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Introduction Linezolid is a broadly used antibiotic to treat complicated infections caused by gram-positive bacteria. Therapeutic drug monitoring of linezolid concentrations is recommended to maximise its efficacy and safety, mainly haematological toxicity. Different pharmacokinetic/pharmacodynamic targets have been proposed to improve linezolid exposure: the ratio of the area under the concentration–time curve during a 24-hour period to minimum inhibitory concentration (MIC) between 80 and 120; percentage of time that the drug concentration remains above the MIC during a dosing interval greater than 85% and the trough concentration between 2 and 7 mg/L. This clinical trial aims to evaluate the safety, efficacy and the clinical and economic utility of personalised dosing of linezolid using Bayesian forecasting methods to attain pharmacokinetic/pharmacodynamic targets, known as model-informed precision dosing.Methods and analysis This is a pragmatic, multicentre, randomised, parallel, controlled, phase IV and low intervention trial. Participants will be randomly assigned 1:1 to each group (n=346 per group). Control group will receive the standard dose of linezolid. Intervention group will receive personalised dosage of linezolid based on pharmacokinetic–pharmacodynamic adjustments. The primary outcome will be the incidence of thrombocytopenia in both groups.Ethics and dissemination This protocol was approved by the Ethical Committee of the Investigation with Medicines of Galicia (code 2022/140) and authorised by the Spanish Agency for Medicines and Medical Devices. The trial is implemented in accordance with the Declaration of Helsinki and the international ethical and scientific quality standard, the Good Clinical Practice. The results will be published in peer-reviewed journals.Trial registration number EudraCT registration code: 2022-000144-30.

Introduction The smoker's narrative during smoking quitting provides insight into aspects not fully explored in daily clinical practice. The aim of the study was to analyze the smoker narrative using two types of methodologies: content analysis and grounded theory, before and after smoking cessation intervention, provided to the smoker in a specialized Smoking Cessation Unit accredited by the Spanish Society of Pneumology and Thoracic Surgery. Methods A prospective observational study of current smokers included in a tobacco cessation program between 2017 and 2020 was conducted at the Smoking Cessation Unit of Santiago de Compostela Health Area, Spain. Routine clinical variables and patient narrative data were collected. A descriptive analysis of the sample, the content of the textual corpus, and a grounded theory were performed in semi-structured interviews at baseline and at follow-up at 6 months. Results A total of 116 patients were included (mean age 55.6 ± 10.6 years; 56.9% male; mean nicotine dependence score 5.7 ± 1.6). Quantitative analysis of the narrative shows that the most frequent phrases and words are associated with smoking, nicotine craving, and predisposition for smoking cessation. After the intervention, phrases related to the manifestation of abstinence, response to pharmacological treatment, and self-perception of smoking cessation were predominant. In the qualitative analysis, the most frequent categories in the smoker's textual corpus were dependence, motivation, and emotionality, which decreased after the intervention (11.4%, 21.4%, and 9.9%, respectively) accompanied by increased satisfaction (19.2%) and the manifestation of abstinence (21.5%). Conclusions Motivation, nicotine dependence, and sensitivity to emotions are all closely intertwined in the current smoker narrative and can be modified as a consequence of treatment.

BACKGROUND: Although pulmonary rehabilitation (PR) is recommended in patients with chronic obstructive pulmonary disease (COPD), there is a scarcity of data demonstrating the cost-effectiveness and effectiveness of PR in reducing exacerbations. METHODS: A quasi-experimental study in 200 patients with COPD was conducted to determine the number of exacerbations 1 year before and after their participation in a PR program. Quality of life was measured using the COPD assessment test and EuroQol-5D. The costs of the program and exacerbations were assessed the year before and after participation in the PR program. The incremental cost-effectiveness ratio (ICER) was estimated in terms of quality-adjusted life years (QALYs). RESULTS: The number of admissions, length of hospital stay, and admissions to the emergency department decreased after participation in the PR program by 48.2%, 46.6%, and 42.5%, respectively (P < 0.001 for all). Results on quality of life tests improved significantly (P < 0.001 for the two tests). The cost of PR per patient and the cost of pre-PR and post-PR exacerbations were €1867.7 and €7895.2 and €4201.9, respectively. The PR resulted in a cost saving of €1826 (total, €365,200) per patient/year, and the gain in QALYs was+0.107. ICER was −€17,056. The total cost was

