Systemic Lupus Erythematosus Disease Activity Score Remission and Low Disease Activity States Discriminate Drug From Placebo and Better Health-Related Quality of Life.

OBJECTIVE: Our objective was to evaluate the ability of Systemic Lupus Erythematosus Disease Activity Score (SLE-DAS) remission and low disease activity (LDA) to discriminate active drug from placebo and to discriminate outcomes in the patients' perspective (health-related quality of life [HR-QoL]) in SLE trials. METHODS: This was a post hoc analysis of the pooled Belimumab in Subjects With SLE (BLISS)-52 (NCT00424476) and BLISS-76 (NCT00410384) trials data. SLE-DAS remission and LDA attainment and discrimination between belimumab and placebo at 52 weeks were compared using chi-square tests. At week 52, 36-item Short Form Health Survey (SF-36) and Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) scores were compared between patients attaining SLE-DAS remission versus nonremission and SLE-DAS LDA versus non-LDA using the t-test and Mann-Whitney test. Mean changes from week 0 to 52 in SF-36 and FACIT-F scores were compared between groups using multivariate regression analysis adjusted for baseline scores. RESULTS: At week 52, significantly more patients attained SLE-DAS LDA taking belimumab 1 mg/kg (17.9% vs 13.0%; P = 0.023; odds ratio [OR] 1.459; relative risk [RR] 1.377; number needed to treat [NNT] 20.4) and 10 mg/kg (21.7% vs 13.0%; P < 0.001; OR 1.853; RR 1.668; NNT 11.5) compared with placebo. Likewise, more patients attained SLE-DAS remission taking belimumab 10 mg/kg compared to placebo (14.7% vs 10.1%; P = 0.019; OR 1.532; RR 1.454; NNT 21.7). At week 52, patients attaining SLE-DAS remission and LDA presented higher SF-36 domain and summary scores (all P < 0.001) and FACIT-F scores (both P < 0.001). Mean improvements from baseline in SF-36 and FACIT-F scores were significantly higher in patients achieving SLE-DAS remission and LDA. CONCLUSION: SLE-DAS remission and LDA showed discriminant ability for identifying patients receiving active drug in SLE clinical trials. Attainment of these SLE-DAS targets are associated with better HR-QoL.

A Case of Optic Chiasm Stroke, A Condition Rarely Described in the Literature.

Acute bilateral blindness is an emergent condition that may signal life-threatening disease. The approach focuses on identification of life-threatening disease processes, while differentiating between ocular, psychogenic and neurologic aetiologies. We present the case of an 88-year-old man with multiple cardiovascular risk factors and bilateral chronic glaucoma and cataracts. He presented to the emergency department with sudden onset bilateral loss of visual acuity with no other relevant changes on physical examination, including other neurologic deficits. Ophthalmologic observation showed no sign of acute disease. Contrast orbit and cranioencephalic CT was unremarkable, so the patient underwent an orbit and cranioencephalic MRI that showed changes in fluid-attenuated inversion recovery (FLAIR) sequences and diffusion restriction involving the optic chiasm and the initial segment of the optic radiations bilaterally. Optic chiasm strokes are rare, owing to the rich supply of collateral circulation. The most frequent presentation is bitemporal hemianopsia but rarer presentations are described. Bilateral loss of visual acuity is very rare and infarction of the whole optic chiasm is unusual. LEARNING POINTS: Acute bilateral blindness has an extensive differential diagnosis but chiasmopathy of ischaemic aetiology is rare.Optic chiasm stroke is rarely described in the literature and can pose a diagnostic challenge as its presentation can vary greatly.

The relationship between acute pain and other types of suffering in pre-hospital trauma victims: An observational study.

BACKGROUND: Acute pain is an important complaint reported by trauma victims, however, the relationship between it and other types of discomfort, such as discomfort caused by cold, discomfort caused by immobilization, and psychological distress such as fear, anxiety, and sadness is limitedly studied and documented. AIM: To assess the relationship between acute trauma pain and other types of suffering in pre-hospital trauma victims. METHODS: This is a prospective multicentre cohort study conducted in Immediate Life Support Ambulances in Portugal. All adult trauma victims with a mechanism of blunt and penetrating injuries, falls, road accidents and explosions, were included. RESULTS: 605 trauma victims were included, mainly male, with a mean age of 53.4 years. Before the intervention of the rescue teams, 90.5 % of the victims reported some level of pain, 39.0 % reported discomfort caused by cold, while 15.7 % felt fear, 8.4 % sadness, 49.8 % anxiety and 4.5 % apathy. Victims with high discomfort caused by cold tend to have higher pain levels. Significantly higher pain intensity were observed in victims with fear and anxiety. Univariate and multivariate analysis indicates that immobilization is associated with increased pain levels. CONCLUSIONS: There is a statistically significant relationship between acute trauma pain, anxiety, fear, cold and immobilization.

