Prediction of outpatient waiting time: using machine learning in a tertiary children's hospital.

Background: Accurately predicting waiting time for patients is crucial for effective hospital management. The present study examined the prediction of outpatient waiting time in a Chinese pediatric hospital through the use of machine learning algorithms. If patients are informed about their waiting time in advance, they can make more informed decisions and better plan their visit on the day of admission. Methods: First, a novel classification method for the outpatient clinic in the Chinese pediatric hospital was proposed, which was based on medical knowledge and statistical analysis. Subsequently, four machine learning algorithms [linear regression (LR), random forest (RF), gradient boosting decision tree (GBDT), and K-nearest neighbor (KNN)] were used to construct prediction models of the waiting time of patients in four department categories. Results: The three machine learning algorithms outperformed LR in the four department categories. The optimal model for Internal Medicine Department I was the RF model, with a mean absolute error (MAE) of 5.03 minutes, which was 47.60% lower than that of the LR model. The optimal model for the other three categories was the GBDT model. The MAE of the GBDT model was decreased by 28.26%, 35.86%, and 33.10%, respectively compared to that of the LR model. Conclusions: Machine learning can predict the outpatient waiting time of pediatric hospitals well and ease patient anxiety when waiting in line without medical appointments. This study offers key insights into enhancing healthcare services and reaffirms the dedication of Chinese pediatric hospitals to providing efficient and patient-centric care.

Artificial intelligence promotes shared decision-making through recommending tests to febrile pediatric outpatients.

BACKGROUND: To promote the shared decision-making (SDM) between patients and doctors in pediatric outpatient departments, this study was designed to validate artificial intelligence (AI) -initiated medical tests for children with fever. METHODS: We designed an AI model, named Xiaoyi, to suggest necessary tests for a febrile child before visiting a pediatric outpatient clinic. We calculated the sensitivity, specificity, and F1 score to evaluate the efficacy of Xiaoyi's recommendations. The patients were divided into the rejection and acceptance groups. Then we analyzed the rejected examination items in order to obtain the corresponding reasons. RESULTS: We recruited a total of 11,867 children with fever who had used Xiaoyi in outpatient clinics. The recommended examinations given by Xiaoyi for 10,636 (89.6%) patients were qualified. The average F1 score reached 0.94. A total of 58.4% of the patients accepted Xiaoyi's suggestions (acceptance group), and 41.6% refused (rejection group). Imaging examinations were rejected by most patients (46.7%). The tests being time-consuming were rejected by 2,133 patients (43.2%), including rejecting pathogen studies in 1,347 patients (68.5%) and image studies in 732 patients (31.8%). The difficulty of sampling was the main reason for rejecting routine tests (41.9%). CONCLUSION: Our model has high accuracy and acceptability in recommending medical tests to febrile pediatric patients, and is worth promoting in facilitating SDM.

Prediction of osteoporosis and osteopenia by routine computed tomography of the lumbar spine in different regions of interest.

BACKGROUND: We aimed to investigate the utility of Hounsfield units (HU) obtained from different regions of interest in opportunistic lumbar computed tomography (CT) to predict osteoporosis coupling with data of dual-energy X-ray absorptiometry (DXA). METHODS: A total of 100 patients who attended a university hospital in Shanghai, China, and had undergone CT and DXA tests of the lumbar spine within 3 months were included in this retrospective review. Images were reviewed on axial sections, and regions of interest (ROI) markers were placed on the round, oval, anterior, left, and right of the L1-L4 vertebra to measure the HU. The mean values of CT HU were then compared to the bone mineral density (BMD) measured by DXA. Receiver operator characteristic curves were generated to determine the threshold for diagnosis and its sensitivity and specificity values. RESULTS: The differences in CT HU of different ROI based on DXA definitions of osteoporosis, osteopenia, and normal individuals were statistically significant (p < 0.01). The HU values of the different ROI correlated well with the BMD values (Spearman coefficient all > 0.75, p < 0.01). The threshold for diagnosing osteoporosis varies from 87 to 111 HU in different ROIs, and the threshold for excluding osteoporosis or osteopenia is 99-125 HU. CONCLUSION: This is the first study on osteoporosis diagnosis of different ROI with routine CT lumbar scans. There is a strong correlation between CT HU of different ROI in the lumbar spine and BMD, and HU measurements can be used to predict osteoporosis.

