A wearable device perspective on the standard definitions of disability progression in multiple sclerosis.

INTRODUCTION: Multiple sclerosis (MS) is a leading cause of disability among young adults, but standard clinical scales may not accurately detect subtle changes in disability occurring between visits. This study aims to explore whether wearable device data provides more granular and objective measures of disability progression in MS. METHODS: Remote Assessment of Disease and Relapse in Central Nervous System Disorders (RADAR-CNS) is a longitudinal multicenter observational study in which 400 MS patients have been recruited since June 2018 and prospectively followed up for 24 months. Monitoring of patients included standard clinical visits with assessment of disability through use of the Expanded Disability Status Scale (EDSS), 6-minute walking test (6MWT) and timed 25-foot walk (T25FW), as well as remote monitoring through the use of a Fitbit. RESULTS: Among the 306 patients who completed the study (mean age, 45.6 years; females 67%), confirmed disability progression defined by the EDSS was observed in 74 patients, who had approximately 1392 fewer daily steps than patients without disability progression. However, the decrease in the number of steps experienced over time by patients with EDSS progression and stable patients was not significantly different. Similar results were obtained with disability progression defined by the 6MWT and the T25FW. CONCLUSION: The use of continuous activity monitoring holds great promise as a sensitive and ecologically valid measure of disability progression in MS.

The 2023 wearable photoplethysmography roadmap.

Photoplethysmography is a key sensing technology which is used in wearable devices such as smartwatches and fitness trackers. Currently, photoplethysmography sensors are used to monitor physiological parameters including heart rate and heart rhythm, and to track activities like sleep and exercise. Yet, wearable photoplethysmography has potential to provide much more information on health and wellbeing, which could inform clinical decision making. This Roadmap outlines directions for research and development to realise the full potential of wearable photoplethysmography. Experts discuss key topics within the areas of sensor design, signal processing, clinical applications, and research directions. Their perspectives provide valuable guidance to researchers developing wearable photoplethysmography technology.

Automatic Assessment of the 2-Minute Walk Distance for Remote Monitoring of People with Multiple Sclerosis.

The aim of this study was to investigate the feasibility of automatically assessing the 2-Minute Walk Distance (2MWD) for monitoring people with multiple sclerosis (pwMS). For 154 pwMS, MS-related clinical outcomes as well as the 2MWDs as evaluated by clinicians and derived from accelerometer data were collected from a total of 323 periodic clinical visits. Accelerometer data from a wearable device during 100 home-based 2MWD assessments were also acquired. The error in estimating the 2MWD was validated for walk tests performed at hospital, and then the correlation (r) between clinical outcomes and home-based 2MWD assessments was evaluated. Robust performance in estimating the 2MWD from the wearable device was obtained, yielding an error of less than 10% in about two-thirds of clinical visits. Correlation analysis showed that there is a strong association between the actual and the estimated 2MWD obtained either at hospital (r = 0.71) or at home (r = 0.58). Furthermore, the estimated 2MWD exhibits moderate-to-strong correlation with various MS-related clinical outcomes, including disability and fatigue severity scores. Automatic assessment of the 2MWD in pwMS is feasible with the usage of a consumer-friendly wearable device in clinical and non-clinical settings. Wearable devices can also enhance the assessment of MS-related clinical outcomes.

Autonomic response to walk tests is useful for assessing outcome measures in people with multiple sclerosis.

