| 1. |
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| 2. |
- Ahmed, Mobyen Uddin, et al.
(författare)
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A fuzzy rule-based decision support system for Duodopa treatment in Parkinson
- 2006
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Ingår i: 23rd annual workshop of the Swedish Artificial Intelligence Society. - Umeå.
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Konferensbidrag (refereegranskat)abstract
- A decision support system (DSS) was implemented based on a fuzzy logic inference system (FIS) to provide assistance in dose alteration of Duodopa infusion in patients with advanced Parkinson’s disease, using data from motor state assessments and dosage. Three-tier architecture with an object oriented approach was used. The DSS has a web enabled graphical user interface that presents alerts indicating non optimal dosage and states, new recommendations, namely typical advice with typical dose and statistical measurements. One data set was used for design and tuning of the FIS and another data set was used for evaluating performance compared with actual given dose. Overall goodness-of-fit for the new patients (design data) was 0.65 and for the ongoing patients (evaluation data) 0.98. User evaluation is now ongoing. The system could work as an assistant to clinical staff for Duodopa treatment in advanced Parkinson’s disease.
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| 3. |
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| 4. |
- Eggers, Kai, et al.
(författare)
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Artificial neural network algorithms for early diagnosis of acute myocardial infarction and prediction of infarct size in chest pain patients
- 2007
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Ingår i: Int J Cardiol. - : Elsevier BV. - 1874-1754 .- 0167-5273. ; 114:3, s. 366-74
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: To prospectively validate artificial neural network (ANN)-algorithms for early diagnosis of myocardial infarction (AMI) and prediction of 'major infarct' size in patients with chest pain and without ECG changes diagnostic for AMI. METHODS: Results of early and frequent Stratus CS measurements of troponin I (TnI) and myoglobin in 310 patients were used to validate four prespecified ANN-algorithms with use of cross-validation techniques. Two separate biochemical criteria for diagnosis of AMI were applied: TnI > or = 0.1 microg/L within 24 h ('TnI 0.1 AMI') and TnI > or = 0.4 microg/L within 24 h ('TnI 0.4 AMI'). To be considered clinically useful, the ANN-indications of AMI had to achieve a predefined positive predictive value (PPV) > or = 78% and a negative predictive value (NPV) > or = 94% at 2 h after admission. 'Major infarct' size was defined by peak levels of CK-MB within 24 h. RESULTS: For the best performing ANN-algorithms, the PPV and NPV for the indication of 'TnI 0.1 AMI' were 87% (p=0.009) and 99% (p=0.0001) at 2 h, respectively. For the indication of 'TnI 0.4 AMI', the PPV and NPV were 90% (p=0.006) and 99% (p=0.0004), respectively. Another ANN-algorithm predicted 'major AMI' at 2 h with a sensitivity of 96% and a specificity of 78%. Corresponding PPV and NPV were 73% and 97%, respectively. CONCLUSIONS: Specially designed ANN-algorithms allow diagnosis of AMI within 2 h of monitoring. These algorithms also allow early prediction of 'major AMI' size and could thus, be used as a valuable instrument for rapid assessment of chest pain patients.
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| 5. |
- Ellenius, Johan, et al.
(författare)
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Dynamic decision support graph : Visualization of ANN-generated diagnostic indications of pathological conditions developing over time
- 2008
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Ingår i: Artificial Intelligence in Medicine. - : Elsevier BV. - 0933-3657 .- 1873-2860. ; 42:3, s. 189-198
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: A common objection to using artificial neural networks in clinical decision support systems is that the reasoning behind diagnostic indications cannot be sufficiently well explained. This paper presents a method for visualizing diagnostic indications generated from an artificial neural network-based decision support algorithm (ANN-algorithm) in conditions developing over time. Methods: The main idea behind the method is first to calculate and graphically present the decision regions corresponding to the diagnostic indications given as output from the ANN-algorithm, in the space of two selected, clinically established 'display variables'. Secondly, the trajectory of time series measurement results of these, often biochemical markers, together with the respective 95% confidence intervals are superimposed on the decision regions. This wilt permit a nurse or clinician to grasp the diagnostic indication graphically at a glance. The indication is further presented in relation to clinical variables that the clinician is already familiar with, thus providing a sort of explanation. The predictive value of the indication is expressed by the proximity of the measurement result to the decision boundary, separating the decision regions, and by a numerically calculated individualized predictive value. Results: The method is illustrated as applied to a previously published ANN-algorithm for the early ruling-in and ruling-out of acute myocardial infarction, using monitoring of measurement results of myoglobin and troponin-1 in plasma. Conclusion: The method is appropriate when there is a limited number of clinically established variables, i.e. variables which the clinician is used to taking into account in clinical reasoning.
