[Impact of days elapsed from the onset of symptoms to hospitalization in COVID-19 in-hospital mortality: Time matters]. / Impacto de los días transcurridos desde el inicio de los síntomas hasta la hospitalización en la mortalidad hospitalaria por COVID-19: el tiempo importa.

Background: COVID-19 shows different clinical and pathophysiological stages over time. Theeffect of days elapsed from the onset of symptoms (DEOS) to hospitalization on COVID-19prognostic factors remains uncertain. We analyzed the impact on mortality of DEOS to hospital-ization and how other independent prognostic factors perform when taking this time elapsedinto account. Methods: This retrospective, nationwide cohort study, included patients with confirmed COVID-19 from February 20th and May 6th, 2020. The data was collected in a standardized online datacapture registry. Univariate and multivariate COX-regression were performed in the generalcohort and the final multivariate model was subjected to a sensitivity analysis in an earlypresenting (EP; < 5 DEOS) and late presenting (LP; ≥5 DEOS) group. Results: 7915 COVID-19 patients were included in the analysis, 2324 in the EP and 5591 in theLP group. DEOS to hospitalization was an independent prognostic factor of in-hospital mortalityin the multivariate Cox regression model along with other 9 variables. Each DEOS incrementaccounted for a 4.3% mortality risk reduction (HR 0.957; 95% CI 0.93---0.98). Regarding variationsin other mortality predictors in the sensitivity analysis, the Charlson Comorbidity Index onlyremained significant in the EP group while D-dimer only remained significant in the LP group. Conclusion: When caring for COVID-19 patients, DEOS to hospitalization should be consideredas their need for early hospitalization confers a higher risk of mortality. Different prognosticfactors vary over time and should be studied within a fixed timeframe of the disease.

Clinical Predictive Model of Multidrug Resistance in Neutropenic Cancer Patients with Bloodstream Infection Due to Pseudomonas aeruginosa.

We aimed to assess the rate and predictive factors of bloodstream infection (BSI) due to multidrug-resistant (MDR) Pseudomonas aeruginosa in neutropenic cancer patients. We performed a multicenter, retrospective cohort study including oncohematological neutropenic patients with BSI due to P. aeruginosa conducted across 34 centers in 12 countries from January 2006 to May 2018. A mixed logistic regression model was used to estimate a model to predict the multidrug resistance of the causative pathogens. Of a total of 1,217 episodes of BSI due to P. aeruginosa, 309 episodes (25.4%) were caused by MDR strains. The rate of multidrug resistance increased significantly over the study period (P = 0.033). Predictors of MDR P. aeruginosa BSI were prior therapy with piperacillin-tazobactam (odds ratio [OR], 3.48; 95% confidence interval [CI], 2.29 to 5.30), prior antipseudomonal carbapenem use (OR, 2.53; 95% CI, 1.65 to 3.87), fluoroquinolone prophylaxis (OR, 2.99; 95% CI, 1.92 to 4.64), underlying hematological disease (OR, 2.09; 95% CI, 1.26 to 3.44), and the presence of a urinary catheter (OR, 2.54; 95% CI, 1.65 to 3.91), whereas older age (OR, 0.98; 95% CI, 0.97 to 0.99) was found to be protective. Our prediction model achieves good discrimination and calibration, thereby identifying neutropenic patients at higher risk of BSI due to MDR P. aeruginosa The application of this model using a web-based calculator may be a simple strategy to identify high-risk patients who may benefit from the early administration of broad-spectrum antibiotic coverage against MDR strains according to the local susceptibility patterns, thus avoiding the use of broad-spectrum antibiotics in patients at a low risk of resistance development.

Effects of early administration of acetazolamide on the duration of mechanical ventilation in patients with chronic obstructive pulmonary disease or obesity-hypoventilation syndrome with metabolic alkalosis. A randomized trial.

