Stable Outpatients Research Articles

The Validity of the SQoL-18 in Patients with Bipolar and Depressive Disorders: A Psychometric Study from the PREMIUM Project.

The S-QoL 18 is a self-administered questionnaire that assesses quality of life (QoL) among individuals with schizophrenia. This study aims to validate the S-QoL 18 in bipolar and depressive disorders for a more widespread use in psychiatric settings. This study was conducted in a non-selected sample of individuals with bipolar and depressive disorders in the day hospital of a regional psychiatric academic hospital. Two-hundred and seventy-two stable outpatients with bipolar (n = 73) and recurrent and persistent depressive (n = 199) disorders were recruited over a 12 month-period. The S-QoL 18 was tested for construct validity, reliability, and external validity. The eight-factor structure of the S-QoL 18 was confirmed by confirmatory factor analysis (RMSEA = 0.075 (0.064–0.086), CFI = 0.972, TLI = 0.961). Internal consistency and reliability were satisfactory. External validity was confirmed via correlations between S-QoL 18 dimension scores, symptomatology, and functioning. The percentage of missing data for the eight dimensions did not exceed 5%. INFIT statistics were ranged from 0.7 to 1.2, ensuring that all items of the scale measured the same QoL concept. In conclusion, the S-QoL 18 appears to be a valid and reliable instrument for measuring QoL in patients with bipolar and depressive disorders. The S-QoL 18 may be used by healthcare professionals in clinical settings to accurately assess QoL in individuals with bipolar and depressive disorders, as well as in schizophrenia.

Computerized analysis of facial expressions in serious mental illness

Blunted facial affect is a transdiagnostic component of Serious Mental Illness (SMI) and is associated with a host of negative outcomes. However, blunted facial affect is a poorly understood phenomenon, with no known cures or treatments. A critical step in better understanding its phenotypic expression involves clarifying which facial expressions are altered in specific ways and under what contexts. The current literature suggests that individuals with SMI show decreased positive facial expressions, but typical, or even increased negative facial expressions during laboratory tasks. While this literature has coalesced around general trends, significantly more nuance is available regarding what components facial expressions are atypical and how those components are associated with increased severity of clinical ratings. The present project leveraged computerized facial analysis to test whether clinician-rated blunted affect is driven by decreases in duration, intensity, or frequency of positive versus other facial expressions during a structured clinical interview. Stable outpatients meeting criteria for SMI (N = 59) were examined. Facial expression did not generally vary as a function of clinical diagnosis. Overall, clinically-rated blunted affect was not associated with positive expressions, but was associated with decreased surprise and increased anger, sadness, and fear expressions. Blunted affect is not a monolithic lack of expressivity, and increased precision in operationally defining it is critical for uncovering its causes and maintaining factors. Our discussion focuses on this effort, and on advancing digital phenotyping of blunted facial affect more generally.

Atrial electromechanical delay, neutrophil-to-lymphocyte ratio, and echocardiographic changes in patients with acute and stable chronic obstructive pulmonary disease.

