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In a randomized trial involving 4000 patients in the ICU who required sedation for mechanical ventilation, dexmedetomidine had no benefit on 90-day mortality as compared with usual care and was associated with more adverse events. Additional drugs were required for prescribed sedation levels in the two groups.

Whether prehospital administration of tranexamic acid increases the likelihood of survival with a favorable functional outcome among patients with major trauma and suspected trauma-induced coagulopathy who are being treated in advanced trauma systems is uncertain. We randomly assigned adults with major trauma who were at risk for trauma-induced coagulopathy to receive tranexamic acid (administered intravenously as a bolus dose of 1 g before hospital admission, followed by a 1-g infusion over a period of 8 hours after arrival at the hospital) or matched placebo. The primary outcome was survival with a favorable functional outcome at 6 months after injury, as assessed with the use of the Glasgow Outcome Scale-Extended (GOS-E). Levels on the GOS-E range from 1 (death) to 8 (\"upper good recovery\" [no injury-related problems]). We defined survival with a favorable functional outcome as a GOS-E level of 5 (\"lower moderate disability\") or higher. Secondary outcomes included death from any cause within 28 days and within 6 months after injury. A total of 1310 patients were recruited by 15 emergency medical services in Australia, New Zealand, and Germany. Of these patients, 661 were assigned to receive tranexamic acid, and 646 were assigned to receive placebo; the trial-group assignment was unknown for 3 patients. Survival with a favorable functional outcome at 6 months occurred in 307 of 572 patients (53.7%) in the tranexamic acid group and in 299 of 559 (53.5%) in the placebo group (risk ratio, 1.00; 95% confidence interval [CI], 0.90 to 1.12; P = 0.95). At 28 days after injury, 113 of 653 patients (17.3%) in the tranexamic acid group and 139 of 637 (21.8%) in the placebo group had died (risk ratio, 0.79; 95% CI, 0.63 to 0.99). By 6 months, 123 of 648 patients (19.0%) in the tranexamic acid group and 144 of 629 (22.9%) in the placebo group had died (risk ratio, 0.83; 95% CI, 0.67 to 1.03). The number of serious adverse events, including vascular occlusive events, did not differ meaningfully between the groups. Among adults with major trauma and suspected trauma-induced coagulopathy who were being treated in advanced trauma systems, prehospital administration of tranexamic acid followed by an infusion over 8 hours did not result in a greater number of patients surviving with a favorable functional outcome at 6 months than placebo. (Funded by the Australian National Health and Medical Research Council and others; PATCH-Trauma ClinicalTrials.gov number, NCT02187120.).

In a study of fluid resuscitation, patients received 6% hydroxyethyl starch (HES; 130/0.4) or saline until ICU discharge or death or for 90 days. There was no significant difference in 90-day mortality, although more patients in the HES group received renal-replacement therapy. The administration of intravenous fluids to increase intravascular volume is a frequent intervention in the intensive care unit (ICU), but the choice of resuscitation fluid remains controversial. 1 , 2 Globally, 0.9% sodium chloride (saline) is the most commonly used fluid, although colloids are administered as often as crystalloids, and hydroxyethyl starch (HES) is the most frequently used colloid. 3 Several studies have questioned the safety of HES in critically ill patients, with particular concern that its use increases the risk of acute kidney injury. 4 , 5 Most concern has focused on the use of concentrated HES solutions (10%) with a molecular weight of . . .

Choice and intensity of early (first 48 h) sedation may affect short- and long-term outcome. To investigate the relationships between early sedation and time to extubation, delirium, and hospital and 180-day mortality among ventilated critically ill patients in the intensive care unit (ICU). Multicenter (25 Australia and New Zealand hospitals) prospective longitudinal (ICU admission to 28 d) cohort study of medical/surgical patients ventilated and sedated 24 hours or more. We assessed administration of sedative agents, ventilation time, sedation depth using Richmond Agitation Sedation Scale (RASS, four hourly), delirium (daily), and hospital and 180-day mortality. We used multivariable Cox regression to quantify relationships between early deep sedation (RASS, -3 to -5) and patients' outcomes. We studied 251 patients (mean age, 61.7 ± 15.9 yr; mean Acute Physiology and Chronic Health Evaluation [APACHE] II score, 20.8 ± 7.8), with 21.1% (53) hospital and 25.8% (64) 180-day mortality. Over 2,678 study days, we completed 14,736 RASS assessments. Deep sedation occurred in 191 (76.1%) patients within 4 hours of commencing ventilation and in 171 (68%) patients at 48 hours. Delirium occurred in 111 (50.7%) patients with median (interquartile range) duration of 2 (1-4) days. After adjusting for diagnosis, age, sex, APACHE II, operative, elective, hospital type, early use of vasopressors, and dialysis, early deep sedation was an independent predictor of time to extubation (hazard ratio [HR], 0.90; 95% confidence interval [CI], 0.87-0.94; P < 0.001), hospital death (HR, 1.11; 95% CI, 1.02-1.20; P = 0.01), and 180-day mortality (HR, 1.08; 95% CI, 1.01-1.16; P = 0.026) but not delirium occurring after 48 hours (P = 0.19). Early sedation depth independently predicts delayed extubation and increased mortality, making it a potential target for interventional studies.

