Species-specific molecular responses of wild coral reef fishes during a marine heatwave

The marine heatwave of 2016 was one of the longest and hottest thermal anomalies recorded on the Great Barrier Reef, influencing multiple species of marine ectotherms, including coral reef fishes. There is a gap in our understanding of what the physiological consequences of heatwaves in wild fish populations are. Thus, in this study, we used liver transcriptomes to understand the molecular response of five species to the 2016 heatwave conditions. Gene expression was species specific, yet we detected overlap in functional responses associated with thermal stress previously reported in experimental setups. The molecular response was also influenced by the duration of exposure to elevated temperatures. This study highlights the importance of considering the effects of extreme warming events when evaluating the consequences of climate change on fish communities

The Genome Sequence of the Wild Tomato Solanum pimpinellifolium Provides Insights Into Salinity Tolerance

Solanum pimpinellifolium, a wild relative of cultivated tomato, offers a wealth of breeding potential for desirable traits such as tolerance to abiotic and biotic stresses. Here, we report the genome assembly and annotation of S. pimpinellifolium ‘LA0480.’ Moreover, we present phenotypic data from one field experiment that demonstrate a greater salinity tolerance for fruit- and yield-related traits in S. pimpinellifolium compared with cultivated tomato. The ‘LA0480’ genome assembly size (811 Mb) and the number of annotated genes (25,970) are within the range observed for other sequenced tomato species. We developed and utilized the Dragon Eukaryotic Analyses Platform (DEAP) to functionally annotate the ‘LA0480’ protein-coding genes. Additionally, we used DEAP to compare protein function between S. pimpinellifolium and cultivated tomato. Our data suggest enrichment in genes involved in biotic and abiotic stress responses. To understand the genomic basis for these differences in S. pimpinellifolium and S. lycopersicum, we analyzed 15 genes that have previously been shown to mediate salinity tolerance in plants. We show that S. pimpinellifolium has a higher copy number of the inositol-3-phosphate synthase and phosphatase genes, which are both key enzymes in the production of inositol and its derivatives. Moreover, our analysis indicates that changes occurring in the inositol phosphate pathway may contribute to the observed higher salinity tolerance in ‘LA0480.’ Altogether, our work provides essential resources to understand and unlock the genetic and breeding potential of S. pimpinellifolium, and to discover the genomic basis underlying its environmental robustness

Quality indicators for patients with traumatic brain injury in European intensive care units

Background: The aim of this study is to validate a previously published consensus-based quality indicator set for the management of patients with traumatic brain injury (TBI) at intensive care units (ICUs) in Europe and to study its potential for quality measur

Changing care pathways and between-center practice variations in intensive care for traumatic brain injury across Europe

Purpose: To describe ICU stay, selected management aspects, and outcome of Intensive Care Unit (ICU) patients with traumatic brain injury (TBI) in Europe, and to quantify variation across centers. Methods: This is a prospective observational multicenter study conducted across 18 countries in Europe and Israel. Admission characteristics, clinical data, and outcome were described at patient- and center levels. Between-center variation in the total ICU population was quantified with the median odds ratio (MOR), with correction for case-mix and random variation between centers. Results: A total of 2138 patients were admitted to the ICU, with median age of 49 years; 36% of which were mild TBI (Glasgow Coma Scale; GCS 13–15). Within, 72 h 636 (30%) were discharged and 128 (6%) died. Early deaths and long-stay patients (> 72 h) had more severe injuries based on the GCS and neuroimaging characteristics, compared with short-stay patients. Long-stay patients received more monitoring and were treated at higher intensity, and experienced worse 6-month outcome compared to short-stay patients. Between-center variations were prominent in the proportion of short-stay patients (MOR = 2.3, p < 0.001), use of intracranial pressure (ICP) monitoring (MOR = 2.5, p < 0.001) and aggressive treatme

Machine learning algorithms performed no better than regression models for prognostication in traumatic brain injury

