La influencia del bajo peso al nacer en el desarrollo durante los dos primeros años de vida. Un estudio longitudinal en gemelos

Trabajo Investigación. Univ. Granada. Departamento de Psicología Evolutiva y de la Educación. Leída el 21 de septiembre de 199

A psycho‑educational intervention programme for parents with SGA foetuses supported by an adaptive mHealth system: design, proof of concept and usability assessment

Background: Technology-based approaches during pregnancy can facilitate the self-reporting of emotional health issues and improve well-being. There is evidence to suggest that stress during pregnancy can affect the foetus and result in restricted growth and preterm birth. Although a number of mobile health (mHealth) approaches are designed to monitor pregnancy and provide information about a specific aspect, no proposal specifically addresses the interventions in parents at risk of having small-for-gestational-age (SGA) or premature babies. Very few studies, however, follow any design and usability guidelines which aim to ensure end-user satisfaction when using these systems. Results: We have developed an interactive, adaptable mHealth system to support a psycho-educational intervention programme for parents with SGA foetuses. The relevant results include a metamodel to support the task of modelling current or new intervention programmes, an mHealth system model with runtime adaptation to changes in the programme, the design of a usable app (called VivEmbarazo) and an architectural design and prototype implementation. The developed mHealth system has also enabled us to conduct a proof of concept based on the use of the mHealth systems and this includes data analysis and assesses usability and acceptance. Conclusions: The proof of concept confirms that parents are satisfied and that they are enthusiastic about the mHealth-supported intervention programme. It helps to technically validate the results obtained in the other stages relating to the development of the solution. The data analysis resulting from the proof of concept confirms that the stress experienced by parents who followed the mHealth-supported intervention programme was significantly lower than among those who did not follow it. This implies an improvement in the emotional health not only of the parents but also of their child. In fact, the babies of couples who followed the mHealth-supported programme weigh more than the babies of couples under traditional care. In terms of user acceptance and usability, the analysis confirms that mothers place greater value on the app design, usefulness and ease of use and are generally more satisfied than their partners. Although these results are promising in comparison with more traditional and other more recent technology- based approaches.MCIN/AEI PID2019-109644RB-I00Andalusia Ministry of Health (Junta de Andalucia-Spain) PC-0526-2016052

E-Service-Learning. Video library proposal for educational innovation

Higher Education immersed in the process of digital literacy has the challenge of promoting its understanding and development in an inclusive way. "Educational and interactive Storytelling Video Library" is created, a repository of audiovisual, interactive and digital educational materials to improve executive functions, language and values through the methodology of E-Service-Learning and TICs. Materials created by university students to be implemented in the early childhood education stage and aimed at facilitating teaching work in a digital and inclusive society. Resulting in an educational environment that generates a network between University, School and Family where knowledge is shared and transferred.La Educación Superior inmersa en el proceso de alfabetización digital tiene el reto de favorecer su comprensión y desarrollo de forma inclusiva. Se crea “Videoteca de Storytelling educativas e interactivas”, repositorio de materiales educativos audiovisuales, interactivos y digitales para mejorar las funciones ejecutivas, lenguaje y valores mediante la metodología de E-Aprendizaje-Servicio y TICs. Materiales creados por alumnado universitario para ser implementados en la etapa de educación infantil y dirigidos a facilitar la labor docente en una sociedad digital e inclusiva. Resultando un entorno educativo que genera una red entre Universidad, Escuela y Familia donde se comparten y transfieren conocimientos.Proyecto de la Universidad de Granada Medialab (2021) “Videoteca de Storytelling educativas e interactivas con acceso abierto: E-Aprendizaje-Servicio”, el cual está vinculado a los proyectos FEJYLEN (2020) (INV-INC123-2020) “Aprendizaje-Servicio en la Universidad de Granada. Desarrollo de las funciones ejecutivas y del lenguaje en aulas inclusivas de Educación Infantil y FEJYLENVAL (2021) (INV-INC139-2021) “Más Educación Inclusiva, más inclusión en la Educación. Un modelo de aprendizaje-servicio en la era digital para una Educación Inclusiva de calidad”

Moderating Effect of Changes in Perceived Social Support during Pregnancy on the Emotional Health of Mothers and Fathers and on Baby’s Anthropometric Parameters at Birth

