Randomised controlled trial of oxygen therapy and high-flow nasal therapy in African children with pneumonia.

PURPOSE: The life-saving role of oxygen therapy in African children with severe pneumonia is not yet established. METHODS: The open-label fractional-factorial COAST trial randomised eligible Ugandan and Kenyan children aged > 28 days with severe pneumonia and severe hypoxaemia stratum (SpO2 < 80%) to high-flow nasal therapy (HFNT) or low-flow oxygen (LFO: standard care) and hypoxaemia stratum (SpO2 80-91%) to HFNT or LFO (liberal strategies) or permissive hypoxaemia (ratio 1:1:2). Children with cyanotic heart disease, chronic lung disease or > 3 h receipt of oxygen were excluded. The primary endpoint was 48 h mortality; secondary endpoints included mortality or neurocognitive sequelae at 28 days. RESULTS: The trial was stopped early after enrolling 1852/4200 children, including 388 in the severe hypoxaemia stratum (median 7 months; median SpO2 75%) randomised to HFNT (n = 194) or LFO (n = 194) and 1454 in the hypoxaemia stratum (median 9 months; median SpO2 88%) randomised to HFNT (n = 363) vs LFO (n = 364) vs permissive hypoxaemia (n = 727). Per-protocol 15% of patients in the permissive hypoxaemia group received oxygen (when SpO2 < 80%). In the severe hypoxaemia stratum, 48-h mortality was 9.3% for HFNT vs. 13.4% for LFO groups. In the hypoxaemia stratum, 48-h mortality was 1.1% for HFNT vs. 2.5% LFO and 1.4% for permissive hypoxaemia. In the hypoxaemia stratum, adjusted odds ratio for 48-h mortality in liberal vs permissive comparison was 1.16 (0.49-2.74; p = 0.73); HFNT vs LFO comparison was 0.60 (0.33-1.06; p = 0.08). Strata-specific 28 day mortality rates were, respectively: 18.6, 23.4 and 3.3, 4.1, 3.9%. Neurocognitive sequelae were rare. CONCLUSIONS: Respiratory support with HFNT showing potential benefit should prompt further trials.

Changes in temperature management and outcome after out-of-hospital cardiac arrest in United Kingdom intensive care units following publication of the targeted temperature management trial.

AIM: To investigate how the publication of the targeted temperature management (TTM) trial in December 2013 affected the trends in temperature management and outcome following admission to UK intensive care units (ICUs) after out-of-hospital cardiac arrest (OHCA). METHODS: We used a national ICU database of 1,181,405 consecutive admissions to 235 adult ICUs. OHCA admissions mechanically ventilated in the first 24 h in the ICU were divided into a pre-TTM trial cohort of patients admitted before publication of the TTM trial (January 2010-December 2013) and post-TTM cohort of patients admitted after TTM trial publication (January 2014-December 2017). The primary outcome variables were lowest temperature in the first 24 h in ICU and survival to hospital discharge. RESULTS: The lowest temperature recorded in the first-24 h of admission was significantly higher in the post-TTM cohort (n = 18,106) than in the pre-TTM cohort (n = 12,162) (mean 34.7 (±1.6) versus 33.6 °C (±1.8); absolute difference 1.12 °C (95% CI 1.08-1.16). The post-TTM cohort had a greater prevalence of fever (>38.0 °C) (24.8% vs 14.7%; (odds ratio (OR) 1.91 (95% CI 1.80-2.03); p < 0.001)) and higher unadjusted in-hospital mortality (63.7% vs 61.6%). In a multilevel model, accounting for time trend and including site as a random effect, neither the step change in acute hospital mortality following publication of the TTM trial result (OR 1.04, 95% CI 0.95-1.15; p = 0.37), nor the change in slope (from OR 1.00 per year, 95% CI 0.97-1.04, to 1.04 per year, 95% CI 1.02-1.07; p = 0.059), was statistically significant. Adjusted analyses were limited by the models' dependence on temperature and temperature-related variables. CONCLUSIONS: The lowest temperature recorded in the first-24 h of admission in OHCA patients was higher in the post-TTM cohort compared with the pre-TTM cohort. There has been an increase in the proportion of patients with fever (>38 °C) in the first 24 h. Although crude mortality was slightly higher in the post-TTM cohort, an analysis accounting for time trend and variation between critical care units, found no significant change associated with the TTM publication.

