SN - Artigos publicados em revistas indexadas na Pubmed/Medline
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- Admission and Readmission/Death Patterns in Hospitalized and Non-hospitalized First-Ever-in-a-Lifetime Stroke Patients During the First Year: A Population-Based Incidence StudyPublication . Abreu, Pedro; Magalhães, Rui; Baptista, Diana; Azevedo, Elsa; Correia, ManuelBackground: Hospitalization and readmission rates after a first-ever-in-a-lifetime stroke (FELS) are considered measures of quality of care and, importantly, may give valuable information to better allocate health-related resources. We aimed to investigate the hospitalization pattern and the unplanned readmissions or death of hospitalized (HospS) and non-hospitalized stroke (NHospS) patients 1 year after a FELS, based on a community register. Methods: Data about hospitalization and unplanned readmissions and case fatality 1 year after a FELS were retrieved from the population-based register undertaken in Northern Portugal (ACIN2), comprising all FELS in 2009-2011. We used the Kaplan-Meier method to estimate 1-year readmission/death-free survival and Cox proportional hazard models to identify independent factors for readmission/death. Results: Of the 720 FELS, 35.7% were not hospitalized. Unplanned readmission/death within 1 year occurred in 33.0 and 24.9% of HospS and NHospS patients, respectively. The leading causes of readmission were infections, recurrent stroke, and cardiovascular events. Stroke-related readmissions were observed in more than half of the patients in both groups. Male sex, age, pre- and post-stroke functional status, and diabetes were independent factors of readmission/death within 1 year. Conclusion: About one-third of stroke patients were not hospitalized, and the readmission/death rate was higher in HospS patients. Still, that readmission/death rate difference was likely due to other factors than hospitalization itself. Our research provides novel information that may help implement targeted health-related policies to reduce the burden of stroke and its complications.
- Advantages of an Automated Method Compared With Manual Methods for the Quantification of Intraepidermal Nerve Fiber in Skin BiopsyPublication . Corrà, Marta; Sousa, Mafalda; Reis, Inês; Tanganelli, Fabiana; Vila-Chã, Nuno; Sousa, Ana Paula; Magalhães, Rui; Sampaio, Paula; Taipa, Ricardo; Maia, LuisIntraepidermal nerve fiber density (IENFD) measurements in skin biopsy are performed manually by 1-3 operators. To improve diagnostic accuracy and applicability in clinical practice, we developed an automated method for fast IENFD determination with low operator-dependency. Sixty skin biopsy specimens were stained with the axonal marker PGP9.5 and imaged using a widefield fluorescence microscope. IENFD was first determined manually by 3 independent observers. Subsequently, images were processed in their Z-max projection and the intradermal line was delineated automatically. IENFD was calculated automatically (fluorescent images automated counting [FIAC]) and compared with manual counting on the same fluorescence images (fluorescent images manual counting [FIMC]), and with classical manual counting (CMC) data. A FIMC showed lower variability among observers compared with CMC (interclass correlation [ICC] = 0.996 vs 0.950). FIMC and FIAC showed high reliability (ICC = 0.999). A moderate-to-high (ICC = 0.705) was observed between CMC and FIAC counting. The algorithm process took on average 15 seconds to perform FIAC counting, compared with 10 minutes for FIMC counting. This automated method rapidly and reliably detects small nerve fibers in skin biopsies with clear advantages over the classical manual technique.