Abstract Introduction Inhaled antibiotics reduce the frequency of exacerbations. The objective was to assess the efficacy of inhaled ceftazidime in patients with non‐cystic fibrosis bronchiectasis (NCFB) and concomitant chronic bronchial infection (CBI) caused by potentially pathogenic microorganisms (PPM) other than Pseudomonas aeruginosa (PA). Material and Method Quasi‐experimental study in 21 patients with exacerbations who developed CBI by a PPM other than PA. Results Bacterial infection was resolved in 85.7% patients. Rehospitalizations, length of hospital stay, moderate exacerbations and blood levels of CRP decreased significantly. In addition, SGRQ questionnaire also decreased more than 4 points in 57.1% of the patients. Conclusion The results suggest that inhaled ceftazidime in NCFB unrelated to PA is a plausible alternative to the standard therapies used in clinical practice.

Although pleural effusion is a frequent finding in clinical practice, determining its aetiology may be challenging, and up to 20% of cases remain undiagnosed. Pleural effusion may occur secondary to a nonmalignant gastrointestinal disease. A gastrointestinal origin is confirmed based on a review of the medical history of the patient, thorough physical examination and abdominal ultrasonography. In this process, it is crucial to correctly interpret findings on pleural fluid obtained by thoracentesis. In the absence of high clinical suspicion, identifying the aetiology of this type of effusion may be difficult. Clinical symptoms will be determined by the gastrointestinal process causing pleural effusion. In this setting, correct diagnosis relies on the specialist's ability to evaluate pleural fluid appearance, test for the appropriate biochemical parameters and determine whether it is necessary or not to send a specimen for culture. The established diagnosis will determine how pleural effusion is approached. Although this clinical condition is self-limited, many cases will require a multidisciplinary approach because some effusions can only be resolved with specific therapies.

Abstract It is not known whether residential radon exposure may be linked to the development of chronic obstructive pulmonary disease (COPD) and/or have an influence on the functional characteristics or exacerbations of COPD. The aim of this study was therefore to ascertain whether there might be an association between residential radon concentrations and certain characteristics of COPD. We analyzed COPD cases drawn from a case–control study conducted in an area of high radon exposure. Data were collected on spirometric pulmonary function variables, hospital admissions, and smoking. Radon measurements were taken using alpha-track-type CR-39 detectors individually placed in patients’ homes. All statistical analyses were performed using the IBM SPSS v22 computer software program. The study included 189 COPD cases (79.4% men; median age 64 years). The median radon concentration was 157 Bq/m3. No differences were found between radon concentration and sex, age or severity of breathing obstruction as measured by FEV1%. It should be noted, however, that 48.1% of patients with FEV1% 600 Bq/m3 exhibited no different characteristics in lung function. Exposure to radon does not appear to have an influence on the clinical characteristics of smokers and ex-smokers with COPD. As exposure to residential radon increases, there is no trend towards a worsening of FEV1%. Further studies are thus needed to analyze this possible association in never-smokers with COPD.

The economic viability of the companies is a more significant gap in rural tourism. The quality standards can be a new instrument to help consolidate rural businesses, because of its positive direct and indirect effects: improve professionalism, increase the size of rural companies, protect the architecture and traditional culture, and facilitate segments of tourists of smaller size but of higher economic value. However, the interest of rural businesspeople for rural quality marks will depend on the economic benefits that they provide, at least to initially support the investment and costs of implementation. The article reviews the literature and its findings on the perceived benefits of quality standards, paying particular attention to rural accommodation. The research develops an empirical work with an extensive database. It contained the economic results obtained by a set of rural hotels in a specific region of Spain. These rural accommodations operate with a public quality standard called “Casonas Asturianas” (Old Asturian Palaces). The results provide evidence about the relationship between the quality rural standard and the economicperformance of the hotels. Also, the conclusions suggest the presence of some nuances in the self-selection bias, explicitly referring to high season tariffs.