Using artificial intelligence to reduce queuing time and improve satisfaction in pediatric outpatient service: A randomized clinical trial.

Introduction: Complicated outpatient procedures are associated with excessive paperwork and long waiting times. We aimed to shorten queuing times and improve visiting satisfaction. Methods: We developed an artificial intelligence (AI)-assisted program named Smart-doctor. A randomized controlled trial was conducted at Shanghai Children's Medical Center. Participants were randomly divided into an AI-assisted and conventional group. Smart-doctor was used as a medical assistant in the AI-assisted group. At the end of the visit, an e-medical satisfaction questionnaire was asked to be done. The primary outcome was the queuing time, while secondary outcomes included the consulting time, test time, total time, and satisfaction score. Wilcoxon rank sum test, multiple linear regression and ordinal regression were also used. Results: We enrolled 740 eligible patients (114 withdrew, response rate: 84.59%). The median queuing time was 8.78 (interquartile range [IQR] 3.97,33.88) minutes for the AI-assisted group versus 21.81 (IQR 6.66,73.10) minutes for the conventional group (p < 0.01), and the AI-assisted group had a shorter consulting time (0.35 [IQR 0.18, 0.99] vs. 2.68 [IQR 1.82, 3.80] minutes, p < 0.01), and total time (40.20 [IQR 26.40, 73.80] vs. 110.40 [IQR 68.40, 164.40] minutes, p < 0.01). The overall satisfaction score was increased by 17.53% (p < 0.01) in the AI-assisted group. In addition, multiple linear regression and ordinal regression showed that the queuing time and satisfaction were mainly affected by group (p < 0.01), and missing the turn (p < 0.01). Conclusions: Using AI to simplify the outpatient service procedure can shorten the queuing time of patients and improve visit satisfaction.

Establishment of a Simple Pediatric Lower Respiratory Tract Infections Database Based on the Structured Electronic Medical Records.

Objective: This study aimed to establish a pediatric lower respiratory tract infections (PLRTIs) database based on the structured electronic medical records (SEMRs), to provide a brief overview and the usage process of the SEMRs and the database. Methods: All the medical information is recorded by a clinical information system developed by Eureka Systems Company. A plugin of the software was used to set the properties of items of the SEMR. Children with lower respiratory tract infections (LRTIs) who were admitted to the department of respiratory medicine of our hospital from May 2020 were included. PostgreSQL 13.1 software was used to construct the PLRTIs database. Results: Seven kinds of SEMRs were established, and the admission record was the most important and complex among them. It was mainly composed of 10 parts, i.e., basic information, history of present illness, past history (without respiratory disease), past history of respiratory diseases, personal history, family history, physical examination, the score of LRTIs, auxiliary examination, and diagnosis. With the three-level doctor ward round, the recorded information of the SEMR would be checked repeatedly, thus guaranteeing the correctness of the information. The data of the SEMR and laboratory tests could be extracted directly from the hospital information system (HIS) by PostgreSQL 13.1 software with the specific structured query language (SQL) code. After manually checking the original records, the datasets were imported into PostgreSQL 13.1 software, and a simple PLRTIs database was constructed. According to the inclusion criteria of this study, a total of 1,184 children with LRTIs were included in this database from 1 May 2020 to 30 April 2021. Conclusion: A series of SEMRs for PLRTIs were designed and used during the hospitalization. A simple PLRTIs database was established based on the SEMR. The SEMRs will provide complete and high-quality data on LRTIs in children.

Automatic Detection of Secundum Atrial Septal Defect in Children Based on Color Doppler Echocardiographic Images Using Convolutional Neural Networks.

