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1.
J Endocrinol Invest ; 46(7): 1423-1428, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-36652191

RESUMEN

PURPOSE: Aspirin use among patients with diabetes in primary prevention is still a matter of debate. We aimed to evaluate the potential cardiovascular risk benefit of aspirin in primary prevention, using data from a contemporary cohort. METHODS: Retrospective analysis of the VITAL cohort with > 20,000 individuals at primary prevention who were followed for a median of 5.3 years. The population was evaluated according to the baseline diabetes status, and then aspirin use was evaluated among diabetic patients. Cox regression models were used to estimate the risks of mortality and cardiovascular outcomes. The estimates were reported using adjusted hazard ratio (HR) and 95% confidence intervals (95%CI). RESULTS: Diabetic patients (n = 3549; 13.7%) showed to increase the risk of all-cause mortality (HR 1.61, 95%CI 1.33-1.94), and major adverse cardiovascular events (MACE) (HR 1.36 95%CI 1.11-1.68) than non-diabetic population. Diabetic patients taking aspirin were older, more frequently man, hypertensive, current users of statins, and current smokers compared with diabetic patients who did not use aspirin at baseline. There was no difference between diabetic aspirin users and non-users regarding all-cause mortality (HR 0.80, 95%CI 0.59, 1.10), MACE (HR 0.92, 95%CI 0.64, 1.33), coronary heart disease (HR 0.98, 95%CI 0.67, 1.43), or stroke (HR 0.87, 95%CI 0.48, 1.58). CONCLUSIONS: The VITAL data confirmed diabetes as an important risk factor for cardiovascular events in a contemporary cohort but did not show cardiovascular benefits of aspirin in primary prevention among people with diabetes who were shown to be at higher risk of cardiovascular events.


Asunto(s)
Enfermedades Cardiovasculares , Diabetes Mellitus , Hipertensión , Masculino , Humanos , Aspirina/efectos adversos , Enfermedades Cardiovasculares/epidemiología , Estudios Retrospectivos
3.
Eur J Neurol ; 27(6): 985-994, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32096289

RESUMEN

BACKGROUND AND PURPOSE: Contingent negative variation (CNV) is a negative cortical wave that precedes a pre-cued imperative stimulus requiring a quick motor response. It has been related to motor preparation and anticipatory attention. The aim was to ascertain whether the clinical improvement of functional movement disorders after physiotherapy would be associated with faster reaction times and modulation of CNV. METHODS: Motor performance and CNV were analysed during a pre-cued choice reaction time task with varying cue validity. Twenty-one patients with functional movement disorders and 13 healthy controls at baseline were compared. Patients then underwent physiotherapy. At follow-up after physiotherapy, patients were categorized as clinically improved (responders) or not improved (non-responders) and retested. RESULTS: At baseline, patients did not generate CNV, contrary to controls [mean amplitude (µV) at the end of preparation to move: patients -0.47 (95% CI -1.94, 1.00) versus controls -2.59 (95% CI -4.46, -0.72)]. Responders performed faster after physiotherapy [mean natural logarithm (ln) reaction time (RT) (ms): follow-up 6.112 (95% CI 5.923, 6.301) versus baseline 6.206 (95% CI 6.019, 6.394), P = 0.010], contrary to non-responders. Simultaneously, responders showed a recovery of CNV after physiotherapy [follow-up -1.95 (95% CI -3.49, -0.41) versus baseline -0.19 (95% CI -1.73, 1.35), P < 0.001], contrary to non-responders [follow-up -0.32 (95% CI -1.79, 1.14) versus baseline -0.72 (95% CI -2.19, 0.75), P = 0.381]. CONCLUSIONS: Clinical improvement of functional movement disorders after physiotherapy was associated with faster reaction times and normalization of CNV, which was absent at baseline. These findings suggest that CNV may constitute a useful neurophysiological biomarker related to abnormal attention in functional movement disorders.


