Artificial Intelligence-enabled Chest X-ray Classifies Osteoporosis and Identifies Mortality Risk.

A deep learning model was developed to identify osteoporosis from chest X-ray (CXR) features with high accuracy in internal and external validation. It has significant prognostic implications, identifying individuals at higher risk of all-cause mortality. This Artificial Intelligence (AI)-enabled CXR strategy may function as an early detection screening tool for osteoporosis. The aim of this study was to develop a deep learning model (DLM) to identify osteoporosis via CXR features and investigate the performance and clinical implications. This study collected 48,353 CXRs with the corresponding T score according to Dual energy X-ray Absorptiometry (DXA) from the academic medical center. Among these, 35,633 CXRs were used to identify CXR- Osteoporosis (CXR-OP). Another 12,720 CXRs were used to validate the performance, which was evaluated by the area under the receiver operating characteristic curve (AUC). Furthermore, CXR-OP was tested to assess the long-term risks of mortality, which were evaluated by Kaplan‒Meier survival analysis and the Cox proportional hazards model. The DLM utilizing CXR achieved AUCs of 0.930 and 0.892 during internal and external validation, respectively. The group that underwent DXA with CXR-OP had a higher risk of all-cause mortality (hazard ratio [HR] 2.59, 95% CI: 1.83-3.67), and those classified as CXR-OP in the group without DXA also had higher all-cause mortality (HR: 1.67, 95% CI: 1.61-1.72) in the internal validation set. The external validation set produced similar results. Our DLM uses CXRs for early detection of osteoporosis, aiding physicians to identify those at risk. It has significant prognostic implications, improving life quality and reducing mortality. AI-enabled CXR strategy may serve as a screening tool.

Artificial Intelligence-Enabled Electrocardiography Predicts Future Pacemaker Implantation and Adverse Cardiovascular Events.

Medical advances prolonging life have led to more permanent pacemaker implants. When pacemaker implantation (PMI) is commonly caused by sick sinus syndrome or conduction disorders, predicting PMI is challenging, as patients often experience related symptoms. This study was designed to create a deep learning model (DLM) for predicting future PMI from ECG data and assess its ability to predict future cardiovascular events. In this study, a DLM was trained on a dataset of 158,471 ECGs from 42,903 academic medical center patients, with additional validation involving 25,640 medical center patients and 26,538 community hospital patients. Primary analysis focused on predicting PMI within 90 days, while all-cause mortality, cardiovascular disease (CVD) mortality, and the development of various cardiovascular conditions were addressed with secondary analysis. The study's raw ECG DLM achieved area under the curve (AUC) values of 0.870, 0.878, and 0.883 for PMI prediction within 30, 60, and 90 days, respectively, along with sensitivities exceeding 82.0% and specificities over 81.9% in the internal validation. Significant ECG features included the PR interval, corrected QT interval, heart rate, QRS duration, P-wave axis, T-wave axis, and QRS complex axis. The AI-predicted PMI group had higher risks of PMI after 90 days (hazard ratio [HR]: 7.49, 95% CI: 5.40-10.39), all-cause mortality (HR: 1.91, 95% CI: 1.74-2.10), CVD mortality (HR: 3.53, 95% CI: 2.73-4.57), and new-onset adverse cardiovascular events. External validation confirmed the model's accuracy. Through ECG analyses, our AI DLM can alert clinicians and patients to the possibility of future PMI and related mortality and cardiovascular risks, aiding in timely patient intervention.

An AI-Enabled Dynamic Risk Stratification for Emergency Department Patients with ECG and CXR Integration.

Emergency department (ED) triage scale determines the priority of patient care and foretells the prognosis. However, the information retrieved from the initial assessment is limited, hindering the risk identification accuracy of triage. Therefore, we sought to develop a 'dynamic' triage system as secondary screening, using artificial intelligence (AI) techniques to integrate information from initial assessment data and subsequent examinations. This retrospective cohort study included 134,112 ED visits with at least one electrocardiography (ECG) and chest X-ray (CXR) in a medical center from 2012 to 2022. Additionally, an independent community hospital provided 45,614 ED visits as an external validation set. We trained an eXtreme gradient boosting (XGB) model using initial assessment data to predict all-cause mortality in 7 days. Two deep learning models (DLMs) using ECG and CXR were trained to stratify mortality risks. The dynamic triage levels were based on output from the XGB-triage and DLMs from ECG and CXR. During the internal and external validation, the area under the receiver operating characteristic curve (AUC) of the XGB-triage model was >0.866; furthermore, the AUCs of DLMs using ECG and CXR were >0.862 and >0.886, respectively. The dynamic triage scale provided a higher C-index (0.914-0.920 vs. 0.827-0.843) than the original one and demonstrated better predictive ability for 5-year mortality, 30-day ED revisit, and 30-day discharge. The AI-based risk scale provides a more accurate and dynamic stratification of mortality risk in ED patients, particularly in identifying patients who tend to be overlooked due to atypical symptoms.

