scholarly journals A systematic review of blood biomarkers with individual participant data meta-analysis of matrix-metalloproteinase-7 in IPF

2021 ◽  
pp. 2101612
Author(s):  
Fasihul A. Khan ◽  
Iain Stewart ◽  
Gauri Saini ◽  
Karen A. Robinson ◽  
R. Gisli Jenkins
Keyword(s):  
Systematic Review ◽  
Matrix Metalloproteinase ◽  
Disease Progression ◽  
Meta Analysis ◽  
Secondary Outcome ◽  
Individual Participant Data ◽  
Increased Risk ◽  
Matrix Metalloproteinase 7 ◽  
Individual Participant ◽  
Poor Outcomes

BackgroundBlood derived biomarkers have been extensively described as potential prognostic markers in idiopathic pulmonary fibrosis (IPF), but studies have been limited by analyses using data-dependent thresholds, inconsistent adjustment for confounders and an array of endpoints, thus often yielding ungeneralisable results. Meta-analysis of individual participant data (IPD) is a powerful tool to overcome these limitations. Through systematic review of blood derived biomarkers, sufficient studies with measurements of Matrix Metalloproteinase-7 (MMP-7) were identified to facilitate standardised analyses of the prognostic potential of this biomarker in IPF.MethodsElectronic databases were searched on 12th November 2020 to identify prospective studies reporting outcomes in patients with untreated IPF, stratified according to at least one pre-specified biomarker, measured at either baseline, or change over three months. Individual participant data (IPD) was sought for studies investigating MMP-7 as a prognostic factor. The primary outcome was overall mortality according to standardised MMP-7 z-scores, with a secondary outcome of disease progression in 12 months, all adjusted for age, gender, smoking and baseline FVC.ResultsIPD was available for nine studies out of twelve identified, reporting outcomes from 1664 participants. Baseline MMP-7 levels were associated with increased mortality risk (adjusted HR1.23, 95%CI 1.03;1.48, I2=64.3%) and disease progression (adjusted OR1.27, 95%CI 1.11;1.46, I2=5.9%). In limited studies, three-month change in MMP-7 was not associated with outcomes.ConclusionIPD meta-analysis demonstrated greater baseline MMP-7 levels were independently associated with an increased risk of poor outcomes in patients with untreated IPF, whilst short term changes did not reflect disease progression.

scholarly journals An individual participant data meta-analysis of prognostic blood biomarkers in IPF

2021 ◽  
Author(s):  
Fasihul A Khan ◽  
Iain Stewart ◽  
Gauri Saini ◽  
Karen A. Robinson ◽  
R Gisli Jenkins
Keyword(s):  
Disease Progression ◽  
Meta Analysis ◽  
Individual Participant Data ◽  
Blood Biomarkers ◽  
Disease Trajectory ◽  
Increased Risk ◽  
Matrix Metalloproteinase 7 ◽  
Individual Participant ◽  
Fibrotic Lung Disease ◽  
Overall Mortality

ABSTRACTBackgroundIdiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease with variable disease trajectory. Blood biomarkers reflecting disease severity that can accurately predict outcomes are urgently needed. Through systematic review and meta-analysis, we evaluate the prognostic potential of matrix-metalloproteinase-7 (MMP-7) and other frequently studied blood biomarkers in patients with IPF.MethodsElectronic databases were searched on 12th November 2020 to identify prospective studies reporting outcomes in patients with untreated IPF, stratified according to at least one pre-specified biomarker, measured at either baseline or change over three months. Individual participant data (IPD) was sought for studies investigating MMP-7 as a prognostic factor. The primary outcome was overall mortality, with secondary outcomes including disease progression, defined as >10% relative FVC decline or death.Results29 studies reporting outcomes from 3950 IPF participants were included, investigating a total of 16 biomarkers. IPD from MMP-7 studies was available for eleven cohorts. Baseline MMP-7 levels were associated with increased mortality (adjusted HR1.23 per SD increase, 95%CI 1.03;1.48, I2=64.3%) and disease progression (adjusted OR1.27 per SD increase, 95%CI 1.11;1.46, I2=5.9%), but change in MMP-7 over three-months was not associated with any of the measured outcomes. There was insufficient data for quantitative analysis in non-MMP7 studies, and whilst many biomarkers showed an association with clinical outcomes, replication of effects across studies was weak.ConclusionBaseline MMP-7 levels were associated with an increased risk of overall mortality and disease progression in patients with untreated IPF. The evidence for other biomarkers is currently insufficient with further studies needed.