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| 6. |
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| 7. |
- Ellenius, Johan, et al.
(författare)
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Methods for selection of adequate neural network structures with application to early assessment of chest pain patients by biochemical monitoring
- 2000
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Ingår i: International Journal of Medical Informatics. - 1386-5056 .- 1872-8243. ; 57:2-3, s. 181-202
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Tidskriftsartikel (refereegranskat)abstract
- A methodology for selecting, training and estimating the performance of adequate artificial neural network (ANN) structures and incorporating them with algorithms that are optimized for clinical decision making is presented. The methodology was applied to the problem of early ruling-in/ruling-out of patients with suspected acute myocardial infarction using frequent biochemical monitoring. The selection of adequate ANN structures from a set of candidates was based on criteria for model compatibility, parameter identifiability and diagnostic performance. The candidate ANN structures evaluated were the single-layer perceptron (SLP), the fuzzified SLP, the multiple SLP, the gated multiple SLP, the multi-layer perceptron (MLP) and the discrete-time recursive neural network. The identifiability of the ANNs was assessed in terms of the conditioning of the Hessian of the objective function, and variability of parameter estimates and decision boundaries in the trials of leave-one-out cross-validation. The commonly used MLP was shown to be non-identifiable for the present problem and available amount of data, despite artificially reducing the model complexity with use of regularization methods. The investigation is concluded by recommending a number of guidelines in order to obtain an adequate ANN model.
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| 8. |
- Ellenius, Johan, et al.
(författare)
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Transferability of neural network-based decision support algorithms for early assessment of chest-pain patients
- 2000
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Ingår i: International Journal of Medical Informatics. - 1386-5056 .- 1872-8243. ; 60:1, s. 1-20
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Tidskriftsartikel (refereegranskat)abstract
- The present investigation concerns methodological and epidemiological aspects of the transferability of artificial neural network-based algorithms, as key-components for classification in decision support systems (DSS). The prevalence of pathological conditions to be detected must be known in order to tune an artificial neural networks (ANN)-decision algorithm so that the predictive values of the outcome fulfil medical requirements. Another aspect of transferability, when clinical laboratory results are used, concerns differences in analytical performance of measuring instruments. The relative bias between two instruments is not known exactly, but must be estimated and corrected for. A general method, based on original measured data sets and statistical modeling, was developed for simulating the impact of various correction procedures when using different analytical instruments. The simulation methodology was applied to a real clinical problem of ruling-in/ruling-out of patients with suspected acute myocardial infarction (AMI) by biochemical monitoring. The recommended correction procedure was based on method comparison with use of five duplicate measurements on a common set of patient samples covering the relevant measuring interval. Transferability of laboratory data over time was also studied. The design of quality assurance procedures should be based on analytical quality requirement specifications related to medical needs. Limits of critically sized systematic errors were assessed by calculating the decrease in diagnostic performance of the ANN-algorithm as a result of temporary analytical disturbances. The consequences for the design of QA procedures was illustrated. It is concluded that the actual ANN-decision algorithm for early assessment of chest-pain patients should be possible to transfer to new sites under realistic conditions.
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| 18. |
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| 19. |
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| 20. |
- Laugier, Allan, et al.
(författare)
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Remote instrument telemaintenance
- 1996
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Ingår i: Computer Methods and Programs in Biomedicine. ; 50, s. 187-
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Tidskriftsartikel (refereegranskat)
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| 21. |
- Lindqvist, Ulla, et al.
