RESUMO
Parkinson's disease (PD) is affecting about 1.2 million patients in Europe with a prevalence that is expected to have an exponential increment, in the next decades. This epidemiological evolution will be challenged by the low number of neurologists able to deliver expert care for PD. As PD is better recognized, there is an increasing demand from patients for rigorous control of their symptoms and for therapeutic education. In addition, the highly variable nature of symtoms between patients and the fluctuations within the same patient requires innovative tools to help doctors and patients monitor the disease in their usual living environment and adapt treatment in a more relevant way. Nowadays, there are various body-worn sensors (BWS) proposed to monitor parkinsonian clinical features, such as motor fluctuations, dyskinesia, tremor, bradykinesia, freezing of gait (FoG) or gait disturbances. BWS have been used as add-on tool for patients' management or research purpose. Here, we propose a practical anthology, summarizing the characteristics of the most used BWS for PD patients in Europe, focusing on their role as tools to improve treatment management. Consideration regarding the use of technology to monitor non-motor features is also included. BWS obviously offer new opportunities for improving management strategy in PD but their precise scope of use in daily routine care should be clarified.
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This study aimed to correlate REM sleep without atonia (RSWA) and neuropsychological data in patients with idiopathic/isolated REM sleep behaviour disorder (iRBD) and those with RBD associated with Parkinson's disease (PDRBD), in order to assess whether higher degrees of RSWA are related to poorer cognitive performance. A total of 142 subjects were enrolled: 48 with iRBD, 55 with PDRBD, and 39 PD without RBD (PDnoRBD). All participants underwent video-polysomnographic recording, clinical and neuropsychological assessment. RSWA was quantified according to two manual scoring methods (Montréal, SINBAR) and one automated (REM atonia index, RAI). Mild cognitive impairment (MCI) was diagnosed according to diagnostic criteria for MCI in Parkinson's disease. The relationship between neuropsychological scores and RSWA metrics was explored by multiple linear regression analysis and logistic regression models. Patients with iRBD showed significantly lower visuospatial functions and working memory, compared with the others. More severe RSWA was associated with a higher risk of reduced visuospatial abilities (OR 0.15), working memory (OR 2.48), attention (OR 2.53), and semantic fluency (OR 0.15) in the iRBD. In the whole group, a greater RSWA was associated with an increased risk for depressive symptoms (OR 3.6). A total of 57(40%) MCI subjects were found (17 iRBD, 26 PDRBD, and 14 PDnoRBD). Preserved REM-atonia was associated with a reduced odds of multi-domain MCI in the whole study population (OR 0.54). In conclusion, a greater severity of RSWA was associated with an increased risk for poor cognitive performance and depressive mood in patients with RBD. Moreover, higher RAI was associated with a lower risk of multi-domain MCI.
Assuntos
Disfunção Cognitiva , Doença de Parkinson , Transtorno do Comportamento do Sono REM , Humanos , Transtorno do Comportamento do Sono REM/complicações , Transtorno do Comportamento do Sono REM/diagnóstico , Depressão/complicações , Depressão/diagnóstico , Doença de Parkinson/complicações , Doença de Parkinson/diagnóstico , Sono REM , Hipotonia Muscular/complicações , Hipotonia Muscular/diagnóstico , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/complicaçõesRESUMO
BACKGROUND: Iron content is increased in the substantia nigra of persons with Parkinson's disease and may contribute to the pathophysiology of the disorder. Early research suggests that the iron chelator deferiprone can reduce nigrostriatal iron content in persons with Parkinson's disease, but its effects on disease progression are unclear. METHODS: We conducted a multicenter, phase 2, randomized, double-blind trial involving participants with newly diagnosed Parkinson's disease who had never received levodopa. Participants were assigned (in a 1:1 ratio) to receive oral deferiprone at a dose of 15 mg per kilogram of body weight twice daily or matched placebo for 36 weeks. Dopaminergic therapy was withheld unless deemed necessary for symptom control. The primary outcome was the change in the total score on the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS; range, 0 to 260, with higher scores indicating more severe impairment) at 36 weeks. Secondary and exploratory clinical outcomes at up to 40 weeks included measures of motor and nonmotor disability. Brain iron content measured with the use of magnetic resonance imaging was also an exploratory outcome. RESULTS: A total of 372 participants were enrolled; 186 were assigned to receive deferiprone and 186 to receive placebo. Progression of symptoms led to the initiation of dopaminergic therapy in 22.0% of the participants in the deferiprone group and 2.7% of those in the placebo group. The mean MDS-UPDRS total score at baseline was 34.3 in the deferiprone group and 33.2 in the placebo group and increased (worsened) by 15.6 points and 6.3 points, respectively (difference, 9.3 points; 95% confidence interval, 6.3 to 12.2; P<0.001). Nigrostriatal iron content decreased more in the deferiprone group than in the placebo group. The main serious adverse events with deferiprone were agranulocytosis in 2 participants and neutropenia in 3 participants. CONCLUSIONS: In participants with early Parkinson's disease who had never received levodopa and in whom treatment with dopaminergic medications was not planned, deferiprone was associated with worse scores in measures of parkinsonism than those with placebo over a period of 36 weeks. (Funded by the European Union Horizon 2020 program; FAIRPARK-II ClinicalTrials.gov number, NCT02655315.).
