Construction of a Prediction Model for Voriconazole-Induced Hepatotoxicity Based on Mixed-Effects Random Forest.

Voriconazole is a second-generation triazole antifungal agent with strong antifungal activity against a variety of clinically significant pathogens. Controlling blood concentrations within guideline limits through blood concentration monitoring can reduce the probability of hepatotoxicity in patients with voriconazole. However, statistical analysis based on real-world data found that there were still several patients who had blood concentration monitoring developed voriconazole induced hepatotoxicity. Therefore, it has important clinical significance to predict whether hepatotoxicity will occur in patients who meet the guidelines for voriconazole plasma concentration requirements. In this study, based on real-world data, the mixed-effects random forest was used to analyze the electronic medical record data of patients who met the guidelines for voriconazole blood concentration requirements during hospitalization, and a predictive model was constructed to predict whether patients would develop hepatotoxicity within 30 days after using voriconazole.

A survey of artificial intelligence in rheumatoid arthritis.

The article offers a survey of currently notable artificial intelligence methods (released between 2019-2023), with a particular emphasis on the latest advancements in detecting rheumatoid arthritis (RA) at an early stage, providing early treatment, and managing the disease. We discussed challenges in these areas followed by specific artificial intelligence (AI) techniques and summarized advances, relevant strengths, and obstacles. Overall, the application of AI in the fields of RA has the potential to enable healthcare professionals to detect RA at an earlier stage, thereby facilitating timely intervention and better disease management. However, more research is required to confirm the precision and dependability of AI in RA, and several problems such as technological and ethical concerns related to these approaches must be resolved before their widespread adoption.

Improving the Prognosis of Colon Cancer through Knowledge-Based Clinical-Molecular Integrated Analysis.

BACKGROUND: Colon cancer has high morbidity and mortality rates among cancers. Existing clinical staging systems cannot accurately assess the prognostic risk of colon cancer patients. This study was aimed at improving the prognostic performance of the colon cancer clinical staging system through knowledge-based clinical-molecular integrated analysis. METHODS: 374 samples from The Cancer Genome Atlas Colon Adenocarcinoma (TCGA-COAD) dataset were used as the discovery set. 98 samples from the Clinical Proteomic Tumor Analysis Consortium (CPTAC) dataset were used as the validation set. After converting gene expression data into pathway dysregulation scores (PDSs), the random survival forest and Cox model were used to identify the best prognostic supplementary factors. The corresponding clinical-molecular integrated prognostic model was built, and the improvement of prognostic performance was assessed by comparing with the clinical prognostic model. RESULTS: The PDS of 14 pathways played important roles in prognostic prediction together with clinical prognostic factors through the random survival forest. Further screening with the Cox model revealed that the PDS of the pathway hsa00532 was the best clinical prognostic supplementary factor. The integrated prognostic model constructed with clinical factors and the identified molecular factor was superior to the clinical prognostic model in discriminative performance. Kaplan-Meier (KM) curves of patients grouped by PDS suggested that patients with a higher PDS had a poorer prognosis, and stage II patients could be distinctly distinguished. CONCLUSIONS: Based on the knowledge-based clinical-molecular integrated analysis, a clinical-molecular integrated prognostic model and corresponding nomogram for colon cancer overall survival prognosis was built, which showed better prognostic performance than the clinical prognostic model. The PDS of the pathway hsa00532 is a considerable clinical prognostic supplementary factor for colon cancer and may represent a potential prognostic marker for stage II colon cancer. The PDS calculation involves only 16 genes, which supports its potential for clinical application.

Improving prediction performance of colon cancer prognosis based on the integration of clinical and multi-omics data.

