Validating A Smartphone-Based Biomarker Tool Lyfas in Screening Anxiety Disorders

Lyfas is a smartphone-based biomedical application that captures the cardiovascular autonomic biomarkers (CVb), surrogating for mental health attributes. SD1/SD2 biomarker assesses the sympathovagal balance and is considered to be a potential indicator of Lyfas anxiety score (LAS). A total of 1837 males and 973 females took Lyfas (hypersensitivity-checked) and Hamilton Anxiety Rating Scale (HAM-A) self-scoring tests. LAS has been statistically validated by Linear regressions, one-way ANOVA, t-stat, correlations (r), and Bland Altman agreement assessment with respect to HAM-A. Sensitivity, specificity, precision, accuracy, Fscore, and Youden’s index (j-stat) are computed. Results show that (i) Lyfas is not a very hypersensitive instrument (mean-variance is 0.6). (ii) It can predict HAM-A with 94.7% accuracy (R2) and is a statistically significant model (p <0.05). (iii) LAS and HAM-A are positively correlated by 97%, the t-stat value of 5.38 for the population indicates that the two instruments have a significant mean difference. (iv) Bland Altman test showcases the overall agreement of 12.95% due to different modes and scales of measurements. (v) on average, LAS is 87.78% accurate, 86.82% precise, and its’ 65.2% j-stat value proves that Lyfas is a novel industry-standard smartphone biomarker application that can be used to accurately screen anxiety disorders.

Combining a Pharmacological Network Model with a Bayesian Signal Detection Algorithm to Improve the Detection of Adverse Drug Events

Introduction: Improving adverse drug event (ADE) detection is important for post-marketing drug safety surveillance. Existing statistical approaches can be further optimized owing to their high efficiency and low cost.Objective: The objective of this study was to evaluate the proposed approach for use in pharmacovigilance, the early detection of potential ADEs, and the improvement of drug safety.Methods: We developed a novel integrated approach, the Bayesian signal detection algorithm, based on the pharmacological network model (ICPNM) using the FDA Adverse Event Reporting System (FAERS) data published from 2004 to 2009 and from 2014 to 2019Q2, PubChem, and DrugBank database. First, we used a pharmacological network model to generate the probabilities for drug-ADE associations, which comprised the proper prior information component (IC). We then defined the probability of the propensity score adjustment based on a logistic regression model to control for the confounding bias. Finally, we chose the Side Effect Resource (SIDER) and the Observational Medical Outcomes Partnership (OMOP) data to evaluate the detection performance and robustness of the ICPNM compared with the statistical approaches [disproportionality analysis (DPA)] by using the area under the receiver operator characteristics curve (AUC) and Youden’s index.Results: Of the statistical approaches implemented, the ICPNM showed the best performance (AUC, 0.8291; Youden’s index, 0.5836). Meanwhile, the AUCs of the IC, EBGM, ROR, and PRR were 0.7343, 0.7231, 0.6828, and 0.6721, respectively.Conclusion: The proposed ICPNM combined the strengths of the pharmacological network model and the Bayesian signal detection algorithm and performed better in detecting true drug-ADE associations. It also detected newer ADE signals than a DPA and may be complementary to the existing statistical approaches.

A comparison of the 33-item Hypomania Checklist with the 33-item Hypomania Checklist-external assessment for the detection of bipolar disorder in adolescents

Background Adolescents with bipolar disorder (BD) are often misdiagnosed as having major depressive disorder (MDD), which delays appropriate treatment and leads to adverse outcomes. The aim of this study was to compare the performance of the 33-item Hypomania Checklist (HCL-33) with the 33-item Hypomania Checklist- external assessment (HCL-33-EA) in adolescents with BD or MDD. Methods 147 adolescents with BD and 113 adolescents with MDD were consecutively recruited. The HCL-33 and HCL-33-EA were completed by patients and their carers, respectively. The sensitivity, positive predictive value (PPV), specificity, negative predictive value (NPV), and area under the curve (AUC) were calculated and compared between the two instruments, using cut-off values based on the Youden’s index. Results The total scores of the HCL-33 and HCL-33-EA were positively and significantly correlated (rs = 0.309, P < 0.001). Compared to the HCL-33, the HCL-33-EA had higher sensitivity and NPV (HCL-33: sensitivity = 0.58, NPV = 0.53; HCL-33-EA: sensitivity = 0.81, NPV = 0.60), while the HCL-33 had higher specificity and PPV (HCL-33: specificity = 0.61, PPV = 0.66; HCL-33-EA: specificity = 0.37, PPV = 0.63). Conclusion Both the HCL-33 and HCL-33-EA seem to be useful for screening depressed adolescents for BD. The HCL-33-EA would be more appropriate for distinguishing BD from MDD in adolescents due to its high sensitivity in Chinese clinical settings.