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Antiparkinsonianos , Deferiprona , Quelantes de Ferro , Ferro , Doença de Parkinson , Substância Negra , Humanos , Deferiprona/administração & dosagem , Deferiprona/efeitos adversos , Deferiprona/farmacologia , Deferiprona/uso terapêutico , Ferro/análise , Ferro/metabolismo , Levodopa/uso terapêutico , Neutropenia/induzido quimicamente , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo , Doença de Parkinson/fisiopatologia , Quelantes de Ferro/administração & dosagem , Quelantes de Ferro/efeitos adversos , Quelantes de Ferro/farmacologia , Quelantes de Ferro/uso terapêutico , Substância Negra/química , Substância Negra/diagnóstico por imagem , Substância Negra/efeitos dos fármacos , Substância Negra/metabolismo , Progressão da Doença , Método Duplo-Cego , Administração Oral , Encéfalo/diagnóstico por imagem , Química Encefálica , Dopaminérgicos/administração & dosagem , Dopaminérgicos/efeitos adversos , Dopaminérgicos/farmacologia , Dopaminérgicos/uso terapêutico , Antiparkinsonianos/administração & dosagem , Antiparkinsonianos/efeitos adversos , Antiparkinsonianos/farmacologia , Antiparkinsonianos/uso terapêuticoRESUMO
INTRODUCTION: There is a growing interest in personality evaluation in Parkinson's disease (PD), following observations of specific temperaments in PD patients. Therefore, our objective was to evaluate personality dimensions from the Temperament and Character Inventory (TCI) in a cohort of fluctuating PD patients considered for deep brain stimulation. METHODS: Fluctuating PD patients from the PREDISTIM cohort were included. Description of TCI dimensions and comparison with a French normative cohort were performed. Pearson correlations between TCI dimensions and motor, behavioral and cognitive variables were investigated. Structural and internal consistency analysis of the TCI were further assessed. RESULTS: The 570 PD patients presented significant higher scores in Harm Avoidance, Reward Dependence, Persistence, Self-Directedness and Cooperativeness and significant lower scores in Self-Transcendence compared to the French normative cohort; only Novelty Seeking scores were not different. Harm Avoidance and Self-directedness scores were correlated with PDQ-39 total, HAMD, HAMA scores, and anxiolytic/antidepressant treatment. Novelty Seeking scores were correlated with impulsivity. Pearson correlations between TCI dimensions, principal component analysis of TCI sub-dimensions and Cronbach's alpha coefficients showed adequate psychometric proprieties. CONCLUSION: The TCI seems to be an adequate tool to evaluate personality dimensions in PD with good structural and internal consistencies. These fluctuating PD patients also have specific personality dimensions compared to normative French population. Moreover, Harm Avoidance and Self-Directedness scores are associated with anxio-depressive state or quality of life and, and Novelty Seeking scores with impulsivity.
