| 1. |
- Rota, Silvia, et al.
(författare)
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Why do ‘OFF’ periods still occur during continuous drug delivery in Parkinson’s disease?
- 2022
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Ingår i: Translational Neurodegeneration. - : Springer Science and Business Media LLC. - 2047-9158. ; 11:1
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Forskningsöversikt (refereegranskat)abstract
- Continuous drug delivery (CDD) is used in moderately advanced and late-stage Parkinson’s disease (PD) to control motor and non-motor fluctuations (‘OFF’ periods). Transdermal rotigotine is indicated for early fluctuations, while subcutaneous apomorphine infusion and levodopa-carbidopa intestinal gel are utilised in advanced PD. All three strategies are considered examples of continuous dopaminergic stimulation achieved through CDD. A central premise of the CDD is to achieve stable control of the parkinsonian motor and non-motor states and avoid emergence of ‘OFF’ periods. However, data suggest that despite their efficacy in reducing the number and duration of ‘OFF’ periods, these strategies still do not prevent ‘OFF’ periods in the middle to late stages of PD, thus contradicting the widely held concepts of continuous drug delivery and continuous dopaminergic stimulation. Why these emergent ‘OFF’ periods still occur is unknown. In this review, we analyse the potential reasons for their persistence. The contribution of drug- and device-related involvement, and the problems related to site-specific drug delivery are analysed. We propose that changes in dopaminergic and non-dopaminergic mechanisms in the basal ganglia might render these persistent ‘OFF’ periods unresponsive to dopaminergic therapy delivered via CDD.
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| 2. |
- van Wamelen, Daniel J., et al.
(författare)
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The Non-Motor Symptoms Scale in Parkinson’s disease : Validation and use
- 2021
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Ingår i: Acta Neurologica Scandinavica. - : Hindawi Limited. - 0001-6314 .- 1600-0404. ; 143:1, s. 3-12
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Forskningsöversikt (refereegranskat)abstract
- The Non-Motor Symptoms Scale (NMSS) was developed and validated in 2007 as the first instrument for the comprehensive assessment of a range of non-motor symptoms in Parkinson's disease (PD). Thirteen years have elapsed since its introduction and extensive international validation with good psychometric attributes has been carried out. Here, we review the validation data of the NMSS and its cross-validity with other scales, and describe the key evidence derived from use of the NMSS in clinical studies. To date, over 100 clinical studies and trials have made use of it as an outcome measure, showing consistent and strong correlations between NMSS burden and health-related quality of life measures. Moreover, the scale has shown to be capable of detecting longitudinal changes in non-motor symptoms, where studies have shown differential changes over time of several of the NMSS domains. The scale has become a key outcome in several randomized clinical trials. Highlighting the prevalence and importance of non-motor symptoms to quality of life in patients with PD, the development of NMSS has also been useful in signposting clinical and biomarker based research addressing non-motor symptoms in PD.
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| 3. |
- Leta, Valentina, et al.
(författare)
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Personalised advanced therapies in parkinson’s disease : The role of non-motor symptoms profile
- 2021
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Ingår i: Journal of Personalized Medicine. - : MDPI AG. - 2075-4426. ; 11:8
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Tidskriftsartikel (refereegranskat)abstract
- Device-aided therapies, including levodopa-carbidopa intestinal gel infusion, apomorphine subcutaneous infusion, and deep brain stimulation, are available in many countries for the management of the advanced stage of Parkinson’s disease (PD). Currently, selection of device-aided therapies is mainly focused on patients’ motor profile while non-motor symptoms play a role limited to being regarded as possible exclusion criteria in the decision-making process for the delivery and sustenance of a successful treatment. Differential beneficial effects on specific non-motor symptoms of the currently available device-aided therapies for PD are emerging and these could hold relevant clinical implications. In this viewpoint, we suggest that specific non-motor symptoms could be used as an additional anchor to motor symptoms and not merely as exclusion criteria to deliver bespoke and patient-specific personalised therapy for advanced PD.
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| 4. |
- Smilowska, Katarzyna, et al.
