Assessment of the disease severity in patients hospitalized for COVID-19 based on the National Early Warning Score (NEWS) using statistical and machine learning methods: An electronic health records database analysis.

BACKGROUND: The coronavirus disease 2019 (COVID-19) was a cause of concern in the healthcare system and increased the need for disease severity indicators. However, they still vary in use to evaluate in-hospital outcomes and severity. The National Early Warning Score (NEWS) is routinely used to evaluate patient health status at the hospital. Further research is needed to ensure if NEWS can be a good instrument for an overall health status assessment with or without additional information like laboratory tests, intensive care needs, and history of chronic diseases. OBJECTIVE: To evaluate if NEWS can be an indicator to measure COVID-19 patient status in-hospital. METHODS: We used the fully anonymized Electronic Health Records (EHR) characterizing patients admitted to the hospital with COVID-19. Data was obtained from Vilnius University Hospital Santaros Klinikos EHR system (SANTA-HIS) from 01-03-2020 to 31-12-2022. The study sample included 3875 patients. We created several statistical and machine learning models for discrimination between in-hospital death/discharge for evaluation NEWS as a disease severity measure for COVID-19 patients. In these models, two variable sets were considered: median NEWS and its combination with clinical parameters and medians of laboratory test results. Assessment of models' performance was based on the scoring metrics: accuracy, sensitivity, specificity, area under the ROC curve (AUC), and F1-score. RESULTS: Our analysis revealed that NEWS predictive ability for describing patient health status during the stay in the hospital can be increased by adding the patient's age at hospitalization, gender, clinical and laboratory variables (0.853 sensitivity, 0.992 specificity and F1-score - 0.859) in comparison with single NEWS (0.603, 0.995, 0.719, respectively). A comparison of different models showed that stepwise logistic regression was the best method for in-hospital mortality classification. Our findings suggest employing models like ours for advisory routine usage. CONCLUSION: Our model demonstrated incremental value for COVID-19 patient's status evaluation.

The association of catestatin and endocan with the effects of cardiac shock wave therapy: Biomarker sub-study of the randomized, sham procedure-controlled trial.

Introduction: Cardiac shock-wave therapy (CSWT) is a non-invasive regenerative treatment method based on low-frequency ultrasound waves, which stimulate angiogenesis. Current data about the effects of revascularization procedures on angiogenesis biomarkers is limited. Recently, an association of catestatin and endocan with coronary collateral development was shown in several trials. In this study, we aimed to evaluate the impact of CSWT on the dynamics of catestatin and endocan levels and to assess their correlation with parameters of myocardial perfusion and function. Methods: Prospective, randomized, triple-blind, sham procedure-controlled study enrolled 72 adult subjects who complied with defined inclusion criteria (NCT02339454). We measured biomarkers in 48 patients with stable angina (24 patients of CSWT group, 24 patients of sham-procedure group). Additionally, patients were divided into responders and non-responders according to improvement in myocardial perfusion and/or contractility assessed by myocardial scintigraphy and dobutamine echocardiography (30 and 13 patients, respectively). The blood samples were collected at baseline, after the last treatment procedure (9th treatment week) and at 6-month follow-up to evaluate biomarkers concentration and stored at -80° until analysis. Serum catestatin and endocan levels were determined by commercially available ELISA kits. Results: Serum catestatin concentration significantly increased in all patients. While endocan levels significantly decreased in the responders sub-group. The increase in catestatin levels at 9th week and 6 months was positively associated with improvement in summed difference score (rho = 0.356, p = 0.028) and wall motion score, WMS (rho = 0.397, p = 0.009) at 6 months in the whole study population. Meanwhile, the decrease in endocan levels over 6 months was positively correlated with improvement in WMS at 3- and 6- months (r = 0.378, p = 0.015 and r = 0.311, p = 0.045, respectively). ROC analysis revealed that a change at 6 months in catestatin and endocan levels significantly predicted improvement in myocardial perfusion and contractile function with 68.9% sensitivity and 75.0% specificity (p = 0.039) and 51.7% sensitivity, and 91.7% specificity (p = 0.017), respectively. Baseline endocan concentration and its change at 6 months predicted response to CSWT with 68.8% sensitivity and 83.3% specificity (p = 0.039) and 81.3% sensitivity and 100% specificity (p < 0.0001), respectively. Conclusion: This study demonstrates the association of increase in catestatin and decrease in endocan levels with the improvement of myocardial perfusion and contractile function. The potential predictive value of catestatin and endocan dynamics for the response to regenerative therapy is shown.

