Care of Late-Stage Parkinsonism: Resource Utilization of the Disease in Five European Countries.

BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disease that leads to progressive disability. Cost studies have mainly explored the early stages of the disease, whereas late-stage patients are underrepresented. OBJECTIVE: The aim is to evaluate the resource utilization and costs of PD management in people with late-stage disease. METHODS: The Care of Late-Stage Parkinsonism (CLaSP) study collected economic data from patients with late-stage PD and their caregivers in five European countries (France, Germany, the Netherlands, UK, Sweden) in a range of different settings. Patients were eligible to be included if they were in Hoehn and Yahr stage >3 in the on state or Schwab and England stage at 50% or less. In total, 592 patients met the inclusion criteria and provided information on their resource utilization. Costs were calculated from a societal perspective for a 3-month period. A least absolute shrinkage and selection operator approach was utilized to identify the most influential independent variables for explaining and predicting costs. RESULTS: During the 3-month period, the costs were €20,573 (France), €19,959 (Germany), €18,319 (the Netherlands), €25,649 (Sweden), and €12,156 (UK). The main contributors across sites were formal care, hospitalization, and informal care. Gender, age, duration of the disease, Unified Parkinson's Disease Rating Scale 2, the EQ-5D-3L, and the Schwab and England Scale were identified as predictors of costs. CONCLUSION: Costs in this cohort of individuals with late-stage PD were substantially higher compared to previously published data on individuals living in earlier stages of the disease. Resource utilization in the individual sites differed in part considerably among these three parameters mentioned. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Non-Motor Symptom Management: Insights into Adherence to Treatment Guidelines in Parkinson's Disease Patients.

Background: Non-motor symptoms (NMS) reduce quality of life in Parkinson's disease (PD) patients, who experience three times more NMS than individuals without PD. While there are international and national NMS treatment guidelines, their implication in clinical practice remains unclear. Objective: This study aimed to investigate the adherence to pharmacological NMS treatment guidelines in patients with mild to moderately severe PD. Methods: 220 PD patients with ≥1 NMS based on the Non-Motor Symptom Questionnaire and a Hoehn and Yahr stage ≤4 were randomly selected from the Swedish Parkinson registry and screened for inclusion. NMS were evaluated using the International Parkinson and Movement Disorder Society-Non-Motor Rating Scale (MDS-NMS), Parkinson's Disease Sleep Scale 2, Epworth Sleepiness Scale, and Hospital Anxiety and Depression Scale. Treatment was compared with Swedish national guidelines and international guidelines from the MDS Evidence-Based Medicine Committee. Results: Among 165 included patients, the median number of NMS was 14, and in median 7 symptoms were estimated to require treatment. The most common NMS requiring treatment were pain (69%) and urinary problems (56%). Treatment of depression and constipation demonstrated the highest adherence to guidelines (79% and 77%), while dysphagia and excessive daytime sleepiness exhibited the lowest adherence (0% and 4%). On average, only 32% of NMS were treated in accordance with guidelines. Conclusions: Adherence to pharmacological guidelines for NMS in patients with mild to severe PD was low. This study highlights the need for improved evaluation and treatment of NMS to enhance symptom management and quality of life among PD patients.

Economic Burden of Parkinson's Disease: A Multinational, Real-World, Cost-of-Illness Study.

