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Abstract Background First generation Bruton tyrosine kinase inhibitors (BTKi) such as ibrutinib have been associated with cardiovascular toxicities. Newer generation BTKi (e.g.,acalabrutinib and zanabrutinib) have been associated with lower incidence of cardiotoxicity in clinical trials. Objective Given paucity in real-world data on the overall cardiac risk factor profile, especially with the newer BTKi, our study evaluated the incidence of cardiotoxicity with various BTKi among a large, commercially insured population of patients. Methods We performed a retrospective cohort analysis of all adults with a diagnosis of B-cell malignancy undergoing treatment with BTKi acalabrutinib and ibrutinib between January 2018 and June 2020 using Optum’s de-identified Clinformatics® Data Mart Database. We then identified patients who had pre-existing cardiac disease one year prior to starting BTKi. New incidence of atrial fibrillation/flutter, hypertension, bleeding, ventricular tachycardia/fibrillation and sudden cardiac death from the time of index presciption were compared with standard Chi Square or Student t-test where appropriate. Multivariate logistic regression models were also estimated to evaluate for confounding. Results A total of 1691 patients were included in the final analysis. 1595 (94%, median age 75 (19–90) years, 61% male gender) patients received ibrutinib, and 96 (6%, median age 73.5 (32–90) years, 62.5% male gender) patients received acalabrutinib. The median duration of drug exposure of ibrutinib was 238 (2-1084) days vs. 150 (30–870) days for acalabrutinib. There was lower new incidence of atrial fibrillation/flutter (4.6%-vs-17%, p = 0.013), hypertension (6.3%-vs-25%, p = NS), sudden cardiac arrest/death (0% vs. 1.5%, p = NS) in the acalabrutinib group compared to ibrutinib, of which only the lower incidence of atrial fibrillation/flutter was statistically significant. This was despite the finding of a higher prevalence of atrial fibrillation/flutter at baseline in patients receiving acalabrutinib. Conclusions There was lower incidence of new atrial fibrillation/flutter with acalabrutinib when compared to ibrutinib in a real-world cohort of patients. more...

This paper advances real-time cursor control for individuals with motor impairments through a novel brain–computer interface (BCI) system based solely on motor imagery. We introduce an enhanced deep neural network (DNN) classifier integrated with a Four-Class Iterative Filtering (FCIF) technique for efficient preprocessing of neural signals. The underlying approach is the Four-Class Filter Bank Common Spatial Pattern (FCFBCSP) and it utilizes a customized filter bank for robust feature extraction, thereby significantly improving signal quality and cursor control responsiveness. Extensive testing under varied conditions demonstrates that our system achieves an average classification accuracy of 89.1% and response times of 663 milliseconds, illustrating high precision in feature discrimination. Evaluations using metrics such as Recall, Precision, and F1-Score confirm the system’s effectiveness and accuracy in practical applications, making it a valuable tool for enhancing accessibility for individuals with motor disabilities. more...

This paper presents an advanced approach for EEG artifact removal and motor imagery classification using a combination of Four Class Iterative Filtering and Filter Bank Common Spatial Pattern Algorithm with a Modified Deep Neural Network (DNN) classifier. The research aims to enhance the accuracy and reliability of BCI systems by addressing the challenges posed by EEG artifacts and complex motor imagery tasks.The methodology begins by introducing FCIF, a novel technique for ocular artifact removal, utilizing iterative filtering and filter banks. FCIF's mathematical formulation allows for effective artifact mitigation, thereby improving the quality of EEG data. In tandem, the FC-FBCSP algorithm is introduced, extending the Filter Bank Common Spatial Pattern approach to handle four-class motor imagery classification. The Modified DNN classifier enhances the discriminatory power of the FC-FBCSP features, optimizing the classification process.The paper showcases a comprehensive experimental setup, featuring the utilization of BCI Competition IV Dataset 2a & 2b. Detailed preprocessing steps, including filtering and feature extraction, are presented with mathematical rigor. Results demonstrate the remarkable artifact removal capabilities of FCIF and the classification prowess of FC-FBCSP combined with the Modified DNN classifier. Comparative analysis highlights the superiority of the proposed approach over baseline methods and the method achieves the mean accuracy of 98.575%. more...

