climate change. [ABSTRACT FROM AUTHOR]

Environmental exposures transported across air, land and water can affect our health making us more susceptible to developing a disease. Therefore, researchers need to face the complex task of integrating environmental exposures and linking them to health events with the relevant spatiotemporal and health context for individuals or populations. We present a usability evaluation approach and study of a semantic framework (i.e. Knowledge Graph, Methodology and User Interface) to enable Health Data Researchers (HDR) to link particular health events with environmental data for rare disease research. The usability study includes 17 HDRs with expertise in health data related to Anti-Neutrophil Cytoplasmic Antibody (ANCA)-associated vasculitis (AAV) in Ireland and Kawasaki Disease in Japan, and with no previous practical experience in using Semantic Web (SW) technologies. The evaluation results are promising in that they indicate that the framework is useful in allowing researchers themselves to link health and environmental data whilst hiding the complexities of SW technologies. As a result of this work, we also discuss the limitations of the approach together with the applicability to other domains. Beyond the direct impact on environmental health studies, the description of the evaluation approach can guide researchers in making SW technologies more accessible to domain experts through usability studies. [ABSTRACT FROM AUTHOR]

Objectives. Rituximab is effective in inducing remission in ANCA-associated vasculitis (AAV), with randomized evidence to support its use as four infusions of 375 mg/m2 (the conventional lymphoma dosing schedule). As B cell depletion (BCD) appears to occur very rapidly after the first dose, we questioned the need for repeat dosing and adopted a standard single-dose protocol of 375 mg/m2 to treat active AAV.Methods. All consecutive cases with newly diagnosed or relapsing AAV for whom conventional immunosuppression was contraindicated or ineffective were enrolled. All were rituximab naive. Circulating CD19+ B cells and clinical and serological markers of disease activity were recorded at regular intervals. Complete remission (CR) was defined as the absence of clinical features of AAV with a prednisolone dose <10 mg/day.Results. Nineteen patients were included, 17 (89%) with generalized disease and 2 (11%) with severe disease (creatinine level >500 μM). Eight (42%) were on additional immunosuppression at the time of rituximab treatment. Satisfactory BCD (<0.005 cells/μl) was achieved in 89% of patients after a median of 13 days. Three-month BCD probability was 89%. Median time to CR following a single dose of rituximab was 38 days and the 3-month probability of CR was 80%. Median time to B cell repopulation was 9.2 months and to disease relapse/redose was 27 months. Use of this single-dose protocol saved an estimated £4533/patient (US$7103; €5276) compared with a 4 × 375 mg/m2 dosing schedule.Conclusion. Our single-centre experience suggests that a single dose of rituximab of 375 mg/m2 is a reasonable and more cost-effective therapy for inducing remission in patients with AAV. [ABSTRACT FROM PUBLISHER]