- Age-specific periictal electroclinical features of generalized tonic-clonic seizures and potential risk of sudden unexpected death in epilepsy (SUDEP)Publication . Freitas, J.; Kaur, G.; Baca-Vaca Fernandez, G.; Tatsuoka, C.; Kaffashi, F.; A. Loparo, K.; Rao, S.; Loplumlert, J.; Kaiboriboon, K.; Amina, S.Generalized tonic–clonic seizure (GTCS) is the commonest seizure type associated with sudden unexpected death in epilepsy (SUDEP). This study examined the semiological and electroencephalographic differences (EEG) in the GTCSs of adults as compared with those of children. The rationale lies on epidemiological observations that have noted a tenfold higher incidence of SUDEP in adults.Weanalyzed the video-EEG data of 105 GTCS events in 61 consecutive patients (12 children, 23 seizure events and 49 adults, 82 seizure events) recruited from the Epilepsy Monitoring Unit. Semiological, EEG, and 3-channel EKG features were studied. Periictal seizure phase durations were analyzed including tonic, clonic, total seizure, postictal EEG suppression (PGES), and recovery phases. Heart rate variability (HRV)measures includingRMSSD (root mean square successive difference of RR intervals), SDNN (standard deviation of NN intervals), and SDSD (standard deviation of differences) were analyzed (including low frequency/high frequency power ratios) during preictal baseline and ictal and postictal phases. Generalized estimating equations (GEEs)were used to find associations between electroclinical features. Separate subgroup analyses were carried out on adult and pediatric age groups as well as medication groups (no antiepileptic medication cessation versus unchanged or reduced medication) during admission.Major differences were seen in adult and pediatric seizures with total seizure duration, tonic phase, PGES, and recovery phases being significantly shorter in children (p b 0.01). Generalized estimating equation analysis, using tonic phase duration as the dependent variable, found age to correlate significantly (p b 0.001), and this remained significant during subgroup analysis (adults and children) such that each 0.12-second increase in tonic phase duration correlated with a 1-second increase in PGES duration. Postictal EEG suppression durations were on average 28 s shorter in children. With cessation of medication, total seizure duration was significantly increased by a mean value of 8 s in children and 11 s in adults (p b 0.05). Tonic phase duration also significantly increased with medication cessation, and although PGES durations increased, this was not significant. Root mean square successive difference was negatively correlated with PGES duration (longer PGES durations were associated with decreased vagally mediated heart rate variability; p b 0.05) but not with tonic phase duration. This study clearly points out identifiable electroclinical differences between adult and pediatric GTCSs that may be relevant in explaining lower SUDEP risk in children. The findings suggest that some prolonged seizure phases and prolonged PGES duration may be electroclinical markers of SUDEP risk and merit further study.
- Antiplatelet agents and/or anticoagulants are not associated with worse outcome following nonvariceal upper gastrointestinal bleedingPublication . Teles-Sampaio, E.; Maia, L.; Salgueiro, P.; Marcos-Pinto, R.; Dinis-Ribeiro, M.; Pedroto, I.BACKGROUND: Nonvariceal upper gastrointestinal bleeding emerges as a major complication of using antiplatelet agents and/or anticoagulants and represents a clinical challenge in patients undergoing these therapies. AIM: To characterize patients with nonvariceal upper gastrointestinal bleeding related to antithrombotics and their management, and to determine clinical predictors of adverse outcomes. METHODS: Retrospective cohort of adults who underwent upper gastrointestinal endoscopy after nonvariceal upper gastrointestinal bleeding from 2010 to 2012. The outcomes were compared between patients exposed and not exposed to antithrombotics. RESULTS: Five hundred and forty-eight patients with nonvariceal upper gastrointestinal bleeding (67% men; mean age 66.5 ± 16.4 years) were included, of which 43% received antithrombotics. Most patients had comorbidities. Peptic ulcer was the main diagnosis and endoscopic therapy was performed in 46% of cases. The 30-day mortality rate was 7.7% (n = 42), and 36% were bleeding-related. The recurrence rate was 9% and 14% of patients with initial endoscopic treatment needed endoscopic retreatment. There were no significant differences between the exposed and non-exposed groups in most outcomes. Co-morbidities, hemodynamic instability, high Rockall score, low hemoglobin (7.76 ± 2.72 g/dL) and higher international normalized ratio (1.63 ± 1.13) were associated significantly with mortality in a univariate analysis. CONCLUSIONS: Adverse outcomes were not associated with antithrombotic use. The management of nonvariceal upper gastrointestinal bleeding constitutes a challenge to clinical performance optimization and clinical cooperation.
