Detailed clinical phenotyping and generalisability in prognostic models of functioning in at-risk populations

2021 ◽  
pp. 1-4
Author(s):  
Marlene Rosen ◽  
Linda T. Betz ◽  
Natalie Kaiser ◽  
Nora Penzel ◽  
Dominic Dwyer ◽  
...  

Summary Personalised prediction of functional outcomes is a promising approach for targeted early intervention in psychiatry. However, generalisability and resource efficiency of such prognostic models represent challenges. In the PRONIA study (German Clinical Trials Register: DRKS00005042), we demonstrate excellent generalisability of prognostic models in individuals at clinical high-risk for psychosis or with recent-onset depression, and substantial contributions of detailed clinical phenotyping, particularly to the prediction of role functioning. These results indicate that it is possible that functioning prediction models based only on clinical data could be effectively applied in diverse healthcare settings, so that neuroimaging data may not be needed at early assessment stages.

2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S122-S122
Author(s):  
Marlene Rosen ◽  
Nathalie Kaiser ◽  
Linda Betz ◽  
Theresa Haidl ◽  
Mauro Seves ◽  
...  

Abstract Background Psychotic disorders are associated with serious deterioration in functioning even before the first psychotic episode. Also on clinical high risk (CHR) states of developing a first psychotic episode, several studies reported a decreased global functioning. In a considerable proportion of CHR individuals, functional deterioration remains even after (transient) remission of symptomatic risk indicators. Furthermore, deficits in functioning cause immense costs for the health care system and are often more debilitating for individuals than positive symptoms. However in the past, CHR research has mostly focused on clinical outcomes like transition. Prediction of functioning in CHR populations has received less attention. Therefore, the current study aims at predicting functioning in CHR individuals at a single subject level applying multi pattern recognition to clinical data. Patients with a first depressive episode who frequently have persistent functional deficits comparable to patients in the CHR state were investigated in addition. Methods PRONIA (‘Personalized Prognostic Tools for Early Psychosis Management’) is a prospective collaboration project funded by the European Union under the 7th Framework Programme (grant agreement n°602152). Considering a broad set of variables (MRI, clinical data, neurocognition, genomics and other blood derived parameters) as well as advanced statistical methods, PRONIA aims at developing an innovative multivariate prognostic tool enabling an individualized prediction of illness trajectories and outcome. 11 university centers in five European countries and in Australia (Munich, Basel, Birmingham, Cologne, Düsseldorf, Münster, Melbourne, Milan, Udine, Bari, Turku) participate in the evaluation of three clinical groups (subjects clinically at high risk of developing a psychosis [CHR], patients with a recent onset psychosis [ROP] and patients with a recent onset depression [ROD]) as well as healthy controls. In the current study, we analysed data of 114 CHR and 106 ROD patients. Functioning was measured by the ‘Global Functioning: Social and Role’ Scales (GF S/R). In a repeated, nested cross validation framework we trained a l1-regularized SVM to predict good versus bad outcome. Multivariate pattern recognition analysis allowed to identify most predictive variables from a multitude of clinical, environmental as well as sociodemographic potential predictors assessed in PRONIA. Results Based on the 5 to 20 identified most predictive features, prediction models revealed a balanced accuracy (BAC) up to 77/72 for social functioning in CHR/ROD patients and up to 73/69 for role functioning. These models showed satisfying performance of BACs up to 69/63 for social functioning and 67/60 for role functioning in an independent test sample. As expected, prior functioning levels were identified as main predictive factor but also distinct protective and risk factors were selected into the prediction models. Discussion Results suggest that especially prediction of the multi-faceted construct of role functioning could benefit from inclusion of a rich set of clinical variables. To the best of our knowledge this is the first study that has validated clinical prediction models of functioning in an independent test sample. Identification of predictive variables enables a much more efficient prognostic process. Moreover, understanding the mechanisms underlying functional decline and its illness related pattern might enable an improved definition of targets for intervention. Future research should aim at further maximisation of prediction accuracy and cross-centre generalisation capacity. In addition, other functioning outcomes as well as clinical outcomes need to be focused on.


2018 ◽  
Vol 75 (11) ◽  
pp. 1156 ◽  
Author(s):  
Nikolaos Koutsouleris ◽  
Lana Kambeitz-Ilankovic ◽  
Stephan Ruhrmann ◽  
Marlene Rosen ◽  
Anne Ruef ◽  
...  

2020 ◽  
Author(s):  
Nan Xiang ◽  
Fangyuan Dong ◽  
Xuebing Zhan ◽  
Shuhan Wang ◽  
Junjie Wang ◽  
...  

