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The 1,8-Diazaanthracene-2,9,10-triones, their 5,8-dihydro derivatives, and 1,8-diazaanthracene-2,7,9,10-tetraones, structurally related to the diazaquinomycin family of natural products, were synthesized in a regioselective fashion employing Diels-Alder strategies. These libraries were studied for their cytotoxicity in a variety of human cancer cell lines in order to establish structure-activity relationships. From the results obtained, we conclude that some representatives of the 1,8-diazaanthracene-2,9,10-trione framework show potent and selective cytotoxicity against solid tumors. Similar findings were made for the related 1-azaanthracene-2,9,10-trione derivatives, structurally similar to the marcanine natural products, which showed improved activity over their natural counterparts. An enantioselective protocol based on the use of a SAMP-related chiral auxiliary derived was developed for the case of chiral 5-substituted 1,8-diazaanthracene-2,9,10-triones, and showed that their cytotoxicity was not enantiospecific.
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Antracenos , Produtos Biológicos , Humanos , Linhagem Celular , Relação Estrutura-AtividadeRESUMO
INTRODUCTION: The drug allergy alert system reduces the frequency of adverse drug events, although it is subjected to collateral effects, since 80-90% of alerts are not real, and a large percentage of alerts are overridden (46.2-96.2%). We reviewed how the alert system is used at University Hospital Fundación Alcorcon (HUFA). METHODS: Data were obtained from the drug allergy alert and the alert overriding notification forms (both in the period 2011-20). We also recorded drug allergy diagnoses at HUFA, drug consumption in primary care in 2016. We calculated the incidence of drug allergy alert activation, temporal trends in use, and correlations between the number of drugs in several datasets. RESULTS: We collected 15,535 alerts. NSAIDs and penicillins were the drugs with the highest number of drug allergy alerts (36.55% and 26.91%, respectively). A correlation was found between the number of drug alerts and the type of drug allergy in HUFA in 2016. Only 6.83% of the alerts were removed, and, of these, 21.77% were reactivated. Approximately 100 overrides were recorded per year from 2016 (6.8% of 8,434 activated alerts during 2014-2020). CONCLUSIONS: The number of drug allergy alerts recorded via the drug allergy alert system of HUFA correlates with the distribution of drug allergy diagnoses in the hospital, although many of the alerts could be false positives (as per current published evidence). We detected a very low frequency of removed alerts (6.83%), a relevant frequency of reactivations (one quarter), and a very low frequency of overrides (6.8%).
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Hipersensibilidade a Drogas , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Sistemas de Registro de Ordens Médicas , Humanos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/epidemiologia , HospitaisRESUMO
BACKGROUND: Penicillin allergy is a common problem in the management of infectious diseases. The aim of this study was to determine the impact of penicillin allergy on length of hospital stay (LOHS) among hospitalized adult patients and on in-hospital mortality at a national level. METHODS: A retrospective cohort study of adult patients discharged from the Spanish Hospital System between 2006 and 2015 was conducted using the Minimum Basic Data Set (MBDS). We compared LOHS and in-hospital mortality of adult patients whose records contained penicillin allergy code V14.0 (International Classification of Diseases, Ninth Revision, Clinical Modification) as a secondary diagnosis, with a random sample without such a code. RESULTS: We identified 981,291 admissions with code V14.0, which corresponded to 2.63% of all hospitalizations. Adults patients with a penicillin allergy label were significantly older than patients without such a label, with a median of 70 years (interquartile range [IQR]: 51-80) versus 63 years (IQR: 40-77). The proportion of women and the prevalence of infectious diseases were higher in the group with a penicillin allergy label (61.40% vs. 53.84%; 34.04% vs. 30.01%; respectively). We found a higher median Elixhauser-Van Walraven score in hospitalized patients with an allergy label. The median LOHS for hospitalizations with a penicillin allergy label (5 [IQR: 2-9]) was significantly longer than that in those without such a label (4 [IQR: 2-9]). Multivariate analysis showed an increase in LOHS due to the penicillin allergy label (odds ratio [OR] [95% confidence interval [CI]: 1.061 [1.057-1.065]) and a decrease in mortality in penicillin allergy records (OR [95% CI]: 0.834 [0.825-0.844]). CONCLUSION: In our study, the prevalence of a penicillin allergy label in hospitalized patients, using the MBDS, is low. Hospitalizations with an allergy label was associated with a longer LOHS. However, penicillin-allergic patients did not show higher mortality rates. Inaccurate reporting of penicillin allergies may have an impact on healthcare resources.
