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.

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.

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.

Occurrence of sensitive topics during ward round: an ancillary analysis of the BEDSIDE-OUTSIDE trial.

OBJECTIVE: Discussing sensitive topics (eg, medical uncertainty, social issues, non-adherence) during ward rounds is challenging and may negatively impact patient satisfaction with the healthcare they are receiving. In the previous multicentre randomised BEDSIDE-OUTSIDE trial focusing on communication during ward rounds, we investigated the interplay between sensitive topics and low reported satisfaction with care. DESIGN: Pre-planned secondary analysis of a randomised controlled trial. For this analysis data of the original trial was pooled across intervention groups. SETTING: Three Swiss teaching hospitals. PARTICIPANTS: Adult patients hospitalised for medical care. INTERVENTIONS: We analysed predefined sensitive health topics and specific elements of communication from audiotapes recorded during ward rounds, for both patients dealing with and without sensitive topics. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary endpoint was overall patient satisfaction with care; measured on a Visual Analogue Scale from 0 to 100. Secondary endpoints included duration of ward rounds and further satisfaction outcomes. RESULTS: Of the 919 included patients, 474 had at least one sensitive topic including medical uncertainty (n=251), psychiatric comorbidities (n=161), tumour diagnosis (n=137) and social issues (n=125). Compared with patients without sensitive topics, patients with sensitive topics reported lower satisfaction with care (mean (SD), 87.7 (±14.6) vs 90.2 (±12.1), adjusted difference -2.5 (95% CI -4.28 to -0.72), p=0.006. Among patients with sensitive topics, risk factors for low satisfaction included several parameters concerning patient-physician interaction such as disagreements during ward rounds (mean (SD), 14/212 (6.6%) vs 41/254 (16.1%), adjusted OR 2.78 (95% CI 1.47 to 5.27), p=0.002). CONCLUSIONS: A large proportion of medical inpatients must deal with sensitive health topics. This is associated with lower satisfaction with care, particularly if the patient perceives the interaction with doctors during ward rounds as unsatisfactory. Educating physicians on specific communication techniques may help improve care for these patients. TRIAL REGISTRATION NUMBER: NCT03210987.

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.

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.

Association of Interprofessional Discharge Planning Using an Electronic Health Record Tool With Hospital Length of Stay Among Patients with Multimorbidity: A Nonrandomized Controlled Trial.

Importance: Whether interprofessional collaboration is effective and safe in decreasing hospital length of stay remains controversial. Objective: To evaluate the outcomes and safety associated with an electronic interprofessional-led discharge planning tool vs standard discharge planning to safely reduce length of stay among medical inpatients with multimorbidity. Design, Setting, and Participants: This multicenter prospective nonrandomized controlled trial used interrupted time series analysis to examine medical acute hospitalizations at 82 hospitals in Switzerland. It was conducted from February 2017 through January 2019. Data analysis was conducted from March 2021 to July 2022. Intervention: After a 12-month preintervention phase (February 2017 through January 2018), an electronic interprofessional-led discharge planning tool was implemented in February 2018 in 7 intervention hospitals in addition to standard discharge planning. Main Outcomes and Measures: Mixed-effects segmented regression analyses were used to compare monthly changes in trends of length of stay, hospital readmission, in-hospital mortality, and facility discharge after the implementation of the tool with changes in trends among control hospitals. Results: There were 54 695 hospitalizations at intervention hospitals, with 27 219 in the preintervention period (median [IQR] age, 72 [59-82] years; 14 400 [52.9%] men) and 27 476 in the intervention phase (median [IQR] age, 72 [59-82] years; 14 448 [52.6%] men) and 438 791 at control hospitals, with 216 261 in the preintervention period (median [IQR] age, 74 [60-83] years; 109 770 [50.8%] men) and 222 530 in the intervention phase (median [IQR] age, 74 [60-83] years; 113 053 [50.8%] men). The mean (SD) length of stay in the preintervention phase was 7.6 (7.1) days for intervention hospitals and 7.5 (7.4) days for control hospitals. During the preintervention phase, population-averaged length of stay decreased by -0.344 hr/mo (95% CI, -0.599 to -0.090 hr/mo) in control hospitals; however, no change in trend was observed among intervention hospitals (-0.034 hr/mo; 95% CI, -0.646 to 0.714 hr/mo; difference in slopes, P = .09). Over the intervention phase (February 2018 through January 2019), length of stay remained unchanged in control hospitals (slope, -0.011 hr/mo; 95% CI, -0.281 to 0.260 hr/mo; change in slope, P = .03), but decreased steadily among intervention hospitals by -0.879 hr/mo (95% CI, -1.607 to -0.150 hr/mo; change in slope, P = .04, difference in slopes, P = .03). Safety analyses showed no change in trends of hospital readmission, in-hospital mortality, or facility discharge over the whole study time. Conclusions and Relevance: In this nonrandomized controlled trial, the implementation of an electronic interprofessional-led discharge planning tool was associated with a decline in length of stay without an increase in hospital readmission, in-hospital mortality, or facility discharge. Trial Registration: isrctn.org Identifier: ISRCTN83274049.