(1) Background: this study is based on a model of how changes in protective factors may affect the emotional health of mothers and fathers and thus influence the development of the baby. Our research goal is to determine whether variations in perceived social support moderate levels of stress and depression during pregnancy and/or the effect of parents’ emotional health on the baby’s anthropometric parameters. (2) Methods: to achieve these aims, a longitudinal study was made of 132 couples and babies, who were evaluated at weeks 12 and 32 of gestation and at birth. Separate analyses were performed for the mothers and fathers, focused on the role of social support in moderating their levels of depression and stress during pregnancy, and the consequent impact on the baby. (3) Results: the results obtained show the moderating effects of changes in social support on maternal and paternal stress and depression. Reduced social support during pregnancy is associated with higher levels of stress and depression in both parents and with a high cephalisation index in their babies. (4) Conclusions: special attention should be paid to social support, which can have a strong impact on the evolution of emotional health during pregnancy and concomitantly on the development of the baby.University of Granada (Spain)Andalusian Public Foundation for Biosanitary Research Eastern Andalusia (Spain)Regional Ministry of Health within Junta de Andalucia (Spain) PC-0526-2016-052

Psychological distress and resilience of mothers and fathers with respect to the neurobehavioral performance of small-forgestational- age newborns

The existence of psychological distress (PD) during pregnancy is well established. Nevertheless, few studies have analyzed the PD and resilience of mothers and fathers during high-risk pregnancy. This study analyzes the differences between parents’ PD and resilience and the relation between them and the neurobehavioral performance of their SGA newborns. Multivariate analysis of variance showed, in gender comparisons, that mothers obtained higher scores than fathers for psychological distress but lower ones for resilience. Similar differences were obtained in the comparison of parents’ distress to intrauterine growth by SGA vs. AGA newborns. Mothers of SGA newborns were more distressed than the other groups. However, there were no differences between the fathers of SGA vs. AGA newborns. Regarding neurobehavioral performance, the profiles of SGA newborns reflected a lower degree of maturity than those of AGA newborns. Hierarchical regression analyses showed that high stress and low resilience among mothers partially predict low neurobehavioral performance in SGA newborns. These findings indicate that mothers of SGA newborns may need psychological support to relieve stress and improve their resilience. Furthermore, attention should be paid to the neurobehavioral performance of their babies in case early attention is neededThis study was supported by University of Granada (Spain), Andalusian Public Foundation for Biosanitary Research Eastern Andalusia (Spain), and Ministry of Health, Junta de Andalucía (Spain) Award Number: PC-0526-2016-0526

Potential benefit and lack of serious risk from corticosteroids in drug-induced liver injury: an international, multicentre, propensity score-matched analysis

Background: The use of corticosteroids to treat patients with idiosyncratic drug-induced liver injury (DILI) relies on empirical clinical decisions. Aim: To investigate the relationship between corticosteroids and risk of acute liver failure (ALF) in patients with DILI and to assess if corticosteroid therapy was associated with improved outcomes in DILI patients. Methods: We analysed bona fide idiosyncratic DILI cases from the Spanish DILI Registry and Indiana University School of Medicine. Patients treated with corticosteroids were compared to those who did not receive any treatment. Nearest neighbour propensity score matching analyses were conducted. Results: We enrolled 724 patients, 106 under corticosteroid therapy, in whom there was over-representation of more severe injury and autoimmune features, and 618 who did not receive any treatment. In an analysis of 80 pairs of propensity score-matched patients, corticosteroid administration was not associated with an increased risk of developing ALF (odds ratio = 0.65; 95% confidence interval [CI]: 0.18–2.40; p = 0.518). Furthermore, in an additional analysis, a Cox regression model that included 41 propensity score-matched pairs showed that patients receiving corticosteroids had a significantly higher normalisation rate of liver enzymes than untreated patients (hazard ratio [HR] = 1.84; 95% CI: 1.02–3.32; p = 0.043), particularly in patients with serious injury who did not resolve within 30 days (HR = 2.79; 95% CI: 1.20–6.50; p = 0.018). Conclusion: Corticosteroid therapy did not worsen outcome in DILI patients. Indeed, corticosteroid administration was associated with a greater rate of normalisation of liver enzymes in patients with serious DILI.Funding for open access charge: Universidad de Málaga / CBUA. This study was funded by Instituto de Salud Carlos III (ISCIII) cofounded by Fondo Europeo de Desarrollo Regional - FEDER (contract numbers: PI18/00901, PI19/00883, PI21/01248 and PT20/000127), Consejería de Salud de Junta de Andalucía (contract number: PI-0310-2018), and Agencia Española de Medicamentos y Productos Sanitarios. CIBERehd and Plataforma ISCIII Ensayos Clínicos are funded by ISCIII. HN holds a postdoctoral research contract funded by Junta de Andalucia (POSTDOC_21_00780). I.A.-A. holds a Sara Borrell contract funded by ISCIII (CD20/00083). This article/publication is based upon work from COST Action CA17112, supported by COST (European Cooperation in Science and Technology). www.cost.eu

