Nicotine's Effects on Schizophrenia-like Symptoms in a Mice Model: Time Matters.

Tobacco consumption in schizophrenia (SCHZ) patients is highly prevalent. Data support the occurrence of sequential events during comorbidity establishment, and both smoking first, SCHZ second and SCHZ first, smoking second sequences have been proposed. To investigate whether these two possibilities lead to distinct outcomes of comorbidity, we used a phencyclidine-induced SCHZ model and nicotine exposure as a surrogate of smoking. C57Bl/6 mice were submitted to a protocol that either began with 4 days of phencyclidine exposure or 4 days of nicotine exposure. This period was followed by 5 days of combined phencyclidine + nicotine exposure. Locomotor sensitization and pre-pulse inhibition (PPI) were assessed due to their well-known associations with SCHZ as opposed to rearing, an unrelated behavior. Nicotine priming potentiated phencyclidine-evoked sensitization. However, nicotine exposure after SCHZ modeling did not interfere with phencyclidine's effects. In the PPI test, nicotine after SCHZ modeling worsened the phencyclidine-evoked deficiency in males. In contrast, nicotine priming had no effects. Regarding rearing, nicotine priming failed to interfere with phencyclidine-mediated inhibition. Similarly, phencyclidine priming did not modify nicotine-mediated inhibition. The present results indicate that the sequence, either SCHZ-first or nicotine-first, differentially impacts comorbidity outcomes, a finding that is relevant for the identification of mechanisms of nicotine interference in the neurobiology of SCHZ.

Construction of a Guide for Assessment and Physiotherapeutic Management of Pain in Cancer Patients / Construction of a Guide for Assessment and Physiotherapeutic Management of Pain in Cancer Patients / Construção de um Guia para Avaliação e Manejo Fisioterapêutico da Dor em Pacientes com Câncer

Physiotherapy can contribute to control pain in cancer patients and educational strategies should be developed to increase physiotherapeutic actions in this context. Objective: To develop a guide for the assessment and physiotherapeutic management of cancer pain. Method: Study developed in three stages: 1. Descriptive analysis of sociodemographic, clinical, functional data, pain characteristics and physiotherapeutic treatments performed on cancer patients receiving palliative care; 2. Development of the preliminary version of the guide based on the results of the first stage and theoretical content; 3. Focus group formed by physiotherapists that resulted in the final version of the guide. Results: 62 patients were included, mainly females (69.3%). The most common tumor site was gynecological (25.8%) and half presented bone metastasis. Neuropathic pain (51.6%), located in the spine (29.0%) was the most prevalent type of pain. The physiotherapeutic treatments most used were: positioning (98.0%), kinesiotherapy (68.0%), walking (39.0%), orthoses (32.0%) and transcutaneous electrical nerve stimulation (21.0%). The focus group suggested changes and positively evaluated the preliminary version of the guide, highlighting that, in addition to an easy-to-understand language, it provided a comprehensive view of the methods for evaluating and physiotherapy treatment of pain.

A fisioterapia pode contribuir para o controle da dor em pacientes com câncer e estratégias educativas devem ser desenvolvidas para aumentar as ações fisioterapêuticas nesse contexto. Objetivo: Elaborar um guia para avaliação e manejo fisioterapêutico da dor no câncer. Método:Estudo desenvolvido em três etapas: 1. Análise descritiva de dados sociodemográficos, clínicos, funcionais, características da dor e tratamentos fisioterapêuticos realizados em pacientes com câncer em cuidados paliativos; 2. Desenvolvimento da versão preliminar do guia a partir dos resultados da primeira etapa e de conteúdo teórico na temática; 3. Realização de grupo focal composto por fisioterapeutas que originou a versão final do guia. Resultados: Foram incluídos 62 pacientes, principalmente do sexo feminino (69,3%). O sítio tumoral mais frequente foi o ginecológico (25,8%) e metade apresentou metástase óssea. O tipo de dor mais prevalente foi a neuropática (51,6%), localizada na coluna (29,0%). Os tratamentos fisioterapêuticos mais utilizados foram: posicionamento (98,0%), cinesioterapia (68,0%), deambulação (39,0%), uso de órteses (32,0%) e transcutaneous electrical nerve stimulation (21,0%). O grupo focal sugeriu alterações e avaliou positivamente a versão preliminar do guia, ressaltando que, além de ser elaborado com linguagem de fácil compreensão, possibilitou a visão integral sobre os métodos para avaliação e tratamento fisioterapêutico da dor.