Objective: The aim of this study was to evaluate the association between changes in the autonomic control of cardiorespiratory system induced by walk tests and outcome measures in people with Multiple Sclerosis (pwMS). Methods: Electrocardiogram (ECG) recordings of 148 people with Relapsing-Remitting MS (RRMS) and 58 with Secondary Progressive MS (SPMS) were acquired using a wearable device before, during, and after walk test performance from a total of 386 periodical clinical visits. A subset of 90 participants repeated a walk test at home. Various MS-related symptoms, including fatigue, disability, and walking capacity were evaluated at each clinical visit, while heart rate variability (HRV) and ECG-derived respiration (EDR) were analyzed to assess autonomic nervous system (ANS) function. Statistical tests were conducted to assess differences in ANS control between pwMS grouped based on the phenotype or the severity of MS-related symptoms. Furthermore, correlation coefficients (r) were calculated to assess the association between the most significant ANS parameters and MS-outcome measures. Results: People with SPMS, compared to RRMS, reached higher mean heart rate (HRM) values during walk test, and larger sympathovagal balance after test performance. Furthermore, pwMS who were able to adjust their HRM and ventilatory values, such as respiratory rate and standard deviation of the ECG-derived respiration, were associated with better clinical outcomes. Correlation analyses showed weak associations between ANS parameters and clinical outcomes when the Multiple Sclerosis phenotype is not taken into account. Blunted autonomic response, in particular HRM reactivity, was related with worse walking capacity, yielding r = 0.36 r = 0.29 (RRMS) and r > 0.5 (SPMS). A positive strong correlation r > 0.7 r > 0.65 between cardiorespiratory parameters derived at hospital and at home was also found. Conclusion: Autonomic function, as measured by HRV, differs according to MS phenotype. Autonomic response to walk tests may be useful for assessing clinical outcomes, mainly in the progressive stage of MS. Participants with larger changes in HRM are able to walk longer distance, while reduced ventilatory function during and after walk test performance is associated with higher fatigue and disability severity scores. Monitoring of disorder severity could also be feasible using ECG-derived cardiac and respiratory parameters recorded with a wearable device at home.

The Impact of COVID-19 Lockdown on Adults with Major Depressive Disorder from Catalonia: A Decentralized Longitudinal Study.

The present study analyzes the effects of each containment phase of the first COVID-19 wave on depression levels in a cohort of 121 adults with a history of major depressive disorder (MDD) from Catalonia recruited from 1 November 2019, to 16 October 2020. This analysis is part of the Remote Assessment of Disease and Relapse-MDD (RADAR-MDD) study. Depression was evaluated with the Patient Health Questionnaire-8 (PHQ-8), and anxiety was evaluated with the Generalized Anxiety Disorder-7 (GAD-7). Depression's levels were explored across the phases (pre-lockdown, lockdown, and four post-lockdown phases) according to the restrictions of Spanish/Catalan governments. Then, a mixed model was fitted to estimate how depression varied over the phases. A significant rise in depression severity was found during the lockdown and phase 0 (early post-lockdown), compared with the pre-lockdown. Those with low pre-lockdown depression experienced an increase in depression severity during the "new normality", while those with high pre-lockdown depression decreased compared with the pre-lockdown. These findings suggest that COVID-19 restrictions affected the depression level depending on their pre-lockdown depression severity. Individuals with low levels of depression are more reactive to external stimuli than those with more severe depression, so the lockdown may have worse detrimental effects on them.

Biopsychosocial Response to the COVID-19 Lockdown in People with Major Depressive Disorder and Multiple Sclerosis.

BACKGROUND: Changes in lifestyle, finances and work status during COVID-19 lockdowns may have led to biopsychosocial changes in people with pre-existing vulnerabilities such as Major Depressive Disorders (MDDs) and Multiple Sclerosis (MS). METHODS: Data were collected as a part of the RADAR-CNS (Remote Assessment of Disease and Relapse-Central Nervous System) program. We analyzed the following data from long-term participants in a decentralized multinational study: symptoms of depression, heart rate (HR) during the day and night; social activity; sedentary state, steps and physical activity of varying intensity. Linear mixed-effects regression analyses with repeated measures were fitted to assess the changes among three time periods (pre, during and post-lockdown) across the groups, adjusting for depression severity before the pandemic and gender. RESULTS: Participants with MDDs (N = 255) and MS (N = 214) were included in the analyses. Overall, depressive symptoms remained stable across the three periods in both groups. A lower mean HR and HR variation were observed between pre and during lockdown during the day for MDDs and during the night for MS. HR variation during rest periods also decreased between pre- and post-lockdown in both clinical conditions. We observed a reduction in physical activity for MDDs and MS upon the introduction of lockdowns. The group with MDDs exhibited a net increase in social interaction via social network apps over the three periods. CONCLUSIONS: Behavioral responses to the lockdown measured by social activity, physical activity and HR may reflect changes in stress in people with MDDs and MS. Remote technology monitoring might promptly activate an early warning of physical and social alterations in these stressful situations. Future studies must explore how stress does or does not impact depression severity.

Fitbeat: COVID-19 estimation based on wristband heart rate using a contrastive convolutional auto-encoder.