Incidence and prevalence of acute hepatitis E virus infection in patients with suspected Drug-Induced Liver Injury in the Spanish DILI Registry

Background and Aims: Drug-induced liver injury (DILI) presents with a wide phenotypic spectrum requiring an extensive differential diagnosis. Hepatitis E virus (HEV) is not systematically ruled out during acute hepatitis assessment in Spain. The aims of this study were to establish the role of HEV infection and its phenotypic presentation in patients initially suspected of DILI and to determine the anti-HEV seroprevalence rate. Methods: An analysis of 265 patients with suspected DILI and considered for enrolment in the Spanish DILI Registry and 108 controls with normal liver profiles was undertaken. Anti-HEV Immunoglobulin (Ig) G antibodies were analyzed in serum from all subjects. In those with serum samples extracted within 6 months from liver damage onset (n=144), HEV antigen (Ag) and anti- HEV IgM antibodies were tested in duplicate by ELISA. In addition, RT-PCR was performed externally in 8 patients. Results: Out of 144 patients, 12 (8%) were positive for anti-HEV IgM, mean age 61 years. Underlying hepatic diseases (OR=23.4, p20 folds upper limit of normal (OR=10.9, p=0.002) were associated with the diagnosis of acute hepatitis E. The overall anti-HEV IgG seroprevalence rate was 35%, evenly distributed between patients with suspected DILI (34%), and controls (39%). Conclusions: HEV seroprevalence and acute hepatitis E rates are relatively high in Spain. A search for active HEV infection is therefore advised in patients assessed for suspicion of DILI, particularly in patients with underlying liver diseases and high transaminase levels.The present study has been supported by grants of the Instituto de Salud Carlos III cofounded by Fondo Europeo de Desarrollo Regional FEDER (contract numbers: FIS PI0274-2016, PI-0285- 2016, PI 18-01804, PI 18-00901, PT17/0017/0020, CM17/00243, JR16/00015, B-0002-2019, UMA-18-FEDERJA-193 and by the Agencia Española del Medicamento. SCReN and CIBERehd are funded by Instituto de Salud Carlos III. European Cooperation in Science & Technology (COST) ACTION CA17112 Prospective European Drug-Induced Liver Injury Network, IMI2-Translational Safety Biomarker Pipeline (TransBioLine). The funding sources had no involvement in the study design, in the collection, analysis, and interpretation of data, in the writing of the report or in the decision to submit the manuscript for publicatio

Evaluation of diagnostic and prognostic candidate biomarkers in drug-induced liver injury vs. other forms of acute liver damage

Aims Detection and characterization of idiosyncratic drug-induced liver injury (DILI) currently rely on standard liver tests, which are suboptimal in terms of specificity, sensitivity and prognosis. Therefore, DILI diagnosis can be delayed, with important consequences for the patient. In this study, we aimed to evaluate the potential of osteopontin, cytokeratin-18 (caspase-cleaved: ccK18 and total: K18), α-glutathione-S-transferase and microRNA-122 as new DILI biomarkers. Methods Serial blood samples were collected from 32 DILI and 34 non-DILI acute liver injury (ALI) cases and a single sample from 43 population controls without liver injury (HLC) and analysed using enzyme-linked immunosorbent assay (ELISA) or single-molecule arrays. Results All biomarkers differentiated DILI and ALI from HLC with an area under receiver operator characteristic curve (AUC) value of >0.75 but were less efficient in distinguishing DILI from ALI, with ccK18 (0.79) and K18 (0.76) demonstrating highest potential. However, the AUC improved considerably (0.98) for ccK18 when comparing DILI and a subgroup of autoimmune hepatitis cases. Cytokeratin-18, microRNA-122 and α-glutathione-S-transferase correlated well with traditional transaminases, while osteopontin correlated most strongly with the international normalized ratio (INR). Conclusions ccK18 appears promising in distinguishing DILI from autoimmune hepatitis but less so from other forms of acute liver injury. Osteopontin demonstrates prognostic potential with higher levels detected in more severe cases regardless of aetiology.Consejería de Salud y Familia de la Junta de Andalucía, Grant/Award Numbers: PI 0274-2016, P18-RT-3364; Instituto de Salud Carlos III (ISCIII) cofounded by Fondo Europeo de Desarrollo Regional - FEDER, Grant/Award Numbers: PI19/00883, PI18/00901, UMA18-FEDERJA-193; Universidad de Málaga/CBUA for open access charge: Universidad de Málaga / CBUA. Funding for open access charge: Universidad de Málaga / CBU

