bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel digital twin strategy to enable the translation of evidence from randomized control trials to new populations
Authors: Thangaraj P , Vasisht Shankar S , Oikonomou E , Khera R 
Published: October 2024

Abstract

Background
Randomized clinical trials (RCTs) are essential to guide medical practice; however, their generalizability to a given population is often uncertain. Between the SPRINT and ACCORD trials, only SPRINT found a significant reduction in major cardiovascular events (MACE) with intensive blood pressure control, but ACCORD did not, without clear evidence of whether this reflected differences in enrolled patients.

Purpose
To use a novel RCT digital twin-based approach to demonstrate the translation of an RCT to a different population, leveraging the differences in populations and treatment effects in SPRINT and ACCORD.

Methods
We developed a statistically informed Generative Adversarial Network (GAN) model that leverages relationships between covariates and outcomes using Directed Acyclic Graphs (DAGs). This model can generate a digital twin of an RCT (RCT-Twin) conditioned on covariate distributions from a second patient population while maintaining these relationships (Fig A). Using this, we generated the (i) RCT-Twin of SPRINT, which was conditioned on the 10 most disparate covariates drawn from ACCORD, and (ii) an RCT-Twin of ACCORD conditioned on SPRINT. To demonstrate treatment effect estimates of each RCT conditioned on the other RCT’s patient population, we evaluated the cardiovascular event-free survival of 10 iterations of these cross-trained RCT-Twins against the original trials.

Results
Using 9361 SPRINT participants and conditioning on 4733 ACCORD participants, we generated 10 ACCORD-conditioned SPRINT-Twin datasets. We confirmed that the RCT-Twins were consistently balanced between treatment and controls across all measured covariates (mean absolute standardized mean difference (MASMD) 0.019, SD 0.018), as expected for real RCTs. We also confirmed that covariates of the ACCORD-conditioned SPRINT-Twins were closer to ACCORD than SPRINT (MASMD 0.0082 vs 0.46, SD 0.016 vs 0.20), suggestive of successful conditioning. Most importantly, across iterations, ACCORD-conditioned SPRINT-Twin datasets reproduced the overall non-significant effect size seen in ACCORD (5-year MACE hazard ratio (95% confidence interval) of 0.88 (0.73-1.06) in ACCORD vs median 0.87 (0.68-1.13) in the ACCORD-conditioned SPRINT-Twins, Fig B), while the SPRINT-conditioned ACCORD-Twin datasets reproduced the significant effect size seen in SPRINT (0.75 (0.64-0.89) vs median 0.79 (0.72-0.86) in the SPRINT-conditioned ACCORD-Twins, Fig C).

Conclusions
Our novel conditioned digital twin approach simulates RCT-derived effects in different patient populations by translating these effects to the covariate distributions of the patients. This key methodological advance may enable the direct translation of RCT-derived effects into disparate patient populations and may enable causal inference in real-world settings.
Multiomic comparison of GLP1R analogues interaction networks
Authors: Wicik Z , Koutentakis M , Eyileten C , Nowak A , Motamedi P , Sourij H , Von Lewinski D , Postula M 
Published: October 2024

Abstract

Background
GLP1R analogs are drugs increasingly used in clinical practice in patients with type 2 diabetes, and obesity. Subsequent clinical trials indicate their beneficial effects, including cardioprotection, but the exact mechanisms of those actions are still not known.
Aim of the study: This study aims to understand how GLP1R analogs exert cardioprotective and therapeutic effects in patients with type 2 diabetes and obesity. Through analyzing GLP1R interaction networks and associated metabolomic and lipidomic data, we seek to uncover the molecular mechanisms underlying these effects and their potential therapeutic implications.

Methods
We performed an integrative analysis of four GLP1Ri interaction networks and associated metabolomic and lipidomic datasets. Interactomics revealed 130 common genes among semaglutide, exenatide, tirzapeptide, and retatrutide, primarily associated with diabetes-related processes, including obesity and hyperglycemia. Noteworthy findings encompassed ontological terms related to cardiovascular diseases (CVDs), such as hypertension, calcium regulation in cardiac cells, and amino acid accumulation-induced mTOR activation. Additionally, enrichment in gene sets linked to longevity, less recognized terms like fatty liver disease, chemokine signaling, and sirtuin interactome, were observed.