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Ansiolíticos , Doença de Parkinson , Humanos , Temperamento , Inventário de Personalidade , Doença de Parkinson/diagnóstico , Qualidade de Vida , Determinação da Personalidade , AntidepressivosRESUMO
INTRODUCTION: To investigate glutamatergic metabolism changes in the putamen of patients with de novo Parkinson's Disease (PD) and test the hypothesis that glutamate (Glu) levels are abnormally elevated in the putamen contralateral to where the motor clinical signs predominate as expected from observations in animal models. METHODS: 1H NMR spectra from 17 healthy control volunteers were compared with spectra from 17 de novo PD patients of who 14 were evaluated again after 2-3 years of disease progression. Statistical analysis used random-effects models. RESULTS: The only significant difference between PD patients and controls was a higher glutamine (Gln) concentration in the putamen ipsilateral to the hemibody with predominant motor signs (Visit 1: 6.0 ± 0.4 mM vs. 5.2 ± 0.2 mM, p < 0.05; Visit 2: 6.2 ± 0.3 mM vs. 5.2 ± 0.2 mM, p < 0.05). At Visit 1, PD patients had higher Glu and Gln levels in the putamen ipsilateral versus contralateral to dominant clinical signs (Glu: 12.2 ± 0.6 mM vs. 10.4 ± 0.6 mM, p < 0.05; Gln: 6.0 ± 0.4 mM vs. 4.8 ± 0.4 mM, p < 0.05; Glu and Gln pool (Glx): 17.9 ± 0.8 mM vs. 14.7 ± 1.1 mM, p < 0.05). At Visit 2, the sum of the two metabolites remained significantly higher in the ipsilateral versus contralateral putamen (Glx: 18.3 ± 0.6 mM vs. 16.1 ± 0.9 mM, p < 0.05). CONCLUSION: In de novo PD patients, the putamen ipsilateral to the more affected hemibody showed elevated Gln versus controls and elevated Glu and Gln concentrations versus the contralateral side. Abnormalities in Glu metabolism therefore occur early in PD but unexpectedly in the putamen contralateral to the more damaged hemisphere, suggesting they are not dependent solely on dopamine loss.
Assuntos
Ácido Glutâmico , Doença de Parkinson , Animais , Ácido Glutâmico/metabolismo , Glutamina/metabolismo , Humanos , Doença de Parkinson/metabolismo , Espectroscopia de Prótons por Ressonância Magnética , Putamen/diagnóstico por imagem , Putamen/metabolismoRESUMO
BACKGROUND: Deep brain stimulation of the sub-thalamic nucleus (DBS-STN) reduces symptoms in Parkinson's disease (PD) patients with motor fluctuations. However, some patients may not feel ameliorated afterwards, despite an objective motor improvement. It is thus important to find new predictors of patients' quality of life (QoL) amelioration after DBS-STN. We hypothesized that personality dimensions might affect QoL after DBS-STN. OBJECTIVE: To evaluate associations between personality dimensions and QoL improvement one year after DBS-STN. METHODS: DBS-STN-PD patients (nâ=â303) having answered the "Temperament and Character Inventory" (TCI) before surgery and the PDQ-39 before and one year after surgery were included, from the cohort study PREDI-STIM. Linear regression models were used to evaluate associations between TCI dimensions and change in PDQ-39 scores after DBS-STN. RESULTS: Novelty Seeking and Cooperativeness scores before surgery were positively associated with PDQ-39 scores improvement after DBS-STN (FDR-adjusted pâ<â0.01). Moreover, paradoxically unimproved patients with deterioration of their PDQ-39 scores after DBS-STN despite improvement of their MDS-UPDRS-IV scores had lower Cooperativeness scores, while paradoxically improved patients with amelioration of their PDQ-39 scores despite deterioration of their MDS-UPDRS-IV scores had higher Reward Dependence scores. CONCLUSION: Some presurgical personality dimensions were significantly associated with QoL amelioration and discrepancy between motor state and QoL changes after DBS-STN in PD. Educational programs before DBS-STN should take in account patient personality dimensions to better deal with their expectations.
