scholarly journals Development and external validation of a prognostic multivariable model on admission for hospitalized patients with COVID-19

Author(s):  
Jianfeng Xie ◽  
Daniel Hungerford ◽  
Hui Chen ◽  
Simon T Abrams ◽  
Shusheng Li ◽  
...  

SummaryBackgroundCOVID-19 pandemic has developed rapidly and the ability to stratify the most vulnerable patients is vital. However, routinely used severity scoring systems are often low on diagnosis, even in non-survivors. Therefore, clinical prediction models for mortality are urgently required.MethodsWe developed and internally validated a multivariable logistic regression model to predict inpatient mortality in COVID-19 positive patients using data collected retrospectively from Tongji Hospital, Wuhan (299 patients). External validation was conducted using a retrospective cohort from Jinyintan Hospital, Wuhan (145 patients). Nine variables commonly measured in these acute settings were considered for model development, including age, biomarkers and comorbidities. Backwards stepwise selection and bootstrap resampling were used for model development and internal validation. We assessed discrimination via the C statistic, and calibration using calibration-in-the-large, calibration slopes and plots.FindingsThe final model included age, lymphocyte count, lactate dehydrogenase and SpO2 as independent predictors of mortality. Discrimination of the model was excellent in both internal (c=0·89) and external (c=0·98) validation. Internal calibration was excellent (calibration slope=1). External validation showed some over-prediction of risk in low-risk individuals and under-prediction of risk in high-risk individuals prior to recalibration. Recalibration of the intercept and slope led to excellent performance of the model in independent data.InterpretationCOVID-19 is a new disease and behaves differently from common critical illnesses. This study provides a new prediction model to identify patients with lethal COVID-19. Its practical reliance on commonly available parameters should improve usage of limited healthcare resources and patient survival rate.FundingThis study was supported by following funding: Key Research and Development Plan of Jiangsu Province (BE2018743 and BE2019749), National Institute for Health Research (NIHR) (PDF-2018-11-ST2-006), British Heart Foundation (BHF) (PG/16/65/32313) and Liverpool University Hospitals NHS Foundation Trust in UK.Research in contextEvidence before this studySince the outbreak of COVID-19, there has been a pressing need for development of a prognostic tool that is easy for clinicians to use. Recently, a Lancet publication showed that in a cohort of 191 patients with COVID-19, age, SOFA score and D-dimer measurements were associated with mortality. No other publication involving prognostic factors or models has been identified to date.Added value of this studyIn our cohorts of 444 patients from two hospitals, SOFA scores were low in the majority of patients on admission. The relevance of D-dimer could not be verified, as it is not included in routine laboratory tests. In this study, we have established a multivariable clinical prediction model using a development cohort of 299 patients from one hospital. After backwards selection, four variables, including age, lymphocyte count, lactate dehydrogenase and SpO2 remained in the model to predict mortality. This has been validated internally and externally with a cohort of 145 patients from a different hospital. Discrimination of the model was excellent in both internal (c=0·89) and external (c=0·98) validation. Calibration plots showed excellent agreement between predicted and observed probabilities of mortality after recalibration of the model to account for underlying differences in the risk profile of the datasets. This demonstrated that the model is able to make reliable predictions in patients from different hospitals. In addition, these variables agree with pathological mechanisms and the model is easy to use in all types of clinical settings.Implication of all the available evidenceAfter further external validation in different countries the model will enable better risk stratification and more targeted management of patients with COVID-19. With the nomogram, this model that is based on readily available parameters can help clinicians to stratify COVID-19 patients on diagnosis to use limited healthcare resources effectively and improve patient outcome.