Purpose: The aim of this study is to assess the diagnostic value of magnetic resonance imaging (MRI), alone or combined with positron emission tomography (PET), for evaluation of mediastinal disease in lymphoma in comparison with PET/computed tomography (CT). Material and methods: Eighteen prospective studies with sample size ranging between 17 and 140 patients were included in this analysis. MRI, regardless of the sequence obtained, where used for the evaluation of lymphoma. Histopathology results and clinical or imaging follow-up were used as the reference standard. Studies were excluded if the sample size was less than 15 cases or if less than 15 lymph nodes assessment were presented. Papers not reporting sufficient data were also excluded. Results: As compared to PET/CT, MRI proved to be an alternative to use in evaluation of mediastinal disease of lymphoma. MRI has high sensitivity and specificity for nodal and extranodal involvement in lymphoma and the agreement between MRI with the standard technique was high. The ALARA principle reinforces these findings because it is a radiation-free technique and its use is preferred in young population at risk of being subjected to several studies. Conclusion: MRI seems to be a promising and free-radiation alternative due to its high sensitivity and specificity, as well as its high level of agreement with the standard reference. This suggests that MRI could play a significant role in lymphoma study. Resumen: Objetivo: El objetivo de este estudio es evaluar el valor diagnóstico de la resonancia magnética (RM), sola o combinada con la tomografía por emisión de positrones (PET), para la valoración de la afectación mediastínica en el linfoma en comparación con la tomografía computarizada (TC)/PET. Material y métodos: Se incluyeron en el análisis 18 estudios prospectivos con un tamaño de muestra que oscilaba entre los 17 y los 140 pacientes. Se utilizó la resonancia magnética, independientemente de la secuencia obtenida para la evaluación del linfoma. Los resultados de histopatología y el seguimiento clínico o de imagen se utilizaron como estándar de referencia. Se excluyeron los estudios si el tamaño de la muestra era inferior a 15 casos, o si se presentaron evaluaciones de menos de 15 ganglios linfáticos. Los artículos que no proporcionaban datos suficientes también fueron excluidos. Resultados: En comparación con PET/TC, la RM demostró ser una alternativa útil en la evaluación de la afectación mediastínica del linfoma. La RM tiene una alta sensibilidad y especificidad para detectar afectación nodal y extranodal en el linfoma y la concordancia entre la RMy la técnica estándar fue alta. El principio ALARA refuerza estos hallazgos porque es una técnica libre de radiación y su uso se prefiere en la población joven en peligro de ser sometida a varios estudios. Conclusión: La RM parece ser una alternativa prometedora y libre de radiación debido a su alta sensibilidad y especificidad, así como a su alto nivel de concordancia con la referencia estándar. Esto sugiere que la RM podría desempeñar un papel importante en el estudio del linfoma.

Introduction. This study assesses the impact of an electronic physician-to-physician consultation program on the waiting list and the costs of a Pulmonology Unit. Materials and Methods. A prepost intervention study was conducted after a new ambulatory pulmonary care protocol was implemented and the capacity of the unit was adopted. In the new model, physicians at all levels of healthcare send electronic consultations to specialists. Results. In the preintervention year (2019), the Unit of Pulmonology attended 7,055 consultations (466 e-consultations and 6,589 first face-to-face visits), which decreased to 6,157 (3,934 e-consultations and 2,223 first face-to-face visits; 12.7% reduction) in the postintervention year (all were e-consultations). The mean wait time for the first appointment was 25.7 days in 2019 versus 3.2 days in 2021 (p