(författare)
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A hyaluronan-loading test applied to patients with liver and joint diseases
- 1992
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Ingår i: Clinica Chimica Acta. - 0009-8981 .- 1873-3492. ; 210:1-2, s. 119-132
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Tidskriftsartikel (refereegranskat)abstract
- The serum hyaluronan disappearance data, after an intravenous bolus injection of hyaluronan, were evaluated in terms of model-based parameters. The loading test was performed in 10 healthy persons (basal serum hyaluronan concentration, C0, 24.9 +/- 8.9 micrograms/l [mean +/- S.D.]), 6 patients with joint disease (62.3 +/- 41.1 micrograms/l) and 19 patients with liver disease (206 +/- 214 micrograms/l). The highest maximum Michaelis-Menten elimination rate (Vmax = 287 +/- 86 micrograms/min) was found in patients with joint disease, significantly higher than in healthy persons (Vmax = 179 +/- 16, P = 0.0015) and in patients with liver disease (Vmax = 149 +/- 59, P = 0.0002). C0 and Vmax were evaluated as discriminants for assessment of residual liver function. In patients with liver disease C0 correlated with liver function score (r = 0.875, P < 0.0001) and serum albumin concentration (r = -0.813, P < 0.0001). The Vmax parameter did not correlate with conventional liver function tests or with the liver score but a significantly negative correlation of Vmax with C0 was found in patients with liver disease. A combination of the C0 level and the Vmax parameter was found to discriminate between healthy persons, patients with joint disease and patients with liver disease and should be of benefit in separating patients, with or without elevated serum hyaluronan levels, into groups having increased influx or reduced elimination, respectively, of circulating hyaluronan.
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| 22. |
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| 23. |
- Memedi, Mevludin, et al.
(författare)
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A web application for follow-up of results from a mobile device test battery for parkinson’s disease patients
- 2010
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Ingår i: European Journal of Neurology. - Buenos Aires. - 1351-5101 .- 1468-1331.
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 24. |
- Memedi, Mevludin, 1983-, et al.
(författare)
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A web application for follow-up of results from a mobile device test battery for Parkinson’s disease patients
- 2011
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Ingår i: Computer Methods and Programs in Biomedicine. - Amsterdam : Elsevier BV. - 0169-2607 .- 1872-7565. ; 104:2, s. 219-226
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Tidskriftsartikel (refereegranskat)abstract
- A test battery consisting of self-assessments and motor tests for patients with Parkinson’s disease (PD) was constructed and implemented on a hand computer with touch screen in a telemedicine setting. In this work, a Web-based system was developed to deliver decision support information to treating clinical staff for assessing PD symptoms in their patients. Test results from the hand unit are transferred to a central server and processed into scores for different symptom dimensions and an “overall test score” reflecting the overall condition of the patient during a test period. The IBM Computer System Usability Questionnaire was administered to assess the users’ satisfaction with the system. Results showed that a majority of users who completed the evaluation were quite satisfied with the usability although a sizeable minority were not. Response times were tested by simulating up to 100 users accessing the web application at the same time. The average page completion times were in the range of 0.5 seconds indicating fast response. The system was able to summarize the test-battery data and present them in a useful manner. Its main contribution is a novel way to easily access symptom information from the home environment of patients.
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| 25. |
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| 26. |
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| 27. |
- Torsteinsdottir, Ingunn, et al.
