Bridging the gap between researchers and patients: The role of the Institutional Review Boards in the informed consent process

Background: The Institutional-Review-Boards (IRB) frequently give unfavorable opinions to evaluated studies due to deficiencies in informed consent forms (ICFs), which delays the ethical approval of the study and increases waste in research. Objective: To analyze the extent to which IRB in our center gives unfavorable opinions due to documents deficiencies and to evaluate types of objection. Material and methods: Retrospective observational study of decisions during the first review by the IRB in our center (2012-2015). We carried out a systematic review of minutes when decisions on approval of studies are collected. If not approval, we analyzed appealed objections. Results: 1858 clinical studies were evaluated by the IRB. 1558 required informed consent for participating (83.9%, CI95%:82.1-85.5), 987 were not approved during the first review due to deficiencies in ICFs (63.3%, CI95%:60.9-65.7). The main causes of objections for non-approval were unreadability (11.7%, CI95%:10.6-12.9), inadequate information given about access to personal data rights (9.2%, CI95%:8.1-10.2), biological samples management (7.8%, IC95%:6.9-8.8), and expected benefits (7.6%, IC95%:6.7-8.6). Conclusions: Deficiencies in ICFs are an important reason for non-approval of protocols evaluated by an IRB. There are three fundamental weaknesses on which the IRB plays a key role: 1) improving readability; 2) adapting them to regulations concerning data protection and biological materials management; 3) avoiding misleading information towards enrollment

Bridging the gap between researchers and patients: The role of the Institutional Review Boards in the informed consent process

Background: The Institutional-Review-Boards (IRB) frequently give unfavorable opinions to evaluated studies due to deficiencies in informed consent forms (ICFs), which delays the ethical approval of the study and increases waste in research. Objective: To analyze the extent to which IRB in our center gives unfavorable opinions due to documents deficiencies and to evaluate types of objection. Material and methods: Retrospective observational study of decisions during the first review by the IRB in our center (2012-2015). We carried out a systematic review of minutes when decisions on approval of studies are collected. If not approval, we analyzed appealed objections. Results: 1858 clinical studies were evaluated by the IRB. 1558 required informed consent for participating (83.9%, CI95%:82.1-85.5), 987 were not approved during the first review due to deficiencies in ICFs (63.3%, CI95%:60.9-65.7). The main causes of objections for non-approval were unreadability (11.7%, CI95%:10.6-12.9), inadequate information given about access to personal data rights (9.2%, CI95%:8.1-10.2), biological samples management (7.8%, IC95%:6.9-8.8), and expected benefits (7.6%, IC95%:6.7-8.6). Conclusions: Deficiencies in ICFs are an important reason for non-approval of protocols evaluated by an IRB. There are three fundamental weaknesses on which the IRB plays a key role: 1) improving readability; 2) adapting them to regulations concerning data protection and biological materials management; 3) avoiding misleading information towards enrollment

A cohort of patients with COVID-19 in a major teaching hospital in Europe

Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración, si le hubiere, y los autores pertenecientes a la UAMArtículo escrito en nombre del COVID@HULP Working GroupSince the confirmation of the first patient infected with SARS-CoV-2 in Spain in January 2020, the epidemic has grown rapidly, with the greatest impact on the region of Madrid. This article describes the first 2226 adult patients with COVID-19, consecutively admitted to La Paz University Hospital in Madrid. Methods: Our cohort included all patients consecutively hospitalized who had a final outcome (death or discharge) in a 1286-bed hospital of Madrid (Spain) from 25 February (first case admitted) to 19 April 2020. The data were manually entered into an electronic case report form, which was monitored prior to the analysis. Results: We consecutively included 2226 adult patients admitted to the hospital who either died (460) or were discharged (1766). The patients’ median age was 61 years, and 51.8% were women. The most common comorbidity was arterial hypertension (41.3%), and the most common symptom on admission was fever (71.2%). The median time from disease onset to hospital admission was 6 days. The overall mortality was 20.7% and was higher in men (26.6% vs. 15.1%). Seventy-five patients with a final outcome were transferred to the intensive care unit (ICU) (3.4%). Most patients admitted to the ICU were men, and the median age was 64 years. Baseline laboratory values on admission were consistent with an impaired immune-inflammatory profile. Conclusions: We provide a description of the first large cohort of hospitalized patients with COVID-19 in Europe. Advanced age, male sex, the presence of comorbidities and abnormal laboratory values were more common among the patients with fatal outcome

