Trial of early, goal-directed resuscitation for septic shock.

BACKGROUND: Early, goal-directed therapy (EGDT) is recommended in international guidelines for the resuscitation of patients presenting with early septic shock. However, adoption has been limited, and uncertainty about its effectiveness remains. METHODS: We conducted a pragmatic randomized trial with an integrated cost-effectiveness analysis in 56 hospitals in England. Patients were randomly assigned to receive either EGDT (a 6-hour resuscitation protocol) or usual care. The primary clinical outcome was all-cause mortality at 90 days. RESULTS: We enrolled 1260 patients, with 630 assigned to EGDT and 630 to usual care. By 90 days, 184 of 623 patients (29.5%) in the EGDT group and 181 of 620 patients (29.2%) in the usual-care group had died (relative risk in the EGDT group, 1.01; 95% confidence interval [CI], 0.85 to 1.20; P=0.90), for an absolute risk reduction in the EGDT group of -0.3 percentage points (95% CI, -5.4 to 4.7). Increased treatment intensity in the EGDT group was indicated by increased use of intravenous fluids, vasoactive drugs, and red-cell transfusions and reflected by significantly worse organ-failure scores, more days receiving advanced cardiovascular support, and longer stays in the intensive care unit. There were no significant differences in any other secondary outcomes, including health-related quality of life, or in rates of serious adverse events. On average, EGDT increased costs, and the probability that it was cost-effective was below 20%. CONCLUSIONS: In patients with septic shock who were identified early and received intravenous antibiotics and adequate fluid resuscitation, hemodynamic management according to a strict EGDT protocol did not lead to an improvement in outcome. (Funded by the United Kingdom National Institute for Health Research Health Technology Assessment Programme; ProMISe Current Controlled Trials number, ISRCTN36307479.)

Protocolised Management In Sepsis (ProMISe): a multicentre randomised controlled trial of the clinical effectiveness and cost-effectiveness of early, goal-directed, protocolised resuscitation for emerging septic shock.

BACKGROUND: Early goal-directed therapy (EGDT) is recommended in international guidance for the resuscitation of patients presenting with early septic shock. However, adoption has been limited and uncertainty remains over its clinical effectiveness and cost-effectiveness. OBJECTIVES: The primary objective was to estimate the effect of EGDT compared with usual resuscitation on mortality at 90 days following randomisation and on incremental cost-effectiveness at 1 year. The secondary objectives were to compare EGDT with usual resuscitation for requirement for, and duration of, critical care unit organ support; length of stay in the emergency department (ED), critical care unit and acute hospital; health-related quality of life, resource use and costs at 90 days and at 1 year; all-cause mortality at 28 days, at acute hospital discharge and at 1 year; and estimated lifetime incremental cost-effectiveness. DESIGN: A pragmatic, open, multicentre, parallel-group randomised controlled trial with an integrated economic evaluation. SETTING: Fifty-six NHS hospitals in England. PARTICIPANTS: A total of 1260 patients who presented at EDs with septic shock. INTERVENTIONS: EGDT (n = 630) or usual resuscitation (n = 630). Patients were randomly allocated 1 : 1. MAIN OUTCOME MEASURES: All-cause mortality at 90 days after randomisation and incremental net benefit (at £20,000 per quality-adjusted life-year) at 1 year. RESULTS: Following withdrawals, data on 1243 (EGDT, n = 623; usual resuscitation, n = 620) patients were included in the analysis. By 90 days, 184 (29.5%) in the EGDT and 181 (29.2%) patients in the usual-resuscitation group had died [p = 0.90; absolute risk reduction -0.3%, 95% confidence interval (CI) -5.4 to 4.7; relative risk 1.01, 95% CI 0.85 to 1.20]. Treatment intensity was greater for the EGDT group, indicated by the increased use of intravenous fluids, vasoactive drugs and red blood cell transfusions. Increased treatment intensity was reflected by significantly higher Sequential Organ Failure Assessment scores and more advanced cardiovascular support days in critical care for the EGDT group. At 1 year, the incremental net benefit for EGDT versus usual resuscitation was negative at -£725 (95% CI -£3000 to £1550). The probability that EGDT was more cost-effective than usual resuscitation was below 30%. There were no significant differences in any other secondary outcomes, including health-related quality of life, or adverse events. LIMITATIONS: Recruitment was lower at weekends and out of hours. The intervention could not be blinded. CONCLUSIONS: There was no significant difference in all-cause mortality at 90 days for EGDT compared with usual resuscitation among adults identified with early septic shock presenting to EDs in England. On average, costs were higher in the EGDT group than in the usual-resuscitation group while quality-adjusted life-years were similar in both groups; the probability that it is cost-effective is < 30%. FUTURE WORK: The ProMISe (Protocolised Management In Sepsis) trial completes the planned trio of evaluations of EGDT across the USA, Australasia and England; all have indicated that EGDT is not superior to usual resuscitation. Recognising that each of the three individual, large trials has limited power for evaluating potentially important subgroups, the harmonised approach adopted provides the opportunity to conduct an individual patient data meta-analysis, enhancing both knowledge and generalisability. TRIAL REGISTRATION: Current Controlled Trials ISRCTN36307479. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 19, No. 97. See the NIHR Journals Library website for further project information