Objective: We aimed to explore the added value of common machine learning (ML) algorithms for prediction of outcome for moderate and severe traumatic brain injury. Study Design and Setting: We performed logistic regression (LR), lasso regression, and ridge regression with key baseline predictors in the IMPACT-II database (15 studies, n = 11,022). ML algorithms included support vector machines, random forests, gradient boosting machines, and artificial neural networks and were trained using the same predictors. To assess generalizability of predictions, we performed internal, internal-external, and external validation on the recent CENTER-TBI study (patients with Glasgow Coma Scale <13, n = 1,554). Both calibration (calibration slope/intercept) and discrimination (area under the curve) was quantified. Results: In the IMPACT-II database, 3,332/11,022 (30%) died and 5,233(48%) had unfavorable outcome (Glasgow Outcome Scale less than 4). In the CENTER-TBI study, 348/1,554(29%) died and 651(54%) had unfavorable outcome. Discrimination and calibration varied widely between the studies and less so between the studied algorithms. The mean area under the curve was 0.82 for mortality and 0.77 for unfavorable outcomes in the CENTER-TBI study. Conclusion: ML algorithms may not outperform traditional regression approaches in a low-dimensional setting for outcome prediction after moderate or severe traumatic brain injury. Similar to regression-based prediction models, ML algorithms should be rigorously validated to ensure applicability to new populations

Variation in Structure and Process of Care in Traumatic Brain Injury: Provider Profiles of European Neurotrauma Centers Participating in the CENTER-TBI Study.

INTRODUCTION: The strength of evidence underpinning care and treatment recommendations in traumatic brain injury (TBI) is low. Comparative effectiveness research (CER) has been proposed as a framework to provide evidence for optimal care for TBI patients. The first step in CER is to map the existing variation. The aim of current study is to quantify variation in general structural and process characteristics among centers participating in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. METHODS: We designed a set of 11 provider profiling questionnaires with 321 questions about various aspects of TBI care, chosen based on literature and expert opinion. After pilot testing, questionnaires were disseminated to 71 centers from 20 countries participating in the CENTER-TBI study. Reliability of questionnaires was estimated by calculating a concordance rate among 5% duplicate questions. RESULTS: All 71 centers completed the questionnaires. Median concordance rate among duplicate questions was 0.85. The majority of centers were academic hospitals (n = 65, 92%), designated as a level I trauma center (n = 48, 68%) and situated in an urban location (n = 70, 99%). The availability of facilities for neuro-trauma care varied across centers; e.g. 40 (57%) had a dedicated neuro-intensive care unit (ICU), 36 (51%) had an in-hospital rehabilitation unit and the organization of the ICU was closed in 64% (n = 45) of the centers. In addition, we found wide variation in processes of care, such as the ICU admission policy and intracranial pressure monitoring policy among centers. CONCLUSION: Even among high-volume, specialized neurotrauma centers there is substantial variation in structures and processes of TBI care. This variation provides an opportunity to study effectiveness of specific aspects of TBI care and to identify best practices with CER approaches

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P &lt; 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Quality indicators for patients with traumatic brain injury in European intensive care units: a CENTER-TBI study

Abstract: Background: The aim of this study is to validate a previously published consensus-based quality indicator set for the management of patients with traumatic brain injury (TBI) at intensive care units (ICUs) in Europe and to study its potential for quality measurement and improvement. Methods: Our analysis was based on 2006 adult patients admitted to 54 ICUs between 2014 and 2018, enrolled in the CENTER-TBI study. Indicator scores were calculated as percentage adherence for structure and process indicators and as event rates or median scores for outcome indicators. Feasibility was quantified by the completeness of the variables. Discriminability was determined by the between-centre variation, estimated with a random effect regression model adjusted for case-mix severity and quantified by the median odds ratio (MOR). Statistical uncertainty of outcome indicators was determined by the median number of events per centre, using a cut-off of 10. Results: A total of 26/42 indicators could be calculated from the CENTER-TBI database. Most quality indicators proved feasible to obtain with more than 70% completeness. Sub-optimal adherence was found for most quality indicators, ranging from 26 to 93% and 20 to 99% for structure and process indicators. Significant (p < 0.001) between-centre variation was found in seven process and five outcome indicators with MORs ranging from 1.51 to 4.14. Statistical uncertainty of outcome indicators was generally high; five out of seven had less than 10 events per centre. Conclusions: Overall, nine structures, five processes, but none of the outcome indicators showed potential for quality improvement purposes for TBI patients in the ICU. Future research should focus on implementation efforts and continuous reevaluation of quality indicators. Trial registration: The core study was registered with ClinicalTrials.gov, number NCT02210221, registered on August 06, 2014, with Resource Identification Portal (RRID: SCR_015582)