10-Fold Quantum Yield Improvement of Ag2S Nanoparticles by Fine Compositional Tuning.

Ag2S semiconductor nanoparticles (NPs) are near-infrared luminescent probes with outstanding properties (good biocompatibility, optimum spectral operation range, and easy biofunctionalization) that make them ideal probes for in vivo imaging. Ag2S NPs have, indeed, made possible amazing challenges including in vivo brain imaging and advanced diagnosis of the cardiovascular system. Despite the continuous redesign of synthesis routes, the emission quantum yield (QY) of Ag2S NPs is typically below 0.2%. This leads to a low luminescent brightness that avoids their translation into the clinics. In this work, an innovative synthetic methodology that permits a 10-fold increment in the absolute QY from 0.2 up to 2.3% is presented. Such an increment in the QY is accompanied by an enlargement of photoluminescence lifetimes from 184 to 1200 ns. The optimized synthetic route presented here is based on a fine control over both the Ag core and the Ag/S ratio within the NPs. Such control reduces the density of structural defects and decreases the nonradiative pathways. In addition, we demonstrate that the superior performance of the Ag2S NPs allows for high-contrast in vivo bioimaging.

Admission patterns and survival from status epilepticus in critical care in the UK: an analysis of the Intensive Care National Audit and Research Centre Case Mix Programme database.

BACKGROUND AND PURPOSE: Factors influencing the outcome after the critical care unit (CCU) for patients with status epilepticus (SE) are poorly understood. Survival for these patients was examined to establish (i) whether the risk of mortality has changed over time and (ii) whether admission to different unit types affects mortality risk over and above other risk factors. METHODS: The Intensive Care National Audit and Research Centre database and the Case Mix Programme database (January 2001 to December 2016) were analysed. Units were defined as neuro-CCU (NCCU), general CCU with 24-h neurological support (GCCU-N) or general CCU with limited neurological support (GCCU-L). RESULTS: There were 35 595 CCU cases of SE with a 3-fold increase over time (4739 in 2001-2004 to 14 166 in 2013-2016). More recent admissions were older and were more often unsedated on admission. Mortality declined for all units although this was more marked for NCCUs (8.1% in 2001-2004 to 4.4% in 2013-2016 compared to 5.1% and 4.1% for GCCU-L). Acute hospital mortality was two to three times higher than CCU mortality although this has also declined with time. GCCU-L appeared to have lower mortality than NCCUs (odds ratio 0.84, 95% confidence interval 0.72, 0.98) but after post hoc adjustment for case mix there were no differences. Older age and markers of seriousness of morbidity were all associated with increased mortality risk. CONCLUSIONS: The number of patients admitted to a CCU for SE is rising but critical care and acute hospital mortality is decreasing. Patients treated in an NCCU have higher mortality but this is explicable by more severe underlying disease.

Correction: Perspectives for Ag2S NIR-II nanoparticles in biomedicine: from imaging to multifunctionality.

Correction for 'Perspectives for Ag2S NIR-II nanoparticles in biomedicine: from imaging to multifunctionality' by Yingli Shen, et al., Nanoscale, 2019, DOI: 10.1039/c9nr05733a.

Perspectives for Ag2S NIR-II nanoparticles in biomedicine: from imaging to multifunctionality.

Research on near-infrared (NIR) bioimaging has progressed very quickly in the past few years, as fluorescence imaging is reaching a credible implementation as a preclinical technique. The applications of NIR bioimaging in theranostics have contributed to its increasing impact. This has brought about the development of novel technologies and, simultaneously, of new contrast agents capable of acting as efficient NIR optical probes. Among these probes, Ag2S nanoparticles (NPs) have attracted increasing attention due to their temperature-sensitive NIR-II emission, which can be exploited for deep-tissue imaging and thermometry, and their heat delivery capabilities. This multifunctionality makes Ag2S NPs ideal candidates for theranostics. This review presents a critical analysis of the synthesis routes, properties and optical features of Ag2S NPs. We also discuss the latest and most remarkable achievements enabled by these NPs in preclinical imaging and theranostics, together with a critical assessment of their potential to face forthcoming challenges in biomedicine.

