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1. Supplemental Material, sj-doc-1-jgp-10.1177_0891988720964250 - Sleep Problems Are Related to a Worse Quality of Life and a Greater Non-Motor Symptoms Burden in Parkinson’s Disease

Author

Santos-García, Diego, Castro, E. Suárez, de Deus Fonticoba, T., Panceiras, M. J. Feal, Enriquez, J. G. Muñoz, González, J. M. Paz, Bartolomé, C. Cores, Planellas, L. L., Caldentey, J. García, Caballol, N., Legarda, I., López, I. Cabo, Manzanares, L. López, Rivera, M. A. Ávila, Catalán, M. J., Nogueira, V., Borrué, C., Sauco, M. Álvarez, Vela, L., Cubo, E., Castrillo, J. C. Martínez, Alonso, P. Sánchez, Losada, M. G. Alonso, Ariztegui, N. López, Gastón, M. I., Kulisevsky, J., Pagonabarraga, J., Seijo, M., Martínez, J. Ruíz, Valero, C., Kurtis, M., Ardura, J. González, Prieto, C., Mir, P., and Martinez-Martin, P.

Subjects
FOS: Psychology, FOS: Clinical medicine, 170199 Psychology not elsewhere classified, 110319 Psychiatry (incl. Psychotherapy), 110308 Geriatrics and Gerontology, 110904 Neurology and Neuromuscular Diseases, Neuroscience
Abstract

Supplemental Material, sj-doc-1-jgp-10.1177_0891988720964250 for Sleep Problems Are Related to a Worse Quality of Life and a Greater Non-Motor Symptoms Burden in Parkinson’s Disease by Diego Santos-García, E. Suárez Castro, T. de Deus Fonticoba, M. J. Feal Panceiras, J. G. Muñoz Enriquez, J. M. Paz González, C. Cores Bartolomé, L. L. Planellas, J. García Caldentey, N. Caballol, I. Legarda, I. Cabo López, L. López Manzanares, M. A. Ávila Rivera, M. J. Catalán, V. Nogueira, C. Borrué, M. Álvarez Sauco, L. Vela, E. Cubo, J. C. Martínez Castrillo, P. Sánchez Alonso, M. G. Alonso Losada, N. López Ariztegui, M. I. Gastón, J. Kulisevsky, J. Pagonabarraga, M. Seijo, J. Ruíz Martínez, C. Valero, M. Kurtis, J. González Ardura, C. Prieto, P. Mir, P. Martinez-Martin and on behalf of the COPPADIS Study Group in Journal of Geriatric Psychiatry and Neurology

Published
2023
Full Text
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2. Supplemental Material, sj-pdf-2-jgp-10.1177_0891988720964250 - Sleep Problems Are Related to a Worse Quality of Life and a Greater Non-Motor Symptoms Burden in Parkinson’s Disease

Author

Santos-García, Diego, Castro, E. Suárez, de Deus Fonticoba, T., Panceiras, M. J. Feal, Enriquez, J. G. Muñoz, González, J. M. Paz, Bartolomé, C. Cores, Planellas, L. L., Caldentey, J. García, Caballol, N., Legarda, I., López, I. Cabo, Manzanares, L. López, Rivera, M. A. Ávila, Catalán, M. J., Nogueira, V., Borrué, C., Sauco, M. Álvarez, Vela, L., Cubo, E., Castrillo, J. C. Martínez, Alonso, P. Sánchez, Losada, M. G. Alonso, Ariztegui, N. López, Gastón, M. I., Kulisevsky, J., Pagonabarraga, J., Seijo, M., Martínez, J. Ruíz, Valero, C., Kurtis, M., Ardura, J. González, Prieto, C., Mir, P., and Martinez-Martin, P.

Subjects
FOS: Psychology, FOS: Clinical medicine, 170199 Psychology not elsewhere classified, 110319 Psychiatry (incl. Psychotherapy), 110308 Geriatrics and Gerontology, 110904 Neurology and Neuromuscular Diseases, Neuroscience
Abstract

Supplemental Material, sj-pdf-2-jgp-10.1177_0891988720964250 for Sleep Problems Are Related to a Worse Quality of Life and a Greater Non-Motor Symptoms Burden in Parkinson’s Disease by Diego Santos-García, E. Suárez Castro, T. de Deus Fonticoba, M. J. Feal Panceiras, J. G. Muñoz Enriquez, J. M. Paz González, C. Cores Bartolomé, L. L. Planellas, J. García Caldentey, N. Caballol, I. Legarda, I. Cabo López, L. López Manzanares, M. A. Ávila Rivera, M. J. Catalán, V. Nogueira, C. Borrué, M. Álvarez Sauco, L. Vela, E. Cubo, J. C. Martínez Castrillo, P. Sánchez Alonso, M. G. Alonso Losada, N. López Ariztegui, M. I. Gastón, J. Kulisevsky, J. Pagonabarraga, M. Seijo, J. Ruíz Martínez, C. Valero, M. Kurtis, J. González Ardura, C. Prieto, P. Mir, P. Martinez-Martin and on behalf of the COPPADIS Study Group in Journal of Geriatric Psychiatry and Neurology

Published
2023
Full Text
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3. Supplemental Material, sj-pdf-1-jgp-10.1177_0891988720964250 - Sleep Problems Are Related to a Worse Quality of Life and a Greater Non-Motor Symptoms Burden in Parkinson’s Disease

Author

Santos-García, Diego, Castro, E. Suárez, de Deus Fonticoba, T., Panceiras, M. J. Feal, Enriquez, J. G. Muñoz, González, J. M. Paz, Bartolomé, C. Cores, Planellas, L. L., Caldentey, J. García, Caballol, N., Legarda, I., López, I. Cabo, Manzanares, L. López, Rivera, M. A. Ávila, Catalán, M. J., Nogueira, V., Borrué, C., Sauco, M. Álvarez, Vela, L., Cubo, E., Castrillo, J. C. Martínez, Alonso, P. Sánchez, Losada, M. G. Alonso, Ariztegui, N. López, Gastón, M. I., Kulisevsky, J., Pagonabarraga, J., Seijo, M., Martínez, J. Ruíz, Valero, C., Kurtis, M., Ardura, J. González, Prieto, C., Mir, P., and Martinez-Martin, P.

Subjects
FOS: Psychology, FOS: Clinical medicine, 170199 Psychology not elsewhere classified, 110319 Psychiatry (incl. Psychotherapy), 110308 Geriatrics and Gerontology, 110904 Neurology and Neuromuscular Diseases, Neuroscience
Abstract

Supplemental Material, sj-pdf-1-jgp-10.1177_0891988720964250 for Sleep Problems Are Related to a Worse Quality of Life and a Greater Non-Motor Symptoms Burden in Parkinson’s Disease by Diego Santos-García, E. Suárez Castro, T. de Deus Fonticoba, M. J. Feal Panceiras, J. G. Muñoz Enriquez, J. M. Paz González, C. Cores Bartolomé, L. L. Planellas, J. García Caldentey, N. Caballol, I. Legarda, I. Cabo López, L. López Manzanares, M. A. Ávila Rivera, M. J. Catalán, V. Nogueira, C. Borrué, M. Álvarez Sauco, L. Vela, E. Cubo, J. C. Martínez Castrillo, P. Sánchez Alonso, M. G. Alonso Losada, N. López Ariztegui, M. I. Gastón, J. Kulisevsky, J. Pagonabarraga, M. Seijo, J. Ruíz Martínez, C. Valero, M. Kurtis, J. González Ardura, C. Prieto, P. Mir, P. Martinez-Martin and on behalf of the COPPADIS Study Group in Journal of Geriatric Psychiatry and Neurology

Published
2023
Full Text
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4. Constipation Predicts Cognitive Decline in Parkinson's Disease: Results from the COPPADIS Cohort at 2-Year Follow-up and Comparison with a Control Group

Author

Santos García D, García Roca L, de Deus Fonticoba T, Cores Bartolomé C, Naya Ríos L, Canfield H, Paz González JM, Martínez Miró C, Jesús S, Aguilar M, Pastor P, Planellas L, Cosgaya M, García Caldentey J, Caballol N, Legarda I, Hernández Vara J, Cabo I, López Manzanares L, González Aramburu I, Ávila Rivera MA, Gómez Mayordomo V, Nogueira V, Puente V, Dotor García-Soto J, Borrué C, Solano Vila B, Álvarez Sauco M, Vela L, Escalante S, Cubo E, Carrillo Padilla F, Martínez Castrillo JC, Sánchez Alonso P, Alonso Losada MG, López Ariztegui N, Gastón I, Kulisevsky J, Blázquez Estrada M, Seijo M, Rúiz Martínez J, Valero C, Kurtis M, de Fábregues O, González Ardura J, Alonso Redondo R, Ordás C, López Díaz L LM, McAfee D, Martinez-Martin P, Mir P, and COPPADIS Study Group

Subjects
impairment, Cognition, Parkinson's disease, constipation, non-motor symptoms
Abstract

Background: Constipation has been linked to cognitive impairment development in Parkinson's disease (PD). Objective: Our aim was to analyze cognitive changes observed in PD patients and controls from a Spanish cohort with regards to the presence or not of constipation. Methods: PD patients and controls recruited from 35 centers of Spain from the COPPADIS cohort from January 2016 to November 2017 were followed-up during 2 years. The change in cognitive status from baseline (V0) to 2-year follow-up was assessed with the PD-CRS (Parkinson's Disease Cognitive Rating Scale). Subjects with a score >= 1 on item 21 of the NMSS (Non-Motor Symptoms Scale) at baseline (V0) were considered as "with constipation". Regression analyses were applied for determining the contribution of constipation in cognitive changes. Results: At V0, 39.7% (198/499) of PD patients presented constipation compared to 11.4% of controls (14/123) (p < 0.0001). No change was observed in cognitive status (PD-CRS total score) neither in controls without constipation (from 100.24 +/- 13.72 to 100.27 +/- 13.68; p = 0.971) and with constipation (from 94.71 +/- 10.96 to 93.93 +/- 13.03; p = 0.615). The PD-CRS total score decreased significantly in PD patients with constipation (from 89.14 +/- 15.36 to 85.97 +/- 18.09; p

Published
2022

5. Predictors of clinically significant quality of life impairment in Parkinson's disease

Author

Garcia D, Fonticoba T, Cores C, Munoz G, Gonzalez J, Miro C, Suarez E, Jesus S, Aguilar M, Pastor P, Planellas L, Cosgaya M, Caldentey J, Caballol N, Legarda I, Vara J, Cabo I, Manzanares L, Aramburu I, Rivera M, Catalan M, Nogueira V, Puente V, de Arcos M, Borrue C, Vila B, Sauco M, Vela L, Escalante S, Cubo E, Padilla F, Castrillo J, Alonso P, Losada M, Ariztegui N, Gaston I, Clavero P, Kulisevsky J, Estrada M, Seijo M, Martinez J, Valero C, Kurtis M, de Fabregues O, Ardura J, Ordas C, Diaz L, McAfee D, Martinez-Martin P, Mir P, and COPPADIS Study Grp

Abstract

Quality of life (QOL) plays an important role in independent living in Parkinson's disease (PD) patients, being crucial to know what factors impact QoL throughout the course of the disease. Here we identified predictors of QoL impairment in PD patients from a Spanish cohort. PD patients recruited from 35 centers of Spain from the COPPADIS cohort from January 2016, to November 2017, were followed up during 2 years. Health-related QoL (HRQoL) and global QoL (GQoL) were assessed with the 39-item Parkinson's disease Questionnaire (PDQ-39) and the EUROHIS-QOL 8-item index (EUROHIS-QOL8), respectively, at baseline (V0) and at 24 months +/- 1 month (V2). Clinically significant QoL impairment was defined as presenting an increase (PDQ-39SI) or decrement (EUROHIS-QOL8) at V2 >= 10% of the score at baseline (V0). A comparison with a control group was conducted for GQoL. GQoL did not change significantly in PD patients (N = 507; p = 0.686) or in the control group (N = 119; p = 0.192). The mean PDQ-39SI was significantly increased in PD patients (62.7 +/- 8.5 years old; 58.8% males; N = 500) by 21.6% (from 16.7 +/- 13 to 20.3 +/- 16.4; p < 0.0001) at V2. Ninety-three patients (18.6%) presented a clinically significant HRQoL impairment at V2. To be younger (OR = 0.896; 95% CI 0.829-0.968; p = 0.006), to be a female (OR = 4.181; 95% CI 1.422-12.290; p = 0.009), and to have a greater increase in BDI-II (Beck Depression Inventory-II) (OR = 1.139; 95% CI 1.053-1.231; p = 0.001) and NMSS (Non-Motor Symptoms Scale) (OR = 1.052; 95% CI 1.027-1.113; p < 0.0001) total scores from V0 to V2 were associated with clinically significant HRQoL impairment at the 2-year follow-up (Hosmer-Lemeshow test, p = 0.665; R-2 = 0.655). An increase in >= 5 and >= 10 points of BDI-II and NMSS total score at V2 multiplied the probability of presenting clinically significant HRQoL impairment by 5 (OR = 5.453; 95% CI 1.663-17.876; p = 0.005) and 8 (OR = 8.217; 95% CI, 2.975-22.696; p = 0.002), respectively. In conclusion, age, gender, mood, and non-motor impairment were associated with clinically significant HRQoL impairment after the 2-year follow-up in PD patients.

Published
2021

6. Investigation of Autosomal Genetic Sex Differences in Parkinson's Disease

Author

Leonard H, Lake J, Kim JJ, Gibbs JR, Ruskey JA, Pihlstrøm L, Eerola-Rautio J, Tienari PJ, Grosset DG, Wood N, Noyce AJ, Middlehurst B, Kia DA, Tan M, Houlden H, Storm CS, Morris HR, Plun-Favreau H, Holmans P, Hardy J, Trabzuni D, Quinn J, Bubb V, Mok KY, Kinghorn KJ, Wood NW, Lewis P, Schreglmann SR, Lovering R, R'Bibo L, Manzoni C, Rizig M, Ryten M, Guelfi S, Escott-Price V, Chelban V, Foltynie T, Williams N, Morrison KE, Clarke C, Harvey K, Jacobs BM, Brice A, Danjou F, Lesage S, Corvol JC, Martinez M, Schulte C, Brockmann K, Simón-Sánchez J, Heutink P, Rizzu P, Sharma M, Gasser T, Schneider SA, Cookson MR, Bandres-Ciga S, Blauwendraat C, Craig DW, Billingsley K, Makarious MB, Narendra DP, Faghri F, Hernandez DG, Van Keuren-Jensen K, Shulman JM, Iwaki H, Leonard HL, Nalls MA, Robak L, Bras J, Guerreiro R, Lubbe S, Troycoco T, Finkbeiner S, Mencacci NE, Lungu C, Singleton AB, Scholz SW, Reed X, Uitti RJ, Ross OA, Grenn FP, Moore A, Alcalay RN, Wszolek ZK, Gan-Or Z, Rouleau GA, Krohn L, Mufti K, van Hilten JJ, Marinus J, Adarmes-Gómez AD, Aguilar M, Alvarez I, Alvarez V, Barrero FJ, Yarza JAB, Bernal-Bernal I, Blazquez M, Bonilla-Toribio M, Botía JA, Boungiorno MT, Buiza-Rueda D, Cámara A, Carrillo F, Carrión-Claro M, Cerdan D, Clarimón J, Compta Y, Diez-Fairen M, Dols-Icardo O, Duarte J, Duran R, Escamilla-Sevilla F, Ezquerra M, Feliz C, Fernández M, Fernández-Santiago R, Garcia C, García-Ruiz P, Gómez-Garre P, Heredia MJG, Gonzalez-Aramburu I, Pagola AG, Hoenicka J, Infante J, Jesús S, Jimenez-Escrig A, Kulisevsky J, Labrador-Espinosa MA, Lopez-Sendon JL, de Munain Arregui AL, Macias D, Torres IM, Marín J, Marti MJ, Martínez-Castrillo JC, Méndez-Del-Barrio C, González MM, Mata M, Mínguez A, Mir P, Rezola EM, Muñoz E, Pagonabarraga J, Pastor P, Errazquin FP, Periñán-Tocino T, Ruiz-Martínez J, Ruz C, Rodriguez AS, Sierra M, Suarez-Sanmartin E, Tabernero C, Tartari JP, Tejera-Parrado C, Tolosa E, Valldeoriola F, Vargas-González L, Vela L, Vives F, Zimprich A, Pihlstrom L, Toft M, Taba P, Koks S, Hassin-Baer S, Majamaa K, Siitonen A, Tienari P, Okubadejo NU, Ojo OO, Kaiyrzhanov R, Shashkin C, Zharkinbekova N, Akhmetzhanov V, Kaishybayeva G, Karimova A, Khaibullin T, Lynch TL, and International Parkinson's Disease Genomics Consortium (IPDGC)

Abstract

OBJECTIVE: Parkinson's disease (PD) is a complex neurodegenerative disorder. Men are on average ~ 1.5 times more likely to develop PD compared to women with European ancestry. Over the years, genomewide association studies (GWAS) have identified numerous genetic risk factors for PD, however, it is unclear whether genetics contribute to disease etiology in a sex-specific manner. METHODS: In an effort to study sex-specific genetic factors associated with PD, we explored 2 large genetic datasets from the International Parkinson's Disease Genomics Consortium and the UK Biobank consisting of 13,020 male PD cases, 7,936 paternal proxy cases, 89,660 male controls, 7,947 female PD cases, 5,473 maternal proxy cases, and 90,662 female controls. We performed GWAS meta-analyses to identify distinct patterns of genetic risk contributing to disease in male versus female PD cases. RESULTS: In total, 19 genomewide significant regions were identified and no sex-specific effects were observed. A high genetic correlation between the male and female PD GWAS were identified (rg = 0.877) and heritability estimates were identical between male and female PD cases (~ 20%). INTERPRETATION: We did not detect any significant genetic differences between male or female PD cases. Our study does not support the notion that common genetic variation on the autosomes could explain the difference in prevalence of PD between males and females cases at least when considering the current sample size under study. Further studies are warranted to investigate the genetic architecture of PD explained by X and Y chromosomes and further evaluate environmental effects that could potentially contribute to PD etiology in male versus female patients. ANN NEUROL 2021;90:41-48.

