The Imperative for Patient-Centred Research to Develop Better Quality Services in Rare Diseases

Facey, Karen; Hansen, Helle Ploug

doi:10.1007/s40271-015-0113-4

Cited by 6 publications

(18 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…IP-10 (CXCL10) has been used as a target engagement and renal inflammation biomarker in a clinical trial assessing the effectiveness of JAK inhibition in patients with diabetic kidney disease treated with baricitinib 16 , but was not used to generate the STAT1 activation score. The STAT1 activation score strongly correlated with CXCL10 mRNA levels in both the discovery (Figure 7a, r=0.81, p<0.001, n=68) and validation (Figure 7b, r=0.58, p<0.001, n=166) AAV and NS datasets, as it did in DKD in confirmation of the clinical trial observation 17,18 (Supplemental Figure 3). Because STAT1 activation can be considered a reflection of the intra-renal inflammatory state and has been reported to drive tissue fibrosis 19 , the interaction of the STAT1 activation score with interstitial fibrosis was assessed.…”

Section: Resultssupporting

confidence: 68%

Inflammatory and JAK-STAT Pathways as Shared Molecular Targets for ANCA-Associated Vasculitis and Nephrotic Syndrome

Eddy

Nair

Mariani

et al. 2018

Preprint

View full text Add to dashboard Cite

249 words ABSTRACT Background: Glomerular diseases of the kidney are presently differentiated, diagnosed and treated according to conventional clinical or structural features. While etiologically diverse, these diseases share common clinical features including but not limited to reduced glomerular filtration rate, increased serum creatinine and proteinuria suggesting shared pathogenic mechanisms across diseases. Renal biopsies from patients with nephrotic syndrome (NS) or ANCA-associated vasculitis (AAV) were evaluated for molecular signals cutting across conventional disease categories as candidates for therapeutic targets. Methods: Renal biopsies were obtained from patients with NS (minimal change disease, focal segmental glomerulosclerosis, or membranous nephropathy) (n=187) or AAV (granulomatosis with polyangiitis or microscopic polyangiitis) (n=80) from the Nephrotic Syndrome Study Network (NEPTUNE) and the European Renal cDNA Bank. Transcriptional profiles were assessed for shared disease mechanisms.Results: In the discovery cohort, 10-25% transcripts were differentially regulated versus healthy controls in both NS and AAV, >500 transcripts were shared across diseases. The majority of shared transcripts (60-77%) were validated in independent samples. Therapeutically targetable networks were identified, including inflammatory JAK-STAT signaling. STAT1 eQTLs were identified and STAT1 expression associated with GFRbased outcome. A transcriptional STAT1 activity score was generated from STAT1-regulated target genes which correlated with CXCL10 (p<0.001), a JAK-STAT biomarker, predictors of CKD progression, interstitial fibrosis (r=0.41, p<0.001), and urinary EGF (r=-0.51, p<0.001).Conclusion: AAV and NS caused from histopathologically distinct disease categories share common intra-renal molecular pathways cutting across conventional disease classifications. This approach provides a starting point for de novo drug development, and repurposing efforts in rare kidney diseases.

show abstract

Section: Resultssupporting

confidence: 68%

Inflammatory and JAK-STAT Pathways as Shared Molecular Targets for ANCA-Associated Vasculitis and Nephrotic Syndrome

Eddy

Nair

Mariani

et al. 2018

Preprint

View full text Add to dashboard Cite

show abstract

“…Bridging and filling the equity gap in access to care for people with rare diseases requires patient-oriented research that can inform decision-making concerned with care quality improvement [ 35 ]. It also demands involvement of multiple stakeholders.…”

Section: Discussionmentioning

confidence: 99%

Public and patient involvement in needs assessment and social innovation: a people-centred approach to care and research for congenital disorders of glycosylation

Freitas

Reis

Silva

et al. 2017

BMC Health Serv Res

View full text Add to dashboard Cite

Background: Public and patient involvement in the design of people-centred care and research is vital for communities whose needs are underserved, as are people with rare diseases. Innovations devised collectively by patients, caregivers, professionals and other members of the public can foster transformative change toward more responsive services and research. However, attempts to involve lay and professional stakeholders in devising community-framed strategies to address the unmet needs of rare diseases are lacking. In this study, we engaged with the community of Congenital Disorders of Glycosylation (CDG) to assess its needs and elicit social innovations to promote people-centred care and research. Methods: Drawing on a qualitative study, we conducted three think tanks in France with a total of 48 participants, including patients/family members (n = 18), health care professionals (n = 7), researchers (n = 7) and people combining several of these roles (n = 16). Participants came from 20 countries across five continents. They were selected from the registry of the Second World Conference on CDG through heterogeneity and simple random sampling. Inductive and deductive approaches were employed to conduct interpretational analysis using open, axial and selective coding, and the constant-comparison method to facilitate the emergence of categories and core themes. Results: The CDG community has unmet needs for information, quality health care, psychosocial support and representation in decision-making concerned with care and research. According to participants, these needs can be addressed through a range of social innovations, including peer-support communities, web-based information resources and a CDG expertise platform. Conclusion: This is one of the few studies to engage lay and professional experts in needs assessment and innovation for CDG at a global level. Implementing the innovations proposed by the CDG community is likely to have ethical, legal and social implications associated with the potential donation of patients' clinical and biological material that need to be assessed and regulated with involvement from all stakeholders. To promote people-centred care for the CDG community, and increase its participation in the governance of care and research, it is necessary to create participatory spaces in which the views of people affected by CDG can be fully expressed.

show abstract

“…In our review, we found a range of practices to identify attributes, including literature review, 16,19 consulting clinicians, 15 and more in-depth qualitative research techniques such as interviews and/or focus groups with patients and/or clinicians. 14,20,21 In all studies, the final selection of attributes was made by the researchers or a facilitated discussion with the project team. Only one study specifically stated that the patients had to rank and rate the attributes, from which the top attributes were determined.…”

Section: Resultsmentioning

confidence: 99%

Individual Value Clarification Methods Based on Conjoint Analysis: A Systematic Review of Common Practice in Task Design, Statistical Analysis, and Presentation of Results

et al. 2018

View full text Add to dashboard Cite

show abstract

The Imperative for Patient-Centred Research to Develop Better Quality Services in Rare Diseases

Cited by 6 publications

References 12 publications

Inflammatory and JAK-STAT Pathways as Shared Molecular Targets for ANCA-Associated Vasculitis and Nephrotic Syndrome

Inflammatory and JAK-STAT Pathways as Shared Molecular Targets for ANCA-Associated Vasculitis and Nephrotic Syndrome

Public and patient involvement in needs assessment and social innovation: a people-centred approach to care and research for congenital disorders of glycosylation

Individual Value Clarification Methods Based on Conjoint Analysis: A Systematic Review of Common Practice in Task Design, Statistical Analysis, and Presentation of Results

Contact Info

Product

Resources

About