BACKGROUND: Metabolic alkalosis (MA) inhibits respiratory drive and may delay weaning from mechanical ventilation (MV). MA is common in CO2-retainer patients that need MV. Acetazolamide (ACTZ) decreases serum bicarbonate concentration and stimulates respiratory drive. This study evaluated the effects of ACTZ on the duration of MV in patients with MA and COPD or obesity hypoventilation syndrome (OHS) intubated with acute respiratory failure. METHODS: Multicenter, randomized, controlled, double-blind study, with COPD or OHS patients with MV < 72 h and initial bicarbonate >28 mmol/L and pH > 7.35. Test-treatment, ACTZ 500 mg or placebo, was daily administered if pH > 7.35 and bicarbonate >26 mmol/L. Clinical, respiratory and laboratory parameters were recorded. RESULTS: 47 patients (36 men) were randomized. There were no significant differences between groups in comorbidities, baseline characteristics or arterial blood gases at inclusion. The mean difference in the duration of MV between placebo and ACTZ group was 1.3 days (95%CI, -2.1-4.8; p = 0.44). Kaplan-Meier curves showed no differences in the duration of MV (Log-Rank p = 0.41). Between-group comparison of estimated marginal means (CI 95%) during MV were, respectively: PaCO2 55 (51-59) vs 48 (47-50) mm Hg, p = 0.002; bicarbonate concentration 34 (32-35) vs 29 (28-30) mmol/L, p < 0.0001; and minute volume 9.7 (8.9-10.4) vs 10.6 (9.2-12.0) L/min, p = 0.26. There were no severe adverse effects with ACTZ administration. CONCLUSIONS: Among patients with MA and COPD or OHS, early treatment with ACTZ did not shorten significantly the duration of MV compared with placebo. TRIAL REGISTRY: clinical.trials.gov; NCT01499485; URL:.www.clinicaltrials.gov.

Application of Medical Information Systems for the detection of high risk patients: rapid care alerts. Pilot study of the ARA-Son Llàtzer Project.

OBJECTIVE: To describe the implementation of a Medical Information System (MIS) in the Critical Care Departament (CCD). DESIGN: A prospective observational cohort study was carried out. SETTING: Clinical and Surgical wards in Son Llàtzer Hospital. PATIENTS: Patients with criteria of rapid care alert (RCA) without treatment, cardiac arrest (CA), and unexpected ward deaths (UWD), during 2010. MAIN VARIABLES: Age, sex, nursing shift, nursing alert, vital signs, unplanned admission to intensive care, CA, UWD and death. RESULTS: The MIS detected 9647 episodes with RCA signs in 4020 patients (26.4 episodes/day). A total of 8547 episodes were reviewed. Sixty-five patients required rapid response by the intensive care staff; 61.5% were detected in the afternoon shift (15:00 a 22:00), and 61.5% were admitted to the CCD. Diminished consciousness (DC) and respiratory failure were the most frequent problems. The sepsis rate was 23%. We reviewed 45 CA and 35 UWD. Of the total cases of CA, 33 patients died (73.3%) and 66.7% had criteria of untreated RCA. Monitoring (P<.05) and rhythms amenable to defibrillation (P<.002) were associated to survival. As regards the UWD, 75% had criteria of untreated RCA, and 40.6% presented diminished consciousness. In the last 6 months there was a significant reduction in UWD (P=.01) CONCLUSIONS: The MIS could be a complimentary tool in the activity of the CCD to improve the prognosis of hospitalized patients.

Impact of days elapsed from the onset of symptoms to hospitalization in COVID-19 in-hospital mortality: time matters.

BACKGROUND: COVID-19 shows different clinical and pathophysiological stages over time. The effect of days elapsed from the onset of symptoms (DEOS) to hospitalization on COVID-19 prognostic factors remains uncertain. We analyzed the impact on mortality of DEOS to hospitalization and how other independent prognostic factors perform when taking this time elapsed into account. METHODS: This retrospective, nationwide cohort study, included patients with confirmed COVID-19 from February 20th and May 6th, 2020. The data was collected in a standardized online data capture registry. Univariate and multivariate COX-regression were performed in the general cohort and the final multivariate model was subjected to a sensitivity analysis in an early presenting (EP; <5 DEOS) and late presenting (LP; ≥5 DEOS) group. RESULTS: 7915 COVID-19 patients were included in the analysis, 2324 in the EP and 5591 in the LP group. DEOS to hospitalization was an independent prognostic factor of in-hospital mortality in the multivariate Cox regression model along with other 9 variables. Each DEOS increment accounted for a 4.3% mortality risk reduction (HR 0.957; 95% CI 0.93-0.98). Regarding variations in other mortality predictors in the sensitivity analysis, the Charlson Comorbidity Index only remained significant in the EP group while D-dimer only remained significant in the LP group. CONCLUSION: When caring for COVID-19 patients, DEOS to hospitalization should be considered as their need for early hospitalization confers a higher risk of mortality. Different prognostic factors vary over time and should be studied within a fixed timeframe of the disease.