Neonatal testosterone voids sexually differentiated microglia morphology and behavior.

The involvement of immunity in psychiatric disorders, such as anxiety, is typified by the morphologic adaptation of microglia, immune cells of the brain, to anxiogenic stimuli. We previously reported sexually differentiated microglia morphology in adult rodents, in brain locations implicated in anxiety, including the pre-frontal cortex. These physiologic differences likely drive sex-dependent patterns of microglia morphologic remodeling in response to varied stress conditions in different periods of life, that correlate with sex-dependent behavioral adaptation to anxiogenic stimuli. The time-window of appearance of sex differences in microglia, correlating with sex-specific behavioral performance in anxiogenic conditions are still unknown. In rodents, a postnatal peak of the sexual hormone testosterone is determinant for the so-called brain masculinization and sex-determined behavioral traits. In the present work we aim to clarify if differences in microglia morphology are present at birth or can be driven by postnatal testosterone and impacts on the ability to deal with an anxiogenic context. Differences in microglia morphology are not present at birth, but are observable at adolescence (increased complexity of male microglia, particularly in branches more proximal to the soma), when differences in behavior are also observed. Our data also show that adolescent females neonatally treated with testosterone exhibit masculinized microglia and behavior. Importantly, between adolescence and adulthood, a sex-determined shift in the pattern of complexity takes place and microglia from females become more complex. When testosterone is administered, this morphological effect is partially abolished, approximating microglia and behavior to the male phenotype.

Assessing the performance of exchange traded funds in the energy sector: a hybrid DEA multiobjective linear programming approach.

This paper proposes a two-step approach to build portfolio models. The first step employs the Data Envelopment Analysis (DEA) to select assets attaining efficient financial performance according to a set of indicators used as inputs and outputs. The second step builds interval multiobjective portfolio models to obtain the optimal composition of efficient portfolios previously identified with respect to investor preferences. The usefulness of this proposed methodology is illustrated through a selected sample of diversified Exchange Traded Funds (ETFs) operating in the US energy sector. Our results with respect to all models and time horizons mainly show that: (i) ETFs related to nuclear energy are more often viewed as efficient according to all DEA models considered; (ii) the efficient portfolios do not contain any ETFs related to the renewable energy sector; and (iii) natural gas and oil are the sectors that have the most ETFs represented in efficient portfolios. Supplementary Information: The online version contains supplementary material available at 10.1007/s10479-021-04323-6.

Definition of low disease activity state based on the SLE-DAS: derivation and validation in a multicentre real-life cohort.

OBJECTIVES: To derive and validate a definition of low disease activity (LDA) for SLE based on the SLE Disease Activity Score (SLE-DAS), in a real-life multicentre cohort of SLE patients. METHODS: Derivation was conducted using data from a monocentric cohort of SLE (Portugal), and validation was performed in a multicentre cohort (Italy, France and Spain). The Lupus Low Disease Activity State (LLDAS) was used as comparator. We applied receiver operating characteristics curve analysis against the LLDAS to determine the cut-off of SLE-DAS for LDA using bootstrap methodology. In a second step, we tested a definition of SLE-DAS LDA that included: (i) the statistically derived SLE-DAS upper threshold for LDA and (ii) prednisone dose ≤7.5 mg/day. In the multicentre validation cohort, we assessed the classification performance of this SLE-DAS LDA definition. RESULTS: We included 774 patients, 300 in the derivation and 474 in the validation cohort. In the derivation cohort, the optimal cut-off to identify patients in LLDAS was SLE-DAS ≤2.48, presenting an area under the curve of 0.965 (95% CI 0.935, 0.994). When applied to the multicentre validation cohort, the SLE-DAS LDA definition showed a sensitivity of 97.1% and a specificity of 97.7% for LLDAS and an almost perfect agreement (Cohen's Kappa = 0.933; P < 0.001). McNemar's test found no significant differences between the two definitions (P = 0.092). CONCLUSION: The SLE-DAS LDA is a validated, accurate and easy-to-use definition for classifying SLE patients in LDA state.