(författare)
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Production and elimination of hyaluronan in rheumatoid arthritis patients : estimation with a loading test
- 1999
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Ingår i: Seminars in Arthritis & Rheumatism. - 0049-0172 .- 1532-866X. ; 28:4, s. 268-279
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To evaluate the benefit of determining the maximal elimination rate (Vmax) and the endogenous production of hyaluronan (HYA) in relation to the basal HYA concentration (c0) in rheumatoid arthritis (RA) patients; and to evaluate the compatibility of a new model for HYA kinetics, taking renal elimination into separate account in the overall clearance of HYA from the blood. METHODS: The calculations of production and elimination of HYA were based on the HYA loading test, which was performed in 21 patients with RA and 15 healthy controls. A blood sample was drawn before the loading test, followed by an intravenous (i.v.) injection of HYA as a single bolus dose of 7.5 mg. Blood samples were taken regularly during the next 60 minutes. A theoretical model with computational analysis of the data collected was used for calculating HYA production and elimination. RESULTS: Patients with RA had significantly higher c0 than healthy controls, although in 10 of 21 patients c0 was within the normal range. The RA patients also had higher Vmax than healthy controls, but the difference was not significant. The calculated production of HYA was increased in RA patients (P = .001) and correlated with c0 (P < .0001). The new model for HYA kinetics, in which the renal elimination was taken separately into account, proved to be more compatible than the previous model. CONCLUSION: The HYA loading test can help determine whether the increased serum level of HYA in RA patients is due to a high production or reduced elimination of HYA or both.
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| 28. |
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| 29. |
- Westin, Jerker, et al.
(författare)
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12-month results from a novel test battery used in a duodenal levodopa infusion trial
- 2010
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Ingår i: European Journal of Neurology. - Buenos Aires. - 1351-5101 .- 1468-1331. ; 17:s3, s. 21-21
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 30. |
- Westin, Jerker, 1971-, et al.
(författare)
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A home environment test battery for status assessment in patients with advanced Parkinson's disease
- 2010
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Ingår i: Computer Methods and Programs in Biomedicine. - : Elsevier BV. - 0169-2607 .- 1872-7565. ; 98:1, s. 27-35
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Tidskriftsartikel (refereegranskat)abstract
- A test battery for assessing patient state in advanced Parkinson's disease, consisting of self-assessments and motor tests, was constructed and implemented on a hand computer with touch screen in a telemedicine setting. The aim of this work was to construct an assessment device, applicable during motor fluctuations in the patient's home environment. Selection of self-assessment questions was based on questions from an e-diary, previously used in a clinical trial. Both un-cued and cued tapping tests and spiral drawing tests were designed for capturing upper limb stiffnes, slowness and involuntary movements. The patient interface gave an audible signal at scheduled response times and was locked otherwise. Data messages in an XML-format were sent from the hand unit to a central server for storage, processing and presentation. In tapping tests, speed and accuracy were calculated and in spiral tests, standard deviation of frequency filtered radial drawing velocity was calculated. An overall test score, combining repeated assessments of the different test items during a test period, was defined based on principal component analysis and linear regression. An evaluation with two pilot patients before and after receiving new types of treatments was performed. Compliance and usability was assessed in a clinical trial (65 patients with advanced Parkinson's disease) and correlations between different test items and internal consistency were investigated. The test battery could detect treatment effect in the two pilot patients, both in self-assessments, tapping tests' results and spiral scores. It had good patient compliance and acceptable usability according to nine nurses. Correlation analysis showed that tapping results provided different information as compared to diary responses. Internal consistency of the test battery was good and learning effects in the tapping tests were small.
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| 31. |
- Westin, Jerker, et al.
(författare)
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A home environment test battery for status assessment in patients with motor fluctuations
- 2006
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Ingår i: European Journal of Neurology. - Glasgow, UK. ; , s. 213-14
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Konferensbidrag (refereegranskat)abstract
- Background and aims Evaluating status in patients with motor fluctuations is complex and occasional observations/measurements do not give an adequate picture as to the time spent in different states. We developed a test battery to assess advanced Parkinson patients' status consisting of diary assessments and motor tests. This battery was constructed and implemented on a handheld computer with built-in mobile communication. In fluctuating patients, it should typically be used several times daily in the home environment, over periods of about one week. The aim of this battery is to provide status information in order to evaluate treatment effects in clinical practice and research, follow up treatments and disease progression and predict outcome to optimize treatment strategy. Methods Selection of diary questions was based on a previous study with Duodopa® (DIREQT). Tapping tests (with and without visual cueing) and a spiral drawing test were added. Rapid prototyping was used in development of the user interface. An evaluation with two pilot patients was performed before and after receiving new treatments for advanced disease (one received Duodopa® and one received DBS). Speed and proportion missed taps were calculated for the tapping tests and entropy of the radial drawing velocity was calculated for the spiral tests. Test variables were evaluated using non-parametric statistics. Results Post-treatment improvement was detected in both patients in many of the test variables. Conclusions Although validation work remains, preliminary results are promising and the test battery is currently being evaluated in a long-term health economics study with Duodopa® (DAPHNE).
