Free-living core body temperature monitoring using a wrist-worn sensor after COVID-19 booster vaccination: a pilot study.

Core body temperature (CBT) is a key vital sign and fever is an important indicator of disease. In the past decade, there has been growing interest for vital sign monitoring technology that may be embedded in wearable devices, and the COVID-19 pandemic has highlighted the need for remote patient monitoring systems. While wrist-worn sensors allow continuous assessment of heart rate and oxygen saturation, reliable measurement of CBT at the wrist remains challenging. In this study, CBT was measured continuously in a free-living setting using a novel technology worn at the wrist and compared to reference core body temperature measurements, i.e., CBT values acquired with an ingestible temperature-sensing pill. Fifty individuals who received the COVID-19 booster vaccination were included. The datasets of 33 individuals were used to develop the CBT prediction algorithm, and the algorithm was then validated on the datasets of 17 participants. Mean observation time was 26.4 h and CBT > 38.0 °C occurred in 66% of the participants. CBT predicted by the wrist-worn sensor showed good correlation to the reference CBT (r = 0.72). Bland-Altman statistics showed an average bias of 0.11 °C of CBT predicted by the wrist-worn device compared to reference CBT, and limits of agreement were - 0.67 to + 0.93 °C, which is comparable to the bias and limits of agreement of commonly used tympanic membrane thermometers. The small size of the components needed for this technology would allow its integration into a variety of wearable monitoring systems assessing other vital signs and at the same time allowing maximal freedom of movement to the user.

The SMILe integrated care model in allogeneic SteM cell TransplantatIon faciLitated by eHealth: a protocol for a hybrid effectiveness-implementation randomised controlled trial.

BACKGROUND: While effectiveness outcomes of eHealth-facilitated integrated care models (eICMs) in transplant and oncological populations are promising, implementing and sustaining them in real-world settings remain challenging. Allogeneic stem cell transplant (alloSCT) patients could benefit from an eICM to enhance health outcomes. To combat health deterioration, integrating chronic illness management, including continuous symptom and health behaviour monitoring, can shorten reaction times. We will test the 1st-year post-alloSCT effectiveness and evaluate bundled implementation strategies to support the implementation of a newly developed and adapted eICM in allogeneic stem cell transplantation facilitated by eHealth (SMILe-ICM). SMILe-ICM has been designed by combining implementation, behavioural, and computer science methods. Adaptions were guided by FRAME and FRAME-IS. It consists of four modules: 1) monitoring & follow-up; 2) infection prevention; 3) physical activity; and 4) medication adherence, delivered via eHealth and a care coordinator (an Advanced Practice Nurse). The implementation was supported by contextually adapted implementation strategies (e.g., creating new clinical teams, informing local opinion leaders). METHODS: Using a hybrid effectiveness-implementation randomised controlled trial, we will include a consecutive sample of 80 adult alloSCT patients who were transplanted and followed by University Hospital Basel (Switzerland). Inclusion criteria are basic German proficiency; elementary computer literacy; internet access; and written informed consent. Patients will be excluded if their condition prevents the use of technology, or if they are followed up only at external centres. Patient-level (1:1) stratified randomisation into a usual care group and a SMILe-ICM group will take place 10 days pre-transplantation. To gauge the SMILe-ICM's effectiveness primary outcome (re-hospitalisation rate), secondary outcomes (healthcare utilization costs; length of inpatient re-hospitalizations, medication adherence; treatment and self-management burden; HRQoL; Graft-versus-Host Disease rate; survival; overall survival rate) and implementation outcomes (acceptability, appropriateness, feasibility, fidelity), we will use multi-method, multi-informant assessment (via questionnaires, interviews, electronic health record data, cost capture methods). DISCUSSION: The SMILe-ICM has major innovative potential for reengineering alloSCT follow-up care, particularly regarding short- and medium-term outcomes. Our dual focus on implementation and effectiveness will both inform optimization of the SMILe-ICM and provide insights regarding implementation strategies and pathway, understudied in eHealth-facilitated ICMs in chronically ill populations. TRIAL REGISTRATION: ClinicalTrials.gov. Identifier: NCT04789863 . Registered April 01, 2021.

Effect of Bedside Compared With Outside the Room Patient Case Presentation on Patients' Knowledge About Their Medical Care : A Randomized, Controlled, Multicenter Trial.