Published
2021

7. Predictors of clinically significant quality of life impairment in Parkinson's disease

Author

Garcia, DS, Fonticoba, TD, Cores, C, Munoz, G, Gonzalez, JMP, Miro, CM, Suarez, E, Jesus, S, Aguilar, M, Pastor, P, Planellas, L, Cosgaya, M, Caldentey, JG, Caballol, N, Legarda, I, Vara, JH, Cabo, I, Manzanares, LL, Aramburu, IG, Rivera, MAA, Catalan, MJ, Nogueira, V, Puente, V, de Arcos, MR, Borrue, C, Vila, BS, Sauco, MA, Vela, L, Escalante, S, Cubo, E, Padilla, FC, Castrillo, JCM, Alonso, PS, Losada, MGA, Ariztegui, NL, Gaston, I, Clavero, P, Kulisevsky, J, Estrada, MB, Seijo, M, Martinez, JR, Valero, C, Kurtis, M, de Fabregues, O, Ardura, JG, Ordas, C, Diaz, LML, McAfee, D, Martinez-Martin, P, and Mir, P

Subjects
humanities
Abstract

Quality of life (QOL) plays an important role in independent living in Parkinson's disease (PD) patients, being crucial to know what factors impact QoL throughout the course of the disease. Here we identified predictors of QoL impairment in PD patients from a Spanish cohort. PD patients recruited from 35 centers of Spain from the COPPADIS cohort from January 2016, to November 2017, were followed up during 2 years. Health-related QoL (HRQoL) and global QoL (GQoL) were assessed with the 39-item Parkinson's disease Questionnaire (PDQ-39) and the EUROHIS-QOL 8-item index (EUROHIS-QOL8), respectively, at baseline (V0) and at 24 months +/- 1 month (V2). Clinically significant QoL impairment was defined as presenting an increase (PDQ-39SI) or decrement (EUROHIS-QOL8) at V2 >= 10% of the score at baseline (V0). A comparison with a control group was conducted for GQoL. GQoL did not change significantly in PD patients (N = 507; p = 0.686) or in the control group (N = 119; p = 0.192). The mean PDQ-39SI was significantly increased in PD patients (62.7 +/- 8.5 years old; 58.8% males; N = 500) by 21.6% (from 16.7 +/- 13 to 20.3 +/- 16.4; p < 0.0001) at V2. Ninety-three patients (18.6%) presented a clinically significant HRQoL impairment at V2. To be younger (OR = 0.896; 95% CI 0.829-0.968; p = 0.006), to be a female (OR = 4.181; 95% CI 1.422-12.290; p = 0.009), and to have a greater increase in BDI-II (Beck Depression Inventory-II) (OR = 1.139; 95% CI 1.053-1.231; p = 0.001) and NMSS (Non-Motor Symptoms Scale) (OR = 1.052; 95% CI 1.027-1.113; p < 0.0001) total scores from V0 to V2 were associated with clinically significant HRQoL impairment at the 2-year follow-up (Hosmer-Lemeshow test, p = 0.665; R-2 = 0.655). An increase in >= 5 and >= 10 points of BDI-II and NMSS total score at V2 multiplied the probability of presenting clinically significant HRQoL impairment by 5 (OR = 5.453; 95% CI 1.663-17.876; p = 0.005) and 8 (OR = 8.217; 95% CI, 2.975-22.696; p = 0.002), respectively. In conclusion, age, gender, mood, and non-motor impairment were associated with clinically significant HRQoL impairment after the 2-year follow-up in PD patients.

Published
2021

8. Mood in Parkinson's disease: From early- to late-stage disease

Author

Santos-Garcia D, De Deus F, Cores B, Valdes A, Suarez C, Aneiros A, Jesus S, Aguilar M, Pastor P, Planellas L, Cosgaya M, Garcia C, Caballol N, Legarda I, Hernandez V, Cabo I, Lopez M, Gonzalez A, Avila R, Jose C, Nogueira V, Puente V, Garcia M, Borrue C, Solano V, Alvarez S, Vela L, Escalante S, Cubo E, Carrillo P, Martinez C, Sanchez A, Alonso L, Lopez A, Gaston I, Kulisevsky J, Blazquez E, Seijo M, Ruiz M, Valero C, Kurtis M, de Fabregues-Boixar O, Prieto J, Lopez D, McAfee D, Mir P, and COPPADIS Study Grp

Subjects
s disease, quality of life, mood, depression, disease duration, Parkinson&apos, Parkinson's disease
Abstract

BACKGROUND: Although depression is known to be frequent in Parkinson's disease (PD), it is unclear how mood can change and/or impact on patient's quality of life (QoL) over time. Our aim was to analyze the frequency of depression, mood related factors and the contribution of mood to a patient's QoL perception in regard to disease duration. METHODS: PD patients recruited from the COPPADIS cohort from January 2016 to November 2017 were included in this cross-sectional study. Three groups were defined

Published
2021

9. Diplopia Is Frequent and Associated with Motor and Non-Motor Severity in Parkinson’s Disease: Results from the COPPADIS Cohort at 2-Year Follow-Up

Author

Garcia D, Rios L, Fonticoba T, Bartolome C, Roca L, Painceiras M, Miro C, Canfield H, Jesus S, Aguilar M, Pastor P, Cosgaya M, Caldentey J, Caballol N, Legarda I, Vara J, Cabo I, Manzanares L, Aramburu I, Rivera M, Mayordomo V, Nogueira V, Puente V, Dotor J, Borrue C, Vila B, Sauco M, Vela L, Escalante S, Cubo E, Padilla F, Castrillo J, Alonso P, Losada M, Ariztegui N, Gaston I, Kulisevsky J, Estrada M, Seijo M, Martinez J, Valero C, Kurtis M, de Fabregues O, Ardura J, Redondo R, Ordas C, Diaz L, McAfee D, Martinez-Martin P, Mir P, COPPADIS Study Grp, Instituto de Salud Carlos III, Takeda Pharmaceutical Company, International Parkinson and Movement Disorder Society, AbbVie Pharmaceuticals, Abbott Laboratories, Allergan Foundation, BIAL Foundation, Merz Pharma, UCB Pharma, Zambon, Ministerio de Economía y Competitividad (España), European Commission, Junta de Andalucía, Sociedad Andaluza de Neurología, Jacques and Gloria Gossweiler Foundation, Fundación Alicia Koplowitz, Fundación Mutua Madrileña, Institut Català de la Salut, [Santos-García D, Naya Rios L, Cores Bartolomé C, García Roca L, Feal Painceiras M, Martínez Miró C] Complejo Hospitalario Universitario de A Coruña (CHUAC), A Coruña, Spain. [de Deus Fonticoba T, Canfield H] Complejo Hospitalario Universitario de Ferrol (CHUF), A Coruña, Spain. [Jesús S, Mir P] Unidad de Trastornos del Movimiento, Servicio de Neurología y Neurofisiología Clínica, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío, Universidad de Sevilla, Sevilla, Spain. Centro de Investigación Biomédica en Red Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain. [Aguilar M, Pastor P] Hospital Universitari Mutua de Terrassa, Terrassa , Spain. [Cosgaya M] Hospital Clínic de Barcelona, Barcelona, Spain. [García-Caldentey J] Centro Neurológico Oms, Palma de Mallorca, Spain. [Caballol N] Consorci Sanitari Integral, Hospital Moisés Broggi, Barcelona, Spain. [Legarda I] Hospital Universitari Son Espases, Palma de Mallorca, Spain. [Hernández-Vara J, de Fábregues O] Vall d'Hebron Hospital Universitari, Barcelona, Spain. [Cabo López I, Seijo M] Complexo Hospitalario Universitario de Pontevedra (CHOP), Pontevedra, Spain. [López Manzanares L] Hospital Universitario La Princesa, Madrid, Spain. [González Aramburu I] Centro de Investigación Biomédica en Red Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain. Hospital Universitario Marqués de Valdecilla, Santander, Spain. [Ávila Rivera MA] Consorci Sanitari Integral, Hospital General de L'Hospitalet, L'Hospitalet de Llobregat, Spain. [Gómez-Mayordomo V] Hospital Universitario Clínico San Carlos, Madrid, Spain. [Nogueira V] Hospital Da Costa, Burela, Lugo, Spain. [Puente V] Hospital del Mar, Barcelona, Spain. [Dotor J] Hospital Universitario Virgen Macarena, Sevilla, Spain. [Borrué C] Hospital Infanta Sofía, Madrid, Spain. [Solano Vila B] Institut d'Assistència Sanitària (IAS), Institut Català de la Salut (ICS), Salt, Spain. [Álvarez Sauco M] Hospital General Universitario de Elche, Elche, Spain. [Vela-Desojo L] Fundación Hospital de Alcorcón, Madrid, Spain. [Escalante S] Hospital de Tortosa Verge de la Cinta (HTVC), Tortosa, Spain. [Cubo E] Complejo Asistencial Universitario de Burgos, Burgos, Spain. [Carrillo-Padilla F] Hospital Universitario de Canarias, Santa Cruz de Tenerife, Spain. [Martínez Castrillo JC] Hospital Universitario Ramón y Cajal, IRYCIS, Madrid, Spain. [Sánchez Alonso P] Hospital Universitario Puerta de Hierro, Madrid, Spain. [Alonso Losada MG] Hospital Álvaro Cunqueiro, Complexo Hospitalario Universitario de Vigo (CHUVI), Vigo, Spain. [López-Ariztegui N] Complejo Hospitalario de Toledo, Toledo, Spain. [Gastón I] Complejo Hospitalario de Navarra, Pamplona, Spain. [Kulisevsky J] Centro de Investigación Biomédica en Red Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain. Hospital de Sant Pau, Barcelona, Spain. [Blázquez Estrada M] Hospital Universitario Central de Asturias, Oviedo, Spain. [Ruiz-Martínez J] Hospital Universitario Donostia, San Sebastián, Spain. [Valero C] Hospital Arnau de Vilanova, València, Spain. [Kurtis M] Hospital Ruber Internacional, Madrid, Spain. [González Ardura J] Hospital de Cabueñes, Gijón, Spain. [Alonso Redondo R] Universitario Lucus Augusti (HULA), Lugo, Spain. [Ordás C] Hospital Rey Juan Carlos, Madrid, Spain. [López Díaz LM] Complexo Hospitalario Universitario de Ourense (CHUO), Ourense, Spain. [McAfee D] University of Maryland School of Medicine, Baltimore, USA. [Martinez-Martin P] Centro de Investigación Biomédica en Red Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain, and Institut d'Assistència Sanitària

Subjects
enfermedades del sistema nervioso::enfermedades del sistema nervioso central::enfermedades del sistema nervioso::enfermedades del sistema nervioso central::trastornos del movimiento::trastornos parkinsonianos::enfermedades del sistema nervioso::enfermedad de Parkinson [ENFERMEDADES], Medicine (General), changes, motor, Parkinson’s disease, phenotype, PIGD, Tremor, endocrine system diseases, genetic structures, Parkinson's disease, Clinical Biochemistry, Tremolor, Nervous System Diseases::Central Nervous System Diseases::Nervous System Diseases::Central Nervous System Diseases::Movement Disorders::Parkinsonian Disorders::Nervous System Diseases::Parkinson Disease [DISEASES], enfermedades del sistema nervioso::manifestaciones neurológicas::discinesias::temblor [ENFERMEDADES], Article, eye diseases, Fenotip, R5-920, Genetic Phenomena::Phenotype [PHENOMENA AND PROCESSES], Parkinson, Malaltia de, fenómenos genéticos::fenotipo [FENÓMENOS Y PROCESOS], Pathological Conditions, Signs and Symptoms::Signs and Symptoms::Neurologic Manifestations::Dyskinesias::Tremor [DISEASES]
Abstract

[Background and objective] Diplopia is relatively common in Parkinson’s disease (PD) but is still understudied. Our aim was to analyze the frequency of diplopia in PD patients from a multicenter Spanish cohort, to compare the frequency with a control group, and to identify factors associated with it., [Patients and Methods] PD patients who were recruited from January 2016 to November 2017 (baseline visit; V0) and evaluated again at a 2-year ± 30 days follow-up (V2) from 35 centers of Spain from the COPPADIS cohort were included in this longitudinal prospective study. The patients and controls were classified as “with diplopia” or “without diplopia” according to item 15 of the Non-Motor Symptoms Scale (NMSS) at V0, V1 (1-year ± 15 days), and V2 for the patients and at V0 and V2 for the controls., [Results] The frequency of diplopia in the PD patients was 13.6% (94/691) at V0 (1.9% in controls [4/206]; p < 0.0001), 14.2% (86/604) at V1, and 17.1% (86/502) at V2 (0.8% in controls [1/124]; p < 0.0001), with a period prevalence of 24.9% (120/481). Visual hallucinations at any visit from V0 to V2 (OR = 2.264; 95%CI, 1.269–4.039; p = 0.006), a higher score on the NMSS at V0 (OR = 1.009; 95%CI, 1.012–1.024; p = 0.015), and a greater increase from V0 to V2 on the Unified Parkinson’s Disease Rating Scale–III (OR = 1.039; 95%CI, 1.023–1.083; p < 0.0001) and Neuropsychiatric Inventory (OR = 1.028; 95%CI, 1.001–1.057; p = 0.049) scores were independent factors associated with diplopia (R2 = 0.25; Hosmer and Lemeshow test, p = 0.716)., [Conclusions] Diplopia represents a frequent symptom in PD patients and is associated with motor and non-motor severity., Martínez-Martin P. has received honoraria from National School of Public Health (ISCIII), Editori-al Viguera and Takeda Pharmaceuticals for lecturing in courses, and from the International Parkinson and Movement Disorder Society (MDS) for management of the Program on Rating Scales. Mir P. has received honoraria from AbbVie, Abbott, Allergan, Bial, Merz, UCB, and Zambon and have received grants from the Spanish Ministry of Economy and Competitiveness [PI16/01575], co-founded by ISCIII (Subdirección General de Evaluación y Fomento de la Investigación) and by Fondo Europeo de Desarrollo Regional (FEDER), the Consejería de Economía, Innovación, Ciencia y Empleo de la Junta de Andalucía [CVI-02526, CTS-7685], the Consejería de Salud y Bienestar Social de la Junta de Andalucía [ PI-0437-2012, PI-0471-2013], the Sociedad Andaluza de Neurología, the Jacques and Gloria Gossweiler Foundation, the Fundación Alicia Koplowitz, the Fundación Mutua Madrileña.

Published
2021

10. Supplemental Material, Table.1.SM.Sleep.Problems.PD.COPPADIS - Sleep Problems Are Related to a Worse Quality of Life and a Greater Non-Motor Symptoms Burden in Parkinson’s Disease

Author

Santos-García, Diego, Castro, E. Suárez, de Deus Fonticoba, T., Panceiras, M. J. Feal, Enriquez, J. G. Muñoz, González, J. M. Paz, Bartolomé, C. Cores, Planellas, L. L., Caldentey, J. García, Caballol, N., Legarda, I., López, I. Cabo, Manzanares, L. López, Rivera, M. A. Ávila, Catalán, M. J., Nogueira, V., Borrué, C., Sauco, M. Álvarez, Vela, L., Cubo, E., Castrillo, J. C. Martínez, Alonso, P. Sánchez, Losada, M. G. Alonso, Ariztegui, N. López, Gastón, M. I., Kulisevsky, J., Pagonabarraga, J., Seijo, M., Martínez, J. Ruíz, Valero, C., Kurtis, M., Ardura, J. González, Prieto, C., Mir, P., and Martinez-Martin, P.

