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Rationale: Hypercapnia may affect the outcome of sepsis. Very few clinical studies conducted in noncritically ill patients have investigated the effects of hypercapnia and hypercapnic acidemia in the context of sepsis. The effect of hypercapnia in critically ill patients with sepsis remains inadequately studied. Objectives: To investigate the association of hypercapnia with hospital mortality in critically ill patients with sepsis. Methods: This is a retrospective study conducted in three tertiary public hospitals. Critically ill patients with sepsis from three intensive care units between January 2011 and May 2019 were included. Five cohorts (exposure of at least 24, 48, 72, 120, and 168 hours) were created to account for immortal time bias and informative censoring. The association between hypercapnia exposure and hospital mortality was assessed with multivariable models. Subgroup analyses compared ventilated versus nonventilated and pulmonary versus nonpulmonary sepsis patients. Results: We analyzed 84,819 arterial carbon dioxide pressure measurements in 3,153 patients (57.6% male; median age was 62.5 years). After adjustment for key confounders, both in mechanically ventilated and nonventilated patients and in patients with pulmonary or nonpulmonary sepsis, there was no independent association of hypercapnia with hospital mortality. In contrast, in ventilated patients, the presence of prolonged exposure to both hypercapnia and acidemia was associated with increased mortality (highest odds ratio of 16.5 for ⩾120 hours of potential exposure; P = 0.007). Conclusions: After adjustment, isolated hypercapnia was not associated with increased mortality in patients with sepsis, whereas prolonged hypercapnic acidemia was associated with increased risk of mortality. These hypothesis-generating observations suggest that as hypercapnia is not an independent risk factor for mortality, trials of permissive hypercapnia avoiding or minimizing acidemia in sepsis may be safe.

Background: Despite advances in surgery and pharmacotherapy, there remains significant residual ischemic risk after coronary artery bypass grafting surgery. Methods: In REDUCE-IT (Reduction of Cardiovascular Events With Icosapent Ethyl–Intervention Trial), a multicenter, placebo-controlled, double-blind trial, statin-treated patients with controlled low-density lipoprotein cholesterol and mild to moderate hypertriglyceridemia were randomized to 4 g daily of icosapent ethyl or placebo. They experienced a 25% reduction in risk of a primary efficacy end point (composite of cardiovascular death, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina) and a 26% reduction in risk of a key secondary efficacy end point (composite of cardiovascular death, myocardial infarction, or stroke) when compared with placebo. The current analysis reports on the subgroup of patients from the trial with a history of coronary artery bypass grafting. Results: Of the 8179 patients randomized in REDUCE-IT, a total of 1837 (22.5%) had a history of coronary artery bypass grafting, with 897 patients randomized to icosapent ethyl and 940 to placebo. Baseline characteristics were similar between treatment groups. Randomization to icosapent ethyl was associated with a significant reduction in the primary end point (hazard ratio [HR], 0.76 [95% CI, 0.63–0.92]; P =0.004), in the key secondary end point (HR, 0.69 [95% CI, 0.56–0.87]; P =0.001), and in total (first plus subsequent or recurrent) ischemic events (rate ratio, 0.64 [95% CI, 0.50–0.81]; P =0.0002) compared with placebo. This yielded an absolute risk reduction of 6.2% (95% CI, 2.3%–10.2%) in first events, with a number needed to treat of 16 (95% CI, 10–44) during a median follow-up time of 4.8 years. Safety findings were similar to the overall study: beyond an increased rate of atrial fibrillation/flutter requiring hospitalization for at least 24 hours (5.0% vs 3.1%; P =0.03) and a nonsignificant increase in bleeding, occurrences of adverse events were comparable between groups. Conclusions: In REDUCE-IT patients with a history of coronary artery bypass grafting, treatment with icosapent ethyl was associated with significant reductions in first and recurrent ischemic events. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01492361.

Purpose To investigate the association between sex and illness severity and mortality of ICU patients. Methods We performed systematic searches of MEDLINE and EMBASE for observational studies of adult ICU patients that explicitly examined the association between sex and illness severity or mortality. We used a random effects model to calculate standardised mean differences in illness severity scores and pooled odds ratios for mortality of women compared to men. Results We identified 21 studies with 505,138 participants in total (43.1% women). There was substantial heterogeneity among studies. Only two studies were at low risk of bias overall. At ICU admission, there was a pattern of higher illness severity scores among women (standardised mean difference 0.04, 95% CI -0.01-0.09). Women had higher risk-adjusted mortality than men at ICU discharge (OR 1.25 95% CI 1.03–1.50) and 1 year (OR 1.08, 95% CI 1.02–1.13), however this finding was not robust to sensitivity analysis. Conclusions Women tend to have higher illness severity scores at ICU admission. Women also appear to have higher risk-adjusted mortality than men at ICU discharge and at 1 year. Given the heterogeneity and risk of bias in the existing literature, additional studies are needed to confirm or refute these findings.

Male sexual orientation is influenced by environmental and complex genetic factors. Childhood gender nonconformity (CGN) is one of the strongest correlates of homosexuality with substantial familiality. We studied brothers in families with two or more homosexual brothers (409 concordant sibling pairs in 384 families, as well as their heterosexual brothers), who self-recalled their CGN. To map loci for CGN, we conducted a genome-wide linkage scan (GWLS) using SNP genotypes. The strongest linkage peaks, each with significant or suggestive two-point LOD scores and multipoint LOD score support, were on chromosomes 5q31 (maximum two-point LOD = 4.45), 6q12 (maximum two-point LOD = 3.64), 7q33 (maximum two-point LOD = 3.09), and 8q24 (maximum two-point LOD = 3.67), with the latter not overlapping with previously reported strongest linkage region for male sexual orientation on pericentromeric chromosome 8. Family-based association analyses were used to identify associated variants in the linkage regions, with a cluster of SNPs (minimum association p = 1.3 × 10–8) found at the 5q31 linkage peak. Genome-wide, clusters of multiple SNPs in the 10–6 to 10–8p-value range were found at chromosomes 5p13, 5q31, 7q32, 8p22, and 10q23, highlighting glutamate-related genes. This is the first reported GWLS and genome-wide association study on CGN. Further increasing genetic knowledge about CGN and its relationships to male sexual orientation should help advance our understanding of the biology of these associated traits.

Rationale: Both 2009 pandemic influenza A (H1N1) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are transmitted by respiratory secretions and in severe cases result in a viral pneumonitis, requiring intensive care unit (ICU) admission. However, no studies have compared the clinical characteristics and outcomes of such patients. Objectives: To report and compare the demographic characteristics, treatments, use of critical care resources, and outcomes of patients admitted to an Australian ICU with H1N1 influenza during the winter of 2009, and SARS-CoV-2 during the winter of 2020. Methods: This was a multicenter project, using national data from previous and ongoing epidemiological studies concerning severe acute respiratory infections in Australia. All ICUs admitting patients with H1N1 or coronavirus disease (COVID-19) were included and contributed data. We compared clinical characteristics and outcomes of patients with H1N1 admitted to ICU in the winter of 2009 versus patients with COVID-19 admitted to ICU in the winter of 2020. The primary outcome was in-hospital mortality. Potential years of life lost (PYLL) were calculated according to sex-adjusted life expectancy in Australia. Results: Across the two epochs, 861 patients were admitted to ICUs; 236 (27.4%) with COVID-19 and 625 (72.6%) with H1N1 influenza. The number of ICU admissions and bed-days occupied were higher with 2009 H1N1 influenza. Patients with COVID-19 were older, more often male and overweight, and had lower Acute Physiology and Chronic Health Evaluation II scores at ICU admission. The highest age-specific incidence of ICU admission was among infants (0–1 yr of age) for H1N1, and among the elderly (≥65 yr) for COVID-19. Unadjusted in-hospital mortality was similar (11.5% in COVID-19 vs. 16.1% in H1N1; odds ratio, 0.68 [95% confidence interval (95% CI), 0.42–1.06]; P = 0.10). The PYLL was greater with H1N1 influenza than with COVID-19 at 154.1 (95% CI, 148.7–159.4) versus 13.6 (95% CI, 12.2–15.1) PYLL per million inhabitants. Conclusions: In comparison with 2009 H1N1 influenza, COVID-19 admissions overwinter in Australia resulted in fewer ICU admissions, and lower bed-day occupancy. Crude in-hospital mortality was similar, but because of demographic differences in affected patients, deaths due to 2009 H1N1 influenza led to an 11-fold increase in the number of PYLL in critically ill patients.

