Seguridad del paciente en atención primaria de salud : magnitud del problema

La seguridad del paciente (SP) ha preocupado desde siempre a los profesionales sanitarios en todos los escenarios de la práctica clínica. Es importante asumir una taxonomía común para hablar de SP y conocer cuales son las amenazas mediante el estudio de los eventos adversos (EA). El estudio APEAS mostró una prevalencia de EA de un 11,18‰, de los cuales un 47,8% estaban relacionados con la medicación. Al analizar la gravedad e impacto de los mismos pudo observarse que la mayor parte eran leves y se resolvían en el propio centro de salud. La causalidad de los EA es compleja. La medicación prescrita es un factor causal esencial en casi la mitad de los EA, junto con factores como la comunicación, la gestión y los cuidados. Aplicando el conocimiento disponible, el 70% de los EA que aparecen en el primer nivel asistencial fueron valorados por los propios profesionales como evitables. En el primer nivel asistencial confluyen varios factores diferenciales en relación con la SP que podrían incrementar el riesgo de aparición de EA e incidentes relacionados con la SP: la elevada presión asistencial, la hiperfrecuentación, la ambulatorización de cuidados y seguimientos, la deficiente continuidad asistencial y escasa comunicación entre atención primaria y especializada, la medicalización incontrolada y desmedida de procesos banales, al igual que la generalización de pruebas diagnósticas y tratamientos sin evidencia razonable de efectividad son una amenaza para la SP. El hecho de que los incidentes relacionados con la SP y los EA sean un problema común y en gran parte evitable, sitúa la mejora de la SP en el primer nivel asistencial como una estrategia prioritaria, siendo conscientes de que se trata de un problema crónico que requiere perseverancia y tratamiento continuado

A DNA damage repair gene-associated signature predicts responses of patients with advanced soft-tissue sarcoma to treatment with trabectedin

Predictive biomarkers of trabectedin represent an unmet need in advanced soft-tissue sarcomas (STS). DNA damage repair (DDR) genes, involved in homologous recombination or nucleotide excision repair, had been previously described as biomarkers of trabectedin resistance or sensitivity, respectively. The majority of these studies only focused on specific factors (ERCC1, ERCC5, and BRCA1) and did not evaluate several other DDR-related genes that could have a relevant role for trabectedin efficacy. In this retrospective translational study, 118 genes involved in DDR were evaluated to determine, by transcriptomics, a predictive gene signature of trabectedin efficacy. A six-gene predictive signature of trabectedin efficacy was built in a series of 139 tumor samples from patients with advanced STS. Patients in the high-risk gene signature group showed a significantly worse progression-free survival compared with patients in the low-risk group (2.1 vs 6.0 months, respectively). Differential gene expression analysis defined new potential predictive biomarkers of trabectedin sensitivity (PARP3 and CCNH) or resistance (DNAJB11 and PARP1). Our study identified a new gene signature that significantly predicts patients with higher probability to respond to treatment with trabectedin. Targeting some genes of this signature emerges as a potential strategy to enhance trabectedin efficacy.This study was funded by the Spanish Group for Research on Sarcoma (GEIS) and partially by PharmaMar. The authors would like to thank the GEIS data center for data management. The authors also thank the donors and the Hospital Universitario Virgen del Rocío—Instituto de Biomedicina de Sevilla Biobank (Andalusian Public Health System Biobank and ISCIII-Red de Biobancos PT17/0015/0041) for part of the human specimens used in this study. David S. Moura is recipient of a Sara Borrell postdoctoral fellowship funded by the National Institute of Health Carlos III (ISCIII) (CD20/00155)

Steroid-Resistant Graves’ Orbitopathy Treated with Tocilizumab in Real-World Clinical Practice: A 9-Year Single-Center Experience