Secundum atrial septal defect (ASD) is one of the most common congenital heart diseases (CHDs). This study aims to evaluate the feasibility and accuracy of automatic detection of ASD in children based on color Doppler echocardiographic images using convolutional neural networks. In this study, we propose a fully automatic detection system for ASD, which includes three stages. The first stage is used to identify four target echocardiographic views (that is, the subcostal view focusing on the atrium septum, the apical four-chamber view, the low parasternal four-chamber view, and the parasternal short-axis view). These four echocardiographic views are most useful for the diagnosis of ASD clinically. The second stage aims to segment the target cardiac structure and detect candidates for ASD. The third stage is to infer the final detection by utilizing the segmentation and detection results of the second stage. The proposed ASD detection system was developed and validated using a training set of 4,031 cases containing 370,057 echocardiographic images and an independent test set of 229 cases containing 203,619 images, of which 105 cases with ASD and 124 cases with intact atrial septum. Experimental results showed that the proposed ASD detection system achieved accuracy, recall, precision, specificity, and F1 score of 0.8833, 0.8545, 0.8577, 0.9136, and 0.8546, respectively on the image-level averages of the four most clinically useful echocardiographic views. The proposed system can automatically and accurately identify ASD, laying a good foundation for the subsequent artificial intelligence diagnosis of CHDs.

Quality and efficiency of a standardized e-handover system for pediatric nursing: A prospective interventional study.

AIM: This study examined the effect on pediatric nursing handover quality and efficiency when a standardized e-handover system was implemented. BACKGROUND: Handover quality is an important aspect of nursing quality management; however, handover quality among nursing staff is poor. METHODS: A prospective interventional study was carried out in a general pediatrics ward from December 2019 to November 2020. The tools included a standardized e-handover system. The intervention strategies included workflow remodeling and employee training on oral handover using the standardized e-handover system. RESULTS: The omission frequency of critical handover elements decreased from 47.32% to 2.94% (p < .01), among which the omission frequencies of nine out of 16 key elements significantly decreased. Integrity also showed improvement. Specifically, the integrity of five types of critical information was significantly improved, including vital signs, signs and symptoms, laboratory test results, radiologic examination results, and treatment regimen (2.00 vs. 5.00, p < .01; 3.00 vs. 5.00, p < .01; 3.00 vs. 5.00, p < .01; 5.00 vs. 5.00, p = .009; 3.00 vs. 4.00, p < .01, respectively). Information accuracy was 100%. Workflow and efficiency significantly improved, communication duration with patient/family during work hours significantly increased (24.00 vs. 56.00, p < .01), and prehandover preparation duration significantly decreased (32.00 vs. 2.50, p < .01). Nurse handover satisfaction showed improvement (56.88 ± 15.08 vs. 74.31 ± 9.22, p < .01). CONCLUSION: The standardized e-handover system effectively improved nurse handover quality, optimized workflow, increased work efficiency, and promoted teamwork. IMPLICATIONS FOR NURSING MANAGEMENT: Standardized e-handover systems have great potential for ensuring the safety of pediatric patients and improving the quality of handover.

The Associations of Caesarean Delivery With Risk of Wheezing Diseases and Changes of T Cells in Children.

Objectives: This study aimed to assess the associations of caesarean delivery (CD) with risk of wheezing diseases and changes of immune cells in children. Design: The cross-sectional study was conducted between May, 2020 and April, 2021. Setting and participants: The study was conducted in Shanghai Children's Medical Center, Shanghai, China. A total of 2079 children with a mean age of 36.97 ± 40.27 months and their guardians were included in the present study via face-to-face inquiry and physical examination by clinicians. Methods: Logistic regression was applied to estimate odds ratio (ORs) and 95% confidence intervals (CIs) for the association between CD and first episode of wheezing (FEW) or asthma. Models were adjusted for premature or full-term delivery, exclusive breastfeeding (at least 4 months) or not. Results: Among the 2079 children, 987 children (47.47%) were born by CD and 1092 (52.53%) by vaginal delivery (VD). Children delivered by caesarean had significantly lower gestational age (P<0.01) compared with those who delivered vaginally. Our results also showed that CD was related to increased risk of FEW by the age of 3(adjusted OR 1.50, 95%CI 1.06, 2.12) and increased tendency to develop asthma by the age of 4 (adjusted OR 3.16, 95%CI 1.25, 9.01). The subgroup analysis revealed that the negative effects of CD on asthma were more obvious in children without exclusive breastfeeding (adjusted OR 4.93, 95%CI 1.53, 21.96) or without postnatal smoking exposure (adjusted OR 3.58, 95%CI 1.20, 13.13). Furthermore, compared with children born through VD, a significant change of the T cells (increased proportion of CD4+ T cells and decreased number and proportion of CD8+ T cells) were observed before the age of one in the CD group. However, the changes were insignificant in children over 1 year old. Conclusions: This study showed age-dependent associations of CD with asthma and FEW in offspring. Moreover, CD appeared to have an effect on the cellular immunity in infants, the disorder of which may contribute to the development of asthma in children.

