Is Drotrecogin alfa (activated) for adults with severe sepsis, cost-effective in routine clinical practice?

INTRODUCTION: Previous cost-effectiveness analyses (CEA) reported that Drotrecogin alfa (DrotAA) is cost-effective based on a Phase III clinical trial (PROWESS). There is little evidence on whether DrotAA is cost-effective in routine clinical practice. We assessed whether DrotAA is cost-effective in routine practice for adult patients with severe sepsis and multiple organ systems failing. METHODS: This CEA used data from a prospective cohort study that compared DrotAA versus no DrotAA (control) for severe sepsis patients with multiple organ systems failing admitted to critical care units in England, Wales, and Northern Ireland. The cohort study used case-mix and mortality data from a national audit, linked with a separate audit of DrotAA infusions. Re-admissions to critical care and corresponding mortality were recorded for four years. Patients receiving DrotAA (n = 1,076) were matched to controls (n = 1,650) with a propensity score (Pscore), and Genetic Matching (GenMatch). The CEA projected long-term survival to report lifetime incremental costs per quality-adjusted life year (QALY) overall, and for subgroups with two or three to five organ systems failing at baseline. RESULTS: The incremental costs per QALY for DrotAA were £30,000 overall, and £16,000 for the subgroups with three to five organ systems failing. For patients with two organ systems failing, DrotAA resulted in an average loss of one QALY at an incremental cost of £15,000. When the subgroup with two organ systems was restricted to patients receiving DrotAA within 24 hours, DrotAA led to a gain of 1.2 QALYs at a cost per QALY of £11,000. The results were robust to other assumptions including the approach taken to projecting long-term outcomes. CONCLUSIONS: DrotAA is cost-effective in routine practice for severe sepsis patients with three to five organ systems failing. For patients with two organ systems failing, this study could not provide unequivocal evidence on the cost-effectiveness of DrotAA

Development and validation of risk models to predict outcomes following in-hospital cardiac arrest attended by a hospital-based resuscitation team

Aim The National Cardiac Arrest Audit (NCAA) is the UK national clinical audit for in-hospital cardiac arrest. To make fair comparisons among health care providers, clinical indicators require case mix adjustment using a validated risk model. The aim of this study was to develop and validate risk models to predict outcomes following in-hospital cardiac arrest attended by a hospital-based resuscitation team in UK hospitals. Methods Risk models for two outcomes—return of spontaneous circulation (ROSC) for greater than 20 min and survival to hospital discharge—were developed and validated using data for in-hospital cardiac arrests between April 2011 and March 2013. For each outcome, a full model was fitted and then simplified by testing for non-linearity, combining categories and stepwise reduction. Finally, interactions between predictors were considered. Models were assessed for discrimination, calibration and accuracy. Results 22,479 in-hospital cardiac arrests in 143 hospitals were included (14,688 development, 7791 validation). The final risk model for ROSC > 20 min included: age (non-linear), sex, prior length of stay in hospital, reason for attendance, location of arrest, presenting rhythm, and interactions between presenting rhythm and location of arrest. The model for hospital survival included the same predictors, excluding sex. Both models had acceptable performance across the range of measures, although discrimination for hospital mortality exceeded that for ROSC > 20 min (c index 0.81 versus 0.72). Conclusions Validated risk models for ROSC > 20 min and hospital survival following in-hospital cardiac arrest have been developed. These models will strengthen comparative reporting in NCAA and support local quality improvement

Analysis of Benefit of Intensive Care Unit Transfer for Deteriorating Ward Patients: A Patient-Centered Approach to Clinical Evaluation.

