Search

Abstract Drug development for mood disorders can greatly benefit from the development of robust, reliable, and objective biomarkers. The incorporation of smartphones and wearable devices in clinical trials provide a unique opportunity to monitor behavior in a non-invasive manner. The objective of this study is to identify the correlations between remotely monitored self-reported assessments and objectively measured activities with depression severity assessments often applied in clinical trials. 30 unipolar depressed patients and 29 age- and gender-matched healthy controls were enrolled in this study. Each participant’s daily physiological, physical, and social activity were monitored using a smartphone-based application (CHDR MORE™) for 3 weeks continuously. Self-reported depression anxiety stress scale-21 (DASS-21) and positive and negative affect schedule (PANAS) were administered via smartphone weekly and daily respectively. The structured interview guide for the Hamilton depression scale and inventory of depressive symptomatology–clinical rated (SIGHD-IDSC) was administered in-clinic weekly. Nested cross-validated linear mixed-effects models were used to identify the correlation between the CHDR MORE™ features with the weekly in-clinic SIGHD-IDSC scores. The SIGHD-IDSC regression model demonstrated an explained variance (R2) of 0.80, and a Root Mean Square Error (RMSE) of ± 15 points. The SIGHD-IDSC total scores were positively correlated with the DASS and mean steps-per-minute, and negatively correlated with the travel duration. Unobtrusive, remotely monitored behavior and self-reported outcomes are correlated with depression severity. While these features cannot replace the SIGHD-IDSC for estimating depression severity, it can serve as a complementary approach for assessing depression and drug effects outside the clinic.

Abstract Current methods of pharmacovigilance result in severe under-reporting of adverse drug events (ADEs). Patient forums have the potential to complement current pharmacovigilance practices by providing real-time uncensored and unsolicited information. We are the first to explore the value of patient forums for rare cancers. To this end, we conduct a case study on a patient forum for Gastrointestinal Stromal Tumor patients. We have developed machine learning algorithms to automatically extract and aggregate side effects from messages on open online discussion forums. We show that patient forum data can provide suggestions for which ADEs impact quality of life the most: For many side effects the relative reporting rate differs decidedly from that of the registration trials, including for example cognitive impairment and alopecia as side effects of avapritinib. We also show that our methods can provide real-world data for long-term ADEs, such as osteoporosis and tremors for imatinib, and novel ADEs not found in registration trials, such as dry eyes and muscle cramping for imatinib. We thus posit that automated pharmacovigilance from patient forums can provide real-world data for ADEs and should be employed as input for medical hypotheses for rare cancers.

BackgroundFacioscapulohumeral muscular dystrophy (FSHD) is a progressive neuromuscular disease. Its slow and variable progression makes the development of new treatments highly dependent on validated biomarkers that can quantify disease progression and response to drug interventions. ObjectiveWe aimed to build a tool that estimates FSHD clinical severity based on behavioral features captured using smartphone and remote sensor data. The adoption of remote monitoring tools, such as smartphones and wearables, would provide a novel opportunity for continuous, passive, and objective monitoring of FSHD symptom severity outside the clinic. MethodsIn total, 38 genetically confirmed patients with FSHD were enrolled. The FSHD Clinical Score and the Timed Up and Go (TUG) test were used to assess FSHD symptom severity at days 0 and 42. Remote sensor data were collected using an Android smartphone, Withings Steel HR+, Body+, and BPM Connect+ for 6 continuous weeks. We created 2 single-task regression models that estimated the FSHD Clinical Score and TUG separately. Further, we built 1 multitask regression model that estimated the 2 clinical assessments simultaneously. Further, we assessed how an increasingly incremental time window affected the model performance. To do so, we trained the models on an incrementally increasing time window (from day 1 until day 14) and evaluated the predictions of the clinical severity on the remaining 4 weeks of data. ResultsThe single-task regression models achieved an R2 of 0.57 and 0.59 and a root-mean-square error (RMSE) of 2.09 and 1.66 when estimating FSHD Clinical Score and TUG, respectively. Time spent at a health-related location (such as a gym or hospital) and call duration were features that were predictive of both clinical assessments. The multitask model achieved an R2 of 0.66 and 0.81 and an RMSE of 1.97 and 1.61 for the FSHD Clinical Score and TUG, respectively, and therefore outperformed the single-task models in estimating clinical severity. The 3 most important features selected by the multitask model were light sleep duration, total steps per day, and mean steps per minute. Using an increasing time window (starting from day 1 to day 14) for the FSHD Clinical Score, TUG, and multitask estimation yielded an average R2 of 0.65, 0.79, and 0.76 and an average RMSE of 3.37, 2.05, and 4.37, respectively. ConclusionsWe demonstrated that smartphone and remote sensor data could be used to estimate FSHD clinical severity and therefore complement the assessment of FSHD outside the clinic. In addition, our results illustrated that training the models on the first week of data allows for consistent and stable prediction of FSHD symptom severity. Longitudinal follow-up studies should be conducted to further validate the reliability and validity of the multitask model as a tool to monitor disease progression over a longer period. Trial RegistrationClinicalTrials.gov NCT04999735; https://www.clinicaltrials.gov/ct2/show/NCT04999735

