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  • 1.
    Aghanavesi, Somayeh
    et al.
    Högskolan Dalarna, Akademin Industri och samhälle, Mikrodataanalys.
    Memedi, Mevludin
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik.
    Dougherty, Mark
    Högskolan Dalarna, Akademin Industri och samhälle, Mikrodataanalys.
    Nyholm, Dag
    Westin, Jerker
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik.
    Verification of a method for measuring Parkinson’s disease related temporal irregularity in spiral drawings2017Ingår i: Sensors, ISSN 1424-8220, E-ISSN 1424-8220, Vol. 17, nr 10, artikel-id 2341Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Parkinson's disease (PD) is a progressive movement disorder caused by the death of dopamine-producing cells in the midbrain. There is a need for frequent symptom assessment, since the treatment needs to be individualized as the disease progresses. The aim of this paper was to verify and further investigate the clinimetric properties of an entropy-based method for measuring PD-related upper limb temporal irregularities during spiral drawing tasks. More specifically, properties of a temporal irregularity score (TIS) for patients at different stages of PD, and medication time points were investigated. Nineteen PD patients and 22 healthy controls performed repeated spiral drawing tasks on a smartphone. Patients performed the tests before a single levodopa dose and at specific time intervals after the dose was given. Three movement disorder specialists rated videos of the patients based on the unified PD rating scale (UPDRS) and the Dyskinesia scale. Differences in mean TIS between the groups of patients and healthy subjects were assessed. Test-retest reliability of the TIS was measured. The ability of TIS to detect changes from baseline (before medication) to later time points was investigated. Correlations between TIS and clinical rating scores were assessed. The mean TIS was significantly different between healthy subjects and patients in advanced groups (p-value = 0.02). Test-retest reliability of TIS was good with Intra-class Correlation Coefficient of 0.81. When assessing changes in relation to treatment, TIS contained some information to capture changes from Off to On and wearing off effects. However, the correlations between TIS and clinical scores (UPDRS and Dyskinesia) were weak. TIS was able to differentiate spiral drawings drawn by patients in an advanced stage from those drawn by healthy subjects, and TIS had good test-retest reliability. TIS was somewhat responsive to single-dose levodopa treatment. Since TIS is an upper limb high-frequency-based measure, it cannot be detected during clinical assessment.

  • 2.
    Aghanavesi, Somayeh
    et al.
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik.
    Memedi, Mevludin
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik.
    Nyholm, Dag
    Senek, Marina
    Medvedev, Alexander
    Askmark, Håkan
    Equilonius, Sten-Magnus
    Bergquist, Filip
    Gonstantinescu, Radu
    Ohlsson, Fredrik
    Spira, Jack
    Sara, Lycke
    Ericsson, Enders
    Quantification of upper limb motor symptoms of Parkinson’s disease using a smartphone2016Ingår i: Abstracts of the Twentieth International Congress of Parkinson's Disease and Movement Disorders / [ed] Somayeh Aghanavesi, 2016, Vol. 31, s. S640-, artikel-id 1948Konferensbidrag (Övrigt vetenskapligt)
  • 3.
    Aghanavesi, Somayeh
    et al.
    Högskolan Dalarna, Akademin Industri och samhälle, Mikrodataanalys.
    Nyholm, Dag
    Marina, Senek
    Bergquist, Filip
    Memedi, Mevludin
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik.
    A smartphone-based system to quantify dexterity in Parkinson's disease patients2017Ingår i: Informatics in Medicine Unlocked, ISSN 2352-9148, Vol. 9, s. 11-17Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: The aim of this paper is to investigate whether a smartphone-based system can be used to quantify dexterity in Parkinson’s disease (PD). More specifically, the aim was to develop data-driven methods to quantify and characterize dexterity in PD. Methods: Nineteen advanced PD patients and 22 healthy controls participated in a clinical trial in Uppsala, Sweden. The subjects were asked to perform tapping and spiral drawing tests using a smartphone. Patients performed the tests before, and at pre-specified time points after they received 150% of their usual levodopa morning dose. Patients were video recorded and their motor symptoms were assessed by three movement disorder specialists using three Unified PD Rating Scale (UPDRS) motor items from part III, the dyskinesia scoring and the treatment response scale (TRS). The raw tapping and spiral data were processed and analyzed with time series analysis techniques to extract 37 spatiotemporal features. For each of the five scales, separate machine learning models were built and tested by using principal components of the features as predictors and mean ratings of the three specialists as target variables. Results: There were weak to moderate correlations between smartphone-based scores and mean ratings of UPDRS item #23 (0.52; finger tapping), UPDRS #25 (0.47; rapid alternating movements of hands), UPDRS #31 (0.57; body bradykinesia and hypokinesia), sum of the three UPDRS items (0.46), dyskinesia (0.64), and TRS (0.59). When assessing the test-retest reliability of the scores it was found that, in general, the clinical scores had better test-retest reliability than the smartphone-based scores. Only the smartphone-based predicted scores on the TRS and dyskinesia scales had good repeatability with intra-class correlation coefficients of 0.51 and 0.84, respectively. Clinician-based scores had higher effect sizes than smartphone-based scores indicating a better responsiveness in detecting changes in relation to treatment interventions. However, the first principal component of the 37 features was able to capture changes throughout the levodopa cycle and had trends similar to the clinical TRS and dyskinesia scales. Smartphone-based scores differed significantly between patients and healthy controls. Conclusions: Quantifying PD motor symptoms via instrumented, dexterity tests employed in a smartphone is feasible and data from such tests can also be used for measuring treatment-related changes in patients.

  • 4.
    Forsman, Anders
    et al.
    Högskolan Dalarna, Akademin Industri och samhälle, Informatik.
    Larsson, Hed Kerstin
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Naturvetenskap.
    Memedi, Mevludin
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik.
    Rosendahl, Hans
    Högskolan Dalarna, Akademin Industri och samhälle, Informatik.
    Hur kan man flippa klassrum – några exempel på "blended learning" från olika kurser på campus och distans2015Konferensbidrag (Övrigt vetenskapligt)
    Abstract [sv]

    Syftet var att beskriva och jämföra hur vi arbetar med blended learning/flipped classroom (FC) i fyra olika kurser (campus och/eller distans) vid Högskolan Dalarna, där målet var att få syn på den egna praktiken, dela erfarenheter och inspirera varandra. Inventering av och diskussioner om hur vi arbetar med blended learning/FC och varför. De tre kurserna Forskningsmetodikkurs i informatik (campus), kurs i informatik om webbsidor (campus) och Datateknikkurs i programmering (distans) ges i princip enligt "klassiskt" FC, dvs. med inspelad föreläsning följt av diskussion vid efterföljande seminarium/motsvarande (med viss variation). I den fjärde kursen, naturvetenskap i lärarutbildningen (campus/distans), blandas inspelade och streamade föreläsningar, och laborationer och seminarier genomförs både på campus och distans (gäller både campus- och distanskurser). Vi arbetar både på liknande sätt men även olika beroende av "ämneskultur", ämnenas olika karaktär och olika kursers karaktär, men vi har ungefär samma mål: att försöka få bättre förberedda och mer aktiva studenter, dvs. försöka att gynna djupinlärning. Men möjligheterna till mer genomgripande förändringar i arbetssätt beror också av hur "öppen" ämneskulturen är för detta. En gemensam slutsats är att det är viktigt att fundera över hur man kan använda tekniken i pedagogikens tjänst för att möjliggöra/iscensätta FC. Vi upplever allihop att FC är en möjlighet att göra något på ett nytt och förhoppningsvis bättre sätt. Vi är också överens om betydelsen av att få igång studenterna och att få dem att samarbeta - kruxet är hur man kan åstadkomma detta. Nya arbetssätt ska inte medföra att studenterna sitter och tittar på när vi arbetar, om än vi gör det på ett annat sätt än vid t.ex. traditionella föreläsningar, för då är vi tillbaka i den "envägskommunikation" man vill komma bort från FC. Vi har också fått upp ögonen för att olika ämnen/kurser har olika förutsättningar/utmaningar vilket lett till att vi använder delvis olika strategier och metoder. En skillnad gentemot litteraturens beskrivningar av FC är att vi alla även använder detta i våra distanskurser, vilket ger ytterligare en dimension vad gäller utmaningar, både pedagogiskt och tekniskt, jämfört med att "flippa" på campus. Det har varit inspirerande och utvecklande att ventilera hur vi resonerar om och genomför våra olika versioner av FC, och samtalen har även medfört att vi haft möjlighet att reflektera över den egna praktiken och att spegla den i de andras praktiker, vilket både inspirerat och gett praktiska tips.

  • 5.
    Jusufi, Ilir
    et al.
    Department of Computer Science, University of California Davis, CA, USA.
    Nyholm, Dag
    Neuroscience, Neurology, Uppsala University, Uppsala, Sweden.
    Memedi, Mevludin
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik.
    Visualization of spiral drawing data of patients with Parkinson's disease2014Ingår i: IEEE International Conference on Information Visualization, IEEE Press, 2014, s. 346-350Konferensbidrag (Refereegranskat)
    Abstract [en]

    Patients with Parkinson's disease (PD) need to be frequently monitored in order to assess their individual symptoms and treatment-related complications. Advances in technology have introduced telemedicine for patients in remote locations. However, data produced in such settings lack much information and are not easy to analyze or interpret compared to traditional, direct contact between the patient and clinician. Therefore, there is a need to present the data using visualization techniques in order to communicate in an understandable and objective manner to the clinician. This paper presents interaction and visualization approaches used to aid clinicians in the analysis of repeated measures of spirography of PD patients gathered by means of a telemetry touch screen device. The proposed approach enables clinicians to observe fine motor impairments and identify motor fluctuations of their patients while they perform the tests from their homes using the telemetry device.

  • 6.
    Khan, Taha
    et al.
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik.
    Memedi, Mevludin
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik.
    Song, William Wei
    Högskolan Dalarna, Akademin Industri och samhälle, Informatik.
    Westin, Jerker
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik.
    A case study in healthcare informatics: a telemedicine framework for automated parkinson’s disease symptom assessment2014Ingår i: Smart Health: International Conference, ICSH 2014, Beijing, China, July 10-11, 2014. Proceedings / [ed] Zheng X. et al., Springer, 2014, s. 197-199Konferensbidrag (Refereegranskat)
    Abstract [en]

    This paper reports the development and evaluation of a mobile-based telemedicine framework for enabling remote monitoring of Parkinson’s disease (PD) symptoms. The system consists of different measurement devices for remote collection, processing and presentation of symptom data of advanced PD patients. Different numerical analysis techniques were applied on the raw symptom data to extract clinically symptom information which in turn were then used in a machine learning process to be mapped to the standard clinician-based measures. The methods for quantitative and automatic assessment of symptoms were then evaluated for their clinimetric properties such as validity, reliability and sensitivity to change. Results from several studies indicate that the methods had good metrics suggesting that they are appropriate to quantitatively and objectively assess the severity of motor impairments of PD patients.

