Healthcare data for achieving a more personalized treatment of chronic kidney disease

Producción CientíficaThe current concept of healthcare incites a more personalized treatment of diseases. To this aim, biomarkers are needed to improve decision-making facing chronic kidney disease (CKD) patients. Prognostic markers provided by real-world (observational) evidence are proposed in this Special Issue entitled “Biomarkers in Chronic Kidney Disease”, with the intention to identify high-risk patients. These markers do not target measurable parameters in patients but clinical endpoints that may be in turn transformed to benefits under the effect of future interventions

Tolerancia Inmunologica en trasplante renal

El papel crucial de las células T reguladoras en la tolerancia de los injertos se ha visto claramente en numerosos modelos animales. No obstante, delimitar este rol en trasplante con humanos es complicado. Alternativamente, la exploración del componente regulador de la respuesta alo-inmune podría convertirse en un biomarcador diagnóstico y pronóstico muy útil para el seguimiento a largo plazo de los pacientes trasplantados. Las células T reguladoras circulantes se correlacionan con la tasa de filtrado glomerular, con una influencia importante de la insuficiencia renal y de la inmunosupresión sobre el número y función de las mismas, además de otras situaciones que también pueden oponerse a una regulación de la respuesta inmune por estas células, favoreciendo un estado pro-inflamatorio persistente, y predisponiendo al rechazo. Si la adquisición o restauración de un estado de tolerancia inmunitaria constituye uno de los objetivos principales en trasplante, éste es por el contrario deletérea para la respuesta contra agentes infecciosos y células tumorales. La comunidad científica plantea poder inducir un estado de "tolerancia operacional", es decir la ausencia de respuesta inmunitaria patógena frente a los antígenos del injerto, sin que se afecte la capacidad del receptor para reaccionar de manera eficaz contra diversos antígenos exógenos. No obstante, los nexos entre células reguladoras y la malignidad o las infecciones en el postrasplante no se conocen bien del todo, sobre todo si se quiere entender los mecanismos en juego bajo la influencia de la inmunosupresión. De momento, el seguimiento del número circulante de estas células en el trasplantado renal puede alertar de una predisposición al rechazo en caso de recuentos bajos en un contexto clínico a favor de un estado pro-inflamatorio. Igualmente, los recuentos altos pueden dejar entrever una predisposición al desarrollo de cánceres e infecciones, que la inmunosupresión puede influenciar vía mecanismos tolerógenos y no tolerógenos.Departamento de Medicína, Dermatología y Toxicologí

Population-based registry analysis of antidiabetics dispensations: trend use in Spain between 2015 and 2018 with reference to driving

Producción CientíficaInsulins and some oral antidiabetics are considered to be driving-impairing medicines (DIM) and they belong to the Driving under the Influence of Drugs, alcohol, and medicines (DRUID) category I (minor influence on fitness to drive). The trend of antidiabetics use in Castilla y León from 2015 to 2018 is presented through a population-based registry study. Treatment duration with these medicines and the concomitant use of other DIMs were observed. An adjustment method was used with information from the drivers’ license census. For all calculations, age and gender were taken into account. 3.98% of the general population used at least one antidiabetic, as well as 2.92% of drivers. The consumption of antidiabetics in men was higher than in women (4.35% vs. 3.61%, p = 0.001), and the use increases with age, especially from 35–39 years to 75–79 years in men and 85–89 years in women. Antidiabetics were consumed chronically, specifically 100% in the case of insulins and 95% in the case of oral antidiabetics. In addition to antidiabetics, 2.5 ± 1.86 DIMs were consumed, mainly anxiolytics (25.53%), opioids (23.03%), other analgesics and antipiretics (19.13%), and antidepressants (17.73%). Collaboration between pharmacists and physicians is a priority to clearly transmitting risks to patients. It is necessary that the health authorities include information on DIMs, such as the DRUID classification, in the prescription and dispensing software.Instituto de Salud Carlos III - Fondo Europeo de Desarrollo Regional (RD16/0017/0006

Positivity to cocaine and/or benzoylecgonine in confirmation analyses for on-road tests in Spain

Producción CientíficaWe are using real-life data in order to determine the prevalence of driving with the presence of cocaine and/or benzoylecgonine (BZE), their concentrations, and their use in combination with other drugs. This study assessed data on Spanish drivers with confirmed drug-positive results recorded by the Spanish National Traffic Agency from 2011–2016. Frequencies of positivity for cocaine and/or BZE and concentration of such substances were obtained. Comparisons and univariate and multivariate regression analyses were performed. Drivers who tested positive for cocaine and/or BZE accounted for 48.59% of the total positive results for drugs. In positive cases for both cocaine and BZE, other substances were detected in 81.74%: delta-9-tetrahydrocannabinol (THC) (68.19%), opioids (20.78%) and amphetamine-like substances (16.76%). In the multivariate logistic regression analysis, the frequency of cocaine and/or BZE positive cases decreased with age (OR:0.97) and were less likely among women (OR:0.63). Concentrations (ng/mL) of cocaine (249.30) and BZE (137.90) were higher when both substances were detected together than when detected alone. Positivity to cocaine represented an important proportion among Spanish drivers who tested positive for drugs, and polysubstance use was especially observed in more than 8 out of 10 positive cases for cocaine and/or BZE.Instituto de Salud Carlos III y Fondo Europeo de Desarrollo Regional (FEDER) - (RD16/0017/0006