BACKGROUND: Although bedside case presentation contributes to patient-centered care through active patient participation in medical discussions, the complexity of medical information and jargon-induced confusion may cause misunderstandings and patient discomfort. OBJECTIVE: To compare bedside versus outside the room patient case presentation regarding patients' knowledge about their medical care. DESIGN: Randomized, controlled, parallel-group trial. (ClinicalTrials.gov: NCT03210987). SETTING: 3 Swiss teaching hospitals. PATIENTS: Adult medical patients who were hospitalized. INTERVENTION: Patients were randomly assigned to bedside or outside the room case presentation. MEASUREMENTS: The primary endpoint was patients' average knowledge of 3 dimensions of their medical care (each rated on a visual analogue scale from 0 to 100): understanding their disease, the therapeutic approach being used, and further plans for care. RESULTS: Compared with patients in the outside the room group (n = 443), those in the bedside presentation group (n = 476) reported similar knowledge about their medical care (mean, 79.5 points [SD, 21.6] vs. 79.4 points [SD, 19.8]; adjusted difference, 0.09 points [95% CI, -2.58 to 2.76 points]; P = 0.95). Also, an objective rating of patient knowledge by the study team was similar for the 2 groups, but the bedside presentation group had higher ratings of confusion about medical jargon and uncertainty caused by team discussions. Bedside ward rounds were more efficient (mean, 11.89 minutes per patient [SD, 4.92] vs. 14.14 minutes per patient [SD, 5.65]; adjusted difference, -2.31 minutes [CI, -2.98 to -1.63 minutes]; P < 0.001). LIMITATION: Only Swiss hospitals and medical patients were included. CONCLUSION: Compared with outside the room case presentation, bedside case presentation was shorter and resulted in similar patient knowledge, but sensitive topics were more often avoided and patient confusion was higher. Physicians presenting at the bedside need to be skilled in the use of medical language to avoid confusion and misunderstandings. PRIMARY FUNDING SOURCE: Swiss National Foundation (10531C_ 182422).

Rivaroxaban for Stroke Prevention after Embolic Stroke of Undetermined Source.

BACKGROUND: Embolic strokes of undetermined source represent 20% of ischemic strokes and are associated with a high rate of recurrence. Anticoagulant treatment with rivaroxaban, an oral factor Xa inhibitor, may result in a lower risk of recurrent stroke than aspirin. METHODS: We compared the efficacy and safety of rivaroxaban (at a daily dose of 15 mg) with aspirin (at a daily dose of 100 mg) for the prevention of recurrent stroke in patients with recent ischemic stroke that was presumed to be from cerebral embolism but without arterial stenosis, lacune, or an identified cardioembolic source. The primary efficacy outcome was the first recurrence of ischemic or hemorrhagic stroke or systemic embolism in a time-to-event analysis; the primary safety outcome was the rate of major bleeding. RESULTS: A total of 7213 participants were enrolled at 459 sites; 3609 patients were randomly assigned to receive rivaroxaban and 3604 to receive aspirin. Patients had been followed for a median of 11 months when the trial was terminated early because of a lack of benefit with regard to stroke risk and because of bleeding associated with rivaroxaban. The primary efficacy outcome occurred in 172 patients in the rivaroxaban group (annualized rate, 5.1%) and in 160 in the aspirin group (annualized rate, 4.8%) (hazard ratio, 1.07; 95% confidence interval [CI], 0.87 to 1.33; P=0.52). Recurrent ischemic stroke occurred in 158 patients in the rivaroxaban group (annualized rate, 4.7%) and in 156 in the aspirin group (annualized rate, 4.7%). Major bleeding occurred in 62 patients in the rivaroxaban group (annualized rate, 1.8%) and in 23 in the aspirin group (annualized rate, 0.7%) (hazard ratio, 2.72; 95% CI, 1.68 to 4.39; P<0.001). CONCLUSIONS: Rivaroxaban was not superior to aspirin with regard to the prevention of recurrent stroke after an initial embolic stroke of undetermined source and was associated with a higher risk of bleeding. (Funded by Bayer and Janssen Research and Development; NAVIGATE ESUS ClinicalTrials.gov number, NCT02313909 .).

iPhone App compared with standard blood pressure measurement -The iPARR trial.