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| 32. |
- Westin, Jerker, et al.
(författare)
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A new computer method for assessing drawing impairment in Parkinson's disease
- 2010
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Ingår i: Journal of Neuroscience Methods. - Amsterdam : Elsevier. - 0165-0270 .- 1872-678X. ; 190:1, s. 143-148
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 33. |
- Westin, Jerker, et al.
(författare)
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A pharmacokinetic-pharmacodynamic model for duodenal levodopa infusion
- 2007
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Ingår i: Parkinsonism & Related Disorders. - Amsterdam, Netherlands. ; , s. S102-S103
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Konferensbidrag (refereegranskat)abstract
- Objective Levodopa in presence of decarboxylase inhibitors is following two-compartment kinetics and its effect is typically modelled using sigmoid Emax models. Pharmacokinetic modelling of the absorption phase of oral distributions is problematic because of irregular gastric emptying. The purpose of this work was to identify and estimate a population pharmacokinetic- pharmacodynamic model for duodenal infusion of levodopa/carbidopa (Duodopa®) that can be used for in numero simulation of treatment strategies. Methods The modelling involved pooling data from two studies and fixing some parameters to values found in literature (Chan et al. J Pharmacokinet Pharmacodyn. 2005 Aug;32(3-4):307-31). The first study involved 12 patients on 3 occasions and is described in Nyholm et al. Clinical Neuropharmacology 2003:26:156-63. The second study, PEDAL, involved 3 patients on 2 occasions. A bolus dose (normal morning dose plus 50%) was given after a washout during night. Plasma samples and motor ratings (clinical assessment of motor function from video recordings on a treatment response scale between -3 and 3, where -3 represents severe parkinsonism and 3 represents severe dyskinesia.) were repeatedly collected until the clinical effect was back at baseline. At this point, the usual infusion rate was started and sampling continued for another two hours. Different structural absorption models and effect models were evaluated using the value of the objective function in the NONMEM package. Population mean parameter values, standard error of estimates (SE) and if possible, interindividual/interoccasion variability (IIV/IOV) were estimated. Results Our results indicate that Duodopa absorption can be modelled with an absorption compartment with an added bioavailability fraction and a lag time. The most successful effect model was of sigmoid Emax type with a steep Hill coefficient and an effect compartment delay. Estimated parameter values are presented in the table. Conclusions The absorption and effect models were reasonably successful in fitting observed data and can be used in simulation experiments.
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| 34. |
- Westin, Jerker, 1971-, et al.
(författare)
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A pharmacokinetic-pharmacodynamic model for duodenal levodopa infusion
- 2011
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Ingår i: Clinical neuropharmacology. - Lippincott : Williams & Wilkins. - 0362-5664 .- 1537-162X. ; 34:2, s. 61-65
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The purpose of this work was to identify and estimate a population pharmacokinetic-pharmacodynamic model for duodenal infusion of a levodopa/carbidopa gel (Duodopa) to examine pharmacological properties of this treatment. Methods: The modeling involved pooling data from 3 studies (on advanced Parkinson disease) and fixing some parameters to values found in literature. The first study involved 12 patients studied on 3 occasions each and was previously published. The second study involved 3 patients on 2 occasions. A bolus dose was given after a washout during night. Plasma samples and motor ratings (clinical assessment of motor function on a 7-point treatment response scale ranging from "very off" to "very hyperkinetic") were collected until the clinical effect returned to baseline. The third study involved 5 patients on 3 occasions receiving 5 different dose levels. Different structural models were evaluated using the nonlinear mixed-effects modeling program NONMEM VI. Population mean parameter values, and interindividual, interoccasion, and residual variabilities were estimated. Results: Absorption of the levodopa/carbidopa gel can be adequately described with first-order absorption with bioavailability and lag time. Estimated population parameter values were a mean absorption time of 28.5 minutes, a lag time of 2.9 minutes, and a bioavailability of 88%. The pharmacodynamic model for motor ratings had the following population values: a half-life of effect delay of 21 minutes, a concentration at 50% effect of 1.55 mg/L, an E-max of 2.39 U on the treatment response scale, and a sigmoidicity of the E-max function of 11.6. Conclusions: For the typical unmedicated subject, it will take 51.4 minutes until the peak levodopa effect is reached after a bolus dose. This delay is, like the magnitude of the effect, highly variable in this patient group. The residual error magnitudes of 20% for levodopa concentrations and 0.92 U (SD) for motor ratings indicate that the models developed provide predictions of a relevant quality. The developed model may be a first step toward model-guided treatment individualization of duodenal infusion of levodopa.
