687 results on '"Marras C"'
Search Results
302. Disparities in Deep Brain Stimulation Use for Parkinson's Disease in Ontario, Canada.
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Crispo JAG, Lam M, Le B, Richard L, Shariff SZ, Ansell DR, Squarzolo M, Marras C, Willis AW, and Seitz D
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- Aged, Case-Control Studies, Cohort Studies, Humans, Ontario epidemiology, Deep Brain Stimulation, Parkinson Disease epidemiology, Parkinson Disease therapy
- Abstract
Objective: To examine whether sociodemographic characteristics and health care utilization are associated with receiving deep brain stimulation (DBS) surgery for Parkinson's disease (PD) in Ontario, Canada., Methods: Using health administrative data, we identified a cohort of individuals aged 40 years or older diagnosed with incident PD between 1995 and 2009. A case-control study was used to examine whether select factors were associated with DBS for PD. Patients were classified as cases if they underwent DBS surgery at any point 1-year after cohort entry until December 31, 2016. Conditional logistic regression modeling was used to estimate the adjusted odds of DBS surgery for sociodemographic and health care utilization indicators., Results: A total of 46,237 individuals with PD were identified, with 543 (1.2%) receiving DBS surgery. Individuals residing in northern Ontario were more likely than southern patients to receive DBS surgery [adjusted odds ratio (AOR) = 2.23, 95% confidence interval (CI) = 1.15-4.34]; however, regional variations were not observed after accounting for medication use among older adults (AOR = 1.04, 95% CI = 0.26-4.21). Patients living in neighborhoods with the highest concentration of visible minorities were less likely to receive DBS surgery compared to patients living in predominantly white neighborhoods (AOR = 0.27, 95% CI = 0.16-0.46). Regular neurologist care and use of multiple PD medications were positively associated with DBS surgery., Conclusions: Variations in use of DBS may reflect differences in access to care, specialist referral pathways, health-seeking behavior, or need for DBS. Future studies are needed to understand drivers of potential disparities in DBS use.
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- 2020
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303. Reply to Comment on: The Most Bothersome Aspects of off Periods Reported by Individuals with Parkinson's Disease.
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Chahine LM, Edison B, Mantri S, Kopil C, and Marras C
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- 2020
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304. Identifying drugs with disease-modifying potential in Parkinson's disease using artificial intelligence and pharmacoepidemiology.
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Maclagan LC, Visanji NP, Cheng Y, Tadrous M, Lacoste AMB, Kalia LV, Bronskill SE, and Marras C
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- Aged, Aged, 80 and over, Case-Control Studies, Dexamethasone therapeutic use, Female, Humans, Insurance Claim Review, Male, Ontario epidemiology, Parkinson Disease drug therapy, Pentoxifylline therapeutic use, Pharmacoepidemiology, Theophylline therapeutic use, Antiparkinson Agents therapeutic use, Artificial Intelligence, Parkinson Disease epidemiology
- Abstract
Purpose: The aim of the study was to assess the feasibility of an approach combining computational methods and pharmacoepidemiology to identify potentially disease-modifying drugs in Parkinson's disease (PD)., Methods: We used a two-step approach; (a) computational method using artificial intelligence to rank 620 drugs in the Ontario Drug Benefit formulary based on their predicted ability to inhibit alpha-synucleinaggregation, a pathogenic hallmark of PD; and (b) case-control study using administrative databases in Ontario, Canada. Persons aged 70-110 years with incident PD from April 2002-March 2013. Controls were randomly selected from persons with no previous diagnosis of PD., Results: A total of 15 of the top 50 drugs were deemed feasible for pharmacoepidemiologic analysis, of which seven were significantly associated with incident PD after adjustment, with five of these seven associated with a decreased odds of PD. Methylxanthine drugs pentoxifylline (OR, 0.72; 95% CI, 0.59-0.89) and theophylline (OR, 0.77; 95% CI, 0.66-0.91), and the corticosteroid dexamethasone (OR, 0.72; 95% CI, 0.61-0.85) were associated with decreased odds of PD., Conclusions: Our findings demonstrate the feasibility of this approach to focus the search for disease-modifying drugs. Corticosteroids and methylxanthines should be further investigated as potential disease-modifyingdrugs in PD., (© 2020 John Wiley & Sons Ltd.)
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- 2020
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305. Progressive Supranuclear Palsy and Statin Use.
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Bayram E, Marras C, Standaert DG, Kluger BM, Bordelon YM, Shprecher DR, and Litvan I
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- Case-Control Studies, Humans, Prospective Studies, Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use, Supranuclear Palsy, Progressive drug therapy, Supranuclear Palsy, Progressive epidemiology, Tauopathies
- Abstract
Introduction: Statins were proposed to be neuroprotective; however, the effects are unknown in progressive supranuclear palsy (PSP), a pure tauopathy., Methods: Data of 284 PSP cases and 284 age-matched, sex-matched, and race-matched controls were obtained from the environmental and genetic PSP (ENGENE-PSP) study. Cases were evaluated with the PSP Rating Scale, Unified Parkinson's Disease Rating Scale, Mattis Dementia Rating Scale, and Neuropsychiatric Inventory. Statin associations with PSP risk, onset age, and disease features were analyzed., Results: Univariate models showed lower PSP risk for type 1 statin users (simvastatin, lovastatin, pravastatin). After adjusting for confounding variables, statin use and lower PSP risk association remained only at a trend level. For PSP cases, type 1 statins were associated with 1-year older onset age; type 2 statins (atorvastatin, rosuvastatin) were associated with the lower PSP Rating Scale and Unified Parkinson's Disease Rating Scale., Conclusion: Statins may have inverse associations with PSP risk and motor impairment. Randomized prospective studies are required to confirm this effect. © 2020 International Parkinson and Movement Disorder Society., (© 2020 International Parkinson and Movement Disorder Society.)
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- 2020
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306. Beta Agonists and Progression of Parkinson's Disease in Older Adults: A Retrospective Cohort Study.
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Marras C, Pequeno P, Austin PC, Gershon AS, Iqbal J, Rochon PA, and Lang AE
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- Aged, Cohort Studies, Disease Progression, Humans, Retrospective Studies, Risk Factors, Parkinson Disease drug therapy
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- 2020
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307. Age-Related Parkinsonian Signs in Microdeletion 22q11.2.
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Boot E, Mentzel TQ, Palmer LD, van Harten PN, Marras C, Lang AE, and Bassett AS
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- Adult, Humans, Hypokinesia, Tremor, DiGeorge Syndrome complications, DiGeorge Syndrome genetics, Parkinson Disease complications, Parkinson Disease genetics, Parkinsonian Disorders genetics
- Abstract
Background: The recurrent hemizygous 22q11.2 deletion associated with 22q11.2 deletion syndrome has been identified as a genetic risk factor for early-onset PD. However, little is known about early motor signs in this condition., Objectives: We examined the presence, severity and possible factors associated with parkinsonism in adults with 22q11.2 deletion syndrome and without PD., Methods: We compared motor signs between 82 adults with 22q11.2 deletion syndrome and 25 healthy controls, using the MDS-UPDRS part III, and three-dimensional motion-tracker technology to quantify components of bradykinesia., Results: Median MDS-UPDRS part III total and bradykinesia subscores were significantly higher in 22q11.2 deletion syndrome (median age: 26 years; range, 17-65) than in controls (P = 0.000; P = 0.000, respectively). Age was a significant contributor to bradykinesia subscore (B = 0.06; P = 0.01) and to the electronic bradykinesia component, velocity (B = -0.02; P = 0.000); psychotic illness did not significantly impact these analyses. In 22q11.2 deletion syndrome, MDS-UPDRS-defined bradykinesia was present in 18.3%, rigidity in 14.6%, and rest tremor in 12.2%., Conclusions: Parkinsonian motor signs appear to be common and age related in 22q11.2 deletion syndrome. Longitudinal studies are needed to investigate possible symptom progression to PD. © 2020 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society., (© 2020 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.)
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- 2020
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308. Huntington's Disease and Hypertension: Sorting Out Mixed Messages.
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Marras C, Mestre T, and McDermott MP
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- Humans, Huntington Disease genetics, Hypertension
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- 2020
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309. Human Peripheral Blood Neutrophil Isolation for Interrogating the Parkinson's Associated LRRK2 Kinase Pathway by Assessing Rab10 Phosphorylation.
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Fan Y, Tonelli F, Padmanabhan S, Baptista MAS, Riley L, Smith D, Marras C, Howden A, Alessi DR, and Sammler E
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- Humans, Mutation, Phosphorylation, Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 genetics, Neutrophils metabolism, Parkinson Disease genetics, rab GTP-Binding Proteins genetics
- Abstract
The leucine rich repeat kinase 2 (LRRK2) is the most frequently mutated gene in hereditary Parkinson' disease (PD) and all pathogenic LRRK2 mutations result in hyperactivation of its kinase function. Here, we describe an easy and robust assay to quantify LRRK2 kinase pathway activity in human peripheral blood neutrophils by measuring LRRK2-controlled phosphorylation of one of its physiological substrates, Rab10 at threonine 73. The immunoblotting analysis described requires a fully selective and phosphospecific antibody that recognizes the Rab10 Thr73 epitope phosphorylated by LRRK2, such as the MJFF-pRab10 rabbit monoclonal antibody. It uses human peripheral blood neutrophils, because peripheral blood is easily accessible and neutrophils are an abundant and homogenous constituent. Importantly, neutrophils express relatively high levels of both LRRK2 and Rab10. A potential drawback of neutrophils is their high intrinsic serine protease activity, which necessitates the use of very potent protease inhibitors such as the organophosphorus neurotoxin diisopropylfluorophosphate (DIFP) as part of the lysis buffer. Nevertheless, neutrophils are a valuable resource for research into LRRK2 kinase pathway activity in vivo and should be considered for inclusion into PD biorepository collections.
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- 2020
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310. The Most Bothersome Aspects of Off Periods Reported by Individuals with Parkinson's Disease.
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Chahine LM, Edison B, Daeschler M, Mantri S, Kahl S, Rapoport R, Goyle A, Precht C, Kopil C, and Marras C
- Abstract
Introduction: The off periods in Parkinson's disease have a significantly negative impact on quality of life. What the most bothersome aspects of off periods are from the patient's perspective are not well studied, nor is the degree to which screening tools for wearing off such as the Wearing Off Questionnaires (WOQs) capture what bothers patients most., Methods: A questionnaire was deployed to eligible participants of Fox Insight, an online study of individuals with self-reported Parkinson's disease. Inclusion criteria were the use of ≥1 dopaminergic medications and an affirmative response to a question on experiencing off periods. Participants provided free-text responses regarding the top 3 most bothersome symptoms they experience when off . A determination was made regarding whether each response would have been captured by the 32-item, 19-item, and 9-item WOQs., Results: The final sample had 2106 participants, a mean age of 66.6 years, 52.3% were men, and had a disease duration of 4.9 years. The WOQ-32 items covered all of the most bothersome symptoms for 53.2% of respondents. Among bothersome aspects of off not captured by the WOQs, 597 (66.2%) were specific symptoms, with freezing of gait, apathy, and memory problems being the most common. The functional consequences of off periods were most bothersome to 232 (25.7%), with walking problems being the most common. The emotional response to off periods was the most bothersome aspect to 169 respondents (18.7%)., Discussion: This study emphasizes the value of narrative data in understanding patient experiences, and what bothers patients most about off periods. The WOQs, although of established utility in the screening for wearing off , may not capture those symptoms most bothersome to patients., (© 2020 International Parkinson and Movement Disorder Society.)