Understanding and sustainably managing complex environments such as marine ecosystems benefits from an integrated approach to ensure that information about all relevant components and their interactions at multiple and nested spatiotemporal scales are considered. This information is based on a wide range of ocean observations using different systems and approaches. An integrated approach thus requires effective collaboration between areas of expertise in order to improve coordination at each step of the ocean observing value chain, from the design and deployment of multi-platform observations to their analysis and the delivery of products, sometimes through data assimilation in numerical models. Despite significant advances over the last two decades in more cooperation across the ocean observing activities, this integrated approach has not yet been fully realized. The ocean observing system still suffers from organizational silos due to independent and often disconnected initiatives, the strong and sometimes destructive competition across disciplines and among scientists, and the absence of a well-established overall governance framework. Here, we address the need for enhanced organizational integration among all the actors of ocean observing, focusing on the occidental systems. We advocate for a major evolution in the way we collaborate, calling for transformative scientific, cultural, behavioral, and management changes. This is timely because we now have the scientific and technical capabilities as well as urgent societal and political drivers. The ambition of the United Nations Decade of Ocean Science for Sustainable Development (2021–2030) and the various efforts to grow a sustainable ocean economy and effective ocean protection efforts all require a more integrated approach to ocean observing. After analyzing the barriers that currently prevent this full integration within the occidental systems, we suggest nine approaches for breaking down the silos and promoting better coordination and sharing. These recommendations are related to the organizational framework, the ocean science culture, the system of recognition and rewards, the data management system, the ocean governance structure, and the ocean observing drivers and funding. These reflections are intended to provide food for thought for further dialogue between all parties involved and trigger concrete actions to foster a real transformational change in ocean observing.

Primary immunodeficiencies are a group of conditions characterized by developmental or functional alterations in the immune system caused by hereditary genetic defects. Primary immunodeficiencies may affect either the innate or the adaptive (humoral and cellular) immune system. Pulmonary complications in primary humoral deficiencies are frequent and varied and are associated with high morbidity and mortality rates. The types of complications include bronchiectasis secondary to recurrent respiratory infections and interstitial pulmonary involvement, which can be associated with autoimmune cytopenias, lymphoproliferation, and a range of immunological manifestations. Early detection is key to timely management. Immunoglobulin replacement therapy reduces the severity of disease, the frequency of exacerbations, and hospital admissions in some primary humoral deficiencies. Therefore, the presence of pulmonary disease with concomitant infectious and/or autoimmune complications should raise suspicion of primary humoral deficiencies and warrants a request for immunoglobulin determination in blood. Once diagnosis is confirmed; early immunoglobulin replacement therapy will improve the course of the disease. Further studies are needed to better understand the pathogenesis of pulmonary disease related to primary humoral deficiencies and favor the development of targeted therapies that improve the prognosis of patients.

INTRODUCTION: Diagnosis of pleural infection (PI) may be challenging. The purpose of this paper is to develop and validate a clinical prediction model for the diagnosis of PI based on pleural fluid (PF) biomarkers. METHODS: A prospective study was conducted on pleural effusion. Logistic regression was used to estimate the likelihood of having PI. Two models were built using PF biomarkers. The power of discrimination (area under the curve) and calibration of the two models were evaluated. RESULTS: The sample was composed of 706 pleural effusion (248 malignant; 28 tuberculous; 177 infectious; 48 miscellaneous exudates; and 212 transudates). Areas under the curve for Model 1 (leukocytes, percentage of neutrophils, and C-reactive protein) and Model 2 (the same markers plus interleukin-6 [IL-6]) were 0.896 and 0.909, respectively (not significant differences). However, both models showed higher capacity of discrimination than their biomarkers when used separately (P < 0.001 for all). Rates of correct classification for Models 1 and 2 were 88.2% (623/706: 160/177 [90.4%] with infectious pleural effusion [IPE] and 463/529 [87.5%] with non-IPE) and 89.2% (630/706: 153/177 [86.4%] of IPE and 477/529 [90.2%] of non-IPE), respectively. CONCLUSIONS: The two predictive models developed for IPE showed a good diagnostic performance, superior to that of any of the markers when used separately. Although IL-6 contributes a slight greater capacity of discrimination to the model that includes it, its routine determination does not seem justified.

