Desarrollo de un registro de ensayos clínicos en España

Tesis doctoral inédita leida en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Farmacología. Fecha de lectura: 30-3-199

The need to implement nonindustry COVID-19 clinical trials in non-high-income countries

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Effect of CYP4F2, VKORC1, and CYP2C9 in Influencing Coumarin Dose: A Single-Patient Data Meta-Analysis in More Than 15,000 Individuals

The cytochrome P450 (CYP)4F2 gene is known to influence mean coumarin dose. The aim of the present study was to undertake a meta-analysis at the individual patients level to capture the possible effect of ethnicity, gene—gene interaction, or other drugs on the association and to verify if inclusion of CYP4F2*3 variant into dosing algorithms improves the prediction of mean coumarin dose. We asked the authors of our previous meta-analysis (30 articles) and of 38 new articles retrieved by a systematic review to send us individual patients’ data. The final collection consists of 15,754 patients split into a derivation and validation cohort. The CYP4F2*3 polymorphism was consistently associated with an increase in mean coumarin dose (+9% (95% confidence interval (CI) 7–10%), with a higher effect in women, in patients taking acenocoumarol, and in white patients. The inclusion of the CYP4F2*3 in dosing algorithms slightly improved the prediction of stable coumarin dose. New pharmacogenetic equations potentially useful for clinical practice were derived

Participando en Oliver.Proyecto Intercultural de Atención Comunitaria desde la Ludopedagogía.

Los movimientos migratorios y la diversidad de culturas, han constituido una realidad a lo largo de toda la historia de la humanidad. Por lo tanto, la participación, el desarrollo y la organización de la comunidad, son elementos imprescindibles para lograr una sociedad cohesionada. Este proyecto comunitario presenta una herramienta utilizada para sensibilizar a la ciudadanía en materia intercultural a través del juego.Se utiliza la ludopedagogía como instrumento para llevar a cabo una intervención en materia de acción social. La finalidad de este proyecto es promover la cohesión y la convivencia intercultural, contribuyendo al desarrollo del espacio local y público compartidos. Palabras clave: comunidad, interculturalidad,ludopedagogía

Appropriate use of red blood cell transfusion in emergency departments: A study in five emergency departments

BACKGROUND: Transfusion of blood components continues to be an important therapeutic resource into the 21st century. Between 5 and 58% of transfusions carried out are estimated to be unnecessary. According to several studies, at least 20% of packed red blood cell transfusions (RBCT) are administered in hospital emergency departments (ED), but few data are available about the appropriateness of RBCT in this setting. This multicentre, cross-sectional observational study aims to assess the appropriateness of RBCT indications and transfused volumes in patients who attend ED. MATERIALS AND METHODS: The study cohort is made up of consecutive consenting adult patients (≥18 years old) who received RBCT in ED over a 3-month period and for whom relevant clinical data were collected and analysed. RESULTS: Data from 908 RBCT episodes (2±1 units per transfused patient) were analysed. RBCT was considered appropriate in 21.4% (n=195), with significant differences according to RBCT indication (p<0.001), hospital level (p<0.001) and prescribing physician (p=0.002). Pre-transfusion haemoglobin level (Hb) negatively correlated with RBCT appropriateness (r=-0.616; p<0.01). Only 72.4% of appropriate RBCT had a post-transfusion Hb assessment (n=516). Of these, 45% were considered to be over-transfused (n=232), with significant differences according to RBCT indication (p=0.012) and prescribing physician (p=0.047). Overall, 584/1,433 (41%) of evaluable RBC units were unnecessarily transfused. DISCUSSION: The appropriateness of RBCT in ED is similar to other hospital departments, but the rate of over-transfusion was high. These data support the need for a reassessment after transfusion of each RBC unit before further units are prescribed. In view of these results, we recommend that physicians should be made more aware of the need to prescribe RBCT appropriately in order to reduce over-transfusionThis project has received funding from the Spanish Ministry of Health, Social Policy and Equality through the SAS/2377/2010 call for granting aid for the promotion of independent clinical research (Department of Pharmacy and Health Products), file n. EC10-21

Kehityskeskustelumalli osana kasvuyrityksen henkilöstön osaamisen ja työhyvinvoinnin johtamista