Clinical profile, treatment and predictors during the first COVID-19 wave: a population-based registry analysis from Castile and Leon hospitals

Producción CientíficaThe first wave of the COVID-19 pandemic collapsed the hospitals in Castile and Leon (Spain). An analysis of the clinical characteristics, drug therapies and principal outcome predictors in the COVID-19 hospitalized patients from 1 March to 31 May 2020 is presented through a population-based registry study. Hospital stay variables, ventilation mode data and clinical outcomes were observed. In Castile and Leon hospitals, 7307 COVID-19 patients were admitted, with 57.05% being male and a median of 76 years. The mortality rate was 24.43%, with a high incidence of severe acute respiratory syndrome (SARS) (14.03%) and acute kidney injury (AKI) (10.87%). The most used medicines were antibiotics (90.83%), antimalarials (42.63%), steroids (44.37%) and antivirals, such as lopinavir/ritonavir (42.63%). The use of tocilizumab (9.37%) and anti-SIRS (systemic inflammatory response syndrome) medicines (7.34%) were remarkable. Fundamentally, death occurred more likely over 65 years of age (OR: 9.05). In addition, the need for ventilation was associated with a higher probability of death (OR: 3.59), SARS (OR: 5.14) and AKI (OR: 2.31). The drug-use pattern had been modified throughout the COVID-19 first wave. Multiple factors, such as age, gender and the need for mechanical ventilation, were related to the worst evolution prognosis of the disease.Gerencia Regional de Salud - (Proyecto GRS COVID 10/A/20

The problem of benzodiazepine use and Its extent in the driver population: A population-based registry study

Producción CientíficaBackground: Benzodiazepines are driving-impairing medicines (DIM). This study presents current consumption of dispensed benzodiazepines in the Spanish general population, with a focus in pattern of use and concomitant medicines consumed with. Methods: A population-based registry study was carried out to assess the year-2016 granted benzodiazepines dispensation in Castile and León. Weighting was performed to obtain the adjusted benzodiazepine consumption for licensed drivers according to age and gender using our national drivers' license census data. Results: Benzodiazepines were used by 15.38% of the general population and 10.97% of drivers. Nearly 2% of the population and more than 1% of drivers took these medicines every day. The amount consumed (until 3 or more benzodiazepines per day) and concomitant use of other DIM were also higher. Women were the most frequent consumers, and anxiolytic use was usual. Consumption increases with age, but there were differences between men and women drivers from 60 years old. Conclusions: The current use of benzodiazepines must serve to awareness of the healthcare personnel, patients, and authorities on their risks, above all on the road safety.Instituto de Salud Carlos III (grant RD16/0017/0006

The trends in opioid use in Castile and Leon, Spain: A population-based registry analysis of dispensations in 2015 to 2018

Producción CientíficaOpioids are driving-impairing medicines (DIM). To assess the evolution and trends of opioid analgesics use between 2015 and 2018 in Castile and Leon (Spain), a population-based registry study was conceived. The length of opioid use and its concomitant use with other DIMs were studied. Analyses were done considering age and gender distributions. Adjusted consumption for licensed drivers is also presented. Of the 5 million dispensations recorded between 2015 and 2018, opioid analgesics were dispensed to 11.44% of the general population and 8.72% of vehicle drivers. Increases among daily users (2.6 times higher) and chronic users (1.5% higher) were noted, supporting the overall increase in opioid use (1.5%). The use of multiple drugs including other DIMs was a common finding (mean ± SD, 2.54 ± 0.01). Acute use (5.26%) and chronic use (3.20%) were also frequent. Formulations combining opioid analgesics with nonopioid analgesics were preferred. The use of opioids increased in Spain between 2015 and 2018. Concomitant use with other DIMS especially affects women and the elderly. Frequent use of opioid analgesics with other DIMs is a serious problem for drivers and increases the risk of accidents. Promoting safe driving should be a main objective of health authorities, to be achieved by developing and implementing educational activities for healthcare professionals and patients.Instituto de Salud Carlos III - Fondo Europeo de Desarrollo Regional (grant RD16/0017/0006

Drivers who tested positive for cannabis in oral fluid: a longitudinal analysis of administrative data for Spain between 2011 and 2016