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- 2020
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311. Cervical dystonia incidence and diagnostic delay in a multiethnic population.
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LaHue SC, Albers K, Goldman S, Lo RY, Gu Z, Leimpeter A, Fross R, Comyns K, Marras C, de Kleijn A, Smit R, Katz M, Ozelius LJ, Bressman S, Saunders-Pullman R, Comella C, Klingman J, Nelson LM, Van Den Eeden SK, and Tanner CM
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- Female, Humans, Incidence, Logistic Models, Male, Odds Ratio, Delayed Diagnosis, Torticollis diagnosis, Torticollis epidemiology
- Abstract
Background: Current cervical dystonia (CD) incidence estimates are based on small numbers in relatively ethnically homogenous populations. The frequency and consequences of delayed CD diagnosis is poorly characterized., Objectives: To determine CD incidence and characterize CD diagnostic delay within a large, multiethnic integrated health maintenance organization., Methods: We identified incident CD cases using electronic medical records and multistage screening of more than 3 million Kaiser Permanente Northern California members from January 1, 2003, to December 31, 2007. A final diagnosis was made by movement disorders specialist consensus. Diagnostic delay was measured by questionnaire and health utilization data. Incidence rates were estimated assuming a Poisson distribution of cases and directly standardized to the 2000 U.S. census. Multivariate logistic regression models were employed to assess diagnoses and behaviors preceding CD compared with matched controls, adjusting for age, sex, and membership duration., Results: CD incidence was 1.18/100,000 person-years (95% confidence interval [CI], 0.35-2.0; women, 1.81; men, 0.52) based on 200 cases over 15.4 million person-years. Incidence increased with age. Half of the CD patients interviewed reported diagnostic delay. Diagnoses more common in CD patients before the index date included essential tremor (odds ratio [OR] 68.1; 95% CI, 28.2-164.5), cervical disc disease (OR 3.83; 95% CI, 2.8-5.2), neck sprain/strain (OR 2.77; 95% CI, 1.99-3.62), anxiety (OR 2.24; 95% CI, 1.63-3.11) and depression (OR 1.94; 95% CI, 1.4-2.68)., Conclusions: CD incidence is greater in women and increases with age. Diagnostic delay is common and associated with adverse effects. © 2019 International Parkinson and Movement Disorder Society., (© 2019 International Parkinson and Movement Disorder Society.)
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- 2020
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312. Survival in Restless Legs Syndrome: An 11-Year Surveillance, Community-Based Population Study.
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Cubo E, Collazo Riobo C, Gallego-Nieto C, Elizari-Roncal M, Barroso-Pérez T, Calvo S, Echavarria A, and Marras C
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- Adult, Aged, Aged, 80 and over, Cardiovascular Diseases epidemiology, Cardiovascular Diseases etiology, Cardiovascular Diseases mortality, Female, Humans, Longitudinal Studies, Male, Middle Aged, Retrospective Studies, Risk Factors, Time Factors, Restless Legs Syndrome complications, Restless Legs Syndrome mortality
- Abstract
Background: A growing body of evidence relates restless legs syndrome (RLS) to an increased risk of mortality attributable to both cerebrovascular and cardiovascular events. The aim was to investigate survival in patients with RLS., Methods: This was an observational, retrospective longitudinal study of a cohort of patients followed up for 11 years. RLS was diagnosed by a physician using the International RLS Study Group criteria. Mortality was analyzed using age-standardized mortality ratios (SMR: observed/expected deaths) and Cox regression analysis., Results: Vital status was studied in a cohort of 232 patients: 181 women (78%), 96 with RLS (41.4%) with a mean age at baseline of 49.8 ± 15.0 years and a mean RLS duration of 14.1 ± 1.9 years, and 136 non-RLS (58.6%) with a mean age of 51.3 ± 14.9 years. This RLS cohort was followed up for a period of 10.4 ± 2.0 years. As of September 2019, 17 (7.3%) patients died (6 with RLS, 6.3%), and the most frequent cause was oncological (66.7%). A total of 944 person-years of observations were available for survival analysis. RLS was not associated with increased mortality in adjusted Cox regression analysis (HR = 1.12, 95% CI: 0.40-3.15), and survival was similar to that expected for the general population (SMR = 0.61, 95% CI: 0.27-1.36)., Conclusions: RLS seems not to be associated with increased mortality compared to the general population. Still, studies with prospective data collection with large samples are needed to study the long-term mortality risk factors in RLS cohorts., (© 2020 S. Karger AG, Basel.)
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- 2020
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313. Differences in clinical manifestations and increased severity of systemic lupus erythematosus between two groups of Hispanics: European Caucasians versus Latin American mestizos (data from the RELESSER registry).
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Hernández Cruz B, Alonso F, Calvo Alén J, Pego-Reigosa JM, López-Longo FJ, Galindo-Izquierdo M, Olivé A, Tomero E, Horcada L, Uriarte E, Erausquin C, Sánchez-Atrio A, Montilla C, Santos Soler G, Fernández-Nebro A, Blanco R, Rodríguez-Gómez M, Vela P, Freire M, Díez-Álvarez E, Boteanu AL, Narváez J, Martínez Taboada V, Ruiz-Lucea E, Andreu JL, Fernández-Berrizbeitia O, Hernández-Beriain JÁ, Gantes M, Pérez-Venegas JJ, Ibáñez-Barceló M, Pecondón-Español Á, Marras C, Bonilla G, Castellví I, Moreno M, Raya E, Quevedo Vila VE, Vázquez T, Ruán JI, Muñoz S, and Rúa-Figueroa Í
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- Female, Humans, Latin America ethnology, Lupus Erythematosus, Systemic physiopathology, Male, Registries, Retrospective Studies, Severity of Illness Index, Spain epidemiology, White People statistics & numerical data, Disease Progression, Lupus Erythematosus, Systemic ethnology
- Abstract
Background: Systemic lupus erythematosus (SLE) is regarded as a prototype autoimmune disease because it can serve as a means for studying differences between ethnic minorities and sex. Traditionally, all Hispanics have been bracketed within the same ethnic group, but there are differences between Hispanics from Spain and those from Latin America, not to mention other Spanish-speaking populations., Objectives: This study aimed to determine the demographic and clinical characteristics, severity, activity, damage, mortality and co-morbidity of SLE in Hispanics belonging to the two ethnic groups resident in Spain, and to identify any differences., Methods: This was an observational, multi-centre, retrospective study. The demographic and clinical variables of patients with SLE from 45 rheumatology units were collected. The study was conducted in accordance with Good Clinical Practice guidelines. Hispanic patients from the registry were divided into two groups: Spaniards or European Caucasians (EC) and Latin American mestizos (LAM). Comparative univariate and multivariate statistical analyses were carried out., Results: A total of 3490 SLE patients were included, 90% of whom were female; 3305 (92%) EC and 185 (5%) LAM. LAM patients experienced their first lupus symptoms four years earlier than EC patients and were diagnosed and included in the registry younger, and their SLE was of a shorter duration. The time in months from the first SLE symptoms to diagnosis was longer in EC patients, as were the follow-up periods. LAM patients exhibited higher prevalence rates of myositis, haemolytic anaemia and nephritis, but there were no differences in histological type or serositis. Anti-Sm, anti-Ro and anti-RNP antibodies were more frequently found in LAM patients. LAM patients also had higher levels of disease activity, severity and hospital admissions. However, there were no differences in damage index, mortality or co-morbidity index. In the multivariate analysis, after adjusting for confounders, in several models the odds ratio (95% confidence interval) for a Katz severity index >3 in LAM patients was 1.45 (1.038-2.026; p = 0.02). This difference did not extend to activity levels (i.e. SLEDAI >3; 0.98 (0.30-1.66))., Conclusion: SLE in Hispanic EC patients showed clinical differences compared to Hispanic LAM patients. The latter more frequently suffered nephritis and higher severity indices. This study shows that where lupus is concerned, not all Hispanics are equal.
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- 2020
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314. Innovative Recruitment Strategies to Increase Diversity of Participation in Parkinson's Disease Research: The Fox Insight Cohort Experience.
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Dobkin RD, Amondikar N, Kopil C, Caspell-Garcia C, Brown E, Chahine LM, Marras C, Dahodwala N, Mantri S, Standaert DG, Dean M, Shoulson I, Marek K, Katz A, Korell M, Riley L, and Tanner CM
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- Adult, Aged, Aged, 80 and over, Female, Humans, Longitudinal Studies, Male, Middle Aged, Patient Reported Outcome Measures, Young Adult, Biomedical Research economics, Biomedical Research ethics, Biomedical Research standards, Cultural Diversity, Internet economics, Marketing of Health Services economics, Marketing of Health Services standards, Minority Groups, Parkinson Disease, Patient Selection ethics, Social Media economics
- Abstract
Background: Clinical research in Parkinson's disease (PD) faces practical and ethical challenges due to two interrelated problems: participant under-recruitment and lack of diversity. Fox Insight (FI) is a web-based longitudinal study collecting patient-reported outcomes and genetic data worldwide to inform therapeutic studies. FI's online platform provides an opportunity to evaluate online strategies for recruiting large, diverse research cohorts., Objective: This project aimed to determine 1) whether FI's digital marketing was associated with increased enrollment overall and from under-represented patient groups, compared to traditional recruitment methods; 2) the clinical and demographic characteristics of samples recruited online, and 3) the cost of this online recruitment., Method: FI recruitment during a 6-week baseline period without digital promotion was compared to recruitment during several periods of digital outreach. Separate online recruiting intervals included general online study promotion and unique Facebook and Google ad campaigns targeting under-represented subgroups: early PD, late/advanced PD, and residents of underrepresented/rural geographic areas., Results: Early PD, late PD, and geotargeting campaigns enrolled more individuals in their respective cohorts compared to baseline. All online campaigns also yielded greater total FI enrollment, attracting more participants who were non-White, Hispanic, older, female, and had lower educational attainment and income, and more medical comorbidities. Cost per new participant ranged from $21 (Facebook) to $108 (Google)., Conclusion: Digital marketing may allow researchers to increase, accelerate, and diversify recruitment for PD clinical studies, by tailoring digital ads to target PD cohort characteristics.
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- 2020
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315. Understanding the links between cardiovascular disease and Parkinson's disease.
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Potashkin J, Huang X, Becker C, Chen H, Foltynie T, and Marras C
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- Cardiovascular Diseases diagnosis, Cardiovascular Diseases therapy, Diabetes Mellitus, Type 2 complications, Diabetes Mellitus, Type 2 diagnosis, Diabetes Mellitus, Type 2 therapy, Disease Progression, Humans, Parkinson Disease diagnosis, Risk Factors, Cardiovascular Diseases epidemiology, Comorbidity, Parkinson Disease epidemiology, Parkinson Disease therapy
- Abstract
Studies investigating the associations between genetic or environmental factors and Parkinson's disease (PD) have uncovered a number of factors shared with cardiovascular disease, either as risk factors or manifestations of cardiovascular disease itself. Older age, male sex, and possibly type 2 diabetes are examples. On the other hand, coffee consumption and physical activity are each associated with a lower risk of both PD and cardiovascular disease. This observation raises questions about the underlying pathophysiological links between cardiovascular disease and PD. There is evidence for common mechanisms in the areas of glucose metabolism, cellular stress, lipid metabolism, and inflammation. On the other hand, smoking and total/low-density lipoprotein cholesterol appear to have opposite associations with cardiovascular disease and PD. Thus, it is uncertain whether the treatment of cardiovascular risk factors will impact on the onset or progression of PD. The available data suggest that a nuanced approach is necessary to manage risk factors such as cholesterol levels once the associations are better understood. Ultimately, the choice of therapy may be tailored to a patient's comorbidity profile. This review presents the epidemiological evidence for both concordant and discordant associations between cardiovascular disease and PD, discusses the cellular and metabolic processes that may underlie these links, and explores the implications this has for patient care and future research. © 2019 International Parkinson and Movement Disorder Society., (© 2019 International Parkinson and Movement Disorder Society.)