Predicting asymptomatic neurosyphilis using peripheral blood indicators

Background The high misdiagnosis rate of asymptomatic neurosyphilis (ANS) has long challenged infectious disease clinicians. We aim to develop a model for diagnosing ANS in asymptomatic syphilis (AS) patients without CSF indicators. Results 277 AS patients with HIV-negative and underwent lumbar puncture were enrolled in this horizontal study.The area under the curve for predicting ANS by CSF leukocytes and protein was 0.643 and 0.675 [95% CI, 0.583–0.699VS.0.616–0.729]. Through LRM, the AUC increased to 0.806 [95% CI, 0.732–0.832], and the Youden's index was 0.430. If the score is ≤ 0.159, ANS can be excluded with a predictive value of 92.9%; we can identify ANS while the score is over 0.819, with a predictive value of 91.7% and a specificity of 99.25%. This study showed that the LRM can diagnose ANS in AS patients effectively. Conclusion Given a large number of misdiagnosis ANS patients and CSF results' insufficiency, the model is more practical. Our research will help clinicians track suspected syphilis, especially those who cannot accept the CSF test.

Early Bone Marrow Assessment after 7+3 Induction Chemotherapy Is Predictable of Outcome in AML with Adverse Cytogenetics

Introduction Although many new therapeutic agents have been introduced in the field of AML, the most important intensive induction regimen of AML patients is still 7+3 chemotherapy based on cytarabine and anthracycline. Currently, major guidelines recommend to exam bone marrow (BM) assessment in 14-21 days after the initiation of induction to determine whether to proceed with intensification chemotherapy. However, there is no solid evidence that these timings are most optimal. If the evaluation at an earlier time point is prognostic for response, earlier intensification could be considered. In this regard, we investigated if the BM blast rate at the 7th day after the start of 7+3 chemotherapy (D7 BM blast) was useful in predicting the treatment response of induction chemotherapy. Methods We retrospectively collected the data of patients who were newly diagnosed with AML from February 2002 to February 2021, received induction chemotherapy by 7+3, had a D7 BM examination without any intensification. A total of 665 patients were enrolled and we analyzed the prognostic significance of the D7 BM blast for the induction treatment response (complete remission or complete remission with incomplete hematologic recovery (CR/CRi)). In addition, we analyzed whether the predictive significance of the D7 BM blast varies by the patient's cytogenetic features by Medical Research Council classification (MRC risk). Then, we evaluated the diagnostic ability of the D7 BM blast by the receiver operating characteristic (ROC) curve for treatment response prediction. To find an optimal D7 BM blast cut-off value, the value that maximizes Youden's index was investigated. Results Among 665 AML patients who underwent 7+3 without intensification, the proportion of patients who acquired CR/CRi after single induction was 68.3%. A significant decrease in the CR/CRi rate was observed in the intermediate/adverse MRC group according to the increase of the D7 BM blast (tests for the trends in the intermediate and adverse group, p&lt;0.001 and p=0.008, respectively; Figure 1). In univariable/multivariable (using covariates of age, sex, etiology, and MRC risk) logistic regression models, the D7 BM blast showed a significant correlation with the CR/CRi rate in the intermediate/adverse cytogenetic group (Table 1). To evaluate the usability of the D7 BM blast as a predictive tool, the ROC curve for the treatment response prediction was plotted (Figure 2) and the D7 BM blast was significantly predictable only in the adverse MRC risk group (Area under the curve: 0.7007, Mann-Whitney test statistics p=0.002). The D7 blast cut-off in the adverse MRC risk group which maximizes Youden's index was 4-4.9%, near to 5%, which is the cut-off used to evaluate the treatment response. The sensitivity and specificity for treatment response prediction according to D7 BM blast &lt;5% or not were 82.8% and 61.1%, respectively. Conclusion The BM assessment performed at 7 days after 7+3 chemotherapy was available to predict the treatment response in intermediate and adverse cytogenetic risk patients. In particular, it can be practically used in patients with adverse cytogenetics, and a value of around BM blast 5% can be used as cut-off for response prediction. Early intensification in these patients could be considered, which would be beneficial in various aspects such as shorter nadir period or hospital stay and possibly better treatment response compared with the current strategies of later intensification or second induction. Figure 1 Figure 1. Disclosures Kim: Novartis: Research Funding; BMS: Research Funding; Pfizer: Research Funding; ILYANG: Research Funding; Takeda: Research Funding. Lee: Alexion, AstraZeneca Rare Disease: Honoraria, Membership on an entity's Board of Directors or advisory committees. Kim: AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; AIMS Biosciense: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; AML-Hub: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Astellas: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BL & H: Research Funding; BMS & Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Boryung Pharm Co.: Consultancy; Daiichi Sankyo: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Handok: Consultancy, Honoraria; LG Chem: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria; Pintherapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sanofi Genzyme: Honoraria, Speakers Bureau; SL VaxiGen: Consultancy, Honoraria; VigenCell: Consultancy, Honoraria.

