La influencia de la gestión organizativa en el tiempo puerta-aguja del tratamiento fibrinolítico / The influence of organisational management on door-to-needle times for fibrinolytic treatment

Introducción: El tiempo puerta-aguja (TPA) es el principal indicador del proceso del código ictus (CI). Según la guía de 2018 de la American Heart Association/American Stroke Associa-tion, el objetivo TPA debe ser inferior a 45 minutos. Para conseguirlo son necesarios protocolos eficaces y revisados de actuación extrahospitalaria e intrahospitalaria. Método: Analizamos la influencia de cambios organizativos entre 2011 y 2019 en el TPA y en la evolución clínica de los pacientes tratados con fibrinólisis. Utilizamos los datos de nuestro centro monitorizados y custodiados por el Pla Director en l’àmbit de la Malaltia Vascular Cerebral dela Generalitat de Catalunya. Entre otras medidas se han analizado las diferencias entre los a ̃nos y las derivadas de la implantación del modelo Helsinki. Resultados: Se estudiaron 447 pacientes, existiendo diferencias estadísticamente significativas en el TPA entre los diferentes a ̃nos. La activación del CI de forma extrahospitalaria en 315(70,5%) pacientes redujo el TPA una mediana de 14 minutos. Sin embargo, el modelo de regresión lineal sólo evidenció una relación inversamente proporcional entre la adopción del modelo deCI Helsinki (MH) y el TPA (coeficiente beta −0,42; p < 0,001). La eliminación de la figura delneurólogo vascular tras la adopción del MH empeoró el TPA y la mortalidad a los 90 días.Conclusión: El modelo organizativo influye en el TPA, siendo en nuestra muestra la aplicacióndel MH, la existencia de la figura del neurólogo vascular referente y la prenotificación del CIfactores claves para la reducción del TPA y la mejora clínica del paciente.(AU)

Introduction: Door-to-needle time (DNT) has been established as the main indicator in codestroke protocols. According to the 2018 guidelines of the American Heart Association/AmericanStroke Association, DNT should be less than 45 minutes; therefore, effective and revised pre-admission and in-hospital protocols are required. Method: We analysed organisational changes made between 2011 and 2019 and their influenceon DNT and the clinical progression of patients treated with fibrinolysis. We collected datafrom our centre, stored and monitored under the Master Plan for Cerebrovascular Disease ofthe regional government of Catalonia. Among other measures, we analysed the differencesbetween years and differences derived from the implementation of the Helsinki model.Results: The study included 447 patients, and we observed significant differences in DNTbetween different years. Pre-hospital code stroke activation, recorded in 315 cases (70.5%),reduced DNT by a median of 14 minutes. However, the linear regression model only showed aninversely proportional relationship between the adoption of the Helsinki code stroke model andDNT (beta coefficient, —0.42; P < .001). The removal of vascular neurologists after the adoptionof the Helsinki model increased DNT and the 90-day mortality rate. Conclusion: DNT is influenced by the organisational model. In our sample, the application ofthe Helsinki model, the role of the lead vascular neurologist, and notification of code strokeby pre-hospital emergency services are key factors for the reduction of DNT and the clinicalimprovement of the patient.(AU)

The influence of organisational management on door-to-needle times for fibrinolytic treatment.

INTRODUCTION: Door-to-needle time (DNT) has been established as the main indicator in code stroke protocols. According to the 2018 guidelines of the American Heart Association/American Stroke Association, DNT should be less than 45minuts; therefore, effective and revised pre-admission and in-hospital protocols are required. METHOD: We analysed organisational changes made between 2011 and 2019 and their influence on DNT and the clinical progression of patients treated with fibrinolysis. We collected data from our centre, stored and monitored under the Master Plan for Cerebrovascular Disease of the regional government of Catalonia. Among other measures, we analysed the differences between years and differences derived from the implementation of the Helsinki model. RESULTS: The study included 447 patients, and we observed significant differences in DNT between different years. Pre-hospital code stroke activation, recorded in 315 cases (70.5%), reduced DNT by a median of 14minutes. However, the linear regression model only showed an inversely proportional relationship between the adoption of the Helsinki code stroke model and DNT (beta coefficient, -0.42; P<.001). The removal of vascular neurologists after the adoption of the Helsinki model increased DNT and the 90-day mortality rate. CONCLUSION: DNT is influenced by the organisational model. In our sample, the application of the Helsinki model, the role of the lead vascular neurologist, and notification of code stroke by pre-hospital emergency services are key factors for the reduction of DNT and the clinical improvement of the patient.