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.

Wearable Technologies for Pediatric Patients with Surgical Infections-More than Counting Steps?

Reliable vital sign assessments are crucial for the management of patients with infectious diseases. Wearable devices enable easy and comfortable continuous monitoring across settings, especially in pediatric patients, but information about their performance in acutely unwell children is scarce. Vital signs were continuously measured with a multi-sensor wearable device (Everion®, Biofourmis, Zurich, Switzerland) in 21 pediatric patients during their hospitalization for appendicitis, osteomyelitis, or septic arthritis to describe acceptance and feasibility and to compare validity and reliability with conventional measurements. Using a wearable device was highly accepted and feasible for health-care workers, parents, and children. There were substantial data gaps in continuous monitoring up to 24 h. The wearable device measured heart rate and oxygen saturation reliably (mean difference, 2.5 bpm and 0.4% SpO2) but underestimated body temperature by 1.7 °C. Data availability was suboptimal during the study period, but a good relationship was determined between wearable device and conventional measurements for heart rate and oxygen saturation. Acceptance and feasibility were high in all study groups. We recommend that wearable devices designed for medical use in children be validated in the targeted population to assure future high-quality continuous vital sign assessments in an easy and non-burdening way.

Comparability of a Blood-Pressure-Monitoring Smartphone Application with Conventional Measurements-A Pilot Study.

(1) Background: New cuffless technologies attempting blood-pressure measurements (BPM) offer possibilities to improve hypertension awareness and control. The aim of this study was to compare a smartphone application (app)-based algorithm with office BPM (OBPM). (2) Methods: We included consecutive patients with an indication for ambulatory BPM. The smartphone app (RIVA digital) acquired the pulse wave in the fingers' arterial bed using the phone's camera and estimated BP based on photoplethysmographic (PPG) waveforms. Measurements were alternatingly taken with an oscillometric cuff-based device and smartphone BPM (AppBP) on two consecutive days. AppBP were calibrated to the first OBPM. Each AppBP was compared to its CuffBP (mean of the previous/following OBPM). (3) Results: 50 participants were included, resulting in 50 AppBP values on Day 1 and 33 on Day 2 after exclusion of 225 AppBP due to insufficient quality. The mean ± SD of the differences between AppBP and CuffBP was 0.7 ± 9.4/1.0 ± 4.5 mmHg (p-value 0.739/0.201) on Day 1 and 2.6 ± 8.2/1.3 ± 4.1 mmHg (p-value 0.106/0.091) on Day 2 for systolic/diastolic values, respectively. There were no significant differences between the deviations on Day 1 and Day 2 (p-value 0.297/0.533 for systolic/diastolic values). Overall, there were 10 (12%) systolic measurement pairs differing by >15 mmHg. (4) Conclusions: In this pilot evaluation, the RIVA Digital app shows promising results when compared to oscillometric cuff-based measurements, especially regarding diastolic values. Its differences between AppBP−CuffBP have a good stability one day after calibration. Before clinical use, signal acquisition needs improvement and the algorithm needs to undergo formal validation against a gold-standard BPM method.

A Novel Diagnostic Decision Support System for Medical Professionals: Prospective Feasibility Study.

