Neurocognitive Functioning in Individuals at Clinical High Risk for Psychosis

IMPORTANCE: Neurocognitive functioning is a potential biomarker to advance detection, prognosis, and preventive care for individuals at clinical high risk for psychosis (CHR-P). The current consistency and magnitude of neurocognitive functioning in individuals at CHR-P are undetermined. OBJECTIVE: To provide an updated synthesis of evidence on the consistency and magnitude of neurocognitive functioning in individuals at CHR-P. DATA SOURCES: Web of Science database, Cochrane Central Register of Reviews, and Ovid/PsycINFO and trial registries up to July 1, 2020. STUDY SELECTION: Multistep literature search compliant with Preferred Reporting Items for Systematic Reviews and Meta-analyses and Meta-analysis of Observational Studies in Epidemiology performed by independent researchers to identify original studies reporting on neurocognitive functioning in individuals at CHR-P. DATA EXTRACTION AND SYNTHESIS: Independent researchers extracted the data, clustering the neurocognitive tasks according to 7 Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) domains and 8 CHR-P domains. Random-effect model meta-analyses, assessment of publication biases and study quality, and meta-regressions were conducted. MAIN OUTCOMES AND MEASURES: The primary effect size measure was Hedges g of neurocognitive functioning in individuals at CHR-P (1) compared with healthy control (HC) individuals or (2) compared with individuals with first-episode psychosis (FEP) or (3) stratified for the longitudinal transition to psychosis. RESULTS: A total of 78 independent studies were included, consisting of 5162 individuals at CHR-P (mean [SD; range] age, 20.2 [3.3; 12.0-29.0] years; 2529 [49.0%] were female), 2865 HC individuals (mean [SD; range] age, 21.1 [3.6; 12.6-29.2] years; 1490 [52.0%] were female), and 486 individuals with FEP (mean [SD; range] age, 23.0 [2.0; 19.1-26.4] years; 267 [55.9%] were female). Compared with HC individuals, individuals at CHR-P showed medium to large deficits on the Stroop color word reading task (g = −1.17; 95% CI, −1.86 to −0.48), Hopkins Verbal Learning Test–Revised (g = −0.86; 95% CI, −1.43 to −0.28), digit symbol coding test (g = −0.74; 95% CI, −1.19 to −0.29), Brief Assessment of Cognition Scale Symbol Coding (g = −0.67; 95% CI, −0.95 to −0.39), University of Pennsylvania Smell Identification Test (g = −0.55; 95% CI, −0.97 to −0.12), Hinting Task (g = −0.53; 95% CI, −0.77 to −0.28), Rey Auditory Verbal Learning Test (g = −0.50; 95% CI, −0.78 to −0.21), California Verbal Learning Test (CVLT) (g = −0.50; 95% CI, −0.64 to −0.36), and National Adult Reading Test (g = −0.52; 95% CI, −1.01 to −0.03). Individuals at CHR-P were less impaired than individuals with FEP. Longitudinal transition to psychosis from a CHR-P state was associated with medium to large deficits in the CVLT task (g = −0.58; 95% CI, −1.12 to −0.05). Meta-regressions found significant effects for age and education on processing speed. CONCLUSIONS AND RELEVANCE: Findings from this meta-analysis support neurocognitive dysfunction as a potential detection and prognostic biomarker in individuals at CHR-P. These findings may advance clinical research and inform preventive approaches