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Hipersensibilidade a Drogas , Penicilinas , Adulto , Antibacterianos/uso terapêutico , Atenção à Saúde , Hipersensibilidade a Drogas/tratamento farmacológico , Feminino , Humanos , Tempo de Internação , Penicilinas/efeitos adversos , Estudos RetrospectivosRESUMO
PURPOSE: The study's main objective was to evaluate, in the short-term, the result of the autologous acellular matrix-induced chondrogenesis (AMIC) technique in a selected group of patients with 2-4 cm2 full-thickness chondral lesions, undergoing hip arthroscopy for femoroacetabular impingement (FAI). METHODS: A retrospective single-center Level IV case series of 25 patients (28 hips) who underwent an arthroscopic hip surgery with a liquid acellular collagen matrix. Inclusion criteria for implantation were FAI diagnosis (cam or pincer type), grade IV chondral lesions (Outerbridge size 2-4 cm2); Tönnis stage 0-II, minimum follow-up of 24 months, and 1 year (12-15 months) evaluation with very high field 3-T MRI arthrography. Exclusion criteria were Tönnis III, joint space <2 mm, center-edge angle <20°, and <24 months of follow-up. Clinical assessments involved symptoms duration until surgery, changes in physical and work activity and range of motion, modified Harris Hip Score, reporting percentages of patient acceptable symptomatic state (PASS) and minimal clinically important difference (MCID), pain with a VAS, and level of satisfaction. Radiological assessments: Tönnis stage, articular space, alpha and lateral center edge angle (Wiberg), and generated tissue characteristics at 1 year (based on the MOCART score), through 3-T MRI. RESULTS: 25 patients (28 hips) treated; 19 men and 6 women (mean age: 40.5 years; range: 25-55). Two women underwent joint replacement surgery. Thus, 23 patients (26 hips) were analyzed. At 29 months following surgery (range: 24-48), a significant improvement was obtained in all parameters assessed, focusing on the characteristics of the generated tissue in the MRI (MOCART scores). 95% of the patients met the MCID (improvement >12 points in the modified Harris Hip Score), and 100% scored >74 points, achieving the PASS. Patients' satisfaction was 86.6% (SD 16.4). All patients who practiced sports resumed them. CONCLUSIONS: The liquid AMIC is a safe technique that shows good clinical and radiological outcomes in a 2-year follow-up in patients with femoroacetabular impingement and grade IV acetabular 2-4 cm2 chondral defects. LEVEL OF EVIDENCE: Level IV, retrospective case series.
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Impacto Femoroacetabular , Adulto , Artroscopia , Condrogênese , Feminino , Impacto Femoroacetabular/complicações , Impacto Femoroacetabular/diagnóstico por imagem , Impacto Femoroacetabular/cirurgia , Articulação do Quadril/cirurgia , Humanos , Masculino , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Anaphylaxis is a life-threatening allergic reaction that occurs suddenly after contact with an allergen. Epidemiological studies about anaphylaxis are very important in planning and evaluating new strategies that prevent this reaction, but also in providing a guide to the treatment of patients who have just suffered an anaphylactic reaction. Electronic Medical Records (EMR) are one of the most effective and richest sources for the epidemiology of anaphylaxis, because they provide a low-cost way of accessing rich longitudinal data on large populations. However, a negative aspect is that researchers have to manually review a huge amount of information, which is a very costly and highly time consuming task. Therefore, our goal is to explore different machine learning techniques to process Big Data EMR, lessening the needed efforts for performing epidemiological studies about anaphylaxis. In particular, we aim to study the incidence of anaphylaxis by the automatic classification of EMR. To do this, we employ the most widely used and efficient classifiers in text classification and compare different document representations, which range from well-known methods such as Bag Of Words (BoW) to more recent ones based on word embedding models, such as a simple average of word embeddings or a bag of centroids of word embeddings. Because the identification of anaphylaxis cases in EMR is a class-imbalanced problem (less than 1% describe anaphylaxis cases), we employ a novel undersampling technique based on clustering to balance our dataset. In addition to classical machine learning algorithms, we also use a Convolutional Neural Network (CNN) to classify our dataset. In general, experiments show that the most classifiers and representations are effective (F1 above 90%). Logistic Regression, Linear SVM, Multilayer Perceptron and Random Forest achieve an F1 around 95%, however linear methods have considerably lower training times. CNN provides slightly better performance (F1â¯=â¯95.6%).