BACKGROUND: Continuously growing medical knowledge and the increasing amount of data make it difficult for medical professionals to keep track of all new information and to place it in the context of existing information. A variety of digital technologies and artificial intelligence-based methods are currently available as persuasive tools to empower physicians in clinical decision-making and improve health care quality. A novel diagnostic decision support system (DDSS) prototype developed by Ada Health GmbH with a focus on traceability, transparency, and usability will be examined more closely in this study. OBJECTIVE: The aim of this study is to test the feasibility and functionality of a novel DDSS prototype, exploring its potential and performance in identifying the underlying cause of acute dyspnea in patients at the University Hospital Basel. METHODS: A prospective, observational feasibility study was conducted at the emergency department (ED) and internal medicine ward of the University Hospital Basel, Switzerland. A convenience sample of 20 adult patients admitted to the ED with dyspnea as the chief complaint and a high probability of inpatient admission was selected. A study physician followed the patients admitted to the ED throughout the hospitalization without interfering with the routine clinical work. Routinely collected health-related personal data from these patients were entered into the DDSS prototype. The DDSS prototype's resulting disease probability list was compared with the gold-standard main diagnosis provided by the treating physician. RESULTS: The DDSS presented information with high clarity and had a user-friendly, novel, and transparent interface. The DDSS prototype was not perfectly suited for the ED as case entry was time-consuming (1.5-2 hours per case). It provided accurate decision support in the clinical inpatient setting (average of cases in which the correct diagnosis was the first diagnosis listed: 6/20, 30%, SD 2.10%; average of cases in which the correct diagnosis was listed as one of the top 3: 11/20, 55%, SD 2.39%; average of cases in which the correct diagnosis was listed as one of the top 5: 14/20, 70%, SD 2.26%) in patients with dyspnea as the main presenting complaint. CONCLUSIONS: The study of the feasibility and functionality of the tool was successful, with some limitations. Used in the right place, the DDSS has the potential to support physicians in their decision-making process by showing new pathways and unintentionally ignored diagnoses. The DDSS prototype had some limitations regarding the process of data input, diagnostic accuracy, and completeness of the integrated medical knowledge. The results of this study provide a basis for the tool's further development. In addition, future studies should be conducted with the aim to overcome the current limitations of the tool and study design. TRIAL REGISTRATION: ClinicalTrials.gov NCT04827342; https://clinicaltrials.gov/ct2/show/NCT04827342.

Perception of physicians and nursing staff members regarding outside versus bedside ward rounds: ancillary analysis of the randomised BEDSIDE-OUTSIDE trial.

BACKGROUND: We recently compared the effects of bedside and outside the room ward rounds on patients' knowledge about their medical care. Here, we report preferences of medical and nursing staff members regarding outside versus bedside ward rounds. METHODS: Within this ancillary project of a large multicentre randomised controlled trial, we prospectively conducted a survey of medical and nursing staff members participating in the weekly consultant ward rounds in the internal medicine division of three Swiss teaching hospitals between July 2017 and October 2019. Participants were asked about their preferences on outside versus bedside ward rounds. The primary endpoint was satisfaction of healthcare workers with the ward round measured with a visual analogue scale from 0 to 100. RESULTS: Between July 2017 and October 2019, 919 patients were included in the trial, and we received 891 survey responses (nurses 15.6%, residents 26.8%, attending physicians 29.6%, consultants 7.8% and chief physicians 20.2%. In the overall analysis, mean (± standard deviation) satisfaction of healthcare workers was higher with outside the room than bedside ward rounds (78.03 ± 16.96 versus 68.25 ± 21.10 respectively; age-, gender- and centre-adjusted difference of -10.46, 95% confidence interval [CI] -12.73 to -8.19; p <0.001). Healthcare workers reported better time management, more discussion of sensitive topics and less discomfort when case presentations were conducted outside the room. A stratified subgroup analysis considering the profession, however, showed strong differences, with nurses being more satisfied with bedside rounds (69.20 ± 20.32 versus 65.32 ± 20.92, respectively; adjusted difference 4.35, 95% CI -1.79 to 10.51; p <0.001), whereas attending physicians showed higher satisfaction with outside the room rounds (82.63 ± 13.87 versus 66.59 ± 21.82; adjusted difference -16.51, 95% CI -20.29 to -12.72; p = 0.002). CONCLUSIONS: While bedside ward rounds are considered more patient centred and are preferred by the nursing staff, physicians prefer outside the room presentation of patients during ward rounds because of the perceived better discussion of sensitive topics, better time management and less staff discomfort. Continuous training including medical communication techniques may help to increase satisfaction of physicians with bedside ward rounds. Trial registration: https://clinicaltrials.gov/ct2/show/NCT03210987.