Identifying and preventing burnout in young oncologists, an overwhelming challenge in the COVID-19 era: a study of the Spanish Society of Medical Oncology (SEOM).

BACKGROUND: Young oncologists are at particular risk of professional burnout, and this could have a significant impact on their health and care of their patients. The coronavirus disease 2019 (COVID-19) pandemic has forced rapid changes in professionals' jobs and training, with the consequent physical and psychological effects. We aimed to characterize burnout levels and determinants in young oncologists, and the effects of the pandemic on their training and health. METHODS: Two online surveys were conducted among oncology residents and young oncology specialists in Spain. The first addressed professional burnout and its determinants before the COVID-19 pandemic, while the second analyzed the impact of the pandemic on health care organization, training, and physical and psychological health in the same population. RESULTS: In total, 243 respondents completed the first survey, and 263 the second; 25.1% reported significant levels of professional burnout. Burnout was more common among medical oncology residents (28.2%), mainly in their second year of training. It was significantly associated with a poor work-life balance, inadequate vacation time, and the burnout score. Nearly three-quarters of respondents (72%) were reassigned to COVID-19 care and 84.3% of residents missed part of their training rotations. Overall, 17.2% of this population reported that they had contracted COVID-19, 37.3% had scores indicating anxiety, and 30.4% moderate to severe depression. Almost a quarter of young oncologists (23.3%) had doubts about their medical vocation. CONCLUSIONS: Burnout affects a considerable number of young oncologists. The COVID-19 pandemic has had a profound impact on causes of burnout, making it even more necessary to periodically monitor it to define appropriate detection and prevention strategies.

The influence of organisational management on door-to-needle times for fibrinolytic treatment. / La influencia de la gestión organizativa en el tiempo puerta-aguja del tratamiento fibrinolítico.

INTRODUCTION: Door-to-needle time (DNT) has been established as the main indicator in code stroke protocols. According to the 2018 guidelines of the American Heart Association/American Stroke Association, DNT should be less than 45minutes; therefore, effective and revised pre-admission and in-hospital protocols are required. METHOD: We analysed organisational changes made between 2011 and 2019 and their influence on DNT and the clinical progression of patients treated with fibrinolysis. We collected data from our centre, stored and monitored under the Master Plan for Cerebrovascular Disease of the regional government of Catalonia. Among other measures, we analysed the differences between years and differences derived from the implementation of the Helsinki model. RESULTS: The study included 447 patients, and we observed significant differences in DNT between different years. Pre-hospital code stroke activation, recorded in 315 cases (70.5%), reduced DNT by a median of 14minutes. However, the linear regression model only showed an inversely proportional relationship between the adoption of the Helsinki code stroke model and DNT (beta coefficient, -0.42; P<.001). The removal of vascular neurologists after the adoption of the Helsinki model increased DNT and the 90-day mortality rate. CONCLUSION: DNT is influenced by the organisational model. In our sample, the application of the Helsinki model, the role of the lead vascular neurologist, and notification of code stroke by pre-hospital emergency services are key factors for the reduction of DNT and the clinical improvement of the patient.

Potential therapeutic applications of the genus Annona: Local and traditional uses and pharmacology.

