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Abstract Taurine is a conditionally essential amino acid that has been reported to have antioxidative and immunomodulatory effects either directly or through its interactions with gut microbiome. Although taurine has been widely used as a health supplement and also for treatment of congestive heart failure in Japan, its roles in the perioperative setting have not been well characterized. The purpose of this systematic review and meta-analysis was to assess whether oral or intravenous taurine, or its derivatives such as taurolidine, can offer benefits compared to placebo in the perioperative setting. Non-randomized studies, trials assessed topical taurine or taurolidine, or trials did not report clinical outcomes were excluded. Six randomized-controlled-trials (RCTs) involving a total of 596 adult surgical patients, in PubMed, MEDLINE and EMBASE databases on September 14, 2023 were identified and meta-analyzed using a fixed-effect model. Biases were assessed by reporting individual trial elements. Taurine or taurolidine (which is readily metabolized by hydrolysis to taurine) supplementation was associated with a reduction in all-cause infection (5 trials: pooled odds ratio (OR) 0.59; 95% confidence interval (CI) 0.38–0.92; p = 0.020) but not delirium (2 trials: OR 0.63, 95% CI 0.38–1.04; p = 0.071) or mortality (4 trials: OR 0.82, 95% CI 0.43–1.58; p = 0.557) compared to placebo. Using the ‘trim and fill’ technique to adjust for publication bias did not change the favorable effect of taurine on risk of infection (OR 0.61, 95% CI 0.40–0.95). Because the number of studies included was small, the promising benefits of taurine on risks of perioperative infection should be confirmed by adequately-powered RCTs.

Summary: Background: Poor functional capacity has been identified as an important modifiable risk factor for postoperative complications. Cardiopulmonary exercise testing (CPET) provides objective parameters of functional capacity (e.g., oxygen consumption at peak exercise, peak VO2), with significant prognostication for postoperative complications. However, sex-specific thresholds for functional capacity to predict surgical risk are yet to be established. Therefore, we performed a post hoc analysis of the international, multicentre, prospective observational METS (Measurement of Exercise Tolerance before Surgery) study to evaluate if sex-specific thresholds of peak VO2 improve risk prediction of postoperative complications. Methods: We undertook a post hoc analysis (HREC/71824/PMCC) of the METS study, which was performed between March 2013 and March 2016. We investigated whether sex-specific differences exist for CPET-derived parameters and associated thresholds for predicting postoperative complications in this large cohort of patients that had major non-cardiac surgery (n = 1266). Logistic regression models were analyzed for the association of low peak VO2 with moderate-to-severe in-hospital postoperative complications. Optimal sex-specific peak VO2 thresholds were obtained by maximizing the Youden index of receiver operating characteristic (ROC) curves. Finally, multivariable logistic regression models tested the resulting sex-specific thresholds against the established non-sex-specific peak VO2 threshold (14 mL kg−1 min−1) adjusted for clinically relevant features such as comorbidities and surgical complexity. Models were evaluated by bootstrapping optimism-corrected area under the ROC curve and the net reclassification improvement index (NRI). Findings: Female patients (n = 480) had a lower mean (SD) peak VO2 than males (16.7 (4.9) mL kg−1 min−1 versus 21.2 (6.5) mL kg−1 min−1, p

Abstract Background To test the hypothesis that Intensive Care Unit (ICU) doctors and nurses differ in their personal preferences for treatment from the general population, and whether doctors and nurses make different choices when thinking about themselves, as compared to when they are treating a patient. Methods Cross sectional, observational study conducted in 13 ICUs in Australia in 2017 using a discrete choice experiment survey. Respondents completed a series of choice sets, based on hypothetical situations which varied in the severity or likelihood of: death, cognitive impairment, need for prolonged treatment, need for assistance with care or requiring residential care. Results A total of 980 ICU staff (233 doctors and 747 nurses) participated in the study. ICU staff place the highest value on avoiding ending up in a dependent state. The ICU staff were more likely to choose to discontinue therapy when the prognosis was worse, compared with the general population. There was consensus between ICU staff personal views and the treatment pathway likely to be followed in 69% of the choices considered by nurses and 70% of those faced by doctors. In 27% (1614/5945 responses) of the nurses and 23% of the doctors (435/1870 responses), they felt that aggressive treatment would be continued for the hypothetical patient but they would not want that for themselves. Conclusion The likelihood of returning to independence (or not requiring care assistance) was reported as the most important factor for ICU staff (and the general population) in deciding whether to receive ongoing treatments. Goals of care discussions should focus on this, over likelihood of survival.

