30 research outputs found
Effect of tibolone on breast cancer cell proliferation in postmenopausal ER+ patients: Results from STEM trial
Purpose: Tibolone is a selective tissue estrogenic activity regulator, approved for the treatment of vasomotor symptoms in postmenopausal women. We have done an exploratory, double-blind, randomized, placebo-controlled pilot trial to investigate the tissue-specific effects of 2.5 mg tibolone on breast cancer in postmenopausal women, in particular on tissue proliferation (STEM, Study of Tibolone Effects on Mamma carcinoma tissue).
Experimental Design: Postmenopausal women with initially stage I/II, estrogen receptor-positive (ER+) primary breast cancer, were randomly assigned to 14 days of placebo or 2.5 mg/d tibolone. Core biopsies of the primary tumor were obtained before and after treatment. Ki-67 and apoptosis index were analyzed in baseline and corresponding posttreatment specimen.
Results: Of 102 enrolled patients, 95 had evaluable data. Baseline characteristics were comparable between both treatment groups. Breast cancer cases are mainly invasive (99%), stage I or II (42% and 50% respectively), and ER+ (99%). Median intratumoral Ki-67 expression at baseline was 13.0%, in the tibolone group and 17.8% in the placebo group, and decreased to 12.0% after 14 days of tibolone while increasing to 19.0% in the placebo group. This change from baseline was not significantly different between tibolone and placebo (Wilcoxon test; P = 0.17). A significant difference was observed between the treatment groups when the median change from baseline apoptosis index was compared between the treatment groups (tibolone, 0.0%; placebo, +0.3%; Wilcoxon test; P = 0.031). The incidence of adverse effects was comparable.
Conclusions: In ER+ breast tumors, 2.5 mg/d tibolone given for 14 days has no significant effect on tumor cell proliferation
Evaluation of C-reactive protein, Haptoglobin and cardiac Troponin 1 levels in brachycephalic dogs with upper airway obstructive syndrome
Background: Brachycephalic dogs have unique upper respiratory anatomy with abnormal breathing patterns similar to those in humans with obstructive sleep apnea syndrome (OSAS). The objective of this study was to evaluate the correlation between anatomical components, clinical signs and several biomarkers, used to determine systemic inflammation and myocardial damage (C-reactive protein, CRP; Haptoglobin, Hp; cardiac troponin I, cTnI), in dogs with brachycephalic upper airway obstructive syndrome (BAOS). Results: Fifty brachycephalic dogs were included in the study and the following information was studied: signalment, clinical signs, thoracic radiographs, blood work, ECG, components of BAOS, and CRP, Hp and cTnI levels. A high proportion of dogs with BAOS (88%) had gastrointestinal signs. The prevalence of anatomic components of BAOS was: elongated soft palate (100%), stenotic nares (96%), everted laryngeal saccules (32%) and tracheal hypoplasia (29.1%). Increased serum levels of biomarkers were found in a variable proportion of dogs: 14% (7/50) had values of CRPâ>â20 mg/L, 22.9% (11/48) had values of Hpâ>â3 g/L and 47.8% (22/46) had levels of cTnIâ>â0.05 ng/dl. Dogs with everted laryngeal saccules had more severe respiratory signs (p<0.02) and higher values of CRP (p<0.044). No other statistical association between biomarkers levels and severity of clinical signs was found. Conclusions: According to the low percentage of patients with elevated levels of CRP and Hp, BAOS does not seem to cause an evident systemic inflammatory status. Some degree of myocardial damage may occur in dogs with BAOS that can be detected by cTnI concentration
Predictors of clinically significant quality of life impairment in Parkinson's disease.