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Anafilaxia/diagnóstico , Anafilaxia/epidemiologia , Registros Eletrônicos de Saúde , Aprendizado de Máquina , Informática Médica/métodos , Redes Neurais de Computação , Algoritmos , Big Data , Análise por Conglomerados , Tomada de Decisões , Humanos , Idioma , Modelos Lineares , Análise de RegressãoRESUMO
BACKGROUND: Charcot-Marie-Tooth neuropathy has been reported to be associated with renal diseases, mostly focal segmental glomerulosclerosis (FSGS). However, the common mechanisms underlying the neuropathy and FSGS remain unknown. Mutations in INF2 were recently identified in patients with autosomal dominant FSGS. INF2 encodes a formin protein that interacts with the Rho-GTPase CDC42 and myelin and lymphocyte protein (MAL) that are implicated in essential steps of myelination and myelin maintenance. We therefore hypothesized that INF2 may be responsible for cases of Charcot-Marie-Tooth neuropathy associated with FSGS. METHODS: We performed direct genotyping of INF2 in 16 index patients with Charcot-Marie-Tooth neuropathy and FSGS who did not have a mutation in PMP22 or MPZ, encoding peripheral myelin protein 22 and myelin protein zero, respectively. Histologic and functional studies were also conducted. RESULTS: We identified nine new heterozygous mutations in 12 of the 16 index patients (75%), all located in exons 2 and 3, encoding the diaphanous-inhibitory domain of INF2. Patients presented with an intermediate form of Charcot-Marie-Tooth neuropathy as well as a glomerulopathy with FSGS on kidney biopsy. Immunohistochemical analysis revealed strong INF2 expression in Schwann-cell cytoplasm and podocytes. Moreover, we demonstrated that INF2 colocalizes and interacts with MAL in Schwann cells. The INF2 mutants perturbed the INF2-MAL-CDC42 pathway, resulting in cytoskeleton disorganization, enhanced INF2 binding to CDC42 and mislocalization of INF2, MAL, and CDC42. CONCLUSIONS: INF2 mutations appear to cause many cases of FSGS-associated Charcot-Marie-Tooth neuropathy, showing that INF2 is involved in a disease affecting both the kidney glomerulus and the peripheral nervous system. These findings provide new insights into the pathophysiological mechanisms linking formin proteins to podocyte and Schwann-cell function. (Funded by the Agence Nationale de la Recherche and others.).
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Doença de Charcot-Marie-Tooth/genética , Glomerulosclerose Segmentar e Focal/etiologia , Rim/metabolismo , Proteínas dos Microfilamentos/genética , Células de Schwann/metabolismo , Actinas/metabolismo , Adolescente , Adulto , Idade de Início , Animais , Doença de Charcot-Marie-Tooth/complicações , Criança , Feminino , Forminas , Heterozigoto , Humanos , Masculino , Proteínas de Membrana Transportadoras/metabolismo , Camundongos , Proteínas dos Microfilamentos/metabolismo , Pessoa de Meia-Idade , Mutação , Proteínas da Mielina/metabolismo , Proteínas Proteolipídicas Associadas a Linfócitos e Mielina , Fenótipo , Proteolipídeos/metabolismo , Adulto JovemRESUMO
(1) Background: University students, often constrained by time and influenced by socio-economic factors such as culture and religion, frequently adopt diets centred on ultra-processed foods (UPFs), increasing the risk of long-term non-communicable diseases. This study aimed to assess UPF consumption among Spanish university students and explore the potential impact of religion and the academic year on their eating habits. (2) Methods: In a cross-sectional study of 257 university students aged 18-31, UPF consumption was assessed using NOVA food classification at the academic year's start and end. Chi-square and Wilcoxon tests analysed UPF consumption changes, while binary logistic regression identified associations between religion and weekly UPF consumption. (3) Results: Muslim students had a consumption of industrial bakery products almost five times [95% CI: 2.694-9.259] higher than that observed among Christians. Similar data were observed for artificial juice consumption (OR = 3.897, 95% CI = 2.291-6.627) and candy consumption (OR = 3.724, 95% CI = 2.051-6.762). Moreover, a greater percentage of calories and grams of saturated fats from UPFs was observed for Muslims at the end of the study. (4) Conclusions: Highlighting the impact of religion on UPF consumption among students underscores the necessity of monitoring and intervening in dietary habits to prevent undesirable long-term complications such as cardiovascular diseases.
