RESULTS: Thus, this study presents comprehensive robustness evaluations of seven widely used pathway activity inference methods using six cancer datasets based on two assessments. The first assessment seeks to investigate the robustness of pathway activity in pathway activity inference methods, while the second assessment aims to assess the robustness of risk-active pathways and genes predicted by these methods. The mean reproducibility power and total number of identified informative pathways and genes were evaluated. Based on the first assessment, the mean reproducibility power of pathway activity inference methods generally decreased as the number of pathway selections increased. Entropy-based Directed Random Walk (e-DRW) distinctly outperformed other methods in exhibiting the greatest reproducibility power across all cancer datasets. On the other hand, the second assessment shows that no methods provide satisfactory results across datasets.
CONCLUSION: However, PTB methods generally appear to perform better in producing greater reproducibility power and identifying potential cancer markers compared to non-TB methods.
OBJECTIVE: To employ machine learning (ML) and stacked ensemble learning (EL) methods in predicting short- and long-term mortality in Asian patients diagnosed with NSTEMI/UA and to identify the associated features, subsequently evaluating these findings against established risk scores.
METHODS: We analyzed data from the National Cardiovascular Disease Database for Malaysia (2006-2019), representing a diverse NSTEMI/UA Asian cohort. Algorithm development utilized in-hospital records of 9,518 patients, 30-day data from 7,133 patients, and 1-year data from 7,031 patients. This study utilized 39 features, including demographic, cardiovascular risk, medication, and clinical features. In the development of the stacked EL model, four base learner algorithms were employed: eXtreme Gradient Boosting (XGB), Support Vector Machine (SVM), Naive Bayes (NB), and Random Forest (RF), with the Generalized Linear Model (GLM) serving as the meta learner. Significant features were chosen and ranked using ML feature importance with backward elimination. The predictive performance of the algorithms was assessed using the area under the curve (AUC) as a metric. Validation of the algorithms was conducted against the TIMI for NSTEMI/UA using a separate validation dataset, and the net reclassification index (NRI) was subsequently determined.
RESULTS: Using both complete and reduced features, the algorithm performance achieved an AUC ranging from 0.73 to 0.89. The top-performing ML algorithm consistently surpassed the TIMI risk score for in-hospital, 30-day, and 1-year predictions (with AUC values of 0.88, 0.88, and 0.81, respectively, all p < 0.001), while the TIMI scores registered significantly lower at 0.55, 0.54, and 0.61. This suggests the TIMI score tends to underestimate patient mortality risk. The net reclassification index (NRI) of the best ML algorithm for NSTEMI/UA patients across these periods yielded an NRI between 40-60% (p < 0.001) relative to the TIMI NSTEMI/UA risk score. Key features identified for both short- and long-term mortality included age, Killip class, heart rate, and Low-Molecular-Weight Heparin (LMWH) administration.
CONCLUSIONS: In a broad multi-ethnic population, ML approaches outperformed conventional TIMI scoring in classifying patients with NSTEMI and UA. ML allows for the precise identification of unique characteristics within individual Asian populations, improving the accuracy of mortality predictions. Continuous development, testing, and validation of these ML algorithms holds the promise of enhanced risk stratification, thereby revolutionizing future management strategies and patient outcomes.
METHODS: We surveyed HFrEF patients from two hospitals in Malaysia, using Malay, English or Chinese versions of EQ-5D-5L. EQ-5D-5L dimensional scores were converted to utility scores using the Malaysian value set. A confirmatory factor analysis longitudinal model was constructed. The utility and visual analog scale (VAS) scores were evaluated for validity (convergent, known-group, responsiveness), and measurement equivalence of the three language versions.
RESULTS: 200 HFrEF patients (mean age = 61 years), predominantly male (74%) of Malay ethnicity (55%), completed the admission and discharge EQ-5D-5L questionnaire in Malay (49%), English (26%) or Chinese (25%) languages. 173 patients (86.5%) were followed up at 1-month post-discharge (1MPD). The standardized factor loadings and average variance extracted were ≥ 0.5 while composite reliability was ≥ 0.7, suggesting convergent validity. Patients with older age and higher New York Heart Association (NYHA) class reported significantly lower utility and VAS scores. The change in utility and VAS scores between admission and discharge was large, while the change between discharge and 1MPD was minimal. The minimal clinically important difference for utility and VAS scores was ±0.19 and ±11.01, respectively. Malay and English questionnaire were equivalent while the equivalence of Malay and Chinese questionnaire was inconclusive.
