Systematic review and consensus definitions for the Standardised Endpoints in Perioperative Medicine (StEP) initiative: renal endpoints.

BACKGROUND: Renal injury is a common perioperative complication. The adoption of renal endpoints, standardised and valid for use in perioperative clinical trials, would enhance the quality of perioperative clinical research. The Standardised Endpoints in Perioperative Medicine (StEP) initiative was established to derive standardised endpoints for use in perioperative clinical trials. METHODS: A systematic review was conducted to identify renal endpoints currently reported in perioperative clinical trials. In parallel, an initial list of candidate endpoints was developed based on renal theme group expertise. A multi-round Delphi consensus process was used to refine this list and produce a suite of recommended perioperative renal outcome measures. RESULTS: Based on our systematic review, 63 studies were included for analysis. Marked heterogeneity and imprecision of endpoint definitions were observed. Our initial list of candidate endpoints included 10 endpoints for consideration. The response rates for Delphi rounds 1, 2, and 3 were 89% (n=16), 90% (n=75), and 100% (n=6), respectively. A final list of four renal endpoints was identified: acute kidney injury defined by the Kidney Disease: Improving Global Outcomes (KDIGO) consensus criteria, acute kidney disease defined by ≥30% decline in estimated glomerular filtration rate from baseline at 30 days after operation in patients meeting the acute-kidney-injury criteria within 7 days of surgery, the composite of death or renal replacement therapy, and the Major Adverse Kidney Events (MAKE) composite. CONCLUSIONS: We identified four key renal outcome measures that should be considered for use in perioperative clinical trials. Using standardised definitions to capture and report these endpoints will facilitate improved benchmarking and meta-analysis of future trials.

Threefold growth efficiency improvement of silica nanosprings by using silica nanosprings as a substrate.

The growth efficiency of one-dimension (1D) nanostructures via the vapor-liquid-solid process is commonly attributed to parameters such as precursor vapor pressure, substrate temperature, and the choice of the catalyst. The work presented herein is an investigation of the use of silica nanosprings (SNs) as a 3D substrate for improving the growth efficiency of SN themselves. SNs are a 1D nanomaterial that form a nonwoven structure with optimal geometric characteristics and surface properties that mitigate collisions between growing nanosprings and ripening of the gold catalyst, which should improve SN yield. Nanospring growth, for an eight hour period, on an SN coated surface relative to an equivalent flat substrate increased from ≈25 mgh-1 to ≈80 mgh-1, respectively. All things being equal, by splitting the typical amount of catalyst, in this case gold, between the first and second growth, the double growth procedure produced more than three times more nanosprings than the equivalent single growth of a SN. In addition, using an SN as a substrate increased the sustained growth condition from four to eight hours, and thus increased by a factor of ten the gravimetric yield of SNs relative to the mass of gold used.

Neuraxial block and postoperative epidural analgesia: effects on outcomes in the POISE-2 trial†.

BACKGROUND: We assessed associations between intraoperative neuraxial block and postoperative epidural analgesia, and a composite primary outcome of death or non-fatal myocardial infarction, at 30 days post-randomization in POISE-2 Trial subjects. METHODS: 10 010 high-risk noncardiac surgical patients were randomized aspirin or placebo and clonidine or placebo. Neuraxial block was defined as intraoperative spinal anaesthesia, or thoracic or lumbar epidural anaesthesia. Postoperative epidural analgesia was defined as postoperative epidural local anaesthetic and/or opioid administration. We used logistic regression with weighting using estimated propensity scores. RESULTS: Neuraxial block was not associated with the primary outcome [7.5% vs 6.5%; odds ratio (OR), 0.89; 95% CI (confidence interval), 0.73-1.08; P=0.24], death (1.0% vs 1.4%; OR, 0.84; 95% CI, 0.53-1.35; P=0.48), myocardial infarction (6.9% vs 5.5%; OR, 0.91; 95% CI, 0.74-1.12; P=0.36) or stroke (0.3% vs 0.4%; OR, 1.05; 95% CI, 0.44-2.49; P=0.91). Neuraxial block was associated with less clinically important hypotension (39% vs 46%; OR, 0.90; 95% CI, 0.81-1.00; P=0.04). Postoperative epidural analgesia was not associated with the primary outcome (11.8% vs 6.2%; OR, 1.48; 95% CI, 0.89-2.48; P=0.13), death (1.3% vs 0.8%; OR, 0.84; 95% CI, 0.35-1.99; P=0.68], myocardial infarction (11.0% vs 5.7%; OR, 1.53; 95% CI, 0.90-2.61; P=0.11], stroke (0.4% vs 0.4%; OR, 0.65; 95% CI, 0.18-2.32; P=0.50] or clinically important hypotension (63% vs 36%; OR, 1.40; 95% CI, 0.95-2.09; P=0.09). CONCLUSIONS: Neuraxial block and postoperative epidural analgesia were not associated with adverse cardiovascular outcomes among POISE-2 subjects.