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Fast Foods , Comportamento Alimentar , Estudantes , Humanos , Estudos Transversais , Adulto Jovem , Masculino , Feminino , Estudantes/estatística & dados numéricos , Estudantes/psicologia , Adulto , Adolescente , Fast Foods/estatística & dados numéricos , Universidades , Espanha , Religião , Dieta/estatística & dados numéricos , Islamismo , Alimento ProcessadoRESUMO
BACKGROUND: Recent studies suggest that the age at first pregnancy, number of children and the lapse between births may protect against breast cancer. Furthermore, serum levels of estrogen, prolactin and progesterone appear to contribute to the development of this tumors in obese women. AIM: To verify whether the variables age at first pregnancy, number of children, birth interval, hormone levels and nutritional status are associated with the age at diagnosis of breast cancer. MATERIAL AND METHODS: Retrospective analysis of medical records of 550 female patients, diagnosed and treated for breast cancer at a hospital in Spain between 2009 and 2012. RESULTS: We found a significant and positive association between age at diagnosis of cancer and the variables age at first pregnancy, parity and interval between pregnancies. There was also a significant correlation (p < 0.000) between serum levels of estrogen, prolactin and progesterone and nutritional status of patients. CONCLUSIONS: In this sample, age at first pregnancy or number of children, hormone levels and nutritional status are related to the age of onset of cancer.
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Intervalo entre Nascimentos , Neoplasias da Mama/etiologia , Número de Gestações , Estado Nutricional/fisiologia , Paridade/fisiologia , Adulto , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/sangue , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/epidemiologia , Estrogênios/sangue , Feminino , Humanos , Pessoa de Meia-Idade , Obesidade/sangue , Gravidez , Progesterona/sangue , Prolactina/sangue , Sistema de Registros , Estudos Retrospectivos , Espanha/epidemiologia , Adulto JovemRESUMO
BACKGROUND: The relation between cardiac motion artefact (CMA) in optical coherence tomography (OCT) and the phases of cardiac cycle is unclear. METHODS: Optical coherence tomography pullbacks containing metallic stents were co-registered with angiography and retrospectively analyzed. The beginning of three phases, namely ejection, rapid-inflow and diastasis, was identified in angiography. Rotation, shortening, elongation and repetition were qualitatively labelled as CMA artefacts. Platforms with coaxial longitudinal connectors (ML8 and Magmaris) entered a quantitative sub-study, consisting of measuring the length of their connector at the beginning of each phase. RESULTS: A total of 261 stents (127 patients) were analyzed, including 105 stents for quantitative sub-study. CMA was detected in 61 (23.4%) stents: rotation in 6 (2.3%), shortening in 50 (19.2%), elongation in 51 (19.5%) and repetition in 12 (4.6%). Shortening was always observed during ejection phase, while elongation and repetition were always observed during rapid-inflow. Rotation occurred in both ejection and rapid-inflow phases, while no artefact was reported during diastasis. Longitudinal connectors measured in early ejection phase and in early rapid-inflow phase were shorter and longer, respectively, than those measured in diastasis, irrespective of the presence of CMA in the qualitative assessment. CONCLUSIONS: Cardiac motion artefact is prevalent in OCT studies, but shortening and elongation of vascular structures occur during early ejection and during early rapid-inflow, respectively, to a greater or lesser extent in all cases. Diastasis is free of CMA and hence the period in which longitudinal measurements can be more accurately quantified.
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Doença da Artéria Coronariana , Intervenção Coronária Percutânea , Humanos , Angiografia Coronária/métodos , Estudos Retrospectivos , Tomografia de Coerência Óptica/métodos , Stents , Vasos Coronários/diagnóstico por imagem , Resultado do TratamentoRESUMO
Extracorporeal photopheresis (ECP) has shown efficacy in treating graft-versus-host disease (GVHD). We aim to summarize eight years of real-world experience with off-line ECP in our institution, in order to validate this treatment schedule and analyze predictive factors. All consecutive adult patients with steroid-dependent or steroid-refractory GVHD undergoing off-line ECP were included in this single-center retrospective study. ECP was performed with a Spectra Optia device, processing 1 total blood volume, at a twice-weekly frequency for acute GVHD (aGVHD) and once weekly for chronic GVHD (cGVHD), and tapered individually according to clinical response. The cumulative incidence of response, including complete response (CR) and partial response (PR), were compared among patients grouped by different baseline, apheresis, and disease characteristics. Between January 2015 and May 2022, a total of 1382 ECP procedures were proposed for 82 patients. No incidents were reported in 97% of the ECP sessions. GVHD responded in 78% of patients (aGVHD: 57% CR and 4% PR; cGVHD, 39% CR and 48% PR). Overall survival was statistically greater for aGVHD patients who responded to ECP compared to those who did not respond (67.5% versus 26% at 1 year; P = 0.037). Severity was an independent predictor of response in aGVHD, whereas the absence of mouth involvement and lower lymphocyte counts in the apheresis product correlated with a higher response in cGVHD. Our findings support the effectiveness of this treatment schedule for GVHD. Further investigation is required to identify ECP-specific predictive factors, given that findings are not homogeneous across studies.