  • 7.
    Memedi, Mevludin
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik.
    A mobile-based system can assess Parkinson's disease symptoms from home environments of patients2014Ingår i: Neurologi i Sverige, ISSN 2000-8538, nr 3, s. 5s. 24-28Artikel i tidskrift (Övrig (populärvetenskap, debatt, mm))
    Abstract [en]

    Treatment of Parkinson's disease (PD) patients involves major challenges like the large within- and between-patient variability in symptom profiles and the emergence of motor complications. As PD progresses, the symptoms develop slowly and they represent a significant source of disability in advanced patients. During evaluation of treatments and symptoms, both the physician- and patient-oriented outcomes offer complementary information. In addition, quantitative assessments of symptoms using sensing technologies can potentially complement and enhance both patient and clinician perspectives. At Högskolan Dalarna, the Lecturer Mevludin Memedi has developed a telemetry system that assesses symptoms via analysis of self-assessments and motor tests to objectively measure disease-related outcomes and to improve the management of PD.

  • 8.
    Memedi, Mevludin
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik.
    Constructive alignment in Computer Engineering and Informatics departments at Dalarna University: An empirical investigation2015Studentarbete övrigtStudentuppsats (Examensarbete)
    Abstract [en]

    Background: Constructive alignment (CA) is a pedagogical approach that emphasizes the alignment between the intended learning outcomes (ILOs), teaching and learning activities (TLAs) and assessment tasks (ATs) as well as creation of a teaching/learning environment where students will be able to actively create their knowledge.

    Objectives: This paper aims at investigating the extent of constructively-aligned courses in Computer Engineering and Informatics department at Dalarna University, Sweden. This study is based on empirical observations of teacher’s perceptions of implementation of CA in their courses.

    Methods: Ten teachers (5 from each department) were asked to fill a paper-based questionnaire, which included a number of questions related to issues of implementing CA in courses.

    Results: Responses to the items of the questionnaire were mixed. Teachers clearly state the ILOs in their courses and try to align the TLAs and ATs to the ILOs. Computer Engineering teachers do not explicitly communicate the ILOs to the students as compared to Informatics teachers. In addition, Computer Engineering teachers stated that their students are less active in learning activities as compared to Informatics teachers. When asked about their subjective ratings of teaching methods all teachers stated that their current teaching is teacher-centered but they try to shift the focus of activity from them to the students.

    Conclusions: From teachers’ perspectives, the courses are partially constructively-aligned. Their courses are “aligned”, i.e. ILOs, TLAs and ATs are aligned to each other but they are not “constructive” since, according to them, there was a low student engagement in learning activities, especially in Computer Engineering department.

  • 9.
    Memedi, Mevludin
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik. School of Science and Technology, Örebro University.
    Mobile systems for monitoring Parkinson's disease2014Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    A challenge for the clinical management of Parkinson's disease (PD) is the large within- and between-patient variability in symptom profiles as well as the emergence of motor complications which represent a significant source of disability in patients. This thesis deals with the development and evaluation of methods and systems for supporting the management of PD by using repeated measures, consisting of subjective assessments of symptoms and objective assessments of motor function through fine motor tests (spirography and tapping), collected by means of a telemetry touch screen device.

    One aim of the thesis was to develop methods for objective quantification and analysis of the severity of motor impairments being represented in spiral drawings and tapping results. This was accomplished by first quantifying the digitized movement data with time series analysis and then using them in data-driven modelling for automating the process of assessment of symptom severity. The objective measures were then analysed with respect to subjective assessments of motor conditions. Another aim was to develop a method for providing comparable information content as clinical rating scales by combining subjective and objective measures into composite scores, using time series analysis and data-driven methods. The scores represent six symptom dimensions and an overall test score for reflecting the global health condition of the patient. In addition, the thesis presents the development of a web-based system for providing a visual representation of symptoms over time allowing clinicians to remotely monitor the symptom profiles of their patients. The quality of the methods was assessed by reporting different metrics of validity, reliability and sensitivity to treatment interventions and natural PD progression over time.

    Results from two studies demonstrated that the methods developed for the fine motor tests had good metrics indicating that they are appropriate to quantitatively and objectively assess the severity of motor impairments of PD patients. The fine motor tests captured different symptoms; spiral drawing impairment and tapping accuracy related to dyskinesias (involuntary movements) whereas tapping speed related to bradykinesia (slowness of movements). A longitudinal data analysis indicated that the six symptom dimensions and the overall test score contained important elements of information of the clinical scales and can be used to measure effects of PD treatment interventions and disease progression. A usability evaluation of the web-based system showed that the information presented in the system was comparable to qualitative clinical observations and the system was recognized as a tool that will assist in the management of patients.

  • 10.
    Memedi, Mevludin
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik.
    Mobile systems for monitoring Parkinson's disease2011Licentiatavhandling, monografi (Övrigt vetenskapligt)
    Abstract [en]

    This thesis presents the development and evaluation of IT-based methods and systems for supporting assessment of symptoms and enabling remote monitoring of Parkinson's disease (PD) patients. PD is a common neurological disorder associated with impaired body movements. Its clinical management regarding treatment outcomes and follow-up of patients is complex. In order to reveal the full extent of a patient's condition, there is a need for repeated and time-stamped assessments related to both patient's perception towards common symptoms and motor function. In this thesis, data from a mobile device test battery, collected during a three year clinical study, was used for the development and evaluation of methods. The data was gathered from a series of tests, consisting of selfassessments and motor tests (tapping and spiral drawing). These tests were carried out repeatedly in a telemedicine setting during week-long test periods. One objective was to develop a computer method that would process tracedspiral drawings and generate a score representing PD-related drawing impairments. The data processing part consisted of using the discrete wavelet transform and principal component analysis. When this computer method was evaluated against human clinical ratings, the results showed that it could perform quantitative assessments of drawing impairment in spirals comparatively well. As a part of this objective, a review of systems and methods for detecting the handwriting and drawing impairment using touch screens was performed. The review showed that measures concerning forces, accelerations, and radial displacements were the most important ones in detecting fine motor movement anomalies. Another objective of this thesis work was to design and evaluate an information system for delivering assessment support information to the treating clinical staff for monitoring PD symptoms in their patients. The system consisted of a patient node for data collection based on the mobile device test battery, a service node for data storage and processing, and a web application for data presentation. A system module was designed for compiling the test battery time series into summary scores on a test period level. The web application allowed adequate graphic feedback of the summary scores to the treating clinical staff. The evaluation results for this integrated system indicate that it can be used as a tool for frequent PD symptom assessments in home environments.

  • 11.
    Memedi, Mevludin
    et al.
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik.
    Aghanavesi, Somayeh
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik.
    Westin, Jerker
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik.
    A method for measuring Parkinson's disease related temporal irregularity in spiral drawings2016Ingår i: 2016 IEEE International Conference on Biomedical and Health Informatics, 2016, s. 410-413Konferensbidrag (Refereegranskat)
    Abstract [en]

    The objective of this paper was to develop and evaluate clinimetric properties of a method for measuring Parkinson's disease (PD)-related temporal irregularities using digital spiral analysis. In total, 108 (98 patients in different stages of PD and 10 healthy elderly subjects) performed repeated spiral drawing tasks in their home environments using a touch screen device. A score was developed for representing the amount of temporal irregularity during spiral drawing tasks, using Approximate Entropy (ApEn) technique. In addition, two previously published spiral scoring methods were adapted and their scores were analyzed. The mean temporal irregularity score differed significantly between healthy elderly subjects and advanced PD patients (P<0.005). The ApEn-based method had a better responsiveness and test-retest reliability when compared to the other two methods. In contrast to the other methods, the mean scores of the ApEn-based method improved significantly during a 3 year clinical study, indicating a possible impact of pathological basal ganglia oscillations in temporal control during spiral drawing tasks. In conclusion, the ApEn-based method could be used for differentiating between patients in different stages of PD and healthy subjects. The responsiveness and test-retest reliability were good for the ApEn-based method indicating that this method is useful for measuring upper limb temporal irregularity at a micro-level.

  • 12.
    Memedi, Mevludin
    et al.
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik.
    Aghanavesi, Somayeh
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik.
    Westin, Jerker
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik.
    Digital spiral analysis for objective assessment of fine motor timing variability in Parkinson's disease2015Konferensbidrag (Övrigt vetenskapligt)
    Abstract [en]

    OBJECTIVES: To develop a method for objective assessment of fine motor timing variability in Parkinson’s disease (PD) patients, using digital spiral data gathered by a touch screen device.

    BACKGROUND: A retrospective analysis was conducted on data from 105 subjects including65 patients with advanced PD (group A), 15 intermediate patients experiencing motor fluctuations (group I), 15 early stage patients (group S), and 10 healthy elderly subjects (HE) were examined. The subjects were asked to perform repeated upper limb motor tasks by tracing a pre-drawn Archimedes spiral as shown on the screen of the device. The spiral tracing test was performed using an ergonomic pen stylus, using dominant hand. The test was repeated three times per test occasion and the subjects were instructed to complete it within 10 seconds. Digital spiral data including stylus position (x-ycoordinates) and timestamps (milliseconds) were collected and used in subsequent analysis. The total number of observations with the test battery were as follows: Swedish group (n=10079), Italian I group (n=822), Italian S group (n = 811), and HE (n=299).

    METHODS: The raw spiral data were processed with three data processing methods. To quantify motor timing variability during spiral drawing tasks Approximate Entropy (APEN) method was applied on digitized spiral data. APEN is designed to capture the amount of irregularity or complexity in time series. APEN requires determination of two parameters, namely, the window size and similarity measure. In our work and after experimentation, window size was set to 4 and similarity measure to 0.2 (20% of the standard deviation of the time series). The final score obtained by APEN was normalized by total drawing completion time and used in subsequent analysis. The score generated by this method is hence on denoted APEN. In addition, two more methods were applied on digital spiral data and their scores were used in subsequent analysis. The first method was based on Digital Wavelet Transform and Principal Component Analysis and generated a score representing spiral drawing impairment. The score generated by this method is hence on denoted WAV. The second method was based on standard deviation of frequency filtered drawing velocity. The score generated by this method is hence on denoted SDDV. Linear mixed-effects (LME) models were used to evaluate mean differences of the spiral scores of the three methods across the four subject groups. Test-retest reliability of the three scores was assessed after taking mean of the three possible correlations (Spearman’s rank coefficients) between the three test trials. Internal consistency of the methods was assessed by calculating correlations between their scores.