BACKGROUND: The possibility to use built-in smartphone-cameras for photoplethysmographic (PPG) recording of pulse waves lead to the release of numerous health apps, claiming to measure blood pressure (BP) based on PPG signals. Even though these apps are highly popular, not a single one is clinically validated. Aim of the current study was to test systolic BP (sBP) estimation by a promising new algorithm in a large clinical setting. METHODS: The study was designed based on the European Society of Hypertension International Protocol Revision 2010. Each individual received 7 sequential BP measurements, starting with the reference device - an automated oscillometric cuff device - followed by the PPG recording at the patients' index finger. RESULTS: A total 1,036 subjects were recruited of which 965 could be included for final analysis leading to 2,895 pairs of comparison. Mean (±SD) error between test and reference device was -0.41 (±16.52) mmHg. Only 38.1% of all 2,895 BP comparisons reached a delta within ±5 mmHg, while 29.3% reached a delta larger than 15 mmHg. Bland-Altman plot showed an overestimation of smartphone sBP in comparison to reference sBP in low range and an underestimation in high sBP range. CONCLUSIONS: According to the European Society of Hypertension International Protocol Revision 2010 specifications the algorithm failed validation criteria for sBP measurement and was not commercialized. These findings emphasize that health apps should be rigorously validated according to common guidelines before market release as under- and/or overestimation of BP is potentially exposing persons at health risks in short and long term. TRIAL REGISTRATION: ClinicalTrials.gov, number NCT02552030.

Next-Generation Digital Biomarkers for Tuberculosis and Antibiotic Stewardship: Perspective on Novel Molecular Digital Biomarkers in Sweat, Saliva, and Exhaled Breath.

The internet of health care things enables a remote connection between health care professionals and patients wearing smart biosensors. Wearable smart devices are potentially affordable, sensitive, specific, user-friendly, rapid, robust, lab-independent, and deliverable to the end user for point-of-care testing. The datasets derived from these devices are known as digital biomarkers. They represent a novel patient-centered approach to collecting longitudinal, context-derived health insights. Adding automated, analytical smartphone applications will enable their use in high-, middle-, and low-income countries. So far, digital biomarkers have been focused primarily on accelerometer data and heart rate due to well-established sensors originating from the consumer market. Novel emerging smart biosensors will detect biomarkers (or compounds) independent of a lab and noninvasively in sweat, saliva, and exhaled breath. These molecular digital biomarkers are a promising novel approach to reduce the burden from 2 major infectious diseases with urgent unmet needs: tuberculosis and infections with multidrug resistant pathogens. Active tuberculosis (aTbc) is one of the deadliest diseases from an infectious agent. However, a simple and reliable test for its detection is still missing. Furthermore, inappropriate antimicrobial use leads to the development of antimicrobial resistance, which is associated with high mortality and health care costs. From this perspective, we discuss the innovative approach of a noninvasive and lab-independent collection of novel biomarkers to detect aTbc, which at the same time may additionally serve as a scalable therapeutic drug monitoring approach for antibiotics. These molecular digital biomarkers are next-generation digital biomarkers and have the potential to shape the future of infectious diseases.

Comparison and Combination of Single-Lead ECG and Photoplethysmography Algorithms for Wearable-Based Atrial Fibrillation Screening.

Background: Atrial fibrillation (AF), the most common cardiac arrhythmia, can be detected by smartphones and smartwatches. Introduction: Single-lead ECGs (iECGs) and photoplethysmography (PPG) sensors provide the opportunity for a broad, simple, and easily repeatable cardiac rhythm analysis. To reduce unnecessary medical follow-up testing due to false positive results, our aim was to find a screening approach applicable on smart devices with a focus on high specificity. Methods: We used PPG measurements from smartphones and smartwatches and iECG data from two previous validation trials. Two AF detection algorithms (A and B) were applied on the iECG dataset and compared directly. Further, we used 1-min PPG measurements as a first-pass filter for arrhythmia detection and simulated a sequential testing: Once an arrhythmia was detected in the PPG, the iECG counterpart of the patient was analyzed by algorithm A, B, or A + B combined although algorithm B was primarily designed for PPG analysis. Results: The iECGs from 1,288 participants were analyzed. Algorithm A did not show a diagnosis in 16.1%. In the remaining, sensitivity and specificity were 99.6%, and 97.4% respectively. Accuracy was 98.5%, and correct classification rate (CCR) was 82.7%. Algorithm B always differentiated between normal and arrhythmic and reached an overall sensitivity of 95.4%, a specificity of 91.6%, and an accuracy and CCR of 93.3%. Sequential testing by combining both algorithms into a three-phase test (Test positive PPG, then iECG analysis by A and B combined) resulted in a 100% specificity. Conclusion: Algorithm B performed strongly in PPG analysis as well as iECG analysis. PPG signals and consecutive iECG combined when an arrhythmia was detected by PPG resulted in a specificity that was higher than 99%. Discussion: The analysis allows a direct comparison of iECG algorithms without possible dilution by different measurement procedures or recording-devices. We improved specificity in AF-screening approaches with wearables by simulating a novel approach. Results rely on signal quality.

