Tier-1 and Tier-2A Scenario Parameterisation and Example Calculations. In Support of the Revision of the Guidance Document on Persistence in Soil under Council Directive 91/414/EEC and Parliament and Council Regulation (EC) 1107/2009 (SANCO/9188/VI/97 rev. 8, 12.07.2000)

European scenarios for exposure of soil organisms to Plant Protection Products are currently not available (EFSA Panel on Plant Protection Products and their Residues (PPR), 2010). In this document, the parameterisation of realistic worst-case scenarios for Tier-1 and Tier-2A simulations is described which are part of a tiered approach. The aim of this scheme is to assess such Predicted Environmental Concentrations (PEC), chosen to be the 90th spatial percentile, resulting from the use of the plant protection product. In order to account for the uncertainty in substance and soil properties, the Tier-2A scenarios are combinations of soil and climatic properties within a zone, for which the predicted concentration is equal to the 95th percentile of all concentrations within the area of annual crops. The selected soil profiles are based on digitised information from topsoil (organic matter and texture) combined with calculated average soil profiles available in the SPADE-1 database. The daily weather information for the scenarios is taken from the MARS database using the period 1990-2009. In order to have a sufficient overview on the differences between simulations performed with the analytical Tier-1 model and the numerical Tier-2A models, PEARL and PELMO test runs are performed covering all relevant substance properties and all evaluation depths. For each of the totalsoil scenarios, both models simulate nearly the same concentration. Small differences between PEARL and PELMO can be found for the pore-water scenarios due to differences in the calculation of soil moisture contents. The comparison with the analytical model shows that Tier-1 concentrations are usually above the respective Tier-2A concentrations in accordance with the philosophy of the tiered assessment scheme. However, due to the different handling of soil moisture, Tier-1 simulations may occasionally give concentrations below those of Tier 2A, which occurrence necessitates additional calibration using special model-adjustment factor

Intracranial pressure monitoring in patients with acute brain injury in the intensive care unit (SYNAPSE-ICU): an international, prospective observational cohort study

Background: The indications for intracranial pressure (ICP) monitoring in patients with acute brain injury and the effects of ICP on patients’ outcomes are uncertain. The aims of this study were to describe current ICP monitoring practises for patients with acute brain injury at centres around the world and to assess variations in indications for ICP monitoring and interventions, and their association with long-term patient outcomes. Methods: We did a prospective, observational cohort study at 146 intensive care units (ICUs) in 42 countries. We assessed for eligibility all patients aged 18 years or older who were admitted to the ICU with either acute brain injury due to primary haemorrhagic stroke (including intracranial haemorrhage or subarachnoid haemorrhage) or traumatic brain injury. We included patients with altered levels of consciousness at ICU admission or within the first 48 h after the brain injury, as defined by the Glasgow Coma Scale (GCS) eye response score of 1 (no eye opening) and a GCS motor response score of at least 5 (not obeying commands). Patients not admitted to the ICU or with other forms of acute brain injury were excluded from the study. Between-centre differences in use of ICP monitoring were quantified by using the median odds ratio (MOR). We used the therapy intensity level (TIL) to quantify practice variations in ICP interventions. Primary endpoints were 6 month mortality and 6 month Glasgow Outcome Scale Extended (GOSE) score. A propensity score method with inverse probability of treatment weighting was used to estimate the association between use of ICP monitoring and these 6 month outcomes, independently of measured baseline covariates. This study is registered with ClinicalTrial.gov, NCT03257904. Findings: Between March 15, 2018, and April 30, 2019, 4776 patients were assessed for eligibility and 2395 patients were included in the study, including 1287 (54%) with traumatic brain injury, 587 (25%) with intracranial haemorrhage, and 521 (22%) with subarachnoid haemorrhage. The median age of patients was 55 years (IQR 39–69) and 1567 (65%) patients were male. Considerable variability was recorded in the use of ICP monitoring across centres (MOR 4·5, 95% CI 3·8–4·9 between two randomly selected centres for patients with similar covariates). 6 month mortality was lower in patients who had ICP monitoring (441/1318 [34%]) than in those who were not monitored (517/1049 [49%]; p<0·0001). ICP monitoring was associated with significantly lower 6 month mortality in patients with at least one unreactive pupil (hazard ratio [HR] 0·35, 95% CI 0·26–0·47; p<0·0001), and better neurological outcome at 6 months (odds ratio 0·38, 95% CI 0·26–0·56; p=0·0025). Median TIL was higher in patients with ICP monitoring (9 [IQR 7–12]) than in those who were not monitored (5 [3–8]; p<0·0001) and an increment of one point in TIL was associated with a reduction in mortality (HR 0·94, 95% CI 0·91–0·98; p=0·0011). Interpretation: The use of ICP monitoring and ICP management varies greatly across centres and countries. The use of ICP monitoring might be associated with a more intensive therapeutic approach and with lower 6-month mortality in more severe cases. Intracranial hypertension treatment guided by monitoring might be considered in severe cases due to the potential associated improvement in long-term clinical results. Funding: University of Milano-Bicocca and the European Society of Intensive Care Medicine