Combining genetic risk score with artificial neural network to predict the efficacy of folic acid therapy to hyperhomocysteinemia

Artificial neural network (ANN) is the main tool to dig data and was inspired by the human brain and nervous system. Several studies clarified its application in medicine. However, none has applied ANN to predict the efficacy of folic acid treatment to Hyperhomocysteinemia (HHcy). The efficacy has been proved to associate with both genetic and environmental factors while previous studies just focused on the latter one. The explained variance genetic risk score (EV-GRS) had better power and could represent the effect of genetic architectures. Our aim was to add EV-GRS into environmental factors to establish ANN to predict the efficacy of folic acid therapy to HHcy. We performed the prospective cohort research enrolling 638 HHcy patients. The multilayer perception algorithm was applied to construct ANN. To evaluate the effect of ANN, we also established logistic regression (LR) model to compare with ANN. According to our results, EV-GRS was statistically associated with the efficacy no matter analyzed as a continuous variable (OR = 3.301, 95%CI 1.954–5.576, P < 0.001) or category variable (OR = 3.870, 95%CI 2.092–7.159, P < 0.001). In our ANN model, the accuracy was 84.78%, the Youden’s index was 0.7073 and the AUC was 0.938. These indexes above indicated higher power. When compared with LR, the AUC, accuracy, and Youden’s index of the ANN model (84.78%, 0.938, 0.7073) were all slightly higher than the LR model (83.33% 0.910, 0.6687). Therefore, clinical application of the ANN model may be able to better predict the folic acid efficacy to HHcy than the traditional LR model. When testing two models in the validation set, we got the same conclusion. This study appears to be the first one to establish the ANN model which added EV-GRS into environmental factors to predict the efficacy of folic acid to HHcy. This model would be able to offer clinicians a new method to make decisions and individual therapeutic plans.

Respiratory symptoms (COPD Assessment Test and modified Medical Research Council dyspnea scores) and GOLD-ABCD COPD classification: the LASSYC study

Objective: To assess the frequency and severity of 24-hour respiratory symptoms according to COPD GOLD-ABCD classification (2017-version), the distribution of the patients with COPD into GOLD categories using mMRC (=2) or CAT (=10) scores, and agreement between these cut-off points. Methods: In this cross-sectional study (LASSYC study), 24-hour day respiratory symptoms were assessed by the Evaluating Respiratory Symptoms in COPD (E-RS) questionnaire, Nighttime Symptoms of COPD Instrument (NiSCI), Early Morning Symptoms of COPD Instrument (EMSCI), CAT and mMRC scores. Results: Among the 734 patients with COPD, 61% were male, age 69.6±8.7 years, FEV1% post-BD 49.1±17.5%, mMRC 1.8±1.0 and CAT 15.3±.8.1. By mMRC 33.7% were group-A, 29.2% group-B, 10.2% group-C and 26.9% group-D. By CAT 22.3% were group-A, 41% group-B, 4.8% group-C and 31.9% group-D. Using the mMRC the severity of E-RS, NiSCI and EMSCI scores increased from group A to D. Using the CAT, the groups B and D had the higher scores. Agreement between mMRC and CAT was 89.5% (Kappa statistics=75.7%). For mMRC score of 2, CAT score of =11 showed the maximum Youden's index (1.34). For mMRC score of 1, CAT score of =9 and =10 showed the maximum Youden's index (1.48). Conclusion: GOLD COPD classification by CAT seems to better discriminate 24-hour symptoms. Results do not support the equivalent use of CAT=10 and mMRC=2 for assessing symptoms.