Tratamento pré-hospitalar da dor traumática aguda: um estudo observacional / Tratamiento prehospitalario del dolor traumático agudo: un estudio observacional / Pre-hospital treatment of acute trauma pain: an observational study

Resumo Objetivo Descrever e analisar a eficácia das intervenções levadas a cabo pelos enfermeiros para reduzir a dor dos doentes com lesões traumáticas. Métodos Estudo de coorte prospetivo realizado junto das Ambulâncias de Suporte Imediato de Vida em Portugal, entre 1 de março de 2019 e 30 de abril de 2020. Foram recolhidos dados sobre o tipo de intervenções implementadas e sobre o tempo que durou a aplicação dos procedimentos de salvamento. De forma a poder estudar a evolução das dores traumáticas agudas, foi utilizada uma Escala de Classificação Numérica composta por 11 pontos. As alterações do nível de dor registadas ao longo dos três momentos de avaliação realizados foram estudadas utilizando modelos lineares mistos com interceptos aleatórios para se poder analisar as medidas repetidas aplicadas ao mesmo paciente. Estas alterações foram avaliadas antes e depois da aplicação das intervenções para alívio da dor. Resultados 596 pacientes foram incluídos neste estudo. A maioria era do sexo masculino (65,9%) e tinha média de idade de 53,05±19,72 anos. Houve redução na intensidade média da dor na ordem dos 2,44 pontos (p<0,005) entre o início e o fim da avaliação, e redução de 39,62% entre os pacientes que apresentavam nível de dor igual ou superior a 7 (46,7% contra 7,08%, p<0,05). As medidas que envolvem o uso de morfina, crioterapia e intervenções de suporte emocional provaram ser eficazes. As medidas de conforto como um todo não parecem ser capazes de ter um impacto significativo no alívio da dor. Conclusão As intervenções pré-hospitalares farmacológicas e não farmacológicas levadas a cabo pelos enfermeiros provaram ser eficazes na redução da dor. As medidas de conforto não provaram ser eficazes, pelo que o seu potencial deve ser repensado e reforçado.

Resumen Objetivo Describir y analizar la eficacia de las intervenciones llevadas a cabo por los enfermeros para reducir el dolor de los enfermos con lesiones traumáticas. Métodos Estudio de corte prospectivo realizado con las Ambulancias de Soporte Inmediato de Vida en Portugal, entre el 1º de marzo de 2019 y el 30 de abril de 2020. Se recopilaron datos sobre el tipo de intervenciones implementadas y sobre el tiempo que duró la aplicación de los procedimientos de salvamento. De forma a poder estudiar la evolución de los dolores traumáticos agudos, se utilizó una Escala de Clasificación Numérica compuesta por 11 puntos. Las alteraciones en el nivel de dolor registradas a lo largo de los tres momentos de evaluación realizados fueron estudiadas utilizando modelos lineales mixtos con interceptos aleatorios para posibilitar el análisis de medidas repetidas aplicadas con el mismo paciente. Estas alteraciones fueron evaluadas antes y después de la aplicación de las intervenciones para el alivio del dolor. Resultados 596 pacientes fueron incluidos en este estudio. La mayoría era del sexo masculino (65,9 %), con un promedio de edad entre de 53,05±19,72 años. Hubo una reducción en la intensidad promedio del dolor del orden de 2,44 puntos (p<0,005) entre el inicio y el fin de la evaluación y una reducción del 39,62 % entre los pacientes que presentaban un nivel de dolor igual o superior a 7 (46,7 % contra 7,08 %, p<0,05). Las medidas que involucran el uso de morfina, crioterapia e intervenciones de soporte emocional probaron que son eficaces. No parece que las medidas de confort, de forma general, sean capaces de tener un impacto significativo en el alivio del dolor. Conclusión Las intervenciones prehospitalarias farmacológicas y no farmacológicas llevadas a cabo por los enfermeros comprobaron que son eficaces en la reducción del dolor. Las medidas de confort no comprobaron ser eficaces, motivo este por el que se debe volver a pensar su potencial y reforzarlo.

Abstract Objective To describe and analyze the effectiveness of nurses' interventions in pain reduction among patients with traumatic injury. Methods Prospective cohort study conducted in the Immediate Life Support Ambulances in Portugal from March 1, 2019 to April 30, 2020. We have collected data on the kind of interventions implemented and the time elapsed during rescue procedures. To investigate the course of acute trauma pain, a 11-point Numeric Rating Scale was used. Changes in the level of pain registered throughout the three assessment moments were studied using linear mixed-effects models with random intercepts to account for the repeated measurements conducted on the same patient. These changes were assessed before and after the administration of the pain relief interventions. Results 596 patients were included in this study. Most of them were male (65.9%) and had a mean age of 53.05±19.72 years. There was a reduction in the average pain intensity of 2.44 points (p<0.005), between the beginning and end of the assessment, and a reduction of 39.62% among the patients who were experiencing a level of pain equal to or greater than 7 (46.7% vs 7.08%, p<0.05). Measures involving the use of morphine, cryotherapy and relationship-based measures have proven to be effective. Comfort measures as a whole do not seem to have a significant impact on pain relief. Conclusion Pre-hospital pharmacological and non-pharmacological nurses' interventions have proven to be effective in reducing pain. Comfort measures have not been proved to be effective, so their potential must be rethought and enhanced.