Epidemiology of Chronic Obstructive Pulmonary Disease (COPD) Comorbidities in Lithuanian National Database: A Cluster Analysis.

Various comorbidities and multimorbidity frequently occur in chronic obstructive pulmonary disease (COPD), leading to the overload of health care systems and increased mortality. We aimed to assess the impact of COPD on the probability and clustering of comorbidities. The cross-sectional analysis of the nationwide Lithuanian database was performed based on the entries of the codes of chronic diseases. COPD was defined on the code J44.8 entry and six-month consumption of bronchodilators. Descriptive statistics and odds ratios (ORs) for associations and agglomerative hierarchical clustering were carried out. 321,297 patients aged 40-79 years were included; 4834 of them had COPD. A significantly higher prevalence of cardiovascular diseases (CVD), lung cancer, kidney diseases, and the association of COPD with six-fold higher odds of lung cancer (OR 6.66; p < 0.0001), a two-fold of heart failure (OR 2.61; p < 0.0001), and CVD (OR 1.83; p < 0.0001) was found. Six clusters in COPD males and five in females were pointed out, in patients without COPD-five and four clusters accordingly. The most prevalent cardiovascular cluster had no significant difference according to sex or COPD presence, but a different linkage of dyslipidemia was found. The study raises the need to elaborate adjusted multimorbidity case management and screening tools enabling better outcomes.

Structure and Distribution of Health Care Costs across Age Groups of Patients with Multimorbidity in Lithuania.

BACKGROUND: Patients with multimorbidity account for ever-increasing healthcare resource usage and are often summarised as big spenders. Comprehensive analysis of health care resource usage in different age groups in patients with at least two non-communicable diseases is still scarce, limiting the quality of health care management decisions, which are often backed by limited, small-scale database analysis. The health care system in Lithuania is based on mandatory social health insurance and is covered by the National Health Insurance Fund. Based on a national Health Insurance database. The study aimed to explore the distribution, change, and interrelationships of health care costs across the age groups of patients with multimorbidity, suggesting different priorities at different age groups. METHOD: The study identified all adults with at least one chronic disease when any health care services were used over a three-year period between 2012 and 2014. Further data analysis excluded patients with single chronic conditions and further analysed patients with multimorbidity, accounting for increasing resource usage. The costs of primary, outpatient health care services; hospitalizations; reimbursed and paid out-of-pocket medications were analysed in eight age groups starting at 18 and up to 85 years and over. RESULTS: The study identified a total of 428,430 adults in Lithuania with at least two different chronic diseases from the 32 chronic disease list. Out of the total expenditure within the group, 51.54% of the expenses were consumed for inpatient treatment, 30.90% for reimbursed medications. Across different age groups of patients with multimorbidity in Lithuania, 60% of the total cost is attributed to the age group of 65-84 years. The share in the total spending was the highest in the 75-84 years age group amounting to 29.53% of the overall expenditure, with an increase in hospitalization and a decrease in outpatient services. A decrease in health care expenses per capita in patients with multimorbidity after 85 years of age was observed. CONCLUSIONS: The highest proportion of health care expenses in patients with multimorbidity relates to hospitalization and reimbursed medications, increasing with age, but varies through different services. The study identifies the need to personalise the care of patients with multimorbidity in the primary-outpatient setting, aiming to reduce hospitalizations with proactive disease management.

The effect of cardiac shock wave therapy on myocardial function and perfusion in the randomized, triple-blind, sham-procedure controlled study.