BACKGROUND: Parkinson's disease is now one of the fastest-growing neurodegenerative disorders in the developed world, with an increasing prevalence and associated socioeconomic costs. Progression of the disease leads to a gradual deterioration in patients' quality of life, despite optimal treatment, and both medical and societal needs increase, often with the assistance of paid and/or unpaid caregivers. OBJECTIVE: We aimed to quantify the incremental economic burden of Parkinson's disease by disease severity in a real-world setting across differing geographic regions. METHODS: Demographics, clinical characteristics, health status, patient quality of life, caregiver burden, and healthcare resource utilization data were drawn from the Adelphi Parkinson's Disease Specific Program™, conducted in the USA, five European countries, and Japan. RESULTS: A total of 563 neurologists provided data for 5299 individuals with Parkinson's disease; 61% were male, with a mean age of 64 years. Approximately 15% of individuals were deemed to have advanced disease, with significantly more comorbidities, and a poorer quality of life, than those with non-advanced disease. Overall, the mean annual healthcare resource utilization increased significantly with advancing disease, and resulted in a three-fold difference in the USA and Europe. The main drivers behind the high economic burden included hospitalizations, prescription medications, and indirect costs. CONCLUSIONS: People with Parkinson's disease, and their caregivers, incur a higher economic burden as their disease progresses. Future interventions that can control symptoms or slow disease progression could reduce the burden on people with Parkinson's disease and their caregivers, whilst also substantially impacting societal costs.

The Care Needs of Patients With Cognitive Impairment in Late-Stage Parkinson's Disease.

BACKGROUND: Cognitive impairment is common in Parkinson's disease (PD), but care needs and resource use for those with significant cognitive impairment are not well established. METHODS: 675 participants with PD from the international Care of Late-Stage Parkinsonism (CLaSP) study were grouped into those without (n = 333, 49%) and with cognitive impairment (MMSE < 24/30 or diagnosis of dementia or Mild Cognitive Impairment; n = 342, 51%) and their clinical features, care needs and healthcare utilisation compared. The relationship between cognition and healthcare consultations was investigated through logistic regression. RESULTS: Cognitive impairment was associated with more motor and non-motor symptoms, less antiparkinsonian but higher rates of dementia and antipsychotic medication, worse subjective health status and greater caregiver burden. A considerable proportion did not have a pre-established cognitive diagnosis. Care needs were high across the whole sample but higher in the cognitive impairment group. Home care and care home use was higher in the cognitive impairment group. However, use of healthcare consultations was similar between the groups and significantly fewer participants with cognitive impairment had had recent PD Nurse consultations. Worse cognitive impairment was associated with lower frequency of recent PD nurse and multidisciplinary therapy consultation (physiotherapy, massage, occupational therapy, speech training and general nursing). CONCLUSIONS: Those with cognitive impairment have more severe PD, higher care needs and greater social care utilisation than those with normal cognition, yet use of health care services is similar or less. Cognitive impairment appears to be a barrier to PD nurse and multidisciplinary therapy consultations. This challenges current models of care: alternative models of care may be required to serve this population. PLAIN LANGUAGE SUMMARY: Parkinson's disease is a long-term progressive health condition. Over time, many people with Parkinson's develop problems with thinking and memory, called cognitive impairment. This can negatively impact the daily lives of the person with Parkinson's and their caregiver. It is also thought to be a barrier to accessing healthcare. How people with Parkinson's who have cognitive impairment use healthcare and detail of their care needs is not well known.We analysed data from a large sample of people with advanced Parkinson's from six European countries to investigate their symptoms, care needs and healthcare use. We compared those with cognitive impairment to (342 people) to those without cognitive impairment (333 people).We found that those with cognitive impairment had more severe Parkinson's across a range of symptoms compared to those without cognitive impairment. They also had more care needs, reported their health status to be worse, and their caregivers experienced greater strain from caring. Whilst use of other healthcare services was similar between the two groups, those with cognitive impairment were less likely to have recently seen a Parkinson's nurse than those without cognitive impairment. Further analysis showed an association between cognitive impairment and not having seen a Parkinson's nurse or therapist recently, taking psychiatric symptoms, functional disability and care home residence into account. Therapists included were physiotherapy, massage, occupational therapy, speech training and general nursing. These findings highlight unmet need. We suggest that healthcare should be more targeted to help this group of people, given their higher care needs.

A systematic practice review: Providing palliative care for people with Parkinson's disease and their caregivers.

