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      Diagnostic accuracy of keystroke dynamics as digital biomarkers for fine motor decline in neuropsychiatric disorders: a systematic review and meta-analysis

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          Abstract

          The unmet timely diagnosis requirements, that take place years after substantial neural loss and neuroperturbations in neuropsychiatric disorders, affirm the dire need for biomarkers with proven efficacy. In Parkinson’s disease (PD), Mild Cognitive impairment (MCI), Alzheimers disease (AD) and psychiatric disorders, it is difficult to detect early symptoms given their mild nature. We hypothesize that employing fine motor patterns, derived from natural interactions with keyboards, also knwon as keystroke dynamics, could translate classic finger dexterity tests from clinics to populations in-the-wild for timely diagnosis, yet, further evidence is required to prove this efficiency. We have searched PubMED, Medline, IEEEXplore, EBSCO and Web of Science for eligible diagnostic accuracy studies employing keystroke dynamics as an index test for the detection of neuropsychiatric disorders as the main target condition. We evaluated the diagnostic performance of keystroke dynamics across 41 studies published between 2014 and March 2022, comprising 3791 PD patients, 254 MCI patients, and 374 psychiatric disease patients. Of these, 25 studies were included in univariate random-effect meta-analysis models for diagnostic performance assessment. Pooled sensitivity and specificity are 0.86 (95% Confidence Interval (CI) 0.82–0.90, I 2 = 79.49%) and 0.83 (CI 0.79–0.87, I 2 = 83.45%) for PD, 0.83 (95% CI 0.65–1.00, I 2 = 79.10%) and 0.87 (95% CI 0.80–0.93, I 2 = 0%) for psychomotor impairment, and 0.85 (95% CI 0.74–0.96, I 2 = 50.39%) and 0.82 (95% CI 0.70–0.94, I 2 = 87.73%) for MCI and early AD, respectively. Our subgroup analyses conveyed the diagnosis efficiency of keystroke dynamics for naturalistic self-reported data, and the promising performance of multimodal analysis of naturalistic behavioral data and deep learning methods in detecting disease-induced phenotypes. The meta-regression models showed the increase in diagnostic accuracy and fine motor impairment severity index with age and disease duration for PD and MCI. The risk of bias, based on the QUADAS-2 tool, is deemed low to moderate and overall, we rated the quality of evidence to be moderate. We conveyed the feasibility of keystroke dynamics as digital biomarkers for fine motor decline in naturalistic environments. Future work to evaluate their performance for longitudinal disease monitoring and therapeutic implications is yet to be performed. We eventually propose a partnership strategy based on a “co-creation” approach that stems from mechanistic explanations of patients’ characteristics derived from data obtained in-clinics and under ecologically valid settings. The protocol of this systematic review and meta-analysis is registered in PROSPERO; identifier CRD42021278707. The presented work is supported by the KU-KAIST joint research center.

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          Rayyan—a web and mobile app for systematic reviews

          Background Synthesis of multiple randomized controlled trials (RCTs) in a systematic review can summarize the effects of individual outcomes and provide numerical answers about the effectiveness of interventions. Filtering of searches is time consuming, and no single method fulfills the principal requirements of speed with accuracy. Automation of systematic reviews is driven by a necessity to expedite the availability of current best evidence for policy and clinical decision-making. We developed Rayyan (http://rayyan.qcri.org), a free web and mobile app, that helps expedite the initial screening of abstracts and titles using a process of semi-automation while incorporating a high level of usability. For the beta testing phase, we used two published Cochrane reviews in which included studies had been selected manually. Their searches, with 1030 records and 273 records, were uploaded to Rayyan. Different features of Rayyan were tested using these two reviews. We also conducted a survey of Rayyan’s users and collected feedback through a built-in feature. Results Pilot testing of Rayyan focused on usability, accuracy against manual methods, and the added value of the prediction feature. The “taster” review (273 records) allowed a quick overview of Rayyan for early comments on usability. The second review (1030 records) required several iterations to identify the previously identified 11 trials. The “suggestions” and “hints,” based on the “prediction model,” appeared as testing progressed beyond five included studies. Post rollout user experiences and a reflexive response by the developers enabled real-time modifications and improvements. The survey respondents reported 40% average time savings when using Rayyan compared to others tools, with 34% of the respondents reporting more than 50% time savings. In addition, around 75% of the respondents mentioned that screening and labeling studies as well as collaborating on reviews to be the two most important features of Rayyan. As of November 2016, Rayyan users exceed 2000 from over 60 countries conducting hundreds of reviews totaling more than 1.6M citations. Feedback from users, obtained mostly through the app web site and a recent survey, has highlighted the ease in exploration of searches, the time saved, and simplicity in sharing and comparing include-exclude decisions. The strongest features of the app, identified and reported in user feedback, were its ability to help in screening and collaboration as well as the time savings it affords to users. Conclusions Rayyan is responsive and intuitive in use with significant potential to lighten the load of reviewers.
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            QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies.