Pre-Consultation System Based on the Artificial Intelligence Has a Better Diagnostic Performance Than the Physicians in the Outpatient Department of Pediatrics.

Artificial intelligence (AI) has been deeply applied in the medical field and has shown broad application prospects. Pre-consultation system is an important supplement to the traditional face-to-face consultation. The combination of the AI and the pre-consultation system can help to raise the efficiency of the clinical work. However, it is still challenging for the AI to analyze and process the complicated electronic health record (EHR) data. Our pre-consultation system uses an automated natural language processing (NLP) system to communicate with the patients through the mobile terminals, applying the deep learning (DL) techniques to extract the symptomatic information, and finally outputs the structured electronic medical records. From November 2019 to May 2020, a total of 2,648 pediatric patients used our model to provide their medical history and get the primary diagnosis before visiting the physicians in the outpatient department of the Shanghai Children's Medical Center. Our task is to evaluate the ability of the AI and doctors to obtain the primary diagnosis and to analyze the effect of the consistency between the medical history described by our model and the physicians on the diagnostic performance. The results showed that if we do not consider whether the medical history recorded by the AI and doctors was consistent or not, our model performed worse compared to the physicians and had a lower average F1 score (0.825 vs. 0.912). However, when the chief complaint or the history of present illness described by the AI and doctors was consistent, our model had a higher average F1 score and was closer to the doctors. Finally, when the AI had the same diagnostic conditions with doctors, our model achieved a higher average F1 score (0.931) compared to the physicians (0.92). This study demonstrated that our model could obtain a more structured medical history and had a good diagnostic logic, which would help to improve the diagnostic accuracy of the outpatient doctors and reduce the misdiagnosis and missed diagnosis. But, our model still needs a good deal of training to obtain more accurate symptomatic information.

LungAttn: advanced lung sound classification using attention mechanism with dual TQWT and triple STFT spectrogram.

Objective. Auscultation of lung sound plays an important role in the early diagnosis of lung diseases. This work aims to develop an automated adventitious lung sound detection method to reduce the workload of physicians.Approach. We propose a deep learning architecture, LungAttn, which incorporates augmented attention convolution into ResNet block to improve the classification accuracy of lung sound. We adopt a feature extraction method based on dual tunableQ-factor wavelet transform and triple short-time Fourier transform to obtain a multi-channel spectrogram. Mixup method is introduced to augment adventitious lung sound recordings to address the imbalance dataset problem.Main results. Based on the ICBHI 2017 challenge dataset, we implement our framework and compare with the state-of-the-art works. Experimental results show that LungAttn has achieved theSensitivity, Se,Specificity, SpandScoreof 36.36%, 71.44% and 53.90%, respectively. Of which, our work has improved theScoreby 1.69% compared to the state-of-the-art models based on the official ICBHI 2017 dataset splitting method.Significance. Multi-channel spectrogram based on different oscillatory behavior of adventitious lung sound provides necessary information of lung sound recordings. Attention mechanism is introduced to lung sound classification methods and has proved to be effective. The proposed LungAttn model can potentially improve the speed and accuracy of lung sound classification in clinical practice.

Machine Learning for Early Warning of Septic Shock in Children With Hematological Malignancies Accompanied by Fever or Neutropenia: A Single Center Retrospective Study.