Background Evidence prior to the coronavirus disease 2019 (COVID-19) pandemic suggested that, compared with conventional ventilation strategies, airway pressure release ventilation (APRV) can improve oxygenation and reduce mortality in patients with acute respiratory distress syndrome. We aimed to assess the association between APRV use and clinical outcomes among adult patients receiving mechanical ventilation for COVID-19 and hypothesized that APRV use would be associated with improved survival compared with conventional ventilation. Methods A total of 25 patients with COVID-19 pneumonitis was admitted to intensive care units (ICUs) for invasive ventilation in Perth, Western Australia, between February and May 2020. Eleven of these patients received APRV. The primary outcome was survival to day 90. Secondary outcomes were ventilation-free survival days to day 90, mechanical complications from ventilation, and number of days ventilated. Results Patients who received APRV had a lower probability of survival than did those on other forms of ventilation (hazard ratio, 0.17; 95% confidence interval, 0.03–0.89; P=0.036). This finding was independent of indices of severity of illness to predict the use of APRV. Patients who received APRV also had fewer ventilator-free survival days up to 90 days after initiation of ventilation compared to patients who did not receive APRV, and survivors who received APRV had fewer ventilator-free days than survivors who received other forms of ventilation. There were no differences in mechanical complications according to mode of ventilation. Conclusions Based on the findings of this study, we urge caution with the use of APRV in COVID-19.

Abstract Rationale Delirium is defined as acute organic brain dysfunction characterised by inattention and disturbance of cognition. It is common in the intensive care unit and is associated with poorer outcomes. Good quality sleep is important in the prevention and management of delirium. Melatonin is a natural hormone secreted by the pineal gland which helps in the regulation of the sleep-wake cycle. It is possible that melatonin supplementation in intensive care improves sleep and prevents delirium. Methods and design The ‘Prophylactic Melatonin for Delirium in Intensive Care’ study is a multi-centre, randomised, double-blinded, placebo-controlled trial. The primary objective of this study is to determine whether melatonin given prophylactically decreases delirium in critically ill patients. A total of 850 ICU patients have been randomised (1:1) to receive either melatonin or a placebo. Participants were monitored twice daily for symptoms of delirium. Results This paper and the attached additional files describe the statistical analysis plan (SAP) for the trial. The SAP has been developed and submitted for publication before the database has been locked and before the treatment allocation has been unblinded. The SAP contains details of analyses to be undertaken, which will be reported in the primary and secondary publications. Discussion The SAP details the analyses that will be done to avoid bias coming from knowledge of the results in advance. This trial will determine whether prophylactic melatonin administered to intensive care unit patients helps decrease the rate and the severity of delirium. Trial registration Australian and New Zealand Clinical Trial Registry (ANZCTR) ACTRN1261600043647 , registration date: 06 April 2016. WHO Trial Number – U1111-1175-1814

Abstract Background Persistent critical illness is common in critically ill patients and is associated with vast medical resource use and poor clinical outcomes. This study aimed to define when patients with sepsis would be stabilized and transitioned to persistent critical illness, and whether such transition time varies between latent classes of patients. Methods This was a retrospective cohort study involving sepsis patients in the eICU Collaborative Research Database. Persistent critical illness was defined at the time when acute physiological characteristics were no longer more predictive of in-hospital mortality (i.e., vital status at hospital discharge) than antecedent characteristics. Latent growth mixture modeling was used to identify distinct trajectory classes by using Sequential Organ Failure Assessment score measured during intensive care unit stay as the outcome, and persistent critical illness transition time was explored in each latent class. Results The mortality was 16.7% (3828/22,868) in the study cohort. Acute physiological model was no longer more predictive of in-hospital mortality than antecedent characteristics at 15 days after intensive care unit admission in the overall population. Only a minority of the study subjects (n = 643, 2.8%) developed persistent critical illness, but they accounted for 19% (15,834/83,125) and 10% (19,975/198,833) of the total intensive care unit and hospital bed-days, respectively. Five latent classes were identified. Classes 1 and 2 showed increasing Sequential Organ Failure Assessment score over time and transition to persistent critical illness occurred at 16 and 27 days, respectively. The remaining classes showed a steady decline in Sequential Organ Failure Assessment scores and the transition to persistent critical illness occurred between 6 and 8 days. Elevated urea-to-creatinine ratio was a good biochemical signature of persistent critical illness. Conclusions While persistent critical illness occurred in a minority of patients with sepsis, it consumed vast medical resources. The transition time differs substantially across latent classes, indicating that the allocation of medical resources should be tailored to different classes of patients.