BACKGROUND: Colon cancer is common worldwide and is the leading cause of cancer-related death. Multiple levels of omics data are available due to the development of sequencing technologies. In this study, we proposed an integrative prognostic model for colon cancer based on the integration of clinical and multi-omics data. METHODS: In total, 344 patients were included in this study. Clinical, gene expression, DNA methylation and miRNA expression data were retrieved from The Cancer Genome Atlas (TCGA). To accommodate the high dimensionality of omics data, unsupervised clustering was used as dimension reduction method. The bias-corrected Harrell's concordance index was used to verify which clustering result provided the best prognostic performance. Finally, we proposed a prognostic prediction model based on the integration of clinical data and multi-omics data. Uno's concordance index with cross-validation was used to compare the discriminative performance of the prognostic model constructed with different covariates. RESULTS: Combinations of clinical and multi-omics data can improve prognostic performance, as shown by the increase of the bias-corrected Harrell's concordance of the prognostic model from 0.7424 (clinical features only) to 0.7604 (clinical features and three types of omics features). Additionally, 2-year, 3-year and 5-year Uno's concordance statistics increased from 0.7329, 0.7043, and 0.7002 (clinical features only) to 0.7639, 0.7474 and 0.7597 (clinical features and three types of omics features), respectively. CONCLUSION: In conclusion, this study successfully combined clinical and multi-omics data for better prediction of colon cancer prognosis.

Spatially varying effects of predictors for the survival prediction of nonmetastatic colorectal Cancer.

BACKGROUND: An increasing number of studies have identified spatial differences in colorectal cancer survival. However, little is known about the spatially varying effects of predictors in survival prediction modeling studies of colorectal cancer that have focused on estimating the absolute survival risk for patients from a wide range of populations. This study aimed to demonstrate the spatially varying effects of predictors of survival for nonmetastatic colorectal cancer patients. METHODS: Patients diagnosed with nonmetastatic colorectal cancer from 2004 to 2013 who were followed up through the end of 2013 were extracted from the Surveillance Epidemiology End Results registry (Patients: 128061). The log-rank test and the restricted mean survival time were used to evaluate survival outcome differences among spatial clusters corresponding to a widely used clinical predictor: stage determined by AJCC 7th edition staging system. The heterogeneity test, which is used in meta-analyses, revealed the spatially varying effects of single predictors. Then, considering the above predictors in a standard survival prediction model based on spatially clustered data, the spatially varying coefficients of these models revealed that some covariate effects may not be constant across the geographic regions of the study. Then, two types of survival prediction models (a statistical model and a machine learning model) were built; these models considered the predictors and enabled survival prediction for patients from a wide range of geographic regions. RESULTS: Based on univariate and multivariate analysis, some prognostic factors, such as "TNM stage", "tumor size" and "age at diagnosis," have significant spatially varying effects among different regions. When considering these spatially varying effects, machine learning models have fewer assumption constraints (such as proportional hazard assumptions) and better predictive performance compared with statistical models. Upon comparing the concordance indexes of these two models, the machine learning model was found to be more accurate (0.898[0.895,0.902]) than the statistical model (0.732 [0.726, 0.738]). CONCLUSIONS: Based on this study, it's recommended that the spatially varying effect of predictors should be considered when building survival prediction models involving large-scale and multicenter research data. Machine learning models that are not limited by the requirement of a statistical hypothesis are promising alternative models.

POPCORN: A web service for individual PrognOsis prediction based on multi-center clinical data CollabORatioN without patient-level data sharing.

BACKGROUND AND OBJECTIVE: Clinical prognosis prediction plays an important role in clinical research and practice. The construction of prediction models based on electronic health record data has recently become a research focus. Due to the lack of external validation, prediction models based on single-center, hospital-specific datasets may not perform well with datasets from other medical institutions. Therefore, research investigating prognosis prediction model construction based on a collaborative analysis of multi-center electronic health record data could increase the number and coverage of patients used for model training, enrich patient prognostic features and ultimately improve the accuracy and generalization of prognosis prediction. MATERIALS AND METHODS: A web service for individual prognosis prediction based on multi-center clinical data collaboration without patient-level data sharing (POPCORN) was proposed. POPCORN focuses on solving key issues in multi-center collaborative research based on electronic health record systems; these issues include the standardization of clinical data expression, the preservation of patient privacy during model training and the effect of case mix variance on the prediction model construction and application. POPCORN is based on a multivariable meta-analysis and a Bayesian framework and can construct suitable prediction models for multiple clinical scenarios that can effectively adapt to complex clinical application environments. RESULTS: POPCORN was validated using a joint, multi-center collaborative research network between China and the United States with patients diagnosed with colorectal cancer. The performance of the models based on POPCORN was comparable to that of the standard prognosis prediction model; however, POPCORN did not expose raw patient data. The prediction models had similar AUC, but the BMA model had the lowest ECI across all prediction models, indicating that this model had better calibration performance than the other models, especially for patients in Chinese hospitals. CONCLUSIONS: The POPCORN system can build prediction models that perform well in complex clinical application scenarios and can provide effective decision support for individual patient prognostic predictions.