2021 ◽  
Author(s):  
Steven J. Staffa ◽  
David Zurakowski

Summary Clinical prediction models in anesthesia and surgery research have many clinical applications including preoperative risk stratification with implications for clinical utility in decision-making, resource utilization, and costs. It is imperative that predictive algorithms and multivariable models are validated in a suitable and comprehensive way in order to establish the robustness of the model in terms of accuracy, predictive ability, reliability, and generalizability. The purpose of this article is to educate anesthesia researchers at an introductory level on important statistical concepts involved with development and validation of multivariable prediction models for a binary outcome. Methods covered include assessments of discrimination and calibration through internal and external validation. An anesthesia research publication is examined to illustrate the process and presentation of multivariable prediction model development and validation for a binary outcome. Properly assessing the statistical and clinical validity of a multivariable prediction model is essential for reassuring the generalizability and reproducibility of the published tool.


2021 ◽  
Author(s):  
Cynthia Yang ◽  
Jan A. Kors ◽  
Solomon Ioannou ◽  
Luis H. John ◽  
Aniek F. Markus ◽  
...  

Objectives This systematic review aims to provide further insights into the conduct and reporting of clinical prediction model development and validation over time. We focus on assessing the reporting of information necessary to enable external validation by other investigators. Materials and Methods We searched Embase, Medline, Web-of-Science, Cochrane Library and Google Scholar to identify studies that developed one or more multivariable prognostic prediction models using electronic health record (EHR) data published in the period 2009-2019. Results We identified 422 studies that developed a total of 579 clinical prediction models using EHR data. We observed a steep increase over the years in the number of developed models. The percentage of models externally validated in the same paper remained at around 10%. Throughout 2009-2019, for both the target population and the outcome definitions, code lists were provided for less than 20% of the models. For about half of the models that were developed using regression analysis, the final model was not completely presented. Discussion Overall, we observed limited improvement over time in the conduct and reporting of clinical prediction model development and validation. In particular, the prediction problem definition was often not clearly reported, and the final model was often not completely presented. Conclusion Improvement in the reporting of information necessary to enable external validation by other investigators is still urgently needed to increase clinical adoption of developed models.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
A Youssef

Abstract Study question Which models that predict pregnancy outcome in couples with unexplained RPL exist and what is the performance of the most used model? Summary answer We identified seven prediction models; none followed the recommended prediction model development steps. Moreover, the most used model showed poor predictive performance. What is known already RPL remains unexplained in 50–75% of couples For these couples, there is no effective treatment option and clinical management rests on supportive care. Essential part of supportive care consists of counselling on the prognosis of subsequent pregnancies. Indeed, multiple prediction models exist, however the quality and validity of these models varies. In addition, the prediction model developed by Brigham et al is the most widely used model, but has never been externally validated. Study design, size, duration We performed a systematic review to identify prediction models for pregnancy outcome after unexplained RPL. In addition we performed an external validation of the Brigham model in a retrospective cohort, consisting of 668 couples with unexplained RPL that visited our RPL clinic between 2004 and 2019. Participants/materials, setting, methods A systematic search was performed in December 2020 in Pubmed, Embase, Web of Science and Cochrane library to identify relevant studies. Eligible studies were selected and assessed according to the TRIPOD) guidelines, covering topics on model performance and validation statement. The performance of predicting live birth in the Brigham model was evaluated through calibration and discrimination, in which the observed pregnancy rates were compared to the predicted pregnancy rates. Main results and the role of chance Seven models were compared and assessed according to the TRIPOD statement. This resulted in two studies of low, three of moderate and two of above average reporting quality. These studies did not follow the recommended steps for model development and did not calculate a sample size. Furthermore, the predictive performance of neither of these models was internally- or externally validated. We performed an external validation of Brigham model. Calibration showed overestimation of the model and too extreme predictions, with a negative calibration intercept of –0.52 (CI 95% –0.68 – –0.36), with a calibration slope of 0.39 (CI 95% 0.07 – 0.71). The discriminative ability of the model was very low with a concordance statistic of 0.55 (CI 95% 0.50 – 0.59). Limitations, reasons for caution None of the studies are specifically named prediction models, therefore models may have been missed in the selection process. The external validation cohort used a retrospective design, in which only the first pregnancy after intake was registered. Follow-up time was not limited, which is important in counselling unexplained RPL couples. Wider implications of the findings: Currently, there are no suitable models that predict on pregnancy outcome after RPL. Moreover, we are in need of a model with several variables such that prognosis is individualized, and factors from both the female as the male to enable a couple specific prognosis. Trial registration number Not applicable


2021 ◽  
Author(s):  
Wei-Ju Chang ◽  
Justine Naylor ◽  
Pragadesh Natarajan ◽  
Spiro Menounos ◽  
Masiath Monuja ◽  
...  