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Estimulação Encefálica Profunda , Doença de Parkinson , Núcleo Subtalâmico , Estudos de Coortes , Estimulação Encefálica Profunda/métodos , Humanos , Doença de Parkinson/cirurgia , Doença de Parkinson/terapia , Personalidade , Qualidade de Vida , Núcleo Subtalâmico/fisiologiaRESUMO
BACKGROUND: Studies assessing personality dimensions by the "Temperament and Character Inventory" (TCI) have previously found an association between Parkinson's disease (PD) and lower Novelty Seeking and higher Harm Avoidance scores. Here, we aimed to describe personality dimensions of PD patients with motor fluctuations and compare them to a normative population and other PD populations. METHODS: All PD patients awaiting Deep Brain Stimulation (DBS) answered the TCI before neurosurgery. Their results were compared to those of historical cohorts (a French normative population, a de novo PD population, and a PD population with motor fluctuations). RESULTS: Most personality dimensions of our 333 included PD patients with motor fluctuations who are candidates for DBS were different from those of the normative population and some were also different from those of the De Novo PD population, whereas they were similar to those of another population of PD patients with motor fluctuations. CONCLUSIONS: During the course of PD, personality dimensions can change in parallel with the development of motor fluctuations, either due to the evolution of the disease and/or dopaminergic treatments.
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Caráter , Doença de Parkinson/psicologia , Transtornos da Personalidade/psicologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inventário de PersonalidadeRESUMO
BACKGROUND: Parkinson's disease (PD) negatively affects patients' Quality of Life (QoL) which depends on both objective criteria such as physical health and subjective ones such as worries and norms according to personal believes. Therefore, QoL could be also associated to personality dimensions in chronic neurological diseases such as PD. OBJECTIVE: Our objective was thus to study the potential association between personality dimensions and QoL in PD patients with motor fluctuations before Deep Brain Stimulation of the Sub-Thalamic Nucleus (DBS-STN). METHODS: Data were obtained from the French multicentric cohort study Predi-Stim. All PD patients awaiting DBS-STN and responding to the inclusion criteria at the time of the study were included. All participants answered the "Temperament and Character Inventory" (TCI) and the PDQ-39 before surgery. Analyses were made using adjusted univariate generalized linear regression models to evaluate a potential association between TCI dimensions and PDQ-39 scores. RESULTS: Three hundred thirty-three consecutive patients were included. The temperament Harm Avoidance was negatively associated with QoL (pâ=â1e-4, R2=â0.33), whereas the character Self-Directedness was positively associated with mental component of QoL (pâ=â2e-4, R2=â0.33) in PD patients with motor fluctuations awaiting DBS-STN. CONCLUSIONS: PD patients with motor fluctuations, with lower Harm Avoidance and higher Self-Directedness scores have the best QoL mainly at an emotional and social level. Therapeutic education of these PD patients focusing on their personal resources may thus be important to improve their well-being.
Assuntos
Caráter , Doença de Parkinson/fisiopatologia , Doença de Parkinson/psicologia , Qualidade de Vida , Temperamento/fisiologia , Estudos de Coortes , Estimulação Encefálica Profunda , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/terapia , Qualidade de Vida/psicologia , Núcleo SubtalâmicoRESUMO
OBJECTIVE: To assess the association between rapid eye movement sleep behavior disorder (RBD) and other determinants and incident impulse control disorder behaviors (ICBs) in patients with early Parkinson disease (PD) using longitudinal data from the Parkinson's Progression Markers Initiative. METHODS: Four hundred one newly diagnosed PD patients were prospectively evaluated at baseline (BL), month 6, and annually for 5 years. Probable RBD (pRBD) was assessed with the RBD Screening Questionnaire (RBDSQ) and dichotomized using a cutoff value of ≥6. The association of BL and time-dependent (TD) pRBD and other covariates with the development of ICB symptoms was evaluated using Cox proportional hazards regression and general estimating equation logistic regression. Models considered adjustment for age, sex, Movement Disorders Society Unified Parkinson's Disease Rating Scale part III, Geriatric Depression Scale (GDS-15), RBD medication use, total levodopa equivalent daily dose, and dopamine agonist (DA) and antidepressant medication use. RESULTS: Both BL pRBD and TD pRBD were not associated with an increased risk for incident ICB symptoms after adjustment for covariates (adjusted hazard ratio [HR] = 1.17, p = 0.458 and HR = 1.27, p = 0.257, respectively). In a modified TD pRBD model (ie, considering subjects as pRBD onward from the first time point with RBDSQ score ≥ 6), the risk for incident ICB symptoms was higher in pRBD in unadjusted (HR = 1.48, p = 0.038) but not adjusted (HR = 1.29, p = 0.203) models. TD DA use (HR = 1.64, p = 0.039), TD GDS-15 score (HR = 1.12, p < 0.001), and male sex (year 3: HR = 2.10, p = 0.009; year 4: HR = 3.04, p = 0.006; year 5: HR = 4.40, p = 0.007) were associated with increased ICB symptom risk. INTERPRETATION: pRBD is not clearly associated with ICB symptom development in early PD, in contrast to DA use, depression, and male sex. ANN NEUROL 2020;88:759-770.
