Early indicators of disease progression in Fabry disease that may indicate the need for disease-specific treatment initiation: findings from the opinion-based PREDICT-FD modified Delphi consensus initiative

Hughes, Derralynn; Aguiar, Pedro M. Q.; Deegan, Patrick; Ezgu, Fatih Süheyl; Frustaci, Andrea; Lidove, Olivier; Linhart, Aleš; Lubanda, Jean-Claude; Moon, James; Nicholls, Kathleen; Niu, Dau‐Ming; Nowak, Albina; Ramaswami, Uma; Reisin, Ricardo; Rozenfeld, Paula; Schiffmann, Raphael; Svarstad, Einar; Thomas, Mark; Torrá, Roser; Vujkovac, Bojan; Warnock, David G.; West, Michael; Johnson, J.; Rolfe, Mark; Feriozzi, Sandro

doi:10.1136/bmjopen-2019-035182

Cited by 28 publications

(54 citation statements)

References 25 publications

(35 reference statements)

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“…Achievement of a consensus is the standard for completing the Delphi process. On one hand, consensus was defined as the score of the first‐level indicators' importance and the score of the second‐level indicators' appropriate degree of assignment ≥4 was awarded by >67% of the panelists (Hughes et al., 2020; Koch et al., 2020). On the other hand, the coefficient of variation (CV) and the Kendall coefficient of concordance (W) reflect the degree of agreement.…”

Section: Methodsmentioning

confidence: 99%

Design of assessment tool for unplanned endotracheal extubation of artificial airway patients

Zhang

Liu

2021

Nursing Open

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Aim Unplanned endotracheal extubation (UEE) is one of the most common adverse events reported in patients with artificial airway. Current research in UEE is mostly limited to the summary of risk factors and analysis of prevention strategies. The aim of the study was to develop an assessment tool for medical staff to assess the risk of unplanned extubation in endotracheal intubation patients. Design The design was a qualitative study. Methods Based on literature review, group discussion, pre‐investigation, the initial risk assessment scale on unplanned extubation for endotracheal intubation patients was established. Fifteen experts from thirteen tertiary‐A hospitals across eight provinces participated in two rounds of Delphi panel. Results The risk assessment tool on unplanned extubation for endotracheal intubation patients was established by the Delphi method. It was composed of 11 indicators, which got agreement among two rounds panel.

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Section: Methodsmentioning

confidence: 99%

Design of assessment tool for unplanned endotracheal extubation of artificial airway patients

Zhang

Liu

2021

Nursing Open

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“…However, it remains unclear whether treatment-related reductions in LysoGb3 levels are associated with improved long-term outcomes. The PRoposing Early Disease Indicators for Clinical Tracking in Fabry Disease (PREDICT-FD) initiative established expert consensus on indicators of FD progression that clinicians can use to inform treatment-initiation decisions [11]. A key motivation was to investigate whether collective clinical experience supports initiation of FD-specific treatment based on signs and symptoms that may present at an earlier stage of disease than do those underpinning existing guidance [11].…”

Section: Introductionmentioning

confidence: 99%

“…The PRoposing Early Disease Indicators for Clinical Tracking in Fabry Disease (PREDICT-FD) initiative established expert consensus on indicators of FD progression that clinicians can use to inform treatment-initiation decisions [11]. A key motivation was to investigate whether collective clinical experience supports initiation of FD-specific treatment based on signs and symptoms that may present at an earlier stage of disease than do those underpinning existing guidance [11]. There are two approved FD-specific treatment modalities: intravenous enzyme replacement therapy (ERT) and oral chaperone therapy.…”

Section: Introductionmentioning

confidence: 99%

“…As well as examining the clinical case for appropriate FD-specific treatment initiation [11], PREDICT-FD required participants to suggest and to vote on factors that may drive or impede treatment initiation. Here, we report the consensus reached on these drivers of and barriers to treatment initiation and examine whether current treatment guidelines might contribute to delays in starting treatment.…”

Section: Introductionmentioning

confidence: 99%

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Do clinical guidelines facilitate or impede drivers of treatment in Fabry disease?