Atrial electromechanical delay (AEMD) is the time interval between the beginning of P wave on surface electrocardiography and starting of the late diastolic wave on tissue Doppler imaging. We investigated the prolongation of AEMD, echocardiographic changes, and correlation of these findings with neutrophil-to-lymphocyte ratio (NLR) in patients with chronic obstructive pulmonary disease (COPD). The study consisted of 105 (49 females and 56 males; mean age: 65.1 ± 9) patients with COPD exacerbation and 104 (21 females and 83 males; mean age: 64.8 ± 9.6) stable COPD outpatients. Demographics, body mass index, pulmonary function tests, and transthoracic echocardiography of the patients were evaluated. Echocardiography was performed in the first 6 h for stable COPD outpatients and in the first 24 h for COPD exacerbation patients. Diameters of right ventricle (RV), left ventricle (LV) and left atrium, aortic root diameters, left ventricular ejection fraction (LVEF), Emax, Amax, Emax/Amax, tricuspid annular plane systolic excursion (TAPSE), Ea, Aa, Ea/Aa, Emax/Ea, and tricuspid regurgitation velocity (TRV) were evaluated. AEMD measurements were obtained from lateral/tricuspid, lateral/mitral, and septal annulus from apical four-chamber views with tissue Doppler imaging and corrected for heart rate. Complete blood count including NLR was also assessed. The mean age of patients in exacerbation period (65.1 ± 9) was higher than the stable group (64.8 ± 9.6). RV basal and mid diameters (P < 0.001), Amax (P < 0.001), Ea tricuspid (P = 0.040), Aa tricuspid (P < 0.001), TRV, and systolic pulmonary artery pressure (P < 0.001) were higher; TAPSE and tricuspid Emax/Amax (P < 0.001) were significantly lower in patients with COPD exacerbation. LV end-diastolic diameter (P = 0.002) and LVEF (P = 0.005), Emax/Amax mitral (P < 0.001), Ea/Aa mitral (P < 0.001), and Ea/Aa septal (P < 0.001) were significantly lower; Amax mitral (P = 0.002), Aa mitral (P < 0.001), Aa septal (P < 0.001), and systolic motion mitral (P = 0.011) were significantly higher in patients with exacerbation. AEMD lateral/tricuspid (P < 0.001), lateral/mitral (P < 0.001), and septal (P < 0.001) were significantly higher in patients with COPD exacerbation. Neutrophil and lymphocyte count (P < 0.001) and NLR (P = 0.003) were significantly higher in the acute group. A weak correlation of NLR with LV end-diastolic diameter (P = 0.003; r = 0.357), Emax/Ea mitral (P = 0.019; r = 0.285), Emax tricuspid (P = 0.045; r = -0.244), and systolic motion septal (P = 0.003; r = 0.352) was detected in patients with stable COPD. In COPD exacerbation patients, prolongation of AEMD intervals was determined. Acute period of COPD may trigger atrial dysrhythmias including atrial fibrillation and flutter, multifocal atrial tachycardia, premature beats, and both systolic and diastolic dysfunctions frequently.

Upper Arm Muscular Echogenicity Predicts Intensive Care Unit-acquired Weakness in Critically Ill Patients.

ABSTRACTObjectives:This retrospective observational study investigated whether the degree of muscular echogenicity in patients admitted to the intensive care unit (ICU) could help with the early detection of ICU-acquired weakness (ICU-AW) and predict physical function at hospital discharge.Methods:Twenty-five patients who were mechanically ventilated for more than 48 h in the ICU were enrolled. We also enrolled 23 outpatients with nonmuscular diseases as the control group. The target sites for measuring muscular echogenicity were the upper arm and lower leg. First, the muscular echogenicity was compared between surviving nonsurgical patients admitted to the ICU and stable outpatients with nonmuscular diseases. Second, we investigated the relationship between muscular echogenicity and clinical features, e.g., the manual muscle test (MMT), Medical Research Council (MRC) sum score, and Functional Independence Measure (FIM).Results:Muscular echogenicity in the upper arm in the ICU group was significantly higher than that in the control group. In the ICU group, the degree of muscular echogenicity of the upper arm was inversely correlated with the MMT of elbow flexion (P=0.006; r=−0.532) and the MRC sum score (P=0.002; r=−0.591). However, muscular echogenicity of the upper arm did not correlate with functional FIM (P=0.100; r=−0.344) at hospital discharge.Conclusions:Critically ill patients can experience pathological muscle weakness associated with increased muscular echogenicity in the upper arm. Additionally, the degree of muscular echogenicity in the upper arm correlated with the MRC sum score and can facilitate early detection of ICU-AW. The relationship between echogenicity and functional outcome at discharge requires elucidation.

Linguistic Validation of the Japanese Version of the Multidimensional Dyspnea Profile and Relation to Physical Activity in Patients with COPD.

PurposeThis study aimed to develop a linguistically validated Japanese translation of the multidimensional dyspnea profile (MDP) and assess whether worsening of dyspnea’s sensory and affective domains during exercise had detrimental effects on physical activity in stable outpatients with chronic obstructive pulmonary disease (COPD).Materials and MethodsThe Japanese version of the MDP was prepared in collaboration with Mapi Research Trust (Lyon, France) after the approval of the developer. Physical activity was assessed using a 3-axis accelerometer. Dyspnea upon exertion was investigated using a 3-minute step test.ResultsThe Japanese version of the MDP was obtained and validated linguistically. Air-hunger was significantly associated with total calories from walking (r = − 0.47, p < 0.05), while anxiety and depression were significantly correlated with both the amount and intensity of physical activity (r = − 0.49, p < 0.05, and r = − 0.46, p < 0.05, respectively).ConclusionThe Japanese version of the MDP was suggested to reflect both pulmonary functions, ventilatory response during exercise, and intensity and amount of physical activity in patients with COPD.

Getting the Most out of Spirometry: A Tool to Guide Dry Powder Inhaler Use.