Asunto(s)
Variación Contingente Negativa , Trastornos del Movimiento , Adulto , Atención , Biomarcadores , Electroencefalografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Movimiento , Trastornos del Movimiento/diagnóstico , Trastornos del Movimiento/terapia , Tiempo de Reacción
4.
Eur J Neurol ; 27(2): 288-296, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31454134

RESUMEN

BACKGROUND AND PURPOSE: The impact of Parkinson's disease (PD) on the risk of cardiovascular disease is poorly known. The aim was to systematically review observational studies evaluating the association between PD and cardiovascular events. METHODS: MEDLINE through PubMed, the Web of Science and Cochrane Central Register of Controlled Trials with conference proceedings were searched from inception to 4 July 2019. Two reviewers independently selected studies comparing cardiovascular events between Parkinson's disease and control groups. Ischaemic stroke, myocardial infarction and cardiovascular mortality were the outcomes of interest. Pooled estimates of odds ratios (ORs) and 95% confidence intervals (CIs) were derived by random effects meta-analysis. Heterogeneity was assessed using the I2 test. The study protocol was registered at PROSPERO: CRD42017076527. RESULTS: Eleven studies were included: nine cohort studies and two case-control studies. PD was associated with a significantly increased risk of stroke (nine studies: OR 1.66, 95% CI 1.19, 2.34; I2  = 50%). No significant differences were detected regarding myocardial infarction risks (eight studies: OR 1.15, 95% CI 0.72, 1.83; I2  = 76%) nor cardiovascular mortality risks (seven studies: OR 1.11, 95% CI 0.85, 1.45; I2  = 47%) in PD patients. CONCLUSIONS: The best evidence available showed an association between PD and increased risk of stroke. The risk of myocardial infarction and cardiovascular mortality was not different in PD and non-PD individuals.


Asunto(s)
Enfermedades Cardiovasculares , Enfermedad de Parkinson , Isquemia Encefálica , Enfermedades Cardiovasculares/epidemiología , Estudios de Casos y Controles , Humanos , Infarto del Miocardio , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/epidemiología , Accidente Cerebrovascular/epidemiología
6.
Arq. bras. med. vet. zootec. (Online) ; 71(5): 1677-1685, set.-out. 2019. tab
Artículo en Inglés | LILACS, VETINDEX | ID: biblio-1038650

RESUMEN

Forty eight crossbred calves, 24 males and 24 females, with weight and age of 203.6±3.7kg and 11.8±1.0 months were allotted to the following treatments: MT- mineral salt ad libitum and sugar cane mixed with 10g kg-1 mixture of urea and ammonium sulfate in a 9:1 proportion; MA - sugar cane mixed with 16g kg-1 of a concentrate of urea (550g kg-1), ammonium sulfate (60g kg-1) and minerals (390g kg-1); SU - sugar cane mixed with 50g kg-1 of a concentrate of soybean meal (830g kg-1), urea (52g kg-1) and minerals (118g kg-1) and MC - corn silage mixed with 10g kg-1 of a concentrate of urea (500g kg-1), ammonium sulfate (50g kg-1) and minerals (450g kg-1). Minerals mixed with sugar cane (MA) resulted in greater weight gain (0.258 x 0.188kg d-1) for similar intakes of DM (3.29 x 3.30kg d-1). Substitution of part of urea nitrogen in the MA by soybean meal (SU) resulted in greater ADG (0.538 x 0.258kg d-1), due to higher sugar cane intake (4.10 x 3.13kg d-1). ADG of calves receiving corn silage was greater (0.406 x 0.258kg d-1) than for calves receiving sugar cane.(AU)