    RESULTS: When comparing mean spiral scores between the four subject groups, the APEN scores were different between HE subjects and three patient groups (P=0.626 for S group with 9.9% mean value difference, P=0.089 for I group with 30.2%, and P=0.0019 for A group with 44.1%). However, there were no significant differences in mean scores of the other two methods, except for the WAV between the HE and A groups (P<0.001). WAV and SDDV were highly and significantly correlated to each other with a coefficient of 0.69. However, APEN was not correlated to neither WAV nor SDDV with coefficients of 0.11 and 0.12, respectively. Test-retest reliability coefficients of the three scores were as follows: APEN (0.9), WAV(0.83) and SD-DV (0.55).

    CONCLUSIONS: The results show that the digital spiral analysis-based objective APEN measure is able to significantly differentiate the healthy subjects from patients at advanced level. In contrast to the other two methods (WAV and SDDV) that are designed to quantify dyskinesias (over-medications), this method can be useful for characterizing Off symptoms in PD. The APEN was not correlated to none of the other two methods indicating that it measures a different construct of upper limb motor function in PD patients than WAV and SDDV. The APEN also had a better test-retest reliability indicating that it is more stable and consistent over time than WAV and SDDV.

  • 13.
    Memedi, Mevludin
    et al.
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik.
    Aghanavesi, Somayeh
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik.
    Westin, Jerker
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik.
    Objective quantification of Parkinson's disease upper limb motor timing variability using spirography2015Konferensbidrag (Refereegranskat)
    Abstract [en]

    Objective quantification of the upper limb motor timing variability of Parkinson’s disease (PD) patients was evaluated using traces of spirals by groups of patients at different disease stages, stable (S), intermediate (I), advanced (A) and a healthy elderly (HE) group. The approximate entropy (APEN) method of quantifying motor timing variability in time series was applied to capture the amount of irregularity during the spiral drawing process. The APEN score was then normalized by total drawing completion time and used in subsequent analysis. In addition, two previously published methods (WAV and SDDV) were applied on the spiral data. Comparing subject groups’ APEN mean scores, they were found to be significantly different from HE group, for group A (P<0.001) indicating this method’s ability in distinguishing patients at advanced disease stage. Comparing the three methods’ ability to track response to advanced treatment, APEN scores were all significantly different between base-line and levodopa-carbidopa intestinal gel (LCIG) treatment, during the 36 month study period as opposed to WAV and SDDV as they were not significantly improving for all periods. APEN scores were weakly correlated to WAV and SDDV, indicating that they measure different aspects of symptom severity.

  • 14.
    Memedi, Mevludin
    et al.
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik.
    Bergqvist, Ulf
    Nordforce Technology AB.
    Westin, Jerker
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik.
    Grenholm, Peter
    Neuroscience, Neurology, Uppsala University.
    Nyholm, Dag
    Neuroscience, Neurology, Uppsala University.
    A web-based system for visualizing upper limb motor performance of Parkinson’s disease patients2013Ingår i: Movement Disorders: Supplement: Abstracts of the Seventeenth International Congress of Parkinson's Disease and Movement Disorders, Wiley-Blackwell, 2013, s. S112-S113Konferensbidrag (Refereegranskat)
    Abstract [en]

    Objective

    To design, develop and set up a web-based system for enabling graphical visualization of upper limb motor performance (ULMP) of Parkinson’s disease (PD) patients to clinicians.

    Background

    Sixty-five patients diagnosed with advanced PD have used a test battery, implemented in a touch-screen handheld computer, in their home environment settings over the course of a 3-year clinical study. The test items consisted of objective measures of ULMP through a set of upper limb motor tests (finger to tapping and spiral drawings). For the tapping tests, patients were asked to perform alternate tapping of two buttons as fast and accurate as possible, first using the right hand and then the left hand. The test duration was 20 seconds. For the spiral drawing test, patients traced a pre-drawn Archimedes spiral using the dominant hand, and the test was repeated 3 times per test occasion. In total, the study database consisted of symptom assessments during 10079 test occasions.

    Methods

    Visualization of ULMP

    The web-based system is used by two neurologists for assessing the performance of PD patients during motor tests collected over the course of the said study. The system employs animations, scatter plots and time series graphs to visualize the ULMP of patients to the neurologists. The performance during spiral tests is depicted by animating the three spiral drawings, allowing the neurologists to observe real-time accelerations or hesitations and sharp changes during the actual drawing process. The tapping performance is visualized by displaying different types of graphs. Information presented included distribution of taps over the two buttons, horizontal tap distance vs. time, vertical tap distance vs. time, and tapping reaction time over the test length.

    Assessments

    Different scales are utilized by the neurologists to assess the observed impairments. For the spiral drawing performance, the neurologists rated firstly the ‘impairment’ using a 0 (no impairment) – 10 (extremely severe) scale, secondly three kinematic properties: ‘drawing speed’, ‘irregularity’ and ‘hesitation’ using a 0 (normal) – 4 (extremely severe) scale, and thirdly the probable ‘cause’ for the said impairment using 3 choices including Tremor, Bradykinesia/Rigidity and Dyskinesia. For the tapping performance, a 0 (normal) – 4 (extremely severe) scale is used for first rating four tapping properties: ‘tapping speed’, ‘accuracy’, ‘fatigue’, ‘arrhythmia’, and then the ‘global tapping severity’ (GTS). To achieve a common basis for assessment, initially one neurologist (DN) performed preliminary ratings by browsing through the database to collect and rate at least 20 samples of each GTS level and at least 33 samples of each ‘cause’ category. These preliminary ratings were then observed by the two neurologists (DN and PG) to be used as templates for rating of tests afterwards. In another track, the system randomly selected one test occasion per patient and visualized its items, that is tapping and spiral drawings, to the two neurologists.

    Statistical methods

    Inter-rater agreements were assessed using weighted Kappa coefficient. The internal consistency of properties of tapping and spiral drawing tests were assessed using Cronbach’s α test. One-way ANOVA test followed by Tukey multiple comparisons test was used to test if mean scores of properties of tapping and spiral drawing tests were different among GTS and ‘cause’ categories, respectively.

    Results

    When rating tapping graphs, inter-rater agreements (Kappa) were as follows: GTS (0.61), ‘tapping speed’ (0.89), ‘accuracy’ (0.66), ‘fatigue’ (0.57) and ‘arrhythmia’ (0.33). The poor inter-rater agreement when assessing “arrhythmia” may be as a result of observation of different things in the graphs, among the two raters. When rating animated spirals, both raters had very good agreement when assessing severity of spiral drawings, that is, ‘impairment’ (0.85) and irregularity (0.72). However, there were poor agreements between the two raters when assessing ‘cause’ (0.38) and time-information properties like ‘drawing speed’ (0.25) and ‘hesitation’ (0.21). Tapping properties, that is ‘tapping speed’, ‘accuracy’, ‘fatigue’ and ‘arrhythmia’ had satisfactory internal consistency with a Cronbach’s α coefficient of 0.77. In general, the trends of mean scores of tapping properties worsened with increasing levels of GTS. The mean scores of the four properties were significantly different to each other, only at different levels. In contrast from tapping properties, kinematic properties of spirals, that is ‘drawing speed’, ‘irregularity’ and ‘hesitation’ had a questionable consistency among them with a coefficient of 0.66. Bradykinetic spirals were associated with more impaired speed (mean = 83.7 % worse, P < 0.001) and hesitation (mean = 77.8% worse, P < 0.001), compared to dyskinetic spirals. Both these ‘cause’ categories had similar mean scores of ‘impairment’ and ‘irregularity’.

    Conclusions

    In contrast from current approaches used in clinical setting for the assessment of PD symptoms, this system enables clinicians to animate easily and realistically the ULMP of patients who at the same time are at their homes. Dynamic access of visualized motor tests may also be useful when observing and evaluating therapy-related complications such as under- and over-medications. In future, we foresee to utilize these manual ratings for developing and validating computer methods for automating the process of assessing ULMP of PD patients.

  • 15.
    Memedi, Mevludin
    et al.
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik.
    Jusufi, Ilir
    Computer Science, University of California, Davis, USA.
    Nyholm, Dag
    Uppsala University, Neuroscience, Neurology.
    Visualization of spirography-based objective measures in Parkinson's disease2014Ingår i: Movement Disorders Supplement: Abstracts of the Eighteenth International Congress of Parkinson's Disease and Movement Disorders, Wiley-Blackwell, 2014, s. S187-S189Konferensbidrag (Övrigt vetenskapligt)
    Abstract [en]

    Objective: To investigate whether advanced visualizations of spirography-based objective measures are useful in differentiating drug-related motor dysfunctions between Off and dyskinesia in Parkinson’s disease (PD).

    Background: During the course of a 3 year longitudinal clinical study, in total 65 patients (43 males and 22 females with mean age of 65) with advanced PD and 10 healthy elderly (HE) subjects (5 males and 5 females with mean age of 61) were assessed. Both patients and HE subjects performed repeated and time-stamped assessments of their objective health indicators using a test battery implemented on a telemetry touch screen handheld computer, in their home environment settings. Among other tasks, the subjects were asked to trace a pre-drawn Archimedes spiral using the dominant hand and repeat the test three times per test occasion.

    Methods: A web-based framework was developed to enable a visual exploration of relevant spirography-based kinematic features by clinicians so they can in turn evaluate the motor states of the patients i.e. Off and dyskinesia. The system uses different visualization techniques such as time series plots, animation, and interaction and organizes them into different views to aid clinicians in measuring spatial and time-dependent irregularities that could be associated with the motor states. Along with the animation view, the system displays two time series plots for representing drawing speed (blue line) and displacement from ideal trajectory (orange line). The views are coordinated and linked i.e. user interactions in one of the views will be reflected in other views. For instance, when the user points in one of the pixels in the spiral view, the circle size of the underlying pixel increases and a vertical line appears in the time series views to depict the corresponding position. In addition, in order to enable clinicians to observe erratic movements more clearly and thus improve the detection of irregularities, the system displays a color-map which gives an idea of the longevity of the spirography task. Figure 2 shows single randomly selected spirals drawn by a: A) patient who experienced dyskinesias, B) HE subject, and C) patient in Off state.

    Results: According to a domain expert (DN), the spirals drawn in the Off and dyskinesia motor states are characterized by different spatial and time features. For instance, the spiral shown in Fig. 2A was drawn by a patient who showed symptoms of dyskinesia; the drawing speed was relatively high (cf. blue-colored time series plot and the short timestamp scale in the x axis) and the spatial displacement was high (cf. orange-colored time series plot) associated with smooth deviations as a result of uncontrollable movements. The patient also exhibited low amount of hesitation which could be reflected both in the animation of the spiral as well as time series plots. In contrast, the patient who was in the Off state exhibited different kinematic features, as shown in Fig. 2C. In the case of spirals drawn by a HE subject, there was a great precision during the drawing process as well as unchanging levels of time-dependent features over the test trial, as seen in Fig. 2B.

