Search

Background and Purpose The cardiovascular risk in Parkinson’s disease (PD) remains uncertain and controversial. Some studies suggest PD patients present an increased risk of cerebrovascular disease. We aimed to study the prevalence of neuroimaging cerebrovascular biomarkers in PD patients compared to controls, using an accurate and complete magnetic resonance (MR) imaging evaluation. Material and Methods Neuroimaging sub-study within a larger cross-sectional case–control study. An enriched subgroup of PD patients (≤10 years since diagnosis) with at least a moderate cardiovascular mortality risk based on a Systematic COronary Risk Evaluation (SCORE) was compared to community-based controls regarding neuroimaging biomarkers. Patients underwent a high-resolution T1-weighted MR imaging sequence at 3.0 T to visualize neuromelanin. A 3D SWI FFE, sagittal 3D T1-weighted, axial FLAIR and diffusion-weighted image sequences were obtained. Results The study included 47 patients, 24 with PD and 23 controls. PD patients presented a reduced area and signal intensity of the substantia nigra and locus coeruleus on neuromelanin-sensitive MR. The median SCORE was 5% in both groups. No significant differences regarding white matter hyperintensities (OR 4.84, 95% CI 0.50, 47.06), lacunes (OR 0.43, 95% CI 0.07, 2.63), microbleeds (OR 0.64, 95% CI 0.13, 3.26), or infarcts (0.95, 95% CI 0.12, 7.41) was found. The frequency of these neuroimaging biomarkers was very low in both groups. Conclusion The present study does not support an increased prevalence of neuroimaging cerebrovascular biomarkers in PD patients.

Levodopa treatment remains the gold standard for Parkinson's disease, but shortcomings related to the pharmacological profile, notably, oral administration and the consequent occurrence of motor complications, have led to the development of several add-on levodopa treatments or to research to improve the method of delivery. Motor fluctuations, and to a lesser extent non-motor fluctuations, concern half of the patients with Parkinson's disease after 5 years of disease and patients identified them as one of their most bothersome symptoms. Catechol-O-methyl transferase inhibitors (COMT-Is) are one of the recommended first-line levodopa add-on therapies for the amelioration of end-of dose motor fluctuations in patient with advanced Parkinson's disease. Currently, two peripheral COMT-Is are considered as first-line choices - entacapone (ENT), which was approved by the US Food and Drug Administration in 1999 and the European Committee in 1998; and opicapone (OPC), which was approved by the European Committee in 2016. A second-line COMT-I that requires regular hepatic monitoring, tolcapone (TOL), was approved by the Food and Drug Administration in 1998 and the European Committee in 1997. Of note, OPC also received Food and Drug Administration approval in 2021, but it is still only marketed in a few countries, including Germany, UK, Spain, Portugal, Italy, Japan, and USA, while ENT and TOL have a wider market. Our narrative review summarizes the pharmacokinetic/pharmacodynamic properties, clinical efficacy in terms of motor fluctuations, motor/non-motor symptoms, quality of life, and safety data of these three COMT-Is, as evidenced by randomized clinical trials, as well as by real-life observational studies. Overall, a phase III non-inferiority trial showed a similar effect between ENT and OPC on off-time (-60.8 min/day and -40.3 min/day, vs placebo, respectively), with a possible additional off-time reduction of 39 min/day, obtained when there is a switch from ENT to OPC. Concomitantly, TOL can reduce off-time by an average of 98 min/day. A significant though discrete concomitant reduction on the Unified Parkinson's Disease Rating Scale motor section (2-3 points) is obtained with all three drugs vs placebo. Data on quality of life are fewer and more heterogeneous, with positive results obtained especially in open-label studies. Effects on non-motor symptoms were investigated as secondary outcome only in a few studies, frequently by means of non-specific scales and a benefit was observed in open-label studies. Dopaminergic adverse effects were the most frequent, dyskinesia being the most common for the three drugs eventually requiring levodopa dose reductions. No urine discoloration and a very low incidence of diarrhea were found with OPC compared with ENT and TOL. Regular hepatic monitoring is needed only for TOL. A combination of COMT-Is with new formulations of levodopa, including the subcutaneous, intrajejunal, or new extended-release formulation, merits further exploration to improve the management of both mild and severe motor fluctuations.

Contains fulltext : 248871.pdf (Publisher’s version ) (Open Access) BACKGROUND: Previous studies showed that lifestyle behaviors (cigarette smoking, alcohol, coffee) are inversely associated with Parkinson's disease (PD). The prodromal phase of PD raises the possibility that these associations may be explained by reverse causation. OBJECTIVE: To examine associations of lifestyle behaviors with PD using two-sample Mendelian randomisation (MR) and the potential for survival and incidence-prevalence biases. METHODS: We used summary statistics from publicly available studies to estimate the association of genetic polymorphisms with lifestyle behaviors, and from Courage-PD (7,369 cases, 7,018 controls; European ancestry) to estimate the association of these variants with PD. We used the inverse-variance weighted method to compute odds ratios (ORIVW) of PD and 95%confidence intervals (CI). Significance was determined using a Bonferroni-corrected significance threshold (p = 0.017). RESULTS: We found a significant inverse association between smoking initiation and PD (ORIVW per 1-SD increase in the prevalence of ever smoking = 0.74, 95%CI = 0.60-0.93, p = 0.009) without significant directional pleiotropy. Associations in participants ≤67 years old and cases with disease duration ≤7 years were of a similar size. No significant associations were observed for alcohol and coffee drinking. In reverse MR, genetic liability toward PD was not associated with smoking or coffee drinking but was positively associated with alcohol drinking. CONCLUSION: Our findings are in favor of an inverse association between smoking and PD that is not explained by reverse causation, confounding, and survival or incidence-prevalence biases. Genetic liability toward PD was positively associated with alcohol drinking. Conclusions on the association of alcohol and coffee drinking with PD are hampered by insufficient statistical power.

© 2021 International Parkinson and Movement Disorder Society, Background: Huntington's disease (HD) is a rare neurodegenerative disorder with protean clinical manifestations. Its management is challenging, consisting mainly of off-label treatments. Objectives: The International Parkinson and Movement Disorder Society commissioned a task force to review and evaluate the evidence of available therapies for HD gene expansion carriers. Methods: We followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Eligible randomized controlled trials were identified via an electronic search of the CENTRAL, MEDLINE, and EMBASE databases. All eligible trials that evaluated one or more of 33 predetermined clinical questions were included. Risk of bias was evaluated using the Cochrane Risk of Bias tool. A framework was adapted to allow for efficacy and safety conclusions to be drawn from the balance between the GRADE level of evidence and the importance of the benefit/harm of the intervention. Results: Twenty-two eligible studies involving 17 interventions were included, providing data to address 8 clinical questions. These data supported a likely effect of deutetrabenazine on motor impairment, chorea, and dystonia and of tetrabenazine on chorea. The data did not support a disease-modifying effect for premanifest and manifest HD. There was no eligible evidence to support the use of specific treatments for depression, psychosis, irritability, apathy, or suicidality. Similarly, no evidence was eligible to support the use of physiotherapy, occupational therapy, exercise, dietary, or surgical treatments. Conclusions: Data for therapeutic interventions in HD are limited and support only the use of VMAT2 inhibitors for specific motor symptoms.

Background: Drooling is a clinically relevant non-motor symptom of people with Parkinson’s disease (PwP). Several drooling rating scales are available. Nevertheless, the compelling scientific evidence supporting their validity is limited. This study aims to evaluate clinical rating scales for drooling, assessing their characteristics, clinimetric properties, and clinical utility classification. Methods: A systematic review was undertaken. Two reviewers performed independent literature searches using the CENTRAL®, CINAHL®, Embase®, MEDLINE®, SciElo®, and SPEECH BITE® databases. We used consensusbased standards for the selection of health measurement instruments (COSMIN) and the International Parkinson’s disease and the Movement Disorders (MDS) criteria to evaluate the included rating scales. Results: The following six rating scales were identified: Drooling Impact Scale (DIS), Sialorrhea Scoring Scale (SSS), Drooling Severity and Frequency Scale (DSFS), Drooling Rating Scale (DRS), Sialorrhea Clinical Scale for Parkinson Disease (SCS-PD), and the Radboud Oral Motor inventory for Parkinson’s disease – Saliva (ROMPsaliva). The scales had heterogeneous characteristics: (i) not all were created/adapted for PwP; (ii) different dimensions associated with drooling are assessed; (iii) cross-cultural adaptations are limited to some languages. The clinimetric properties showed: (i) target population size limitations; (ii) incomplete reliability analysis; (iii) lack of robust validity; (iv) sensitivity to change not fully explored. Following the MDS criteria, only one tool was classified as “recommended”, the ROMP-saliva. Conclusions: This review provides information for an adequate selection of a drooling rating scale for clinical and/or research purposes. To date, ROMP-saliva is the only scale with substantial evidence of its clinimetric properties adequacy and data in PwP. info:eu-repo/semantics/publishedVersion