Frequency and Predictors of Major Bleeding in Patients With Embolic Strokes of Undetermined Source: NAVIGATE-ESUS Trial.

BACKGROUND AND PURPOSE: Risks, sites, and predictors of major bleeding during antithrombotic therapies have not been well defined for patients with recent embolic stroke of undetermined source. METHODS: Exploratory analysis of major bleeds defined by International Society of Thrombosis and Hemostasis criteria occurring among 7213 participants in international NAVIGATE (New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial) embolic stroke of undetermined source randomized trial comparing rivaroxaban 15 mg daily with aspirin 100 mg daily. RESULTS: During a median follow-up of 11 months, 85 major bleeds occurred. The most frequent site was gastrointestinal (38%), followed by intracranial (29%). Assignment to rivaroxaban (hazard ratio [HR], 2.7 [95% CI, 1.7-4.3]), East Asia region (HR, 2.5 [95% CI, 1.6-3.9]), systolic blood pressure ≥160 mm Hg (HR, 2.2 [95% CI, 1.2-3.8]), and reduced estimated glomerular filtration rate (HR, 1.2 per 10 mL/min per 1.73 m2 decrease, [95% CI, 1.0-1.3]) were independently associated with presence of major bleeds. Five (6%) were fatal. Among 15 patients with intracerebral hemorrhage, 2 (13%) were fatal. There was no evidence of an early high-risk period following initiation of rivaroxaban. The annualized rate of intracerebral hemorrhage was 6-fold higher among East Asian participants (0.67%) versus all other regions (0.11%; HR, 6.3 [95% CI, 2.2-18.0]). Distribution of bleeding sites was similar for rivaroxaban and aspirin. CONCLUSIONS: Among embolic stroke of undetermined source patients participating in an international randomized trial, independent predictors of major bleeding were assignment to rivaroxaban, East Asia region, increased systolic blood pressure, and impaired renal function. East Asia as a region was strongly associated with risk of intracerebral hemorrhage. Estimated glomerular filtration rate should be a consideration for stratifying bleeding risk. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02313909.

Detection of atrial fibrillation with a smartphone camera: first prospective, international, two-centre, clinical validation study (DETECT AF PRO).

AIMS: Early detection of atrial fibrillation (AF) is essential for stroke prevention. Emerging technologies such as smartphone cameras using photoplethysmography (PPG) and mobile, internet-enabled electrocardiography (iECG) are effective for AF screening. This study compared a PPG-based algorithm against a cardiologist's iECG diagnosis to distinguish between AF and sinus rhythm (SR). METHODS AND RESULTS: In this prospective, two-centre, international, clinical validation study, we recruited in-house patients with presumed AF and matched controls in SR at two university hospitals in Switzerland and Germany. In each patient, a PPG recording on the index fingertip using a regular smartphone camera followed by iECG was obtained. Photoplethysmography recordings were analysed using an automated algorithm and compared with the blinded cardiologist's iECG diagnosis. Of 672 patients recruited, 80 were excluded mainly due to insufficient PPG/iECG quality, leaving 592 patients (SR: n = 344, AF: n = 248). Based on 5 min of PPG heart rhythm analysis, the algorithm detected AF with a sensitivity of 91.5% (95% confidence interval 85.9-95.4) and specificity of 99.6% (97.8-100). By reducing analysis time to 1 min, sensitivity was reduced to 89.9% (85.5-93.4) and specificity to 99.1% (97.5-99.8). Correctly classified rate was 88.8% for 1-min PPG analysis and dropped to 60.9% when the threshold for the analysed file was set to 5 min of good signal quality. CONCLUSION: This is the first prospective clinical two-centre study to demonstrate that detection of AF by using a smartphone camera alone is feasible, with high specificity and sensitivity. Photoplethysmography signal analysis appears to be suitable for extended AF screening. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, number NCT02949180, https://clinicaltrials.gov/ct2/show/NCT02949180.

Integrative hospital treatment in older patients to benchmark and improve outcome and length of stay - the In-HospiTOOL study.