OBJECTIVES: Previous case series reported an association between dexmedetomidine use and hyperthermia. Temperature data have not been systematically reported in previous randomized controlled trials evaluating dexmedetomidine. A causal link between dexmedetomidine administration and elevated temperature has not been demonstrated. DESIGN: Post hoc analysis. SETTING: Four ICUs in Australia and New Zealand. PATIENTS: About 703 mechanically ventilated ICU patients. INTERVENTIONS: Early sedation with dexmedetomidine versus usual care. MEASUREMENTS AND MAIN RESULTS: The primary outcome was mean daily body temperature. Secondary outcomes included the proportions of patients with body temperatures greater than or equal to 38.3°C and greater than or equal to 39°C, respectively. Outcomes were recorded for 5 days postrandomization in the ICU. The mean daily temperature was not different between the dexmedetomidine (n = 351) and usual care (n = 352) groups (36.84°C ± sd vs 36.78°C ± sd; p = 0.16). Over the first 5 ICU days, more dexmedetomidine group (vs usual care) patients had a temperature greater than or equal to 38.3°C (43.3% vs 32.7%, p = 0.004; absolute difference 10.6 percentage points) and greater than or equal to 39.0°C (19.4% vs 12.5%, p = 0.013; absolute difference 6.9 percentage points). Results were similar after adjusting for diagnosis, admitting temperature, age, weight, study site, sepsis occurrence, and the time from dexmedetomidine initiation to first hyperthermia recorded. There was a significant dose response relationship with temperature increasing by 0.30°C ±0.08 for every additional 1 μg/kg/hr of dexmedetomidine received p < 0.0002. CONCLUSIONS: Our study suggests potentially important elevations in body temperature are associated with early dexmedetomidine sedation, in adults who are mechanically ventilated in the ICU.

BACKGROUND: Studies comparing mortality following massive transfusion (MT) with fresher versus longer-stored red blood cells (RBCs) have focused on trauma patients. The Australian and New Zealand Massive Transfusion Registry collects data on all adult MT cases (≥5 RBCs within 4 hours, any bleeding context, ≥18 years) at participating hospitals. METHODS: Years 2007 to 2018 data from 29 hospitals were analyzed to quantify the association between mortality and RBC storage time in adult MT cases. We ran three logistic regression models separately on each of seven bleeding contexts, with in-hospital mortality as the outcome and, in turn, (1) mean storage time (STmean) quartiles, (2) proportion of RBCs ≥30 days old (propOLD), and (3) scalar age of blood index as predictors. RESULTS: A total of 8,685 adult MT cases involving transfusion of 126,622 RBCs were analyzed with Australian and New Zealand data analyzed separately. Mean storage times for these cases were (by quartile in ascending order) as follows: Australia, 12.5 days (range, 3.1-15.5 days), 17.7 (15.5-19.9), 22.3 (19.9-24.9), and 29.8 (24.9-41.7); New Zealand, 11.3 days (3.6-13.7), 15.3 (13.7-16.8), 18.7 (16.8-20.7), and 24.5 (20.7-35.6). The odds ratios comparing in-hospital mortality for each quartile with that of the control first quartile (freshest blood), proportion of longer-stored (≥30 days) RBCs, and scalar age of blood index were not statistically significant across all bleeding contexts. CONCLUSION: We find no correlation between in-hospital mortality and storage time of transfused RBCs in a large cohort of adult MT patients representing all bleeding contexts. These results are consistent with those of recent large multicenter trials. LEVEL OF EVIDENCE: Epidemiologic, level III; Therapeutic, level IV.

Background The Clinical Frailty Scale (CFS) is the most commonly used frailty measure in intensive care unit (ICU) patients. The hospital frailty risk score (HFRS) was recently proposed for the quantification of frailty. We aimed to compare the HFRS with the CFS in critically ill patients in predicting long-term survival up to one year following ICU admission. Methods In this retrospective multicentre cohort study from 16 public ICUs in the state of Victoria, Australia between 1st January 2017 and 30th June 2018, ICU admission episodes listed in the Australian and New Zealand Intensive Care Society Adult Patient Database registry with a documented CFS, which had been linked with the Victorian Admitted Episode Dataset and the Victorian Death Index were examined. The HFRS was calculated for each patient using the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes that represented pre-existing conditions at the time of index hospital admission. Descriptive methods, Cox proportional hazards and area under the receiver operating characteristic (AUROC) were used to investigate the association between each frailty score and long-term survival up to 1 year, after adjusting for confounders including sex and baseline severity of illness on admission to ICU (Australia New Zealand risk-of-death, ANZROD). Results 7001 ICU patients with both frailty measures were analysed. The overall median (IQR) age was 63.7 (49.1–74.0) years; 59.5% (n = 4166) were male; the median (IQR) APACHE II score 14 (10–20). Almost half (46.7%, n = 3266) were mechanically ventilated. The hospital mortality was 9.5% (n = 642) and 1-year mortality was 14.4% (n = 1005). HFRS correlated weakly with CFS (Spearman’s rho 0.13 (95% CI 0.10–0.15) and had a poor agreement (kappa = 0.12, 95% CI 0.10–0.15). Both frailty measures predicted 1-year survival after adjusting for confounders, CFS (HR 1.26, 95% CI 1.21–1.31) and HFRS (HR 1.08, 95% CI 1.02–1.15). The CFS had better discrimination of 1-year mortality than HFRS (AUROC 0.66 vs 0.63 p Conclusion Both HFRS and CFS independently predicted up to 1-year survival following an ICU admission with moderate discrimination. The CFS was a better predictor of 1-year survival than the HFRS.

Background Over the last two decades, technological advancements in the delivery of extra corporeal membrane oxygenation (ECMO) have seen its use broaden and results improve. However, in the post cardiotomy ECMO patient group, survival remains very poor without significant improvements over the last two decades. Our study aims to report on the Australian experience, with the intention of providing background data for the formation of guidelines in the future. Methods Retrospective analysis of prospectively collected data from the Australian and New Zealand Society of Cardiothoracic Surgeons (ANZSCTS) Database was performed. The ANZSCTS database captures at least 60% of cardiac surgical data in Australia, annually. Data was collected on adult patients who received ECMO post cardiotomy from September 2016 to November 2017 inclusive. Transplant and primary cardiomyopathy patients were excluded. Results Of the 16,605 adult patients undergoing cardiac surgery in the 15-month period of the study, 87 patients required post cardiotomy ECMO (0.52%). The average age of the entire cohort was 56 years. Overall survival to discharge was 43.7% (n=38). Multivariable logistic regression analysis demonstrated that multiorgan failure (MOF), increasing age and longer cardiopulmonary bypass time were significant predictors of in hospital mortality. Conclusions Post cardiotomy ECMO support is an uncommon condition. Survival in this study appears to be better than historical reports. Identification of poor prognostic indicators in this study may help inform the development of guidelines for the most appropriate use of this support modality.

Rationale: ICU discharge delay occurs when a patient is considered ready to be discharged but remains in the ICU. The effect of discharge delay on patient outcomes is uncertain.Objectives: To investigate the association between discharge delay and patient outcomes including hospital mortality, readmission to ICU, and length of hospital stay after ICU discharge.Methods: Data were accessed from the Australian and New Zealand Intensive Care Society Adult Patient Database between 2011 and 2019. Descriptive analyses and hierarchical logistic and Cox proportional hazards regression were used to examine association between discharge delay and adjusted outcomes. Patients were stratified and analyzed by categories of mortality risk at ICU admission.Measurements and Main Results: The study included 1,014,540 patients from 190 ICUs: 756,131 (75%) were discharged within 6 hours of being deemed ready, with 137,042 (13%) discharged in the next 6 hours; 17,656 (2%) were delayed 48-72 hours; 31,389 (3.1%) died in hospital; and 45,899 (4.5%) patients were readmitted to ICU. Risk-adjusted mortality declined with increasing discharge delay and was lowest at 48-72 hours (adjusted odds ratio, 0.87; 95% confidence interval, 0.79-0.94). The effect was seen in patients with predicted risk of death on admission to ICU of greater than 5% (adjusted odds ratio, 0.77; 95% confidence interval, 0.70-0.84). There was a progressive reduction in adjusted odds of readmission with increasing discharge delay.Conclusions: Increasing discharge delay in ICUs is associated with reduced likelihood of mortality and ICU readmission in high-risk patients. Consideration should be given to delay the discharge of patients with high risk of death on ICU admission.

BackgroundMen sexually interested in children of a specific combination of maturity and sex tend to show some lesser interest in other categories of persons. Patterns of men's sexual interest across erotic targets' categories of maturity and sex have both clinical and basic scientific implications.MethodWe examined the structure of men's sexual interest in adult, pubescent, and prepubescent males and females using multidimensional scaling (MDS) across four datasets, using three large samples and three indicators of sexual interest: phallometric response to erotic stimuli, sexual offense history, and self-reported sexual attraction. The samples were highly enriched for men sexually interested in children and men accused of sexual offenses.ResultsResults supported a two-dimensional MDS solution, with one dimension representing erotic targets' biological sex and the other dimension representing their sexual maturity. The dimension of sexual maturity placed adults and prepubescent children on opposite ends, and pubescent children intermediate. Differences between men's sexual interest in adults and prepubescent children of the same sex were similar in magnitude to the differences between their sexual interest in adult men and women. Sexual interest in adult men was no more associated with sexual interest in boys than sexual interest in adult women was associated with sexual interest in girls.ConclusionsErotic targets' sexual maturity and biological sex play important roles in men's preferences, which are predictive of sexual offending. The magnitude of men's preferences for prepubescent children v. adults of their preferred sex is large.