Systemic Lupus Erythematosus Disease Activity Score (SLE-DAS) enables accurate and user-friendly definitions of clinical remission and categories of disease activity.

OBJECTIVES: There is an unmet need for accurate and user-friendly definitions of systemic lupus erythematosus (SLE) disease activity and remission. We aimed to derive and validate the SLE Disease Activity Score (SLE-DAS) definitions for disease activity categories and clinical remission state. METHODS: Derivation was conducted at Padova Lupus Clinic (Italy). Validation was prospectively performed at Cochin Lupus Clinic (France) and by post hoc analysis of BLISS-76 trial. At each clinic, an expert classified patients in three categories: remission, mild or moderate/severe activity. The SLE-DAS cut-offs were derived using the receiver operating characteristic curve analysis in Padova cohort; its performance was assessed against expert classification in Cochin cohort and British Isles Lupus Assessment Group (BILAG) index in BLISS-76. Gold standard for clinical remission state was the fulfilment of Definition Of Remission In SLE. A Boolean and an index-based definitions of remission were sustained by chi-square automatic interaction detection algorithm. An SLE-DAS online calculator was developed and tested. RESULTS: We included 1190 patients with SLE: 221 in the derivation cohort and 969 in the validation cohorts (150 from Cochin; 819 from BLISS-76). Derived cut-offs were: remission, SLE-DAS ≤2.08; mild activity, 2.087.64. Regarding validation in Cochin cohort, sensitivity and specificity are above 90%, 82% and 95% for remission, mild and moderate/severe activity, respectively. The SLE-DAS Boolean-based and index-based remission showed sensitivity of 100% and specificity above 97%. CONCLUSION: The SLE-DAS is an accurate and easy-to-use tool for defining SLE clinical remission state and disease activity categories, validated against expert assessment and BILAG.

Trauma Prehospital Hypothermia Prevention and Treatment: An Observational Study.

BACKGROUND: Hypothermia in trauma patients causes increased morbidity and mortality. Swift recognition and treatment are important to prevent any further heat loss. In addition, patient discomfort from cold decreases satisfaction with care. The administration of active and passive rewarming measures is important in the prevention and treatment of hypothermia, but their use in prehospital trauma patients in Portugal has not been previously reported. OBJECTIVE: To assess the prevalence of hypothermia, the impact of rewarming measures, and the management of the discomfort caused by cold. METHODS: This is a prospective cohort study conducted in Immediate Life Support Ambulances in Portugal between March 1, 2019, and April 30, 2020. RESULTS: This study included records of 586 trauma patients; of whom, 66.2% were men. Cranioencephalic trauma was the most common trauma observed, followed by lower limb and thoracic traumas. Mean body temperature increased 0.12 °C between the first and last assessments (p < .05). Most patients experiencing a level of discomfort of 5 or more on a 0-10 scale reported improvement (from 17.2% to 2.4% after nurses' intervention). Warmed intravenous fluids proved to be effective (p < .05) in increasing body temperature, and passive rewarming measures were effective in preventing hypothermia. CONCLUSIONS: Hypothermia management has to consider the initial temperature, the season, the available rewarming measures, and the objectives to be achieved. The optimization of resources for the monitoring and treatment of hypothermia should be a priority in prehospital assistance. The implementation of rewarming measures improves patients' outcomes and decreases the discomfort caused by cold in prehospital care.