This study aimed to assess the effectiveness and safety of tocilizumab use for the treatment of active steroid-resistant Graves’ orbitopathy (GO). A retrospective longitudinal study was conducted by reviewing the medical records at a single center between November 2009 and December 2018. A total of 114 patients with steroid-resistant Graves’ orbitopathy were examined and treated with tocilizumab, of which 54 adults met the inclusion criteria. No concomitant medication for the treatment of orbitopathy was used. The main primary outcomes included changes from baseline in the Clinical Activity Score (CAS) and thyrotropin receptor antibody (TRAb) levels throughout therapy with tocilizumab. The absolute responses to treatment were defined as the achievement of CAS ≤ 1 and TRAb ≤ 10 U/L. A composite ophthalmic score including CAS, proptosis, eyelid retraction, and diplopia was used to evaluate individual improvement in GO. Adverse drug reactions were also assessed. Analysis of the patient’s CAS and TRAb levels showed meaningful reductions during tocilizumab treatment. Differences between values at baseline and subsequent time points were statistically significant (p < 0.001 for all comparisons). The absolute CAS response (CAS = 0 or 1) was achieved in 74% (37/50) of patients after the fourth dose of tocilizumab (at week 16), with a TRAb response being achieved in 55% (23/42) of patients. The relative CAS response (reduction ≥ 2 points) was achieved in 90.9% of patients (40/44) after the first dose of tocilizumab (at week 4). Measurements of proptosis (reduction ≥ 2 mm in 78% of patients, 42/54) and eyelid retraction (reduction ≥ 2 mm in 75%, 33/44), and the prevalence of diplopia (improvement in 68%, 19/28) were significantly reduced after the last dose of tocilizumab (p < 0.001 for all comparisons). GO improved in 98% (53/54) of patients when at least two criteria of the composite evaluation were required. Four patients exhibited disease recurrence, defined as an increase in CAS of ≥2 points in the six months following the date of inactivation. Most adverse drug reactions were mild or moderate in severity. In conclusion, our data suggest that a course of at least 4 months (one monthly dose) of tocilizumab therapy provides a significant benefit to patients with active moderate-to-severe steroid-resistant GO

Steroid-Resistant Graves' Orbitopathy Treated with Tocilizumab in Real-World Clinical Practice: A 9-Year Single-Center Experience

This study aimed to assess the effectiveness and safety of tocilizumab use for the treatment of active steroid-resistant Graves' orbitopathy (GO). A retrospective longitudinal study was conducted by reviewing the medical records at a single center between November 2009 and December 2018. A total of 114 patients with steroid-resistant Graves' orbitopathy were examined and treated with tocilizumab, of which 54 adults met the inclusion criteria. No concomitant medication for the treatment of orbitopathy was used. The main primary outcomes included changes from baseline in the Clinical Activity Score (CAS) and thyrotropin receptor antibody (TRAb) levels throughout therapy with tocilizumab. The absolute responses to treatment were defined as the achievement of CAS /= 2 points) was achieved in 90.9% of patients (40/44) after the first dose of tocilizumab (at week 4). Measurements of proptosis (reduction >/= 2 mm in 78% of patients, 42/54) and eyelid retraction (reduction >/= 2 mm in 75%, 33/44), and the prevalence of diplopia (improvement in 68%, 19/28) were significantly reduced after the last dose of tocilizumab (p /=2 points in the six months following the date of inactivation. Most adverse drug reactions were mild or moderate in severity. In conclusion, our data suggest that a course of at least 4 months (one monthly dose) of tocilizumab therapy provides a significant benefit to patients with active moderate-to-severe steroid-resistant GO

Seguridad del paciente en atención primaria de salud : magnitud del problema

La seguridad del paciente (SP) ha preocupado desde siempre a los profesionales sanitarios en todos los escenarios de la práctica clínica. Es importante asumir una taxonomía común para hablar de SP y conocer cuales son las amenazas mediante el estudio de los eventos adversos (EA). El estudio APEAS mostró una prevalencia de EA de un 11,18‰, de los cuales un 47,8% estaban relacionados con la medicación. Al analizar la gravedad e impacto de los mismos pudo observarse que la mayor parte eran leves y se resolvían en el propio centro de salud. La causalidad de los EA es compleja. La medicación prescrita es un factor causal esencial en casi la mitad de los EA, junto con factores como la comunicación, la gestión y los cuidados. Aplicando el conocimiento disponible, el 70% de los EA que aparecen en el primer nivel asistencial fueron valorados por los propios profesionales como evitables. En el primer nivel asistencial confluyen varios factores diferenciales en relación con la SP que podrían incrementar el riesgo de aparición de EA e incidentes relacionados con la SP: la elevada presión asistencial, la hiperfrecuentación, la ambulatorización de cuidados y seguimientos, la deficiente continuidad asistencial y escasa comunicación entre atención primaria y especializada, la medicalización incontrolada y desmedida de procesos banales, al igual que la generalización de pruebas diagnósticas y tratamientos sin evidencia razonable de efectividad son una amenaza para la SP. El hecho de que los incidentes relacionados con la SP y los EA sean un problema común y en gran parte evitable, sitúa la mejora de la SP en el primer nivel asistencial como una estrategia prioritaria, siendo conscientes de que se trata de un problema crónico que requiere perseverancia y tratamiento continuado