Results
Specific processes for tirzepatide included behavior-related terms and hydrochloric acid secretion, while retatrutide exhibited associations with fibrosarcoma, thinking and speaking disturbances, and adipogenesis signaling. Shared processes like primary ciliary dyskinesia differed in implicated genes. Metabolomics identified shared metabolites associated with diverse pathways, including galactose metabolism and nitric oxide-related pathways. Lipidomics highlighted enriched phenotypes and pathways, such as arachidonic acid metabolism and cholesterol biosynthesis.

Conclusion
Integration of interaction networks with metabolomic and lipidomic data revealed top interactors and impacted metabolites, shedding light on the intricate molecular landscape of GLP1Ri. These findings contribute valuable insights into the potential therapeutic implications and broader health considerations of GLP1R drugsfig1fig2
Association between warfarin and direct oral anticoagulants users and risk of mortality: cohort studies in England and Hong Kong
Authors: Wang Z , Matthewman J , Tazare J , Cheung K S , Chui C S L , Chan E W , Bhaskaran K , Smeeth L , Wong I C K , Douglas I J , Wong A 
Published: October 2024

Abstract

Background
The evidence of the association between warfarin and risk of mortality compared with direct oral anticoagulants (DOACs) has been mixed in current literature.

Purpose
To investigate the association between all-cause mortality and warfarin, compared with DOACs.

Methods
Population-based cohort studies were conducted using the data from the Hong Kong Clinical Data Analysis and Reporting System (CDARS) and United Kingdom Clinical Practice Research Datalink (CPRD) Aurum. People with atrial fibrillation aged ≥18 years who initiated warfarin or a DOAC during the study period (1st Jan 2014 - 31st Dec 2019) were identified. Follow-up started from the first date of oral anticoagulant prescription and ended at earliest of the date of death, the day before drug switching (between warfarin and DOACs), transferring out of the practice (CPRD Aurum only), last data collection date for the practice (CPRD Aurum only) or the end of study period. We estimated propensity score (PS) based on the list of potential confounders including demographics, co-morbidities, co-medications and polypharmacy. Cox proportional hazards regression model with PS-weighting was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).

Results
Among 227,190 new oral anticoagulant users, 54,367 (23.93%) died. The median follow-up was 2.96 and 2.45 years in CPRD and CDARS, respectively. Compared with DOAC use, a lower hazard of all-cause mortality was found in warfarin use (PS-weighted hazard ratio [HR]=0.94, 95% confidence interval [CI]=0.89-0.99) in CPRD; while a higher hazard was observed in warfarin users (PS-weighted HR=1.31, 95% CI=1.24-1.39) in CDARS, versus DOAC users. Consistent results were seen in both databases when stratified warfarin users by Time in Therapeutic Range (TTR). We observed a lower hazard of all-cause mortality in warfarin users with TTR≥65% (PS-weighted HR=0.90, 95% CI=0.85-0.94 in CPRD; 0.87, 0.79-0.96 in CDARS) and increased hazard in warfarin users with TTR&lt;65% (PS-weighted HR=1.37, 95% CI=1.25-1.49 in CPRD; 1.57, 1.48-1.66 in CDARS), versus DOAC users.

Conclusions
The hazard of all-cause mortality associated with warfarin compared with DOACs were found to be conflicting across databases. However, both databases consistently showed that an increased hazard of all-cause mortality was only found in warfarin users with TTR&lt;65% but not in those with TTR≥65%, suggesting that the differences in hazard of all-cause mortality associated with warfarin compared with DOAC, in part may depend on anticoagulation control in warfarin users. We recommend that warfarin users with poor INR control warrant closer clinical attention and could be considered for a switch to DOACs.
Comprehensive cardiac interval analysis in the WEAR-TECH study cohort by comparing the Apple Watch Series 6 against a simultaneous 12-lead ECG
Authors: Schramm D , Varini R , Briosa E Gala A , Banerjee A , Betts T 
Published: October 2024

Abstract

Background
Wearable devices capable of single-lead electrocardiograms (ECGs) are becoming increasingly prevalent. Exploring their potential for screening conditions beyond atrial fibrillation presents a compelling research opportunity.