Symptomatic malignant pleural effusion is a common clinical problem. This condition is associated with very high mortality, with life expectancy ranging from 3 to 12 months. Studies are contributing evidence on an increasing number of therapeutic options (therapeutic thoracentesis, thoracoscopic pleurodesis or thoracic drainage, indwelling pleural catheter, surgery, or a combination of these therapies). Despite the availability of therapies, the management of malignant pleural effusion is challenging and is mainly focused on the relief of symptoms. The therapy to be administered needs to be designed on a case-by-case basis considering patient’s preferences, life expectancy, tumour type, presence of a trapped lung, resources available, and experience of the treating team. At present, the management of malignant pleural effusion has evolved towards less invasive approaches based on ambulatory care. This approach spares the patient the discomfort caused by more invasive interventions and reduces the economic burden of the disease. A review was performed of the diagnosis and the different approaches to the management of malignant pleural effusion, with special emphasis on their indications, usefulness, cost-effectiveness, and complications. Further research is needed to shed light on the current matters of controversy and help establish a standardized, more effective management of this clinical problem.

Malignant pleural effusion (MPE) is common in clinical practice, and despite the existence of studies to guide clinical decisions, it often poses diagnostic and therapeutic dilemmas. Once it is diagnosed, median survival does not usually exceed 6 months. The management of these patients focuses on symptom relief since no treatments have been shown to increase survival to date. Conversely, poor management can shorten survival. The approach must be multidisciplinary and allow for individualized care. Initial diagnostic procedures should be minimally invasive and, according to the results and other factors, procedures of increasing complexity will be selecting. Likewise, the treatment of MPEs should be individualized according to factors such as type of tumor, patient functional status, means available, benefits of each procedure, or life expectancy. Currently, treatment seems to tend toward less interventional approaches, in which patients can be managed on an outpatient basis, thus minimizing both the discomfort that more aggressive approaches involve and the costs of care associated with this disease. This article reviews the pleural procedures employed in the management of MPEs with special emphasis on the indication for each one, its usefulness, benefits, and complications.

Introduction. Influenza A H1N1 community-acquired pneumonia (CAP) is a quite frequent respiratory disease. Despite being considered more serious than other CAPs, there are very few studies comparing its characteristics with noninfluenza CAP. We aim to establish the differences between pneumonia due to H1N1 virus and pneumonia not caused by H1N1 influenza virus and to determine the probability that a pneumonia is due to an H1N1 virus infection based on the most relevant variables. Methods. We used a case-control study where cases were H1N1 CAP patients with confirmed microbiological diagnosis and controls were patients with CAP admitted to hospital. H1N1 and other influenza types were discarded among controls. We calculated the probability of being a case or control using multivariate logistic regression. Results. We included 99 cases and 270 controls. Cases were younger than controls (53 vs 71 years, respectively). Mortality was much higher for H1N1 patients (13% vs 0.3%), and admission to intensive care unit was more frequent for H1N1 cases. The variables most associated with presenting H1N1 CAP were bilateral affectation on chest X-rays (OR: 5.70; 95% CI 2.69–10.40), followed by presence of arthromyalgias, with cases presenting close to three times more arthromyalgias compared to controls. Low leukocytes count and high AST values were also significantly associated with H1N1 CAP. H1N1 CAPs are characterized by bilateral affectation, low leukocyte count, presence of arthromyalgias, and high AST. Conclusions. A few and easy to obtain clinical parameters might be extremely useful to distinguish H1N1 CAP from CAPs of other origin.