ETHNO-PHARMACOLOGICAL RELEVANCE: Annona species (Annonaceae) have long been used as traditional herbal medicines by native peoples in tropical areas. In different countries they are used against a large variety of illnesses, such as parasitic and infectious diseases, cancer, diabetes, peptic ulcers, and mental disorders. AIM OF THE STUDY: This review aims to achieve a comprehensive understanding of the research conducted so far on the local and traditional uses, pharmacological activities, mechanism of actions of active compounds, toxicity, and possible interactions with other drugs of the Annona species. Through analysis of these findings, evidences supporting their applications in ethno-medicines are described. We discuss the possible research opportunities and stand out the weak points in our knowledge that deserves further investigation. MATERIAL AND METHODS: Information on ethno-medicinal uses and pharmacological activities of the Annona genus was collected. The main scientific biomedical literature databases (Cochrane, PubMed, Scopus, Lilacs, SeCiMed, Elsevier, SpringerLink, Google Scholar, SciFinder) were consulted. The search covered all the literature available until September 2017. National and regional databases of Herbal Medicine and Complementary and Alternative Medicine were also revised in order to explore further data. For a better understanding of the therapeutic importance of these species, we have classified the pharmacological activities within each group of disorders. The International Classification of Diseases (ICD), used from WHO Member States, was chosen as the reference classification. RESULTS: From among the 27 species revised, four species are highlighted for their important pharmacological activities in most of the groups of illnesses: A. muricata, A. squamosa, A. senegalensis, and A. cherimola. Many investigations have been performed with extracts from the leaves, bark, fruit and seeds and have shown a wide range of pharmacological activities, such as antiprotozoal, antitumoural, antidiabetic, hepato-protective, anti-inflammatory and anxiolytic activities. The chemistry on the annonaceous acetogenins (ACGs) has been extensively investigated due to their potent antitumoural activity. Many of the assays were carried out with the isolated acetogenins in different lines of tumour culture cells and were found effective at very low doses even in multidrug-resistant tumours, and hence constitute promising compounds in the treatment of different types of cancers. No studies were found with extracts rich in acetogenins in the clinical field. CONCLUSIONS: The experimental results from the pharmacological research enable the validation of their traditional uses in several of the groups of diseases in the countries of origin and reveal these plants to be a valuable source for therapeutic molecules. However, more toxicity assays and clinical trials would be necessary to establish optimal and safe doses of consumption on the application of these medicinal plants.

Real-time parameter estimation of Zika outbreaks using model averaging.

Early prediction of the final size of any epidemic and in particular for Zika disease outbreaks can be useful for health authorities in order to plan the response to the outbreak. The Richards model is often been used to estimate epidemiological parameters for arboviral diseases based on the reported cumulative cases in single- and multi-wave outbreaks. However, other non-linear models can also fit the data as well. Typically, one follows the so called post selection estimation procedure, i.e., selects the best fitting model out of the set of candidate models and ignores the model uncertainty in both estimation and inference since these procedures are based on a single model. In this paper we focus on the estimation of the final size and the turning point of the epidemic and conduct a real-time prediction for the final size of the outbreak using several non-linear models in which these parameters are estimated via model averaging. The proposed method is applied to Zika outbreak data in four cities from Colombia, during the outbreak ocurred in 2015-2016.

Hallazgos de angiografía por tomografía computarizada de la mediólisis arterial segmentaria / Segmental arterial mediolysis: findings at computed tomography angiography

Objetivo. Repasar los principales hallazgos de angiografía por tomografía computarizada de la mediólisis arterial segmentaria y enfatizar aquellos puntos que ayuden a diferenciarla de otras vasculopatías, como las vasculitis. Asimismo, se repasarán los protocolos de seguimiento y las diversas opciones terapéuticas. Conclusión. La mediólisis arterial segmentaria es una enfermedad rara que se define como una vasculopatía no ateroesclerótica, no hereditaria y no inflamatoria, caracterizada por la lisis de la capa media de la pared arterial. Debe sospecharse en pacientes de edad media con aneurismas, disecciones o roturas espontáneas de arterias viscerales de etiología desconocida, que no cumplen los criterios clínicos y analíticos de vasculitis. Las arterias viscerales abdominales son las más frecuentemente afectadas, entre ellas el tronco celíaco y las arterias mesentéricas superior e inferior. Sus formas de presentación radiológica incluyen la dilatación arterial, los aneurismas (saculares o fusiformes) únicos o múltiples, las estenosis y las disecciones (AU)

Objective. To review the principal findings on computed tomography angiography for segmental arterial mediolysis, and to emphasize the points that help to differentiate it from other vasculopathies such as vasculitis. We also review the protocols for follow-up and the various treatment options. Conclusion. Segmental arterial mediolysis is a rare disease that is defined as a non-atherosclerotic, non-hereditary, and non-inflammatory vasculopathy characterized by lysis of the medial layer of the arterial wall. It should be suspected in middle-aged patients with aneurysms, dissections, or spontaneous ruptures of visceral arteries of unknown etiology who do not fulfill the clinical and laboratory criteria for vasculitis. The arteries of the abdominal organs are the most commonly affected, including the arteries of the celiac trunk and the superior and inferior mesenteric arteries. Radiologically, segmental arterial mediolysis can present as arterial dilation; single or multiple, saccular or fusiform aneurysms; stenoses; or dissections (AU)

Segmental arterial mediolysis: findings at computed tomography angiography. / Hallazgos de angiografía por tomografía computarizada de la mediólisis arterial segmentaria.

