Effectiveness of a cognitive behavioral intervention in patients with medically unexplained symptoms: cluster randomized trial

BACKGROUND: Medically unexplained symptoms are an important mental health problem in primary care and generate a high cost in health services.Cognitive behavioral therapy and psychodynamic therapy have proven effective in these patients. However, there are few studies on the effectiveness of psychosocial interventions by primary health care. The project aims to determine whether a cognitive-behavioral group intervention in patients with medically unexplained symptoms, is more effective than routine clinical practice to improve the quality of life measured by the SF-12 questionary at 12 month. METHODS/DESIGN: This study involves a community based cluster randomized trial in primary healthcare centres in Madrid (Spain). The number of patients required is 242 (121 in each arm), all between 18 and 65 of age with medically unexplained symptoms that had seeked medical attention in primary care at least 10 times during the previous year. The main outcome variable is the quality of life measured by the SF-12 questionnaire on Mental Healthcare. Secondary outcome variables include number of consultations, number of drug (prescriptions) and number of days of sick leave together with other prognosis and descriptive variables. Main effectiveness will be analyzed by comparing the percentage of patients that improve at least 4 points on the SF-12 questionnaire between intervention and control groups at 12 months. All statistical tests will be performed with intention to treat. Logistic regression with random effects will be used to adjust for prognostic factors. Confounding factors or factors that might alter the effect recorded will be taken into account in this analysis. DISCUSSION: This study aims to provide more insight to address medically unexplained symptoms, highly prevalent in primary care, from a quantitative methodology. It involves intervention group conducted by previously trained nursing staff to diminish the progression to the chronicity of the symptoms, improve quality of life, and reduce frequency of medical consultations. TRIAL REGISTRATION: The trial was registered with ClinicalTrials.gov, number NCT01484223 [http://ClinicalTrials.gov].S

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Evolution of the Use of Corticosteroids for the Treatment of Hospitalised COVID-19 Patients in Spain between March and November 2020 SEMI-COVID National Registry

Objectives: Since the results of the RECOVERY trial, WHO recommendations about the use of corticosteroids (CTs) in COVID-19 have changed. The aim of the study is to analyse the evolutive use of CTs in Spain during the pandemic to assess the potential influence of new recommendations. Material and methods: A retrospective, descriptive, and observational study was conducted on adults hospitalised due to COVID-19 in Spain who were included in the SEMI-COVID-19 Registry from March to November 2020. Results: CTs were used in 6053 (36.21%) of the included patients. The patients were older (mean (SD)) (69.6 (14.6) vs. 66.0 (16.8) years; p < 0.001), with hypertension (57.0% vs. 47.7%; p < 0.001), obesity (26.4% vs. 19.3%; p < 0.0001), and multimorbidity prevalence (20.6% vs. 16.1%; p < 0.001). These patients had higher values (mean (95% CI)) of C-reactive protein (CRP) (86 (32.7–160) vs. 49.3 (16–109) mg/dL; p < 0.001), ferritin (791 (393–1534) vs. 470 (236–996) µg/dL; p < 0.001), D dimer (750 (430–1400) vs. 617 (345–1180) µg/dL; p < 0.001), and lower Sp02/Fi02 (266 (91.1) vs. 301 (101); p < 0.001). Since June 2020, there was an increment in the use of CTs (March vs. September; p < 0.001). Overall, 20% did not receive steroids, and 40% received less than 200 mg accumulated prednisone equivalent dose (APED). Severe patients are treated with higher doses. The mortality benefit was observed in patients with oxygen saturation </=90%. Conclusions: Patients with greater comorbidity, severity, and inflammatory markers were those treated with CTs. In severe patients, there is a trend towards the use of higher doses. The mortality benefit was observed in patients with oxygen saturation </=90%

Predicting anti-TNF treatment response in rheumatoid arthritis: An artificial intelligence-driven model using cytokine profile and routine clinical practice parameters

Introduction: Rheumatoid arthritis (RA) is a heterogeneous disease in which therapeutic strategies used have evolved dramatically. Despite significant progress in treatment strategies such as the development of anti-TNF drugs, it is still not possible to differentiate those patients who will respond from who will not. This can lead to effective-treatment delays and unnecessary costs. The aim of this study was to utilize a profile of the patient's characteristics, clinical parameters, immune status (cytokine profile) and artificial intelligence to assess the feasibility of developing a tool that could allow us to predict which patients will respond to treatment with anti-TNF drugs. Methods: This study included 38 patients with RA from the RA-Paz cohort. Clinical activity was measured at baseline and after 6 months of treatment. The cytokines measured before the start of anti-TNF treatment were IL-1, IL-12, IL-10, IL-2, IL-4, IFNg, TNFa, and IL-6. Statistical analyses were performed using the Wilcoxon-Rank-Sum Test and the Benjamini-Hochberg method. The predictive model viability was explored using the 5-fold cross-validation scheme in order to train the logistic regression models. Results: Statistically significant differences were found in parameters such as IL-6, IL-2, CRP and DAS-ESR. The predictive model performed to an acceptable level in correctly classifying patients (ROC-AUC 0.804167 to 0.891667), suggesting that it would be possible to develop a clinical classification tool. Conclusions: Using a combination of parameters such as IL-6, IL-2, CRP and DAS-ESR, it was possible to develop a predictive model that can acceptably discriminate between remitters and non-remitters. However, this model needs to be replicated in a larger cohort to confirm these findings