A Deep-Learning Algorithm-Enhanced Electrocardiogram Interpretation for Detecting Pulmonary Embolism.

Background: The early diagnosis of pulmonary embolism (PE) remains a challenge. Electrocardiograms (ECGs) and D-dimer levels are used to screen potential cases. Objective: To develop a deep learning model (DLM) to detect PE using ECGs and investigate the clinical value of false detections in patients without PE. Methods: Among patients who visited the emergency department between 2011 and 2019, PE cases were identified through a review of medical records. Non-PE ECGs were collected from patients without a diagnostic code for PE. There were 113 PE and 51,456 non-PE ECGs in the training and validation sets for developing the DLM, respectively, and 27 PE and 13,105 non-PE cases in an independent testing set for performance validation. A human-machine competition was conducted from the testing set to compare the performance of the DLM with that of physicians. Receiver operating characteristic (ROC) curves, sensitivity, and specificity were used to determine the diagnostic value. Survival analysis was used to assess the prognosis of the patients without PE, stratified by DLM prediction. Results: The DLM was as effective as physicians in diagnosing PE, with 70.8% sensitivity and 69.7% specificity. The area under the ROC curve of DLM was 0.778 in the testing set and up to 0.9 with D-dimer and demographic data. The non-PE patients whose ECG was misclassified as PE by DLM had higher all-cause mortality [hazard ratio (HR) 2.13 (1.51-3.02)] and risk of non-cardiovascular hospitalization [HR 1.55 (1.42-1.68)] than those correctly classified. Conclusions: A DLM-enhanced ECG system may prompt PE recognition and provide prognostic outcomes in patients with false-positive predictions.

A Technology Acceptance Model for Deploying Masks to Combat the COVID-19 Pandemic in Taiwan (My Health Bank): Web-Based Cross-sectional Survey Study.

BACKGROUND: The successful completion of medical practices often relies on information collection and analysis. Government agencies and medical institutions have encouraged people to use medical information technology (MIT) to manage their conditions and promote personal health. In 2014, Taiwan established the first electronic personal health record (PHR) platform, My Health Bank (MHB), which allows people to access and manage their PHRs at any time. In the face of the COVID-19 pandemic in 2020, Taiwan has used MIT to effectively prevent the spread of COVID-19 and undertaken various prevention measures before the onset of the outbreak. Using MHB to purchase masks in an efficient and orderly way and thoroughly implementing personal protection efforts is highly important to contain disease spread. OBJECTIVE: This study aims to understand people's intention to use the electronic PHR platform MHB and to investigate the factors affecting their intention to use this platform. METHODS: From March 31 to April 9, 2014, in a promotion via email and Facebook, participants were asked to fill out a structured questionnaire after watching an introductory video about MHB on YouTube. The questionnaire included seven dimensions: perceived usefulness, perceived ease of use, health literacy, privacy and security, computer self-efficacy, attitude toward use, and behavioral intention to use. Each question was measured on a 5-point Likert scale ranging from "strongly disagree" (1 point) to "strongly agree" (5 points). Descriptive statistics and structural equation analysis were performed using SPSS 21 and AMOS 21 software. RESULTS: A total of 350 valid questionnaire responses were collected (female: 219/350, 62.6%; age: 21-30 years: 238/350, 68.0%; university-level education: 228/350, 65.1%; occupation as student: 195/350, 56.6%; average monthly income

Compensating additional optical power in the central zone of a multifocal contact lens forminimization of the shrinkage error of the shell mold in the injection molding process.

This study aims to develop a compensating method to minimize the shrinkage error of the shell mold (SM) in the injection molding (IM) process to obtain uniform optical power in the central optical zone of soft axial symmetric multifocal contact lenses (CL). The Z-shrinkage error along the Z axis or axial axis of the anterior SM corresponding to the anterior surface of a dry contact lens in the IM process can be minimized by optimizing IM process parameters and then by compensating for additional (Add) powers in the central zone of the original lens design. First, the shrinkage error is minimized by optimizing three levels of four IM parameters, including mold temperature, injection velocity, packing pressure, and cooling time in 18 IM simulations based on an orthogonal array L18 (21×34). Then, based on the Z-shrinkage error from IM simulation, three new contact lens designs are obtained by increasing the Add power in the central zone of the original multifocal CL design to compensate for the optical power errors. Results obtained from IM process simulations and the optical simulations show that the new CL design with 0.1 D increasing in Add power has the closest shrinkage profile to the original anterior SM profile with percentage of reduction in absolute Z-shrinkage error of 55% and more uniform power in the central zone than in the other two cases. Moreover, actual experiments of IM of SM for casting soft multifocal CLs have been performed. The final product of wet CLs has been completed for the original design and the new design. Results of the optical performance have verified the improvement of the compensated design of CLs. The feasibility of this compensating method has been proven based on the measurement results of the produced soft multifocal CLs of the new design. Results of this study can be further applied to predict or compensate for the total optical power errors of the soft multifocal CLs.