Changing care pathways and between-center practice variations in intensive care for traumatic brain injury across Europe: a CENTER-TBI analysis

Abstract: Purpose: To describe ICU stay, selected management aspects, and outcome of Intensive Care Unit (ICU) patients with traumatic brain injury (TBI) in Europe, and to quantify variation across centers. Methods: This is a prospective observational multicenter study conducted across 18 countries in Europe and Israel. Admission characteristics, clinical data, and outcome were described at patient- and center levels. Between-center variation in the total ICU population was quantified with the median odds ratio (MOR), with correction for case-mix and random variation between centers. Results: A total of 2138 patients were admitted to the ICU, with median age of 49 years; 36% of which were mild TBI (Glasgow Coma Scale; GCS 13–15). Within, 72 h 636 (30%) were discharged and 128 (6%) died. Early deaths and long-stay patients (> 72 h) had more severe injuries based on the GCS and neuroimaging characteristics, compared with short-stay patients. Long-stay patients received more monitoring and were treated at higher intensity, and experienced worse 6-month outcome compared to short-stay patients. Between-center variations were prominent in the proportion of short-stay patients (MOR = 2.3, p < 0.001), use of intracranial pressure (ICP) monitoring (MOR = 2.5, p < 0.001) and aggressive treatments (MOR = 2.9, p < 0.001); and smaller in 6-month outcome (MOR = 1.2, p = 0.01). Conclusions: Half of contemporary TBI patients at the ICU have mild to moderate head injury. Substantial between-center variations exist in ICU stay and treatment policies, and less so in outcome. It remains unclear whether admission of short-stay patients represents appropriate prudence or inappropriate use of clinical resources

Use and impact of high intensity treatments in patients with traumatic brain injury across Europe: a CENTER-TBI analysis

Abstract: Purpose: To study variation in, and clinical impact of high Therapy Intensity Level (TIL) treatments for elevated intracranial pressure (ICP) in patients with traumatic brain injury (TBI) across European Intensive Care Units (ICUs). Methods: We studied high TIL treatments (metabolic suppression, hypothermia (< 35 °C), intensive hyperventilation (PaCO2 < 4 kPa), and secondary decompressive craniectomy) in patients receiving ICP monitoring in the ICU stratum of the CENTER-TBI study. A random effect logistic regression model was used to determine between-centre variation in their use. A propensity score-matched model was used to study the impact on outcome (6-months Glasgow Outcome Score-extended (GOSE)), whilst adjusting for case-mix severity, signs of brain herniation on imaging, and ICP. Results: 313 of 758 patients from 52 European centres (41%) received at least one high TIL treatment with significant variation between centres (median odds ratio = 2.26). Patients often transiently received high TIL therapies without escalation from lower tier treatments. 38% of patients with high TIL treatment had favourable outcomes (GOSE ≥ 5). The use of high TIL treatment was not significantly associated with worse outcome (285 matched pairs, OR 1.4, 95% CI [1.0–2.0]). However, a sensitivity analysis excluding high TIL treatments at day 1 or use of metabolic suppression at any day did reveal a statistically significant association with worse outcome. Conclusion: Substantial between-centre variation in use of high TIL treatments for TBI was found and treatment escalation to higher TIL treatments were often not preceded by more conventional lower TIL treatments. The significant association between high TIL treatments after day 1 and worse outcomes may reflect aggressive use or unmeasured confounders or inappropriate escalation strategies. Take home message: Substantial variation was found in the use of highly intensive ICP-lowering treatments across European ICUs and a stepwise escalation strategy from lower to higher intensity level therapy is often lacking. Further research is necessary to study the impact of high therapy intensity treatments. Trial registration: The core study was registered with ClinicalTrials.gov, number NCT02210221, registered 08/06/2014, https://clinicaltrials.gov/ct2/show/NCT02210221?id=NCT02210221&draw=1&rank=1 and with Resource Identification Portal (RRID: SCR_015582)