Abstract Background and objectives Excess fluid balance in acute kidney injury (AKI) may be harmful, and conversely, some patients may respond to fluid challenges. This study aimed to develop a prediction model that can be used to differentiate between volume-responsive (VR) and volume-unresponsive (VU) AKI. Methods AKI patients with urine output 5 l in the following 6 h in the US-based critical care database (Medical Information Mart for Intensive Care (MIMIC-III)) were considered. Patients who received diuretics and renal replacement on day 1 were excluded. Two predictive models, using either machine learning extreme gradient boosting (XGBoost) or logistic regression, were developed to predict urine output > 0.65 ml/kg/h during 18 h succeeding the initial 6 h for assessing oliguria. Established models were assessed by using out-of-sample validation. The whole sample was split into training and testing samples by the ratio of 3:1. Main results Of the 6682 patients included in the analysis, 2456 (36.8%) patients were volume responsive with an increase in urine output after receiving > 5 l fluid. Urinary creatinine, blood urea nitrogen (BUN), age, and albumin were the important predictors of VR. The machine learning XGBoost model outperformed the traditional logistic regression model in differentiating between the VR and VU groups (AU-ROC, 0.860; 95% CI, 0.842 to 0.878 vs. 0.728; 95% CI 0.703 to 0.753, respectively). Conclusions The XGBoost model was able to differentiate between patients who would and would not respond to fluid intake in urine output better than a traditional logistic regression model. This result suggests that machine learning techniques have the potential to improve the development and validation of predictive modeling in critical care research.

Abstract Background Venous thromboembolism (VTE) is a complication following surgery. Low-molecular-weight heparin (LMWH) or direct oral anticoagulants (DOACs) are efficacious but come with inherent bleeding risk. Mechanical prophylaxis, such as intermittent pneumatic compression (IPC), does not induce bleeding but may be difficult to implement beyond the immediate post-operative period. This study compared the cost and quality-adjusted life years (QALYs) saved of commonly used VTE prophylaxis regimens after lower limb arthroplasty. Methods A previously published cost-utility model considering major efficacy and safety endpoints was updated to estimate the 1-year cost-effectiveness of different VTE prophylaxis regimens. The VTE strategies assessed included apixaban, dabigatran, rivaroxaban, LMWH, IPC, IPC + LMWH and IPC + apixaban. Efficacy data were derived from studies in PubMed, and cost data came from the 2017 Australian AR-DRG and PBS pricing schemes. Results Costs for VTE prophylaxis including treatment of its associated complications over the first year after surgery ranged from AUD $644 (IPC) to AUD $956 (rivaroxaban). Across 500 simulations, IPC was the cheapest measure in 73% of simulations. In 97% of simulations, a DOAC was associated with the highest resulting QALYs. Compared to IPC, apixaban was cost-effective in 76.4% of simulations and apixaban + IPC in 87.8% of simulations. For VTE events avoided, the DOACs and IPC were on par. LMWH and LMWH + IPC were negatively dominated. Conclusions Apixaban, IPC or a sequential/simultaneous combination of both is currently the most cost-effective VTE prophylaxis regimens. The choice between them is best guided by the relative VTE and bleeding risks of individual patients.