Artificial Intelligence Learning Semantics via External Resources for Classifying Diagnosis Codes in Discharge Notes.

BACKGROUND: Automated disease code classification using free-text medical information is important for public health surveillance. However, traditional natural language processing (NLP) pipelines are limited, so we propose a method combining word embedding with a convolutional neural network (CNN). OBJECTIVE: Our objective was to compare the performance of traditional pipelines (NLP plus supervised machine learning models) with that of word embedding combined with a CNN in conducting a classification task identifying International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) diagnosis codes in discharge notes. METHODS: We used 2 classification methods: (1) extracting from discharge notes some features (terms, n-gram phrases, and SNOMED CT categories) that we used to train a set of supervised machine learning models (support vector machine, random forests, and gradient boosting machine), and (2) building a feature matrix, by a pretrained word embedding model, that we used to train a CNN. We used these methods to identify the chapter-level ICD-10-CM diagnosis codes in a set of discharge notes. We conducted the evaluation using 103,390 discharge notes covering patients hospitalized from June 1, 2015 to January 31, 2017 in the Tri-Service General Hospital in Taipei, Taiwan. We used the receiver operating characteristic curve as an evaluation measure, and calculated the area under the curve (AUC) and F-measure as the global measure of effectiveness. RESULTS: In 5-fold cross-validation tests, our method had a higher testing accuracy (mean AUC 0.9696; mean F-measure 0.9086) than traditional NLP-based approaches (mean AUC range 0.8183-0.9571; mean F-measure range 0.5050-0.8739). A real-world simulation that split the training sample and the testing sample by date verified this result (mean AUC 0.9645; mean F-measure 0.9003 using the proposed method). Further analysis showed that the convolutional layers of the CNN effectively identified a large number of keywords and automatically extracted enough concepts to predict the diagnosis codes. CONCLUSIONS: Word embedding combined with a CNN showed outstanding performance compared with traditional methods, needing very little data preprocessing. This shows that future studies will not be limited by incomplete dictionaries. A large amount of unstructured information from free-text medical writing will be extracted by automated approaches in the future, and we believe that the health care field is about to enter the age of big data.

Effects of language experience and stimulus context on the neural organization and categorical perception of speech.

Categorical perception (CP) represents a fundamental process in converting continuous speech acoustics into invariant percepts. Using scalp-recorded event-related brain potentials (ERPs), we investigated how tone-language experience and stimulus context influence the CP for lexical tones-pitch patterns used by a majority of the world's languages to signal word meaning. Stimuli were vowel pairs overlaid with a high-level tone (T1) followed by a pitch continuum spanning between dipping (T3) and rising (T2) contours of the Mandarin tonal space. To vary context, T1 either preceded or followed the critical T2/T3 continuum. Behaviorally, native Chinese showed stronger CP as evident by their steeper, more dichotomous psychometric functions and faster identification of linguistic pitch patterns than native English-speaking controls. Stimulus context produced shifts in both groups' categorical boundary but was more exaggerated in native listeners. Analysis of source activity extracted from primary auditory cortex revealed overall stronger neural encoding of tone in Chinese compared to English, indicating experience-dependent plasticity in cortical pitch processing. More critically, "neurometric" functions derived from multidimensional scaling and clustering of source ERPs established: (i) early auditory cortical activity could accurately predict listeners' psychometric speech identification and contextual shifts in the perceptual boundary; (ii) neurometric profiles were organized more categorically in native speakers. Our data show that tone-language experience refines early auditory cortical brain representations so as to supply more faithful templates to neural mechanisms subserving lexical pitch categorization. We infer that contextual influence on the CP for tones is determined by language experience and the frequency of pitch patterns as they occur in listeners' native lexicon.

Artificial intelligence-enabled electrocardiography contributes to hyperthyroidism detection and outcome prediction.