Blanchard proposed that autogynephilia is a natal male's paraphilic sexual arousal in response to the thought or fantasy of being a woman. Furthermore, based on evidence collected from natal males with gender dysphoria, Blanchard argued that autogynephilia is the fundamental motivation among nonhomosexual males (i.e., those not exclusively attracted to men) who pursue sex reassignment surgery or live as transgender women. These ideas have been challenged by several writers who have asserted, or offered evidence, that autogynephilia is common among women. However, their evidence was weakened by problematic measures and limited comparison groups. We compared four samples of autogynephilic natal males (N = 1549), four samples of non-autogynephilic natal males (N = 1339), and two samples of natal females (N = 500), using Blanchard's original measure: the Core Autogynephilia Scale. The autogynephilic samples had much higher mean scores compared with non-autogynephilic natal males and natal females, who were similar. Our findings refute the contention that autogynephilia is common among natal females.

Purpose Sepsis is a common reason for intensive care unit (ICU) admission and mortality in ICU patients. Despite increasing interest in treatment strategies limiting oxygen exposure in ICU patients, no trials have compared conservative vs. usual oxygen in patients with sepsis. Methods We undertook a post hoc analysis of the 251 patients with sepsis enrolled in a trial that compared conservative oxygen therapy with usual oxygen therapy in 1000 mechanically ventilated ICU patients. The primary end point for the current analysis was 90-day mortality. Key secondary outcomes were cause-specific mortality, ICU and hospital length of stay, ventilator-free days, vasopressor-free days, and the proportion of patients receiving renal replacement therapy in the ICU. Results Patients with sepsis allocated to conservative oxygen therapy spent less time in the ICU with an SpO2 ≥ 97% (23.5 h [interquartile range (IQR) 8–70] vs. 47 h [IQR 11–93], absolute difference, 23 h; 95% CI 8–38), and more time receiving an FiO2 of 0.21 than patients allocated to usual oxygen therapy (20.5 h [IQR 1–79] vs. 0 h [IQR 0–10], absolute difference, 20 h; 95% CI 14–26). At 90-days, 47 of 130 patients (36.2%) assigned to conservative oxygen and 35 of 120 patients (29.2%) assigned to usual oxygen had died (absolute difference, 7 percentage points; 95% CI − 4.6 to 18.6% points; P = 0.24; interaction P = 0.35 for sepsis vs. non-sepsis). There were no statistically significant differences between groups for secondary outcomes but point estimates of treatment effects consistently favored usual oxygen therapy. Conclusions Point estimates for the treatment effect of conservative oxygen therapy on 90-day mortality raise the possibility of clinically important harm with this intervention in patients with sepsis; however, our post hoc analysis was not powered to detect the effects suggested and our data do not exclude clinically important benefit or harm from conservative oxygen therapy in this patient group. Clinical Trials Registry ICU-ROX Australian and New Zealand Clinical Trials Registry number ACTRN12615000957594. Electronic supplementary material The online version of this article (10.1007/s00134-019-05857-x) contains supplementary material, which is available to authorized users.

BACKGROUND AND AIM: To study the management of coagulation and hematological derangements among severe acute liver failure (ALF) patients in Australia and New Zealand liver transplant intensive care units (ICUs). METHODS: Analysis of key baseline characteristics, etiology, coagulation and hematological tests, use of blood products, thrombotic complications, and clinical outcomes during the first ICU week. RESULTS: We studied 62 ALF patients. The first day median peak international normalized ratio was 5.5 (inter-quartile range [IQR] 3.8-8.7), median longest activated partial thromboplastin time was 62 s (IQR 44-87), and median lowest fibrinogen was 1.1 (IQR 0.8-1.6) g/L. Fibrinogen was only measured in 85% of patients, which was less than other tests (P

To compare the effects of fluid bolus therapy using 20% albumin versus crystalloid on fluid balance, hemodynamic parameters, and intensive care unit (ICU) treatment effects in post-cardiac surgery patients.Sequential period open-label pilot study.University teaching hospital.One hundred adult cardiac surgery patients who were prescribed fluid bolus therapy to correct hypotension or perceived hypovolemia or to optimize cardiac index during the first 24 hours in the ICU.The first 50 patients were treated with crystalloid fluid bolus therapy in the first period (control), and 50 patients with up to 2 treatments of 100 mL of 20% albumin fluid bolus therapy in the second period (intervention), followed by crystalloid therapy if needed.Demographic characteristics were similar at baseline. The intervention was associated with a less positive median fluid balance in the first 24 hours (albumin: 1,100 [650-1,960] v crystalloid: 1,970 [1,430-2,550] p = 0.001), fewer episodes of fluid bolus therapy (3 [2-5] v 5 [4-7]; p0.0001) and a lesser volume of fluid bolus therapy (700 [200-1,450] v 1,500 mL/24 h [1,100-2,250]; p0.0001). The intervention also was associated with a decreased median overall dose of norepinephrine in the first 24 hours of ICU stay (19 [0-52] v 47 µg/kg/24 hours [0-134]; p = 0.025) and shorter median time to cessation of norepinephrine (17 [5-28] v 28 hours [20-48]; p = 0.002).Post-cardiac surgery fluid bolus therapy with 20% albumin when compared with crystalloid fluid resulted in less positive fluid balance as well as several hemodynamic and potential ICU treatment advantages.

Background Pain is a common stressor for ICU patients, necessitating routine assessment. For patients who are unable to communicate, self-report tools are unsuitable, and the use of an observational tool is required to assess pain appropriately. The Critical Care Pain Observation Tool (CPOT) is the most reliable tool currently available to assess pain in these patients. We investigated whether the implementation of the CPOT in one Australian ICU could increase frequency of appropriate pain assessments, and if this would affect the administration of analgesia and sedation. Methods In this before and after study, we first performed a retrospective chart audit on 441 adult ICU patient charts, over 49 days. Data collected included frequency and type of pain assessments, sedation and analgesia administered, communication and CAM-ICU status, and bedside nurse-perceived pain. During the implementation phase, new policy and guideline documents were released, and ICU charts were redesigned to incorporate the CPOT. All nursing staff attended an education session on pain assessment and correct use of the CPOT. The chart audit was repeated, capturing 344 charts over 43 days. Results Mean total assessments in 24 hours increased from 7.2 to 7.9 for communicative, 3.0 to 8.9 for non-communicative, and 5.1 to 9.1 for transitioning patients. For non-communicative patients there was a significant increase in observational assessments including the CPOT (1.7 to 8.3), and a decrease in inappropriate use of self-report tools (1.3 to 0.2). We also observed significant increases in administration of paracetamol, opiates, propofol, patient-controlled analgesia, modified-release opiates, and neuropathic pain agents. Conclusions Implementation of the CPOT using standardised education and resources led to increased frequency of pain assessment, particularly for non-communicative patients. Appropriate observational assessments were also more frequently used for these patients. Analgesic administration generally increased, as did the use of propofol.

The EPO-TBI multi-national randomized controlled trial found that erythropoietin (EPO), when compared to placebo, did not affect 6-month neurological outcome, but reduced illness severity-adjusted mortality in patients with traumatic brain injury (TBI), making the cost-effectiveness of EPO in TBI uncertain. The current study uses patient-level data from the EPO-TBI trial to evaluate the cost-effectiveness of EPO in patients with moderate or severe TBI from the healthcare payers' perspective. We addressed the issue of transferability in multi-national trials by estimating costs and effects for specific geographical regions of the study (Australia/New Zealand, Europe, and Saudi Arabia). Unadjusted mean quality-adjusted life-years (QALYs; 95% confidence interval [CI]) at 6 months were 0.027 (0.020-0.034; p

Background There is a lack of knowledge about tasks intensive care unit liaison nurses (ICU LNs) perform during patient review, despite this role operating in at least 31 acute care hospitals in Australia. Objectives To evaluate the tasks that ICU LNs perform during patient review in the following referral subcategories: review after ICU discharge, rapid response team (RRT) review, and ward referral. Methods A 2-month prospective observational study using standardised case report forms to collect data on patients reviewed by ICU LNs in 20 Australian hospitals was conducted. Results From 3799 patients screened, 3542 were included, among whom 1933 (54.6%) were men, and the mean (standard deviation) age was 63 (19.4) years. The admitting units were surgical 1765 (49.8%) and medical 1696 (47.9%), and the breakdown of referral types were routine review after ICU discharge (1732; 47.9%), RRT review (1208; 34.1%), and ward referral (602; 17.0%). Patients subject to ward and RRT reviews were older, more likely to be medical admissions with less favourable vital signs on the initial review, and less likely to have repeat reviews. Of note, ward reviews were more likely to receive palliative care. Intensive care liaison nurse–initiated medication prescription and investigation ordering was uncommon. The most common interventions included consultation with medical staff, bedside education, adjusting oxygen flow and patient position, and directing the change in frequency of vital sign measurement. In-hospital mortality was lower in patients reviewed after ICU discharge (2.3%), compared with those after RRT review (2.8%) and ward referral (4.4%). Conclusions Most patients were reviewed after ICU discharge or in the context of the RRT. RRT and ward patients were less physiologically stable and more likely to die in hospital. The most common interventions performed by the ICU LN were nontechnical skills including clinical education, consultation with medical staff, and changes to vital sign frequency. Finally, the most common medication therapies administered related to intravenous therapy and electrolyte administration.

