Publications by authors named "Núria Fabrellas"

40 Publications

Prevalence of SARS-CoV-2 Infection at the University of Barcelona during the Third COVID-19 Pandemic Wave in Spain.

Int J Environ Res Public Health 2021 Jun 17;18(12). Epub 2021 Jun 17.

Pharmacology Unit, Department of Pathology and Experimental Therapeutics, School of Medicine and Health Sciences, IDIBELL, University of Barcelona, L'Hospitalet de Llobregat, 08907 Barcelona, Spain.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic started in December 2019 and still is a major global health challenge. Lockdown measures and social distancing sparked a global shift towards online learning, which deeply impacted universities' daily life, and the University of Barcelona (UB) was not an exception. Accordingly, we aimed to determine the impact of the SARS-CoV-2 pandemic at the UB. To that end, we performed a cross-sectional study on a sample of 2784 UB members ( = 52,529). Participants answered a brief, ad hoc, online epidemiological questionnaire and provided a nasal swab for reverse transcription polymerase chain reaction (RT-PCR) SARS-CoV-2 analysis and a venous blood sample for SARS-CoV-2 IgG antibody assay. Total prevalence of SARS-CoV-2 infection (positive RT-PCR or positive IgG) was 14.9% (95%CI 13.3 to 17.0%). Forty-four participants (1.6%, 95%CI: 1.2-2.1%) were positive for SARS-CoV-2 RT-PCR. IgG against SARS-CoV-2 was observed in 12.8% (95%CI: 11.6-14.1%) of participants. Overall, while waiting for population vaccination and/or increased herd immunity, we should concentrate on identifying and isolating new cases and their contacts.
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June 2021

Evaluation of Safety and Efficacy of ReHub in Patients Who Underwent Primary Total Knee Arthroplasty: Study Protocol for a Randomized Controlled Trial.

Int J Surg Protoc 2021 Apr 19;25(1):34-41. Epub 2021 Apr 19.

Clinic Institute of Medical and Surgical Specialties (ICEMEQ), Knee Unit, Hospital Clínic of Barcelona, C.Villarroel 170, 08036, Barcelona, Spain.

Background: Total Knee Arthroplasty (TKA) is an intervention that can significantly improve the quality of life of patients with advanced knee osteoarthritis. Early start of rehabilitation and its continuation at home once the patient is discharged are key factors for the success of the process.This study aims to assess the effectiveness of a home-based telerehabilitation solution (ReHub) on improving functional capacity and clinical outcomes for patients who underwent TKA.

Methods/design: The study is a randomized, open-label with blinded outcome assessor, parallel assignment clinical trial with a sample size of 52 patients that is conducted according to the SPIRIT recommendations. After the TKA intervention, the patients are randomly allocated to the control group or the experimental group with a 1:1 ratio. Both groups follow a Fast Track recovery protocol which includes discharge after 2-3 days from surgery, a daily plan of 5 exercises for autonomous rehabilitation and domiciliary visits by a physiotherapist starting approximately 2 weeks after surgery. The experimental group uses the sensor-based telerehabilitation system ReHub to perform the exercises. The primary outcome measure is the range of motion of the knee. Secondary outcomes include physical performance, quality of life, pain intensity, muscle strength, treatment adherence and satisfaction with the ReHub system. The outcomes assessment is performed at hospital discharge (baseline), at stitch removal (2 weeks after baseline) and 2 weeks after stitch removal (4 weeks after baseline).The study conforms to the guidelines of the Declaration of Helsinki and was approved by the hospital's ethics committee.

Discussion: The study will address an important gap in the evidence base by reporting the effectiveness of an affordable and low-cost home-based telerehabilitation solution in patients who underwent TKA.

Ethics And Dissemination: The study was approved by the hospital's ethics committee ("Comité Ético de Investigación Clínica del HCB", reg. HCB/2019/0571). The trial was registred at (NCT04155957). The results of this study will be published in peer-reviewed journals as well as national and international conferences.

Trial Registration: NCT04155957 (

Highlights: Assessing a home-based telerehabilitation solution effectiveness in knee surgery.In situations such as the CoVid-19 pandemic, it is a resolutive intervention method.Telerehabilitation is an alternative to conventional face-to-face physical therapy.This system is far less demanding in terms of human resources.Range of motion assessment is the primary outcome measure.
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April 2021

Implementing dedicated education units in 6 European undergraduate nursing and midwifery students clinical placements.

BMC Nurs 2021 Apr 13;20(1):61. Epub 2021 Apr 13.

Hospital Clinic de Barcelona, Barcelona, Spain.

Background: Undergraduate students' clinical experience, working directly with patients and the healthcare team is essential to ensure students acquire the necessary competence for practice. There are differences in the quality of clinical environments and in students' clinical placement experiences and not all clinical sites are optimal learning environments. The Dedicated Education Unit clinical education model allows students to develop the practical knowledge, skills and professionalism they will need as nurses/midwives.

Methods: We employed the Consolidated Framework for Implementation Research to identify and compare barriers and facilitators in the implementation of the Dedicated Education Unit in 6 European undergraduate nursing/midwifery student clinical placement settings and to describe the experience of nurses/midwives involved in the Dedicated Education Unit model implementation and evaluation. A pre-post implementation interpretive assessment was based on participants' responses to the Consolidated Framework for Implementation Research construct questions.

Results: Although Dedicated Education Unit model implementation in our project was heterogeneous, no main implementation barriers were perceived. Qualitative data showed that educational-service collaboration, including a focus on mutual goals, organizational communication and networking, satisfaction of educational and healthcare professionals, and the establishment of a safe space for professional discussion and feedback, were considered facilitators.

Conclusions: This study describes the key elements guiding educational and healthcare stakeholders in Dedicated Education Unit implementation, engaging participants in the entire process, and offering other organizations the opportunity to consider the benefits of this clinical education model.
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April 2021

Interaction between metabolic syndrome and alcohol consumption, risk factors of liver fibrosis: A population-based study.

Liver Int 2021 07 11;41(7):1556-1564. Epub 2021 Mar 11.

Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Barcelona, Spain.

Background And Aims: Alcohol and metabolic syndrome (MS) coexist frequently as cofactors of liver disease. Previous studies suggest a deleterious effect of MS in advanced alcohol-related liver disease (ArLD). However, it is unknow whether MS can increase the risk of liver fibrosis in early stages of ArLD. The aim of this study was to investigate the effect of MS on liver fibrosis in subjects with alcohol consumption from a population-based cohort.

Methods: The number of subjects include 1760(58%) of 3014 who were randomly selected from the community consumed alcohol and were classified as current drinkers, divided in moderate (n = 1222) or high-risk drinkers (n = 275) (>21 units/week men, >14 units/week women for high-risk drinkers), or former drinkers (n = 263). Liver fibrosis was estimated by measuring liver stiffness(LS) with transient elastography (TE).