Opinnäytetyön tarkoituksena on perehtyä kehityskeskusteluun kasvuyrityksen henkilöstön osaamisen ja työhyvinvoinnin johtamisen näkökulmasta, ja tuottaa toimiva lomake tukemaan kasvuyrityksen kehityskeskusteluprosessia. Tavoitteena on kehittää tulevalle kasvuyrityksen henkilöstövastaavalle osaamisen ja työhyvinvoinnin johtamiseen joustava, yrityksen kasvun mukaan vuosittain päivittyvä kehityskeskustelumalli. Työn toimeksiantaja on kasvuyritys Era Content Oy. Tämän toiminnallisen opinnäytetyön kehityskeskustelumallin suunnittelu käynnistyi tammikuussa 2017, ja työ valmistui elokuussa 2017. Aineistoa mallin suunnitteluun hankittiin kehityskeskustelua käsittelevästä kirjallisuudesta sekä haastattelemalla huhtikuussa 2017 Era Content Oy:n toimitusjohtajaa sekä yrityksen kahdeksaa työntekijää ensimmäisen kehityskeskustelukierroksen jälkeen, jossa käytössä oli ensimmäinen tuotettu versio kehityskeskustelulomakkeesta. Haastattelut toteutettiin teemahaastatteluna ja lähettämällä puolistrukturoitu kyselylomake sähköpostitse. Tietoperustan ja haastatteluista saatujen vastausten perusteella suunniteltiin ja laadittiin kehityskeskustelumalli. Työ valmistui ajallaan. Työn tuotoksena syntynyt kehityskeskustelumalli toimii ohjeistuksena HR-tehtävistä vastaavalle henkilölle kohdeyrityksessä. Ohjeistus kuvaa kaikkia niitä toimenpiteitä, joiden tulee toteutua kehityskeskusteluprosessin aikana. Toimeksiantaja oli tyytyväinen kehityskeskustelumalliin ja otti sen heti käyttöön. Opinnäytetyön tekijä työllistyi itse opinnäytetyöprosessin aikana toisen toimialan kasvuyrityksen HR-tehtäviin, jossa kehityskeskustelumallia ryhdytään heti hyödyntämään

Incidence of suspected serious adverse drug reactions in corona virus Ddsease-19 patients detected by a pharmacovigilance program by laboratory signals in a tertiary hospital in Spain: Cautionary data

BACKGROUND: From March to April 2020, Spain was the center of the SARS-CoV-2 pandemic, particularly Madrid with approximately 30% of the cases in Spain. The aim of this study is to report the suspected serious adverse drug reactions (SADRs) in COVID-19 patients vs. non-COVID-19 patients detected by the prospective pharmacovigilance program based on automatic laboratory signals (ALSs) in the hospital (PPLSH) during that period. We also compared the results with the suspected SADRs detected during the same period for 2019. METHODS: All ALSs that reflected potential SADRs including neutropenia, pancytopenia, thrombocytopenia, anemia, eosinophilia, leukocytes in cerebrospinal fluid, hepatitis, pancreatitis, acute kidney injury, rhabdomyolysis, and hyponatremia were prospectively monitored in hospitalized patients during the study periods. We analyzed the incidence and the distribution of causative drugs for the COVID-19 patients. RESULTS: The incidence rate of SADRs detected in the COVID-19 patients was 760.63 (95% CI 707.89–816.01) per 10,000 patients, 4.75-fold higher than the SADR rate for non-COVID-19 patients (160.15 per 10,000 patients, 95% CI 137.09–186.80), and 5.84-fold higher than the SADR rate detected for the same period in 2019 (130.19 per 10,000 patients, 95% CI 109.53–154.36). The most frequently related drugs were tocilizumab (59.84%), dexketoprofen (13.93%), azithromycin (8.43%), lopinavir-ritonavir (7.35%), dexamethasone (7.62%), and chloroquine/hydroxychloroquine (6.91%). CONCLUSIONS: The incidence rate of SADRs detected by the PPSLH in patients with COVID-19 was 4.75-fold higher than that of the non-COVID-19 patients. Caution is recommended when using medications for COVID-19 patients, especially drugs that are hepatotoxic, myotoxic, and those that induce thromboembolic events

Identification and validation of clinical phenotypes with prognostic implications in patients admitted to hospital with COVID-19: a multicentre cohort study