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- 2020
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316. Experience and Impact of OFF Periods in Parkinson's Disease: A Survey of Physicians, Patients, and Carepartners.
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Rastgardani T, Armstrong MJ, Gagliardi AR, Grabovsky A, and Marras C
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- Adult, Aged, Anxiety etiology, Anxiety physiopathology, Caregivers, Cognitive Dysfunction etiology, Dyskinesias etiology, Family, Female, Gait Disorders, Neurologic etiology, Humans, Male, Middle Aged, Neurologists, Pain etiology, Parkinson Disease complications, Patients, Qualitative Research, Cognitive Dysfunction physiopathology, Disease Progression, Dyskinesias physiopathology, Gait Disorders, Neurologic physiopathology, Pain physiopathology, Parkinson Disease physiopathology, Sweating physiology
- Abstract
Background: OFF periods impair quality of life in Parkinson's disease but the nature and degree of this impact is largely unquantified. Optimal treatment relies on assessing the experience and impact of these periods on patients and their carepartners., Objectives: To understand the experience and impact of OFF periods on their lives., Methods: Informed by qualitative interviews we designed questionnaires and surveyed neurologists, people with Parkinson's disease and carepartners., Results: 50 general neurologists, 50 movement disorder neurologists, 442 patients (median disease duration 5 years) and 97 carepartners were included. The most common OFF symptoms reported by patients and carepartners were stiffness, slowness of movement and changes in gait. Non-motor symptoms were less common. A higher proportion of carepartners reported each symptom. A minority of neurologists recognized pain, sweating and anxiety as possible symptoms of OFF periods. The three OFF symptoms most frequently designated as having great impact by people with Parkinson's disease were changes in gait, slowness and stiffness. In contrast, cognitive impairment was most frequently rated as having great impact on carepartners. OFF periods were reported to impact many aspects of the lives of both patients and carepartners., Conclusions: In people with Parkinson's disease of under 10 years duration, motor symptoms of OFF periods predominate in impact, however cognitive impairment has great impact on carepartners. Education is needed for neurologists regarding the non-motor aspects of OFF. The importance of involving carepartners in the assessment regarding OFF periods is supported by the higher frequency of symptom reporting by carepartners, and the significant impact on their lives.
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- 2020
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317. Comparison of an Online-Only Parkinson's Disease Research Cohort to Cohorts Assessed In Person.
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Chahine LM, Chin I, Caspell-Garcia C, Standaert DG, Brown E, Smolensky L, Arnedo V, Daeschler D, Riley L, Korell M, Dobkin R, Amondikar N, Gradinscak S, Shoulson I, Dean M, Kwok K, Cannon P, Marek K, Kopil C, Tanner CM, and Marras C
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Cohort Studies, Female, Humans, Male, Middle Aged, Young Adult, Internet, Observational Studies as Topic statistics & numerical data, Parkinson Disease diagnosis, Parkinson Disease epidemiology, Patient Reported Outcome Measures, Self Report statistics & numerical data
- Abstract
Background: Online tools for data collection could be of value in patient-oriented research. The Fox Insight (FI) study collects data online from individuals with self-reported Parkinson's disease (PD). Comparing the FI cohort to other cohorts assessed through more traditional (in-person) observational research studies would inform the representativeness and utility of FI data., Objective: To compare self-reported demographic characteristics, symptoms, medical history, and PD medication use of the FI PD cohort to other recent observational research study cohorts assessed with in-person visits., Methods: The FI PD cohort (n = 12,654) was compared to 3 other cohorts, selected based on data accessibility and breadth of assessments: Parkinson's Progression Markers Initiative (PPMI; PD n = 422), Parkinson's Disease Biomarker Program (PDBP; n = 700), and PD participants in the LRRK2 consortium without LRRK2 mutations (n = 508). Demographics, motor and non-motor assessments, and medications were compared across cohorts. Where available, identical items on surveys and assessments were compared; otherwise, expert opinion was used to determine comparable definitions for a given variable., Results: The proportion of females was significantly higher in FI (45.56%) compared to PPMI (34.36%) and PDBP (35.71%). The FI cohort had greater educational attainment as compared to all other cohorts. Overall, prevalence of difficulties with motor experiences of daily living and non-motor symptoms in the FI cohort was similar to other cohorts, with only a few significant differences that were generally small in magnitude. Missing data were rare for the FI cohort, except on a few variables., Discussion: Patterns of responses to patient-reported assessments obtained online on the PD cohort of the FI study were similar to PD cohorts assessed in-person.
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- 2020
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318. Understanding the Lexicon of Fatigue in Parkinson's Disease.
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Mantri S, Klawson E, Albert S, Nabieva K, Lepore M, Kahl S, Daeschler M, Mamikonyan E, Kopil C, Marras C, and Chahine LM
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- Aged, Aged, 80 and over, Fatigue etiology, Female, Health Surveys, Humans, Male, Middle Aged, Parkinson Disease complications, Qualitative Research, Diagnostic Self Evaluation, Fatigue physiopathology, Parkinson Disease physiopathology
- Abstract
Background: Fatigue in Parkinson's disease (PD) is multifaceted and associated with reduced quality of life. In turn, the language used by people with PD to describe fatigue is variable and poorly understood. We sought to elucidate the lexicon of fatigue using a qualitative grounded theory approach., Objective: The objective of this study was to understand how patients with PD describe fatigue., Methods: A pre-study phase of online journaling (Phase 1) provided information regarding topics of importance to patients. Following this, two independent samples of fatigued subjects were studied. Individuals with PD participated in a telephone interview (Phase 2); interview transcripts were analyzed to develop a detailed codebook. To ensure trustworthiness of the findings, an online survey (Phase 3) was administered to individuals with self-reported PD participating in the online study Fox Insight. The survey included the following question: "How do you define fatigue? Please provide your definition in the space below." The codebook developed from Phase 2 was applied to the Phase 3 responses., Results: Fifteen individuals participated in Phase 2 and 413 individuals completed Phase 3. Fatigue was subdivided into three domains: cognitive, emotional, and physical. Nearly all individuals experienced more than one domain of fatigue. The most common themes included tiredness, lack of energy, and negative motivation., Conclusion: Fatigue in PD is multidimensional. Questionnaires that only assess the physical impact of fatigue may not be adequate to capture the broad range of experiences of fatigue among people with PD.
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- 2020
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319. Recommendations for the Organization of Multidisciplinary Clinical Care Teams in Parkinson's Disease.
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Radder DLM, Nonnekes J, van Nimwegen M, Eggers C, Abbruzzese G, Alves G, Browner N, Chaudhuri KR, Ebersbach G, Ferreira JJ, Fleisher JE, Fletcher P, Frazzitta G, Giladi N, Guttman M, Iansek R, Khandhar S, Klucken J, Lafontaine AL, Marras C, Nutt J, Okun MS, Parashos SA, Munneke M, and Bloem BR
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- Checklist, Consensus, Health Care Surveys, Humans, Patient Advocacy, Delivery of Health Care organization & administration, Delivery of Health Care standards, Evidence-Based Practice organization & administration, Evidence-Based Practice standards, Neurologists, Parkinson Disease therapy, Patient Care Team organization & administration, Patient Care Team standards, Patient Preference, Patient-Centered Care organization & administration, Patient-Centered Care standards, Practice Guidelines as Topic standards, Tertiary Care Centers organization & administration, Tertiary Care Centers standards
- Abstract
Background: Optimal management in expert centers for Parkinson's disease (PD) usually involves pharmacological and non-pharmacological interventions, delivered by a multidisciplinary approach. However, there is no guideline specifying how this model should be organized. Consequently, the nature of multidisciplinary care varies widely., Objective: To optimize care delivery, we aimed to provide recommendations for the organization of multidisciplinary care in PD., Methods: Twenty expert centers in the field of multidisciplinary PD care participated. Their leading neurologists completed a survey covering eight themes: elements for optimal multidisciplinary care; team members; role of patients and care partners; team coordination; team meetings; inpatient versus outpatient care; telehealth; and challenges towards multidisciplinary care. During a consensus meeting, outcomes were incorporated into concept recommendations that were reviewed by each center's multidisciplinary team. Three patient organizations rated the recommendations according to patient priorities. Based on this feedback, a final set of recommendations (essential elements for delivery of multidisciplinary care) and considerations (desirable elements) was developed., Results: We developed 30 recommendations and 10 considerations. The patient organizations rated the following recommendations as most important: care is organized in a patient-centered way; every newly diagnosed patient has access to a core multidisciplinary team; and each team has a coordinator. A checklist was created to further facilitate its implementation., Conclusion: We provide a practical tool to improve multidisciplinary care for persons with PD at the organizational level. Future studies should focus on implementing these recommendations in clinical practice, evaluating their potential applicability and effectiveness, and comparing alternative models of PD care.
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- 2020
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320. Are the International Parkinson disease and Movement Disorder Society progressive supranuclear palsy (IPMDS-PSP) diagnostic criteria accurate enough to differentiate common PSP phenotypes?
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Shoeibi A, Litvan I, Juncos JL, Bordelon Y, Riley D, Standaert D, Reich SG, Shprecher D, Hall D, Marras C, Kluger B, Olfati N, and Jankovic J
- Subjects
- Humans, Phenotype, Societies, Medical, Supranuclear Palsy, Progressive classification, Supranuclear Palsy, Progressive diagnosis
- Abstract
The International Parkinson Disease and Movement Disorder Society PSP study group (IPMDS-PSP) recently published new clinical diagnostic criteria for progressive supranuclear palsy (PSP). Currently, there is no data regarding the accuracy of these sets of criteria for differentiating various PSP phenotypes. We discuss the accuracy of the IPMDS-PSP criteria for differentiation of patients with the PSP- Richardson phenotype (PSP-RS) from those with the PSP-Parkinsonism (PSP-P) using data from a sample of 274 clinically diagnosed PSP patients participating in the Environmental Genetic PSP (ENGENE-PSP) case control study. Using National Institute of Neurological Disorders and Stroke and the Society for PSP (NINDS-SPSP) criteria and the Williams criteria we categorized 259 of these patients as probable PSP-RS and 15 as PSP-P. The IPD-MDS PSP-RS and PSP-P criteria were unable to distinguish the PSP-RS from the PSP-P phenotypes in this sample. Nearly all (92.6%; 240 out of 259) the PSP-RS patients and over half (60%; 9 out of 15) of the PSP-P patients fulfilled both the IPMDS criteria for PSP-RS and PSP-P. Applying the newly proposed multiple allocation extinction rules decreased the number of overlapping diagnoses among the NINDS-SPSP PSP-RS patients, however problems remained in the PSP-P group. Diagnostic accuracy might be improved by modification of timelines for development of falls and other parkinsonian features., (Copyright © 2019 Elsevier Ltd. All rights reserved.)