La fisioterapia puede contribuir al control del dolor en pacientes con cáncer y se deben desarrollar estrategias educativas para incrementar las acciones fisioterapéuticas en este contexto. Objetivo:Desarrollar una guía para la evaluación y manejo fisioterapéutico del dolor oncológico. Método: Estudio desarrollado en tres etapas: 1. Análisis descriptivo de datos sociodemográficos, clínicos, funcionales, características del dolor y tratamientos fisioterapéuticos realizados a pacientes con cáncer que reciben cuidados paliativos; 2. Elaboración de la versión preliminar de la guía con base en los resultados de la primera etapa y contenidos teóricos sobre el tema; 3. Realización de un grupo focal compuesto por fisioterapeutas que dio como resultado la versión final de la guía. Resultados: Se incluyeron 62 pacientes, principalmente mujeres (69,3%). La localización tumoral más frecuente fue ginecológica (25,8%) y la mitad presentó metástasis óseas. El tipo de dolor más prevalente fue el neuropático (51,6%), localizado en la columna (29,0%). Los tratamientos fisioterapéuticos más utilizados fueron: posicionamiento (98,0%), kinesioterapia (68,0%), marcha (39,0%), uso de órtesis (32,0%) y estimulación nerviosa eléctrica transcutánea (21,0%). El grupo focal sugirió cambios y evaluó positivamente la versión preliminar de la guía, destacando que, además de estar elaborada en un lenguaje fácil de entender, proporcionó una visión integral de los métodos de evaluación y tratamiento fisioterapéutico del dolor.

Telemedicine-Based Management of Oral Anticoagulation Therapy: Systematic Review and Meta-analysis.

BACKGROUND: Oral anticoagulation is the cornerstone treatment of several diseases. Its management is often challenging, and different telemedicine strategies have been implemented to support it. OBJECTIVE: The aim of the study is to systematically review the evidence on the impact of telemedicine-based oral anticoagulation management compared to usual care on thromboembolic and bleeding events. METHODS: Randomized controlled trials were searched in 5 databases from inception to September 2021. Two independent reviewers performed study selection and data extraction. Total thromboembolic events, major bleeding, mortality, and time in therapeutic range were assessed. Results were pooled using random effect models. RESULTS: In total, 25 randomized controlled trials were included (n=25,746 patients) and classified as moderate to high risk of bias by the Cochrane tool. Telemedicine resulted in lower rates of thromboembolic events, though not statistically significant (n=13 studies, relative risk [RR] 0.75, 95% CI 0.53-1.07; I2=42%), comparable rates of major bleeding (n=11 studies, RR 0.94, 95% CI 0.82-1.07; I2=0%) and mortality (n=12 studies, RR 0.96, 95% CI 0.78-1.20; I2=11%), and an improved time in therapeutic range (n=16 studies, mean difference 3.38, 95% CI 1.12-5.65; I2=90%). In the subgroup of the multitasking intervention, telemedicine resulted in an important reduction of thromboembolic events (RR 0.20, 95% CI 0.08-0.48). CONCLUSIONS: Telemedicine-based oral anticoagulation management resulted in similar rates of major bleeding and mortality, a trend for fewer thromboembolic events, and better anticoagulation quality compared to standard care. Given the potential benefits of telemedicine-based care, such as greater access to remote populations or people with ambulatory restrictions, these findings may encourage further implementation of eHealth strategies for anticoagulation management, particularly as part of multifaceted interventions for integrated care of chronic diseases. Meanwhile, researchers should develop higher-quality evidence focusing on hard clinical outcomes, cost-effectiveness, and quality of life. TRIAL REGISTRATION: PROSPERO International Prospective Register of Systematic Reviews CRD42020159208; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=159208.

Sickle-Cell Disease and Stroke: Quality of Life of Patients in a Chronic Transfusion Regimen from the Caregivers' Perspective.

Strokes affect up to 10% of children with sickle-cell disease (SCD). The most commonly used strategy to prevent a first-time stroke or its recurrence is to perform periodic red blood cell transfusions. This article aims to evaluate the quality of life (QoL) of children and adolescents with SCD undergoing a chronic transfusion regimen (CTR) for stroke prophylaxis, according to their caregivers' perception. A cross-sectional study was conducted using a sociodemographic interview with an application of a validated instrument (Pediatric Quality of Life Inventory) involving 16 caregivers of patients with SCD aged <18 years undergoing CTR in a reference center. The data were processed using STATA version 13.0. The caregivers were predominantly the mothers of the minors that were part of the study cohort (87.5%), an income of <2 minimum wages (81.2% of cases) and >8 years of schooling (56.2%). The patients had a mean age of 10.4 years, 68.8% were male, 75% were mixed-race and came from small towns and rural areas (68.8%). The overall mean QoL was 45.8 (95% confidence interval [CI] 42.5-49.2). Female patients and those aged <12 years had lower levels of overall QoL. The emotional dimension of the children was the least compromised as per the caregivers' perception. The mean QoL of children with SCD on a CTR is lower than the estimated global mean QoL reported in the literature. It is possible that the occurrence of a stroke enhances the caregivers' negative perceptions about the QoL of patients with SCD.

Adolescent nicotine potentiates the inhibitory effect of raclopride, a D2R antagonist, on phencyclidine-sensitized psychotic-like behavior in mice.