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Doença Enxerto-Hospedeiro , Fotoferese , Humanos , Adulto , Fotoferese/efeitos adversos , Fotoferese/métodos , Estudos Retrospectivos , Doença Enxerto-Hospedeiro/terapia , Esteroides/uso terapêutico , Indução de RemissãoRESUMO
Objectives: Our purpose was to establish different cut-off points based on the lung ultrasound score (LUS) to classify COVID-19 pneumonia severity. Methods: Initially, we conducted a systematic review among previously proposed LUS cut-off points. Then, these results were validated by a single-centre prospective cohort study of adult patients with confirmed SARS-CoV-2 infection. Studied variables were poor outcome (ventilation support, intensive care unit admission or 28-days mortality) and 28-days mortality. Results: From 510 articles, 11 articles were included. Among the cut-off points proposed in the articles included, only the LUS > 15 cut-off point could be validated for its original endpoint, demonstrating also the strongest relation with poor outcome (odds ratio [OR] = 3.636, confidence interval [CI] 1.411-9.374). Regarding our cohort, 127 patients were admitted. In these patients, LUS was statistically associated with poor outcome (OR = 1.303, CI 1.137-1.493), and with 28-days mortality (OR = 1.024, CI 1.006-1.042). LUS > 15 showed the best diagnostic performance when choosing a single cut-off point in our cohort (area under the curve 0.650). LUS ≤ 7 showed high sensitivity to rule out poor outcome (0.89, CI 0.695-0.955), while LUS > 20 revealed high specificity to predict poor outcome (0.86, CI 0.776-0.917). Conclusions: LUS is a good predictor of poor outcome and 28-days mortality in COVID-19. LUS ≤ 7 cut-off point is associated with mild pneumonia, LUS 8-20 with moderate pneumonia and ≥20 with severe pneumonia. If a single cut-off point were used, LUS > 15 would be the point which better discriminates mild from severe disease.
Objetivos: Establecer diferentes puntos de corte basados en el Lung Ultrasound Score (LUS) para clasificar la gravedad de la neumonía COVID-19. Métodos: Inicialmente, realizamos una revisión sistemática entre los puntos de corte LUS propuestos previamente. Estos resultados fueron validados por una cohorte prospectiva unicéntrica de pacientes adultos con infección confirmada por SARS-CoV-2. Las variables analizadas fueron la mala evolución y la mortalidad a los 28 días. Resultados: De 510 artículos, se incluyeron 11. Entre los puntos de corte propuestos en los artículos incluidos, solo LUS > 15 pudo ser validado para su objetivo original, demostrando también la relación más fuerte con mala evolución (odds ratio [OR] = 3,636, intervalo de confianza [IC] 1,411-9,374). Respecto a nuestra cohorte, se incluyeron 127 pacientes. En estos pacientes, el LUS se asoció estadísticamente con mala evolución (OR = 1,303, IC 1,137-1,493) y con mortalidad a los 28 días (OR = 1,024, IC 1,006-1,042). LUS > 15 mostró el mejor rendimiento diagnóstico al elegir un único punto de corte en nuestra cohorte (área bajo la curva 0,650). LUS ≤ 7 mostró una alta sensibilidad para descartar mal resultado (0,89, IC 0,695-0,955), mientras que LUS > 20 reveló gran especificidad para predecir mala evolución (0,86, IC 0,776-0,917). Conclusiones: LUS es un buen predictor de mala evolución y mortalidad a 28 días en COVID-19. LUS ≤ 7 se asocia con neumonía leve, LUS 8-20 con neumonía moderada y ≥ 20 con neumonía grave. Si se utilizara un único punto de corte, LUS > 15 sería el que mejor discriminaría la enfermedad leve de la grave.