Dry powder inhaler (DPI) use requires sufficient peak inspiratory flow over the DPI internal resistance (PIFR). We examined whether spirometric peak inspiratory flow (PIFspiro) could serve to predict PIFR in patients with obstructive lung disease. Thirty healthy nonsmokers and 140 stable outpatients (70 COPD, 70 asthma) performed spirometry according to the 2019 ERS/ATS spirometry update, yielding PIFspiro. Using a PIFR measurement device with varying orifices, all subjects' PIFR values were recorded for 5 predefined resistance levels, characterized by 5 orifice cross sections (SR). A test group including all healthy subjects, 30 of the asthma, and 30 of the COPD patients was used to establish the relationship between PIFR and both PIFspiro and SR by multiple regression. A validation group including the remaining 40 asthma and 40 COPD patients, served to verify whether their predicted PIFR value corresponded to the measured PIFR for each resistance level. The asthma (FEV1 = 78 ± 17 [SD] %pred) and COPD (FEV1 = 46 ± 17 [SD] %pred) patients under study had varying airway obstruction. In the test group, PIFR could be predicted by ln[PIFspiro] (p < 0.0001), SR (p < 0.0001), and SR2 (p = 0.006), with an adjusted R2 = 0.71. In the validation group, estimated PIFR did not significantly differ from measured PIFR (p > 0.05 for the 5 resistance levels). We propose a simple method to predict PIFR for a range of common DPI resistances, based on the device characteristics and on the patient's characteristics reflected in PIFspiro. As such, routine spirometry can serve to estimate a patient's specific PIFR without the need for additional testing.

A New Approach to Bicarbonate Addition During Hemodialysis: Testing Model Predictions in a Patient Cohort

In this study, we present a new protocol for kidney replacement therapy (hemodialysis), based on an explicitly solvable mathematical model. With current protocols, the high and constant level of bath bicarbonate (HCO₃^&#x2212;) used to prevent metabolic acidosis leads to very rapid delivery of HCO₃^&#x2212; into the patient during the first part of the therapy. This rapid alkalinization elicits a robust buffer response that, paradoxically, consumes more HCO₃^&#x2212; than is added during the remainder of the treatment. In previous studies, we developed an analytical model that allows one to quantify these events and tested alternative protocols manipulating the rate of rise in blood bicarbonate concentration (HCO₃^&#x2212;). The protocol tested in this paper enforces a more gradual increase in blood HCO₃^&#x2212;, by means of a model-based staircase adjustment of bath HCO₃^&#x2212;. Model equations predict a reduction of buffer response and rate of organic acid production. These predictions are tested in 20 stable outpatients receiving hemodialysis. We find that the proposed protocol achieves the desired profile of blood HCO₃^&#x2212; with good accuracy and reduces the total buffer response by 1/3 and the rate of lactic acid production by at least 1/4, as compared to conventional therapy. Although more studies are needed, we believe that our work will pave the way for a more rational approach to correction of acidosis during hemodialysis. Article Highlights <list list-type="bullet"><list-item><label>&#x2022;</label> Our study tests an analytic model designed to enforce a more gradual rate of bicarbonate delivery during hemodialysis. </list-item><list-item><label>&#x2022;</label> Using our model, we show that we can reduce the excessive buffer response and lactic acid production that occur with the conventional approach. </list-item><list-item><label>&#x2022;</label> We demonstrate that our model can provide a rational approach to bicarbonate addition during treatment. </list-item> </list>

A machine learning–based clinical decision support algorithm for reducing unnecessary coronary angiograms

BackgroundConventional clinical risk scores and diagnostic algorithms are proving to be suboptimal in the prediction of obstructive coronary artery disease, contributing to the low diagnostic yield of invasive angiography. Machine learning could help better predict which patients would benefit from invasive angiography vs other noninvasive diagnostic modalities.ObjectiveTo reduce patient risk and cost to the healthcare system by improving the diagnostic yield of invasive coronary angiography through optimized outpatient selection.MethodsRetrospective analysis of 12 years of referral data from a provincial cardiac registry, including all patients referred for invasive angiography of more than 1.4 million individuals in Ontario, Canada. Stable outpatients undergoing coronary angiography during the study period were included in the analysis. The training set (80% random sample, n = 23,750) was used to develop 8 prediction models in Python using grid-search cross-validation. The test set (20% random sample, n = 5938), evaluated the discrimination performance of each model.ResultsThe machine-learning model achieved a substantially better performance (area under the receiver operating characteristics curve: 0.81) than existing models for predicting obstructive coronary artery disease in patients referred for invasive angiography. It significantly outperformed both the reference model and current clinical practice with a net reclassification index of 27.8% (95% confidence interval [CI]: [24.9%–30.8%], P value <.01) and 44.7% (95% CI: [42.4%–47.0%], P value <.01), respectively.ConclusionThis prediction model, when coupled with a point-of-care, online decision support tool to be used by referring physicians, could improve the diagnostic yield of invasive coronary angiography in stable, elective outpatients, thus improving patient safety and reducing healthcare costs.

