Meta-DiSc 2.0:a web application for meta-analysis of diagnostic test accuracy data

BACKGROUND: Diagnostic evidence of the accuracy of a test for identifying a target condition of interest can be estimated using systematic approaches following standardized methodologies. Statistical methods for the meta-analysis of diagnostic test accuracy (DTA) studies are relatively complex, presenting a challenge for reviewers without extensive statistical expertise. In 2006, we developed Meta-DiSc, a free user-friendly software to perform test accuracy meta-analysis. This statistical program is now widely used for performing DTA meta-analyses. We aimed to build a new version of the Meta-DiSc software to include statistical methods based on hierarchical models and an enhanced web-based interface to improve user experience. RESULTS: In this article, we present the updated version, Meta-DiSc 2.0, a web-based application developed using the R Shiny package. This new version implements recommended state-of-the-art statistical models to overcome the limitations of the statistical approaches included in the previous version. Meta-DiSc 2.0 performs statistical analyses of DTA reviews using a bivariate random effects model. The application offers a thorough analysis of heterogeneity, calculating logit variance estimates of sensitivity and specificity, the bivariate I-squared, the area of the 95% prediction ellipse, and the median odds ratios for sensitivity and specificity, and facilitating subgroup and meta-regression analyses. Furthermore, univariate random effects models can be applied to meta-analyses with few studies or with non-convergent bivariate models. The application interface has an intuitive design set out in four main menus: file upload; graphical description (forest and ROC plane plots); meta-analysis (pooling of sensitivity and specificity, estimation of likelihood ratios and diagnostic odds ratio, sROC curve); and summary of findings (impact of test through downstream consequences in a hypothetical population with a given prevalence). All computational algorithms have been validated in several real datasets by comparing results obtained with STATA/SAS and MetaDTA packages. CONCLUSION: We have developed and validated an updated version of the Meta-DiSc software that is more accessible and statistically sound. The web application is freely available at www.metadisc.es

El feedback a la UOC

Guia dirigida al professorat de la UOC amb orientacions sobre com plantejar un bon feedback a les seves assignatures.Guía dirigida al profesorado de la UOC con orientaciones sobre como plantear un buen feedback a sus asignaturas.Guide to the UOC teaching staff with guidelines on how to propose good feedback to their subjects

Long-term cardiac assessment in a sample of adolescent-onset anorexia nervosa

Background: High mortality rates have been reported in patients with anorexia nervosa, mainly due to cardiovascular alterations. The purpose of the present study was to assess cardiac structural and functional abnormalities some 20 years after initial treatment in a sample of adolescent-onset anorexia nervosa (A-AN) and to compare them with matched healthy controls (HC). Methods: A sample of 29 women diagnosed and treated for AN during adolescence (A-AN) were assessed more than 20 years later. A complete cardiac evaluation was carried out including an electrocardiogram (ECG) and a standard 2D echocardiography. Thirty matched HC were also assessed. Results: In the A-AN group, four subjects had a body mass index lower than 18.5 and met full DSM 5 criteria for AN at follow-up (Low-Weight group). They were compared with the rest of the sample (n = 25) who had normalized their weight (Normal-Weight group), though some still showed some eating disorder symptoms. Both groups were compared with the HC group. Subjects in the Low-Weight group presented statistically significant decreases in the left ventricular end-diastolic and left atrium dimensions and left ventricular mass in comparison with the Normal-Weight group and the HC. No other differences in cardiac parameters were found between groups. Conclusions: Echocardiographic and ECG parameters of adults who had presented A-AN twenty years earlier and currently maintained normal weight were similar to those of HC who had never been treated or diagnosed with AN. Adult subjects with A-AN who still had low weight in the long term present certain cardiac abnormalities similar to those seen in short-lasting disease. More studies are needed to confirm these results in a larger sample

Response to fluoxetine in children and adolescents: a weighted gene co-expression network analysis of peripheral blood