Abstract Background Prediction models for poor patient-reported surgical outcomes after total hip replacement (THR) and total knee replacement (TKR) may provide a method for improving appropriate surgical care for hip and knee osteoarthritis. There are concerns about methodological issues and the risk of bias of studies producing prediction models. A critical evaluation of the methodological quality of prediction modelling studies in THR and TKR is needed to ensure their clinical usefulness. This systematic review aims to: 1) evaluate and report the quality of risk stratification and prediction modelling studies that predict patient-reported outcomes after THR and TKR; 2) identify areas of methodological deficit and provide recommendations for future research; and 3) synthesise the evidence on prediction models associated with post-operative patient-reported outcomes after THR and TKR surgeries. Methods MEDLINE, EMBASE and CINAHL electronic databases will be searched to identify relevant studies. Title and abstract and full-text screening will be performed by two independent reviewers. We will include: 1) prediction model development studies without external validation; 2) prediction model development studies with external validation of independent data; 3) external model validation studies; and 4) studies updating a previously developed prediction model. Data extraction spreadsheets will be developed based on the CHARMS checklist and TRIPOD statement and piloted on two relevant studies. Study quality and risk of bias will be assessed using the PROBAST tool. Prediction models will be summarised qualitatively. Meta-analyses on the predictive performance of included models will be conducted if appropriate. Discussion This systematic review will evaluate the methodological quality and usefulness of prediction models for poor outcomes after THR or TKR. This information is essential to provide evidence-based healthcare for end-stage hip and knee osteoarthritis. Findings of this review will contribute to the identification of key areas for improvement in conducting prognostic research in this field and facilitate the progress in evidence-based tailored treatments for hip and knee osteoarthritis. Systematic review registration: Submitted to PROSPERO on 30 August 2021.


2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Samaneh Asgari ◽  
Davood Khalili ◽  
Farhad Hosseinpanah ◽  
Farzad Hadaegh

Objectives: This study aimed to provide an overview of prediction models of undiagnosed type 2 diabetes mellitus (U-T2DM) or the incident T2DM (I-T2DM) using the transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD) checklist and the prediction model risk of the bias assessment tool (PROBAST). Data Sources: Both PUBMED and EMBASE databases were searched to guarantee adequate and efficient coverage. Study Selection: Articles published between December 2011 and October 2019 were considered. Data Extraction: For each article, information on model development requirements, discrimination measures, calibration, overall performance, clinical usefulness, overfitting, and risk of bias (ROB) was reported. Results: The median (interquartile range; IQR) number of the 46 study populations for model development was 5711 (1971 - 27426) and 2457 (2060 - 6995) individuals for I-T2DM and U-T2DM, respectively. The most common reported predictors were age and body mass index, and only the Qrisk-2017 study included social factors (e.g., Townsend score). Univariable analysis was reported in 46% of the studies, and the variable selection procedure was not clear in 17.4% of them. Moreover, internal and external validation was reported in 43% the studies, while over 63% of them reported calibration. The median (IQR) of AUC for I-T2DM models was 0.78 (0.74 - 0.82); the corresponding value for studies derived before October 2011 was 0.80 (0.77 - 0.83). The highest discrimination index was reported for Qrisk-2017 with C-statistics of 0.89 for women and 0.87 for men. Low ROB for I-T2DM and U-T2DM was assessed at 18% and 41%, respectively. Conclusions: Among prediction models, an intermediate to poor quality were reassessed in several aspects of model development and validation, even though there was a comprehensive protocol. Generally, despite its new risk factors or new methodological aspects, the newly developed model did not increase our capability in screening/predicting T2DM, mainly in the analysis part. It was due to the lack of external validation of the prediction models.