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; R2 = 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 patient
Sleep Problems Are Related to a Worse Quality of Life and a Greater Non-Motor Symptoms Burden in Parkinsonâs Disease
COPPADIS Study Group.[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 Parkinsonâs 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 1.015â1.043; p < 0.0001) and impulse control behaviors (QUIP-RS; OR = 1.054; 95%CI 1.009â1.101; 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.Peer reviewe
Predictors of Global Non-Motor Symptoms Burden Progression in Parkinsonâs Disease. Results from the COPPADIS Cohort at 2-Year Follow-Up
Background and Objective: Non-motor symptoms (NMS) progress in different ways between Parkinson's disease (PD) patients. The aim of the present study was to (1) analyze the change in global NMS burden in a PD cohort after a 2-year follow-up, (2) to compare the changes with a control group, and (3) to identify predictors of global NMS burden progression in the PD group. Material and Methods: PD patients and controls, recruited from 35 centers of Spain from the COPPADIS cohort from January 2016 to November 2017, were followed-up with after 2 years. The Non-Motor Symptoms Scale (NMSS) was administered at baseline (V0) and at 24 months ± 1 month (V2). Linear regression models were used for determining predictive factors of global NMS burden progression (NMSS total score change from V0 to V2 as dependent variable). Results: After the 2-year follow-up, the mean NMS burden (NMSS total score) significantly increased in PD patients by 18.8% (from 45.08 ± 37.62 to 53.55 ± 42.28; p < 0.0001; N = 501; 60.2% males, mean age 62.59 ± 8.91) compared to no change observed in controls (from 14.74 ± 18.72 to 14.65 ± 21.82; p = 0.428; N = 122; 49.5% males, mean age 60.99 ± 8.32) (p < 0.0001). NMSS total score at baseline (ÎČ = -0.52), change from V0 to V2 in PDSS (Parkinson's Disease Sleep Scale) (ÎČ = -0.34), and change from V0 to V2 in NPI (Neuropsychiatric Inventory) (ÎČ = 0.25) provided the highest contributions to the model (adjusted R-squared 0.41; Durbin-Watson test = 1.865). Conclusions: Global NMS burden demonstrates short-term progression in PD patients but not in controls and identifies worsening sleep problems and neuropsychiatric symptoms as significant independent predictors of this NMS progression
Staging Parkinsonâs Disease According to the MNCD (Motor/Non-motor/Cognition/Dependency) Classification Correlates with Disease Severity and Quality of Life
Background: Recently, a novel simple classification called MNCD, based on 4 axes (Motor; Non-motor; Cognition; Dependency) and 5 stages, has been proposed to classify Parkinson's disease (PD). Objective: Our aim was to apply the MNCD classification in a cohort of PD patients for the first time and also to analyze the correlation with quality of life (QoL) and disease severity. Methods: Data from the baseline visit of PD patients recruited from 35 centers in Spain from the COPPADIS cohort from January 2016 to November 2017 were used to apply the MNCD classification. Three instruments were used to assess QoL: 1) the 39-item Parkinson's disease Questionnaire [PDQ-39]); PQ-10; the EUROHIS-QOL 8-item index (EUROHIS-QOL8). Results: Four hundred and thirty-nine PD patients (62.05 +/- 7.84 years old; 59% males) were included. MNCD stage was: stage 1, 8.4% (N = 37); stage 2, 62% (N = 272); stage 3, 28.2% (N = 124); stage 4-5, 1.4% (N = 6). A more advanced MNCD stage was associated with a higher score on the PDQ39SI (p < 0.0001) and a lower score on the PQ-10 (p < 0.0001) and EUROHIS-QOL8 (p < 0.0001). In many other aspects of the disease, such as disease duration, levodopa equivalent daily dose, motor symptoms, non-motor symptoms, and autonomy for activities of daily living, an association between the stage and severity was observed, with data indicating a progressive worsening related to disease progression throughout the proposed stages. Conclusion: Staging PD according to the MNCD classification correlated with QoL and disease severity. The MNCD could be a proper tool to monitor the progression of PD
Staging Parkinson's Disease Combining Motor and Nonmotor Symptoms Correlates with Disability and Quality of Life.