BACKGROUND:Warfarin is an anticoagulant medication proven effective in the initial treatment and secondary prevention of venous thromboembolism. Anti-Xa direct oral anticoagulants are alternatives to warfarin; however there is limited data assessing satisfaction after switching from warfarin to an anti-Xa direct oral anticoagulant in patients for treatment of venous thromboembolism. OBJECTIVES:To assess medication satisfaction in patients requiring anticoagulation for venous thromboembolism after conversion from warfarin to an anti-Xa direct oral anticoagulant. METHODS:A retrospective cohort study with prospective assessment of satisfaction and review of adverse events following anti-Xa direct oral anticoagulant replacement of warfarin for treatment of venous thromboembolism. Out of 165 patients who had switched from warfarin to rivaroxaban or apixaban from an outpatient haematology practice, 126 patients consented for a survey of patient's relative satisfaction of anti-Xa direct oral anticoagulant therapy compared with previous warfarin therapy using the Anti-Clot Burden and Benefits Treatment Scale and SWAN Score. RESULTS:The mean Anti-Clot Burden and Benefits and SWAN Score was 93% (56/60) and 83% (24.8/30) respectively reflecting high satisfaction with anti-Xa direct oral anticoagulants. 120 patients stated preference for anti-Xa direct oral anticoagulants over warfarin. Leading perceptions driving this was the reduction in frequency of medical contact and fewer bleeding side effects. Thirteen patients (10.3%) experienced an adverse event after the anti-Xa direct oral anticoagulant switch (majority were non-major bleeding) but most remained on anti-Xa direct oral anticoagulant treatment after management options were implemented with continued high satisfaction scores. CONCLUSIONS:Patient satisfaction with anti-Xa direct oral anticoagulant therapy for the treatment and prevention of venous thromboembolism after switching from warfarin in routine clinical practice appeared high. Improved patient convenience including reduced frequency of medical contact and fewer unpredictable side effects were perceived as significant advantages of anti-Xa direct oral anticoagulants compared to warfarin.

Abstract Background It is uncertain whether we can predict contrast-induced nephropathy (CIN) after CT pulmonary angiography (CTPA). This study compared the ability of a validated CIN prediction score with the Pulmonary Embolism Severity Index (PESI) in predicting CIN after CTPA. Methods This cohort study involved critically ill adult patients who required a CTPA to exclude acute pulmonary embolism (PE). Patients with end-stage renal failure requiring dialysis were excluded. CIN was defined as an elevation in plasma creatinine concentrations > 44.2μmol/l (or 0.5 mg/dl) within 48 h after CTPA. Results Of the 137 patients included, 77 (51%) were hypotensive, 54 (39%) required inotropic support, and 68 (50%) were mechanically ventilated prior to the CTPA. Acute PE was confirmed in 21 patients (15%) with 14 (10%) being bilateral. CIN occurred in 56 patients (41%) with 35 (26%) required dialysis subsequent to CTPA. The CIN prediction score had a good ability to discriminate between patients with and without developing CIN (Area under the receiver-operating-characteristic (AUROC) curve 0.864, 95% confidence interval [CI] 0.795–0.916) and requiring subsequent dialysis (AUROC 0.897, 95% CI 0.833–0.942) and was better than the PESI in predicting both outcomes (AUROC 0.731, 95% CI 0.649–0.804 and 0.775, 95% CI 0.696–0.842, respectively). A CIN risk score > 10 and 12 had an 82.1 and 85.7% sensitivity and 81.5 and 78.4% specificity to predict subsequent CIN and dialysis, respectively. The CIN prediction model tended to underestimate the observed risks of dialysis, but this was improved after recalibrating the slope and intercept of the original prediction equation. Conclusions The CIN prediction score had a good ability to discriminate between critically ill patients with and without developing CIN after CTPA. Used together for critically ill patients with suspected acute PE, the CIN prediction score and PESI may be useful to inform clinicians when the benefits of a CTPA scan will outweigh its potential harms.

Resveratrol has been shown to preserve organ function and improve survival in hemorrhagic shock rat models. This study investigated whether seven days of oral resveratrol could improve hemodynamic response to hemorrhage and confer benefits on risk of acute kidney injury (AKI) without inducing coagulopathy in a canine model. Twelve greyhound dogs were randomly allocated to receive oral resveratrol (1000 mg/day) or placebo for seven days prior to inducing hemorrhage until a targeted mean blood pressure of ≤40 mmHg was achieved. AKI biomarkers and coagulation parameters were measured before, immediately following, and two hours after hemorrhage. Dogs were euthanized, and renal tissues were examined at the end of the experiment. All investigators were blinded to the treatment allocation. A linear mixed model was used to assess effect of resveratrol on AKI biomarkers and coagulation parameters while adjusting for volume of blood loss. A significant larger volume of blood loss was required to achieve the hypotension target in the resveratrol group compared to placebo group (median 64 vs. 55 mL/kg respectively, p = 0.041). Although histological evidence of AKI was evident in all dogs, the renal tubular injury scores were not significantly different between the two groups, neither were the AKI biomarkers. Baseline (pre-hemorrhage) maximum clot firmness on the Rotational Thromboelastometry (ROTEM®) was stronger in the resveratrol group than the placebo group (median 54 vs. 43 mm respectively, p = 0.009). In summary, seven days of oral resveratrol did not appear to induce increased bleeding risk and could improve greyhound dogs’ blood pressure tolerance to severe hemorrhage. Renal protective effect of resveratrol was, however, not observed.