Nanoinformatics: developing new computing applications for nanomedicine.

Nanoinformatics has recently emerged to address the need of computing applications at the nano level. In this regard, the authors have participated in various initiatives to identify its concepts, foundations and challenges. While nanomaterials open up the possibility for developing new devices in many industrial and scientific areas, they also offer breakthrough perspectives for the prevention, diagnosis and treatment of diseases. In this paper, we analyze the different aspects of nanoinformatics and suggest five research topics to help catalyze new research and development in the area, particularly focused on nanomedicine. We also encompass the use of informatics to further the biological and clinical applications of basic research in nanoscience and nanotechnology, and the related concept of an extended "nanotype" to coalesce information related to nanoparticles. We suggest how nanoinformatics could accelerate developments in nanomedicine, similarly to what happened with the Human Genome and other -omics projects, on issues like exchanging modeling and simulation methods and tools, linking toxicity information to clinical and personal databases or developing new approaches for scientific ontologies, among many others.

[Incidence of intravenous colistin nephrotoxicity in hospitalized patients]. / Incidencia de nefrotoxicidad inducida por colistina intravenosa en pacientes hospitalizados.

OBJECTIVE: The increase in infections with multidrug resistant bacteria has forced to return to the use of colistin, antibiotic with known nephrotoxicity. The aim of the study is to determine the incidence of colistin nephrotoxicity nowadays. METHODS: Retrospective-observational-unicentric study was collected hospitalized patients in intravenous colistin treatment during the years 2018-2019. Nephrotoxicity was defined according to the RIFLE scale. The variables to determine it were serum creatinine (sCr) and glomerular filtration (GF). The variables analyzed were age, sex, treatment duration, loading and cumulative dose, empirical/targeted treatment, chronic kidney disease, concomitant use of intravenous contrast and nephrotoxic drugs. RESULTS: A total of 90 patients (60% men) were included, with an average age of 58.2±18.1 years. The mean duration of treatment was 9±8.3 days, with an average cumulative dose of 69.8±71MU. There were no differences between sCr and GF at the beginning and end of treatment. The incidence of nephrotoxicity was 1.73 cases/100 days of treatment (prevalence of 15.56%). CONCLUSIONS: Colistin nephrotoxicity has an important incidence, without developing severe illness.

Narrative review of pediatric critical care humanization: Where we are? / Revisión narrativa sobre humanización en cuidados intensivos pediátricos: ¿dónde estamos?

The humanization of care emerges as a response to something that seems indisputable: the scientific and technological developments in Intensive Care Units. Such development has improved the care of the critically ill patient in quantitative terms, but has perhaps caused the emotional needs of patients, families and professionals to be regarded as secondary concerns. The humanization of healthcare should be discussed without confusing or discussing the humanity displayed by professionals. In this paper we review and describe the different strategic lines proposed in order to secure humanized care, and adopt a critical approach to their adaptation and current status in the field of pediatric critical care.

Main information requests of family members of patients in Intensive Care Units. / Principales demandas informativas de los familiares de pacientes ingresados en Unidades de Cuidados Intensivos.