Background: Adults with rare autoimmune rheumatic diseases face unique challenges and struggles to navigate health-care systems designed to manage common conditions. Evidence to inform an optimal service framework for their care is scarce. Using systemic vasculitis as an exemplar, we aimed to identify and explain the key service components underpinning effective care for rare diseases., Methods: In this mixed-methods study, data were collected as part of a survey of vasculitis service providers across the UK and Ireland, interviews with patients, and from organisational case studies to identify key service components that enable good care. The association between these components and patient outcomes (eg, serious infections, mortality) and provider outcomes (eg, emergency hospital admissions) were examined in a population-based data linkage study using routine health-care data obtained from patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis from national health datasets in Scotland. We did univariable and multivariable analyses using Bayesian poisson and negative binomial regression to estimate incident rate ratios (IRRs), and Cox proportional hazards models to estimate hazard ratios (HRs). People with lived experiences were involved in the research and writing process., Findings: Good care was characterised by service components that supported timely access to services, integrated care, and expertise. In 1420 patients with ANCA-associated vasculitis identified from national health datasets, service-reported average waiting times for new patients of less than 1 week were associated with fewer serious infections (IRR 0·70 [95% credibility interval 0·55-0·88]) and fewer emergency hospital admissions (0·78 [0·68-0·92]). Nurse-led advice lines were associated with fewer serious infections (0·76 [0·58-0·93]) and fewer emergency hospital admissions (0·85 [0·74-0·96]). Average waiting times for new patients of less than 1 week were also associated with reduced mortality (HR 0·59 [95% credibility interval 0·37-0·93]). Cohorted clinics, nurse-led clinics, and specialist vasculitis multi-disciplinary team meetings were associated with fewer serious infections (IRR 0·75 [0·59-0·96] for cohorted clinics; 0·65 [0·39-0·84] for nurse-led clinics; 0·72 [0·57-0·90] for specialist vasculitis multi-disciplinary team meetings) and emergency hospital admissions (0·81 [0·71-0·91]; 0·75 [0·65-0·94]; 0·86 [0·75-0·96]). Key components were characterised by their ability to overcome professional tensions between specialties., Interpretation: Key service components associated with important health outcomes and underpinning factors were identified to inform initiatives to improve the design, delivery, and effectiveness of health-care models for rare autoimmune rheumatic diseases., Funding: Versus Arthritis., Competing Interests: Declaration of interest NB has received speaker fees and research funding from VSL Vifor. RJH has received funding for the present study from Versus Arthritis; is clinical lead of the Scottish Systemic Vasculitis Managed Clinical Network; and has received speaker fees from CSL Vifor. PCL is co-chair of the Rare Autoimmune Rheumatic Disease Alliance (RAIRDA), the joint national clinical lead for the Rheumatology, Getting It Right First Time programme, NHS England, and the clinical lead for Rare Diseases, National Disease Registration Service, NHS England; has received speaker fees from CSL Vifor and Pfizer; and expenses for attending conferences and research funding from CSL Vifor. MAL has received speaker fees from CSL Vifor. LL's research time for this study was supported by the Health Services Research Unit, University of Aberdeen, which received core funding from the Chief Scientist's Office (Scotland). All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.)

Approximately 500 monogenic causes of chronic kidney disease (CKD) have been identified, mainly in pediatric populations. The frequency of monogenic causes among adults with CKD has been less extensively studied. To determine the likelihood of detecting monogenic causes of CKD in adults presenting to nephrology services in Ireland, we conducted whole exome sequencing (WES) in a multi-centre cohort of 114 families including 138 affected individuals with CKD. Affected adults were recruited from 78 families with a positive family history, 16 families with extra-renal features, and 20 families with neither a family history nor extra-renal features. We detected a pathogenic mutation in a known CKD gene in 42 of 114 families (37%). A monogenic cause was identified in 36% of affected families with a positive family history of CKD, 69% of those with extra-renal features, and only 15% of those without a family history or extra-renal features. There was no difference in the rate of genetic diagnosis in individuals with childhood versus adult onset CKD. Among the 42 families in whom a monogenic cause was identified, WES confirmed the clinical diagnosis in 17 (40%), corrected the clinical diagnosis in 9 (22%), and established a diagnosis for the first time in 16 families referred with CKD of unknown etiology (38%). In this multi-centre study of adults with CKD, a molecular genetic diagnosis was established in over one-third of families. In the evolving era of precision medicine, WES may be an important tool to identify the cause of CKD in adults., (Copyright © 2019 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Background: Socioeconomic position (SEP) is an important determinant of health and it is dynamic across the entire lifespan. We sought to investigate the relationship between life-course SEP and chronic kidney disease (CKD) using 3 conceptual models: critical period, pathway and accumulation., Methods: Cross-sectional analysis of 4,996 participants from The Irish Longitudinal Study on Ageing, a nationally representative cohort of community-dwelling adults aged ≥50 years. We defined childhood and adulthood SEP according to father's and respondent's occupation respectively. SEP was categorised as high (reference), intermediate, low and never worked. CKD was defined as a glomerular filtration rate < 60 mL/min/1.73 m2 estimated from the combination of creatinine and cystatin C. We used logistic regression to estimate the age-adjusted association between SEP and CKD separately in men and women., Results: Low childhood SEP was strongly associated with CKD in women, after adjusting for adulthood SEP (OR 1.90 [95% CI 1.24-2.92]), supporting the critical period hypothesis. This association was not explained by traditional CKD risk factors. Women who experienced low childhood SEP and whose circumstances improved in adulthood also had increased odds of CKD, further supporting a critical period effect in childhood. There was comparatively less evidence in support of the pathway or accumulation models. We did not observe a statistically significant association between SEP and CKD in men., Conclusions: Our findings suggest that women exposed to disadvantaged SEP in childhood represent an at-risk group in whom there may be opportunities for identification of CKD and facilitation of health-promoting behaviours from an early age., (© 2018 S. Karger AG, Basel.)