BACKGROUND: A comprehensive in-hospital patient management with reasonable and economic resource allocation is arguably the major challenge of health-care systems worldwide, especially in elderly, frail, and polymorbid patients. The need for patient management tools to improve the transition process and allocation of health care resources in routine clinical care particularly for the inpatient setting is obvious. To address these issues, a large prospective trial is warranted. METHODS: The "Integrative Hospital Treatment in Older patients to benchmark and improve Outcome and Length of stay" (In-HospiTOOL) study is an investigator-initiated, multicenter effectiveness trial to compare the effects of a novel in-hospital management tool on length of hospital stay, readmission rate, quality of care, and other clinical outcomes using a time-series model. The study aims to include approximately 35`000 polymorbid medical patients over an 18-month period, divided in an observation, implementation, and intervention phase. Detailed data on treatment and outcome of polymorbid medical patients during the in-hospital stay and after 30 days will be gathered to investigate differences in resource use, inter-professional collaborations and to establish representative benchmarking data to promote measurement and display of quality of care data across seven Swiss hospitals. The trial will inform whether the "In-HospiTOOL" optimizes inter-professional collaboration and thereby reduces length of hospital stay without harming subjective and objective patient-oriented outcome markers. DISCUSSION: Many of the current quality-mirroring tools do not reflect the real need and use of resources, especially in polymorbid and elderly patients. In addition, a validated tool for optimization of patient transition and discharge processes is still missing. The proposed multicenter effectiveness trial has potential to improve interprofessional collaboration and optimizes resource allocation from hospital admission to discharge. The results will enable inter-hospital comparison of transition processes and accomplish a benchmarking for inpatient care quality.

Effect of Na+-channel blockade on the three-dimensional substrate of atrial fibrillation in a model of endo-epicardial dissociation and transmural conduction.

AIMS: Atrial fibrillation (AF) is a progressive arrhythmia characterized by structural alterations that increase its stability. Both clinical and experimental studies showed a concomitant loss of antiarrhythmic drug efficacy in later stages of AF. The mechanisms underlying this loss of efficacy are not well understood. We hypothesized that structural remodelling may explain this reduced efficacy by making the substrate more three-dimensional. To investigate this, we simulated the effect of sodium (Na+)-channel block on AF in a model of progressive transmural uncoupling. METHODS AND RESULTS: In a computer model consisting of two cross-connected atrial layers, with realistic atrial membrane behaviour, structural remodelling was simulated by reducing the number of connections between the layers. 100% of endo-epicardial connectivity represented a healthy atrium. At various degrees of structural remodelling, we assessed the effect of 60% sodium channel block on AF stability, endo-epicardial electrical activity dissociation (EED), and fibrillatory conduction pattern complexity quantified by number of waves, phase singularities (PSs), and transmural conduction ('breakthrough', BT). Sodium channel block terminated AF in non-remodelled but not in remodelled atria. The temporal excitable gap (EG) and AF cycle length increased at all degrees of remodelling when compared with control. Despite an increase of EED and EG, sodium channel block decreased the incidence of BT because of transmural conduction block. Sodium channel block decreased the number of waves and PSs in normal atrium but not in structurally remodelled atrium. CONCLUSION: This simple atrial model explains the loss of efficacy of sodium channel blockers in terminating AF in the presence of severe structural remodelling as has been observed experimentally and clinically. Atrial fibrillation termination in atria with moderate structural remodelling in the presence of sodium channel block is caused by reduction of AF complexity. With more severe structural remodelling, sodium channel block fails to promote synchronization of the two layers of the model.

Characterization of Patients with Embolic Strokes of Undetermined Source in the NAVIGATE ESUS Randomized Trial.

BACKGROUND: The New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial vs. ASA to Prevent Embolism in Embolic Stroke of Undetermined Source (NAVIGATE-ESUS) trial is a randomized phase-III trial comparing rivaroxaban versus aspirin in patients with recent ESUS. AIMS: We aimed to describe the baseline characteristics of this large ESUS cohort to explore relationships among key subgroups. METHODS: We enrolled 7213 patients at 459 sites in 31 countries. Prespecified subgroups for primary safety and efficacy analyses included age, sex, race, global region, stroke or transient ischemic attack prior to qualifying event, time to randomization, hypertension, and diabetes mellitus. RESULTS: Mean age was 66.9 ± 9.8 years; 24% were under 60 years. Older patients had more hypertension, coronary disease, and cancer. Strokes in older subjects were more frequently cortical and accompanied by radiographic evidence of prior infarction. Women comprised 38% of participants and were older than men. Patients from East Asia were oldest whereas those from Latin America were youngest. Patients in the Americas more frequently were on aspirin prior to the qualifying stroke. Acute cortical infarction was more common in the United States, Canada, and Western Europe, whereas prior radiographic infarctions were most common in East Asia. Approximately forty-five percent of subjects were enrolled within 30 days of the qualifying stroke, with earliest enrollments in Asia and Eastern Europe. CONCLUSIONS: NAVIGATE-ESUS is the largest randomized trial comparing antithrombotic strategies for secondary stroke prevention in patients with ESUS. The study population encompasses a broad array of patients across multiple continents and these subgroups provide ample opportunities for future research.