The association between schizophrenia and nicotine addiction becomes evident during adolescence. Here, to investigate interactive events that might underlie the early establishment of this comorbidity, we used phencyclidine-evoked locomotor sensitization, a proxy model of psychotic behavior, and nicotine minipump infusions in adolescent mice. Considering the involvement of dopamine D2 receptors in both schizophrenia and addiction, we further tested their role by exposing mice to raclopride. Adolescent mice that were either exposed to nicotine (24 mg/Kg/day) or not, received single daily raclopride (0.5 mg/kg, s.c.) or saline followed by phencyclidine injections (10 mg/Kg, s.c.) during open field testing for 6 consecutive days (Acquisition phase, ACQ). Phencyclidine and nicotine challenges (Sensitization Test, ST) were carried out after a 5-day withdrawal. Ambulation escalated in response to repeated phencyclidine exposure during ACQ and was increased after phencyclidine challenge, evidencing development and expression of locomotor sensitization. Raclopride prevented phencyclidine-evoked development of sensitization. However, raclopride pre-exposure during ACQ only shortened its expression in phencyclidine-challenged mice. Nicotine failed to interfere with phencyclidine stimulatory effects during ACQ but potentiated raclopride inhibition during the first ACQ days. During ST, nicotine history shortened the expression of phencyclidine-evoked sensitization. Nicotine challenge had no impact on locomotion, which is consistent with a lack of nicotine/phencyclidine cross-sensitization. In conclusion, our results show that nicotine does not worsen, and may even ameliorate phencyclidine-sensitized psychotic-like behavior in adolescent mice. The potentiation of raclopride-mediated inhibition further suggests that nicotine transiently improves the therapeutic efficacy of medication on psychotic symptoms through mechanisms that converge on D2 receptors.

Development and validation of the MMCD score to predict kidney replacement therapy in COVID-19 patients.

BACKGROUND: Acute kidney injury (AKI) is frequently associated with COVID-19, and the need for kidney replacement therapy (KRT) is considered an indicator of disease severity. This study aimed to develop a prognostic score for predicting the need for KRT in hospitalised COVID-19 patients, and to assess the incidence of AKI and KRT requirement. METHODS: This study is part of a multicentre cohort, the Brazilian COVID-19 Registry. A total of 5212 adult COVID-19 patients were included between March/2020 and September/2020. Variable selection was performed using generalised additive models (GAM), and least absolute shrinkage and selection operator (LASSO) regression was used for score derivation. Accuracy was assessed using the area under the receiver operating characteristic curve (AUC-ROC). RESULTS: The median age of the model-derivation cohort was 59 (IQR 47-70) years, 54.5% were men, 34.3% required ICU admission, 20.9% evolved with AKI, 9.3% required KRT, and 15.1% died during hospitalisation. The temporal validation cohort had similar age, sex, ICU admission, AKI, required KRT distribution and in-hospital mortality. The geographic validation cohort had similar age and sex; however, this cohort had higher rates of ICU admission, AKI, need for KRT and in-hospital mortality. Four predictors of the need for KRT were identified using GAM: need for mechanical ventilation, male sex, higher creatinine at hospital presentation and diabetes. The MMCD score had excellent discrimination in derivation (AUROC 0.929, 95% CI 0.918-0.939) and validation (temporal AUROC 0.927, 95% CI 0.911-0.941; geographic AUROC 0.819, 95% CI 0.792-0.845) cohorts and good overall performance (Brier score: 0.057, 0.056 and 0.122, respectively). The score is implemented in a freely available online risk calculator ( https://www.mmcdscore.com/ ). CONCLUSIONS: The use of the MMCD score to predict the need for KRT may assist healthcare workers in identifying hospitalised COVID-19 patients who may require more intensive monitoring, and can be useful for resource allocation.

Predictors of venous thromboembolism in COVID-19 patients: results of the COVID-19 Brazilian Registry.

Previous studies that assessed risk factors for venous thromboembolism (VTE) in COVID-19 patients have shown inconsistent results. Our aim was to investigate VTE predictors by both logistic regression (LR) and machine learning (ML) approaches, due to their potential complementarity. This cohort study of a large Brazilian COVID-19 Registry included 4120 COVID-19 adult patients from 16 hospitals. Symptomatic VTE was confirmed by objective imaging. LR analysis, tree-based boosting, and bagging were used to investigate the association of variables upon hospital presentation with VTE. Among 4,120 patients (55.5% men, 39.3% critical patients), VTE was confirmed in 6.7%. In multivariate LR analysis, obesity (OR 1.50, 95% CI 1.11-2.02); being an ex-smoker (OR 1.44, 95% CI 1.03-2.01); surgery ≤ 90 days (OR 2.20, 95% CI 1.14-4.23); axillary temperature (OR 1.41, 95% CI 1.22-1.63); D-dimer ≥ 4 times above the upper limit of reference value (OR 2.16, 95% CI 1.26-3.67), lactate (OR 1.10, 95% CI 1.02-1.19), C-reactive protein levels (CRP, OR 1.09, 95% CI 1.01-1.18); and neutrophil count (OR 1.04, 95% CI 1.005-1.075) were independent predictors of VTE. Atrial fibrillation, peripheral oxygen saturation/inspired oxygen fraction (SF) ratio and prophylactic use of anticoagulants were protective. Temperature at admission, SF ratio, neutrophil count, D-dimer, CRP and lactate levels were also identified as predictors by ML methods. By using ML and LR analyses, we showed that D-dimer, axillary temperature, neutrophil count, CRP and lactate levels are risk factors for VTE in COVID-19 patients.