In a large, blinded, randomized trial involving critically ill adults, no significant difference in 90-day mortality was noted between those who received red cells stored for a mean of 11.8 days and those who received red cells stored for a mean of 22.4 days.

Purpose To quantify potential heterogeneity of treatment effect (HTE), of early sedation with dexmedetomidine (DEX) compared with usual care, and identify patients who have a high probability of lower or higher 90-day mortality according to age, and other identified clusters. Methods Bayesian analysis of 3904 critically ill adult patients expected to receive invasive ventilation > 24 h and enrolled in a multinational randomized controlled trial comparing early DEX with usual care sedation. Results HTE was assessed according to age and clusters (based on 12 baseline characteristics) using a Bayesian hierarchical models. DEX was associated with lower 90-day mortality compared to usual care in patients > 65 years (odds ratio [OR], 0.83 [95% credible interval [CrI] 0.68–1.00], with 97.7% probability of reduced mortality across broad categories of illness severity. Conversely, the probability of increased mortality in patients ≤ 65 years was 98.5% (OR 1.26 [95% CrI 1.02–1.56]. Two clusters were identified: cluster 1 (976 patients) mostly operative, and cluster 2 (2346 patients), predominantly non-operative. There was a greater probability of benefit with DEX in cluster 1 (OR 0.86 [95% CrI 0.65–1.14]) across broad categories of age, with 86.4% probability that DEX is more beneficial in cluster 1 than cluster 2. Conclusion In critically ill mechanically ventilated patients, early sedation with dexmedetomidine exhibited a high probability of reduced 90-day mortality in older patients regardless of operative or non-operative cluster status. Conversely, a high probability of increased 90-day mortality was observed in younger patients of non-operative status. Further studies are needed to confirm these findings.

Delayed graft function (DGF) is a major adverse complication of deceased donor kidney transplantation. Intravenous fluids are routinely given to patients receiving a transplant to maintain intravascular volume and optimise graft function. Saline (0·9% sodium chloride) is widely used but might increase the risk of DGF due to its high chloride content. We aimed to test our hypothesis that using a balanced low-chloride crystalloid solution (Plasma-Lyte 148) instead of saline would reduce the incidence of DGF. BEST-Fluids was a pragmatic, registry-embedded, multicentre, double-blind, randomised, controlled trial at 16 hospitals in Australia and New Zealand. Adults and children of any age receiving a deceased donor kidney transplant were eligible; those receiving a multi-organ transplant or weighing less than 20 kg were excluded. Participants were randomly assigned (1:1) using an adaptive minimisation algorithm to intravenous balanced crystalloid solution (Plasma-Lyte 148) or saline during surgery and up until 48 h after transplantation. Trial fluids were supplied in identical bags and clinicians determined the fluid volume, rate, and time of discontinuation. The primary outcome was DGF, defined as receiving dialysis within 7 days after transplantation. All participants who consented and received a transplant were included in the intention-to-treat analysis of the primary outcome. Safety was analysed in all randomly assigned eligible participants who commenced surgery and received trial fluids, whether or not they received a transplant. This study is registered with Australian New Zealand Clinical Trials Registry, (ACTRN12617000358347), and ClinicalTrials.gov (NCT03829488). Between Jan 26, 2018, and Aug 10, 2020, 808 participants were randomly assigned to balanced crystalloid (n=404) or saline (n=404) and received a transplant (512 [63%] were male and 296 [37%] were female). One participant in the saline group withdrew before 7 days and was excluded, leaving 404 participants in the balanced crystalloid group and 403 in the saline group that were included in the primary analysis. DGF occurred in 121 (30%) of 404 participants in the balanced crystalloid group versus 160 (40%) of 403 in the saline group (adjusted relative risk 0·74 [95% CI 0·66 to 0·84; p<0·0001]; adjusted risk difference 10·1% [95% CI 3·5 to 16·6]). In the safety analysis, numbers of investigator-reported serious adverse events were similar in both groups, being reported in three (<1%) of 406 participants in the balanced crystalloid group versus five (1%) of 409 participants in the saline group (adjusted risk difference –0·5%, 95% CI –1·8 to 0·9; p=0·48). Among patients receiving a deceased donor kidney transplant, intravenous fluid therapy with balanced crystalloid solution reduced the incidence of DGF compared with saline. Balanced crystalloid solution should be the standard-of-care intravenous fluid used in deceased donor kidney transplantation. Medical Research Future Fund and National Health and Medical Research Council (Australia), Health Research Council (New Zealand), Royal Australasian College of Physicians, and Baxter.