BACKGROUND: Hyperthyroidism is frequently under-recognized and leads to heart failure and mortality. Timely identification of high-risk patients is a prerequisite to effective antithyroid therapy. Since the heart is very sensitive to hyperthyroidism and its electrical signature can be demonstrated by electrocardiography, we developed an artificial intelligence model to detect hyperthyroidism by electrocardiography and examined its potential for outcome prediction. METHODS: The deep learning model was trained using a large dataset of 47,245 electrocardiograms from 33,246 patients at an academic medical center. Patients were included if electrocardiograms and measurements of serum thyroid-stimulating hormone were available that had been obtained within a three day period. Serum thyroid-stimulating hormone and free thyroxine were used to define overt and subclinical hyperthyroidism. We tested the model internally using 14,420 patients and externally using two additional test sets comprising 11,498 and 596 patients, respectively. RESULTS: The performance of the deep learning model achieves areas under the receiver operating characteristic curves (AUCs) of 0.725-0.761 for hyperthyroidism detection, AUCs of 0.867-0.876 for overt hyperthyroidism, and AUC of 0.631-0.701 for subclinical hyperthyroidism, superior to a traditional features-based machine learning model. Patients identified as hyperthyroidism-positive by the deep learning model have a significantly higher risk (1.97-2.94 fold) of all-cause mortality and new-onset heart failure compared to hyperthyroidism-negative patients. This cardiovascular disease stratification is particularly pronounced in subclinical hyperthyroidism, surpassing that observed in overt hyperthyroidism. CONCLUSIONS: An innovative algorithm effectively identifies overt and subclinical hyperthyroidism and contributes to cardiovascular risk assessment.

Hyperthyroidism occurs when the thyroid gland produces too much hormone and can cause various symptoms including faster heartbeat, weight loss, and nervousness. Diagnosis is often missed, which can lead to heart problems and even death. Measurements of the heart's electrical activity can be obtained using Electrocardiograms (ECGs). We made a computational model that can detect hyperthyroidism from ECGs. Our model was better able to identify people with hyperthyroidism than currently available methods, especially the more severe forms of the condition. If future work demonstrates our model is safe and accurate, it could potentially be used to detect hyperthyroidism sooner, enabling faster treatment and improved health of people with hyperthyroidism.

AI-enabled electrocardiography alert intervention and all-cause mortality: a pragmatic randomized clinical trial.

The early identification of vulnerable patients has the potential to improve outcomes but poses a substantial challenge in clinical practice. This study evaluated the ability of an artificial intelligence (AI)-enabled electrocardiogram (ECG) to identify hospitalized patients with a high risk of mortality in a multisite randomized controlled trial involving 39 physicians and 15,965 patients. The AI-ECG alert intervention included an AI report and warning messages delivered to the physicians, flagging patients predicted to be at high risk of mortality. The trial met its primary outcome, finding that implementation of the AI-ECG alert was associated with a significant reduction in all-cause mortality within 90 days: 3.6% patients in the intervention group died within 90 days, compared to 4.3% in the control group (4.3%) (hazard ratio (HR) = 0.83, 95% confidence interval (CI) = 0.70-0.99). A prespecified analysis showed that reduction in all-cause mortality associated with the AI-ECG alert was observed primarily in patients with high-risk ECGs (HR = 0.69, 95% CI = 0.53-0.90). In analyses of secondary outcomes, patients in the intervention group with high-risk ECGs received increased levels of intensive care compared to the control group; for the high-risk ECG group of patients, implementation of the AI-ECG alert was associated with a significant reduction in the risk of cardiac death (0.2% in the intervention arm versus 2.4% in the control arm, HR = 0.07, 95% CI = 0.01-0.56). While the precise means by which implementation of the AI-ECG alert led to decreased mortality are to be fully elucidated, these results indicate that such implementation assists in the detection of high-risk patients, prompting timely clinical care and reducing mortality. ClinicalTrials.gov registration: NCT05118035 .

Extensive deep learning model to enhance electrocardiogram application via latent cardiovascular feature extraction from identity identification.

