CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

The evolution of the ventilatory ratio is a prognostic factor in mechanically ventilated COVID-19 ARDS patients

Background: Mortality due to COVID-19 is high, especially in patients requiring mechanical ventilation. The purpose of the study is to investigate associations between mortality and variables measured during the first three days of mechanical ventilation in patients with COVID-19 intubated at ICU admission. Methods: Multicenter, observational, cohort study includes consecutive patients with COVID-19 admitted to 44 Spanish ICUs between February 25 and July 31, 2020, who required intubation at ICU admission and mechanical ventilation for more than three days. We collected demographic and clinical data prior to admission; information about clinical evolution at days 1 and 3 of mechanical ventilation; and outcomes. Results: Of the 2,095 patients with COVID-19 admitted to the ICU, 1,118 (53.3%) were intubated at day 1 and remained under mechanical ventilation at day three. From days 1 to 3, PaO2/FiO2 increased from 115.6 [80.0-171.2] to 180.0 [135.4-227.9] mmHg and the ventilatory ratio from 1.73 [1.33-2.25] to 1.96 [1.61-2.40]. In-hospital mortality was 38.7%. A higher increase between ICU admission and day 3 in the ventilatory ratio (OR 1.04 [CI 1.01-1.07], p = 0.030) and creatinine levels (OR 1.05 [CI 1.01-1.09], p = 0.005) and a lower increase in platelet counts (OR 0.96 [CI 0.93-1.00], p = 0.037) were independently associated with a higher risk of death. No association between mortality and the PaO2/FiO2 variation was observed (OR 0.99 [CI 0.95 to 1.02], p = 0.47). Conclusions: Higher ventilatory ratio and its increase at day 3 is associated with mortality in patients with COVID-19 receiving mechanical ventilation at ICU admission. No association was found in the PaO2/FiO2 variation

“Mother Ireland, get off our backs”: Gender, Republicanism and State Politics in Prison Short Stories by Northern Irish Women Writers

Looking into prison short fiction, this article discusses how a number of Northern Irish women writers have challenged male-centred narratives of the Troubles. Mary Beckett, Frances Molloy and Brenda Murphy have created alternative discourses of political violence which differ from the dominant narratives of incarceration. They confront established discourses of masculinity and femininity by subverting social constructs of gender, particularly the models of the rebel-hero and Mother Ireland ingrained in the nationalist/republican traditions. Their prison short stories are excellent examples of how state politics is superseded by gender politics in women’s writing and they are also proof of an emerging gender consciousness that challenged dominant readings of the Troubles in the last decades of the twentieth century

Neurological comorbidity is a predictor of death in Covid-19 disease: A cohort study on 576 patients

[Introduction]: Prognosis of Coronavirus disease 2019 (Covid-19) patients with vascular risk factors, and certain comorbidities is worse. The impact of chronic neurological disorders (CND) on prognosis is unclear. We evaluated if the presence of CND in Covid-19 patients is a predictor of a higher in-hospital mortality. As secondary endpoints, we analyzed the association between CND, Covid-19 severity, and laboratory abnormalities during admission.[Methods]: Retrospective cohort study that included all the consecutive hospitalized patients with confirmed Covid-19 disease from March 8th to April 11th, 2020. The study setting was Hospital Clínico, tertiary academic hospital from Valladolid. CND was defined as those neurological conditions causing permanent disability. We assessed demography, clinical variables, Covid-19 severity, laboratory parameters and outcome. The primary endpoint was in-hospital all-cause mortality, evaluated by multivariate cox-regression log rank test. We analyzed the association between CND, covid-19 severity and laboratory abnormalities.[Results]: We included 576 patients, 43.3% female, aged 67.2 years in mean. CND were present in 105 (18.3%) patients. Patients with CND were older, more disabled, had more vascular risk factors and comorbidities and fewer clinical symptoms of Covid-19. They presented 1.43 days earlier to the emergency department. Need of ventilation support was similar. Presence of CND was an independent predictor of death (HR 2.129, 95% CI: 1.382–3.280) but not a severer Covid-19 disease (OR: 1.75, 95% CI: 0.970–3.158). Frequency of laboratory abnormalities was similar, except for procalcitonin and INR.[Conclusions]: The presence of CND is an independent predictor of mortality in hospitalized Covid-19 patients. That was not explained neither by a worse immune response to Covid-19 nor by differences in the level of care received by patients with CND.Peer reviewe