BACKGROUND: Recent triple-blind sham procedure-controlled study revealed neutral effects of the cardiac shock wave therapy (CSWT) on exercise tolerance and symptoms in patients with stable angina. Current data about the effects of CSWT on global and regional myocardial contractility and perfusion is limited. Hereby we report the results of an imaging sub-study that evaluated the capacity of CSWT to ameliorate myocardial ischemia induced during dobutamine stress echocardiography (DSE) and cardiac single photon emission computed tomography (SPECT). METHODS: Prospective, randomized, triple-blind, sham procedure-controlled study enrolled 72 adult subjects who complied with defined inclusion criteria. The subjects were assigned to the OMT + CSWT and the OMT + sham procedure study groups with 1:1 ratio. Application of the CSWT covered all segments of the left ventricle. Imaging ischemia tests were performed in 59 study patients: DSE and SPECT before the CSWT treatment and after 6 months, with DSE carried out additionally at 3 months after randomization. Co-primary endpoints of the study were: change in wall motion score index (WMSI), representing the stress-induced impairment of regional myocardial function, and change in summed difference score (SDS), representing the amount of perfusion defect. RESULTS: OMT + CSWT and OMT + sham procedure study groups included 30 and 29 patients, respectively. Regional myocardial contractility during DSE significantly improved at 3 months follow-up in OMT + CSWT group compared to baseline as shown by WMSI at stress (1.4 ± 0.4 vs 1.6 ± 0.4, p = 0.001), but not in OMT + sham procedure group (1.5 ± 0.3 vs 1.6 ± 0.4, p = 0.136). The difference in stress DSE results between both study groups disappeared after 6 months. SPECT results demonstrated a significant reduction of inducible ischemia in OMT + CSWT group compared to OMT + sham procedure group at 6 months follow-up (SDS dropped from 5.4 ± 3.7 to 3.6 ± 3.8 vs 6.4 ± 5.9 to 6.2 ± 5 respectively, p = 0.034). CONCLUSIONS: Cardiac shock wave treatment showed the ability to reduce stress-induced myocardial ischemia, as assessed by wall motion abnormalities and perfusion defects, compared to sham procedure. TRIAL REGISTRATION: Clinicaltrials.gov ( NCT02339454 ). The trial was registered retrospectively on 12 January 2015.

A randomized, triple-blind trial of cardiac shock-wave therapy on exercise tolerance and symptoms in patients with stable angina pectoris.

BACKGROUND: Despite major advances in managing coronary artery disease and continuous research on alternative techniques to enhance myocardial perfusion and reduce symptoms, coronary artery disease is still one of the leading causes of adult disability worldwide. Cardiac shock-wave therapy (CSWT) has shown promising results in the amelioration of myocardial ischemia in experimental studies; however, clinical results are limited to single-center, mostly uncontrolled and underpowered trials. The current study aimed to evaluate whether CSWT can improve exercise tolerance and relieve angina symptoms in addition to optimal medical treatment in patients with stable angina. PARTICIPANTS AND METHODS: A prospective, randomized, triple blind, sham-procedure-controlled study was carried out. The primary endpoint was total exercise duration in the modified Bruce treadmill test at the 6-month follow-up. The secondary endpoints were changes in ST-segment depression during the treadmill test, angina symptoms during the treadmill test, number of angina attacks per week, number of sublingual nitroglycerin consumption per week, Canadian Cardiovascular Society angina functional class, and the Seattle Angina Questionnaire score at the 6-month follow-up. Patients were randomized at a 1 : 1 ratio to optimal medical plus cardiac shock-wave therapy (OMT+CSWT) and optimal medical therapy with sham procedure (OMT+placebo) groups. RESULTS: The mean exercise time improved in both study arms - CSWT and placebo treatment - at the 3- and 6-month follow-up, without a significant difference between groups. The magnitude and frequency of peak exercise ST-segment depression reduced significantly in the CSWT+OMT group compared with the OMT+placebo group at the 6-month follow-up (51.4 vs. 90.6%, P=0.001). Percentage of angina-free patients increased progressively in both groups throughout the study. The Seattle Angina Questionnaire scores improved significantly in both arms for four of five domains at the 3- and the 6-month follow-up. Numerically, although insignificant, the decrease in the number of angina episodes was more prominent in the OMT+CSWT group compared with the OMT+placebo group. CONCLUSION: The total exercise duration in the modified Bruce treadmill test at the 6-month follow-up did not differ significantly in patients treated with CSWT compared with optimal medical therapy alone. In addition, CSWT exerted a neutral effect on the quality of life and level of angina.

Efficacy of cardiac shock wave therapy in patients with stable angina: The design of randomized, triple blind, sham-procedure controlled study.