The inconclusive and non-replicated results of pharmacogenetic studies of antidepressant response could be related to the lack of acknowledgement of its mechanism of action. In this scenario, gene expression studies provide and interesting framework to reveal new candidate genes for pharmacogenetic studies or peripheral biomarkers of fluoxetine response. We propose a system biology approach to analyse changes in gene expression induced by eight weeks of treatment with fluoxetine in peripheral blood. 21 naïve child and adolescents participated in the present study. Our analysis include the identification of gene co-expression modules, using Weighted Gene Co-expression Network Analysis (WGCNA), followed by protein-protein interaction (PPi) network construction coupled with functional annotation. Our results revealed two modules of co-expression genes related to fluoxetine treatment. The constructed networks from these modules were enriched for biological processes related to cellular and metabolic processes, cell communication, immune system processes, cell death, response to stimulus and neurogenesis. Some of these processes, such as immune system, replicated previous findings in the literature, whereas, neurogenesis, a mechanism proposed to be involved in fluoxetine response, had been identified for first time using peripheral tissues. In conclusion, our study identifies several biological processes in relation to fluoxetine treatment in peripheral blood, offer new candidate genes for pharmacogenetic studies and valuable markers for peripheral moderator biomarkers discovery

Increase in admission rates and symptom severity of childhood and adolescent anorexia nervosa in Europe during the COVID-19 pandemic: data from specialized eating disorder units in different European countries

Background: The COVID-19 pandemic, associated with confinement and social isolation, seems to have impacted the course of many mental disorders in children and adolescents. An increase in hospital admission rates for juvenile anorexia nervosa (AN) has been documented in many regions of the world. However, data from Europe are scarce. Methods: We asked clinicians in specialized eating disorder units in hospitals of maximum care in France, Germany, Italy, Spain, Sweden, and the Netherlands to report on (i) overall (inpatient and outpatient) and (ii) inpatient admission rates for adolescents with AN during 2019 and 2020. Additionally, a modified version of the COVID Isolation Eating Scale (CIES) was used to assess the child and adolescent psychiatrists' estimations of a possible increase in symptom severity in children and adolescents with AN during the COVID-19 pandemic and to (iii) inquire about the contributing factors perceived by the caring professionals. Results: Four out of six representatives of European hospitals described a higher rate of overall admissions during the pandemic. Three hospitals out of six reported an increase in inpatient admissions, and two centres had constant high numbers of admissions of both outpatients and inpatients. The clinicians perceived a higher symptom severity in 2020 than in 2019, especially involving more frequent use of social media, longer duration of exercising, and more restrictive eating. They supposed an increase in social media consumption, a perceived 'loss of control', and a lack of in-person assessments and weight controls as the main contributing factors for the deterioration in AN numbers and symptomatology. Conclusions: The COVID-19 pandemic seems to have had a deep impact on symptom severity in AN, which is mirrored by a large increase in admission rates across Europe. An increase in exercise, social media consumption, a perceived 'loss of control', and a lack of face-to-face health care seem to have contributed to this development. Further investigation is required to identify which factors may lead to the increase in incidence and deterioration of childhood and adolescent AN. Possible preventive means for the future could include educating paediatricians and health care workers about AN, regular weight assessment, and home-based treatments

Long-term efficacy and safety of inotersen for hereditary transthyretin amyloidosis: NEURO-TTR open-label extension 3-year update