Hughes

Aguiar

Lidove

et al. 2022

Orphanet J Rare Dis

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Background Variable disease progression confounds accurate prognosis in Fabry disease. Evidence supports the long-term benefit of early intervention with disease-specific therapy, but current guidelines recommend treatment initiation based on signs that may present too late to avoid irreversible organ damage. Findings from the ‘PRoposing Early Disease Indicators for Clinical Tracking in Fabry Disease’ (PREDICT-FD) initiative included expert consensus on 27 early indicators of disease progression in Fabry disease and on drivers of and barriers to treatment initiation in Fabry disease. Here, we compared the PREDICT-FD indicators with guidance from the European Fabry Working Group and various national guidelines to identify differences in signs supporting treatment initiation and how guidelines themselves might affect initiation. Finally, anonymized patient histories were reviewed by PREDICT-FD experts to determine whether PREDICT-FD indicators supported earlier treatment than existing guidance. Results Current guidelines generally aligned with PREDICT-FD on indicators of renal involvement, but most lacked specificity regarding cardiac indicators. The prognostic significance of neurological indicators such as white matter lesions (excluded by PREDICT-FD) was questioned in some guidelines and excluded from most. Some PREDICT-FD patient-reported signs (e.g., febrile crises) did not feature elsewhere. Key drivers of treatment initiation in PREDICT-FD were: (A) male sex, young age, and clinical findings (e.g., severe pain, organ involvement), (B) improving clinical outcomes and preventing disease progression, and (C) a family history of Fabry disease (especially if outcomes were severe). All guidelines aligned with (A) and several advocated therapy for asymptomatic male patients. There was scant evidence of (B) in current guidance: for example, no countries mandated ancillary symptomatic therapy, and no guidance advocated familial screening with (C) when diagnosis was confirmed. Barriers were misdiagnosis and a lack of biomarkers to inform timing of treatment. Review of patient histories generally found equal or greater support for treatment initiation with PREDICT-FD indicators than with other guidelines and revealed that the same case and guideline criteria often yielded different treatment recommendations. Conclusions Wider adoption of PREDICT-FD indicators at a national level could promote earlier treatment in Fabry disease. Clearer, more concise guidance is needed to harmonize treatment initiation in Fabry disease internationally.

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“…The GLA variants can lead to the deficiency of the lysosomal enzyme ɑ-galactosidase A (α-gal A) [ 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ]. This enzyme is active in glycosphingolipid catabolism and accumulation of neutral glycosphingolipids, namely, globotriaosylceramide (Gb3), which is the hallmark pathogenesis leading to clinical syndromes [ 20 , 28 ]. The incidence of FD in the general population ranges from ~1:40,000 to 1:60,000 among male patients [ 29 , 30 , 31 ].…”

Section: Introductionmentioning

confidence: 99%

Outcomes of Kidney Transplantation in Fabry Disease: A Meta-Analysis

et al. 2020

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Background: Fabry disease (FD) is a rare X-linked lysosomal storage disorder with progressive systemic deposition of globotriaosylceramide, leading to life-threatening cardiac, central nervous system, and kidney disease. Current therapy involves symptomatic medical management, enzyme replacement therapy (ERT), dialysis, kidney transplantation, and, more recently, gene therapy. The aim of this systematic review was to assess outcomes of kidney transplantation among patients with FD. Methods: A comprehensive literature review was conducted utilizing MEDLINE, EMBASE, and Cochrane Database, from inception through to 28 February 2020, to identify studies that evaluate outcomes of kidney transplantation including patient and allograft survival among kidney transplant patients with FD. Effect estimates from each study were extracted and combined using the random-effects generic inverse variance method of DerSimonian and Laird. Results: In total, 11 studies, including 424 kidney transplant recipients with FD, were enrolled. The post-transplant median follow-up time ranged from 3 to 11.5 years. Overall, the pooled estimated rates of all-cause graft failure, graft failure before death, and allograft rejection were 32.5% (95%CI: 23.9%–42.5%), 14.5% (95%CI: 8.4%–23.7%), and 20.2% (95%CI: 15.4%–25.9%), respectively. In the sensitivity analysis, limited only to the recent studies (year 2001 or newer when ERT became available), the pooled estimated rates of all-cause graft failure, graft failure before death, and allograft rejection were 28.1% (95%CI: 20.5%–37.3%), 11.7% (95%CI: 8.4%–16.0%), and 20.2% (95%CI: 15.5%–26.0%), respectively. The pooled estimated rate of biopsy proven FD recurrence was 11.1% (95%CI: 3.6%–29.4%), respectively. There are no significant differences in the risks of all-cause graft failure (p = 0.10) or mortality (0.48) among recipients with vs. without FD. Conclusions: Despite possible FD recurrence after transplantation of 11.1%, allograft and patient survival are comparable among kidney transplant recipients with vs. without FD.

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Early indicators of disease progression in Fabry disease that may indicate the need for disease-specific treatment initiation: findings from the opinion-based PREDICT-FD modified Delphi consensus initiative

Cited by 28 publications

References 25 publications

Design of assessment tool for unplanned endotracheal extubation of artificial airway patients

Design of assessment tool for unplanned endotracheal extubation of artificial airway patients

Do clinical guidelines facilitate or impede drivers of treatment in Fabry disease?

Outcomes of Kidney Transplantation in Fabry Disease: A Meta-Analysis

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