Inhaled administration of ethanol in the early stages of COVID-19 would favor its location on the initial replication sites, being able to reduce the progression of the disease and improving its prognosis. Before evaluating the efficacy and safety of this novel therapeutic strategy in humans, its characterization is required. The developed 65° ethanol formulation is stable at room temperature and protected from light for 15 days, maintaining its physicochemical and microbiological properties. Two oxygen flows have been tested for its administration (2 and 3 L/min) using an automated headspace gas chromatographic analysis technique (HS-GC-MS), with that of 2 L/min being the most appropriate one, ensuring the inhalation of an ethanol daily dose of 33.6 ± 3.6 mg/min and achieving more stable concentrations during the entire treatment (45 min). Under these conditions of administration, the formulation has proven to be safe, based on histological studies of the respiratory tracts and lungs of rats. On the other hand, these results are accompanied by the first preclinical molecular imaging study with radiolabeled ethanol administered by this route. The current ethanol formulation has received approval from the Spanish Agency of Medicines and Medical Devices for a phase II clinical trial for early-stage COVID-19 patients, which is currently in the recruitment phase (ALCOVID-19; EudraCT number: 2020-001760-29).

Una de las políticas económicas utilizadas por los diversos gobiernos para el desarrollo local y regional es el fomento del emprendimiento a través de los viveros de empresas, que contribuyen a la creación de empresas, de puestos de trabajo, incrementar las tasas de supervivencia empresarial y el pago de impuestos y cotizaciones sociales a las administraciones públicas. Pero como contrapartida son consumidores de recursos ajenos, con gran dependencia del sector público. En este estudio se pretende analizar la contribución neta de estos centros de iniciativas empresariales en Galicia (España), mediante la utilización del «Modelo integral de la rentabilidad de los viveros de empresas» basado en ecuaciones estructurales.

OBJETIVO: Avaliar a exposição da população infantil à FCA em nossa comunidade e sua relação com os sintomas de asma. MÉTODOS: Foi realizado um estudo transversal usando o questionário de estudo ISAAC em crianças e adolescentes da nossa comunidade. Pelo questionário, fez-se a definição por "já ocorreu sibilância", "asma atual", "asma grave" e "asma induzida pelo exercício". O tabagismo parental foi classificado em quatro categorias mutuamente excludentes: 1) nenhum dos pais fuma; 2) somente a mãe fuma; 3) somente o pai fuma; e 4) ambos os pais fumam. Calculou-se a odds ratio da prevalência de sintomas de asma, de acordo com a exposição à FCA, usando regressão logística. RESULTADOS: Foram incluídas, no total, 10.314 crianças e 10.453 adolescentes. Mais de 51% das crianças e adolescentes foram expostos à FCA em casa. A FCA se associa a uma prevalência mais alta de sintomas de asma, particularmente se a mãe ou ambos os pais fumam. CONCLUSÕES: A prevalência da FCA continua a ser alta em nossa comunidade, embora com uma tendência para diminuição nos últimos 15 anos. A FCA se associa a uma prevalência mais alta de asma.

Objetive: To evaluate the exposure to environmental tobacco smoke (ETS) of the child- hood population in this community and its relationship with asthma symptoms. Methods: A cross-sectional study was conducted using the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire on children and adolescents in this community. The symptoms “wheezing ever”, “current asthma”, “severe asthma”, and “exercise-induced asthma” were defined by this questionnaire. Parental smoking was classified into four mutually exclusive categories: 1) no parent smokes; 2) only the mother smokes; 3) only the father smokes; and 4) both parents smoke. The odds ratio of the prevalence of asthma symptoms according to ETS exposure was calculated using logistic regression. Results: A total of 10,314 children and 10,453 adolescents were included. Over 51% of the children and adolescents were exposed to ETS at home. ETS is associated with a hig- her prevalence of asthma symptoms, particularly if the mother or both parents smoke. Conclusion: The prevalence of ETS is still high in this community, although there has been a decreasing tendency in the last 15 years. ETS is associated with higher prevalence of asthma.