Erythropoietin might have neurocytoprotective effects. In this trial, we studied its effect on neurological recovery, mortality, and venous thrombotic events in patients with traumatic brain injury. Erythropoietin in Traumatic Brain Injury (EPO-TBI) was a double-blind, placebo-controlled trial undertaken in 29 centres (all university-affiliated teaching hospitals) in seven countries (Australia, New Zealand, France, Germany, Finland, Ireland, and Saudi Arabia). Within 24 h of brain injury, 606 patients were randomly assigned by a concealed web-based computer-generated randomisation schedule to erythropoietin (40 000 units subcutaneously) or placebo (0·9% sodium chloride subcutaneously) once per week for a maximum of three doses. Randomisation was stratified by severity of traumatic brain injury (moderate vs severe) and participating site. With the exception of designated site pharmacists, the site dosing nurses at all sites, and the pharmacists at the central pharmacy in France, all study personnel, patients, and patients' relatives were masked to treatment assignment. The primary outcome, assessed at 6 months by modified intention-to-treat analysis, was improvement in the patients' neurological status, summarised as a reduction in the proportion of patients with an Extended Glasgow Outcome Scale (GOS-E) of 1–4 (death, vegetative state, and severe disability). Two equally spaced preplanned interim analyses were done (after 202 and 404 participants were enrolled). This study is registered with ClinicalTrials.gov, number NCT00987454. Between May 3, 2010, and Nov 1, 2014, 606 patients were enrolled and randomly assigned to erythropoietin (n=308) or placebo (n=298). Ten of these patients (six in the erythropoietin group and four in the placebo group) were lost to follow up at 6 months; therefore, data for the primary outcome analysis was available for 596 patients (302 in the erythropoietin group and 294 in the placebo group). Compared with placebo, erythropoietin did not reduce the proportion of patients with a GOS-E level of 1–4 (134 [44%] of 302 patients in the erythropoietin group vs 132 [45%] of 294 in the placebo group; relative risk [RR] 0·99 [95% CI 0·83–1·18], p=0·90). In terms of safety, erythropoietin did not significantly affect 6-month mortality versus placebo (32 [11%] of 305 patients had died at 6 months in the erythropoietin group vs 46 [16%] of 297 [16%] in the placebo group; RR 0·68 [95% CI 0·44–1·03], p=0·07) or increase the occurrence of deep venous thrombosis of the lower limbs (48 [16%] of 305 vs 54 [18%] of 298; RR 0·87 [95% CI 0·61–1·24], p=0·44). Following moderate or severe traumatic brain injury, erythropoietin did not reduce the number of patients with severe neurological dysfunction (GOS-E level 1–4) or increase the incidence of deep venous thrombosis of the lower limbs. The effect of erythropoietin on mortality remains uncertain. The National Health and Medical Research Council and the Transport Accident Commission.

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/m 2 . Significantly greater energy (mean (SD) 1712 (511) calories vs. 1130 (601) calories, p  < 0.0001) and proportion of estimated energy requirement (mean (SD) 83 (25) % vs. 53 (29) %, p  < 0.0001) from EN and/or PN was delivered to the intervention group compared to usual care. Delivery of protein and proportion of estimated protein requirements were also greater in the intervention group (mean (SD) 86 (25) g, 86 (23) %) compared to usual care (mean (SD) 53 (29) g, 51 (25) %, p  < 0.0001). Antibiotic use, ICU and hospital length of stay, mortality and functional outcomes were similar between the two groups. Conclusions This individually titrated supplemental PN strategy applied over 7 days significantly increased energy delivery when compared to usual care delivery. Clinical and functional outcomes were similar between the two patient groups. Trial registration Clinical Trial registry details: NCT01847534 (First registered 22 April 2013, last updated 31 July 2016)

Respiratory syncytial virus (RSV) is increasingly recognized as an important cause of illness in adults; however, data on RSV disease and economic burden in this age group remain limited. We aimed to provide comprehensive estimates of RSV disease burden among adults aged ≥18 years. During 2012-2015, population-based, active surveillance of acute respiratory infection (ARI) hospitalizations enabled estimation of the seasonal incidence of RSV hospitalizations and direct health costs in adults aged ≥18 years in Auckland, New Zealand. Of 4,600 ARI hospitalizations tested for RSV, 348 (7.6%) were RSV positive. The median (interquartile range) length of hospital stay for RSV positive patients was 4 (2-6) days. The seasonal incidence rate (IR) of RSV hospitalizations, corrected for non-testing, was 23.6 (95% confidence intervals [CI] 21.0-26.1) per 100,000 adults aged ≥18 years. Hospitalization risk increased with age with the highest incidence among adults aged ≥80 years (IR 190.8 per 100,000, 95% CI 137.6-244.0). Being of Māori or Pacific ethnicity or living in a neighborhood with low socioeconomic status (SES) were independently associated with increased RSV hospitalization rates. We estimate RSV-associated hospitalizations among adults aged ≥18 years to cost on average NZD $4,758 per event. RSV infection is associated with considerable disease and economic cost in adults. RSV disproportionally affects adult sub-groups defined by age, ethnicity, and neighborhood SES. An effective RSV vaccine or RSV treatment may offer benefits for older adults.