OBJECTIVES: To determine whether randomization of patients undergoing extracorporeal membrane oxygenation to either therapeutic or a low-dose anticoagulation protocol results in a difference in activated partial thromboplastin time and anti-Xa. DESIGN: Randomized, controlled, unblinded study. SETTING: Two ICUs of two university hospitals. PATIENTS: Patients admitted to the ICU, who required extracorporeal membrane oxygenation (venovenous or venoarterial) and who did not have a preexisting indication for therapeutic anticoagulation. INTERVENTIONS: Therapeutic anticoagulation with heparin (target activated partial thromboplastin time between 50 and 70 s) or lower dose heparin (up to 12,000 U/24 hr aiming for activated partial thromboplastin time < 45 s). MEASUREMENTS AND MAIN RESULTS: Thirty-two patients were randomized into two study groups that were not significantly different in demographics and extracorporeal membrane oxygenation characteristics. There was a significant difference in the daily geometric mean heparin dose (11,742 U [95% CI, 8,601-16,031 U] vs 20,710 U [95% CI, 15,343-27,954 U]; p = 0.004), daily geometric mean activated partial thromboplastin time (48.1 s [95% CI, 43.5-53.2 s] vs 55.5 s [95% CI, 50.4-61.2 s]; p = 0.04), and daily geometric mean anti-Xa (0.11 international units/mL [95% CI, 0.07-0.18] vs 0.27 [95% CI, 0.17-0.42]; p = 0.01). We found similar results when considering only venovenous extracorporeal membrane oxygenation episodes; however, no difference in daily geometric mean activated partial thromboplastin time between groups when considering only venoarterial extracorporeal membrane oxygenation episodes. CONCLUSIONS: Allocating patients on extracorporeal membrane oxygenation to two different anticoagulation protocols led to a significant difference in mean daily activated partial thromboplastin time and anti-Xa levels between groups. When considering subgroups analyses, these results were consistent in patients on venovenous extracorporeal membrane oxygenation. Our results support the feasibility of a larger trial in patients undergoing venovenous extracorporeal membrane oxygenation to compare different anticoagulation protocols; however, this study does not provide evidence on the optimal anticoagulation protocol for patients undergoing extracorporeal membrane oxygenation.

Individuals who report mostly heterosexual orientations (i.e., mostly sexually attracted to the opposite sex, but occasionally attracted to the same sex) outnumber all other non-heterosexual individuals combined. The present study examined whether mostly heterosexual men and women view same- and other-sex sexual stimuli differently than exclusively heterosexual men and women. A novel eye-tracking paradigm was used with 162 mostly and exclusively heterosexual men and women. Compared to exclusively heterosexual men, mostly heterosexual men demonstrated greater attention to sexually explicit features (i.e., genital regions and genital contact regions) of solo male and male-male erotic stimuli, while demonstrating equivalent attention to sexually explicit features of solo female and female-female erotic stimuli. Mediation analyses suggested that differences between mostly and exclusively heterosexual profiles in men could be explained by mostly heterosexual men's increased sexual attraction to solo male erotica, and their increased sexual attraction and reduced disgust to the male-male erotica. No comparable differences in attention were observed between mostly and exclusively heterosexual women-although mostly heterosexual women did demonstrate greater fixation on visual erotica overall-a pattern of response that was found to be mediated by reduced disgust.

Furries are individuals who are especially interested in anthropomorphic or cartoon animals (e.g., Bugs Bunny). They often strongly identify with anthropomorphic animals and create fursonas, identities of themselves as those anthropomorphic animals. Some practice fursuiting, or wearing costumes that resemble anthropomorphic animals. Furries have been portrayed as sexually motivated in the media and popular culture, although little empirical research has addressed this issue. If some furries are sexually motivated, they may be motivated by an erotic target identity inversion (ETII): sexual arousal by the fantasy of being the same kinds of individuals to whom they are sexually attracted. Furries with ETIIs would experience both sexual attraction to anthropomorphic animals and sexual arousal by fantasizing about being anthropomorphic animals, because they often change their appearance and behavior to become more like anthropomorphic animals. We surveyed 334 male furries recruited from the Internet about their sexual orientation, sexual motivation, and sexual interests. A large majority of our sample reported non-heterosexual identities (84%) and some degree of sexual motivation for being furries (99%). Male furries also tended to report a pattern of sexual interests consistent with an ETII involving anthropomorphic animals. Both sexual attraction to anthropomorphic animals and sexual arousal by fantasizing about being anthropomorphic animals were nearly universal. Furthermore, male furries tended to be sexually aroused by fantasizing about being the same kinds of anthropomorphic animals to whom they were sexually attracted, with respect to gender and species. This sexual motivation and these unusual sexual interests do not justify discrimination or stigmatization.

In less than nine months, the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) killed over a million people, including >25,000 in New York City (NYC) alone. The COVID-19 pandemic caused by SARS-CoV-2 highlights clinical needs to detect infection, track strain evolution, and identify biomarkers of disease course. To address these challenges, we designed a fast (30-minute) colorimetric test (LAMP) for SARS-CoV-2 infection from naso/oropharyngeal swabs and a large-scale shotgun metatranscriptomics platform (total-RNA-seq) for host, viral, and microbial profiling. We applied these methods to clinical specimens gathered from 669 patients in New York City during the first two months of the outbreak, yielding a broad molecular portrait of the emerging COVID-19 disease. We find significant enrichment of a NYC-distinctive clade of the virus (20C), as well as host responses in interferon, ACE, hematological, and olfaction pathways. In addition, we use 50,821 patient records to find that renin–angiotensin–aldosterone system inhibitors have a protective effect for severe COVID-19 outcomes, unlike similar drugs. Finally, spatial transcriptomic data from COVID-19 patient autopsy tissues reveal distinct ACE2 expression loci, with macrophage and neutrophil infiltration in the lungs. These findings can inform public health and may help develop and drive SARS-CoV-2 diagnostic, prevention, and treatment strategies.

Frailty is associated with poor outcomes in critical illness. However, it is unclear whether frailty screening on admission to the ICU can be conducted routinely at the population level and whether it has prognostic importance.Can population-scale frailty screening with the Clinical Frailty Scale (CFS) be implemented for critically ill adults in Australia and New Zealand (ANZ) and can it identify patients at risk of negative outcomes?We conducted a binational prospective cohort study of critically ill adult patients admitted between July 1, 2018, and June 30, 2020, in 175 ICUs in ANZ. We classified frailty with the CFS on admission to the ICU. The primary outcome was in-hospital mortality; secondary outcomes were length of stay (LOS), discharge destination, complications (delirium, pressure injury), and duration of survival.We included 234,568 critically ill patients; 45,245 (19%) were diagnosed as living with frailty before ICU admission. Patients with vs without frailty had higher in-hospital mortality (16% vs 5%; P .001), delirium (10% vs 4%; P .001), longer LOS in the ICU and hospital, and increased new chronic care discharge (3% vs 1%; P .001), with worse outcomes associated with increasing CFS category. Of patients with very severe frailty (CFS score, 8), 39% died in hospital vs 2% of very fit patients (CFS score, 1; multivariate categorical CFS score, 8 [reference, 1]; OR, 7.83 [95% CI, 6.39-9.59]; P .001). After adjustment for illness severity, frailty remained highly significantly predictive of mortality, including among patients younger than 50 years, with improvement in the area under the receiver operating characteristic curve of the Acute Physiology and Chronic Health Evaluation III-j score to 0.882 (95% CI, 0.879-0.885) from 0.868 (95% CI, 0.866-0.871) with the addition of frailty (P .001).Large-scale population screening for frailty degree in critical illness was possible and prognostically important, with greater frailty (especially CFS score of ≥ 6) associated with worse outcomes, including among younger patients.