Aspirin and coronary artery surgery: a systematic review and meta-analysis.

BACKGROUND: Aspirin administration before cardiac surgery represents a balance between preventing perioperative thrombotic events and promoting surgical bleeding. Clear evidence to guide the preoperative use of aspirin in patients undergoing cardiac surgery is lacking.This systematic review and meta-analysis was performed to evaluate the efficacy and safety of preoperative aspirin, in patients undergoing coronary artery surgery. METHODS: We conducted a systematic review and meta-analysis of randomized trials involving patients undergoing coronary artery surgery assigned to preoperative aspirin therapy or no aspirin/placebo. The MEDLINE and EMBASE databases and Cochrane Central Register of Controlled Trials were searched up to March 2014 without language restrictions. Two reviewers performed independent quality review and data extraction. Efficacy outcomes of myocardial infarction (MI) and mortality, and safety outcomes of blood loss, red cell transfusion, and surgical re-exploration were compared. RESULTS: In 13 trials (n=2399), preoperative aspirin therapy reduced the risk of MI (OR, 0.56; 95% CI, 0.33-0.96; P=0.03), without a reduction in mortality (OR, 1.16; 95% CI, 0.42-3.22; P=0.77). Preoperative aspirin increased postoperative chest tube drainage (mean difference 168 ml; 95% CI, 39-297 ml; P=0.01), red cell transfusion (mean difference 141 ml; 95% CI, 55-226; P=0.001) and need for surgical re-exploration (OR, 1.85, 95% CI, 1.15-2.96; P=0.01). Studies were of low methodological quality, with significant heterogeneity identified. CONCLUSIONS: In patients undergoing coronary artery surgery, preoperative aspirin reduces perioperative MI, but at a cost of increased bleeding, blood transfusion, and surgical re-exploration.

Acute alcohol intoxication and bispectral index monitoring.

BACKGROUND: Bispectral index (BIS) monitoring is commonly used to decrease the risk of awareness during anaesthesia. We aimed to determine the relationship between blood alcohol concentration and brain function (as measured by BIS) in healthy adults. METHODS: In this prospective observational study, 21 anaesthetic registrars self-regulated alcohol consumption over a 3-h period. Expired alcohol concentration (breathalyser) and BIS measurements were performed hourly for 4 h. A venous blood alcohol sample was taken at the conclusion of the study period. RESULTS: The main outcome measures were the correlation between blood alcohol and brain function as measured by BIS and the change in BIS from baseline (∆BIS) at 4 h. The median number of standard drinks consumed was 9.1 (IQR 7.7-12.3), range 5.4-17. At 4 h, there was a moderate inverse correlation between BIS and blood alcohol (r = -0.49, P = 0.029) and between ∆BIS and blood alcohol (r = -0.46, P =0.043). CONCLUSION: In healthy young adults, we found a moderate correlation between venous blood alcohol concentration and BIS. This suggests that acute alcohol consumption can decrease BIS. This information may be relevant when providing anaesthesia to intoxicated patients who require urgent or time-critical surgery, although certain limitations of this study should be kept in mind.

Automated preoperative assessment of endothelial dysfunction and risk stratification for perioperative myocardial injury in patients undergoing non-cardiac surgery.

