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OBJECTIVE: Cerebral cavernous malformations (CCMs) can happen anywhere in the body, although they most commonly produce symptoms in the brain. The role of CCM genes in other vascular beds outside the brain and retina is not well-examined, although the 3 CCM-associated genes (CCM1, CCM2, and CCM3) are ubiquitously expressed in all tissues. We aimed to determine the role of CCM gene in lymphatics. Approach and Results: Mice with an inducible pan-endothelial cell (EC) or lymphatic EC deletion of Ccm3 (Pdcd10ECKO or Pdcd10LECKO) exhibit dilated lymphatic capillaries and collecting vessels with abnormal valve structure. Morphological alterations were correlated with lymphatic dysfunction in Pdcd10LECKO mice as determined by Evans blue dye and fluorescein isothiocyanate(FITC)-dextran transport assays. Pdcd10LECKO lymphatics had increased VEGFR3 (vascular endothelial growth factor receptor-3)-ERK1/2 (extracellular signal-regulated kinase 1/2) signaling with lymphatic hyperplasia. Mechanistic studies suggested that VEGFR3 is primarily regulated at a transcriptional level in Ccm3-deficient lymphatic ECs, in an NF-κB (nuclear factor κB)-dependent manner. CCM3 binds to importin alpha 2/KPNA2 (karyopherin subunit alpha 2), and a CCM3 deletion releases KPNA2 to activate NF-κB P65 by facilitating its nuclear translocation and P65-dependent VEGFR3 transcription. Moreover, increased VEGFR3 in lymphatic EC preferentially activates ERK1/2 signaling, which is critical for lymphatic EC proliferation. Importantly, inhibition of VEGFR3 or ERK1/2 rescued the lymphatic defects in structure and function. CONCLUSIONS: Our data demonstrate that CCM3 deletion augments the VEGFR3-ERK1/2 signaling in lymphatic EC that drives lymphatic hyperplasia and malformation and warrant further investigation on the potential clinical relevance of lymphatic dysfunction in patients with CCM.
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Endotélio Linfático/fisiopatologia , Hemangioma Cavernoso do Sistema Nervoso Central/fisiopatologia , Sistema de Sinalização das MAP Quinases/fisiologia , Receptor 3 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Animais , Proteínas Reguladoras de Apoptose/genética , Células Cultivadas , Células Endoteliais/fisiologia , Endotélio Linfático/patologia , Feminino , Deleção de Genes , Hemangioma Cavernoso do Sistema Nervoso Central/patologia , Hiperplasia , Masculino , Camundongos Endogâmicos , Modelos Animais , NF-kappa B/genética , Translocação GenéticaRESUMO
Muscle functional MRI identifies changes in metabolic activity in each muscle and provides a quantitative index of muscle activation and damage. No previous studies have analyzed the hamstrings activation over a football match. This study aimed at detecting different patterns of hamstring muscles activation after a football game, and to examine inter- and intramuscular differences (proximal-middle-distal) in hamstring muscles activation using transverse relaxation time (T2)-weighted magnetic resonance images. Eleven healthy football players were recruited for this study. T2 relaxation time mapping-MRI was performed before (2 hours) and immediately after a match (on average 13 min). The T2 values of each hamstring muscle at the distal, middle, and proximal portions were measured. The primary outcome measure was the increase in T2 relaxation time value after a match. Linear mixed models were used to detect differences pre and postmatch. MRI examination showed that there was no obvious abnormality in the shape and the conventional T2 weighted signal of the hamstring muscles after a match. On the other hand, muscle functional MRI T2 analysis revealed that T2 relaxation time significantly increased at distal and middle portions of the semitendinosus muscle (p = 0.0003 in both cases). By employing T2 relaxation time mapping, we have identified alterations within the hamstring muscles being the semitendinosus as the most engaged muscle, particularly within its middle and distal thirds. This investigation underscores the utility of T2 relaxation time mapping in evaluating muscle activation patterns during football matches, facilitating the detection of anomalous activation patterns that may warrant injury reduction interventions.