A modified TNM staging system for non-metastatic colorectal cancer based on nomogram analysis of SEER database.

BACKGROUND: To revise the American Joint Committee on Cancer TNM staging system for colorectal cancer (CRC) based on a nomogram analysis of Surveillance, Epidemiology, and End Results (SEER) database, and to prove the rationality of enhancing T stage's weighting in our previously proposed T-plus staging system. METHODS: Total 115,377 non-metastatic CRC patients from SEER were randomly grouped as training and testing set by ratio 1:1. The Nomo-staging system was established via three nomograms based on 1-year, 2-year and 3-year disease specific survival (DSS) Logistic regression analysis of the training set. The predictive value of Nomo-staging system for the testing set was evaluated by concordance index (c-index), likelihood ratio (L.R.) and Akaike information criteria (AIC) for 1-year, 2-year, 3-year overall survival (OS) and DSS. Kaplan-Meier survival curve was used to valuate discrimination and gradient monotonicity. And an external validation was performed on database from the Second Affiliated Hospital of Zhejiang University (SAHZU). RESULTS: Patients with T1-2 N1 and T1N2a were classified into stage II while T4 N0 patients were classified into stage III in Nomo-staging system. Kaplan-Meier survival curves of OS and DSS in testing set showed Nomo-staging system performed better in discrimination and gradient monotonicity, and the external validation in SAHZU database also showed distinctly better discrimination. The Nomo-staging system showed higher value in L.R. and c-index, and lower value in AIC when predicting OS and DSS in testing set. CONCLUSION: The Nomo-staging system showed better performance in prognosis prediction and the weight of lymph nodes status in prognosis prediction should be cautiously reconsidered.

Time-dependent and nonlinear effects of prognostic factors in nonmetastatic colorectal cancer.

The survival risk following curative surgery for nonmetastatic colorectal cancer (CRC) may be over- or underestimated due to a lack of attention to nonlinear effects and violation of the proportional hazards assumption. In this paper, we aimed to detect and interpret the shape of time-dependent and nonlinear effects to improve the predictive performance of models of prognoses in nonmetastatic CRC patients. Data for nonmetastatic CRC patients diagnosed between 2004 and 2012 were obtained from the Surveillance Epidemiology End Results registry. Time-dependent and nonlinear effects were tested and plotted. A nonlinear model that used random survival forests was implemented. The estimated 5-year cancer-specific death rate was 17.95% (95% CI, 17.70-18.20%). Tumor invasion depth, lymph node status, age at diagnosis, tumor grade, histology and tumor site were significantly associated with cancer-specific death. Nonlinear and time-dependent effects on survival were detected. Positive lymph node number had a larger effect per unit of measurement at low values than at high values, whereas age at diagnosis showed the opposite pattern. Moreover, nonproportional hazards were detected for all covariates, indicating that the contributions of these risks to survival outcomes decreased over time. The nonlinear model predicted prognoses more accurately (C-index: 0.7934, 0.7933-0.7934) than did the Fine and Gray model (C-index: 0.7550, 0.7510-0.7583). The three-dimensional cumulative incidence curves derived from nonlinear model were used to identify the change points of the risk trends. It would be useful to implement these findings in treatment plans and follow-up surveillance in nonmetastatic CRC patients.