BACKGROUND: Myocardial injury after non-cardiac surgery (MINS) is a common complication with associated serious morbidity and mortality. Endothelial dysfunction might play an important role in MINS, and its rapid assessment could provide a novel method of risk stratification before surgery. METHODS: We studied 238 subjects scheduled to undergo intermediate or high-risk surgery in a two-centre prospective study to determine whether preoperative endothelial dysfunction identified by a reactive hyperaemia-peripheral arterial tonometry (RH-PAT) index could provide effective risk stratification for MINS, defined as serum troponin ≥0.04 µg litre(-1), within 3 postoperative days. RESULTS: The primary outcome occurred in 35 subjects (14.7%). Endothelial dysfunction was defined as an RH-PAT index of ≤1.22. Adjusted for age, Lee index and a composite measure of the extent of surgery, endothelial dysfunction was associated with MINS [odds ratio 10.1, 95% confidence interval (CI) 3.3-30.9, P=0.001] and increased time to discharge from hospital after surgery (hazard ratio 0.39, 95% CI 0.23-0.65, P=0.001). Endothelial dysfunction identified MINS with a sensitivity of 31%, a specificity of 96%, and a positive diagnostic likelihood ratio of 8.0. Risk classification for MINS was improved by the addition of RH-PAT-defined endothelial dysfunction to the Lee index (c-statistic increased from 0.69 to 0.77; integrated discrimination improvement 0.11, P=0.003). However, prognostic utility varied widely between sites. CONCLUSIONS: For patients undergoing non-cardiac surgery, non-invasive assessment of endothelial function might enhance preoperative risk stratification for perioperative myocardial injury. However, unexplained large inter-site variation in prognostic utility could limit widespread application and needs to be further understood.

A retrospective observational study examining the admission arterial to end-tidal carbon dioxide gradient in intubated major trauma patients.

Major trauma patients who are intubated and ventilated are exposed to the potential risk of iatrogenic hypercapnic and hypocapnic physiological stress. In the pre-hospital setting, end-tidal capnography is used as a practical means of estimating arterial carbon dioxide concentrations and to guide the adequacy of ventilation. In our study, potentially deleterious hypercapnia (mean 47 mmHg, range 26 to 83 mmHg) due to hypoventilation was demonstrated in 49% of 100 intubated major trauma patients arriving at a major Australian trauma centre. A mean gradient of 15 mmHg arterial to end-tidal carbon dioxide concentration difference was found, highlighting the limitations of capnography in this setting. Moreover, 80% of the patients in the study had a head injury. Physiological deadspace due to hypovolaemia in these patients is commonly thought to contribute to the increased arterial to end-tidal carbon dioxide gradient in trauma patients. However in this study, scene and arrival patient hypoxia was more predictive of hypoventilation and an increased arterial to end-tidal carbon dioxide gradient than physiological markers of shock. Greater vigilance for hypercapnia in intubated trauma patients is required. Additionally, a larger study may confirm that lower end-tidal carbon dioxide levels could be safely targeted in the pre-hospital and emergency department ventilation strategies of the subgroup of major trauma patients with scene hypoxia.

Interaction of hybrid nanowire-nanoparticle structures with carbon monoxide.

A gas-phase sensor based on a GaN nanowire mat decorated with Au nanoparticles was studied both experimentally and theoretically. The sensor is responsive to CO and H(2) and could be used to study the water-gas-shift reaction, which involves combining CO and H(2)O to produce H(2). It was shown that for catalyzing this reaction using support Au nanoparticles, the sequence in which the reactants are exposed to the catalyst surface is critical. To quantitatively evaluate the sensor response to gas exposure a depletion model was developed that considered the Au nanoparticle-semiconductor interface as a nano-Schottky barrier where variation in the depletion region caused changes in the electrical conductivity of the nanowires.

Does anaesthetic management affect early outcomes after lung transplant? An exploratory analysis.