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| 35. |
- Westin, Jerker, et al.
(författare)
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Analysis of response to enteral infusion of levodopa in patients with Parkinson's disease
- 2004
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Ingår i: Movement Disorders 2004; 19(S9):165-166. - Rome.
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Konferensbidrag (refereegranskat)abstract
- Objective: We present a new evaluation of levodopa plasma concentrations and clinical effects during duodenal infusion of a levodopa/carbidopa gel (Duodopa ) in 12 patients with advanced Parkinson s disease (PD), from a study reported previously (Nyholm et al, Clin Neuropharmacol 2003; 26(3): 156-163). One objective was to investigate in what state of PD we can see the greatest benefits with infusion compared with corresponding oral treatment (Sinemet CR). Another objective was to identify fluctuating response to levodopa and correlate to variables related to disease progression. Methods: We have computed mean absolute error (MAE) and mean squared error (MSE) for the clinical rating from -3 (severe parkinsonism) to +3 (severe dyskinesia) as measures of the clinical state over the treatment periods of the study. Standard deviation (SD) of the rating was used as a measure of response fluctuations. Linear regression and visual inspection of graphs were used to estimate relationships between these measures and variables related to disease progression such as years on levodopa (YLD) or unified PD rating scale part II (UPDRS II). Results: We found that MAE for infusion had a strong linear correlation to YLD (r2=0.80) while the corresponding relation for oral treatment looked more sigmoid, particularly for the more advanced patients (YLD>18).
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| 36. |
- Westin, Jerker, et al.
(författare)
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Analysis of tapping test results in a test battery for advanced PD patients
- 2008
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Ingår i: Movement Disorders, 2008;. - Chicago, IL, USA. ; , s. 84-85
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Konferensbidrag (refereegranskat)abstract
- Objective: To compare results from various tapping tests with diary responses in advanced PD. Background: A home environment test battery for assessing patient state in advanced PD, consisting of diary assessments and motor tests was constructed for a hand computer with touch screen and mobile communication. The diary questions: 1. walking, 2. time in off , on and dyskinetic states, 3. off at worst, 4. dyskinetic at worst, 5. cramps, and 6. satisfied with function, relate to the recent past. Question 7, self-assessment, allows seven steps from -3 ( very off ) to +3 ( very dyskinetic ) and relate to right now. Tapping tests outline: 8. Alternately tapping two fields (un-cued) with right hand 9. Same as 8 but using left hand 10. Tapping an active field (out of two) following a system-generated rhythm (increasing speed) with the dominant hand 11. Tapping an active field (out of four) that randomly changes location when tapped using the dominant hand Methods: 65 patients (currently on Duodopa, or candidates for this treatment) entered diary responses and performed tapping tests four times per day during one to six periods of seven days length. In total there were 224 test periods and 6039 test occasions. Speed for tapping test 10 was discardedand tests 8 and 9 were combined by taking means. Descriptive statistics were used to present the variation of the test variables in relation to self assessment (question 7). Pearson correlation coefficients between speed and accuracy (percent correct) in tapping tests and diary responses were calculated. Results: Mean compliance (percentage completed test occasions per test period) was 83% and the median was 93%. There were large differences in both mean tapping speed and accuracy between the different self-assessed states. Correlations between diary responses and tapping results were small (-0.2 to 0.3, negative values for off-time and dyskinetic-time that had opposite scale directions). Correlations between tapping results were all positive (0.1 to 0.6). Conclusions: The diary responses and tapping results provided different information. The low correlations can partly be explained by the fact that questions related to the past and by random variability, which could be reduced by taking means over test periods. Both tapping speed and accuracy reflect the motor function of the patient to a large extent.