Temperature induced changes in physiological traits and expression of selected candidate genes in black tiger shrimp (Penaeus monodon) larvae

Temperature is an important abiotic factor influencing growth, development, metabolic performance and sex determination of aquatic organisms. The present study was conducted to test the effect of six different temperature levels (24℃, 26℃, 28℃ as control, 30℃, 32℃ and 34℃) on the physiological (growth, developmental durations, survivability, sex ratios and O2 consumption) and genetic (changes in expression pattern of seven candidate genes: three male sex determining genes, three female sex determining genes and a single thermal stress response gene) aspects of black tiger shrimp (Penaeus monodon) larvae. Temperature treatments significantly altered the growth performance of shrimp individuals (P P. monodon individuals; significantly higher (P P. monodon that in turn can help to improve aquaculture production

Suitability of different fish species for cultivation in integrated floating cage aquageoponics system (IFCAS) in Bangladesh

Farmer participatory action research was performed to assess production performance of tilapia (Oreochromis niloticus) and Vietnamese perch (Anabas testudineus) in monoculture and polyculture systems via integrated floating cage aquageoponics system in Bangladesh. The term aquageoponics is the combination of aqua, geo and ponics which mean pond water, pond mud/soil and cultivation, respectively (Haque et al., 2015). Three treatments, namely T1 (tilapia), T2 (Vietnamese perch) and T3 (tilapia and Vietnamese perch = 1:1) in moderately shaded ponds (MSP) and 3 treatments, namely T4 (tilapia), T5 (Vietnamese perch) and T6 (tilapia and Vietnamese perch = 1:1), in heavily shaded ponds (HSP) were used each with 3 replicates and fish were stocked at a rate of 56 m−2 per cage. Fish were fed floating feed twice daily and significantly higher (P  0.05) between treatments. While higher (P > 0.05) specific growth rate was observed in monoculture compared with polyculture for tilapia; no significantly difference was observed for Vietnamese perch. There was also no significant difference (P > 0.05) in growth performance for Vietnamese perch between the MSP and HSP treatments. While females participated more actively in action research in the HSP condition with production of vegetables and fish in IFCAS; vegetables production were not different (P > 0.05) among treatments. The benefit-cost ratio of different treatments was >1, indicating that investment was financially efficient for all treatments

Additional file 3: Figure S3. of Atopic Dermatitis Anti-IgE Paediatric Trial (ADAPT): the role of anti-IgE in severe paediatric eczema: study protocol for a randomised controlled trial

Gantt chart (timeline of the study, DOC). (DOCX 16 kb

Additional file 1: Figure S1. of Atopic Dermatitis Anti-IgE Paediatric Trial (ADAPT): the role of anti-IgE in severe paediatric eczema: study protocol for a randomised controlled trial

SPIRIT 2013 Checklist. (DOC 272 kb

Validation of a classification system for causes of death in critical care: an assessment of inter-rater reliability

Objective: Trials in critical care have previously used unvalidated systems to classify cause of death. We aimed to provide initial validation of a method to classify cause of death in intensive care unit patients. Design, setting and participants: One hundred case scenarios of patients who died in an ICU were presented online to raters, who were asked to select a proximate and an underlying cause of death for each, using the ICU Deaths Classification and Reason (ICU-DECLARE) system. We evaluated two methods of categorising proximate cause of death (designated Lists A and B) and one method of categorising underlying cause of death. Raters were ICU specialists and research coordinators from Australia, New Zealand and the United Kingdom. Main outcome measures: Inter-rater reliability, as measured by the Fleiss multirater kappa, and the median proportion of raters choosing the most likely diagnosis (defined as the most popular classification choice in each case). Results: Across all raters and cases, for proximate cause of death List A, kappa was 0.54 (95% Cl, 0.49–0.60), and for proximate cause of death List B, kappa was 0.58 (95% Cl, 0.53–0.63). For the underlying cause of death, kappa was 0.48 (95% Cl, 0.44–0.53). The median proportion of raters choosing the most likely diagnosis for proximate cause of death, List A, was 77.5% (interquartile range [IQR], 60.0%–93.8%), and the median proportion choosing the most likely diagnosis for proximate cause of death, List B, was 82.5% (IQR, 60.0%–92.5%). The median proportion choosing the most likely diagnosis for underlying cause was 65.0% (IQR, 50.0%–81.3%). Kappa and median agreement were similar between countries. ICU specialists showed higher kappa and median agreement than research coordinators. Conclusions: The ICU-DECLARE system allowed ICU doctors to classify the proximate cause of death of patients who died in the ICU with substantial reliability