Quarenta e oito bezerros cruzados, com peso vivo de 203,6±3,7kg e idade de 11,8±1,0 meses, sendo 24 machos e 24 fêmeas, foram distribuídos nos tratamentos: MT - sal mineral à vontade e cana-de-açúcar adicionada de 10g kg -1 de uma mistura de ureia e sulfato de amônio na proporção de 9:1; MA - cana-de-açúcar adicionada de 16g kg -1 de uma mistura de ureia (55%), sulfato de amônio (6%) e minerais (39%); SU - cana-de-açúcar adicionada de 50g kg -1 de uma mistura de farelo de soja (83%), ureia (5,2%) e minerais (11,8%); e MC - silagem de milho adicionada de 10g kg -1 de uma mistura de ureia (50%), sulfato de amônio (5%) e minerais (45%). Minerais misturados no volumoso resultaram em maior ganho de peso (0, 258 x 0,188kg/dia) com consumos semelhantes de matéria seca (3,29 x 3,30kg/dia). Substituição de parte do nitrogênio da ureia no MA pelo do farelo de soja resultou em aumento do ganho de peso (0,258 x 0,538kg/dia) e no consumo de cana (3,13 x 4,10kg/dia). Ganho de peso dos bezerros que receberam silagem de milho foi superior ao dos bezerros que receberam o MA (0,406 x 0,258kg/dia), devido ao maior consumo de silagem (4,71 x 3,13kg/dia).(AU)


Asunto(s)
Animales , Bovinos , Urea , Bovinos/crecimiento & desarrollo , Zea mays , Saccharum , Alimentación Animal/análisis , Minerales/administración & dosificación
7.
Eur J Neurol ; 26(7): 953-960, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-30681754

RESUMEN

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


Asunto(s)
Antiparkinsonianos/uso terapéutico , Oxadiazoles/uso terapéutico , Enfermedad de Parkinson/tratamiento farmacológico , Anciano , Método Doble Ciego , Quimioterapia Combinada , Femenino , Humanos , Levodopa/uso terapéutico , Masculino , Persona de Mediana Edad , Resultado del Tratamiento
8.
Eur J Neurol ; 26(3): 490-496, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30347489

RESUMEN

BACKGROUND AND PURPOSE: Weight loss (WL) is a frequent yet under-recognized complication of levodopa/carbidopa intestinal gel (LCIG) infusion, as well as a milestone of Parkinson's disease (PD) disability progression. The complex association between WL, poor nutritional status, motor complications and PD progression, however, remains unclear. METHODS: Consecutive consenting patients with PD treated with LCIG (n = 44; PD duration, 18.3 ± 6.5 years) were enrolled in an open-label observational study assessing the extent of WL occurring during LCIG treatment. As secondary aims, we correlated the nutritional status, as detected by the Mini Nutritional Assessment, with the severity of motor symptoms [Movement Disorder Society Unified Parkinson's Disease Rating Scale part III], motor complications (Unified Parkinson's Disease Rating Scale part IV), activities of daily living (Schwab and England scale), cognitive impairment (Mini Mental State Examination), depression (Beck Depression Inventory), difficulties in feeding (Edinburgh Feeding Evaluation in Dementia Questionnaire) and levodopa equivalent daily dose (LEDD). RESULTS: There was an average WL of 9.9 ± 10.5% (7.6 ± 7.1 kg) over an LCIG treatment period of 51.6 ± 28.5 months. The extent of WL correlated with the percentage of the waking day spent with dyskinesia (P < 0.05). The nutritional status correlated with motor symptom severity (P < 0.01), dysphagia (P < 0.01) and LEDD (P < 0.01). CONCLUSIONS: Weight loss may occur in patients with PD undergoing LCIG in correlation with the percentage of the waking day spent with dyskinesia. Regardless of the extent of WL, the nutritional status correlated with higher LEDD, as well as with indices of disease progression, such as motor symptom severity and dysphagia.


Asunto(s)
Antiparkinsonianos/efectos adversos , Carbidopa/efectos adversos , Geles/efectos adversos , Infusiones Parenterales/efectos adversos , Levodopa/efectos adversos , Enfermedad de Parkinson/tratamiento farmacológico , Pérdida de Peso/efectos de los fármacos , Anciano , Anciano de 80 o más Años , Antiparkinsonianos/administración & dosificación , Carbidopa/administración & dosificación , Combinación de Medicamentos , Femenino , Humanos , Levodopa/administración & dosificación , Masculino , Persona de Mediana Edad
9.
Eur J Neurol ; 25(2): 275-283, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-29053896