BACKGROUND: People with Parkinson's disease has significant and increasing physical, psychosocial and spiritual needs, as well as problems with coordination and continuity of care. Despite the benefits that palliative care could offer, there is no consensus on how it should be delivered. AIM: The aim of this study is to provide a pragmatic overview of the evidence to make clinical recommendations to improve palliative care for people with Parkinson's disease and their caregivers. DESIGN: A systematic review method was adopted to determine the strength of evidence, supported by feedback from an expert panel, to generate the 'do', 'do not do' and 'do not know' recommendations for palliative care. DATA SOURCES: Searches were conducted via OVID to access CINAHL, MEDLINE, EMBASE and the Cochrane Library from 01/01/2006 to 31/05/2021. An additional search was conducted in December 2022. The search was limited to articles that included empirical studies of approaches to enabling palliative care. RESULTS: A total of 62 studies met inclusion criteria. There is evidence that education about palliative care and movement disorders is essential. palliative care should be multi-disciplinary, individualised and coordinated. Proactive involvement and support of caregivers throughout the illness is recommended. Limited data provide referral indicators for palliative care integration. Discussions about advance care planning should be held early. CONCLUSIONS: Consideration of palliative care integration based on symptom burden and personal preferences, coordination and continuity of care are needed to maintain the quality of life of people with Parkinson's disease and their caregivers.

Dopamine agonist serum concentrations and impulse control disorders in Parkinson's disease.

BACKGROUND AND PURPOSE: Impulse control disorders (ICDs) are common among Parkinson's disease patients using dopamine agonists. We wanted to determine whether ICD patients have higher dopamine agonist serum concentrations than those without any sign of ICD. METHODS: Patients who used either pramipexole or ropinirole depot once daily were screened for ICDs using the validated Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale. Those who scored above the cut-off for one or more of the four defined ICDs (gambling, compulsive sexual behavior, compulsive shopping, and binge-eating) were compared in a case-control study to patients who scored zero points (no evidence of ICD) on the same items. They were examined clinically and evaluated using relevant scales. Three blood samples were taken on the same day: before daily dose, and then 6 and 12 h later. RESULTS: Forty-six patients were included: 19 ICD-positive and 27 controls. Ropinirole serum concentrations 6 h after daily intake (Cmax ) were higher in the case group compared to the control group, as was the daily ropinirole dosage. No differences were observed in serum concentrations, dosage or total drug exposure for pramipexole. Disease duration and length of dopamine agonist treatment was significantly longer among ICD patients for ropinirole, but not for pramipexole. CONCLUSIONS: The use of pramipexole may in itself confer high ICD risk, whereas ICDs among ropinirole users depend more on serum concentration and drug exposure. The pharmacokinetic properties of ropinirole make it challenging to predict its effects on patients, which supports the need for therapeutic drug monitoring to reduce risk of ICD.

Meaning in Life in Late-Stage Parkinson's Disease: Results from the Care of Late-Stage Parkinsonism Study (CLaSP) in Six European Countries.

The Care of Late-Stage Parkinsonism (CLaSP) study is a longitudinal, multicentre, prospective cohort study to assess the needs and provision of care for people with late-stage Parkinson's disease and their caregivers in six European countries. As a cross-sectional study within the CLaSP study, 509 people with Parkinson's disease completed the "Schedule-for-Meaning-in-Life-Evaluation" (SMiLE) questionnaire. We compared the results to those of a representative sample of healthy participants (n = 856). People with late-stage Parkinson's disease reported family, partnership and spirituality as the greatest areas of importance. Overall, they had lower SMiLE indices compared to healthy participants. People with late-stage Parkinson's disease rated the importance of core meaning in life areas (namely family, social relations and health) as significantly lower than the representative cohort and they also rated satisfaction as significantly lower in most areas. In conclusion, people with late-stage Parkinson's disease do have areas where they can find meaning, such as family, partnership and spirituality. However, they indicate a lack of fulfilment of their individual MiL, reflected by low satisfaction rates in the majority of meaning in life categories. The need for spiritual support for people with Parkinson's disease indicates the important role of chaplains to help people with Parkinson's disease maintain meaning in life.