Subjects
FOS: Psychology, FOS: Clinical medicine, 170199 Psychology not elsewhere classified, 110319 Psychiatry (incl. Psychotherapy), 110308 Geriatrics and Gerontology, 110904 Neurology and Neuromuscular Diseases, Neuroscience
Abstract

Supplemental Material, Table.1.SM.Sleep.Problems.PD.COPPADIS for Sleep Problems Are Related to a Worse Quality of Life and a Greater Non-Motor Symptoms Burden in Parkinson’s Disease by Diego Santos-García, E. Suárez Castro, T. de Deus Fonticoba, M. J. Feal Panceiras, J. G. Muñoz Enriquez, J. M. Paz González, C. Cores Bartolomé, L. L. Planellas, J. García Caldentey, N. Caballol, I. Legarda, I. Cabo López, L. López Manzanares, M. A. Ávila Rivera, M. J. Catalán, V. Nogueira, C. Borrué, M. Álvarez Sauco, L. Vela, E. Cubo, J. C. Martínez Castrillo, P. Sánchez Alonso, M. G. Alonso Losada, N. López Ariztegui, M. I. Gastón, J. Kulisevsky, J. Pagonabarraga, M. Seijo, J. Ruíz Martínez, C. Valero, M. Kurtis, J. González Ardura, C. Prieto, P. Mir, P. Martinez-Martin and on behalf of the COPPADIS Study Group in Journal of Geriatric Psychiatry and Neurology

Published
2020
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11. Quality of life and non-motor symptoms in Parkinson's disease patients with subthreshold depression

Author

Santos-Garcia, D, Fonticoba, TD, Castro, ES, Diaz, AA, Bartolome, CC, Panceiras, MJF, Gonzalez, JMP, Aymerich, LV, Moreno, JMG, Estrada, MB, Jesus, S, Mir, P, Aguilar, M, Planellas, L, Caldentey, JG, Caballol, N, Legarda, I, Lopez, IC, Manzanares, LL, Rivera, MAA, Catalan, MJ, Diaz, LML, Borrue, C, Sauco, MA, Vela, L, Cubo, E, Castrillo, JCM, Alonso, PS, Losada, MGA, Ariztegui, NL, Gaston, I, Pascual-Sedano, B, Seijo, M, Martinez, JR, Valero, C, Kurtis, M, Ardura, JG, Jurczynska, CP, Martinez-Martin, P, and COPPADIS Study Grp

Subjects
Quality of life, Depression, Parkinson's disease, Mood, Non-motor symptoms
Abstract

Background: The role of subthreshold depression (subD) in Parkinson's Disease (PD) is not clear. The present study aimed to compare the quality of life (QoL) in PD patients with subD vs patients with no depressive disorder (nonD). Factors related to subD were identified. Material and methods: PD patients and controls recruited from the COPPADIS cohort were included. SubD was defined as Judd criteria. The 39-item Parkinson's disease Questionnaire (PDQ-39) and the EUROHIS-QOL 8-item index (EUROHIS-QOL8) were used to assess QoL. Results: The frequency of depressive symptoms was higher in PD patients (n = 694) than in controls (n = 207) (p < 0.0001): major depression, 16.1% vs 7.8%; minor depression, 16.7% vs 7.3%; subD, 17.4% vs 5.8%. Both health-related QoL (PDQ-39; 18.1 +/- 12.8 vs 11.6 +/- 10; p < 0.0001) and global QoL (EUROHIS-QOL8; 3.7 +/- 0.5 vs 4 +/- 0.5; p < 0.0001) were significantly worse in subD (n = 120) than nonD (n = 348) PD patients. Non-motor Symptoms Scale (NMSS) total score was higher in subD patients (45.9 +/- 32 vs 29.1 +/- 25.8;p < 0.0001). Non-motor symptoms burden (NMSS;OR = 1.019;95%CI 1.011-1.028; p < 0.0001), neuropsychiatric symptoms (NPI; OR = 1.091; 95%CI 1.045-1.139; p < 0.0001), impulse control behaviors (QUIP-RS; OR = 1.035; 95%CI 1.007-1063; p = 0.013), quality of sleep (PDSS; OR = 0.991; 95%CI 0.983-0.999; p = 0.042), and fatigue (VAFS-physical; OR = 1.185; 95%CI 1.086-1.293; p < 0.0001; VAFS-mental; OR = 1.164; 95%CI 1.058-1.280; p = 0.0001) were related to subD after adjustment to age, disease duration, daily equivalent levodopa dose, motor status (UPDRS-III), and living alone. Conclusions: SubD is a frequent problem in patients with PD and is more prevalent in these patients than in controls. QoL is worse and non-motor symptoms burden is greater in subD PD patients.

Published
2020

12. Supplemental Material, Table.2.SM.Sleep.Problems.PD.COPPADIS - Sleep Problems Are Related to a Worse Quality of Life and a Greater Non-Motor Symptoms Burden in Parkinson’s Disease

Author

Santos-García, Diego, Castro, E. Suárez, de Deus Fonticoba, T., Panceiras, M. J. Feal, Enriquez, J. G. Muñoz, González, J. M. Paz, Bartolomé, C. Cores, Planellas, L. L., Caldentey, J. García, Caballol, N., Legarda, I., López, I. Cabo, Manzanares, L. López, Rivera, M. A. Ávila, Catalán, M. J., Nogueira, V., Borrué, C., Sauco, M. Álvarez, Vela, L., Cubo, E., Castrillo, J. C. Martínez, Alonso, P. Sánchez, Losada, M. G. Alonso, Ariztegui, N. López, Gastón, M. I., Kulisevsky, J., Pagonabarraga, J., Seijo, M., Martínez, J. Ruíz, Valero, C., Kurtis, M., Ardura, J. González, Prieto, C., Mir, P., and Martinez-Martin, P.

Subjects
FOS: Psychology, FOS: Clinical medicine, 170199 Psychology not elsewhere classified, 110319 Psychiatry (incl. Psychotherapy), 110308 Geriatrics and Gerontology, 110904 Neurology and Neuromuscular Diseases, Neuroscience
Abstract

Supplemental Material, Table.2.SM.Sleep.Problems.PD.COPPADIS for Sleep Problems Are Related to a Worse Quality of Life and a Greater Non-Motor Symptoms Burden in Parkinson’s Disease by Diego Santos-García, E. Suárez Castro, T. de Deus Fonticoba, M. J. Feal Panceiras, J. G. Muñoz Enriquez, J. M. Paz González, C. Cores Bartolomé, L. L. Planellas, J. García Caldentey, N. Caballol, I. Legarda, I. Cabo López, L. López Manzanares, M. A. Ávila Rivera, M. J. Catalán, V. Nogueira, C. Borrué, M. Álvarez Sauco, L. Vela, E. Cubo, J. C. Martínez Castrillo, P. Sánchez Alonso, M. G. Alonso Losada, N. López Ariztegui, M. I. Gastón, J. Kulisevsky, J. Pagonabarraga, M. Seijo, J. Ruíz Martínez, C. Valero, M. Kurtis, J. González Ardura, C. Prieto, P. Mir, P. Martinez-Martin and on behalf of the COPPADIS Study Group in Journal of Geriatric Psychiatry and Neurology

Published
2020
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13. Regulatory sites for splicing in human basal ganglia are enriched for disease-relevant information

Author

Guelfi S., D’Sa K., Botía J.A., Vandrovcova J., Reynolds R.H., Zhang D., Trabzuni D., Collado-Torres L., Thomason A., Quijada Leyton P., Gagliano Taliun S.A., Nalls M.A., Noyce A.J., Nicolas A., Cookson M.R., Bandres-Ciga S., Gibbs J.R., Hernandez D.G., Singleton A.B., Reed X., Leonard H., Blauwendraat C., Faghri F., Bras J., Guerreiro R., Tucci A., Kia D.A., Houlden H., Plun-Favreau H., Mok K.Y., Wood N.W., Lovering R., R’Bibo L., Rizig M., Chelban V., Tan M., Morris H.R., Middlehurst B., Quinn J., Billingsley K., Holmans P., Kinghorn K.J., Lewis P., Escott-Price V., Williams N., Foltynie T., Brice A., Danjou F., Lesage S., Corvol J.-C., Martinez M., Giri A., Schulte C., Brockmann K., Simón-Sánchez J., Heutink P., Gasser T., Rizzu P., Sharma M., Shulman J.M., Robak L., Lubbe S., Mencacci N.E., Finkbeiner S., Lungu C., Scholz S.W., Gan-Or Z., Rouleau G.A., Krohan L., van Hilten J.J., Marinus J., Adarmes-Gómez A.D., Bernal-Bernal I., Bonilla-Toribio M., Buiza-Rueda D., Carrillo F., Carrión-Claro M., Mir P., Gómez-Garre P., Jesús S., Labrador-Espinosa M.A., Macias D., Vargas-González L., Méndez-del-Barrio C., Periñán-Tocino T., Tejera-Parrado C., Diez-Fairen M., Aguilar M., Alvarez I., Boungiorno M.T., Carcel M., Pastor P., Tartari J.P., Alvarez V., González M.M., Blazquez M., Garcia C., Suarez-Sanmartin E., Barrero F.J., Rezola E.M., Yarza J.A.B., Pagola A.G., Arregui A.L.M., Ruiz-Martínez J., Cerdan D., Duarte J., Clarimón J., Dols-Icardo O., Infante J., Marín J., Kulisevsky J., Pagonabarraga J., Gonzalez-Aramburu I., Rodriguez A.S., Sierra M., Duran R., Ruz C., Vives F., Escamilla-Sevilla F., Mínguez A., Cámara A., Compta Y., Ezquerra M., Marti M.J., Fernández M., Muñoz E., Fernández-Santiago R., Tolosa E., Valldeoriola F., García-Ruiz P., Heredia M.J.G., Errazquin F.P., Hoenicka J., Jimenez-Escrig A., Martínez-Castrillo J.C., Lopez-Sendon J.L., Torres I.M., Tabernero C., Vela L., Zimprich A., Pihlstrom L., Koks S., Taba P., Majamaa K., Siitonen A., Okubadejo N.U., Ojo O.O., Forabosco P., Walker R., Small K.S., Smith C., Ramasamy A., Hardy J., Weale M.E., and Ryten M.

Subjects
medicine, RNA splicing, phenotype, brain, genotype, Quantitative Trait Loci, genetic analysis, Polymorphism, Single Nucleotide, Article, genetic regulation, mental disease, transcriptomics, quantitative trait locus, expression quantitative trait locus, single nucleotide polymorphism, Humans, genetics, human, reproducibility, Alleles, Neurons, genome-wide association study, human cell, allele, Putamen, Reproducibility of Results, RNA sequencing, Parkinson Disease, gene expression regulation, cell, cohort analysis, neurologic disease, human tissue, schizophrenia, Substantia Nigra, disease incidence, physiology, gene expression, RNA, physiological response, Nervous System Diseases, nerve cell, Transcriptome, nervous system disorder, basal ganglion
Abstract

Genome-wide association studies have generated an increasing number of common genetic variants associated with neurological and psychiatric disease risk. An improved understanding of the genetic control of gene expression in human brain is vital considering this is the likely modus operandum for many causal variants. However, human brain sampling complexities limit the explanatory power of brain-related expression quantitative trait loci (eQTL) and allele-specific expression (ASE) signals. We address this, using paired genomic and transcriptomic data from putamen and substantia nigra from 117 human brains, interrogating regulation at different RNA processing stages and uncovering novel transcripts. We identify disease-relevant regulatory loci, find that splicing eQTLs are enriched for regulatory information of neuron-specific genes, that ASEs provide cell-specific regulatory information with evidence for cellular specificity, and that incomplete annotation of the brain transcriptome limits interpretation of risk loci for neuropsychiatric disease. This resource of regulatory data is accessible through our web server, http://braineacv2.inf.um.es/. © 2020, The Author(s).

Published
2020

14. Sleep Problems Are Related to a Worse Quality of Life and a Greater Non-Motor Symptoms Burden in Parkinson's Disease

Author

Santos-Garcia, D, Castro, E, Fonticoba, T, Panceiras, M, Enriquez, J, Gonzalez, J, Bartolome, C, Planellas, L, Caldentey, J, Caballol, N, Legarda, I, Lopez, I, Manzanares, L, Rivera, M, Catalan, M, Nogueira, V, Borrue, C, Sauco, M, Vela, L, Cubo, E, Castrillo, J, Alonso, P, Losada, M, Ariztegui, N, Gaston, M, Kulisevsky, J, Pagonabarraga, J, Seijo, M, Martinez, J, Valero, C, Kurtis, M, Ardura, J, Prieto, C, Mir, P, Martinez-Martin, P, and COPPADIS Study Grp

Subjects
Parkinson's disease sleep scale, quality of life, Parkinson's disease, sleep, non-motor symptoms
Abstract

Introduction: The aim of the present study was to examine the frequency of self-reported sleep problems and their associated factors in a large cohort of PD patients. Methods: PD patients and controls, recruited from 35 centers of Spain from the COPPADIS cohort were included in this cross-sectional study. Sleep problems were assessed by the Spanish version of the Parkinson's disease Sleep Scale version 1 (PDSS-1). An overall score below 82 or a score below 5 on at least 1 item was defined as sleep problems. Results: The frequency of sleep problems was nearly double in PD patients compared to controls: 65.8% (448/681) vs 33.5% (65/206) (p < 0.0001). Mean total PDSS score was lower in PD patients than controls: 114.9 +/- 28.8 vs 132.8 +/- 16.3 (p < 0.0001). Quality of life (QoL) was worse in PD patients with sleep problems compared to those without: PDQ-39SI, 19.3 +/- 14 vs 13 +/- 11.6 (p < 0.0001); EUROHIS-QoL8, 3.7 +/- 0.5 vs 3.9 +/- 0.5 (p < 0.0001). Non-motor symptoms burden (NMSS; OR = 1.029; 95%CI 1.015-1.043; p < 0.0001) and impulse control behaviors (QUIP-RS; OR = 1.054; 95%CI 1.009-1.101; p = 0.018) were associated with sleep problems after adjustment for age, gender, disease duration, daily equivalent levodopa dose, H&Y, UPDRS-III, UPDRS-IV, PD-CRS, BDI-II, NPI, VAS-Pain, VAFS, FOGQ, and total number of non-antiparkinsonian treatments. Conclusion: Sleep problems were frequent in PD patients and were related to both a worse QoL and a greater non-motor symptoms burden in PD. These findings call for increased awareness of sleep problems in PD patients.

Published
2020

15. SNCA and mTOR Pathway Single Nucleotide Polymorphisms Interact to Modulate the Age at Onset of Parkinson's Disease

Author

Fernandez-Santiago, R., Martin-Flores, N., Antonelli, F., Cerquera, C., Moreno, V., Bandres-Ciga, S., Manduchi, E., Tolosa, E., Singleton, A.B., Moore, J.H., Noyce, A.J., Kaiyrzhanov, R., Middlehurst, B., Kia, D.A., Tan, M., Houlden, H., Morris, H.R., Plun-Favreau, H., Holmans, P., Hardy, J., Trabzuni, D., Bras, J., Quinn, J., Mok, K.Y., Kinghorn, K.J., Billingsley, K., Wood, N.W., Lewis, P., Schreglmann, S., Guerreiro, R., Lovering, R., R'Bibo, L., Manzoni, C., Rizig, M., Ryten, M., Guelfi, S., Escott-Price, V., Chelban, V., Foltynie, T., Williams, N., Morrison, K.E., Clarke, C., Brice, A., Danjou, F., Lesage, S., Corvol, J.C., Martinez, M., Schulte, C., Brockmann, K., Simoon-Saanchez, J., Heutink, P., Rizzu, P., Sharma, M., Gasser, T., Nicolas, A., Cookson, M.R., Blauwendraat, C., Craig, D.W., Faghri, F., Gibbs, J.R., Hernandez, D.G., Keuren-Jensen, K. van, Shulman, J.M., Iwaki, H., Leonard, H.L., Nalls, M.A., Robak, L., Lubbe, S., Finkbeiner, S., Mencacci, N.E., Lungu, C., Scholz, S.W., Reed, X., Alcalay, R.N., Gan-Or, Z., Rouleau, G.A., Krohn, L., Hilten, J.J. van, Marinus, J., Adarmes-Goomez, A.D., Aguilar, I., Alvarez, I., Alvarez, V., Barrero, F.J., Yarza, J.A.B., Bernal-Bernal, I., Blazquez, M., Bonilla-Toribio, M., Botia, J.A., Boungiorno, M.T., Buiza-Rueda, D., Camara, A., Carrillo, F., Carrion-Claro, M., Cerdan, D., Clarimon, J., Compta, Y., Casa, B. de la, Diez-Fairen, M., Dols-Icardo, O., Duarte, J., Duran, R., Escamilla-Sevilla, F., Ezquerra, M., Feliz, C., Fernandez, M., Garcia, C., Garcia-Ruiz, P., Gomez-Garre, P., Heredia, M.J.G., Gonzalez-Aramburu, I., Pagola, A.G., Hoenicka, J., Infante, J., Jesus, S., Jimenez-Escrig, A., Kulisevsky, J., Labrador-Espinosa, M.A., Lopez-Sendon, J.L., Arregui, A.L.D., Macias, D., Torres, I.M., Marin, J., Marti, M.J., Martinez-Castrillo, C., Mendez-del-Barrio, C., Gonzalez, M.M., Mata, M., Minguez, A., Mir, P., Rezola, E.M., Munoz, E., Pagonabarraga, J., Pascual-Sedano, B., Pastor, P., Errazquin, F.P., Perinan-Tocino, T., Ruiz-Martinez, J., Ruz, C., Rodriguez, A.S., Sierra, M., Suarez-Sanmartin, E., Tabernero, C., Tartari, J.P., Tejera-Parrado, C., Valldeoriola, F., Vargas-Gonzalez, L., Vela, L., Vives, F., Zimprich, A., Pihlstrom, L., Toft, M., Koks, S., Taba, P., Hassin-Baer, S., Malagelada, C., Int Parkinson's Dis Genomics Conso, Fundació La Marató de TV3, Michael J. Fox Foundation for Parkinson's Research, National Institutes of Health (US), Ministerio de Economía y Competitividad (España), Agencia Estatal de Investigación (España), and Ministerio de Ciencia, Innovación y Universidades (España)