Introduction: Acute kidney diseases and disorders (AKD) encompass acute kidney injury (AKI) and subacute or persistent alterations in kidney function that occur after an initiating event. Unlike AKI, accurate estimates of the incidence and prognosis of AKD are not available and its clinical significance is uncertain. Methods: We studied the epidemiology and long-term outcome of AKD (as defined by the KDIGO criteria), with or without AKI, in a retrospective cohort of adults hospitalized at a single centre for >24 h between 2012 and 2016 who had a baseline eGFR ≥60 mL/min/1.73 m2 and were alive at 30 days. In patients for whom follow-up data were available, the risks of major adverse kidney events (MAKEs), CKD, kidney failure, and death were examined by Cox and competing risk regression analyses. Results: Among 62,977 patients, 906 (1%) had AKD with AKI and 485 (1%) had AKD without AKI. Follow-up data were available for 36,118 patients. In this cohort, compared to no kidney disease, AKD with AKI was associated with a higher risk of MAKEs (40.25 per 100 person-years; hazard ratio [HR] 2.51, 95% confidence interval [CI] 2.16–2.91), CKD (27.84 per 100 person-years); subhazard ratio [SHR] 3.18, 95% CI 2.60–3.89), kidney failure (0.56 per 100 person-years; SHR 24.84, 95% CI 5.93–104.03), and death (14.86 per 100 person-years; HR 1.52, 95% CI 1.20–1.92). Patients who had AKD without AKI also had a higher risk of MAKEs (36.21 per 100 person-years; HR 2.26, 95% CI 1.89–2.70), CKD (22.94 per 100 person-years; SHR 2.69, 95% CI 2.11–3.43), kidney failure (0.28 per 100 person-years; SHR 12.63, 95% CI 1.48–107.64), and death (14.86 per 100 person-years; HR 1.57, 95% CI 1.19–2.07). MAKEs after AKD were driven by CKD, especially in the first 3 months. Conclusions: These findings establish the burden and poor prognosis of AKD and support prioritisation of clinical initiatives and research strategies to mitigate such risk.

Both Feinstein and Galupo (1) and Zivony (2) argue that skepticism about male bisexual orientation has long been beyond the scientific pale. As researchers who have studied this issue for two decades, we disagree. Regardless, scientific questions are settled by evidence rather than by votes among scientific experts (much less assertions about what such votes would reveal). We believe that Jabbour et al. (3) provide compelling evidence that men whose self-reported Kinsey scores indicate attraction to both sexes tend to have genital arousal patterns consistent with those reports. Both Zivony and … [↵][1]1Email: jm-bailey{at}northwestern.edu. [1]: #xref-corresp-1-1

Background Use of donation after circulatory death (DCD) hearts is becoming more prevalent in cardiac transplantation. However, there is no standardized approach to myocardial preservation, and little data exists on ultrastructural changes in DCD hearts. We have previously identified increased proapoptotic and proinflammatory activity in brain dead donor (BDD) hearts that subsequently exhibit primary graft failure and lower levels in DCD left atrial tissue. This study further investigates these markers and correlates them with cardiac function in DCD hearts. Methods This prospective study used donor hearts deemed unsuitable for transplant after gaining institutional ethics approval; 11 human hearts were obtained from 5 DCD donors and 6 BDDs. All hearts were preserved by continuous microperfusion for 4 hours with a cold crystalloid solution and then were evaluated on a blood perfusion bench rig. After 4 hours perfusion and working assessment, tissues from all cardiac chambers were stored for later messenger RNA (mRNA) analysis for proapoptotic and proinflammatory markers. Results Significantly raised levels of caspase-1, BNIP3, and NADPH oxidase mRNA expression were identified in cardiac chambers from BDD hearts compared to DCD hearts, and these differences were exaggerated in older donors. In the pooled analysis, lower expression of caspase-1, NF-κB1, and BNIP3 mRNA correlated with developed pressure at 1 hour after reperfusion in the right ventricle, but not the left. Conclusion Compared to BDD hearts, DCD hearts exhibit less stimulation of proapoptotic cascades and reactive oxygen species, potentially reducing their susceptibility to ischemic reperfusion injury.

Significance There has long been skepticism among both scientists and laypersons that male bisexual orientation exists. Skeptics have claimed that men who self-identify as bisexual are actually homosexual or heterosexual. (The existence of female bisexuality has been less controversial.) This controversy can be resolved using objective, genital responses of men to male and female erotic stimuli. We combined nearly all available data (from eight previous American, British, and Canadian studies) to form a dataset of more than 500 men, much larger than any previous individual study, and conducted rigorous statistical tests. Results provided compelling evidence that bisexual-identified men tend to show bisexual genital and subjective arousal patterns. Male sexual orientation is expressed on a continuum rather than dichotomously., The question whether some men have a bisexual orientation—that is, whether they are substantially sexually aroused and attracted to both sexes—has remained controversial among both scientists and laypersons. Skeptics believe that male sexual orientation can only be homosexual or heterosexual, and that bisexual identification reflects nonsexual concerns, such as a desire to deemphasize homosexuality. Although most bisexual-identified men report that they are attracted to both men and women, self-report data cannot refute these claims. Patterns of physiological (genital) arousal to male and female erotic stimuli can provide compelling evidence for male sexual orientation. (In contrast, most women provide similar physiological responses to male and female stimuli.) We investigated whether men who self-report bisexual feelings tend to produce bisexual arousal patterns. Prior studies of this issue have been small, used potentially invalid statistical tests, and produced inconsistent findings. We combined nearly all previously published data (from eight previous studies in the United States, United Kingdom, and Canada), yielding a sample of 474 to 588 men (depending on analysis). All participants were cisgender males. Highly robust results showed that bisexual-identified men’s genital and subjective arousal patterns were more bisexual than were those who identified as exclusively heterosexual or homosexual. These findings support the view that male sexual orientation contains a range, from heterosexuality, to bisexuality, to homosexuality.

Introduction Multiple rib fractures have been shown to reduce quality of life both in the short and long term. Treatment of rib fractures with operative fixation reduces ventilator requirements, intensive care unit stay, and pulmonary complications in flail chest patients but has not been shown to improve quality of life in comparative studies to date. We therefore wanted to analyse a large cohort of multiple fractured rib trauma patients to see if rib fixation improved their quality of life. Methods Retrospective review (January 2012 - April 2015) of prospectively collected data on 1482 consecutive major trauma patients admitted to The Alfred Hospital with rib fractures. The main outcome measures were Quality of Life over 24 months post injury assessed using the Glasgow Outcome Scale Extended (GOSErate) and Short Form (SF12) health assessment forms and a pain questionnaire. Results 67 (4.5%) patients underwent rib fixation and were older, with a higher incidence of flail chest injury, and higher AIS and ISS scores than the remainder of the cohort. Rib fixation provided no benefit in pain, SF-12 or GOSErate scores over 24 months post injury. Conclusions This study has not been able to demonstrate any quality of life benefit of rib fixation over 24 months post injury in patients with major trauma.

OBJECTIVES: To evaluate what proportion of unplanned ICU admissions from hospital wards occurred after rapid response team review and compare baseline characteristics and outcomes of patients admitted after rapid response team review with non-rapid response team-related admissions. DESIGN: Multicenter binational retrospective cohort study. SETTING: One-hundred seventy-eight ICUs across Australia and New Zealand. PATIENTS: All adults (≥ 17 yr) in the Australian and New Zealand Intensive Care Society Adult Patient Database between 2012 and 2017. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 97,181 unplanned ICU admissions from the ward, prior rapid response team review occurred in 55,084 cases (56.7%). Rapid response team patients were slightly older (65.4 [16.9] vs 63.3 [18]), had a higher Acute Physiology and Chronic Health Evaluation III score (64.6 [27.1] vs 54.7 [25.3]) and more frequently had limitations of medical treatment (13.1% vs 8.5%) compared with patients with no rapid response team review. The strongest independent associations with ICU admission following rapid response team review included age, ICU admission diagnosis (especially sepsis-, neurologic-, respiratory-, and cardiovascular-related), tertiary ICU status, and presence of limitations of medical treatment (p < 0.0001 all comparisons). Rapid response team-related ICU admissions had a longer median ICU (2.4 d [1.2-4.6 d] vs 2.1 d [1.0-4.2 d]) and hospital (12.8 d [7.0-23.6 d] vs 10.8 d [5.9-20.3 d]) length of stay, and were more likely to die in the ICU (12.3% vs 7.5%) and in-hospital (20.8% vs 13.5%) (p < 0.0001). After adjusting for illness severity and institution, patients admitted following rapid response team review stayed longer in hospital but were not at increased risk of dying in-hospital (adjusted odds ratio, 1.03; 0.98-1.07). CONCLUSIONS: In Australia and New Zealand, hospital ward patients admitted to ICU following rapid response team review represent the majority of ward-based ICU admissions, are more chronically and acutely ill, and more frequently have sepsis than those admitted from the ward without rapid response team review. Their unadjusted outcomes are worse, but after adjustment their mortality is similar.