BACKGROUND AND OBJECTIVE: Deep learning models (DLMs) have been successfully applied in biomedicine primarily using supervised learning with large, annotated databases. However, scarce training resources limit the potential of DLMs for electrocardiogram (ECG) analysis. METHODS: We have developed a novel pre-training strategy for unsupervised identity identification with an area under the receiver operating characteristic curve (AUC) >0.98. Accordingly, a DLM pre-trained with identity identification can be applied to 70 patient characteristic predictions using transfer learning (TL). These ECG-based patient characteristics were then used for cardiovascular disease (CVD) risk prediction. The DLMs were trained using 507,729 ECGs from 222,473 patients and validated using two independent validation sets (n = 27,824/31,925). RESULTS: The DLMs using our method exhibited better performance than directly trained DLMs. Additionally, our DLM performed better than those of previous studies in terms of gender (AUC [internal/external] = 0.982/0.968), age (correlation = 0.886/0.892), low ejection fraction (AUC = 0.942/0.951), and critical markers not addressed previously, including high B-type natriuretic peptide (AUC = 0.921/0.899). Additionally, approximately 50% of the ECG-based characteristics provided significantly more prediction information for cardiovascular risk than real characteristics. CONCLUSIONS: This is the first study to use identity identification as a pre-training task for TL in ECG analysis. An extensive exploration of the relationship between ECG and 70 patient characteristics was conducted. Our DLM-enhanced ECG interpretation system extensively advanced ECG-related patient characteristic prediction and mortality risk management for cardiovascular diseases.

Mortality risk prediction of the electrocardiogram as an informative indicator of cardiovascular diseases.

Background: The electrocardiogram (ECG) may be the most popular test in the management of cardiovascular disease (CVD). Although wide applications of artificial intelligence (AI)-enabled ECG have been developed, an integrating indicator for CVD risk stratification was not investigated. Since mortality may be the most important global outcome, this study aimed to develop a survival deep learning model (DLM) to establish a critical ECG value and explore the associations with various CVD events. Methods: We trained a DLM with 451,950 12-lead resting ECGs obtained from 210,552 patients, for whom 23,592 events occurred. The internal validation set included 27,808 patients with one ECG for each patient. The external validations were performed in a community hospital with 33,047 patients and two transnational data sets with 233,647 and 1631 ECGs. We distinguished the cause of mortality and additionally investigated CVD-related outcomes, including new-onset acute myocardial infarction (AMI), stroke (STK), and heart failure (HF). Results: The DLM achieved C-indices of 0.858/0.836 in internal/external validation sets by using ECG over a 10-year period. The high-mortality-risk group identified by the proposed DLM presented a hazard ratio (HR) of 14.16 (95% confidence interval (CI): 11.33-17.70) compared to the low-risk group in the internal validation and presented a higher risk of cardiovascular (CV) mortality (HR: 18.50, 95% CI: 9.82-34.84), non-CV mortality (HR: 13.68, 95% CI: 10.76-17.38), AMI (HR: 4.01, 95% CI: 2.24-7.17), STK (HR: 2.15, 95% CI: 1.70-2.72), and HF (HR: 6.66, 95% CI: 4.54-9.77), which was consistent in an independent community hospital. The transnational validation also revealed HRs of 4.91 (95% CI: 2.63-9.16) and 2.29 (95% CI: 2.15-2.44) for all-cause mortality in the SaMi-Trop and Clinical Outcomes in Digital Electrocardiography 15% (CODE15) cohorts. Conclusions: The mortality risk by AI-enabled ECG may be applied in passive electronic-health-record-based CVD risk screening, which may identify more asymptomatic and unaware high-risk patients.

Artificial Intelligence-Enabled Electrocardiography Detects B-Type Natriuretic Peptide and N-Terminal Pro-Brain Natriuretic Peptide.

BACKGROUND: The B-type natriuretic peptide (BNP) and N-terminal pro-brain natriuretic peptide (pBNP) are predictors of cardiovascular morbidity and mortality. Since the artificial intelligence (AI)-enabled electrocardiogram (ECG) system is widely used in the management of many cardiovascular diseases (CVDs), patients requiring intensive monitoring may benefit from an AI-ECG with BNP/pBNP predictions. This study aimed to develop an AI-ECG to predict BNP/pBNP and compare their values for future mortality. METHODS: The development, tuning, internal validation, and external validation sets included 47,709, 16,249, 4001, and 6042 ECGs, respectively. Deep learning models (DLMs) were trained using a development set for estimating ECG-based BNP/pBNP (ECG-BNP/ECG-pBNP), and the tuning set was used to guide the training process. The ECGs in internal and external validation sets belonging to nonrepeating patients were used to validate the DLMs. We also followed-up all-cause mortality to explore the prognostic value. RESULTS: The DLMs accurately distinguished mild (≥500 pg/mL) and severe (≥1000 pg/mL) an abnormal BNP/pBNP with AUCs of ≥0.85 in the internal and external validation sets, which provided sensitivities of 68.0-85.0% and specificities of 77.9-86.2%. In continuous predictions, the Pearson correlation coefficient between ECG-BNP and ECG-pBNP was 0.93, and they were both associated with similar ECG features, such as the T wave axis and correct QT interval. ECG-pBNP provided a higher all-cause mortality predictive value than ECG-BNP. CONCLUSIONS: The AI-ECG can accurately estimate BNP/pBNP and may be useful for monitoring the risk of CVDs. Moreover, ECG-pBNP may be a better indicator to manage the risk of future mortality.