Correction to: Paediatric intensive care admission blood pressure and risk of death in 30,334 children.

The authors of the article entitled "Paediatric Intensive Care admission blood pressure and risk of death in 30,334 children" inform that due to an error in their database extraction, the following corrections to the data published should be notified.

Variation between hospitals in outcomes following cardiac surgery in the UK.

INTRODUCTION: We examine the influence of variations in provision of cardiac surgery in the UK at hospital level on patient outcomes and also to assess whether there is an inequality of access and delivery of healthcare. Cardiothoracic surgery has pioneered the reporting of surgeon-specific outcomes, which other specialties have followed. We set out to identify factors other than the individual surgeon, which can affect outcomes and enable other surgical specialties to adopt a similar model. MATERIALS AND METHODS: A retrospective analysis of prospectively collected data of patient and hospital level factors between 2013 and 2016 from 16 cardiac surgical units in the UK were analysed through the Society for Cardiothoracic Surgery of Great Britain and Ireland and the Royal College of Surgeons Research Collaborative. Patient demographic data, risks factors, postoperative complications and in-hospital mortality, as well as hospital-level factors such as number of beds and operating theatres, were collected. Correlation between outcome measures was assessed using Pearson's correlation coefficient. Associations between hospital-level factors and outcomes were assessed using univariable and multivariable regression models. RESULTS: Of 50,871 patients (60.5% of UK caseload), 25% were older than 75 years and 29% were female. There was considerable variation between units in patient comorbidities, bed distribution and staffing. All hospitals had dedicated cardiothoracic intensive care beds and consultants. Median survival was 97.9% (range 96.3-98.6%). Postoperative complications included re-sternotomy for bleeding (median 4.8%; range 3.5-6.9%) and mediastinitis (0.4%; 0.1-1.0%), transient ischaemic attack/cerebrovascular accident (1.7%; range 0.3-3.0%), haemofiltration (3.7%; range 0.8-6.8%), intra-aortic balloon pump use (3.3%; range 0.4-7.4%), tracheostomy (1.6%; range 1.3-2.6%) and laparotomy (0.3%; range 0.2-0.6%). There was variation in outcomes between hospitals. Univariable analysis showed a small number of positive associations between hospital-level factors and outcomes but none remained significant in multivariable models. CONCLUSIONS: Variations among hospital level factors exists in both delivery of, and outcomes, following cardiac surgery in the UK. However, there was no clear association between these factors and patient outcomes. This negative finding could be explained by differences in outcome definition, differences in risk factors between centres that are not captured by standard risk stratification scores or individual surgeon/team performance.

The organisation of critical care for burn patients in the UK: epidemiology and comparison of mortality prediction models.

In the UK, a network of specialist centres has been set up to provide critical care for burn patients. However, some burn patients are admitted to general intensive care units. Little is known about the casemix of these patients and how it compares with patients in specialist burn centres. It is not known whether burn-specific or generic risk prediction models perform better when applied to patients managed in intensive care units. We examined admissions for burns in the Case Mix Programme Database from April 2010 to March 2016. The casemix, activity and outcome in general and specialist burn intensive care units were compared and the fit of two burn-specific risk prediction models (revised Baux and Belgian Outcome in Burn Injury models) and one generic model (Intensive Care National Audit and Research Centre model) were compared. Patients in burn intensive care units had more extensive injuries compared with patients in general intensive care units (median (IQR [range]) burn surface area 16 (7-32 [0-98])% vs. 8 (1-18 [0-100])%, respectively) but in-hospital mortality was similar (22.8% vs. 19.0%, respectively). The discrimination and calibration of the generic Intensive Care National Audit and Research Centre model was superior to the revised Baux and Belgian Outcome in Burn Injury burn-specific models for patients managed on both specialist burn and general intensive care units.

Epidemiology of sepsis and septic shock in critical care units: comparison between sepsis-2 and sepsis-3 populations using a national critical care database.