OBJECTIVE: To compile an inventory of information requests prioritized by the family members, to find out which professionals them consider able to respond these requests, and to explore the differences in perception between family members and professionals. DESIGN: Qualitative analysis of content validation and descriptive cross-sectional study. SCOPE: 41 Spanish ICU. PARTICIPANTS: Relatives, physicians and nurses of critical patients. INTERVENTION: From an initial list of questions extracted from literature review, physicians, nurses, and relatives of critical patients incorporated issues that they considered not included. After analyzing content validity, a new list was obtained, which was again submitted to the participants' assessment to evaluate the level of importance that they assigned to each question and which professional they considered appropriate to answer it. RESULTS: most important questions for the relatives: concern about the clinical situation, measures to be taken, prognosis and information. There was a coincidence between relatives and professionals in the priority issues for families. There were significant differences in the importance given to each question: between doctors and relatives (72/82 questions), and between nurses and relatives (66/82 questions) (P<.05). For the relatives, 63% of the questions could be answered by doctors or nurses, 27% preferably by doctors and 10% by nurses. CONCLUSIONS: The most relevant issues for families were prognosis and severity, but also the need for information. Healthcare professionals tend to underestimate the importance of many of the questions that concern families. Relatives feel that most of their concerns can be resolved either by doctors or nurses.

Using web services for linking genomic data to medical information systems.

OBJECTIVES: To develop a new perspective for biomedical information systems, regarding the introduction of ideas, methods and tools related to the new scenario of genomic medicine. METHODS: Technological aspects related to the analysis and integration of heterogeneous clinical and genomic data include mapping clinical and genetic concepts, potential future standards or the development of integrated biomedical ontologies. In this clinicomics scenario, we describe the use of Web services technologies to improve access to and integrate different information sources. We give a concrete example of the use of Web services technologies: the OntoFusion project. RESULTS: Web services provide new biomedical informatics (BMI) approaches related to genomic medicine. Customized workflows will aid research tasks by linking heterogeneous Web services. Two significant examples of these European Commission-funded efforts are the INFOBIOMED Network of Excellence and the Advancing Clinico-Genomic Trials on Cancer (ACGT) integrated project. CONCLUSIONS: Supplying medical researchers and practitioners with omics data and biologists with clinical datasets can help to develop genomic medicine. BMI is contributing by providing the informatics methods and technological infrastructure needed for these collaborative efforts.

[Treatment of vancomycin-resistant Enterococcus with linezolid in paediatric hospitals]. / Tratamiento de infecciones por Enterococcus resistente a vancomicina con linezolid en un hospital pediátrico.

OBJECTIVE: To describe the use of linezolid in vancomycin-resistant Enterococcus infections in a paediatric hospital. METHOD: Retrospective, observational study of hospitalised patients at the "Juan P. Garrahan" paediatric hospital receiving linezolid for the treatment of vancomycin-resistant Enterococcus, during the period between January 2002 and July 2004. RESULTS: During 18 months, linezolid was prescribed 17 times for a total of 15 seriously ill patients. The median age was 7 years old (range: 1 month-15 years) and the median length of the treatment was 15 days, with an average hospital stay of 74 days. Infection with vancomycin-resistant Enterococcus was microbiologically documented in 11 (73.3%) patients; they all responded to treatment with linezolid with the exception of two, who died while receiving treatment. The most frequently reported adverse reactions were of a haematological nature (55.5%). CONCLUSIONS: Linezolid was effective and moderately well tolerated for the treatment of vancomycin-resistant Enterococcus in children with life-threatening infections.

Clinical efficacy of ß-lactam/ß-lactamase inhibitor combinations for the treatment of bloodstream infection due to extended-spectrum ß-lactamase-producing Enterobacteriaceae in haematological patients with neutropaenia: a study protocol for a retrospective observational study (BICAR).

INTRODUCTION: Bloodstream infection (BSI) due to extended-spectrum ß-lactamase-producing Gram-negative bacilli (ESBL-GNB) is increasing at an alarming pace worldwide. Although ß-lactam/ß-lactamase inhibitor (BLBLI) combinations have been suggested as an alternative to carbapenems for the treatment of BSI due to these resistant organisms in the general population, their usefulness for the treatment of BSI due to ESBL-GNB in haematological patients with neutropaenia is yet to be elucidated. The aim of the BICAR study is to compare the efficacy of BLBLI combinations with that of carbapenems for the treatment of BSI due to an ESBL-GNB in this population. METHODS AND ANALYSIS: A multinational, multicentre, observational retrospective study. Episodes of BSI due to ESBL-GNB occurring in haematological patients and haematopoietic stem cell transplant recipients with neutropaenia from 1 January 2006 to 31 March 2015 will be analysed. The primary end point will be case-fatality rate within 30 days of onset of BSI. The secondary end points will be 7-day and 14-day case-fatality rates, microbiological failure, colonisation/infection by resistant bacteria, superinfection, intensive care unit admission and development of adverse events. SAMPLE SIZE: The number of expected episodes of BSI due to ESBL-GNB in the participant centres will be 260 with a ratio of control to experimental participants of 2. ETHICS AND DISSEMINATION: The protocol of the study was approved at the first site by the Research Ethics Committee (REC) of Hospital Universitari de Bellvitge. Approval will be also sought from all relevant RECs. Any formal presentation or publication of data from this study will be considered as a joint publication by the participating investigators and will follow the recommendations of the International Committee of Medical Journal Editors (ICMJE). The study has been endorsed by the European Study Group for Bloodstream Infection and Sepsis (ESGBIS) and the European Study Group for Infections in Compromised Hosts (ESGICH).