Objective: The objective was to evaluate the clinical experience and treatment patterns of generic dapagliflozin usage in different patient profiles in Indian settings. Materials and Methods: A retrospective, multicentric, real-world study included patients with type 2 diabetes mellitus (T2DM) (aged >18 years), inadequately controlled by existing antidiabetic therapy and receiving generic dapagliflozin as an add-on to existing oral antidiabetic drug(s) with or without insulin or switch therapy. Baseline characteristics and treatment-related outcomes were retrieved from the medical records and analyzed. Results: A total of 1935 patients were included, of which 1279 (66.1%) were males. The mean age was 57.4 years, and around half of the patients (51.4%) were aged from 45 to 60 years. Hypertension (55.9%) and dyslipidemia (19.8%) were the common comorbidities. The majority (n = 1122; 60%) of patients received dapagliflozin in combination with one or two antihyperglycemic drugs. More than half of the patients received metformin (56.8%) or sulfonylurea (52.3%) in combination with dapagliflozin. A dose of 10 mg (93.4%) was the most commonly used dose of dapagliflozin. The mean levels of glycated hemoglobin, fasting plasma glucose, and postprandial plasma glucose were significantly reduced to 1.1% (1.0–1.1), 30.5 mg/dL (29.2–31.9), and 57.5 mg/dL (55.1–59.9), respectively, after the initiation of dapagliflozin. A total of 1935 patients experienced weight changes during the treatment, of which 90.5% of patients showed weight loss. Hypoglycemic events were reported in 12.5% of patients. Physician global evaluation of efficacy and tolerability showed a majority of patients on a good-to-excellent scale (97.3% and 97.1%). Conclusion: Generic dapagliflozin showed a significant improvement in glycemic parameters and reduced body weight with low hypoglycemic events. The administration of dapagliflozin provided a good-to-excellent efficacy and tolerability profile in patients with T2DM. To the best of our knowledge, this is the first study confirming the efficacy, safety, and usefulness of generic dapagliflozin in patients with T2DM. more...

The coronavirus disease 2019 (COVID-19) public health emergency necessitated changes in health care delivery that will have lasting implications. The University of Pennsylvania Health System is a large multihospital system with an academic medical center at its core. To continue to care for patients with and without COVID-19, the system had to rapidly deploy telemedicine. We describe the challenges faced with the existing telemedicine infrastructures, the central mechanisms created to facilitate the necessary conversions, and the workflow changes instituted to support both inpatient and outpatient activities for thousands of providers, many of whom had little or no experience with telemedicine. We also discuss innovations that occurred as a result of this transition and the future of telemedicine at our institution. more...

Background: There is limited evidence regarding the impact of cardiology involvement in the care of cancer patients. Objectives: This study evaluated the impact of cardiology involvement on guideline-adherent cardiovascular monitoring and risk factor management in patients with breast cancer treated with trastuzumab. Methods: In a single-center retrospective cohort study, electronic health records from 1,047 patients with breast cancer receiving trastuzumab between January 2009 and July 2018 were evaluated. A visit to a cardiology provider beginning from the 3 months before cancer therapy initiation until the last contact date defined cardiology involvement. Guideline-adherent monitoring, defined by echocardiography assessment within the 4 months before trastuzumab initiation and follow-up echocardiography at least every 4 months during therapy, was compared in patients with and without cardiology involvement before treatment initiation. Multivariable associations between cardiology involvement and the time-varying risk factors blood pressure and body mass index (BMI) were assessed by using generalized estimating equations. Results: Cardiology involvement occurred in 293 (28%) patients. A higher proportion of patients with cardiology involvement before trastuzumab initiation had guideline-adherent monitoring (76.4% vs. 60.1%; p = 0.007). Cardiology involvement was associated with an average 1.5 mm Hg (95% CI: –2.9 to –0.1; p = 0.035) lower systolic blood pressure, which was more pronounced in those with hypertension (–2.7 mm Hg; 95% CI: –4.6 to –0.7; p = 0.007). Cardiology involvement was associated with a lower BMI in patients with baseline BMI ≥25 kg/m2 (mean difference: –0.5 kg/m2; 95% CI: –1.0 to –0.1; p = 0.027). Conclusions: Cardiology involvement in patients with breast cancer treated with trastuzumab is associated with greater adherence to cardiovascular monitoring and modest improvements in risk factor control. more...

Telemedicine utilization increased significantly in the United States during the COVID-19 pandemic. However, there is concern that disadvantaged groups face barriers to access based on single-center studies. Whether there has been equitable access to telemedicine services across the US and during later parts of the pandemic is unclear. This study retrospectively analyzes outpatient medical encounters for patients 18 years of age and older using Healthjump-a national electronic medical record database-from March 1 to December 31, 2020. A mixed effects multivariable logistic regression model was used to assess the association between telemedicine utilization and patient and area-level factors and the odds of having at least one telemedicine encounter during the study period. Among 1,999,534 unique patients 21.6% had a telemedicine encounter during the study period. In the multivariable model, age [OR = 0.995 (95% CI 0.993, 0.997); p more...