Graeme Jones, Erica Darian-Smith, Michael Kwok, Tania WinzenbergMenzies Research Institute, University of Tasmania, Tasmania, AustraliaAbstract: There have been substantial advances in the treatment of rheumatoid arthritis in recent years. Traditional disease-modifying antirheumatic drugs (DMARDs) have been shown to have small effects on the progression of radiographic damage. This quantitative overview summarizes the evidence for biologic DMARDS and radiographic damage either alone or in combination with methotrexate. Two outcomes were used (standardized mean difference and odds of progression). A total of 21 trials were identified of which 18 had useable data. For biologic monotherapy, tocilizumab, adalimumab, and etanercept were significantly better than methotrexate, with tocilizumab ranking first in both outcomes while golimumab was ineffective in both outcomes. For a biologic in combination with methotrexate compared with methotrexate alone, most therapies studied (etanercept, adalimumab, infliximab, certolizumab, tocilizumab, and rituximab) were effective at slowing X-ray progression using either outcome, with infliximab ranking first in both outcomes. The exceptions to this were golimumab (no effect on standardized mean difference) and abatacept (no effect on odds of progression). This effect was additional to methotrexate; thus, the overall benefit is moderate to large in magnitude, which is clearly of major clinical significance for sufferers of rheumatoid arthritis and supports the use of biologic DMARDs in those with a poor disease prognosis.Keywords: rheumatoid, trials, meta-analysis, radiographs, biologic, disease-modifying antirheumatic drugs, DMARDs

BackgroundRoad trauma is a leading cause of death and injury in young people. Traffic offences are common, but their importance as a risk indicator for subsequent road trauma is unknown. This cohort study assessed whether severe road trauma could be predicted by a history of prior traffic offences.Methodology and principal findingsClinical data of all adult road trauma patients admitted to the Western Australia (WA) State Trauma Centre between 1998 and 2013 were linked to traffic offences records at the WA Department of Transport. The primary outcomes were alcohol exposure prior to road trauma, severe trauma (defined by Injury Severity Score >15), and intensive care admission (ICU) or death, analyzed by logistic regression. Traffic offences directly leading to the road trauma admissions were excluded. Of the 10,330 patients included (median age 34 years-old, 78% male), 1955 (18.9%) had alcohol-exposure before road trauma, 2415 (23.4%) had severe trauma, 1360 (13.2%) required ICU admission, and 267 (2.6%) died. Prior traffic offences were recorded in 6269 (60.7%) patients. The number of prior traffic offences was significantly associated with alcohol-related road trauma (odds ratio [OR] per offence 1.03, 95% confidence interval [CI] 1.02-1.05), severe trauma (OR 1.13, 95%CI 1.14-1.15), and ICU admission or death (OR 1.10, 95%CI 1.08-1.11). Drink-drinking, seat-belt, and use of handheld electronic device offences were specific offences strongly associated with road trauma leading to ICU admission or death--all in a 'dose-related' fashion. For those who recovered from road trauma after an ICU admission, there was a significant reduction in subsequent traffic offences (mean difference 1.8, 95%CI 1.5 to 2.0) and demerit points (mean difference 7.0, 95%CI 6.5 to 7.6) compared to before the trauma event.SignificancePrevious traffic offences were a significant risk factor for alcohol-related road trauma and severe road trauma leading to ICU admission or death.