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- 2019
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321. Increased markers of cardiac vagal activity in leucine-rich repeat kinase 2-associated Parkinson's disease.
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Carricarte Naranjo C, Marras C, Visanji NP, Cornforth DJ, Sanchez-Rodriguez L, Schüle B, Goldman SM, Estévez M, Stein PK, Lang AE, Jelinek HF, and Machado A
- Subjects
- Aged, Female, Heart Rate physiology, Humans, Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 genetics, Male, Middle Aged, Mutation, Vagus Nerve physiopathology, Parkinson Disease complications, Parkinson Disease genetics, Parkinson Disease physiopathology, Primary Dysautonomias etiology
- Abstract
Purpose: Cardiac autonomic dysfunction manifests as reduced heart rate variability (HRV) in idiopathic Parkinson's disease (PD), but no significant reduction has been found in PD patients who carry the LRRK2 mutation. Novel HRV features have not been investigated in these individuals. We aimed to assess cardiac autonomic modulation through standard and novel approaches to HRV analysis in individuals who carry the LRRK2 G2019S mutation., Methods: Short-term electrocardiograms were recorded in 14 LRRK2-associated PD patients, 25 LRRK2-non-manifesting carriers, 32 related non-carriers, 20 idiopathic PD patients, and 27 healthy controls. HRV measures were compared using regression modeling, controlling for age, sex, mean heart rate, and disease duration. Discriminant analysis highlighted the feature combination that best distinguished LRRK2-associated PD from controls., Results: Beat-to-beat and global HRV measures were significantly increased in LRRK2-associated PD patients compared with controls (e.g., deceleration capacity of heart rate: p = 0.006) and idiopathic PD patients (e.g., 8th standardized moment of the interbeat interval distribution: p = 0.0003), respectively. LRRK2-associated PD patients also showed significantly increased irregularity of heart rate dynamics, as quantified by Rényi entropy, when compared with controls (p = 0.002) and idiopathic PD patients (p = 0.0004). Ordinal pattern statistics permitted the identification of LRRK2-associated PD individuals with 93% sensitivity and 93% specificity. Consistent results were found in a subgroup of LRRK2-non-manifesting carriers when compared with controls., Conclusions: Increased beat-to-beat HRV in LRRK2 G2019S mutation carriers compared with controls and idiopathic PD patients may indicate augmented cardiac autonomic cholinergic activity, suggesting early impairment of central vagal feedback loops in LRRK2-associated PD.
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- 2019
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322. Association Between Social Cognition Changes and Resting State Functional Connectivity in Frontotemporal Dementia, Alzheimer's Disease, Parkinson's Disease, and Healthy Controls.
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Multani N, Taghdiri F, Anor CJ, Varriano B, Misquitta K, Tang-Wai DF, Keren R, Fox S, Lang AE, Vijverman AC, Marras C, and Tartaglia MC
- Abstract
Objective: To determine the relationship between alterations in resting state functional connectivity and social cognition dysfunction among patients with frontotemporal dementia (FTD), Alzheimer's disease (AD), Parkinson's disease (PD), and healthy controls (HC)., Methods: Fifty-seven participants (FTD = 10, AD = 18, PD = 19, and HC = 10) underwent structural and functional imaging and completed the Awareness of Social Inference Test-Emotion Evaluation Test (TASIT-EET), Behavioral Inhibition System/Behavioral Activation System (BIS/BAS) scale, Revised Self-Monitoring Scale (RSMS), Interpersonal Reactivity Index (IRI), and Social Norms Questionnaire (SNQ). A multi-variate pattern analysis (MVPA) was carried out to determine activation differences between the groups. The clusters from the MVPA were used as seeds for the ROI-to-voxel analysis. Relationship between social cognition deficits and uncinate integrity was also investigated., Results: BOLD signal activation differed among the four groups of AD, PD, FTD, and HC in the left inferior temporal gyrus-anterior division [L-ITG (ant)], right central opercular cortex (R-COp), right supramarginal gyrus, posterior division (R-SMG, post), right angular gyrus (R-AG), and R-ITG. The BOLD co-activation of the L-ITG (ant) with bilateral frontal pole (FP) and paracingulate gyrus was positively associated with IRI-perspective taking (PT) ( r = 0.38, p = 0.007), SNQ total ( r = 0.37, p = 0.009), and TASIT-EET ( r = 0.47, p < 0.001)., Conclusion: Patients with neurodegenerative diseases showed alterations in connectivity in brain regions important for social cognition compared with HCs. Functional connectivity correlated with performance on social cognition tasks and alterations could be responsible for some of the social cognition deficits observed in all neurodegenerative diseases., (Copyright © 2019 Multani, Taghdiri, Anor, Varriano, Misquitta, Tang-Wai, Keren, Fox, Lang, Vijverman, Marras and Tartaglia.)
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- 2019
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323. Nomenclature of Genetically Determined Myoclonus Syndromes: Recommendations of the International Parkinson and Movement Disorder Society Task Force.
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van der Veen S, Zutt R, Klein C, Marras C, Berkovic SF, Caviness JN, Shibasaki H, de Koning TJ, and Tijssen MAJ
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- Cognitive Dysfunction diagnosis, Cognitive Dysfunction genetics, Dystonia diagnosis, Dystonic Disorders diagnosis, Humans, Parkinson Disease diagnosis, Parkinsonian Disorders diagnosis, Phenotype, Dystonia genetics, Dystonic Disorders genetics, Parkinson Disease genetics, Parkinsonian Disorders genetics
- Abstract
Genetically determined myoclonus disorders are a result of a large number of genes. They have wide clinical variation and no systematic nomenclature. With next-generation sequencing, genetic diagnostics require stringent criteria to associate genes and phenotype. To improve (future) classification and recognition of genetically determined movement disorders, the Movement Disorder Society Task Force for Nomenclature of Genetic Movement Disorders (2012) advocates and renews the naming system of locus symbols. Here, we propose a nomenclature for myoclonus syndromes and related disorders with myoclonic jerks (hyperekplexia and myoclonic epileptic encephalopathies) to guide clinicians in their diagnostic approach to patients with these disorders. Sixty-seven genes were included in the nomenclature. They were divided into 3 subgroups: prominent myoclonus syndromes, 35 genes; prominent myoclonus syndromes combined with another prominent movement disorder, 9 genes; disorders that present usually with other phenotypes but can manifest as a prominent myoclonus syndrome, 23 genes. An additional movement disorder is seen in nearly all myoclonus syndromes: ataxia (n = 41), ataxia and dystonia (n = 6), and dystonia (n = 5). However, no additional movement disorders were seen in related disorders. Cognitive decline and epilepsy are present in the vast majority. The anatomical origin of myoclonus is known in 64% of genetic disorders: cortical (n = 34), noncortical areas (n = 8), and both (n = 1). Cortical myoclonus is commonly seen in association with ataxia, and noncortical myoclonus is often seen with myoclonus-dystonia. This new nomenclature of myoclonus will guide diagnostic testing and phenotype classification. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society., (© 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.)
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- 2019
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324. Recent developments in drug-induced movement disorders: a mixed picture.
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Factor SA, Burkhard PR, Caroff S, Friedman JH, Marras C, Tinazzi M, and Comella CL
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- Disease Management, Dyskinesia, Drug-Induced prevention & control, Dyskinesia, Drug-Induced therapy, Humans, Antipsychotic Agents adverse effects, Dyskinesia, Drug-Induced diagnosis
- Abstract
A large and ever-growing number of medications can induce various movement disorders. Drug-induced movement disorders are disabling but are often under-recognised and inappropriately managed. In particular, second generation antipsychotics, like first generation agents, are associated with potentially debilitating side-effects, most notably tardive syndromes and parkinsonism, as well as potentially fatal acute syndromes. Appropriate, evidence-based management is essential as these drugs are being prescribed to a growing population vulnerable to these side-effects, including children and elderly people. Prevention of the development of drug-induced movement disorders is an important consideration when prescribing medications that can induce movement disorders. Recent developments in diagnosis, such as the use of dopamine transporter imaging for drug-induced parkinsonism, and treatment, with the approval of valbenazine and deutetrabenazine, the first drugs indicated for tardive syndromes, have improved outcomes for many patients with drug-induced movement disorders. Future research should focus on development of safer antipsychotics and specific therapies for the different tardive syndromes and the treatment of drug-induced parkinsonism., (Copyright © 2019 Elsevier Ltd. All rights reserved.)
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- 2019
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325. Hypertension and progressive supranuclear palsy.
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Rabadia SV, Litvan I, Juncos J, Bordelon Y, Riley DE, Standaert D, Reich SG, Hall DA, Kluger B, Shprecher D, Marras C, and Jankovic J
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- Aged, Case-Control Studies, Comorbidity, Female, Humans, Male, Middle Aged, Risk Factors, Hypertension epidemiology, Supranuclear Palsy, Progressive epidemiology
- Abstract
Background: The epidemiologic evidence of whether hypertension is associated with Progressive Supranuclear Palsy (PSP) is inconsistent. The ENGENE-PSP case-control study determined various PSP risk factors including whether hypertension preceded PSP onset., Methods: Incident PSP cases per NINDS-PSP criteria and age-, sex-, race- matched controls were recruited from similar North American geographic areas. All study participants were administered standardized interviews to obtain data on demographics, medical history and medications., Statistics: We used univariate and multivariate conditional logistic regression models to measure the associations between PSP and the following predictor variables: education level, hypertension, comorbid vascular conditions (diabetes mellitus and hyperlipidemia), and classes of anti-hypertensive medications using odds ratios and 95% confidence intervals., Results: There were significant associations seen between PSP and hypertension (OR: 1.569; 95% CI 1.129-2.181; p-value = 0.007), education level (OR: 0.733; 95% CI 0.637-0.843; p-value<0.001) and beta-blocker use (OR: 2.000; 95% CI 1.053-3.799; p-value = 0.034). However, in the multi-variate analysis hypertension (OR: 1.492; 95% CI 1.045-2.129; p-value = 0.027) and education level (OR: 0.730; 95% CI 0.633-0.841; p-value<0.001) were the only significant associations., Conclusion: These results suggest that there is a modest, yet significant association between hypertension and PSP. Further studies will be needed to better understand the pathophysiological basis for this finding., (Copyright © 2019. Published by Elsevier Ltd.)
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- 2019
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326. Reply to "Studying reproducibility of data-driven Parkinson's disease subtypes".
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Mestre TA, Eberly S, Tanner C, Grimes D, Lang AE, Oakes D, and Marras C
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- Disease Progression, Humans, Reproducibility of Results, Parkinson Disease
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- 2019
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327. Communication About OFF Periods in Parkinson's Disease: A Survey of Physicians, Patients, and Carepartners.