How disruption of endo-epicardial electrical connections enhances endo-epicardial conduction during atrial fibrillation.

Aims: Loss of side-to-side electrical connections between atrial muscle bundles is thought to underlie conduction disturbances predisposing to atrial fibrillation (AF). Putatively, disruption of electrical connections occurs not only within the epicardial layer but also between the epicardial layer and the endocardial bundle network, thus impeding transmural conductions ('breakthroughs'). However, both clinical and experimental studies have shown an enhancement of breakthroughs during later stages of AF. We tested the hypothesis that endo-epicardial uncoupling enhances endo-epicardial electrical dyssynchrony, breakthrough rate (BTR), and AF stability. Methods and Results: In a novel dual-layer computer model of the human atria, 100% connectivity between the two layers served as healthy control. Atrial structural remodelling was simulated by reducing the number of connections between the layers from 96 to 6 randomly chosen locations. With progressive elimination of connections, AF stability increased. Reduction in the number of connections from 96 to 24 resulted in an increase in endo-epicardial dyssynchrony from 6.6 ± 1.9 to 24.6 ± 1.3%, with a concomitant increase in BTR. A further reduction to 12 and 6 resulted in more pronounced endo-epicardial dyssynchrony of 34.4 ± 1.15 and 40.2 ± 0.52% but with BTR reduction. This biphasic relationship between endo-epicardial coupling and BTR was found independently from whether AF was maintained by re-entry or by ectopic focal discharges. Conclusion: Loss of endo-epicardial coupling increases AF stability. There is a biphasic relation between endo-epicardial coupling and BTR. While at high degrees of endo-epicardial connectivity, the BTR is limited by the endo-epicardial synchronicity, at low degrees of connectivity, it is limited by the number of endo-epicardial connections.

Smart detection of atrial fibrillation†.

AIMS: Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice, and its paroxysmal nature makes its detection challenging. In this trial, we evaluated a novel App for its accuracy to differentiate between patients in AF and patients in sinus rhythm (SR) using the plethysmographic sensor of an iPhone 4S and the integrated LED only. METHODS AND RESULTS: For signal acquisition, we used an iPhone 4S, positioned with the camera lens and LED light on the index fingertip. A 5 min video file was recorded with the pulse wave extracted from the green light spectrum of the signal. RR intervals were automatically identified. For discrimination between AF and SR, we tested three different statistical methods. Normalized root mean square of successive difference of RR intervals (nRMSSD), Shannon entropy (ShE), and SD1/SD2 index extracted from a Poincaré plot. Eighty patients were included in the study (40 patients in AF and 40 patients in SR at the time of examination). For discrimination between AF and SR, ShE yielded the highest sensitivity and specificity with 85 and 95%, respectively. Applying a tachogram filter resulted in an improved sensitivity of 87.5%, when combining ShE and nRMSSD, while specificity remained stable at 95%. A combination of SD1/SD2 index and nRMSSD led to further improvement and resulted in a sensitivity and specificity of 95%. CONCLUSION: The algorithm tested reliably discriminated between SR and AF based on pulse wave signals from a smartphone camera only. Implementation of this algorithm into a smartwatch is the next logical step.

Validation of a New Heart Rate Measurement Algorithm for Fingertip Recording of Video Signals with Smartphones.

INTRODUCTION: This study investigates the accuracy of a heart rate (HR) measurement algorithm applied to a pulse wave. This was based on video signals recorded with a smartphone. The results of electrocardiographic HR and standard linear heart rate variability (HRV) analysis were used for reference. MATERIALS AND METHODS: On a total of 68 subjects, an electrocardiogram (ECG) and the pulse curve were simultaneously recorded on an Apple iPhone 4S. The HR was measured using an algorithm developed by the authors that works according to a method combining the detection of the steepest slope of every pulse wave with the correlation to an optimized pulse wave pattern. RESULTS: The results of the HR measured by pulse curves were extremely consistent (R > 0.99) with the HR measured on ECGs. For most standard linear HRV parameters as well, high correlations of R ≥ 0.90 in the analysis were achieved in the time and frequency domain. CONCLUSION: In conclusion, the overall accuracy of HR and HRV indices of pulse wave analysis, based on video signals of a smartphone, with the developed algorithm was sufficient for preclinical screening applications.