Objective
This study evaluates the agreement between the Apple Watch Series 6 (APW) and simultaneous 12-lead ECG (12L) recordings in measuring PR, QRS, RR, QT, and QTc intervals in a cohort of National Health Service (NHS) cardiology patients.

Methods
We analysed data from the WEAR-TECH study, which included 400 simultaneous recordings from the APW and 12L ECGs. We included patients with ECGs in sinus rhythm and excluded patients with poor-quality ECGs. No exclusions were made based on underlying cardiac conditions. Measurements of the best three consecutive waveforms in leads I, II, and V5 were performed using EP Calipers (EP Studio) by a single observer. Leads I and II were compared for PR, QRS, and RR intervals, while leads I, II, and V5 were compared for QT and QTc intervals. QTc was calculated using Bazett’s formula. Differences between APW and 12L ECGs were assessed using linear mixed effects regression models with random intercepts and type II Wald chi-square tests. Clinical agreement was measured by averaging the waveforms from 12L leads and the APW and calculating the difference between the means.

Results
Out of 324 paired ECGs from 162 patients, 8 were excluded due to missing or uninterpretable data. The median age was 64 (IQR: 54 - 74) years, with 117 (75%) being male. PR, QRS, and RR intervals from the APW agreed best with 12L lead II, and QT and QTc intervals from APW agreed best with 12L lead V5, with no significant difference found in any of these comparisons. PR and RR intervals significantly differed between APW and 12L lead I, with the APW tending to overestimate relative to the 12L. Additionally, significant differences were found in 12L leads I and II for QT and QTc, with APW also tending to overestimate these intervals (see Table 1). Clinical agreement between the APW and all 12L leads was a minimum of 21% for a &lt;10ms difference, 45% for a &lt;20ms difference, and 71% for a &lt;40ms difference (see Figure 1).

Conclusions
The Apple Watch Series 6 demonstrates promising potential for initial outpatient monitoring of PR, QRS, RR, QT, and QTc intervals with reasonable agreement to 12L ECG. This is especially true in lead II for PR, QRS, and RR intervals and lead V5 for QT and QTc intervals. Further reductions in variance between APW and 12L ECG measurements could enhance clinical decision-making accuracy.Table 1:The p-values of APW vs 12L leadFigure 1:Agreement of APW to 12L leads
Meta-Heart Team: enhancing multidisciplinary heart teams through virtual reality in the metaverse
Authors: Skalidis I , Koliastasis L , Apostolos A , Mylonas K , Antiochos P , Maurizi N , Arangalage D 
Published: October 2024

Abstract

Introduction
Cardiovascular Multidisciplinary Heart Teams (MDHTs) are integral for patient management, but persistent challenges, including limited subspecialty expertise and time constraints, necessitate innovative approaches. This study explores the viability of conducting international Meta-Heart Team sessions utilizing virtual reality (VR) within the metaverse, aiming to address these challenges.

Methods
The Meta-Heart Team, comprising participants from diverse medical specialties and countries, engaged in VR sessions facilitated by VR headsets and web browsers. The immersive Aimedis metaverse platform recreated a three-dimensional hospital setting, complete with a dedicated Meta-Heart Team room featuring large screens displaying patient data such as coronary angiograms and echocardiograms. A 0-10 scale questionnaire evaluated participant experiences, covering technical quality, immersion, willingness to participate again, and overall satisfaction.

Results
The virtual environment effectively facilitated discussions on valvular heart disease cases among 10 participants, dedicating 15 minutes to each case. Technical stability was robust (90%), with only one participant experiencing internet disconnection. Positive participant feedback highlighted high ratings for technical quality (8.0±1.8) and engagement, a good immersive experience (8.0±1.3), willingness to participate again (9.2±0.8), and confidence in treatment decisions (80%). Despite a sense of digital fatigue reported by a few participants, the majority expressed that the VR session saved time compared to traditional meetings. Privacy concerns were acknowledged by 80% of participants.