© The Author(s) 2022 Open Access This article is licensed under a Creative Commons Attri- bution 4.0 International License, which permits use, sharing, adapta- tion, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/Background: Hereditary transthyretin amyloidosis (hATTR/ATTRv) results from the deposition of misfolded transthyretin (TTR) throughout the body, including peripheral nerves. Inotersen, an antisense oligonucleotide inhibitor of hepatic TTR production, demonstrated a favorable efficacy and safety profile in patients with the polyneuropathy associated with hATTR in the NEURO-TTR (NCT01737398) study. We report longer-term efficacy and safety data for inotersen, with a median treatment exposure of 3 years. Methods: Patients who satisfactorily completed NEURO-TTR were enrolled in its open-label extension (OLE) study. Efficacy assessments included the modified Neuropathy Impairment Score + 7 (mNIS + 7), Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QoL-DN) questionnaire total score, and the Short Form 36 (SF-36v2) Health Survey Physical Component Summary score. Safety and tolerability were also assessed. Efficacy is reported for patients living in Europe and North America (this cohort completed the study approximately 9 months before the remaining group of patients outside these regions); safety is reported for the full safety dataset, comprising patients living in Europe, North America, and Latin America/Australasia. This study is registered with ClinicalTrials.gov, identifier NCT02175004. Results: In the Europe and North America cohort of the NEURO-TTR study, 113/141 patients (80.1%) completed the study, and 109 patients participated in the OLE study. A total of 70 patients continued to receive inotersen (inotersen-inotersen) and 39 switched from placebo to inotersen (placebo-inotersen). The placebo-inotersen group demonstrated sustained improvement in neurological disease progression as measured by mNIS + 7, compared with predicted worsening based on projection of the NEURO-TTR placebo data (estimated natural history). The inotersen-inotersen group demonstrated sustained benefit, as measured by mNIS + 7, Norfolk QoL-DN, and SF-36v2, compared with estimated natural history as well as compared with the placebo-inotersen group. With a maximum exposure of 6.2 years, inotersen was not associated with any additional safety concerns or increased toxicity in the OLE study. Platelet and renal monitoring were effective in reducing the risk of severe adverse events in the OLE study. Conclusion: Inotersen treatment for > 3 years slowed progression of the polyneuropathy associated with hATTR, and no new safety signals were observed.info:eu-repo/semantics/publishedVersio

Mental impact of Covid-19 among Spanish healthcare workers. A large longitudinal survey

Altres ajuts: Fondo Europeo de Desarrollo Regional (FEDER); Ministerio de Ciencia e Innovación; Gerencia Regional de Salud de Castilla y León (SACYL, GRS COVID 32/A/20).Aims Longitudinal data on the mental health impact of the coronavirus disease 2019 (Covid-19) pandemic in healthcare workers is limited. We estimated prevalence, incidence and persistence of probable mental disorders in a cohort of Spanish healthcare workers (Covid-19 waves 1 and 2) -and identified associated risk factors. Methods 8996 healthcare workers evaluated on 5 May-7 September 2020 (baseline) were invited to a second web-based survey (October-December 2020). Major depressive disorder (PHQ-8 ≥ 10), generalised anxiety disorder (GAD-7 ≥ 10), panic attacks, post-traumatic stress disorder (PCL-5 ≥ 7), and alcohol use disorder (CAGE-AID ≥ 2) were assessed. Distal (pre-pandemic) and proximal (pandemic) risk factors were included. We estimated the incidence of probable mental disorders (among those without disorders at baseline) and persistence (among those with disorders at baseline). Logistic regression of individual-level [odds ratios (OR)] and population-level (population attributable risk proportions) associations were estimated, adjusting by all distal risk factors, health care centre and time of baseline interview. Results 4809 healthcare workers participated at four months follow-up (cooperation rate = 65.7%; mean = 120 days s.d. = 22 days from baseline assessment). Follow-up prevalence of any disorder was 41.5%, (v. 45.4% at baseline, p < 0.001); incidence, 19.7% (s.e. = 1.6) and persistence, 67.7% (s.e. = 2.3). Proximal factors showing significant bivariate-adjusted associations with incidence included: work-related factors [prioritising Covid-19 patients (OR = 1.62)], stress factors [personal health-related stress (OR = 1.61)], interpersonal stress (OR = 1.53) and financial factors [significant income loss (OR = 1.37)]. Risk factors associated with persistence were largely similar. Conclusions Our study indicates that the prevalence of probable mental disorders among Spanish healthcare workers during the second wave of the Covid-19 pandemic was similarly high to that after the first wave. This was in good part due to the persistence of mental disorders detected at the baseline, but with a relevant incidence of about 1 in 5 of HCWs without mental disorders during the first wave of the Covid-19 pandemic. Health-related factors, work-related factors and interpersonal stress are important risks of persistence of mental disorders and of incidence of mental disorders. Adequately addressing these factors might have prevented a considerable amount of mental health impact of the pandemic among this vulnerable population. Addressing health-related stress, work-related factors and interpersonal stress might reduce the prevalence of these disorders substantially. Study registration number: NCT0455656