Procalcitonin and C-reactive protein to rule out early bacterial coinfection in COVID-19 critically ill patients

Although the prevalence of community-acquired respiratory bacterial coinfection upon hospital admission in patients with coronavirus disease 2019 (COVID-19) has been reported to be < 5%, almost three-quarters of patients received antibiotics. We aim to investigate whether procalcitonin (PCT) or C-reactive protein (CRP) upon admission could be helpful biomarkers to identify bacterial coinfection among patients with COVID-19 pneumonia. We carried out a multicentre, observational cohort study including consecutive COVID-19 patients admitted to 55 Spanish intensive care units (ICUs). The primary outcome was to explore whether PCT or CRP serum levels upon hospital admission could predict bacterial coinfection among patients with COVID-19 pneumonia. The secondary outcome was the evaluation of their association with mortality. We also conducted subgroups analyses in higher risk profile populations. Between 5 February 2020 and 21 December 2021, 4076 patients were included, 133 (3%) of whom presented bacterial coinfection. PCT and CRP had low area under curve (AUC) scores at the receiver operating characteristic (ROC) curve analysis [0.57 (95% confidence interval (CI) 0.51-0.61) and 0.6 (95% CI, 0.55-0.64), respectively], but high negative predictive values (NPV) [97.5% (95% CI 96.5-98.5) and 98.2% (95% CI 97.5-98.9) for PCT and CRP, respectively]. CRP alone was associated with bacterial coinfection (OR 2, 95% CI 1.25-3.19; p = 0.004). The overall 15, 30 and 90 days mortality had a higher trend in the bacterial coinfection group, but without significant difference. PCT ≥ 0.12 ng/mL was associated with higher 90 days mortality. Our study suggests that measurements of PCT and CRP, alone and at a single time point, are not useful for ruling in or out bacterial coinfection in viral pneumonia by COVID-19

Antimicrobial Lessons From a Large Observational Cohort on Intra-abdominal Infections in Intensive Care Units

evere intra-abdominal infection commonly requires intensive care. Mortality is high and is mainly determined by disease-specific characteristics, i.e. setting of infection onset, anatomical barrier disruption, and severity of disease expression. Recent observations revealed that antimicrobial resistance appears equally common in community-acquired and late-onset hospital-acquired infection. This challenges basic principles in anti-infective therapy guidelines, including the paradigm that pathogens involved in community-acquired infection are covered by standard empiric antimicrobial regimens, and second, the concept of nosocomial acquisition as the main driver for resistance involvement. In this study, we report on resistance profiles of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterococcus faecalis and Enterococcus faecium in distinct European geographic regions based on an observational cohort study on intra-abdominal infections in intensive care unit (ICU) patients. Resistance against aminopenicillins, fluoroquinolones, and third-generation cephalosporins in E. coli, K. pneumoniae and P. aeruginosa is problematic, as is carbapenem-resistance in the latter pathogen. For E. coli and K. pneumoniae, resistance is mainly an issue in Central Europe, Eastern and South-East Europe, and Southern Europe, while resistance in P. aeruginosa is additionally problematic in Western Europe. Vancomycin-resistance in E. faecalis is of lesser concern but requires vigilance in E. faecium in Central and Eastern and South-East Europe. In the subcohort of patients with secondary peritonitis presenting with either sepsis or septic shock, the appropriateness of empiric antimicrobial therapy was not associated with mortality. In contrast, failure of source control was strongly associated with mortality. The relevance of these new insights for future recommendations regarding empiric antimicrobial therapy in intra-abdominal infections is discussed.Severe intra-abdominal infection commonly requires intensive care. Mortality is high and is mainly determined by diseasespecific characteristics, i.e. setting of infection onset, anatomical barrier disruption, and severity of disease expression. Recent observations revealed that antimicrobial resistance appears equally common in community-acquired and late-onset hospital-acquired infection. This challenges basic principles in anti-infective therapy guidelines, including the paradigm that pathogens involved in community-acquired infection are covered by standard empiric antimicrobial regimens, and second, the concept of nosocomial acquisition as the main driver for resistance involvement. In this study, we report on resistance profiles of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterococcus faecalis and Enterococcus faecium in distinct European geographic regions based on an observational cohort study on intra-abdominal infections in intensive care unit (ICU) patients. Resistance against aminopenicillins, fluoroquinolones, and third-generation cephalosporins in E. coli, K. pneumoniae and P. aeruginosa is problematic, as is carbapenem-resistance in the latter pathogen. For E. coli and K. pneumoniae, resistance is mainly an issue in Central Europe, Eastern and South-East Europe, and Southern Europe, while resistance in P. aeruginosa is additionally problematic in Western Europe. Vancomycin-resistance in E. faecalis is of lesser concern but requires vigilance in E. faecium in Central and Eastern and South-East Europe. In the subcohort of patients with secondary peritonitis presenting with either sepsis or septic shock, the appropriateness of empiric antimicrobial therapy was not associated with mortality. In contrast, failure of source control was strongly associated with mortality. The relevance of these new insights for future recommendations regarding empiric antimicrobial therapy in intra-abdominal infections is discussed