BACKGROUND: New sepsis and septic shock definitions could change the epidemiology of sepsis because of differences in criteria. We therefore compared the sepsis populations identified by the old and new definitions. METHODS: We used a high-quality, national, intensive care unit (ICU) database of 654 918 consecutive admissions to 189 adult ICUs in England, from January 2011 to December 2015. Primary outcome was acute hospital mortality. We compared old (Sepsis-2) and new (Sepsis-3) incidence, outcomes, trends in outcomes, and predictive validity of sepsis and septic shock populations. RESULTS: From among 197 724 Sepsis-2 severe sepsis and 197 142 Sepsis-3 sepsis cases, we identified 153 257 Sepsis-2 septic shock and 39 262 Sepsis-3 septic shock cases. The extrapolated population incidence of Sepsis-3 sepsis and Sepsis-3 septic shock was 101.8 and 19.3 per 100 000 person-years, respectively, in 2015. Sepsis-2 severe sepsis and Sepsis-3 sepsis had similar incidence, similar mortality and showed significant risk-adjusted improvements in mortality over time. Sepsis-3 septic shock had a much higher Acute Physiology And Chronic Health Evaluation II (APACHE II) score, greater mortality and no risk-adjusted trends in mortality improvement compared with Sepsis-2 septic shock. ICU admissions identified either as Sepsis-3 sepsis or septic shock and as Sepsis-2 severe sepsis or septic shock had significantly greater risk-adjusted odds of death compared with non-sepsis admissions (P<0.001). The predictive validity was greatest for Sepsis-3 septic shock. CONCLUSIONS: In an ICU database, compared with Sepsis-2, Sepsis-3 identifies a similar sepsis population with 92% overlap and much smaller septic shock population with improved predictive validity.

Association between day and time of admission to critical care and acute hospital outcome for unplanned admissions to adult general critical care units: cohort study exploring the 'weekend effect'.

BACKGROUND: We aimed to identify any association between day and time of admission to critical care and acute hospital outcome. METHODS: We conducted a cohort study using prospectively collected data from the national clinical audit of adult critical care. We included 195 428 unplanned admissions from 212 adult general critical care units in England, Wales and Northern Ireland, between April 1, 2013 and March 31, 2015 in the analysis. RESULTS: Hourly admission rates for unplanned admissions varied more than three-fold during the 24 h cycle. Overall acute hospital mortality was 26.8%. Before adjustment, acute hospital mortality was similar between weekends and weekdays but was significantly lower for admissions at night compared with the daytime (-3.4%, -3.8 to -3.0%; P<0.001). After adjustment for casemix, there remained no difference between weekends and weekdays (-0.0%, -0.4 to +0.3%; P=0.87) or between nighttime and daytime (-0.2%, -0.5 to +0.1%; P=0.21). Delays in admission were reported for 4.3% of admissions and were slightly more common during weekdays than weekends and in the daytime than at night. Delayed admission was associated with a small increase in acute hospital mortality, but adjusting for this did not affect the estimates of the effect of day and time of admission. CONCLUSIONS: The day of week and time of admission have no influence on patient mortality for unplanned admissions to adult general critical care units within the UK. Ways to improve critical care and hospital systems to minimize delays in admission and potentially improve outcomes need to be ascertained in future research.

The Assessment of Risk in Cardiothoracic Intensive Care (ARCtIC): prediction of hospital mortality after admission to cardiothoracic critical care.

The models used to predict outcome after adult general critical care may not be applicable to cardiothoracic critical care. Therefore, we analysed data from the Case Mix Programme to identify variables associated with hospital mortality after admission to cardiothoracic critical care units and to develop a risk-prediction model. We derived predictive models for hospital mortality from variables measured in 17,002 patients within 24 h of admission to five cardiothoracic critical care units. The final model included 10 variables: creatinine; white blood count; mean arterial blood pressure; functional dependency; platelet count; arterial pH; age; Glasgow Coma Score; arterial lactate; and route of admission. We included additional interaction terms between creatinine, lactate, platelet count and cardiac surgery as the admitting diagnosis. We validated this model against 10,238 other admissions, for which the c index (95% CI) was 0.904 (0.89-0.92) and the Brier score was 0.055, while the slope and intercept of the calibration plot were 0.961 and -0.183, respectively. The discrimination and calibration of our model suggest that it might be used to predict hospital mortality after admission to cardiothoracic critical care units.