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Rastgardani T, Armstrong MJ, Gagliardi AR, Grabovsky A, and Marras C
- Abstract
Background: OFF periods impair quality of life in Parkinson's disease and are often amenable to treatment. Optimal treatment decisions rely on effective communication between physicians, patients and carepartners regarding this highly variable and complex phenomenon. Little is published in the literature about communication about OFF periods. Methods: Informed by interviews with physicians, patients and carepartners we designed questionnaires for each group. We surveyed these parties using an online platform to investigate the frequency, content and ease of communication about OFF periods and barriers and facilitators of communication with physicians. Results: Fifty movement disorder neurologists, 50 general neurologists, 442 patients and 97 carepartners participated. A free-flowing dialogue is the mainstay of communication according to all parties. Motor aspects of OFF periods are discussed more frequently than non-motor aspects (90 vs. <50% according to both general neurologists and movement disorder neurologists). The most common physician-reported barriers to communication are patient cognitive impairment, patient difficulty recognizing OFF periods and poor patient understanding of OFF periods' relationship to medication timing. The barriers most commonly cited as major by patients were that they perceived OFF periods to be part of the disease (i.e., not a clinical aspect that could be improved by a physician), variability of symptoms, and difficulty in describing symptoms. The most commonly described facilitator (by physicians) was the input of a caregiver. Positively viewed but less commonly used facilitators included pre-visit questionnaires or diaries, digital apps and wearable devices to monitor fluctuations. The majority of patients and carepartners identified a free-flowing dialogue with their physicians and having an agenda as helpful facilitators of communication about OFF periods which they already use. The majority of both groups felt that keeping a diary and pre-visit questionnaires were potentially helpful facilitators that were not currently in use. Conclusions: Perceived barriers and facilitators to communication about OFF periods are different between health care providers and receivers of health care. Modifiable barriers and facilitators that could be implemented were identified by both groups. Future research should develop and test strategies based on this input to optimize communication and thus clinical care for this common and debilitating problem.
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- 2019
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328. The experience of off periods: Qualitative analysis of interviews with persons with Parkinson's and carepartners.
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Armstrong MJ, Rastgardani T, Gagliardi AR, and Marras C
- Abstract
Introduction: Off period research in Parkinson's disease commonly relies on questionnaires. We aimed to investigate the breadth of off period experiences by interviewing persons with Parkinson's disease (PwP) and carepartners., Methods: Investigators performed PwP and carepartner dyad interviews using a semi-structured questionnaire to describe off period experiences. Investigators analyzed interview transcripts using a qualitative descriptive approach to identify and compare themes between groups., Results: Twenty PwP and their carepartners participated in interviews. PwP were on average 65.1 years-old (SD 8.3) and 7.8 years (SD 4.7) after their Parkinson's disease diagnosis. PwP and carepartners identified 13 motor symptoms, 5 of which (immobility, gait changes, freezing, trouble swallowing, and having to concentrate on movements) were not in the wearing off questionnaires recommended by the International Parkinson and Movement Disorders Society. PwP and carepartners identified 15 non-motor symptoms, 8 of which (behavior changes, irritability, fatigue, language difficulties, dizziness, dry mouth, urinary symptoms, and swollen feet) were not in recommended questionnaires. Certain symptoms were reported only by PwP (e.g. dizziness, urinary symptoms) or carepartners (e.g. behavioral changes), or were reported by dyad members to different degrees (e.g. fatigue, anxiety)., Conclusion: Wearing off questionnaires capture the presence of fluctuations and can facilitate patient-physician communication regarding off periods. However, they may miss the breadth of individual PwP experiences. PwP and carepartners also report different PwP experiences during off periods. To fully appreciate an individual's off experiences, clinicians likely need to use multiple approaches to gathering information including questionnaires and both PwP and carepartner report., Competing Interests: MJA: Dr. Armstrong receives compensation from the AAN for work as an evidence-based medicine methodology consultant and serves on the level of evidence editorial board for Neurology and related publications (uncompensated). She receives research support from 10.13039/100000133AHRQ (K08HS24159), The Michael J. Fox Foundation for Parkinson's Research, a 1Florida ADRC pilot grant, and as the local PI of a Lewy Body Dementia Association Research Center of Excellence. She receives royalties from the publication of the book Parkinson's Disease: Improving Patient Care and she has received honoraria for presenting at the AAN annual meeting (2017) and participating in Medscape CME. TR: None. ARG: Dr. Gagliardi was funded by the 10.13039/100000864Michael J. Fox Foundation for work on this study. CM: Dr. Marras has served as a consultant for Acorda Therapeutics. She receives honoraria for serving on the steering committee for the Michael J. Fox Foundation and for teaching from EMD Serono. She receives research support from The Michael J. Fox Foundation for Parkinson's Research, 10.13039/501100000024Canadian Institutes of Health Research, 10.13039/100013301Parkinson's Foundation (U.S.), 10.13039/100000002NIH, and The International Parkinson and Movement Disorder Society., (© 2019 The Authors. Published by Elsevier Ltd.)
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- 2019
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329. Environment, lifestyle, and Parkinson's disease: Implications for prevention in the next decade.
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Marras C, Canning CG, and Goldman SM
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- Environmental Exposure, Humans, Parkinson Disease genetics, Environment, Gene-Environment Interaction, Life Style, Parkinson Disease etiology
- Abstract
There is evidence from observational studies for a role of a number of environmental exposures and lifestyle habits in modulating the risk for Parkinson's disease. Environmental and lifestyle associations, if causal, represent opportunities for Parkinson's disease prevention or disease modification at individual and population levels. In the past decade, additional evidence has been published that improves causal inference and/or enhances our understanding of the complexity of these associations. A number of gene-environment interactions have been elucidated, and our understanding of the roles of physical activity, pesticide and other chemical exposures, dietary habits, emotional stress, head injury, and smoking has been refined. In the next decade, better techniques will help us to close the gaps in our knowledge, including taking into account Parkinson's disease heterogeneity and gene and risk factor interactions in observational studies. To do this, larger datasets, global consortia, genomewide environment interaction studies, prospective studies throughout the lifespan, and improvements in the methodology of clinical trials of physical activity will be key. Despite the caveats of observational studies, a number of low-risk and potentially high-yield recommendations for lifestyle modification could be made to minimize the individual and societal burdens of Parkinson's disease, including dietary modifications, increasing physical activity, and head injury avoidance. Furthermore, a reduction in pesticide use could have a major impact on global health related to and beyond Parkinson's disease. Given the increasing prevalence of this disorder, formulating and promoting these recommendations should be a high priority. © 2019 International Parkinson and Movement Disorder Society., (© 2019 International Parkinson and Movement Disorder Society.)
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- 2019
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330. Reply to 'Neuropathological progression of clinical Parkinson disease subtypes'.
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Espay AJ and Marras C
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- Disease Progression, Humans, Tremor, Nervous System Diseases, Parkinson Disease
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- 2019
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331. Improving patient-centred care for persons with Parkinson's: Qualitative interviews with care partners about their engagement in discussions of "off" periods.
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Rastgardani T, Armstrong MJ, Marras C, and Gagliardi AR
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- Aged, Female, Humans, Male, Middle Aged, Qualitative Research, Quality of Life, Caregivers education, Caregivers psychology, Parkinson Disease nursing, Patient-Centered Care standards
- Abstract
Objective: This study explored how care partners (CPs) of persons with Parkinson's (PwP) are engaged in discussions of "off" symptoms., Methods: During qualitative interviews, CPs of PwP sampled by convenience through the Michael J Fox Foundation online clinical trial matching service were asked to describe their familiarity with "off" symptoms, how "off" symptoms were discussed with clinicians, and the impact of "off" symptoms on them. Data were analysed using constant comparative technique by all members of the research team., Results: A total of 20 CPs were interviewed. Compared with PwP, they were more likely to describe "off" symptoms to clinicians. CPs identified important aspects of patient-centred care for PD: establishing a therapeutic relationship, soliciting and actively listening to information about symptoms, and providing self-management support to both PwP and CPs. CPs said that clinicians did not always engage CPs, ask about "off" symptoms or provide self-management guidance, limiting their ability to function as caregivers., Conclusion: By not engaging and educating CPs, "off" symptoms may not be identified or addressed, leading to suboptimal medical management and quality of life for PwP. These findings must be confirmed on a broader scale through ongoing research but suggest the potential need for interventions targeted at clinicians and at CPs to promote patient-centred care for PwP., (© 2019 The Authors Health Expectations published by John Wiley & Sons Ltd.)
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- 2019
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332. Relationship between damage and mortality in juvenile-onset systemic lupus erythematosus: Cluster analyses in a large cohort from the Spanish Society of Rheumatology Lupus Registry (RELESSER).
- Author
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Torrente-Segarra V, Salman Monte TC, Rúa-Figueroa I, De Uña-Álvarez J, Balboa-Barreiro V, López-Longo FJ, Galindo-Izquierdo M, Calvo-Alén J, Olivé-Marqués A, Mouriño-Rodríguez C, Horcada L, Sánchez-Atrio A, Montilla C, Salgado E, Díez-Álvarez E, Blanco R, Andreu JL, Fernández-Berrizbeitia O, Hernández-Beriain JA, Gantes M, Hernández-Cruz B, Pecondón-Español A, Marras C, Bonilla G, and Pego-Reigosa JM
- Subjects
- Adolescent, Child, Cross-Sectional Studies, Female, Humans, Lupus Erythematosus, Systemic pathology, Male, Registries, Spain, Survival Rate, Lupus Erythematosus, Systemic mortality
- Abstract
Objectives: To identify patterns (clusters) of damage manifestation within a large cohort of juvenile SLE (jSLE) patients and evaluate their possible association with mortality., Methods: This is a multicentre, descriptive, cross-sectional study of a cohort of 345 jSLE patients from the Spanish Society of Rheumatology Lupus Registry. Organ damage was ascertained using the Systemic Lupus International Collaborating Clinics Damage Index. Using cluster analysis, groups of patients with similar patterns of damage manifestation were identified and compared., Results: Mean age (years) ± S.D. at diagnosis was 14.2 ± 2.89; 88.7% were female and 93.4% were Caucasian. Mean SLICC/ACR DI ± S.D. was 1.27 ± 1.63. A total of 12 (3.5%) patients died. Three damage clusters were identified: Cluster 1 (72.7% of patients) presented a lower number of individuals with damage (22.3% vs. 100% in Clusters 2 and 3, P < 0.001); Cluster 2 (14.5% of patients) was characterized by renal damage in 60% of patients, significantly more than Clusters 1 and 3 (P < 0.001), in addition to increased more ocular, cardiovascular and gonadal damage; Cluster 3 (12.7%) was the only group with musculoskeletal damage (100%), significantly higher than in Clusters 1 and 2 (P < 0.001). The overall mortality rate in Cluster 2 was 2.2 times higher than that in Cluster 3 and 5 times higher than that in Cluster 1 (P < 0.017 for both comparisons)., Conclusions: In a large cohort of jSLE patients, renal and musculoskeletal damage manifestations were the two dominant forms of damage by which patients were sorted into clinically meaningful clusters. We found two clusters of jSLE with important clinical damage that were associated with higher rates of mortality, especially for the cluster of patients with predominant renal damage. Physicians should be particularly vigilant to the early prevention of damage in this subset of jSLE patients with kidney involvement., (Copyright © 2018 Elsevier Inc. All rights reserved.)
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- 2019
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333. A composite indicator to assess the quality of care in the management of patients with rheumatoid arthritis in outpatient rheumatology clinics.