7th Drug hypersensitivity meeting: part two

No abstract availabl

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Aspectos éticos de la investigación clínica en neumología

La investigación clínica en neumología desempeña un papel cada vez más relevante en el desarrollo de la especialidad. Por ello se hace necesario el conocimiento de los aspectos éticos en investigación con seres humanos y, en concreto, en ensayos clínicos con medicamentos. Se comienza la revisión con una breve introducción a los aspectos éticos en investigación clínica resaltando su importancia y obligado conocimiento y cumplimiento a la hora de llevar a cabo cualquier tipo de experimentación en seres humanos. Posteriormente, se realiza una breve descripción de los códigos éticos históricos y de los principios de la bioética mencionando su origen, así como las consecuencias que de ellos se derivan. Nos detenemos en el reciente Real Decreto 223/2004, de 6 de febrero, que entró en vigor en España el pasado 1 de mayo de 2004, para destacar sus principios generales y analizar los principales problemas que de él se derivan, fundamentalmente 2: los que son consecuencia de la exigencia del "dictamen único", y los relativos a los investigadores cuando actúan como promotores independientes de la industria farmacéutica. Se describe el papel de la neumología dentro de la investigación clínica con medicamentos en nuestro hospital, para posteriormente proponer los 7 requisitos del grupo de Emanuel como guía práctica para ayudar a los investigadores en neumología a analizar y valorar si un determinado ensayo cumple las mínimas exigencias de la ética clínica

Evolution of the COPD Assessment Test Score during Chronic Obstructive Pulmonary Disease Exacerbations: Determinants and Prognostic Value

BACKGROUND: An adequate evaluation of exacerbations is a primary objective in managing patients with chronic obstructive pulmonary disease (COPD)

Monocytes from cystic fibrosis patients are locked in an LPS tolerance state: down-regulation of TREM-1 as putative underlying mechanism.

Cystic Fibrosis (CF) is an inherited pleiotropic disease that results from abnormalities in the gene that codes for the chloride channel, Cystic Fibrosis Transmembrane Conductance Regulator (CFTR). CF patients are frequently colonized by several pathogens, but the mechanisms that allow colonization in spite of apparently functional immune systems are incompletely understood. In this paper we show that blood peripheral monocytes isolated from CF patients are found in an endotoxin tolerance state, yet this is not due to a deficient TLR activation. On the other hand, levels of the amplifier of inflammatory responses, TREM-1 (Triggering Receptor Expressed on Myeloid cells), are notably down-regulated in monocytes from patients, in comparison to those extracted from healthy volunteers. Furthermore, the soluble form of TREM-1 (sTREM-1) was not detected in the sera of patients. Additionally, and in strict contrast to patients who suffer from Chronic Obstructive Pulmonary Disease (COPD), CF monocytes challenged ex vivo with LPS neither up-regulated membrane-anchored TREM-1 nor sTREM-1. Finally, similar levels of PGE(2) expression and p65 translocation into the nucleus were found in both patients and healthy volunteers, thus suggesting that TREM-1 regulation is neither controlled by PGE(2) levels nor by p65 activation in this case. However, PU.1 translocation into the nucleus was significantly higher in CF monocytes than in controls, suggesting a role for this transcription factor in the control of TREM-1 expression. We conclude that down-regulation of TREM-1 expression in cystic fibrosis patients is at least partly responsible for the endotoxin tolerance state in which their monocytes are locked