2020 ◽  
Author(s):  
Fernanda Gonçalves Silva ◽  
Leonardo Oliveira Pena Costa ◽  
Mark J Hancock ◽  
Gabriele Alves Palomo ◽  
Luciola da Cunha Menezes Costa ◽  
...  

Abstract Background: The prognosis of acute low back pain is generally favourable in terms of pain and disability; however, outcomes vary substantially between individual patients. Clinical prediction models help in estimating the likelihood of an outcome at a certain time point. There are existing clinical prediction models focused on prognosis for patients with low back pain. To date, there is only one previous systematic review summarising the discrimination of validated clinical prediction models to identify the prognosis in patients with low back pain of less than 3 months duration. The aim of this systematic review is to identify existing developed and/or validated clinical prediction models on prognosis of patients with low back pain of less than 3 months duration, and to summarise their performance in terms of discrimination and calibration. Methods: MEDLINE, Embase and CINAHL databases will be searched, from the inception of these databases until January 2020. Eligibility criteria will be: (1) prognostic model development studies with or without external validation, or prognostic external validation studies with or without model updating; (2) with adults aged 18 or over, with ‘recent onset’ low back pain (i.e. less than 3 months duration), with or without leg pain; (3) outcomes of pain, disability, sick leave or days absent from work or return to work status, and self-reported recovery; and (4) study with a follow-up of at least 12 weeks duration. The risk of bias of the included studies will be assessed by the Prediction model Risk Of Bias ASsessment Tool, and the overall quality of evidence will be rated using the Hierarchy of Evidence for Clinical Prediction Rules. Discussion: This systematic review will identify, appraise, and summarize evidence on the performance of existing prediction models for prognosis of low back pain, and may help clinicians to choose the best option of prediction model to better inform patients about their likely prognosis. Systematic review registration: PROSPERO reference number CRD42020160988


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sharmala Thuraisingam ◽  
Patty Chondros ◽  
Michelle M. Dowsey ◽  
Tim Spelman ◽  
Stephanie Garies ◽  
...  

Abstract Background The use of general practice electronic health records (EHRs) for research purposes is in its infancy in Australia. Given these data were collected for clinical purposes, questions remain around data quality and whether these data are suitable for use in prediction model development. In this study we assess the quality of data recorded in 201,462 patient EHRs from 483 Australian general practices to determine its usefulness in the development of a clinical prediction model for total knee replacement (TKR) surgery in patients with osteoarthritis (OA). Methods Variables to be used in model development were assessed for completeness and plausibility. Accuracy for the outcome and competing risk were assessed through record level linkage with two gold standard national registries, Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) and National Death Index (NDI). The validity of the EHR data was tested using participant characteristics from the 2014–15 Australian National Health Survey (NHS). Results There were substantial missing data for body mass index and weight gain between early adulthood and middle age. TKR and death were recorded with good accuracy, however, year of TKR, year of death and side of TKR were poorly recorded. Patient characteristics recorded in the EHR were comparable to participant characteristics from the NHS, except for OA medication and metastatic solid tumour. Conclusions In this study, data relating to the outcome, competing risk and two predictors were unfit for prediction model development. This study highlights the need for more accurate and complete recording of patient data within EHRs if these data are to be used to develop clinical prediction models. Data linkage with other gold standard data sets/registries may in the meantime help overcome some of the current data quality challenges in general practice EHRs when developing prediction models.


2018 ◽  
Vol 22 (66) ◽  
pp. 1-294 ◽  
Author(s):  
Rachel Archer ◽  
Emma Hock ◽  
Jean Hamilton ◽  
John Stevens ◽  
Munira Essat ◽  
...  