Subjects
0301 basic medicine, epistasis, Male, Parkinson's disease, very elderly, alpha-synuclein, Alpha‐synuclein, regulatory associated protein of mTOR, Cohort Studies, 0302 clinical medicine, single nucleotide polymorphism, genetics, Age of Onset, Genetics, Aged, 80 and over, Polymorphism, Single Nucleoti, biology, TOR Serine-Threonine Kinases, target of rapamycin kinase, fchsd1 gene, Age at onset, Chromosome Mapping, glycogen synthase kinase 3beta, Parkinson Disease, Middle Aged, cohort analysis, LRRK2, priority journal, Neurology, chromosomal mapping, neuromodulation, mTOR, alpha-Synuclein, Female, age at onset, Signal Transduction, onset age, Adult, MTOR protein, human, protein kinase LKB1, gene locus, Genotype, multifactor dimensionality reduction, SNP, Single-nucleotide polymorphism, rps6ka2 gene, Polymorphism, Single Nucleotide, Risk Assessment, Article, brain function, 03 medical and health sciences, alpha synuclein, medicine, Humans, controlled study, Genetic Predisposition to Disease, human, ddc:610, SNCA protein, human, gene, Mechanistic target of rapamycin, PI3K/AKT/mTOR pathway, mammalian target of rapamycin, Aged, RPTOR, Epistasis, Genetic, Odds ratio, medicine.disease, major clinical study, nervous system diseases, 030104 developmental biology, mTOR signaling, biology.protein, Epistasis, pathology, Neurology (clinical), genetic predisposition, 030217 neurology & neurosurgery
Abstract

Special Issue: Focused Ultrasound in Parkinson's Disease., [Background] Single nucleotide polymorphisms (SNPs) in the α‐synuclein (SNCA ) gene are associated with differential risk and age at onset (AAO) of both idiopathic and Leucine‐rich repeat kinase 2 (LRRK2)‐associated Parkinson's disease (PD). Yet potential combinatory or synergistic effects among several modulatory SNPs for PD risk or AAO remain largely underexplored., [Objectives] The mechanistic target of rapamycin (mTOR ) signaling pathway is functionally impaired in PD. Here we explored whether SNPs in the mTOR pathway, alone or by epistatic interaction with known susceptibility factors, can modulate PD risk and AAO., [Methods] Based on functional relevance, we selected a total of 64 SNPs mapping to a total of 57 genes from the mTOR pathway and genotyped a discovery series cohort encompassing 898 PD patients and 921 controls. As a replication series, we screened 4170 PD and 3014 controls available from the International Parkinson's Disease Genomics Consortium., [Results] In the discovery series cohort, we found a 4‐loci interaction involving STK11 rs8111699, FCHSD1 rs456998, GSK3B rs1732170, and SNCA rs356219, which was associated with an increased risk of PD (odds ratio = 2.59, P, [Conclusions] These findings indicate that genetic variability in the mTOR pathway contributes to SNCA effects in a nonlinear epistatic manner to modulate differential AAO in PD, unraveling the contribution of this cascade in the pathogenesis of the disease. © 2019 International Parkinson and Movement Disorder Society, Funding Information; Fundació la Marató de TV3. Grant Number: 60510; Michael J. Fox Foundation for Parkinson's Research. Grant Numbers: Dyskinesia Challenge 2014, MJF_PPMI_10_001, PI044024; National Institutes of Health. Grant Number: LM010098; Secretaría de Estado de Investigación, Desarrollo e Innovación. Grant Number: SAF2014‐57160R and SAF2017‐88812R.

Published
2019
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16. High ultrasensitive serum C-reactive protein may be related to freezing of gait in Parkinson's disease patients

Author

Santos-Garcia, D, Fonticoba, TD, Castro, ES, Diaz, AA, Gonzalez, JMP, Panceiras, MJF, Sancho, CG, Jesus, S, Mir, P, Aguilar, M, Pastor, P, Vara, JH, de Fabregues-Boixar, O, Puente, V, Cuevas, AC, Gonzalez-Aramburu, I, Infante, J, Padilla, FC, Pueyo, M, Escalante, S, Bernardo, N, Solano, B, Foraster, AC, Martinez-Martin, P, Astrid, DA, Almeria, M, Losada, MGA, Canovas, AA, Frech, FA, Sauco, MA, Arnaiz, S, Arribas, S, Vidondo, AA, Avila, MA, Bejr-Kasem, H, Estrada, MB, Boti, M, Borrue, C, Gonzalez, CC, Lopez, IC, Caballol, N, Lorenzo, AC, Carrillo, F, Casas, E, Catalan, MJ, Clavero, P, Fernandez, AC, Cubo, E, Diez-Fairen, M, Erro, E, Peyret, EE, Guillan, NF, Gamez, P, Gallego, M, Caldentey, JG, Campos, CG, Moreno, JMG, Gaston, I, Garre, MPG, Aloy, JG, Ardura, JG, Garcia, BG, Palmas, MJG, Toledo, GRG, Diaz, AG, Sola, MG, Guardia, G, Horta-Barba, A, Kulisevsky, J, Kurtis, M, Labandeira, C, Labrador, MA, Lacruz, F, Castro, ML, Legarda, I, Ariztegui, NL, Diaz, LML, Manzanares, LL, Seoane, BL, Macias, Y, Mata, M, Andres, GM, Marti, MJ, Castrillo, JCM, McAfee, D, Meitin, MT, Gonzalez, MM, del Barrio, CM, Santiago, JM, Casado, MIM, Dieguez, AM, Nogueira, V, Amado, AN, Ponte, SN, Ordas, C, Pagonabarraga, J, Parees, I, Pascual-Sedano, B, Fuertes, AP, Noguera, RP, Planellas, L, Prats, MA, Jurczynska, CP, Rafales, NR, Mendez, LR, Perez, ABR, Roldan, F, De Arcos, MR, Martinez, JR, Alonso, PS, Sanchez-Carpintero, M, Diez, GS, Rodriguez, AS, Santacruz, P, Rodriguez, JCS, Seijo, M, Serarols, A, Pena, MS, Tartari, JP, Valero, C, Vargas, L, Gomez, RV, Vela, L, Villanueva, C, Vives, B, and Villar, MD

Subjects
Inflammation, genetic structures, Parkinson's disease, Freezing, C-Reactive protein, Gait
Abstract

C-reactive protein (CRP) is a biomarker of systemic inflammation that has been linked to accelerated decline in walking speed in older adults. The aim of the present study was to compare the CRP levels of PD patients with vs patients without freezing of gait (FOG). Patients and controls participating in the COPPADIS-2015 study that performed blood extraction for determining molecular serum biomarkers were included. Patients with FOG were identified as those with a score of 1 or greater on item-3 of the Freezing of Gait Questionnaire (FOG-Q). Immunoassay was used for determining ultrasensitive CRP (US-CRP) level (mg/dL). In the PD group (n = 225; 61.8 +/- 9.5 years old, 61.8% males), 32% of the patients presented FOG but none in the control group (n = 65; 60.3 +/- 6.1 years old, 56.9% males) (p < 0.0001). Differences in US-CRP level were significant in patients with FOG vs patients without FOG and vs controls (0.31 +/- 0.52 vs 0.16 +/- 0.21 vs 0.21 +/- 0.22; p = 0.04). Significant differences were also observed between patients with vs without FOG (p = 0.001) but not between patients and controls (p = 0.163). US-CRP level was related to FOG (OR = 4.369; 95% CI 1.105-17.275; p = 0.036) along with H&Y (OR = 2.974; 95% CI 1.113-7.943; p = 0.030) and non-motor symptoms burden (NMSS total score; OR = 1.017; 95% CI 1.005-1.029; p = 0.006) after adjusting for age, gender, disease duration, equivalent daily levodopa dose, number of non-antiparkinsonian drugs per day, motor fluctuations, cognition, motor phenotype, and chronic use of anti-inflammatory drugs. The present study suggests that serum US-CRP level is related to FOG in PD patients. Inflammation could be linked to FOG development.

Published
2019

17. COPPADIS-2015 (COhort of Patients with PArkinson's DIsease in Spain, 2015): an ongoing global Parkinson's disease project about disease progression with more than 1000 subjects included. Results from the baseline evaluation

Author

Garcia, DS, Jesus, S, Aguilar, M, Planellas, LL, Caldentey, JG, Caballol, N, Legarda, I, Vara, JH, Cabo, I, Manzanares, LL, Aramburu, IG, Rivera, MAA, Catalan, MJ, Diaz, LL, Puente, V, Moreno, JMG, Borrue, C, Vila, BS, Sauco, MA, Vela, L, Escalante, S, Cubo, E, Padilla, FC, Castrillo, JCM, Alonso, PS, Losada, MGA, Ariztegui, NL, Gaston, I, Kulisevsky, J, Gonzalez, MM, Seijo, M, Martinez, JR, Valero, C, Kurtis, M, de Fabregues-Boixar, O, Ardura, JG, Jurczynska, CP, Martinez-Martin, P, Mir, P, Astrid, DA, Almeria, M, Canovas, AA, Frech, FA, Diaz, AA, Arnaiz, S, Arribas, S, Vidondo, AA, Lambrich, NB, Bejr-Kasem, H, Estrada, MB, Boti, M, Gonzalez, CC, Lorenzo, AC, Carrillo, F, Casas, E, Clavero, P, Fernandez, AC, Foraster, AC, Cuevas, AC, Fonticoba, TD, Diez-Fairen, M, Erro, E, Peyret, EE, Guillan, NF, Gamez, P, Gallego, M, Campos, CG, Garre, MPG, Aloy, JG, Garcia, BG, Palmas, MJG, Toledo, GRG, Diaz, AG, Sola, MG, Guardia, G, Horta-Barba, A, Infante, J, Labandeira, C, Labrador, MA, Lacruz, F, Castro, ML, Seoane, BL, Macias, Y, Mata, M, Andres, GM, Marti, MJ, McAfee, D, Meitin, MT, del Barrio, CM, Santiago, JM, Casado, MIM, Dieguez, AM, Nogueira, V, Amado, AN, Ponte, SN, Ordas, C, Pagonabarraga, J, Parees, I, Pascual-Sedano, B, Pastor, P, Fuertes, AP, Noguera, RP, Prats, MA, Morlans, MP, Rafales, NR, Mendez, LR, Perez, ABR, Roldan, F, De Arcos, MR, Sanchez-Carpintero, M, Diez, GS, Rodriguez, AS, Santacruz, P, Rodriguez, JCS, Serarols, A, Pena, MS, Castro, ES, Tartari, JP, Vargas, L, Gomez, RV, Villanueva, C, Vives, B, and Villar, MD

Subjects
motor fluctuations, quality of life, mood, Parkinson's disease, gait, non-motor symptoms
Abstract

Background and purpose In Parkinson's disease (PD), the course of the disorder is highly variable between patients. Well-designed, prospective studies for identifying PD progression biomarkers are necessary. Our aim was to show the results of baseline evaluations of an ongoing global PD project, COPPADIS-2015 (Cohort of Patients with PArkinson's DIsease in Spain, 2015). Methods This was an observational, descriptive, nationwide study (Spain). The recruitment period ended in October 2017. Baseline evaluation included more than 15 validated scales and complementary studies in a subgroup of participants. Results In total, 1174 subjects from 35 centres were considered valid for baseline analysis: 694 patients (62.6 +/- 8.9 years old, 60.3% males), 273 caregivers (58.5 +/- 11.9 years old, 31.8% males) and 207 controls (61 +/- 8.3 years old, 49.5% males). The mean disease duration was 5.5 +/- 4.4 years. Hoehn and Yahr stage was 1 or 2 in 90.7% of the patients whilst 33.9% and 18.1% of them presented motor fluctuations and dyskinesias, respectively. The mean Non-Motor Symptoms Scale total score was 45.4 +/- 38.1, and 30.4% of the patients presented cognitive impairment, 16.1% major depression, 12.7% impulse control disorder, 7.2% compulsive behaviour, 57.2% pain and 13.2% falls. Compared to the control group, PD patients presented a significantly higher burden of non-motor symptoms and a worse quality of life. More than 300 subjects conducted complementary studies (serum biomarkers, genetic and neuroimaging). Conclusions Parkinson's disease is a complex disorder and different non-motor symptoms are frequently present and are more prevalent than in controls. In real clinical practice it is important to ask for them.

Published
2019

18. Mitochondria function associated genes contribute to Parkinson’s Disease risk and later age at onset

Author

Billingsley K.J., Barbosa I.A., Bandrés-Ciga S., Quinn J.P., Bubb V.J., Deshpande C., Botia J.A., Reynolds R.H., Zhang D., Simpson M.A., Blauwendraat C., Gan-Or Z., Gibbs J.R., Nalls M.A., Singleton A., Noyce A., Tucci A., Middlehurst B., Kia D., Tan M., Houlden H., Morris H.R., Plun-Favreau H., Holmans P., Hardy J., Trabzuni D., Bras J., Mok K., Kinghorn K., Wood N., Lewis P., Guerreiro R., Lovering R., R’Bibo L., Rizig M., Escott-Price V., Chelban V., Foltynie T., Williams N., Brice A., Danjou F., Lesage S., Martinez M., Giri A., Schulte C., Brockmann K., Simón-Sánchez J., Heutink P., Rizzu P., Sharma M., Gasser T., Nicolas A., Cookson M., Faghri F., Hernandez D., Shulman J., Robak L., Lubbe S., Finkbeiner S., Mencacci N., Lungu C., Scholz S., Reed X., Leonard H., Rouleau G., Krohan L., van Hilten J., Marinus J., Adarmes-Gómez A., Aguilar M., Alvarez I., Alvarez V., Javier Barrero F., Bergareche Yarza J., Bernal-Bernal I., Blazquez M., Bernal M.B.-T., Boungiorno M., Buiza-Rueda D., Cámara A., Carcel M., Carrillo F., Carrión-Claro M., Cerdan D., Clarimón J., Compta Y., Diez-Fairen M., Dols-Icardo O., Duarte J., Duran R., Escamilla-Sevilla F., Ezquerra M., Fernández M., Fernández-Santiago R., Garcia C., García-Ruiz P., Gómez-Garre P., Heredia M.G., Gonzalez-Aramburu I., Pagola A.G., Hoenicka J., Infante J., Jesús S., Jimenez-Escrig A., Kulisevsky J., Labrador-Espinosa M., Lopez-Sendon J., de Munain Arregui A.L., Macias D., Torres I.M., Marín J., Marti M.J., Martínez-Castrillo J., Méndez-del-Barrio C., Menéndez González M., Mínguez A., Mir P., Rezola E.M., Muñoz E., Pagonabarraga J., Pastor P., Errazquin F.P., Periñán-Tocino T., Ruiz-Martínez J., Ruz C., Rodriguez A.S., Sierra M., Suarez-Sanmartin E., Tabernero C., Tartari J.P., Tejera-Parrado C., Tolosa E., Valldeoriola F., Vargas-González L., Vela L., Vives F., Zimprich A., Pihlstrom L., Taba P., Majamaa K., Siitonen A., Okubadejo N., Ojo O., Ryten M., and Koks S.

Subjects
genotype, Mendelian randomization analysis, CLN8 gene, MUC1 gene, genetic analysis, bioenergy, genetic risk, genetic risk score, Article, ATG14 gene, disorders of mitochondrial functions, MRPS34 gene, degenerative disease, mitochondrial gene, EP300 gene, gene mutation, human, MPI gene, gene, molecular phylogeny, LMBRD1 gene, genome-wide association study, monogenic disorder, mitochondrial dynamics, Parkinson disease, E2F1 gene, mitophagy, CAPRIN2 gene, priority journal, risk factor, LGALS3 gene, disease exacerbation, gene expression, gene ontology, meta analysis
Abstract

Mitochondrial dysfunction has been implicated in the etiology of monogenic Parkinson’s disease (PD). Yet the role that mitochondrial processes play in the most common form of the disease; sporadic PD, is yet to be fully established. Here, we comprehensively assessed the role of mitochondrial function-associated genes in sporadic PD by leveraging improvements in the scale and analysis of PD GWAS data with recent advances in our understanding of the genetics of mitochondrial disease. We calculated a mitochondrial-specific polygenic risk score (PRS) and showed that cumulative small effect variants within both our primary and secondary gene lists are significantly associated with increased PD risk. We further reported that the PRS of the secondary mitochondrial gene list was significantly associated with later age at onset. Finally, to identify possible functional genomic associations we implemented Mendelian randomization, which showed that 14 of these mitochondrial function-associated genes showed functional consequence associated with PD risk. Further analysis suggested that the 14 identified genes are not only involved in mitophagy, but implicate new mitochondrial processes. Our data suggests that therapeutics targeting mitochondrial bioenergetics and proteostasis pathways distinct from mitophagy could be beneficial to treating the early stage of PD. © 2019, The Author(s).