- Are Stroke Occurrence and Outcome Related to Weather Parameters? Results from a Population-Based Study in Northern PortugalPublication . Magalhães, R.; Silva, M.; Correia, M.; Bailey, T.Background: Changes in meteorological parameters have been associated with cardiovascular mortality and stroke. The high incidence of stroke in Portugal may be modelled by short- or long-term weather changes whose effect may be different across stroke types and severity. Methods: Data include all patients with a first-ever-in-a-lifetime stroke registered in a population of 86,023 residents in the city of Porto from October 1998 to September 2000. Specific stroke types were considered and ischaemic stroke (IS) subtype was defined according to the Oxfordshire Community Stroke Projet classification and the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. Information on daily temperature, humidity and air pressure was obtained from the National Meteorological Office. The Poisson distribution was used to model the daily number of events as a function of each weather parameter measured over different hazard periods, and the binomial model to contrast effects across subgroups. Differential effects of meteorological parameters and hazard periods upon stroke occurrence and outcome were analysed in a stepwise model. Results: Among the 462 patients registered, 19.6% had a primary intracerebral haemorrhage (PICH) and 75.3% an IS. Among patients with IS, 21.6% were total anterior circulation infarcts (TACIs), 19.8% partial anterior circulation infarcts (PACIs), 19.5% posterior circulation infarcts (POCIs) and 39.1% were lacunar infarcts (LACIs). The aetiology of IS was large artery atherosclerosis in 6.9%, cardioembolism in 23.3% and small artery occlusion in 35.6%. The incidence of PICH increased by 11.8% (95% CI: 3.8–20.4%) for each degree drop in the diurnal temperature range in the preceding day. The incidence of IS increased by 3.9% (95% CI: 1.6–6.3%) and cardioembolic IS by 5.0% (95% CI: 0.2–10.1%) for a 1 ° C drop in minimum temperature in the same hazard period. The incidence of TACIs followed the IS pattern while for PACIs and POCIs there were stronger effects of longer hazard periods and no association was found for LACIs. The relative risk of a fatal versus a non-fatal stroke increased by 15.5% (95% CI: 6.1–25.4%) for a 1 ° C drop in maximum temperature over the previous day. Conclusions: Outdoor temperature and related meteorological parameters are associated with stroke occurrence and severity. The different hazard periods for temperature effects and the absence of association with LACIs may explain the heterogeneous effects of weather on stroke occurrence found in community- based and hospital admission studies. Emergency services should be aware that specific weather conditions are more likely to prompt calls for more severe strokes.
- Assessing risk factors for migraine: differences in gender transmissionPublication . Lemos, C.; Alonso, I.; Barros, J.; Sequeiros, J.; Pereira-Monteiro, J.; Mendonça, D.; Sousa, A.Abstract AIM: Our aim was to assess which specific factors are contributing to an increased risk of migraine in a group of 131 Portuguese families. METHODS: We studied 319 first-degree relatives, using a multilevel approach to account for the dependency among members from the same family. We included in the model relative's gender, the proband's gender and age-at-onset, to evaluate if any of these variables were associated with relative's affection status. We also included in the model proband's migraine subtype. We further assessed female and male transmissions within the proband nuclear family. RESULTS: Relatives' gender was found to be a risk factor for migraine (Odds Ratio = 2.86; 95% CI = 1.75-4.67), with females at a higher risk. When splitting probands according to their migraine subtype, we found that none of the variables studied contributed to relatives of MA-probands affection-status. Our results also show a significant difference between proband's transmission and the gender of the parents and offspring. CONCLUSIONS: With this study, we showed that gender is truly a risk factor for migraine and that a gender-biased transmission is also observed. This reinforce the importance of identifying genes associated with migraine that are modulated by genes located in the sex chromosomes and the study of mitochondrial DNA or X-chromosome and hormonal-related effects associated with migraine susceptibility