Background Rheumatoid arthritis (RA) is a chronic, debilitating disease associated with reduced quality of life and substantial costs. It is unclear which tests and assessment tools allow the best assessment of prognosis in people with early RA and whether or not variables predict the response of patients to different drug treatments. Objective To systematically review evidence on the use of selected tests and assessment tools in patients with early RA (1) in the evaluation of a prognosis (review 1) and (2) as predictive markers of treatment response (review 2). Data sources Electronic databases (e.g. MEDLINE, EMBASE, The Cochrane Library, Web of Science Conference Proceedings; searched to September 2016), registers, key websites, hand-searching of reference lists of included studies and key systematic reviews and contact with experts. Study selection Review 1 – primary studies on the development, external validation and impact of clinical prediction models for selected outcomes in adult early RA patients. Review 2 – primary studies on the interaction between selected baseline covariates and treatment (conventional and biological disease-modifying antirheumatic drugs) on salient outcomes in adult early RA patients. Results Review 1 – 22 model development studies and one combined model development/external validation study reporting 39 clinical prediction models were included. Five external validation studies evaluating eight clinical prediction models for radiographic joint damage were also included. c-statistics from internal validation ranged from 0.63 to 0.87 for radiographic progression (different definitions, six studies) and 0.78 to 0.82 for the Health Assessment Questionnaire (HAQ). Predictive performance in external validations varied considerably. Three models [(1) Active controlled Study of Patients receiving Infliximab for the treatment of Rheumatoid arthritis of Early onset (ASPIRE) C-reactive protein (ASPIRE CRP), (2) ASPIRE erythrocyte sedimentation rate (ASPIRE ESR) and (3) Behandelings Strategie (BeSt)] were externally validated using the same outcome definition in more than one population. Results of the random-effects meta-analysis suggested substantial uncertainty in the expected predictive performance of models in a new sample of patients. Review 2 – 12 studies were identified. Covariates examined included anti-citrullinated protein/peptide anti-body (ACPA) status, smoking status, erosions, rheumatoid factor status, C-reactive protein level, erythrocyte sedimentation rate, swollen joint count (SJC), body mass index and vascularity of synovium on power Doppler ultrasound (PDUS). Outcomes examined included erosions/radiographic progression, disease activity, physical function and Disease Activity Score-28 remission. There was statistical evidence to suggest that ACPA status, SJC and PDUS status at baseline may be treatment effect modifiers, but not necessarily that they are prognostic of response for all treatments. Most of the results were subject to considerable uncertainty and were not statistically significant. Limitations The meta-analysis in review 1 was limited by the availability of only a small number of external validation studies. Studies rarely investigated the interaction between predictors and treatment. Suggested research priorities Collaborative research (including the use of individual participant data) is needed to further develop and externally validate the clinical prediction models. The clinical prediction models should be validated with respect to individual treatments. Future assessments of treatment by covariate interactions should follow good statistical practice. Conclusions Review 1 – uncertainty remains over the optimal prediction model(s) for use in clinical practice. Review 2 – in general, there was insufficient evidence that the effect of treatment depended on baseline characteristics. Study registration This study is registered as PROSPERO CRD42016042402. Funding The National Institute for Health Research Health Technology Assessment programme.


2021 ◽  
Author(s):  
Arjun Chandna ◽  
Raman Mahajan ◽  
Priyanka Gautam ◽  
Lazaro Mwandigha ◽  
Karthik Gunasekaran ◽  
...  