    Conclusions: Visualizing spirography-based objective measures enables identification of trends and patterns of drug-related motor dysfunctions at the patient’s individual level. Dynamic access of visualized motor tests may be useful during the evaluation of drug-related complications such as under- and over-medications, providing decision support to clinicians during evaluation of treatment effects as well as improve the quality of life of patients and their caregivers. In future, we plan to evaluate the proposed approach by assessing within- and between-clinician variability in ratings in order to determine its actual usefulness and then use these ratings as target outcomes in supervised machine learning, similarly as it was previously done in the study performed by Memedi et al. (2013).

  • 16.
    Memedi, Mevludin
    et al.
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik.
    Khan, Taha
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik.
    Grenholm, Peter
    Department of Neuroscience, Neurology, Uppsala University.
    Nyholm, Dag
    Department of Neuroscience, Neurology, Uppsala University.
    Westin, Jerker
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik.
    Automatic and objective assessment of alternating tapping performance in Parkinson’s disease2013Ingår i: Sensors, ISSN 1424-8220, E-ISSN 1424-8220, Vol. 13, nr 12, s. 16965-16984Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    This paper presents the development and evaluation of a method for enabling quantitative and automatic scoring of alternating tapping performance of patients with Parkinson’s disease (PD). Ten healthy elderly subjects and 95 patients in different clinical stages of PD have utilized a touch-pad handheld computer to perform alternate tapping tests in their home environments. First, a neurologist used a web-based system to visually assess impairments in four tapping dimensions (‘speed’, ‘accuracy’, ‘fatigue’ and ‘arrhythmia’) and a global tapping severity (GTS). Second, tapping signals were processed with time series analysis and statistical methods to derive 24 quantitative parameters. Third, principal component analysis was used to reduce the dimensions of these parameters and to obtain scores for the four dimensions. Finally, a logistic regression classifier was trained using a 10-fold stratified cross-validation to map the reduced parameters to the corresponding visually assessed GTS scores. Results showed that the computed scores correlated well to visually assessed scores and were significantly different across Unified Parkinson’s Disease Rating Scale scores of upper limb motor performance. In addition, they had good internal consistency, had good ability to discriminate between healthy elderly and patients in different disease stages, had good sensitivity to treatment interventions and could reflect the natural disease progression over time. In conclusion, the automatic method can be useful to objectively assess the tapping performance of PD patients and can be included in telemedicine tools for remote monitoring of tapping.

  • 17.
    Memedi, Mevludin
    et al.
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik.
    Nyholm, Dag
    Neuroscience, Neurology, Uppsala University.
    Computerized identification of motor complications in Parkinson's disease2014Ingår i: Movement Disorders Supplement: Abstracts of the Eighteenth International Congress of Parkinson's Disease and Movement Disorders, 2014, s. S187-S188Konferensbidrag (Övrigt vetenskapligt)
    Abstract [en]

    Objective: To investigate whether spirography-based objective measures are able to effectively characterize the severity of unwanted symptom states (Off and dyskinesia) and discriminate them from motor state of healthy elderly subjects.

    Background: Sixty-five patients with advanced Parkinson’s disease (PD) and 10 healthy elderly (HE) subjects performed repeated assessments of spirography, using a touch screen telemetry device in their home environments. On inclusion, the patients were either treated with levodopa-carbidopa intestinal gel or were candidates for switching to this treatment. On each test occasion, the subjects were asked trace a pre-drawn Archimedes spiral shown on the screen, using an ergonomic pen stylus. The test was repeated three times and was performed using dominant hand. A clinician used a web interface which animated the spiral drawings, allowing him to observe different kinematic features, like accelerations and spatial changes, during the drawing process and to rate different motor impairments. Initially, the motor impairments of drawing speed, irregularity and hesitation were rated on a 0 (normal) to 4 (extremely severe) scales followed by marking the momentary motor state of the patient into 2 categories that is Off and Dyskinesia. A sample of spirals drawn by HE subjects was randomly selected and used in subsequent analysis.

    Methods: The raw spiral data, consisting of stylus position and timestamp, were processed using time series analysis techniques like discrete wavelet transform, approximate entropy and dynamic time warping in order to extract 13 quantitative measures for representing meaningful motor impairment information. A principal component analysis (PCA) was used to reduce the dimensions of the quantitative measures into 4 principal components (PC). In order to classify the motor states into 3 categories that is Off, HE and dyskinesia, a logistic regression model was used as a classifier to map the 4 PCs to the corresponding clinically assigned motor state categories. A stratified 10-fold cross-validation (also known as rotation estimation) was applied to assess the generalization ability of the logistic regression classifier to future independent data sets. To investigate mean differences of the 4 PCs across the three categories, a one-way ANOVA test followed by Tukey multiple comparisons was used.

    Results: The agreements between computed and clinician ratings were very good with a weighted area under the receiver operating characteristic curve (AUC) coefficient of 0.91. The mean PC scores were different across the three motor state categories, only at different levels. The first 2 PCs were good at discriminating between the motor states whereas the PC3 was good at discriminating between HE subjects and PD patients. The mean scores of PC4 showed a trend across the three states but without significant differences. The Spearman’s rank correlations between the first 2 PCs and clinically assessed motor impairments were as follows: drawing speed (PC1, 0.34; PC2, 0.83), irregularity (PC1, 0.17; PC2, 0.17), and hesitation (PC1, 0.27; PC2, 0.77).

    Conclusions: These findings suggest that spirography-based objective measures are valid measures of spatial- and time-dependent deficits and can be used to distinguish drug-related motor dysfunctions between Off and dyskinesia in PD. These measures can be potentially useful during clinical evaluation of individualized drug-related complications such as over- and under-medications thus maximizing the amount of time the patients spend in the On state.

  • 18.
    Memedi, Mevludin
    et al.
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik. School of Science and Technology, Örebro University.
    Nyholm, Dag
    Department of Neuroscience, Neurology, Uppsala University.
    Johansson, Anders
    Department of Clinical Neuroscience, Neurology, Karolinska Institutet.
    Pålhagen, Sven
    Department of Clinical Neuroscience, Neurology, Karolinska Institutet.
    Willows, Thomas
    Department of Neurology, Karolinska University Hospital.
    Widner, Håkan
    Department of Neurology, Skåne University Hospital.
    Linder, Jan
    Department of Pharmacology and Clinical Neuroscience, Umeå University.
    Westin, Jerker
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik.
    Self-assessments and motor tests via telemetry in a 36-month levodopa-carbidopa intestinal gel infusion trial2014Manuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Objective: The aim of this study was to investigate if a telemetry test battery can be used to measure effects of Parkinson’s disease (PD) treatment intervention and disease progression.

    Methods: Sixty-five patients diagnosed with advanced PD were recruited in an open longitudinal 36-month study; 35 treated with levodopa-carbidopa intestinal gel (LCIG) and 30 were candidates for switching from oral PD treatment to LCIG. They utilized a test battery, consisting of self-assessments of symptoms and fine motor tests (tapping and spiral drawings), four times per day in their homes during week-long test periods. The repeated measurements were summarized into an overall test score (OTS) to represent the global condition of the patient during a test period. Clinical assessments included ratings on Unified PD Rating Scale (UPDRS) and 39-item PD Questionnaire (PDQ-39) scales.

    Results: In LCIG-naïve patients, mean OTS compared to baseline was significantly improved from the first test period on LCIG treatment until month 24. In LCIG-non-naïve patients, there were no significant changes in mean OTS, except at month 36 (P<0.01). The OTS correlated adequately with total UPDRS (rho = 0.59) and total PDQ-39 (0.59).

    Conclusions: PD symptoms can be remotely monitored over time with this test battery. The trends of the test scores were similar to the trends of clinical rating scores. Correlations between OTS and clinical rating scales were adequate indicating that the test battery contains important elements of the information of the well-established scales.

  • 19.
    Memedi, Mevludin
    et al.
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik.
    Nyholm, Dag
    Department of Neuroscience, Neurology, Uppsala University, Uppsala, Sweden.
    Johansson, Anders
    Department of Clinical Neuroscience, Neurology, Karolinska Institutet, Stockholm, Sweden.
    Pålhagen, Sven
    Department of Neurology, Karolinska University Hospital, Stockholm, Sweden.
    Willows, Thomas
    Department of Neurology, Karolinska University Hospital, Stockholm, Sweden.
    Widner, Håkan
    Department of Neurology, Skåne University Hospital, Lund, Sweden.
    Linder, Jan
    Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden.
    Westin, Jerker
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik.
    Validity and responsiveness of at-home touch-screen assessments in advanced Parkinson's disease2015Ingår i: IEEE journal of biomedical and health informatics, ISSN 2168-2194, E-ISSN 2168-2208, Vol. 19, nr 6, s. 1829-1834Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The aim of this study was to investigate if a telemetry test battery can be used to measure effects of Parkinson’s disease (PD) treatment intervention and disease progression in patients with fluctuations. Sixty-five patients diagnosed with advanced PD were recruited in an open longitudinal 36-month study; 35 treated with levodopa-carbidopa intestinal gel (LCIG) and 30 were candidates for switching from oral PD treatment to LCIG. They utilized a test battery, consisting of self-assessments of symptoms and fine motor tests (tapping and spiral drawings), four times per day in their homes during week-long test periods. The repeated measurements were summarized into an overall test score (OTS) to represent the global condition of the patient during a test period. Clinical assessments included ratings on Unified PD Rating Scale (UPDRS) and 39-item PD Questionnaire (PDQ-39) scales. In LCIG-naïve patients, mean OTS compared to baseline was significantly improved from the first test period on LCIG treatment until month 24. In LCIG-non-naïve patients, there were no significant changes in mean OTS until month 36. The OTS correlated adequately with total UPDRS (rho = 0.59) and total PDQ-39 (0.59). Responsiveness measured as effect size was 0.696 and 0.536 for OTS and UPDRS respectively. The trends of the test scores were similar to the trends of clinical rating scores but dropout rate was high. Correlations between OTS and clinical rating scales were adequate indicating that the test battery contains important elements of the information of well-established scales. The responsiveness and reproducibility were better for OTS than for total UPDRS.

  • 20.
    Memedi, Mevludin
    et al.
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik.
    Nyholm, Dag
    Neuroscience, Neurology, Uppsala University.
    Johansson, Anders
    Clinical Neuroscience, Karolinska Institutet.
    Pålhagen, Sven
    Clinical Neuroscience, Karolinska Institutet.
    Willows, Thomas
    Neurology, Karolinska University Hospital.
    Widner, Håkan
    Neurology, Skåne University Hospital.
    Westin, Jerker
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik.
    Self-reported symptoms and motor tests via telemetry in a 36-month levodopa-carbidopa intestinal gel infusion trial2013Ingår i: Movement Disorders :  Supplement: Abstracts of the Seventeenth International Congress of Parkinson's Disease and Movement Disorders S1, Wiley-Blackwell, 2013, s. S168-S168Konferensbidrag (Refereegranskat)
    Abstract [en]

    Objective

    To investigate if a home environment test battery can be used to measure effects of Parkinson’s disease (PD) treatment intervention and disease progression.