OBJECTIVES: The purpose of this article was to establish and validate clinically applicable septic shock early warning model (SSEW model) that can identify septic shock in hospitalized children with onco-hematological malignancies accompanied with fever or neutropenia. METHODS: Data from EMRs were collected from hospitalized pediatric patients with hematological and oncological disease at Shanghai Children's Medical Center. Medical records of patients (>30 days and <19 years old) with fever (≥38°C) or absolute neutrophil count (ANC) below 1.0 × 109/L hospitalized with hematological or oncological disease between January 1, 2017 and August 1, 2019 were considered. Patients in whom septic shock was diagnosed during the observation period formed the septic shock group, whereas non-septic-shock group was the control group. In the septic shock group, the time points at 4, 8, 12, and 24 hours prior to septic shock were taken as observation points, and corresponding observation points were obtained in the control group after matching. We employed machine learning artificial intelligence (AI) to filter features and used XGBoost algorithm to build SSEW model. Area under the ROC curve (AU-ROC) was used to compare the effectiveness among the SSEW Model, logistic regression model, and pediatric sequential organ failure score (pSOFA) for early warning of septic shock. MAIN RESULTS: A total of 64 observation periods in the septic shock group and 2191 in the control group were included. AU-ROC of the SSEW model had higher predictive value for septic shock compared with the pSOFA score (0.93 vs. 0.76, Z = -2.73, P = 0.006). Further analysis showed that the AU-ROC of the SSEW model was superior to the pSOFA score at the observation points 4, 8, 12, and 24 h before septic shock. At the 24 h observation point, the SSEW model incorporated 14 module root features and 23 derived features. CONCLUSION: The SSEW model for hematological or oncological pediatric patients could help clinicians to predict the risk of septic shock in patients with fever or neutropenia 24 h in advance. Further prospective studies on clinical application scenarios are needed to determine the clinical utility of this AI model.

Development and Evaluation of a Leukemia Diagnosis System Using Deep Learning in Real Clinical Scenarios.

Leukemia is the most common malignancy affecting children. The morphologic analysis of bone marrow smears is an important initial step for diagnosis. Recent publications demonstrated that artificial intelligence is able to classify blood cells but a long way from clinical use. A total of 1,732 bone marrow images were used for the training of a convolutional neural network (CNN). New techniques of deep learning were integrated and an end-to-end leukemia diagnosis system was developed by using raw images without pre-processing. The system creatively imitated the workflow of a hematologist by detecting and excluding uncountable and crushed cells, then classifying and counting the remain cells to make a diagnosis. The performance of the CNN in classifying WBCs achieved an accuracy of 82.93%, precision of 86.07% and F1 score of 82.02%. And the performance in diagnosing acute lymphoid leukemia achieved an accuracy of 89%, sensitivity of 86% and specificity of 95%. The system also performs well at detecting the bone marrow metastasis of lymphoma and neuroblastoma, achieving an average accuracy of 82.93%. This is the first study which included a wider variety of cell types in leukemia diagnosis, and achieved a relatively high performance in real clinical scenarios.

Real-World Verification of Artificial Intelligence Algorithm-Assisted Auscultation of Breath Sounds in Children.