Ultra-Early Versus Early Aneurysm Surgery After Subarachnoid Hemorrhage: A Retrospective Outcome Analysis

Object The timing of definitive management of ruptured intracranial aneurysms has been the subject of considerable debate, although the benefits of early surgery (until 72 hours postictus) are widely accepted. The aim of the present study is to evaluate the potential benefit of ultra-early surgery (until 24 hours) when compared with early surgery, in those patients who were treated by surgical clipping at the Neurosurgery Department of the Coimbra Hospital and University Centre. Methods A 17-year database of consecutive ruptured and surgically treated intracranial aneurysms was analyzed. Outcome was measured by the Glasgow Outcome Scale (GOS). Baseline characteristics were analyzed by the Fisher exact test, the chi-squared and Mann-Whitney tests. Logistic regression was used to assess the impact of good grade according to the World Federation of Neurological Surgeons (WFNS) scale and ultra-early surgery in a good GOS outcome. Results 343 patients who were submitted to surgical clipping in the first 72 hours postictus were included, 165 of whom have undergone ultra-early surgery. Demographics and preoperative characteristics of ultra-early and early surgery patients were similar. Goodgrade patients according to the WFNS scale submitted to ultra-early surgery demonstrated an improvedGOS at discharge and at 6months. Poor-grade patients according to theWFNS scale submitted to ultra-early surgery demonstrated an improved GOS at discharge. Conclusions Ultra-early surgery for aneurysmal subarachnoid hemorrhage patients improves outcome mainly on good-grade patients. Efforts should be made on the logistics of emergency departments to consider achieving treatment on this timeframe as a standard of care.

Arteriolar C4d in IgA Nephropathy: A Cohort Study.

RATIONALE & OBJECTIVE: Glomerular C4d (C4dG) as an indicator of the lectin pathway of complement activation in immunoglobulin A nephropathy (IgAN) has been associated with more severe kidney damage. Recent studies have suggested that vascular lesions in IgAN biopsy specimens with complement deposition are also associated with disease progression. We aimed to study the clinical significance of arteriolar C4d (C4dA) in IgAN kidney biopsy tissue. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Kidney biopsy specimens from 126 adults with IgAN diagnosed by Oxford classification criteria were stained using immunohistochemistry and classified according to C4dG and C4dA deposition. Additionally, vascular lesions including acute and chronic microangiopathy, arteriolar hyalinosis, and arterial intima fibrosis were characterized. PREDICTOR: C4dA. OUTCOME: Progressive kidney disease, defined as a decline in estimated glomerular filtration rate by≥50% or occurrence of kidney failure. ANALYTICAL APPROACH: The association of C4dA and C4dG with baseline clinical and histologic characteristics, as well as progressive kidney disease, were assessed with survival analysis using multivariable Cox regression analysis. RESULTS: C4dA was identified in 21 (17%) patients and was associated with mean arterial pressure, arterial intima fibrosis, and chronic microangiopathy. C4dA was also significantly associated with C4dG and both were associated with progressive kidney disease. In regression analysis, C4dA remained significantly associated with progressive kidney disease after adjusting for other significant predictors, including baseline estimated glomerular filtration rate, mean arterial pressure, and the presence of crescents. LIMITATIONS: Findings based on the retrospective evaluation of a single center's experience, limited number of events, a small number of patients with a broad range of kidney disease stages, and use of immunohistochemistry rather than immunofluorescence to detect C4d. CONCLUSIONS: C4dA is a potential biomarker for disease progression in IgAN. It should be further investigated in larger cohorts to determine the value of C4dA in improving prediction of IgAN disease progression.

Microglia cytoarchitecture in the brain of adenosine A2A receptor knockout mice: Brain region and sex specificities.

Microglia cells exert a critical role in brain development, mainly supported by their immune functions, which predicts an impact on the genesis of psychiatric disorders. In fact, microglia stress during gestation is, for instance, associated with chronic anxiety and cognitive deficits accompanied by long-lasting, region- and sex-specific changes in microglia morphology. We recently reported that the pattern of microglia morphologic plasticity, which is sex-determined, impacts on anxious-like behaviour and cognition. We also reported that the pharmacologic blockade of adenosine A2A receptors (A2A R) is able to reshape microglia morphology, in a sex-specific manner and with behavioural sequelae. In order to better understand the role of A2A R in the sex differentiation of microglia, we now compared their morphology in wild-type and A2A R knockout male and female C57BL/6 mice in two cardinal brain regions implicated in anxiety-like behaviour and cognition, the prefrontal cortex (PFC) and the dorsal hippocampus (dHIP). We report interregional differences between PFC and dHIP in a sex-specific manner: while males presented more complex microglia in the dHIP, microglia from females had a more complex morphology in the PFC. Surprisingly, the genetic deletion of A2A R did not alter these sex differences, but promoted the exclusive remodelling (increase in complexity) in PFC microglia from females. These findings further support the existence of a heterogeneous microglial network, distinct between sexes and brain regions, and help characterizing the role of A2A R in the sex- and brain region-specific morphologic differentiation of microglia.

Application of Risks Scores in Acute Coronary Syndromes. How Does ProACS Hold Up Against Other Risks Scores?