Development and validation of a dynamic deep learning algorithm using electrocardiogram to predict dyskalaemias in patients with multiple visits.

Aims: Deep learning models (DLMs) have shown superiority in electrocardiogram (ECG) analysis and have been applied to diagnose dyskalaemias. However, no study has explored the performance of DLM-enabled ECG in continuous follow-up scenarios. Therefore, we proposed a dynamic revision of DLM-enabled ECG to use personal pre-annotated ECGs to enhance the accuracy in patients with multiple visits. Methods and results: We retrospectively collected 168 450 ECGs with corresponding serum potassium (K+) levels from 103 091 patients as development samples. In the internal/external validation sets, the numbers of ECGs with corresponding K+ were 37 246/47 604 from 13 555/20 058 patients. Our dynamic revision method showed better performance than the traditional direct prediction for diagnosing hypokalaemia [area under the receiver operating characteristic curve (AUC) = 0.730/0.720-0.788/0.778] and hyperkalaemia (AUC = 0.884/0.888-0.915/0.908) in patients with multiple visits. Conclusion: Our method has shown a distinguishable improvement in DLMs for diagnosing dyskalaemias in patients with multiple visits, and we also proved its application in ejection fraction prediction, which could further improve daily clinical practice.

Safety and Efficacy of Oral Nalbuphine on Postoperative Pain in Hemorrhoidectomy Patients: A Randomized, Double-blind, Placebo-controlled, Pivotal Trial.

OBJECTIVES: Severe postoperative pain requiring opioid treatment has been reported in 20% to 40% of hemorrhoidectomy patients. Compared with morphine, nalbuphine offers better hemodynamic stability, a lower risk of respiratory depression, and a lower potential for addiction. Nalbuphine was developed from the intravenous form into an oral form (PHN131) to alleviate moderate-to-severe pain. MATERIALS AND METHODS: A randomized, double-blind, placebo-controlled, multiple-dose, parallel-design trial was conducted to evaluate the safety and efficacy of PHN131 in patients undergoing hemorrhoidectomy. Eligible patients were randomly assigned to receive either PHN131 soft capsules containing nalbuphine hydrochloride 60 mg or placebo capsules. Intramuscular diclofenac was the rescue analgesic. Pain was measured by the area under the curve of mean Visual Analog Scale pain intensity scores. RESULTS: Visual Analog Scale results in patients receiving PHN131 were significantly lower than placebo group scores through 48 hours postoperatively (149.2±75.52 vs. 179.6±65.97; P =0.0301). According to Brief Pain Inventory Short-Form scores, the impact of pain on quality of life was significantly smaller for the PHN131 group than for the placebo group. Time to the first use of diclofenac postoperatively was significantly longer in the PHN131 group than in the placebo group. The cumulative dosage of diclofenac in the PHN131 group was only around half of that in the placebo group ( P <0.0001). Drug-related adverse events were mild-to-moderate and resolved by the treatment end. No drug-related severe adverse events were observed. DISCUSSION: Our findings demonstrate that PHN131 is effective and well-tolerated in the treatment of moderate-to-severe post hemorrhoidectomy pain and may provide another option for patients to control their pain.

Development and Validation of an Artificial Intelligence Electrocardiogram Recommendation System in the Emergency Department.

The machine learning-assisted electrocardiogram (ECG) is increasingly recognized for its unprecedented capabilities in diagnosing and predicting cardiovascular diseases. Identifying the need for ECG examination early in emergency department (ED) triage is key to timely artificial intelligence-assisted analysis. We used machine learning to develop and validate a clinical decision support tool to predict ED triage patients' need for ECG. Data from 301,658 ED visits from August 2017 to November 2020 in a tertiary hospital were divided into a development cohort, validation cohort, and two test cohorts that included admissions before and during the COVID-19 pandemic. Models were developed using logistic regression, decision tree, random forest, and XGBoost methods. Their areas under the receiver operating characteristic curves (AUCs), positive predictive values (PPVs), and negative predictive values (NPVs) were compared and validated. In the validation cohort, the AUCs were 0.887 for the XGBoost model, 0.885 for the logistic regression model, 0.878 for the random forest model, and 0.845 for the decision tree model. The XGBoost model was selected for subsequent application. In test cohort 1, the AUC was 0.891, with sensitivity of 0.812, specificity of 0.814, PPV of 0.708 and NPV of 0.886. In test cohort 2, the AUC was 0.885, with sensitivity of 0.816, specificity of 0.812, PPV of 0.659, and NPV of 0.908. In the cumulative incidence analysis, patients not receiving an ECG yet positively predicted by the model had significantly higher probability of receiving the examination within 48 h compared with those negatively predicted by the model. A machine learning model based on triage datasets was developed to predict ECG acquisition with high accuracy. The ECG recommendation can effectively predict whether patients presenting at ED triage will require an ECG, prompting subsequent analysis and decision-making in the ED.