OBJECTIVE: Despite revascularization and optimal medical treatment (OMT), patients with angina often have a reduced quality of life due to inadequate relief from symptoms. Recent studies have shown that the application of shock waves may reduce angina symptoms and improve quality of life, exercise capacity, and myocardial perfusion due to the stimulation of angiogenesis. However, there is limited evidence due to small, single-arm, single-center studies of low to moderate quality. The purpose of this study is to evaluate the impact of cardiac shock wave therapy (CSWT) on exercise tolerance and angina symptoms in patients with coronary artery disease and objective evidence of myocardial ischemia who cannot undergo traditional revascularization and experience angina despite OMT in comparison to sham procedure. METHODS: We designed a randomized, triple-blind, placebo-controlled, multicentre trial (NCT02339454) to assess the efficacy of CSWT in addition to OMT in patients with stable angina and myocardial ischemia documented by exercise treadmill test (ETT). All patients were treated with stable doses of standard medical treatment 4 weeks before screening. An increase in the total exercise duration on ETT by ≥90 s from the baseline at the end of the study was set as the primary endpoint. Secondary endpoints included angina class, Seattle angina questionnaire scores, symptoms, and ECG changes during stress test. Patients underwent nine sessions of CSWT or corresponding sham procedure applied to all segments of the left ventricle, within 9 weeks. Endpoint assessments were performed at 6-month follow-up. The imaging substudies assessed the potential of CSWT to reduce stress-induced myocardial ischemia detected by dobutamine stress echocardiography, cardiac single-photon emission computed tomography, and cardiac magnetic resonance imaging. RESULTS: At two centers, 72 of the 323 screened patients were randomized in two groups (ratio 1:1): active treatment and placebo control. Study patients were predominantly males (70.8%); the mean age of the patients was 68.4±8.3 years. Of these, 44 patients had angina Canadian Cardiovascular Society class III, and 66.7% of the patients had a history of myocardial infarction. CONCLUSION: Using sham applicators, blinding study participants, investigators, and endpoints assessors to the study data as well as centralized randomization ensures rigorous methodology and low risk of bias in this large randomized controlled CSWT study.

Cardiac shock-wave therapy in the treatment of coronary artery disease: systematic review and meta-analysis.

AIM: To systematically review currently available cardiac shock-wave therapy (CSWT) studies in humans and perform meta-analysis regarding anti-anginal efficacy of CSWT. METHODS: The Cochrane Controlled Trials Register, Medline, Medscape, Research Gate, Science Direct, and Web of Science databases were explored. In total 39 studies evaluating the efficacy of CSWT in patients with stable angina were identified including single arm, non- and randomized trials. Information on study design, subject's characteristics, clinical data and endpoints were obtained. Assessment of publication risk of bias was performed and heterogeneity across the studies was calculated by using random effects model. RESULTS: Totally, 1189 patients were included in 39 reviewed studies, with 1006 patients treated with CSWT. The largest patient sample of single arm study consisted of 111 patients. All selected studies demonstrated significant improvement in subjective measures of angina symptoms and/or quality of life, in the majority of studies left ventricular function and myocardial perfusion improved. In 12 controlled studies with 483 patients included (183 controls) angina class, Seattle Angina Questionnaire (SAQ) score, nitrates consumption were significantly improved after the treatment. In 593 participants across 22 studies the exercise capacity was significantly improved after CSWT, as compared with the baseline values (in meta-analysis standardized mean difference SMD = -0.74; 95% CI, -0.97 to -0.5; p < 0.001). CONCLUSIONS: Systematic review of CSWT studies in stable coronary artery disease (CAD) demonstrated consistent improvement of clinical variables. Meta-analysis showed a moderate improvement of exercise capacity. Overall, CSWT is a promising non-invasive option for patients with end-stage CAD, but evidence is limited to small sample single-center studies. Multi-center adequately powered randomised double blind studies are warranted.

Combination of single quantitative parameters into multiparametric model for ischemia detection is not superior to visual assessment during dobutamine stress echocardiography.

BACKGROUND: To evaluate if the combination of several quantitative parameters into a mathematical model would enhance the detection of myocardial ischemia during dobutamine stress echocardiography (DSE) when compared to conventional wall motion analysis. METHODS: In a prospective study design 151 patients (age 61.8 ± 9.2) in test group and 105 patients (age 64.0 ± 10.6) in validation group were selected and underwent DSE between January 2008 and December 2012. In all patients coronary angiography was performed within 6-8 weeks from DSE, considering at least one stenosis ≥50% per patient as significant coronary artery disease (CAD). Results of DSE visual assessment and myocardial velocity, strain and strain rate parameters derived from speckle tracking imaging were imported automatically to an originally created software. A mathematical model calculating prognosis of at least one stenosis per patient and stenosis in separate arteries was constructed. RESULTS: Myocardial ischemia was visually detected in 60 (39.7 %) and in 58 (54.2 %) patients of the test and validation group, respectively. A total of 76 (50.3 %) patients in the test group and 69 patients (65.7 %) in the validation group had ≥50% coronary stenosis. Sensitivity and specificity of the mathematical model per patient in the test group were 91.6 % and 86.3 % compared to 76.8 % and 89.0 % of the visual assessment, respectively. However, in the validation group the sensitivity, specificity, positive predictive value and negative predictive value dropped down significantly becoming lower to visual assessment. CONCLUSIONS: Myocardial deformation imaging may potentially replace visual assessment with an automated predictive model for stress-induced ischemia detection. However, a multiparametric mathematical model based on quantitative deformation markers did not demonstrate incremental value to visual assessment of wall motion.