Levodopa remains the gold-standard Parkinson's disease (PD) treatment, but the inevitable development of motor complications has led to intense activity in pursuit of its optimal delivery.Peripheral inhibition of dopa-decarboxylase has long been considered an essential component of levodopa treatment at every stage of illness. In contrast, only relatively recently have catechol-O-methyltransferase (COMT) inhibitors been utilized to block the other major pathway of degradation and optimize levodopa delivery to the brain. First and second-generation COMT inhibitors were deficient because of toxicity, sub-optimal pharmacokinetics or a short duration of effect. As such, they have only been employed once 'wearing-off' has developed. However, the third-generation COMT inhibitor, opicapone has overcome these difficulties and exhibits long-lasting enzyme inhibition without the toxicity observed with previous generations of COMT inhibitors. In clinical trials and real-world PD studies opicapone improves the levodopa plasma profile and results in a significant improvement in ON time in 'fluctuating' disease, but it has not yet been included in the algorithm for early treatment.This review argues for a shift in the positioning of COMT inhibition with opicapone in the PD algorithm and lays out a pathway for proving its effectiveness in early disease.

Inhibiting catechol-O-methyltransferase extends the plasma half-life of levodopa, potentially allowing physicians to optimize the levodopa regimen in patients with Parkinson's disease (PD) experiencing motor fluctuations.To evaluate the effects of once-daily opicapone on levodopa plasma pharmacokinetics and motor response when added to two different levodopa dosing regimens.A total of 24 patients with PD and motor fluctuations were enrolled in an exploratory, open-label, modified cross-over trial. Participants first received levodopa/carbidopa 500/125 mg (five intakes) for 2 weeks and were then randomly assigned (1:1) to levodopa/carbidopa 400/100 mg given over either four or five daily intakes plus opicapone 50 mg for an additional 2 weeks. Levodopa 12-hour pharmacokinetics was the primary outcome (ie, excluding the effect of last/evening levodopa/carbidopa intake), with motor complications evaluated as secondary outcomes.Over 12-hour pharmacokinetics and compared with five-intake levodopa/carbidopa 500/125 mg without opicapone, maximal levodopa concentrations were similar or nonsignificantly higher on both levodopa/carbidopa 400/100 mg regimens plus opicapone. Despite a 100 mg lower total levodopa/carbidopa daily dose, adding opicapone 50 mg at least doubled the levodopa plasma half-life and minimal concentrations, with a significant ≈30% increase in total exposure. The levodopa fluctuation index was only significantly lower for the five intakes plus opicapone regimen (difference of -71.8%; P lt; 0.0001). Modifications to levodopa pharmacokinetics were associated with decreased off time and increased on time.Combining opicapone 50 mg with a 100 mg lower daily dose of levodopa provides higher levodopa bioavailability with avoidance of trough levels. Despite the lower levodopa dose, modifying the levodopa pharmacokinetic profile with opicapone was associated with decreased off time and increased on time. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

© 2021 International Parkinson and Movement Disorder Society, The landscape of genetic forms of Parkinson's diseases (PD) has grown exponentially in recent years. Today, around 10% of PD cases are estimated to be of genetic etiology. However, the link between parkinsonism or tremor and chromosome disorders, both numerical and structural, has been neglected. We reviewed the occurrence and characteristics of parkinsonism and tremor syndromes in patients with chromosomic disorders. We searched PubMed for articles published until December 2018, using the non-MESH terms "Chromosomopathy," "karyotype," "chromosome," "aneuploidy," "deletion," "inversion," "insertion," "duplication," and "Parkinson," "Parkinsonism," "Tremor," and "Parkinsonian disorder." We restricted the search to human studies and selected articles for further analysis after abstract review. Tremor syndromes in which patients had another possible clinical reason for syndromes were excluded, as well as tremor syndromes associated with point mutations, imprinting syndromes, and patients presenting with other hyperkinetic disorders. Fifty-four articles were reviewed. Aneuploidies of sex chromosomes were the most common chromosomopathy. These patients more commonly exhibited postural and kinetic tremor, often meeting the description of essential tremor. In structural chromosomopathies, the most frequent association was PD and 22q11.2 deletion syndrome, but we found case reports and case series of several additional deletion and duplication syndromes.

Background: A global overview of drug development programs in Parkinson’s disease over the last few decades is lacking, while such programs are challenging given the multifaceted and heterogeneous nature of the disease. Objective: To indirectly assess drug development programs in Parkinson’s disease, exploring some factors associated with compound attrition at different trial phases. Methods: We assessed all Parkinson’s disease trials in the WHO trials portal, from inception (1999) to September 2019. Independent authors selected trials and extracted data. The success rate was the number of compounds that progressed to the next drug development phase divided by the number of compounds in that phase. Results: Overall, 357 trials (studying 152 compounds) fulfilled our inclusion criteria, with 62 (17.3%) phase 1 trials, 135 (37.8%) phase 2 trials, 85 (23.8%) phase 3 trials, and 53 (14.8%) phase 4 trials. The success rate was 42.4% from phase 2 to 3. Original compounds received regulatory approval by the FDA in 21.4% of cases, compared with 6.7% of repurposed compounds, representing an overall success rate of 14.9%. We found 172 trials (48.2%) conducted for repurposing previously licensed compounds. These figures were approximately the same regarding approval by the EMA. Most compounds were approved to treat parkinsonism and motor fluctuations. Conclusion: We found a moderate-to-high success rate in all phases of drug development. This was largely based on the success of original compounds, despite almost half of the identified trials attempting compound repurposing.

There is growing interest in monitoring gait patterns in people with neurological conditions. The democratisation of wearable inertial sensors has enabled the study of gait in free living environments. One pivotal aspect of gait assessment in uncontrolled environments is the ability to accurately recognise gait instances. Previous work has focused on wavelet transform methods or general machine learning models to detect gait; the former assume a comparable gait pattern between people and the latter assume training datasets that represent a diverse population. In this paper, we argue that these approaches are unsuitable for people with severe motor impairments and their distinct gait patterns, and make the case for a lightweight personalised alternative. We propose an approach that builds on top of a general model, fine-tuning it with personalised data. A comparative proof-of-concept evaluation with general machine learning (NN and CNN) approaches and personalised counterparts showed that the latter improved the overall accuracy in 3.5% for the NN and 5.3% for the CNN. More importantly, participants that were ill-represented by the general model (the most extreme cases) had the recognition of gait instances improved by up to 16.9% for NN and 20.5% for CNN with the personalised approaches. It is common to say that people with neurological conditions, such as Parkinson’s disease, present very individual motor patterns, and that in a sense they are all outliers; we expect that our results will motivate researchers to explore alternative approaches that value personalisation rather than harvesting datasets that are may be able to represent these differences.

© 2020 Georg Thieme Verlag KG., OBJECTIVE: To undertake a systematic review and meta-analysis to assess the satisfaction of patients receiving nonvitamin K anticoagulants (NOACs), compared with vitamin K antagonists (VKAs). METHODS: We searched CENTRAL, MEDLINE, Embase, and Clinicaltrials.gov for randomized controlled trials (RCTs) and observational studies. Two reviewers screened, extracted, and appraised data independently. We pooled data using a random-effects model. Outcome included treatment satisfaction, which was assessed by scores of Duke Anticoagulation Satisfaction Scale (DASS), Anticlot Treatment Scale (ACTS), Perception of Anticoagulant Treatment Questionnaire 2 (PACT-Q2), or Treatment Satisfaction Questionnaire for Medication version II (TSQM-VII) and their domains reported with 95% confidence intervals (95% CIs). We followed MOOSE and PRISMA guidelines. RESULTS: We included four RCTs and 16 observational studies, enrolling 18,684 participants overall. Compared with VKAs, treatment with NOACs improved the ACTS Burdens score by 4.21 points (95% CI: 2.99-5.43, I 2 = 95%, combined n = 6,180), and ACTS Benefits by 0.49 points (95% CI: 0.18-0.81, I 2 = 85%, combined n = 6,171). Switching from VKAs to NOACs improved the ACTS Burdens score by 5.33 points (95% CI: 3.53-7.14, combined n = 3,097). Compared with VKAs, treatment with NOACs improved the TSQM-VII Global Satisfaction score by 6.86 points (95% CI: 3.00-10.73, combined n = 5,535). CONCLUSION: In patients with nonvalvular atrial fibrillation or venous thromboembolism, NOAC treatment is associated with greater satisfaction compared with VKAs. The switch from VKAs to NOACs was associated with improved patients’ satisfaction. These effects were largely due to a lower degree of treatment burden with NOAC treatment.