Outcomes in African Americans and Hispanics with lupus nephritis

Poor outcomes have been reported in African Americans and Hispanics compared to Caucasians with lupus nephritis. The purpose of this retrospective analysis was to identify independent predictors of outcomes in African Americans and Hispanics with lupus nephritis. In total, 93 African Americans, 100 Hispanics, and 20 Caucasians with a mean age of 28±13 years and an annual household income of 32.9±17.3 (in $1000) were studied. World Health Organization (WHO) lupus nephritis classes II, III, IV, and V were seen in 9, 13, 52, and 26$1000; P<0.05). Lower prevalence of WHO class IV was seen in Caucasians (30%) compared to Hispanics (57%, P=0.03) and African Americans (51%, P=0.09). Development of doubling creatinine or end-stage renal disease was higher in African Americans and Hispanics than in Caucasians (31, 18, and 10%; P<0.05), as was the development of renal events or death (34, 20, and 10%; P<0.025). Our results suggest that both biological factors indicating an aggressive disease and low household income are common in African Americans and Hispanics with lupus nephritis, and outcomes in these groups are worse than in Caucasians

The value of mouse models of rare diseases: a spanish experience

Animal models are invaluable for biomedical research, especially in the context of rare diseases, which have a very low prevalence and are often complex. Concretely mouse models provide key information on rare disease mechanisms and therapeutic strategies that cannot be obtained by using only alternative methods, and greatly contribute to accelerate the development of new therapeutic options for rare diseases. Despite this, the use of experimental animals remains controversial. The combination of respectful management, ethical laws and transparency regarding animal experimentation contributes to improve society's opinion about biomedical research and positively impacts on research quality, which eventually also benefits patients. Here we present examples of current advances in preclinical research in rare diseases using mouse models, together with our perspective on future directions and challenges.This work was supported by a grant from the Center for Biomedical Research on Rare Diseases (CIBERER) (ER18GDT761) to SM-C. Additional support came from: Multi Target and View FEDER/CM-B2017/BMD-3688 and MINECO/FEDER SAF2017-86107-R grants to SM-C and IV-N; CERCA Program/Generalitat de Catalunya, Autonomous Government of Catalonia (2017SGR1206), and CIBERER (ACCI18-27) to AP; Miguel Servet program CPII16/00016 (Instituto de Salud Carlos III co-funded by European Social Fund ESF) to SF; CNIC (ISCIII, Ministerio de Ciencia, Innovación y Universidades), Pro CNIC Foundation, Severo Ochoa Center of Excellence (SEV-2015-0505) to BI and EO; Generalitat de Catalunya (Grups consolidats 2017 SGR 926) to MD. EO was beneficiary of a grant from “Programa de Atracción de Talento” of Comunidad de Madrid (2017-T1/BMD-5185). SM-C holds a ISCiii CIBER postdoctoral researcher contract. The work at CRG was supported by grants from the Spanish Ministry of Science and Innovation to the EMBL partnership, the Centro de Excelencia Severo Ochoa and the CERCA Programme/Generalitat de Catalunya

Factors associated with poor outcomes in patients with lupus nephritis

The objective of this study was to identify the factors associated with important clinical outcomes in a case-control study of 213 patients with lupus nephritis. Included were 47% Hispanics, 44% African Americans and 9% Caucasians with a mean age of 28 years. Fifty-four (25%) patients reached the primary composite outcome of doubling serum creatinine, end-stage renal disease or death during a mean follow-up of 37 months. Thirty-four percent African Americans, 20% Hispanics and 10% Caucasians reached the primary composite outcome (P < 0.05). Patients reaching the composite outcome had predominantly proliferative lupus nephritis (WHO classes: 30% III, 32% IV, 18% V and 5% II, P < 0.025) with higher activity index score (7 ± 6 versus 5 ± 5, P<0.05), chronicity index (CI) score (4 ± 3 versus 2 ± 2 unit, P<0.025), higher baseline mean arterial pressure (MAP) (111 ± 21 versus 102 ± 14 mmHg, P<0.025) and serum creatinine (1.9 ± 1.3 versus 1.3 ± 1.0 mg/dL, P<0.025), but lower baseline hematocrit (29 ± 6 versus 31 + 5%, P<0.025) and complement C3 (54 ± 26 versus 65 + 33 mg/dL, P<0.025) compared to controls. More patients reaching the composite outcome had nephrotic range proteinuria compared to controls (74% versus 56%, P<0.025). By multivariate analysis, CI (hazard ratio [95% CI] 1.18 [1.07-1.30] per point), MAP (HR 1.02 [1.00-1.03] per mmHg), and baseline serum creatinine (HR 1.26 [1.04-1.54] per mg/dL) were independently associated with the composite outcome. We concluded that hypertension and elevated serum creatinine at the time of the kidney biopsy as well as a high CI are associated with an increased the risk for chronic renal failure or death in patients with lupus nephritis