LIMITATION: This study only sampled HFrEF patients from two teaching hospitals, thus limiting the generalizability of results to the entire heart failure population.
CONCLUSION: EQ-5D-5L is a valid questionnaire to measure health-related quality of life and estimate utility values among HFrEF patients in Malaysia. The Malay and English versions of EQ-5D-5L appear equivalent for clinical and economic assessments.
METHODS: A systematic search of English articles and gray literature, published from January 2010, was performed on databases including MEDLINE, Embase, Scopus, NHSEED, health technology assessment, Cochrane Library, etc. The included studies were EEs with DAMs that compared the costs and outcomes of angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, angiotensin-receptor neprilysin inhibitors, beta-blockers, mineralocorticoid-receptor agonists, and sodium-glucose cotransporter-2 inhibitors. The study quality was evaluated using the Bias in Economic Evaluation (ECOBIAS) 2015 checklist and Consolidated Health Economic Evaluation Reporting Standards (CHEERS) 2022 checklists.
RESULTS: A total of 59 EEs were included. Markov model, with a lifetime horizon and a monthly cycle length, was most commonly used in evaluating GDMTs for HFrEF. Most EEs conducted in the high-income countries demonstrated that novel GDMTs for HFrEF were cost-effective compared with the standard of care, with the standardized median incremental cost-effectiveness ratio (ICER) of $21 361/quality-adjusted life-year. The key factors influencing ICERs and study conclusions included model structures, input parameters, clinical heterogeneity, and country-specific willingness-to-pay threshold.
CONCLUSIONS: Novel GDMTs were cost-effective compared with the standard of care. Given the heterogeneity of the DAMs and ICERs, alongside variations in willingness-to-pay thresholds across countries, there is a need to conduct country-specific EEs, particularly in low- and middle-income countries, using model structures that are coherent with the local decision context.
METHODS: The DROP-Asian ACS is a prospective, stepped wedge, cluster-randomized trial enrolling 4260 participants presenting with chest pain to the ED of 12 acute care hospitals in five Asian countries (UMIN; 000042461). Consecutive patients presenting with suspected acute coronary syndrome between July 2022 and Apr 2024 were included. Initially, all clusters will apply "usual care" according to local standard operating procedures including hs-cTnT but not the 0/1-h algorithm. The primary outcome is the incidence of major adverse cardiac events (MACE), the composite of all-cause death, myocardial infarction, unstable angina, or unplanned revascularization within 30 days. The difference in MACE (with one-sided 95% CI) was estimated to evaluate non-inferiority. The non-inferiority margin was prespecified at 1.5%. Secondary efficacy outcomes include costs for healthcare resources and duration of stay in ED.
CONCLUSIONS: This study provides important evidence concerning the safety and efficacy of the 0/1-h algorithm in Asian countries and may help to reduce congestion of the ED as well as medical costs.
OBJECTIVE: To derive a single algorithm using deep learning and machine learning for the prediction and identification of factors associated with in-hospital mortality in Asian patients with ACS and to compare performance to a conventional risk score.
METHODS: The Malaysian National Cardiovascular Disease Database (NCVD) registry, is a multi-ethnic, heterogeneous database spanning from 2006-2017. It was used for in-hospital mortality model development with 54 variables considered for patients with STEMI and Non-STEMI (NSTEMI). Mortality prediction was analyzed using feature selection methods with machine learning algorithms. Deep learning algorithm using features selected from machine learning was compared to Thrombolysis in Myocardial Infarction (TIMI) score.
RESULTS: A total of 68528 patients were included in the analysis. Deep learning models constructed using all features and selected features from machine learning resulted in higher performance than machine learning and TIMI risk score (p < 0.0001 for all). The best model in this study is the combination of features selected from the SVM algorithm with a deep learning classifier. The DL (SVM selected var) algorithm demonstrated the highest predictive performance with the least number of predictors (14 predictors) for in-hospital prediction of STEMI patients (AUC = 0.96, 95% CI: 0.95-0.96). In NSTEMI in-hospital prediction, DL (RF selected var) (AUC = 0.96, 95% CI: 0.95-0.96, reported slightly higher AUC compared to DL (SVM selected var) (AUC = 0.95, 95% CI: 0.94-0.95). There was no significant difference between DL (SVM selected var) algorithm and DL (RF selected var) algorithm (p = 0.5). When compared to the DL (SVM selected var) model, the TIMI score underestimates patients' risk of mortality. TIMI risk score correctly identified 13.08% of the high-risk patient's non-survival vs 24.7% for the DL model and 4.65% vs 19.7% of the high-risk patient's non-survival for NSTEMI. Age, heart rate, Killip class, cardiac catheterization, oral hypoglycemia use and antiarrhythmic agent were found to be common predictors of in-hospital mortality across all ML feature selection models in this study. The final algorithm was converted into an online tool with a database for continuous data archiving for prospective validation.