This study proposes a contrastive convolutional auto-encoder (contrastive CAE), a combined architecture of an auto-encoder and contrastive loss, to identify individuals with suspected COVID-19 infection using heart-rate data from participants with multiple sclerosis (MS) in the ongoing RADAR-CNS mHealth research project. Heart-rate data was remotely collected using a Fitbit wristband. COVID-19 infection was either confirmed through a positive swab test, or inferred through a self-reported set of recognised symptoms of the virus. The contrastive CAE outperforms a conventional convolutional neural network (CNN), a long short-term memory (LSTM) model, and a convolutional auto-encoder without contrastive loss (CAE). On a test set of 19 participants with MS with reported symptoms of COVID-19, each one paired with a participant with MS with no COVID-19 symptoms, the contrastive CAE achieves an unweighted average recall of 95.3 % , a sensitivity of 100 % and a specificity of 90.6 % , an area under the receiver operating characteristic curve (AUC-ROC) of 0.944, indicating a maximum successful detection of symptoms in the given heart rate measurement period, whilst at the same time keeping a low false alarm rate.

The Added Value of Nonlinear Cardiorespiratory Coupling Indices in the Assessment of Depression.

The present study investigates the differences in autonomic nervous system (ANS) function and stress response between patients with major depressive disorder (MDD) and healthy subjects by measuring changes in ANS biomarkers. ANS-related parameters are derived from various biosignals during a mental stress protocol consisting of a basal, stress, and recovery phase. The feature set consists of ANS biomarkers such as the heart rate (HR) derived from the electrocardiogram, the respiratory rate derived from the respiration signal, vascular parameters obtained from a model-based photoplethysmographic pulse waveform analysis, and cardiorespiratory coupling indices derived from the joint analysis of the heart rate variability (HRV) and respiratory signals. In particular, linear cardiorespiratory interactions are quantified by means of time-frequency coherence, while interactions of quadratic nonlinear nature between HRV and respiration are quantified by means of real wavelet biphase. The intra-subject difference of a feature value between two phases of the protocol, the so-called autonomic reactivity, is considered as a ANS biomarker as well. The performance of ANS biomarkers on discriminating MDD patients is evaluated using a classification pipeline. The results show that the most discriminative ANS biomarkers are related with differences in HR and autonomic reactivity of both vascular and nonlinear cardiorespiratory coupling indices. Differences in autonomic reactivity imply that MDD and healthy subjects differ in their ability to cope with stress. Considering only HR and vascular characteristics a linear support-vector machine classifier yields to accuracy 72.5% and F1-score 73.2%. However, taking into account the nonlinear cardiorespiratory coupling indices, the classification performance improves, yielding to accuracy 77.5% and F1-score 78.0%.Clinical relevance- Changes in the nonlinear properties of the cardiorespiratory system during stress may yield additional information on the assessment of depression.

Photoplethysmographic Waveform Analysis for Autonomic Reactivity Assessment in Depression.

OBJECTIVE: In the present study, a photoplethysmographic (PPG) waveform analysis for assessing differences in autonomic reactivity to mental stress between patients with Major Depressive Disorder (MDD) and healthy control (HC) subjects is presented. METHODS: PPG recordings of 40 MDD and 40 HC subjects were acquired at basal conditions, during the execution of cognitive tasks, and at the post-task relaxation period. PPG pulses are decomposed into three waves (a main wave and two reflected waves) using a pulse decomposition analysis. Pulse waveform characteristics such as the time delay between the position of the main wave and reflected waves, the percentage of amplitude loss in the reflected waves, and the heart rate (HR) are calculated among others. The intra-subject difference of a feature value between two conditions is used as an index of autonomic reactivity. RESULTS: Statistically significant individual differences from stress to recovery were found for HR and the percentage of amplitude loss in the second reflected wave ( A13) in both HC and MDD group. However, autonomic reactivity indices related to  A13 reached higher values in HC than in MDD subjects (Cohen's [Formula: see text]), implying that the stress response in depressed patients is reduced. A statistically significant ( ) negative correlation ( r=-0.5) between depression severity scores and A13 was found. CONCLUSION: A decreased autonomic reactivity is associated with higher degree of depression. SIGNIFICANCE: Stress response quantification by dynamic changes in PPG waveform morphology can be an aid for the diagnosis and monitoring of depression.

A Comparative Study of ECG-derived Respiration in Ambulatory Monitoring using the Single-lead ECG.