Objectives: To compare the characteristics of adults admitted to the ICU in Australia and New Zealand after trauma with nonelective, nontrauma admissions. To describe trends in hospital mortality and rates of discharge home among these two groups. Design: Retrospective review (2005-2017) of the Australia and New Zealand Intensive Care Society's Center for Outcome and Resource Evaluation Adult Patient Database. Setting: Adult ICUs in Australia and New Zealand. Patients: Adult (≥17 yr), nonelective, ICU admissions. Intervention: Observational study. Measurements and Main Results: We compared 77,002 trauma with 741,829 nonelective, nontrauma patients. Trauma patients were younger (49.0 ± 21.6 vs 60.6 ± 18.7 yr; p < 0.0001), predominantly male (73.1% vs 53.9%; p < 0.0001), and more frequently treated in tertiary hospitals (74.7% vs 45.8%; p < 0.0001). The mean age of trauma patients increased over time but was virtually static for nonelective, nontrauma patients (0.72 ± 0.02 yr/yr vs 0.03 ± 0.01 yr/yr; p < 0.0001). Illness severity increased for trauma but fell for nonelective, nontrauma patients (mean Australia and New Zealand risk of death: 0.10% ± 0.02%/yr vs -0.21% ± 0.01%/yr; p < 0.0001). Trauma patients had a lower hospital mortality than nonelective, nontrauma patients (10.0% vs 15.8%; p < 0.0001). Both groups showed an annual decline in the illness severity adjusted odds ratio (odds ratio) of hospital mortality, but this was slower among trauma patients (trauma: odds ratio 0.976/yr [0.968-0.984/yr; p < 0.0001]; nonelective, nontrauma: odds ratio 0.957/yr [0.955-0.959/yr; p < 0.0001]; interaction p < 0.0001). Trauma patients had lower rates of discharge home than nonelective, nontrauma patients (56.7% vs 64.6%; p < 0.0001). There was an annual decline in illness severity adjusted odds ratio of discharge home among trauma patients, whereas nonelective, nontrauma patients displayed an annual increase (trauma: odds ratio 0.986/yr [0.981-0.990/yr; p < 0.0001]; nonelective, nontrauma: odds ratio 1.014/yr [1.012-1.016/yr; p < 0.0001]; interaction: p < 0.0001). Conclusions: The age and illness severity of adult ICU trauma patients in Australia and New Zealand has increased over time. Hospital mortality is lower for trauma than other nonelective ICU patients but has fallen more slowly. Trauma patients have become less likely to be discharged home than other nonelective ICU patients.

To evaluate knowledge translation after publication of the target temperature management 33°C versus 36°C after out-of-hospital cardiac arrest trial and associated patient outcomes. Our primary hypothesis was that target temperature management at 36°C was rapidly adopted in Australian and New Zealand ICUs. Secondary hypotheses were that temporal reductions in mortality would be seen and would have accelerated after publication of the target temperature management trial.Retrospective cohort study (January 2005 to December 2016).The Australian and New Zealand Intensive Care Society Centre for Outcome and Resource Evaluation adult patient database containing greater than 2 million admission episodes from 186 Australian and New Zealand ICUs.Sixteen-thousand two-hundred fifty-two adults from 140 hospitals admitted to ICU after out-of-hospital cardiac arrest.The primary exposure of interest was admission before versus after publication of the target temperature management trial.The primary outcome variable to evaluate changes in temperature management was lowest temperature in the first 24 hours in ICU. The primary clinical outcome variable of interest was inhospital mortality. Secondary outcomes included proportion of patients with fever in the first 24 hours in ICU. Mean ± SD lowest temperature in the first 24 hours in ICU in pre- and posttarget temperature management trial patients was 33.80 ± 1.71°C and 34.70 ± 1.39°C, respectively (absolute difference, 0.98°C [99% CI, 0.89-1.06°C]). Inhospital mortality rate decreased by 1.3 (99% CI, -1.8 to -0.9) percentage points per year from January 2005 until December 2013 and increased by 0.6 (99% CI, -1.4 to 2.6) percentage points per year from January 2014 until December 2016 (change in slope 1.9 percentage points per year [99% CI, -0.6 to 4.4]). Fever occurred in 568 (12.8%) of 4,450 pretarget temperature management trial patients and 853 (16.5%) of 5,184 posttarget temperature management trial patients (odds ratio, 1.35 [99% CI, 1.16-1.57]).The average lowest temperature of postcardiac arrest patients in the first 24 hours in ICU rose after publication of the target temperature management trial. This change was associated with an increased frequency of fever not seen in the target temperature management trial.

There are limited data on the characteristics, incidence, and mortality of patients with myasthenia gravis (MG) admitted to the ICU.To study the epidemiology, characteristics and outcome of patients with MG in Australian and New Zealand (ANZ) ICUs over a decade.We performed a retrospective observational, cross sectional study of data from the Australian and New Zealand Intensive Care Society (ANZICS) Adult Patient Database (APD). We collected data on all adult patients admitted with a primary diagnosis of MG to 159 Australian and 19 New Zealand ICUs between January 1, 2005 and December 31, 2015.We extracted detailed relevant data and performed statistical assessment.We identified 245 patients admitted to ICU with the primary diagnosis of MG, with an incidence increasing from 1 to 2.5 per thousand ICU admissions (P0.0001) and from 1 to 2.2 per million people (P=0.02). Mean age was 60years with more patients being female (53.7% vs 47.3%) and 91 (37.1%) patients received mechanical ventilation. Hospital mortality occurred in 13 (5.3%) patients with a mortality rate lower than in other ICU patients.In ANZ, the ICU and population incidence of MG has increased over the last decade. However, its mortality rate was low.

Background Intravenous fluids may contribute to lower haemoglobin levels in patients with septic shock. We sought to determine the relationship between the changes in haemoglobin concentration and the volume of intravenous fluids administered during resuscitation from septic shock. Methods We performed a retrospective cohort study of patients enrolled in the Australasian Resuscitation in Sepsis Evaluation (ARISE) trial who were not transfused red blood cells (N = 1275). We determined the relationship between haemoglobin concentration, its change over time and volume of intravenous fluids administered over 6, 24 and 72 h using univariate and multivariate analysis. Results Median (IQR) haemoglobin concentration at baseline was 133 (118–146) g/L and decreased to 115 (102–127) g/L within the first 6 h of resuscitation (P

To assess whether a national standard for improving care of deteriorating patients affected ICU admissions following cardiac arrests from hospital wards.Retrospective study assessing changes from baseline (January 1, 2008, to June 30, 2010), rollout (July 1, 2010, to December 31, 2012), and after (January 1, 2013, to 31 December 31, 2014) national standard introduction. Conventional inferential statistics, interrupted time series analysis, and adjusted hierarchical multiple logistic regression analysis.More than 110 ICU-equipped Australian hospitals.Adult patients (≥ 18 yr old) admitted to participating ICUs.Introducing a national framework to improve care of deteriorating patients including color-coded observation charts, mandatory rapid response system, enhanced governance, and staff education for managing deteriorating patients.Cardiac arrest-related ICU admissions from the ward decreased from 5.6% (baseline) to 4.9% (rollout) and 4.1% (intervention period). Interrupted time series analysis revealed a decline in the rate of cardiac arrest-related ICU admissions in the rollout period, compared with the baseline period (p = 0.0009) with a subsequent decrease in the rate in the intervention period (p = 0.01). Cardiac arrest-related ICU admissions were less likely in the intervention period compared with the baseline period (odds ratio, 0.85; 95% CI, 0.78-0.93; p = 0.001), as was in-hospital mortality from cardiac arrests (odds ratio, 0.79; 95% CI, 0.65-0.96; p = 0.02).Introducing a national standard to improve the care of deteriorating patients was associated with reduced cardiac arrest-related ICU admissions and subsequent in-hospital mortality of such patients.

Background Tracheostomy is a relatively common procedure in Intensive Care Unit (ICU) patients. Aims To study the patient characteristics, incidence, technique, outcomes and prediction of tracheostomy in the State of Victoria, Australia. Methods We used data from the Australian and New Zealand Intensive Care Society Adult Patient Database (ANZICS APD) and the Victorian Admitted Episode Dataset (VAED) to identify and match patients who had received a tracheostomy from 2004 to 2014. Results Between 1st January 2004 and 30th June 2014, 9750 patients received a tracheostomy with 7670 available for matching and 6010 (78.4%) successfully matched. Of the matched tracheostomy patients, median age was 61 years, median APACHE IIIJ score was 66 and overall hospital mortality was 21%. The incidence of tracheostomy almost halved over the decade with more than half of tracheostomies (53.5%) being percutaneous. Hospital mortality of patients receiving a tracheostomy decreased from 26.5% in 2004 to 16.5% in 2014 by an average decrease of 6%/year. No robust model could be developed to predict tracheostomy. Conclusion The incidence of tracheostomy and the adjusted mortality rate of patients who received a tracheostomy have significantly decreased over a decade. Day of admission information could not be used to predict subsequent tracheostomy.