RESUMEN

BACKGROUND AND PURPOSE: The quality of clinical practice guidelines on dystonia has not yet been assessed. Our aim was to appraise the methodological quality of guidelines worldwide and to analyze the consistency of their recommendations. METHODS: We searched for clinical practice guidelines on dystonia diagnosis/treatment in the National Guideline Clearinghouse, PubMed, National Institute for Health and Care Excellence, Guidelines International Network and Web of Science databases. We also searched for guidelines on homepages of international neurological societies. We asked for guidelines from every Management Committee member of the BM1101 Action of the Cooperation between Science and Technology European framework and every member of the International Parkinson and Movement Disorders Society with special interest in dystonia. RESULTS: Fifteen guidelines were evaluated. Among guidelines on treatment, only one from the American Academy of Neurology could be considered as high quality. Among guidelines on diagnosis and therapy, the guideline from the European Federation of Neurological Societies was recommended by the appraisers. Clinical applicability and reports of editorial independence were the greatest shortcomings. The rigor of development was poor and stakeholder involvement was also incomplete in most guidelines. Discrepancies among recommendations may result from the weight given to consensus statements and expert opinions due to the lack of evidence, as well as inaccuracy of disease classification. CONCLUSIONS: The quality of appraised guidelines was low. It is necessary to improve the quality of guidelines on dystonia, and the applied terminology of dystonia also needs to be standardized.


Asunto(s)
Distonía/diagnóstico , Distonía/terapia , Trastornos Distónicos/diagnóstico , Trastornos Distónicos/terapia , Guías de Práctica Clínica como Asunto/normas , Humanos
11.
Clin Obes ; 7(6): 377-383, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-28801963

RESUMEN

The aim of this study was to evaluate the postural control of obese young adults with normal body mass index during different static (bipedic and unipedic support) and dynamic postural conditions (gait velocity and limits of stability) in order to compare the static and dynamic balance of these individuals. A cross-sectional quantitative study was carried out to evaluate static and dynamic balance in 25 sedentary individuals. The sample was divided into two groups, 10 in the normal-weight group (24.70 ± 3.89 years and 21.5 ± 1.66 kg m-2 ) and 15 in the obese group (26.80 ± 5.16 years and 35.66 ± 4.29 kg m-2 ). Postural evaluation was performed through visual inspection, and balance analyses were performed using the Timed Up & Go test (TUGT) and Balance System (Biodex). Descriptive analyses, Fisher's exact test and Mann Whitney U-tests were performed using the Statistical Package for Social Sciences (SPSS - 20.0, Armonk, NY) software. Most of the obese volunteers presented postural alterations, such as head protrusion (47.6%), hyperkyphosis (46.7%) and hyperlordosis (26.7%). Medial-lateral dynamic displacement, risk of falls and mean time to perform the limits of stability test and TUGT were higher for obese subjects (P < 0.05), while there were no significant differences between the groups (P > 0.05) for static balance tests for either bipedal or unipedal tasks. The disadvantage presented by the young obese subjects occurs in dynamic activities, representing worse balance and an increase in time needed to accomplish these activities.


Asunto(s)
Índice de Masa Corporal , Obesidad/fisiopatología , Equilibrio Postural , Postura , Adolescente , Adulto , Estudios Transversales , Femenino , Humanos , Masculino , Adulto Joven
12.
Eur J Neurol ; 24(5): 748-750, 2017 05.
Artículo en Inglés | MEDLINE | ID: mdl-28251720

RESUMEN

BACKGROUND AND PURPOSE: Portugal has been identified as one of the countries with a high prevalence of LRRK2-G2019S, considered to be the most frequent known cause of familial and sporadic Parkinson's disease (PD). The aim of this study was to evaluate the prevalence of PD in Portugal using a door-to-door methodology. METHODS: A cross-sectional study was conducted in the Portuguese community-dwelling population; that is, elderly people living in the community on their own, aged ≥50 years and resident in mainland Portugal, in two phases: (i) a questionnaire was applied to screen potential cases of PD; and (ii) screened cases were evaluated by an expert in PD to confirm diagnosis. RESULTS: The adjusted prevalence of PD for the Portuguese community-dwelling population aged ≥50 years was 0.24%. The estimated total number of cases of PD for the Portuguese population is 180/100 000 inhabitants. CONCLUSIONS: The results of this study show that a geographical region with a high frequency of a causal mutation for PD does not automatically imply a high prevalence of patients with PD.