BACKGROUND: Multiple risk scores (RS) are approved in the prediction of worse prognosis in acute coronary syndromes (ACS). Recently, the Portuguese Journal of Cardiology has proposed the ProACS RS. OBJECTIVE: Application of several validated RS, as well as ProACS in patients, admitted for ACS. Evaluation of each RS's performance in predicting in-hospital mortality and the occurrence of all-cause mortality or non-fatal ACS at one-year follow-up and compare them to the ProACS RS. METHODS: A retrospective study of ACS was performed. The following RS were applied: GRACE, ACTION Registry-GWTG, PURSUIT, TIMI, EMMACE, SRI, CHA2DS2-VASc-HS, C-ACS and ProACS. ROC Curves were created to determine the predictive power for each RS and then were directly compared to ProACS. RESULTS: The ProACS, ACTION Registry-GWTG and GRACE showed a c-statistics of 0.908, 0.904 and 0.890 for predicting in-hospital mortality, respectively, performing better in ST-segment elevation myocardial infarction patients. The other RS performed satisfactorily, with c-statistics over 0.750, apart from the CHA2DS2-VASc-HS and C-ACS which underperformed. All RS underperformed in predicting worse long-term prognosis revealing c-statistics under 0.700. CONCLUSION: ProACS is an easily obtained risk score for early stratification of in-hospital mortality. When evaluating all RS, the ProACS, ACTION Registry-GWTG and GRACE RS showed the best performance, demonstrating high capability of predicting a worse prognosis. ProACS was able to demonstrate statistically significant superiority when compared to almost all RS. Thus, the ProACS has showed that it is able to combine simplicity in the calculation of the score with good performance in predicting a worse prognosis.

Application of Risks Scores in Acute Coronary Syndromes. How Does ProACS Hold Up Against Other Risks Scores? / Aplicação de Escores de Risco em Síndromes Coronárias Agudas: Como o ProACS se Comporta Diante de Outros Escores de Risco?

Abstract Background: Multiple risk scores (RS) are approved in the prediction of worse prognosis in acute coronary syndromes (ACS). Recently, the Portuguese Journal of Cardiology has proposed the ProACS RS. Objective: Application of several validated RS, as well as ProACS in patients, admitted for ACS. Evaluation of each RS's performance in predicting in-hospital mortality and the occurrence of all-cause mortality or non-fatal ACS at one-year follow-up and compare them to the ProACS RS. Methods: A retrospective study of ACS was performed. The following RS were applied: GRACE, ACTION Registry-GWTG, PURSUIT, TIMI, EMMACE, SRI, CHA2DS2-VASc-HS, C-ACS and ProACS. ROC Curves were created to determine the predictive power for each RS and then were directly compared to ProACS. Results: The ProACS, ACTION Registry-GWTG and GRACE showed a c-statistics of 0.908, 0.904 and 0.890 for predicting in-hospital mortality, respectively, performing better in ST-segment elevation myocardial infarction patients. The other RS performed satisfactorily, with c-statistics over 0.750, apart from the CHA2DS2-VASc-HS and C-ACS which underperformed. All RS underperformed in predicting worse long-term prognosis revealing c-statistics under 0.700. Conclusion: ProACS is an easily obtained risk score for early stratification of in-hospital mortality. When evaluating all RS, the ProACS, ACTION Registry-GWTG and GRACE RS showed the best performance, demonstrating high capability of predicting a worse prognosis. ProACS was able to demonstrate statistically significant superiority when compared to almost all RS. Thus, the ProACS has showed that it is able to combine simplicity in the calculation of the score with good performance in predicting a worse prognosis.