    Background

    Seventy-seven patients diagnosed with advanced PD were recruited in an open longitudinal 36-month study at 10 clinics in Sweden and Norway; 40 of them were treated with levodopa-carbidopa intestinal gel (LCIG) and 37 patients were candidates for switching from oral PD treatment to LCIG. They utilized a mobile device test battery, consisting of self-assessments of symptoms and objective measures of motor function through a set of fine motor tests (tapping and spiral drawings), in their homes. Both the LCIG-naïve and LCIG-non-naïve patients used the test battery four times per day during week-long test periods.

    Methods

    Assessments

    The LCIG-naïve patients used the test battery at baseline (before LCIG), month 0 (first visit; at least 3 months after intraduodenal LCIG), and thereafter quarterly for the first year and biannually for the second and third years. The LCIG-non-naïve patients used the test battery from the first visit, i.e. month 0. Out of the 77 patients, only 65 utilized the test battery; 35 were LCIG-non-naïve and 30 LCIG-naïve. In 20 of the LCIG-naïve patients, assessments with the test battery were available during oral treatment and at least one test period after having started infusion treatment. Three LCIG-naïve patients did not use the test battery at baseline but had at least one test period of assessments thereafter. Hence, n=23 in the LCIG-naïve group. In total, symptom assessments in the full sample (including both patient groups) were collected during 379 test periods and 10079 test occasions. For 369 of these test periods, clinical assessments including UPDRS and PDQ-39 were performed in afternoons at the start of the test periods. The repeated measurements of the test battery were processed and summarized into scores representing patients’ symptom severities over a test period, using statistical methods. Six conceptual dimensions were defined; four subjectively-reported: ‘walking’, ‘satisfied’, ‘dyskinesia’, and ‘off’ and two objectively-measured: ‘tapping’ and ‘spiral’. In addition, an ‘overall test score’ (OTS) was defined to represent the global health condition of the patient during a test period.

    Statistical methods

    Change in the test battery scores over time, that is at baseline and follow-up test periods, was assessed with linear mixed-effects models with patient ID as a random effect and test period as a fixed effect of interest. The within-patient variability of OTS was assessed using intra-class correlation coefficient (ICC), for the two patient groups. Correlations between clinical rating scores and test battery scores were assessed using Spearman’s rank correlations (rho).

    Results

    In LCIG-naïve patients, mean OTS compared to baseline was significantly improved from the first test period on LCIG treatment until month 24. However, there were no significant changes in mean OTS scores of LCIG-non-naïve patients, except for worse mean OTS at month 36 (p<0.01, n=16). The mean scores of all subjectively-reported dimensions improved significantly throughout the course of the study, except ‘walking’ at month 36 (p=0.41, n=4). However, there were no significant differences in mean scores of objectively-measured dimensions between baseline and other test periods, except improved ‘tapping’ at month 6 and month 36, and ‘spiral’ at month 3 (p<0.05). The LCIG-naïve patients had a higher within-subject variability in their OTS scores (ICC=0.67) compared to LCIG-non-naïve patients (ICC=0.71). The OTS correlated adequately with total UPDRS (rho=0.59) and total PDQ-39 (rho=0.59).

    Conclusions

    In this 3-year follow-up study of advanced PD patients treated with LCIG we found that it is possible to monitor PD progression over time using a home environment test battery. The significant improvements in the mean OTS scores indicate that the test battery is able to measure functional improvement with LCIG sustained over at least 24 months.

  • 21.
    Memedi, Mevludin
    et al.
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik. Örebro University.
    Nyholm, Dag
    Neuroscience, Neurology, Uppsala University.
    Westin, Jerker
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik.
    Combined fine-motor tests and self-assessments for remote detection of motor fluctuations2013Ingår i: Recent Patents on Biomedial Engineering, ISSN 1874-7647, Vol. 6, nr 2, s. 127-135Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A major problem with the clinical management of fluctuating movement disorders, e.g. Parkinson's disease (PD), is the large variability in manifestation of symptoms among patients. In this condition, frequent measurements which account for both patient-reported and objective assessments are needed in order to capture symptom fluctuations, with the purpose to optimize therapy. The main focus of this paper is to present a mobile-based system for enabling remote monitoring of PD patients from their home environment conditions. The system consists of a patient diary section for collecting patient-based self-assessments, a motor test section for collecting fine motor movements through upper limb motor tests, and a scheduler for restricting operation to a multitude of predetermined limited time intervals. The system processes and compiles time series data into different summary scores representing symptom severity. In addition, the paper presents a review of recent inventions which were filed after year 2000 in the field of telemedicine applications. The review includes a summary of systems and methods which enable remote symptom assessments of patients, not necessarily suffering from movement disorders, through repeated measurements and which take into account their subjective and/or objective health indicators. The findings conclude that there are a small number of inventions which collect subjective and objective health measures in telemedicine settings. Consequently, there is a lack of mechanisms that combine these two types of information into scores to provide a more in-depth assessment of the patient's general health, their motor and non-motor symptom fluctuations and treatment effects. The paper also provides a discussion concerning different approaches for analyzing and combining subjective and objective measures, and handling data from longitudinal studies.

  • 22.
    Memedi, Mevludin
    et al.
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik.
    Sadikov, Aleksander
    Faculty of Information Science, Artificial Intelligence Laboratory, University of Ljubljana, Ljubljana, Slovenia.
    Groznik, Vida
    Faculty of Information Science, Artificial Intelligence Laboratory, University of Ljubljana, Ljubljana, Slovenia.
    Žabkar, Jure
    Faculty of Information Science, Artificial Intelligence Laboratory, University of Ljubljana, Ljubljana, Slovenia.
    Možina, Martin
    Faculty of Information Science, Artificial Intelligence Laboratory, University of Ljubljana, Ljubljana, Slovenia.
    Bergquist, Filip
    Sahlgrenska Academy, Department of Pharmacology, University of Gothenburg, Gothenburg, Sweden.
    Johansson, Anders
    Neurology, Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Haubenberger, Dietrich
    NINDS Intramural Research Program, Clinical Trials Unit, National Institutes of Health, Bethesda, MD, USA.
    Nyholm, Dag
    Neurology, Neuroscience, Uppsala University, Uppsala, Sweden.
    Automatic spiral analysis for objective assessment of motor symptoms in Parkinson's disease2015Ingår i: Sensors, ISSN 1424-8220, E-ISSN 1424-8220, Vol. 15, nr 9, s. 23727-23744Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A challenge for the clinical management of advanced Parkinson’s disease (PD) patients is the emergence of fluctuations in motor performance, which represents a significant source of disability during activities of daily living of the patients. There is a lack of objective measurement of treatment effects for in-clinic and at-home use that can provide an overview of the treatment response. The objective of this paper was to develop a method for objective quantification of advanced PD motor symptoms related to off episodes and peak dose dyskinesia, using spiral data gathered by a touch screen telemetry device. More specifically, the aim was to objectively characterize motor symptoms (bradykinesia and dyskinesia), to help in automating the process of visual interpretation of movement anomalies in spirals as rated by movement disorder specialists. Digitized upper limb movement data of 65 advanced PD patients and 10 healthy (HE) subjects were recorded as they performed spiral drawing tasks on a touch screen device in their home environment settings. Several spatiotemporal features were extracted from the time series and used as inputs to machine learning methods. The methods were validated against ratings on animated spirals scored by four movement disorder specialists who visually assessed a set of kinematic features and the motor symptom. The ability of the method to discriminate between PD patients and HE subjects and the test-retest reliability of the computed scores were also evaluated. Computed scores correlated well with mean visual ratings of individual kinematic features. The best performing classifier (Multilayer Perceptron) classified the motor symptom (bradykinesia or dyskinesia) with an accuracy of 84% and area under the receiver operating characteristics curve of 0.86 in relation to visual classifications of the raters. In addition, the method provided high discriminating power when distinguishing between PD patients and HE subjects as well as had good test-retest reliability. This study demonstrated the potential of using digital spiral analysis for objective quantification of PD-specific and/or treatment-induced motor symptoms.

  • 23.
    Memedi, Mevludin
    et al.
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik.
    Sadikov, Aleksander
    Faculty of Information Science, Artificial Intelligence Laboratory, University of Ljubljana, Ljubljana, Slovenia.
    Groznik, Vida
    Faculty of Information Science, Artificial Intelligence Laboratory, University of Ljubljana, Ljubljana, Slovenia.
    Žabkar, Jure
    Faculty of Information Science, Artificial Intelligence Laboratory, University of Ljubljana, Ljubljana, Slovenia.
    Možina, Martin
    Faculty of Information Science, Artificial Intelligence Laboratory, University of Ljubljana, Ljubljana, Slovenia.
    Bergquist, Filip
    Sahlgrenska Academy, Department of Pharmacology, University of Gothenburg, Gothenburg, Sweden.
    Johansson, Anders
    Neurology, Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Haubenberger, Dietrich
    NINDS Intramural Research Program, Clinical Trials Unit, National Institutes of Health, Bethesda, MD, USA.
    Nyholm, Dag
    Neurology, Neuroscience, Uppsala University, Uppsala, Sweden.
    Automatic spiral analysis for objective assessment of motor symptoms in Parkinson's disease2015Konferensbidrag (Övrigt vetenskapligt)
    Abstract [en]

    Objective: To develop a method for objective quantification of PD motor symptoms related to Off episodes and peak dose dyskinesias, using spiral data gathered by using a touch screen telemetry device. The aim was to objectively characterize predominant motor phenotypes (bradykinesia and dyskinesia), to help in automating the process of visual interpretation of movement anomalies in spirals as rated by movement disorder specialists.

    Background: A retrospective analysis was conducted on recordings from 65 patients with advanced idiopathic PD from nine different clinics in Sweden, recruited from January 2006 until August 2010. In addition to the patient group, 10 healthy elderly subjects were recruited. Upper limb movement data were collected using a touch screen telemetry device from home environments of the subjects. Measurements with the device were performed four times per day during week-long test periods. On each test occasion, the subjects were asked to trace pre-drawn Archimedean spirals, using the dominant hand. The pre-drawn spiral was shown on the screen of the device. The spiral test was repeated three times per test occasion and they were instructed to complete it within 10 seconds. The device had a sampling rate of 10Hz and measured both position and time-stamps (in milliseconds) of the pen tip.