- Avaliação da Via Verde do Acidente Vascular Cerebral no Norte de Portugal: Caracterização e Prognóstico dos UtilizadoresPublication . Moutinho, M.; Magalhães, R.; Correia, M.; Silva, C.Introdução: Em 2002 Portugal detinha uma das mais altas taxas de mortalidade por doenças cerebrovasculares entre os países europeus. Várias estratégias foram adoptadas para melhorar a prevenção da doença e o seu tratamento na fase aguda, entre as quais a criação da Via Verde do Acidente Vascular Cerebral. O objectivo deste trabalho é descrever a utilização e resultados desta estratégia no contexto de um registo prospectivo comunitário na Região Norte de Portugal. Material e Métodos: Foram registados todos os AVCs ocorridos entre 1 de Outubro de 2009 e 30 de Setembro de 2010 nos utentes inscritos no agrupamento de centros de saúde do Porto Ocidental e nos de Mirandela e Vila Pouca de Aguiar. Para a detecção de casos utilizaram-se múltiplas fontes de informação: notificação via WEB, e-mail, Alerta P1 e pesquisas sistemáticas em registos disponibilizados pelas entidades envolvidas - urgências hospitalares, listas de altas, procedimentos de diagnóstico, óbitos, Via Verde do Acidente Vascular Cerebral e serviço de atendimento de situações urgentes. Resultados: Ocorreram 600 AVCs em 241 000 habitantes (taxa de incidência de 250 / 100 000), dos quais 434 foram primeiros na vida (180 / 100 000). Foram registados 72 acessos à Via Verde do Acidente Vascular Cerebral, dos quais 66,7% foram diagnosticados como AVC. Considerando os quatro critérios de activação (idade ≤ 80 anos, independência funcional, sinais/sintomas do AVC e tempo após episódio ≤ 3 horas), só 15,9% dos doentes a poderiam utilizar e, dos utilizadores, apenas 56,3% satisfaziam esses critérios. Dos doentes com critérios de activação, foram internados 96,3% pela VV pré-hospitalar, 83,3% pela VV intra/inter-hospitalar e 64,0% dos restantes; a fibrinólise foi realizada em 77,3%, 36,4% e 17,4% dos doentes com enfarte cerebral, respectivamente. O Rankin pós- AVC é mais grave nos utilizadores da VV pré-hospitalar (70,3% vs. 35,3%), mas estes apresentam mais assiduamente os três sinais/ sintomas de AVC (44,4% vs. 16,2%). Ajustando para a idade, sexo e número de sinais, o risco de incapacidade grave pós-AVC não é significativamente diferente no acesso pela VV pré-hospitalar (RP = 2,9; IC 95%: 0,8 - 10,2), bem como a taxa de letalidade. Conclusões: Os critérios para activação da Via Verde do Acidente Vascular Cerebral são muito restritivos. Embora esta seja mais vezes accionada em situações clínicas graves, a proporção de doentes que realizou fibrinólise é relativamente alta em comparação com outros estudos.
- BDNF and CGRP interaction: implications in migraine susceptibilityPublication . Lemos, C.; Mendonça, D.; Pereira-Monteiro, J.; Barros, J.; Sequeiros, J.; Alonso, I.; Sousa, A.Abstract OBJECTIVES: Migraine pathophysiology involves several pathways. Our aims were to explore a possible role of the brain-derived neurotrophic factor gene (BDNF) in migraine susceptibility; to study, for the first time, the calcitonin gene-related peptide gene (CGRP); and a possible interaction between the two. METHODS: Using a case-control approach, four tagging single nucleotide polymorphisms (SNPs) (rs7124442, rs6265, rs11030107, and rs2049046) of BDNF and one tagging SNP-rs1553005-of CGRP were analyzed in 188 cases and 287 controls. A multivariable logistic regression was performed, adjusting for gender. Allelic and haplotypic frequencies were estimated. Interaction was assessed by a stepwise multivariable-logistic regression and confirmed by a multifactor dimensionality reduction analysis. RESULTS: No significant main effects were found; however, a significant interaction was found between BDNF and CGRP, showing an increased risk for the AT-genotype of rs2049046 and the GC-genotype of rs1553005 (odds ratio=1.88, 95% confidence interval: 1.20-2.93) for migraineurs. CONCLUSION: Our data support the hypothesis of an interaction between BDNF and CGRP in migraine susceptibility that should be further explored.