Abstract Background: Primary thyroid lymphoma (PTL) is a rare thyroid malignancy, there are few large sample studies on PTL and no standardized treatment regimen has been established due to the rarity. Objective: The aims of this study were to explore the incidence and prognostic factors of PTL and construct visual prognostic prediction models for post-chemotherapy and postoperative patients.Methods: The incidence of PTL in 1975-2017 was extracted from the US Surveillance, Epidemiology, and End Results (SEER) database, then assessed using joinpoint regression software. A total of 1,616 eligible PTL patients diagnosed in 1998-2016 were brought into prognostic analysis. Multivariate Cox regression analyses were carried out to reveal independent prognostic elements for overall survival (OS) and cancer-specific survival (CSS).Results: PTL incidence showed a relatively steady increase in 1975-1994, which annual percent change (APC) was 4.0%, and steady decreasing in 1994-2017(APC -2.4%). Age, marital status, lymphoma Ann Arbor stage, histological subtypes, surgery, chemotherapy, and radiation were significantly correlated to OS and CSS. The combination of radiotherapy with chemotherapy or surgery was beneficial to the prognosis of patients. Nomograms were constructed to predict OS and CSS in post-chemotherapy and postoperative PTL patients separately, and were verified to have good reliability.Conclusions: The incidence of PTL increased and subsequently decreased. We revealed the prognostic implications and constructed reliable nomograms for post-chemotherapy and postoperative PTL patients.


2020 ◽  
Author(s):  
Nils Rethmeier ◽  
Necip Oğuz Şerbetci ◽  
Sebastian Möller ◽  
Roland Roller

Recent medical prognostic models adapted from high data-resource fields like language processing have quickly grown in complexity and size. However, since medical data typically constitute low data-resource settings, performances on tasks like clinical prediction did not improve expectedly. Instead of following this trend of using complex neural models in combination with small, pre-selected feature sets, we propose EffiCare, which focuses on minimizing hospital resource requirements for assistive clinical prediction models. First, by embedding medical events,we eliminate manual domain feature-engineering and increase the amount of learning data. Second, we use small,but data-efficient models, that compute faster and are easier to interpret. We evaluate our approach on four clinical prediction tasks and achieve substantial performance improvements over highly resource-demanding state-of-the-art methods. Finally, to evaluate our model beyond score improvements, we apply explainability and interpretability methods to analyze the decisions of our model and whether it uses data sources and parameters efficiently.


2020 ◽  
Author(s):  
Jenna Marie Reps ◽  
Ross Williams ◽  
Seng Chan You ◽  
Thomas Falconer ◽  
Evan Minty ◽  
...  

Abstract Objective: To demonstrate how the Observational Healthcare Data Science and Informatics (OHDSI) collaborative network and standardization can be utilized to scale-up external validation of patient-level prediction models by enabling validation across a large number of heterogeneous observational healthcare datasets.Materials & Methods: Five previously published prognostic models (ATRIA, CHADS2, CHADS2VASC, Q-Stroke and Framingham) that predict future risk of stroke in patients with atrial fibrillation were replicated using the OHDSI frameworks. A network study was run that enabled the five models to be externally validated across nine observational healthcare datasets spanning three countries and five independent sites. Results: The five existing models were able to be integrated into the OHDSI framework for patient-level prediction and they obtained mean c-statistics ranging between 0.57-0.63 across the 6 databases with sufficient data to predict stroke within 1 year of initial atrial fibrillation diagnosis for females with atrial fibrillation. This was comparable with existing validation studies. The validation network study was run across nine datasets within 60 days once the models were replicated. An R package for the study was published at https://github.com/OHDSI/StudyProtocolSandbox/tree/master/ExistingStrokeRiskExternalValidation.Discussion: This study demonstrates the ability to scale up external validation of patient-level prediction models using a collaboration of researchers and a data standardization that enable models to be readily shared across data sites. External validation is necessary to understand the transportability or reproducibility of a prediction model, but without collaborative approaches it can take three or more years for a model to be validated by one independent researcher. Conclusion : In this paper we show it is possible to both scale-up and speed-up external validation by showing how validation can be done across multiple databases in less than 2 months. We recommend that researchers developing new prediction models use the OHDSI network to externally validate their models.


Author(s):  
Jenna Marie Reps ◽  
Ross D Williams ◽  
Seng Chan You ◽  
Thomas Falconer ◽  
Evan Minty ◽  
...  