BACKGROUND: Primary graft dysfunction (PGD) is a predominant cause of early morbidity and mortality after lung transplantation. Although substantial work has been done to understand risk factors for PGD in terms of donor, recipient, and surgical factors, little is understood regarding the potential role of anaesthetic management variables in its development. METHODS: We conducted a retrospective exploratory analysis of 107 consecutive lung transplants to determine if anaesthesia factors were associated with early graft function quantified by Pa(O(2))/Fi(O(2)). Multivariate regression techniques were used to explore the association between anaesthetic management variables and Pa(O(2))/Fi(O(2)) ratio 12 h after operation. The relationship between these variables and both time to tracheal extubation and intensive care unit (ICU) length of stay was further examined using the Cox proportional hazards. RESULTS: On multivariate analysis, increasing volume of intraoperative colloid, comprising predominantly Gelofusine (succinylated gelatin), was independently associated with a lower Pa(O(2))/Fi(O(2)) 12 h post-transplantation [beta coefficient -42 mm Hg, 95% confidence interval (CI) -7 to -77 mm Hg, P=0.02] and reduced rate of extubation [hazard ratio (HR) 0.65, 95% CI 0.49-0.84, P=0.001]. There was a trend for intraoperative colloid to be associated with a reduced rate of ICU discharge (HR 0.79, 95% CI 0.31-1.02, P=0.07). CONCLUSIONS: We observed an inverse relationship between volume of intraoperative colloid and early lung allograft function. The association persists, despite detailed sensitivity analyses and adjustment for potential confounding variables. Further studies are required to confirm these findings and explore potential mechanisms through which these associations may act.

Antifibrinolytics in cardiac surgical patients receiving aspirin: a systematic review and meta-analysis.

While conventional practice is to discontinue aspirin prior to elective cardiac surgery there is evidence that its continuation may be associated with improved perioperative outcomes. However, uncertainty exists regarding the efficacy of antifibrinolytic agents in the presence of aspirin. We performed a systematic review and meta-analysis of the literature to address the question of the effects of antifibrinolytic agents in cardiac surgery patients maintained on aspirin in terms of both efficacy and adverse events. We conducted an extensive search for randomized controlled trials of antifibrinolytic use in adult patients undergoing coronary artery bypass grafting +/- valve surgery, where aspirin therapy was maintained or initiated through the preoperative period. Data from 17 trials (n=1620) confirmed the efficacy of antifibrinolytic therapy to reduce both chest-tube drainage (weighted mean difference 374 ml, 95% CI 275-473 ml; P<0.00001) and blood transfusion requirements (odds ratio 0.37, 95% CI 0.27-0.49; P<0.00001) in cardiac surgical patients receiving aspirin. We found no difference in the rates of adverse events between groups but observed a trend towards a reduced risk for the composite outcome of thrombotic complications (odds ratio 0.49, 95% CI 0.21-1.13; P=0.09). Antifibrinolytic agents are effective for reducing both chest-tube drainage and transfusion requirements in cardiac surgical patients receiving aspirin. We found no difference between antifibrinolytic and placebo in terms of adverse events but the population was predominantly low-risk. Further studies are required to determine the optimal balance between antiplatelet and antifibrinolytic effects in cardiac surgery.

Anxiety in recovery from severe burn injury: an experimental comparison.

Adjustment to burn injury is a slow process that often results in high distress and anxiety. This study aimed to investigate the impact on anxiety of viewing various types of photographic stimuli (including burn injuries), comparing a burn-injured and control sample. An experimental design was used comparing those recovering from a burn injury with age- and gender-matched controls. Thirty participants from a burns support group and their matched controls were asked to complete a trait anxiety measure (STAI Y-2). Participants then completed the state anxiety measure (STAI Y-1) after viewing different types of photographic stimuli (burn injuries, uninjured body parts, neutral) under controlled experimental conditions. Results demonstrated significant differences in anxiety levels between groups with respect to trait anxiety and state anxiety after each experimental condition. Age of injury was also found to be a significant influence over trait anxiety. A significant effect of experimental condition was found, as was a significant interaction between group and condition. Those with burn injuries were more anxious than controls - a difference that was further exaggerated when participants viewed photographs of burned or uninjured body parts in an experimental setting.