Impact of citrus fruit intake on the mental health of patients with chronic heart failure

BackgroundThe full impact of the intake of citrus fruits on the risk of depression in individuals with chronic heart failure (HF) is unknown. Here, we examined the associations between the estimated habitual intakes of citrus fruits and depressive symptoms in patients with chronic HF. MethodsWe enrolled 150 stable outpatients with chronic HF who had a history of worsening HF. To assess the patients' daily dietary patterns, we used a brief self-administered diet-history questionnaire to calculate the daily consumption of foods and nutrients. To assess the patients' mental state, we used a nine-item Patient Health Questionnaire (PHQ-9). ResultsTwelve patients (8%) were identified as having moderate-to-severe depression (PHQ-9 score ≥10). The patients with PHQ-9 ≥10 had lower daily intakes of citrus fruits compared to those with no or mild depressive symptoms (PHQ-9 <10). The daily intakes of various antioxidants, including vitamin C, β-carotene, and β-cryptoxanthin, all of which are abundant in citrus fruits, were reduced in the patients with PHQ-9 ≥10, accompanied by higher serum levels of 8-isoprostane (an oxidative stress marker). A multivariate logistic regression analysis using forward selection showed that a lowered daily intake of citrus fruits was an independent predictor of the comorbidity of moderate-to-severe depression in patients with chronic HF, after adjustment for age, gender, and the hemoglobin value. ConclusionsA lower daily consumption of citrus fruits was associated with higher prevalence of depression in patients with chronic HF. Our findings support the hypothesis that a daily consumption of citrus fruits has a beneficial effect on the prevention and treatment of depression in chronic HF patients.

Pimavanserin for negative symptoms of schizophrenia: results from the ADVANCE phase 2 randomised, placebo-controlled trial in North America and Europe

Negative symptoms of schizophrenia are associated with adverse clinical outcomes, but there are few effective treatments. We aimed to assess the effects of pimavanserin, a selective 5-HT2A inverse agonist and antagonist, on negative symptoms of schizophrenia. The ADVANCE study was a phase 2, 26-week, randomised, double-blind, placebo-controlled study of pimavanserin in stable outpatients with schizophrenia aged 18-55 years with predominant negative symptoms. Patients were randomly assigned (1:1) across 83 sites (18 in North America and 65 in Europe) to receive pimavanserin or placebo daily, added to an ongoing antipsychotic medication, per a computer-generated schedule (stratification by geographical region). Eligible patients had a score of at least 20 on the sum of seven Positive and Negative Syndrome Scale (PANSS) Marder negative factor items (and scores of ≥4 on at least three or ≥5 on at least two of negative symptom items). The starting dosage of 20 mg of pimavanserin or placebo could be adjusted to 34 mg or 10 mg within the first 8 weeks of the study, after which dosage remained stable until the end of the study. Both pimavanserin and placebo were administered orally once daily as two individual tablets (pimavanserin tablets were either 10 mg or 17 mg). The primary endpoint was change in total score using the 16-item Negative Symptom Assessment (NSA-16) from baseline to week 26. Primary outcomes were analysed in patients who received at least one dose of the study drug and had NSA-16 assessments at baseline and at least once post-baseline (full analysis set). Safety outcomes were analysed in patients who had received at least one dose of the study drug. This trial is registered with ClinicalTrials.gov, NCT02970305, and is complete. Between Nov 4, 2016, and April 16, 2019, we randomly assigned 403 patients to pimavanserin (n=201; 131 [65%] male; 187 [93%] White) or placebo (n=202; 137 [68%] male, 186 (92%) White), of whom 400 were included in the efficacy analysis (199 in the pimavanserin group, 201 in the placebo group). Mean age was 37·7 years (SD 9·4) in the pimavanserin group and 36·7 (9·2) years in the placebo group. The change in total NSA-16 score from baseline to week 26 was significantly improved with pimavanserin (least squares mean -10·4 [SE 0·67]) versus placebo (least squares mean -8·5 [0·67]; p=0·043; effect size: 0·211). The number of patients with treatment-emergent adverse events (TEAEs) was similar between groups: 80 (40%) patients experienced TEAEs in the pimavanserin group and 71 (35%) in the placebo group. Most TEAEs were headache (6% [n=13] vs 5% [n=10]) and somnolence (5% [n=11] vs 5% [n=10]). One patient from the placebo group reported severe headache (0·5%), rhinorrhoea (0·5%), cough (0·5%), and influenza (0·5%). In the pimavanserin group, one patient reported severe toothache (0·5%), and two patients had worsening of schizophrenia (1%). Mean change in QTcF interval was higher with pimavanerin (4·5 ms [SD 18·0]) than with placebo (0·0 ms [16·0]). Stable patients with predominant negative symptoms of schizophrenia showed a reduction in negative symptoms after treatment with pimavanserin. However, given the small effect size, further investigation with optimised dosing is warranted to determine the clinical significance of this effect. Acadia Pharmaceuticals.