Published
2019

19. SNCA and mTOR Pathway Single Nucleotide Polymorphisms Interact to Modulate the Age at Onset of Parkinson's Disease

Author

Martin-Flores, N, Antonelli, F, Cerquera, C, Moreno, V, Manduchi, E, Moore, JH, Noyce, AJ, Kaiyrzhanov, R, Middlehurst, B, Kia, DA, Tan, M, Houlden, H, Morris, HR, Plun-Favreau, H, Holmans, P, Hardy, J, Trabzuni, D, Bras, J, Quinn, J, Mok, KY, Kinghorn, KJ, Billingsley, K, Wood, NW, Lewis, P, Schreglmann, S, Guerreiro, R, Lovering, R, R'Bibo, L, Manzoni, C, Rizig, M, Ryten, M, Guelfi, S, Escott-Price, V, Chelban, V, Foltynie, T, Williams, N, Morrison, KE, Clarke, C, Brice, A, Danjou, F, Lesage, S, Corvol, JC, Martinez, M, Schulte, C, Brockmann, K, Simoon-Saanchez, J, Heutink, P, Rizzu, P, Sharma, M, Gasser, T, Nicolas, A, Cookson, MR, Bandres-Ciga, S, Blauwendraat, C, Craig, DW, Faghri, F, Gibbs, JR, Hernandez, DG, Van Keuren-Jensen, K, Shulman, JM, Iwaki, H, Leonard, HL, Nalls, MA, Robak, L, Lubbe, S, Finkbeiner, S, Mencacci, NE, Lungu, C, Singleton, AB, Scholz, SW, Reed, X, Alcalay, RN, Gan-Or, Z, Rouleau, GA, Krohn, L, van Hilten, JJ, Marinus, J, Adarmes-Goomez, AD, Aguilar, I, Alvarez, I, Alvarez, V, Barrero, FJ, Yarza, JAB, Bernal-Bernal, I, Blazquez, M, Bonilla-Toribio, M, Botia, JA, Boungiorno, MT, Buiza-Rueda, D, Camara, A, Carrillo, F, Carrion-Claro, M, Cerdan, D, Clarimon, J, Compta, Y, de la Casa, B, Diez-Fairen, M, Dols-Icardo, O, Duarte, J, Duran, R, Escamilla-Sevilla, F, Feliz, C, Fernandez, M, Fernandez-Santiago, R, Garcia, C, Garcia-Ruiz, P, Gomez-Garre, P, Heredia, MJG, Gonzalez-Aramburu, I, Pagola, AG, Hoenicka, J, Infante, J, Jesus, S, Jimenez-Escrig, A, Kulisevsky, J, Labrador-Espinosa, MA, Lopez-Sendon, JL, Arregui, ALD, Macias, D, Torres, IM, Marin, J, Marti, MJ, Martinez-Castrillo, C, Mendez-del-Barrio, C, Gonzalez, MM, Mata, M, Minguez, A, Mir, P, Rezola, EM, Munoz, E, Pagonabarraga, J, Pascual-Sedano, B, Pastor, P, Errazquin, FP, Perinan-Tocino, T, Ruiz-Martinez, J, Ruz, C, Rodriguez, AS, Sierra, M, Suarez-Sanmartin, E, Tabernero, C, Tartari, JP, Tejera-Parrado, C, Tolosa, E, Valldeoriola, F, Vargas-Gonzalez, L, Vela, L, Vives, F, Zimprich, A, Pihlstrom, L, Toft, M, Koks, S, Taba, P, Hassin-Baer, S, Ezquerra, M, Malagelada, C, and Int Parkinson's Dis Genomics Conso

Subjects
epistasis, alpha-synuclein, Parkinson's disease, mTOR, SNP, age at onset
Abstract

Background Single nucleotide polymorphisms (SNPs) in the alpha-synuclein (SNCA) gene are associated with differential risk and age at onset (AAO) of both idiopathic and Leucine-rich repeat kinase 2 (LRRK2)-associated Parkinson's disease (PD). Yet potential combinatory or synergistic effects among several modulatory SNPs for PD risk or AAO remain largely underexplored. Objectives The mechanistic target of rapamycin (mTOR) signaling pathway is functionally impaired in PD. Here we explored whether SNPs in the mTOR pathway, alone or by epistatic interaction with known susceptibility factors, can modulate PD risk and AAO. Methods Based on functional relevance, we selected a total of 64 SNPs mapping to a total of 57 genes from the mTOR pathway and genotyped a discovery series cohort encompassing 898 PD patients and 921 controls. As a replication series, we screened 4170 PD and 3014 controls available from the International Parkinson's Disease Genomics Consortium. Results In the discovery series cohort, we found a 4-loci interaction involving STK11 rs8111699, FCHSD1 rs456998, GSK3B rs1732170, and SNCA rs356219, which was associated with an increased risk of PD (odds ratio = 2.59, P < .001). In addition, we also found a 3-loci epistatic combination of RPTOR rs11868112 and RPS6KA2 rs6456121 with SNCA rs356219, which was associated (odds ratio = 2.89; P < .0001) with differential AAO. The latter was further validated (odds ratio = 1.56; P = 0.046-0.047) in the International Parkinson's Disease Genomics Consortium cohort. Conclusions These findings indicate that genetic variability in the mTOR pathway contributes to SNCA effects in a nonlinear epistatic manner to modulate differential AAO in PD, unraveling the contribution of this cascade in the pathogenesis of the disease. (c) 2019 International Parkinson and Movement Disorder Society

Published
2019

20. COPPADIS-2015 (COhort of Patients with PArkinson's DIsease in Spain, 2015): an ongoing global Parkinson's disease project about disease progression with more than 1000 subjects included. Results from the baseline evaluation

Author

Garcia, D, Jesus, S, Aguilar, M, Planellas, L, Caldentey, J, Caballol, N, Legarda, I, Vara, J, Cabo, I, Manzanares, L, Aramburu, I, Rivera, M, Catalan, M, Diaz, L, Puente, V, Moreno, J, Borrue, C, Vila, B, Sauco, M, Vela, L, Escalante, S, Cubo, E, Padilla, F, Castrillo, J, Alonso, P, Losada, M, Ariztegui, N, Gaston, I, Kulisevsky, J, Gonzalez, M, Seijo, M, Martinez, J, Valero, C, Kurtis, M, de Fabregues-Boixar, O, Ardura, J, Jurczynska, C, Martinez-Martin, P, Mir, P, Astrid, D, Almeria, M, Canovas, A, Frech, F, Diaz, A, Arnaiz, S, Arribas, S, Vidondo, A, Lambrich, N, Bejr-Kasem, H, Estrada, M, Boti, M, Gonzalez, C, Lorenzo, A, Carrillo, F, Casas, E, Clavero, P, Fernandez, A, Foraster, A, Cuevas, A, Fonticoba, T, Diez-Fairen, M, Erro, E, Peyret, E, Guillan, N, Gamez, P, Gallego, M, Campos, C, Garre, M, Aloy, J, Garcia, B, Palmas, M, Toledo, G, Sola, M, Guardia, G, Horta-Barba, A, Infante, J, Labandeira, C, Labrador, M, Lacruz, F, Castro, M, Seoane, B, Macias, Y, Mata, M, Andres, G, Marti, M, McAfee, D, Meitin, M, del Barrio, C, Santiago, J, Casado, M, Dieguez, A, Nogueira, V, Amado, A, Ponte, S, Ordas, C, Pagonabarraga, J, Parees, I, Pascual-Sedano, B, Pastor, P, Fuertes, A, Noguera, R, Prats, M, Morlans, M, Rafales, N, Mendez, L, Perez, A, Roldan, F, De Arcos, M, Sanchez-Carpintero, M, Diez, G, Rodriguez, A, Santacruz, P, Rodriguez, J, Serarols, A, Pena, M, Castro, E, Tartari, J, Vargas, L, Gomez, R, Villanueva, C, Vives, B, Villar, M, and COPPADIS Study Grp

Subjects
motor fluctuations, quality of life, mood, Parkinson's disease, gait, non-motor symptoms
Abstract

Background and purpose In Parkinson's disease (PD), the course of the disorder is highly variable between patients. Well-designed, prospective studies for identifying PD progression biomarkers are necessary. Our aim was to show the results of baseline evaluations of an ongoing global PD project, COPPADIS-2015 (Cohort of Patients with PArkinson's DIsease in Spain, 2015). Methods This was an observational, descriptive, nationwide study (Spain). The recruitment period ended in October 2017. Baseline evaluation included more than 15 validated scales and complementary studies in a subgroup of participants. Results In total, 1174 subjects from 35 centres were considered valid for baseline analysis: 694 patients (62.6 +/- 8.9 years old, 60.3% males), 273 caregivers (58.5 +/- 11.9 years old, 31.8% males) and 207 controls (61 +/- 8.3 years old, 49.5% males). The mean disease duration was 5.5 +/- 4.4 years. Hoehn and Yahr stage was 1 or 2 in 90.7% of the patients whilst 33.9% and 18.1% of them presented motor fluctuations and dyskinesias, respectively. The mean Non-Motor Symptoms Scale total score was 45.4 +/- 38.1, and 30.4% of the patients presented cognitive impairment, 16.1% major depression, 12.7% impulse control disorder, 7.2% compulsive behaviour, 57.2% pain and 13.2% falls. Compared to the control group, PD patients presented a significantly higher burden of non-motor symptoms and a worse quality of life. More than 300 subjects conducted complementary studies (serum biomarkers, genetic and neuroimaging). Conclusions Parkinson's disease is a complex disorder and different non-motor symptoms are frequently present and are more prevalent than in controls. In real clinical practice it is important to ask for them.

Published
2019

21. Non-motor symptoms burden, mood, and gait problems are the most significant factors contributing to a poor quality of life in non-demented Parkinson's disease patients: Results from the COPPADIS Study Cohort

Author

Garcia, D, Fonticoba, T, Castro, E, Borrue, C, Mata, M, Vila, B, Foraster, A, Sauco, M, Perez, A, Vela, L, Macias, Y, Escalante, S, Esteve, P, Villarroya, S, Cubo, E, Casas, E, Arnaiz, S, Padilla, F, Morlans, M, Mir, P, Martinez-Martin, P, Adarmes, A, Almeria, M, Losada, G, Canovas, A, Alonso-Frech, F, Arribas, S, Vidondo, A, Aguilar, M, Avila, M, Lambrich, N, Bejr-Kasem, H, Estrada, M, Boti, M, Gonzalez, C, Lopez, I, Caballol, N, Lorenzo, A, Carrillo, F, Catalan, M, Clavero, P, Fernandez, A, Cuevas, A, de Fabregues-Boixar, O, Diez-Fairen, M, Erro, E, Peyret, E, Guinan, N, Gamez, P, Gallego, M, Caldentey, J, Campos, C, Moreno, J, Gaston, I, Garre, M, Aloy, J, Gonzalez-Aramburu, I, Ardura, J, Garcia, B, Palmas, M, Toledo, G, Diaz, A, Sola, M, Guardia, G, Hernandez-Vara, J, Barba, A, Infante, J, Jesus, S, Kulisevsky, J, Kurtis, M, Labandeira, C, Labrador, M, Lacruz, F, Castro, M, Legarda, I, Ariztegui, N, Diaz, L, Manzanares, L, Seoane, B, Andres, G, Marti, M, Martinez-Castrillo, J, McAfee, D, Meitin, M, Gonzalez, M, del Barrio, C, Santiago, J, Casado, M, Dieguez, A, Nogueira, V, Amado, A, Ponte, S, Ordas, C, Pagonabarraga, J, Parees, I, Pascual-Sedano, B, Pastor, P, Fuertes, A, Noguera, R, Planellas, L, Fuster, J, Prats, M, Jurczynska, C, Puente, V, Rafales, N, Mendez, L, Roldan, F, De Arcos, M, Martinez, J, Alonso, P, Sanchez-Carpintero, M, Diez, G, Rodriguez, A, Santacruz, P, Rodriguez, J, Seijo, M, Serarols, A, Pena, M, Tartari, J, Vargas, L, Gomez, R, Villanueva, C, Vives, B, Villar, M, and Coppadis Study Grp

Subjects
Quality of life, Parkinson's disease, Mood, Non-motor symptoms, Gait, humanities, Motor fluctuations
Abstract

Objective: To identify factors related to a poor health-related and global quality of life (QoL) in a cohort of nondemented Parkinson's disease (PD) patients and compare to a control group. Methods: The data correspond to the baseline evaluation of the COPPADIS-2015 Study, an observational, 5-year follow-up, multicenter, evaluation study. Three instruments were used to assess QoL: (1) the 39-item Parkinson's disease Questionnaire (PDQ-39), (2) a subjective rating of global QoL (PQ-10), and (3) the EUROHIS-QOL 8-item index (EUROHIS-QOL8). Multiple linear regression methods were used to evaluate the direct impact of different variables on these QoL measures. Results: QoL was worse in PD patients (n = 692; 62.6 +/- 8.9 years old, 60.3% males) than controls (n = 206; 61 +/- 8.3 years old, 49.5% males): PDQ-39, 17.1 +/- 13.5 vs 4.4 +/- 6.3 (p < 0.0001); PQ-10, 7.3 +/- 1.6 vs 8.1 +/- 1.2 (p < 0.0001); EUROHIS-Q0L8, 3.8 +/- 0.6 vs 4.2 +/- 0.5 (p < 0.0001). A high correlation was observed between PDQ-39 and Non-Motor Symptoms Scale (NMSS) (r = 0.72; p < 0.0001), and PDQ-39 and Beck Depression Inventory-II (BDI-II) (r = 0.65; p < 0.0001). For health-related QoL (PDQ-39), non-motor symptoms burden (NMSS), mood (BDI-II), and gait problems (Freezing Of Gait Questionnaire [FOGQ]) provided the highest contribution to the model (beta = 0.32, 0.28, and 0.27, respectively; p < 0.0001); whereas mood and gait pro- blems contributed the most to global QoL (PQ-10, beta = -0.46 and -0.21, respectively; EUROHIS-QOL8, beta = - 0.44 and - 0.23, respectively). Conclusions: QoL is worse in PD patients than in controls. Mood, non-motor symptoms burden, and gait problems seem to be the most relevant factors affecting health-related and global perceived QoL in non-demented PD patients.