Hypothyroidism does not lead to worse prognosis in COVID-19: findings from the Brazilian COVID-19 registry.

BACKGROUND: It is not clear whether previous thyroid diseases influence the course and outcomes of COVID-19. METHODS: The study is a part of a multicentric cohort of patients with confirmed COVID-19 diagnosis from 37 hospitals. Matching for age, sex, number of comorbidities, and hospital was performed for the paired analysis. RESULTS: Of 7,762 patients with COVID-19, 526 had previously diagnosed hypothyroidism and 526 were matched controls. The median age was 70 years, and 68.3% were females. The prevalence of comorbidities was similar, except for coronary and chronic kidney diseases that were higher in the hypothyroidism group (p=0.015 and p=0.001). D-dimer levels were lower in patients with hypothyroid (p=0.037). In-hospital management was similar, but hospital length-of-stay (p=0.029) and mechanical ventilation requirement (p=0.006) were lower for patients with hypothyroidism. There was a trend of lower in-hospital mortality in patients with hypothyroidism (22.1% vs 27.0%; p=0.062). CONCLUSION: Patients with hypothyroidism had a lower requirement of mechanical ventilation and showed a trend of lower in-hospital mortality. Therefore, hypothyroidism does not seem to be associated with a worse prognosis.

Pregnancy planning does not interfere with child development in children aged from 11 to 23 months old.

OBJECTIVE: to analyze the correlation between child development and pregnancy planning and other associated aspects. METHOD: a cross-sectional study conducted with 125 mother-child dyads, the children aged from 11 to 23 months old and attending daycare centers located in socially disadvantaged areas. Child development according to domains was assessed using the Ages & Stages Questionnaire-BR and pregnancy planning was evaluated through the London Measure of Unplanned Pregnancy. The mothers were interviewed at their homes and non-parametric tests were used for data analysis. RESULTS: 17.6% of the pregnancies were unplanned, 24.8% were planned and 57.6% were ambivalent. Inadequate development in the different domains ranged from 21% to 40% and was not associated with pregnancy planning. However, the "communication" domain was associated with Bolsa Família and the "personal/social" and "communication" domains, with gender; while "personal/social", "broad motor coordination" and "fine motor coordination" were domains related to the child's age. CONCLUSION: no correlation between pregnancy planning and child development was observed; however, the low frequency of planned pregnancies and the high percentages of inadequate child development show the need to invest in the training of health professionals, both for contraceptive care and preconception health and for the promotion of child development, especially in socioeconomically disadvantaged contexts.

Does nicotine exposure during adolescence modify the course of schizophrenia-like symptoms? Behavioral analysis in a phencyclidine-induced mice model.

The first symptoms of schizophrenia (SCHZ) are usually observed during adolescence, a developmental period during which first exposure to psychoactive drugs also occurs. These epidemiological findings point to adolescence as critical for nicotine addiction and SCHZ comorbidity, however it is not clear whether exposure to nicotine during this period has a detrimental impact on the development of SCHZ symptoms since there is a lack of studies that investigate the interactions between these conditions during this period of development. To elucidate the impact of a short course of nicotine exposure across the spectrum of SCHZ-like symptoms, we used a phencyclidine-induced adolescent mice model of SCHZ (2.5mg/Kg, s.c., daily, postnatal day (PN) 38-PN52; 10mg/Kg on PN53), combined with an established model of nicotine minipump infusions (24mg/Kg/day, PN37-44). Behavioral assessment began 4 days after the end of nicotine exposure (PN48) using the following tests: open field to assess the hyperlocomotion phenotype; novel object recognition, a declarative memory task; three-chamber sociability, to verify social interaction and prepulse inhibition, a measure of sensorimotor gating. Phencyclidine exposure evoked deficits in all analyzed behaviors. Nicotine history reduced the magnitude of phencyclidine-evoked hyperlocomotion and impeded the development of locomotor sensitization. It also mitigated the deficient sociability elicited by phencyclidine. In contrast, memory and sensorimotor gating deficits evoked by phencyclidine were neither improved nor worsened by nicotine history. In conclusion, our results show for the first time that nicotine history, restricted to a short period during adolescence, does not worsen SCHZ-like symptoms evoked by a phencyclidine-induced mice model.

Pregnancy planning does not interfere with child development in children aged from 11 to 23 months old / La planificación del embarazo no interfiere con el desarrollo infantil de los niños de 11 a 23 meses / Planejamento da gravidez não interfere no desenvolvimento infantil de crianças de 11 a 23 meses

Objective: to analyze the correlation between child development and pregnancy planning and other associated aspects. Method: a cross-sectional study conducted with 125 mother-child dyads, the children aged from 11 to 23 months old and attending daycare centers located in socially disadvantaged areas. Child development according to domains was assessed using the Ages & Stages Questionnaire-BR and pregnancy planning was evaluated through the London Measure of Unplanned Pregnancy. The mothers were interviewed at their homes and non-parametric tests were used for data analysis. Results: 17.6% of the pregnancies were unplanned, 24.8% were planned and 57.6% were ambivalent. Inadequate development in the different domains ranged from 21% to 40% and was not associated with pregnancy planning. However, the "communication" domain was associated with Bolsa Família and the "personal/social" and "communication" domains, with gender; while "personal/social", "broad motor coordination" and "fine motor coordination" were domains related to the child's age. Conclusion: no correlation between pregnancy planning and child development was observed; however, the low frequency of planned pregnancies and the high percentages of inadequate child development show the need to invest in the training of health professionals, both for contraceptive care and preconception health and for the promotion of child development, especially in socioeconomically disadvantaged contexts.