CONCLUSIONS: ACS patients were better classified using a combination of machine learning and deep learning in a multi-ethnic Asian population when compared to TIMI scoring. Machine learning enables the identification of distinct factors in individual Asian populations to improve mortality prediction. Continuous testing and validation will allow for better risk stratification in the future, potentially altering management and outcomes.
OBJECTIVE: Apply machine learning for the prediction and identification of factors associated with short and long-term mortality in Asian STEMI patients and compare with a conventional risk score.
METHODS: The National Cardiovascular Disease Database for Malaysia registry, of a multi-ethnic, heterogeneous Asian population was used for in-hospital (6299 patients), 30-days (3130 patients), and 1-year (2939 patients) model development. 50 variables were considered. Mortality prediction was analysed using feature selection methods with machine learning algorithms and compared to Thrombolysis in Myocardial Infarction (TIMI) score. Invasive management of varying degrees was selected as important variables that improved mortality prediction.
RESULTS: Model performance using a complete and reduced variable produced an area under the receiver operating characteristic curve (AUC) from 0.73 to 0.90. The best machine learning model for in-hospital, 30 days, and 1-year outperformed TIMI risk score (AUC = 0.88, 95% CI: 0.846-0.910; vs AUC = 0.81, 95% CI:0.772-0.845, AUC = 0.90, 95% CI: 0.870-0.935; vs AUC = 0.80, 95% CI: 0.746-0.838, AUC = 0.84, 95% CI: 0.798-0.872; vs AUC = 0.76, 95% CI: 0.715-0.802, p < 0.0001 for all). TIMI score underestimates patients' risk of mortality. 90% of non-survival patients are classified as high risk (>50%) by machine learning algorithm compared to 10-30% non-survival patients by TIMI. Common predictors identified for short- and long-term mortality were age, heart rate, Killip class, fasting blood glucose, prior primary PCI or pharmaco-invasive therapy and diuretics. The final algorithm was converted into an online tool with a database for continuous data archiving for algorithm validation.
CONCLUSIONS: In a multi-ethnic population, patients with STEMI were better classified using the machine learning method compared to TIMI scoring. Machine learning allows for the identification of distinct factors in individual Asian populations for better mortality prediction. Ongoing continuous testing and validation will allow for better risk stratification and potentially alter management and outcomes in the future.
Methods: Between May 2014 to April 2017, 268 patients (88% male, mean age 60.1 ± 10.8 years) with 291 coronary lesions were treated with AES. The primary endpoint was major adverse cardiac events (MACE) ie a composite of cardiovascular mortality, myocardial infarction (MI) and target lesion revascularization (TLR) at 12-month follow-up.
Results: The majority of patients presented with acute coronary syndrome (75%) and 75% had multi-vessel disease on angiography. Diabetes mellitus was present in 123 patients (46%). The most common target vessel for PCI was left anterior descending artery (43%) followed by right coronary artery (36%), left circumflex (10%) and left main (6%).The majority of lesions were type B-C (85%) by ACC/AHA lesion classification. An average of 1.25 ± 0.5 AES were used per patient, with mean AES diameter of 3.1 ± 0.4 mm and average total length of 34.8 ± 19.4 mm.At 12-month follow-up, 4% of patients developed MACE. MACE was mainly driven by cardiovascular mortality (1.5%), MI (2%) and TLR (1.5%). The rate of stent thrombosis was 1.5%.
Conclusion: In a contemporary all-comers South-East Asian registry with high rate of diabetes mellitus, AES was found to be efficacious with a low incidence of MACE observed at 12-month follow-up.
METHODS: Seven hundered fifty five individuals from specialist clinics and community health screenings with LDL-c level ≥ 4.0 mmol/L were selected and diagnosed as FH using the DLCC, the SB Register criteria, the US MEDPED and the JFHMC. The sensitivity, specificity, efficiency, positive and negative predictive values of individuals screened with the SB register criteria, US MEDPED and JFHMC were assessed against the DLCC.
RESULTS: We found the SB register criteria identified more individuals with FH compared to the US MEDPED and the JFHMC (212 vs. 105 vs. 195; p