Background: Impaired blood pressure (BP) stabilisation after standing, defined using beat-to-beat measurements, has been shown to predict important health outcomes. We aimed to define the relationship between individual classes of antihypertensive agent and BP stabilisation among hypertensive older adults., Methods: Cross-sectional analysis from The Irish Longitudinal Study on Ageing, a cohort study of Irish adults aged 50 years and over. Beat-to-beat BP was recorded in participants undergoing an active stand test. We defined grade 1 hypertension according to European Society of Cardiology criteria (systolic BP [SBP] 140-159 mmHg ± diastolic BP [DBP] 90-99 mmHg). Outcomes were: (i) initial orthostatic hypotension (IOH) (SBP drop ≥40 mmHg ± DBP drop ≥20 mmHg within 15 seconds [s] of standing accompanied by symptoms); (ii) sustained OH (SBP drop ≥20 mmHg ± DBP drop ≥10 mmHg from 60 to 110 s inclusive); (iii) impaired BP stabilisation (SBP drop ≥20 mmHg ± DBP drop ≥10 mmHg at any 10 s interval during the test). Outcomes were assessed using multivariable-adjusted logistic regression., Results: A total of 536 hypertensive participants were receiving monotherapy with a renin-angiotensin-aldosterone-system inhibitor (n = 317, 59.1%), beta-blocker (n = 89, 16.6%), calcium channel blocker (n = 89, 16.6%) or diuretic (n = 41, 7.6%). A further 783 untreated participants met criteria for grade 1 hypertension. Beta-blockers were associated with increased odds of initial OH (OR 2.05, 95% CI 1.31-3.21) and sustained OH (OR 3.36, 95% CI 1.87-6.03) versus untreated grade 1 hypertension. Multivariable adjustment did not attenuate the results. Impaired BP stabilisation was evident at 20 s (OR 2.59, 95% CI 1.58-4.25) and persisted at 110 s (OR 2.90, 95% CI 1.64-5.11). No association was found between the other agents and any study outcome., Conclusion: Beta-blocker monotherapy was associated with a >2-fold increased odds of initial OH and a >3-fold increased odds of sustained OH and impaired BP stabilisation, compared to untreated grade 1 hypertension. These findings support existing literature questioning the role of beta-blockers as first line agents for essential hypertension.

Background: The prevalence of kidney disease (KD) due to inherited genetic conditions in Ireland is unknown. The aim of this study was to characterise an adult kidney disease population in Ireland and to identify familial clusters of kidney disease within the population., Methods: This was a multicenter cross-sectional study of patients with kidney disease in the Republic of Ireland, from January 2014 to September 2014, recruiting from dialysis units and out-patient renal departments. A survey was performed by collecting data on etiology of kidney disease and whether a family history of kidney disease exists. Medical records were cross-referenced to confirm the etiology of kidney disease., Results: A total of 1,840 patients were recruited with a mean age of 55.9 years (range 17-94.5) and a male predominance (n = 1,095; 59.5%). A positive family history was reported by 629 participants (34.2%). Excluding polycystic kidney disease (n = 134, 7.3%), a positive family history was reported by 495 participants (26.9%). Kidney disease due to an unknown etiology was the commonest etiology in the non-polycystic kidney disease group with a positive family history (10.6%, n = 67). Kidney diseases that are not classically associated with familial inheritance including tubulo-interstitial kidney disease, congenital abnormalities of the kidney and urinary tract and glomerulonephritis demonstrated familial clustering., Conclusion: In an Irish non-polycystic kidney disease population, 26.9% reports a positive family history. The commonest etiology of kidney disease in the positive family history cohort, excluding autosomal dominant polycystic kidney disease, was kidney disease due to unknown etiology. Examining families with kidney disease provides an opportunity to better understand disease pathogenesis and potentially identify genetic predispositions to kidney disease., (© 2015 S. Karger AG, Basel.)