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Martín-Martínez MA, Andreu-Sanchez JL, Sanchez-Alonso F, Corominas H, Perez-Venegas JJ, Roman-Ivorra JA, Alperi M, Blanco-Alonso R, Caliz R, Chamizo-Carmona E, Graña-Gil J, Hernández B, Marras C, Mazzucchelli R, Medina Luezas JA, Naranjo-Hernández A, Ortiz A, Roselló R, Sanchez-Nievas G, Sanmartí R, and Vela-Casasempere P
- Subjects
- Antirheumatic Agents therapeutic use, Delphi Technique, Expert Testimony, Humans, Medical Records, Spain, Arthritis, Rheumatoid therapy, Outpatient Clinics, Hospital, Quality Indicators, Health Care, Quality of Health Care
- Abstract
Objective: The current guidelines in the treatment of rheumatoid arthritis (RA) include the early diagnosis and early use of disease modifying drugs to achieve remission or low disease activity level, known as "Treat to Target" (T2T). The objective of this study is to develop a composite indicator (CI) to evaluate the quality of care in the management of patients with RA, according to the T2T strategy and other general recommendations concerning the management of these patients., Material and Method: The phases of the construction of the CI were: 1) selection of quality criteria through expert judgment; 2) prioritization of the criteria, according to relevance and feasibility, applying the Delphi methodology (two rounds) involving 20 experts; 3) design of quality indicators; and 4) calculation of the weighted CI, using the mean value in relevance and feasibility granted by the experts. The source of information for the calculation of the CI are the medical records of patients with RA., Results: Twelve criteria out of 37 required a second Delphi round. Thirty-one criteria were prioritized. These criteria presented a median in relevance and feasibility greater than or equal to 7.5, with an interquartile range of less than 3.5, and a level of agreement (score greater than or equal to 8) greater than or equal to 80%., Conclusions: The constructed CI allows us to evaluate the quality of care of patients with RA following the T2T strategy in the rheumatology units of Spanish hospitals, offering a valid and easily interpretable summary measure., (Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.)
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- 2019
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334. Barriers and facilitators of communication about off periods in Parkinson's disease: Qualitative analysis of patient, carepartner, and physician Interviews.
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Armstrong MJ, Rastgardani T, Gagliardi AR, and Marras C
- Subjects
- Aged, Female, Humans, Male, Middle Aged, Caregivers, Communication, Communication Barriers, Parkinson Disease psychology, Physician-Patient Relations, Physicians, Surveys and Questionnaires
- Abstract
Background: Successful patient-physician communication is critical for improving health outcomes, but research regarding optimal communication practices in Parkinson's disease is limited. The objective of the current study was to investigate barriers and facilitators of communication between persons with Parkinson's disease, carepartners, and physicians, specifically in the setting of off periods, with the goal of identifying ways to improve patient-carepartner-physician communication., Method: We interviewed persons with Parkinson's, carepartners, and physicians (specialists and non-specialists) using a semi-structured questionnaire to identify and describe experiences, barriers, and facilitators relating to communication about off periods in Parkinson's disease. We used a qualitative descriptive approach to analyze interview transcripts and compare themes between participating groups., Results: Twenty persons with Parkinson's and their carepartners and 20 physicians (10 specialists, 10 non-specialists) participated in interviews. Identified communication barriers included patient-level (e.g. cognitive impairment, reluctance to discuss symptoms), caregiver-level (e.g. caregiver absence), and physician-level (e.g. distraction by technology, lack of appreciation of the burden of off periods) factors. Other barriers included the challenging nature of off periods themselves. Positive physician characteristics such as empathy, respect, and taking time to listen were major facilitators of communication regarding off periods. Persons with Parkinson's, carepartners, and physicians described using various tools (e.g. home diaries, questionnaires, mobile phone videos) to aid communication regarding off periods but participants identified a need for more formal educational materials., Conclusions: Physicians caring for persons with Parkinson's can improve communication through more patient-centered practice but there is a need for improved educational tools regarding off periods. Further research is needed to identify optimal strategies for communication about off periods and preferred approaches for off period education., Competing Interests: MJA receives compensation from the American Academy of Neurology for work as an evidence-based medicine methodology consultant and serves on the level of evidence editorial board for Neurology and related publications (uncompensated). She receives research support from ARHQ (K08HS24159), a 1Florida ADRC (AG047266) pilot grant, and as the local PI of a Lewy Body Dementia Association Research Center of Excellence. In the 5 years prior to submission, she also was a local investigator for studies sponsored by the Parkinson Study Group, the Huntington Study Group, the CHDI Foundation, Abbvie, Biotie, and Insightec and she received funding as a sub-investigator or local investigator on the NIH grants U01 AR057967-01, U01NS080818-01A1 and U01NS080840-01A1 (until 2015). She was a consultant on a TBI endpoints development (TED) seed grant 2016-2017. She receives royalties from the publication of the book Parkinson’s Disease: Improving Patient Care and she has received honoraria for presenting at the Movement Disorders Society congress (2013, 2014) and the AAN annual meeting (2014-2017) and participating in Medscape CME. TR and ARG have declared that no competing interests exist. CM has served as a consultant for Acorda Therapeutics. She receives honoraria for serving on the steering committee for the Michael J. Fox Foundation and for teaching from EMD Serono. She receives research support from the Michael J. Fox Foundation, Canadian Institutes of Health Research, Parkinson Foundation (U.S.), NIH, and International Parkinson and Movement Disorders Society. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
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- 2019
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335. Cognitive Complaints in Nondemented Parkinson's Disease Patients and Their Close Contacts do not Predict Worse Cognitive Outcome.
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AlDakheel A, Gasca-Salas C, Armstrong MJ, Duff-Canning S, and Marras C
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- Aged, Female, Humans, Male, Mental Status and Dementia Tests statistics & numerical data, Neuropsychological Tests statistics & numerical data, Ontario, Prospective Studies, Retrospective Studies, Severity of Illness Index, Cognitive Dysfunction diagnosis, Parkinson Disease complications
- Abstract
Objectives: The main purpose of this study was to investigate 4 methods of eliciting subjective cognitive complaints (SCCs) in Parkinson's disease (PD) patients without dementia and determine the relationship between their SCC and cognitive performance., Design: This study was a retrospective analysis of a prospective cohort study., Setting: Six North American movement disorder clinics., Measurements: SCCs were elicited through a modified Neurobehavioral Inventory administered to patients and close contacts, a general complaint question, and Movement Disorders Society Unified Parkinson's Disease Rating Scale item question 1.1 administered to patients. Clinical evaluation, formal neuropsychological testing and Disability Assessment for Dementia were conducted in Ontario state. Agreement between SCCs eliciting methods was calculated. Associations between SCC, cognitive testing, and mild cognitive impairment (MCI) were assessed., Results: Of 139 participating nondemented PD patients, 42% had PD-MCI at baseline. Agreement between SCC eliciting methods was low. Neither patient-reported nor close contact-reported SCCs were associated with impaired baseline cognitive testing or PD-MCI nor were they associated with cognitive decline over time. In PD patients with normal baseline cognition, 26% of patients with 1-year follow-up and 20% of patients with 2-year follow-up met MCI criteria., Conclusions: Agreement between SCC eliciting methods is poor and no SCC method was associated with cognitive testing or decline over time. With no clear superior method for eliciting SCCs, clinicians should consider performing regular screening.
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- 2019
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336. Concordance for Parkinson's disease in twins: A 20-year update.
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Goldman SM, Marek K, Ottman R, Meng C, Comyns K, Chan P, Ma J, Marras C, Langston JW, Ross GW, and Tanner CM
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- Adult, Aged, Aged, 80 and over, Diseases in Twins epidemiology, Female, Follow-Up Studies, Genetic Predisposition to Disease epidemiology, Humans, Male, Middle Aged, Parkinson Disease epidemiology, Registries, Risk Factors, Diseases in Twins genetics, Genetic Predisposition to Disease genetics, Parkinson Disease genetics, Twins, Dizygotic genetics, Twins, Monozygotic genetics
- Abstract
During the 1990s, we estimated the genetic contribution to Parkinson's disease risk in a large, population-based twin registry. Because many unaffected twins were still alive, previous concordance estimates were based on incomplete information. Ninety-five percent of twins are now deceased. Here, we update concordance and heritability through 2015 using National Death Index data. In total, we identified 30 concordant and 193 discordant pairs. Proband-wise concordance was 0.20 in monozygotic and 0.13 in dizygotic pairs. Heritability was 0.27 overall, 0.83 in pairs diagnosed ≤50, and 0.19 in pairs diagnosed >50. High concordance in dizygotic twins suggests shared effects of early childhood environment. Ann Neurol 2019;85:600-605., (© 2019 American Neurological Association.)
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- 2019
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337. Clinical Parkinson disease subtyping does not predict pathology.
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Espay AJ and Marras C
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- Humans, Parkinson Disease pathology
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- 2019
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338. Risk of Parkinson's disease dementia related to level I MDS PD-MCI.
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Hoogland J, Boel JA, de Bie RMA, Schmand BA, Geskus RB, Dalrymple-Alford JC, Marras C, Adler CH, Weintraub D, Junque C, Pedersen KF, Mollenhauer B, Goldman JG, Tröster AI, Burn DJ, Litvan I, and Geurtsen GJ
- Subjects
- Age Factors, Aged, Female, Humans, Male, Middle Aged, Neuropsychological Tests, Risk Factors, Sex Factors, Cognitive Dysfunction etiology, Dementia etiology, Parkinson Disease complications
- Abstract
Background: The International Parkinson and Movement Disorders Society criteria for mild cognitive impairment in PD need validation. The objectives of this present study were to evaluate prognostic validity of level I (abbreviated) International Parkinson and Movement Disorders Society mild cognitive impairment in PD criteria for development of PD dementia and compared them with level II (comprehensive) criteria., Methods: We analyzed data from 8 international studies (1045 patients) from our consortium that included baseline data on demographics, motor signs, depression, detailed neuropsychological testing, and longitudinal follow-up for conversion to Parkinson's disease dementia. Survival analysis evaluated their contribution to the hazard of Parkinson's disease dementia., Results: Level I mild cognitive impairment in PD, increasing age, male sex, and severity of PD motor signs independently increased the hazard of Parkinson's disease dementia. Level I and level II mild cognitive impairment in PD classification had similar discriminative ability with respect to the time to Parkinson's disease dementia., Conclusions: Level I mild cognitive impairment in PD classification independently contributes to the hazard of Parkinson's disease dementia. This finding supports the prognostic validity of the abbreviated mild cognitive impairment in PD criteria. © 2019 International Parkinson and Movement Disorder Society., (© 2019 International Parkinson and Movement Disorder Society.)
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- 2019
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339. Prevalence of comorbidities in rheumatoid arthritis and evaluation of their monitoring in clinical practice: the spanish cohort of the COMORA study.