Safety and efficacy of factor XIa inhibition with milvexian for secondary stroke prevention (AXIOMATIC-SSP): a phase 2, international, randomised, double-blind, placebo-controlled, dose-finding trial.

BACKGROUND: People with factor XI deficiency have lower rates of ischaemic stroke than the general population and infrequent spontaneous bleeding, suggesting that factor XI has a more important role in thrombosis than in haemostasis. Milvexian, an oral small-molecule inhibitor of activated factor XI, added to standard antiplatelet therapy, might reduce the risk of non-cardioembolic ischaemic stroke without increasing the risk of bleeding. We aimed to estimate the dose-response of milvexian for recurrent ischaemic cerebral events and major bleeding in patients with recent ischaemic stroke or transient ischaemic attack (TIA). METHODS: AXIOMATIC-SSP was a phase 2, randomised, double-blind, placebo-controlled, dose-finding trial done at 367 hospitals in 27 countries. Eligible participants aged 40 years or older, with acute (<48 h) ischaemic stroke or high-risk TIA, were randomly assigned by a web-based interactive response system in a 1:1:1:1:1:2 ratio to receive one of five doses of milvexian (25 mg once daily, 25 mg twice daily, 50 mg twice daily, 100 mg twice daily, or 200 mg twice daily) or matching placebo twice daily for 90 days. All participants received clopidogrel 75 mg daily for the first 21 days and aspirin 100 mg daily for the first 90 days. Investigators, site staff, and participants were masked to treatment assignment. The primary efficacy endpoint was the composite of ischaemic stroke or incident covert brain infarct on MRI at 90 days, assessed in all participants allocated to treatment who completed a follow-up MRI brain scan, and the primary analysis assessed the dose-response relationship with Multiple Comparison Procedure-Modelling (MCP-MOD). The main safety outcome was major bleeding at 90 days, assessed in all participants who received at least one dose of the study drug. This trial is registered with ClinicalTrials.gov (NCT03766581) and the EU Clinical Trials Register (2017-005029-19). FINDINGS: Between Jan 27, 2019, and Dec 24, 2021, 2366 participants were randomly allocated to placebo (n=691); milvexian 25 mg once daily (n=328); or twice-daily doses of milvexian 25 mg (n=318), 50 mg (n=328), 100 mg (n=310), or 200 mg (n=351). The median age of participants was 71 (IQR 62-77) years and 859 (36%) were female. At 90 days, the estimates of the percentage of participants with either symptomatic ischaemic stroke or covert brain infarcts were 16·8 (90·2% CI 14·5-19·1) for placebo, 16·7 (14·8-18·6) for 25 mg milvexian once daily, 16·6 (14·8-18·3) for 25 mg twice daily, 15·6 (13·9-17·5) for 50 mg twice daily, 15·4 (13·4-17·6) for 100 mg twice daily, and 15·3 (12·8-19·7) for 200 mg twice daily. No significant dose-response was observed among the five milvexian doses for the primary composite efficacy outcome. Model-based estimates of the relative risk with milvexian compared with placebo were 0·99 (90·2% CI 0·91-1·05) for 25 mg once daily, 0·99 (0·87-1·11) for 25 mg twice daily, 0·93 (0·78-1·11) for 50 mg twice daily, 0·92 (0·75-1·13) for 100 mg twice daily, and 0·91 (0·72-1·26) for 200 mg twice daily. No apparent dose-response was observed for major bleeding (four [1%] of 682 participants with placebo, two [1%] of 325 with milvexian 25 mg once daily, two [1%] of 313 with 25 mg twice daily, five [2%] of 325 with 50 mg twice daily, five [2%] of 306 with 100 mg twice daily, and five [1%] of 344 with 200 mg twice daily). Five treatment-emergent deaths occurred, four of which were considered unrelated to the study drug by the investigator. INTERPRETATION: Factor XIa inhibition with milvexian, added to dual antiplatelet therapy, did not substantially reduce the composite outcome of symptomatic ischaemic stroke or covert brain infarction and did not meaningfully increase the risk of major bleeding. Findings from our study have informed the design of a phase 3 trial of milvexian for the prevention of ischaemic stroke in patients with acute ischaemic stroke or TIA. FUNDING: Bristol Myers Squibb and Janssen Research & Development.

[Artificial intelligence in internal medicine : From the theory to practical application in practices and hospitals]. / Künstliche Intelligenz in der internistischen Versorgung : Von der Theorie zum praktischen Einsatz in Praxen und Kliniken.