Objective: Lung auscultation plays an important role in the diagnosis of pulmonary diseases in children. The objective of this study was to evaluate the use of an artificial intelligence (AI) algorithm for the detection of breath sounds in a real clinical environment among children with pulmonary diseases. Method: The auscultations of breath sounds were collected in the respiratory department of Shanghai Children's Medical Center (SCMC) by using an electronic stethoscope. The discrimination results for all chest locations with respect to a gold standard (GS) established by 2 experienced pediatric pulmonologists from SCMC and 6 general pediatricians were recorded. The accuracy, sensitivity, specificity, precision, and F1-score of the AI algorithm and general pediatricians with respect to the GS were evaluated. Meanwhile, the performance of the AI algorithm for different patient ages and recording locations was evaluated. Result: A total of 112 hospitalized children with pulmonary diseases were recruited for the study from May to December 2019. A total of 672 breath sounds were collected, and 627 (93.3%) breath sounds, including 159 crackles (23.1%), 264 wheeze (38.4%), and 264 normal breath sounds (38.4%), were fully analyzed by the AI algorithm. The accuracy of the detection of adventitious breath sounds by the AI algorithm and general pediatricians with respect to the GS were 77.7% and 59.9% (p < 0.001), respectively. The sensitivity, specificity, and F1-score in the detection of crackles and wheeze from the AI algorithm were higher than those from the general pediatricians (crackles 81.1 vs. 47.8%, 94.1 vs. 77.1%, and 80.9 vs. 42.74%, respectively; wheeze 86.4 vs. 82.2%, 83.0 vs. 72.1%, and 80.9 vs. 72.5%, respectively; p < 0.001). Performance varied according to the age of the patient, with patients younger than 12 months yielding the highest accuracy (81.3%, p < 0.001) among the age groups. Conclusion: In a real clinical environment, children's breath sounds were collected and transmitted remotely by an electronic stethoscope; these breath sounds could be recognized by both pediatricians and an AI algorithm. The ability of the AI algorithm to analyze adventitious breath sounds was better than that of the general pediatricians.

Artificial intelligence-assisted reduction in patients' waiting time for outpatient process: a retrospective cohort study.

BACKGROUND: Many studies suggest that patient satisfaction is significantly negatively correlated with the waiting time. A well-designed healthcare system should not keep patients waiting too long for an appointment and consultation. However, in China, patients spend notable time waiting, and the actual time spent on diagnosis and treatment in the consulting room is comparatively less. METHODS: We developed an artificial intelligence (AI)-assisted module and name it XIAO YI. It could help outpatients automatically order imaging examinations or laboratory tests based on their chief complaints. Thus, outpatients could get examined or tested before they went to see the doctor. People who saw the doctor in the traditional way were allocated to the conventional group, and those who used XIAO YI were assigned to the AI-assisted group. We conducted a retrospective cohort study from August 1, 2019 to January 31, 2020. Propensity score matching was used to balance the confounding factor between the two groups. And waiting time was defined as the time from registration to preparation for laboratory tests or imaging examinations. The total cost included the registration fee, test fee, examination fee, and drug fee. We used Wilcoxon rank-sum test to compare the differences in time and cost. The statistical significance level was set at 0.05 for two sides. RESULTS: Twelve thousand and three hundred forty-two visits were recruited, consisting of 6171 visits in the conventional group and 6171 visits in the AI-assisted group. The median waiting time was 0.38 (interquartile range: 0.20, 1.33) hours for the AI-assisted group compared with 1.97 (0.76, 3.48) hours for the conventional group (p < 0.05). The total cost was 335.97 (interquartile range: 244.80, 437.60) CNY (Chinese Yuan) for the AI-assisted group and 364.58 (249.70, 497.76) CNY for the conventional group (p < 0.05). CONCLUSIONS: Using XIAO YI can significantly reduce the waiting time of patients, and thus, improve the outpatient service process of hospitals.

Artificial intelligence-assisted auscultation in detecting congenital heart disease.

Aims: Computer-assisted auscultation has become available to assist clinicians with physical examinations to detect congenital heart disease (CHD). However, its accuracy and effectiveness remain to be evaluated. This study seeks to evaluate the accuracy of auscultations of abnormal heart sounds of an artificial intelligence-assisted auscultation (AI-AA) platform we create. Methods and results: Initially, 1397 patients with CHD were enrolled in the study. The samples of their heart sounds were recorded and uploaded to the platform using a digital stethoscope. By the platform, both remote auscultation by a team of experienced cardiologists from Shanghai Children's Medical Center and automatic auscultation of the heart sound samples were conducted. Samples of 35 patients were deemed unsuitable for the analysis; therefore, the remaining samples from 1362 patients (mean age-2.4 ± 3.1 years and 46% female) were analysed. Sensitivity, specificity, and accuracy were calculated for remote auscultation compared to experts' face-to-face auscultation and for artificial intelligence automatic auscultation compared to experts' face-to-face auscultation. Kappa coefficients were measured. Compared to face-to-face auscultation, remote auscultation detected abnormal heart sound with 98% sensitivity, 91% specificity, 97% accuracy, and kappa coefficient 0.87. AI-AA demonstrated 97% sensitivity, 89% specificity, 96% accuracy, and kappa coefficient 0.84. Conclusions: The remote auscultations and automatic auscultations, using the AI-AA platform, reported high auscultation accuracy in detecting abnormal heart sound and showed excellent concordance to experts' face-to-face auscultation. Hence, the platform may provide a feasible way to screen and detect CHD.

