Smartphone-based screening for atrial fibrillation: a pragmatic randomized clinical trial.

Digital smart devices have the capability of detecting atrial fibrillation (AF), but the efficacy of this type of digital screening has not been directly compared to usual care for detection of treatment-relevant AF. In the eBRAVE-AF trial ( NCT04250220 ), we randomly assigned 5,551 policyholders of a German health insurance company who were free of AF at baseline (age 65 years (median; interquartile range (11) years, 31% females)) to digital screening (n = 2,860) or usual care (n = 2,691). In this siteless trial, for digital screening, participants used a certified app on their own smartphones to screen for irregularities in their pulse waves. Abnormal findings were evaluated by 14-day external electrocardiogram (ECG) loop recorders. The primary endpoint was newly diagnosed AF within 6 months treated with oral anti-coagulation by an independent physician not involved in the study. After 6 months, participants were invited to cross-over for a second study phase with reverse assignment for secondary analyses. The primary endpoint of the trial was met, as digital screening more than doubled the detection rate of treatment-relevant AF in both phases of the trial, with odds ratios of 2.12 (95% confidence interval (CI), 1.19-3.76; P = 0.010) and 2.75 (95% CI, 1.42-5.34; P = 0.003) in the first and second phases, respectively. This digital screening technology provides substantial benefits in detecting AF compared to usual care and has the potential for broad applicability due to its wide availability on ordinary smartphones. Future studies are needed to test whether digital screening for AF leads to better treatment outcomes.

Rationale and design of a digital trial using smartphones to detect subclinical atrial fibrillation in a population at risk: The eHealth-based bavarian alternative detection of Atrial Fibrillation (eBRAVE-AF) trial.

Current guidelines recommend opportunistic screening for subclinical atrial fibrillation (AF) taking advantage of e-health-based technologies. However, the efficacy of a fully scalable e-health-based strategy for AF detection in a head-to-head comparison with routine symptom-based screening is unknown. eBRAVE-AF is an investigator-initiated, digital, prospective, randomized, siteless, open-label, cross-over study to evaluate an e-health-based strategy for detection of AF in a real-world setting. 67,488 policyholders of a large German health insurance company (Versicherungskammer Bayern, Germany) selected by age ≥ 50 years and a CHA2DS2-VASc score ≥ 1 (females ≥2) are invited to participate. Subjects with known AF or on treatment with oral anticoagulation are excluded. After obtaining electronic informed consent, at least 4,400 participants will be randomly assigned to an e-health-based screening strategy or routine symptom-based screening. The e-health-based strategy consists of repetitive one-minute photoplethysmographic (PPG) pulse wave assessments using a certified smartphone app (Preventicus Heartbeats, Preventicus, Jena, Germany), followed by a confirmatory 14-day ECG patch (CardioMem CM 100 XT, Getemed, Teltow, Germany) in case of abnormal findings. After 6 months, participants are crossed over to the other study arm. Primary endpoint is the incidence of newly diagnosed AF leading to oral anticoagulation indicated by an independent physician. Clinical follow-up will be at least 12 months. In both groups, follow-up is performed by 4-week app-based questionnaires, personal contact in case of abnormal findings, and matching with claim-based insurance data and medical reports. At time of writing enrollment is completed. First results are expected to be available in mid-2021.

App-Based Tracking of Self-Reported COVID-19 Symptoms: Analysis of Questionnaire Data.