© 2020 International Parkinson and Movement Disorder Society, Despite well-established Parkinson’s disease (PD) diagnostic criteria, diagnosis can still be challenging, with a high rate of misdiagnosis in atypical cases, especially in early disease stages. The majority of misdiagnoses are related to the differential diagnosis of PD with atypical parkinsonian disorders (APD), such as multiple system atrophy–parkinsonian type (MSA-P), progressive supranuclear palsy (PSP), or corticobasal degeneration, as well as essential tremor (ET) and other forms of parkinsonism (drug-induced, vascular, functional).

Parkinson’s disease (PD) is a common neurodegenerative disorder, with a continuously increasing prevalence. With improved clinical and therapeutic management of PD, more patients reach later stages of the disease, meaning they may face new clinical problems that were not commonly approached. This gave way to the description of a new PD stage, late-stage PD (LSPD), which is clinically discernible from the advanced-stage one. Therefore, LSPD patients have new and different needs, regarding pharmacological and non pharmacological interventions, including palliative care and multidisciplinary teams. LSPD patients constitute an‘orphan population’, who traditionally was excluded from previous studies, due to its high disability. With this manuscript, we intend to review specific management challenges of LSPD patients, covering this new concept and its clinical features, how to assess these patients, therapeutic recommendations, as well as discussing ongoing research and future perspectives.

Background Gait impairments are common and highly disabling for Parkinson's disease (PD) patients. With the development of technology-based tools, it is now possible to measure the spatiotemporal parameters of gait with a reduced margin of error, thereby enabling a more accurate characterization of impairment. Objective To summarize and critically appraise the characteristics of technology-based gait analysis in PD and to provide mean and standard deviation values for spatiotemporal gait parameters. Methods A systematic review was conducted using the databases CENTRAL, MEDLINE, Embase, and PEDro from their inception to September 2019 to identify all observational and experimental studies conducted in PD or atypical parkinsonism that included a technology-based gait assessment. Two reviewers independently screened citations and extracted data. Results We included 95 studies, 82.1% (n = 78) reporting a laboratory gait assessment and 61.1% (n = 58 studies) using a wearable sensor. The most frequently reported parameters were gait velocity, stride and step length, and cadence. A statistically significant difference was found when comparing the mean values of each of these parameters in PD patients versus healthy controls. No statistically significant differences were found in the mean value of the parameters when comparing wearable versus non-wearable sensors, different types of wearable sensors, and different sensor locations. Conclusion Our results provide useful information for performing objective technology-based gait assessment in PD, as well as mean values to better interpret the results. Further studies should explore the clinical meaningfulness of each parameter and how they behave in a free-living context and throughout disease progression.

Background Parkinson's disease and cardiovascular disease are highly prevalent conditions in the elderly. Evidence shows inconsistent findings regarding the association between Parkinson's disease and cardiovascular events. Objective We sought to evaluate the proportion of cardiovascular adverse events among Parkinson's disease patients included in the placebo arm of randomized controlled trials. Methods For this systematic review and meta-analysis, we searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials from inception to February 2017. Randomized, placebo-controlled trials in Parkinson's disease were included. The primary outcome was the proportion of major cardiovascular adverse events, defined as myocardial infarction, stroke, peripheral artery disease, and sudden death. A random-effects meta-analysis was performed to derive pooled estimates of the proportion of adverse events and corresponding 95% confidence intervals (CIs). Results 236 randomized controlled trials were included, 80% (n = 189; 14704 patients) of which reported data on cardiovascular adverse events. The pooled proportion of major cardiovascular events ranged from 0.00% to 0.06% and the proportion of all cardiovascular adverse events was 3.33% (95% CI: 2.14, 4.70%), and ranged from 1.71% in de novo Parkinson's disease patients to 4.56% in patients receiving levodopa as their only antiparkinsonian medication. The most common adverse events were hypertension and orthostatic hypotension. Conclusions These results suggest that the proportion of major cardiovascular adverse events is low and that blood pressure abnormalities are the most frequent cardiovascular adverse event.

Introduction: Many patients with advanced Parkinson's disease (PD) have inadequate control of motor symptoms despite optimized treatment. Predictable and unpredictable OFF periods severely interfere with the quality of life. A drug that easily and rapidly reverts the OFF state is still needed. Subcutaneous apomorphine, the only approved drug for this indication, although efficacious, is not widely used probably due to its potential side effects and complicated administration.Levodopa is the most efficacious drug for the treatment of PD motor symptoms. However, issues related to the oral route and intestinal absorption in later disease stages render this route lengthy and inefficacious.Areas covered: Literature on the development of an inhaled formulation of levodopa has been reviewed. Significant advances in the field of pulmonary delivery systems and in dry powders have enabled the development of a new formulation of levodopa that can be inhaled and adequate blood levels rapidly achieved, bypassing intestinal absorption. Several clinical trials have reported efficacy, safety, and tolerability data. Some pulmonary-related adverse events have been reported but are mostly mild.Expert opinion: This new way of administering levodopa is likely to be very welcome and may fill a gap for OFF rescue treatments, at least for some patients.

Introduction There is little information on the late stages of parkinsonism. Methods We conducted a multicentre study in 692 patients with late stage parkinsonism in six European countries. Inclusion criteria were disease duration of ≥7 years and either Hoehn and Yahr stage ≥4 or Schwab and England score of 50 or less. Results Average disease duration was 15.4 (SD 7.7) years and mean total UPDRS score was 82.7 (SD 22.4). Dementia according to MDS-criteria was present in 37% of patients. Mean levodopa equivalence dose was 874.1 (SD 591.1) mg/d. Eighty two percent of patients reported falls, related to freezing (16%) or unrelated to freezing (21% of patients) or occurring both related and unrelated to freezing (45%), and were frequent in 26%. Moderate-severe difficulties were reported for turning in bed by 51%, speech by 43%, swallowing by 16% and tremor by 11%. Off-periods occurred in 68% and were present at least 50% of the day in 13%, with morning dystonia occurring in 35%. Dyskinesias were reported by 45% but were moderate or severe only in 7%. Moderate-severe fatigue, constipation, urinary symptoms and nocturia, concentration and memory problems were encountered by more than half of participants. Hallucinations (44%) or delusions (25%) were present in 63% and were moderate-severe in 15%. The association with overall disability was strongest for severity of falls/postural instability, bradykinesia, cognitive score and speech impairment. Conclusion These data suggest that current treatment of late stage parkinsonism in the community remains insufficiently effective to alleviate disabling symptoms in many patients.

Postural abnormalities (PA) are disabling features of Parkinson's disease (PD). Indirect analyses suggested a higher prevalence of PA among Asian patients compared to Caucasian ones, but no direct comparisons have been performed so far.An international, multicenter, cross-sectional study was performed in 6 European and Asian movement disorders centers with the aim to clarify differences and similarities of prevalence and characteristics of PA in Asian vs. Caucasian PD patients. Axial PA, encompassing antecollis (AC), camptocormia (CC), and Pisa syndrome (PS), and appendicular PA (appPA) were systematically searched and analysed in consecutive patients.88 (27%) of 326 PD patients had PA (29.1% in Asians and 24.3% in Caucasians, p: 0.331). Prevalence of axial PA was 23.6% in Asians and 24.3% in Caucasians (p = 0.886), in spite of a longer disease duration among Caucasians, but a longer PA duration among Asians. No differences in prevalence between AC, CC, and PS were found between the two ethnicities. The prevalence of appPA was higher in Asians (p = 0.036), but the regression analysis did not confirm a significant difference related to ethnicity. Considering the whole population, male gender (OR, 4.036; 95% CI, 1.926-8.456; p 0.005), a longer disease duration (OR, 2.61; 95% CI, 1.024-6.653; p = 0.044), and a higher axial score (OR, 1.242; 95% CI, 1.122-1.375; p 0.0005) were the factors associated with axial PA.The prevalence of axial PA in PD patients is not influenced by ethnicity. However, Asian PD patients tend to develop PA earlier in the disease course, particularly AC.

