Abstract
ObjectiveDosing schedules for oral levodopa in advanced stages of Parkinson’s disease (PD) require careful tailoring to fit the needs of each patient. This study proposes a dosing algorithm for oral administration of levodopa and evaluates its integration into a sensor-based dosing system (SBDS).Materials and methodsIn collaboration with two movement disorder experts a knowledge-driven, simulation based algorithm was designed and integrated into a SBDS. The SBDS uses data from wearable sensors to fit individual patient models, which are then used as input to the dosing algorithm. To access the feasibility of using the SBDS in clinical practice its performance was evaluated during a clinical experiment where dosing optimization of oral levodopa was explored. The supervising neurologist made dosing adjustments based on data from the Parkinson’s KinetiGraph™ (PKG) that the patients wore for a week in a free living setting. The dosing suggestions of the SBDS were compared with the PKG-guided adjustments.ResultsThe SBDS maintenance and morning dosing suggestions had a Pearson’s correlation of 0.80 and 0.95 (with mean relative errors of 21% and 12.5%), to the PKG-guided dosing adjustments. Paired t test indicated no statistical differences between the algorithmic suggestions and the clinician’s adjustments.ConclusionThis study shows that it is possible to use algorithmic sensor-based dosing adjustments to optimize treatment with oral medication for PD patients.
Highlights
Parkinson’s disease (PD) is a movement disorder that is characterized by the cardinal symptoms: bradykinesia, tremor, rigidity and postural instability [1]
The necessity of a sensor-based dosing system (SBDS) emerges from a continuous discussion raised by Espay et al [9] and Titova et al [21]
Espay et al argue that wearable sensors should be used for precision medicine, and that algorithms could be developed to generate specific recommendations
Summary
Parkinson’s disease (PD) is a movement disorder that is characterized by the cardinal symptoms: bradykinesia, tremor, rigidity and postural instability [1]. Physicians prescribe oral administration of levodopa using a generic dosing schedule but as the disease progresses the patients start experiencing shortening of medication effect, wearing-off fluctuations, and sometimes dyskinesia (manifestation of involuntary movements—attributed to overmedication) [2, 3] In those cases, individually tailored dosing routines are given, as a more advanced dosing strategy (second stage). Patient diaries [5] and limited information during clinical visits will often not provide the physician with the information necessary to optimize dosing routines appropriately It is not unusual for the patients on individualized treatment to experience either hour-long periods of “off”, i.e. no effect from medication, or “dyskinesia”, because of ill-adjusted dosing schedules. This can become problematic for the patients, who might require advanced non-oral therapies [6, 7] (third stage)
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