Objetivo: analizar la relación entre el desarrollo infantil y la planificación del embarazo y otros aspectos asociados. Método: estudio transversal realizado con 125 díadas madre e hijo de 11 a 23 meses, que concurren a guarderías infantiles ubicadas en zonas socialmente desfavorables. El desarrollo infantil de acuerdo con los dominios se evaluó mediante el Ages & Stages Questionnaire-BR y la planificación del embarazo mediante la London Measure of Unplanned Pregnancy. Las madres fueron entrevistadas en sus domicilios y se utilizaron pruebas no paramétricas para el análisis de los datos. Resultados: se registró que 17,6% de los embarazos no fue planificados, 24,8% fue planificado y 57,6% ambivalente. El desarrollo inadecuado en los diferentes dominios osciló entre el 21% y el 40% y no estaba asociado con la planificación del embarazo. Sin embargo, el dominio "comunicación" se asoció con Bolsa Familia; los dominios "personal/social" y "comunicación" con el sexo; mientras que los dominios "personal/social", "coordinación motora gruesa" y "coordinación motora fina" estaban relacionados con la edad del niño. Conclusión: no se observó relación entre la planificación del embarazo y el desarrollo infantil, sin embargo, la baja frecuencia de embarazos planificados y los altos porcentajes de desarrollo infantil inadecuado demuestran que es necesario invertir en la capacitación de los profesionales de la salud, tanto para la atención sobre anticoncepción y salud preconcepcional, como para la promoción del desarrollo infantil, especialmente en contextos socioeconómicos desfavorables.

Objetivo: analisar a relação entre desenvolvimento infantil e planejamento da gravidez e outros aspectos associados. Método: estudo transversal conduzido com 125 díades mãe-criança de 11 a 23 meses de idade, frequentadoras de creches localizadas em áreas socialmente desfavoráveis. O desenvolvimento infantil segundo domínios foi avaliado com aplicação do Ages & Stages Questionnaire-BR e o planejamento da gravidez por meio do London Measure of Unplanned Pregnancy. Mães foram entrevistadas nos domicílios e utilizou-se testes não paramétricos para análise dos dados. Resultados: verificou-se 17,6% de gravidez não planejada, 24,8% foram planejadas e 57,6% ambivalentes. O desenvolvimento inadequado nos diferentes domínios variou de 21-40% e não teve associação com o planejamento da gravidez. No entanto, o domínio "comunicação" associou-se com Bolsa Família; os domínios "pessoal/social" e "comunicação" com sexo; ao passo que "pessoal/social", "coordenação motora ampla" e "coordenação motora fina" foram domínios relacionados com a idade da criança. Conclusão: não foi observada relação entre o planejamento da gravidez e o desenvolvimento infantil, porém, a baixa frequência de gestações planejadas e os elevados percentuais de inadequado desenvolvimento infantil mostram a necessidade de se investir na capacitação dos profissionais de saúde, tanto para a atenção em contracepção e saúde pré-concepcional, quanto para a promoção do desenvolvimento infantil, especialmente em contextos socioeconômicos desfavoráveis.

Actividad antimutagénica e identificación de compuestos antioxidantes en la planta Poincianella bracteosa (Fabaceae)