ABSTRACTBackgroundIn locations where few people have received COVID-19 vaccines, health systems remain vulnerable to surges in SARS-CoV-2 infections. Tools to identify patients suitable for community-based management are urgently needed.MethodsWe prospectively recruited adults presenting to two hospitals in India with moderate symptoms of laboratory-confirmed COVID-19 in order to develop and validate a clinical prediction model to rule-out progression to supplemental oxygen requirement. The primary outcome was defined as any of the following: SpO2 < 94%; respiratory rate > 30 bpm; SpO2/FiO2 < 400; or death. We specified a priori that each model would contain three clinical parameters (age, sex and SpO2) and one of seven shortlisted biochemical biomarkers measurable using near-patient tests (CRP, D-dimer, IL-6, NLR, PCT, sTREM-1 or suPAR), to ensure the models would be suitable for resource-limited settings. We evaluated discrimination, calibration and clinical utility of the models in a temporal external validation cohort.Findings426 participants were recruited, of whom 89 (21·0%) met the primary outcome. 257 participants comprised the development cohort and 166 comprised the validation cohort. The three models containing NLR, suPAR or IL-6 demonstrated promising discrimination (c-statistics: 0·72 to 0·74) and calibration (calibration slopes: 1·01 to 1·05) in the validation cohort, and provided greater utility than a model containing the clinical parameters alone.InterpretationWe present three clinical prediction models that could help clinicians identify patients with moderate COVID-19 suitable for community-based management. The models are readily implementable and of particular relevance for locations with limited resources.FundingMédecins Sans Frontières, India.RESEARCH IN CONTEXTEvidence before this studyA living systematic review by Wynants et al. identified 137 COVID-19 prediction models, 47 of which were derived to predict whether patients with COVID-19 will have an adverse outcome. Most lacked external validation, relied on retrospective data, did not focus on patients with moderate disease, were at high risk of bias, and were not practical for use in resource-limited settings. To identify promising biochemical biomarkers which may have been evaluated independently of a prediction model and therefore not captured by this review, we searched PubMed on 1 June 2020 using synonyms of “SARS-CoV-2” AND [“biomarker” OR “prognosis”]. We identified 1,214 studies evaluating biochemical biomarkers of potential value in the prognostication of COVID-19 illness. In consultation with FIND (Geneva, Switzerland) we shortlisted seven candidates for evaluation in this study, all of which are measurable using near-patient tests which are either currently available or in late-stage development.Added value of this studyWe followed the TRIPOD guidelines to develop and validate three promising clinical prediction models to help clinicians identify which patients presenting with moderate COVID-19 can be safely managed in the community. Each model contains three easily ascertained clinical parameters (age, sex, and SpO2) and one biochemical biomarker (NLR, suPAR or IL-6), and would be practical for implementation in high-patient-throughput low resource settings. The models showed promising discrimination and calibration in the validation cohort. The inclusion of a biomarker test improved prognostication compared to a model containing the clinical parameters alone, and extended the range of contexts in which such a tool might provide utility to include situations when bed pressures are less critical, for example at earlier points in a COVID-19 surge.Implications of all the available evidencePrognostic models should be developed for clearly-defined clinical use-cases. We report the development and temporal validation of three clinical prediction models to rule-out progression to supplemental oxygen requirement amongst patients presenting with moderate COVID-19. The models are readily implementable and should prove useful in triage and resource allocation. We provide our full models to enable independent validation.


2018 ◽  
Vol 12 (1) ◽  
pp. 469-481
Author(s):  
Michala Skovlund Sørensen ◽  
Elizabeth C. Silvius ◽  
Saniya Khullar ◽  
Klaus Hindsø ◽  
Jonathan A. Forsberg ◽  
...  

Background: Predicting survival for patients with metastatic bone disease in the extremities (MBDex) is important for ensuring the implant will outlive the patient. Hitherto, prediction models for these patients have been constructed using subjective assessments, mostly lacking biochemical variables. Objectives: To develop a prediction model for survival after surgery due to MBDex using biochemical variables and externally validate the model. Methods: We created Bayesian Belief Network models to estimate likelihood of survival 1, 3, 6, and 12 months after surgery using 140 patients. We validated the models using the data of 130 other patients and calculated the area under the Receiver Operator Characteristic curve (ROC). Variables included: hemoglobin, neutrophil-count, C-reactive protein, alkaline phosphatase, primary cancer, Karnofsky-score, ASA-score, visceral metastases, bone metastases, days from diagnose of primary cancer to index surgery for MBDex, ischemic heart disease, diabetes, fracture/impending-fracture and age. Results: Survival probabilities were influenced by all biochemical variables. Validation showed ROC for the 1, 3, 6, and 12-months model: 68% (C.I.: 55%-80%), 69% (C.I.: 60%-78%), 81% (C.I.: 74%-87%) and 84% (C.I.: 77%-90%). Conclusion: Biochemical markers can be incorporated into a prediction model for survival in patients having surgery for MBDex allowing surgeons to offer more objective and individualized treatment options.


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