La política social desde la constitución de 1991 ¿una década perdida?

Los artículos reunidos en este volumen fueron agrupados en cinco grandes apartados: Transformaciones contemporáneas en las políticas públicas, políticas sectoriales, grupos poblacionales, desplazados y nuevos modelos de ordenamiento y gestión territorial. El primero de ellos recoge las reflexiones de carácter más general concernientes a la relación existente entre los grandes cambios contemporáneos y su influencia en la política social. En él, Juan Carlos Ramírez examina las consecuencias que la globalización ha tenido para América Latina durante la década de los 90 y la manera en que la región se ha insertado en el nuevo orden mundial. El segundo apartado incluye los artículos relacionados con políticas sectoriales. En él se examinan el empleo y la seguridad social, las reformas educativas y las políticas de hábitat y vivienda. El malogrado ministro de Protección Social, Juan Luis Londoño, hace una revisión crítica de las políticas sociales del país durante los últimos años, para concluir presentado las principales estrategias que guiarían el accionar del Ministerio entonces a su cargo. Las políticas sociales concernientes a los grupos poblacionales es el tema de la tercera sección del libro. Cuatro temas están incluidos en este apartado: las políticas relacionadas con el género, con las minorías étnicas, con la infancia y con el adulto mayor. La última sección del libro aborda las reformas asociadas a la descentralización y los nuevos modelos territoriales.Presentación, Carlos Miguel Ortiz; Introducción, Arturo Claudio Laguado; Primera Parte: Transformaciones contemporáneas de la política pública. La nueva ola de la globalización, Juan Carlos Ramírez; Focalización y subsidios: ¿Por la demanda o por la oferta?, Albert Berry; Subsidios a la demanda vs. subsidios a la oferta. Comentarios a la ponencia del profesor Albert Berry, Jorge Iván Bula; Notas sobre exclusión social y acción colectiva. Reflexiones desde Argentina, Emilio Tenti Fanfani; La política antidrogas y la calidad de vida, Eduardo Gamarra; Lo público, lo estatal y lo privado, Jorge Iván González; Segunda Parte: Políticas sectoriales. Trabajo, seguridad social y flexibilidad, Juan Luis Londoño; La revolución educativa. Plan Sectorial 2002-2006, Javier Botero; Gerencialismo y testing. Dos nuevas modalidades de política educativa en Colombia, Víctor Manuel Gómez; Notas sobre hábitat y sostenibilidad, Fabio Giraldo I; Ciudad, hábitat y calidad de vida, Germán Ávila; Tercera Parte: Grupos poblacionales. Las políticas públicas y el género: un esfuerzo de mapeamiento sectorial y evaluación de acciones, Nelly Stromquist; Política para mujeres. Una constante paradoja, Yolanda Puyana; Mujer, género y política social, Piedad Córdoba; Entidades afrocolombianas vacías. Currulaos con maracas, Jaime Arocha; Una mirada a la política social para los pueblos indígenas en Colombia 1990-2002, Gabriel Muyuy; Contribución al análisis de la política pública de infancia en la década de los noventa, María Cristina Torrado y Ernesto Durán; Las políticas púb licas a favor de las personas de la tercera edad: ¿asistencialismo, focalización o exclusión?, Aura Marlén Márquez; Cuarta Parte: Desplazados. Desplazamiento forzado, crisis humanitaria y de derechos humanos y Estado débil, Harvey Danilo Suárez; La política pública de prevención del desplazamiento y de protección de los derechos de la población desplazada en Colombia: una deuda por cancelar, Juan Manuel Bustillo; Desplazados, migraciones y movilidad social, Patricia Luna; Quinta Parte: Nuevos modelos de ordenamiento y gestión territorial. La reforma territorial: Avances, dificultades y perspectivas, Miguel Borja; Nuevos modelos de ordenamiento y gestión territorial, José Oswaldo Espinosa y Óscar Ismael Sánchez; Reordenamiento y gestión territorial, Carlos Córdoba