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Músculos Isquiossurais , Imageamento por Ressonância Magnética , Futebol , Humanos , Imageamento por Ressonância Magnética/métodos , Músculos Isquiossurais/fisiologia , Músculos Isquiossurais/diagnóstico por imagem , Masculino , Adulto , Futebol/fisiologia , Adulto Jovem , Futebol Americano/lesões , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/fisiologiaRESUMO
INTRODUCTION: Innovation in internet connectivity and the Covid 19 pandemic have caused a dramatic change in the management of patients in the medical field, boosting the use of telemedicine. A comparison of clinical outcomes and satisfaction between conventional face-to-face and telemedicine follow-up in general surgery, an economic evaluation is mandatory. The aim of the present study was to compare the differences in economic costs between these two outpatient approaches in a designed randomized controlled trial (RCT). METHODS: A RCT was conducted enrolling 200 patients to compare conventional in-person vs. digital health follow-up using telemedicine in the outpatient clinics in patients of General Surgery Department after their planned discharge. After a demonstration that no differences were found in clinical outcomes and patient satisfaction, we analyzed the medical costs, including staff wages, initial investment, patent's transportation and impact on social costs. RESULTS: After an initial investment of 7527.53, the costs for the Medical institution of in-person conventional follow-up were higher (8180.4) than those using telemedicine (4630.06). In relation to social costs, loss of productivity was also increased in the conventional follow-up. CONCLUSION: The use of digital Health telemedicine is a cost-effective approach compared to conventional face-to-face follow-up in patients of General Surgery after hospital discharge.
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Telemedicina , Humanos , Telemedicina/economia , Masculino , Feminino , COVID-19/epidemiologia , Pessoa de Meia-Idade , Satisfação do Paciente , Assistência Ambulatorial/economia , Assistência Ambulatorial/métodos , Assistência ao Convalescente/economia , Assistência ao Convalescente/métodos , Cirurgia Geral/economia , Seguimentos , Idoso , Adulto , Análise Custo-BenefícioRESUMO
Bureaucratic and administrative tasks associated with health care provision have historically fallen on health care professionals, which is one among the factors contributing to low job satisfaction and lower productivity. Incorporating new professional roles that help to better respond to the needs of both patients and professionals can increase the quality and efficiency of service provision. This article aims to evaluate the impact of the clinical assistant's introduction in the Sant Joan de Déu Barcelona Children's Hospital's pediatric oncology department, in terms of (i) displacement of activity loads carried out by this new professional role and the consequent time freed up for physicians, (ii) physicians' satisfaction and (iii) efficiency of the new care model. This is an observational and retrospective study using administrative data based on the type of activity performed by clinical assistants and the measurement of the time freed up in favor of the physicians. The potential skill mix productivity increase, survey of physicians' satisfaction, and reduction in costs with the new model was analyzed. During the first year of its implementation in the pediatric oncology department, clinical assistants have performed 13,553 requests (69% of the total), representing a total saving of 266.83 hours or 6.67 workweeks of 40 hours. They performed 74% of outpatient surgical requests in the oncology department, 87% of day hospital requests and 54% of total requests in the outpatient consultations area. Physicians are overall satisfied with the new role and think they can use the time gained to do other things such as research or improving the quality of care. The role change allows reducing the cost per request by 56% in relation to the conventional model. In conclusion, the introduction of clinical assistants in the oncology department could be efficient to the extent that it displaces a significant part of the bureaucratic and administrative tasks previously performed by health care professionals and thus enables to reduce the cost of these processes. This delegation allows them to work more closely to the maximum of their competences and the physicians to have more time for higher added value clinical tasks and increase professional satisfaction.
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BACKGROUND: Imported schistosomiasis is an emerging issue in European countries as a result of growing global migration from schistosomiasis-endemic countries, mainly in sub-Saharan Africa. Undetected infection may lead to serious long-term complications with an associated high cost for public healthcare systems especially among long-term migrants. OBJECTIVE: To evaluate from a health economics perspective the introduction of schistosomiasis screening programs in non-endemic countries with high prevalence of long-term migrants. METHODOLOGY: We calculated the costs associated with three approaches-presumptive treatment, test-and-treat and watchful waiting-under different scenarios of prevalence, treatment efficacy and the cost of care resulting from long-term morbidity. Costs were estimated for our study area, in which there are reported to reside 74,000 individuals who have been exposed to the infection. Additionally, we methodically reviewed the potential factors that could affect the cost/benefit ratio of a schistosomiasis screening program and need therefore to be ascertained. RESULTS: Assuming a 24% prevalence of schistosomiasis in the exposed population and 100% treatment efficacy, the estimated associated cost per infected person of a watchful waiting strategy would be 2,424, that of a presumptive treatment strategy would be 970 and that of a test-and-treat strategy would be 360. The difference in averted costs between test-and-treat and watchful waiting strategies ranges from nearly 60 million in scenarios of high prevalence and treatment efficacy, to a neutral costs ratio when these parameters are halved. However, there are important gaps in our understanding of issues such as the efficacy of treatment in infected long-term residents, the natural history of schistosomiasis in long-term migrants and the feasibility of screening programs. CONCLUSION: Our results support the roll-out of a schistosomiasis screening program based on a test-and-treat strategy from a health economics perspective under the most likely projected scenarios, but important knowledge gaps should be addressed for a more accurate estimations among long-term migrants.