© 2021 Elsevier Inc. All rights reserved., Background: Post-operative atrial fibrillation (POAF) is a relevant complication after surgery. Several studies have shown that POAF has important consequences for long-term morbidity and mortality, by increasing the risk of thromboembolic events. However, the use of oral anticoagulation (OAC) is not well established in this context. Methods: We searched MEDLINE, CENTRAL, PsycInfo and Web of Science for clinical trials and observational studies evaluating anticoagulation vs. no anticoagulation in patients with POAF (after cardiac or non-cardiac surgery). Data were screened and extracted by two independent reviewers. We performed a random- effects model to estimate the pooled odds ratio (OR) with 95% Confidence Intervals (CI), and heterogeneity was evaluated by I2 statistics. The outcomes of interest were all-cause mortality, thromboembolic events, and bleeding events. Results: Overall, 10 observational retrospective studies were included: 5 studies with 203,946 cardiac surgery POAF patients, and 5 studies with 29,566 patients with POAF after non-cardiac surgery. In cardiac surgery POAF, the OAC use was associated with lower risk of thromboembolic events (OR 0.68; 95%CI 0.47-0.96, I2 = 31%; 4 studies) and the bleeding risk was significantly increased (OR 4.30; 95%CI 3.69 to 5.02, 1 study). In non-cardiac surgery POAF, OAC did not significantly reduce the risk of thromboembolic events (OR 0.71, 95%CI 0.33-1.15; I2 = 79%; 5 studies) but was associated with increased risk of bleeding (OR 1.20, 95%CI 1.10-1.32, I2 = 0%; 3 studies). Mortality was not significantly reduced in both cardiac and non-cardiac surgery POAF. Conclusion: Oral anticoagulation was associated with a lower risk of thromboembolic events in patients with POAF following cardiac surgery but not in non-cardiac surgery. Bleeding risk was increased in both settings. The confidence on pooled results is at most low, and further data, namely randomized controlled trials are necessary to derive robust conclusions.

Copyright © 2020, © SAGE Publications, Background: Patients in the late stages of parkinsonism are highly dependent on others in their self-care and activities of daily living. However, few studies have assessed the physical, psychological and social consequences of caring for a person with late-stage parkinsonism. Patients and methods: Five hundred and six patients and their caregivers from the Care of Late Stage Parkinsonism (CLaSP) study were included. Patients’ motor and non-motor symptoms were assessed using the UPDRS and Non-motor symptom scale (NMSS), Neuropsychiatric inventory (NPI-12), and caregivers’ health status using the EQ-5D-3 L. Caregiver burden was assessed by the Zarit Burden Interview (ZBI). Results: The majority of caregivers were the spouse or life partner (71.2%), and were living with the patient at home (67%). Approximately half of caregivers reported anxiety/depression and pain/discomfort (45% and 59% respectively). The factors most strongly associated with caregiver burden were patients’ neuropsychiatric features on the total NPI score (r = 0.38, p < 0.0001), total NMSS score (r = 0.28, p < 0.0001), caring for male patients and patients living at home. Being the spouse, the hours per day assisting and supervising the patient as well as caregivers’ EQ-5D mood and pain scores were also associated with higher ZBI scores (all p < 0.001). Conclusion: The care of patients with late stage parkinsonism is associated with significant caregiver burden, particularly when patients manifest many neuropsychiatric and non-motor features and when caring for a male patient at home., The study was funded by the European Commission (Joint Programme-Neurodegenerative Disease Research “European research projects for the evaluation of health care policies, strategies and interventions for Neurodegenerative Diseases”) through national funding bodies in all 6 countries (Economic and Social Research Council ES/L009250/1; BMBF, Marburg, Germany 01ED1403A, Munich, Germany 01ED1403B, Bordeaux, France: ANR-13-JPHC-0001-07, Lisbon, Portugal: HC/0002/2012, Lund, Sweden: HC-559-002, Nijmegen, Holland, 733051003). AS was supported by the National Institute for Health Research UCL/UCLH Biomedical Research Centre. AH was supported by co-funding of Groenhuysen organization and Stichting Beroepsopleiding Huisartsen.

Beyond the direct toxicity resulting from each drug in the poisoned patient, additional toxicities may result from drug-drug interactions (DDIs). We aimed to determine the frequency of potential DDIs in the poisoned patient and investigate whether DDIs are associated with severity. We conducted a 1-year cohort study in a toxicological ICU. DDIs were identified using an electronic interaction-checker tool. Among our 354 ICU poisoned patients, 134 (38%) presented at least one potential DDI between acute poisoning drugs and 180 (51%) at least one potential DDI between acute poisoning and long-term treatment drugs. Using multivariate analyses, previous suicide attempt was associated with the presence of potential DDIs between acute poisoning drugs in suicide attempt patients (P = 0.014). Chronic alcoholism (P = 0.005) and tobacco smoking (P = 0.022) were associated with the presence of potential DDIs between acute poisoning and long-term treatment drugs in recreational drug users. Presence of potential DDIs between acute poisoning and long-term treatment drugs was associated with catecholamine infusion (P = 0.022) in suicidal self-exposure patients. Presence of potential pharmacodynamic DDIs between acute poisoning and long-term treatment drugs was associated with aspiration pneumonia onset in recreational drug users (P = 0.03). ICU poisoned patients present a high rate of potential DDIs that may influence the outcome.

Summary Background Most patients with Parkinson's disease, Parkinson's disease dementia, and dementia with Lewy bodies do not carry mutations in known disease-causing genes. The aim of this study was to identify a novel gene implicated in the development of these disorders. Methods Our study was done in three stages. First, we did genome-wide linkage analysis of an Italian family with dominantly inherited Parkinson's disease to identify the disease locus. Second, we sequenced the candidate gene in an international multicentre series of unrelated probands who were diagnosed either clinically or pathologically with Parkinson's disease, Parkinson's disease dementia, or dementia with Lewy bodies. As a control, we used gene sequencing data from individuals with abdominal aortic aneurysms (who were not examined neurologically). Third, we enrolled an independent series of patients diagnosed clinically with Parkinson's disease and controls with no signs or family history of Parkinson's disease, Parkinson's disease dementia, or dementia with Lewy bodies from centres in Portugal, Sardinia, and Taiwan, and screened them for specific variants. We also did mRNA and brain pathology studies in three patients from the international multicentre series carrying disease-associated variants, and we did functional protein studies in in-vitro models, including neurons from induced pluripotent stem-like cells. Findings Molecular studies were done between Jan 1, 2008, and Dec 31, 2017. In the initial kindred of ten affected Italian individuals (mean age of disease onset 59·8 years [SD 8·7]), we detected significant linkage of Parkinson's disease to chromosome 14 and nominated LRP10 as the disease-causing gene. Among the international series of 660 probands, we identified eight individuals (four with Parkinson's disease, two with Parkinson's disease dementia, and two with dementia with Lewy bodies) who carried different, rare, potentially pathogenic LRP10 variants; one carrier was found among 645 controls with abdominal aortic aneurysms. In the independent series, two of these eight variants were detected in three additional Parkinson's disease probands (two from Sardinia and one from Taiwan) but in none of the controls. Of the 11 probands from the international and independent cohorts with LRP10 variants, ten had a positive family history of disease and DNA was available from ten affected relatives (in seven of these families). The LRP10 variants were present in nine of these ten relatives, providing independent—albeit limited—evidence of co-segregation with disease. Post-mortem studies in three patients carrying distinct LRP10 variants showed severe Lewy body pathology. Of nine variants identified in total (one in the initial family and eight in stage 2), three severely affected LRP10 expression and mRNA stability (1424+5delG, 1424+5G→A, and Ala212Serfs*17, shown by cDNA analysis), four affected protein stability (Tyr307Asn, Gly603Arg, Arg235Cys, and Pro699Ser, shown by cycloheximide-chase experiments), and two affected protein localisation (Asn517del and Arg533Leu; shown by immunocytochemistry), pointing to loss of LRP10 function as a common pathogenic mechanism. Interpretation Our findings implicate LRP10 gene defects in the development of inherited forms of α-synucleinopathies. Future elucidation of the function of the LRP10 protein and pathways could offer novel insights into mechanisms, biomarkers, and therapeutic targets. Funding Stichting ParkinsonFonds, Dorpmans-Wigmans Stichting, Erasmus Medical Center, ZonMw—Memorabel programme, EU Joint Programme Neurodegenerative Disease Research (JPND), Parkinson's UK, Avtal om Lakarutbildning och Forskning (ALF) and Parkinsonfonden (Sweden), Lijf and Leven foundation, and cross-border grant of Alzheimer Netherlands–Ligue Europeene Contre la Maladie d'Alzheimer (LECMA).