Results: Prevalence of significant LS using cutoff values of TE of 8 and 9.1kPa was increased in high-risk compared with moderate or former drinkers and lifetime abstainers. In subjects with alcohol consumption, LS was associated with male gender, AST, ALT, years of consumption, and MS. In high-risk drinkers, MS and intensity of consumption were the only factors associated with significant LS (OR 3.7 and 4.6 for LS ≥ 8 kPa and 3.9 and 9.2 kPa for LS ≥ 9.1 kPa, respectively). Presence of significant liver fibrosis in the liver biopsy was higher among high-risk as compared with moderate or former drinkers.

Conclusion: MS increases the risk of liver fibrosis in subjects with alcohol consumption. Among high-risk drinkers, only MS and consumption of high amount of alcohol are associated with risk of liver fibrosis.
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July 2021

Paediatric nursing clinical competences in primary healthcare: A systematic review.

J Adv Nurs 2021 Jun 16;77(6):2662-2679. Epub 2021 Feb 16.

School of Nursing, Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain.

Aims: To identify and critically appraise the available evidence on paediatric nurses' clinical competencies performed autonomously regarding disease prevention and health promotion activities for children and adolescents in primary healthcare worldwide.

Design: A systematic review design in accordance with the Preferred Reporting Items Systematic Reviews and Meta-Analyses statement.

Data Sources: The search was conducted through MEDLINE (PubMed), Cumulative Index to Nursing and Allied Health Literature, SCOPUS, The Cochrane Library, Scientific Electronic Library Online, Web of Science and The Joanna Briggs Institute EBP (Ovid) databases. The grey literature was reviewed at OpenGrey. Additional studies were located through a references list of selected studies identified on first search.

Review Methods: Database search employed MeSH terms: (paediatric nursing) AND (primary healthcare) AND ((clinical skills) OR (clinical competences)). Studies published from inception to October 2019 exploring paediatric nurses' clinical competencies in primary healthcare were eligible for inclusion. No language restrictions were applied in the main search. Selection was made by two reviewers independently. Three independent reviewers assessed the methodological quality of included studies.

Results: Eighteen studies were included from six countries. The most common nursing competencies independently performed identified and described in studies were Health education and advice, Child and adolescent health and development assessment, Immunizations and Child health checks.

Conclusion: Studies describe clinical competencies of nurses in children care. No consistent scientific evidence is available about clinical competencies of paediatric nurses performed autonomously in primary care.

Impact: Few scientific studies identifying and assessing nurses' child primary healthcare skills were found and therefore recorded. Studies describe nurses' clinical skills in childhood, but results do not show firm consistency assessing their practice scope. Health policy-makers should encourage the development of nurses' competencies if they wish to preserve quality and equity of healthcare services to children. Therefore, the first step is to identify the autonomous competencies of paediatric nurses in primary care.
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June 2021

From NAFLD to MAFLD: Nurse and allied health perspective.

Liver Int 2021 04 2;41(4):683-691. Epub 2021 Feb 2.

Department of Hepatology, Gastroenterology and Endemic Medicine, Faculty of Medicine, Beni-Suef University, Beni-Suef, Egypt.

Fatty liver disease associated with metabolic dysfunction is the most prevalent liver disease worldwide, though both patient and health professional still lack awareness of it. An international consensus panel has produced what is sure to be an influential report renaming the disease from non-alcoholic fatty liver disease (NAFLD) to metabolic (dysfunction) associated fatty liver disease (MAFLD) and suggesting how the disease should be diagnosed. This viewpoint explores the call from the perspective of nurse and allied health practitioners. This group have raised serious concerns on the existing nomenclature, which labels the disease as NAFLD, and its diagnostic criteria, including provoking nurse role confusion and representing a major barrier to various key aspects; patient-nurse communications, patient awareness, partnership working, motivation of patients to undertake lifestyle changes and multiple health behaviour change promotion and nurse-led clinics. Therefore, they are enthusiastically supportive of this call to reframe the disease that we believe will ultimately have a positive impact on nurse-patient communication, and through this, improve patient care and quality of life and reduce burden on health system.
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April 2021

Hyperkalemia influences the outcome of patients with cirrhosis with acute decompensation (AD) and acute-on-chronic liver failure (ACLF).

Dig Liver Dis 2021 Jun 11;53(6):738-745. Epub 2021 Jan 11.

Liver Unit, Hospital Clinic, Spain; Institut d'Investigacions Biomediques August Pi I Sunyer (IDIBAPS), y Centro de Investigaciones en Red Hepaticas y Digestivas (CIBERehd), Barcelona, Catalonia, Spain; Faculty of Medicine and health sciences, University of Barcelona. Electronic address:

Introduction: The presence of hyperkalemia in different clinical scenarios has been described as a risk factor for mortality. Information about this electrolyte disorder in patients with cirrhosis is limited and there are no data in patients with acute-on-chronic liver failure (ACLF).

Aim: The aim of this study was to investigate whether hyperkalemia is a risk factor for mortality in patients with cirrhosis and acute decompensation (AD) with and without ACLF.

Methods: We performed an analysis of the Chronic Liver Failure Consortium CANONIC database in 1,314 consecutive patients admitted to 29 European centers with AD both with and without associated ACLF (294 and 1020 respectively). Hyperkalemia was defined as serum potassium ≥ 5.0 mEq/L. All patients had at least one valid measure of serum potassium from admission and/or through the whole hospitalization.

Results: 1314 patients were admitted with AD and 294 of them had ACLF at admission. Prevalence of hyperkalemia was significantly higher in ACLF versus AD (22.4% and 8.6% respectively, p<0.001). Hyperkalemia was associated with an increased 90, 180 and 360-day mortality risk in ACLF compared to AD (HR 10 vs 2.3 at 90-day p<0.001, 8.9 vs 3.1 at 180-day, p<0.001 and 5.8 vs 3.8 at 360-day, p<0.001). In a multivariate analysis, the presence of hyperkalemia during admission was independently associated with 90-day mortality [HR 2.4 (1.7 - 3.4)]. Variability of potassium between two valid measures ≥ 0.9 mg/dl was always also associated with a higher mortality rate. Addition of hyperkalemia to MELD score (MELD-K model) improved the accuracy to predict 90-day mortality risk.

Conclusions: Hyperkalemia is an independent risk factor of mortality in patients with AD and ACLF. Addition of hyperkalemia to the MELD score improves diagnostic accuracy to predict 90-day mortality in patients with AD and ACLF.
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June 2021

Experiences of nursing students as healthcare aid during the COVID-19 pandemic in Spain: A phemonenological research study.

Nurse Educ Today 2021 Feb 17;97:104711. Epub 2020 Dec 17.