            In 2003, the QUADAS tool for systematic reviews of diagnostic accuracy studies was developed. Experience, anecdotal reports, and feedback suggested areas for improvement; therefore, QUADAS-2 was developed. This tool comprises 4 domains: patient selection, index test, reference standard, and flow and timing. Each domain is assessed in terms of risk of bias, and the first 3 domains are also assessed in terms of concerns regarding applicability. Signalling questions are included to help judge risk of bias. The QUADAS-2 tool is applied in 4 phases: summarize the review question, tailor the tool and produce review-specific guidance, construct a flow diagram for the primary study, and judge bias and applicability. This tool will allow for more transparent rating of bias and applicability of primary diagnostic accuracy studies.
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              GRADE guidelines: 1. Introduction-GRADE evidence profiles and summary of findings tables.

              This article is the first of a series providing guidance for use of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system of rating quality of evidence and grading strength of recommendations in systematic reviews, health technology assessments (HTAs), and clinical practice guidelines addressing alternative management options. The GRADE process begins with asking an explicit question, including specification of all important outcomes. After the evidence is collected and summarized, GRADE provides explicit criteria for rating the quality of evidence that include study design, risk of bias, imprecision, inconsistency, indirectness, and magnitude of effect. Recommendations are characterized as strong or weak (alternative terms conditional or discretionary) according to the quality of the supporting evidence and the balance between desirable and undesirable consequences of the alternative management options. GRADE suggests summarizing evidence in succinct, transparent, and informative summary of findings tables that show the quality of evidence and the magnitude of relative and absolute effects for each important outcome and/or as evidence profiles that provide, in addition, detailed information about the reason for the quality of evidence rating. Subsequent articles in this series will address GRADE's approach to formulating questions, assessing quality of evidence, and developing recommendations. Copyright © 2011 Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                hessa.alfalahi@ku.ac.ae
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                11 May 2022
                11 May 2022
                2022
                : 12
                : 7690
                Affiliations
                [1 ]GRID grid.440568.b, ISNI 0000 0004 1762 9729, Department of Biomedical Engineering, , Khalifa University of Science and Technology, ; P O Box 127788, Abu Dhabi, United Arab Emirates
                [2 ]GRID grid.440568.b, ISNI 0000 0004 1762 9729, Healthcare Engineering Innovation Center (HEIC), , Khalifa University of Science and Technology, ; P O Box 127788, Abu Dhabi, United Arab Emirates
                [3 ]GRID grid.4793.9, ISNI 0000000109457005, Department of Electrical and Computer Engineering, , Aristotle University of Thessaloniki, ; 54124 Thessaloniki, Greece
                [4 ]GRID grid.9983.b, ISNI 0000 0001 2181 4263, CIPER, Faculdade de Motricidade Humana, , Universidade de Lisboa, ; Cruz Quebrada, 1499-002 Lisbon, Portugal
                [5 ]GRID grid.429705.d, ISNI 0000 0004 0489 4320, Parkinson’s Foundation Centre of Excellence, , King’s College Hospital NHS Foundation Trust, ; Denmark Hill, London, SE5 9RS United Kingdom
                [6 ]GRID grid.13097.3c, ISNI 0000 0001 2322 6764, Department of Basic and Clinical Neurosciences, Institute of Psychiatry, Psychology & Neuroscience, , King’s College London, ; De Crespigny Park, London, SE5 8AF United Kingdom
                Article
                11865
                10.1038/s41598-022-11865-7
                9095860
                35546606
                4c153559-a8b8-4969-b95b-6e27b114fc31
                © The Author(s) 2022

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 24 November 2021
                : 25 April 2022
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100004070, Khalifa University of Science, Technology and Research;
                Award ID: 8474000221
                Categories
                Article
                Custom metadata
                © The Author(s) 2022

                Uncategorized
                neuroscience,psychology,biomarkers,diseases,neurology,signs and symptoms,engineering
                Uncategorized
                neuroscience, psychology, biomarkers, diseases, neurology, signs and symptoms, engineering

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