Asunto(s)
Enfermedad de Parkinson/epidemiología , Anciano , Anciano de 80 o más Años , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Portugal/epidemiología , Prevalencia
13.
J Voice ; 31(2): 258.e13-258.e18, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-27397112

RESUMEN

BACKGROUND: Psychosocial impact of dysphonia in people with Parkinson disease (PD) has been described with the Voice Handicap Index (VHI); however, its psychometric properties when applied in this population are not described. OBJECTIVE: The objective of this study was to examine the psychometric properties of the VHI in people with PD. METHODS: A cross-sectional study of 151 subjects without cognitive impairment (90 people with PD and 61 controls) was carried out. The VHI was applied along with clinician-based (Mini Mental State Examination, Hoehn and Yahr staging, and Movement Disorder Society-Unified Parkinson's Disease Rating Scale) and patient-based (self-rated voice severity) outcome measures. The psychometric properties of the VHI analyzed were the feasibility, reliability, and construct validity. RESULTS: The average age of the PD population studied was 67 years; 51% had a primary level of education and 81% were retired. On average, they had disease onset duration of 11 years, a mild disease stage, mild to moderate global motor disability and impairment, and a normal to mild self-rated voice severity. The psychometric attributes of the VHI demonstrated that the questionnaire is feasible (missing data less than 1%), reliable (Cronbach α > 0.9), and valid (71.5% of the total variance is explained by five factors, correlates with voice severity, PD disability, and impairment, and differentiates subjects with PD from subjects without PD). CONCLUSION: The VHI is a reliable and valid tool that can be recommended for the population under study although further work is required to investigate its utility in advanced stages of disease.


Asunto(s)
Evaluación de la Discapacidad , Enfermedad de Parkinson/complicaciones , Psicometría , Encuestas y Cuestionarios , Trastornos de la Voz/diagnóstico , Calidad de la Voz , Adulto , Anciano , Anciano de 80 o más Años , Estudios Transversales , Estudios de Factibilidad , Femenino , Estado de Salud , Humanos , Masculino , Persona de Mediana Edad , Actividad Motora , Enfermedad de Parkinson/diagnóstico , Enfermedad de Parkinson/fisiopatología , Enfermedad de Parkinson/psicología , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Índice de Severidad de la Enfermedad , Trastornos de la Voz/etiología , Trastornos de la Voz/fisiopatología , Trastornos de la Voz/psicología
14.
Eur J Neurol ; 23(4): 772-9, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26826067

RESUMEN

BACKGROUND AND PURPOSE: Dystonia is difficult to recognize due to its large phenomenological complexity. Thus, the use of experts in dystonia is essential for better recognition and management of dystonia syndromes (DS). Our aim was to document managing strategies, facilities and expertise available in various European countries in order to identify which measures should be implemented to improve the management of DS. METHODS: A survey was conducted, funded by the Cooperation in Science and Technology, via the management committee of the European network for the study of DS, which is formed from representatives of the 24 countries involved. RESULTS: Lack of specific training in dystonia by general neurologists, general practitioners as well as other allied health professionals was universal in all countries surveyed. Genetic testing for rare dystonia mutations is not readily available in a significant number of countries and neurophysiological studies are difficult to perform due to a lack of experts in this field of movement disorders. Tetrabenazine is only readily available for treatment of dystonia in half of the surveyed countries. Deep brain stimulation is available in three-quarters of the countries, but other surgical procedures are only available in one-quarter of countries. CONCLUSIONS: Internationally, collaboration in training, advanced diagnosis, treatment and research of DS and, locally, in each country the creation of multidisciplinary teams for the management of dystonia patients could provide the basis for improving all aspects of dystonia management across Europe.