Published
2019

22. Performance of Wendelstein 7-X stellarator plasmas during the first divertor operation phase

Author

Wolf, R. C., Alonso, A., Akaslompolo, S., Baldzuhn, J., Beurskens, M., Beidler, C. D., Biedermann, C., Bosch, H. -S., Bozhenkov, S., Brakel, R., Braune, H., Brezinsek, S., Brunner, K. -J., Damm, H., Dinklage, A., Drewelow, P., Effenberg, F., Feng, Y., Ford, O., Fuchert, G., Gao, Y., Geiger, J., Grulke, O., Harder, N., Hartmann, D., Helander, P., Heinemann, B., Hirsch, M., Hofel, U., Hopf, C., Ida, K., Isobe, M., Jakubowski, M. W., Kazakov, Y. O., Killer, C., Klinger, T., Knauer, J., Konig, R., Krychowiak, M., Langenberg, A., Laqua, H. P., Lazerson, S., Mcneely, P., Marsen, S., Marushchenko, N., Nocentini, R., Ogawa, K., Orozco, G., Osakabe, M., Otte, M., Pablant, N., Pasch, E., Pavone, A., Porkolab, M., Puig Sitjes, A., Rahbarnia, K., Riedl, R., Rust, N., Scott, E., Schilling, J., Schroeder, R., Stange, T., Von Stechow, A., Strumberger, E., Sunn Pedersen, T., Svensson, J., Thomson, H., Turkin, Y., Vano, L., Wauters, T., Wurden, G., Yoshinuma, M., Zanini, M., Zhang, D., Andreeva, T., Brandt, C., Burhenn, R., Buttenschon, B., Geiger, B., Tamura, N., Thomsen, H., Wegner, T., Abramovic, I., Alcuson, J., Aleynikov, P., Aleynikova, K., Ali, A., Anda, G., Ascasibar, E., Bahner, J. P., Baek, S. G., Balden, M., Banduch, M., Barbui, T., Behr, W., Beidler, C., Benndorf, A., Biel, W., Blackwell, B., Blanco, E., Blatzheim, M., Ballinger, S., Bluhm, T., Bockenhoff, D., Boswirth, B., Bottger, L. -G., Borchardt, M., Borsuk, V., Boscary, J., Brand, H., Brauer, T., Bussiahn, R., Bykov, V., Cai, J., Calvo, I., Cannas, B., Cappa, A., Carls, A., Carralero, D., Carraro, L., Carvalho, B., Castejon, F., Charl, A., Chaudhary, N., Chauvin, D., Chernyshev, F., Cianciosa, M., Citarella, R., Claps, G., Coenen, J., Cole, M., Cole, M. J., Cordella, F., Cseh, G., Czarnecka, A., Czerski, K., Czerwinski, M., Czymek, G., Da Molin, A., Da Silva, A., De La Pena, A., Degenkolbe, S., Dhard, C. P., Dibon, M., Dittmar, T., Drevlak, M., Drews, P., Durodie, F., Edlund, E., Van Eeten, P., Ehrke, G., Elgeti, S., Endler, M., Ennis, D., Esteban, H., Estrada, T., Fellinger, J., Flom, E., Fernandes, H., Fietz, W. H., Figacz, W., Fontdecaba, J., Fornal, T., Frerichs, H., Freund, A., Funaba, T., Galkowski, A., Gantenbein, G., Garcia Regana, J., Gates, D., Giannella, V., Gogoleva, A., Goncalves, B., Goriaev, A., Gradic, D., Grahl, M., Green, J., Greuner, H., Grosman, A., Grote, H., Gruca, M., Guerard, C., Hacker, P., Han, X., Harris, J. H., Hathiramani, D., Hein, B., Henneberg, S., Henkel, M., Hernandez Sanchez, J., Hidalgo, C., Hollfeld, K. P., Holting, A., Hoschen, D., Houry, M., Howard, J., Huang, X., Huang, Z., Hubeny, M., Huber, M., Hunger, H., Ilkei, T., Illy, S., Israeli, B., Jablonski, S., Jakubowski, M., Jelonnek, J., Jenzsch, H., Jesche, T., Jia, M., Junghanns, P., Kacmarczyk, J., Kallmeyer, J. -P., Kamionka, U., Kasahara, H., Kasparek, W., Kenmochi, N., Kirschner, A., Kleiber, R., Knaup, M., Knieps, A., Kobarg, T., Kocsis, G., Kochl, F., Kolesnichenko, Y., Konies, A., Kornejew, P., Koschinsky, J. -P., Koster, F., Kramer, M., Krampitz, R., Kramer-Flecken, A., Krawczyk, N., Kremeyer, T., Krom, J., Ksiazek, I., Kubkowska, M., Kuhner, G., Kurki-Suonio, T., Kurz, P. A., Kwak, S., Landreman, M., Lang, P., Lang, R., Langish, S., Laqua, H., Laube, R., Lechte, C., Lennartz, M., Leonhardt, W., Li, C., Li, Y., Liang, Y., Linsmeier, C., Liu, S., Lobsien, J. -F., Loesser, D., Loizu Cisquella, J., Lore, J., Lorenz, A., Losert, M., Lucke, A., Lumsdaine, A., Lutsenko, V., Maassberg, H., Marchuk, O., Matthew, J. H., Marushchenko, M., Masuzaki, S., Maurer, D., Mayer, M., Mccarthy, K., Meier, A., Mellein, D., Mendelevitch, B., Mertens, P., Mikkelsen, D., Mishchenko, A., Missal, B., Mittelstaedt, J., Mizuuchi, T., Mollen, A., Moncada, V., Monnich, T., Morisaki, T., Moseev, D., Murakami, S., Nafradi, G., Nagel, M., Naujoks, D., Neilson, H., Neu, R., Neubauer, O., Neuner, U., Ngo, T., Nicolai, D., Nielsen, S. K., Niemann, H., Nishizawa, T., Nuhrenberg, C., Nuhrenberg, J., Obermayer, S., Offermanns, G., Olmanns, J., Ongena, J., Oosterbeek, J. W., Pacios Rodriguez, L., Panadero, N., Panadero Alvarez, N., Papenfuss, D., Paqay, S., Pawelec, E., Pedersen, T. S., Pelka, G., Perseo, V., Peterson, B., Pilopp, D., Pingel, S., Pisano, F., Plaum, B., Plunk, G., Poloskei, P., Proll, J., Puiatti, M. -E., Purps, F., Rack, M., Recsei, S., Reiman, A., Reimold, F., Reiter, D., Remppel, F., Renard, S., Riemann, J., Risse, K., Rohde, V., Rohlinger, H., Rome, M., Rondeshagen, D., Rong, P., Roth, B., Rudischhauser, L., Rummel, K., Rummel, T., Runov, A., Ryc, L., Ryosuke, S., Sakamoto, R., Salewski, M., Samartsev, A., Sanchez, E., Sano, F., Satake, S., Schacht, J., Satheeswaran, G., Schauer, F., Scherer, T., Schlaich, A., Schlisio, G., Schluck, F., Schluter, K. -H., Schmitt, J., Schmitz, H., Schmitz, O., Schmuck, S., Schneider, M., Schneider, W., Scholz, P., Schrittwieser, R., Schroder, M., Schroder, T., Schumacher, H., Schweer, B., Sereda, S., Shanahan, B., Sibilia, M., Sinha, P., Siplia, S., Slaby, C., Sleczka, M., Smith, H., Spiess, W., Spong, D. A., Spring, A., Stadler, R., Stejner, M., Stephey, L., Stridde, U., Suzuki, C., Szabo, V., Szabolics, T., Szepesi, T., Szokefalvi-Nagy, Z., Tancetti, A., Terry, J., Thomas, J., Thumm, M., Travere, J. M., Traverso, P., Tretter, J., Trimino Mora, H., Tsuchiya, H., Tsujimura, T., Tulipan, S., Unterberg, B., Vakulchyk, I., Valet, S., Van Milligen, B., Van Vuuren, A. J., Vela, L., Velasco, J. -L., Vergote, M., Vervier, M., Vianello, N., Viebke, H., Vilbrandt, R., Vorkoper, A., Wadle, S., Wagner, F., Wang, E., Wang, N., Wang, Z., Warmer, F., Wegener, L., Weggen, J., Wei, Y., Weir, G., Wendorf, J., Wenzel, U., Werner, A., White, A., Wiegel, B., Wilde, F., Windisch, T., Winkler, M., Winter, A., Winters, V., Wolf, S., Wright, A., Xanthopoulos, P., Yamada, H., Yamada, I., Yasuhara, R., Yokoyama, M., Zarnstorff, M., Zeitler, A., Zhang, H., Zhu, J., Zilker, M., Zocco, A., Zoletnik, S., Zuin, M., Science and Technology of Nuclear Fusion, Turbulence in Fusion Plasmas, and W7-X Team, Max Planck Institute for Plasma Physics, Max Planck Society

Subjects
Physics, Technology, Plasma parameters, Divertor, Nuclear engineering, Plasma, Condensed Matter Physics, 01 natural sciences, 7. Clean energy, Electron cyclotron resonance, 010305 fluids & plasmas, law.invention, Magnetic field, law, 0103 physical sciences, Limiter, Wendelstein 7-X, 010306 general physics, ddc:600, Stellarator
Abstract

Wendelstein 7-X is the first comprehensively optimized stellarator aiming at good confinement with plasma parameters relevant to a future stellarator power plant. Plasma operation started in 2015 using a limiter configuration. After installing an uncooled magnetic island divertor, extending the energy limit from 4 to 80 MJ, operation continued in 2017. For this phase, the electron cyclotron resonance heating (ECRH) capability was extended to 7 MW, and hydrogen pellet injection was implemented. The enhancements resulted in the highest triple product (6.5 × 1019 keV m-3 s) achieved in a stellarator until now. Plasma conditions [Te(0) ≈ Ti(0) ≈ 3.8 keV, τE > 200 ms] already were in the stellarator reactor-relevant ion-root plasma transport regime. Stable operation above the 2nd harmonic ECRH X-mode cutoff was demonstrated, which is instrumental for achieving high plasma densities in Wendelstein 7-X. Further important developments include the confirmation of low intrinsic error fields, the observation of current-drive induced instabilities, and first fast ion heating and confinement experiments. The efficacy of the magnetic island divertor was instrumental in achieving high performance in Wendelstein 7-X. Symmetrization of the heat loads between the ten divertor modules could be achieved by external resonant magnetic fields. Full divertor power detachment facilitated the extension of high power plasmas significantly beyond the energy limit of 80 MJ.

Published
2019
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24. Technical evaluation of resistance to compression in concretes made with CPCA cement

Author

Rincon, M., Bolognini, H., Vela, L., Meza, D., and Angulo, C.

Abstract

In recent years Venezuela has presented a crisis on the demand, commercialization and production of cement, the material needed for construction, therefor additive cements are being used without any type of regulations. This work presents the physical-mechanical characterization of three concrete mixtures with water / cement ratio of 0.45 and water / cement ratio of 0.60 with different types of Portland cement, Type I, Type CPCA1,and the third mixture corresponds to Type CPCA1 Rewarding it with a 15% addition in his own weight, developing a mixture of better quality. These concretes were characterized by: settling, setting time, percentage of total porosity, percentage of water absorption and mechanical resistance to compression. The results showed that the concrete mixture produced with CPCA1 does not meet the minimum requirements established in the Venezuelan standard for use in the elaboration of structural concrete, because among other parameters its resistance to compression it's below the design value. As for the CPCA1 giving it 15% addition in its own weight meets the requirements, and can be used in the manufacture of concrete structural elements.

Published
2016

25. COPPADIS-2015 (COhort of Patients with PArkinson's DIsease in Spain, 2015), a global -clinical evaluations, serum biomarkers, genetic studies and neuroimaging- prospective, multicenter, non-interventional, long-term study on Parkinson's disease progression

Author

Santos-Garcia, D, Mir, P, Cubo, E, Vela, L, Rodriguez-Oroz, MC, Marti, MJ, Arbelo, JM, Infante, J, Kulisevsky, J, Martinez-Martin, P, Pagonabarraga J., and Vázquez, R. A.

Subjects
Quality of life, Magnetic resonance imaging, Progression, Parkinson's disease, Non-motor symptoms, Caregiver, Biomarkers, Genetic studies
Abstract

Background: Parkinson's disease (PD) is a progressive neurodegenerative disorder causing motor and non-motor symptoms that can affect independence, social adjustment and the quality of life (QoL) of both patients and caregivers. Studies designed to find diagnostic and/or progression biomarkers of PD are needed. We describe here the study protocol of COPPADIS-2015 (COhort of Patients with PArkinson's DIsease in Spain, 2015), an integral PD project based on four aspects/concepts: 1) PD as a global disease (motor and non-motor symptoms); 2) QoL and caregiver issues; 3) Biomarkers; 4) Disease progression. Methods/design: Observational, descriptive, non-interventional, 5-year follow-up, national (Spain), multicenter (45 centers from 15 autonomous communities), evaluation study. Specific goals: (1) detailed study (clinical evaluations, serum biomarkers, genetic studies and neuroimaging) of a population of PD patients from different areas of Spain, (2) comparison with a control group and (3) follow-up for 5 years. COPPADIS-2015 has been specifically designed to assess 17 proposed objectives. Study population: approximately 800 non-dementia PD patients, 600 principal caregivers and 400 control subjects. Study evaluations: (1) baseline includes motor assessment (e.g., Unified Parkinson's Disease Rating Scale part III), non-motor symptoms (e.g., Non-Motor Symptoms Scale), cognition (e.g., Parkinson's Disease Cognitive Rating Scale), mood and neuropsychiatric symptoms (e.g., Neuropsychiatric Inventory), disability, QoL (e.g., 39-item Parkinson's disease Quality of Life Questionnaire Summary-Index) and caregiver status (e.g., Zarit Caregiver Burden Inventory); (2) follow-up includes annual (patients) or biannual (caregivers and controls) evaluations. Serum biomarkers (S-100b protein, TNF-alpha, IL-1, IL-2, IL-6, vitamin B12, methylmalonic acid, homocysteine, uric acid, C-reactive protein, ferritin, iron) and brain MRI (volumetry, tractography and MTAi [Medial Temporal Atrophy Index]), at baseline and at the end of follow-up, and genetic studies (DNA and RNA) at baseline will be performed in a subgroup of subjects (300 PD patients and 100 control subjects). Study periods: (1) recruitment period, from November, 2015 to February, 2017 (basal assessment); (2) follow-up period, 5 years; (3) closing date of clinical follow-up, May, 2022. Funding: Public/Private. Discussion: COPPADIS-2015 is a challenging initiative. This project will provide important information on the natural history of PD and the value of various biomarkers.

Published
2016

26. Dopaminergic agonists in Parkinson's disease

Author

Canovas, AA, Piudo, RL, Ruiz-Espiga, PG, Burguera, JA, Arillo, VC, Castro, A, Linazasoro, G, del Val, JL, Vela, L, and Castrillo, JCM

Subjects
Pramipexole, Ropinirole, Dopamine agonists, Prolonged release, Rotigotine, Equivalence
Abstract

Background: Non-ergoline dopamine agonists (DA) are effective treatments for Parkinson's disease (PD). This review presents the pharmacology, evidence of efficacy and safety profile of pramipexole, ropinirole, and rotigotine, and practical recommendations are given regarding their use in clinical practice. Results: Extended-release formulations of pramipexole and ropinirole and transdermal continuous delivery rotigotine patches are currently available; these may contribute to stabilising of plasma levels. In early PD, the three drugs significantly improve disability scales, delay time to dyskinesia and allow a later introduction of levodopa. In late PD they reduced total 'off'-time, improved Unified Parkinson's Disease Rating Scale (UPDRS) in both 'on' and 'off' state and allowed a reduction in total levodopa dosage. A significant improvement in quality of life scales has also been demonstrated. Extended-release formulations have proved to be non-inferior to the immediate release formulations and are better tolerated (ropinirole). Despite a generally good safety profile, serious adverse events, such as impulse control disorder and sleep attacks, need to be routinely monitored. Although combination therapy has not been addressed in scientific literature, certain combinations, such as apomorphine and another DA, may be helpful. Switching from one DA to another is feasible and safe, although in the first days an overlap of dopaminergic side effects may occur. When treatment with DA is stopped abruptly, dopamine withdrawal syndrome may present. Suspending any DA, especially pramipexole, has been linked to onset of apathy, which may be severe. Conclusions: New non-ergotine DAs are a valuable option for the treatment of both early and late PD. Despite their good safety profile, serious adverse effects may appear; these effects may have a pathoplastic effect on the course of PD and need to be monitored. (C) 2011 Sociedad Espana de Neurologia. Published by Elsevier Espana, S.L. All rights reserved.

Published
2014

28. Motor Fluctuations development is associated with non-motor symptoms burden progression in Parkinson's disease patients: A 2-year follow-up study

Author

Santos, D., Deus, T., Cores, C., Feal Painceiras, M., Suarez Castro, E., Martinez, C., Jesus, S., Aguilar, M., Pastor, P., Planellas, L., Cosgaya, M., Garcia Caldentey, J., Caballol, N., Legarda, I., Hernandez Vara, J., Cabo, I., Lopez Manzanares, L., Gonzalez Aramburu, I., Avila, M., Gomez Mayordomo, V., Nogueira, V., Puente, V., Dotor, J., Borrue, C., Solano, B., Alvarez Sauco, M., Vela, L., Escalante, S., Cubo, E., Carrillo, F., Martinez Castrillo, J., Sanchez Alonso, P., Alonso Losada, M., Lopez Ariztegui, N., Gaston, I., Jaime Kulisevsky, Blazquez, M., Seijo, M., Ruiz Martinez, J., Valero, C., Kurtis, M., Fabregues, O., Gonzalez, J., Alonso Redondo, R., Ordas, C., Lopez Diaz, L., Mcafee, D., Martinez Martin, P., Mir, P., and Coppadis, C.

Subjects
motor fluctuations, Parkinson's disease, follow-up, non-motor symptoms, burden
Abstract

Objective: The aim of the present study was to analyze the progression of non-motor symptoms (NMS) burden in Parkinson's disease (PD) patients regarding the development of motor fluctuations (MF). Methods: PD patients without MF at baseline, who were recruited from January 2016 to November 2017 (V0) and evaluated again at a 2-year follow-up (V2) from 35 centers of Spain from the COPPADIS cohort, were included in this analysis. MF development at V2 was defined as a score >= 1 in the item-39 of the UPDRS-Part IV, whereas NMS burden was defined according to the Non-motor Symptoms Scale (NMSS) total score. Results: Three hundred and thirty PD patients (62.67 +/- 8.7 years old; 58.8% males) were included. From V0 to V2, 27.6% of the patients developed MF. The mean NMSS total score at baseline was higher in those patients who developed MF after the 2-year follow-up (46.34 +/- 36.48 vs. 34.3 +/- 29.07; p = 0.001). A greater increase in the NMSS total score from V0 to V2 was observed in patients who developed MF (+16.07 +/- 37.37) compared to those who did not develop MF (+6.2 +/- 25.8) (p = 0.021). Development of MF after a 2-year follow-up was associated with an increase in the NMSS total score (beta = 0.128; p = 0.046) after adjustment to age, gender, years from symptoms onset, levodopa equivalent daily dose (LEDD) and the NMSS total score at baseline, and the change in LEDD from V0 to V2. Conclusions: In PD patients, the development of MF is associated with a greater increase in the NMS burden after a 2-year follow-up.