Introducción: Poincianella bracteosa (Tul.) L.P. Queiroz. (Fabaceae), conocida como catingueira, es tradicionalmente utilizada en la medicina para tratar diarrea, hepatitis y anemia. Sin embargo, no hay estudios sobre los efectos tóxico genéticos de la P. bracteosa. Objetivo: En el presente estudio se tuvo como objetivo investigar el perfil fitoquímico y el potencial mutagénico y antimutagénico del extracto acuoso de la cáscara de P. bracteosa en Allium cepa y Mus musculus. Métodos: El extracto de la cáscara fue diluido en agua destilada para fornecer las cuatro concentraciones (2, 4, 8 y 16 mg/ml) utilizadas en el bioensayo A. cepa y las tres dosis (10, 20 y 40 mg / Kg) fueron administradas a los ratones (5 animales por grupo). El perfil fito-químico fue realizado por el test colorimétrico para identificar los principales metabólitos secundarios en el extracto de la cáscara. Tras el tratamiento, 5 000 células meristemáticas fueron analizadas para determinar el índice mitótico, el promedio de alteraciones cromosómicas y el porcentaje de reducción de daños. Para ratones, tras 24, 48 y 72 h, la sangre de la cola de cada animal fue recolectado para la preparación de dos láminas por animal. Para cada animal, 2 000 eritrocitos normocromáticos por ratón fueron evaluados para establecer el número de micronúcleos y el efecto protector. Se analizaron los dados por el test de Kruskal-Wallis (P < 0.05). El estudio fito-químico del extracto detectó azúcares reductores y taninos. Resultados: Ninguna de las concentraciones del extracto fue citotóxica y en todos los tratamientos (pre, simultáneo y después) fue observado el efecto citoprotetor en A. cepa. El promedio total de las alteraciones cromosómicas en todas las concentraciones apuntó actividad no mutagénica de la cáscara. El porcentaje de reducción del daño fue observada en los tratamientos pre (de 77.6 al 90.5 %), simultáneo (del 95.6 al 114.7 %) y tras (de 84.8 al 117.7 %). En los ratones, ninguna de las dosis del extracto presentó efecto mutagénico y el porcentaje de reducción del daño osciló de -21.2 al 78.6 % (pre); de 27.5 al 101.3 % (simultánea) y de 85.5 al 120.6 % (tras-tratamiento). Probablemente, los fito-químicos presentes en el extracto no interfirieron en el ciclo celular (A. cepa), tampoco causaron daños al DNA (A. cepa y ratones) y presentaron efecto protector en las dos especies estudiadas. Los datos observados apuntan la importancia del extracto de la cáscara de P. bracteosa para inhibición del daño y quimio prevención. Sin embargo, más estudios deben ser realizados para garantizar su efecto protector sobre el material genético.

Introduction: Poincianella bracteosa (Tul.) L.P. Queiroz. (Fabaceae), known as catingueira, is traditionally used in medicine to treat diarrhea, hepatitis and anemia. However, there are no studies on their toxicogenetic effects. Objective: The present study aimed to investigate the phytochemical profile as well as the mutagenic and antimutagenic potential of P. bracteosa aqueous bark extract in Allium cepa and Mus musculus. Methods: The extract from barks was diluted in distilled water to yield the four concentrations (2, 4, 8 and 16 mg/ml) used in the A. cepa bioassay and the three doses (10, 20 and 40 mg/Kg) administered to the mice (five animals per group). The phytochemical profile was performed by the colorimetric test to identify the main secondary metabolites in the bark extract. After treatment, five-thousand meristematic cells were analyzed to determine the mitotic index, the mean number of chromosome alterations and the percentage of damage reduction. For mice, after 24, 48 and 72 h, tail blood was collected from each animal for the preparation of two slides per animal. For each animal, 2 000 normochromatic erythrocytes per mice were evaluated to establish the number of micronuclei and the protective effect. Data were analyzed by Kruskal-Wallis test (P < 0.05). Results: The phytochemical analysis of the extract detected reducing sugars and tannins. None of the concentrations of extract was cytotoxic and the cytoprotective effect was observed in A. cepa for all treatments (pre-, simultaneous and post-). The total mean of chromosome alterations in all concentrations indicated a non-mutagenic activity of the bark. The percentage of damage reduction was observed in the pre- (77.6 to 90.5 %), simultaneous (95.6 to 114.7 %) and post- (84.8 to 117.7 %) treatments. In mice, none of the dosages of extract presented mutagenic effect and the percentage of damage reduction varied from -21.16 to 78.63 % (pre-); from 27.51 to 101.28 % (simultaneous) and from 85.47 to 120.63 % (post-treatment). Conclusions: Probably, the phytochemicals in the extract did not interfere with the cell cycle (A. cepa) nor caused damage to the DNA (A. cepa and mice), and exhibited protective effect in both studied species. The observed data indicate the importance of P. bracteosa bark extract for the inhibition of damage and chemoprevention. However, more studies should be carried out to ensure its protective effect on the genetic material.

CODAP: A multidisciplinary consensus among Portuguese experts on the definition, detection and management of atherogenic dyslipidemia. / CODAP: um consenso multidisciplinar sobre a definição, diagnóstico e tratamento da dislipidemia aterogénica em Portugal.

INTRODUCTION AND AIMS: Atherogenic dyslipidemia is an important contributor to residual cardiovascular (CV) risk, but it is underdiagnosed and undertreated. This study aimed to assess the opinion of Portuguese experts to generate a consensus concerning the diagnosis and treatment of atherogenic dyslipidemia, as well as to contribute toward standardization of clinical practice in this disorder. METHODS: The study consisted in the application of a questionnaire to an expert panel, following a modified Delphi methodology. RESULTS: The majority (88.4%) of the proposed items were found to be consensual. The expert panel recognized the importance of the atherogenic dyslipidemia phenotype, the role played by low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol as risk markers and therapeutic targets, the choice of statins as first-line lipid-lowering drugs, and the value of associating statins with fenofibrate as a means to reduce residual CV risk. However, the role played by triglycerides in CV risk and the therapeutic value of fibrates lacked consensus. Taking into consideration the state of the art and the opinions expressed in this study, the scientific committee developed a treatment algorithm aimed to improve the perception and treatment of atherogenic dyslipidemia. CONCLUSIONS: The experts involved in this study were shown to be familiar with the concept and the importance of atherogenic dyslipidemia. The few situations in which a consensus could not be found were mainly related to the interpretation and/or relevance of the available evidence.