Antibiotics for exacerbations of chronic obstructive pulmonary disease

BACKGROUND Many patients with an exacerbation of chronic obstructive pulmonary disease (COPD) are treated with antibiotics. However, the value of antibiotics remains uncertain, as systematic reviews and clinical trials have shown conflicting results. OBJECTIVES To assess effects of antibiotics on treatment failure as observed between seven days and one month after treatment initiation (primary outcome) for management of acute COPD exacerbations, as well as their effects on other patient-important outcomes (mortality, adverse events, length of hospital stay, time to next exacerbation). SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL), in the Cochrane Library, MEDLINE, Embase, and other electronically available databases up to 26 September 2018. SELECTION CRITERIA We sought to find randomised controlled trials (RCTs) including people with acute COPD exacerbations comparing antibiotic therapy and placebo and providing follow-up of at least seven days. DATA COLLECTION AND ANALYSIS Two review authors independently screened references and extracted data from trial reports. We kept the three groups of outpatients, inpatients, and patients admitted to the intensive care unit (ICU) separate for benefit outcomes and mortality because we considered them to be clinically too different to be summarised as a single group. We considered outpatients to have a mild to moderate exacerbation, inpatients to have a severe exacerbation, and ICU patients to have a very severe exacerbation. When authors of primary studies did not report outcomes or study details, we contacted them to request missing data. We calculated pooled risk ratios (RRs) for treatment failure, Peto odds ratios (ORs) for rare events (mortality and adverse events), and mean differences (MDs) for continuous outcomes using random-effects models. We used GRADE to assess the quality of the evidence. The primary outcome was treatment failure as observed between seven days and one month after treatment initiation. MAIN RESULTS We included 19 trials with 2663 participants (11 with outpatients, seven with inpatients, and one with ICU patients).For outpatients (with mild to moderate exacerbations), evidence of low quality suggests that currently available antibiotics statistically significantly reduced the risk for treatment failure between seven days and one month after treatment initiation (RR 0.72, 95% confidence interval (CI) 0.56 to 0.94; I² = 31%; in absolute terms, reduction in treatment failures from 295 to 212 per 1000 treated participants, 95% CI 165 to 277). Studies providing older antibiotics not in use anymore yielded an RR of 0.69 (95% CI 0.53 to 0.90; I² = 31%). Evidence of low quality from one trial in outpatients suggested no effects of antibiotics on mortality (Peto OR 1.27, 95% CI 0.49 to 3.30). One trial reported no effects of antibiotics on re-exacerbations between two and six weeks after treatment initiation. Only one trial (N = 35) reported health-related quality of life but did not show a statistically significant difference between treatment and control groups.Evidence of moderate quality does not show that currently used antibiotics statistically significantly reduced the risk of treatment failure among inpatients with severe exacerbations (i.e. for inpatients excluding ICU patients) (RR 0.65, 95% CI 0.38 to 1.12; I² = 50%), but trial results remain uncertain. In turn, the effect was statistically significant when trials included older antibiotics no longer in clinical use (RR 0.76, 95% CI 0.58 to 1.00; I² = 39%). Evidence of moderate quality from two trials including inpatients shows no beneficial effects of antibiotics on mortality (Peto OR 2.48, 95% CI 0.94 to 6.55). Length of hospital stay (in days) was similar in antibiotic and placebo groups.The only trial with 93 patients admitted to the ICU showed a large and statistically significant effect on treatment failure (RR 0.19, 95% CI 0.08 to 0.45; moderate-quality evidence; in absolute terms, reduction in treatment failures from 565 to 107 per 1000 treated participants, 95% CI 45 to 254). Results of this trial show a statistically significant effect on mortality (Peto OR 0.21, 95% CI 0.06 to 0.72; moderate-quality evidence) and on length of hospital stay (MD -9.60 days, 95% CI -12.84 to -6.36; low-quality evidence).Evidence of moderate quality gathered from trials conducted in all settings shows no statistically significant effect on overall incidence of adverse events (Peto OR 1.20, 95% CI 0.89 to 1.63; moderate-quality evidence) nor on diarrhoea (Peto OR 1.68, 95% CI 0.92 to 3.07; moderate-quality evidence). AUTHORS' CONCLUSIONS Researchers have found that antibiotics have some effect on inpatients and outpatients, but these effects are small, and they are inconsistent for some outcomes (treatment failure) and absent for other outcomes (mortality, length of hospital stay). Analyses show a strong beneficial effect of antibiotics among ICU patients. Few data are available on the effects of antibiotics on health-related quality of life or on other patient-reported symptoms, and data show no statistically significant increase in the risk of adverse events with antibiotics compared to placebo. These inconsistent effects call for research into clinical signs and biomarkers that can help identify patients who would benefit from antibiotics, while sparing antibiotics for patients who are unlikely to experience benefit and for whom downsides of antibiotics (side effects, costs, and multi-resistance) should be avoided