31. Descriptive epidemiology of collegiate women's field hockey injuries: National collegiate athletic association injury surveillance system, 1988-1989 through 2002-2003

Author

Dick, R., Hootman, J. M., Agel, J., Vela, L., Stephen Marshall, and Messina, R.

Subjects
human activities
Abstract

Objective: To review 15 years of National Collegiate Athletic Association (NCAA) injury surveillance data for women’s field hockey and identify potential areas for injury prevention initiatives. Background: Field hockey is one of the most popular sports worldwide and is growing in participation in the United States, particularly among women. From 1988–1989 to 2002–2003, participation in NCAA women’s field hockey increased 12%, with the largest growth among Division III programs. In 2002–2003, 253 colleges offered women’s field hockey and 5385 women participated. Main Results: Game injury rates showed a significant average annual 2.5% decline over 15 years, most likely fueled by drops in ankle ligament sprain, knee internal derangement, and finger fracture injuries. Despite this, ankle ligament sprains were common (13.7% of game and 15.0% of practice injuries) and a frequent cause of severe injuries (resulting in 10+ days of time-loss activity). Concussion and head laceration injuries increased over this same time, and the risk of sustaining a concussion in a game was 6 times higher than the risk of sustaining one during practice. Overall, injury rates were twice as high in games as in practices (7.87 versus 3.70 injuries per 1000 athlete-exposures, rate ratio = 2.1, 95% confidence interval = 2.0, 2.3). Most head/neck/face (71%) and hand/finger/thumb (68%) injuries occurred when the player was near the goal or within the 25-yd line and were caused by contact with the stick or ball (greater than 77% for both body sites), for 34% of head/neck/face injuries, a penalty was called on the play. Recommendations: Equipment (requiring helmets and padded gloves) and rule changes (to decrease field congestion near the goal) as well as evidence-based injury prevention interventions (eg, prophylactic ankle taping/bracing, neuromuscular balance exercise programs) may be viable prevention initiatives for reducing injury rates in women’s collegiate field hockey players.

35. Creation and standardized longitudinal follow-up of a cohort of patients with de novo Parkinson's disease: The VIP project | Creación y protocolo de seguimiento longitudinal de una cohorte multipropósito de pacientes con enfermedad de Parkinson de reciente diagnóstico: Proyecto VIP

Author

Linazasoro, G., Martínez-Martín, P., Kulisevski, J., Aguilar, M., Valldeoriola, F., Rojo, A., Blercom, N., Vela, L., Bergaretxe, A., Luquin, R., Castro, A., Sesar, A., Menéndez-Guisasola, L., Salvador, C., Blázquez, M., González, S., Fernández, J. M., López Del Val, J., Miquel, F., Bayés, A., Burguera, J. A., Chacón, J., Durán, C., Martínez-Castrillo, J. C., García-Ruiz, P., Duarte, J., Mendoza, A., Rodríguez, F., Vivancos, F., Pondal, M., Vaamonde, J., Benito-León, J., Campos, V., García-Muñozguren, S., Catalán, M. J., Palomino, A., Pablo Mir, Carballo, M., Minguez, A., Ortega, A., Leiva, C., Álvarez, M., Posada, I., Balseiro, J., Cubo, E., Frades, B., Forjaz, J., and Arroyo, S.

36. Neuroprotection in Parkinson's disease: analysis though group of expert's methodology

Author

Linazasoro, G., Sesar, A., Valldeoriola, F., Compta, Y., Herrero, M. T., Martinez Castrillo, J. C., Lopez Lozano, J. J., Bergaretxe, A., Vela, L., Fernandez, J. M., Castro, A., Kulisevski, J., Lezcano, E., Vaamonde, J., Lopez Del Val, J., Chacon, J., Vivancos, F., Maria-Rosario Luquin, Aguilar, M., Burguera, J. A., Salvador, C., Menendez Guisasola, L., Catalan, M. J., Mir, P., Campos, V., Grandas, F., Minguez, A., Balaguer, E., Yanez, R., Leiva, C., Garcia Ruiz, P., and Cubo, E.

37. Heart Rate and Mortality in Patients With Acute Symptomatic Pulmonary Embolism

Author

G. Pellejero, Jose Gutierrez, R. Malý, M. Basaglia, L. Chasco, P. Suchon, R. Le Mao, Laurent Bertoletti, F. Martins, J. Caprini, A. Braester, F. Galeano-Valle, Hanh My Bui, J. Alonso, Y. Sato, G. Vidal, Y. Nishimoto, C. Tolosa, E. Nofuentes-Pérez, A.M. Díaz-Brasero, N. Ait Abdallah, M.D. Adarraga, R. Sánchez-Martínez, L. Font, Raquel López-Reyes, Inna Tzoran, Karine Lacut, J. del Toro, Andris Skride, Ana Jaureguizar, Joseph A. Caprini, C. Amado, R. García de la Garza, A.M. Camon, S. Merla, Luciano López-Jiménez, G. Salgueiro, Sebastian Schellong, Alfonso Muriel, F. Bilora, S. Lainez-Justo, B. Suárez-Rodríguez, Carme Font, F. Beddar Chaib, I. Francisco, C. Jiménez-Alfaro, P. Azcarate-Agüero, Maurizio Ciammaichella, J.A. Porras, N. Vo Hong, F. Martín-Martos, Dominique Farge-Bancel, D. Farge-Bancel, José Luis Lobo, M. Giménez-Suau, E. Grau, F. García-Bragado, Ángeles Blanco-Molina, Carmen Fernández-Capitán, María del Carmen Díaz-Pedroche, C. Grange, Adriana Visonà, L. Guirado, P. Villares, P. López-Miguel, José María Pedrajas, S. Accassat, Beatriz Valero, B. Crichi, Juan J. López-Núñez, Luis Jara-Palomares, G. Sarlon-Bartoli, J. Lima, C. Bortoluzzi, Alicia Lorenzo, C. de Ancos, M.A. Fidalgo, Philippe Debourdeau, Pablo Javier Marchena, C. Rodríguez-Matute, A.I. Farfán-Sedano, José Luis Fernández-Reyes, J.C. Escribano, Juan I. Arcelus, M. Barrón, I. Quere, Remedios Otero, A. De Angelis, P. Morange, Peter Verhamme, G. Kenet, P. Prandoni, Pedro Ruiz-Artacho, C. Siniscalchi, A. Zaicenko, M. Olid-Velilla, C. García-Díaz, B. Barrón-Andrés, T. Sancho, Fernando Uresandi, Javier Trujillo-Santos, A. Muñoz-Blanco, A. Villalobos, A. Dubois-Silva, J. Moisés, J. Osorio, M.I. Mercado, J.M. Suriñach, M.A. Aibar, M.D. Joya, Cihan Ay, J.A. Díaz-Peromingo, H. Bounameaux, Diego Martínez-Urbistondo, Thomas Vanassche, L. Bertoletti, Marijan Bosevski, Farès Moustafa, M. Martín del Pozo, J.F. Sánchez-Muñoz-Torrero, H.M. Bui, Ingrid Pabinger, M.C. Olivares, M. García de Herreros, M.J. Núñez-Fernández, B. Zalunardo, J.F. Varona, Stephan Nopp, Behnood Bikdeli, B. Brandolin, B. Bikdeli, Olga Madridano, Manuel Monreal, M.J. Jaras, Alessandra Bura-Rivière, Abílio Reis, J. Portillo, O. Espitia, J. Catella, Aitor Ballaz, F. Esposito, R. Barba, R. Valle, H. Helfer, I. Tzoran, J.B. López-Sáez, P. Ruiz-Artacho, M.A. García, J. Aibar, C. Gómez-Cuervo, C. Gabara, A. Latorre, J. Ruiz-Ruiz, Benjamin Brenner, S. Fonseca, S. Schellong, Raffaele Pesavento, Barry M. Brenner, Silvia Soler, Paolo Prandoni, Victor F. Tapson, Ana Maestre, Pierpaolo Di Micco, M. Muñoz, J. Criado, D. Jiménez, Antonella Tufano, G. Krstevski, B. Valero, Henri Bounameaux, M.I. Torres, G. Poenou, Isabelle Mahé, Aída Gil-Díaz, A. Asuero, S. Otalora, V. Rosa, L. Vela, E. Imbalzano, C. Vandenbriele, C. Barbagelata, Jana Hirmerova, J. Meireles, David Jiménez, Lucia Mazzolai, L. Hernández-Blasco, M. Bosevski, Gili Kenet, C. Mella, M. Monreal, J.R. Vela, P. Di Micco, Carlos Zamora, K. Flores, P. Demelo-Rodríguez, Radovan Malý, J. Birzulis, J.A. Nieto, J. Castro, M.V. Di Campli, Francis Couturaud, Raquel Barba, Jaureguizar, A., Jimenez, D., Bikdeli, B., Ruiz-Artacho, P., Muriel, A., Tapson, V., Lopez-Reyes, R., Valero, B., Kenet, G., Monreal, M., Prandoni, P., Brenner, B., Farge-Bancel, D., Barba, R., Di Micco, P., Bertoletti, L., Schellong, S., Tzoran, I., Reis, A., Bosevski, M., Bounameaux, H., Maly, R., Verhamme, P., Caprini, J. A., Bui, H. M., Adarraga, M. D., Aibar, J., Aibar, M. A., Alonso, J., Amado, C., Arcelus, J. I., Asuero, A., Azcarate-Aguero, P., Ballaz, A., Barbagelata, C., Barron, M., Barron-Andres, B., Blanco-Molina, A., Beddar Chaib, F., Camon, A. M., Castro, J., Chasco, L., Criado, J., de Ancos, C., del Toro, J., Demelo-Rodriguez, P., Diaz-Brasero, A. M., Diaz-Pedroche, M. C., Diaz-Peromingo, J. A., Di Campli, M. V., Dubois-Silva, A., Escribano, J. C., Esposito, F., Farfan-Sedano, A. I., Fernandez-Capitan, C., Fernandez-Reyes, J. L., Fidalgo, M. A., Flores, K., Font, C., Font, L., Francisco, I., Gabara, C., Galeano-Valle, F., Garcia, M. A., Garcia-Bragado, F., Garcia de Herreros, M., Garcia de la Garza, R., Garcia-Diaz, C., Gil-Diaz, A., Gomez-Cuervo, C., Gimenez-Suau, M., Grau, E., Guirado, L., Gutierrez, J., Hernandez-Blasco, L., Jara-Palomares, L., Jaras, M. J., Jimenez-Alfaro, C., Joya, M. D., Lainez-Justo, S., Latorre, A., Lima, J., Lobo, J. L., Lopez-Jimenez, L., Lopez-Miguel, P., Lopez-Nunez, J. J., Lopez-Saez, J. B., Lorenzo, A., Madridano, O., Maestre, A., Marchena, P. J., Martin del Pozo, M., Martin-Martos, F., Martinez-Urbistondo, D., Mella, C., Mercado, M. I., Moises, J., Munoz, M., Munoz-Blanco, A., Nieto, J. A., Nofuentes-Perez, E., Nunez-Fernandez, M. J., Olid-Velilla, M., Olivares, M. C., Osorio, J., Otalora, S., Otero, R., Pedrajas, J. M., Pellejero, G., Porras, J. A., Portillo, J., Rodriguez-Matute, C., Rosa, V., Ruiz-Ruiz, J., Salgueiro, G., Sanchez-Martinez, R., Sanchez-Munoz-Torrero, J. F., Sancho, T., Soler, S., Suarez-Rodriguez, B., Surinach, J. M., Torres, M. I., Tolosa, C., Trujillo-Santos, J., Uresandi, F., Valle, R., Varona, J. F., Vela, L., Vela, J. R., Vidal, G., Villalobos, A., Villares, P., Zamora, C., Ay, C., Nopp, S., Pabinger, I., Vanassche, T., Vandenbriele, C., Hirmerova, J., Accassat, S., Ait Abdallah, N., Bura-Riviere, A., Catella, J., Couturaud, F., Crichi, B., Debourdeau, P., Espitia, O., Grange, C., Helfer, H., Lacut, K., Le Mao, R., Mahe, I., Morange, P., Moustafa, F., Poenou, G., Sarlon-Bartoli, G., Suchon, P., Quere, I., Braester, A., Basaglia, M., Bilora, F., Bortoluzzi, C., Brandolin, B., Ciammaichella, M., De Angelis, A., Imbalzano, E., Merla, S., Pesavento, R., Siniscalchi, C., Tufano, A., Visona, A., Vo Hong, N., Zalunardo, B., Nishimoto, Y., Sato, Y., Birzulis, J., Skride, A., Zaicenko, A., Fonseca, S., Martins, F., Meireles, J., Krstevski, G., and Mazzolai, L.

Subjects
Male, Registrie, Pulmonary and Respiratory Medicine, medicine.medical_specialty, pulmonary embolism, Critical Care and Intensive Care Medicine, Logistic regression, Heart Rate, Internal medicine, Heart rate, medicine, In patient, Aged, Aged, 80 and over, business.industry, medicine.disease, mortality, Pulmonary embolism, Prospective Studie, Increased risk, Spain, Cardiology, Positive relationship, Female, Cardiology and Cardiovascular Medicine, business, Human
Abstract

Background: The association between heart rate (HR) and pulmonary embolism (PE) outcomes has not been well studied. Furthermore, optimal cutoffs to identify low-risk and intermediate- to high-risk patients are not well known. Research Question: Does an association exist between baseline HR and PE outcome across the continuum of HR values? Study Design and Methods: The current study included 44,331 consecutive nonhypotensive patients with symptomatic PE from the Registro Informatizado de la Enfermedad TromboEmbólica registry between 2001 and 2021. Outcomes included 30-day all-cause and PE-specific mortality. We used hierarchical logistic regression to assess the association between admission HR and outcomes. Results: A positive relationship was found between admission HR and 30-day all-cause and PE-related mortality. Considering an HR of 80 to 99 beats/min as a reference, patients in the higher HR strata showed higher rates of all-cause death (adjusted OR, 1.5 for HR of 100-109 beats/min; adjusted OR, 1.7 for HR of 110-119 beats/min; adjusted OR, 1.9 for HR of 120-139 beats/min; and adjusted OR, 2.4 for HR of ≥ 140 beats/min). Patients in the lower strata of HR showed significantly lower rates of 30-day all-cause mortality compared with the same reference group (adjusted OR, 0.6 for HR of 60-79 beats/min; and adjusted OR, 0.5 for HR of < 60 beats/min). The findings for 30-day PE-related mortality were similar. For identification of low-risk patients, a cutoff value of 80 beats/min (vs 110 beats/min) increased the sensitivity of the simplified Pulmonary Embolism Severity Index (sPESI) from 93.4% to 98.8%. For identification of intermediate- to high-risk patients, a cutoff value of 140 beats/min (vs 110 beats/min) increased the specificity of the Bova score from 93.2% to 98.0%. Interpretation: In nonhypotensive patients with acute symptomatic PE, a high HR portends an increased risk of all-cause and PE-related mortality. Modifying the HR cutoff in the sPESI and the Bova score improves prognostication of patients with PE.