Diagnostic and laboratory test ordering in Northern Portuguese Primary Health Care: a cross-sectional study.

OBJECTIVES: To characterise the test ordering pattern in Northern Portugal and to investigate the influence of context-related factors, analysing the test ordered at the level of geographical groups of family physicians and at the level of different healthcare organisations. DESIGN: Cross-sectional study. SETTING: Northern Primary Health Care, Portugal. PARTICIPANTS: Records about diagnostic and laboratory tests ordered from 2035 family physicians working at the Northern Regional Health Administration, who served approximately 3.5 million Portuguese patients, in 2014. OUTCOMES: To determine the 20 most ordered diagnostic and laboratory tests in the Northern Regional Health Administration; to identify the presence and extent of variations in the 20 most ordered diagnostic and laboratory tests between the Groups of Primary Care Centres and between health units; and to study factors that may explain these variations. RESULTS: The 20 most ordered diagnostic and laboratory tests almost entirely comprise laboratory tests and account for 70.9% of the total tests requested. We can trace a major pattern of test ordering for haemogram, glucose, lipid profile, creatinine and urinalysis. There was a significant difference (P<0.001) in test orders for all tests between Groups of Primary Care Centres and for all tests, except glycated haemoglobin (P=0.06), between health units. Generally, the Personalised Healthcare Units ordered more than Family Health Units. CONCLUSIONS: The results from this study show that the most commonly ordered tests in Portugal are laboratory tests, that there is a tendency for overtesting and that there is a large variability in diagnostic and laboratory test ordering in different geographical and organisational Portuguese primary care practices, suggesting that there may be considerable potential for the rationalisation of test ordering. The existence of Family Health Units seems to be a strong determinant in decreasing test ordering by Portuguese family physicians. Approaches to ensuring more rational testing are needed.

Patients' estimations of the importance of preventive health services: a nationwide, population-based cross-sectional study in Portugal.

OBJECTIVES: To determine, in the context of primary care preventive health services, the level of importance that Portuguese patients attribute to different preventive activities. DESIGN: Cross-sectional study. SETTING: Primary Healthcare, Portugal. PARTICIPANTS: 1000 Portuguese adults selected by a stratified cluster sampling design were invited to participate in a computer-assisted telephone survey. Persons with a cognitive or physical disability that hampered the ability to complete a telephone interview and being a nursing home resident or resident in any other type of collective dwelling were excluded. OUTCOMES: Mean level of importance assigned to 20 different medical preventive activities, using a scale of 1-10, with 1 corresponding to 'no importance for you and your health' and 10 indicating 'very important'. RESULTS: The mean level of importance assigned to medical preventive activity was 7.70 (95% CI 7.60 to 7.80). Routine blood and urine tests were considered the most important, with an estimated mean of 9.15 (95% CI 9.07 to 9.24), followed by female-specific interventions (Pap smear, mammography and gynaecological and breast ultrasounds), with mean importance ranging from 8.45 (95% CI 8.23 to 8.63) for mammography to 8.56 (95% CI 8.36 to 8.76) for Pap smear. Advice regarding alcohol consumption (6.18; 95% CI 5.96 to 6.39) and tobacco consumption (5.99; 95% CI 5.75 to 6.23) were considered much less important. CONCLUSIONS: Our results reveal that Portuguese patients overestimate the importance of preventive medical activities, tend to give more importance to diagnostic and laboratory tests than to lifestyle measures, do not discriminate tests that are important and evidence-based, and seem not be aware of the individualisation of risk. Family physicians should be aware of these optimistic expectations, because these can influence the doctor-patient relationship when discussing these interventions and incorporating personalised risk.

Portuguese Family Physicians' Awareness of Diagnostic and Laboratory Test Costs: A Cross-Sectional Study.

BACKGROUND: Physicians' ability to make cost-effective decisions has been shown to be affected by their knowledge of health care costs. This study assessed whether Portuguese family physicians are aware of the costs of the most frequently prescribed diagnostic and laboratory tests. METHODS: A cross-sectional study was conducted in a representative sample of Portuguese family physicians, using computer-assisted telephone interviews for data collection. A Likert scale was used to assess physician's level of agreement with four statements about health care costs. Family physicians were also asked to estimate the costs of diagnostic and laboratory tests. Each physician's cost estimate was compared with the true cost and the absolute error was calculated. RESULTS: One-quarter (24%; 95% confidence interval: 23%-25%) of all cost estimates were accurate to within 25% of the true cost, with 55% (95% IC: 53-56) overestimating and 21% (95% IC: 20-22) underestimating the true actual cost. The majority (76%) of family physicians thought they did not have or were uncertain as to whether they had adequate knowledge of diagnostic and laboratory test costs, and only 7% reported receiving adequate education. The majority of the family physicians (82%) said that they had adequate access to information about the diagnostic and laboratory test costs. Thirty-three percent thought that costs did not influence their decision to order tests, while 27% were uncertain. CONCLUSIONS: Portuguese family physicians have limited awareness of diagnostic and laboratory test costs, and our results demonstrate a need for improved education in this area. Further research should focus on identifying whether interventions in cost knowledge actually change ordering behavior, in identifying optimal methods to disseminate cost information, and on improving the cost-effectiveness of care.