Assuntos
Transtornos Disruptivos, de Controle do Impulso e da Conduta/epidemiologia , Doença de Parkinson/complicações , Transtorno do Comportamento do Sono REM/epidemiologia , Idoso , Transtornos Disruptivos, de Controle do Impulso e da Conduta/etiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Transtorno do Comportamento do Sono REM/etiologia , Fatores de RiscoRESUMO
BACKGROUND/AIM: The need to improve post-bariatric hypoglycemia (PBH) diagnosis and clinical management is well recognized. Our aim was to evaluate the influence of meal nutritional composition on interstitial fluid glucose (IFG) profiles and symptom profile after Roux-en-Y gastric bypass (RYGB). METHODS: Seventeen subjects previously submitted to RYGB were allocated into two groups of symptomatic (n = 9) or control individuals (n = 8), according to spontaneous report of symptoms suggestive of hypoglycemia. Subjects were provided with a food and symptom diary (FSD) to record dietary intake and symptoms experienced, while using a flash glucose monitoring (FGM) system for 14 days. RESULTS: Postprandial symptom reports occurred in 70.5% of subjects (88.9% vs 50.0%, p = 0.0790, symptomatic vs control), although symptoms with concurrent IFG < 54 mg/dL and within 54 to 69 mg/dL were only observed in 31.9% and 4.8% of the events in the symptomatic vs control group, respectively (p = 0.0110). Daily glucose profiles, total energy, and macronutrients intake were not significantly different between the groups. However, nutritional composition of meals preceding reported symptoms had lower protein (3.2 g ± 1.0 g vs 7.7 g ± 0.5 g, p = 0.0286) or higher sugar (11.6 g ± 2.4 g vs 4.3 g ± 0.9 g, p = 0.0333) content. CONCLUSIONS: Postprandial symptoms are often in patients after RYGB. Concurrent hypoglycemia only occurs in up to a third of the symptomatic episodes being more frequent in patients that spontaneously reported complaints. Hypoglycemia is more likely to be triggered by meals with a low protein or high sugar content. These findings highlight the putative role of meal composition in eliciting PBH and reinforce the need to refine nutritional intervention.
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Dieta , Líquido Extracelular/metabolismo , Derivação Gástrica/efeitos adversos , Glucose/metabolismo , Hipoglicemia/terapia , Obesidade Mórbida/cirurgia , Complicações Pós-Operatórias/terapia , Adulto , Glicemia/análise , Glicemia/metabolismo , Estudos de Casos e Controles , Dieta/métodos , Líquido Extracelular/química , Feminino , Seguimentos , Derivação Gástrica/métodos , Derivação Gástrica/reabilitação , Glucose/análise , Humanos , Hipoglicemia/diagnóstico , Hipoglicemia/metabolismo , Masculino , Refeições , Pessoa de Meia-Idade , Valor Nutritivo/fisiologia , Obesidade Mórbida/metabolismo , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/metabolismo , Período Pós-Prandial , Estudos RetrospectivosRESUMO
BACKGROUND: Whether reserve plays a role in Parkinson's disease (PD) patients has received less attention than in dementia and has been mainly examined in relation with cognitive function. OBJECTIVE: To investigate whether reserve plays a role in the severity and progression of motor, cognitive, and nonmotor PD symptoms by examining whether education level (proxy of reserve) is associated with baseline performance and rate of progression. METHODS: We used data from a longitudinal cohort of PD patients (≤5-year disease duration at baseline) annually followed up to 5 years (n = 393; 41% women; mean age = 62.3 years, standard deviation = 10.0; mean disease duration = 2.6 years, standard deviation = 1.5). We examined the relationship of education with time to reach Hoehn and Yahr stage ≥3 using Cox regression and with baseline severity and progression of motor (Movement Disorder Society-Unified Parkinson's Disease Rating Scale parts II and III, gait speed), cognitive (Mini-Mental State Examination), and nonmotor (depression, anxiety, nonmotor symptoms scale, quality of life) symptoms using mixed models. RESULTS: Education level was not associated with age at onset or diagnosis. Compared with the low-education group, the incidence of Hoehn and Yahr ≥3.0 was 0.42 times lower (95% confidence interval, 0.22-0.82, P = 0.012) in the high-education group. Higher education was associated with better baseline motor function (P < 0.001), but not with the rate of motor decline (P > 0.15). Similar results were observed for cognition. Education was not associated with nonmotor symptoms. CONCLUSIONS: Higher education is associated with better baseline motor/cognitive function in PD, but not with rate of decline, and with a lower risk of reaching Hoehn and Yahr ≥3 during the follow-up. Our observations are consistent with a passive reserve hypothesis for motor/cognitive symptoms. © 2019 International Parkinson and Movement Disorder Society.