OBJECTIVE: To review the principal findings on computed tomography angiography for segmental arterial mediolysis, and to emphasize the points that help to differentiate it from other vasculopathies such as vasculitis. We also review the protocols for follow-up and the various treatment options. CONCLUSION: Segmental arterial mediolysis is a rare disease that is defined as a non-atherosclerotic, non-hereditary, and non-inflammatory vasculopathy characterized by lysis of the medial layer of the arterial wall. It should be suspected in middle-aged patients with aneurysms, dissections, or spontaneous ruptures of visceral arteries of unknown etiology who do not fulfill the clinical and laboratory criteria for vasculitis. The arteries of the abdominal organs are the most commonly affected, including the arteries of the celiac trunk and the superior and inferior mesenteric arteries. Radiologically, segmental arterial mediolysis can present as arterial dilation; single or multiple, saccular or fusiform aneurysms; stenoses; or dissections.

The determination of copeptin levels helps management decisions among transient ischaemic attack patients.

BACKGROUND: Most approaches to transient ischaemic attack (TIA) triage use clinical scores and vascular imaging; however, some biomarkers have been suggested to improve the prognosis of TIA patients. METHODS: Serum levels of copeptin, adiponectin, neopterin, neuron-specific enolase, high-sensitivity C-reactive protein, IL-6, N-terminal pro-B-type natriuretic peptide, S100ß, tumour necrosis factor-alpha and IL-1α as well as clinical characteristics were assessed on consecutive TIA patients during the first 24 h of the onset of symptoms. RESULTS: Among 237 consecutive TIA patients, 12 patients (5%) had a stroke within 7 days and 15 (6%) within 90 days. Among all candidate biomarkers analysed, only copeptin was significantly increased in patients with stroke recurrence (SR) within 7 days (P = 0.026) but not within 90 days. A cut-off point of 13.8 pmol/l was established with a great predictive negative value (97.4%). Large artery atherosclerosis (LAA) [hazard ratio (HR) 12.7, 95% CI 3.2-50.1, P < 0.001] and copeptin levels ≥13.8 pmol/l (HR 3.9, 95% CI 1.01-14.4, P = 0.039) were independent predictors of SR at the 7-day follow-up. LAA was the only predictor of 90-day SR (HR 7.4, 95% CI 2.5-21.6, P < 0.001). ABCD3I was associated with 7- and 90-day SRs (P = 0.025 and P = 0.034, respectively). The association between copeptin levels and LAA had a diagnostic accuracy of 90.3%. CONCLUSIONS: Serum copeptin could be an important prognostic biomarker to guide management decisions among TIA patients. Therefore, TIA patients with copeptin levels below 13.8 pmol/l and without LAA have an insignificant risk of 7-day SR and could be managed on an outpatient basis.

Pharmacological effects of mitraphylline from Uncaria tomentosa in primary human monocytes: Skew toward M2 macrophages.

ETHNOPHARMACOLOGICAL RELEVANCE: Uncaria tomentosa (Willdenow ex Roemer & Schultes) DC. (Rubiaceae) is a Peruvian thorny liana, commonly known as "cat׳s claw", and traditionally used in folk medicine to deal with several inflammatory diseases. Mitraphylline (MTP) is the most abundant pentacyclic oxindolic alkaloid (POA) from U. Tomentosa and has been reported to modify the inflammatory response. Herein, we have sought to identify the mechanisms underlying this modulatory effect of MTP on primary human monocytes and its ability to regulate differentiation processes on human primary monocyte and monocyte-derived macrophages. MATERIAL AND METHODS: In vitro studies with human primary monocytes and monocyte-derived macrophages were performed. Monocytes and M0 macrophages were exposed to MTP (25µM) and LPS (100ng/mL). M0 macrophages were polarized to M1 and M2 phenotypes in the absence or presence of MTP. The activation state of monocytes/macrophages was assessed by flow cytometry, gene expression and protein analysis of different specific markers. RESULTS: In human primary monocytes, the incubation of MTP for 24h reduced the number of classical (CD14(++)CD16(-)) and intermediate (CD14(++)CD16(+)) subsets when compared to untreated or LPS-treated cells. MTP also reduced the chemotactic capacity of human primary monocytes. In addition, MTP promoted the polarization of M0 macrophages toward an anti-inflammatory M2 phenotype, the abrogation of the release of pro-inflammatory cytokines such as TNFα, IL-6 or IL-1ß, as well as the restoration of markers for M2 macrophages in LPS-treated M1 macrophages. CONCLUSIONS: Our results suggest that MTP may be a key modulator for regulating the plasticity of monocytes/macrophages and the attenuation of the inflammatory response.