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. http://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/., Background: Despite vitamin K antagonists (VKA) being the gold standard in the prevention of thromboembolic events in antiphospholipid syndrome (APS), non-vitamin K antagonists oral anticoagulants/direct oral anticoagulants (DOACs) have been used off-label. Objective: We aimed to perform a systematic review comparing DOACs to VKA regarding prevention of thromboembolic events, occurrence of bleeding events and mortality in patients with APS. Methods: An electronic database search was performed through MEDLINE, CENTRAL and Web of Science. After data extraction, we pooled the results using risk ratio (RR) and 95% CI. Heterogeneity was assessed using the I². The outcomes considered were all thromboembolic events as primary, and major bleeding, all bleeding events and mortality as secondary. Evidence confidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation methodology. Results: We included 7 studies and a total of 835 patients for analyses. Thromboembolic events were significantly increased in DOACs arm, compared with VKA-RR 1.69, 95% CI 1.09 to 2.62, I²-24%, n=719, 6 studies. In studies using exclusively rivaroxaban, which was the most representative drug in all included studies, the thromboembolic risk was increased threefold (RR 3.36, 95% CI 1.53 to 7.37). The risks of major bleeding, all bleeding events and mortality were not significantly different from control arm. The grade of certainty of our results is very low. Conclusions: Current evidence suggests DOACs use, particularly rivaroxaban, among patients with APS, is less effective than VKA since it is associated with 69% increased risk of thromboembolic events.

© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/)., Mobile health (mHealth) has emerged as a potential solution to providing valuable ecological information about the severity and burden of Parkinson's disease (PD) symptoms in real-life conditions. Objective: The objective of our study was to explore the feasibility and usability of an mHealth system for continuous and objective real-life measures of patients' health and functional mobility, in unsupervised settings. Methods: Patients with a clinical diagnosis of PD, who were able to walk unassisted, and had an Android smartphone were included. Patients were asked to answer a daily survey, to perform three weekly active tests, and to perform a monthly in-person clinical assessment. Feasibility and usability were explored as primary and secondary outcomes. An exploratory analysis was performed to investigate the correlation between data from the mKinetikos app and clinical assessments. Results: Seventeen participants (85%) completed the study. Sixteen participants (94.1%) showed a medium-to-high level of compliance with the mKinetikos system. A 6-point drop in the total score of the Post-Study System Usability Questionnaire was observed. Conclusions: Our results support the feasibility of the mKinetikos system for continuous and objective real-life measures of a patient's health and functional mobility. The observed correlations of mKinetikos metrics with clinical data seem to suggest that this mHealth solution is a promising tool to support clinical decisions.

© 2019 International Parkinson and Movement Disorder Society, Levodopa has long been the mainstay of Parkinson's disease (PD) pharmacological therapy. Upon its introduction, symptom relief was markedly evident, and hope arose on the potential of effect on disease progression. In fact, James Parkinson did remark that there appeared “to be sufficient reason for hoping that some remedial process may ere long be discovered, by which, at least, the progress of the disease may be stopped.”2 Unfortunately, despite recent advances,3 after 2 centuries of effort and hundreds of trials evaluating dozens of different drugs, we are still to conclusively prove a “neuroprotective” or “disease-modifying” effect of any pharmacological treatment for PD.

© 2019 Informa UK Limited, trading as Taylor & Francis Group, Introduction: Influenza vaccination may be beneficial in coronary disease patients; however the infection and vaccination are associated with acute inflammation, a trigger of cardiovascular events. We aimed to review the risk of myocardial infarction (MI) associated with Influenza infection and the safety of vaccination in self-controlled case series (SCCS).Methods: We performed a systematic review with meta-analysis of SCCS studies to evaluate the risk of MI associated with Influenza infection/vaccination. Database search was performed in August/2018. The data were reported using the incident rate ratio (IRR) and 95% confidence interval (95%CI).Results: three studies for Influenza infection and two studies for Influenza vaccination were eligible. The risk of MI following an Influenza infection was significantly increased in the first 3 days (IRR 5.79; 95%CI: 3.59-9.38) and between 4-7 days (IRR 4.52; 95%CI: 2.80-7.32). In the first 4 weeks following the Influenza vaccination, there was a significant decrease of MI risk (IRR 0.84, 95%CI: 0.78-0.91).Conclusions: Short-term MI risk in Influenza infection is significantly increased, with a low-to-moderate confidence in the pooled evidence. The Influenza vaccine was safe regarding the short-term risk for MI, and the risk reduction is possibly related to a healthy period bias.

BACKGROUND Clinical management options for dysphagia include the use of thickeners to increase the consistency of liquids. Health professionals may not be aware of the nutrition value of these products, since there are no such recommendation in clinical guidelines. Our aim was to estimate the added nutrition value of the 2 types of commercial thickeners (starch and xanthan gum) to daily nutrition intake and compare their nutrition value for nectar, honey, and pudding consistencies. Additionally, we compared the nutrition value of both thickeners with a high-energy powder, since they share the same main ingredients. METHODS We collected recommended dosages for obtaining the 3 different consistencies and nutrition content from the technical food labels. Daily intake of fluids was estimated from the Portuguese National Food, Nutrition and Physical Activity Survey. Total daily amount of thickener needed was estimated, as well as their correspondent nutrition contributions. RESULTS Estimated daily fluid intake was 2439 mL. Starch thickeners provide significantly more energy at all consistencies than xanthan gum provides (423-846 kcal, P < 0.05, and 103-308 kcal, P < 0.05, respectively). Significantly more fiber is provided by xanthan gum thickeners (9 g in nectar and 27 g in pudding consistencies, P < 0.05). Median energy and carbohydrate values per 100 g of high-energy powder modules and starch thickeners are similar. CONCLUSION The nutrition value of thickeners should be routinely considered in the nutrition assessment and planning of patients with dysphagia for liquids, since they contribute significantly with energy, carbohydrate, and fiber.

Contains fulltext : 209024.pdf (Publisher’s version ) (Open Access) BACKGROUND: Persons with Parkinson's disease (PD) benefit from continuous exercise through participation in community-based exercise programs. However, community programs often lack PD-specific knowledge needed to provide safe and adequately dosed exercise. OBJECTIVE: To evaluate the acceptability and safety of a PD-specific boxing program in the community. METHODS: We developed specific educational resources to facilitate the boxing instructors. We also organized an educational and practical workshop for patients (n = 26) and instructors (n = 10), and assessed: (a) participants' satisfaction; (b) instructors' appreciation of the educational resources; and (c) numbers of patients interested in participating in the boxing program. After 18 months, patients and instructors completed a questionnaire evaluating: (a) participants' satisfaction; (b) adverse events; (c) facilitators and barriers; and (d) proportion of participants at follow-up. RESULTS: Twenty-six persons with PD (62% men) and 10 boxing instructors participated in the workshop. 81% of patients and 80% of instructors were very satisfied. Instructors found the educational materials "very helpful" (60%) or "helpful" (40%). Patients expressed a clear interest (54%) or possible interest (46%) in the program. We initiated classes with 10 participants. At 18-months follow-up, the program consisted of four boxing sessions/week, led by three instructors, with 40 participants. Seventeen patients responded to the questionnaire at follow-up. Participants were "very satisfied" (53%), "satisfied" (35%) and neither satisfied nor unsatisfied (12%) with the program. Adverse effects were mild (e.g., muscle aches). Transportation and physical disability were the main barriers for participation. CONCLUSIONS: The boxing program was well-received, with increasing numbers of participants at 18 months. The educational resources can support boxing instructors participating in current and future boxing classes being delivered in the community.

© 2019 Elsevier Ltd. All rights reserved., Background: Few data exist on the rate of clinical progression for Parkinson's disease (PD) patients who have entered a late stage of the disease. Objective: Study the clinical progression of a late-stage PD (LSPD) population over one year follow-up. Methods: 50 LSPD patients (Schwab and England ADL Scale 3 in MED ON) underwent an extensive clinical assessment at baseline and after one year and an acute levodopa test at baseline. Results: Mean age of LSPD patients (female 46%) was 77.5 ± 5.9 years and mean disease duration was 15.5 ± 6.5 years. At baseline, 76% had levodopa-induced motor complications (MC), usually non-troublesome, 68% were demented, 54% had psychosis and 68% depression. Caregiver distress was high. l-dopa responsiveness was mild (18% ± 12 of improvement on MDS-UPDRS-III). After one-year, 20% of the patients were dead, institutionalized or HY 5. MDS-UPDRS-motor mean score worsened 7.2 ± 10.3 points although there was heterogeneity between patients, and there was a global worsening of non-motor symptoms, mostly in cognition/mood, urinary and gastrointestinal domains. Nevertheless, MC improved despite similar levodopa equivalent dose. Functional independence and quality of life worsened. Dysphagia severity at baseline predicted a poor outcome (death, institutionalization or HY 5) (Hazard ratio 2.3, 95% CI 1.12-4.4; p = 0.01), whereas magnitude of l-dopa response of LSPD patients did not. Conclusions: LSPD patients still present a significant, although heterogeneous, motor and non-motor progression over 1 year. Dysphagia severity predicts the occurrence of additional disease severity milestones and its management must be prioritized.