BACKGROUND: COVID-19 is an infectious disease characterized by various clinical presentations. Knowledge of possible symptoms and their distribution allows for the early identification of infected patients. OBJECTIVE: To determine the distribution pattern of COVID-19 symptoms as well as possible unreported symptoms, we created an app-based self-reporting tool. METHODS: The COVID-19 Symptom Tracker is an app-based daily self-reporting tool. Between April 8 and May 15, 2020, a total of 22,327 individuals installed this app on their mobile device. An initial questionnaire asked for demographic information (age, gender, postal code) and past medical history comprising relevant chronic diseases. The participants were reminded daily to report whether they were experiencing any symptoms and if they had been tested for SARS-CoV-2 infection. Participants who sought health care services were asked additional questions regarding diagnostics and treatment. Participation was open to all adults (≥18 years). The study was completely anonymous. RESULTS: In total, 11,829 (52.98%) participants completed the symptom questionnaire at least once. Of these, 291 (2.46%) participants stated that they had undergone an RT-PCR (reverse transcription-polymerase chain reaction) test for SARS-CoV-2; 65 (0.55%) reported a positive test result and 226 (1.91%) a negative one. The mean number of reported symptoms among untested participants was 0.81 (SD 1.85). Participants with a positive test result had, on average, 5.63 symptoms (SD 2.82). The most significant risk factors were diabetes (odds ratio [OR] 8.95, 95% CI 3.30-22.37) and chronic heart disease (OR 2.85, 95% CI 1.43-5.69). We identified chills, fever, loss of smell, nausea and vomiting, and shortness of breath as the top five strongest predictors for a COVID-19 infection. The odds ratio for loss of smell was 3.13 (95% CI 1.76-5.58). Nausea and vomiting (OR 2.84, 95% CI 1.61-5.00) had been reported as an uncommon symptom previously; however, our data suggest a significant predictive value. CONCLUSIONS: Self-reported symptom tracking helps to identify novel symptoms of COVID-19 and to estimate the predictive value of certain symptoms. This aids in the development of reliable screening tools. Clinical screening with a high pretest probability allows for the rapid identification of infections and the cost-effective use of testing resources. Based on our results, we suggest that loss of smell and taste be considered cardinal symptoms; we also stress that diabetes is a risk factor for a highly symptomatic course of COVID-19 infection.

Clinical analysis of MatrixMANDIBLE Preformed Reconstruction Plate design.

MatrixMANDIBLE Preformed Reconstruction Plates (MMPRPs) were developed to overcome laborious bending procedures of conventional reconstruction plates. The design comprises three sizes with a nonbendable centerpiece and two bendable sections (proximal and distal). According to the surgical protocol unnecessary parts are trimmed after the last used screw hole. In the present retrospective study postoperative radiographs from 130 patients (average age 63 years) that received treatment with MMPRPs were assessed. There was no statistical correlation between plate-size, location (left/right) or age. 82.98% of the small and 91.80% of the medium MMPRPs were trimmed by at least the terminal screw hole of the ramus part. In all patients receiving a large MMPRP, the terminal screw hole of the ramus was unused accordingly all inserted large MMPRPs were trimmed by at least the terminal screw hole. The majority of the bridged defects were located within the area of the body indicating a feasible plate design. With the emergence of solid free form fabrication of Ti-alloys and economic need to reduce the waste of resources this study may help to further improve the MMPRP design and prevent the loss of medical-grade titanium.

Development of a Modular Research Platform to Create Medical Observational Studies for Mobile Devices.

BACKGROUND: Observational studies have proven to be a valuable resource in medical research, especially when performed on a large scale. Recently, mobile device-based observational studies have been discovered by an increasing number of researchers as a promising new source of information. However, the development and deployment of app-based studies is not trivial and requires profound programming skills. OBJECTIVE: The aim of this project was to develop a modular online research platform that allows researchers to create medical studies for mobile devices without extensive programming skills. METHODS: The platform approach for a modular research platform consists of three major components. A Web-based platform forms the researchers' main workplace. This platform communicates via a shared database with a platform independent mobile app. Furthermore, a separate Web-based login platform for physicians and other health care professionals is outlined and completes the concept. RESULTS: A prototype of the research platform has been developed and is currently in beta testing. Simple questionnaire studies can be created within minutes and published for testing purposes. Screenshots of an example study are provided, and the general working principle is displayed. CONCLUSIONS: In this project, we have created a basis for a novel research platform. The necessity and implications of a modular approach were displayed and an outline for future development given. International researchers are invited and encouraged to participate in this ongoing project.

"Back on Track": A Mobile App Observational Study Using Apple's ResearchKit Framework.