Hospital Clinic of Barcelona, Spain; University of Barcelona (Campus Clinic Nursing School), Spain. Electronic address:

Background: The coronavirus disease (COVID-19) pandemic has caused a worldwide health and social crisis directly impacting the healthcare system. Hospitals had to rearrange its structure to meet clinical needs. Spain has been experiencing a shortage of working nurses. Student nurses in their last year at university were employed to help the National Health System respond to the COVID-19 crisis.

Aim: The aim of this study was to explore and understand the experience of nursing students' roles as healthcare aid in responding to the COVID-19 crisis.

Methods: A qualitative phenomenology design was used to explore undergraduate nursing students' perceptions of their experiences as HAs during the COVID-19 outbreak. Open face-to-face interviews were conducted to nursing students (n = 10) in May 2020. Data was analyzed using the hermeneutic interpretative approach.

Results: All participants were women aged between 21 and 25 years. Seven main themes emerged: learning, ambivalent emotions and adaptation were classified at a personal level; teamwork, patient communication, and unclear care processes were categorized under hospital structure; and coping mechanisms were part of external factors.

Conclusions: Orientation, follow-up, and emotional support in crisis situations are key to unexperienced healthcare workers overcoming stressful emotions. Previous academic education and training may help novice future nurses feel more confident about their tasks and responsibilities as well as improve patient outcomes, resource management, and staff safety.
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February 2021

Effective academic-practice partnership models in nursing students' clinical placement: A systematic literature review.

Nurse Educ Today 2020 Dec 5;95:104582. Epub 2020 Sep 5.

Hospital Clinic of Barcelona, Barcelona, Spain. Electronic address:

Objectives: This systematic review examines the effectiveness of academic-practice partnership models which include clinical faculty and clinical mentor roles in improving nursing students' clinical learning when compared with traditional models.

Review Methods: PubMed, CINAHL, PsycINFO and Cochrane Library were searched to locate Randomized Control Trials and quasi-experimental studies published from 1999 to 2020. The Joanna Briggs Institute critical appraisal tools were used to ensure methodological quality.

Results: Fourteen studies were included in the review. The Collaborative Teaching Model and the Dedicated Education Unit model were tested in randomized controlled trials. Dedicated Education Unit, Dedicated Education Centre, Clinical Education Units, Education Partnership model, Collaborative educational-practice model and Collaborative clinical practicum model were evaluated in four experimental studies and ten quasi-experimental studies. Studies did not include patient participation, and staff and faculty had anecdotal presence.

Conclusion: There is limited evidence on the effectiveness of academic-practice partnership models. However, the complementary roles of clinical faculty and clinical mentor, in addition to education and health institutions managers commitment could successfully facilitate students' clinical learning.
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December 2020

Alterations in Gut Microbiome in Cirrhosis as Assessed by Quantitative Metagenomics: Relationship With Acute-on-Chronic Liver Failure and Prognosis.

Gastroenterology 2021 01 14;160(1):206-218.e13. Epub 2020 Sep 14.

Liver Unit, Hospital Clínic de Barcelona, Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigacion en Red de Enfermedades Hepaticas y Digestivas (CIBEReHD), Madrid, Spain. Electronic address:

Background And Aims: Cirrhosis is associated with changes in gut microbiome composition. Although acute-on-chronic liver failure (ACLF) is the most severe clinical stage of cirrhosis, there is lack of information about gut microbiome alterations in ACLF using quantitative metagenomics. We investigated the gut microbiome in patients with cirrhosis encompassing the whole spectrum of disease (compensated, acutely decompensated without ACLF, and ACLF). A group of healthy subjects was used as control subjects.

Methods: Stool samples were collected prospectively in 182 patients with cirrhosis. DNA library construction and sequencing were performed using the Ion Proton Sequencer (ThermoFisher Scientific, Waltham, MA). Microbial genes were grouped into clusters, denoted as metagenomic species.

Results: Cirrhosis was associated with a remarkable reduction in gene and metagenomic species richness compared with healthy subjects. This loss of richness correlated with disease stages and was particularly marked in patients with ACLF and persisted after adjustment for antibiotic therapy. ACLF was associated with a significant increase of Enterococcus and Peptostreptococcus sp and a reduction of some autochthonous bacteria. Gut microbiome alterations correlated with model for end-stage liver disease and Child-Pugh scores and organ failure and was associated with some complications, particularly hepatic encephalopathy and infections. Interestingly, gut microbiome predicted 3-month survival with good stable predictors. Functional analysis showed that patients with cirrhosis had enriched pathways related to ethanol production, γ-aminobutyric acid metabolism, and endotoxin biosynthesis, among others.

Conclusions: Cirrhosis is characterized by marked alterations in gut microbiome that parallel disease stages with maximal changes in ACLF. Altered gut microbiome was associated with complications of cirrhosis and survival. Gut microbiome may contribute to disease progression and poor prognosis. These results should be confirmed in future studies.
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January 2021

Spanish Validation of the "User Reported Measure of Care Coordination" Questionnaire for Older People with Complex, Chronic Conditions.

Int J Environ Res Public Health 2020 09 11;17(18). Epub 2020 Sep 11.

Department of Public Health, Mental Health and Perinatal Nursing, Universitat de Barcelona, 08907 Barcelona, Spain.

Introduction: Older people with complex, chronic conditions often receive insufficient or inefficient care provision, and few instruments are able to measure their perception of care provision. The "User Reported Measure of Care Coordination" instrument has been satisfactorily used to evaluate chronic care provision and integration. The aim of this study is to validate this instrument in Spanish.

Methods: The questionnaire was adapted and validated in two phases: translation and cultural adaptation of the questionnaire and psychometric property measurement. Study population were chronic care conditions patients.

Results: A total of 332 participants completed test re-test as part of the questionnaire validation process. The final version of the questionnaire had 6 domains: Health and Well-being (D1), Health day to day (D2), Social Services (D3), Planned Care (D4), Urgent Care (D5), and Hospital Care (D6). Cronbach's alpha for the overall questionnaire was 0.86, indicating good internal consistency. When analyzing each domain, only Planned Care (D4) and Urgent Care (D5) had Cronbach's Alphas slightly lower than 0.7, although this could be related to the low number of items in each domain. A good temporal stability was observed for the distinct subscales and items, with intraclass correlation coefficients varying from 0.412 to 0.929 ( < 0.05).

Conclusion: The adapted version of the "User Reported Measure of Care Coordination" into Spanish proved to be a practical tool for use in our daily practice and an efficient instrument for assessment of care coordination in chronic, complex conditions in older people across services and levels of care.
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September 2020

Acuity, nurse staffing and workforce, missed care and patient outcomes: A cluster-unit-level descriptive comparison.

J Nurs Manag 2020 Nov 19;28(8):2216-2229. Epub 2020 Jun 19.

