The BRACELET Study: surveys of mortality in UK neonatal and paediatric intensive care trials.

BACKGROUND: The subject of death and bereavement in the context of randomised controlled trials in neonatal or paediatric intensive care is under-researched. The objectives of this phase of the Bereavement and RAndomised ControlLEd Trials (BRACELET) Study were to determine trial activity in UK neonatal and paediatric intensive care (2002-06); numbers of deaths before hospital discharge; and variation in mortality across intensive care units and trials and to determine whether bereavement support policies were available within trials. These are essential prerequisites to considering the implications of future policies and practice subsequent to bereavement following a child's enrollment in a trial. METHODS: The units survey involved neonatal units providing level 2 or 3 care, and paediatric units providing level II care or above; the trials survey involved trials where allocation was randomized and interventions were delivered to intensive care patients, or to parents but designed to affect patient outcomes. RESULTS: Information was available from 191/220 (87%) neonatal units (149 level 2 or 3 care); and 28/32 (88%) paediatric units. 90/177 (51%) eligible responding units participated in one or more trial (76 neonatal, 14 paediatric) and 54 neonatal units and 6 paediatric units witnessed at least one death. 50 trials were identified (36 neonatal, 14 paediatric). 3,137 babies were enrolled in neonatal trials, 210 children in paediatric trials. Deaths ranged 0-278 (median [IQR interquartile range] 2 [1, 14.5]) per neonatal trial, 0-4 (median [IQR] 1 [0, 2.5]) per paediatric trial. 534 (16%) participants died post-enrollment: 522 (17%) in neonatal trials, 12 (6%) in paediatric trials. Trial participants ranged 1-236 (median [IQR] 21.5 [8, 39.8]) per neonatal unit, 1-53 (median [IQR] 11.5 [2.3, 33.8]) per paediatric unit. Deaths ranged 0-37 (median [IQR] 3.5 [0.3, 8.8]) per neonatal unit, 0-7 (median [IQR] 0.5 [0, 1.8]) per paediatric unit. Three trials had a formal policy for responding to bereavement. CONCLUSIONS: A substantial number of deaths after trial enrollment were identified, distributed over many trials and units. Few trial teams had responses to bereavement in place. Those with the largest numbers of deaths might be best placed to collaborate in developing and assessing responses to bereavement.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Predicting invasive fungal disease due to Candida species in non-neutropenic, critically ill, adult patients in United Kingdom critical care units

Background Given the predominance of invasive fungal disease (IFD) amongst the non-immunocompromised adult critically ill population, the potential benefit of antifungal prophylaxis and the lack of generalisable tools to identify high risk patients, the aim of the current study was to describe the epidemiology of IFD in UK critical care units, and to develop and validate a clinical risk prediction tool to identify non-neutropenic, critically ill adult patients at high risk of IFD who would benefit from antifungal prophylaxis. Methods Data on risk factors for, and outcomes from, IFD were collected for consecutive admissions to adult, general critical care units in the UK participating in the Fungal Infection Risk Evaluation (FIRE) Study. Three risk prediction models were developed to model the risk of subsequent Candida IFD based on information available at three time points: admission to the critical care unit, at the end of 24 h and at the end of calendar day 3 of the critical care unit stay. The final model at each time point was evaluated in the three external validation samples. Results Between July 2009 and April 2011, 60,778 admissions from 96 critical care units were recruited. In total, 359 admissions (0.6 %) were admitted with, or developed, Candida IFD (66 % Candida albicans). At the rate of candidaemia of 3.3 per 1000 admissions, blood was the most common Candida IFD infection site. Of the initial 46 potential variables, the final admission model and the 24-h model both contained seven variables while the end of calendar day 3 model contained five variables. The end of calendar day 3 model performed the best with a c index of 0.709 in the full validation sample. Conclusions Incidence of Candida IFD in UK critical care units in this study was consistent with reports from other European epidemiological studies, but lower than that suggested by previous hospital-wide surveillance in the UK during the 1990s. Risk modeling using classical statistical methods produced relatively simple risk models, and associated clinical decision rules, that provided acceptable discrimination for identifying patients at ‘high risk’ of Candida IFD

Predicting invasive fungal disease due to Candida species in non-neutropenic, critically ill, adult patients in United Kingdom critical care units.

BACKGROUND: Given the predominance of invasive fungal disease (IFD) amongst the non-immunocompromised adult critically ill population, the potential benefit of antifungal prophylaxis and the lack of generalisable tools to identify high risk patients, the aim of the current study was to describe the epidemiology of IFD in UK critical care units, and to develop and validate a clinical risk prediction tool to identify non-neutropenic, critically ill adult patients at high risk of IFD who would benefit from antifungal prophylaxis. METHODS: Data on risk factors for, and outcomes from, IFD were collected for consecutive admissions to adult, general critical care units in the UK participating in the Fungal Infection Risk Evaluation (FIRE) Study. Three risk prediction models were developed to model the risk of subsequent Candida IFD based on information available at three time points: admission to the critical care unit, at the end of 24 h and at the end of calendar day 3 of the critical care unit stay. The final model at each time point was evaluated in the three external validation samples. RESULTS: Between July 2009 and April 2011, 60,778 admissions from 96 critical care units were recruited. In total, 359 admissions (0.6 %) were admitted with, or developed, Candida IFD (66 % Candida albicans). At the rate of candidaemia of 3.3 per 1000 admissions, blood was the most common Candida IFD infection site. Of the initial 46 potential variables, the final admission model and the 24-h model both contained seven variables while the end of calendar day 3 model contained five variables. The end of calendar day 3 model performed the best with a c index of 0.709 in the full validation sample. CONCLUSIONS: Incidence of Candida IFD in UK critical care units in this study was consistent with reports from other European epidemiological studies, but lower than that suggested by previous hospital-wide surveillance in the UK during the 1990s. Risk modeling using classical statistical methods produced relatively simple risk models, and associated clinical decision rules, that provided acceptable discrimination for identifying patients at 'high risk' of Candida IFD. TRIAL REGISTRATION: The FIRE Study was reviewed and approved by the Bolton NHS Research Ethics Committee (reference: 08/H1009/85), the Scotland A Research Ethics Committee (reference: 09/MRE00/76) and the National Information Governance Board (approval number: PIAG 2-10(f)/2005)