Dynamic Monitoring of Probiotics Effect in Parkinson's Disease Patients via Swarm Decomposition and Bispectral Analysis of Electrogastrograms.

People with Parkinson's Disease (PwP) experience a significant deterioration of their daily life quality due to non-motor symptoms, with gastrointestinal dysfunctions manifesting as a vanguard of the latter. Electrogastrography (EGG) is a noninvasive diagnostic tool that can potentially provide biomarkers for the monitoring of dynamic gastric alterations that are related to daily lifestyle and treatment regimens. In this work, a robust analysis of EGG dynamics is introduced to evaluate the effect of probiotic treatment on PwP. The proposed framework, namely biSEGG, introduces a Swarm Decomposition-based enhancement of the EGG, combined with Bispectral feature engineering to model the underlying Quadratic Phase Coupling interactions between the gastric activity oscillatory components of EGG. The biSEGG features are benchmarked against the conventional Power Spectrum-based ones and evaluated through machine learning classifiers. The experimental results, when biSEGG was applied on data epochs from 11 PwP (probiotic vs placebo, AUROC: 0.67, Sensitivity/Specificity: 75/58%), indicate the superiority of biSEGG over Power Spectrum-based approaches and justify the efficiency of biSEGG in capturing and explaining intervention- and meal consumption-related alterations of the gastric activity in PwP.Clinical relevance- biSEGG holds potential for dynamic monitoring of gastrointestinal dysfunction and health status of PwP across diverse daily life scenarios.

A Paradigm Shift in the Management of Patients with Parkinson's Disease.

BACKGROUND: Technological evolution leads to the constant enhancement of monitoring systems and recording symptoms of diverse disorders. SUMMARY: For Parkinson's disease, wearable devices empowered with machine learning analysis are the main modules for objective measurements. Software and hardware improvements have led to the development of reliable systems that can detect symptoms accurately and be implicated in the follow-up and treatment decisions. KEY MESSAGES: Among many different devices developed so far, the most promising ones are those that can record symptoms from all extremities and the trunk, in the home environment during the activities of daily living, assess gait impairment accurately, and be suitable for a long-term follow-up of the patients. Such wearable systems pave the way for a paradigm shift in the management of patients with Parkinson's disease.

Application of single wrist-wearable accelerometry for objective motor diary assessment in fluctuating Parkinson's disease.

Advanced Parkinson's disease (PD) is characterized by motor fluctuations including unpredictable oscillations remarkably impairing quality of life. Effective management and development of novel therapies for these response fluctuations largely depend on clinical rating instruments such as the widely-used PD home diary, which are associated with biases and errors. Recent advancements in digital health technologies provide user-friendly wearables that can be tailored for continuous monitoring of motor fluctuations. Their criterion validity under real-world conditions using clinical examination as the gold standard remains to be determined. We prospectively examined this validity of a wearable accelerometer-based digital Parkinson's Motor Diary (adPMD) using the Parkinson's Kinetigraph (PKG®) in an alternative application by converting its continuous data into one of the three motor categories of the PD home diary (Off, On and Dyskinetic state). Sixty-three out of 91 eligible participants with fluctuating PD (46% men, average age 66) had predefined sufficient adPMD datasets (>70% of half-hour periods) from 2 consecutive days. 92% of per-protocol assessments were completed. adPMD monitoring of daily times in motor states showed moderate validity for Off and Dyskinetic state (ICC = 0.43-0.51), while inter-rating methods agreements on half-hour-level can be characterized as poor (median Cohen's κ = 0.13-0.21). Individualization of adPMD thresholds for transferring accelerometer data into diary categories improved temporal agreements up to moderate level for Dyskinetic state detection (median Cohen's κ = 0.25-0.41). Here we report that adPMD real-world-monitoring captures daily times in Off and Dyskinetic state in advanced PD with moderate validities, while temporal agreement of adPMD and clinical observer diary data is limited.