Published
2022
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38. Clinical outcomes during anticoagulant therapy in fragile patients with venous thromboembolism

Author

Farès Moustafa, Matteo Giorgi Pierfranceschi, Pierpaolo Di Micco, Eugenio Bucherini, Alicia Lorenzo, Aurora Villalobos, José A. Nieto, Beatriz Valero, Ángel L. Sampériz, Manuel Monreal, Hervé Decousus, Paolo Prandoni, Benjamin Brenner, Raquel Barba, Laurent Bertoletti, Inna Tzoran, Abilio Reis, Marijan Bosevski, Henri Bounameaux, Radovan Malý, Philip Wells, Manolis Papadakis, MD Adarraga, P Agudo, MA Aibar, M Alfonso, JI Arcelus, A Ballaz, R Barba, M Barrón, B Barrón‐Andrés, J Bascuñana, A Blanco‐Molina, I Cañas, I Casado, N Chic, R del Pozo, J del Toro, MC Díaz‐Pedroche, JA Díaz‐Peromingo, C Falgá, C Fernández‐Aracil, C Fernández‐Capitán, MA Fidalgo, C Font, L Font, P Gallego, MA García, F García‐Bragado, O Gavín, C Gómez, V Gómez, J González, E Grau, A Grimón, R Guijarro, L Guirado, J Gutiérrez, G Hernández‐Comes, L Hernández‐Blasco, L Jara‐Palomares, MJ Jaras, D Jiménez, J Jiménez, MD Joya, P Llamas, JL Lobo, P López, L López‐Jiménez, R López‐Reyes, JB López‐Sáez, MA Lorente, M Lumbierres, JM Luque, PJ Marchena, F Martín‐Martos, M Mellado, S Nieto, A Núñez, MJ Núñez, S Otalora, R Otero, JM Pedrajas, G Pérez, C Pérez‐Ductor, ML Peris, I Pons, JA Porras, O Reig, A Riera‐Mestre, D Riesco, A Rivas, M Rodríguez, MA Rodríguez‐Dávila, V Rosa, E Rosillo‐Hernández, P Ruiz‐Artacho, N Ruiz‐Giménez, JC Sahuquillo, MC Sala‐Sainz, R Sánchez‐Martínez, O Sanz, S Soler, B Sopeña, JM Suriñach, C Tolosa, MI Torres, J Troya, J Trujillo‐Santos, F Uresandi, E Usandizaga, R Valle, J Vela, L Vela, MP Vicente, B Xifre, T Vanassche, P Verhamme, HHB Yoo, P Wells, J Hirmerova, R Malý, P Dulíček, E Salgado, L Bertoletti, A Bura‐Riviere, D Farge‐Bancel, A Hij, I Mahé, A Merah, A Braester, B Brenner, I Tzoran, G Antonucci, G Barillari, F Bilora, C Bortoluzzi, B Brandolin, C Cattabiani, M Ciammaichella, N Dell'Elce, F Dentali, R Duce, E Grandone, E Imbalzano, G Lessiani, R Maida, D Mastroiacovo, F Pace, R Parisi, M Pellegrinet, R Pesavento, M Pinelli, R Poggio, P Prandoni, R Quintavalla, A Rocci, E Tiraferri, D Tonello, A Tufano, A Visonà, V Gibietis, A Skride, B Vitola, M Bosevski, M Zdraveska, H Bounameaux, L Mazzolai, RIETE Investigators, Decousus, H., Prandoni, P., Brenner, B., Barba, R., Bertoletti, L., Tzoran, I., Reis, A., Bosevski, M., Bounameaux, H., Malý, R., Wells, P., Papadakis, M., Adarraga, M.D., Agudo, P., Aibar, M.A., Alfonso, M., Arcelus, J.I., Ballaz, A., Barrón, M., Barrón-Andrés, B., Bascuñana, J., Blanco-Molina, A., Cañas, I., Casado, I., Chic, N., Del Pozo, R., Del Toro, J., Díaz-Pedroche, M.C., Díaz-Peromingo, J.A., Falgá, C., Fernández-Aracil, C., Fernández-Capitán, C., Fidalgo, M.A., Font, C., Font, L., Gallego, P., García, M.A., García-Bragado, F., Gavín, O., Gómez, C., Gómez, V., González, J., Grau, E., Grimón, A., Guijarro, R., Guirado, L., Gutiérrez, J., Hernández-Comes, G., Hernández-Blasco, L., Jara-Palomares, L., Jaras, M.J., Jiménez, D., Jiménez, J., Joya, M.D., Llamas, P., Lobo, J.L., López, P., López-Jiménez, L., López-Reyes, R., López-Sáez, J.B., Lorente, M.A., Lumbierres, M., Luque, J.M., Marchena, P.J., Martín-Martos, F., Mellado, M., Nieto, S., Núñez, A., Núñez, M.J., Otalora, S., Otero, R., Pedrajas, J.M., Pérez, G., Pérez-Ductor, C., Peris, M.L., Pons, I., Porras, J.A., Reig, O., Riera-Mestre, A., Riesco, D., Rivas, A., Rodríguez, M., Rodríguez-Dávila, M.A., Rosa, V., Rosillo-Hernández, E., Ruiz-Artacho, P., Ruiz-Giménez, N., Sahuquillo, J.C., Sala-Sainz, M.C., Sánchez-Martínez, R., Sanz, O., Soler, S., Sopeña, B., Suriñach, J.M., Tolosa, C., Torres, M.I., Troya, J., Trujillo-Santos, J., Uresandi, F., Usandizaga, E., Valle, R., Vela, J., Vela, L., Vicente, M.P., Xifre, B., Vanassche, T., Verhamme, P., Yoo, H., Hirmerova, J., Dulíček, P., Salgado, E., Bura-Riviere, A., Farge-Bancel, D., Hij, A., Mahé, I., Merah, A., Braester, A., Antonucci, G., Barillari, G., Bilora, F., Bortoluzzi, C., Brandolin, B., Cattabiani, C., Ciammaichella, M., Dell'Elce, N., Dentali, F., Duce, R., Grandone, E., Imbalzano, E., Lessiani, G., Maida, R., Mastroiacovo, D., Pace, F., Parisi, R., Pellegrinet, M., Pesavento, R., Pinelli, M., Poggio, R., Quintavalla, R., Rocci, A., Tiraferri, E., Tonello, D., Tufano, A., Visonà, A., Gibietis, V., Skride, A., Vitola, B., Zdraveska, M., Mazzolai, L., Moustafa, F., Giorgi Pierfranceschi, M., Di Micco, P., Bucherini, E., Lorenzo, A., Villalobos, A., Nieto, J. A., Valero, B., Samperiz, A. L., Monreal, M., Maly, R., Adarraga, M. D., Aibar, M. A., Arcelus, J. I., Barron, M., Barron-Andres, B., Bascunana, J., Canas, I., del Pozo, R., del Toro, J., Diaz-Pedroche, M. C., Diaz-Peromingo, J. A., Falga, C., Fernandez-Aracil, C., Fernandez-Capitan, C., Fidalgo, M. A., Garcia, M. A., Garcia-Bragado, F., Gavin, O., Gomez, C., Gomez, V., Gonzalez, J., Grimon, A., Gutierrez, J., Hernandez-Comes, G., Hernandez-Blasco, L., Jaras, M. J., Jimenez, D., Jimenez, J., Joya, M. D., Lobo, J. L., Lopez, P., Lopez-Jimenez, L., Lopez-Reyes, R., Lopez-Saez, J. B., Lorente, M. A., Luque, J. M., Marchena, P. J., Martin-Martos, F., Nunez, A., Nunez, M. J., Pedrajas, J. M., Perez, G., Perez-Ductor, C., Peris, M. L., Porras, J. A., Rodriguez, M., Rodriguez-Davila, M. A., Rosillo-Hernandez, E., Ruiz-Gimenez, N., Sahuquillo, J. C., Sala-Sainz, M. C., Sanchez-Martinez, R., Sopena, B., Surinach, J. M., Torres, M. I., Vicente, M. P., Yoo, H. H. B., Dulicek, P., Mahe, I., and Visona, A.

Subjects
medicine.medical_specialty, Gastrointestinal bleeding, anticoagulants, recurrence, venous thromboembolism, hemorrhage, mortality, recurrences, Renal function, 030204 cardiovascular system & hematology, Lower risk, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, medicine, 030212 general & internal medicine, business.industry, anticoagulant, Retrospective cohort study, Hematology, Odds ratio, medicine.disease, Confidence interval, Surgery, Natural history, Original Article, business, Original Articles: Thrombosis
Abstract

Essentials Recent randomized trials suggested fewer bleeding events in fragile patients with VTE receiving DOACs.The frequency, clinical characteristics and outcome of these patients have not been reported in real life.Fragile patients with VTE had a higher risk for major bleeding or death and a lower risk for recurrences than non‐fragile. Background Subgroup analyses from randomized trials suggested favorable results for the direct oral anticoagulants in fragile patients with venous thromboembolism (VTE). The frequency and natural history of fragile patients with VTE have not been studied yet. Objectives To compare the clinical characteristics, treatment and outcomes during the first 3 months of anticoagulation in fragile vs non‐fragile patients with VTE. Methods Retrospective study using consecutive patients enrolled in the RIETE (Registro Informatizado Enfermedad TromboEmbolica) registry. Fragile patients were defined as those having age ≥75 years, creatinine clearance (CrCl) levels ≤50 mL/min, and/or body weight ≤50 kg. Results From January 2013 to October 2016, 15 079 patients were recruited. Of these, 6260 (42%) were fragile: 37% were aged ≥75 years, 20% had CrCl levels ≤50 mL/min, and 3.6% weighed ≤50 kg. During the first 3 months of anticoagulant therapy, fragile patients had a lower risk of VTE recurrences (0.78% vs 1.4%; adjusted odds ratio [OR]: 0.52; 95% confidence intervals [CI]: 0.37‐0.74) and a higher risk of major bleeding (2.6% vs 1.4%; adjusted OR: 1.41; 95% CI: 1.10‐1.80), gastrointestinal bleeding (0.86% vs 0.35%; adjusted OR: 1.84; 95% CI: 1.16‐2.92), haematoma (0.51% vs 0.07%; adjusted OR: 5.05; 95% CI: 2.05‐12.4), all‐cause death (9.2% vs 3.5%; adjusted OR: 2.02; 95% CI: 1.75‐2.33), or fatal PE (0.85% vs 0.35%; adjusted OR: 1.77; 95% CI: 1.10‐2.85) than the non‐fragile. Conclusions In real life, 42% of VTE patients were fragile. During anticoagulation, they had fewer VTE recurrences and more major bleeding events than the non‐fragile.

Published
2017

39. Platelet Count and Major Bleeding in Patients Receiving Vitamin K Antagonists for Acute Venous Thromboembolism, Findings From Real World Clinical Practice

Author

Giorgi-Pierfranceschi, Mateo, Di Micco, Pierpaolo, Cattabiani, Chiara, Guida, Anna, Pagán, Barbara, Morales, María del Valle, Salgado, Estuardo, Suriñach, Jose María, Tolosa, Carles, Monreal, Manuel, RIETE Investigators, RIETE Investigators, Adarraga, M.D., Andújar, V., Arcelus, J.I., Ballaz, A., Barba, R., Barrón, M., Blanco-Molina, A., Casado, I., Castejón-Pina, N., de Miguel, J., del Molino, F., del Toro, J., Diaz, J.A., Falga, C., Font, L., Gallego, P., Garcia- Bragado, F., Gómez, V., González, J., Grau, E., Guijarro, R., Guirado, L., ndez-Blasco, L., Hernández- Huerta, S., Jara-Palomares, L., Jaras, M.J., Jiménez, D., Lacruz, B., Lecumberri, R., Lobo, J.L., López-Reyes, R., Sáez, J.B., Lorente, M.A., Lorenzo, A., Madridano, O., Maestre, A., Marchena, P.J., Martin-Martos, F., Monreal, M., Morales, M.V., Nauffal, D., Nieto, J.A., Odriozola, M., Otero, R., Pagán, B., Pedrajas, J.M., Pérez, G., Peris, M.L., Pons, I., Porras, J.A., Riera-Mestre, A., Rivas, A., Rosa, V., Sabio, P., Sampériz, A., Sánchez, R., Sanz, O., Soler, S., Suriñach, J.M., Tiberio, G., Tolosa, C., Trujillo-Santos, J., Uresandi, F., Valero, B., Valle, R., Vela, J., Vela, L., Vidal, G., Vilar, C., Villalobos, A., Villalta, J., Xifre, B., Vanassche, T., Verhamme, P., Wells, P., Hirmerova, J., Maly, R., Salgado, E., Bertoletti, L., Bura-Riviere, A., Farge-Bancel, D., Hij, A., Mahe, I., Merah, A., Moustafa, F., Schellong, S., Babalis, D., Papadakis, M., Tzinieris, I., Braester, A., Brenner, B., Tzoran, I., Apollonio, A., Barillari, G., Bucherini, E., Ciammaichella, M., Cola, S., Di Micco, P., Enea, I., Ferrazzi, P., Guida, A., Lessiani, G., Lodigiani, C., Maida, R., Mastroiacovo, D., Pace, F., Pasca, S., Pesavento, R., Pinelli, M., Piovella, C., Prandoni, P., Rota, L., Tiraferri, E., Tonello, D., Tufano, A., Visona, A., Zalunardo, B., Belovs, A., Sablinskis, K., Skride, A., Ribeiro, F., Ribeiro, J.L., Bosevski, M., Zdraveska, M., Alatri, A., Bounameaux, H., Calanca, L., and Mazzolai, L.

Subjects
Male, medicine.medical_specialty, Vitamin K, Observational Study, Hemorrhage, Abnormal platelet count, Vitamin k, Gastroenterology, Aged, Anticoagulants, Female, Fibrinolytic Agents, Follow-Up Studies, Humans, International Normalized Ratio, Middle Aged, Registries, Treatment Outcome, Venous Thromboembolism, Platelet Count, Internal medicine, medicine, Platelet, In patient, business.industry, General Medicine, Surgery, Clinical Practice, Anticoagulants/adverse effects, Anticoagulants/therapeutic use, Fibrinolytic Agents/adverse effects, Fibrinolytic Agents/therapeutic use, Hemorrhage/chemically induced, Hemorrhage/epidemiology, Venous Thromboembolism/drug therapy, business, Venous thromboembolism, Major bleeding, Fibrinolytic agent, Research Article
Abstract

The outcome of patients with acute venous thromboembolism (VTE) and abnormal platelet count (PlC) at baseline has not been consistently studied. In real-world clinical practice, a number of patients with abnormal PlC receive vitamin K antagonists (VKAs) to treat acute VTE despite their higher risk of bleeding. We used the Registro Informatizado de Enfermedad TromboEmbólica registry database to compare the rate of major bleeding in patients receiving VKA for long-term therapy of acute VTE according to PlC levels at baseline. Patients were categorized as having very low (450,000/μL) PlC at baseline. Of 55,369 patients recruited as of January 2015, 37,000 (67%) received long-term therapy with VKA. Of these, 611 patients (1.6%) had very low PlC, 4006 (10.8%) had low PlC, 25,598 (69%) had normal PlC, 5801 (15.6%) had high PlC, and 984 (2.6%) had very high PlC at baseline. During the course of VKA therapy (mean, 192 days), there were no differences in the duration or intensity (as measured by international normalized ratio levels) of treatment between subgroups. The rate of major bleeding was 3.6%, 2.1%, 1.9%, 2.1%, and 3.7%, respectively, and the rate of fatal bleeding was 0.98%, 0.17%, 0.29%, 0.34%, and 0.50%, respectively. Patients with very low or very high PlC levels were more likely to have severe comorbidities. We found a nonlinear “U-shaped” relationship between PlC at baseline and major bleeding during therapy with VKA for VTE. Consistent alteration of PlC values at baseline suggested a greater frailty.

Published
2015

40. Efficacy and Tolerability of Vardenafil in Men With Mild Depression and Erectile Dysfunction: The Depression-Related Improvement With Vardenafil for Erectile Response Study

Author

Ridwan Shabsigh, Luis Rodriguez-Vela, Mark Berber, Keith Bangerter, Francesco Montorsi, Mathew Menza, Robert Porto, Monica Seger, Pierre Assalian, Raymond C. Rosen, Rosen, R, Shabsigh, R, Berber, M, Assalian, P, Menza, M, Rodriguez Vela, L, Porto, R, Bangerter, K, Seger, M, and Montorsi, Francesco

Subjects
Male, medicine.medical_specialty, Comorbidity, Placebo, Severity of Illness Index, Drug Administration Schedule, Piperazines, law.invention, Placebos, Double-Blind Method, Erectile Dysfunction, Vardenafil Dihydrochloride, Randomized controlled trial, law, Surveys and Questionnaires, Internal medicine, Severity of illness, Humans, Medicine, Sulfones, Least-Squares Analysis, Depression (differential diagnoses), Psychiatric Status Rating Scales, Depressive Disorder, Major, Phosphoric Diester Hydrolases, Triazines, business.industry, Imidazoles, Middle Aged, medicine.disease, Surgery, Psychiatry and Mental health, Treatment Outcome, Erectile dysfunction, Tolerability, Vardenafil, business, medicine.drug
Abstract

Objective: Erectile dysfunction and depression are highly associated. Previous studies have shown benefits of phosphodiesterase-5 inhibitor treatment for erectile dysfunction associated with antidepressant therapy or subsyndromal depression. The present study assessed the safety and efficacy of vardenafil in men with erectile dysfunction and untreated mild depression. Method: In this 12-week, multicenter, randomized, flexible-dose, parallel-group, double-blind study, 280 men with erectile dysfunction for at least 6 months and untreated mild major depression received placebo or vardenafil, 10 mg/day, for 4 weeks, with the option to titrate to 5 mg/day or 20 mg/day after each of two consecutive 4-week intervals. Endpoints included International Index of Erectile Function erectile function domain and 17-item Hamilton Depression Rating Scale (HAM-D) scores. Results: Vardenafil produced statistically significant and clinically meaningful improvement in all erectile function parameters. The International Index of Erectile Function erectile function domain score was 22.9 with vardenafil compared to 14.9 with placebo. The HAM-D score was lower in the vardenafil group (7.9) than in the placebo group (10.1). Treatment with vardenafil was the most important predictor for return to normal erectile function. Improvement in International Index of Erectile Function erectile function domain score was the most important predictor of remission in depressive symptoms. Conclusions: Vardenafil was well tolerated and highly efficacious in men with erectile dysfunction and untreated mild major depression. Significant improvements in erectile function and depression were observed in patients treated with vardenafil versus placebo. Erectile dysfunction treatment should be considered a component of therapy for men with depression and erectile dysfunction.

Published
2006
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