The integration of artificial intelligence (AI) technologies has the potential to improve both the efficiency and the quality of medical care. Applications of AI have already become established in various specialized fields in internal medicine, whereas in other fields the applications are still in various phases of development. An aspect that is important to elucidate is the effects of AI on the interaction between patients and healthcare personnel. A further factor is the comprehensibility of the mode of functioning of the AI-based algorithms involved. In addition to the necessary confidence-building measures, an integration of the technology into existing systems must be strived for to achieve an appropriate acceptance and widespread availability and to relieve pressure on the personnel at the administrative level.

An augmented reality-based method to assess precordial electrocardiogram leads: a feasibility trial.

Aims: It has been demonstrated that several cardiac pathologies, including myocardial ischaemia, can be detected using smartwatch electrocardiograms (ECGs). Correct placement of bipolar chest leads remains a major challenge in the outpatient population. Methods and results: In this feasibility trial, we propose an augmented reality-based smartphone app that guides the user to place the smartwatch in predefined positions on the chest using the front camera of a smartphone. A machine-learning model using MobileNet_v2 as the backbone was trained to detect the bipolar lead positions V1-V6 and visually project them onto the user's chest. Following the smartwatch recordings, a conventional 10 s, 12-lead ECG was recorded for comparison purposes. All 50 patients participating in the study were able to conduct a 9-lead smartwatch ECG using the app and assistance from the study team. Twelve patients were able to record all the limb and chest leads using the app without additional support. Bipolar chest leads recorded with smartwatch ECGs were assigned to standard unipolar Wilson leads by blinded cardiologists based on visual characteristics. In every lead, at least 86% of the ECGs were assigned correctly, indicating the remarkable similarity of the smartwatch to standard ECG recordings. Conclusion: We have introduced an augmented reality-based method to independently record multichannel smartwatch ECGs in an outpatient setting.

A three-level model for therapeutic drug monitoring of antimicrobials at the site of infection.

The silent pandemic of bacterial antimicrobial resistance is a leading cause of death worldwide, prolonging hospital stays and raising health-care costs. Poor incentives to develop novel pharmacological compounds and the misuse of antibiotics contribute to the bacterial antimicrobial resistance crisis. Therapeutic drug monitoring (TDM) based on blood analysis can help alleviate the emergence of bacterial antimicrobial resistance and effectively decreases the risk of toxic drug concentrations in patients' blood. Antibiotic tissue penetration can vary in patients who are critically or chronically ill and can potentially lead to treatment failure. Antibiotics such as ß-lactams and glycopeptides are detectable in non-invasively collectable biofluids, such as sweat and exhaled breath. The emergence of wearable sensors enables easy access to these non-invasive biofluids, and thus a laboratory-independent analysis of various disease-associated biomarkers and drugs. In this Personal View, we introduce a three-level model for TDM of antibiotics to describe concentrations at the site of infection (SOI) by use of wearable sensors. Our model links blood-based drug measurement with the analysis of drug concentrations in non-invasively collectable biofluids stemming from the SOI to characterise drug concentrations at the SOI. Finally, we outline the necessary clinical and technical steps for the development of wearable sensing platforms for SOI applications.

Determine atrial fibrillation burden with a photoplethysmographic mobile sensor: the atrial fibrillation burden trial: detection and quantification of episodes of atrial fibrillation using a cloud analytics service connected to a wearable with photoplethysmographic sensor.

Aims: Recent studies suggest that atrial fibrillation (AF) burden (time AF is present) is an independent risk factor for stroke. The aim of this trial was to study the feasibility and accuracy to identify AF episodes and quantify AF burden in patients with a known history of paroxysmal AF with a photoplethysmography (PPG)-based wearable. Methods and results: In this prospective, single-centre trial, the PPG-based estimation of AF burden was compared with measurements of a conventional 48 h Holter electrocardiogram (ECG), which served as the gold standard. An automated algorithm performed PPG analysis, while a cardiologist, blinded for the PPG data, analysed the ECG data. Detected episodes of AF measured by both methods were aligned timewise.Out of 100 patients recruited, 8 had to be excluded due to technical issues. Data from 92 patients were analysed [55.4% male; age 73.3 years (standard deviation, SD: 10.4)]. Twenty-five patients presented AF during the study period. The intraclass correlation coefficient of total AF burden minutes detected by the two measurement methods was 0.88. The percentage of correctly identified AF burden over all patients was 85.1% and the respective parameter for non-AF time was 99.9%. Conclusion: Our results demonstrate that a PPG-based wearable in combination with an analytical algorithm appears to be suitable for a semiquantitative estimation of AF burden in patients with a known history of paroxysmal AF. Trial Registration number: NCT04563572.