The management of sepsis has substantially improved over the past 15 years. In this study, early, goal-directed therapy, which focuses on the initial resuscitation efforts, was compared with usual ...care for the management of severe sepsis in the United Kingdom.
The incidence of severe sepsis and septic shock in adults is estimated to range from 56 to 91 per 100,000 population per year.
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Affected patients have high rates of death, complications, and resource utilization.
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–
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Since 2002, the Surviving Sepsis Campaign (SSC) has promoted best practice, including early recognition, source control, appropriate and timely antibiotic administration, and resuscitation with intravenous fluids and vasoactive drugs.
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Resuscitation guidance is largely based on a 2001 single-center, proof-of-concept study by Rivers et al., which indicated that protocolized delivery of 6 hours of early, goal-directed therapy (EGDT) to patients presenting to the emergency department . . .
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.
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.
A pragmatic, open, multicentre, parallel-group randomised controlled trial with an integrated economic evaluation.
Fifty-six NHS hospitals in England.
A total of 1260 patients who presented at EDs with septic shock.
EGDT (n = 630) or usual resuscitation (n = 630). Patients were randomly allocated 1 : 1.
All-cause mortality at 90 days after randomisation and incremental net benefit (at £20,000 per quality-adjusted life-year) at 1 year.
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.
Recruitment was lower at weekends and out of hours. The intervention could not be blinded.
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%.
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.
Current Controlled Trials ISRCTN36307479.
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.
The evidence for systemic treatments for severe childhood eczema is limited and largely based on extrapolation of data from adult studies. Current therapies are often immunosuppressant and may be ...associated with both short- and long-term side effects. There is increasing in vitro and murine-model evidence for the role of IgE in the immunopathogenesis of atopic eczema. The aim of the study is to assess whether anti-IgE treatment (omalizumab) improves eczema, compared to placebo.
The Atopic Dermatitis Anti-IgE Paediatric Trial (ADAPT) is a randomised, double-blind, placebo-controlled study assessing the role of anti-IgE in the management of severe paediatric eczema. Children with severe atopic eczema, with an objective SCORing Atopic Dermatitis (SCORAD) score of over 40 will be recruited. These children are candidates for systemic therapy, have failed systemic therapy or have experienced side effects from systemic therapy. Sixty-two patients aged between 4 and 19 years will receive anti-IgE for 6 months. The primary outcome measure will be the validated eczema score, the objective SCORAD at 24 weeks. This study has 90% power to detect a 33% relative reduction in SCORAD between active and placebo groups, with 5% significance.
IgE may have a role to play in eczema, particularly in childhood. This forms the basis for the hypothesis that anti-IgE may be an effective treatment in this patient population. This will be the largest study to evaluate the efficacy of anti-IgE (omalizumab) versus placebo in children with severe eczema. The findings will help to clarify the role of anti-IgE as a potential treatment option in patients with severe childhood eczema.
European Clinical Trials Database (EudraCT) Number: 2010-020841-29 . Assigned on 14 May 2010. ISRCTN Registry, Identifier: ISRCTN15090567 . Retrospectively assigned on 3 December 2014. ClinicalTrials.gov, Identifier: NCT02300701 . First received 21 November 2014.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Background
Evidence for systemic treatments for severe childhood eczema is limited. Systemic immunosuppressants are unlicensed for use in children and are associated with unwanted side effects.
...Objective
To examine the role of anti-immunoglobulin E (IgE) omalizumab (Xolair
®
, Novartis Pharmaceuticals UK Ltd, Frimley, UK) in children and young people with severe eczema.
Design
A double-blind, placebo-controlled, parallel-arm randomised (1 : 1) trial.
Setting
A single specialist centre – Guy’s and St Thomas’ NHS Foundation Trust, London.
Participants
Atopic children and young people (aged 4–19 years) with severe eczema.
Interventions
Treatment with omalizumab or placebo for 24 weeks.
Main outcome measures
The primary outcome was eczema severity, measured using the objective SCORing Atopic Dermatitis (SCORAD) at 24 weeks. Secondary outcomes included validated measures of eczema severity, quality of life (QoL) and potent topical steroid use.