Compliance with National and International Guidelines in the Treatment of Nonmotor Symptoms in Late-Stage Parkinson's Disease.

Background: National as well as international Parkinson's disease (PD) treatment guidelines are available to guide clinicians. Previous research has shown that nonmotor symptoms (NMS) are pronounced in late-stage PD and has suggested that current treatment is insufficient and could be improved. Objectives: The aim of this study was to investigate to which degree the national and international treatment guidelines are followed in the treatment of NMS in late-stage PD. Methods: This Swedish cohort was part of the Care of Late-Stage Parkinsonism (CLaSP) study. Late-stage PD was defined as Hoehn and Yahr stages IV-V in "on" and/or ≤50% on the Schwab and England Activities of Daily Living (ADL) scale. NMS were assessed with the NMS scale (NMSS), cognition with the Mini-Mental State Examination (MMSE), and depressive symptoms with the Geriatric Depression Scale (GDS-30). Symptomatic individuals were defined as ≥ 6 on an item of the NMSS; for dementia, a cutoff of ≤18 on the MMSE; for depression, a cutoff of ≥10 on the GDS. Results: All 107 participants exhibited NMS to various degrees and severities; the median NMSS score was 91. Among symptomatic individuals, for depressive symptoms, 37/63 (59%) were treated with antidepressants; for hallucinations and delusions, 9/18 (50%) and 5/13 (38%) were treated with antipsychotics; and for dementia, 9/27 (33%) were treated with rivastigmine and 1 (4%) was treated with donepezil. For orthostatic hypotension, 11/19 (58%) with lightheadedness and 7/8 (88%) with fainting were treated with antihypotensives; for sialorrhea, 2/42 (5%) were treated with botulinum toxin; and for constipation, 19/35 (54%) were treated with laxatives. For insomnia, 4/16 (25%) were treated with hypnotics, and for daytime sleepiness, 1/29 (3%) was treated with psychostimulants. Conclusions: The present analyses suggest a need for clinicians to further screen for and treat NMS. Optimizing treatment of NMS according to the national and international treatment guidelines may improve symptomatology and enhance quality of life in late-stage PD.

Healthcare resource utilization and device-aided therapy discussions with eligible patients across the Parkinson's disease continuum: Revelations from the MANAGE-PD validation cohort.

INTRODUCTION: Device-aided therapy may improve the quality of life (QoL) for people with advanced Parkinson's disease (PD) and poorly controlled symptoms with oral therapy. MANAGE-PD is a validated tool classifying patients based on symptom control and advanced treatment eligibility. This study focused on patient/caregiver reported outcomes and healthcare resource utilization among patients grouped by MANAGE-PD categories. METHODS: Device-aided therapy-naïve patients receiving oral treatments were identified from the Adelphi Parkinson's Disease Programme. Patients were categorized (category 1 to 3) using MANAGE-PD. PD-specific QoL (PDQ-39), care partner burden (ZBI), satisfaction with current treatment, healthcare resource utilization, associated healthcare costs, and future treatment discussion with providers were measured. Categories were compared using ANOVA, t-test, chi square and adjusted regression analyses. RESULTS: Of the analytical sample (n = 2709), 18.9% were inadequately controlled on current therapy and potentially eligible for device-aided therapies (category 3). As expected, they had worse patient/caregiver reported outcomes versus patients in categories 1 or 2. However, the degree of difference in healthcare resource utilization, including: greater number of hospitalizations, emergency room (ER) visits and consultations, higher likelihood of being recipients of respite care, and greater PD treatment burden, was unexpected. Importantly, of patients in category 3 and their care partners, >40% did not report discussions with providers about device-aided therapies. CONCLUSION: MANAGE-PD category 3 patients had significantly higher burden on healthcare resources versus patients well-controlled with oral treatment or requiring only oral medication adjustments; yet almost half had no discussion on device-aided therapies with providers. Device-aided therapies may be considered in these patients.