Patients with cancer are often at elevated risk for cardiovascular disease due to overlapping risk factors and cardiotoxic anticancer treatments. Their cancer diagnoses may be the predominant focus of clinical care, with less of an emphasis on concurrent cardiovascular risk management. Widely adopted technology platforms, including electronic health records and mobile devices, can be leveraged to improve the cardiovascular outcomes of these patients. These technologies alone may be insufficient to change behavior and may have greater impact if combined with behavior change strategies. Behavioral economics is a scientific field that uses insights from economics and psychology to help explain why individuals are often predictably irrational. Combining insights from behavioral economics with these scalable technology platforms can positively impact medical decision-making and sustained healthy behaviors. This review focuses on the principles of behavioral economics and how “nudges” and scalable technology can be used to positively impact clinician and patient behaviors. more...

Sex- and gender-specific training for cardiovascular clinicians is essential to enhance knowledge and quality of women’s cardiovascular health care. In 2016, the University of Pennsylvania cardiovascular fellowship program established a dedicated women’s cardiovascular health curriculum, motivated by the fellow-in-training desire to gain formal and focused training in this emerging field. more...

Obesity is one of the major factors contributing to noncommunicable diseases (NCDs), which is associated with a high intake of a sugar-rich diet. Sugar blend (a novel combination of sugar and stevia) has half the calories of sugar with the same sweetness at recommended use and offers better compliance. A randomized controlled trial was conducted to evaluate the efficacy and safety of this sugar blend in normal to mildly overweight subjects with a body mass index (BMI) of 23–26 kg/m. Sixty subjects were categorized into Group A: Sugar group (n = 30), and Group B: Sugar blend group (n = 30). The primary outcomes evaluated were weight, waist circumference, hip circumference, waist/hip ratio, BMI, and the secondary outcomes evaluated were lipid profile, random blood sugar, and HbA1c. All these parameters were assessed at baseline, 30 days, 60 days, and 90 days. Group B showed a significantly higher weight loss (p = 0.013) at 90 days compared with Group A. A significant reduction in waist circumference (p < 0.0001) by 4.4 cm was noted at 90 days, in addition to reduction in total cholesterol (p < 0.0001), triglyceride (p = 0.006), LDL cholesterol (p = 0.0490), and VLDL cholesterol (p = 0.006) in Group B compared with the baseline. The study revealed that the sugar blend is an effective formulation in reducing weight, anthropometric factors, and other related metabolic parameters. It has been proven to be well tolerated and promotes weight loss when used in conjunction with a daily balanced diet and exercise plan. more...

Background PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors represent a promising class of lipid‐lowering therapy, although their use has been limited by cost concerns. Methods and Results A retrospective cohort study was conducted using a nationwide commercial claims database comprising patients with atherosclerotic cardiovascular disease (ASCVD), aged 18 to 64 years. We identified the number of patients with ASCVD started on a PCSK9 inhibitor from the dates of US Food and Drug Administration approval in quarter 3 2015 through quarter 2 2019. Secondary objectives identified the proportions of patients started on a PCSK9 inhibitor in various ASCVD risk groups based on statin use and baseline low‐density lipoprotein cholesterol. We identified 126 419 patients with ASCVD on either PCSK9 inhibitor or statin therapy. Among these patients, 1168 (0.9%) filled a prescription for a PCSK9 inhibitor. The number of patients initiating a PCSK9 inhibitor increased from 2 patients in quarter 3 2015 to 119 patients in quarter 2 2019, corresponding to an increase from 0.05% to 2.5% of patients with ASCVD already on statins who started PCSK9 inhibitor therapy. Of patients with ASCVD with high adherence to a high‐intensity statin, 13 643 had low‐density lipoprotein cholesterol ≥70 mg/dL, and in this subgroup, 119 (0.9%) patients initiated a PCSK9 inhibitor. Conclusions Few patients started PCSK9 inhibitors from 2015 through mid‐2019, despite increasing trial evidence of efficacy, guidelines recommending PCSK9 inhibitors in high‐risk patients with ASCVD, and price reductions during this period. The magnitude of price reductions may not yet be sufficient to influence use management strategies aimed to limit PCSK9 inhibitor use. more...

