Development and external validation of a clinical prediction model to aid coeliac disease diagnosis in primary care: An observational study

Elwenspoek, Martha M C; O’Donnell, Rachel; Jackson, Joni; Everitt, Hazel; Gillett, Peter M.; Jones, Hayley E; Robins, Gerry; Watson, Jessica; Mallett, Susan; Whiting, Penny

doi:10.1016/j.eclinm.2022.101376

Cited by 5 publications

(5 citation statements)

References 27 publications

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“…Some of the microbial markers identified by LEfSE, differential abundance expression, and correlation in stool and duodenum samples were also present in the RF models ( Alloprevotella spp., Cutibacterium spp ., Delftia spp ., Neisseria spp., and Rothia spp. ), demonstrating their potential as microbial biomarkers able to discern between the disease and its possible usefulness in combination with other prediction models to estimate the risk of having CeD based on symptoms and risk factors previously described ( Elwenspoek et al, 2022 ). The RF model built with stool samples achieves an outstanding performance even with the validation dataset proving the capability of using a stool as a surrogate marker for changes in the duodenal microbiota of patients with CeD.…”

Section: Discussionmentioning

confidence: 92%

“…Active case findings can help combat underdiagnosis by offering CeD tests to people at higher risk of CeD. In this sense, using prediction models to estimate the risk of having CeD based on symptoms and risk factors is helpful; however, the performance of these models is lower when using only clinical data ( Elwenspoek et al, 2022 ). The use of microbial markers isolated from stool samples, besides being a non-invasive procedure, will help to improve the predictive power of current models.…”

Section: Discussionmentioning

confidence: 99%

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A comprehensive map of microbial biomarkers along the gastrointestinal tract for celiac disease patients

et al. 2022

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Dysbiosis of the microbiome has been related to Celiac disease (CeD) progress, an autoimmune disease characterized by gluten intolerance developed in genetically susceptible individuals under certain environmental factors. The microbiome contributes to CeD pathophysiology, modulating the immune response by the action of short-chain fatty acids (SCFA), affecting gut barrier integrity allowing the entrance of gluten-derived proteins, and degrading immunogenic peptides of gluten through endoprolyl peptidase enzymes. Despite the evidence suggesting the implication of gut microbiome over CeD pathogenesis, there is no consensus about the specific microbial changes observed in this pathology. Here, we compiled the largest dataset of 16S prokaryotic ribosomal RNA gene high-throughput sequencing for consensus profiling. We present for the first time an integrative analysis of metataxonomic data from patients with CeD, including samples from different body sites (saliva, pharynx, duodenum, and stool). We found the presence of coordinated changes through the gastrointestinal tract (GIT) characterized by an increase in Actinobacteria species in the upper GIT (pharynx and duodenum) and an increase in Proteobacteria in the lower GIT (duodenum and stool), as well as site-specific changes evidencing a dysbiosis in patients with CeD’ microbiota. Moreover, we described the effect of adherence to a gluten-free diet (GFD) evidenced by an increase in beneficial bacteria and a decrease in some Betaproteobacteriales but not fully restoring CeD-related dysbiosis. Finally, we built a Random Forest model to classify patients based on the lower GIT composition achieving good performance.

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

A comprehensive map of microbial biomarkers along the gastrointestinal tract for celiac disease patients

et al. 2022

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“…If medical codes are absent in a patient record we will assume that the patient does not have that diagnosis, or that the diagnosis was not considered sufficiently important to have been recorded by the GP in case of symptoms. 34 Concordantly, the analytical cohorts are not expected to have missing data for any of the predictor variables. It is possible that diagnoses may be recorded as free text, data to which we do not have access, rather than as diagnostic codes and this may lead to misclassification of some patients.…”

Section: Methods and Analysismentioning

confidence: 98%

“…For diagnoses, if a medical code is present in the patient record (without a preceding time window limitation) then the variable is classified as being present for the patient. If medical codes are absent in a patient record we will assume that the patient does not have that diagnosis, or that the diagnosis was not considered sufficiently important to have been recorded by the GP in case of symptoms 34. Concordantly, the analytical cohorts are not expected to have missing data for any of the predictor variables.…”

Section: Methods and Analysismentioning

confidence: 99%

Risk of atrial fibrillation and association with other diseases: protocol of the derivation and international external validation of a prediction model using nationwide population-based electronic health records