Homocysteine, vitamin B metabolites, dopamine-substituting compounds, and symptomatology in Parkinson's disease: clinical and therapeutic considerations.

Emerging studies suggest a correlation between elevated plasma homocysteine (hcy) levels and the risk of atherosclerosis, vascular disorders, and neurodegenerative diseases, including Parkinson's disease (PD). This narrative review delves into the intricate relationships between Hcy, vitamin B metabolites, dopamine-substituting compounds, and various symptoms of PD. Patients undergoing a long-term L-dopa/dopa-decarboxylase inhibitor (DDI) regimen, especially without a concurrent catechol-O-methyl transferase (COMT) inhibitor or methyl group-donating vitamin supplementation, such as vitamins B6 and B12, exhibit an elevation in Hcy and a decline in vitamin B metabolites. These altered concentrations appear to be associated with heightened risks of developing non-motor symptoms, including peripheral neuropathy and cognitive disturbances. The review underscores the impact of levodopa metabolism via COMT on homocysteine levels. In light of these findings, we advocate for the supplementation of methyl group-donating vitamins, notably B6 and B12, in patients undergoing a high-dose L-dopa/DDI regimen, particularly those treated with L-dopa/carbidopa intestinal gel (LCIG) infusion.

Tumoral parkinsonism-Parkinsonism secondary to brain tumors, paraneoplastic syndromes, intracranial malformations, or oncological intervention, and the effect of dopaminergic treatment.

INTRODUCTION: Secondary tumoral parkinsonism is a rare phenomenon that develops as a direct or indirect result of brain neoplasms or related conditions. OBJECTIVES: The first objective was to explore to what extent brain neoplasms, cavernomas, cysts, paraneoplastic syndromes (PNSs), and oncological treatment methods cause parkinsonism. The second objective was to investigate the effect of dopaminergic therapy on the symptomatology in patients with tumoral parkinsonism. METHODS: A systematic literature review was conducted in the databases PubMed and Embase. Search terms like "secondary parkinsonism," "astrocytoma," and "cranial irradiation" were used. Articles fulfilling inclusion criteria were included in the review. RESULTS: Out of 316 identified articles from the defined database search strategies, 56 were included in the detailed review. The studies, which were mostly case reports, provided research concerning tumoral parkinsonism and related conditions. It was found that various types of primary brain tumors, such as astrocytoma and meningioma, and more seldom brain metastases, can cause tumoral parkinsonism. Parkinsonism secondary to PNSs, cavernomas, cysts, as well as oncological treatments was reported. Twenty-five of the 56 included studies had tried initiating dopaminergic therapy, and of these 44% reported no, 48% low to moderate, and 8% excellent effect on motor symptomatology. CONCLUSION: Brain neoplasms, PNSs, certain intracranial malformations, and oncological treatments can cause parkinsonism. Dopaminergic therapy has relatively benign side effects and may relieve motor and nonmotor symptomatology in patients with tumoral parkinsonism. Dopaminergic therapy, particularly levodopa, should therefore be considered in patients with tumoral parkinsonism.

Comparison of dyskinesia profiles after L-DOPA dose challenges with or without dopamine agonist coadministration.

Many patients with Parkinson's disease (PD) experiencing l-DOPA-induced dyskinesia (LID) receive adjunct treatment with dopamine agonists, whose functional impact on LID is unknown. We set out to compare temporal and topographic profiles of abnormal involuntary movements (AIMs) after l-DOPA dose challenges including or not the dopamine agonist ropinirole. Twenty-five patients with PD and a history of dyskinesias were sequentially administered either l-DOPA alone (150% of usual morning dose) or an equipotent combination of l-DOPA and ropinirole in random order. Involuntary movements were assessed by two blinded raters prior and every 30 min after drug dosing using the Clinical Dyskinesia Rating Scale (CDRS). A sensor-recording smartphone was secured to the patients' abdomen during the test sessions. The two raters' CDRS scores were highly reliable and concordant with models of hyperkinesia presence and severity trained on accelerometer data. The dyskinesia time curves differed between treatments as the l-DOPA-ropinirole combination resulted in lower peak severity but longer duration of the AIMs compared with l-DOPA alone. At the peak of the AIMs curve (60-120 min), l-DOPA induced a significantly higher total hyperkinesia score, whereas in the end phase (240-270 min), both hyperkinesia and dystonia tended to be more severe after the l-DOPA-ropinirole combination (though reaching statistical significance only for the item, arm dystonia). Our results pave the way for the introduction of a combined l-DOPA-ropinirole challenge test in the early clinical evaluation of antidyskinetic treatments. Furthermore, we propose a machine-learning method to predict CDRS hyperkinesia severity using accelerometer data.

