Antimicrobial Defined Daily Dose in Neonatal Population: Validation in the Clinical Practice

Paediatric Antimicrobial Defined Daily Dose Study Group KiDDDs.Currently, there is no validated method for estimating antimicrobial consumption in the neonatal population, as it exists for adults using Defined Daily Doses (DDD). In neonatology, although there are different methods, each one with advantages and disadvantages, there is no unified criterion for use. The aim of this study is to validate the neonatal DDD designed as a new standardised form of antimicrobial consumption over this population.M.M.-T. received financial support from the Subprograma Río Hortega, Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spain (CM21/00115). The project has been carried out without financial funding but is supported by the Spanish Society of Hospital Pharmacy (SEFH), the Working Group on Pharmaceutical Care in Infectious Diseases of the SEFH (Afinf) and Spanish working group on paediatric pharmacy of the SEFH (gefp).Peer reviewe

Inter-Rater Variability in the Evaluation of Lung Ultrasound in Videos Acquired from COVID-19 Patients

12 páginas, 7 figuras, 1 tablaLung ultrasound (LUS) allows for the detection of a series of manifestations of COVID-19, such as B-lines and consolidations. The objective of this work was to study the inter-rater reliability (IRR) when detecting signs associated with COVID-19 in the LUS, as well as the performance of the test in a longitudinal or transverse orientation. Thirty-three physicians with advanced experience in LUS independently evaluated ultrasound videos previously acquired using the ULTRACOV system on 20 patients with confirmed COVID-19. For each patient, 24 videos of 3 s were acquired (using 12 positions with the probe in longitudinal and transverse orientations). The physicians had no information about the patients or other previous evaluations. The score assigned to each acquisition followed the convention applied in previous studies. A substantial IRR was found in the cases of normal LUS (κ = 0.74), with only a fair IRR for the presence of individual B-lines (κ = 0.36) and for confluent B-lines occupying 50% (κ = 0.50). No statistically significant differences between the longitudinal and transverse scans were found. The IRR for LUS of COVID-19 patients may benefit from more standardized clinical protocols.This research was partially funded by CDTI (Spanish acronym: Centre for Industrial Tech- nological Development), funding number COI-20201153. Partially supported by the Google Cloud Research Credits program with the funding number GCP19980904, by the project RTI2018-099118- A-I00 founded by MCIU/AEI/FEDER UE and by the European Commission–NextGenerationEU, through CSIC’s Global Health Platform (PTI Salud Global)

Recommendations for National Risk Assessment for Disaster Risk Management in EU

Decision No 1313/2013/EU on a Union Civil Protection Mechanism (UCPM) calls Participating States to develop risk assessments periodically and make the summary of their National Risk Assessment (NRA) available to the European Commission as a way to prevent disaster risk in Europe. In order to facilitate countries on this task, the European Commission developed the Guidelines on risk assessment and mapping. In spite of these, the summaries received have revealed several challenges related to the process and the content of the assessments. The current report aims to provide scientific support to the UCPM participant countries in their development of NRA, explaining why and how a risk assessment could be carried out, how the results of this could be used for Disaster Risk Management planning and in general, how science can help civil protection authorities and staff from ministries and agencies engaged in NRA activities. The report is the result of the collaborative effort of the Disaster Risk Management Knowledge Centre team and nine Joint Research Centre expert groups which provided their insight on tools and methods for specific risk assessment related to certain hazards and assets: drought, earthquakes, floods, terrorist attacks, biological disasters, critical infrastructures, chemical accidents, nuclear accidents and Natech accidents. The current document would be improved by a next version that would include scientific guidance on other risks and the collaboration of potential users.JRC.E.1-Disaster Risk Managemen

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

Dispersion and ground deposition of radioactive material according to airflow patterns for enhancing the preparedness to N/R emergencies