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OBJECTIVES: Our purpose was to establish different cut-off points based on the lung ultrasound score (LUS) to classify COVID-19 pneumonia severity. METHODS: Initially, we conducted a systematic review among previously proposed LUS cut-off points. Then, these results were validated by a single-centre prospective cohort study of adult patients with confirmed SARS-CoV-2 infection. Studied variables were poor outcome (ventilation support, intensive care unit admission or 28-days mortality) and 28-days mortality. RESULTS: From 510 articles, 11 articles were included. Among the cut-off points proposed in the articles included, only the LUS>15 cut-off point could be validated for its original endpoint, demonstrating also the strongest relation with poor outcome (odds ratio [OR]=3.636, confidence interval [CI] 1.411-9.374). Regarding our cohort, 127 patients were admitted. In these patients, LUS was statistically associated with poor outcome (OR=1.303, CI 1.137-1.493), and with 28-days mortality (OR=1.024, CI 1.006-1.042). LUS>15 showed the best diagnostic performance when choosing a single cut-off point in our cohort (area under the curve 0.650). LUS≤7 showed high sensitivity to rule out poor outcome (0.89, CI 0.695-0.955), while LUS>20 revealed high specificity to predict poor outcome (0.86, CI 0.776-0.917). CONCLUSIONS: LUS is a good predictor of poor outcome and 28-days mortality in COVID-19. LUS≤7 cut-off point is associated with mild pneumonia, LUS 8-20 with moderate pneumonia and ≥20 with severe pneumonia. If a single cut-off point were used, LUS>15 would be the point which better discriminates mild from severe disease.
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COVID-19 , Adulto , Humanos , COVID-19/diagnóstico por imagem , Estudos Prospectivos , SARS-CoV-2 , Pulmão/diagnóstico por imagem , Hospitalização , Ultrassonografia/métodosRESUMO
BACKGROUND: There is a need for a disease-specific instrument for assessing health-related quality of life in adults with hereditary angioedema due to C1 inhibitor deficiency, a rare, disabling and life-threatening disease. In this paper we report the protocol for the development and validation of a specific questionnaire, with details on the results of the process of item generation, domain selection, and the expert and patient rating phase. METHODS/DESIGN: Semi-structured interviews were completed by 45 patients with hereditary angioedema and 8 experts from 8 regions in Spain. A qualitative content analysis of the responses was carried out. Issues raised by respondents were grouped into categories. Content analysis identified 240 different responses, which were grouped into 10 conceptual domains. Sixty- four items were generated. A total of 8 experts and 16 patients assessed the items for clarity, relevance to the disease, and correct dimension assignment. The preliminary version of the specific health-related quality of life questionnaire for hereditary angioedema (HAE-QoL v 1.1) contained 44 items grouped into 9 domains. DISCUSSION: To the best of our knowledge, this is the first multi-centre research project that aims to develop a specific health-related quality of life questionnaire for adult patients with hereditary angioedema due to C1 inhibitor deficiency. A preliminary version of the specific HAE-QoL questionnaire was obtained. The qualitative analysis of interviews together with the expert and patient rating phase helped to ensure content validity. A pilot study will be performed to assess the psychometric properties of the questionnaire and to decide on the final version.