Asunto(s)
Trastornos Distónicos/terapia , Unión Europea/estadística & datos numéricos , Médicos Generales/estadística & datos numéricos , Neurología/estadística & datos numéricos , Trastornos Distónicos/tratamiento farmacológico , Médicos Generales/educación , Encuestas de Atención de la Salud/estadística & datos numéricos , Humanos , Neurología/educación
15.
Eur J Neurol ; 23(2): 368-74, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26518135

RESUMEN

BACKGROUND AND PURPOSE: Magnetic resonance (MR) studies have demonstrated a significant reduction of neuromelanin in the substantia nigra (SN) of Parkinson's disease (PD) patients with high accuracy for differential diagnosis compared to non-PD controls and essential tremor. However, studies state that not knowing how paramagnetic effects of iron influence neuromelanin signal is a limitation. In this study a neuromelanin-sensitive MR sequence was combined with T2* relaxometry iron quantification analysis to study the SN of early-stage PD patients to investigate the correlation between these parameters. METHODS: The inclusion criteria were untreated de novo PD patients and a 2-5 year disease duration (early PD); in addition, age-matched controls were enrolled. These were studied at 3.0 T with a high-resolution T1-weighted MR sequence to visualize neuromelanin and a relaxometry sequence for iron quantification. The primary outcome was the correlation of the width of the neuromelanin high signal region and the T2* values in the lateral, central and medial segments of the SN. RESULTS: Very weak correlations of T2* values with neuromelanin width, positive for global and negative for the medial and lateral SN segments, were found in both PD groups and control subjects. The SN neuromelanin width was markedly reduced in the de novo and early PD groups compared with controls in all SN segments, but no significant difference in T2* values was found between the groups. CONCLUSIONS: The SN neuromelanin signal does not have a significant correlation with iron content in PD patients or controls. The neuromelanin MR signal reduction in PD does not seem to be significantly influenced by paramagnetic iron effects.


Asunto(s)
Hierro/metabolismo , Imagen por Resonancia Magnética/métodos , Melaninas/metabolismo , Enfermedad de Parkinson/metabolismo , Sustancia Negra/metabolismo , Anciano , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad
16.
Aliment Pharmacol Ther ; 42(11-12): 1239-49, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26434935

RESUMEN

BACKGROUND: Gastrointestinal (GI) bleeding is a common complication among anticoagulated patients. Non-vitamin K antagonist oral anticoagulants (NOACs) are associated with increased risk of GI (major and clinically relevant non-major) bleeding. However, more information is needed regarding severe events. AIM: To evaluate the risk of NOACs major GI bleeding. METHODS: We searched for phase III randomised clinical trials (RCT) evaluating NOACs (apixaban, dabigatran, edoxaban and rivaroxaban) and reporting major GI bleeding events, in MEDLINE, Cochrane Library, SciELO collection and Web of Science databases (July 2015). Meta-analysis was performed to estimate risk ratio (RR) and 95% confidence intervals (95% CIs). Heterogeneity was assessed with the I(2) test. RESULTS: A total of 23 studies were included. Among patients with atrial fibrillation, the risk of major GI bleeding was not different between NOACs and vitamin K antagonists (VKA) (RR 1.08, 95% CI 0.85-1.36, I(2)  = 78%; 5 RCTs) or acetylsalicylic acid (RR 0.78, 95% CI 0.36-1.72; 1 RCT). Similar results were found for patients undergoing orthopaedic surgery and those with venous thromboembolism. NOACs were not found to increase the risk compared to low-molecular-weight heparin (LWMH) alone (RR 1.42, 95% CI 0.55-3.71, I(2)  = 7%; 8 RCTs), the sequential treatment with LMWH-VKA (RR 0.77, 95% CI 0.49-1.21, I(2)  = 43%; 7 RCTs) or placebo (RR 1.48, 95% CI 0.15-14.84, I(2)  = 21%; 2 RCTs). CONCLUSION: Despite previous evidence supporting the association of non-vitamin K antagonist oral anticoagulants and overall GI bleeding, non-vitamin K antagonist oral anticoagulants are not associated with increased risk of major GI bleeding compared to other anticoagulant drugs (with known increased risk of these events).