NT-proBNP as a marker for atrial fibrillation and heart failure in four observational outpatient trials.

AimsHeart failure (HF) and atrial fibrillation (AF) frequently coexist and are both associated with increased levels of N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP). It is known that AF impairs the diagnostic accuracy of NT‐proBNP for HF. The aim of the present study was to compare the diagnostic and predictive accuracy of NT‐proBNP for HF and AF in stable outpatients with cardiovascular risk factors.Methods and resultsData were obtained from the DIAST‐CHF trial, a prospective cohort study that recruited individuals with cardiovascular risk factors and followed them up for 12 years. Data were validated in three independent population‐based cohorts using the same inclusion/exclusion criteria: LIFE‐Adult (n = 2869), SHIP (n = 2013), and SHIP‐TREND (n = 2408). Serum levels of NT‐proBNP were taken once at baseline. The DIAST‐CHF study enrolled 1727 study participants (47.7% female, mean age 66.9 ± 8.1 years). At baseline, patients without AF or HF (n = 1375) had a median NT‐proBNP of 94 pg/mL (interquartile range 51;181). In patients with AF (n = 93), NT‐proBNP amounted to 667 (215;1130) pg/mL. It was significantly higher than in the first group (P < 0.001) and compared with those with only HF [n = 201; 158 (66;363) pg/mL; P < 0.001]. The highest levels of NT‐proBNP [868 (213;1397) pg/mL] were measured in patients with concomitant HF and AF (n = 58; P < 0.001 vs. control and vs. HF, P = 1.0 vs. AF). In patients with AF, NT‐proBNP levels did not differ between those with HF and preserved ejection fraction (EF) > 50% [n = 38; 603 (175;1070) pg/mL] and those without HF (P = 1.0). Receiver‐operating characteristic curves of NT‐proBNP showed a similar area under the curve (AUC) for the detection of AF at baseline (0.84, 95% CI [0.79–0.88]) and for HF with EF < 50% (0.78 [0.72–0.85]; P = 0.18). The AUC for HF with EF > 50% was significantly lower (0.61 [0.56–0.65]) than for AF (P = 0.001). During follow‐up, AF was newly diagnosed in 157 (9.1%) and HF in 141 (9.6%) study participants. NT‐proBNP was a better predictor of incident AF during the first 2 years (AUC: 0.79 [0.75–0.83]) than of newly diagnosed HF (0.59 [0.55–0.63]; P < 0.001). Data were validated in three independent population‐based cohorts (LIFE‐Adult, n = 2869; SHIP, n = 2013; and SHIP‐TREND, n = 2408).ConclusionsIn stable outpatients, NT‐proBNP is a better marker for prevalent and incident AF than for HF. In AF patients, the diagnostic value of NT‐proBNP for HF with EF > 50% is very limited.

Abstract 9856: Associations of a Polygenic Risk Score (PGS) with High Risk Coronary Artery Disease (CAD) in PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain)