The management of acute venous thromboembolism in clinical practice - study rationale and protocol of the European PREFER in VTE Registry

Background: Venous thromboembolism (VTE) is a major health problem, with over one million events every year in Europe. However, there is a paucity of data on the current management in real life, including factors influencing treatment pathways, patient satisfaction, quality of life (QoL), and utilization of health care resources and the corresponding costs. The PREFER in VTE registry has been designed to address this and to understand medical care and needs as well as potential gaps for improvement. Methods/design: The PREFER in VTE registry was a prospective, observational, multicenter study conducted in seven European countries including Austria, France Germany, Italy, Spain, Switzerland, and the UK to assess the characteristics and the management of patients with VTE, the use of health care resources, and to provide data to estimate the costs for 12 months treatment following a first-time and/or recurrent VTE diagnosed in hospitals or specialized or primary care centers. In addition, existing anticoagulant treatment patterns, patient pathways, clinical outcomes, treatment satisfaction, and health related QoL were documented. The centers were chosen to reflect the care environment in which patients with VTE are managed in each of the participating countries. Patients were eligible to be enrolled into the registry if they were at least 18 years old, had a symptomatic, objectively confirmed first time or recurrent acute VTE defined as either distal or proximal deep vein thrombosis, pulmonary embolism or both. After the baseline visit at the time of the acute VTE event, further follow-up documentations occurred at 1, 3, 6 and 12 months. Follow-up data was collected by either routinely scheduled visits or by telephone calls. Results: Overall, 381 centers participated, which enrolled 3,545 patients during an observational period of 1 year. Conclusion: The PREFER in VTE registry will provide valuable insights into the characteristics of patients with VTE and their acute and mid-term management, as well as into drug utilization and the use of health care resources in acute first-time and/or recurrent VTE across Europe in clinical practice. Trial registration: Registered in DRKS register, ID number: DRKS0000479

Poor timing and failure of source control are risk factors for mortality in critically ill patients with secondary peritonitis

Purpose: To describe data on epidemiology, microbiology, clinical characteristics and outcome of adult patients admitted in the intensive care unit (ICU) with secondary peritonitis, with special emphasis on antimicrobial therapy and source control. Methods: Post hoc analysis of a multicenter observational study (Abdominal Sepsis Study, AbSeS) including 2621 adult ICU patients with intra-abdominal infection in 306 ICUs from 42 countries. Time-till-source control intervention was calculated as from time of diagnosis and classified into 'emergency' (&lt; 2 h), 'urgent' (2-6 h), and 'delayed' (&gt; 6 h). Relationships were assessed by logistic regression analysis and reported as odds ratios (OR) and 95% confidence interval (CI). Results: The cohort included 1077 cases of microbiologically confirmed secondary peritonitis. Mortality was 29.7%. The rate of appropriate empiric therapy showed no difference between survivors and non-survivors (66.4% vs. 61.3%, p = 0.1). A stepwise increase in mortality was observed with increasing Sequential Organ Failure Assessment (SOFA) scores (19.6% for a value ≤ 4-55.4% for a value &gt; 12, p &lt; 0.001). The highest odds of death were associated with septic shock (OR 3.08 [1.42-7.00]), late-onset hospital-acquired peritonitis (OR 1.71 [1.16-2.52]) and failed source control evidenced by persistent inflammation at day 7 (OR 5.71 [3.99-8.18]). Compared with 'emergency' source control intervention (&lt; 2 h of diagnosis), 'urgent' source control was the only modifiable covariate associated with lower odds of mortality (OR 0.50 [0.34-0.73]). Conclusion: 'Urgent' and successful source control was associated with improved odds of survival. Appropriateness of empirical antimicrobial treatment did not significantly affect survival suggesting that source control is more determinative for outcome