Mobile health solutions for atrial fibrillation detection and management: a systematic review.

AIM: We aimed to systematically review the available literature on mobile Health (mHealth) solutions, including handheld and wearable devices, implantable loop recorders (ILRs), as well as mobile platforms and support systems in atrial fibrillation (AF) detection and management. METHODS: This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. The electronic databases PubMed (NCBI), Embase (Ovid), and Cochrane were searched for articles published until 10 February 2021, inclusive. Given that the included studies varied widely in their design, interventions, comparators, and outcomes, no synthesis was undertaken, and we undertook a narrative review. RESULTS: We found 208 studies, which were deemed potentially relevant. Of these studies included, 82, 46, and 49 studies aimed at validating handheld devices, wearables, and ILRs for AF detection and/or management, respectively, while 34 studies assessed mobile platforms/support systems. The diagnostic accuracy of mHealth solutions differs with respect to the type (handheld devices vs wearables vs ILRs) and technology used (electrocardiography vs photoplethysmography), as well as application setting (intermittent vs continuous, spot vs longitudinal assessment), and study population. CONCLUSION: While the use of mHealth solutions in the detection and management of AF is becoming increasingly popular, its clinical implications merit further investigation and several barriers to widespread mHealth adaption in healthcare systems need to be overcome. Mobile health solutions for atrial fibrillation detection and management: a systematic review.

Immune thrombocytopenia associated with COVID-19 mRNA vaccine tozinameran - a clinical case and global pharmacovigilance data.

We report the occurrence of immune thrombocytopenia (ITP) in a 77-year-old man a few days after receiving the first dose of the COVID-19 mRNA vaccine tozinameran (Comirnaty®). The patient was treated with systemic corticosteroids, intravenous immunoglobulins and eltrombopag. He elected to proceed with the second dose of tozinameran 14 weeks after the first and his platelet count remained stable under a tapered eltrombopag dose. To our knowledge, this is the first case in which a second tozinameran dose has been administered to a patient who developed presumed secondary ITP after the first vaccination. We also report global pharmacovigilance data for the occurrence of ITP after vaccination with tozinameran.

Body composition analysis in patients with acute heart failure: the Scale Heart Failure trial.

AIMS: In this study, we aimed to investigate whether body composition analysis (BCA) derived from bioelectrical impedance vector analysis (BIVA) could be used to monitor the hydration status of patients with acute heart failure (AHF) during intensified diuretic therapy. METHODS AND RESULTS: This observational, single-centre study involved a novel, validated eight-electrode segmental body composition analyser to perform BCA derived from BIVA with an alternating current of 100 µA at frequencies of 5, 7.5, 50, and 75 kHz. The BCA-derived and BIVA-derived parameters were estimated and compared with daily body weight measurements in hospitalized patients with AHF. A total of 867 BCA and BIVA assessments were conducted in 142 patients (56.3% men; age 76.8 ± 10.7 years). Daily changes in total body water (TBW) and extracellular water (ECW) were significantly associated with changes in body weight in 62.2% and 89.1% of all measurements, respectively (range, ±1 kg). Repeated measures correlation coefficients between weight loss and TBW loss resulted with rho 0.43, P < 0.01, confidence interval (CI) [0.36, 0.50] and rho 0.71, P > 0.01, CI [0.67, 0.75] for ECW loss. Between the first and last assessments, the mean weight loss was -2.5 kg, compared with the -2.6 L mean TBW loss and -1.7 L mean ECW loss. BIVA revealed an increase in mean Resistance R and mean Reactance Xc across all frequencies, with the subsequent reduction in body fluid (including corresponding body weight) between the first and last assessments. CONCLUSIONS: Body composition analysis derived from BIVA with a focus on ECW is a promising approach to detect changes in hydration status in patients undergoing intensified diuretic therapy. Defining personalized BIVA reference values using bioelectrical impedance devices is a promising approach to monitor hydration status.