Risk-taking behavior is a leading cause of injury and death amongst young people.This was a retrospective cohort study on the effectiveness of a 1-day youth injury awareness education program (Prevent Alcohol and Risk-related Trauma in Youth, P.A.R.T.Y.) program in reducing risk taking behaviors and injuries of juvenille justice offenders in Western Australia. Of the 3659 juvenile justice offenders convicted by the court magistrates between 2006 and 2010, 225 were referred to the P.A.R.T.Y. education program. In a before and after survey of these 225 participants, a significant proportion of them stated that they were more receptive to modifying their risk-taking behavior (21% before vs. 57% after). Using data from the Western Australia Police and Department of Health, the incidence of subsequent offences and injuries of all juvenile justice offenders was assessed. The incidence of subsequent traffic or violence-related offences was significantly lower for those who had attended the program compared to those who did not (3.6% vs. 26.8%; absolute risk reduction [ARR] = 23.2%, 95% confidence interval [CI] 19.9%-25.8%; number needed to benefit = 4.3, 95%CI 3.9-5.1; p = 0.001), as were injuries leading to hospitalization (0% vs. 1.6% including 0.2% fatality; ARR = 1.6%, 95%CI 1.2%-2.1%) and alcohol or drug-related offences (0% vs. 2.4%; ARR 2.4%, 95%CI 1.9%-2.9%). In the multivariate analysis, only P.A.R.T.Y. education program attendance (odds ratio [OR] 0.10, 95%CI 0.05-0.21) and a higher socioeconomic background (OR 0.97 per decile increment in Index of Relative Socioeconomic Advantage and Disadvantage, 95%CI 0.93-0.99) were associated with a lower risk of subsequent traffic or violence-related offences.Participation in an injury education program involving real-life trauma scenarios was associated with a reduced subsequent risk of committing violence- or traffic-related offences, injuries, and death for juvenille justice offenders.

Purpose. To compare early functional outcomes, complications, and mortality in elderly patients treated with the less costly, cemented Thompson prosthesis or the cemented bipolar prosthesis in order to identify factors affecting outcomes. Methods. Records of 303 patients with femoral neck fractures treated with the cemented Thompson monoblock prosthesis (n=206) or the cemented bipolar prosthesis (n=97) were reviewed. The choice of prosthesis was solely determined by surgeon's preference. Data relating to patient demographics, clinical and residential status, mobility, mental function, mortality, and complications during hospitalisation and rehabilitation were collected. Results. After adjusting for confounding variables, independent postoperative indoor mobility was associated with preoperative indoor mobility (p=0.002) and mental function (p=0.001), whereas postoperative outdoor mobility was associated with preoperative outdoor mobility (p=0.003), daily living activity (p=0.02), and mental function (p=0.02). Mortality within 6 months was only associated with poor mental function (p=0.009). At 6-month follow-up, there was no significant difference between the 2 types of prosthesis in terms of functional outcomes, mortality and complication rates. Conclusion. In elderly patients with limited mobility, treatment with the bipolar prosthesis was not associated with better short-term outcomes than those receiving the Thompson prosthesis.

BACKGROUND: Long-term survival outcome of critically ill patients is important in assessing effectiveness of new treatments and making treatment decisions. We developed a prognostic model for estimation of long-term survival of critically ill patients. METHODOLOGY AND PRINCIPAL FINDINGS: This was a retrospective linked data cohort study involving 11,930 critically ill patients who survived more than 5 days in a university teaching hospital in Western Australia. Older age, male gender, co-morbidities, severe acute illness as measured by Acute Physiology and Chronic Health Evaluation II predicted mortality, and more days of vasopressor or inotropic support, mechanical ventilation, and hemofiltration within the first 5 days of intensive care unit admission were associated with a worse long-term survival up to 15 years after the onset of critical illness. Among these seven pre-selected predictors, age (explained 50% of the variability of the model, hazard ratio [HR] between 80 and 60 years old = 1.95) and co-morbidity (explained 27% of the variability, HR between Charlson co-morbidity index 5 and 0 = 2.15) were the most important determinants. A nomogram based on the pre-selected predictors is provided to allow estimation of the median survival time and also the 1-year, 3-year, 5-year, 10-year, and 15-year survival probabilities for a patient. The discrimination (adjusted c-index = 0.757, 95% confidence interval 0.745-0.769) and calibration of this prognostic model were acceptable. SIGNIFICANCE: Age, gender, co-morbidities, severity of acute illness, and the intensity and duration of intensive care therapy can be used to estimate long-term survival of critically ill patients. Age and co-morbidity are the most important determinants of long-term prognosis of critically ill patients.