    Methods: Four independent raters (FB, DH, AJ and DN) used a web interface that animated the spiral drawings and allowed them to observe different kinematic features during the drawing process and to rate task performance. Initially, a number of kinematic features were assessed including ‘impairment’, ‘speed’, ‘irregularity’ and ‘hesitation’ followed by marking the predominant motor phenotype on a 3-category scale: tremor, bradykinesia and/or choreatic dyskinesia. There were only 2 test occasions for which all the four raters either classified them as tremor or could not identify the motor phenotype. Therefore, the two main motor phenotype categories were bradykinesia and dyskinesia. ‘Impairment’ was rated on a scale from 0 (no impairment) to 10 (extremely severe) whereas ‘speed’, ‘irregularity’ and ‘hesitation’ were rated on a scale from 0 (normal) to 4 (extremely severe). The proposed data-driven method consisted of the following steps. Initially, 28 spatiotemporal features were extracted from the time series signals before being presented to a Multilayer Perceptron (MLP) classifier. The features were based on different kinematic quantities of spirals including radius, angle, speed and velocity with the aim of measuring the severity of involuntary symptoms and discriminate between PD-specific (bradykinesia) and/or treatment-induced symptoms (dyskinesia). A Principal Component Analysis was applied on the features to reduce their dimensions where 4 relevant principal components (PCs) were retained and used as inputs to the MLP classifier. Finally, the MLP classifier mapped these components to the corresponding visually assessed motor phenotype scores for automating the process of scoring the bradykinesia and dyskinesia in PD patients whilst they draw spirals using the touch screen device. For motor phenotype (bradykinesia vs. dyskinesia) classification, the stratified 10-fold cross validation technique was employed.

    Results: There were good agreements between the four raters when rating the individual kinematic features with intra-class correlation coefficient (ICC) of 0.88 for ‘impairment’, 0.74 for ‘speed’, 0.70 for ‘irregularity’, and moderate agreements when rating ‘hesitation’ with an ICC of 0.49. When assessing the two main motor phenotype categories (bradykinesia or dyskinesia) in animated spirals the agreements between the four raters ranged from fair to moderate. There were good correlations between mean ratings of the four raters on individual kinematic features and computed scores. The MLP classifier classified the motor phenotype that is bradykinesia or dyskinesia with an accuracy of 85% in relation to visual classifications of the four movement disorder specialists. The test-retest reliability of the four PCs across the three spiral test trials was good with Cronbach’s Alpha coefficients of 0.80, 0.82, 0.54 and 0.49, respectively. These results indicate that the computed scores are stable and consistent over time. Significant differences were found between the two groups (patients and healthy elderly subjects) in all the PCs, except for the PC3.

    Conclusions: The proposed method automatically assessed the severity of unwanted symptoms and could reasonably well discriminate between PD-specific and/or treatment-induced motor symptoms, in relation to visual assessments of movement disorder specialists. The objective assessments could provide a time-effect summary score that could be useful for improving decision-making during symptom evaluation of individualized treatment when the goal is to maximize functional On time for patients while minimizing their Off episodes and troublesome dyskinesias.

  • 24.
    Memedi, Mevludin
    et al.
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik.
    Westin, Jerker
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik.
    Methods for detection of handwriting/drawing impairment using inputs from touch screens2011Ingår i: Recent Patents on Signal Processing, ISSN 2210-6863, Vol. 1, nr 2Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Fine motor dysfunction in patients with movement disorders, such as Parkinson’s disease, is characterized by slowness of movements, decrease of reaction time and involuntary movements. In this article, recent patents on detecting and assessing the said dysfunction are reviewed; their implementation in telemedicine settings, design considerations and ability to assist in dose and time adjustments are discussed. These patents explain application of signal processing techniques in analysis and interpretation of digitized handwriting/drawing information of individuals based on data gathered using touch screens. The study reveals that measures concerning forces, accelerations and radial displacements are the most relevant measurements to detect fine movement anomalies. These findings demonstrate that digitized analysis of handwriting/drawing movements may be useful in clinical trials evaluating fine motor control. This review further depicts the role of employing event-based data acquisition and signal processing techniques suitable for nonstationary signals, such as Wavelet transform, in systems for patient home-monitoring.

  • 25.
    Memedi, Mevludin
    et al.
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik.
    Westin, Jerker
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik.
    Spiral drawing during self-rated dyskinesia is more impaired than during self-rated off2011Ingår i: 15th International Congress of Parkinson's Disease and Movement Disorders, Toronto, Canada, 2011Konferensbidrag (Refereegranskat)
    Abstract [en]

    Background: A mobile device test battery, consisting of a patient diary collection section with disease-related questions and a fine motor test section (including spiral drawing tasks), was used by 65 patients with advanced Parkinson's disease (PD)(treated with intraduodenal levodopa/carbidopa gel infusion, Duodopa®, or candidates for this treatment) on 10439 test occasions in their home environments. On each occasion, patients traced three pre-drawn Archimedes spirals using an ergonomic stylus and self-assessed their motor function on a global Treatment Response Scale (TRS) ranging from -3 = very 'off' to 0 = 'on' to +3 = very dyskinetic. The spirals were processed by a computer-based method that generates a "spiral score" representing the PD-related drawing impairment. The scale for the score was based on a modified Bain & Findley rating scale in the range from 0 = no impairment to 5 = moderate impairment to 10 = extremely severe impairment. Objective: To analyze the test battery data for the purpose to find differences in spiral drawing performance of PD patients in relation to their self-assessments of motor function. Methods: Three motor states were used in the analysis; OFF state (including moderate and very 'off'), ON state ('on') and a dyskinetic (DYS) state (moderate and very dyskinetic). In order to avoid the problem of multiple test occasions per patient, 200 random samples of single test occasions per patient were drawn. One-way analysis of variance, ANOVA, test followed by Tukey multiple comparisons test was used to test if mean values of spiral test parameters, i.e. the spiral score and drawing completion times (in seconds), were different among the three motor states. Statistical significance was set at p<0.05. To investigate changes in the spiral score over the time-of-day test sessions for the three motor states, plots of statistical summaries were inspected. Results: The mean spiral score differed significantly across the three self-assessed motor states (p<0.001, ANOVA test). Tukey post-hoc comparisons indicate that the mean spiral score (mean ± SD; [95% CI for mean]) in DYS state (5.2 ± 1.8; [5.12, 5.28]) was higher than the mean spiral score in OFF (4.3 ± 1.7; [4.22, 4.37]) and ON (4.2 ± 1.7; [4.17, 4.29]) states. The mean spiral score was also significantly different among individual TRS values of slightly 'off' (4.02 ± 1.63), 'on' (4.07 ± 1.65) and slightly dyskinetic (4.6 ± 1.71), (p<0.001). There were no differences in drawing completion times among the three motor states (p=0.509). In the OFF and ON states, patients drew slightly more impaired spirals in the afternoon whereas in the DYS state the spiral drawing performance was more impaired in the morning. Conclusion: It was found that when patients considered themselves as being dyskinetic spiral drawing was more impaired (nearly one unit change in a 0-10 scale) compared to when they considered themselves as being 'off' and 'on'. The spiral drawing at patients that self-assessed their motor state as dyskinetic was slightly more impaired in the morning hours, between 8 and 12 o'clock, a situation possibly caused by the morning dose effect.

  • 26.
    Memedi, Mevludin
    et al.
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik.
    Westin, Jerker
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik.
    Nyholm, Dag
    Department of Neuroscience, Neurology, Uppsala University, Uppsala, Sweden.
    Spiral drawing during self-rated dyskinesia is more impaired than during self-rated off2013Ingår i: Parkinsonism & Related Disorders, ISSN 1353-8020, E-ISSN 1873-5126, Vol. 19, nr 5, s. 553-556Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective. The purpose of this study was to examine repeated measures of fine motor function in relation to self-assessed motor conditions in Parkinson's disease (PD).

    Methods. One-hundred PD patients, 65 with advanced PD and 35 patients with different disease stages have utilized a test battery in a telemedicine setting. On each test occasion, they initially self-assessed their motor condition (from ‘very off’ to ‘very dyskinetic’) and then performed a set of fine motor tests (tapping and spiral drawings).

    Results. The motor tests scores were found to be the best during self-rated On. Self-rated dyskinesias caused more impaired spiral drawing performance (mean = 9.8% worse, P < 0.001) but at the same time tapping speed was faster (mean = 5.0% increase, P < 0.001), compared to scores in self-rated Off.

    Conclusions. The fine motor tests of the test battery capture different symptoms; the spiral impairment primarily relates to dyskinesias whereas the tapping speed captures the Off symptoms.

  • 27.
    Memedi, Mevludin
    et al.
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik.
    Westin, Jerker
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik.
    Nyholm, Dag
    Dougherty, Mark
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik.
    Groth, Torgny
    A web application for follow-up of results from a mobile device test battery for Parkinson's disease patients2011Ingår i: Computer Methods and Programs in Biomedicine, ISSN 0169-2607, E-ISSN 1872-7565, Vol. 104, nr 2, s. 219-226Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    This paper describes a web-based system for enabling remote monitoring of patients with Parkinson's disease (PD) and supporting clinicians in treating their patients. The system consists of a patient node for subjective and objective data collection based on a handheld computer, a service node for data storage and processing, and a web application for data presentation. Using statistical and machine learning methods, time series of raw data are summarized into scores for conceptual symptom dimensions and an "overall test score" providing a comprehensive profile of patient's health during a test period of about one week. The handheld unit was used quarterly or biannually by 65 patients with advanced PD for up to four years at nine clinics in Sweden. The IBM Computer System Usability Questionnaire was administered to assess nurses' satisfaction with the web application. Results showed that a majority of the nurses were quite satisfied with the usability although a sizeable minority were not. Our findings support that this system can become an efficient tool to easily access relevant symptom information from the home environment of PD patients. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

  • 28.
    Memedi, Mevludin
    et al.
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik.
    Westin, Jerker
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik.
    Nyholm, Dag
    Dougherty, Mark
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik.
    Groth, Torgny
    A web application for follow-up of results from a mobile device test battery for parkinson’s disease patients2010Ingår i: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: A test battery consisting of self-assessments and motor tests (tapping and spiral drawing) was developed for a hand computer with touch screen in a telemedicine setting.

    Objectives: To develop and evaluate a web-based system that delivers decision support information to the treating clinical staff for assessing PD symptoms in their patients based on the test battery data. Methods: The test battery is currently being used in a clinical trial (DAPHNE, EudraCT No. 2005-002654-21) by sixty five patients with advanced Parkinson’s disease (PD) on 9991 test occasions (four tests per day during in all 362 week-long test periods) at nine clinics around Sweden. Test results are sent continuously from the hand unit over a mobile net to a central computer and processed with statistical methods. They are summarized into scores for different dimensions of the symptom state and an ‘overall test score’ reflecting the overall condition of the patient during a test period. The information in the web application is organized and presented graphically in a way that the general overview of the patient performance per test period is emphasized. Focus is on the overall test score, symptom dimensions and daily summaries. In a recent preliminary user evaluation, the web application was demonstrated to the fifteen study nurses who had used the test battery in the clinical trial. At least one patient per clinic was shown.

    Results: In general, the responses from nurses were positive. They claimed that the test results shown in the system were consistent with their own clinical observations. They could follow complications, changes and trends within their patients.

    Discussion: In conclusion, the system is able to summarise the various time series of motor test results and self-assessments during test periods and present them in a useful manner. Its main contribution is a novel and reliable way to capture and easily access symptom information from patients’ home environment. The convenient access to current symptom profile as well as symptom history provides a basis for individualized evaluation and adjustment of treatments.