Motives for requesting an electrocardiogram in primary health care.

The management of requests for diagnostic exams presents its own inherent characteristics in primary health care and reflects the specific nature of the physician-patient relationship. The scope of the study was to identify the reasons for requesting an electrocardiogram (ECG) in primary health care. A cross-sectional study was conducted in an urban region in Portugal, establishing the motives to ask for an ECG consecutively over two years, starting on 01/03/2007 using data retrieved from structured forms filled out by the physician at the moment of requesting the exam. A total of 870 ECGs of 817 patients were included. Symptoms manifested during the patient visit justified 48.5% of the ECGs, and follow-up of cardiovascular risk factors motivated 25.2%. A global health examination accounted for 22.8% of the requests. Multivariate analysis showed that the presence of symptoms (p < 0.001), presence of any cardiovascular risk factor (p = 0.002), hypertension (p < 0.001), diabetes (p = 0.002), and urgency (p < 0.001) were the main factors associated with the requests. The requests for electrocardiograms are predominantly for clinical reasons as a result of patients symptoms. The integration of expectations and beliefs of the patients is present in the decision-making process.

Motives for requesting an electrocardiogram in primary health care / Motivos para requisitar um eletrocardiograma nos Cuidados de Saúde Primários

The management of requests for diagnostic exams presents its own inherent characteristics in primary health care and reflects the specific nature of the physician-patient relationship. The scope of the study was to identify the reasons for requesting an electrocardiogram (ECG) in primary health care. A cross-sectional study was conducted in an urban region in Portugal, establishing the motives to ask for an ECG consecutively over two years, starting on 01/03/2007 using data retrieved from structured forms filled out by the physician at the moment of requesting the exam. A total of 870 ECGs of 817 patients were included. Symptoms manifested during the patient visit justified 48.5% of the ECGs, and follow-up of cardiovascular risk factors motivated 25.2%. A global health examination accounted for 22.8% of the requests. Multivariate analysis showed that the presence of symptoms (p < 0.001), presence of any cardiovascular risk factor (p = 0.002), hypertension (p < 0.001), diabetes (p = 0.002), and urgency (p < 0.001) were the main factors associated with the requests. The requests for electrocardiograms are predominantly for clinical reasons as a result of patients symptoms. The integration of expectations and beliefs of the patients is present in the decision-making process.

Introdução: A gestão do pedido de testes de diagnóstico apresenta características próprias nos Cuidados de Saúde Primários em função da natureza específica da relação médico-doente. Objetivo: Identificar os motivos para requisitar um eletrocardiograma (ECG) na prática de Cuidados de Saúde Primários. Métodos: Realizou-se um estudo observacional transversal dos motivos para o pedido de um ECG numa região urbana de Portugal, utilizando um formulário preenchido pelo médico no momento da requisição, por um período de 2 anos desde 1/03/2007. Resultados: Foram incluídos 870 ECG de 817 doentes. A presença de sintomas na consulta justificou 48.5%, e o seguimento de fatores de risco cardiovasculares representou 25.2%. O exame global de saúde representou 22.8% dos pedidos. A análise multivariada mostrou que a existência de sintomas (p < 0.001), a presença de qualquer fator de risco cardiovascular (p = 0.002), a hipertensão arterial (p < 0.001), a diabetes mellitus (p = 0.002), e o pedido de urgência na execução (p < 0.001) foram os principais fatores associados aos pedidos. Conclusão: Os ECG são requisitados sobretudo em resposta a questões de natureza clínica perante sintomas que os doentes apresentam. A integração das expectativas e crenças dos doentes está presente no processo de decisão médica. .

Facilitators, barriers and expectations in the self-management of type 2 diabetes--a qualitative study from Portugal.

BACKGROUND: Patients with type 2 diabetes mellitus (DM) have a central role in managing their disease, but the effective adoption of self-management behaviours is often challenging. OBJECTIVES: The main objective of this study was to assess the facilitators, barriers and expectations in the self-management of type 2 DM, as perceived by patients. METHODS: Patients with type 2 DM were recruited at the Portuguese Diabetes Association outpatient clinic, using a convenient sampling technique. Qualitative data was obtained using video-recorded focus groups. Each session had a moderator and an observer, and followed a pre-tested questioning route. Two independent researchers transcribed and analysed the focus groups. RESULTS: Three major themes were identified: diet, physical exercise, and glycaemic control. Difficulties in changing dietary habits were grouped in four main categories: decisional, food quality, food quantity, and dietary schedule. Barriers related to physical exercise also included decisional aspects, as well as fatigue, muscle and joint pain, and other co-morbidities. Information and knowledge translation, as well as family and social ties, were commonly explored aspects across the three themes and were regarded as facilitators in some situations and as barriers in others. CONCLUSION: This study provided new insight on the barriers, facilitators and expectations in type 2 DM self-management, pointing out the importance of tailored guidance. Future research should explore interventions designed to promote and facilitate behaviour change in this population.