Results
Sixty-two participants, with a median baseline total IgE level of 8373 kU/l, received treatment with omalizumab (
n
= 30) or placebo (
n
= 32). The unadjusted mean objective SCORAD score at week 24 was 43.1 standard deviation (SD) 12.5 for participants in the omalizumab arm and 49.2 (SD 11.3) for participants in the placebo arm. After adjustment for baseline objective SCORAD score, age and IgE level, the mean difference between arms at 24 weeks was –6.9 95% confidence interval (CI) –12.2 to –1.5;
p
= 0.013, in favour of omalizumab. The mean objective SCORAD scores improved by –12.4 and –5.1 in the omalizumab and placebo arms, respectively, by 24 weeks. Secondary outcome measure estimates were also in favour of omalizumab for eczema severity at 24 weeks: the adjusted mean treatment arm difference was –8.3 (95% CI –15.1 to –1.1;
p
= 0.024) for total combined objective and subjective SCORAD and –6.7 (95% CI –13.2 to –0.1;
p
= 0.046) for the Eczema Area and Severity Index, with less effect on the Patient-Oriented Eczema Measure (POEM; –1.1, 95% CI –4.6 to 2.4;
p
= 0.527). Treatment estimate precision was limited by the sample size. The QoL measures favoured omalizumab, with an improvement (reduction) in both (Children’s) Dermatology Life Quality Index (C)DLQI score (mean –3.5, 95% CI –6.4 to –0.5;
p
= 0.022) and Paediatric Allergic Disease Quality of Life Questionnaire score (mean –0.5, 95% CI –0.9 to 0.0;
p
= 0.050). The mean (C)DLQI score improved by 50%, from 17.0 (SD 5.6) at baseline to 8.5 (SD 5.9) at week 24, for patients treated with omalizumab. Improvements were seen despite lower potent topical steroid use in the omalizumab arm, with 48% more days of use than (109 days in the placebo arm vs. 161 days in the omalizumab arm) and twice the body surface area coverage of (15.5% in the placebo arm vs. 31.3% in the omalizumab arm) the placebo arm. There were fewer treatment failures and new systemic immunosuppression initiations in the omalizumab arm. There was no difference in the numbers of cases of infective eczema and eczema exacerbation. There was one suspected severe adverse reaction in the omalizumab arm. In each arm, six participants reported a total of seven severe adverse events that were unrelated to treatment. Non-serious respiratory and dermatological adverse event rates were higher in the placebo arm (incidence rate ratio 0.69, 95% CI 0.49 to 0.96).
Conclusions
Omalizumab, in a highly atopic paediatric population with severe eczema, reduced eczema severity and improved QoL despite a reduction in potent steroid use and highly elevated total IgE levels. Omalizumab, with its favourable side effect profile, warrants further study as a treatment option for this difficult-to-manage population. Further studies are needed to clarify the role of omalizumab. Treatment benefit became more apparent towards 24 weeks and persisted after treatment stopped. The optimal duration of treatment needs to be determined.
Trial registration
This trial is registered as ISRCTN15090567, EudraCT 2010-020841-29 and ClinicalTrials.gov NCT02300701.
Funding
This project was funded by the Efficacy and Mechanism Evaluation programme, a Medical Research Council and National Institute for Health and Care Research (NIHR) partnership. This will be published in full in
Efficacy and Mechanism Evaluation
; Vol. 9, No. 5. See the NIHR Journals Library website for further project information. A grant from the Guy’s and St Thomas’ Charity supported the Atopic Dermatitis Anti-IgE Paediatric Trial (ADAPT). Omalizumab and the placebo were supplied by Novartis Pharmaceuticals UK Ltd.
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% CI, 0.49-0.60), and for proximate cause of death List B, kappa was 0.58 (95% CI, 0.53-0.63). For the underlying cause of death, kappa was 0.48 (95% CI, 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.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•Temperature induced changes in selected physiological traits and expression pattern of selected set of sex determining genes were investigated for the black tiger shrimp (Penaeus monodon) under six ...different temperature regimes.•Temperature treatments significantly altered growth performance, sex ratios, survivability and gene expression pattern of P. monodon.•Higher temperature treatments revealed superior growth and higher proportions of females coupled with increased expression of female determining genes.•The highest level of temperature treatment (34℃) imposed severe stress on experimental P. monodon individuals resulting reduced growth and massive mortality.