  • 29.
    Sadikov, Aleksander
    et al.
    University of Ljubljana, Faculty of Computer and Information Science, Večna pot 113, Ljubljana, Slovenia.
    Groznik, Vida
    University of Ljubljana, Faculty of Computer and Information Science, Večna pot 113, Ljubljana, Slovenia.
    Možina, Martin
    University of Ljubljana, Faculty of Computer and Information Science, Večna pot 113, Ljubljana, Slovenia.
    Žabkar, Jure
    University of Ljubljana, Faculty of Computer and Information Science, Večna pot 113, Ljubljana, Slovenia.
    Nyholm, Dag
    Department of Neuroscience, Neurology, Uppsala University, Uppsala, Sweden.
    Memedi, Mevludin
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik. Informatics, School of Business, Örebro University, Örebro, Sweden.
    Georgiev, Dejan
    Ljubljana University Medical Centre, Department of Neurology, Zaloška 2, Ljubljana, Slovenia.
    Feasibility of spirography features for objective assessment of motor function in Parkinson's disease2017Ingår i: Artificial Intelligence in Medicine, ISSN 0933-3657, E-ISSN 1873-2860, Vol. 81, nr SI, s. 54-62Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective

    Parkinson's disease (PD) is currently incurable, however proper treatment can ease the symptoms and significantly improve the quality of life of patients. Since PD is a chronic disease, its efficient monitoring and management is very important. The objective of this paper was to investigate the feasibility of using the features and methodology of a spirography application, originally designed to detect early Parkinson's disease (PD) motoric symptoms, for automatically assessing motor symptoms of advanced PD patients experiencing motor fluctuations. More specifically, the aim was to objectively assess motor symptoms related to bradykinesias (slowness of movements occurring as a result of under-medication) and dyskinesias (involuntary movements occurring as a result of over-medication).

    Materials and methods

    This work combined spirography data and clinical assessments from a longitudinal clinical study in Sweden with the features and pre-processing methodology of a Slovenian spirography application. The study involved 65 advanced PD patients and over 30,000 spiral-drawing measurements over the course of three years. Machine learning methods were used to learn to predict the “cause” (bradykinesia or dyskinesia) of upper limb motor dysfunctions as assessed by a clinician who observed animated spirals in a web interface. The classification model was also tested for comprehensibility. For this purpose a visualisation technique was used to present visual clues to clinicians as to which parts of the spiral drawing (or its animation) are important for the given classification.

    Results

    Using the machine learning methods with feature descriptions and pre-processing from the Slovenian application resulted in 86% classification accuracy and over 0.90 AUC. The clinicians also rated the computer's visual explanations of its classifications as at least meaningful if not necessarily helpful in over 90% of the cases.

    Conclusions

    The relatively high classication accuracy and AUC demonstrates the usefulness of this approach for objective monitoring of PD patients. The positive evaluation of computer's explanations suggests the potential use of this methodology in a decision support setting.

  • 30.
    Sadikov, Aleksander
    et al.
    Faculty of Computer and Information Science, University of Ljubljana, Večna pot 113, Ljubljana, Slovenia .
    Žabkar, Jure
    Faculty of Computer and Information Science, University of Ljubljana, Večna pot 113, Ljubljana, Slovenia .
    Možina, Martin
    Faculty of Computer and Information Science, University of Ljubljana, Večna pot 113, Ljubljana, Slovenia .
    Groznik, Vida
    Faculty of Computer and Information Science, University of Ljubljana, Večna pot 113, Ljubljana, Slovenia .
    Nyholm, Dag
    Dept. of Neuroscience, Neurology, Uppsala University, Uppsala, Sweden.
    Memedi, Mevludin
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik.
    Feasibility of spirography features for objective assessment of motor symptoms in Parkinson's disease2015Ingår i: Artificial Intelligence in Medicine: 15th Conference on Artificial Intelligence in Medicine, AIME 2015, Pavia, Italy, June 17-20, 2015. Proceedings / [ed] John Holmes, Riccardo Bellazzi, Lucia Sacchi and Niels Peek, Springer, 2015, Vol. 9105, s. 267-276Konferensbidrag (Refereegranskat)
    Abstract [en]

    Parkinsons disease (PD) is currently incurable, however the proper treatment can ease the symptoms and significantly improve the quality of patients life. Since PD is a chronic disease, its efficient monitoring and management is very important. The objective of this paper is to investigate the feasibility of using the features and methodology of a spirography device, originally designed to measure early Parkinsons disease (PD) symptoms, for assessing motor symptoms of advanced PD patients suffering from motor fluctuations. More specifically, the aim is to objectively assess motor symptoms related to bradykinesias (slowness of movements occurring as a result of under-medication) and dyskinesias (involuntary movements occurring as a result of over-medication). The work combines spirography data and clinical assessments from a longitudinal clinical study in Sweden with the features and pre-processing methodology of a Slovenian spirography application. The target outcome was to learn to predict the “cause” of upper limb motor dysfunctions as assessed by a clinician who observed animated spirals in a web interface. Using the machine learning methods with feature descriptions from the Slovenian application resulted in 86% classification accuracy and over 90% AUC, demonstrating the usefulness of this approach for objective monitoring of PD patients.

  • 31. Senek, Marina
    et al.
    Aquilonius, Sten-Magnus
    Askmark, Håkan
    Bergquist, Filip
    Constantinescu, Radu
    Ericsson, Anders
    Lycke, Sara
    Memedi, Mevludin
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik.
    Westin, Jerker
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik.
    Nyholm, Dag
    Levodopa/carbidopa microtablets in Parkinson's disease: a study of pharmacokinetics and blinded motor assessment2017Ingår i: European Journal of Clinical Pharmacology, ISSN 0031-6970, E-ISSN 1432-1041, Vol. 73, nr 5, s. 563-571Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Motor function assessments with rating scales in relation to the pharmacokinetics of levodopa may increase the understanding of how to individualize and fine-tune treatments.

    OBJECTIVES: This study aimed to investigate the pharmacokinetic profiles of levodopa-carbidopa and the motor function following a single-dose microtablet administration in Parkinson's disease.

    METHODS: This was a single-center, open-label, single-dose study in 19 patients experiencing motor fluctuations. Patients received 150% of their individual levodopa equivalent morning dose in levodopa-carbidopa microtablets. Blood samples were collected at pre-specified time points. Patients were video recorded and motor function was assessed with six UPDRS part III motor items, dyskinesia score, and the treatment response scale (TRS), rated by three blinded movement disorder specialists.

    RESULTS: AUC0-4/dose and C max/dose for levodopa was found to be higher in Parkinson's disease patients compared with healthy subjects from a previous study, (p = 0.0008 and p = 0.026, respectively). The mean time to maximum improvement in sum of six UPDRS items score was 78 min (±59) (n = 16), and the mean time to TRS score maximum effect was 54 min (±51) (n = 15). Mean time to onset of dyskinesia was 41 min (±38) (n = 13).

    CONCLUSIONS: In the PD population, following levodopa/carbidopa microtablet administration in fasting state, the Cmax and AUC0-4/dose were found to be higher compared with results from a previous study in young, healthy subjects. A large between subject variability in response and duration of effect was observed, highlighting the importance of a continuous and individual assessment of motor function in order to optimize treatment effect.

  • 32.
    Thomas, Ilias
    et al.
    Högskolan Dalarna, Akademin Industri och samhälle, Mikrodataanalys.
    Bergquist, Filip
    Gothenburg University.
    Constantinescu, Radu
    Gothenburg University.
    Nyholm, Dag
    Dept. of Neuroscience, Neurology, Uppsala University.
    Senek, Marina
    Dept. of Neuroscience, Neurology, Uppsala University.
    Memedi, Mevludin
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik. Informatics, School of Business, Örebro University.
    Using measurements from wearable sensors for automatic scoring of Parkinson's disease motor states: Results from 7 patients2017Ingår i: Engineering in Medicine and Biology Society (EMBC), 2017 39th Annual International Conference of the IEEE, IEEE, 2017, s. 131-134Konferensbidrag (Refereegranskat)
    Abstract [en]

    The objective of this study was to investigate the validity of an objective gait measure for assessment of different motor states of advanced Parkinson's disease (PD) patients. Seven PD patients performed a gait task up to 15 times while wearing sensors on their upper and lower limbs. Each task was performed at specific points during a test day, following a single dose of levodopa-carbidopa. At the time of the tasks the patients were video recorded and three movement disorder experts rated their motor function on three clinical scales: a treatment response scale (TRS) that ranged from −3 (very bradykinetic) to 0 (ON) to +3 (very dyskinetic), a dyskinesia score that ranged from 0 (no dyskinesia) to 4 (extreme dyskinesia), and a bradykinesia score that ranged from 0 (no bradykinesia) to 4 (extreme bradykinesia). Raw accelerometer and gyroscope data of the sensors were processed and analyzed with time series analysis methods to extract features. The utilized features quantified separate limb movements as well as movement symmetries between the limbs. The features were processed with principal component analysis and the components were used as predictors for separate support vector machine (SVM) models for each of the three scales. The performance of each model was evaluated in a leave-one-patient out setting where the observations of a single patient were used as the testing set and the observations of the other 6 patients as the training set. Root mean square error (RMSE) and correlation coefficients for the predictions showed a good ability of the models to map the sensor data into the rating scales. There were strong correlations between the SVM models and the mean ratings of TRS (0.79; RMSE=0.70), bradykinesia score (0.79; RMSE=0.47), and bradykinesia score (0.78; RMSE=0.46). The results presented in this paper indicate that the use of wearable sensors when performing gait tasks can generate measurements that have a good correlation to subjective expert assessments.

  • 33.
    Thomas, Ilias
    et al.
    Högskolan Dalarna, Akademin Industri och samhälle, Mikrodataanalys.
    Memedi, Mevludin
    Westin, Jerker
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik.
    Nyholm, Dag
    The effect of continuous levodopa treatment during the afternoon hours2019Ingår i: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 139, nr 1, s. 70-75Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: The aim of this retrospective study was to investigate if patients with PD, who are treated with levodopa-carbidopa intestinal gel (LCIG), clinically worsen during the afternoon hours and if so, to evaluate whether this occurs in all LCIG-treated patients or in a sub-group of patients.

    METHODS: Three published studies were identified and included in the analysis. All studies provided individual response data assessed on the treatment response scale (TRS) and patients were treated with continuous LCIG. Ninety-eight patients from the three studies fulfilled the criteria. T-tests were performed to find differences on the TRS values between the morning and the afternoon hours, linear mixed effect models were fitted on the afternoon hours' evaluations to find trends of wearing-off, and patients were classified into three TRS categories (meaningful increase in TRS, meaningful decrease in TRS, non -meaningful increase or decrease).