Introduction: In a degenerative disorder such as Parkinson's disease (PD), it is important to establish clinical stages that allow to know the course of the disease. Our aim was to analyze whether a scale combining Hoehn and Yahr's motor stage (H&Y) and the nonmotor symptoms burden (NMSB) (assessed by the nonmotor symptoms scale (NMSS)) provides information about the disability and the patient's quality of life (QoL) with regard to a defined clinical stage. Materials and methods: Cross-sectional study in which 603 PD patients from the COPPADIS cohort were classified according to H&Y (1, stage I; 2, stage II; 3, stage III; 4, stage IV/V) and NMSB (A: NMSS = 0-20; B: NMSS = 21-40; C: NMSS = 41-70; D: NMSS ℠71) in 16 stages (HY.NMSB, from 1A to 4D). QoL was assessed with the PDQ-39SI, PQ-10, and EUROHIS-QOL8 and disability with the Schwab&England ADL (Activities of Daily Living) scale. Results: A worse QoL and greater disability were observed at a higher stage of H&Y and NMSB (p < 0.0001). Combining both (HY.NMSB), patients in stages 1C and 1D and 2C and 2D had significantly worse QoL and/or less autonomy for ADL than those in stages 2A and 2B and 3A and 3B, respectively (p < 0.005; e.g., PDQ-39SI in 1D [n = 15] vs 2A [n = 101]: 28.6 ± 17.1 vs 7.9 ± 5.8; p < 0.0001). Conclusion: The HY.NMSB scale is simple and reflects the degree of patient involvement more accurately than the HΚ Patients with a lower H&Y stage may be more affected if they have a greater NMS burden
Predictors of Global Non-Motor Symptoms Burden Progression in Parkinsonâs Disease. Results from the COPPADIS Cohort at 2-Year Follow-Up
COPPADIS Study Group.[Background and Objective] Non-motor symptoms (NMS) progress in different ways between Parkinsonâs disease (PD) patients. The aim of the present study was to (1) analyze the change in global NMS burden in a PD cohort after a 2-year follow-up, (2) to compare the changes with a control group, and (3) to identify predictors of global NMS burden progression in the PD group.[Material and Methods] PD patients and controls, recruited from 35 centers of Spain from the COPPADIS cohort from January 2016 to November 2017, were followed-up with after 2 years. The Non-Motor Symptoms Scale (NMSS) was administered at baseline (V0) and at 24 months ± 1 month (V2). Linear regression models were used for determining predictive factors of global NMS burden progression (NMSS total score change from V0 to V2 as dependent variable).[Results] After the 2-year follow-up, the mean NMS burden (NMSS total score) significantly increased in PD patients by 18.8% (from 45.08 ± 37.62 to 53.55 ± 42.28; p < 0.0001; N = 501; 60.2% males, mean age 62.59 ± 8.91) compared to no change observed in controls (from 14.74 ± 18.72 to 14.65 ± 21.82; p = 0.428; N = 122; 49.5% males, mean age 60.99 ± 8.32) (p < 0.0001). NMSS total score at baseline (ÎČ = â0.52), change from V0 to V2 in PDSS (Parkinsonâs Disease Sleep Scale) (ÎČ = â0.34), and change from V0 to V2 in NPI (Neuropsychiatric Inventory) (ÎČ = 0.25) provided the highest contributions to the model (adjusted R-squared 0.41; Durbin-Watson test = 1.865).[Conclusions] Global NMS burden demonstrates short-term progression in PD patients but not in controls and identifies worsening sleep problems and neuropsychiatric symptoms as significant independent predictors of this NMS progression.This research was funded by FundaciĂłn Española de Ayuda a la InvestigaciĂłn en Parkinson y otras Enfermedades Neuro-degenerativas (Curemos el Parkinson; www.curemoselparkinson.org).Peer reviewe