Proportion and predictors of remission and recovery in first-episode psychosis: Systematic review and meta-analysis

[EN] Background To determine the proportion of patients in symptomatic remission and recovery following a first-episode of psychosis (FEP). Methods A multistep literature search using the Web of Science database, Cochrane Central Register of Reviews, Ovid/PsychINFO, and trial registries from database inception to November 5, 2020, was performed. Cohort studies and randomized control trials (RCT) investigating the proportion of remission and recovery following a FEP were included. Two independent researchers searched, following PRISMA and MOOSE guidelines and using a PROSPERO protocol. We performed meta-analyses regarding the proportion of remission/recovery (symptomatic plus functional outcomes). Heterogeneity was measured employing Q statistics and I-2 test. To identify potential predictors, meta-regression analyses were conducted, as well as qualitative reporting of studies included in a systematic review. Sensitivity analyses were performed regarding different times of follow-up and type of studies. Results One hundred articles (82 cohorts and 18 RCTs) were included in the meta-analysis. The pooled proportion of symptomatic remission was 54% (95%CI [30, 49-58]) over a mean follow-up period of 43.57 months (SD = 51.82) in 76 studies. After excluding RCT from the sample, the proportion of remission remained similar (55%). The pooled proportion of recovery was 32% (95%CI [27-36]) over a mean follow-up period of 71.85 months (SD = 73.54) in 40 studies. After excluding RCT from the sample, the recovery proportion remained the same. No significant effect of any sociodemographic or clinical predictor was found. Conclusions Half of the patients are in symptomatic remission around 4 years after the FEP, while about a third show recovery after 5.5 years

Determinants and outcomes of physical activity in patients with COPD:a systematic review

BACKGROUND The relationship between physical activity, disease severity, health status and prognosis in patients with COPD has not been systematically assessed. Our aim was to identify and summarise studies assessing associations between physical activity and its determinants and/or outcomes in patients with COPD and to develop a conceptual model for physical activity in COPD. METHODS We conducted a systematic search of four databases (Medline, Embase, CINAHL and Psychinfo) prior to November 2012. Teams of two reviewers independently selected articles, extracted data and used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) to assess quality of evidence. RESULTS 86 studies were included: 59 were focused on determinants, 23 on outcomes and 4 on both. Hyperinflation, exercise capacity, dyspnoea, previous exacerbations, gas exchange, systemic inflammation, quality of life and self-efficacy were consistently related to physical activity, but often based on cross-sectional studies and low-quality evidence. Results from studies of pharmacological and non-pharmacological treatments were inconsistent and the quality of evidence was low to very low. As outcomes, COPD exacerbations and mortality were consistently associated with low levels of physical activity based on moderate quality evidence. Physical activity was associated with other outcomes such as dyspnoea, health-related quality of life, exercise capacity and FEV1 but based on cross-sectional studies and low to very low quality evidence. CONCLUSIONS Physical activity level in COPD is consistently associated with mortality and exacerbations, but there is poor evidence about determinants of physical activity, including the impact of treatment

Sistemas de Visualización Gamificados para la mejora de la Motivación Intrínseca en Estudiantes de Arquitectura [Gamified Visual Systems for improving the Intrinsic Motivation of Architectural Students]