Introduction: PGSs summarize the polygenic risk for CAD and may have clinical utility. We tested whether a previously validated PGS for CAD is associated with coronary CT angiography (CTA) findings predictive of future cardiovascular events in the PROMISE trial, which randomized individuals with stable outpatient chest pain to standard of care vs. CTA. Methods: This nested case-control study compared genotyped PROMISE participants with no CAD (0% stenosis), obstructive CAD (oCAD, ≥50% stenosis) or high-risk CAD defined as either oCAD ≥70% stenosis, CAC &gt;400, Leaman Score &gt; 5 (measure of stenosis and plaque burden), or any high-risk plaque feature (positive remodeling, low attenuation, napkin ring sign) on CTA. The Illumina Global Screening Array with imputation from the 1000 Genomes reference panel was used with LDpred to calculate ancestry-adjusted PGS. We calculated adjusted odds ratios (aORs) of oCAD and high-risk CAD for PGS quintiles 2-5 with quintile 1 as the referent using logistic regression and age, sex, and European Society of Cardiology pre-test probability (PTP) for obstructive CAD as covariates. Results: Among the 518 participants, 414=no CAD, 86=oCAD, and 103=high risk CAD (overlap of oCAD and high-risk CAD=85), the median age (±S.D.) was 58 (±7) years, 58% were female, and 13% were of non-white race or Hispanic ethnicity. Baseline characteristics, family history of premature CAD, PTP risk score and medications were similar across PGRS quintiles (all P&gt;0.2). After multivariate adjustment, PGRS quintile 5 was associated with significantly increased odds of oCAD ≥50% (aOR 6.09) and high-risk CAD (aOR 6.13) as compared with quintile 1. Conclusions: In a population of stable symptomatic outpatients, higher PGS was associated with oCAD and high-risk CAD on CTA, even after adjustment for age, sex and pretest probability of CAD. The PGS may be useful for risk stratification of outpatients with suspected CAD.

Abstract 13330: Deep Learning Algorithm Predicts Angiographic Diameter Stenosis in Stable Patients Using Only a Standard 12-lead Electrocardiogram

Introduction: Current standard electrocardiogram analysis algorithms cannot predict the presence and extent of coronary artery disease (CAD), especially in stable patients. Hypothesis: A novel artificial intelligence algorithm (ECGio) is able to predict the presence, location, and severity of coronary artery lesions in a minimally selected stable patient population as verified by coronary angiography. Methods: A cohort of 1659 stable outpatients were randomly divided into training (86%) and validation (14%) subsets, maintaining population characteristics. ECGio was trained and then validated using electrocardiograms paired with angiograms collected from electronic medical records. Coronary artery lesions were evaluated by a continuous measure of stenosis ranging from 0% - 100%. The prediction was then compared to the angiogram result (worst diameter stenosis in each vessel) with the error calculated per patient and per vessel. Results: In the primary analysis of the validation cohort, 22 had no angiographic CAD and were grouped with 56 patients with mild CAD (DS ≤30%), 31 had moderate CAD (DS 30-70%), and 113 had severe CAD (DS ≥70%). On a vessel level ECGio was able to predict stenosis severity with an overall average error of 16% as well as vessel specific errors of 18% in the LAD, 19% in the LCX, 18% in the RCA, and 8% in the Left Main. Absolute Error and Left Main error can be seen in the Figure. Conclusion: This validation study strongly suggests that it is possible to utilize an artificial intelligence algorithm to determine the presence and severity of CAD in stable patients using data from a standard 12- lead electrocardiogram.

Reference Equations for Assessing the Physical Activity of Japanese Patients with Chronic Obstructive Pulmonary Disease.

BackgroundTo improve physical activity (PA) in patients with chronic obstructive pulmonary disease (COPD), providing a target PA value based on the individual patient’s condition may be a useful interventional strategy. However, to determine the target value, a predictive PA value for each patient is required.Research QuestionWhat is the reference equation consisting of PA-related factors to determine the predictive PA value for each patient with COPD?Material and MethodsIn this prospective cross-sectional observational study, we measured the PA with a triaxial accelerometer and several other factors including demographic factors, pulmonary function, dyspnea, exercise capacity, muscle strength, nutrition, and indicators of several comorbidities in stable Japanese outpatients with COPD aged ≥40 years old and detected PA-related factors by a multiple regression analysis and stepwise method. We created reference equations for four indices of PA using multiple linear regression equations.ResultsTwo hundred and twenty-seven patients were registered. The equations of duration at ≥2.0 metabolic equivalents (METs) and step count consisted of 4 factors: 6-minute walk distance, modified Medical Research Council dyspnea scale, anxiety score of the Hospital Anxiety and Depression Scale, and the forced expiratory volume in 1 second % of predicted value. Those of duration at ≥3.0 METs and total activity at ≥3.0 METs consisted of 5 factors: the above 4 factors and age or brain natriuretic peptide. There was no fixed bias or proportional bias between the measured and predictive values in patients with non-high measured PA values.ConclusionWe determined reference equations for four indicators of PA using PA-related factors in Japanese patients with COPD. The predictive values calculated using the equations could be useful for deciding target PA values for each patient.Clinical Trial RegistrationUMIN-CTR; No.: UMIN000025459; URL: https://www.umin.ac.jp/ctr/index.htm.