REIPI-SEIMC COVID-19 group and COVID@HULP group.[Background] The clinical presentation of COVID-19 in patients admitted to hospital is heterogeneous. We aimed to determine whether clinical phenotypes of patients with COVID-19 can be derived from clinical data, to assess the reproducibility of these phenotypes and correlation with prognosis, and to derive and validate a simplified probabilistic model for phenotype assignment. Phenotype identification was not primarily intended as a predictive tool for mortality.[Methods] In this study, we used data from two cohorts: the COVID-19@Spain cohort, a retrospective cohort including 4035 consecutive adult patients admitted to 127 hospitals in Spain with COVID-19 between Feb 2 and March 17, 2020, and the COVID-19@HULP cohort, including 2226 consecutive adult patients admitted to a teaching hospital in Madrid between Feb 25 and April 19, 2020. The COVID-19@Spain cohort was divided into a derivation cohort, comprising 2667 randomly selected patients, and an internal validation cohort, comprising the remaining 1368 patients. The COVID-19@HULP cohort was used as an external validation cohort. A probabilistic model for phenotype assignment was derived in the derivation cohort using multinomial logistic regression and validated in the internal validation cohort. The model was also applied to the external validation cohort. 30-day mortality and other prognostic variables were assessed in the derived phenotypes and in the phenotypes assigned by the probabilistic model.[Findings] Three distinct phenotypes were derived in the derivation cohort (n=2667)—phenotype A (516 [19%] patients), phenotype B (1955 [73%]) and phenotype C (196 [7%])—and reproduced in the internal validation cohort (n=1368)—phenotype A (233 [17%] patients), phenotype B (1019 [74%]), and phenotype C (116 [8%]). Patients with phenotype A were younger, were less frequently male, had mild viral symptoms, and had normal inflammatory parameters. Patients with phenotype B included more patients with obesity, lymphocytopenia, and moderately elevated inflammatory parameters. Patients with phenotype C included older patients with more comorbidities and even higher inflammatory parameters than phenotype B. We developed a simplified probabilistic model (validated in the internal validation cohort) for phenotype assignment, including 16 variables. In the derivation cohort, 30-day mortality rates were 2·5% (95% CI 1·4–4·3) for patients with phenotype A, 30·5% (28·5–32·6) for patients with phenotype B, and 60·7% (53·7–67·2) for patients with phenotype C (log-rank test p<0·0001). The predicted phenotypes in the internal validation cohort and external validation cohort showed similar mortality rates to the assigned phenotypes (internal validation cohort: 5·3% [95% CI 3·4–8·1] for phenotype A, 31·3% [28·5–34·2] for phenotype B, and 59·5% [48·8–69·3] for phenotype C; external validation cohort: 3·7% [2·0–6·4] for phenotype A, 23·7% [21·8–25·7] for phenotype B, and 51·4% [41·9–60·7] for phenotype C).[Interpretation] Patients admitted to hospital with COVID-19 can be classified into three phenotypes that correlate with mortality. We developed and validated a simplified tool for the probabilistic assignment of patients into phenotypes. These results might help to better classify patients for clinical management, but the pathophysiological mechanisms of the phenotypes must be investigated.[Funding] Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation, and Fundación SEIMC/GeSIDA.Funding: Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation, and Fundación SEIMC/GeSIDA.Peer reviewe

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

A new pharmacogenetic algorithm to predict the most appropriate dosage of acenocoumarol for stable anticoagulation in a mixed Spanish population

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.There is a strong association between genetic polymorphisms and the acenocoumarol dosage requirements. Genotyping the polymorphisms involved in the pharmacokinetics and pharmacodynamics of acenocoumarol before starting anticoagulant therapy would result in a better quality of life and a more efficient use of healthcare resources. The objective of this study is to develop a new algorithm that includes clinical and genetic variables to predict the most appropriate acenocoumarol dosage for stable anticoagulation in a wide range of patients. We recruited 685 patients from 2 Spanish hospitals and 1 primary healthcare center. We randomly chose 80% of the patients (n = 556), considering an equitable distribution of genotypes to form the generation cohort. The remaining 20% (n = 129) formed the validation cohort. Multiple linear regression was used to generate the algorithm using the acenocoumarol stable dosage as the dependent variable and the clinical and genotypic variables as the independent variables. The variables included in the algorithm were age, weight, amiodarone use, enzyme inducer status, international normalized ratio target range and the presence of CYP2C9∗2 (rs1799853), CYP2C9∗3 (rs1057910), VKORC1 (rs9923231) and CYP4F2 (rs2108622). The coefficient of determination (R2) explained by the algorithm was 52.8% in the generation cohort and 64% in the validation cohort. The following R2 values were evaluated by pathology: atrial fibrillation, 57.4%; valve replacement, 56.3%; and venous thromboembolic disease, 51.5%. When the patients were classified into 3 dosage groups according to the stable dosage (&lt;11 mg/week, 11-21 mg/week, &gt;21 mg/week), the percentage of correctly classified patients was higher in the intermediate group, whereas differences between pharmacogenetic and clinical algorithms increased in the extreme dosage groups. Our algorithm could improve acenocoumarol dosage selection for patients who will begin treatment with this drug, especially in extreme-dosage patients. The predictability of the pharmacogenetic algorithm did not vary significantly between diseases.This study was funded by a grant from the Spanish Ministry of Health and Social Policy (Instituto de Salud Carlos III, PI07/0710) and the Andalusian Regional Ministry of Health (Progress and Health Foundation, PI-0717-2013