ObjectivesThe onset of many illnesses is confounded with age and sex. Increasing age is a risk factor for the development of many illnesses, and sexual dimorphism influences brain anatomy, function, and cognition. Here, we examine frequency-specific connectivity in resting-state networks in a large sample (n = 406) of healthy aged adults.MethodWe quantify frequency-specific connectivity in three resting-state networks known to be implicated in age-related decline: the default mode, dorsal attention, and salience networks, using multiband functional magnetic resonance imaging. Frequency-specific connectivity was quantified in four bands: low (0.015–0.027 Hz), moderately low (0.027–0.073 Hz), moderately high (0.073–0.198 Hz), and high (0.198–0.5 Hz) frequency bands, using mean intensity and spatial extent. Differences in connectivity between the sexes in each of the three networks were examined.ResultsEach network showed the largest intensity and spatial extent at low frequencies and smallest extent at high frequencies. Males showed greater connectivity than females in the salience network. Females showed greater connectivity than males in the default mode network.DiscussionResults in this healthy aged cohort are compatible with those obtained in young samples, suggesting that frequency-specific connectivity, and differences between the sexes, are maintained into older age. Our results indicate that sex should be considered as an influencing factor in studies of resting-state connectivity.

Background In the critically ill, energy delivery from enteral nutrition (EN) is often less than the estimated energy requirement. Parenteral nutrition (PN) as a supplement to EN may increase energy delivery. We aimed to determine if an individually titrated supplemental PN strategy commenced 48–72 hours following ICU admission and continued for up to 7 days would increase energy delivery to critically ill adults compared to usual care EN delivery. Methods This study was a prospective, parallel group, phase II pilot trial conducted in six intensive care units in Australia and New Zealand. Mechanically ventilated adults with at least one organ failure and EN delivery below 80% of estimated energy requirement in the previous 24 hours received either a supplemental PN strategy (intervention group) or usual care EN delivery. EN in the usual care group could be supplemented with PN if EN remained insufficient after usual methods to optimise delivery were attempted. Results There were 100 patients included in the study and 99 analysed. Overall, 71% of the study population were male, with a mean (SD) age of 59 (17) years, Acute Physiology and Chronic Health Evaluation II score of 18.2 (6.7) and body mass index of 29.6 (5.8) kg/m2. Significantly greater energy (mean (SD) 1712 (511) calories vs. 1130 (601) calories, p

Family and twin studies suggest that genes play a role in male sexual orientation. We conducted a genome-wide association study (GWAS) of male sexual orientation on a primarily European ancestry sample of 1,077 homosexual men and 1,231 heterosexual men using Affymetrix single nucleotide polymorphism (SNP) arrays. We identified several SNPs with p −5, including regions of multiple supporting SNPs on chromosomes 13 (minimum p = 7.5 × 10−7) and 14 (p = 4.7 × 10−7). The genes nearest to these peaks have functions plausibly relevant to the development of sexual orientation. On chromosome 13, SLITRK6 is a neurodevelopmental gene mostly expressed in the diencephalon, which contains a region previously reported as differing in size in men by sexual orientation. On chromosome 14, TSHR genetic variants in intron 1 could conceivably help explain past findings relating familial atypical thyroid function and male homosexuality. Furthermore, skewed X chromosome inactivation has been found in the thyroid condition, Graves’ disease, as well as in mothers of homosexual men. On pericentromeric chromosome 8 within our previously reported linkage peak, we found support (p = 4.1 × 10−3) for a SNP association previously reported (rs77013977, p = 7.1 × 10−8), with the combined analysis yielding p = 6.7 × 10−9, i.e., a genome-wide significant association.

This pilot study aimed to characterise the haemodynamic effect of 1L of IV normal saline (NS) administered as a rapid versus slow infusion on cardiac output (CO), heart rate (HR), systemic blood pressures, and carotid blood flow in six healthy volunteers.Six healthy male volunteers aged 18-65years were randomized to receive 1L NS given over 30min or 120min. On a subsequent study session the alternate fluid regimen was administered. Haemodynamic data was gathered using a non-invasive finger arterial pressure monitor (Nexfin®), echocardiography and carotid duplex sonography. Time to micturition and urine volume was also assessed.Compared to baseline, rapid infusion of 1L of saline over 30min produced a fall in Nexfin®-measured CO by 0.62L/min (p0.001), whereas there was a marginal but significant increase during infusion of 1L NS over 120min of 0.02L/min (p0.001). This effect was mirrored by changes in HR and blood pressure (BP) (p0.001). There were no significant changes in carotid blood flow, time to micturition, or urine volume produced.Slower infusion of 1L NS in healthy male volunteers produced a greater increase in CO, HR and BP than rapid infusion.

Erythropoietin (EPO) may reduce mortality after traumatic brain injury (TBI). Secondary brain injury is exacerbated by multiple trauma, and possibly modifiable by EPO. We hypothesized that EPO decreases mortality more in TBI patients with multiple trauma, than in patients with TBI alone.A post hoc analysis of the EPO-TBI randomized controlled trial conducted in 2009 to 2014. To evaluate the impact of injuries outside the brain, we calculated an extracranial Injury Severity Score (ISS) that included the same components of the ISS, excluding head and face components. We defined multiple trauma as two injured body regions with an Abbreviated Injury Scale (AIS) score of 3 or higher. Cox regression analyses, allowing for potential differential responses per the presence or absence of extracranial injury defined by these injury scores, were used to assess the effect of EPO on time to mortality.Of 603 included patients, the median extracranial ISS was 6 (interquartile range, 1-13) and 258 (43%) had an AIS score of 3 or higher in at least two body regions. On Cox regression, EPO was associated with decreased mortality in patients with greater extracranial ISS (interaction p = 0.048) and weakly associated with differential mortality with multiple trauma (AIS score3 or in two regions, interaction p = 0.17). At 6 months in patients with extracranial ISS higher than 6, 10 (6.8%) of 147 EPO-treated patients compared with 26 (17%) of 154 placebo-treated patients died (risk reduction, 10%; 95% confidence interval, 2.9-17%; p = 0.007).In this post hoc analysis, EPO administration was associated with a potential differential improvement in 6-month mortality in TBI patients with more severe extracranial injury. These findings need confirmation in future clinical and experimental studies.Therapeutic study, level III.

BACKGROUND: After a single-center trial and observational studies suggesting that early, goal-directed therapy (EGDT) reduced mortality from septic shock, three multicenter trials (ProCESS, ARISE, and ProMISe) showed no benefit. This meta-analysis of individual patient data from the three recent trials was designed prospectively to improve statistical power and explore heterogeneity of treatment effect of EGDT. METHODS: We harmonized entry criteria, intervention protocols, outcomes, resource-use measures, and data collection across the trials and specified all analyses before unblinding. After completion of the trials, we pooled data, excluding the protocol-based standard-therapy group from the ProCESS trial, and resolved residual differences. The primary outcome was 90-day mortality. Secondary outcomes included 1-year survival, organ support, and hospitalization costs. We tested for treatment-by-subgroup interactions for 16 patient characteristics and 6 care-delivery characteristics. RESULTS: We studied 3723 patients at 138 hospitals in seven countries. Mortality at 90 days was similar for EGDT (462 of 1852 patients [24.9%]) and usual care (475 of 1871 patients [25.4%]); the adjusted odds ratio was 0.97 (95% confidence interval, 0.82 to 1.14; P=0.68). EGDT was associated with greater mean (±SD) use of intensive care (5.3±7.1 vs. 4.9±7.0 days, P=0.04) and cardiovascular support (1.9±3.7 vs. 1.6±2.9 days, P=0.01) than was usual care; other outcomes did not differ significantly, although average costs were higher with EGDT. Subgroup analyses showed no benefit from EGDT for patients with worse shock (higher serum lactate level, combined hypotension and hyperlactatemia, or higher predicted risk of death) or for hospitals with a lower propensity to use vasopressors or fluids during usual resuscitation. CONCLUSIONS: In this meta-analysis of individual patient data, EGDT did not result in better outcomes than usual care and was associated with higher hospitalization costs across a broad range of patient and hospital characteristics. (Funded by the National Institute of General Medical Sciences and others; PRISM ClinicalTrials.gov number, NCT02030158.)