Chaudhuri's Dashboard of Vitals in Parkinson's syndrome: an unmet need underpinned by real life clinical tests.

We have recently published the notion of the "vitals" of Parkinson's, a conglomeration of signs and symptoms, largely nonmotor, that must not be missed and yet often not considered in neurological consultations, with considerable societal and personal detrimental consequences. This "dashboard," termed the Chaudhuri's vitals of Parkinson's, are summarized as 5 key vital symptoms or signs and comprise of (a) motor, (b) nonmotor, (c) visual, gut, and oral health, (d) bone health and falls, and finally (e) comorbidities, comedication, and dopamine agonist side effects, such as impulse control disorders. Additionally, not addressing the vitals also may reflect inadequate management strategies, leading to worsening quality of life and diminished wellness, a new concept for people with Parkinson's. In this paper, we discuss possible, simple to use, and clinically relevant tests that can be used to monitor the status of these vitals, so that these can be incorporated into clinical practice. We also use the term Parkinson's syndrome to describe Parkinson's disease, as the term "disease" is now abandoned in many countries, such as the U.K., reflecting the heterogeneity of Parkinson's, which is now considered by many as a syndrome.

Time to workforce exit after a Parkinson's disease diagnosis.

The impact of Parkinson's disease (PD) on workforce participation has received little attention even though demographic, lifestyle, and political changes together will result in an increased burden of PD on the working-age population. In this study, we investigate workforce survival after a PD diagnosis, as well as what demographic factors that are associated with workforce survival. As an exploratory outcome, we investigate workforce survival in persons with and without device-aided treatment (DAT). This is a nested case-cohort study based on Swedish national data from 2001-2016. Controls were matched on year of birth, sex, and municipality of residence. The used registers contain data on demographics, social insurance, in- and outpatient visits, filled drug prescriptions, and cause of death on the person-level. A total of 4781 persons with PD and 23,905 controls were included. The median survival until all-cause workforce exit was 43 months among persons that were workforce-active at the time of PD diagnosis, compared to 66 months in non-PD controls. Being female, ≥50 years old at diagnosis, or having a lower education were contributing factors to health-related workforce exit. Persons receiving DAT during follow-up exhibited shorter workforce survival than controls. However, this needs further investigation, particularly as patients have generally already left the workforce at the time for start of DAT. It is evident that PD has grave negative effects on workforce participation. Thus, supportive measures need to start at an early stage after diagnosis, and the development of new interventions is urgently needed.

Levodopa Dose Equivalency in Parkinson's Disease: Updated Systematic Review and Proposals.