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Angioedemas Hereditários/psicologia , Proteínas Inativadoras do Complemento 1/deficiência , Psicometria/métodos , Qualidade de Vida , Inquéritos e Questionários , Adolescente , Adulto , Idoso , Medicina Baseada em Evidências , Feminino , Humanos , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Pesquisa Qualitativa , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , EspanhaRESUMO
BACKGROUND: Reslizumab is an anti-interleukin 5 monoclonal antibody that has demonstrated to reduce the risk of severe exacerbations and to improve symptoms, lung function, and quality of life in randomized controlled trials that included patients with severe eosinophilic uncontrolled asthma (SEUA) and a history of severe exacerbations. OBJECTIVE: The aim of the present study was to evaluate the effectiveness of add-on reslizumab in a cohort of patients with SEUA under real-life conditions. METHODS: This was a multi-centre, retrospective, real-life study that included subjects with SEUA treated with reslizumab in 44 asthma units throughout Spain. Eligible patients were those who had received at least one dose of reslizumab as part of normal clinical practice. The primary endpoint was complete asthma control at 52 weeks, defined as absence of severe exacerbations, ACT ≥20 and no maintenance oral corticosteroids (OCS). Demographic, clinical, and functional data were collected at baseline (T0), after four to six months (T1); after 12 months (T2) and beyond 12 months of therapy (T3). RESULTS: Treatment with reslizumab achieved complete asthma control in 40% of the 208 included SEUA patients and led to a significant reduction in exacerbations (from 3.0; IQR: 2.0-4.0 at V0 to 0.0; IQR: 0.0-0.0 at V2), maintenance OCS use (from 54.8% (95% CI: 48.0-61.6 at T0 to 18.5% (95% CI: 12.5-24.5 at T2) and a meaningful improvement in symptoms in the entire treated population: ACT increased from 12.8 ± 4.5 at V0 to 20.0 ± 5.1 at V2 (p < 0.001). Most of the improvement achieved at 12 months was obtained at 4-6 months. The retention (continuation) rate of reslizumab was 75% through 2 years (95CI%: 1.9-2.1). Overall, reslizumab showed an adequate safety profile. CONCLUSION: Reslizumab is an effective therapy for SEUA with adequate safety profile in real-life conditions.
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BACKGROUND/OBJECTIVE: Few studies have assessed the effect of lockdown on physical activity and eating behaviours in a population from the Autonomous Community of Andalusia in southern Spain. The aim of our study was to describe the effect of COVID-19 pandemic home lockdown on eating habits and lifestyle in the Andalusian population. SUBJECTS/METHODS: A cross-sectional observational study was carried out on a population from southern Spain, Andalusian population. An online questionnaire was shared through social networks and snowball sampling. A total of 1140 people filled in the questionnaire. The questionnaire consisted of 34 items classified into three sections: sociodemographic data, work and leisure activities and questions on food consumption. Each item offered pre- and post-lockdown information. RESULTS: The participants were classified into three age groups: 18-35, 36-65 and over 65. Statistically significant differences were found between the three groups, with the younger age group undergoing greater changes, increasing their physical activity and consumption of fresh food, and decreasing both their consumption of fast food at home and alcohol intake. CONCLUSIONS: These findings suggest that, in the current social and health crisis, the citizens of southern Spain have become aware of the importance of maintaining an appropriate lifestyle to remain healthy, particularly the younger population with less well-consolidated habits.
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COVID-19 , Adolescente , COVID-19/epidemiologia , Controle de Doenças Transmissíveis , Estudos Transversais , Comportamento Alimentar , Humanos , Estilo de Vida , Pandemias , Espanha/epidemiologia , Inquéritos e QuestionáriosRESUMO
BACKGROUND: The ability of optical coherence tomography (OCT) to identify specific types of stent has never been systematically studied. AIMS: The aim of this study was to test the accuracy of OCT imaging to identify patterns of stent platform and subsequently identify the type of stent implanted. METHODS: Consecutive patients from six international centres were retrospectively screened, searching for OCT studies with metallic stents or scaffolds. The sample was analysed by two blinded operators, applying a dedicated protocol in four steps to identify the type of stent: 1) 3D and automatic strut detection (ASD), 2) 3D tissue view, 3) longitudinal view with ASD, 4) mode "stent only" and ASD. RESULTS: A series of 212 patients underwent OCT in the study centres, finding 294 metallic stents or scaffolds in 146 patients. The protocol correctly identified 285 stents (96.9%, kappa 0.965), with excellent interobserver agreement (kappa 0.988). The performance tended to be better in recently implanted stents (kappa 0.993) than in stents implanted ≥3 months before (kappa 0.915), and in pullback speed 18 mm/s as compared with 36 mm/s (kappa 0.969 vs 0.940, respectively). CONCLUSIONS: The type of stent platform can be accurately identified in OCT by trained analysts following a dedicated protocol, combining 3D-OCT, ASD and longitudinal view. This might be clinically helpful in scenarios of device failure and for the quantification of apposition. The blinding of analysts in OCT studies should be revisited.