scholarly journals Three month FVC change: a potential trial endpoint for IPF based on individual participant data meta-analysis

2021 ◽  
Author(s):  
Fasihul Khan ◽  
Iain Stewart ◽  
Samuel Moss ◽  
Laura Fabbri ◽  
Karen A Robinson ◽  
...  
Keyword(s):  
Disease Progression ◽  
Smoking Status ◽  
Meta Analysis ◽  
Secondary Outcome ◽  
Gas Transfer ◽  
Individual Participant Data ◽  
Physiological Variables ◽  
Disease Outcomes ◽  
Individual Participant ◽  
Trial Endpoint

Rationale Novel therapies for idiopathic pulmonary fibrosis (IPF) are in development, but there remains uncertainty about the optimal trial endpoint. An earlier endpoint would enable assessment of a greater number of therapies in adaptive trial designs. Objectives Individual participant data (IPD) from placebo arms of interventional trials were sought to determine whether short-term changes in forced vital capacity (FVC), gas transfer for carbon monoxide (DLCO) and six-minute walk distance (6MWD) could act as surrogate endpoints to accelerate early-phase trials in IPF. Methods Electronic databases were searched on 1st December 2020, and IPD were sought and meta-analysed. The primary outcome was overall mortality according to baseline and/or three-month change in either FVC, DLCO or 6MWD, with a secondary outcome of disease progression at 12 months, adjusted for age, sex, smoking status and baseline physiology. Measurements and main results IPD was available for 10/23 eligible studies totalling 1819 participants. Baseline and three-month change in all physiological variables were independently associated with disease outcomes. A 2.5% relative decline in FVC over three months was associated with mortality (adjusted hazard ratio 1.14, 95%CI 1.06;1.24, I2 = 59.9%) and disease progression (adjusted odds ratio 1.29; 95%CI 1.18;1.40, I2=67%). Optimal thresholds for three-month change in FVC for distinguishing disease outcomes were identified. Conclusions IPD meta-analysis of trial placebo arms demonstrated three-month change in physiological variables, particularly FVC, were associated with mortality and disease progression among individuals with untreated IPF. FVC change over three months may hold potential as a surrogate endpoint in IPF interventional adaptive trials.

scholarly journals 012 Mechanical thrombectomy in pediatric stroke: systematic review, individual patient-data meta-analysis, and case series

2019 ◽  
Vol 90 (e7) ◽  
pp. A5.1-A5
Author(s):  
Kartik Bhatia ◽  
Hans Kortman ◽  
Chris Blair ◽  
Geoffrey Parker ◽  
David Brunacci ◽  
...  
Keyword(s):  
Systematic Review ◽  
Scale Score ◽  
Mechanical Thrombectomy ◽  
Meta Analysis ◽  
Secondary Outcome ◽  
Individual Participant Data ◽  
Neurological Outcomes ◽  
Paediatric Patients ◽  
Individual Participant