Novel Common Genetic Susceptibility Loci for Colorectal Cancer.

BACKGROUND: Previous genome-wide association studies (GWAS) have identified 42 loci (P < 5 × 10-8) associated with risk of colorectal cancer (CRC). Expanded consortium efforts facilitating the discovery of additional susceptibility loci may capture unexplained familial risk. METHODS: We conducted a GWAS in European descent CRC cases and control subjects using a discovery-replication design, followed by examination of novel findings in a multiethnic sample (cumulative n = 163 315). In the discovery stage (36 948 case subjects/30 864 control subjects), we identified genetic variants with a minor allele frequency of 1% or greater associated with risk of CRC using logistic regression followed by a fixed-effects inverse variance weighted meta-analysis. All novel independent variants reaching genome-wide statistical significance (two-sided P < 5 × 10-8) were tested for replication in separate European ancestry samples (12 952 case subjects/48 383 control subjects). Next, we examined the generalizability of discovered variants in East Asians, African Americans, and Hispanics (12 085 case subjects/22 083 control subjects). Finally, we examined the contributions of novel risk variants to familial relative risk and examined the prediction capabilities of a polygenic risk score. All statistical tests were two-sided. RESULTS: The discovery GWAS identified 11 variants associated with CRC at P < 5 × 10-8, of which nine (at 4q22.2/5p15.33/5p13.1/6p21.31/6p12.1/10q11.23/12q24.21/16q24.1/20q13.13) independently replicated at a P value of less than .05. Multiethnic follow-up supported the generalizability of discovery findings. These results demonstrated a 14.7% increase in familial relative risk explained by common risk alleles from 10.3% (95% confidence interval [CI] = 7.9% to 13.7%; known variants) to 11.9% (95% CI = 9.2% to 15.5%; known and novel variants). A polygenic risk score identified 4.3% of the population at an odds ratio for developing CRC of at least 2.0. CONCLUSIONS: This study provides insight into the architecture of common genetic variation contributing to CRC etiology and improves risk prediction for individualized screening.

Physical Extraction and Feature Fusion for Multi-Mode Signals in a Measurement System for Patients in Rehabilitation Exoskeleton.

Measurement system of exoskeleton robots can reflect the state of the patient. In this study, we combined an inertial measurement unit and a visual measurement unit to obtain a repeatable fusion measurement system to compensate for the deficiencies of the single data acquisition mode used by exoskeletons. Inertial measurement unit is comprised four distributed angle sensors. Triaxial acceleration and angular velocity information were transmitted to an upper computer by Bluetooth. The data sent to the control center were processed by a Kalman filter to eliminate any noise. Visual measurement unit uses camera to acquire real time images and related data information. The two data acquisition methods were fused and have its weight. Comparisons of the fusion results with individual measurement results demonstrated that the data fusion method could effectively improve the accuracy of system. It provides a set of accurate real-time measurements for patients in rehabilitation exoskeleton and data support for effective control of exoskeleton robot.

Inclusion of a Genetic Risk Score into a Validated Risk Prediction Model for Colorectal Cancer in Japanese Men Improves Performance.