Increasing survival after admission to UK critical care units following cardiopulmonary resuscitation.

BACKGROUND: In recent years there have been many developments in post-resuscitation care. We have investigated trends in patient characteristics and outcome following admission to UK critical care units following cardiopulmonary resuscitation (CPR) for the period 2004-2014. Our hypothesis is that there has been a reduction in risk-adjusted mortality during this period. METHODS: We undertook a prospectively defined, retrospective analysis of the Intensive Care National Audit & Research Centre (ICNARC) Case Mix Programme Database (CMPD) for the period 1 January 2004 to 31 December 2014. Admissions, mechanically ventilated in the first 24 hours in the critical care unit and admitted following CPR, defined as the delivery of chest compressions in the 24 hours before admission, were identified. Case mix, withdrawal, outcome and activity were described annually for all admissions identified as post-cardiac arrest admissions, and separately for out-of-hospital cardiac arrest and in-hospital cardiac arrest. To assess whether in-hospital mortality had improved over time, hierarchical multivariate logistic regression models were constructed, with in-hospital mortality as the dependent variable, year of admission as the main exposure variable and intensive care unit (ICU) as a random effect. All analyses were repeated using only the data from those ICUs contributing data throughout the study period. RESULTS: During the period 2004-2014 survivors of cardiac arrest accounted for an increasing proportion of mechanically ventilated admissions to ICUs in the ICNARC CMPD (9.0 % in 2004 increasing to 12.2 % in 2014). Risk-adjusted hospital mortality following admission to ICU after cardiac arrest has decreased significantly during this period (OR 0.96 per year). Over this time, the ICU length of stay and time to treatment withdrawal has increased significantly. Re-analysis including only those 116 ICUs contributing data throughout the study period confirmed all the results of the primary analysis. CONCLUSIONS: Risk-adjusted hospital mortality following admission to ICU after cardiac arrest has decreased significantly during the period 2004-2014. Over the same period the ICU length of stay and time to treatment withdrawal has increased significantly.

An evaluation of the clinical and cost-effectiveness of alternative care locations for critically ill adult patients with acute traumatic brain injury.

BACKGROUND: For critically ill adult patients with acute traumatic brain injury (TBI), we assessed the clinical and cost-effectiveness of: (a) Management in dedicated neurocritical care units versus combined neuro/general critical care units within neuroscience centres. (b) 'Early' transfer to a neuroscience centre versus 'no or late' transfer for those who present at a non-neuroscience centre. METHODS: The Risk Adjustment In Neurocritical care (RAIN) Study included prospective admissions following acute TBI to 67 UK adult critical care units during 2009-11. Data were collected on baseline case-mix, mortality, resource use, and at six months, Glasgow Outcome Scale Extended (GOSE), and quality of life (QOL) (EuroQol 5D-3L). We report incremental effectiveness, costs and cost per Quality-Adjusted Life Year (QALY) of the alternative care locations, adjusting for baseline differences with validated risk prediction models. We tested the robustness of results in sensitivity analyses. FINDINGS: Dedicated neurocritical care unit patients (N = 1324) had similar six-month mortality, higher QOL (mean gain 0.048, 95% CI -0.002 to 0.099) and increased average costs compared with those managed in combined neuro/general units (N = 1341), with a lifetime cost per QALY gained of £14,000. 'Early' transfer to a neuroscience centre (N = 584) was associated with lower mortality (odds ratio 0.52, 0.34-0.80), higher QOL for survivors (mean gain 0.13, 0.032-0.225), but positive incremental costs (£15,001, £11,123 to £18,880) compared with 'late or no transfer' (N = 263). The lifetime cost per QALY gained for 'early' transfer was £11,000. CONCLUSIONS: For critically ill adult patients with acute TBI, within neuroscience centres management in dedicated neurocritical care units versus combined neuro/general units led to improved QoL and higher costs, on average, but these differences were not statistically significant. This study finds that 'early' transfer to a neuroscience centre is associated with reduced mortality, improvement in QOL and is cost-effective.

Children with dermatological conditions admitted to paediatric intensive care: analysis of a national clinical audit database.