Artificial Intelligence-Enabled Electrocardiography Detects Hypoalbuminemia and Identifies the Mechanism of Hepatorenal and Cardiovascular Events.

Background: Albumin, an important component of fluid balance, is associated with kidney, liver, nutritional, and cardiovascular diseases (CVD) and is measured by blood tests. Since fluid balance is associated with electrocardiography (ECG) changes, we established a deep learning model (DLM) to estimate albumin via ECG. Objective: This study aimed to develop a DLM to estimate albumin via ECG and explored its contribution to future complications. Materials and Methods: A DLM was trained for estimating ECG-based albumin (ECG-Alb) using 155,078 ECGs corresponding to albumin from 79,111 patients, and another independent 13,335 patients from an academic medical center and 11,370 patients from a community hospital were used for internal and external validation. The primary analysis focused on distinguishing patients with mild to severe hypoalbuminemia, and the secondary analysis aimed to provide additional prognostic value from ECG-Alb for future complications, which included mortality, new-onset hypoalbuminemia, chronic kidney disease (CKD), new onset hepatitis, CVD mortality, new-onset acute myocardial infarction (AMI), new-onset stroke (STK), new-onset coronary artery disease (CAD), new-onset heart failure (HF), and new-onset atrial fibrillation (Afib). Results: The AUC to identify hypoalbuminemia was 0.8771 with a sensitivity of 56.0% and a specificity of 90.7% in the internal validation set, and the Pearson correlation coefficient was 0.69 in the continuous analysis. The most important ECG features contributing to ECG-Alb were ordered in terms of heart rate, corrected QT interval, T wave axis, sinus rhythm, P wave axis, etc. The group with severely low ECG-Alb had a higher risk of all-cause mortality [hazard ratio (HR): 2.45, 95% CI: 1.81-3.33] and the other hepatorenal and cardiovascular events in the internal validation set. The external validation set yielded similar results. Conclusion: Hypoalbuminemia and its complications can be predicted using ECG-Alb as a novel biomarker, which may be a non-invasive tool to warn asymptomatic patients.

Artificial Intelligence-Enabled Electrocardiogram Predicted Left Ventricle Diameter as an Independent Risk Factor of Long-Term Cardiovascular Outcome in Patients With Normal Ejection Fraction.

Background: Heart failure (HF) is a global disease with increasing prevalence in an aging society. However, the survival rate is poor despite the patient receiving standard treatment. Early identification of patients with a high risk of HF is important but challenging. Left ventricular end-diastolic diameter (LV-D) increase was an independent risk factor of HF and adverse cardiovascular (CV) outcomes. In this study, we aimed to develop an artificial intelligence (AI) enabled electrocardiogram (ECG) system to detect LV-D increase early. Objective: We developed a deep learning model (DLM) to predict left ventricular end-diastolic and end-systolic diameter (LV-D and LV-S) with internal and external validations and investigated the relationship between ECG-LV-D and echocardiographic LV-D and explored the contributions of ECG-LV-D on future CV outcomes. Methods: Electrocardiograms and corresponding echocardiography data within 7 days were collected and paired for DLM training with 99,692 ECGs in the development set and 20,197 ECGs in the tuning set. The other 7,551 and 11,644 ECGs were collected from two different hospitals to validate the DLM performance in internal and external validation sets. We analyzed the association and prediction ability of ECG-LVD for CV outcomes, including left ventricular (LV) dysfunction, CV mortality, acute myocardial infarction (AMI), and coronary artery disease (CAD). Results: The mean absolute errors (MAE) of ECG-LV-D were 5.25/5.29, and the area under the receiver operating characteristic (ROC) curves (AUCs) were 0.8297/0.8072 and 0.9295/0.9148 for the detection of mild (56 ≦ LV-D < 65 mm) and severe (LV-D ≧ 65 mm) LV-D dilation in internal/external validation sets, respectively. Patients with normal ejection fraction (EF) who were identified as high ECHO-LV-D had the higher hazard ratios (HRs) of developing new onset LV dysfunction [HR: 2.34, 95% conference interval (CI): 1.78-3.08], CV mortality (HR 2.30, 95% CI 1.05-5.05), new-onset AMI (HR 2.12, 95% CI 1.36-3.29), and CAD (HR 1.59, 95% CI 1.26-2.00) in the internal validation set. In addition, the ECG-LV-D presents a 1.88-fold risk (95% CI 1.47-2.39) on new-onset LV dysfunction in the external validation set. Conclusion: The ECG-LV-D not only identifies high-risk patients with normal EF but also serves as an independent risk factor of long-term CV outcomes.