Background and purpose The aim was to evaluate the efficacy of the catechol‐O‐methyltransferase inhibitor opicapone (25 and 50 mg) as adjunct therapy to levodopa in a pooled population of Parkinson's disease patients who participated in the pivotal double‐blind trials of opicapone and their 1‐year open‐label extensions. Methods Data (placebo, opicapone 25 mg and opicapone 50 mg) from the BIPARK‐1 and BIPARK‐2 double‐blind and open‐label studies were combined. The studies had similar designs, eligibility criteria and assessment methods. The primary efficacy variable in both double‐blind studies was the change from baseline in absolute OFF time based on patient diaries. Results Double‐blind treatment with opicapone (25 and 50 mg) significantly reduced absolute daily OFF time from a baseline of 6.1–6.6 h. The mean (and 95% confidence interval) treatment effect versus placebo was −35.1 (−62.1, −8.2) min (P = 0.0106) for the 25 mg dose and −58.1 (−84.5, −31.7) min (P < 0.0001) for the 50 mg dose. Reductions in OFF time were mirrored by significant increases in ON time without troublesome dyskinesia (P < 0.05 and P < 0.0001 for the 25 and 50 mg doses, respectively). No significant differences were observed for ON time with troublesome dyskinesia. Patient diary results from the open‐label phase indicated a maintenance of effect for patients previously treated with opicapone 50 mg. The group previously treated with the 25 mg dose benefitted with further optimization of therapy during the open‐label phase, whilst switching from placebo to opicapone led to significant reductions in OFF time and increased ON time. Conclusions Over at least 1 year of open‐label therapy, opicapone consistently reduced OFF time and increased ON time without increasing the frequency of troublesome dyskinesia.

Non‐steroidal anti‐inflammatory drugs (NSAIDs) were thought to increase the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) virus entrance into cells. Hence, it was suggested in the media that NSAIDs could lead to a higher risk of infection and/or disease severity. To determine the existence or absence of this association, we aimed to systematically evaluate the risk of SARS‐CoV‐2 infection and mortality and the risk of severe coronavirus disease 2019 (COVID‐19) associated with previous exposure to NSAIDs. MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), and EMBASE were searched in February 2021 for controlled studies. The results were calculated through random‐effect meta‐analyses and reported in terms of odds ratio (OR) with 95% confidence intervals (CI). Heterogeneity was assessed with I2 test. Eleven studies were included, comprising a total of 683 715 patients. NSAID exposure did not increase the risk of having a positive test for SARS‐CoV‐2 infection (OR 0.97, 95% CI 0.85–1.11, I2 = 24%, five studies). The exposure to NSAIDs did not increase the risk of severe/critical COVID‐19 disease (OR 0.92, 95% CI 0.80–1.05, I2 = 0%, 5 studies) nor all‐cause mortality among patients with COVID‐19 (OR 0.86, 95% CI 0.75–0.99, I2 = 14%, four studies). Our data did not suggest that exposure to NSAIDs increases the risk of having SARS‐CoV‐2 infection or increases the severity of COVID‐19 disease. Also, the fragility of the studies included precludes definite conclusions and highlights the need for further robust data. Systematic review registration number: CRD42020216806 This article is protected by copyright. All rights reserved

Describe PSP Study Group, the ProPSP Study Group, and the Movement Disorder Society–Endorsed PSP Study Group., [Background] The Progressive Supranuclear Palsy Rating Scale is a prospectively validated physician-rated measure of disease severity for progressive supranuclear palsy. We hypothesized that, according to experts' opinion, individual scores of items would differ in relevance for patients' quality of life, functionality in daily living, and mortality. Thus, changes in the score may not equate to clinically meaningful changes in the patient's status., [Objective] The aim of this work was to establish a condensed modified version of the scale focusing on meaningful disease milestones., [Methods] Sixteen movement disorders experts evaluated each scale item for its capacity to capture disease milestones (0 = no, 1 = moderate, 2 = severe milestone). Items not capturing severe milestones were eliminated. Remaining items were recalibrated in proportion to milestone severity by collapsing across response categories that yielded identical milestone severity grades. Items with low sensitivity to change were eliminated, based on power calculations using longitudinal 12-month follow-up data from 86 patients with possible or probable progressive supranuclear palsy., [Results] The modified scale retained 14 items (yielding 0–2 points each). The items were rated as functionally relevant to disease milestones with comparable severity. The modified scale was sensitive to change over 6 and 12 months and of similar power for clinical trials of disease-modifying therapy as the original scale (achieving 80% power for two-sample t test to detect a 50% slowing with n = 41 and 25% slowing with n = 159 at 12 months)., [Conclusions] The modified Progressive Supranuclear Palsy Rating Scale may serve as a clinimetrically sound scale to monitor disease progression in clinical trials and routine. © 2021 International Parkinson and Movement Disorder Society., This work was supported by the Munich Cluster for Systems Neurology (Synergy), the Volkswagen Stiftung, the Lower Saxony Ministry for Science, the Niedersächsisches Vorab, and the Petermax-Müller Foundation (Etiology and Therapy of Synucleinopathies and Tauopathies). This project was also supported by the German Center for Neurodegenerative Diseases e.V. (DZNE), German PSP Gesellschaft, and the International Parkinson & Movement Disorder Society.

© 2021 International Parkinson and Movement Disorder Society, Background: Expectations of benefit have an important therapeutic impact. How well study participants understand the concept of slowing disease progression and how their expectations of benefit are shaped in related clinical trials is not well known. Objective: We aimed to assess expectancy and treatment arm preference of participants in a disease-modification trial in Parkinson disease (PD). Methods: Participant expectations and treatment preference were assessed before treatment randomization in the SURE-PD3 trial (NCT02642393). Results: We included 297 PD patients (0.71 ± 0.67 years after diagnosis). Pre-randomization, 90% of participants expressed a preference for inosine (active treatment) allocation (n = 266/297), and 53% (n = 158) expected to be "somewhat" or "a lot better" in their symptoms over 2 years of treatment with inosine. Conclusions: Participants of a disease-modification trial in PD had likely unrealistic expectations of benefit (ie, improvement in symptoms over years), which may affect clinical trial interpretation and calls for improved education in future disease-modification trials in PD. © 2021 International Parkinson and Movement Disorder Society.

© 2021 The Authors. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data., Background: The COVID-19 pandemic continues to rage on, and clinical research has been promoted worldwide. We aimed to assess the clinical and methodological characteristics of treatment clinical trials that have been set forth as an early response to the COVID-19 pandemic. Methods: First, we reviewed all registered clinical trials on COVID-19. The World Health Organization International Trials Registry Platform and national trial registries were searched for COVID-19 trials through April 19th, 2020. For each record, independent researchers extracted interventions, participants, and methodological characteristics. Second, on September 14th, 2020 we evaluated the recruitment status and availability of the results of COVID-19 treatment trials previously identified. Results: In April 2020, a total of 580 trials evaluating COVID-19 treatment were registered. Reporting quality was poor (core participant information was missing in 24.1 to 92.7%). Between 54.0 and 93.8% of the trials did not plan to include older people or those with a higher baseline risk. Most studies were randomised (67.9%), single-centre (58.3%), non-industry-funded (81.1%), to be conducted in China (47.6%), with a median duration of 184 days and a median sample size of 100 participants. Core endpoints (mortality, clinical status, and hospitalization length) were planned to be assessed in 5.2 to 13.1% of the trials. Five months later, 66 trials (11.4%) were reported as "Completed", and only 46 (7.9%) had public results available. One hundred forty-four of 580 trials (24.8%) either had the status "Not yet recruiting" or "Suspended", and 18 (3.1%) trials were prematurely stopped ("Terminated" or "Withdrawn") The number of completed trials and trials with results are much lower than anticipated, considering the planned follow-up. Conclusions: Our results raise concerns about the success of the initial global research effort on COVID-19 treatment. The clinical and methodological characteristics of early COVID-19 treatment trials limit their capability to produce clear answers to critical questions in the shortest possible time.

© 2021 International Parkinson and Movement Disorder Society, COVID-19 brought multiple societal challenges that became a catalyst for worsening health in people with Parkinson’s disease (PwPD) and brought disruption in their social activities. It is hypothesized that the COVID-19 confinement also impacted the functional mobility of PwPD. One of the building blocks of functional mobility is the ability to walk. It enables independence and participation in social activities and contributes to global health. Long-term unsupervised assessments are crucial to quantify walking activity from ecologically valid and patient-relevant environments and overcome the limitations of conventional clinical assessments.