There is little published literature about dermatological conditions in paediatric intensive care units (PICUs). The aim of this study was to describe the range of skin disorders in children admitted to PICUs in the UK and Ireland using data from a national audit. An analysis was conducted using data for 2002 - 2010 from the Paediatric Intensive Care Audit Network (PICANet). In total, 999 admissions of 882 children were identified, representing 0.8% of all PICU admissions. The most frequent dermatological conditions were skin infections, including cellulitis and necrotizing fasciitis, and inflammatory conditions. In 28% of cases, the dermatological diagnosis was considered the reason for PICU admission, in 35% it was a manifestation of systemic disease and in 37% it was considered incidental. Overall mortality was similar to the general PICU population, with 52 deaths (5.2%), but was greater in children with vascular/haematological conditions.

A systematic review and meta-analysis of early goal-directed therapy for septic shock: the ARISE, ProCESS and ProMISe Investigators.

PURPOSE: To determine whether early goal-directed therapy (EGDT) reduces mortality compared with other resuscitation strategies for patients presenting to the emergency department (ED) with septic shock. METHODS: Using a search strategy of PubMed, EmBase and CENTRAL, we selected all relevant randomised clinical trials published from January 2000 to January 2015. We translated non-English papers and contacted authors as necessary. Our primary analysis generated a pooled odds ratio (OR) from a fixed-effect model. Sensitivity analyses explored the effect of including non-ED studies, adjusting for study quality, and conducting a random-effects model. Secondary outcomes included organ support and hospital and ICU length of stay. RESULTS: From 2395 initially eligible abstracts, five randomised clinical trials (n = 4735 patients) met all criteria and generally scored high for quality except for lack of blinding. There was no effect on the primary mortality outcome (EGDT: 23.2% [495/2134] versus control: 22.4% [582/2601]; pooled OR 1.01 [95% CI 0.88-1.16], P = 0.9, with heterogeneity [I(2) = 57%; P = 0.055]). The pooled estimate of 90-day mortality from the three recent multicentre studies (n = 4063) also showed no difference [pooled OR 0.99 (95% CI 0.86-1.15), P = 0.93] with no heterogeneity (I(2) = 0.0%; P = 0.97). EGDT increased vasopressor use (OR 1.25 [95% CI 1.10-1.41]; P < 0.001) and ICU admission [OR 2.19 (95% CI 1.82-2.65); P < 0.001]. Including six non-ED randomised trials increased heterogeneity (I(2) = 71%; P < 0.001) but did not change overall results [pooled OR 0.94 (95% CI 0.82 to 1.07); P = 0.33]. CONCLUSION: EGDT is not superior to usual care for ED patients with septic shock but is associated with increased utilisation of ICU resources.

Observational study of current use of selective decontamination of the digestive tract in UK critical care units.

BACKGROUND: Evidence supporting selective decontamination of the digestive tract (SDD) is reasonably strong. We set out to determine use in UK critical care units and to compare patient outcomes between units that do and those that do not use SDD. METHODS: A total of 250 UK general critical care units were surveyed. Case mix, outcomes, and lengths of stay for admissions to SDD units (with and without an i.v. component) and non-SDD units were compared using data from the Intensive Care National Audit & Research Centre Case Mix Programme database. RESULTS: A response was received from all the 250 critical care units surveyed. Of these, 13 (5.2%) reported using SDD on some or all admissions, and of these, 3 reported using an i.v. component. Data on 284,690 admissions (April 2008-March 2011) from units reporting to the ICNARC Case Mix Programme (CMP) were included in the analyses. Admissions to SDD (n=196) and non-SDD (n=9) units were a similar case mix with similar infection rates and average lengths of stay in the unit and hospital. There was no difference in risk-adjusted unit or hospital mortality. The rate of unit-acquired infections in blood was significantly lower in SDD units using an i.v. component. CONCLUSIONS: Use of SDD in UK critical care is very low. The rate of unit-acquired infections in blood was significantly lower in SDD units using an i.v. component, but did not translate into a difference in acute hospital mortality or length of stay. There is a need to better understand the barriers to adoption of SDD into clinical practice and such work is underway.