Asunto(s)
Anticoagulantes/efectos adversos , Hemorragia Gastrointestinal/inducido químicamente , Heparina de Bajo-Peso-Molecular/efectos adversos , Anticoagulantes/administración & dosificación , Heparina de Bajo-Peso-Molecular/uso terapéutico , Humanos , Oportunidad Relativa , Ensayos Clínicos Controlados Aleatorios como Asunto , Tromboembolia Venosa/tratamiento farmacológico
17.
Eur J Neurol ; 22(5): 815-25, e56, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25649051

RESUMEN

BACKGROUND AND PURPOSE: Opicapone (OPC) is a novel third generation catechol-O-methyltransferase (COMT) inhibitor that enhances levodopa availability. This study investigated the effects of OPC in comparison with placebo on levodopa pharmacokinetics, tolerability and safety, COMT activity and motor response to levodopa in Parkinson's disease (PD) patients with motor fluctuations. METHODS: This was a randomized, multicentre, double-blind and placebo-controlled study in four parallel groups of PD patients treated with standard-release 100/25 mg levodopa/carbidopa or levodopa/benserazide and with motor fluctuations (wearing-OFF phenomenon). Subjects were sequentially assigned to be administered, once-daily, up to 28 days (maintenance phase), placebo (n = 10) or 5 (n = 10), 15 (n = 10) and 30 mg (n = 10) OPC. Two levodopa tests were performed, one at baseline and another following the maintenance phase. Subjects kept a diary to record motor fluctuations (ON/OFF periods) throughout the study. RESULTS: In relation to placebo, levodopa exposure (AUC0-6) increased 24.7%, 53.9% and 65.6% following 5, 15 and 30 mg OPC, respectively. Maximum COMT inhibition (Emax) ranged from 52% (5 mg OPC) to 80% (30 mg OPC). The study was not designed to detect any significant differences in motor performance, but the exploratory analysis performed shows improvement in various motor outcomes, including a dose-dependent change in absolute OFF time corresponding to a percentage decrease of 4.16% (P > 0.05), 29.55% (P > 0.05) and 32.71% (P < 0.05) with 5, 15 and 30 mg OPC, respectively. Treatments were generally well tolerated and safe. CONCLUSIONS: OPC is a promising new COMT inhibitor that significantly decreased COMT activity, increased systemic exposure to levodopa and improved motor response.


Asunto(s)
Antiparkinsonianos/farmacocinética , Inhibidores de Catecol O-Metiltransferasa/farmacología , Catecol O-Metiltransferasa/efectos de los fármacos , Levodopa/farmacocinética , Oxadiazoles/farmacología , Enfermedad de Parkinson/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Antiparkinsonianos/administración & dosificación , Antiparkinsonianos/efectos adversos , Benserazida/administración & dosificación , Carbidopa/administración & dosificación , Inhibidores de Catecol O-Metiltransferasa/administración & dosificación , Método Doble Ciego , Combinación de Medicamentos , Femenino , Humanos , Levodopa/administración & dosificación , Levodopa/efectos adversos , Masculino , Persona de Mediana Edad , Oxadiazoles/administración & dosificación , Resultado del Tratamiento
18.
Eur J Neurol ; 22(2): 305-12, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25220687

RESUMEN

BACKGROUND AND PURPOSE: Handicap has not been explored as a patient-centred outcome measure in Parkinson's disease (PD). The clinical features and medication use in late stages of PD (LS-PD) were reported previously. METHODS: Handicap, medical conditions, use of healthcare resources and the impact of LS-PD upon caregivers were characterized in a cross-sectional study of LS-PD stages 4 or 5 of Hoehn and Yahr (H&Y). Handicap was measured using the London Handicap Scale (LHS: 0, maximal handicap; 1, no handicap). RESULTS: The mean LHS score in 50 patients was 0.33 (SD ±0.15). The presence of dementia, the Unified Parkinson's Disease Rating Scale part I score and the H&Y stage in 'off' independently predicted the LHS score (adjusted R(2) = 0.62; P = 0.000). Comorbidities and past medical conditions were frequent. Thirty-five patients lived at their house. Forty-five received unpaid care. Mean visits to the family doctor in the preceding 6 months were 2.2 (SD ±3.0) and to a neurologist 1.7 (SD ±1.0). Use of other health resources was low. Unpaid caregivers spent much time with patients and reported a high burden. CONCLUSION: Handicap could be measured in LS-PD and the LHS was easily completed by patients and caregivers. The high handicap in our cohort was mostly driven by the presence of dementia, behavioural complaints and the severity of non-dopaminergic motor features. Patients visited doctors infrequently and made low use of health resources, whilst unpaid caregivers reported a high burden.