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Stents , Tomografia de Coerência Óptica , Vasos Coronários , Humanos , Estudos RetrospectivosRESUMO
The practice of Ramadan involves a series of changes in lifestyle, mainly in eating habits. The research aim of this study is to determine the prevalence of overweight-obesity, the degree of compliance with dietary recommendations and the effects of religious fasting on cardiovascular health among a population of Muslim women living in Melilla, a Spanish city in North Africa. A follow-up cohort study was conducted on 62 healthy adult women (33.6 ± 12.7 years). Anthropometric and body composition parameters were obtained using bioimpedance and dietary records. All of the participants were overweight or obese, especially due to the non-compliance with dietary recommendations; however, more than 60% considered their weight was appropriate or even low. By the end of Ramadan, the women's body mass index and fat component values had fallen significantly (p < 0.001), but this loss was later recovered. Dietary records revealed an excessive consumption of lipids and sodium, and the presence of a high waist-to-hip ratio. All of these factors are related to cardiovascular risk. In conclusion, promoting nutritional health and encouraging year-round self-care among adult Muslim women is necessary in order to ensure healthy fasting during Ramadan.
Assuntos
Jejum , Islamismo , Adulto , Índice de Massa Corporal , Feminino , Seguimentos , Humanos , AutocuidadoRESUMO
Our objective was to analyze the incidence and trend of hip fracture in Spain and its distribution by Autonomous Community (AC). In Spain, the age-adjusted incidence rate of hip fracture is decreasing. There is great variability in the incidence and tendency of hip fracture among the different ACs. Genetic, demographic, and climatic factors and cohort effect factors of the civil war explain 96% of this variability. INTRODUCTION: In Spain, there is great variability between the different Autonomous Communities (ACs) in the incidence of hip fracture. The objectives of our study are (1) to estimate the incidence rate and trend of hospital admissions for hip fracture in Spain and by ACs and (2) to analyze risk factors/markers that could explain the variability in the incidence and trend between different ACs. METHOD: This work includes 2 studies (TREND-HIP and VAR-HIP). TREND-HIP: retrospective, national, observational study based on the administrative database of the National Health System that includes a Minimum Basic Data Set (MBDS) of hospital admissions. VAR-HIP: ecological study based on the analysis of the results obtained in TREND-HIP study, with different risk factors/markers obtained from different sources. RESULTS: In the 17 years included in the analysis, there were 744,848 patients diagnosed with hip fracture. The global age-adjusted rate of hip fracture at the national level was 315.38/100,000 person*year (95% CI 312.36-317.45); by AC, the rate varied from 213.97 in the Canary Islands to 363.13 in the Valencia and Cataluña communities. We observe an east-west gradient in Spain. The trend for both sexes was - 0.67% (95% CI 0.9990-0.9957) (p < 0.001). In the analysis of risk factors/markers that explain this distribution, we found significant correlations with genetic factors, demographics, climatic factors and the time a region was on the Republican side of the civil war. The linear regression model that includes the factors that show significant correlation explains 96% of the variability observed. CONCLUSION: In Spain, the age-adjusted incidence rate for hip fracture is decreasing. There is a great variability in the incidence and tendency of hip fracture among the different ACs. Genetic, demographic, climatic factors and the cohort effect of the civil war explain 96% of this variability.
Assuntos
Fraturas do Quadril/epidemiologia , Fraturas por Osteoporose/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Conflitos Armados , Clima , Feminino , Predisposição Genética para Doença , Fraturas do Quadril/etiologia , Fraturas do Quadril/genética , Hospitalização/estatística & dados numéricos , Hospitalização/tendências , Humanos , Incidência , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Fraturas por Osteoporose/etiologia , Fraturas por Osteoporose/genética , Estudos Retrospectivos , Fatores de Risco , Distribuição por Sexo , Espanha/epidemiologiaRESUMO
Inhibiting MYC has long been considered unfeasible, although its key role in human cancers makes it a desirable target for therapeutic intervention. One reason for its perceived undruggability was the fear of catastrophic side effects in normal tissues. However, we previously designed a dominant-negative form of MYC called Omomyc and used its conditional transgenic expression to inhibit MYC function both in vitro and in vivo. MYC inhibition by Omomyc exerted a potent therapeutic impact in various mouse models of cancer, causing only mild, well-tolerated, and reversible side effects. Nevertheless, Omomyc has been so far considered only a proof of principle. In contrast with that preconceived notion, here, we show that the purified Omomyc mini-protein itself spontaneously penetrates into cancer cells and effectively interferes with MYC transcriptional activity therein. Efficacy of the Omomyc mini-protein in various experimental models of non-small cell lung cancer harboring different oncogenic mutation profiles establishes its therapeutic potential after both direct tissue delivery and systemic administration, providing evidence that the Omomyc mini-protein is an effective MYC inhibitor worthy of clinical development.