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 < 0.05) with the highest growth performance obtained at 32℃, moderate levels were obtained at 28−30℃ and the lowest levels were obtained at the remaining temperatures. Temperature treatments significantly shortened the larval developmental durations at 28℃, 30℃ and 32℃ (required 44–46 days for sex differentiation) while 52–63 days were required at 24℃, 26℃ and 34℃. Temperature treatments also altered sex ratios of experimental P. monodon individuals; significantly higher (P < 0.05) proportions of males (coupled with higher expression levels of male sex determining genes) were obtained at lower temperatures (24℃ and 26℃) while larger proportions of females (with higher expression levels of female sex determining genes) were obtained at higher temperature levels (30℃, 32℃ and 34℃). The thermal stress response gene, heat shock protein (HSP70) showed constant expression levels at 28℃ but higher expression levels were obtained at other temperatures. Results imply that higher temperature can significantly increase the expression of female sex determining genes to produce larger proportions of females in P. monodon that in turn can help to improve aquaculture production.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Despite the importance of mud crab species (genus Scylla) in both coastal aquaculture and artisanal fisheries, knowledge of the species diversity and stock structure of mud crab population for their ...sustainable management across the coastal region of Bangladesh remains obscure. Therefore, the present study was conducted to delineate the diversity and stock structure of mud crab species based on the 24 morphometric length measurements and 27 morphometric ratios data collected from the three coastal regions (Chittagong, Cox's Bazar and Bagerhat) of Bangladesh. Based on the taxonomic keys, majority of the species (about 82.4%) were identified as S. olivacea, while the remaining (about 17.6%) was S. serrata. In consistent to our preliminary analysis, both the univariate proportion and multivariate analysis of the collected morphometric lengths and ratios data also distinctly divided the mud crabs population into two multivariate spaces as S. serrata and S. olivacea. For the further analysis of the stock structure of these two species, data were subjected to the univariate ANOVA, multivariate ANOVA, Canonical Variate Analysis (CVA), and Principal Component Analysis (PCA) according to their collection sites. Scatter plots of CVA scores between CV1 and CV2 and PCA scores between PC1 and PC2 showed that the individuals of both species clearly made clusters into three multivariate spaces with minimum overlaps according to their collection sites. In morphometric traits Linear Discriminant Function Analysis (LDFA), the average percentage of correctly classified (PCC) into the original groups of the S. olivacea and S. serrata was 100%. For stock discrimination, the average PCC into their original groups of collection sites were 100% and 99% for the S. olivacea and S. serrata, respectively. Finally, dendrogram based on the Euclidean distances consistently separated S. olivacea and S. serrata and stock structures similar to other multivariate analyses. In conclusion, our study shows that S. olivacea is the dominant mud crab species and S. serrata is the minor one, and the stock discrimination of each species should be considered in the management and conservation policy of these species along the coastal region of Bangladesh.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•Fish and vegetable production was increased in shaded ponds.•Underutilized shaded ponds were used to produce fish and vegetable.•This system helped to fulfill nutritional requirement of poor ...households 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 56m−2 per cage. Fish were fed floating feed twice daily and significantly higher (P<0.05) individual growth rate (161±2.4g) and productivity (76±1.7kg) for tilapia were found in T1 while the individual growth rate (93±12g) and productivity (49±1.3kg) of Vietnamese perch was higher in T2 but this was not significantly different (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.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
At present the military units are running their offices manually which needs careful handling of classified documents. Manual handling of files is no longer the safest option without having any solid ...backup of the files. Considering the above circumstances, making a secured website-only accessible by the unit premises concerned authority to organize various files, policies and other affairs of the unit in a single website is time demanding. In this paper we developed the web based (Army) unit administration management system where all the office sections (ADMIN, Q, G/TRAINING, AC-COUNT) under one military unit will be brought together in a more organized way.
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