BACKGROUND: To compare drug regimens across clinical trials in Parkinson's disease (PD) conversion formulae between antiparkinsonian drugs have been developed. These are reported in relation to levodopa as the benchmark drug in PD pharmacotherapy as 'levodopa equivalent dose' (LED). Currently, the LED conversion formulae proposed in 2010 by Tomlinson et al. based on a systematic review are predominantly used. However, new drugs with established and novel mechanisms of action and novel formulations of longstanding drugs have been developed since 2010. Therefore, consensus proposals for updated LED conversion formulae are needed. OBJECTIVES: To update LED conversion formulae based on a systematic review. METHODS: The MEDLINE, CENTRAL, and Embase databases were searched from January 2010 to July 2021. Additionally, in a standardized process according to the GRADE grid method, consensus proposals were issued for drugs with scarce data on levodopa dose equivalency. RESULTS: The systematic database search yielded 3076 articles of which 682 were eligible for inclusion in the systematic review. Based on these data and the standardized consensus process, we present proposals for LED conversion formulae for a wide range of drugs that are currently available for the pharmacotherapy of PD or are expected to be introduced soon. CONCLUSIONS: The LED conversion formulae issued in this Position Paper will serve as a research tool to compare the equivalence of antiparkinsonian medication across PD study cohorts and facilitate research on the clinical efficacy of pharmacological and surgical treatments as well as other non-pharmacological interventions in PD. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Clinical Impression of Severity Index for Parkinson's Disease and Its Association to Health-Related Quality of Life.

Background: Clinical Impression of Severity Index for Parkinson's Disease (CISI-PD) is a simple tool that can easily be used in clinical practice. Few studies have investigated the relationship between health-related quality of life and the CISI-PD. Objective: To analyze the association of CISI-PD scores with those of generic (EQ-5D-5L) and Parkinson's disease (PD) disease-specific (Parkinson's Disease Questionnaire-8 [PDQ-8]) health-related quality of life assessments. Methods: Persons with idiopathic PD in the Swedish Parkinson's Disease registry with simultaneous registrations of CISI-PD and EQ-5D-5L and/or PDQ-8 were included. Correlations with EQ-5D dimensions were analyzed. The relationships between the CISI-PD, EQ-5D-5L, and PDQ-8 were estimated by linear mixed models with random intercept. Results: In the Swedish Parkinson's Disease registry, 3511 registrations, among 2168 persons, fulfilled the inclusion criteria. The dimensions self-care, mobility, and usual activities correlated moderately with the CISI-PD (r s = 0.60, r s = 0.54, r s = 0.57). Weak correlations were found for anxiety/depression and pain/discomfort (r s = 0.39, r s = 0.29) (P values < 0.001). The fitted model included the CISI-PD, age, sex, and time since diagnosis. The CISI-PD had a statistically significant impact on the EQ-5D and PDQ-8 (P values < 0.001). Conclusions: The CISI-PD provides a moderate correlation with the EQ-5D and could possibly be useful as a basis for defining health states in future health economic models and serving as outcomes in managed entry agreements. Nonetheless, the limitation of capturing nonmotor symptoms of the disease remains a shortcoming of clinical instruments, including the CISI-PD.

The Relationship between PDQ-8 and Costs in Parkinson's Disease-A Swedish Register-Based Study.

Background: Parkinson's disease (PD) is a progressive neurodegenerative disorder associated with substantial costs which increase with progression state. However, few studies have investigated the association between costs and health related quality of life. Objectives: To estimate the relationship between costs and health related quality of life, measured by the Parkinson's disease Quality of Life Questionnaire (PDQ)-8 from a societal perspective, partial societal perspective (excluding productivity loss), and a health care perspective. Methods: The Swedish Parkinson's Disease registry was linked to health care data registries to estimate annual costs. A generalized linear model was used to assess the relationship between instrument items and costs. Results: The results suggest that PDQ-8 captures the increase of costs by PD severity, particularly for costs within the broader societal perspective. From the best to worst PDQ-8 quartile, we observed approximately 7-fold increases within the societal perspective (39,400 to 274,300 SEK) and the partial societal perspective (31,800 to 219,400 SEK), and the increase within the health care perspective more than doubled (21,900 to 49,700 SEK). The PDQ-8 dimensions "mobility," "activities of daily living" and "social support" were associated with high costs in all perspectives. Conclusion: Using a disease-specific measure reflecting the patient's perspective, we found an increase of costs with worsening severity of PD, particularly for costs within the broader societal perspective. High costs were associated with not only motor symptoms, but also the dimension "Social support."