    RESULTS: In all three studies significant statistical differences were found between the morning TRS values and the afternoon TRS values (p-value <= 0.001 in all studies). The linear mixed effect models had significant negative coefficients for time in two studies, and 48 out of 98 patients (49%) showed a meaningful decrease of TRS during the afternoon hours.

    CONCLUSION: The results from all studies were consistent, both in the proportion of patients in the three groups and the value of TRS decrease in the afternoon hours. Based on these findings there seems to be a group of patients with predictable "off" behavior in the later parts of the day. This article is protected by copyright. All rights reserved.

  • 34.
    Thomas, Ilias
    et al.
    Högskolan Dalarna, Akademin Industri och samhälle, Mikrodataanalys.
    Westin, Jerker
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik.
    Alam, Moudud
    Högskolan Dalarna, Akademin Industri och samhälle, Statistik.
    Bergquist, F.
    Nyholm, D.
    Senek, M.
    Memedi, Mevludin
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik.
    A treatment–response index from wearable sensors for quantifying Parkinson's disease motor states2018Ingår i: IEEE journal of biomedical and health informatics, ISSN 2168-2194, E-ISSN 2168-2208, Vol. 22, nr 5, s. 1341-1349Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The goal of this study was to develop an algorithm that automatically quantifies motor states (off,on,dyskinesia) in Parkinson's disease (PD), based on accelerometry during a hand pronation-supination test. Clinician's ratings using the Treatment Response Scale (TRS), ranging from -3 (very Off) to 0 (On) to +3 (very dyskinetic), was used as target. For that purpose, 19 participants with advanced PD and 22 healthy persons were recruited in a single center open label clinical trial in Uppsala, Sweden. The trial consisted of single levodopa dose experiments for the people with PD (PwP), where participants were asked to perform standardized wrist rotation tests, using each hand, before and at pre-specified time points after the dose. The participants used wrist sensors containing a 3D accelerometer and gyroscope. Features to quantify the level, variation and asymmetry of the sensor signals, three-level Discrete Wavelet Transform features and approximate entropy measures were extracted from the sensors data. At the time of the tests, the PwP were video recorded. Three movement disorder specialists rated the participants’ state on the TRS scale. A Treatment Response Index from Sensors (TRIS) was constructed to quantify the motor states based on the wrist rotation tests. Different machine learning algorithms were evaluated to map the features derived from the sensor data to the ratings provided by the three specialists. Results from cross validation, both in 10-fold and a leave-one-individual out setting, showed good predictive power of a support vector machine model and high correlation to the TRS scale. Values at the end tails of the TRS scale were under and over predicted due to the lack of observations at those values but the model managed to accurately capture the dose - effect profiles of the patients. In addition, the TRIS had good test-retest reliability on the baseline levels of the PD participants (Intraclass correlation coefficient of 0.83) and reasonable sensitivity to levodopa treatment (0.33 for the TRIS). For a series of test occasions the proposed algorithms provided dose - effect time profiles for participants with PD, which could be useful during therapy individualization of people suffering from advanced PD

  • 35.
    Westin, Jerker
    et al.
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik.
    Ghiamati Yazdi, Samira
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik.
    Memedi, Mevludin
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik.
    Nyholm, D.
    Johansson, A.
    Dougherty, Mark
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik.
    Groth, T.
    A successful computer method for assessing drawing impairment in Parkinson's disease2009Ingår i: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 16, s. 559-559Artikel i tidskrift (Övrigt vetenskapligt)
  • 36.
    Westin, Jerker
    et al.
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik.
    Ghiamati Yazdi, Samira
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik.
    Memedi, Mevludin
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik.
    Nyholm, Dag
    Johansson, Anders
    Dougherty, Mark
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik.
    Groth, Torgny
    A new computer method for assessing drawing impairment in Parkinson's disease2010Ingår i: Journal of Neuroscience Methods, ISSN 0165-0270, E-ISSN 1872-678X, Vol. 190, nr 1, s. 143-148Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A test battery, consisting of self-assessments and motor tests (tapping and spiral drawing tasks) was used on 9482 test occasions by 62 patients with advanced Parkinson's disease (PD) in a telemedicine setting. On each test occasion, three Archimedes spirals were traced. A new computer method, using wavelet transforms and principal component analysis processed the spiral drawings to generate a spiral score. In a web interface, two PD specialists rated drawing impairment in spiral drawings from three random test occasions per patient, using a modification of the Bain & Findley 10-category scale. A standardised manual rating was defined as the mean of the two raters' assessments. Bland-Altman analysis was used to evaluate agreement between the spiral score and the standardised manual rating. Another selection of spiral drawings was used to estimate the Spearman rank correlations between the raters (r = 0.87), and between the mean rating and the spiral score (r = 0.89). The 95% confidence interval for the method's prediction errors was +/- 1.5 scale units, which was similar to the differences between the human raters. In conclusion, the method could assess PD-related drawing impairments well comparable to trained raters.

  • 37.
    Westin, Jerker
    et al.
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik.
    Memedi, Mevludin
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik.
    Ghiamati Yazdi, Samira
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik.
    Nyholm, Dag
    Dougherty, Mark
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik.
    Groth, Torgny
    Defining a test score for status assessment during motor fluctuations in Parkinson's disease2009Ingår i: The Movement Disorder Society's 13th International Congress of Parkinson's Disease and Movement Disorders, Paris, 2009Konferensbidrag (Refereegranskat)
    Abstract [en]

    Objective: To define and evaluate a computer method for assessing drawing impairment in spiral drawings. To define an overall score, summarizing self-assessments and motor test data from a test battery for patients with advanced Parkinson's disease (PD). Background: A test battery, consisting of self-assessments (modified PDQ-8) and motor tests (tapping and spiral drawing) was developed for a hand computer with touch screen in a telemedicine setting. Assessments and tests were carried out four times per day in a group of 65 patients with advanced PD (Duodopa treated or candidates) during 1-6 weekly test periods each. For most test periods, UPDRS ratings were available. Methods: In a web interface, a PD specialist assessed drawing impairment in 505 selected spiral drawings, representing all categories on the Bain & Findley 10-category scale. A computer method, using wavelet transforms and principal component analysis, processed the same spirals to generate a 'spiral score'. According to the PD specialist and co-author Dr Nyholm, the information content of a test period with the test battery could be descibed by six dimensions, 'off', 'dyskinesia', 'walking', 'satisfaction', 'spiral', and 'tapping'. Each dimension was defined as the first principal component of the level (mean) and fluctuation (standard deviation) for the questions or tests that this dimension is based on. Tapping dimension was based on both speed and accuracy. To obtain weights for an overall score, linear regression of the dimensions vs. simultaneous UPDRS ratings was performed. To assess the internal consistency of the test battery, Cronbach's Alpha for the six dimensions was calculated. Results: Pearson correlation between spiral score and clinical rating of drawing impairment was 0.87. Weights in overall test score were (%): spirals, 41, tapping, 24, satisfied, 19, dyskinetic, 10, walking, 5.4 and off, 0.1. Internal consistency for the dimensions was 0.81. Conclusions: The computer generated spiral score was strongly correlated to clinical assessment of drawing impairment. Spirals were assigned highest weight in overall score, reflecting the high weight of motor function in total UPDRS. Internal consistency was strong, implying all dimensions represent aspects of a common characteristic.

  • 38.
    Westin, Jerker
    et al.
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik.
    Nyholm, Dag
    Johansson, Anders
    Memedi, Mevludin
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik.
    Dougherty, Mark
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik.
    Groth, Torgny
    Pålhagen, Sven
    12-month results from a novel test battery used in a duodenal levodopa infusion trial2010Ingår i: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 17, nr s3, s. 21-21Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A novel test battery consisting of self-assessments and motor tests (tapping and spiral drawing) for patients with Parkinson’s disease (PD) was developed for a hand computer with touch screen in a telemedicine setting. Tests are performed four times per day in the home environment during weeklong test periods. Results are processed into scores for different dimensions of the symptom state and an ‘overall score’ reflecting the global condition of a patient during a test period. The test battery was validated in a separate study recently submitted to Mov Disord. This test battery is currently being used in an open longitudinal trial (DAPHNE, EudraCT No. 2005- 002654-21) by sixty-five patients with advanced PD at nine clinics around Sweden. On inclusion, the patients were either receiving treatment with duodenal levodopa/carbidopa infusion (Duodopa®) (n=36), or they were candidates for receiving this treatment (n=29). We now present interim results for the first twelve months. Test periods were performed in three-month intervals. During most of the periods, UPDRS ratings were performed in afternoons at the start of the week. In twenty of the patients, scores were available during individually optimized oral polypharamacy, before receiving infusion and at least one test period after having started infusion treatment. Usability and compliance with performing tests, this far are good, both with patients and clinical staff. Correlations between test periods 2 and 3 during infusion treatment (three months apart) are stronger for overall test score than for total UPDRS, indicating good reliability. The correlation between overall test score and UPDRS for all test periods is adequate (r=-0.6). In an exact Wilcoxon signed rank test, where the endpoint is the change from the first to the twelve month test period (n=25), there was no change in test results in any of the test battery dimensions for the patients already receiving infusion when included. However, in the patients entering the study before receiving infusion, there was a significant change (improvement) from the baseline to the twelve month test period in dimensions; ‘off’, ‘dyskinesia’ and ‘satisfied’ and in the ‘overall score’ (n=15). The mean improvement in overall score after infusion was 29% (p=0.015). We conclude that the test battery is able to measure a functional improvement with infusion that is sustained over at least twelve months.

  • 39.
    Westin, Jerker
    et al.
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik.
    Schiavella, Mauro
    Memedi, Mevludin
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik.
    Nyholm, Dag
    Dougherty, Mark
    Högskolan Dalarna, Akademin Industri och samhälle, Datateknik.
    Antonini, Angelo
    Validation of a home environment test battery for supporting assessments in advanced Parkinson's disease2012Ingår i: Neurological Sciences, ISSN 1590-1874, E-ISSN 1590-3478, Vol. 3, nr 4, s. 831-838Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Test sequences in a test battery for Parkinson’s disease patients, consisting of self-assessments and motor tests, were carried out repeatedly in a telemedicine setting, during week-long test periods and results were summarized in an ‘overall score’. 35 patients in stable and fluctuating conditions (15 age- and gender-matched pairs) used the test battery for 1 week, and were then assessed with UPDRS and PDQ-39. This procedure was repeated 1 week later, without treatment changes. Reliability was assessed by intraclass correlation coefficients and Cronbach’s alpha. Convergent validity was assessed by Spearman rank correlations and known-groups’ validity, by the Mann–Whitney test. According to anonymous usability questionnaires, the patients could easily complete the tasks. Median compliance (93%) and test–retest reliability (0.88) were good. The correlations between overall score and total UPDRS (-0.64) and PDQ-39 (-0.72) were adequate. Median overall score was 18% better in the stable compared to the fluctuating group (p = 0.0014).

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