Asunto(s)
Demencia/fisiopatología , Personas con Discapacidad , Enfermedad de Parkinson/fisiopatología , Anciano , Anciano de 80 o más Años , Cuidadores , Costo de Enfermedad , Estudios Transversales , Demencia/etiología , Evaluación de la Discapacidad , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Enfermedad de Parkinson/complicaciones , Portugal , Índice de Severidad de la Enfermedad , España
19.
Eur J Neurol ; 22(1): 207-10, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24602222

RESUMEN

BACKGROUND AND PURPOSE: Olfactory dysfunction is common in Parkinson's disease (PD) and it is one of the earliest non-motor symptoms. A few studies have suggested that deep brain stimulation of the subthalamic nucleus (STN-DBS) could improve olfactory function. Our aim was to evaluate the acute effect of bilateral STN-DBS on a commonly used smell test in PD patients. METHODS: Fifteen PD patients who underwent bilateral STN-DBS and 15 controls were recruited. Patients and controls were tested for odor identification. RESULTS: No statistical differences were documented between ON and OFF STN-DBS acute stimulation concerning olfaction. Controls presented a better performance for olfactory identification than patients. CONCLUSIONS: Our exploratory study did not support that bilateral STN-DBS could have an acute effect on olfactory function in PD patients.


Asunto(s)
Estimulación Encefálica Profunda/métodos , Percepción Olfatoria/fisiología , Enfermedad de Parkinson/terapia , Núcleo Subtalámico/fisiología , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Odorantes , Enfermedad de Parkinson/fisiopatología , Resultado del Tratamiento
20.
Eur J Neurol ; 22(3): 540-6, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25534480

RESUMEN

BACKGROUND: Depigmentation of the substantia nigra (SN) and locus coeruleus (LC) is a conspicuous pathological feature of Parkinson's disease (PD) and is related to the loss of neuromelanin, whose paramagnetic properties result in high signal on specific T1-weighted magnetic resonance imaging (MRI). Recent studies have suggested that neuromelanin decrease in the SN and LC of PD patients may emerge as a possible diagnostic biomarker. The SN neuromelanin signal in de novo and early stage PD patients was studied to assess its diagnostic accuracy. This is the first study based on a semi-automated MRI analysis of the neuromelanin signal in de novo PD patients. METHODS: The inclusion criteria were untreated de novo PD and a 2-5 year disease duration; in addition, age matched healthy controls were enrolled. These were studied with a high-resolution T1-weighted MRI sequence at 3 T to visualize neuromelanin. The primary outcome was SN high signal area, length and neuromelanin/midbrain ratio obtained with semi-automated methods. RESULTS: A total of 12 de novo PD patients and 10 PD patients with a 2-5 year disease duration were evaluated. The area, length of the SN T1 high signal and the SN neuromelanin/midbrain ratio were markedly decreased in the PD groups compared with age-matched controls, with a substantial overlap between the two PD groups. CONCLUSIONS: Neuromelanin-sensitive MRI techniques can discriminate PD patients from healthy individuals with high sensitivity and specificity. Our findings are consistent with recent findings showing that PD neuromelanin changes remain stable during the course of the disease.


Asunto(s)
Locus Coeruleus/metabolismo , Imagen por Resonancia Magnética/métodos , Melaninas/metabolismo , Enfermedad de Parkinson/metabolismo , Sustancia Negra/metabolismo , Anciano , Biomarcadores , Femenino , Humanos , Imagen por Resonancia Magnética/normas , Masculino , Persona de Mediana Edad , Sensibilidad y Especificidad
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