INTRODUCTION: The performance of blind closed pleural biopsy (BCPB) in the study of pleural exudates is controversial.

Este artículo tiene como objetivo analizar la estructura del conocimiento turístico en España, especialmente en el ámbito regional y más particularmente describir el funcionamiento del Sistema de Información Turística de Asturias (SITA) como modelo de sistema de información turística para un espacio socioeconómico.

As the only United Nations organization specializing in ocean sciences, the Intergovernmental Oceanographic Commission (IOC) has the responsibility to promote basic marine scientific investigations globally. IOC has always given special attention to planning and forecasting new developments in ocean sciences, taking into account both the steady evolution of knowledge and fundamental changes leading to major scientific breakthroughs. Following that tradition, and in honor of IOC’s fiftieth anniversary, we focus on two distinct objectives in this article. First, we provide a glimpse of past IOC scientific achievements. Second, we share IOC’s vision for a marine science strategy for the next 15 years. For that purpose, IOC has identified three critical elements that will likely provide the scientific and technical means to redefine the future of ocean sciences: (1) science drivers, (2) ocean instrumentation and technological developments, and (3) strategic frameworks for cooperation. The third element is of particular importance because research at unprecedented geographic scales is required to improve our understanding of climate change and ecosystem functioning, including biodiversity conservation and management options. Because this effort calls for extensive national and international efforts, we also discuss the role of comprehensive international core projects.

Este yacimiento es un lugar singular. Con esta afirmación resumimos la información acumulada en 17 años de investigación. Su singularidad estriba en tres aspectos : La exclusividad de su diseño, la calidad de su construcción y la falta de materiales cotidianos. Determinar su función de uso es uno de los grandes logros, al igual que haber obtenido el valor de medida estandar usado, no solo para su construccion sino el aplicado en un terrirorio de mayor extension

After 15 years of absence, dengue reemerged in the municipality of Santiago de Cuba because of increasing migration to the area by people from disease-endemic regions, a high level of vector infestation, and the breakdown of eradication measures. The 1997 epidemic was detected early through an active surveillance system. Of 2,946 laboratory-confirmed cases, 205 were dengue hemorrhagic fever, and 12 were fatal. No deaths were reported in persons under 16 years of age. Now the epidemic is fully controlled.

Obstructive sleep apnea syndrome (OSAS) is a highly prevalent sleep disorder, characterized by repeated disruptions of breathing during sleep. This disease has many potential consequences including excessive daytime sleepiness, neurocognitive deterioration, endocrinologic and metabolic effects, and decreased quality of life. Patients with OSAS experience repetitive episodes of hypoxia and reoxygenation during transient cessation of breathing that provoke systemic effects. Furthermore, there may be increased levels of biomarkers linked to endocrine-metabolic and cardiovascular alterations. Epidemiological studies have identified OSAS as an independent comorbid factor in cardiovascular and cerebrovascular diseases, and physiopathological links may exist with onset and progression of heart failure. In addition, OSAS is associated with other disorders and comorbidities which worsen cardiovascular consequences, such as obesity, diabetes, and metabolic syndrome. Metabolic syndrome is an emerging public health problem that represents a constellation of cardiovascular risk factors. Both OSAS and metabolic syndrome may exert negative synergistic effects on the cardiovascular system through multiple mechanisms (e.g., hypoxemia, sleep disruption, activation of the sympathetic nervous system, and inflammatory activation). It has been found that CPAP therapy for OSAS provides an objective improvement in symptoms and cardiac function, decreases cardiovascular risk, improves insulin sensitivity, and normalises biomarkers. OSAS contributes to the pathogenesis of cardiovascular disease independently and by interaction with comorbidities. The present review focuses on indirect and direct evidence regarding mechanisms implicated in cardiovascular disease among OSAS patients.

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