Accuracy in detecting major depressive episodes in older adults using the Swedish versions of the GDS-15 and PHQ-9

Objectives: The purpose of this study was to evaluate the diagnostic accuracy at different cut-off values for the Swedish versions of the 15-item Geriatric Depression Scale (GDS-15) and Patient Health Questionnaire (PHQ-9) compared with a structured clinical psychiatric interview in older adults. Methods: Community-dwelling participants (N = 113) aged 65 years or older completed the Swedish versions of the GDS-15 and PHQ-9 and were then interviewed using the Mini International Neuropsychiatric Interview (MINI) to establish the presence or absence of current major depressive episodes (MDEs). Areas under the curve (AUC) were calculated for each scale, as well as the sensitivity, specificity, and Youden’s index for different cut-off values. Results: Seventeen participants met the criteria for MDEs. The AUC was 0.97 for the GDS-15 and 0.95 for the PHQ-9. A cut-off of ≥6 on the GDS-15 yielded a sensitivity of 94%, a specificity of 88%, and a Youden’s index of 0.82. A cut-off of ≥5 on the PHQ-9 yielded a sensitivity of 100%, a specificity of 81%, and a Youden’s index of 0.81. The proposed cut-off of ≥10 on the PHQ-9 produced excellent specificity of 95% but a lower sensitivity of 71%. Conclusions: This study indicates that the Swedish versions of the GDS-15 and PHQ-9 have comparable accuracy as screening instruments for older adults with MDEs. However, the proposed cut-off of 10 on the PHQ-9 might be too high when applied to older individuals in Sweden, and further investigations in larger samples in different healthcare settings are warranted.

Vancomycin-induced nephrotoxicity in non-intensive care unit pediatric patients

Previous data suggested several risk factors for vancomycin-induced nephrotoxicity (VIN), including higher daily dose, long-term use, underlying renal disease, intensive care unit (ICU) admission, and concomitant use of nephrotoxic medications. We conducted this study to investigate the prevalence and risk factors of VIN and to estimate the cut-off serum trough level for predicting acute kidney injury (AKI) in non-ICU pediatric patients. This was a retrospective, observational, single-center study at Samsung Medical Center tertiary hospital, located in Seoul, South Korea. We reviewed the medical records of non-ICU pediatric patients, under 19 years of age with no evidence of previous renal insufficiency, who received vancomycin for more than 48 h between January 2009 and December 2018. The clinical characteristics were compared between patients with AKI and those without to identify the risk factors associated with VIN, and the cut-off value of serum trough level to predict the occurrence of VIN was calculated by the Youden’s index. Among 476 cases, 22 patients (4.62%) developed AKI. The Youden’s index indicated that a maximum serum trough level of vancomycin above 24.35 μg/mL predicted VIN. In multivariate analysis, longer hospital stay, concomitant use of piperacillin-tazobactam and serum trough level of vancomycin above 24.35 μg/mL were associated independently with VIN. Our findings suggest that concomitant use of nephrotoxic medication and higher serum trough level of vancomycin might be associated with the risk of VIN. This study suggests that measuring serum trough level of vancomycin can help clinicians prevent VIN in pediatric patients.

The blood pressure control and arteriosclerotic cardiovascular risk among Chinese community hypertensive patients

The present study aimed to describe the blood pressure (BP) control rate and 10-years arteriosclerotic cardiovascular disease (ASCVD) risk estimation among community hypertensive patients. A total of 196,803 subjects were enrolled. The control rates calculated as the intensive (SBP < 130 mmHg and DBP < 80 mmHg) and standard (SBP < 140 mmHg and DBP < 90 mmHg) threshold. Multivariable logistic analysis was employed to assess the associations between cardiovascular factors and BP control. Sensitivity, specificity and Youden’s index were used to identify the ability of high risk of ASCVD estimation by different thresholds. The control rate was 16.34% and 50.25% by the intensive and standard threshold, respectively. Besides regular medication, the risk factors for BP control included older age, male, unhealthy lifestyle, obesity, dyslipidemia and abnormal FPG. 25.08% of subjects had high risk of 10-years ASCVD estimation. The sensitivity, specificity and Youden’s index of intensive threshold was 84.37%, 16.15% and 0.51%, and were significantly different from 50.55%, 50.42% and 0.98% of the standard threshold, respectively. Half of community hypertensive patients did not control BP, and nearly a quarter have high risk of 10-years ASCVD risk estimation. The intensive threshold resulted in a one-third reduction in the control rate compared to the standard threshold. No matter which threshold was used, a single BP control status seemed not a suitable indicator for identification of high risk of 10-years ASCVD risk estimation.