Long-term results of minimally invasive stand-alone bi-atrial surgical ablation with a bipolar ablation device for persistent and longstanding persistent AF: a single-center case series of 91 patients.

BACKGROUND: Minimally invasive surgical treatment of lone atrial fibrillation (AF) is an alternative for AF that is refractory to medical treatment. We present long-term results of standalone surgical ablation of AF using a bipolar ablation device in 91 consecutive patients. METHODS: This was an observational, retrospective study of 91 patients (77 % males; mean age, 53 ± 10 years [range, 23-75 years]) who underwent minimally invasive standalone surgical ablation of persistent and longstanding persistent AF using a bipolar ablation device from 2008 to 2014. Mean follow-up was 60 ± 21 months. The absence of arrhythmia was confirmed at 3, 6, and 12 months, and annually thereafter, with 24-hour Holter monitoring. RESULTS: The mean duration of preoperative AF was 6.5 ± 5.4 years. Persistent AF was present in 86 % of patients and longstanding persistent AF in 14 %. Mean left atrial diameter was 4.3 ± 0.8 cm. There were two postoperative strokes (2 %) and three conversions to median sternotomy (3 %). Permanent pacemakers were implanted in six (7 %) patients. There were no intra- or postoperative deaths. At 1, 2, 3, 4, and 5 years postoperatively, freedom from AF was 59, 45, 41, 38, and 38 % of patients, respectively. The failure to achieve pulmonary vein isolation was the only independent predictor of long-term recurrence of AF (HR -3 [95 % CI 1,858 to 8,586], p = 0,001). There was a tendency towards higher rates of SR at long term follow up in patients with pulmonary vein isolation if division of ligament of Marshall was performed (HR - 2 [95 % CI 0.987 to 4,202], p = 0,067). CONCLUSIONS: In the present series, the efficacy of epicardial surgical ablation was similar to that reported previously. The rate of arrhythmia recurrence increased over time. Achieving pulmonary vein isolation is essential to AF elimination. The division of ligament of Marshall could contribute to improved rates of SR restoration in patients with persistent or long-standing persistent AF if PVI is achieved.

Impact of renal sympathetic denervation on cardiac sympathetic nerve activity evaluated by cardiac MIBG imaging.

AIMS: The objective of the present study was to investigate an effect of renal artery sympathetic denervation (RASD) on patients with resistant hypertension and RASD effect on cardiac sympathetic nerve activity. It is known that an abnormally activated sympathetic tone is associated with progression of heart failure (HF). METHODS AND RESULTS: We investigated 16 patients with resistant arterial hypertension (mean age 54.88±7.89 years, mean 24-hr ambulatory blood pressure [BP] systolic 161.07±20.12 mmHg, diastolic 97.6±16.25 mmHg, using 6.44±0.96 antihypertensive drugs), who underwent bilateral RASD. Echocardiography, 24-hr ambulatory BP and 123I-metaiodobenzylguanidine (123I-MIBG) scintigraphy were performed before and six months after RASD. There were no significant changes in 24-hr ambulatory systolic and diastolic BP before RASD and six months after it: systolic BP before RASD was 161.07±20.12 mmHg and 144.93±17.27 mmHg after (p=0.050); diastolic BP before RASD was 97.6±16.25 mmHg and 89.87±12.33 mmHg after (p=0.182). We observed a significant change in cardiac sympathetic nerve activity assessed by 123I-MIBG scintigraphy, as an increase of late heart-to-mediastinum (H/M) ratio, varying from 2.21±0.47 to 2.35±0.52 m/s (p=0.02). CONCLUSIONS: Selective RASD significantly reduces cardiac sympathetic overdrive assessed by 123I-MIBG scintigraphy. Presumably, this positively affects HF progression in patients with resistant arterial hypertension.