Importance: It is unknown which deteriorating ward patients benefit from intensive care unit (ICU) transfer. Objectives: To use an instrumental variable (IV) method that assesses heterogeneity and to evaluate estimates of person-centered treatment effects of ICU transfer and 28-day hospital mortality by age and illness severity. Design, Setting, and Participants: An analysis of a prospective cohort study from November 1, 2010, to December 31, 2011. The dates of this analysis were June 1, 2017, to June 30, 2018. The setting was a multicenter study of 49 UK National Health Service hospitals. Participants were 9192 deteriorating ward patients assessed for ICU transfer (4596 matched pairs). The study matched on baseline characteristics to strengthen the IV and to balance observed confounders between the comparison groups. Exposures: Transfer to the ICU or continued care on general wards. Main Outcomes and Measures: Mortality at 28 days (primary outcome) and 90 days. To address unobserved confounding, ICU bed availability was the IV for whether or not a patient was transferred. The study used the IV approach to evaluate estimates of treatment effect of ICU transfer and mortality according to age and physiological severity alone and in combination. Results: Both comparison groups included 4596 patients. In the group assessed with "many" ICU beds available (median, 7), 52.8% were male, and the mean (SD) age was 65.2 (17.7) years; in the group assessed with "few" ICU beds available (median, 2), 53.3% were male, and the mean (SD) age was 65.0 (17.3) years. The overall 28-day mortality estimates were 23.2% (2090 predicted deaths) if all of the matched patients were transferred vs 28.1% (2534 predicted deaths) if none of the matched patients were transferred, an estimated risk difference of -4.9% (95% CI, -26.4% to 16.6%). The estimated effects of ICU transfer differed by age and by physiological severity according to the National Early Warning Score (NEWS): the absolute risk differences in 28-day mortality after ICU transfer ranged from 7.7% (95% CI, -5.5% to 21.0%) for ages 18 to 23 years to -5.0% (95% CI -26.5% to 16.6%) for age 78 to 83 years and ranged from 3.7% (95% CI, -12.1% to 19.5%) for NEWS of 0 to -25.4% (95% CI, -50.6% to -0.2%) for NEWS of 19. The absolute risk differences for elderly patients (≥75 years) were -11.6% (95% CI, -39.0% to 15.8%) for those with high NEWS (>6), -4.8% (95% CI, -30.5% to 20.9%) for those with moderate NEWS (5-6), and -1.0% (95% CI, -24.8% to 22.8%) for those with low NEWS (<5). The corresponding estimates for subgroups of younger patients (<75 years) were -8.4% (95% CI, -31.0% to 14.1%), -2.1% (95% CI, -21.1% to 16.9%), and 1.4% (95% CI, -14.5% to 17.4%). Conclusions and Relevance: This study using a this person-centered IV approach found that the benefits of ICU care may increase among patients at high levels of baseline physiological severity across different age groups, especially among elderly patients

Can the UK 24-item family satisfaction in the intensive care unit questionnaire be used to evaluate quality improvement strategies aimed at improving family satisfaction with the ICU? A qualitative study

Acknowledgements We thank the participants in the FREE and EBCD studies who gave their time to participate. We also thank Professor David Harrison for extracting the open-text comments from the FREE study database. Funding The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The FREE Study was funded by the National Institute for Health Research (NIHR) Health Services and Delivery Research (HS&DR) Programme (11/2003/56). The EBCD study was funded by the NIHR HS&DR Programme (10/1009/14). The funder had no involvement in study design; in collection, analysis and interpretation of data; in the writing of this paper; or in the decision to submit the article for publication. LH is supported by the NIHR Oxford Biomedical Research Centre (BRC). LL was employed by the Nuffield Department of Primary Care Health Sciences, University of Oxford and supported by the NIHR Oxford BRC during the period the work was conducted. BC is funded by an NIHR Clinical Trials Fellowship (CTF-2017-06-016). The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the NIHR, NHS or the Department of Health and Social Care.Peer reviewedPostprin

Pre-arrest and intra-arrest prognostic factors associated with survival after in-hospital cardiac arrest : systematic review and meta-analysis

Abstract: Objective: To determine associations between important pre-arrest and intra-arrest prognostic factors and survival after in-hospital cardiac arrest. Design: Systematic review and meta-analysis. Data sources: Medline, PubMed, Embase, Scopus, Web of Science, and the Cochrane Database of Systematic Reviews from inception to 4 February 2019. Primary, unpublished data from the United Kingdom National Cardiac Arrest Audit database. Study selection criteria: English language studies that investigated pre-arrest and intra-arrest prognostic factors and survival after in-hospital cardiac arrest. Data extraction: PROGRESS (prognosis research strategy group) recommendations and the CHARMS (critical appraisal and data extraction for systematic reviews of prediction modelling studies) checklist were followed. Risk of bias was assessed by using the QUIPS tool (quality in prognosis studies). The primary analysis pooled associations only if they were adjusted for relevant confounders. The GRADE approach (grading of recommendations assessment, development, and evaluation) was used to rate certainty in the evidence. Results: The primary analysis included 23 cohort studies. Of the pre-arrest factors, male sex (odds ratio 0.84, 95% confidence interval 0.73 to 0.95, moderate certainty), age 60 or older (0.50, 0.40 to 0.62, low certainty), active malignancy (0.57, 0.45 to 0.71, high certainty), and history of chronic kidney disease (0.56, 0.40 to 0.78, high certainty) were associated with reduced odds of survival after in-hospital cardiac arrest. Of the intra-arrest factors, witnessed arrest (2.71, 2.17 to 3.38, high certainty), monitored arrest (2.23, 1.41 to 3.52, high certainty), arrest during daytime hours (1.41, 1.20 to 1.66, high certainty), and initial shockable rhythm (5.28, 3.78 to 7.39, high certainty) were associated with increased odds of survival. Intubation during arrest (0.54, 0.42 to 0.70, moderate certainty) and duration of resuscitation of at least 15 minutes (0.12, 0.07 to 0.19, high certainty) were associated with reduced odds of survival. Conclusion: Moderate to high certainty evidence was found for associations of pre-arrest and intra-arrest prognostic factors with survival after in-hospital cardiac arrest. Systematic review registration: PROSPERO CRD4201810479