IntroductionIn adults, there is strong evidence demonstrating the superiority of mechanical thrombectomy (MT) plus intravenous thrombolysis over thrombolysis alone for the treatment of acute ischemic stroke due to large vessel occlusion (LVO). The role of MT in the paediatric stroke population is less clear. Here we present an updated systematic review addressing the use of MT in paediatric patients, including three cases from our centre in Sydney, Australia. We have also completed an individual participant data (IPD) meta-analysis of clinical and angiographic outcomes based on these results.MethodOur systematic review and IPD meta-analysis was performed according to PRISMA-IPD (Preferred Reporting Items for Systematic Reviews and Meta-Analyses: Individual Participant Data) guidelines. Primary outcomes measures were change in NIHSS (National Institute of Health Stroke Scale) score following MT, and mRS (modified Rankin Scale) score at final reported follow-up. The secondary outcome measure was final angiographic result using the mTICI (modified Treatment in Cerebral Ischemia) scale.ResultsMT resulted in good long-term neurological outcomes (mRS 0–2) in 60/67 cases (89.6%;follow-up timing µ=4.1 months: 95%CI 2.9–5.3), good short-term neurological outcomes (reduction in NIHSS by 8 or more points or post-MT NIHSS of 0–1) in 37/52 cases (71.2%), and successful recanalization (mTICI 2b/3) in 57/67 cases (85.1%).ConclusionsIn paediatric patients, MT is an effective treatment for ischaemic stroke due to LVO. In the absence of a dedicated prospective registry and with randomized control trails unfeasible, this report represents the best available evidence for the use of MT in the paediatric setting.

scholarly journals Long working hours and alcohol use: systematic review and meta-analysis of published studies and unpublished individual participant data

BMJ ◽  
2015 ◽  
Vol 350 (jan12 13) ◽  
pp. g7772-g7772 ◽  
Author(s):  
M. Virtanen ◽  
M. Jokela ◽  
S. T. Nyberg ◽  
I. E. H. Madsen ◽  
T. Lallukka ◽  
...  
Keyword(s):  
Systematic Review ◽  
Alcohol Use ◽  
Meta Analysis ◽  
Working Hours ◽  
Individual Participant Data ◽  
Long Working Hours ◽  
Individual Participant

scholarly journals Effects of mechanical interventions in the management of knee osteoarthritis: protocol for an OA Trial Bank systematic review and individual participant data meta-analysis

BMJ Open ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. e043026
Author(s):  
Erin M Macri ◽  
Michael Callaghan ◽  
Marienke van Middelkoop ◽  
Miriam Hattle ◽  
Sita M A Bierma-Zeinstra
Keyword(s):  
Systematic Review ◽  
Knee Osteoarthritis ◽  
Broad Class ◽  
Meta Analysis ◽  
Individual Participant Data ◽  
Knee Oa ◽  
International Regulations ◽  
Individual Participant ◽  
Registration Number ◽  
Mechanical Intervention

IntroductionKnee osteoarthritis (OA) is a prevalent and disabling musculoskeletal condition. Biomechanical factors may play a key role in the aetiology of knee OA, therefore, a broad class of interventions involves the application or wear of devices designed to mechanically support knees with OA. These include gait aids, bracing, taping, orthotics and footwear. The literature regarding efficacy of mechanical interventions has been conflicting or inconclusive, and this may be because certain subgroups with knee OA respond better to mechanical interventions. Our primary aim is to identify subgroups with knee OA who respond favourably to mechanical interventions.Methods and analysisWe will conduct a systematic review to identify randomised clinical trials of any mechanical intervention for the treatment of knee OA. We will invite lead authors of eligible studies to share individual participant data (IPD). We will perform an IPD meta-analysis for each type of mechanical intervention to evaluate efficacy, with our main outcome being pain. Where IPD are not available, this will be achieved using aggregate data. We will then evaluate five potential treatment effect modifiers using a two-stage approach. If data permit, we will also evaluate whether biomechanics mediate the effects of mechanical interventions on pain in knee OA.Ethics and disseminationNo new data will be collected in this study. We will adhere to institutional, national and international regulations regarding the secure and confidential sharing of IPD, addressing ethics as indicated. We will disseminate findings via international conferences, open-source publication in peer-reviewed journals and summaries posted on websites serving the public and clinicians.PROSPERO registration numberCRD42020155466.

Sign in / Sign up

Export Citation Format

Share Document