Resumo Fundamento: Existem muitos escores de risco (ERs) aprovados na predição de um pior prognóstico em síndromes coronárias agudas (SCAs). Recentemente, a Revista Portuguesa de Cardiologia propôs o ER ProACS. Objetivo: Aplicar vários ERs validados, bem como o ProACS em pacientes internados por SCA. Avaliar o desempenho de cada ER em predizer mortalidade hospitalar e a ocorrência de mortalidade por todas as causas ou SCA não fatal em um ano de acompanhamento e compará-los com o ProACS. Métodos: Estudo retrospectivo de SCA. Os seguintes ERs foram aplicados: GRACE, ACTION Registry-GWTG, PURSUIT, TIMI, EMMACE, SRI, CHA2DS2-VASc-HS, C-ACS e ProACS. Curvas ROC foram criadas para determinar o poder preditivo de cada ER e diretamente comparadas com a do ProACS. Resultados: Os escores ProACS, ACTION Registry-GWTG e GRACE mostraram estatística-C de 0,908, 0,904 e 0,890, respectivamente, em predizer mortalidade hospitalar, mostrando melhor desempenho em pacientes com infarto do miocárdio com elevação do segmento ST. Os demais ERs mostraram desempenho satisfatório, com estatística-C acima de 0,750, com exceção de CHA2DS2-VASc-HS e C-ACS, que mostraram baixa performance. Todos os ERs apresentaram baixo desempenho em predizer um pior prognóstico em longo prazo, com estatística-C abaixo de 0,700. Conclusão: O ProACS é um escore de risco facilmente obtido para estratificação precoce de mortalidade intra-hospitalar. Ao avaliar todos os ERs, ProACS, ACTION Registry-GWTG e GRACE mostraram o melhor desempenho, com alta capacidade de predizer um pior prognóstico. O ProACS mostrou superioridade estatisticamente significativa em comparação aos outros ERs. Portanto, o ProACS mostrou-se capaz de combinar simplicidade no cálculo do escore com bom desempenho em predizer um pior prognóstico.

Relationship between HbA1c and capillary blood glucose self-monitoring in type 2 diabetics.

INTRODUCTION: Diabetes Control and Complications Trial has established the importance of glycemic control in reducing the progression of retinopathy, nephropathy, and neuropathy in type 1 diabetics. There is little literature linking the frequency of glycemic monitoring with glycated hemoglobin A (HbA1c) in type 2 diabetics. The objectives were to assess the influence of glycemic self-monitoring on HbA1c in three groups of patients with type 2 diabetes (with insulin, with oral antidiabetics and with combination therapy). METHODS: The glucometer capillary surveys of 117 patients were counted in the 30 days prior to the visit to the Integrated Diabetes Unit at Centro Hospitalar Tondela-Viseu. In the three groups considered, sociodemographic characteristics (age, gender, area of residence, household and schooling) were evaluated and compared. RESULTS: There was no statistically significant association between HbA1c and the frequency of capillary glucose in any of the groups. In the evaluation of sociodemographic data, contrary to what was expected, the area of residence and schooling did not influence the value of HbA1c. CONCLUSION: These results question the role of glycemic monitoring in the metabolic control of type 2 diabetics, highlighting the need to implement therapeutic education programs so that these patients can adequately intervene in the therapeutic adjustment as a function of the information obtained by capillary glycemia.

Derivation and validation of the SLE Disease Activity Score (SLE-DAS): a new SLE continuous measure with high sensitivity for changes in disease activity.

OBJECTIVES: To derive and validate a new disease activity measure for systemic lupus erythematosus (SLE), the SLE Disease Activity Score (SLE-DAS), with improved sensitivity to change as compared with SLE Disease Activity Index (SLEDAI), while maintaining high specificity and easiness of use. METHODS: We studied 520 patients with SLE from two tertiary care centres (derivation and validation cohorts). At each visit, disease activity was scored using the Physician Global Assessment (PGA) and SLEDAI 2000 (SLEDAI-2K). To construct the SLE-DAS, we applied multivariate linear regression analysis in the derivation cohort, with PGA as dependent variable. The formula was validated in a different cohort through the study of: (1) correlations between SLE-DAS, PGA and SLEDAI-2K; (2) performance of SLEDAI-2K and SLE-DAS in identifying a clinically meaningful change in disease activity (ΔPGA≥0.3); and (3) accuracy of SLEDAI-2K and SLE-DAS time-adjusted means in predicting damage accrual. RESULTS: The final SLE-DAS instrument included 17 items. SLE-DAS was highly correlated with PGA (r=0.875, p<0.0005) and SLEDAI-2K (r=0.943, p<0.0005) in the validation cohort. The optimal discriminative ΔSLE-DAS cut-off to detect a clinically meaningful change was 1.72. In the validation cohort, SLE-DAS showed a higher sensitivity than SLEDAI-2K (change ≥4) to detect a clinically meaningful improvement (89.5% vs 47.4%, p=0.008) or worsening (95.5% vs 59.1%, p=0.008), while maintaining similar specificities. SLE-DAS performed better in predicting damage accrual than SLEDAI-2K. CONCLUSION: SLE-DAS has a good construct validity and has better performance than SLEDAI-2K in identifying clinically significant changes in disease activity and in predicting damage accrual.

[Diagnostic criteria for the Brugada syndrome: can they be improved?]. / Critérios de diagnóstico da síndrome de Brugada. Podemos melhorar?