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.

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).

The Detection of Vancomycin in Sweat: A Next-Generation Digital Surrogate Marker for Antibiotic Tissue Penetration: A Pilot Study.

BACKGROUND: Assuring adequate antibiotic tissue concentrations at the point of infection, especially in skin and soft tissue infections, is pivotal for an effective treatment and cure. Despite the global issue, a reliable AB monitoring test is missing. Inadequate antibiotic treatment leads to the development of antimicrobial resistances and toxic side effects. ß-lactam antibiotics were already detected in sweat of patients treated with the respective antibiotics intravenously before. With the emergence of smartphone-based biosensors to analyse sweat on the spot of need, next-generation molecular digital biomarkers will be increasingly available for a non-invasive pharmacotherapy monitoring. OBJECTIVE: Here, we investigated if the glycopeptide antibiotic vancomycin is detectable in sweat samples of in-patients treated with intravenous vancomycin. METHODS: Eccrine sweat samples were collected using the Macroduct Sweat Collector®. Along every sweat sample, a blood sample was taken. Bio-fluid analysis was performed by Ultra-high Pressure Liquid Chromatograph-Tandem Quadrupole Mass Spectrometry coupled with tandem mass spectrometry. RESULTS: A total of 5 patients were included. Results demonstrate that vancomycin was detected in 5 out of 5 sweat samples. Specifically, vancomycin concentrations ranged from 0.011 to 0.118 mg/L in sweat and from 4.7 to 8.5 mg/L in blood. CONCLUSION: Our results serve as proof-of-concept that vancomycin is detectable in eccrine sweat and may serve as a surrogate marker for antibiotic tissue penetration. A targeted vancomycin treatment is crucial in patients with repetitive need for antibiotics and a variable antibiotic distribution such as in peripheral artery disease to optimize treatment effectiveness. If combined with on-skin smartphone-based biosensors and smartphone applications, the detection of antibiotic concentrations in sweat might enable a first digital, on-spot, lab-independent and non-invasive therapeutic drug monitoring in skin and soft tissue infections.

How should we measure blood pressure? Implications of the fourth blood pressure measurement in office blood pressure.

According to the European Hypertension Guidelines regarding office blood pressure measurements (OBPMs), the mean between second/third or third/fourth OBPM should be taken if the first two readings differ by ≤10 or >10 mmHg, respectively. Our aim was to explore the value of the fourth OBPM and determine whether a simplified OBPM procedure is feasible without loss of quality. In this cross-sectional study, four standard OBPMs were taken. The mean of the second/third OBPM (S2S3/D2D3) and third/fourth OBPM (S3S4/D3D4) for systolic/diastolic values was calculated. Correlation, agreement, and differences regarding BP classification were explored for the entire cohort and subsets with a difference between the first/second OBPM (S1S2/D1D2) ≤10 and >10 mmHg. Overall (n = 802) and for the subsets with an S1S2 (n = 596) and D1D2 (n = 742) difference ≤10 mmHg, S3S4/D3D4 was in median 0.5 mmHg lower than S2S3/D2D3, respectively (p < .0005 for all). In participants with an S1S2 (n = 206) and D1D2 (n = 60) difference >10 mmHg, S3S4/D3D4 differed numerically from S2S3/D2D3, respectively (p > .1 for all). Overall and for all subsets with an S1S2/D1D2 difference ≤10/>10 mmHg, less subjects were numerically classified as hypertensive with S3S4/D3D4 than with S2S3/D2D3 (p > .04), but BP reclassification occurred in both directions in 1.0%-10.0%, depending on the cohort. In conclusion, the third/fourth OBPM results in lower BP values than the second/third measurement, regardless of the difference between first/second OBPM, whereby BP reclassifications occurred in both directions. Therefore, the cutoff of >10 versus ≤10mmHg difference between first/second OBPM to implement a fourth BPM harbors the risk of distorted results. We therefore recommend using the second/third BPM for standardized OBPM. Trial registration: Registered on clinicaltrials.gov (NCT02552030).