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Cognição/fisiologia , Disfunção Cognitiva/etiologia , Doença de Parkinson/psicologia , Idoso , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/psicologia , Disfunção Cognitiva/complicações , Demência/complicações , Demência/psicologia , Depressão/etiologia , Depressão/psicologia , Transtorno Depressivo/complicações , Transtorno Depressivo/psicologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/complicações , Qualidade de VidaRESUMO
BACKGROUND: Battery life of the most commonly used implantable pulse generators in deep brain stimulation is limited. Device replacement is costly and may expose patients to additional risks. Driven by the observation that in our experience newer generation devices seemed to need earlier replacement than the older generation, we aimed to retrospectively analyze the battery life of two generations of non-rechargeable devices, manufactured by a single company (Medtronic, USA). METHODS: Battery life of 281 devices in 165 patients was taken into account for data analysis. This represented 243 older generation devices (Kinetra and Soletra) and 38 newer generation devices (Activa). RESULTS: The battery life of older generation stimulators was 2-fold longer than the newer generation. CONCLUSIONS: Newer devices are more versatile than the older generation. Their battery life is however significantly shorter. Development of next-generation devices needs to address this issue in order to limit health risks and reduce financial costs.
Assuntos
Estimulação Encefálica Profunda/instrumentação , Fontes de Energia Elétrica/normas , Adulto , Fontes de Energia Elétrica/efeitos adversos , Fontes de Energia Elétrica/economia , Eletrodos Implantados/normas , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To investigate the longitudinal dose-effect relationship between dopamine replacement therapy and impulse control disorders (ICDs) in Parkinson disease (PD). METHODS: We used data from a multicenter longitudinal cohort of consecutive patients with PD with ≤5 years' disease duration at baseline followed up annually up to 5 years. ICDs were evaluated during face-to-face semistructured interviews with movement disorder specialists. Generalized estimating equations and Poisson models with robust variance were used to study the association between several time-dependent definitions of dopamine agonist (DA) use, taking dose and duration of treatment into account, and ICDs at each visit. Other antiparkinsonian drugs were also examined. RESULTS: Among 411 patients (40.6% women, mean age 62.3 years, average follow-up 3.3 years, SD 1.7 years), 356 (86.6%) took a DA at least once since disease onset. In 306 patients without ICDs at baseline, the 5-year cumulative incidence of ICDs was 46.1% (95% confidence interval [CI] 37.4-55.7, DA ever users 51.5% [95% CI 41.8-62.1], DA never users 12.4% [95% CI 4.8-30.0]). ICD prevalence increased from 19.7% at baseline to 32.8% after 5 years. ICDs were associated with ever DA use (prevalence ratio 4.23, 95% CI 1.78-10.09). Lifetime average daily dose and duration of treatment were independently associated with ICDs with significant dose-effect relationships. Similar analyses for levodopa were not in favor of a strong association. ICDs progressively resolved after DA discontinuation. CONCLUSION: In this longitudinal study of patients with PD characterized by a high prevalence of DA treatment, the 5-year cumulative incidence of ICDs was ≈46%. ICDs were strongly associated with DA use with a dose-effect relationship; both increasing duration and dose were associated with ICDs. ICDs progressively resolved after DA discontinuation. CLINICALTRIALSGOV IDENTIFIER: NCT01564992.