We previously developed and validated a risk prediction model for colorectal cancer in Japanese men using modifiable risk factors. To further improve risk prediction, we evaluated the degree of improvement obtained by adding a genetic risk score (GRS) using genome-wide association study (GWAS)-identified risk variants to our validated model. We examined the association between 36 risk variants identified by GWAS and colorectal cancer risk using a weighted Cox proportional hazards model in a nested case-control study within the Japan Public Health Center-based Prospective Study. GRS was constructed using six variants associated with risk in this study of the 36 tested. We assessed three models: a nongenetic model that included the same variables used in our previously validated model; a genetic model that used GRS; and an inclusive model, which included both. The c-statistic, integrated discrimination improvement (IDI), and net reclassification improvement (NRI) were calculated by the 5-fold cross-validation method. We estimated 10-year absolute risks for developing colorectal cancer. A statistically significant association was observed between the weighted GRS and colorectal cancer risk. The mean c-statistic for the inclusive model (0.66) was slightly greater than that for the nongenetic model (0.60). Similarly, the mean IDI and NRI showed improvement when comparing the nongenetic and inclusive models. These models for colorectal cancer were well calibrated. The addition of GRS using GWAS-identified risk variants to our validated model for Japanese men improved the prediction of colorectal cancer risk. Cancer Prev Res; 10(9); 535-41. ©2017 AACR.

Novel colon cancer susceptibility variants identified from a genome-wide association study in African Americans.

Genome-wide association studies (GWAS) in ethnic/racial minority populations can help to fine-map previously identified risk regions or discover new risk loci because of the genetic diversity in these populations. We conducted a GWAS of colorectal cancer (CRC) in 6,597 African Americans (1,894 cases and 4,703 controls) (Stage 1) and followed up the most promising markers in a replication set of 2,041 participants of African descent (891 cases and 1,150 controls) (Stage 2). We identified a novel variant, rs56848936 in the gene SYMPK at 19q13.3, associated with colon cancer risk (odds ratio 0.61 for the risk allele G, p = 2.4 × 10-8 ). The frequency of the G allele was 0.06 in African Americans, compared to <0.01 in Europeans, Asians and Amerindians in the 1000 Genomes project. In addition, a variant previously identified through fine-mapping in this GWAS in the region 19q13.1, rs7252505, was confirmed to be more strongly associated with CRC in the African American replication set than the variant originally reported in Europeans (rs10411210). The association between rs7252505 and CRC was of borderline significance (p = 0.05) in a Hispanic population GWAS with 1,611 CRC cases and 4,330 controls. With the three datasets combined, the odds ratio was 0.84 for the risk allele A (95% confidence interval 0.79-0.89, p = 3.7 × 10-8 ). This study further highlights the importance of conducting GWAS studies in diverse ancestry populations.

Interaction between Red Meat Intake and NAT2 Genotype in Increasing the Risk of Colorectal Cancer in Japanese and African Americans.

Heterocyclic aromatic amines formed in cooked meat may be an underlying mechanism for the red meat-colorectal cancer (CRC) association. These compounds require bioactivaction by N-acetyltransferase 2 (NAT2). An interaction effect between red meat consumption and NAT2 in increasing CRC risk has been inconsistently reported in whites. We investigated this interaction in two populations in which the high-activity rapid NAT2 phenotype is 10- and 2-fold more common than in whites. We meta-analyzed four studies of Japanese (2,217 cases, 3,788 controls) and three studies of African Americans (527 cases, 4,527 controls). NAT2 phenotype was inferred from an optimized seven-SNP genotyping panel. Processed and total red meat intakes were associated with an increased CRC risk in Japanese and in both ethnic groups combined (P's ≤ 0.002). We observed an interaction between processed meat intake and NAT2 in Japanese (P = 0.04), African Americans (P = 0.02), and in both groups combined (P = 0.006). The association of processed meat with CRC was strongest among individuals with the rapid NAT2 phenotype (combined analysis, OR for highest vs. lowest quartile: 1.62, 95% CI: 1.28-2.05; Ptrend = 8.0×10-5), intermediate among those with the intermediate NAT2 phenotype (1.29, 95% CI: 1.05-1.59; Ptrend = 0.05) and null among those with the slow phenotype (Ptrend = 0.45). A similar interaction was found for NAT2 and total red meat (Pinteraction = 0.03). Our findings support a role for NAT2 in modifying the association between red meat consumption and CRC in Japanese and African Americans.