El artículo presenta y analiza los resultados obtenidos en el proceso de incorporar sistemas gamificados de visualización 3D para proyectos urbanos en los estudios de grado y máster de Arquitectura. El proceso se ha diseñado a partir de una primera de recogida de datos iniciales para evaluar el perfil de los estudiantes, un segundo proceso práctico de formación y trabajo en entornos urbanos reales con el fin de diseñar nuevos usos a partir de una reordenación del espacio, todo ello utilizando sistemas digitales interactivos con el fin de gamificar la experiencia, y una tercera fase de recogida de resultados ligados a motivación, satisfacción y usabilidad de la experiencia. Los datos presentados se centran en la motivación inicial recogida de los estudiantes. Los resultados nos revelan una baja motivación inicial del estudiante, no entendiendo las utilidades que los juegos y entornos virtuales pueden aportar a la visualización del proyecto arquitectónico. No obstante, la propuesta utilizada ha conseguido mejorar dicha percepción inicial, mejorando el interés por la materia y en definitiva en las competencias de trabajo en equipo y en presentación tridimensional de proyectos. [The article analyzes the results obtained in the process of incorporating gamified 3D visual systems for urban projects into the degree and master of architecture. The process has been designed through a first collection of profile student’s data, followed by the practical process of working in real urban environments, and finally collecting the results lined to motivation, satisfaction and usability of the process. This project seeks to design new applications from a rearrangement of urban space using gamify-interactive digital systems in order to improve the user experience. The results reveal a low initial motivation in the students, not understanding that the usefulness of the games and the virtual environments can contribute to the visualization of the architectural and urban project. Nevertheless, the proposal has improved the initial perception, raising the interest in the subject and, ultimately, the teamwork skills and the three-dimensional presentation of the project.

LA SOCIEDAD FRENTE A LA GESTIÓN DEL RIESGO: CASO SOBRE LA AMENAZA SÍSMICA EN LA CIUDAD DE VILLAVICENCIO.

RESUMENEl alto riesgo que representan los eventos sísmicos para la ciudad de Villavicencio (Colombia), es un aspecto muy relevante a considerar por parte de las autoridades competentes, locales y regionales, con el fin de establecer políticas de desarrollo a corto, mediano y largo plazos. Ante esta situación, diferentes universidades y centros de investigación, en representación de la academia, han aportado conocimientos relacionados con el alcance de la amenaza sísmica en esta región de Colombia y han lanzado llamados de alerta ante el alto nivel de vulnerabilidad de la ciudad.En el presente trabajo se exponen algunos antecedentes históricos relacionados con la amenaza sísmica en Villavicencio, se presenta un análisis de los registros instrumentales existentes, se analiza la vulnerabilidad y el papel desempeñado por los entes involucrados (las autoridades político-administrativas y la academia), se hace una descripción de un posible escenario post-sísmico, y son presentadas ciertas recomendaciones para mitigar los efectos de un sismo de importancia. Con el análisis aquí presentado, se hace un llamado desde la academia con el fin de buscar nuevas estrategias para que en el corto plazo se consiga aumentar la efectividad de la gestión del riesgo en Colombia.Palabras Claves: Amenaza Sísmica, Villavicencio, Colombia, Gestión de Riesgo, Desarrollo Sostenible, Recuperación. THE SOCIETY IN FRONT OF THE RISK MANAGEMENT: ABOUT THE SEISMIC HAZARD IN VILLAVICENCIO CITY, COLOMBIA ABSTRACTThe high risk that represents an earthquake for Villavicencio city (Colombia), it is a very important aspect that civil local and regional authorities should assume and establish in the development plans in short, medium and long terms. In front of this situation, universities and research groups, like representatives of academy sector have contributed with knowledge related with the reach of the seismic hazard in this Colombian region and make alert calls due to the high level of vulnerability of the city. In this work some historical antecedents related with the seismic hazard in Villavicencio city are show, an analysis of the existent seismic instrumental registrations is presented, the vulnerability is analyzed and the role carried out by the involved entities is analyzed (the government authorities and the academy), a description of a possible post-seismic scenario is made, and certain recommendations to mitigate the effects of an earthquake of importance are presented. With the analysis here realized, the academy call to society is with the purpose of search new strategies so that in the short term it is possible to increase the effectiveness of the risk management in Colombia.Key Words: Seismic Hazard, Villavicencio, Colombia, Risk Management, Sustainable Development, Recovery

Aberrant Epstein-Barr virus antibody patterns and chronic lymphocytic leukemia in a Spanish multicentric case-control study