Nursing Research Group, IDIBELL, Bellvitge Biomedical Research Institute, Barcelona, Spain.

Aim: To compare the patient acuity, nurse staffing and workforce, missed nursing care and patient outcomes among hospital unit-clusters.

Background: Relationships among acuity, nurse staffing and workforce, missed nursing care and patient outcomes are not completely understood.

Method: Descriptive design with data from four unit-clusters: medical, surgical, combined and step-down units. Descriptive statistics were used to compare acuity, nurse staffing coverage, education and expertise, missed nursing care and selected nurse-sensitive outcomes.

Results: Patient acuity in general (medical, surgical and combined) floors is similar to step-down units, with an average of 5.6 required RN hours per patient day. In general wards, available RN hours per patient day reach only 50% of required RN hours to meet patient needs. Workforce measures are comparable among unit-clusters, and average missed nursing care is 21%. Patient outcomes vary among unit-clusters.

Conclusion: Patient acuity is similar among unit-clusters, while nurse staffing coverage is halved in general wards. While RN education, expertise and missed care are comparable among unit-clusters, mortality, skin injuries and risk of family compassion fatigue rates are higher in general wards.

Implications For Nursing Management: Nurse managers play a pivotal role in hustling policymakers to address structural understaffing in general wards, to maximize patient safety outcomes.
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November 2020

Psychological Burden of Hepatic Encephalopathy on Patients and Caregivers.

Clin Transl Gastroenterol 2020 04;11(4):e00159

School of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain.

Objectives: Hepatic encephalopathy (HE) is common in advanced cirrhosis and is characterized by marked neuropsychiatric abnormalities. However, despite its severity and effects on brain function, the impact of HE on psychological status of patients has not been adequately assessed. The aim of this study was to evaluate the effect of HE on psychological status of patients and their informal caregivers.

Methods: Fifteen patients with cirrhosis and episodic or persistent HE and their corresponding informal caregivers were included. Semistructured interviews were performed in patients and caregivers. Quality of life (QoL) was assessed by the short-form 36 in both patients and caregivers, and the Zarit burden score was measured in caregivers. The analysis of interviews was performed using qualitative methodology.

Results: HE causes a major psychological impact on patients with HE. The first episode of HE caused a very significant impact that was reported with deep feelings, mainly of fear, anger, misery, anxiety, and sorrow, which persisted with time. Symptoms causing more psychological impact on patients were impaired ability to walk and speak. All effects were associated with a marked impairment in QoL. The psychological impact was also marked in caregivers who had a major burden, as assessed by the Zarit score. Moreover, QoL, particularly the mental component score, was markedly impaired in caregivers in intensity similar to that of patients.

Discussion: HE has a profound psychological impact on patients and their informal caregivers, associated with a marked negative influence on QoL. The psychological effects of HE on patients and caregivers should be evaluated and treated.
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April 2020

Development of chronic kidney disease after acute kidney injury in patients with cirrhosis is common and impairs clinical outcomes.

J Hepatol 2020 06 15;72(6):1132-1139. Epub 2020 Jan 15.

Liver Unit, Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Catalonia, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEReHD), Barcelona, Catalonia, Spain; Faculty of Medicine and Life Sciences, University of Barcelona, Barcelona, Catalonia, Spain. Electronic address:

Background & Aims: Acute kidney injury (AKI) is common in cirrhosis and is associated with poor prognosis. In patients who survive after AKI, it is not known whether the acute injury leads to chronic impairment of kidney function (chronic kidney disease [CKD]). The aim of the study was to determine the frequency of CKD at 3 months after an AKI episode and its effects on patient outcomes.

Methods: Patients admitted for complications of cirrhosis during a 6.5-year period were evaluated using the same protocol, with assessment of kidney function at regular intervals during and after hospitalization. CKD was defined as estimated glomerular filtration rate (eGFR) <60 ml/min/1.73m at 3 months after AKI.

Results: A total of 409 patients (168 with AKI and 241 without AKI) were included. After 3 months, 97 patients with AKI and 188 patients without AKI had survived. Of the 97 patients with AKI, 24 had developed CKD at 3 months compared to only 2 of the 188 patients without AKI (25% vs. 1%, odds ratio 31; p <0.0001). Risk factors independently associated with CKD were nosocomial AKI and severity of AKI (stage ≥1B). At diagnosis of CKD, all patients had stage 3A CKD and one-quarter of them progressed to stages 3B and 4 after 1 year. The transition from AKI to CKD was associated with an increased rate of 3-month hospital readmission, increased frequency of AKI, bacterial infections, ascites, and refractory ascites and a trend towards a higher need for liver transplantation. Transplant-free survival was not impaired.

Conclusions: CKD frequently develops in patients with cirrhosis who survive AKI and has a negative impact on relevant clinical outcomes. The transition from AKI to CKD is common and should be considered a high-risk condition in patients with cirrhosis.

Lay Summary: Episodes of acute impairment of kidney function are common in patients with cirrhosis. This study shows that the development of chronic impairment of kidney function is frequent in patients surviving these acute episodes and that it is associated with a higher risk of developing other complications of cirrhosis and to a higher rate of 3-month hospital readmissions.
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June 2020

Nursing Care of Patients With Cirrhosis: The LiverHope Nursing Project.

Hepatology 2020 03;71(3):1106-1116

Department of Nursing, Mayo Clinic, Rochester, MN.

Cirrhosis is a complex disease that is associated with disturbances in different organs besides the liver, including kidneys, heart, arterial circulation, lungs, gut, and brain. As a consequence, patients develop a number of complications that result in frequent hospital admissions and high morbidity and mortality. Patients with cirrhosis require constant and rigorous monitoring both in and outside the hospital. In this context, the role of nurses in the care of patients with cirrhosis has not been sufficiently emphasized and there is very limited information about nursing care of patients with cirrhosis compared with other chronic diseases. The current article provides a review of nursing care for the different complications of patients with cirrhosis. Nurses with specific knowledge on liver diseases should be incorporated into multidisciplinary teams managing patients with cirrhosis, both inpatient and outpatient. Conclusion: Nurses play an important role in the management and prevention of complications of the disease and improvement in patients' quality of life and bridge the gap between clinicians and families, between primary care and hospital care, and provide medical education to patients and caregivers.
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March 2020

Predicting patient acuity according to their main problem.

J Nurs Manag 2019 Nov 30;27(8):1845-1858. Epub 2019 Oct 30.

Nursing Research Group, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Catalonia, Spain.

Aim: To assess the ability of the patient main problem to predict acuity in adults admitted to hospital wards and step-down units.

Background: Acuity refers to the categorization of patients based on their required nursing intensity. The relationship between acuity and nurses' clinical judgment on the patient problems, including their prioritization, is an underexplored issue.