BACKGROUND: In March 2015, Apple Inc announced ResearchKit, a novel open-source framework intended to help medical researchers to easily create apps for medical studies. With the announcement of this framework, Apple presented 5 apps built in a beta phase based on this framework. OBJECTIVE: The objective of this study was to better understand decision making in patients with acute anterior cruciate ligament (ACL) ruptures. Here, we describe the development of a ResearchKit app for this study. METHODS: A multilanguage observatory study was conducted. At first a suitable research topic, target groups, participating territories, and programming method were carefully identified. The ResearchKit framework was used to program the app. A secure server connection was realized via Secure Sockets Layer. A data storage and security concept separating personal information and study data was proposed. Furthermore, an efficient method to allow multilanguage support and distribute the app in many territories was presented. Ethical implications were considered and taken into account regarding privacy policies. RESULTS: An app study based on ResearchKit was developed without comprehensive iPhone Operating System (iOS) development experience. The Apple App Store is a major distribution channel causing significant download rates (>1.200/y) without active recruitment. Preliminary data analysis showed moderate dropout rates and a good quality of data. A total of 180 participants were currently enrolled with 107 actively participating and producing 424 completed surveys in 9 out of 24 months. CONCLUSIONS: ResearchKit is an easy-to-use framework and powerful tool to create medical studies. Advantages are the modular built, the extensive reach of iOS devices, and the convenient programming environment.

Polydimethylsiloxane pressure sensors for force analysis in tension band wiring of the olecranon.

BACKGROUND: Several different surgical techniques are used in the treatment of olecranon fractures. Tension band wiring is one of the most preferred options by surgeons worldwide. The concept of this technique is to transform a tensile force into a compression force that adjoins two surfaces of a fractured bone. Currently, little is known about the resulting compression force within a fracture. OBJECTIVE: Sensor devices are needed that directly transduce the compression force into a measurement quality. This allows the comparison of different surgical techniques. Ideally the sensor devices ought to be placed in the gap between the fractured segments. METHODS: The design, development and characterization of miniaturized pressure sensors fabricated entirely from polydimethylsiloxane (PDMS) for a placement within a fracture is presented. The pressure sensors presented in this work are tested, calibrated and used in an experimental in vitro study. RESULTS: The pressure sensors are highly sensitive with an accuracy of approximately 3 kPa. A flexible fabrication process for various possible applications is described. The first in vitro study shows that using a single-twist or double-twist technique in tension band wiring of the olecranon has no significant effect on the resulting compression forces. CONCLUSIONS: The in vitro study shows the feasibility of the proposed measurement technique and the results of a first exemplary study.

Novel approach to dynamic knee laxity measurement using capacitive strain gauges.

PURPOSE: Knee joint laxities are observed in patients after severe trauma to the joint, resulting in ligament tears. Specifically, injuries to the anterior cruciate ligament may cause a significant instability. The degree of these laxities is essential in diagnostics and may affect which treatment option is suggested. METHODS: Polydimethylsiloxane (PDMS) strain gauges are proposed as a non-invasive, highly accurate and easy-to-use measurement method to quantify anterolateral and rotational laxities of the knee joint during active and passive motion. In this work, proof-of-concept measurements and a prototype of the proposed device are displayed. The measurements were taken using a knee test rig, which has specifically been designed for this purpose. This apparatus allows the simulation of isolated knee joint instabilities with a motor-controlled model of a human knee. RESULTS: The absolute sensitivity [Formula: see text] of an exemplary sensor was determined to be 2.038 [Formula: see text]; the relative sensitivity [Formula: see text] was 1.121 [Formula: see text]. Optimal positions of sensors to capture bone-to-bone displacement as projected displacement on the skin were identified. CONCLUSION: PDMS strain gauges are capable of measuring bone-to-bone displacements on the skin. We present an experimental in vitro study using an artificial knee test rig to simulate knee joint laxities and display the feasibility of our novel measurement approach.

Length Changes of the Anterolateral Ligament During Passive Knee Motion: A Human Cadaveric Study.