Artificial Intelligence-Enabled Electrocardiogram Estimates Left Atrium Enlargement as a Predictor of Future Cardiovascular Disease.

BACKGROUND: Left atrium enlargement (LAE) can be used as a predictor of future cardiovascular diseases, including hypertension (HTN) and atrial fibrillation (Afib). Typical electrocardiogram (ECG) changes have been reported in patients with LAE. This study developed a deep learning model (DLM)-enabled ECG system to identify patients with LAE. METHOD: Patients who had ECG records with corresponding echocardiography (ECHO) were included. There were 101,077 ECGs, 20,510 ECGs, 7611 ECGs, and 11,753 ECGs in the development, tuning, internal validation, and external validation sets, respectively. We evaluated the performance of a DLM-enabled ECG for diagnosing LAE and explored the prognostic value of ECG-LAE for new-onset HTN, new-onset stroke (STK), new-onset mitral regurgitation (MR), and new-onset Afib. RESULTS: The DLM-enabled ECG achieved AUCs of 0.8127/0.8176 for diagnosing mild LAE, 0.8587/0.8688 for diagnosing moderate LAE, and 0.8899/0.8990 for diagnosing severe LAE in the internal/external validation sets. Notably, ECG-LAE had higher prognostic value compared to ECHO-LAE, which had C-indices of 0.711/0.714 compared to 0.695/0.692 for new-onset HTN, 0.676/0.688 compared to 0.663/0.677 for new-onset STK, 0.696/0.695 compared to 0.676/0.673 for new-onset MR, and 0.800/0.806 compared to 0.786/0.760 for new-onset Afib in internal/external validation sets, respectively. CONCLUSIONS: A DLM-enabled ECG could be considered as a LAE screening tool and provide better prognostic information for related cardiovascular diseases.

Artificial Intelligence-Enabled Electrocardiography Predicts Left Ventricular Dysfunction and Future Cardiovascular Outcomes: A Retrospective Analysis.

BACKGROUND: The ejection fraction (EF) provides critical information about heart failure (HF) and its management. Electrocardiography (ECG) is a noninvasive screening tool for cardiac electrophysiological activities that has been used to detect patients with low EF based on a deep learning model (DLM) trained via large amounts of data. However, no studies have widely investigated its clinical impacts. OBJECTIVE: This study developed a DLM to estimate EF via ECG (ECG-EF). We further investigated the relationship between ECG-EF and echo-based EF (ECHO-EF) and explored their contributions to future cardiovascular adverse events. METHODS: There were 57,206 ECGs with corresponding echocardiograms used to train our DLM. We compared a series of training strategies and selected the best DLM. The architecture of the DLM was based on ECG12Net, developed previously. Next, 10,762 ECGs were used for validation, and another 20,629 ECGs were employed to conduct the accuracy test. The changes between ECG-EF and ECHO-EF were evaluated. The primary follow-up adverse events included future ECHO-EF changes and major adverse cardiovascular events (MACEs). RESULTS: The sex-/age-matching strategy-trained DLM achieved the best area under the curve (AUC) of 0.9472 with a sensitivity of 86.9% and specificity of 89.6% in the follow-up cohort, with a correlation of 0.603 and a mean absolute error of 7.436. In patients with accurate prediction (initial difference < 10%), the change traces of ECG-EF and ECHO-EF were more consistent (R-square = 0.351) than in all patients (R-square = 0.115). Patients with lower ECG-EF (≤35%) exhibited a greater risk of cardiovascular (CV) complications, delayed ECHO-EF recovery, and earlier ECHO-EF deterioration than patients with normal ECG-EF (>50%). Importantly, ECG-EF demonstrated an independent impact on MACEs and all CV adverse outcomes, with better prediction of CV outcomes than ECHO-EF. CONCLUSIONS: The ECG-EF could be used to initially screen asymptomatic left ventricular dysfunction (LVD) and it could also independently contribute to the predictions of future CV adverse events. Although further large-scale studies are warranted, DLM-based ECG-EF could serve as a promising diagnostic supportive and management-guided tool for CV disease prediction and the care of patients with LVD.