Fibrinogen may be reduced following traumatic injury due to loss from haemorrhage, increased consumption and reduced synthesis. In the absence of clinical trials, guidelines for fibrinogen replacement are based on expert opinion and vary internationally. We aimed to determine prevalence and predictors of low fibrinogen on admission in major trauma patients and investigate association of fibrinogen levels with patient outcomes.Data on all major trauma patients (January 2007-July 2011) identified through a prospective statewide trauma registry in Victoria, Australia were linked with laboratory and transfusion data. Major trauma included any of the following: death after injury, injury severity score (ISS)15, admission to intensive care unit requiring mechanical ventilation, or urgent surgery for intrathoracic, intracranial, intra-abdominal procedures or fixation of pelvic or spinal fractures. Associations between initial fibrinogen level and in-hospital mortality were analysed using multiple logistic regression.Of 4773 patients identified, 114 (2.4%) had fibrinogen less than 1g/L, 283 (5.9%) 1.0-1.5g/L, 617 (12.9%) 1.6-1.9g/L, 3024 (63.4%) 2-4g/L and 735 (15%) 4g/L. Median fibrinogen was 2.6g/L (interquartile range 2.1-3.4). After adjusting for age, gender, ISS, injury type, pH, temperature, Glasgow Coma Score (GCS), initial international normalised ratio and platelet count, the lowest fibrinogen categories, compared with normal range, were associated with increased in-hospital mortality (adjusted odds ratio [OR] for less than 1g/L 3.28 [95% CI 1.71-6.28, p0.01], 1-1.5g/L adjusted OR 2.08 [95% CI 1.36-3.16, p0.01] and 1.6-1.9g/L adjusted OR 1.39 [95% CI 0.97-2.00, p=0.08]). Predictors of initial fibrinogen1.5g/L were younger age, lower GCS, systolic blood pressure90mmHg, chest decompression, penetrating injury, ISS25 and lower pH and temperature.Initial fibrinogen levels less than the normal range are independently associated with higher in-hospital mortality in major trauma patients. Future studies are warranted to investigate whether earlier and/or greater fibrinogen replacement improves clinical outcomes.

INTRODUCTION: A study was conducted to describe the sedation practices of intensive care units (ICUs) in Singapore in terms of drug use, sedation depth and the incidence of delirium in both early (< 48 hours) and late (> 48 hours) periods of ICU admission. METHODS: A prospective multicentre cohort study was conducted on patients who were expected to be sedated and ventilated for over 24 hours in seven ICUs (surgical ICU, n = 4; medical ICU, n = 3) of four major public hospitals in Singapore. Patients were followed up to 28 days or until ICU discharge, with four-hourly sedation monitoring and daily delirium assessment by trained nurses. The Richmond Agitation and Sedation Scale (RASS) and Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) were used. RESULTS: We enrolled 198 patients over a five-month period. The mean Acute Physiology and Chronic Health Evaluation (APACHE) II score was 25.3 ± 9.2, and 90.9% were emergency hospital admissions. Patients were followed up for 1,417 ICU patient days, of which 396 days were in the early period and 1,021 days were in the late period. 7,354 RASS assessments were performed. Propofol and fentanyl were the sedative agents of choice in the early and late periods, respectively. Patients were mostly in the light sedation range, especially in the late period. At least one episode of delirium was seen in 23.7% of patients. CONCLUSION: Sedation practices in Singapore ICUs are characterised by light sedation depth and low incidence of delirium, possibly due to the drugs used.

The optimal osmotic agent to treat intracranial hypertension in patients with severe traumatic brain injury (TBI) remains uncertain. We aimed to test whether the choice of mannitol or hypertonic saline (HTS) as early (first 96 h) osmotherapy in these patients might be associated with a difference in mortality. We retrospectively analyzed data from 2015 from 14 tertiary intensive care units (ICUs) in Australia, UK, and Europe treating severe TBI patients with intracranial pressure (ICP) monitoring and compared mortality in those who received mannitol only versus HTS only. We performed multi-variable analysis adjusting for site and illness severity (Injury Severity Score, extended IMPACT score, and mean ICP over the first 96 h) using Cox proportional hazards regression. We collected data on 262 patients and compared patients who received early osmotherapy with mannitol alone (n = 46) with those who received HTS alone (n = 46). Mannitol patients were older (median age, 49.2 (19.2) vs. 40.5 (16.8) years; p = 0.02), with higher Injury Severity Scores (42 (15.9) vs. 32.1 [11.3]; p = 0.001), and IMPACT-TBI predicted 6-month mortality (34.5% [23-46] vs. 25% [13-38]; p = 0.02), but had similar APACHE-II scores, and mean and maximum ICPs over the first 96 h. The unadjusted hazard ratio for in-hospital mortality in patients receiving only mannitol was 3.35 (95% confidence interval [CI], 1.60-7.03; p = 0.001). After adjustment for key mortality predictors, the hazard ratio for in-hospital mortality in patients receiving only mannitol was 2.64 (95% CI, 0.96-7.30; p = 0.06). The choice of early osmotherapy in severe TBI patients may affect survival, or simply reflect clinician beliefs about their different roles, and warrants controlled investigation.

Background Hospital-acquired acute kidney injury (AKI) in humans and dogs increases morbidity and nonsurvival. Azotemia at presentation has been associated with a poor outcome in horses; however, prevalence and consequences of hospital-acquired AKI are unreported. Hypothesis/objectives To evaluate the prevalence of AKI in hospitalized horses, risk factors associated with AKI, and the effect of AKI on short-term survival. We hypothesized that the prevalence of AKI in horses is similar to that reported in other domestic mammalian species and would be associated with nonsurvival. Animals Adult horses hospitalized for >2 days from which a minimum of 2 measurements of serum creatinine concentration were available. Methods Retrospective cohort study. Clinical records were reviewed and horses grouped according to their baseline serum creatinine concentration and change in serum creatinine concentration from baseline. The associations between signalment, diagnosis, and treatment variables, and the presence of azotemia or AKI were assessed using multinomial logistic regression. The relationship between these conditions and survival to discharge was evaluated. Results Three hundred twenty-five horses were included; 4.3% (14/325) had azotemia at baseline and 14.8% (48/325) developed AKI. There were no significant associations between investigated risk factors and development of AKI. The presence of azotemia and AKI did not significantly affect survival to discharge (P = .08 and .81, respectively). Conclusions and clinical importance The prevalence of AKI in this population of hospitalized horses is similar to that reported in dogs and humans; however, in this study population, there was less impact on morbidity and short-term survival.

It is unknown whether protocols targeting systematic prevention and treatment of fever achieve lower mean body temperature than usual care in intensive care unit (ICU) patients. The objective of the Randomised Evaluation of Active Control of temperature vs. ORdinary temperature management trial was to confirm the feasibility of such a protocol with a view to conducting a larger trial. We randomly assigned 184 adults without acute brain pathologies who had a fever in the previous 12 h, and were expected to be ventilated beyond the calendar day after recruitment, to systematic prevention and treatment of fever or usual care. The primary outcome was mean body temperature in the ICU within 7 days of randomisation. Secondary outcomes included in-hospital mortality, ICU-free days and survival time censored at hospital discharge. Compared with usual temperature management, active management significantly reduced mean temperature. In both groups, fever generally abated within 72 h. The mean temperature difference between groups was greatest in the first 48 h, when it was generally in the order of 0.5 °C. Overall, 23 of 89 patients assigned to active management (25.8%) and 23 of 89 patients assigned to usual management (25.8%) died in hospital (odds ratio 1.0, 95% CI 0.51–1.96, P = 1.0). There were no statistically significant differences between groups in ICU-free days or survival to day 90. Active temperature management reduced body temperature compared with usual care; however, fever abated rapidly, even in patients assigned to usual care, and the magnitude of temperature separation was small. Australian and New Zealand Clinical Trials Registry Number, ACTRN12616001285448

BACKGROUND: Traumatic brain injury (TBI) and subarachnoid hemorrhage (SAH) are the most common causes of severe acute brain injury in younger Intensive Care Unit (ICU) patients. Dysglycemia (abnormal peak glycemia, glycemic variability, mean glycemia, nadir glycemia) is common in these patients but its comparative outcome associations are unclear. METHODS: In a retrospective, cross-sectional, study of adults admitted to Australian and New Zealand ICUs with TBI and SAH from 2005 to 2015, we studied the relationship between multiple aspects of early (first 24 hours) dysglycemia and mortality and compared TBI and SAH patients with the general ICU population and with each other. RESULTS: Among 670,301 patients, 11,812 had TBI and 6,098 had SAH. After adjustment for illness severity, we found that the mortality rate increased with each quintile of glycemia for each aspect of early dysglycemia (peak glycemia, glycemic variability, mean glycemia, nadir glycemia; P

Background The HeartMate III (HM3) left ventricular assist device (LVAD) is the most recent LVAD to receive CE Mark and the Food and Drug Administration approval. It is a fully magnetically levitated pump with no reported haemolysis, pump thrombosis or pump failure in the first in-man study (a previous stody). It has now received market approval in the European Union, United States of America, and Australia. We reviewed our real-life experience with the device, to assess outcomes over the medium term. Methods We conducted a retrospective review of prospectively collected data for 33 consecutive patients implanted with a HM3 LVAD between November 2014 and October 2018 at The Alfred Hospital, Melbourne, Australia. Results Of the 33 patients, 31 remained alive at the census date, with only two early deaths and 11 patients transplanted. There were no pump thromboses, but there were three cases of clot ingestion (two on the right and one on the left). Seven patients required permanent biventricular assist device support. The duration of HM3 support at the time of census was a median of 196 (interquartile range, 118-386) days. Conclusion This series demonstrates excellent results of the HM3 LVAD in an uncensored, real-life, consecutive group of patients in a single institution.