Nadarajah,

Wu,

Arbel

et al. 2023

BMJ Open

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IntroductionAtrial fibrillation (AF) is a major public health issue and there is rationale for the early diagnosis of AF before the first complication occurs. Previous AF screening research is limited by low yields of new cases and strokes prevented in the screened populations. For AF screening to be clinically and cost-effective, the efficiency of identification of newly diagnosed AF needs to be improved and the intervention offered may have to extend beyond oral anticoagulation for stroke prophylaxis. Previous prediction models for incident AF have been limited by their data sources and methodologies.Methods and analysisWe will investigate the application of random forest and multivariable logistic regression to predict incident AF within a 6-month prediction horizon, that is, a time-window consistent with conducting investigation for AF. The Clinical Practice Research Datalink (CPRD)-GOLD dataset will be used for derivation, and the Clalit Health Services (CHS) dataset will be used for international external geographical validation. Analyses will include metrics of prediction performance and clinical utility. We will create Kaplan-Meier plots for individuals identified as higher and lower predicted risk of AF and derive the cumulative incidence rate for non-AF cardio-renal-metabolic diseases and death over the longer term to establish how predicted AF risk is associated with a range of new non-AF disease states.Ethics and disseminationPermission for CPRD-GOLD was obtained from CPRD (ref no: 19_076). The CPRD ethical approval committee approved the study. CHS Helsinki committee approval 21-0169 and data usage committee approval 901. The results will be submitted as a research paper for publication to a peer-reviewed journal and presented at peer-reviewed conferences.Trial registration numberA systematic review to guide the overall project was registered on PROSPERO (registration number CRD42021245093). The study was registered on ClinicalTrials.gov (NCT05837364).

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“…For diagnoses, if medical codes are absent in a patient record, we will assume that the patient does not have that diagnosis, or that the diagnosis was not considered sufficiently important to have been recorded by the GP in case of symptoms. 31 Ethnicity information is routinely Open access collected in the UK NHS and so has increasingly high completeness, 32 and we will include an 'ethnicity unrecorded' category where it is unavailable because missingness is considered to be informative. 33 Accordingly, we do not expect any missing data for any of the predictor variables in the analytical cohort.…”

Section: Predictor Variablesmentioning

confidence: 99%

Predicting incident heart failure from population-based nationwide electronic health records: protocol for a model development and validation study

Nakao,

Nadarajah,

Shuweihdi

et al. 2024

BMJ Open

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IntroductionHeart failure (HF) is increasingly common and associated with excess morbidity, mortality, and healthcare costs. Treatment of HF can alter the disease trajectory and reduce clinical events in HF. However, many cases of HF remain undetected until presentation with more advanced symptoms, often requiring hospitalisation. Predicting incident HF is challenging and statistical models are limited by performance and scalability in routine clinical practice. An HF prediction model implementable in nationwide electronic health records (EHRs) could enable targeted diagnostics to enable earlier identification of HF.Methods and analysisWe will investigate a range of development techniques (including logistic regression and supervised machine learning methods) on routinely collected primary care EHRs to predict risk of new-onset HF over 1, 5 and 10 years prediction horizons. The Clinical Practice Research Datalink (CPRD)-GOLD dataset will be used for derivation (training and testing) and the CPRD-AURUM dataset for external validation. Both comprise large cohorts of patients, representative of the population of England in terms of age, sex and ethnicity. Primary care records are linked at patient level to secondary care and mortality data. The performance of the prediction model will be assessed by discrimination, calibration and clinical utility. We will only use variables routinely accessible in primary care.Ethics and disseminationPermissions for CPRD-GOLD and CPRD-AURUM datasets were obtained from CPRD (ref no: 21_000324). The CPRD ethical approval committee approved the study. The results will be submitted as a research paper for publication to a peer-reviewed journal and presented at peer-reviewed conferences.Trial registration detailsThe study was registered on Clinical Trials.gov (NCT 05756127). A systematic review for the project was registered on PROSPERO (registration number: CRD42022380892).

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Development and external validation of a clinical prediction model to aid coeliac disease diagnosis in primary care: An observational study

Cited by 5 publications

References 27 publications

A comprehensive map of microbial biomarkers along the gastrointestinal tract for celiac disease patients

A comprehensive map of microbial biomarkers along the gastrointestinal tract for celiac disease patients

Risk of atrial fibrillation and association with other diseases: protocol of the derivation and international external validation of a prediction model using nationwide population-based electronic health records

Predicting incident heart failure from population-based nationwide electronic health records: protocol for a model development and validation study

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