Background: REQUITE (validating pREdictive models and biomarkers of radiotherapy toxicity to reduce side effects and improve QUalITy of lifE in cancer survivors) is an international prospective cohort study. The purpose of this project was to analyse a cohort of patients recruited into REQUITE using a deep learning algorithm to identify patient-specific features associated with the development of toxicity, and test the approach by attempting to validate previously published genetic risk factors. Methods: The study involved REQUITE prostate cancer patients treated with external beam radiotherapy who had complete 2-year follow-up. We used five separate late toxicity endpoints: ≥grade 1 late rectal bleeding, ≥grade 2 urinary frequency, ≥grade 1 haematuria, ≥ grade 2 nocturia, ≥ grade 1 decreased urinary stream. Forty-three single nucleotide polymorphisms (SNPs) already reported in the literature to be associated with the toxicity endpoints were included in the analysis. No SNP had been studied before in the REQUITE cohort. Deep Sparse AutoEncoders (DSAE) were trained to recognize features (SNPs) identifying patients with no toxicity and tested on a different independent mixed population including patients without and with toxicity. Results: One thousand, four hundred and one patients were included, and toxicity rates were: rectal bleeding 11.7%, urinary frequency 4%, haematuria 5.5%, nocturia 7.8%, decreased urinary stream 17.1%. Twenty-four of the 43 SNPs that were associated with the toxicity endpoints were validated as identifying patients with toxicity. Twenty of the 24 SNPs were associated with the same toxicity endpoint as reported in the literature: 9 SNPs for urinary symptoms and 11 SNPs for overall toxicity. The other 4 SNPs were associated with a different endpoint. Conclusion: Deep learning algorithms can validate SNPs associated with toxicity after radiotherapy for prostate cancer. The method should be studied further to identify polygenic SNP risk signatures for radiotherapy toxicity. The signatures could then be included in integrated normal tissue complication probability models and tested for their ability to personalize radiotherapy treatment planning.
Background: The healthcare sector is an interesting target for fraudsters. The availability of a great amount of data makes it possible to tackle this issue with the adoption of data mining techniques, making the auditing process more efficient and effective. This research has the objective of developing a novel data mining model devoted to fraud detection among hospitals using Hospital Discharge Charts (HDC) in Administrative Databases. In particular, it is focused on the DRG upcoding practice, i.e., the tendency of registering codes for provided services and inpatients health status so to make the hospitalization fall within a more remunerative DRG class. Methods: We propose a two-step algorithm: the first step entails kmeans clustering of providers to identify locally consistent and locally similar groups of hospitals, according to their characteristics and behavior treating a specific disease, in order to spot outliers within this groups of peers. An initial grid search for the best number of features to be selected (through Principal Feature Analysis) and the best number of local groups makes the algorithm extremely flexible. In the second step, we propose a human-decision support system that helps auditors cross-validating the identified outliers, analyzing them w.r.t. fraud-related variables, and the complexity of patients' casemix they treated. The proposed algorithm was tested on a database relative to HDC collected by Regione Lombardia (Italy) in a time period of three years (2013-2015), focusing on the treatment of Heart Failure. Results: The model identified 6 clusters of hospitals and 10 outliers among the 183 units. Out of those providers, we report the in depth the application of Step Two on three Hospitals (two private and one public). Cross-validating with the patients' population and the hospitals' characteristics, the public hospital seemed justified in its outlierness, while the two private providers were deemed interesting for a further investigation by auditors.
Aim: To identify the effect of single nucleotide polymorphism (SNP) interactions on the risk of toxicity following radiotherapy (RT) for prostate cancer (PCa) and propose a new method for polygenic risk score incorporating SNP-SNP interactions (PRSi). Materials and methods: Analysis included the REQUITE PCa cohort that received external beam RT and was followed for 2 years. Late toxicity endpoints were: rectal bleeding, urinary frequency, haematuria,
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