Cardiorespiratory monitoring is crucial for the diagnosis and management of multiple conditions such as stress and sleep disorders. Therefore, the development of ambulatory systems providing continuous, comfortable, and inexpensive means for monitoring represents an important research topic. Several techniques have been proposed in the literature to derive respiratory information from the ECG signal. Ten methods to compute single-lead ECG-derived respiration (EDR) were compared under multiple conditions, including different recording systems, baseline wander, normal and abnormal breathing patterns, changes in breathing rate, noise, and artifacts. Respiratory rates, wave morphology, and cardiorespiratory information were derived from the ECG and compared to those extracted from a reference respiratory signal. Three datasets were considered for analysis, involving a total 59 482 one-min, single-lead ECG segments recorded from 156 subjects. The results indicate that the methods based on QRS slopes outperform the other methods. This result is particularly interesting since simplicity is crucial for the development of ECG-based ambulatory systems.

ECG-Derived Respiratory Rate in Atrial Fibrillation.

OBJECTIVE: The present study addresses the problem of estimating the respiratory rate from the morphological ECG variations in the presence of atrial fibrillatory waves (f-waves). The significance of performing f-wave suppression before respiratory rate estimation is investigated. METHODS: The performance of a novel approach to ECG-derived respiration, named "slope range" (SR) and designed particularly for operation in atrial fibrillation (AF), is compared to that of two well-known methods based on either R-wave angle (RA) or QRS loop rotation angle (LA). A novel rule is proposed for spectral peak selection in respiratory rate estimation. The suppression of f-waves is accomplished using signal- and noise-dependent QRS weighted averaging. The performance evaluation embraces real as well as simulated ECG signals acquired from patients with persistent AF; the estimation error of the respiratory rate is determined for both types of signals. RESULTS: Using real ECG signals and reference respiratory signals, rate estimation without f-wave suppression resulted in a median error of 0.015 ± 0.021 Hz and 0.019 ± 0.025 Hz for SR and RA, respectively, whereas LA with f-wave suppression resulted in 0.034 ± 0.039 Hz. Using simulated signals, the results also demonstrate that f-wave suppression is superfluous for SR and RA, whereas it is essential for LA. CONCLUSION: The results show that SR offers the best performance as well as computational simplicity since f-wave suppression is not needed. SIGNIFICANCE: The respiratory rate can be robustly estimated from the ECG in the presence of AF.

Assessment of Quadratic Nonlinear Cardiorespiratory Couplings During Tilt-Table Test by Means of Real Wavelet Biphase.

OBJECTIVE: In this paper, a method for assessment of quadratic phase coupling (QPC) between respiration and heart rate variability (HRV) is presented. METHODS: First, a method for QPC detection is proposed named real wavelet biphase (RWB). Then, a method for QPC quantification is proposed based on the normalized wavelet biamplitude (NWB). A simulation study has been conducted to test the reliability of RWB to identify QPC, even in the presence of constant delays between interacting oscillations, and to discriminate it from quadratic phase uncoupling. Significant QPC was assessed based on surrogate data analysis. Then, quadratic cardiorespiratory couplings were studied during a tilt-table test protocol of 17 young healthy subjects. RESULTS: Simulation study showed that RWB is able to detect even weak QPC with delays in the range of [Formula: see text] s, which are usual in the autonomic nervous system (ANS) control of heart rate. Results from the database revealed a significant reduction ([Formula: see text]) of NWB between respiration and both low and high frequencies of HRV in head-up tilt position compared to early supine. CONCLUSION: The proposed technique detects and quantifies robustly QPC and is able to track the coupling between respiration and various HRV components during ANS changes. SIGNIFICANCE: The proposed method can help to assess alternations of nonlinear cardiorespiratory interactions related to ANS dysfunction and physiological regulation of HRV in cardiovascular diseases.

Respiratory Rate Derived from Pulse Photoplethysmographic Signal by Pulse Decomposition Analysis.

A novel technique to derive respiratory rate from pulse photoplethysmographic (PPG) signals is presented. It exploits some morphological features of the PPG pulse that are known to be modulated by respiration: amplitude, slope transit time, and width of the main wave, and time to the first reflected wave. A pulse decomposition analysis technique is proposed to measure these features. This technique allows to decompose the PPG pulse into its main wave and its subsequent reflected waves, improving the robustness against noise and morphological changes that usually occur in long-term recordings. Proposed methods were evaluated with a data base containing PPG and plethysmography-based respiratory signals simultaneously recorded during a paced-breathing experiment. Results suggest that normal ranges of spontaneous respiratory rate (0.1-0.5 Hz) can be accurately estimated (median and interquartile range of relative error less than 5%) from PPG signals by using the studied features.