(författare)
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Cost-Effectiveness of Device-Aided Therapies in Parkinson's Disease : A Structured Review
- 2021
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Ingår i: Journal of Parkinson's Disease. - 1877-7171. ; 11:2, s. 475-489
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Forskningsöversikt (refereegranskat)abstract
- Background: Despite optimal dopaminergic treatment most patients in moderate to advanced stages of Parkinson's disease (PD) experience progressively increasing disabilities, necessitating a shift from oral medication to device-aided therapies, including deep brain stimulation (DBS), intrajejunal levodopa-carbidopa infusion (IJLI), and continuous subcutaneous apomorphine infusion (CSAI). However, these therapies are costly, limiting their implementation. Objectives: To perform a systematic review on cost-effectiveness analyses for device-aided therapies in PD. Methods: References were identified by performing a systematic search in the PubMed and Web of Science databases in accordance with the PRISMA statement. In the absence of universal cost-effectiveness definitions, the gross domestic product per capita (GDP) in the country where a study was performed was used as a cut-off for cost-effectiveness based on cost per quality adjusted life year (QALY) gained. Results: In total 30 studies were retrieved. All device-aided therapies improved quality of life compared to best medical treatment, with improvements in QALYs between 0.88 and 1.26 in the studies with long temporal horizons. For DBS, nearly all studies showed that cost per QALY was below the GDP threshold. For infusion therapies only three studies showed a cost per QALY below this threshold, with several studies with long temporal horizons showing costs below or near the GDP threshold. Conclusion: Of the device-aided therapies, DBS can be considered cost-effective, but the majority of infusion therapy studies showed that these were less cost-effective. However, long-term use of the infusion therapies appears to improve their cost-effectiveness and in addition, several strategies are underway to reduce these high costs.
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| 5. |
- Van Wamelen, Daniel J., et al.
(författare)
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Continuous drug delivery aiming continuous dopaminergic stimulation in Parkinson's disease
- 2018
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Ingår i: Journal of Parkinson's Disease. - 1877-7171. ; 8:s1, s. 65-72
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Forskningsöversikt (refereegranskat)abstract
- Continuous dopaminergic stimulation in Parkinson's disease (PD) has several advantages over pulsatile, noncontinuous, stimulation. These therapies currently consist of pump-based and transcutaneous therapies and are based on a more constant delivery of the dopaminergic drug resulting in continuous dopaminergic stimulation and a more stable treatment effect. Several clinical and experimental observations have shown that continuous stimulation of dopaminergic receptors induces fewer complications, such as dyskinesia, compared to pulsatile stimulation. Currently available nonoral pharmacological continuous therapies in PD include the transdermal Rotigotine (RTG) patch, infusion therapies with Apomorphine and Intrajejunal Levodopa (IJLI) and the Rivastigmine patch. Here we aim to provide a concise review of these current therapies and discuss ongoing and future developments of continuous non-oral pharmacological dopaminergic therapies in PD.
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| 6. |
- van Wamelen, Daniel J., et al.
(författare)
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Digital health technology for non-motor symptoms in people with Parkinson's disease : Futile or future?
- 2021
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Ingår i: Parkinsonism and Related Disorders. - : Elsevier BV. - 1353-8020. ; 89, s. 186-194
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Forskningsöversikt (refereegranskat)abstract
- Introduction: There is an ongoing digital revolution in the field of Parkinson's disease (PD) for the objective measurement of motor aspects, to be used in clinical trials and possibly support therapeutic choices. The focus of remote technologies is now also slowly shifting towards the broad but more “hidden” spectrum of non-motor symptoms (NMS). Methods: A narrative review of digital health technologies for measuring NMS in people with PD was conducted. These digital technologies were defined as assessment tools for NMS offered remotely in the form of a wearable, downloadable as a mobile app, or any other objective measurement of NMS in PD that did not require a hospital visit and could be performed remotely. Searches were performed using peer-reviewed literature indexed databases (MEDLINE, Embase, PsycINFO, Cochrane Database of Systematic Reviews, Cochrane CENTRAL Register of Controlled Trials), as well as Google and Google Scholar. Results: Eighteen studies deploying digital health technology in PD were identified, for example for the measurement of sleep disorders, cognitive dysfunction and orthostatic hypotension. In addition, we describe promising developments in other conditions that could be translated for use in PD. Conclusion: Unlike motor symptoms, non-motor features of PD are difficult to measure directly using remote digital technologies. Nonetheless, it is currently possible to reliably measure several NMS and further digital technology developments are underway to offer further capture of often under-reported and under-recognised NMS.
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