Clinical characteristics and outcome of drug-induced liver injury in the older patients: from the young-old to the oldest-old

Old patients with hepatotoxicity have been scarcely studied in idiosyncratic drug-induced liver injury (DILI) cohorts. We sought for the distinctive characteristics of DILI in older patients across age groups. A total of 882 DILI patients included in the Spanish DILI Registry (33% ≥65 years) were categorized according to age: “young” (<65y); “young-old” (65-74y); “middle-old” (75-84y); and “oldest-old” (≥85y). All elderly groups had increasingly higher comorbidity burden (p<0.001) and polypharmacy (p<0.001). There was a relationship between jaundice and hospitalization (p<0.001), and both were more prevalent in the elderly age groups, especially in the oldest-old (88% and 69%, respectively) and the DILI episode was more severe (p=0.029). The proportion of females decreased across age groups from the young to the middle-old, yet in the oldest-old there was a distinct female predominance. Pattern of liver injury shifted towards cholestatic with increasing age among top culprit drugs amoxicillin- clavulanate, atorvastatin, levofloxacin, ibuprofen, and ticlopidine. The best cut-off point for increased odds of cholestatic DILI was 65y. Older patients had increased non-liver related mortality (p=0.030) as shown by the predictive capacity of MELD (OR=1.116; p<0.001), and comorbidity burden (OR=4.188; p=0.001) in the 6-month mortality. Older patients with DILI exhibited an increasingly predominant cholestatic phenotype across a range of culprit drugs other that amoxicillin-clavulanate, with increased non-liver related mortality and require a different approach to predict outcome. The oldest DILI patients exhibited a particular phenotype with more severe DILI episodes and need to be considered when stratifying older DILI populations.The present study has been supported by grants of Instituto de Salud Carlos III cofounded by Fondo Europeo de Desarrollo Regional - FEDER (contract numbers: PI 18/01804; PT17/0017/0020) and Agencia Española del Medicamento. SCReN and CIBERehd are funded by ISCIII. JSC holds a Rio Hortega (CM17/00243) and MR a “Joan Rodes” (JR16/00015) research contract from the National Health System, ISCIII. RAW held a University of Málaga visiting scientist scholarship

Serious liver injury induced by Nimesulide: an international collaboration study reporting 57 cases

Nimesulide is a non-steroidal anti-inflammatory drug still marketed in many countries. We aim to analyze the clinical phenotype, outcome, and histological features of nimesulide-induced liver injury (nimesulide-DILI). We analyzed 57 cases recruited from the Spanish and LATIN DILI registries. Causality was assessed by the RUCAM scale. Mean age of the whole case series was 59 years (86% women) with a median time to onset of 40 days. A total of 46 patients (81%) were jaundiced. Nimesulide-DILI pattern was hepatocellular in 38 (67%), mixed in 12 (21%), and cholestatic in 7 (12%) cases. Transaminases were elevated with a mean of nearly 20-fold the upper limit of normality (ULN), while alkaline phosphatase showed a 2-fold mean elevation above ULN. Total bilirubin showed a mean elevation of 13-fold the ULN. Liver histology was obtained in 14 cases (25%), most of them with a hepatocellular pattern. Median time to recovery was 60 days. Overall, 12 patients (21%) developed acute liver failure (ALF), five (8.8%) died, three underwent liver transplantation (5.3%), and the remaining four resolved. Latency was ≤15 days in 12 patients (21%) and one patient developed ALF within seven days from treatment initiation. Increased total bilirubin and aspartate transaminase levels were independently associated with the development of ALF. In summary, nimesulide-DILI affects mainly women and presents typically with a hepatocellular pattern. It is associated with ALF and death in a high proportion of patients. Shorter (≤15 days) duration of therapy does not prevent serious nimesulide hepatotoxicity, making its risk/benefit ratio clearly unfavorable.The present study has been supported by grants of Instituto de Salud Carlos III cofounded by Fondo Europeo de Desarrollo Regional - FEDER (contract numbers: PI18-00901; PI 18/01804; PT20/00127) and Agencia Española del Medicamento. Plataforma ISCiii de Investigación Clínica and CIBERehd are funded by ISCIII. MRD holds a Joan Rodes (JR16/00015)/Acción B clinicos investigadores (B-0002-2019) research contract from ISCIII and Consejería de Salud de Andalucía, IAA holds a Sara Borrell research contract from the National Health System, ISCIII (CD 20/00083)