Evolution and bad prognostic value of advanced glycation end products after acute heart failure: relation with body composition

Abstract Aim The role of advanced glycation end products (AGEs) and their soluble receptor (sRAGE) on the progression and prognosis of acute heart failure (HF) was analysed in relation with metabolic parameters as body composition and nutritional status. Methods A hundred and fifty consecutive patients were included in a prospective clinical study during hospitalization by acute HF. Detailed medical history, physical examination, electrocardiogram, echocardiogram and vein peripheral blood were taken for all patients. During the follow-up period [297 days (88–422 days)] blood samples for biochemical measurements were obtained 1 and 6 months after the inclusion. Dual-energy X-ray absorptiometry analyses were performed 1 week after discharge. Results AGEs and sRAGE levels continuously increased, up to 6 months, after acute HF, but AGEs increase was mainly observed in those patients with incident HF. Both AGEs and sRAGE levels were related with bad renal function and clinical malnutrition (CONUT score) and they were negatively related with body mass index or percentage of body fat. AGEs levels (≥40 a.u.) 1 month after discharge and basal sRAGE levels (>1000 pg/mL) were related with worse prognosis in terms of patient death and HF readmission (Log-rank <0.05 in Kaplan–Meier survival test), independently of age, gender, body mass index and other risk factors. Regression models also corroborated this finding. Conclusions AGEs and sRAGE are bad prognostic biomarkers for HF and useful markers of HF progression. Since their levels seem to be related with clinical malnutrition and body composition these parameters could serve to modulate them

Prevention of ventilator-associated pneumonia: the multimodal approach of the Spanish ICU "Pneumonia Zero" program

OBJECTIVES: The "Pneumonia Zero" project is a nationwide multimodal intervention based on the simultaneous implementation of a comprehensive evidence-based bundle measures to prevent ventilator-associated pneumonia in critically ill patients admitted to the ICU. DESIGN: Prospective, interventional, and multicenter study. SETTING: A total of 181 ICUs throughout Spain. PATIENTS: All patients admitted for more than 24 hours to the participating ICUs between April 1, 2011, and December 31, 2012. INTERVENTION: Ten ventilator-associated pneumonia prevention measures were implemented (seven were mandatory and three highly recommended). The database of the National ICU-Acquired Infections Surveillance Study (Estudio Nacional de Vigilancia de Infecciones Nosocomiales [ENVIN]) was used for data collection. Ventilator-associated pneumonia rate was expressed as incidence density per 1,000 ventilator days. Ventilator-associated pneumonia rates from the incorporation of the ICUs to the project, every 3 months, were compared with data of the ENVIN registry (April-June 2010) as the baseline period. Ventilator-associated pneumonia rates were adjusted by characteristics of the hospital, including size, type (public or private), and teaching (postgraduate) or university-affiliated (undergraduate) status. MEASUREMENTS AND MAIN RESULTS: The 181 participating ICUs accounted for 75% of all ICUs in Spain. In a total of 171,237 ICU admissions, an artificial airway was present on 505,802 days (50.0% of days of stay in the ICU). A total of 3,474 ventilator-associated pneumonia episodes were diagnosed in 3,186 patients. The adjusted ventilator-associated pneumonia incidence density rate decreased from 9.83 (95% CI, 8.42-11.48) per 1,000 ventilator days in the baseline period to 4.34 (95% CI, 3.22-5.84) after 19-21 months of participation. CONCLUSIONS: Implementation of the bundle measures included in the "Pneumonia Zero" project resulted in a significant reduction of more than 50% of the incidence of ventilator-associated pneumonia in Spanish ICUs. This reduction was sustained 21 months after implementation