Discussion
The virtual environment demonstrated potential in augmenting MDHT collaboration, providing advantages in global accessibility, multidimensional analysis, and adaptability. Participants recognized limitations in non-verbal communication and interpersonal connections but underscored the adaptability and effectiveness of the virtual setting. Technical challenges, including a single internet disconnection, emphasized the importance of a robust technical infrastructure. Privacy issues, digital fatigue, and potential exclusions were highlighted, prompting consideration of ethical guidelines and ongoing technological advancements.

Conclusion
Leveraging VR in the metaverse for MDHT sessions is feasible and offers substantial benefits. Despite challenges such as technical issues and privacy concerns, the Meta-Heart Team complements traditional interactions, ushering in a new era in collaborative decision-making while demanding ongoing attention to technological and ethical considerations.Two presenters explaining the processThe Metaverse-based Heart Team room
Effectiveness of telephone clinics for assessment of new onset chest pain - a retrospective single-centre observational study
Authors: Faizur Rahman M , Singh J K , Batcha S R , Iqbal J 
Published: October 2024

Abstract

Background
The COVID-19 pandemic led to a significant shift in the way clinical consultations are conducted with a rapid transition towards remote consultations (teleclinics). Although face-to-face (F2F) clinics are being re-introduced in the post-pandemic era, a significant proportion of clinics continue to run remotely. Despite the inability to physically examine the patient, remote clinics have notable advantages such as increased accessibility and flexibility for both the clinician and the patient.

Purpose
As the healthcare model moves increasingly towards a hybrid system where both F2F and teleclinics coexist, we sought to analyse the differences in practice between the two groups.

Methods
This single-centre retrospective analysis of patients referred to specialist cardiology services with NOCP compared face-to-face (F2F) consultations with teleclinic consultations. 70 patients were randomly selected in each category from a list of patients with NOCP that were referred to a tertiary cardiac centre from January to December 2021. Teleclinic appointments were conducted via telephone while F2F clinics had the patients visit the hospital for their appointments.

Results
The main findings are tabulated in Table 1. The samples for the two categories were evenly matched. Teleclinic appointments had a significantly reduced waiting time compared to F2F clinic (4 vs 6 weeks, p= 0.0009). As expected, the teleclinic group had reduced access to examination findings such as blood pressure, heart rate, and ECG. There was no significant difference in an initial working diagnosis of typical angina between the F2F group and the teleclinic group (30% and 25.7% respectively, p=0.706). However, patients in the F2F group were more likely to have anti-anginal therapy commenced compared to teleclinic group (50% vs 27.1% respectively, p=0.0089) following initial clinic review. Also, they were more likely to undergo an invasive coronary angiogram (30% vs 12.9% in F2F and teleclinic groups respectively, p=0.0224). However, this did not lead to a significant increase in PCIs performed in the F2F group. More patients had non-invasive tests requested in the teleclinic group compared to the F2F clinic group (62.9% vs 50% respectively, p=0.17) although this was not significant the median number of total investigations requested were the same in both the group.

Conclusion
Telephone consultations appear to be a reasonable alternative to F2F consultations with reduced waiting times and no significant impact on investigations ordered. However, lack of key examination findings may have hampered prescription of anti-anginal medications. Provisions such as readily available access to GP health care records on examination findings along with a streamlined remote prescription system can help overcome reluctance to prescribe antianginals. Further research is needed to assess clinical outcomes of teleclinic consultations.Table 1
Hypertensive myocardial disease screening in low-income settings using smartphone-based technologies: a prospective multicenter trial
Authors: Maurizi N , Skaldis I , Fumagalli C , Ochooa E , Tamba M , Olivotto I 
Published: October 2024

Abstract

Background
Mobile health technologies are revolutionizing cardiovascular (CV) medicine. However, more than 80% of heart disease related deaths occur in low-income settings, that are unable to take advantage of such technologies for healthcare awareness and prevention.

Purpose
To assess the feasibility of a pilot telemedicine-based CV screening campaign with D-Heart, a validated low-cost 8-lead smartphone portable ECG, coupled with blood-pressure (BP) monitoring in three regions of Africa.