Method: Cross-sectional, multi-centre study in a sample of 200,000 adults. Multivariate analysis of main problems potentially associated with acuity levels higher than acute was performed. Distribution of patients and outcome differences among acuity clusters were evaluated.

Results: The main problems identified are strongly associated with patient acuity. The model exhibits remarkable ability to predict acuity (AUC, 0.814; 95% CI, 0.81-0.816). Most patients (64.8%) match higher than acute categories. Significant differences in terms of mortality, hospital readmission and other outcomes are observed (p < .005).

Conclusion: The patient main problem predicts acuity. Most inpatients require more intensive than acute nursing care and their outcomes are adversely affected.

Implications For Nursing Management: Prospective measurement of acuity, considering nurses' clinical judgments on the patient main problem, is feasible and may contribute to support nurse management workforce planning and staffing decision-making, and to optimize patients, nurses and organizational outcomes.
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November 2019

Transient elastography for screening of liver fibrosis: Cost-effectiveness analysis from six prospective cohorts in Europe and Asia.

J Hepatol 2019 12 27;71(6):1141-1151. Epub 2019 Aug 27.

Department of Medicine II, Saarland University Medical Center, Saarland University, Homburg, Germany. Electronic address:

Background & Aims: Non-alcoholic fatty liver disease and alcohol-related liver disease pose an important challenge to current clinical healthcare pathways because of the large number of at-risk patients. Therefore, we aimed to explore the cost-effectiveness of transient elastography (TE) as a screening method to detect liver fibrosis in a primary care pathway.

Methods: Cost-effectiveness analysis was performed using real-life individual patient data from 6 independent prospective cohorts (5 from Europe and 1 from Asia). A diagnostic algorithm with conditional inference trees was developed to explore the relationships between liver stiffness, socio-demographics, comorbidities, and hepatic fibrosis, the latter assessed by fibrosis scores (FIB-4, NFS) and liver biopsies in a subset of 352 patients. We compared the incremental cost-effectiveness of a screening strategy against standard of care alongside the numbers needed to screen to diagnose a patient with fibrosis stage ≥F2.

Results: The data set encompassed 6,295 participants (mean age 55 ± 12 years, BMI 27 ± 5 kg/m, liver stiffness 5.6 ± 5.0 kPa). A 9.1 kPa TE cut-off provided the best accuracy for the diagnosis of significant fibrosis (≥F2) in general population settings, whereas a threshold of 9.5 kPa was optimal for populations at-risk of alcohol-related liver disease. TE with the proposed cut-offs outperformed fibrosis scores in terms of accuracy. Screening with TE was cost-effective with mean incremental cost-effectiveness ratios ranging from 2,570 €/QALY (95% CI 2,456-2,683) for a population at-risk of alcohol-related liver disease (age ≥45 years) to 6,217 €/QALY (95% CI 5,832-6,601) in the general population. Overall, there was a 12% chance of TE screening being cost saving across countries and populations.

Conclusions: Screening for liver fibrosis with TE in primary care is a cost-effective intervention for European and Asian populations and may even be cost saving.

Lay Summary: The lack of optimized public health screening strategies for the detection of liver fibrosis in adults without known liver disease presents a major healthcare challenge. Analyses from 6 independent international cohorts, with transient elastography measurements, show that a community-based risk-stratification strategy for alcohol-related and non-alcoholic fatty liver diseases is cost-effective and potentially cost saving for our healthcare systems, as it leads to earlier identification of patients.
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December 2019

Neutrophil Gelatinase-Associated Lipocalin for Assessment of Acute Kidney Injury in Cirrhosis: A Prospective Study.

Hepatology 2019 07 25;70(1):319-333. Epub 2019 Apr 25.

Liver Unit, Hospital Clínic, Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Catalonia, Spain.

Kidney biomarkers appear to be useful in differential diagnosis between acute tubular necrosis (ATN) and other types of acute kidney injury (AKI) in cirrhosis, particularly hepatorenal syndrome (HRS-AKI). Distinction is important because treatment is different. However, kidney biomarkers are still not used in clinical practice. The aim of the current study was to investigate the accuracy of several biomarkers in differential diagnosis of AKI and in predicting kidney outcome and patient survival. This was a prospective study of 320 consecutive cases of AKI in patients hospitalized for decompensated cirrhosis. Evaluation of AKI was made with a diagnostic algorithm that included identification and removal/treatment of precipitating factors and albumin administration (1 g/kg for 2 days) to patients with AKI stage 1B or greater. Urinary neutrophil gelatinase-associated lipocalin (NGAL), monomeric NGAL (mNGAL), interleukin-18, and standard biomarkers were measured at diagnosis and on days 3, 7, and 14. Of the 320 cases, 153 were hypovolemia-induced AKI (48%), 93 were HRS-AKI (29%), 39 were ATN (12%), and 35 were due to miscellaneous causes (11%). Among all biomarkers, urinary NGAL measured at day 3 had the greatest accuracy for differential diagnosis between ATN and other types of AKI (area under the receiver operating characteristic curve, 0.87; 95% confidence interval, 0.78-0.95). The cutoff with the best predictive accuracy for ATN diagnosis was 220 µg/g creatinine. Progression of AKI during hospitalization was associated with persistently high NGAL levels, and NGAL was an independent predictive factor of AKI progression. Likewise, NGAL was also an independent predictive factor of 28-day mortality together with Model for End-Stage Liver Disease score. Conclusion: These results support the use of NGAL in clinical practice within the context of a diagnostic algorithm for differential diagnosis of AKI and outcome prediction in cirrhosis.
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July 2019

Characterization of inflammatory response in hepatorenal syndrome: Relationship with kidney outcome and survival.

Liver Int 2019 07 17;39(7):1246-1255. Epub 2019 Feb 17.

Liver Unit, Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain.

Background: Several lines of evidence indicate that decompensated cirrhosis is characterized by the presence of systemic inflammation. Hepatorenal syndrome (HRS-AKI) is a unique type of renal failure that occurs at late stages of cirrhosis. However, confirmation of the presence and significance of such inflammatory response in HRS-AKI is lacking.

Aim And Methods: To characterize the systemic inflammatory response, as estimated by measuring a large number of cytokines, in 161 patients hospitalized for an acute decompensation of cirrhosis: 44 patients without acute kidney injury (AKI), 63 patients with hypovolaemia-induced AKI and 58 patients with HRS-AKI.

Results: HRS-AKI was characterized by an altered cytokine profile compared to the other two groups, particularly IL-6, IL-8, TNF-α, VCAM-1, fractalkine and MIP-1α. The inflammatory response was not related to presence of bacterial infection, concomitant acute-on-chronic liver failure or severity of renal dysfunction. Patients who responded to terlipressin and albumin had only a decrease in TNF-α and RANTES after treatment without changes in other cytokines. Interestingly, patients with persistent HRS-AKI had higher levels of IP-10 and VCAM-1 compared to those with resolution of HRS-AKI. VCAM-1 was also an independent predictor of 3-month mortality. A systems biology analysis approach showed that the inflammatory status of HRS-AKI was similar to that of chronic nonhepatic inflammatory conditions, such as lupus erythematosus or inflammatory bowel disease.