Humanizar los cuidados reduce la mortalidad en el enfermo crítico / Humanizing care reduces mortality in critically ill patients

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The gamut of paracoccidioidomycosis.

Paracoccidioidomycosis is a systemic mycosis of importance in Latin America. Because of its polymorphic manifestations, it is not always suspected and patients are sometimes misdiagnosed. Case histories of patients with paracoccidioidomycosis are presented in order to illustrate its various manifestations, with emphasis on the primary pulmonary localization.

[Congenital aneurysm of the sinus of Valsalva ruptured to right ventricle with a ventricular septal defect and aortic regurgitation]. / Aneurisma congénito del seno de Valsalva roto a ventrículo derecho, comunicación interventricular e insuficiencia aórtica.

We report the case of a patient with a congenital aneurysm of the sinus of Valsalva ruptured in the right ventricle, aortic valvular regurgitation and ventricular septal defect that remained asymptomatic for many years and presented clinically with severe volume overload of the heart and congestive heart failure. We describe the anatomic, echocardiographic and angiographic findings of this unusual entity with a review of the literature.

[Acute endocarditis of the native aortic valve caused by Propionibacterium acnes]. / Endocarditis aguda sobre válvula aórtica nativa por Propionibacterium acnes.

Propionibacterium acnes is often considered to be a contaminant but it has also been found to be the principal pathogen in serious infections. P. acnes is a rare cause of infective endocarditis. It has been suggested that aortic root abscesses are caused by bacteria that are particularly virulent. The strongest risk factor for serious infections by this bacteria is the presence of foreign bodies. A case is presented in which endocarditis of a native aortic valve caused by P. acnes was associated with an aortic root abscess. Transesophageal echocardiography is particularly helpful in the diagnosis of this severe complication of infective endocarditis. The literature for P. acnes endocarditis is reviewed.

[Cardiac papillary fibroelastoma. Different forms of the clinical presentation]. / Fibroelastoma papilar cardíaco. Diferentes formas de presentación clínica.

Papillary fibroelastoma is an uncommon cardiac tumor rarely diagnosed during life. Although most fibroelastomas are incidental findings at autopsy, a few cases have been associated with cardiac symptoms that include angina, arterial embolism and sudden death. We report the case of two patients, a 35-year-old male with an acute myocardial infarction and ventricular fibrillation and a 53-year-old asymptomatic female, with cardiac masses first detected by transthoracic echocardiography. A more detailed morphological study was provided by transesophageal echocardiography. After cardiac surgery, the anatomical study demonstrated that both tumors were papillary fibroelastomas. The literature concerning papillary fibroelastoma is reviewed.

[A hydatid cyst in the vena cava inferior and right atrium with venous flow obstruction and pulmonary dissemination]. / Quiste hidatídico en vena cava inferior y aurícula derecha con obstrucción del flujo venoso y diseminación pulmonar.

We report the case of a 62-year-old female patient operated for a hepatic hydatid cyst that years later was found to have a hydatid cyst in the inferior vena cava and right atrium that was the source of disseminated pulmonary spread of the disease and occlusion of the inferior vena cava blood flow. Cardiac hydatid disease is very uncommon and is frequently associated with a poor prognosis. The literature for hydatid disease of the heart is reviewed and the clinical and echocardiographic relevant findings of this patient are discussed.