BACKGROUND: Epstein-Barr virus (EBV)-related malignancies harbour distinct serological responses to EBV antigens. We hypothesized that EBV serological patterns can be useful to identify different stages of chronic lymphocytic leukemia. METHODS: Information on 150 cases with chronic lymphocytic leukemia and 157 frequency-matched (by age, sex and region) population-based controls from a Spanish multicentre case-control study was obtained. EBV immunoglobulin G serostatus was evaluated through a peptide-based ELISA and further by immunoblot analysis to EBV early antigens (EA), nuclear antigen (EBNA1), VCA-p18, VCA-p40 and Zebra. Two independent individuals categorized the serological patterns of the western blot analysis. Patients with very high response and diversity in EBV-specific polypeptides, in particular with clear responses to EA-associated proteins, were categorized as having an abnormal reactive pattern (ab_EBV). Adjusted odds ratios (OR) and 95% confidence interval (CI) were estimated using logistic regression models. RESULTS: Almost all subjects were EBV-IgG positive (>95% of cases and controls) whereas ab_EBV patterns were detected in 23% of cases (N = 34) and 11% of controls (N = 17; OR: 2.44, 95% CI, 1.29 to 4.62; P = 0.006), particularly in intermediate/high risk patients. Although based on small numbers, the association was modified by smoking with a gradual reduction of ab_EBV-related OR for all Rai stages from never smokers to current smokers. CONCLUSIONS: Highly distinct EBV antibody diversity patterns revealed by immunoblot analysis were detected in cases compared to controls, detectable at very early stages of the disease and particularly among non smokers. This study provides further evidence of an abnormal immunological response against EBV in patients with chronic lymphocytic leukemia

Aberrant Epstein-Barr virus antibody patterns and chronic lymphocytic leukemia in a Spanish multicentric case-control study

Background: Epstein-Barr virus (EBV)-related malignancies harbour distinct serological responses to EBV antigens. We hypothesized that EBV serological patterns can be useful to identify different stages of chronic lymphocytic leukemia. Methods: Information on 150 cases with chronic lymphocytic leukemia and 157 frequency-matched (by age, sex and region) population-based controls from a Spanish multicentre case-control study was obtained. EBV immunoglobulin G serostatus was evaluated through a peptide-based ELISA and further by immunoblot analysis to EBV early antigens (EA), nuclear antigen (EBNA1), VCA-p18, VCA-p40 and Zebra. Two independent individuals categorized the serological patterns of the western blot analysis. Patients with very high response and diversity in EBV-specific polypeptides, in particular with clear responses to EA-associated proteins, were categorized as having an abnormal reactive pattern (ab_EBV). Adjusted odds ratios (OR) and 95% confidence interval (CI) were estimated using logistic regression models. Results: Almost all subjects were EBV-IgG positive (>95% of cases and controls) whereas ab_EBV patterns were detected in 23% of cases (N = 34) and 11% of controls (N = 17; OR: 2.44, 95% CI, 1.29 to 4.62; P = 0.006), particularly in intermediate/high risk patients. Although based on small numbers, the association was modified by smoking with a gradual reduction of ab_EBV-related OR for all Rai stages from never smokers to current smokers. Conclusions: Highly distinct EBV antibody diversity patterns revealed by immunoblot analysis were detected in cases compared to controls, detectable at very early stages of the disease and particularly among non smokers. This study provides further evidence of an abnormal immunological response against EBV in patients with chronic lymphocytic leukemia

LA SOCIEDAD FRENTE A LA GESTIÓN DEL RIESGO: CASO SOBRE LA AMENAZA SÍSMICA EN LA CIUDAD DE VILLAVICENCIO.