Abstract Background Recent developments in machine learning have shown its potential impact for clinical use such as risk prediction, prognosis, and treatment selection. However, relevant data are often scattered across different stakeholders and their use is regulated, e.g. by GDPR or HIPAA. As a concrete use-case, hospital Erasmus MC and health insurance company Achmea have data on individuals in the city of Rotterdam, which would in theory enable them to train a regression model in order to identify high-impact lifestyle factors for heart failure. However, privacy and confidentiality concerns make it unfeasible to exchange these data. Methods This article describes a solution where vertically-partitioned synthetic data of Achmea and of Erasmus MC are combined using Secure Multi-Party Computation. First, a secure inner join protocol takes place to securely determine the identifiers of the patients that are represented in both datasets. Then, a secure Lasso Regression model is trained on the securely combined data. The involved parties thus obtain the prediction model but no further information on the input data of the other parties. Results We implement our secure solution and describe its performance and scalability: we can train a prediction model on two datasets with 5000 records each and a total of 30 features in less than one hour, with a minimal difference from the results of standard (non-secure) methods. Conclusions This article shows that it is possible to combine datasets and train a Lasso regression model on this combination in a secure way. Such a solution thus further expands the potential of privacy-preserving data analysis in the medical domain.

Background: Central nervous system (CNS) disorders benefit from ongoing monitoring to assess disease progression and treatment efficacy. Mobile health (mHealth) technologies offer a means for the remote and continuous symptom monitoring of patients. Machine Learning (ML) techniques can process and engineer mHealth data into a precise and multidimensional biomarker of disease activity. Objective: This narrative literature review aims to provide an overview of the current landscape of biomarker development using mHealth technologies and ML. Additionally, it proposes recommendations to ensure the accuracy, reliability, and interpretability of these biomarkers. Methods: This review extracted relevant publications from databases such as PubMed, IEEE, and CTTI. The ML methods employed across the selected publications were then extracted, aggregated, and reviewed. Results: This review synthesized and presented the diverse approaches of 66 publications that address creating mHealth-based biomarkers using ML. The reviewed publications provide a foundation for effective biomarker development and offer recommendations for creating representative, reproducible, and interpretable biomarkers for future clinical trials. Conclusion: mHealth-based and ML-derived biomarkers have great potential for the remote monitoring of CNS disorders. However, further research and standardization of study designs are needed to advance this field. With continued innovation, mHealth-based biomarkers hold promise for improving the monitoring of CNS disorders.

BackgroundHeart rate (HR) is an important and commonly measured physiological parameter in wearables. HR is often measured at the wrist with the photoplethysmography (PPG) technique, which determines HR based on blood volume changes, and is therefore influenced by blood pressure. In individuals with spinal cord injury (SCI), blood pressure control is often altered and could therefore influence HR accuracy measured by the PPG technique. ObjectiveThe objective of this study is to investigate the HR accuracy measured with the PPG technique with a Fitbit Charge 2 (Fitbit Inc) in wheelchair users with SCI, how the activity intensity affects the HR accuracy, and whether this HR accuracy is affected by lesion level. MethodsThe HR of participants with (38/48, 79%) and without (10/48, 21%) SCI was measured during 11 wheelchair activities and a 30-minute strength exercise block. In addition, a 5-minute seated rest period was measured in people with SCI. HR was measured with a Fitbit Charge 2, which was compared with the HR measured by a Polar H7 HR monitor used as a reference device. Participants were grouped into 4 groups—the no SCI group and based on lesion level into the T1 (cervical) group. Mean absolute percentage error (MAPE) and concordance correlation coefficient were determined for each group for each activity type, that is, rest, wheelchair activities, and strength exercise. ResultsWith an overall MAPEall lesions of 12.99%, the accuracy fell below the standard acceptable MAPE of –10% to +10% with a moderate agreement (concordance correlation coefficient=0.577). The HR accuracy of Fitbit Charge 2 seems to be reduced in those with cervical lesion level in all activities (MAPEno SCI=8.09%; MAPET1=20.43%). The accuracy of the Fitbit Charge 2 decreased with increasing intensity in all lesions (MAPErest=6.5%, MAPEactivity=12.97%, and MAPEstrength=14.2%). ConclusionsHR measured with the PPG technique showed lower accuracy in people with SCI than in those without SCI. The accuracy was just above the acceptable level in people with paraplegia, whereas in people with tetraplegia, a worse accuracy was found. The accuracy seemed to worsen with increasing intensities. Therefore, high-intensity HR data, especially in people with cervical lesions, should be used with caution.

The recent surge of data-driven methods in social policy have created new opportunities to assess existing poverty programs. The expectation is that the combination of advanced methods and more data can calculate the effectiveness of public interventions more accurately and tailor local initiatives accordingly. Specifically, nonmonetary indicators are increasingly being measured at micro levels in order to target social exclusion in combination with poverty. However, the multidimensional character of poverty, local context, and data matching pose challenges to data-driven analyses. By linking Dutch household-level data with policy-initiative-specific data at local level, we present an explorative study on the uptake of a local poverty pass. The goal is to unravel pass usage in terms of household income and location as well as the age of users. We find that income and age play a role in whether the pass is used, and usage differs per neighborhood. With this, the paper feeds into the discourse on how to operationalize and design data matching work in the multidimensional space of poverty and nonmonetary government initiatives.

In the medical domain, user-generated social media text is increasingly used as a valuablecomplementary knowledge source to scientific medical literature. The extraction of this knowledge iscomplicated by colloquial language use and misspellings. However, lexical normalization of suchdata has not been addressed effectively. This paper presents a data-driven lexical normalizationpipeline with a novel spelling correction module for medical social media. Our method significantlyoutperforms state-of-the-art spelling correction methods and can detect mistakes with an F1 of 0.63despite extreme imbalance in the data. We also present the first corpus for spelling mistake detectionand correction in a medical patient forum.