The intent of minimizing the impact of the large amount of radioactive material potentially released into the atmosphere in a nuclear event implies preparedness activities. In the early phase and in absence of field observations, countermeasures beyond the Emergency Planning Zone would largely rely on a previous characterization of the transport and dispersion of radioactive particles and the potential levels of radioactive contamination. This study presents a methodology to estimate the atmospheric transport, dispersion and ground deposition of radioactive particles based on an ensemble approach. The methodology starts identifying the main airflow directions by means of the air mass trajectories calculated by the HYSPLIT model, and, secondly, the dispersion and the ground deposition characteristics associated with each airflow pattern by running the RIMPUFF atmospheric dispersion model. From the basis of these results, different products for protective measures in early phases of a nuclear emergency can be obtained, such as the most probable transport direction, spatial probability distribution of deposits and the geographical probability distribution of deposits above certain predefined threshold. The method is tested based on the HYSPLIT trajectories and RIMPUFF simulations during five consecutive years (2012-2016) at the Almaraz Nuclear Power Plant, in Spain. 3644 forward air mass trajectories were calculated (at 00 and 12 UTC, and with duration of 36 hours). Eight airflow patterns were identified, and within each pattern, the “pure days”, i.e. those days in which trajectories at 00 and 12 UTC grouped into the same airflow pattern, were extracted to simulate for each day the atmospheric dispersion and ground deposition following a hypothetical ISLOCA accident sequence of 35 hours. In total, 833 simulations were carried out, in which ground contamination was estimated at cell level on a non-homogeneous geographical grid spacing up to 800 km from Almaraz. The corresponding outcomes show a large variability in the area covered and in deposits between airflow patterns, which provide comprehensive and oriented information and resources to decision makers to emergency management.JRC.G.10-Knowledge for Nuclear Security and Safet

Efficacy and Safety of Tinzaparin in Prophylactic, Intermediate and Therapeutic Doses in Non-Critically Ill Patients Hospitalized with COVID-19: The PROTHROMCOVID Randomized Controlled Trial

Hospitalized patients with COVID-19 are at increased risk of thrombosis, acute respiratory distress syndrome and death. The optimal dosage of thromboprophylaxis is unknown. The aim was to evaluate the efficacy and safety of tinzaparin in prophylactic, intermediate, and therapeutic doses in non-critical patients admitted for COVID-19 pneumonia. PROTHROMCOVID is a randomized, unblinded, controlled, multicenter trial enrolling non-critical, hospitalized adult patients with COVID-19 pneumonia. Patients were randomized to prophylactic (4500 IU), intermediate (100 IU/kg), or therapeutic (175 IU/kg) groups. All tinzaparin doses were administered once daily during hospitalization, followed by 7 days of prophylactic tinzaparin at discharge. The primary efficacy outcome was a composite endpoint of symptomatic systemic thrombotic events, need for invasive or non-invasive mechanical ventilation, or death within 30 days. The main safety outcome was major bleeding at 30 days. Of the 311 subjects randomized, 300 were included in the prespecified interim analysis (mean [SD] age, 56.7 [14.6] years; males, 182 [60.7%]). The composite endpoint at 30 days from randomization occurred in 58 patients (19.3%) of the total population; 19 (17.1 %) in the prophylactic group, 20 (22.1%) in the intermediate group, and 19 (18.5%) in the therapeutic dose group (p = 0.72). No major bleeding event was reported; non-major bleeding was observed in 3.7% of patients, with no intergroup differences. Due to these results and the futility analysis, the trial was stopped. In non-critically ill COVID-19 patients, intermediate or full-dose tinzaparin compared to standard prophylactic doses did not appear to affect the risk of thrombotic event, non-invasive ventilation, or mechanical ventilation or death. Trial RegistrationClinicalTrials.gov Identifier (NCT04730856). Edura-CT registration number: 2020-004279-42

Inter-Rater Variability in the Evaluation of Lung Ultrasound in Videos Acquired from COVID-19 Patients