Guia per desenvolupar la competència transversal. Comunicació escrita i oral

Les competències transversals són un aspecte clau en la formació dels estudiants de la Universitat. El Grup d'innovació docent de la Facultat de Veterinària ha desenvolupat unes guies amb l'objectiu d'estandarditzar l'ensenyament de les competències transversals al graus impartits a la Facultat, oferir eines i recursos a l'alumnat per ajudar-los a desenvolupar aquestes competències, i oferir eines i recursos al professorat per facilitar l'ensenyament i l'avaluació de les competències en el marc de les assignatures pròpies. La guia per desenvolupar la competència transversal de comunicació escrita i oral estableix tres nivells de domini i 7 indicadors d'aprenentatge que l'estudiant ha d'assolir de forma progressiva al llarg del grau. En acabar els estudis l'estudiant ha de demostrar que ha adquirit l'habilitat d'expressar-se oralment i per escrit en un registre científic

Impact of COVID-19 Lockdown in Eating Disorders: A Multicentre Collaborative International Study

Background. The COVID-19 lockdown has had a significant impact on mental health. Patients with eating disorders (ED) have been particularly vulnerable. Aims. (1) To explore changes in eating-related symptoms and general psychopathology during lockdown in patients with an ED from various European and Asian countries; and (2) to assess differences related to diagnostic ED subtypes, age, and geography. Methods. The sample comprised 829 participants, diagnosed with an ED according to DSM-5 criteria from specialized ED units in Europe and Asia. Participants were assessed using the COVID-19 Isolation Scale (CIES). Results. Patients with binge eating disorder (BED) experienced the highest impact on weight and ED symptoms in comparison with other ED subtypes during lockdown, whereas individuals with other specified feeding and eating disorders (OFSED) had greater deterioration in general psychological functioning than subjects with other ED subtypes. Finally, Asian and younger individuals appeared to be more resilient. Conclusions. The psychopathological changes in ED patients during the COVID-19 lockdown varied by cultural context and individual variation in age and ED diagnosis. Clinical services may need to target preventive measures and adapt therapeutic approaches for the most vulnerable patients

KAP Degradation by Calpain Is Associated with CK2 Phosphorylation and Provides a Novel Mechanism for Cyclosporine A-Induced Proximal Tubule Injury

The use of cyclosporine A (CsA) is limited by its severe nephrotoxicity that includes reversible vasoconstrictor effects and proximal tubule cell injury, the latter associated whith chronic kidney disease progression. The mechanisms of CsA-induced tubular injury, mainly on the S3 segment, have not been completely elucidated. Kidney androgen-regulated protein (KAP) is exclusively expressed in kidney proximal tubule cells, interacts with the CsA-binding protein cyclophilin B and its expression diminishes in kidneys of CsA-treated mice. Since we reported that KAP protects against CsA toxicity in cultured proximal tubule cells, we hypothesized that low KAP levels found in kidneys of CsA-treated mice might correlate with proximal tubule cell injury. To test this hypothesis, we used KAP Tg mice developed in our laboratory and showed that these mice are more resistant to CsA-induced tubular injury than control littermates. Furthermore, we found that calpain, which was activated by CsA in cell cultures and kidney, is involved in KAP degradation and observed that phosphorylation of serine and threonine residues found in KAP PEST sequences by protein kinase CK2 enhances KAP degradation by calpain. Moreover, we also observed that CK2 inhibition protected against CsA-induced cytotoxicity. These findings point to a novel mechanism for CsA-induced kidney toxicity that might be useful in developing therapeutic strategies aimed at preventing tubular cell damage while maintaining the immunosuppressive effects of CsA