RESUMENEl alto riesgo que representan los eventos sísmicos para la ciudad de Villavicencio (Colombia), es un aspecto muy relevante a considerar por parte de las autoridades competentes, locales y regionales, con el fin de establecer políticas de desarrollo a corto, mediano y largo plazos. Ante esta situación, diferentes universidades y centros de investigación, en representación de la academia, han aportado conocimientos relacionados con el alcance de la amenaza sísmica en esta región de Colombia y han lanzado llamados de alerta ante el alto nivel de vulnerabilidad de la ciudad.En el presente trabajo se exponen algunos antecedentes históricos relacionados con la amenaza sísmica en Villavicencio, se presenta un análisis de los registros instrumentales existentes, se analiza la vulnerabilidad y el papel desempeñado por los entes involucrados (las autoridades político-administrativas y la academia), se hace una descripción de un posible escenario post-sísmico, y son presentadas ciertas recomendaciones para mitigar los efectos de un sismo de importancia. Con el análisis aquí presentado, se hace un llamado desde la academia con el fin de buscar nuevas estrategias para que en el corto plazo se consiga aumentar la efectividad de la gestión del riesgo en Colombia.Palabras Claves: Amenaza Sísmica, Villavicencio, Colombia, Gestión de Riesgo, Desarrollo Sostenible, Recuperación. THE SOCIETY IN FRONT OF THE RISK MANAGEMENT: ABOUT THE SEISMIC HAZARD IN VILLAVICENCIO CITY, COLOMBIA ABSTRACTThe high risk that represents an earthquake for Villavicencio city (Colombia), it is a very important aspect that civil local and regional authorities should assume and establish in the development plans in short, medium and long terms. In front of this situation, universities and research groups, like representatives of academy sector have contributed with knowledge related with the reach of the seismic hazard in this Colombian region and make alert calls due to the high level of vulnerability of the city. In this work some historical antecedents related with the seismic hazard in Villavicencio city are show, an analysis of the existent seismic instrumental registrations is presented, the vulnerability is analyzed and the role carried out by the involved entities is analyzed (the government authorities and the academy), a description of a possible post-seismic scenario is made, and certain recommendations to mitigate the effects of an earthquake of importance are presented. With the analysis here realized, the academy call to society is with the purpose of search new strategies so that in the short term it is possible to increase the effectiveness of the risk management in Colombia.Key Words: Seismic Hazard, Villavicencio, Colombia, Risk Management, Sustainable Development, Recovery

An umbrella review of candidate predictors of response, remission, recovery, and relapse across mental disorders

We aimed to identify diagnosis-specific/transdiagnostic/transoutcome multivariable candidate predictors (MCPs) of key outcomes in mental disorders. We conducted an umbrella review (protocol  link ), searching MEDLINE/Embase (19/07/2022), including systematic reviews of studies reporting on MCPs of response, remission, recovery, or relapse, in DSM/ICD-defined mental disorders. From published predictors, we filtered MCPs, validating MCP criteria. AMSTAR2/PROBAST measured quality/risk of bias of systematic reviews/individual studies. We included 117 systematic reviews, 403 studies, 299,888 individuals with mental disorders, testing 796 prediction models. Only 4.3%/1.2% of the systematic reviews/individual studies were at low risk of bias. The most frequently targeted outcome was remission (36.9%), the least frequent was recovery (2.5%). Studies mainly focused on depressive (39.4%), substance-use (17.9%), and schizophrenia-spectrum (11.9%) disorders. We identified numerous MCPs within disorders for response, remission and relapse, but none for recovery. Transdiagnostic MCPs of remission included lower disease-specific symptoms (disorders = 5), female sex/higher education (disorders = 3), and quality of life/functioning (disorders = 2). Transdiagnostic MCPs of relapse included higher disease-specific symptoms (disorders = 5), higher depressive symptoms (disorders = 3), and younger age/higher anxiety symptoms/global illness severity/ number of previous episodes/negative life events (disorders = 2). Finally, positive trans-outcome MCPs for depression included less negative life events/depressive symptoms (response, remission, less relapse), female sex (response, remission) and better functioning (response, less relapse); for schizophrenia, less positive symptoms/higher depressive symptoms (remission, less relapse); for substance use disorder, marital status/higher education (remission, less relapse). Male sex, younger age, more clinical symptoms and comorbid mental/physical symptoms/disorders were poor prognostic factors, while positive factors included social contacts and employment, absent negative life events, higher education, early access/intervention, lower disease-specific and comorbid mental and physical symptoms/conditions, across mental disorders. Current data limitations include high risk of bias of studies and extraction of single predictors from multivariable models. Identified MCPs can inform future development, validation or refinement of prediction models of key outcomes in mental disorders