Abstract Background: To demonstrate how the Observational Healthcare Data Science and Informatics (OHDSI) collaborative network and standardization can be utilized to scale-up external validation of patient-level prediction models by enabling validation across a large number of heterogeneous observational healthcare datasets.Methods: Five previously published prognostic models (ATRIA, CHADS2, CHADS2VASC, Q-Stroke and Framingham) that predict future risk of stroke in patients with atrial fibrillation were replicated using the OHDSI frameworks. A network study was run that enabled the five models to be externally validated across nine observational healthcare datasets spanning three countries and five independent sites. Results: The five existing models were able to be integrated into the OHDSI framework for patient-level prediction and they obtained mean c-statistics ranging between 0.57-0.63 across the 6 databases with sufficient data to predict stroke within 1 year of initial atrial fibrillation diagnosis for females with atrial fibrillation. This was comparable with existing validation studies. The validation network study was run across nine datasets within 60 days once the models were replicated. An R package for the study was published at https://github.com/OHDSI/StudyProtocolSandbox/tree/master/ExistingStrokeRiskExternalValidation.Conclusion : This study demonstrates the ability to scale up external validation of patient-level prediction models using a collaboration of researchers and a data standardization that enable models to be readily shared across data sites. External validation is necessary to understand the transportability or reproducibility of a prediction model, but without collaborative approaches it can take three or more years for a model to be validated by one independent researcher. In this paper we show it is possible to both scale-up and speed-up external validation by showing how validation can be done across multiple databases in less than 2 months. We recommend that researchers developing new prediction models use the OHDSI network to externally validate their models.


BMJ Open ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. e034564
Author(s):  
Ralph K Akyea ◽  
Jo Leonardi-Bee ◽  
Folkert W Asselbergs ◽  
Riyaz S Patel ◽  
Paul Durrington ◽  
...  

IntroductionCardiovascular disease (CVD) is the leading cause of morbidity and mortality globally. With advances in early diagnosis and treatment of CVD and increasing life expectancy, more people are surviving initial CVD events. However, models for stratifying disease severity risk in patients with established CVD for effective secondary prevention strategies are inadequate. Multivariable prognostic models to stratify CVD risk may allow personalised treatment interventions. This review aims to systematically review the existing multivariable prognostic models for the recurrence of CVD or major adverse cardiovascular events in adults with established CVD diagnosis.Methods and analysisBibliographic databases (Ovid MEDLINE, EMBASE, PsycINFO and Web of Science) will be searched, from database inception to April 2020, using terms relating to the clinical area and prognosis. A hand search of the reference lists of included studies will also be done to identify additional published studies. No restrictions on language of publications will be applied. Eligible studies present multivariable models (derived or validated) of adults (aged 16 years and over) with an established diagnosis of CVD, reporting at least one of the components of the primary outcome of major adverse cardiovascular events (defined as either coronary heart disease, stroke, peripheral artery disease, heart failure or CVD-related mortality). Reviewing will be done by two reviewers independently using the pre-defined criteria. Data will be extracted for included full-text articles. Risk of bias will be assessed using the Prediction model study Risk Of Bias ASsessment Tool (PROBAST). Prognostic models will be summarised narratively. If a model is tested in multiple validation studies, the predictive performance will be summarised using a random-effects meta-analysis model to account for any between-study heterogeneity.Ethics and disseminationEthics approval is not required. The results of this study will be submitted to relevant conferences for presentation and a peer-reviewed journal for publication.PROSPERO registration numberCRD42019149111.


Gut ◽  
2018 ◽  
Vol 68 (4) ◽  
pp. 672-683 ◽  
Author(s):  
Todd Smith ◽  
David C Muller ◽  
Karel G M Moons ◽  
Amanda J Cross ◽  
Mattias Johansson ◽  
...  

ObjectiveTo systematically identify and validate published colorectal cancer risk prediction models that do not require invasive testing in two large population-based prospective cohorts.DesignModels were identified through an update of a published systematic review and validated in the European Prospective Investigation into Cancer and Nutrition (EPIC) and the UK Biobank. The performance of the models to predict the occurrence of colorectal cancer within 5 or 10 years after study enrolment was assessed by discrimination (C-statistic) and calibration (plots of observed vs predicted probability).ResultsThe systematic review and its update identified 16 models from 8 publications (8 colorectal, 5 colon and 3 rectal). The number of participants included in each model validation ranged from 41 587 to 396 515, and the number of cases ranged from 115 to 1781. Eligible and ineligible participants across the models were largely comparable. Calibration of the models, where assessable, was very good and further improved by recalibration. The C-statistics of the models were largely similar between validation cohorts with the highest values achieved being 0.70 (95% CI 0.68 to 0.72) in the UK Biobank and 0.71 (95% CI 0.67 to 0.74) in EPIC.ConclusionSeveral of these non-invasive models exhibited good calibration and discrimination within both external validation populations and are therefore potentially suitable candidates for the facilitation of risk stratification in population-based colorectal screening programmes. Future work should both evaluate this potential, through modelling and impact studies, and ascertain if further enhancement in their performance can be obtained.


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