Background: Focused cardiac ultrasound (FCU) is a safe and efficient diagnostic intervention for internal medicine physicians. FCU is a highly teachable skill, but is used in routine cardiac assessment in only 20% of surveyed training programs. We developed an FCU curriculum for internal medicine residents and an assessment tool to evaluate the impact of the curriculum on trainee knowledge and confidence. Methods: Internal medicine residents rotating through clinical cardiology services underwent 30 minutes of didactic and 60 minutes of hands-on teaching on acquisition and interpretation of FCU. A 20 item pre and post-curriculum online survey was administered (November 2018-December 2019) to assess confidence and knowledge in FCU. Results: 79 of 116 (68%) residents completed the pre-survey and 50 completed the post-survey, of whom 34 received the curriculum. The mean change in confidence score in those who received versus did not receive the curriculum was 0.99 versus 0.39 (p=0.046) on a 5-point Likert scale. Among 33 residents who had paired pre- and post-surveys the mean change in confidence score was 1.2 versus 0.85 (p more...

The development of pulmonary hypertension (PH) in patients with heart failure is associated with increased morbidity and mortality. In this article, the authors examine recent changes to the definition of PH in the setting of left heart disease (PH-LHD), and discuss its epidemiology, pathophysiology and prognosis. They also explore the complexities of diagnosing PH-LHD and the current evidence for the use of medical therapies, promising clinical trials and the role of left ventricular assist device and transplantation. more...

ABSTRACT IMPACT: Measuring and analyzing qualitative and quantitative traits using phenomics approaches will yield previously unrecognized heart failure subphenotypes and has the potential to improve our knowledge of heart failure pathophysiology, identify novel biomarkers of disease, and guide the development of targeted therapeutics for heart failure. OBJECTIVES/GOALS: Current classification schemes fail to capture the broader pathophysiologic heterogeneity in heart failure. Phenomics offers a newer unbiased approach to identify subtypes of complex disease syndromes, like heart failure. The goal of this research is to use data-driven associations to redefine the classification of the heart failure syndrome. METHODS/STUDY POPULATION: We will identify < 10 subphenotypes of patients with heart failure using unsupervised machine learning approaches for dense multidimensional quantitative (i.e. demographics, comorbid conditions, physiologic measurements, clinical laboratory, imaging, and medication variables; disease diagnosis, procedure, and billing codes) and qualitative data extracted from an integrated health system electronic health record. The heart failure subphenotypes we identify from the integrated health system electronic health record will be replicated in other heart failure population datasets using unsupervised learning approaches. We will explore the potential to establish associations between identified subphenotypes and clinical outcomes (e.g. all-cause mortality, cardiovascular mortality). RESULTS/ANTICIPATED RESULTS: We expect to identify < 10 mutually exclusive phenogroups of patients with heart failure that have differential risk profiles and clinical trajectories. DISCUSSION/SIGNIFICANCE OF FINDINGS: We will attempt to derive and validate a data-driven unbiased approach to the categorization of novel phenogroups in heart failure. This has the potential to improve our knowledge of heart failure pathophysiology, identify novel biomarkers of disease, and guide the development of targeted therapeutics for heart failure. more...

Background Regular physical activity reduces the risk of cardiovascular events, but most ischemic heart disease (IHD) patients do not obtain enough. Methods and Results ACTIVE REWARD (A Clinical Trial Investigating Effects of a Randomized Evaluation of Wearable Activity Trackers with Financial Rewards) was a 24‐week home‐based, remotely monitored, randomized trial with a 16‐week intervention (8‐week ramp‐up incentive phase and 8‐week maintenance incentive phase) and an 8‐week follow‐up. Patients used wearable devices to track step counts and establish a baseline. Patients in control received no other interventions. Patients in the incentive arm received personalized step goals and daily feedback for all 24 weeks. In the ramp‐up incentive phase, daily step goals increased weekly by 15% from baseline with a maximum of 10 000 steps and then remained fixed. Each week, $14 was allocated to a virtual account; $2 could be lost per day for not achieving step goals. The primary outcome was change in mean daily steps from baseline to the maintenance incentive phase. Ischemic heart disease patients had a mean (SD) age of 60 (11) years and 70% were male. Compared with control, patients in the incentive arm had a significantly greater increase in mean daily steps from baseline during ramp‐up (1388 versus 385; adjusted difference, 1061 [95% confidence interval, 386–1736]; P more...