Family satisfaction with critical care in the UK: a multicentre cohort study.

OBJECTIVE: To assess family satisfaction with intensive care units (ICUs) in the UK using the Family Satisfaction in the Intensive Care Unit 24-item (FS-ICU-24) questionnaire, and to investigate how characteristics of patients and their family members impact on family satisfaction. DESIGN: Prospective cohort study nested within a national clinical audit database. SETTING: Stratified, random sample of 20 adult general ICUs participating in the Intensive Care National Audit & Research Centre Case Mix Programme. PARTICIPANTS: Family members of patients staying at least 24 hours in ICU were recruited between May 2013 and June 2014. INTERVENTIONS: Consenting family members were sent a postal questionnaire 3 weeks after the patient died or was discharged from ICU. Up to four family members were recruited per patient. MAIN OUTCOME MEASURES: Family satisfaction was measured using the FS-ICU-24 questionnaire. MAIN RESULTS: A total of 12 346 family members of 6380 patients were recruited and 7173 (58%) family members of 4615 patients returned a completed questionnaire. Overall and domain-specific family satisfaction scores were high (mean overall family satisfaction 80, satisfaction with care 83, satisfaction with information 76 and satisfaction with decision-making 73 out of 100) but varied significantly across adult general ICUs studied and by whether the patient survived ICU. For family members of ICU survivors, characteristics of both the family member (age, ethnicity, relationship to patient (next-of-kin and/or lived with patient) and visit frequency) and the patient (acute severity of illness and receipt of invasive mechanical ventilation) were significant determinants of family satisfaction, whereas, for family members of ICU non-survivors, only patient characteristics (age, acute severity of illness and duration of stay) were significant. CONCLUSIONS: Overall family satisfaction in UK adult general ICUs was high but varied significantly. Adjustment for differences in family member/patient characteristics is important to avoid falsely identifying ICUs as statistical outliers. TRIAL REGISTRATION NUMBER: ISRCTN47363549

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

‘Re-reading Raphael Samuel: Politics, Personality and Performance’

For British historian Raphael Samuel, history and politics were inextricable. Best known as the founder of the history workshop movement, the controversial historian took his stance on the democratisation of history-making, becoming an outspoken advocate for public history. Despite making a significant contribution to contemporary historiography, he remains a neglected, even disparaged, figure. This paper contends that the most significant aspect of Samuel’s historical work was not one or other theory of history or argument about the past but his entire way of being an historian. Samuel embodied as much as expressed his ideas, consciously using his personality as a powerful political tool. It is further argued that conventional approaches to intellectual history, focusing on textual outputs, do not fully recognise the significance of performative modes of thinking. Theoretical approaches to performance as identity offer important insight here but can be too schematic in their view of applied and enacted thought. A biographical approach, by contrast, provides the intimate perspective necessary to fully appreciate the fluidity and complexity of such a personality. The paper first situates Samuel in the context of his earlier life, focusing on how and why he created such a public persona and how he adapted it in response to changing circumstances. It then considers the implications and effectiveness of this persona by assessing how it was perceived and narrated by others, acknowledging, in the process, why different groups engaged with and interpreted it differently

Survey radiography and computerized tomography imaging of the thorax in female dogs with mammary tumors

<p>Abstract</p> <p>Background</p> <p>Accurate early diagnosis of lung metastases is important for establishing therapeutic measures. Therefore, the present study aimed to compare survey thoracic radiographs and computerized tomography (CT) scans to specifically identify lung metastases in female dogs with mammary tumors.</p> <p>Methods</p> <p>Twenty-one female dogs, weighing 3 to 34 kg and aged from 5 years to 14 years and 10 months, with mammary tumors were studied. In all dogs before the imaging examinations, fine-needle aspiration cytology of the mammary tumors was performed to confirm the diagnosis. Three-view thoracic radiographs were accomplished: right lateral, left lateral and ventrodorsal views. Sequential transverse images of the thorax were acquired on a spiral Scanner, before and after intravenous bolus injection of nonionic iodine contrast. Soft-tissue and lung windows were applied. All the mammary tumors were surgically removed and examined histologically.</p> <p>Results</p> <p>The correlation between the cytological and histological results regarding presence of malignancy was observed in only 17 cases. In radiographic examinations, no dog displayed signs of lung metastases or thorax chest lesions. CT detected lung metastasis in two cases, while small areas of lung atelectasis located peripherally were found in 28.57% of the dogs.</p> <p>Conclusion</p> <p>In this study population, spiral CT showed higher sensitivity than chest radiographies to detect lung metastasis; this indicates that CT should be performed on all female dogs with malignant mammary tumors.</p