Deconstructing emotion regulation in schizophrenia: the nature and consequences of abnormalities at the identification stage.

Existing evidence suggests that emotion regulation is abnormal in schizophrenia and associated with undesirable clinical outcomes. However, this literature is based predominantly on trait self-report and does not indicate which stages of emotion regulation (identification, selection, implementation) are impaired. The current study focused on determining the nature of abnormalities at the identification stage using ecological momentary assessment (EMA). Participants included clinically stable outpatients with schizophrenia (SZ; n = 48) and healthy controls (CN; n = 52) who completed 6days of EMA. The EMA surveys assessed emotional experience, emotion regulation, and symptoms. Results indicated that SZ identified the need to regulate at a higher rate than CN. Specifically, SZ displayed an inefficient threshold for identifying the need to regulate, such that they regulated too much when negative affect was low and too little when negative affect was high. Emotion regulation effort exertion was also inefficient, such that effort was too high at low levels of negative affect and too low at high levels of negative affect in SZ. These identification stage abnormalities also demonstrated differential associations with positive and negative symptoms. Findings suggest that identification stage abnormalities may create a bottleneck that feeds forward and impacts subsequent stages of emotion regulation in SZ that are critically related to symptoms. Targeting the psychological processes underlying these identification stage abnormalities might offer a novel means of treating positive and negative symptoms in schizophrenia.

Mindfulness, mood symptom tendencies and quality of life in bipolar disorder: An examination of the mediating influence of emotion regulation difficulties

BackgroundThe aim of this cross-sectional study was to investigate dispositional mindfulness and its association with depression and manic tendencies, and subjective life quality in bipolar disorder (BD). Furthermore, this study sought to examine the potential mediating effects of emotion regulation difficulties on these relationships. MethodTwenty-eight healthy controls (HC) and 66 clinically stable outpatients with a DSM-IV-TR diagnosis of BD completed the Mindfulness Attention Awareness Scale (MAAS), Difficulties in Emotion Regulation Scale (DERS), Seven Up (7 Up) Seven Down (7 Down) and the Quality of Life in Bipolar Disorder Questionnaire (QoL.BD). These variables were compared between groups and entered into a series of mediation analyzes using PROCESS in the BD group only. ResultsLower MAAS scores were detected amongst the BD patients compared to HCs. Lower MAAS scores in BD patients predicted higher 7 Up, 7 Down and lower QoL.BD scores. For the 7 Down and QoL.BD, the associations were completely mediated by DERS scores, with difficulties in strategy use and emotional clarity mediating the association between mindfulness and depressive tendencies and quality of life, respectively. No significant direct or indirect effects were detected for the 7 Up model. LimitationsThe cross-sectional design precludes causal inference. The MAAS conceptualises mindfulness as unidimensional. Self-report scales of depressive and manic tendencies utilised. ConclusionsThis study detected a significant association between dispositional mindfulness and depressive tendencies and life quality in BD, and found that these associations were influenced by emotion regulation difficulties. These findings encourage further investigation of mindfulness-based interventions in BD.

Prognostic value of changes in high-sensitivity cardiac troponin T beyond biological variation in stable outpatients with cardiovascular disease: a validation study

ObjectiveTo evaluate the prognostic implications of longitudinal long-term changes beyond the biological variation of high-sensitivity cardiac troponin T (hs-cTnT) in outpatients with stable or asymptomatic cardiovascular disease (CV) and to assess possible differences in the prognostic value while using reference change value (RCV) and minimal important differences (MID) as metric for biological variation.MethodsHs-cTnT was measured at index visit and after 12 months in outpatients presenting for routine follow-up. The prognostic relevance of a concentration change of hs-cTnT values exceeding the biological variation defined by RCV and MID of a healthy population within the next 12 months following the stable initial period was determined regarding three endpoints: all-cause mortality (EP1), a composite of all-cause mortality, non-fatal myocardial infarction and stroke (EP2), and a composite of all-cause mortality, non-fatal myocardial infarction, stroke, hospitalization for acute coronary syndrome (ACS) or decompensated heart failure, and planned and unplanned percutaneous coronary interventions (PCI, EP3).ResultsChange in hs-cTnT values exceeding the biovariability defined by MID but not by RCV discriminated a group with a higher cardiovascular risk profile. Changes within MID were associated with uneventful course (NPV 91.6–99.7%) while changes exceeding MID were associated with a higher occurrence of all endpoints within the next 365 days indicating a 5.5-fold increased risk for EP 1 (p = 0.041) a 2.4-fold increased risk for EP 2 (p = 0.049) and a 1.9-fold increased risk for EP 3 (p < 0.0001).ConclusionsIn stable outpatients MID calculated from hs-cTnT changes measured 365 ± 120 days apart are helpful to predict an uneventful clinical course.Clinical trials identifierNCT01954303.Graphic abstract