Determinants of between-hospital variations in outcomes for patients admitted with COPD exacerbations: findings from a nationwide clinical audit (AUDIPOC) in Spain.

BACKGROUND: Previous studies have demonstrated significant variability in the processes of care and outcomes of chronic obstructive pulmonary disease (COPD) exacerbations. The AUDIPOC is a Spanish nationwide clinical audit that identified large between-hospital variations in care and clinical outcomes. Here, we test the hypothesis that these variations can be attributed to either patient characteristics, hospital characteristics and/or the so-called hospital-clustering effect, which indicates that patients with similar characteristics may experience different processes of care and outcomes depending on the hospital to which they are admitted. METHODS: A clinical audit of 5178 COPD patients consecutively admitted to 129 Spanish public hospitals was performed, with a 90-day follow-up. Multilevel regression analysis was conducted to model the probability of patients experiencing adverse outcomes. For each outcome, an empty model (with no independent variables) was fitted to assess the clustering effect, followed by a model adjusted for the patient- and hospital-level covariables. The hospital-clustering effect was estimated using the intracluster correlation coefficient (ICC); the cluster heterogeneity was estimated with the median odds ratio (MOR), and the coefficients of predictors were estimated with the odds ratio (OR). RESULTS: In the empty models, the ICC (MOR) for inpatient mortality and the follow-up mortality and readmission were 0.10 (1.80), 0.08 (1.65) and 0.01 (1.24), respectively. In the adjusted models, the variables that most represented the patients' clinical conditions and interventions were identified as outcome predictors and further reduced the hospital variations. By contrast, the resource factors were primarily unrelated with outcomes. CONCLUSIONS: This study demonstrates a noteworthy reduction in the observed crude between-hospital variation in outcomes after accounting for the hospital-cluster effect and the variables representing patient's clinical conditions. This emphasises the predictor importance of the patients' clinical conditions and interventions, and understates the impacts of hospital resources and organisational factors.

Prediction of myocardial infarction in patients with transient ischaemic attack.

BACKGROUND: Determinants of risk of myocardial infarction (MI) after transient ischaemic attack (TIA) are not well defined. The aim of our study was to determine the risk and risk factors for MI after TIA. METHODS: We prospectively recruited patients within 24 h of transient ischaemic cerebrovascular events between October 2006 and January 2013. A total of 628 TIA patients were followed for six months or more. MI and stroke recurrence (SR) were recorded. The duration and typology of clinical symptoms, vascular risk factors and aetiological work-ups were prospectively recorded and established prognostic scores (ABCD2, ABCD2I, ABCD3I, Essen Stroke Risk Score, California Risk Score and Stroke Prognosis Instrument) were calculated. RESULTS: Twenty-eight (4.5%) MI and 68 (11.0%) recurrent strokes occurred during a median follow-up period of 31.2 months (16.1-44.9). In Cox proportional hazards multivariate analyses, we identify previous coronary heart disease (CHD) (hazard ratio [HR] 5.65, 95% confidence interval [CI] 2.45-13.04, P < 0.001) and sex male (HR 2.72, 95% CI 1.02-7.30, P = 0.046) as independent predictors of MI. Discrimination for the prognostic scores only ranged from 0.60 to 0.71. The incidence of MI did not vary among the different aetiological subtypes. Positive diffusion weighted imaging (DWI) (7.5% vs 2.5%, P = 0.007), and ECG abnormalities (Q wave or ST-T wave changes) (13.6% vs 3.6%, P = 0.001) were associated to MI. CONCLUSION: According to our results, discrimination was poor for all previous risk prediction models evaluated. Variables such as previous CHD, male sex, DWI and ECG abnormalities should be considered in new prediction models.