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Esquistossomose , Humanos , Espanha/epidemiologia , Esquistossomose/diagnóstico , Esquistossomose/epidemiologia , Esquistossomose/prevenção & controle , Europa (Continente) , Prevalência , Análise Custo-Benefício , PesquisaRESUMO
The COVID-19 pandemic has had major impacts on population health not only through COVID-positive cases, but also via the disruption of healthcare services, which in turn has impacted the diagnosis and treatment of all other diseases during this time. We study changes in all new registered diagnoses in ICD-10 groups during 2020 with respect to a 2019 baseline. We compare new diagnoses in 2019 and 2020 based on administrative records of the public primary health system in Central Catalonia, Spain, which cover over 400,000 patients and 3 million patient visits. We study the ratio of new diagnoses between 2019 and 2020 and find an average decline of 31.1% in new diagnoses, with substantial drops in April (61.1%), May (55.6%), and November (52%). Neoplasms experience the largest decline (49.7%), with heterogeneity in the magnitudes of the declines across different types of cancer diagnoses. While we find evidence of temporal variation in new diagnoses, reductions in diagnoses early in the year are not recouped by the year end. The observed decline in new diagnoses across all diagnosis groups suggest a large number of untreated and undetected cases across conditions. Our findings provide a year-end summary of the impact of the pandemic on healthcare activities and can help guide health authorities to design evidence-based plans to target under-diagnosed conditions in 2021.
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COVID-19 , Pandemias , Humanos , Diagnóstico Ausente , SARS-CoV-2 , Espanha/epidemiologiaRESUMO
(1) Background: In epidemiological terms, it has been possible to calculate the savings in health resources and the reduction in the health effects of COVID vaccines. Conducting an economic evaluation, some studies have estimated its cost-effectiveness; the vaccination shows highly favorable results, cost-saving in some cases. (2) Methods: Cost-benefit analysis of the vaccination campaign in the North Metropolitan Health Region (Catalonia). An epidemiological model based on observational data and before and after comparison is used. The information on the doses used and the assigned resources (conventional hospital beds, ICU, number of tests) was extracted from administrative data from the largest primary care provider in the region (Catalan Institute of Health). A distinction was made between the social perspective and the health system. (3) Results: the costs of vaccination are estimated at 137 million euros (48.05/dose administered). This figure is significantly lower than the positive impacts of the vaccination campaign, which are estimated at 470 million euros (164/dose administered). Of these, 18% corresponds to the reduction in ICU discharges, 16% to the reduction in conventional hospital discharges, 5% to the reduction in PCR tests and 1% to the reduction in RAT tests. The monetization of deaths and cases that avoid sequelae account for 53% and 5% of total savings, respectively. The benefit/cost ratio is estimated at 3.4 from a social perspective and 1.4 from a health system perspective. The social benefits of vaccination are estimated at 116.67 per vaccine dose (19.93 from the perspective of the health system). (4) Conclusions: The mass vaccination campaign against COVID is cost-saving. From a social perspective, most of these savings come from the monetization of the reduction in mortality and cases with sequelae, although the intervention is equally widely cost-effective from the health system perspective thanks to the reduction in the use of resources. It is concluded that, from an economic perspective, the vaccination campaign has high social returns.
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BACKGROUND: It is well known that obesity is a risk factor for severe cardiovascular complications, such as coronary heart disease, heart failure, stroke, venous thromboembolic disease, and atrial fibrillation. Left ventricle (LV) and left atrium (LA) enlargement is a characteristic feature of these patients with the consequent cardiovascular risk. Factors other than hemodynamic may influence LA remodeling. The aim of the study is to evaluate the relationship between adiponectin and LA size in uncomplicated obese patients. METHODS: Seventy-four asymptomatic obese patients and an age- and sex-matched control group (N = 70) were recruited. A detailed clinical, echocardiographic, and analytical study was performed. Insulin resistance was assessed using the homeostasis model assessment for insulin resistance (HOMA-IR) method. Insulin sensitivity was assessed measuring serum total adiponectin concentrations. RESULTS: Adiponectin levels were lower in the obese group (P < 0.001) and particularly so in those obese participants with enlarged LA (32%; P < 0.0005). LA sizes were higher in the obese group (P < 0.0005). Adiponectin displayed significant correlations with body mass index, glucose, insulin, high-density lipoprotein cholesterol, and triglyceride concentrations as well as HOMA-IR (P < 0.001 for all). Adiponectin displayed significant correlations with LV mass and LA size, diastolic and systolic cardiac volumes and diameters, and cardiac output (P < 0.001 for all). Adiponectin correlations with LA size (r = -0.429; P < 0.001) persisted after adjustment for HOMA-IR, age, sex, and LV mass. CONCLUSIONS: A novel inverse relationship between adiponectin and LA size independent of age, sex, insulin resistance, and LV mass appears in our series. Adiponectin could be a link between adipose tissue and the heart, having an influence on cardiac remodeling.