Introduction: Sacubitril-valsartan is a recently approved drug. However, there are few data regarding safety issues. We aimed to summarize the available evidence regarding sacubitril-valsartan’s safety and tolerability. Methods: We conducted a systematic review with meta-analysis of randomized controlled trials (RCTs) enrolling patients receiving sacubitril-valsartan for any condition, compared with standard therapy or placebo. Database search was performed in October 2019. Outcomes were adverse events (AEs), serious AEs (SAEs), discontinuation due to AEs, and five AEs of special interest. Data were reported using risk ratio (RR) and 95% confidence interval (95%CI). Results: We included 20 RCTs (22510 participants). When compared with active controls, there were no differences in SAEs (RR=0.93, 95%CI 0.86–1.01) and AEs (RR=1.00, 95%CI 0.97–1.03). However, sacubitril-valsartan resulted in an 8% risk reduction in discontinuation due to AEs (95%CI 0.85–0.99) and an increased risk of hypotension (RR=1.45, 95%CI 1.27–1.67). The risk of angioedema was higher with follow-ups greater than 12 months (RR=2.36, 95%CI 1.29–4.33). There were no further significant differences in the remaining AEs' risk. Conclusions: Sacubitril-valsartan was at least as safe and tolerable as active control, with a similar need of administration cautiousness, except for a higher risk of hypotension. However, one should consider the study’s limitations.

© 2021 European Academy of Neurology, Background: The relationship between Parkinson's disease (PD) and cardiovascular and cerebrovascular disease is not yet well established. Recent data suggest an increased risk of myocardial infarction and stroke in PD patients. Therefore, we designed a study to assess surrogate markers of cardiovascular and cerebrovascular risk in PD. Methods: We conducted a case-control study comparing PD patients recruited from a Movement Disorders Unit with controls randomly invited from a primary healthcare center. All participants underwent a detailed clinical evaluation, including medical history, physical assessment, carotid ultrasound, blood and urine analysis, and 24-h ambulatory blood pressure monitoring. The primary outcome was the carotid intima-media thickness (CIMT). Results: We included 102 participants in each study arm. No significant difference was found in the CIMT among groups (MD: 0.01, 95% CI: -0.02, 0.04). Carotid plaques were more frequent in PD patients (OR: 1.90, 95% CI: 1.02, 3.55), although the lipid profile was more favorable in this group (LDL MD: -18.75; 95% CI: -10.69, -26.81). Nocturnal systolic blood pressure was significantly higher in PD patients (MD: 4.37, 95% CI: 0.27, 8.47) and more than half of the PD patients were non-dippers or reverse dippers (OR: 1.83, 95% CI: 1.04, 3.20). Conclusion: We did not find a difference in CIMT between PD and controls. A higher frequency of carotid plaques and abnormal dipper profile supports the hypothesis that PD patients are not protected from cardiovascular and cerebrovascular disease., M.A. was awarded a scholarship from Fundação para a Ciência e Tecnologia (SFRH/BD/129700/2017). IMM - UID/BIM/50005/2019, project funded by Fundação para a Ciência e a Tecnologia (FCT)/Ministério da Ciência, Tecnologia e Ensino Superior (MCTES) through Fundos do Orçamento de Estado

© The Author(s). 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data., Background: Gait impairments are among the most common and impactful symptoms of Parkinson’s disease (PD). Recent technological advances aim to quantify these impairments using low-cost wearable systems for use in either supervised clinical consultations or long-term unsupervised monitoring of gait in ecological environments. However, very few of these wearable systems have been validated comparatively to a criterion of established validity. Objective: We developed two movement analysis solutions (3D full-body kinematics based on inertial sensors, and a smartphone application) in which validity was assessed versus the optoelectronic criterion in a population of PD patients. Methods: Nineteen subjects with PD (7 female) participated in the study (age: 62 ± 12.27 years; disease duration: 6.39 ± 3.70 years; HY: 2 ± 0.23). Each participant underwent a gait analysis whilst barefoot, at a self-selected speed, for a distance of 3 times 10 m in a straight line, assessed simultaneously with all three systems. Results: Our results show excellent agreement between either solution and the optoelectronic criterion. Both systems differentiate between PD patients and healthy controls, and between PD patients in ON or OFF medication states (normal difference distributions pooled from published research in PD patients in ON and OFF states that included an age-matched healthy control group). Fair to high waveform similarity and mean absolute errors below the mean relative orientation accuracy of the equipment were found when comparing the angular kinematics between the full-body inertial sensor-based system and the optoelectronic criterion. Conclusions: We conclude that the presented solutions produce accurate results and can capture clinically relevant parameters using commodity wearable sensors or a simple smartphone. This validation will hopefully enable the adoption of these systems for supervised and unsupervised gait analysis in clinical practice and clinical trials.

Contains fulltext : 234434.pdf (Publisher’s version ) (Open Access) OBJECTIVES: To determine clinical characteristics and treatment complications of patients with late-stage Parkinsonism living in nursing homes compared with those living at home. DESIGN: Cross-sectional analysis. SETTING AND PARTICIPANTS: This study is an analysis of 692 patients with late stage Parkinsonism recruited to an in-depth international study, Care of Late-Stage Parkinsonism (CLaSP). MEASURES: Sociodemographic characteristics were compared between patients who were living in a nursing home (n = 194) and those living at home (n = 498). Clinical assessments included the Unified Parkinson's Disease Rating Scale (UPDRS), the nonmotor symptom scale, the neuropsychiatric inventory, and a structured interview of patients and carers. Predictors of nursing home status were determined in a multivariate analysis. RESULTS: Nursing home placement was strongly associated with more severe cognitive impairment, worse UPDRS motor scores and disability, and with being unmarried and older. Although nursing home residents had significantly higher axial scores, falls were less common. Despite similar levodopa equivalence doses, they had less dyskinesia. Nonmotor symptom burden, particularly delusion, hallucination, and depression scores were higher in nursing home residents, and they were more frequently on psychotropic medication. They had lower rates of dopamine agonist use and lower rates of impulse control disorders. In multivariate analysis, being unmarried, presence of cognitive impairment, worse disease severity as assessed on the UPDRS parts II and III, severity of delusions, and lower rate of dyskinesia were associated with nursing home placement. CONCLUSIONS AND IMPLICATIONS: These clinical characteristics suggest that in patients with Parkinsonsim who are nursing home residents, presence of cognitive impairment and delusions particularly add to the higher overall symptom burden, and more often require specific treatments, including clozapine. Despite similar levodopa equivalent daily dose, motor severity is higher, and dyskinesias, indicative of a response to levodopa, are less common. Falls, however, also occur less commonly, and dopamine agonists are less frequently used, with lower rates of impulse control disorder.

Background: A greater understanding of the everyday experiences of people with Parkinson’s disease (PD) and their carers may help improve clinical practice. Objective: The Parkinson’s Real-world Impact assesSMent (PRISM) study evaluated medication use, health-related quality of life (HRQoL) and the use of healthcare resources by people with PD and their carers. Methods: PRISM is an observational cross-sectional study, in which people with PD and their carers completed an online survey using structured questionnaires, including the Parkinson’s Disease Quality of Life Questionnaire (PDQ-39), Non-Motor Symptoms Questionnaire (NMSQuest) and Zarit Burden Interview (ZBI). Results: Data were collected from 861 people with PD (mean age, 65.0 years; mean disease duration, 7.7 years) and 256 carers from six European countries. People with PD reported a large number of different co-morbidities, non-motor symptoms (mean NMSQuest score, 12.8), and impaired HRQoL (median PDQ-39 summary score, 29.1). Forty-five percent of people with PD reported at least one impulse control behaviour. Treatment patterns varied considerably between different European countries. Levodopa was taken in the last 12 months by 85.9% of participants, and as monotherapy by 21.8%. Carers, who were mostly female (64.8%) and the partner/spouse of the person with PD (82.1%), reported mild to moderate burden (mean ZBI total score, 26.6). Conclusions: The PRISM study sheds light on the lives of people with PD and those who care for them, re-emphasising the many challenges they face in everyday life. The study also provides insights into the current treatment of PD in Europe.