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| 37. |
- Westin, Jerker, 1971-
(författare)
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Decision Support for Treatment of Patients with Advanced Parkinson’s Disease
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The overall aim of this thesis was to develop, deploy and evaluate new IT-based methods for supporting treatment and assessment of treatment of advanced Parkinson’s disease. In this condition a number of different motor and non-motor symptoms occur in episodes of varying frequency, duration and severity. In order to determine outcome of treatment changes, repeated assessments are necessary. Hospitalization for observation is expensive and may not be representative for the situation at home. Paper home diaries have questionable reliability and storage and retrieval of results are problematic. Approaches for monitoring using wearable sensors are unable to address important non-motor symptoms. A test battery system consisting of both self-assessments of symptoms and motor function tests was constructed for a touch screen mobile phone. Tests are performed on several occasions per day during test periods of one week. Data is transmitted over the mobile net to a central server where summaries in different symptom dimensions and an overall test score per patient and test period are calculated. There is a web application that graphically presents the results to treating clinical staff. As part of this work, a novel method for assessment of spiral drawing impairment useful during event-driven sampling was developed. To date, the system has been used by over 100 patients in 10 clinics in Sweden and Italy. Evidence is growing that the test battery is useful, reliable and valid for assessment of symptoms during advanced Parkinson’s disease. Infusion of a levodopa/carbidopa gel into the small intestine has been shown to reduce variation in plasma drug levels and improve clinical response in this patient category. A pharmacokinetic-pharmacodynamic model of this intestinal gel infusion was constructed. Possibly this model can assist the process of individualization of dosage for this treatment through in numero simulations. Results from an exploratory data analysis indicate that severity measures during oral levodopa treatment may be factors to consider when deciding candidates for infusion treatment.
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| 38. |
- Westin, Jerker, et al.
(författare)
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Defining a test score for status assessment during motor fluctuations in Parkinson's disease
- 2009
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Ingår i: The Movement Disorder Society's 13th International Congress of Parkinson's Disease and Movement Disorders. - Paris.
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Konferensbidrag (refereegranskat)abstract
- 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.
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| 39. |
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| 40. |
- Westin, Jerker, et al.
(författare)
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Movement disorder monitoring
- 2006
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Patent (populärvet., debatt m.m.)abstract
- A test battery (10) for patients having fluctuating movement disorder, e.g. Parkinson's disease, comprises both a motor test section (17) and a patient diary collection section (19) collecting data representing patient subjective experiences. The test battery (10) further comprises a scheduler (20), which is arranged to restrict operation of the motor test section (17) and the patient diary collection section (19) to a multitude of predetermined limited time intervals. This restriction in time provides an association in time between the two types of tests, as well as a possibility for timing the test intervals dependent on e.g. the medication schedule or the daily activity schedule. The limited time intervals are preferably shorter than or equal to one hour, and preferably there is at least one limited time interval each 24 hours. The test battery (10) is preferably implemented as a portable device, enabling monitoring under home environment conditions.
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| 41. |
- Westin, Jerker, 1971-, et al.
(författare)
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Outcome prediction of enteral levodopa/carbidopa infusion in advanced Parkinson's disease
- 2006
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Ingår i: Parkinsonism & Related Disorders. - : Elsevier BV. - 1353-8020 .- 1873-5126. ; 12:8, s. 509-513
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Tidskriftsartikel (refereegranskat)abstract
- Two studies comparing intraduodenal infusion of a levodopa/carbidopa gel with oral treatments in advanced PD patients demonstrated improvement in UPDRS scores and in frequent clinical ratings on a global treatment response scale. Further analysis of data from these studies was performed to find predictive factors related to degree of improvement with infusion. Pearson's correlation coefficients between measures of improvement and baseline variables were calculated. Using data from one study, a prediction model was designed and was then evaluated using the other study's data. Correlations were found indicating that patients with more severe symptoms at baseline were most improved after infusion.
