The role and structure of the multidisciplinary team in the management of advanced Parkinson's disease with a focus on the use of levodopa-carbidopa intestinal gel

A multidisciplinary team (MDT) approach is increasingly recommended in Parkinson's disease (PD) treatment guidelines, but no standard of care exists for such an approach, and the guidelines do not provide clarification on how it should be implemented. This paper reviews evidence of MDT interventions in people with PD and provides expert clinical perspectives for an MDT approach, with a focus on advanced PD and levodopa-carbidopa intestinal gel (carbidopa-levodopa enteral suspension in the USA). The key recommendations are to enable the best possible treatment of people with PD locally by facilitating a close structured collaboration of different health care professionals working in a fixed network structure; to refer people with PD to established MDT centers in a timely manner; to establish regular meetings for the MDT enabling interdisciplinary exchange and learning; to optimize individual treatment and carefully evaluate available treatment options; to ensure treatment decisions are agreed jointly between people with PD, their caregivers, family, and health care professional; and to include specialists outside of neurology from adjuvant medical departments as necessary when implementing advanced therapies

Characterisation of advanced Parkinson's disease: OBSERVE-PD observational study - results of the Swiss subgroup.

AIMS OF THE STUDY Currently, the characterisation of advanced Parkinson’s disease (APD) does not follow standardised diagnostic criteria, which complicates the evaluation of ongoing care and treatment strategies, such as eligibility for device-aided treatment (DAT). Therefore, this study aimed to determine the proportion of APD and non-advanced Parkinson’s disease (non-APD) patients treated at specialised movement disorder centres in Switzerland, to compare clinical characteristics of APD versus non-APD patients and to assess eligibility for and use of DAT. Furthermore, potential differences between the Swiss and international situation should be uncovered. METHODS OBSERVE-PD was a cross-sectional, international, observational study including 2615 patients from 128 movement disorder centres in 18 countries. For the Swiss subgroup of the study analysed here, which included 134 patients from 5 movement disorder centres, motor and non-motor symptoms, activities of daily living and quality of life were assessed as endpoints. The correlation between physician’s judgement of APD and the Delphi criteria for APD, which were developed by an international expert group, as well as the clinical burden in APD and non-APD patients and eligibility for and use of DAT were evaluated. The results for the Swiss subgroup were subsequently compared with the international full analysis set of the OBSERVE-PD study. RESULTS Based on physician’s judgement, 69.4% of patients included in the Swiss study suffered from APD. A moderate correlation between physician’s judgement and the Delphi criteria for APD was observed (Κ = 0.480, 95% confidence interval 0.317–0.642). Clinical burden was higher for APD patients, as shown by worse scores for activities of daily living, motor symptom severity, dyskinesia duration/disability, duration of “off” time, non-motor symptoms and quality of life as compared with non-APD patients (p <0.0001 for all). The Swiss data for disease burden were comparable to the international findings, except that the Swiss patients showed less “off” time. Amongst APD patients eligible for DAT, the main reason for no DAT in Switzerland was patient refusal, whereas patients needing more time to decide about it was the most frequent reason in the international analysis. CONCLUSIONS The study shows that the burden of APD in tertiary care centres in Switzerland is comparable to the international situation. Patient refusal is the main reason for no DAT amongst eligible APD patients in such centres. The identification of standard APD classification parameters and evaluation of the reasons for no DAT are relevant for optimising treatment strategies and the transition to DAT

Characteristics of advanced Parkinson's disease patients seen in movement disorder clinics - Australian results from the cross-sectional OBSERVE study