Background This is an update of a Cochrane Review first published in 2005. Cervical dystonia is the most common form of focal dystonia, and is a highly disabling movement disorder, characterised by involuntary, usually painful, head posturing. Currently, botulinum toxin type A (BtA) is considered the first line therapy for this condition. Objectives To compare the efficacy, safety, and tolerability of BtA versus placebo, in people with cervical dystonia. Search methods We searched Cochrane Movement Disorders' Trials Register, CENTRAL, MEDLINE, Embase, reference lists of articles, and conference proceedings in July 2020. All elements of the search, with no language restrictions, were last run in July 2020. Selection criteria Double-blind, parallel, randomised, placebo-controlled trials (RCTs) of BtA versus placebo in adults with cervical dystonia. Data collection and analysis Two review authors independently assessed records, selected included studies, extracted data using a paper pro forma, and evaluated the risk of bias. We resolved disagreements by consensus or by consulting a third review author. We performed meta-analyses using a random-effects model, for the comparison of BtA versus placebo, to estimate pooled effects and corresponding 95% confidence intervals (95% CI). We performed preplanned subgroup analyses according to BtA dose used, the BtA formulation used, and the use (or not) of guidance for BtA injections. The primary efficacy outcome was improvement in cervical dystonia-specific impairment. The primary safety outcome was the proportion of participants with any adverse event. Main results We included nine RCTs, with moderate, overall risk of bias, that included 1144 participants with cervical dystonia. Seven studies excluded participants with poorer responses to BtA treatment, therefore, including an enriched population with a higher probability of benefiting from this therapy. Only one trial was independently funded. All RCTs evaluated the effect of a single BtA treatment session, using doses from 150 U to 500 U of onabotulinumtoxinA (Botox), 120 U to 240 U of incobotulinumtoxinA (Xeomin), and 250 U to 1000 U of abobotulinumtoxinA (Dysport). BtA resulted in a moderate to large improvement from the participant's baseline clinical status, assessed by the investigators, with a mean reduction of 8.09 points in the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS total score) at week four after injection (95% CI 6.22 to 9.96; I² = 0%) compared to placebo. This corresponded, on average, to a 18.4% improvement from baseline. The mean difference (MD) in TWSTRS pain subscore at week four was 2.11 (95% CI 1.38 to 2.83; I² = 0%) compared to placebo. Overall, both participants and clinicians reported an improvement of subjective clinical status. It was unclear if dropouts due to adverse events differed (risk ratio (RR) 2.51; 95% CI 0.42 to 14.94; I² = 0%) However, BtA treatment increased the risk of experiencing an adverse event (R) 1.23; 95% CI 1.05 to 1.43; I² = 28%). Neck weakness (14%; RR 3.40; 95% CI 1.19 to 9.71; I² = 15%), dysphagia (11%; RR 3.19; 95% CI 1.79 to 5.70; I² = 0%), and diffuse weakness or tiredness (8%; RR 1.80; 95% CI 1.10 to 2.95; I² = 0%) were the most common treatment-related adverse events. Treatment with BtA resulted in a decreased risk of dropouts. We have moderate certainty in the evidence across all of the aforementioned outcomes, with the exception of subjective assessment and tolerability, in which we have high confidence in the evidence. We found no evidence supporting the existence of a clear dose-response relationship between BtA and improvement in cervical dystonia-specific impairment, a destinction between BtA formulations, or a variation with use of EMG-guided injection for efficacy outcomes. Due to clinical heterogeneity, we did not pool health-related quality of life data, duration of clinical effect, or the development of secondary non-responsiveness. Authors' conclusions We are moderately certain in the evidence that a single BtA treatment session resulted in a clinically relevant reduction of cervical dystonia-specific impairment, and pain, and highly certain that it is well tolerated, compared with placebo. There is moderate-certainty evidence that people treated with BtA are at an increased risk of developing adverse events, most notably, dysphagia, neckweakness and diffuse weakness or tiredness. There are no data from RCTs evaluating the effectiveness and safety of repeated BtA injection cycles. There is no evidence from RCTs to allow us to draw definitive conclusions on the optimal treatment intervals and doses, the usefulness of guidance techniques for injection, the impact on quality of life, or the duration of treatment effect.

Previous studies stated that high oxygen supply in patients with myocardial infarction (MI) was not associated with improved outcomes. However, the particularities of ST-elevation myocardial infarction (STEMI) and the results of a recent trial raised the question if this subgroup of patients benefits from high oxygen supply. This study aims to evaluate the clinical effect of high oxygen supply in patients with STEMI using a systematic review of the available literature. All randomized controlled trials (RCTs) evaluating the systematic use of high oxygen (6 L/min or higher) versus room air or lower oxygen supply in STEMI patients were included. Systematic review with meta-analysis of trials retrieved in July 2020. Six databases were searched. The confidence in the pooled estimates was ascertained through the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Risk of bias was evaluated using the Cochrane risk of bias tool. There were five eligible RCTs (7703 patients). High oxygen supply was associated with a significant risk reduction of short-term mortality [risk ratio (RR) 0.83; 95% confidence interval (CI), 0.70-0.98; I2 = 0%]. Mortality (longest follow-up) (RR 0.83; 95% CI, 0.71-0.97; I2 = 0%) and heart failure (RR 0.84; 95% CI, 0.60-1.18; I2 = 0%) did not present a risk reduction. Recurrent MI presented a contradictory result, favouring the lower oxygen protocol (RR 1.47; 95% CI, 0.84-2.56; I2 = 0%). The GRADE analysis was very low. High oxygen supply may be associated with a decrease in short-term mortality in STEMI patients, but the pooled data are not robust enough to allow definitive conclusions.

We read with great interest the article by Waldvogel et al.1 The researchers report the cases of 9 patients who underwent deep brain stimulation (DBS) who found their swimming ability deteriorated after DBS.

© 2020 – IOS Press and the authors. All rights reserved, The purpose of this letter is not just to bring to the discussion the possibility that happiness and well-being are two different outcomes but also alert for other forgotten global health outcomes that deserve further exploration, such as fitness, frailty, autonomy, general mobility, social functioning, ability to remain in own home, hospital admissions, falls resulting in fracture, among others.

Background: Parkinson’s disease (PD) is a neurological condition characterized by the development of daily disabling symptoms. Although the architecture and design of a PD patient’s environment can hinder or facilitate full participation in daily activities, their putative role in the management of these patients has received little attention to date. Objective: We conducted a systematic review to evaluate the evidence of architectural and design features in the management of people with PD. Methods: An electronic database search of observational and experimental studies was conducted in MEDLINE and Embase from inception to May 2020, with two independent reviewers identifying the studies. Falls, fear of falling, postural instability, gait impairment/disability, and functional mobility were our outcomes of interest. Results: Thirty-six studies were included, among which nineteen were observational and seventeen were experimental studies (overall participants = 2,965). Pavement characteristics, notably unstable surfaces and level differences, were found to be a major cause of falling. Ground-based obstacles and confined/narrowed spaces were found to disturb gait, increase postural instability, and decrease functional mobility. Housing type did not appear to increase risk of falling, nor to significantly explain concerns about falling. Conclusion: Findings suggest a need to adjust architectural features of the surrounding space to ensure appropriate care and provide a safe environment to PD patients. More evidence about the impact of such modifications on PD outcomes is needed.

© 2020 Informa UK Limited, trading as Taylor & Francis Group, Introduction: To date, no valid outcome measure has been developed in European Portuguese (EP) to evaluate the Parkinsons' Disease (PD) patients' (PwP) reports regarding their swallowing disturbances. Objectives: The aim of this study was to translate and cross-culturally adapt the Swallowing Disturbance Questionnaire (SDQ) and the Sialorrhea Clinical Scale for PD (SCS-PD) into EP and to determine its clinimetric properties in PwP. Materials and methods: The original English SDQ and SCS-PD versions were cross-culturally adapted following recommendations established in international guidelines. The validation process involved 75 PwP and 65 healthy sex- and age-matched participants. Results: The EP versions of the SDQ and SCS-PD are equivalent to the original versions (content, depth, and scoring). Statistical analyses for the SDQ tool revealed good feasibility (missing data

Background Botulinum neurotoxin type A (BoNT-A) is an effective pharmacological treatment for the management of cervical dystonia (CD) that requires repeated administration at variable intervals. We explored patient perceptions of the impact of CD and the waning of BoNT-A therapeutic effects. Methods An internet-based survey was conducted through Carenity, a global online patient community, from May to September 2019. Eligible respondents were adults with CD who had ≥ 2 previous BoNT-A injections. Results 209 respondents (81% females; mean age of 49.7 years) met the screening criteria. The mean BoNT-A injection frequency was 3.9 injections/year. The mean reported onset of BoNT-A therapeutic effect was 11.7 days and the time to peak effect was 4.5 weeks. Symptom re-emergence between injections was common (88%); the time from injection to symptom re-emergence was 73.6 days (~ 10.5 weeks). Treatment was not reported to completely abolish symptoms, even at peak effect. However, symptom severity was rated (0 = no symptoms; 10 = very strong symptoms) as lowest at the peak of treatment effects (mean scores ~ 3/10), increasing as the effects of treatment start waning (~ 5.5/10) and was strongest one day before the next session (~ 7–8/10). The impact of CD on quality of life followed the same ‘rollercoaster’ pattern. Conclusions This survey highlights the burden of CD symptoms, even in patients undergoing regular treatment. Symptom re-emergence is common and has significant impact on daily activities and quality of life. Greater awareness of the therapeutic profile of BoNT-A treatment should lead to better informed therapeutic discussions and planning.