Lung ultrasound (LUS) allows for the detection of a series of manifestations of COVID-19, such as B-lines and consolidations. The objective of this work was to study the inter-rater reliability (IRR) when detecting signs associated with COVID-19 in the LUS, as well as the performance of the test in a longitudinal or transverse orientation. Thirty-three physicians with advanced experience in LUS independently evaluated ultrasound videos previously acquired using the ULTRACOV system on 20 patients with confirmed COVID-19. For each patient, 24 videos of 3 s were acquired (using 12 positions with the probe in longitudinal and transverse orientations). The physicians had no information about the patients or other previous evaluations. The score assigned to each acquisition followed the convention applied in previous studies. A substantial IRR was found in the cases of normal LUS (κ = 0.74), with only a fair IRR for the presence of individual B-lines (κ = 0.36) and for confluent B-lines occupying < 50% (κ = 0.26) and a moderate IRR in consolidations and B-lines > 50% (κ = 0.50). No statistically significant differences between the longitudinal and transverse scans were found. The IRR for LUS of COVID-19 patients may benefit from more standardized clinical protocols

Metabolomic Identification of Subtypes of Nonalcoholic Steatohepatitis

BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) is a consequence of defects in diverse metabolic pathways that involve hepatic accumulation of triglycerides. Features of these aberrations might determine whether NAFLD progresses to nonalcoholic steatohepatitis (NASH). We investigated whether the diverse defects observed in patients with NAFLD are caused by different NAFLD subtypes with specific serum metabolomic profiles, and whether these can distinguish patients with NASH from patients with simple steatosis. METHODS: We collected liver and serum from methionine adenosyltransferase 1a knockout (MAT1A-KO) mice, which have chronically low levels of hepatic S-adenosylmethionine (SAMe) and spontaneously develop steatohepatitis, as well as C57Bl/6 mice (controls); the metabolomes of all samples were determined. We also analyzed serum metabolomes of 535 patients with biopsy-proven NAFLD (353 with simple steatosis and 182 with NASH) and compared them with serum metabolomes of mice. MAT1A-KO mice were also given SAMe (30 mg/kg/day for 8 weeks); liver samples were collected and analyzed histologically for steatohepatitis. RESULTS: Livers of MAT1A-KO mice were characterized by high levels of triglycerides, diglycerides, fatty acids, ceramides, and oxidized fatty acids, as well as low levels of SAMe and downstream metabolites. There was a correlation between liver and serum metabolomes. We identified a serum metabolomic signature associated with MAT1A-KO mice that also was present in 49% of the patients; based on this signature, we identified 2 NAFLD subtypes. We identified specific panels of markers that could distinguish patients with NASH from patients with simple steatosis for each subtype of NAFLD. Administration of SAMe reduced features of steatohepatitis in MAT1A-KO mice. CONCLUSIONS: In an analysis of serum metabolomes of patients with NAFLD and MAT1A-KO mice with steatohepatitis, we identified 2 major subtypes of NAFLD and markers that differentiate steatosis from NASH in each subtype. These might be used to monitor disease progression and identify therapeutic targets for patients

Guía de Terapéutica Antimicrobiana del Área Aljarafe, 3ª edición

Coordinadora: Rocío Fernández Urrusuno. Co-coordinadora: Carmen Serrano Martino.YesEstas guías son un recurso indispensable en los Programas de Optimización de Antibióticos (PROA). No sólo constituyen una herramienta de ayuda para la toma de decisiones en los principales síndromes infecciosos, proporcionando recomendaciones para el abordaje empírico de dichos procesos, sino que son el patrón/estándar de referencia que permitirá determinar la calidad o adecuación de los tratamientos realizados. Las guías pueden ser utilizadas, además, como herramienta de base para la formación y actualización en antibioterapia, ya que permiten mantener actualizados los conocimientos sobre las nuevas evidencias en el abordaje de las infecciones. Por último, deberían incorporar herramientas que faciliten el proceso de toma de decisiones compartidas con el paciente. El objetivo de esta guía es proporcionar recomendaciones para el abordaje de las enfermedades infecciosas más prevalentes en la comunidad, basadas en las últimas evidencias disponibles y los datos de resistencias de los principales patógenos que contribuyan a mejorar la calidad de la prescripción de antimicrobianos