Objectives: To evaluate the proportion of Parkinson's disease (PD) patients identified as having advanced Parkinson's disease (APD) according to physician's judgement in Australia. Methods: This cross-sectional, non-interventional observational study was performed in movement disorder clinics from 18 countries. Results from Australia are presented. Participants included consecutive adults with PD attending routine clinical visits, or inpatients, who could speak English. The primary outcome was the proportion of patients diagnosed with APD via physician judgement. Results: 100 patients were recruited in Australia: 61.0% (95% CI 51.4–70.6%) diagnosed with APD by physician judgement. Patients were 66.6 ± 8.5 years, 65% were male, were living at home (97%), and diagnosed with PD for median 10.7 years (0–30.5 years). Motor fluctuations were present in 68%. For those with APD, referral was predominantly to enable access to device assisted therapies (DAT) (49%), while for non-APD, referral was largely for diagnostic purposes (41%). Patients had a median follow-up at the movement disorder clinic of 4.8 years for those with APD, or 3.6 years for non-APD. While 62% were eligible for DAT, only two-thirds of these received them. The most commonly used DAT was deep brain stimulation (64.3%). There was fair agreement between physician's judgement and the APD criteria by Delphi method (Cohen's kappa) 0.325 (95% CI 0.150–0.500) in the Australian subset. Conclusions: The definition of APD requires refinement in order to facilitate greater agreement among movement disorder specialists. A third of APD patients eligible for DAT remain untreated. Better referral and education of patients with APD is needed

Developing consensus among movement disorder specialists on clinical indicators for identification and management of advanced Parkinson’s disease : a multi-country Delphi-panel approach

Background: Lack of a global consensus on the definition of advanced Parkinson’s disease (APD) and considerations for timing of device-aided therapies may result in heterogeneity in care. Objectives: To reach consensus among movement disorder specialists regarding key patient characteristics indicating transition to APD and guiding appropriate use of device-aided therapies in the management of PD symptoms. Methods: A Delphi-panel approach was utilized to synthesize opinions of movement disorder specialists and build consensus. Results: A panel was comprised of movement disorder specialists from 10 European countries with extensive experience of treating PD patients (mean =24.8 ± 7.2 years). Consensus on indicators of suspected APD and eligibility for device-aided therapies were based on motor symptoms, non-motor symptoms, and functional impairments. Key indicators of APD included: (i) motor—moderate troublesome motor fluctuations, ≥1 h of troublesome dyskinesia/day, ≥2 h “off” symptoms/day, and ≥5-times oral levodopa doses/day; (ii) non-motor—mild dementia, and non-transitory troublesome hallucinations; (iii) functional impairment—repeated falls despite optimal treatment, and difficulty with activities of daily living. Patients with good levodopa response, good cognition, and <70 years of age were deemed as good candidates for all three device-aided therapies. Patients with troublesome dyskinesia were considered good candidates for both levodopa-carbidopa intestinal gel and Deep Brain Stimulation (DBS). PD patients with levodopa-resistant tremor were considered good candidates for DBS. Conclusion: Identifying patients progressing to APD and suitable for device-aided therapies will enable general neurologists to assess the need for referral to movement disorder specialists and improve the quality of care and patient outcomes

Levodopa-carbidopa intestinal gel in advanced Parkinson's: Final results of the GLORIA registry

INTRODUCTION: This registry evaluated the 24-month safety and efficacy of levodopa-carbidopa intestinal gel (LCIG) treatment in advanced Parkinson's disease (PD) patients under routine clinical care. METHODS: Motor fluctuations, dyskinesia, non-motor symptoms, quality of life, and safety were evaluated. Observations were fully prospective for treatment-naïve patients (60% of patients) and partially retrospective for patients with ≤12 months of pre-treatment with LCIG (40% of patients). Hours of "On" and "Off" time were assessed with a modified version of the Unified Parkinson's Disease Rating Scale part IV items 32 and 39. RESULTS: Overall, 375 patients were enrolled by 75 movement disorder centers in 18 countries and 258 patients completed the registry. At 24 months LCIG treatment led to significant reductions from baseline in "Off" time (hours/day) (mean ± SD = -4.1 ± 3.5, P < 0.001), "On" time with dyskinesia (hours/day) (-1.1 ± 4.8, P = 0.006), Non-Motor Symptom Scale total (-16.7 ± 43.2, P < 0.001) and individual domains scores, and Parkinson's Disease Questionnaire-8 item total score (-7.1 ± 21.0, P < 0.001). Adverse events deemed to have a possible/probable causal relationship to treatment drug/device were reported in 194 (54%) patients; the most frequently reported were decreased weight (6.7%), device related infections (5.9%), device dislocations (4.8%), device issues (4.8%), and polyneuropathy (4.5%). CONCLUSIONS: LCIG treatment led to sustained improvements in motor fluctuations, non-motor symptoms particularly sleep/fatigue, mood/cognition and gastrointestinal domains, as well as quality of life in advanced PD patients over 24 months. Safety events were consistent with the established safety profile of LCIG