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Balsa A, Lojo-Oliveira L, Alperi-López M, García-Manrique M, Ordóñez-Cañizares C, Pérez L, Ruiz-Esquide V, Corrales A, Narváez J, Rey-Rey J, Rodríguez-Lozano C, Ojeda S, Muñoz-Fernández S, Nolla JM, García-Torrón J, Gamero F, García-Vicuña R, Hernández-Cruz B, Campos J, Rosas J, García-Llorente JF, Gómez-Centeno A, Cáliz R, Sanmartí R, Bermúdez A, Abasolo-Alcázar L, Fernández-Nebro A, Rodríguez-Rodríguez L, Marras C, González-Gay MÁ, Hmamouchi I, and Martín-Mola E
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Comorbidity, Cross-Sectional Studies, Female, Humans, Male, Middle Aged, Prevalence, Risk Factors, Spain epidemiology, Young Adult, Arthritis, Rheumatoid epidemiology
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Objectives: To describe the prevalence of comorbidities in patients with RA in Spain and discuss their management and implications using data from the Spanish cohort of the multinational study on COMOrbidities in Rheumatoid Arthritis (COMORA)., Methods: This is a national sub-analysis of the COMORA study. We studied the demographics and disease characteristics of 200 adults patients diagnosed with RA (1987 ACR), and routine practices for screening and preventing the following selected comorbidities: cardiovascular, infections, cancer, gastrointestinal, pulmonary, osteoporosis and depression., Results: Patients had a mean age of 58 years and a mean RA duration of 10 years. Mean DAS28 score was 3.3 and approximately 25% of patients were in remission (DAS28 <2.6). Forty-four (22%) patients had ≥1 comorbidity, the most frequent being depression (27%) and obesity (26%). A history of myocardial infarction or stroke was observed in 5% and 1% of patients, respectively, and any solid tumor in 6%. Having a Framingham Risk Score >20% (51%), hypercholesterolemia (46%) or hypertension (41%) and smoking (25%) were the most common CV risk factors. For prostate, colon and skin cancers, only 9%, 10% and 18% of patients, respectively, were optimally monitored. Infections were also inadequately managed, with 7% and 17% of patients vaccinated against influenza and pneumococcal, respectively, as was osteoporosis, with 47% of patients supplemented with vitamin D and 56% with a bone densitometry performed., Conclusions: In Spain, the prevalence of comorbidities and CV risk factors in RA patients with established and advanced disease is relatively high, and their management in clinical daily practice remains suboptimal., (Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.)
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- 2019
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340. Responsiveness to Change of the Montreal Cognitive Assessment, Mini-Mental State Examination, and SCOPA-Cog in Non-Demented Patients with Parkinson's Disease.
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Faust-Socher A, Duff-Canning S, Grabovsky A, Armstrong MJ, Rothberg B, Eslinger PJ, Meaney CA, Schneider RB, Tang-Wai DF, Fox SH, Zadikoff C, Kennedy N, Chou KL, Persad C, Litvan I, Mast BT, Gerstenecker AT, Weintraub S, Reginold W, and Marras C
- Subjects
- Aged, Aged, 80 and over, Cognition, Cognitive Dysfunction diagnosis, Cognitive Dysfunction etiology, Cognitive Dysfunction psychology, Dementia diagnosis, Dementia etiology, Disease Progression, Female, Humans, Male, Mental Status and Dementia Tests, Middle Aged, Parkinson Disease complications, Parkinson Disease diagnosis, ROC Curve, Reproducibility of Results, Sensitivity and Specificity, Dementia psychology, Neuropsychological Tests, Parkinson Disease psychology
- Abstract
Background: Clinical monitoring of patients with Parkinson's disease (PD) for cognitive decline is an important element of care. The Montreal Cognitive Assessment (MoCA) has been proposed to be a sensitive tool for assessing cognitive impairment in PD. The aim of our study was to compare the responsiveness of the MoCA to decline in cognition to the responsiveness of the Mini Mental State Examination (MMSE) and the Scales for Outcomes of Parkinson's disease-cognition (SCOPA-Cog)., Methods: PD patients without dementia were enrolled at 6 North American movement disorders centers between 2008 and 2011. Participants received annual evaluations including the MoCA, MMSE, and SCOPA-Cog followed by formal neuropsychological testing. The gold standard for change in cognition was defined as the change on the neuropsychological test scores over the annual assessments. The Reliable Change Method was used to provide an estimate of the probability that a given difference score would be obtained by chance. The sensitivity of the MoCA, MMSE, and SCOPA-Cog to change was quantified using receiver operating characteristics (ROC) curves., Results: One hundred seventeen patients were included in the analysis. Participants were followed at mean intervals of 11 ± 2 months for a median of 2 (maximum 5) visits. According to the reliable change index, 56 intervals of cognitive testing showed a decline in global cognition. ROC analysis of change in MoCA, MMSE, and SCOPA-Cog global scores compared to gold standard testing found an area under the curve (AUC) of 0.55 (95% CI 0.48-0.62), 0.56 (0.48-0.63), and 0.63 (0.55-0.70) respectively. There were no significant differences in the AUCs across the tests. The sensitivity of the MoCA, MMSE, and SCOPA-Cog to change at various thresholds for decline in scores reached a maximum of 71% for a cut-off of 1 point change on the SCOPA-Cog., Conclusion: Using neuropsychological testing as a gold standard comparator, the performance of the MoCA, MMSE, and SCOPA-Cog for detecting decline in non-demented PD patients over a 1-year interval is poor. This has implications for clinical practice; stable scores may not be taken as reassurance of the absence of cognitive decline., (© 2019 S. Karger AG, Basel.)
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- 2019
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341. Pure Membranous Lupus Nephritis: Description of a Cohort of 150 Patients and Review of the Literature.
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Silva-Fernández L, Otón T, Askanase A, Carreira P, López-Longo FJ, Olivé A, Rúa-Figueroa Í, Narváez J, Ruiz-Lucea E, Andrés M, Calvo E, Toyos F, Alegre-Sancho JJ, Tomero E, Montilla C, Zea A, Uriarte E, Calvo-Alén J, Marras C, Martínez-Taboada VM, Belmonte-López MÁ, Rosas J, Raya E, Bonilla G, Freire M, Pego-Reigosa JM, Millán I, Hughes-Morley A, and Andreu JL
- Subjects
- Adult, Female, Follow-Up Studies, Glomerulonephritis, Membranous mortality, Glomerulonephritis, Membranous physiopathology, Glomerulonephritis, Membranous therapy, Humans, Lupus Nephritis mortality, Lupus Nephritis physiopathology, Lupus Nephritis therapy, Male, Middle Aged, Prognosis, Retrospective Studies, Glomerulonephritis, Membranous diagnosis, Lupus Nephritis diagnosis
- Abstract
Objectives: The course and long-term outcome of pure membranous lupus nephritis (MLN) are little understood. The aims of this study are to evaluate the clinical features, course, outcome and prognostic indicators in pure MLN and to determine the impact of ethnicity and the type of health insurance on the course and prognosis of pure MLN., Methods: We conducted a retrospective review of medical records of 150 patients with pure MLN from Spain and the USA., Results: Mean age was 34.2±12.5 and 80% were women. Sixty-eight percent of patients had nephrotic syndrome at diagnosis. The average serum creatinine was 0.98±0.78mg/dl. Six percent of patients died and 5.3% developed end-stage renal disease (ESRD). ESRD was predicted by male sex, hypertension, dyslipidemia, high basal 24h-proteinuria, high basal serum creatinine and a low basal creatinine clearance. Age, cardiac insufficiency, peripheral artheriopathy, hemodialysis and not having received mycophenolate mofetil or antimalarials for MLN predicted death., Conclusions: Pure MLN frequently presents with nephrotic syndrome, high proteinuria and normal serum creatinine. Its prognosis is favourable in maintaining renal function although proteinuria usually persists over time. Baseline cardiovascular disease and not having a health insurance are related with poor prognosis., (Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.)
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- 2019
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342. We are what we eat - editors' note on the role of diet in Parkinson's disease.
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Marras C and Obeso JA
- Subjects
- Humans, Movement Disorders etiology, Risk Factors, Diet, Parkinson Disease etiology
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- 2019
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343. Serum Inflammatory Profile for the Discrimination of Clinical Subtypes in Parkinson's Disease.
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Yilmaz R, Strafella AP, Bernard A, Schulte C, van den Heuvel L, Schneiderhan-Marra N, Knorpp T, Joos TO, Leypoldt F, Geritz J, Hansen C, Heinzel S, Apel A, Gasser T, Lang AE, Berg D, Maetzler W, and Marras C
- Abstract
Background: Blood levels of immune markers have been proposed to discriminate patients with Parkinson's disease (PD) from controls. However, differences between clinical PD subgroups regarding these markers still need to be identified. Objective: To investigate whether clinical phenotypes can be predicted by the assessment of immune marker profiles in the serum of PD patients. Methods: Phenotypes of clinical PD from Tübingen, Germany ( n = 145) and Toronto, Canada ( n = 90) were defined regarding clinical subtype, disease onset, severity, and progression as well as presence of cognitive and/or autonomic dysfunction. A panel of serum immune markers was assessed using principal component analysis (PCA) and regression models to define the marker(s) that were associated with clinical phenotypes after adjusting for potential confounders. Findings of both centers were compared for validation. Further, a [18F] FEPPA-PET was performed in a group of patients with high and low values of candidate markers for the assessment of in vivo brain microglial activation. Results: Overall, serum immune markers did not cluster to define a pro/anti-inflammatory profile in PCA. Out of 25 markers only IL-12p40 showed a trend to discriminate between PD subgroups in both cohorts which could not be replicated by [18F] FEPPA-PET. Conclusions: Assessment of cytokines in serum does not reliably differentiate clinical PD subtypes. Accompanying subtype-irrelevant inflammation in PD, dual activity, and lack of specificity of the immune markers, the complex function of microglia, probable effects of treatment, disease stage, and progression on inflammation as well as current technical limitations may limit the usefulness of serum immune markers for the differentiation of subtypes.
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- 2018
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344. Antipsychotic Drug Dispensing in Older Adults With Parkinsonism.
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Marras C, Austin PC, Bronskill SE, Diong C, and Rochon PA
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- Aged, Aged, 80 and over, Female, Humans, Male, Ontario, Parkinson Disease drug therapy, Retrospective Studies, Antipsychotic Agents therapeutic use, Drug Prescriptions statistics & numerical data, Parkinsonian Disorders drug therapy, Physicians, Primary Care statistics & numerical data
- Abstract
Background: Antipsychotic drugs are commonly used to treat psychosis in patients with Parkinson disease; however, individuals with parkinsonism are at risk for serious adverse effects with antipsychotic use. The choice of antipsychotic is critical., Objective: To examine the frequency and pattern of antipsychotic prescribing to patients with Parkinson disease and parkinsonism over time., Methods: Individuals with parkinsonism aged 66 or older in Ontario were studied in a retrospective cohort study from 2005-2013 and followed for prevalent and/or incident antipsychotic drug dispensing., Results: In 2005, 15% of 22,837 individuals with prevalent parkinsonism were dispensed an antipsychotic drug. By 2013, the proportion was 11% of 34,262 individuals. Primary care physicians represented the vast majority of prescribers. Of individuals receiving antipsychotics in 2013, 20% were dispensed a typical antipsychotic drug. Among individuals with incident parkinsonism, living in a nursing home, older age, male sex, a greater number of comorbidities, and a prior diagnosis of dementia were significantly associated with an increased rate of receiving an antipsychotic during follow-up. Among those who received an antipsychotic, factors associated with typical antipsychotic exposure were absence of a prior diagnosis of dementia, higher Charlson comorbidity index, more concurrent medications, more recent year of first parkinsonism diagnosis and not having seen a neurologist, psychiatrist, or geriatrician., Conclusion: A substantial proportion of individuals with parkinsonism are exposed to antipsychotic drugs, including typical antipsychotics. Given the risks of these drugs to individuals with parkinsonism, education of prescribers, particularly primary care physicians, is needed., (Copyright © 2018 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)
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- 2018
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345. Genotype-phenotype relations for the Parkinson's disease genes SNCA, LRRK2, VPS35: MDSGene systematic review.