Producción CientíficaObjectives: This study aimed to assess the association between positive roadside tests for delta-9-tetrahydrocannabinol (THC) and other driving-impairing substances and THC concentrations and the age and gender of THC-positive drivers. Design: This study is based on administrative data. Setting,: participants and exposures National administrative data on drivers who tested positive in confirmation analysis of driving-impairing substances in oral fluid were assessed (2011–2016, 179 645 tests). Primary and secondary outcome measures Frequencies of positivity for THC, THC alone and THC plus non-THC substances (stratification by age and gender in 2016) and THC concentration were obtained. Comparisons and univariate and multivariate regression analyses were performed. Results: Of the 65 244 confirmed drug-positive tests, 51 869 were positive for THC (79.5%). In 50.8% of the THC-positive tests, cocaine and amphetamines were also detected. Positivity for THC and non-THC substances predominated among drivers with low THC concentrations and represented 58.6% of those with levels lower than 25 ng/mL. The mean±SD for age was 29.6±7.7 years (year 2016, n=24 941). Men accounted for 96.3% of all THC-positive drivers. With increasing age, positivity for THC decreased (OR 0.948; 95% CI 0.945 to 0.952; p<0.0001), and positivity for THC and non-THC substances increased (OR 1.021; 95% CI 1.017 to 1.024; p<0.0001). Men were associated with higher THC concentrations (OR 1.394; 95% CI 1.188 to 1.636; p<0.0001). Conclusions: Cannabis positivity is frequent among drivers, and polysubstance use is common. Hence, focusing on younger drivers and those with low THC concentrations is encouraged. This study provides evidence on the current implementation of roadside drug testing in Spain and aims to characterise driving under the influence (DUI) of cannabis to increase the awareness of all involved to help them avoid DUI. This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.Instituto de Salud Carlos III (grant RD16/0017/0006

Une hypergammaglobulinémie considérable A huge hypergammaglobulinemia

Producción CientíficaUn homme de 22 ans était adressé en médecine interne pour le bilan d’une fièvre prolongée avec frissons, altération de l’état général et pesanteur de l’hypochondre droit, évoluant depuis six mois environ. Son seul antécédent remarquable était la notion d’une splénectomie à l’âge de sept ans pour un abcès splénique à Salmonella sp. Les examens faits en ville avaient révélé une cytolyse modérée (transaminases à 2N) et une lymphocytose (5 à 6 G/l). L’examen révélait une micropolyadénopathie généralisée et une hépatomégalie sensible. Les examens biologiques initiaux montraient un taux d’hémoglobine à 12 g/dl, des lymphocytes à 4 G/l et des monocytes à 2 G/l. Les plaquettes et l’hémostase étaient normales, la créatininémie à 69 !mol/l, la protéine C réactive à 20 mg/l, les ALAT/ALAT à 8N, les phosphatases alcalines à 4N, les LDH à 3N, les triglycérides à 5 g/l, les gammaglobulines à 60 g/l sur l’électrophorèse des protéines (Fig. 1). De nombreuses perturbations immunologiques étaient détectées avec un test de Coombs positif de type IgG, une présence d’anticorps antinucléaires (1/80 mouchetés) et d’anticorps antimuscles lisses de type antiactine (1/160), un facteur rhumatoïde IgG, et une présence de cryoglobuline non typée. L’imagerie ne révélait qu’une hépatomégalie homogène. La sérologie du VIH était négative et aucun facteur d’immunodépression n’était retrouvé en dehors de la splénectomie

Near-infrared spectroscopy monitoring in cardiac and noncardiac surgery: Pairwise and network meta-analyses

Producción CientíficaGoal-directed therapy based on brain-oxygen saturation (bSo2) is controversial and hotly debated. While meta-analyses of aggregated data have shown no clinical benefit for brain near-infrared spectroscopy (NIRS)-based interventions after cardiac surgery, no network meta-analyses involving both major cardiac and noncardiac procedures have yet been undertaken. Randomized controlled trials involving NIRS monitoring in both major cardiac and noncardiac surgery were included. Aggregate-level data summary estimates of critical outcomes (postoperative cognitive decline (POCD)/postoperative delirium (POD), acute kidney injury, cardiovascular events, bleeding/need for transfusion, and postoperative mortality) were obtained. NIRS was only associated with protection against POCD/POD in cardiac surgery patients (pooled odds ratio (OR)/95% confidence interval (CI)/I2/number of studies (n): 0.34/0.14–0.85/75%/7), although a favorable effect was observed in the analysis, including both cardiac and noncardiac procedures. However, the benefit of the use of NIRS monitoring was undetectable in Bayesian network meta-analysis, although maintaining bSo2 > 80% of the baseline appeared to have the most pronounced impact. Evidence was imprecise regarding acute kidney injury, cardiovascular events, bleeding/need for transfusion, and postoperative mortality. There is evidence that brain NIRS-based algorithms are effective in preventing POCD/POD in cardiac surgery, but not in major noncardiac surgery. However, the specific target bSo2 threshold has yet to be determined.Junta de Castilla y León (project VA161G18