Bayesian hierarchical Poisson models with a hidden Markov structure for the detection of influenza epidemic outbreaks.

Considerable effort has been devoted to the development of statistical algorithms for the automated monitoring of influenza surveillance data. In this article, we introduce a framework of models for the early detection of the onset of an influenza epidemic which is applicable to different kinds of surveillance data. In particular, the process of the observed cases is modelled via a Bayesian Hierarchical Poisson model in which the intensity parameter is a function of the incidence rate. The key point is to consider this incidence rate as a normal distribution in which both parameters (mean and variance) are modelled differently, depending on whether the system is in an epidemic or non-epidemic phase. To do so, we propose a hidden Markov model in which the transition between both phases is modelled as a function of the epidemic state of the previous week. Different options for modelling the rates are described, including the option of modelling the mean at each phase as autoregressive processes of order 0, 1 or 2. Bayesian inference is carried out to provide the probability of being in an epidemic state at any given moment. The methodology is applied to various influenza data sets. The results indicate that our methods outperform previous approaches in terms of sensitivity, specificity and timeliness.

N-terminal pro-brain natriuretic peptide level determined at different times identifies transient ischaemic attack patients with atrial fibrillation.

BACKGROUND AND PURPOSE: The etiological classification of patients with transient ischaemic attack (TIA) is a difficult endeavor and the use of serum biomarkers could improve the diagnostic accuracy. The aim of this study was to correlate atrial fibrillation, the main cardioembolic etiology (CE), with different serum biomarkers measured in consecutive TIA patients. METHODS: The concentrations of interleukin-6 (IL-6), tumor necrosis factor-alpha, neuron-specific enolase, high-sensitivity C-reactive protein, IL-1-α and the N-terminal pro-B type natriuretic peptide (NT-proBNP) were quantified in the serum of 140 patients with TIA and 44 non-stroke subjects. Measurements were performed at different times throughout evolution: within 24 h of symptoms onset and at days 7 and 90. RESULTS: With the exception of IL-6, all biomarkers were higher in TIA patients than in controls. NT-proBNP was significantly related to the presence or new diagnosis of AF at all time points analyzed. Furthermore, the baseline NT-proBNP level was significantly higher than values at the 7-day and 90-day follow-up. For this reason, different cut-off values were obtained at different times: 313 pg/ml at baseline [odds ratio (OR) = 18.99, P < 0.001], 181 pg/ml at 7 days (OR = 11.4, P = 0.001) and 174 pg/ml (OR = 8.46, P < 0.001) at 90 days. CONCLUSION: High levels of NT-proBNP determined during the first 3 months after a TIA were associated with AF. Consequently, this biomarker may be useful to reclassify undetermined TIA patients as having disease of CE.

Spatial moving average risk smoothing.

This paper introduces spatial moving average risk smoothing (SMARS) as a new way of carrying out disease mapping. This proposal applies the moving average ideas of time series theory to the spatial domain, making use of a spatial moving average process of unknown order to define dependence on the risk of a disease occurring. Correlation of the risks for different locations will be a function of m values (m being unknown), providing a rich class of correlation functions that may be reproduced by SMARS. Moreover, the distance (in terms of neighborhoods) that should be covered for two units to be found to make the correlation of their risks 0 is a quantity to be fitted by the model. This way, we reproduce patterns that range from spatially independent to long-range spatially dependent. We will also show a theoretical study of the correlation structure induced by SMARS, illustrating the wide variety of correlation functions that this proposal is able to reproduce. We will also present three applications of SMARS to both simulated and real datasets. These applications will show SMARS to be a competitive disease mapping model when compared with alternative proposals that have already appeared in the literature. Finally, the application of SMARS to the study of mortality for 21 causes of death in the Comunitat Valenciana will allow us to identify some qualitative differences in the patterns of those diseases.

Prevalence and immunological spectrum of temporal lobe epilepsy with glutamic acid decarboxylase antibodies.