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Antiparkinsonianos/efeitos adversos , Transtornos Disruptivos, de Controle do Impulso e da Conduta/induzido quimicamente , Transtornos Disruptivos, de Controle do Impulso e da Conduta/diagnóstico , Agonistas de Dopamina/efeitos adversos , Doença de Parkinson/diagnóstico , Doença de Parkinson/tratamento farmacológico , Idoso , Estudos de Coortes , Transtornos Disruptivos, de Controle do Impulso e da Conduta/epidemiologia , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/epidemiologiaRESUMO
RESUMO Objetivo Avaliar a eficácia da memantina no tratamento das perturbações da ansiedade. Métodos Foi realizada uma revisão sistemática na Medline, outras bases de dados baseadas na evidência e Índex das Revistas Médicas Portuguesas, nos últimos 10 anos, em inglês, espanhol e português, utilizando os seguintes termos “MESH memantine”, “treatment” e “anxiety disorders”. Para avaliar a qualidade dos estudos e a força de recomendação, foi utilizada a escala de Strength of Recommendation Taxonomy da American Family Physician. Resultados Obtiveram-se 131 artigos, dos quais seis cumpriam os critérios de inclusão: dois ensaios clínicos aleatorizados e controlados (ECAC), uma revisão sistemática (RS), uma norma de orientação clínica (NOC) e dois ensaios clínicos não controlados (ECNC). A NOC não recomenda o uso de memantina no tratamento da perturbação generalizada da ansiedade (PGA) (SOR C), mas recomenda o uso da memantina como tratamento adjuvante de segunda linha na perturbação obsessivo-compulsiva (POC) e como terceira linha na perturbação do estresse pós-traumático (SORT C). Os dois ECAC sugerem que o tratamento adjuvante com memantina melhorou a sintomatologia dos pacientes com POC severa. A RS revelou que o uso da memantina tem alguns benefícios na diminuição dos sintomas da POC. Os dois ECNC sugerem que a memantina pode ser eficaz como tratamento adjuvante em pacientes sintomáticos apesar de tratamento adequado com antidepressivos convencionais. Conclusão A evidência atual sugere que o uso de memantina como adjuvante no tratamento da POC parece ser eficaz (SORT B). O uso de memantina no tratamento da PGA não é recomendado (SORT C).
ABSTRACT Objective Review the evidence on the efficacy of memantine in the treatment of the anxiety disorders. Methods A systematic review of articles published in the last ten years, in Portuguese, English and Spanish, was performed in Medline, other places of Evidence Medicine and Index of Portuguese Databases, using the following MESH terms: memantine, treatment and anxiety disorders. We used the Strength of Recommendation Taxonomy (SORT) scale of American Family Physician to assign levels of evidence and strength of recommendations. Results A total of 131 papers were identified, and after the application of inclusion criteria, 6 papers remained, including two randomized controlled trials (RCT), one clinical guideline (CG), two open clinical trials and one systematic review (SR). The CG does not recommend the use of memantine in the treatment of the generalized anxiety disorder (SORT C) but does recommend the use of memantine as second-line adjunctive therapy for obsessive compulsive disorder and as third-line therapy for post-traumatic stress (SORT C). The two RCT suggest that an add-on of memantine does improve the symptoms of patients suffering from severe obsessive compulsive disorder. The SR showed that the use of memantine had some benefit in relieving obsessive compulsive disorder symptoms. The two other studies showed memantine may be an effective augmentation therapy in patients with anxiety who remain symptomatic despite adequate treatment with conventional antidepressant anxiolytics. Conclusion The current available evidence suggests the benefit of memantine as an adjunctive therapy for the treatment for obsessive compulsive disorder (SORT B). Most studies does not show the benefit of the use of memantine for the treatment of generalized anxiety disorder (SORT C).
RESUMO
Tunisia is one of the largest phosphate producers in the world (more than 10 million tons per year since the early nineties). The Kalaat Khasba mine (NW of Tunisia) has operated from 1893 until 1993 and data demonstrate that, in the phosphorites of Kalaat Khasba, Cd is enriched 105-208 times, when compared with shales, and U is enriched by a factor varying between 18 and 44. The general trend shows an increase in heavy elements content with decreasing particle size. On the other hand, concentrations of Sr, Cr and U exhibit the same distribution for the different size fractions. It was found that Cd concentrations exceed the allowed EC soil limits for growing crops. Hence, owing to the tailings exposure and to the mobilisation of the finest particles by rainfall and wind, Cd could have detrimental effects on human health and on the environment because a significant portion of Cd was found in the exchangeable form.