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Adiponectina/sangue , Átrios do Coração/patologia , Obesidade/sangue , Obesidade/patologia , Adulto , Idoso , Índice de Massa Corporal , Estudos de Casos e Controles , Ecocardiografia Doppler , Feminino , Átrios do Coração/diagnóstico por imagem , Humanos , Resistência à Insulina , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Volume Sistólico , Adulto JovemRESUMO
Leptospirosis is an emerging zoonotic disease with more than 1 million cases annually. Currently there is lack of evidence for signaling pathways involved during the infection process of Leptospira. In our comprehensive genomic analysis of 20 Leptospira spp. we identified seven pathogen-specific Two-Component System (TCS) proteins. Disruption of two these TCS genes in pathogenic Leptospira strain resulted in loss-of-virulence in a hamster model of leptospirosis. Corresponding genes lvrA and lvrB (leptospira virulence regulator) are juxtaposed in an operon and are predicted to encode a hybrid histidine kinase and a hybrid response regulator, respectively. Transcriptome analysis of lvr mutant strains with disruption of one (lvrB) or both genes (lvrA/B) revealed global transcriptional regulation of 850 differentially expressed genes. Phosphotransfer assays demonstrated that LvrA phosphorylates LvrB and predicted further signaling downstream to one or more DNA-binding response regulators, suggesting that it is a branched pathway. Phylogenetic analyses indicated that lvrA and lvrB evolved independently within different ecological lineages in Leptospira via gene duplication. This study uncovers a novel-signaling pathway that regulates virulence in pathogenic Leptospira (Lvr), providing a framework to understand the molecular bases of regulation in this life-threatening bacterium.
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Proteínas de Bactérias/metabolismo , Regulação Bacteriana da Expressão Gênica , Leptospira/fisiologia , Leptospirose/microbiologia , Transdução de Sinais , Evolução Molecular , Genoma Bacteriano , Humanos , Leptospira/patogenicidade , Viabilidade Microbiana , Modelos Biológicos , Mutação , Transcrição Gênica , Virulência/genética , Sequenciamento Completo do GenomaRESUMO
INTRODUCTION AND OBJECTIVES: The natural history of idiopathic atrial fibrillation is not well understood. The aim of this study was to investigate the frequency of and risk factors for disease recurrence. METHODS: The study involved 115 patients with a first episode of paroxysmal atrial fibrillation of unknown origin who were included the FAP registry, which contains data from 11 district hospitals in Catalonia, Spain. All patients underwent comprehensive clinical, laboratory, electro-cardiographic and echocardiographic investigations at baseline and were followed up periodically every 6 months to identify the occurrence of new symptomatic episodes and their complications. RESULTS: During a mean follow-up period of 912 (445) days, 32 (27.8%) patients experienced recurrence of atrial fibrillation. Those who experienced recurrence had a significantly higher left ventricular ejection fraction (P=.023) and smaller end-systolic volume (P<.001), and they were more likely to consume alcohol regularly (P=.013). Cox regression analysis confirmed that these variables had independent prognostic value. In contrast, the occurrence of syncope during the initial episode was associated with a lower likelihood of recurrence (P=.017). CONCLUSIONS: The risk of recurrence of idiopathic atrial fibrillation was high, and was enhanced by moderate alcohol consumption and increased left ventricular activity, probably of sympathetic origin. This trend was less marked in paroxysmal atrial fibrillation of vagal origin.