Mismatch negativity as an index of target engagement for excitation/inhibition-based treatment development: a double-blind, placebo-controlled, randomized, single-dose cross-over study of the serotonin type-3 receptor antagonist CVN058.

Serotonin type-3 receptor (5-HT3R) antagonists show potential as a treatment for cognitive deficits in schizophrenia. CVN058, a brain-penetrant, potent and selective 5-HT3R antagonist, shows efficacy in rodent models of cognition and was well-tolerated in Phase-1 studies. We evaluated the target engagement of CVN058 using mismatch negativity (MMN) in a randomized, double-blind, placebo-controlled, cross-over study. Subjects were stable outpatients with schizophrenia or schizoaffective disorder treated with antipsychotics. Subjects were not permitted to use other 5-HT3R modulators or serotonin reuptake inhibitors. Each subject received a high (150 mg) and low (15 mg or 75 mg) oral dose of CVN058 and placebo in a randomized order across 3 single-day treatment visits separated by at least 1 week. The primary pre-registered outcome was amplitude of duration MMN. Amplitude of other MMN deviants (frequency, intensity, frequency modulation, and location), P50, P300 and auditory steady-state response (ASSR) were exploratory endpoints. 19 of 22 randomized subjects (86.4%) completed the study. Baseline PANSS scores indicated moderate impairment. CVN058 150 mg led to significant improvement vs. placebo on the primary outcome of duration MMN (p = 0.02, Cohen's d = 0.48). A significant treatment effect was also seen in a combined analysis across all MMN deviants (p < 0.001, d = 0.57). Effects on location MMN were independently significant (p < 0.007, d = 0.46). No other significant effects were seen for other deviants, doses or EEG measures. There were no clinically significant treatment related adverse effects. These results show MMN to be a sensitive target engagement biomarker for 5-HT3R, and support the potential utility of CVN058 in correcting the excitatory/inhibitory imbalance in schizophrenia.

247: Evaluation of an educational intervention that supports patient self-management of medications in stable adult outpatients with cystic fibrosis

247: Evaluation of an educational intervention that supports patient self-management of medications in stable adult outpatients with cystic fibrosis

Deep learning algorithm predicts angiographic coronary artery disease in stable patients using only a standard 12-lead electrocardiogram

Abstract Background Current standard electrocardiogram analysis algorithms cannot predict the presence and extent of coronary artery disease (CAD), especially in stable patients. Objectives This study assessed the ability of a novel artificial intelligence algorithm (ECGio) to predict the presence, location, and severity of coronary artery lesions in an unselected stable patient population. Methods A cohort of 1659 stable outpatients were randomly divided into training (86%) and validation (14%) subsets, maintaining population characteristics. ECGio was trained and then validated using electrocardiograms paired with angiograms collected from electronic medical records. Coronary artery lesions were classified in two analyses. The primary classification was no/mild (≤30% diameter stenosis [DS]) vs moderate (30–70% DS) vs severe (≥70% DS) CAD; and the secondary classification was yes/no based on ≥50% DS in any vessel. Results In the primary analysis of the validation cohort, 22 had no angiographic CAD and were grouped with 56 patients with mild CAD (DS ≤30%), 31 had moderate CAD (DS 30–70%), and 113 had severe CAD (DS ≥70%). The weighted average sensitivity was 93.6%, and the weighted average specificity was 96.5%. In the secondary analysis of the validation cohort, 93 had significant CAD; and 128 did not have significant CAD. There was a sensitivity of 93.1% and specificity of 85.6% in determining the presence of clinically significant disease (≥50% DS) in at least one vessel. On a vessel level ECGio was able to predict stenosis severity with average error in the LAD of 18%, the LCX of 19%, the RCA of 18%, and the LM of 8%. Conclusion This validation study strongly suggests that it is possible to utilize an artificial intelligence algorithm to determine the presence and severity of CAD in stable patients using data from a standard 12-lead electrocardiogram. Funding Acknowledgement Type of funding sources: None. Confusion MatrixROC Curve