BACKGROUND AND PURPOSE: High levels of glutamic acid decarboxylase (GAD)-ab were initially described in patients with stiff person syndrome, and have since also been observed in patients with other neurological diseases. Temporal lobe epilepsy (TLE) seems to be specially associated. Our purpose is to describe the prevalence of GAD-ab in patients with TLE, and to characterize the clinical-immunological profile of TLE patients with high levels of GAD-ab. METHODS: An immunological profile including GAD-ab and antinuclear, anti-DNA, anti-cardiolipin, anti-transglutaminase and antithyroid antibodies was determined in a consecutive series of patients with TLE. As adulthood onset is the least common onset in TLE + hipocampal sclerosis and febrile seizures, we selected patients whose onset was after 30 years of age, to expand the spectrum of aetiologies. Patients were divided into two groups: known aetiology, 19 patients (45%) and unknown aetiology, 23 (55%). The clinical-immunological study included TLE patients with high GAD-ab levels (>1000 IU). RESULTS: Amongst 42 patients, serum GAD-ab levels were positive in 5 (152-11, 963 IU/ml), all from the unknown aetiology group. Thus, GAD-ab levels were positive in 21.7% and high in 8.7% of the unknown aetiology group. The immunological profile study included nine patients (seven pharmacoresistant), of whom six were women (66%) with mean age 41 years. Three patients reported acute debut, four (44%) insulin-dependent diabetes mellitus, five (55%) other concomitant autoimmune diseases, four (44%) memory impairment and four moderate-to-severe mood disturbance. Intrathecal synthesis of GAD-ab was observed in seven patients (77%). CONCLUSIONS: Temporal lobe epilepsy with GAD-ab is not a rare condition. In the subgroup of patients with high titres, this epilepsy is often pharmacoresistant and associated with memory impairment, depression and other autoimmune diseases.

Uncaria tomentosa (Willd. ex. Roem. & Schult.) DC. and Eucalyptus globulus Labill. interactions when administered with diazepam.

The safety of natural drugs is defined by their side effects and toxicity as well as any interactions that may occur if taken together with other drugs. In particular, it is essential to identify synergies, antagonisms and other types of interference with other drugs so that the correct choice can be made from the range of phytomedicines available. The aim of this work was to investigate changes in the pharmacological effect of diazepam (2 mg/kg) on the CNS when administered together with a medicinal plant: Eucalyptus globulus Labill. (eucalyptus 6 mg/kg and 3.25 mg/kg) or Uncaria tomentosa (Willd. ex Roem. & Schult). DC. (cat's claw, 7.14 mg/kg and 3.54 mg/kg). Various different psychopharmacological effects were evaluated through assessing exploratory behavior, muscle relaxation and spontaneous motor activity. Both phytodrugs interacted with the benzodiazepine. Eucalyptus had an inhibitory effect at both doses and could be useful at the highest dose in cases where the desired effect of the depressant is moderate anxiolytic activity without marked muscle relaxation. Cat's claw, at both doses, enhanced the action of diazepam on spontaneous motor activity and, at the lowest dose, exploratory ability. These herbal drugs could be useful for their antiinflammatory activity in musculoskeletal pathologies treated with benzodiazepines.

Patterns of diffusion-weighted magnetic resonance imaging associated with etiology improve the accuracy of prognosis after transient ischaemic attack.

OBJECTIVE: diffusion-weighted magnetic resonance imaging (DWI) is a sensitive diagnostic tool for detecting acute ischaemic lesions in patients with transient ischaemic attacks (TIAs). The additional predictive value of DWI lesion patterns is not well known. METHODS: two hundred and fifty-four consecutive patients with TIA underwent DWI within 7 days of symptom onset. The presence and pattern of acute ischaemic lesions were related to clinical features, etiology, and stroke recurrence at seven- and 90-day follow-up. RESULTS: diffusion-weighted images abnormalities were identified in 117 (46.1%) patients. The distribution of DWI lesions was cortical, 31; subcortical, 32; scattered lesions in one arterial territory (SPOT) 42; and in multiple areas, 12. SPOT were significantly associated with motor weakness, large-artery atherosclerosis (LAA), and the cardioembolic subtype of TIA. Single cortical lesions were also associated with cardioembolism, whereas subcortical acute lesions were associated with recurrent episodes, dysarthria, and motor weakness. During follow-up, seven patients had a stroke within 7 days (2.8%, 95% CI 2.9-6.4%), and 12 had a stroke within 3 months (4.7%%, 95% CI 2.9-6.4%). In the Cox logistic regression model, the combination of LAA and positive DWI remained as independent predictors of stroke recurrence at 90-day follow-up (HR 5.78, 95 CI 1.74-19.21, P = 0.004). CONCLUSION: according to our results, MRI, including DWI, should be considered a preferred diagnostic test when investigating patients with potential TIAs. The combination of neuroimaging and vascular information could improve prognostic accuracy in patients with TIA.