Conclusion: Hepatorenal syndrome is characterized by a marked systemic inflammatory state, reminiscent of that of nonhepatic inflammatory diseases, that correlates with patient outcomes.
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July 2019

Prevalence of hepatic steatosis as assessed by controlled attenuation parameter (CAP) in subjects with metabolic risk factors in primary care. A population-based study.

PLoS One 2018 18;13(9):e0200656. Epub 2018 Sep 18.

Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain.

Background: Primary care is the ideal setting for early identification of patients with non-alcoholic fatty liver disease (NAFLD). NAFLD is a potentially progressive disease that may lead to cirrhosis and liver cancer but is frequently underrecognized because subjects at risk are often not evaluated. Controlled attenuation parameter (CAP) is a reliable method for non-invasive quantification of liver fat. It has the advantage of simultaneous measurement of liver stiffness (LS), an estimate of liver fibrosis. There is no information on CAP in subjects with risk factors from primary care.

Aim: To investigate the prevalence of hepatic steatosis, as estimated by CAP, in subjects from the community with metabolic risk factors and correlate findings with clinical and biochemical characteristics and LS.

Patients And Methods: Population-based study of 215 subjects with metabolic risk factors without known liver disease identified randomly from a primary care center. A control group of 80 subjects matched by age and sex without metabolic risk factors was also studied. CAP and LS were assessed using Fibroscan.

Results: Subjects with risk factors had CAP values higher than those of control group (268±64 vs 243±49dB/m,p<0.001). Prevalence of severe steatosis (CAP> 280dB/m) in subjects with risk factors was 43%. In multivariate analysis, fatty liver index (FLI) and HOMA were independent predictive factors of severe steatosis. There was a direct correlation between CAP and FLI values (r = 0.52,p<0.001). Interestingly, prevalence of increased LS was 12.6% in the risk group vs 0% in the control group (p<0.001). Increased LS occurred predominantly in subjects with high CAP values.

Conclusions: A high proportion of subjects with metabolic risk factors seen in primary care have severe steatosis. FLI could be used as a surrogate of CAP. Increased LS was found in a significant proportion of subjects with risk factors but not in control subjects.
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February 2019

Nurses' characteristics and practice environments: Comparison between clusters with different attitude and utilisation profiles regarding nursing diagnosis.

J Nurs Manag 2019 Jan 10;27(1):93-102. Epub 2018 Sep 10.

University of Cádiz, Research Group under the Andalusian Research, Development and Innovation Scheme CTS-1019, Cádiz, Spain.

Aim: To identify clusters of nurses in relation to the utilisation and attitude towards nursing diagnosis and to compare their profiles considering demographics, professional characteristics and nursing practice environments.

Background: Nursing diagnosis has benefits for both patients and nurses, and the attitude of nurses towards nursing diagnosis has been proposed as a determinant of its use. Therefore, an adequate understanding of nurses' attitude and utilisation profiles regarding nursing diagnosis is essential for the nursing managers who want to adopt nursing diagnosis as a practice framework.

Methods: A cross-sectional survey design was used. A sample of 239 nurses working in the Catalan primary health care system were categorised into clusters with similar attitude and utilisation profiles, which were compared with each other a posteriori.

Results: Nursing managers were grouped into more positive attitude clusters than clinical nurses. Nurses working in supportive nursing practice environments were classified into more positive attitude and higher utilisation clusters.

Conclusion: The field of work and nursing practice environments were found as differential factors in profiles of nurses with different attitudes towards and/or utilisation of nursing diagnosis.

Implications For Nursing Management: The promotion of supportive nursing practice environments could enhance the implementation and maintenance of nursing diagnosis as a practice framework in primary health care.
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January 2019

Range of Normal Liver Stiffness and Factors Associated With Increased Stiffness Measurements in Apparently Healthy Individuals.

Clin Gastroenterol Hepatol 2019 01 7;17(1):54-64.e1. Epub 2018 Sep 7.

Department of Gastroenterology and Hepatology, "Victor Babeș" University of Medicine and Pharmacy, Timișoara, Romania.

Background & Aims: Transient elastography (TE) is a noninvasive technique used to measure liver stiffness to estimate the severity of fibrosis. The range of liver stiffness measurements (LSMs) in healthy individuals is unclear. We performed a systematic review to determine the range of LSMs, examined by TE, in healthy individuals and individuals who are susceptible to fibrosis.

Methods: We collected data from 16,082 individuals, in 26 cohorts, identified from systematic searches of Embase, Ovid MEDLINE, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews for studies of liver stiffness measurements. Studies analyzed included apparently healthy adults (normal levels of liver enzymes, low-risk alcohol use patterns, and negative for markers of viral hepatitis). The presence of diabetes, hypertension, dyslipidemia, or steatosis, based on ultrasound examination, was known for most participants. We performed a meta-analysis of data from individual participants. The cohort was divided into 4 groups; participants with a body mass index <30 kg/m were examined with the medium probe and those with a body mass index ≥30 kg/m were examined with the extra-large probe. Linear regression models were conducted after adjusting for potential confounding factors of LSMs. We performed several sensitivity analyses.

Results: We established LSM ranges for healthy individuals measured with both probes-these did not change significantly in sensitivity analyses of individuals with platelets ≥150,000/mm and levels of alanine aminotransferase ≤33 IU/L in men or ≤25 IU/L in women. In multivariate analysis, factors that modified LSMs with statistical significance included diabetes, dyslipidemia, waist circumference, level of aspartate aminotransferase, and systolic blood pressure at examination time. Significant increases in LSMs were associated with the metabolic syndrome in individuals examined by either probe. Diabetes in obese individuals increased the risk of LSMs in the range associated with advanced fibrosis.

Conclusions: In a systematic review and meta-analysis of data from individual participants, we established a comprehensive set of LSM ranges, measured by TE in large cohorts of healthy individuals and persons susceptible to hepatic fibrosis. Regression analyses identified factors associated with increased LSMs obtained by TE with the medium and extra-large probes.
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January 2019

Midodrine and albumin for prevention of complications in patients with cirrhosis awaiting liver transplantation. A randomized placebo-controlled trial.

J Hepatol 2018 12 21;69(6):1250-1259. Epub 2018 Aug 21.