INTRODUCTION: Diagnosis of Brugada syndrome (BS) currently requires documentation of a characteristic repolarization pattern (type 1 Brugada ECG). Mutations in the SCN5A gene, which codes for sodium channel Na(v) 1.5, are found in 38% of familial cases of BS. Sodium current dysfunction negatively affects the cardiac fast response action potential, particularly in atrial and ventricular myocytes and in the fast-conducting Purkinje system. OBJECTIVES: To detect carriers of SCN5A mutations without using the characteristic repolarization pattern (type 1 Brugada ECG). METHODS: Of a total of 141 members of three different families including 55 carriers of two nonsense SCN5A mutations causing BS, all those aged over 16 (113 individuals, 42 carriers) were studied. The PR interval (PR) and QT dispersion (QTd) between leads V1 and V3 were measured on conventional ECG. Using signal-averaged ECG the total duration of the filtered QRS complex (fQRS), the root-mean-square (RMS40) and the low-amplitude signal (LAS) were measured. The following procedures were developed to detect carriers/To detect carriers the following procedures were developed: (1) a screening test (ScreenTest) with PS (PR+fQRS) > or = 250 (250ms is 80% of the theoretical maximum in healthy individuals); and (2) a diagnostic test (DiagTest) for the simultaneous fulfillment of four conditions: PS > or = 250 and QTd > or = 10 and LAS > 26 and RMS40 < or = 29 (the latter two cut-offs are approximately 70% of the theoretical maximum in healthy carriers). RESULTS: Significant differences in PR, QTd, QRSf, RMS40 and LAS were found between carriers and non-carriers. The SCN5A gene was associated with all these variables, the strongest association being with PR. Both tests were applied to 63 family members (38 carriers). The ScreenTest was positive in 38 of 38 carriers, with eight false positives in 27 non-carriers (sensitivity [SE] = 100% and specificity [SP] = 66.67%). From ROC curve analysis a cut-off of PS = 252.5 shows SE = 100% and SP = 76% and a cut-off of PS = 260 shows SE=94.7% and SP = 84%. The DiagTest was positive in 36 of 38 carriers, with three false positives: SE = 94.74% and SP = 88.89%. From ROC curve analysis a multivariate logistic model identifies a cut-off with SE = 92% and SP = 92%. In the same group the SE and SP of the characteristic spontaneous repolarization pattern (type 1 Brugada ECG) to detect carriers were 52.4% and 97.2%, respectively, and the difference between the SE of the DiagTest and of the typical repolarization pattern is statistically significant. CONCLUSIONS: The ScreenTest and DiagTest are more effective tools than the characteristic repolarization pattern to discriminate between carriers and non-carriers of these two nonsense SCN5A mutations. We suggest their use in first-degree relatives of Brugada patients when the results of genetic testing are not available, in a score of disease probability in individuals with idiopathic Brugada ECG, and in patients with arrhythmias or other Brugada-related symptoms presenting type 2 or type 3 Brugada ECG.

Criteria to predict carriers of a novel SCN5A mutation in a large Portuguese family affected by the Brugada syndrome.

AIMS: Brugada syndrome (BrS) is a life-threatening arrhythmia disorder associated with autosomal-dominant mutations in the SCN5A gene. We aimed to characterize the diagnostic challenges and clinical manifestations of a novel SCN5A mutation associated with BrS. METHODS AND RESULTS: From a novel SCN5A mutation (c.664C>T; p.Arg222X) identified in a proband with the characteristic electrocardiographic pattern and the history of sudden collapse, 122 family members were studied including 40 carriers of the mutation. The electrocardiographic diagnosis of BrS requires type 1 Brugada electrocardiogram (ECG) pattern in >1 right precordial lead (V1-V3), but recently an isolated lead with coved-type ECG was proposed to be enough for the diagnosis. In this family, these proposed criteria (PC) were more sensitive in detecting mutation carriers than the conventional criteria without repercussion on the specificity. Carriers had, on average, longer P-wave duration, PR, and QRS intervals and higher transmural dispersion of repolarization. The prevalence of late potentials was higher in carriers, and individual signal average ECG (SAECG) parameters (QRSf, LAS, and RMS40) also were related to SCN5A gene mutation. Three non-carriers were found to be affected by BrS, two with a spontaneous type 1 ECG with alternative placement of the precordial electrodes, and one only after the pharmacological provocative test, suggesting that other genes may play a role in the pathophysiology of this disease. CONCLUSION: The PC for BrS diagnosis should be implemented. Some parameters from the spontaneous ECG and the SAECG are more effective tools than the characteristic repolarization pattern to discriminate between carriers of SCN5A mutations.