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| 42. |
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| 43. |
- Westin, Jerker, et al.
(författare)
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Pedal : identification of models for duodenal administration of levodopa
- 2006
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Ingår i: European Journal of Neurology. - Glasgow, UK. ; , s. 220-21
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Konferensbidrag (refereegranskat)abstract
- Backgound and aims: The main purpose of the PEDAL study is to identify and estimate sample individual pharmacokinetic- pharmacodynamic (PK/PD) models for duodenal infusion of levodopa/carbidopa (Duodopa®) that can be used for in numero simulation of treatment strategies. Other objectives are to study the absorption of Duodopa® and to form a basis for power calculation for a future larger study. PK/PD based on oral levodopa is problematic because of irregular gastric emptying. Preliminary work with data from [Gundert-Remy U et al. Eur J Clin Pharmacol 1983;25:69-72] suggested that levodopa infusion pharmacokinetics can be described by a two-compartment model. Background research led to a hypothesis for an effect model incorporating concentration-unrelated fluctuations, more complex than standard E-max models. Methods: PEDAL involved a few patients already on Duodopa®. A bolus dose (normal morning dose plus 50%) was given after a washout during night. Data collection continued until the clinical effect was back at baseline. The procedure was repeated on two non-consecutive days per patient. The following data were collected in 5 to 15 minutes intervals: i) Accelerometer data. ii) Three e-diary questions about ability to walk, feelings of “off” and “dyskinesia”. iii) Clinical assessment of motor function by a physician. iv) Plasma concentrations of levodopa, carbidopa and the metabolite 3-O-methyldopa. The main effect variable will be the clinical assessment. Results: At date of abstract submission, lab analyses were currently being performed. Modelling results, simulation experiments and conclusions will be presented in our poster.
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| 44. |
- Westin, Jerker, et al.
(författare)
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The most severe parkinsonian patients are most improved with duodenal levodopa infusion
- 2005
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Ingår i: Parkinsonism & Related Disorders 2005; 11(S2):216. - Berlin.
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Konferensbidrag (refereegranskat)abstract
- Objectives: To find variables correlated to improvement with intraduodenal levodopa/carbidopa infusion (Duodopa) in order to identify potential candidates for this treatment. Two clinical studies comparing Duodopa with oral treatments in patients with advanced Parkinson’s disease have shown significant improvement in percent on-time on a global treatment response scale (TRS) based on hourly and half-hourly clinical ratings and in median UPDRS scores. Methods: Data from study 1 comparing infusion with Sinemet CR (12 patients, Nyholm et al, Clin Neuropharmacol 2003; 26(3): 156-163) and study 2 comparing infusion with individually optimised conventional combination therapies (18 patients, Nyholm et al, Neurology, in press) were used. Measures of severity were defined as total UPDRS score and scores for sections II and III, percent functional on-time and mean squared error of ratings on the TRS and as mean of diary questions about mobility and satisfaction (only study 2). Absolute improvement was defined as difference in severity, and relative improvement was defined as percent absolute improvement/severity on oral treatment. Pearson correlation coefficients between measures of improvement and other variables were calculated. Results: Correlations (r2>0.28, p<0.05) between severity during oral treatment and absolute improvement on infusion were found for: Total UPDRS, UPDRS III and TRS ratings (studies 1 and 2) and for diary question 1 (mobility) and UPDRS II (study 2). Correlation to relative improvement was found for total UPDRS (study 2, r2=0.47). Figure 1 illustrates absolute improvement in total UPDRS vs. total UPDRS during oral treatment (study 2). Conclusion: Correlating different measures of severity and improvement revealed that patients with more severe symptoms were most improved and that the relation between severity and improvement was linear within the studied groups. The result, which was reproducible between two clinical studies, could be useful when deciding candidates for the treatment.
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