Liver Unit, Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEReHD), Barcelona, Spain. Electronic address:

Background & Aims: Patients with decompensated cirrhosis on the waiting list for liver transplantation (LT) commonly develop complications that may preclude them from reaching LT. Circulatory dysfunction leading to effective arterial hypovolemia and activation of vasoconstrictor systems is a key factor in the pathophysiology of complications of cirrhosis. The aim of this study was to investigate whether treatment with midodrine, an alpha-adrenergic vasoconstrictor, together with intravenous albumin improves circulatory dysfunction and prevents complications of cirrhosis in patients awaiting LT.

Methods: A multicenter, randomized, double-blind, placebo-controlled trial (NCT00839358) was conducted, including 196 consecutive patients with cirrhosis and ascites awaiting LT. Patients were randomly assigned to receive midodrine (15-30 mg/day) and albumin (40 g/15 days) or matching placebos for one year, until LT or drop-off from inclusion on the waiting list. The primary endpoint was incidence of any complication (renal failure, hyponatremia, infections, hepatic encephalopathy or gastrointestinal bleeding). Secondary endpoints were mortality, activity of endogenous vasoconstrictor systems and plasma cytokine levels.

Results: There were no significant differences between both groups in the probability of developing complications of cirrhosis during follow-up (p = 0.402) or one-year mortality (p = 0.527). Treatment with midodrine and albumin was associated with a slight but significant decrease in plasma renin activity and aldosterone compared to placebo (renin -4.3 vs. 0.1 ng/ml.h, p < 0.001; aldosterone -38 vs. 6 ng/dl, p = 0.02, at week 48 vs. baseline). Plasma norepinephrine only decreased slightly at week 4. Neither arterial pressure nor plasma cytokine levels changed significantly.

Conclusions: In patients with cirrhosis awaiting LT, treatment with midodrine and albumin, at the doses used in this study, slightly suppressed the activity of vasoconstrictor systems, but did not prevent complications of cirrhosis or improve survival.

Lay Summary: Patients with cirrhosis who are on the liver transplant waiting list often develop complications which prevent them from receiving a transplant. Circulatory dysfunction is a key factor behind a number of complications. This study was aimed at investigating whether treating patients with midodrine (a vasoconstrictor) and albumin would improve circulatory dysfunction and prevent complications. This combined treatment, at least at the doses administered in this study, did not prevent the complications of cirrhosis or improve the survival of these patients.
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December 2018

High Prevalence of Liver Fibrosis Among European Adults With Unknown Liver Disease: A Population-Based Study.

Clin Gastroenterol Hepatol 2018 07 13;16(7):1138-1145.e5. Epub 2018 Feb 13.

Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Barcelona, Spain; Liver Unit, Hospital Clínic, Barcelona, Spain; Institut d'Investigacions Biomèdiques, August Pi i Sunyer, Barcelona, Spain. Electronic address:

Background & Aims: Liver fibrosis is the main determinant of long-term outcome in chronic liver diseases. Little is known about the prevalence of liver fibrosis in the general population. The aim of the study was to investigate the prevalence of liver fibrosis in the general adult population with unknown liver disease.

Methods: This was a population-based, cross-sectional study performed in the Barcelona metropolitan area. Subjects aged 18 to 75 years old were identified randomly from citizens included in the primary health care registry. Of 4866 subjects invited, 3076 participated (63.2%). Liver fibrosis was estimated by measuring liver stiffness (LS) with transient elastography (TE). Liver histology was assessed in 92 subjects with increased LS.

Results: Prevalence estimates of increased LS (≥6.8, ≥8.0, and ≥9.0 kPa) were 9.0%, 5.8%, and 3.6%, respectively. The etiology of liver disease was mainly nonalcoholic fatty liver disease (NAFLD), followed by alcohol risk consumption (consumption of ≥21 standard drinking units/wk in men and ≥14 standard drinking units/wk in women). Factors independently associated with increased LS were male sex, abdominal obesity, type 2 diabetes, serum glucose, high-density lipoprotein, and triglyceride levels. Subjects without risk factors for NAFLD or without alcohol risk consumption had a very low prevalence of increased LS. The best cut-off value of LS for significant liver fibrosis (F2-F4) was 9.2 kPa, with high sensitivity and specificity. TE was more accurate than alanine aminotransferase, NAFLD fibrosis score, or Fibrosis 4. An algorithm for screening for liver fibrosis using TE in the community setting is proposed.

Conclusions: These findings show a high prevalence of silent liver disease with advanced fibrosis mainly related to NAFLD in adult European subjects without known liver disease. An LS value less than 9.2 kPa predicts the absence of significant liver fibrosis with high accuracy and could be used for screening purposes.
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July 2018

Research About Nursing Care for Persons With Liver Disease: A Step in the Right Direction.

Núria Fabrellas

Nurs Res 2017 Nov/Dec;66(6):419-420

Núria Fabrellas, PhD, RN, School of Nursing, Faculty of Medicine and Health Sciences, University of Barcelona, Spain.

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February 2018

Nursing care of patients with chronic liver diseases: Time for action.

J Adv Nurs 2018 Mar 5;74(3):498-500. Epub 2017 Jul 5.

Liver unit, Hospital Clinic, Institut d'investigacions biomediques August Pi Sunyer (IDIBAPS), Barcelona, Spain.

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March 2018

Adipocyte Fatty-Acid Binding Protein is Overexpressed in Cirrhosis and Correlates with Clinical Outcomes.

Sci Rep 2017 05 12;7(1):1829. Epub 2017 May 12.

Liver Unit, Hospital Clinic, University of Barcelona, Barcelona, Spain.

Fatty-acid-binding proteins (FABPs) are small intracellular proteins that coordinate lipid-mediated processes by targeting metabolic and immune response pathways. The aim of the study was to investigate plasma FABPs levels and their relationship with clinical outcomes in cirrhosis. Plasma levels of L-FABP1(liver and kidney), I-FABP2(intestine), and A-FABP4(adipocyte and macrophages) were measured in 274 patients with decompensated cirrhosis. Hepatic gene expression of FABPs was assessed in liver biopsies from patients with decompensated cirrhosis and in liver cell types from mice with cirrhosis. Immunohistochemistry of A-FABP4 in human liver biopsy was also performed. Plasma levels of FABPs were increased in patients with decompensated cirrhosis compared to those of healthy subjects (L-FABP1: 25 (17-39) vs 10 (9-17) ng/mL p = 0.001, I-FABP2: 1.1 (0.5-2.1) vs 0.6 (0.4-1) ng/mL p = 0.04 and A-FABP4: 37 (20-68) vs 16 (11-33) ng/mL p = 0.002), respectively. Increased A-FABP4 levels were associated with complications of cirrhosis, acute-on-chronic liver failure and poor survival. Hepatic A-FABP4 gene expression was upregulated in decompensated cirrhosis. Macrophages were the main liver cell that over-expressed A-FABP4 in experimental cirrhosis and increased A-FABP4 was found in macrophages of human biopsies by immunohistochemistry. A-FABP4 levels are increased in decompensated cirrhosis and correlate with poor outcomes. Liver macrophages appear to be the main source of A-FABP4 in decompensated cirrhosis.
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May 2017

Towards the implementation of OSCE in undergraduate nursing curriculum: A qualitative study.