Outcomes following a shortage of high dependency unit beds for surgical patients.

In an environment of resource rationing there are numerous patients who are unable to be admitted to a high-dependency unit (HDU) postoperatively despite the belief that this is the optimal discharge destination for them from the recovery room. It is unknown if this is associated with an increase in adverse outcomes. We performed an observational study, over a two-month period, comparing outcomes between patients who were admitted to HDU postoperatively and patients who, although an HDU bed was preferred, were discharged from the recovery room to the general ward due to an unavailability of HDU beds. Our primary outcome variable was hospital length-of-stay. We found an almost twofold increase in hospital length-of-stay in the group of patients admitted to the HDU. ASA IV patients were more likely to be admitted to HDU. However, the increased length-of-stay in the HDU group persisted even after stratifying patients according to ASA status. There was no difference between groups in all other baseline demographic variables, including POSSUM score, which is used as a predictor of postoperative morbidity and mortality. We believe that the most likely explanation for our findings is that the baseline risk between groups is, in fact, subtly different. This is not detected by preoperative scoring systems. However, clinical judgement in the recovery room appears to select a group of patients for HDU admission who subsequently have a slower postoperative recovery, despite no measurable increase in complication rate. That there was no increase in adverse events in the group of patients unable to be admitted to HDU due to a lack of bed availability suggests that current clinical judgement in a resource-rationed environment is functioning adequately, but the study was not powered to detect such a difference.

Polymorphism in the proximal promoter region of the perforin gene and its impact on the course of HIV infection.

Cytotoxic T lymphocytes (CTLs) play an essential role in the control of viral replication during human immunodeficiency virus (HIV) infection. However, the efficacy of the CTL response varies between individuals. We tested the hypothesis that genetic polymorphisms in the lytic effector molecule perforin could influence the progression of HIV infection. The perforin gene was screened for single nucleotide polymorphisms (SNPs) by denaturing high-performance liquid chromatography (dHPLC). Correlations were sought between perforin genotype, perforin expression and lytic function of CD8+ T lymphocytes from HIV-positive patients. Association of perforin genotype with disease progression was investigated in 426 seroconverters enrolled in the French SEROCO cohort. AIDS-free survival curves were constructed using the Kaplan-Meier method and compared using the log-rank test. Three SNPs were found in the proximal promoter region of the perforin gene: 63G (allelic frequency 0.029), 112G (allelic frequency 0.071) and 1012T (allelic frequency 0.070). The presence of the 1012T genotype correlated with fewer perforin+ cells among circulating CD8+ CTL. However, CTL lines from HIV(-positive) individuals heterozygous for the perforin 1012T SNP displayed normal lysis of target cells, and within the SEROCO cohort, patients heterozygous for the 1012T SNP showed normal disease progression. However, 1012T/T homozygotes showed a tendency towards slower disease progression (P = 0.08). In conclusion, polymorphism in the perforin gene is limited, and although the 1012T genotype appears to influence perforin expression, it was not conclusively associated with disease progression in HIV infection.

Transport properties of hybrid nanoparticle-nanowire systems and their application to gas sensing.

Experimental data and theoretical modelling of the I-V characteristics of a gas sensor constructed from a mat of Au nanoparticle-coated GaN nanowires are presented. The principal mechanism for the response of the gas sensor to methane is explained in terms of the formation of a depletion layer within the nanowires due to the presence of the gold nanoparticles. The depth of the depletion layer is modulated by the potential induced by the physisorption of gas molecules onto the Au nanoparticles. A statistical model of the temperature-dependent I-V characteristics of bare and Au nanoparticle-decorated mats of GaN nanowires based on Poisson's equation has been used to determine the depth of the depletion layers of the nanowires. The room-temperature carrier concentration for the GaN nanowires was determined to be approximately 2.2 × 10(17) cm(-3). The induced potential due to methane physisorption onto the Au nanoparticles that decorate the GaN nanowires was determined to be approximately -37 mV.

Investigation of human spleen dendritic cell phenotype and distribution reveals evidence of in vivo activation in a subset of organ donors.