- Brain Calcifications in Complex Sexual AneuploidyPublication . Oliveira, Vanessa; Pedro Rocha, José; Candeias, Cristina; Oliva‐Teles, Natália; Damásio, Joana
- Cardiac phenotype in ATP1A3-related syndromesPublication . Balestrini, Simona; Mikati, Mohamad A.; Álvarez-García-Rovés, Reyes; Carboni, Michael; Hunanyan, Arsen S.; Kherallah, Bassil; McLean, Melissa; Prange, Lyndsey; De Grandis, Elisa; Gagliardi, Alessandra; Pisciotta, Livia; Stagnaro, Michela; Veneselli, Edvige; Campistol, Jaume; Fons, Carmen; Pias-Peleteiro, Leticia; Brashear, Allison; Miller, Charlotte; Samões, Raquel; Brankovic, Vesna; Padiath, Quasar S.; Potic, Ana; Pilch, Jacek; Vezyroglou, Aikaterini; Bye, Ann M.E.; Davis, Andrew M.; Ryan, Monique M.; Semsarian, Christopher; Hollingsworth, Georgina; Scheffer, Ingrid E.; Granata, Tiziana; Nardocci, Nardo; Ragona, Francesca; Arzimanoglou, Alexis; Panagiotakaki, Eleni; Carrilho, Inês; Zucca, Claudio; Novy, Jan; Dzieżyc, Karolina; Parowicz, Marek; Mazurkiewicz-Bełdzińska, Maria; Weckhuysen, Sarah; Pons, Roser; Groppa, Sergiu; Sinden, Daniel S.; Pitt, Geoffrey S.; Tinker, Andrew; Ashworth, Michael; Michalak, Zuzanna; Thom, Maria; Cross, J. Helen; Vavassori, Rosaria; Kaski, Juan P.; Sisodiya, Sanjay M.Objective: To define the risks and consequences of cardiac abnormalities in ATP1A3-related syndromes. Methods: Patients meeting clinical diagnostic criteria for rapid-onset dystonia-parkinsonism (RDP), alternating hemiplegia of childhood (AHC), and cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS) with ATP1A3 genetic analysis and at least 1 cardiac assessment were included. We evaluated the cardiac phenotype in an Atp1a3 knock-in mouse (Mashl+/-) to determine the sequence of events in seizure-related cardiac death. Results: Ninety-eight patients with AHC, 9 with RDP, and 3 with CAPOS (63 female, mean age 17 years) were included. Resting ECG abnormalities were found in 52 of 87 (60%) with AHC, 2 of 3 (67%) with CAPOS, and 6 of 9 (67%) with RDP. Serial ECGs showed dynamic changes in 10 of 18 patients with AHC. The first Holter ECG was abnormal in 24 of 65 (37%) cases with AHC and RDP with either repolarization or conduction abnormalities. Echocardiography was normal. Cardiac intervention was required in 3 of 98 (≈3%) patients with AHC. In the mouse model, resting ECGs showed intracardiac conduction delay; during induced seizures, heart block or complete sinus arrest led to death. Conclusions: We found increased prevalence of ECG dynamic abnormalities in all ATP1A3-related syndromes, with a risk of life-threatening cardiac rhythm abnormalities equivalent to that in established cardiac channelopathies (≈3%). Sudden cardiac death due to conduction abnormality emerged as a seizure-related outcome in murine Atp1a3-related disease. ATP1A3-related syndromes are cardiac diseases and neurologic diseases. We provide guidance to identify patients potentially at higher risk of sudden cardiac death who may benefit from insertion of a pacemaker or implantable cardioverter-defibrillator.