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Trinh J, Zeldenrust FMJ, Huang J, Kasten M, Schaake S, Petkovic S, Madoev H, Grünewald A, Almuammar S, König IR, Lill CM, Lohmann K, Klein C, and Marras C
- Subjects
- Humans, Parkinson Disease genetics, Genotype, Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 genetics, Phenotype, Vesicular Transport Proteins genetics, alpha-Synuclein genetics
- Abstract
This comprehensive MDSGene review is devoted to the three autosomal-dominant PD forms: PARK-SNCA, PARK-LRRK2, and PARK-VPS35. It follows MDSGene's standardized data extraction protocol, screened a total of 2,972 citations, and is based on fully curated phenotypic and genotypic data on 937 patients with dominantly inherited PD attributed to 44 different mutations in SNCA, LRRK2, or VPS35. All of these data are also available in an easily searchable online database (www.mdsgene.org), which additionally provides descriptive summary statistics on phenotypic and genetic data. Despite the high degree of missingness of phenotypic features and unsystematic reporting of genotype data in the original literature, the present review recapitulates many of the previously described findings including later onset of disease (median age at onset: ∼49 years) compared to recessive forms of PD of an overall excellent treatment response. Our systematic review validates previous reports showing that SNCA mutation carriers have a younger age at onset compared to LRRK2 and VPS35 (P < 0.001). SNCA mutation carriers often have additional psychiatric symptoms, and although not exclusive to only LRRK2 or VPS35 mutation carriers, LRRK2 mutation carriers have a typical form of PD, and, lastly, VPS35 mutation carriers have good response to l-dopa. © 2018 International Parkinson and Movement Disorder Society., (© 2018 International Parkinson and Movement Disorder Society.)
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- 2018
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346. The miR-139-5p regulates proliferation of supratentorial paediatric low-grade gliomas by targeting the PI3K/AKT/mTORC1 signalling.
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Catanzaro G, Besharat ZM, Miele E, Chiacchiarini M, Po A, Carai A, Marras CE, Antonelli M, Badiali M, Raso A, Mascelli S, Schrimpf D, Stichel D, Tartaglia M, Capper D, von Deimling A, Giangaspero F, Mastronuzzi A, Locatelli F, and Ferretti E
- Subjects
- Adolescent, Child, Child, Preschool, Female, Glioma metabolism, Glioma pathology, Humans, Infant, Male, Mechanistic Target of Rapamycin Complex 1 metabolism, MicroRNAs metabolism, Neoplasm Grading, Phosphatidylinositol 3-Kinases metabolism, Proto-Oncogene Proteins c-akt metabolism, Supratentorial Neoplasms metabolism, Supratentorial Neoplasms pathology, Cell Proliferation genetics, Down-Regulation, Gene Expression Regulation, Neoplastic, Glioma genetics, MicroRNAs genetics, Signal Transduction genetics, Supratentorial Neoplasms genetics
- Abstract
Aims: Paediatric low-grade gliomas (pLGGs) are a heterogeneous group of brain tumours associated with a high overall survival: however, they are prone to recur and supratentorial lesions are difficult to resect, being associated with high percentage of disease recurrence. Our aim was to shed light on the biology of pLGGs., Methods: We performed microRNA profiling on 45 fresh-frozen grade I tumour samples of various histological classes, resected from patients aged ≤16 years. We identified 93 microRNAs specifically dysregulated in tumours as compared to non-neoplastic brain tissue. Pathway analysis of the microRNAs signature revealed PI3K/AKT signalling as one of the centrally enriched oncogenic signalling. To date, activation of the PI3K/AKT pathway in pLGGs has been reported, although activation mechanisms have not been fully investigated yet., Results: One of the most markedly down-regulated microRNAs in our supratentorial pLGGs cohort was miR-139-5p, whose targets include the gene encoding the PI3K's (phosphatidylinositol 3-kinase) catalytic unit, PIK3CA. We investigated the role of miR-139-5p in regulating PI3K/AKT signalling by the use of human cell cultures derived from supratentorial pLGGs. MiR-139-5p overexpression inhibited pLGG cell proliferation and decreased the phosphorylation of PI3K target AKT and phosphorylated-p70 S6 kinase (p-p70 S6K), a hallmark of PI3K/AKT/mTORC1 signalling activation. The effect of miR-139-5p was mediated by PI3K inhibition, as suggested by the decrease in proliferation and phosphorylation of AKT and p70 S6K after treatment with the direct PI3K inhibitor LY294002., Conclusions: These findings provide the first evidence that down-regulation of miR-139-5p in supratentorial pLGG drives cell proliferation by derepressing PI3K/AKT signalling., (© 2018 The Authors. Neuropathology and Applied Neurobiology published by John Wiley & Sons Ltd on behalf of British Neuropathological Society.)
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- 2018
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347. 22q11.2 Deletion Syndrome-Associated Parkinson's Disease.
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Boot E, Bassett AS, and Marras C
- Abstract
Background: 22q11.2 deletion syndrome (22q11.2DS) is a multisystem condition associated with an increased risk of early-onset Parkinson's disease (PD)., Methods: We review the clinical, neuroimaging, and neuropathological observations, as well as diagnostic challenges, of PD in 22q11.2DS. We conducted a search of PubMed up until June 1, 2018 and personal files to identify relevant publications., Results: 22q11.2DS-associated PD is responsible for approximately 0.5% of early-onset PD. The hallmark motor symptoms and neuropathology of PD, and typical findings of reduced striatal dopamine transporter binding with molecular imaging, are present in 22q11.2DS-associated PD. Mean age at PD onset in 22q11.2DS is relatively young (∼40 years). Patients with 22q11.2DS-associated PD show a good response to levodopa., Conclusions: Further recognition of 22q11.2DS and study of PD in people with 22q11.2DS could provide insights into the mechanisms that cause PD in the general population. 22q11.2DS may serve as an identifiable PD model to study prodromal PD and disease-modifying treatments.
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- 2018
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348. Reproducibility of data-driven Parkinson's disease subtypes for clinical research.
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Mestre TA, Eberly S, Tanner C, Grimes D, Lang AE, Oakes D, and Marras C
- Subjects
- Biomarkers blood, Biomedical Research statistics & numerical data, Cohort Studies, Cross-Sectional Studies, Female, Humans, Male, Parkinson Disease blood, Reproducibility of Results, Biomedical Research standards, Data Analysis, Parkinson Disease classification, Parkinson Disease diagnosis
- Abstract
Introduction: PD subtype classification systems attempt to address heterogeneity in PD, a widely recognized feature of the disease with implications in prognosis and therapeutic development. There is no consensus on a valid PD subtype classification system, and its use in clinical research is sparse. Reproducibility has not been systematically assessed as a step for the validation of a PD subtype classification system. We aimed at assessing reproducibility of previously published data-driven PD subtype classification systems in a well-characterized cohort created for clinical research purposes, the Longitudinal and Biomarker Study in Parkinson's Disease (LABS-PD)., Methods: We identified all published studies of data-driven PD subtype classification systems and included those with variables that conceptually matched the variables available in LABS-PD. We reproduced the cluster analyses of the included studies in LABS-PD. Reproducibility was determined by a panel of experts using a modified Delphi consensus process., Results: We included eight studies of data-driven PD subtype classification systems and completed the replication in LABS-PD of the analyses conducted in each original study. After two iterations of the modified Delphi consensus process, no study was reproducible in LABS-PD., Conclusions: Currently published data-driven PD subtype classification systems lack reproducibility in a well-characterized cohort of patients initially recruited for a clinical trial of a disease-modifying intervention. The results raise concerns about the utility of the widely-discussed concept of data-driven PD subtypes. This gap is a barrier for a meaningful use of PD subtypes and calls for the establishment of standards for the validation and use of these subtype classification systems., (Copyright © 2018. Published by Elsevier Ltd.)
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- 2018
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349. Detecting Mild Cognitive Deficits in Parkinson's Disease: Comparison of Neuropsychological Tests.
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Hoogland J, van Wanrooij LL, Boel JA, Goldman JG, Stebbins GT, Dalrymple-Alford JC, Marras C, Adler CH, Junque C, Pedersen KF, Mollenhauer B, Zabetian CP, Eslinger PJ, Lewis SJG, Wu RM, Klein M, Rodriguez-Oroz MC, Cammisuli DM, Barone P, Biundo R, de Bie RMA, Schmand BA, Tröster AI, Burn DJ, Litvan I, Filoteo JV, Geurtsen GJ, and Weintraub D
- Subjects
- Aged, Databases, Bibliographic, Female, Humans, Male, Middle Aged, Cognitive Dysfunction diagnosis, Cognitive Dysfunction etiology, Neuropsychological Tests, Parkinson Disease complications
- Abstract
Background: Numerous neuropsychological tests and test versions are used in Parkinson's disease research, but their relative capacity to detect mild cognitive deficits and their comparability across studies are unknown. The objective of this study was to identify neuropsychological tests that consistently detect cognitive decline in PD across studies., Methods: Data from 30 normed neuropsychological tests across 20 international studies in up to 2908 nondemented PD patients were analyzed. A subset of 17 tests was administered to up to 1247 healthy controls. A 2-step meta-analytic approach using standardized scores compared performance in PD with normative data., Results: Pooled estimates of the differences between PD and site-specific healthy controls identified significant cognitive deficits in PD patients on 14 test scores across 5 commonly assessed cognitive domains (attention or working memory, executive, language, memory, and visuospatial abilities), but healthy control performance was statistically above average on 7 of these tests. Analyses based on published norms only, as opposed to direct assessment of healthy controls, showed high between-study variability that could not be accounted for and led to inconclusive results., Conclusions: Normed neuropsychological tests across multiple cognitive domains consistently detect cognitive deficits in PD when compared with site-specific healthy control performance, but relative PD performance was significantly affected by the inclusion and type of healthy controls versus the use of published norms only. Additional research is needed to identify a cognitive battery that can be administered in multisite international studies and that is sensitive to cognitive decline, responsive to therapeutic interventions, and superior to individual cognitive tests. © 2018 International Parkinson and Movement Disorder Society., (© 2018 International Parkinson and Movement Disorder Society.)
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- 2018
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350. Understanding, Impact, and Communication of "Off" Periods in Parkinson's Disease: A Scoping Review.
- Author
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Rastgardani T, Armstrong MJ, Gagliardi AR, and Marras C
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Background: Off periods are a common and disabling symptom of Parkinson's disease. We reviewed published research on understanding, impact, and communication regarding off periods to identify issues warranting further research., Methods: We performed a scoping review, searching MEDLINE, EMBASE, Cochrane Library, CINAHL, and PsycINFO from 2006 to January 2018 for studies examining the impact of, understanding of, or communication about off periods., Results: Twenty-six papers met eligibility criteria. Twenty-three studies evaluated the impact or experience of off periods in patients, three evaluated the impact upon carepartners, two papers addressed understanding of off periods, one study evaluated communication about off periods, and three studies evaluated a facilitator of communication about off periods. The findings indicate that (1) off periods are among the most troublesome symptoms to patients and that their impact on activities is broad; (2) the understanding of off periods by patients, carepartners, and nurses may be suboptimal; and (3) questionnaires hold promise as a mechanism for facilitating communication given the findings that they may enhance the detection of off periods and are rated as useful by physicians. No studies evaluated interventions to promote knowledge about off periods, and no studies identified barriers of communication about off periods., Conclusions: There is a paucity of knowledge regarding the lived experiences of off periods, particularly for carepartners. Additionally, little knowledge exists in the literature regarding understanding of and communication about off periods between patients or carepartners and treating physicians. Further research is required to explore these issues to ultimately improve the treatment of off periods.
- Published
- 2018
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