Staging Parkinsonâs Disease Combining Motor and Nonmotor Symptoms Correlates with Disability and Quality of Life
COPPADIS Study Group.[Introduction] In a degenerative disorder such as Parkinsonâs disease (PD), it is important to establish clinical stages that allow to know the course of the disease. Our aim was to analyze whether a scale combining Hoehn and Yahrâs motor stage (H&Y) and the nonmotor symptoms burden (NMSB) (assessed by the nonmotor symptoms scale (NMSS)) provides information about the disability and the patientâs quality of life (QoL) with regard to a defined clinical stage.[Materials and Methods] Cross-sectional study in which 603 PD patients from the COPPADIS cohort were classified according to H&Y (1, stage I; 2, stage II; 3, stage III; 4, stage IV/V) and NMSB (A: NMSSâ=â0â20; B: NMSSâ=â21â40; C: NMSSâ=â41â70; D: NMSSââ„â71) in 16 stages (HY.NMSB, from 1A to 4D). QoL was assessed with the PDQ-39SI, PQ-10, and EUROHIS-QOL8 and disability with the Schwab&England ADL (Activities of Daily Living) scale.[Results] A worse QoL and greater disability were observed at a higher stage of H&Y and NMSB (). Combining both (HY.NMSB), patients in stages 1C and 1D and 2C and 2D had significantly worse QoL and/or less autonomy for ADL than those in stages 2A and 2B and 3A and 3B, respectively (; e.g., PDQ-39SI in 1D [nâ=â15] vs 2A [nâ=â101]: 28.6â±â17.1 vs 7.9â±â5.8; ).[Conclusion] The HY.NMSB scale is simple and reflects the degree of patient involvement more accurately than the H&Y. Patients with a lower H&Y stage may be more affected if they have a greater NMS burden.Peer reviewe
Predictors of clinically significant quality of life impairment in Parkinsonâs disease
COPPADIS Study Group.Quality of life (QOL) plays an important role in independent living in Parkinsonâs 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 Parkinsonâs 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 â„ 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 (Nâ=â507; pâ=â0.686) or in the control group (Nâ=â119; pâ=â0.192). The mean PDQ-39SI was significantly increased in PD patients (62.7â±â8.5 years old; 58.8% males; Nâ=â500) by 21.6% (from 16.7â±â13 to 20.3â±â16.4; pâ<â0.0001) at V2. Ninety-three patients (18.6%) presented a clinically significant HRQoL impairment at V2. To be younger (ORâ=â0.896; 95% CI 0.829â0.968; pâ=â0.006), to be a female (ORâ=â4.181; 95% CI 1.422â12.290; pâ=â0.009), and to have a greater increase in BDI-II (Beck Depression Inventory-II) (ORâ=â1.139; 95% CI 1.053â1.231; pâ=â0.001) and NMSS (Non-Motor Symptoms Scale) (ORâ=â1.052; 95% CI 1.027â1.113; pâ<â0.0001) total scores from V0 to V2 were associated with clinically significant HRQoL impairment at the 2-year follow-up (HosmerâLemeshow test, pâ=â0.665; R 2â=â0.655). An increase in â„5 and â„10 points of BDI-II and NMSS total score at V2 multiplied the probability of presenting clinically significant HRQoL impairment by 5 (ORâ=â5.453; 95% CI 1.663â17.876; pâ=â0.005) and 8 (ORâ=â8.217; 95% CI, 2.975â22.696; pâ=â0.002), 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.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 (SubdirecciĂłn General de EvaluaciĂłn y Fomento de la InvestigaciĂłn) and by Fondo Europeo de Desarrollo Regional (FEDER), the ConsejerĂa de EconomĂa, InnovaciĂłn, Ciencia y Empleo de la Junta de AndalucĂa [CVI-02526, CTS-7685], the ConsejerĂa de Salud y Bienestar Social de la Junta de AndalucĂa [PI-0437-2012, PI-0471-2013], the Sociedad Andaluza de NeurologĂa, the Jacques and Gloria Gossweiler Foundation, the FundaciĂłn Alicia Koplowitz, the FundaciĂłn Mutua Madrileña.Peer reviewe