Characterizing advanced Parkinson’s disease: OBSERVE-PD observational study results of 2615 patients

Abstract Background There are currently no standard diagnostic criteria for characterizing advanced Parkinson’s disease (APD) in clinical practice, a critical component in determining ongoing clinical care and therapeutic strategies, including transitioning to device-aided treatment. The goal of this analysis was to determine the proportion of APD vs. non-advanced PD (non-APD) patients attending specialist PD clinics and to demonstrate the clinical burden of APD. Methods OBSERVE-PD, a cross-sectional, international, observational study, was conducted with 2615 PD patients at 128 movement disorder centers in 18 countries. Motor and non-motor symptoms, activities of daily living, and quality-of-life end points were assessed. The correlation between physician’s global assessment of advanced PD and the advanced PD criteria from a consensus of an international group of experts (Delphi criteria for APD) were evaluated. Results According to physician’s judgment, 51% of patients were considered to have APD. There was a moderate correlation between physician’s judgment and Delphi criteria for APD (K = 0.430; 95% CI 0.406–0.473). Activities of daily living, motor symptom severity, dyskinesia duration/disability, “Off” time duration, non-motor symptoms, and quality-of-life scores were worse among APD vs. non-APD patients (p < 0.0001 for all). APD patients (assessed by physicians) had higher disease burden by motor and non-motor symptoms compared with non-APD patients and a negative impact on activities of daily living and quality of life. Conclusions These findings aid in identifying standard APD classification parameters for use in practicing physicians. Improvements in identification of APD patients may be particularly relevant for optimizing treatment strategies including transitioning to device-aided treatment

Characterizing Advanced Parkinson’s Disease: Romanian Subanalysis from the OBSERVE-PD Study

OBSERVE-PD was a cross-sectional, multicountry, observational study conducted in 128 Movement Disorders Centers (MDCs) in 18 countries. Overall, the study enrolled 2615 patients. The aim was to determine the proportion of patients with advanced Parkinson’s disease (APD) versus non-APD from MDCs and to uncover the clinical burden of APD, as well as a correlation between overall assessment of APD and several indicators of APD. The advanced stage of the disease and severity were assessed by investigators using their clinical judgement. Data were collected during a single visit between February 2015 and January 2016. Agreement on physician judgement of APD diagnosis and fulfillment of at least one previously established APD indicator was calculated. Motor and nonmotor symptoms (NMSs), activities of daily living, treatment complications, quality of life (QoL), conventional treatments, and device-aided therapy (DAT) eligibility were assessed. Here, country-specific results of 161 Romanian patients with PD are presented. In total, 59.0% of patients were diagnosed with APD and 78.8% met at least one APD indicator. There was only moderate agreement between clinical judgement of APD and overall fulfillment of APD indicators. All scores related to motor symptoms, NMSs, and treatment complications, as well as to QoL, showed a higher disease burden for patients with APD versus non-APD. Physicians considered 73.7% of patients with APD eligible for DAT. The majority of patients eligible for DAT (54.3%) did not receive such treatment. Our results highlight the importance of earlier recognition of APD, by combining clinical judgement with more standardized clinical tools, such as generally recognized APD criteria. However, timely diagnosis of APD alone is not enough to improve patient outcomes. Other critical factors include patient acceptance and access to appropriate treatment

Semi-Analytic Correlation for Predicting Permeability of Micro-Square-Pillar Array

In this study, we consider the permeability of hexagonal arrays of micro-square pillars. A semi-analytic model for predicting the permeability of micro-square pillar arrays is developed. In addition, a numerical analysis is performed with taking into account the effect of meniscus curvature. The analytic and numerical results are in good agreement, within an error of 3%. Based on our analytic and numerical results, the effects of the contact angle (0 < theta < 90 degrees), nondimensional pillar diagonal length (0.1 < d* < 0.5), and nondimensional pillar height (0.5 < H* < 2.5) are investigated The meniscus curvature is shown to reduce the permeability significantly, particularly when the contact angle is small or the pillar height is low The permeability of the square pillar array is shown to be larger than that of a circular pillar arra.ope