BACKGROUND: Persistent rotatory instability after anterior cruciate ligament (ACL) reconstruction may be a result of unaddressed insufficiency of the anterolateral structures. Recent publications about the anatomy of the anterolateral ligament (ALL) have led to a renewed interest in lateral extra-articular procedures, and several authors have proposed ALL reconstruction to supplement intra-articular ACL reconstruction. However, only limited knowledge about the biomechanical characteristics of the ALL exists. PURPOSE/HYPOTHESIS: The purpose of this study was to analyze length changes of the ALL during passive knee motion. The study hypothesis was that the ALL lengthens with knee flexion and internal tibial rotation. STUDY DESIGN: Controlled laboratory study. METHODS: The ALL of 6 cadaveric knees was dissected. Specimens were mounted in a specifically designed test rig that allowed unconstrained passive flexion/extension movement between 0° and 90° as well as external/internal tibial rotation of 25° at various flexion angles. Highly elastic, capacitive polydimethylsiloxane strain gauges were attached to the insertion sites of the ALL. Length changes were recorded continuously at flexion angles between 0° and 90° and during internal/external tibial rotation at 0°, 15°, 30°, 45°, 60°, 75°, and 90°. All measurements were calculated as the relative length change (%) of the ALL compared with 0° of flexion and neutral rotation. RESULTS: The mean relative length of the ALL significantly increased with increasing knee flexion (P < .001), with an estimated mean length change of +0.15% per degree. Both internal and external tibial rotation were independent determinants for length change; internal rotation significantly increased the length of the ALL (P < .001), whereas external rotation significantly decreased its length (P < .001). The mean length change with internal rotation increased with knee flexion, with a significantly greater length change at 90° compared with 0° (P = .048), 15° (P = .033), and 30° (P = .015). The maximum mean length change was +33.77% ± 9.62%, which was observed at 25° of internal rotation and 90° of flexion. CONCLUSION: The ALL is a nonisometric structure that tensions with knee flexion and internal tibial rotation. Length changes with internal rotation were greater at higher flexion angles, with the greatest length change of the ALL observed at 90° of flexion. CLINICAL RELEVANCE: The ALL can be considered a stabilizer against internal tibial rotation, especially at deep flexion angles. With regard to ALL reconstruction procedures, tensioning and fixation of the graft should be performed near 90° of flexion because graft tensioning near extension may cause excessive ligament strain with increasing knee flexion.

Mechanical tensile properties of the anterolateral ligament.

BACKGROUND: In a noticeable percentage of patients anterolateral rotational instabilities (ALRI) remain after an isolated ACL reconstruction. Those instabilities may occur due to an insufficiently directed damage of anterolateral structures that is often associated with ACL ruptures. Recent publications describe an anatomical structure, termed the anterolateral ligament (ALL), and suggest that this ligament plays a significant role in the pathogenesis of ALRI of the knee joint. However, only limited knowledge about the biomechanical characteristics and tensile properties of the anterolateral ligament exists. METHODS: The anterolateral ligament was dissected in four fresh-frozen human cadaveric specimens and all surrounding tissue removed. The initial length of the anterolateral ligament was measured using a digital caliper. Tensile tests with load to failure were performed using a materials testing machine. The explanted anterolateral ligaments were histologically examined to measure the cross-sectional area. RESULTS: The mean ultimate load to failure of the anterolateral ligament was 49.90 N (± 14.62 N) and the mean ultimate strain was 35.96% (± 4.47%). The mean length of the ligament was 33.08 mm (± 2.24) and the mean cross-sectional area was 1.54 m m (2) (± 0.48 m m (2)). Including the areal measurements the maximum tension was calculated to be 32.78 [Formula: see text] (± 4.04 [Formula: see text]). CONCLUSIONS: The anterolateral ligament is an anatomical structure with tensile properties that are considerably weaker compared to other peripheral structures of the knee. Knowledge of the anterolateral ligament's tensile strengths may help to better understand its function and with graft choices for reconstruction procedures.

A new approach to determine ligament strain using polydimethylsiloxane strain gauges: exemplary measurements of the anterolateral ligament.

A thorough understanding of ligament strains and behavior is necessary to create biomechanical models, comprehend trauma mechanisms, and surgically reconstruct those ligaments in a manner that restores a physiological performance. Measurement techniques and sensors are needed to conduct this data with high accuracy in an in vitro environment. In this work, we present a novel sensor device that is capable of continuously recording ligament strains with high resolution. The sensor principle of this biocompatible strain gauge may be used for in vitro measurements and can easily be applied to any ligament in the human body. The recently rediscovered anterolateral ligament (ALL) of the knee joint was chosen to display the capability of this novel sensor system. Three cadaver knees were tested to successfully demonstrate the concept of the sensor device and display first results regarding the elongation of the ALL during flexion/extension of the knee.