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Fibrilação Atrial/diagnóstico , Fibrilação Atrial/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Recidiva , Sistema de Registros , Fatores de RiscoRESUMO
OBJECTIVE: To assess the usefulness of hand-held cardiac ultrasound (HCU) performed by family doctors (FDs) in primary care, with web-based remote expert support interpretation, in a cohort of patient with symptoms or physical examination signs suggestive of cardiovascular disease. METHODS: This prospective observational study included 1312 consecutive patients, in three remote primary care areas, with symptoms or physical examination signs suggestive of cardiovascular disease. In 859 patients (group A), FDs had indicated conventional echocardiography (CE), and in 453 (Group B) the study was performed to complement the physical examination. HCU was carried out by 14 FDs after a short training period. The scans and preliminary FD reports were uploaded on a web-based program for remote expert support interpretation in <24â h. RESULTS: Experts considered HCU to be inconclusive in 116 (8.8%) patients. FD and expert agreement on diagnosis was moderate (K=0.40-0.70) except in mitral stenosis (K=0.29) and in left atrial dilation (K=0.38). Diagnostic agreement between expert interpretation and CE was good (K=0.66-0.85) except in mitral stenosis (K=0.43). After remote expert interpretation, conventional echocardiograms were finally requested by FDs in only 276 (32.1%) patients, and discharges increased by 10.2%. Furthermore, significant heart diseases were diagnosed in 32 (7%) patients of group B. CONCLUSIONS: HCU performed at the point of care by FDs with remote expert support interpretation using a web-based system is feasible, rapid and useful for detecting significant echocardiographic abnormalities and reducing the number of unnecessary echocardiographic studies.
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Diagnóstico por Computador/métodos , Ecocardiografia Doppler em Cores/métodos , Cardiopatias/diagnóstico por imagem , Médicos de Família , Testes Imediatos , Atenção Primária à Saúde , Consulta Remota/métodos , Serviços de Saúde Rural , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Ecocardiografia Doppler em Cores/instrumentação , Educação Médica Continuada , Desenho de Equipamento , Estudos de Viabilidade , Feminino , Cardiopatias/terapia , Humanos , Capacitação em Serviço , Internet , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Médicos de Família/educação , Sistemas Automatizados de Assistência Junto ao Leito , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Reprodutibilidade dos Testes , Espanha , Transdutores , Procedimentos Desnecessários , Adulto JovemAssuntos
Cardiomiopatia Hipertrófica/genética , Miosinas Cardíacas/genética , Cardiomiopatia Hipertrófica/diagnóstico , Cardiomiopatia Hipertrófica/mortalidade , Morte Súbita Cardíaca/etiologia , Feminino , Genótipo , Humanos , Masculino , Mutação , Cadeias Pesadas de Miosina/genética , Miosinas/genética , Fenótipo , Polimorfismo Genético , Prevalência , Prognóstico , Troponina/genéticaRESUMO
OBJECTIVE: Sleep-disordered breathing (SDB) is often encountered in morbid obesity (MO) in conjunction with insulin resistance (IR) and several cardio-vascular risk factors. Aminoterminal pro-brain natriuretic peptide (NT-proBNP) is a promising marker for left ventricular dysfunction (LVD) in MO. The aim of this study was to look for possible correlations between SDB, IR, heart structure and function indexes and NT-proBNP levels in MO female subjects. MATERIALS AND METHODS: Cross-sectional study involving 110 MO (44.5+/-0.7 kg m(-2)) apparently healthy, young (37.8+/-1.0 y.o.) female patients. NT-proBNP was measured using an ELISA kit (Roche). Echo-cardiograms were performed to quantify left ventricular ejection fraction values (LVEF), cardiac output (CO), left ventricular mass (LVM), left atria size (LA) and left ventricular filling pressures (the E/Em ratio). The Berlin Questionnaire (BQ) was used to assess the risk of SDB. IR and sensitivity were assessed using the HOMA index and adiponectin measurements, respectively. RESULTS: All patients had a normal LVEF (>50%). Hypertension and Type 2 diabetes mellitus prevalences were 34.5 and 4.5% (respectively). Log-transformed NT-proBNP levels correlated with BQ categories (P<0.0005), creatinine (P<0.001), age (P<0.05), LVM (P<0.001), CO (P<0.001), LA (P<0.0005) and E/Em (P<0.01). NT-proBNP levels, LVD and LVM increased significantly along with BQ scores (P<0.0001). Stepwise multiple regression analysis identified BQ and log-transformed HOMA as independent variables predicting as much as 48.0% of log-transformed NT-proBNP's variability (dependent variable). CONCLUSIONS: NT-proBNP levels are independently predicted by SDB and IR in asymptomatic MO women. Additionally, SDB worsens along with LVH and diastolic dysfunction. Larger prospective studies are warranted.