Anti-secretory, anti-inflammatory and anti-Helicobacter pylori activities of several fractions isolated from Piper carpunya Ruiz & Pav.

ETHNOPHARMACOLOGICAL RELEVANCE: The leaves of Piper carpunya Ruiz & Pav. (syn Piper lenticellosum C.D.C.) (Piperaceae), are widely used in folk medicine in tropical and subtropical countries of South America as an anti-inflammatory, anti-ulcer, anti-diarrheal and anti-parasitical remedy as well as an ailment for skin irritations. AIMS OF THE STUDY: To study the anti-inflammatory, anti-secretory and anti-Helicobacter pylori activities of different fractions isolated from an ethanolic extract of the leaves of Piper carpunya, in order to provide evidence for the use of this plant as an anti-ulcer remedy. Moreover, to isolate the main compounds of the extract and relate their biological activity to the experimental results obtained with the fractions. MATERIALS AND METHODS: Sixteen fractions were obtained from the ethanolic extract (F I-XVI) and 16 pure compounds were isolated and identified from these fractions. We studied the effects of the fractions (0.1-400microg/mL) on the release of myeloperoxidase (MPO) enzyme from rat peritoneal leukocytes, on rabbit gastric microsomal H(+), K(+)-ATPase activity and anti-Helicobacter pylori anti-microbial activity using the microdilution method (MM). The main compounds contained in the fractions were isolated and identified by (1)H- and (13)C NMR spectra analysis and comparison with the literature data. RESULTS: Eight fractions showed inhibition of MPO enzyme (F I-IV, X, XII, XIV and XV). The highest inhibition was observed with F XIV (50microg/mL, 60.9%, p<0.001). F X and XII were the most active ones, inhibiting the gastric H(+), K(+)-ATPase activity with IC(50) values equal to 22.3microg/mL and 28.1microg/mL, respectively. All fractions, except F XV, presented detectable anti-Helicobacter pylori activity, with a diameter of inhibition zones ranging from 11mm up to 50mm. The best anti-Helicobacter pylori activity was obtained with F III and V. Both fractions killed Helicobacter pylori with lowest concentration values, about 6.25mug/mL. Sixteen pure compounds were isolated, five of them are flavonoids that possess strong anti-oxidant and free radical scavenging activity, e.g. vitexin, isovitexin, and rhamnopyranosylvitexin. Terpenoids like sitosterol, stigmasterol and phytol, which have shown gastroprotective activity, and dihydrochalcones, like asebogenin, with anti-bacterial activity, were also isolated. Furthermore, the rare neolignan 1, that is a DNA polymerase beta lyase inhibitor, and (6S, 9S)-roseoside, that shows strong anti-bacterial activity, were isolated, for the first time, from the genus Piper. CONCLUSIONS: We suggest that the flavonoids isolated from F I and II (vitexin, isovitexin, rhamnopyranosylvitexin and isoembigenin) contribute to the anti-MPO activity, as well as to their anti-Helicobacter pylori activity. These flavonoids may also be responsible for the important inhibition of H(+), K(+)-ATPase activity. Also the phytosterols and phytol obtained from F XIV and XV could be involved in these gastroprotective activities. These results encourage us to continue phytochemical studies on these fractions in order to obtain full scientific validation for this species.

Bayesian methods in cost-effectiveness studies: objectivity, computation and other relevant aspects.

In a probabilistic sensitivity analysis (PSA) of a cost-effectiveness (CE) study, the unknown parameters are considered as random variables. A crucial question is what probabilistic distribution is suitable for synthesizing the available information (mainly data from clinical trials) about these parameters. In this context, the important role of Bayesian methodology has been recognized, where the parameters are of a random nature. We explore, in the context of CE analyses, how formal objective Bayesian methods can be implemented. We fully illustrate the methodology using two CE problems that frequently appear in the CE literature. The results are compared with those obtained with other popular approaches to PSA. We find that the discrepancies can be quite marked, specially when the number of patients enrolled in the simulated cohort under study is large. Finally, we describe in detail the numerical methods that need to be used to obtain the results.