Purpose Delirium is common in the critically ill, highly distressing to patients and families and associated with increased morbidity and mortality. Results of studies on preventative use of melatonin in various patient groups have produced mixed results. The aim of this study was to determine whether administration of melatonin decreases the prevalence of delirium in critically ill patients. Methods Multicentre, randomized, placebo-controlled, double-blind trial across 12 Australian ICUs recruiting patients from July 2016 to September 2019. Patients of at least 18 years requiring ICU admission with an expected length of stay (LOS) greater than 72 h; enrolled within 48 h of ICU admission. Indistinguishable liquid melatonin (4 mg; n = 419) or placebo (n = 422) was administered enterally at 21:00 h for 14 consecutive nights or until ICU discharge. The primary outcome was the proportion of delirium-free assessments, as a marker of delirium prevalence, within 14 days or before ICU discharge. Delirium was assessed twice daily using the Confusion Assessment Method for ICU (CAM-ICU) score. Secondary outcomes included sleep quality and quantity, hospital and ICU LOS, and hospital and 90-day mortality. Results A total of 847 patients were randomized into the study with 841 included in data analysis. Baseline characteristics of the participants were similar. There was no significant difference in the average proportion of delirium-free assessments per patient between the melatonin and placebo groups (79.2 vs 80% respectively, p = 0.547). There was no significant difference in any secondary outcomes including ICU LOS (median: 5 vs 5 days, p = 0.135), hospital LOS (median: 14 vs 12 days, p = 0816), mortality at any time point including at 90 days (15.5 vs 15.6% p = 0.948), nor in the quantity or quality of sleep. There were no serious adverse events reported in either group. Conclusion Enteral melatonin initiated within 48 h of ICU admission did not reduce the prevalence of delirium compared to placebo. These findings do not support the routine early use of melatonin in the critically ill., Author(s): Bradley Wibrow [sup.1] [sup.2], F. Eduardo Martinez [sup.3] [sup.4], Erina Myers [sup.1] [sup.5], Andrew Chapman [sup.6], Edward Litton [sup.2] [sup.7], Kwok. M. Ho [sup.2] [sup.6] [sup.19], Adrian Regli [sup.2] [...]

Background: Low cardiac power (product of flow and pressure) has been shown to be associated with mortality in patients with cardiogenic shock after acute myocardial infarction, but has not been studied in cardiac surgical patients. This study's hypothesis was that cardiac power during cardiopulmonary bypass for cardiac surgery would have a greater association with adverse events than either flow or MAP (mean arterial pressure) alone. Methods: We undertook a retrospective observational study using patient data from February 2015 to March 2022 undergoing cardiac surgery at Fiona Stanley Hospital in Perth Australia. Excluded were patient age less than 18 years old, patients undergoing thoracic transplantation, ventricular assist devices, off pump cardiac surgery and aortic surgery. The primary outcome was a composite outcome of 30-days mortality, stroke or new-onset renal insufficiency. Results: Overall, 1984 cardiac surgeries were included in the analysis. Neither duration nor area below thresholds tested for power, MAP or flow was associated with the primary composite outcome. However, we found that an area below MAP thresholds 35–50 mmHg was associated with new renal insufficiency (adjusted odds ratio 1.17 [95% CI 1.02 to 1.35] for patients spending 10 min at 10 mmHg below 50 mmHg MAP compared to those who did not). Conclusions: This study suggests that MAP during cardiopulmonary bypass, but not power or flow, was an independent risk factor for adverse renal outcomes for cardiac surgical patients. [ABSTRACT FROM AUTHOR]

Shared understanding is often achieved in communication interactions at the point in which the participants come to an agreement upon meaning. Without shared meaning, misunderstandings can lead to a breakdown in communication, and possibly failure on collaborative tasks. The purpose of the present study was to examine how students, preservice, and in-service teachers used different strategies to attempt to reach shared meaning during a spatial visualization task in a STEM instructional context. The data included 15 transcribed recordings analyzed through constant comparative analysis to identify the characteristics of the communication during clarification exchanges. Findings highlight three features of these exchanges: confirmation, rethinking, and misdirection. Within these exchanges, communication involved precise, technical language as well as analogous, everyday language to attempt to reach shared meaning. Exchanges that were successful (in moving toward task completion) illustrated the use of this language to affirm or move toward shared vocabulary. Unsuccessful exchanges (that hindered task completion) resulted from misunderstandings due to lack of shared language or meaning. Classroom implications for teaching and learning include recognizing that everyday language and technical language can potentially serve as points of confusion, and embracing the importance of accurately assessing and responding to students' current understandings.