Nurse Educ Today 2017 Feb 7;49:163-167. Epub 2016 Dec 7.

School of Nursing, University of Barcelona, Spain; IDIBELL Institute of Biomedical Research, Spain. Electronic address:

Background: Despite the fact that Objective Structured Clinical Examination is considered to be an efficient assessment method, their implementation in the undergraduate nursing curriculum encounters difficulties. However, the initiative of the European Higher Education Area to promote competency-based assessment may represent an opportunity to introduce this instrument in undergraduate nursing curriculum.

Objective: To explore the perception of nursing faculty members regarding the implementation of the OSCE as an assessment tool in Catalan Nursing Schools.

Design/participants/setting: In this qualitative study, fifteen teachers participated in semi-structured interviews in eight Catalan Nursing Schools.

Methods: Semi-structured interviews were conducted. A thematic content analysis was used to identify major themes in the interview data and collaborative analysis was undertaken to ensure rigorous results.

Results: The relevant aspects that are emphasized by teachers included the consideration of the dual purpose of the OSCE via its formative and evaluative facets by enhancing the feedback received by students about their performance on the OSCE. The OSCE should be administered towards the end of the degree program and should complement other methods of assessment. Despite its high cost, the OSCE was deemed to be efficient as it enables student competencies to be assessed with objective criteria, which is a difficult task with other instruments. OSCE implementation is feasible with the institutional support of and collaborative work between schools.

Conclusions: The implementation of the OSCE in the Catalan undergraduate nursing degree programs is feasible if the project receives the support of all involved parties and if creative strategies are determined to reduce economic costs and optimize resources. With adequate feedback, the OSCE is an assessment tool that can provide high-impact training to students.
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February 2017

Plasma copeptin as biomarker of disease progression and prognosis in cirrhosis.

J Hepatol 2016 11 12;65(5):914-920. Epub 2016 Jul 12.

Liver Unit, Hospital Clínic, University of Barcelona, Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain.

Background & Aims: Research on vasopressin (AVP) in cirrhosis and its role in the assessment of prognosis has been hindered by the difficulty of measuring AVP levels accurately. Copeptin, a 39-aminoacid glycopeptide, is released from the neurohypophysis together with AVP. Copeptin could have a role as biomarker of prognosis in cirrhosis as it may reflect circulatory dysfunction. The aim of this study is to investigate the role of copeptin as biomarker of disease progression and prognosis in cirrhosis.

Methods: This prospective study is divided in 2 study protocols including 321 consecutive patients. Plasma copeptin levels were measured in all patients at study inclusion. Protocol 1: to investigate the relationship of copeptin with kidney and circulatory function (56 patients). Protocol 2: to investigate the relationship between copeptin and prognosis, as assessed by the development of complications of cirrhosis or mortality at 3months (265 patients admitted to hospital for complications of cirrhosis).

Results: Patients with decompensated cirrhosis showed significantly higher plasma copeptin levels compared to those of patients with compensated cirrhosis. Copeptin levels had a significant positive correlation with model for end-satge liver disease (MELD) score, AVP, endogenous vasoconstrictor systems, and kidney function parameters. Patients developing complications of cirrhosis or mortality had significantly higher plasma copeptin levels compared to those of the remaining patients. Plasma copeptin levels were an independent predictive factor of both the development of complications and mortality at 3months. This was confirmed in a validation series of 120 patients.

Conclusions: Copeptin is a novel biomarker of disease progression and prognosis in cirrhosis.

Lay Summary: Copeptin is a fragment of the vasopressin precursor, a hormone that is known to be increased in patients with cirrhosis and that plays a role in the development of complications of the disease. Vasopressin is difficult to measure, but copeptin is a more stable molecule and is easier to measure in blood. Solà and Kerbert and colleagues have shown in a series of 361 patients that copeptin is markedly increased in patients with cirrhosis who develop complications during the following 3months, compared to those patients who do not develop complications. Moreover, copeptin correlates with prognosis.
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November 2016

Validation of a Staging System for Acute Kidney Injury in Patients With Cirrhosis and Association With Acute-on-Chronic Liver Failure.

Clin Gastroenterol Hepatol 2017 03 5;15(3):438-445.e5. Epub 2016 Oct 5.

Liver Unit, Hospital Clinic, University of Barcelona, Barcelona, Catalonia, Spain; Institut d'Investigacions Biomèdiques Agust Pi i Sunyer, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Barcelona, Spain. Electronic address:

Background & Aims: In patients with cirrhosis of the liver, acute kidney injury (AKI) is classified into 3 stages. Recent studies indicate that there are 2 subgroups of stage 1 disease, associated with different outcomes and serum levels of creatinine (SCr): stage 1A (SCr <1.5 mg/dL) and stage 1B (SCr ≥1.5 mg/dL). We performed a prospective study to validate, in a large series of patients with cirrhosis, the association between this new description and patient outcomes, and assess the relationship between AKI stage and the presence of acute-on-chronic liver failure.

Methods: We collected data from 547 consecutive patients admitted for cirrhosis with acute decompensation to 2 tertiary hospitals (Italy and Spain), from February 2011 through June 2015. A total of 290 patients had AKI (53%; 197 had stage 1 disease); AKI stages were determined based on levels of SCr at diagnosis. Patients were followed up until death, liver transplantation, or for 90 days. The primary outcome was 90-day survival; secondary outcomes were progression and resolution of AKI and association with acute-on-chronic liver failure.

Results: Based on level of sCr at diagnosis, 58 patients had stage 1A disease and 139 had stage 1B disease. Of patients with stage 1A disease, 82% survived for 90 days; of patients with stage 1B disease, 55% survived for 90 days (P = .001). Hepatorenal syndrome and acute tubular necrosis were the most common causes of stage 1B AKI, and hypovolemia was the most common cause of stage 1A AKI. AKI progressed in a higher proportion of patients with 1B than 1A AKI (31% vs 15%; P = .017) and resolved in a higher proportion of patients with 1A disease (90% vs 52% of patients with stage 1B; P < .001). Stage 1B disease, but not 1A, was an independent predictor of AKI progression and mortality. ACLF developed in a significantly greater proportion of patients with stage 1B disease (76%) than stage 1A disease (22%; P < .001), which could account for the poor outcomes of patients with stage 1B disease.

Conclusions: In a large group of patients with decompensated cirrhosis, we validated the association between AKI stages IA and IB (based on level of sCR) with survival times and AKI progression. We also associated these subgroups of AKI with development of acute-on-chronic liver failure. These findings are important for management of patients with decompensated cirrhosis.
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March 2017