Although the mouse spleen dendritic cell (DC) is perhaps the most intensively studied DC type, little has been published concerning its human equivalent. In this report, rare event flow cytometry and in situ immunofluorescence were used to study the surface phenotype and distribution of HLA-DR(+) CD3(-)14(-)16(-)19(-) human spleen DC. Spleens from organ donors with different clinical histories were used. Most (81% +/- 9%; n = 14) spleen DCs expressed high levels of the integrin CD11c. CD11c(+) DCs were distributed in 3 distinct regions-the peri-arteriolar T-cell zones, the B-cell zones, and the marginal zone, where they formed a ring of cells surrounding the white pulp, just inside a ring of CD14(+) red pulp macrophages, apparently more regularly organized than the previously described marginating DC population in the mouse spleen. The T-cell zones contained CD86(+) DCs, among which a subpopulation expressed CD83. These mature/activated CD86(+) DCs represented a minority (12% +/- 8%) of total spleen DCs in most organ donors: most spleen DCs are immature. In 3 of 18 (17%) donors, however, most (54%-81%) of spleen DCs were CD86(+), suggesting that in vivo DC activation had occurred. In one donor, a radical shift in DC distribution from the marginal zone to the T-cell zones was also observed. This activation of spleen DCs in vivo was reminiscent of the effects of experimental microbial product injection in mice, and it seemed to correlate with bacterial infection or multiple trauma. (Blood. 2001;97:3470-3477)

An evaluation of the factor structure and predictive utility of a test anxiety scale with reference to students' past performance and personality indices.

BACKGROUND: Scales of test anxiety have developed in parallel with the evolution of the test anxiety construct. A recently refined version of the Revised Test Anxiety scale offers the prospect of independently assessing different test anxiety factors. AIMS: The study aims to ascertain if the four-factor structure of the RTA scale found in Egyptian and American samples can be replicated in an Irish sample, and to examine the comparative predictive utility of cognitive and emotionality factors in relation to examination performance. The study also examines whether results support an Interference or Deficits Model of test anxiety, and assesses the relationship of test anxiety to personality variables believed to be relevant to academic performance. SAMPLE: The participants were 117 male and female psychology students from the University of Ulster. Their average age was 23 years. METHOD: Data were analysed using correlation analysis, multiple regression, factor analysis and ANOVA. Examination performance was the criterion variable; predictor variables were the four factors of test anxiety, three personality measures and previous examination performance. RESULTS: Four-factor test anxiety invariance across diverse population is supported by the model in the analysis. Cognitive factors are significant negative predictors of performance. The data do not support either an Interference or Deficits Model of test anxiety, and personality factors, especially self-efficacy, were significantly (negatively) related to test anxiety. CONCLUSIONS: The two cognitive factors have emerged as the most substantial negative predictors of examination performance. Attention to these factors and to relevant personality indices are commended as a potentially fruitful strategy for remedial intervention.

An auxiliary mode of apoptotic DNA fragmentation provided by phagocytes.

CAD (caspase-activated DNase) can cause DNA fragmentation in apoptotic cells. Transgenic mice that ubiquitously express a caspase-resistant form of the CAD inhibitor (ICAD) were generated. Thymocytes prepared from the mice were resistant to DNA fragmentation induced by a variety of stimuli. However, similar numbers of TUNEL-positive cells were present in adult tissues of transgenic and wild-type mice. Exposure to gamma-irradiation caused a striking increase in the number of TUNEL-positive cells in the thymus of wild-type, but not transgenic, mice. TUNEL-positive nuclei in transgenic mice were confined to thymic macrophages. When apoptotic thymocytes from the transgenic mice were cocultured with macrophages, the thymocytes underwent phagocytosis and their chromosomal DNA underwent fragmentation. This DNA fragmentation was sensitive to inhibitors that block the acidification of lysosomes. Hence, we conclude that the DNA fragmentation that occurs during apoptosis not only can result cell-autonomously from CAD activity but can also be attributed to a lysosomal acid DNase(s), most likely DNase II, after the apoptotic cells are engulfed.