Methods
A total of 950 patients (60%) men, age 29±21) were enrolled at 5 African rural dispensaries, 2 in Kenya, 2 in Senegal and at a hospital (Uganda). ECGs recording were obtained by community health workers with D- Heart smartphone ECG; BP was measured with a validated smartphone BP recorder. Global burden of ECG abnormalities was defined by a semi-quantitative score based on the sum of 9 criteria, identifying four classes of increasing severity. ECGs that were moderately and severely abnormal and from patients with severe hypertension, were sent for consultation via smartphone to D-Heart tele-cardiology centre: an advice on how to manage the patient was sent back to the community health worker’s smartphone within 15 minutes. If referral was needed, patients were sent to the local hospital.

Results
Mean BMI was 26.2 ± 8.5 (men 22.3±1.5 vs women 27.2±1.1, p&lt;0.01). Active/recent history of smoking and alcohol intake were 327 (45%, 298 men) and 232/590 (40%, 198 men) respectively. A total of 142 (15%) patients had been previously diagnosed with diabetes, 199(25%) had known hypertension of whom 95/199 on treatment), whereas 43(4%) had a previous myocardial infarction. A total of 487 (51%) patients never had their blood pressure measured, whereas 798(91%) never received an ECG. Mean SBP/DBP were 138±31/71±12 mmHg respectively. Patients with normal BP were 304(32%), whereas 380(40%) were mildly-moderately hypertensive (SBP/DBP 148±7/91±5 mmHg) and 130 (29%) with severe hypertension (SBP/DBP 162±8/99±6 mmHg). D-Heart ECGs tracings were respectively classified as: normal: 361(38%); mildly abnormal: 332(35%); moderately abnormal: 199 (21%) and severely abnormal 58(6%). Most common ECG abnormality was a positive Romhilt-Estes index in 361, 38%. For 174(18%) patients smartphone tele-report advised referral to the local hospital, but only 121 69%) presented to the visit: 9 (8%) were found to have normal hearts, 57(47%) with hypertensive heart disease, 35 (29%) with rheumatic heart disease, 20 (16%) with HFrEF. Visit time was 8±2 minutes; cost of screening per patient was 1.10€: 0,30€ for consumable electrodes, 0.80€ for the community health worker visit time.

Conclusions
D-Heart ECG screening combined with smartphone BP measurement proved feasible and cost-effective. This should encourage to develop and extend low-cost/high-technology community-based CV screening programs in low-income settings.
Remote monitoring of patients with chronic heart failure class II-III (NYHA) using the mobile application 'M-cardio' in residents of Kyrgyzstan
Authors: Rustambekova A , Abbasova M A , Noruzbaeva A M 
Published: October 2024

Abstract

Background
This study aimed to assess the impact of remote monitoring through the "M-cardio" mobile application on patients with chronic heart failure (CHF) of NYHA class II-III, particularly those of ischemic etiology, residing in Kyrgyzstan.

Methods
A total of 244 patients with NYHA class II-III heart failure due to ischemic etiology were included in the study. During the inpatient phase, patients underwent training on self-monitoring and self-help strategies for heart failure. The intervention group received additional training on using the "M-cardio" mobile application. Patients were randomized into two groups: 1) intervention group with remote monitoring using the mobile application (n=127), and 2) control group under standard outpatient observation at their residence (n=117). The intervention group used the mobile application with a developed algorithm for clinical indicators, allowing real-time assessment of the patient's condition. The observation period extended for 12 months.

Results
The study evaluated changes in quality of life (MLHFQ), self-care ability (EHFSBS), and physical activity tolerance (6MWT). Initially, there were no significant differences between the groups. However, improvements in quality of life and self-care ability in the intervention group were evident at 6 months and persisted up to 12 months (44.8 ± 6.7 points and 56.5 ± 7.9 points, p &lt; 0.01, in the intervention and control groups, respectively). Significant differences were also observed in physical activity tolerance after 12 months (6MWT) - 319 ± 79 meters in the intervention group and 233 ± 64 meters in the control group (p &lt; 0.001). Moreover, there was a notable decrease in the proportion of patients discontinuing essential medications in the intervention group compared to the control group, particularly in ACE inhibitors/ARBs and beta-blockers.

Conclusions
The preliminary results indicate that the "M-cardio" mobile application for remote monitoring significantly improved the quality of life, self-care capabilities, and functional status of heart failure patients. The application demonstrated effectiveness in reducing recurrent hospitalizations and enhancing medication adherence, suggesting its potential for improving long-term outcomes and survival.