Impact on mortality of prompt admission to critical care for deteriorating ward patients: an instrumental variable analysis using critical care bed strain.

PURPOSE: To estimate the effect of prompt admission to critical care on mortality for deteriorating ward patients. METHODS: We performed a prospective cohort study of consecutive ward patients assessed for critical care. Prompt admissions (within 4 h of assessment) were compared to a 'watchful waiting' cohort. We used critical care strain (bed occupancy) as a natural randomisation event that would predict prompt transfer to critical care. Strain was classified as low, medium or high (2+, 1 or 0 empty beds). This instrumental variable (IV) analysis was repeated for the subgroup of referrals with a recommendation for critical care once assessed. Risk-adjusted 90-day survival models were also constructed. RESULTS: A total of 12,380 patients from 48 hospitals were available for analysis. There were 2411 (19%) prompt admissions (median delay 1 h, IQR 1-2) and 9969 (81%) controls; 1990 (20%) controls were admitted later (median delay 11 h, IQR 6-26). Prompt admissions were less frequent (p < 0.0001) as strain increased from low (22%), to medium (15%) to high (9%); the median delay to admission was 3, 4 and 5 h respectively. In the IV analysis, prompt admission reduced 90-day mortality by 7.4% (95% CI 1.7-18.5%, p = 0.117) overall, and 16.2% (95% CI 1.1-31.3%, p = 0.036) for those recommended for critical care. In the risk-adjust survival model, 90-day mortality was similar. CONCLUSION: After allowing for unobserved prognostic differences between the groups, we find that prompt admission to critical care leads to lower 90-day mortality for patients assessed and recommended to critical care

Early and late withdrawal of life-sustaining treatment after out-of-hospital cardiac arrest in the United Kingdom: institutional variation and association with hospital mortality

Aim Frequency and timing of Withdrawal of Life-Sustaining Treatment (WLST) after Out-of-Hospital Cardiac Arrest (OHCA) vary across Intensive Care Units (ICUs) in the United Kingdom (UK) and may be a marker of lower healthcare quality if instituted too frequently or too early. We aimed to describe WLST practice, quantify its variability across UK ICUs, and assess the effect of institutional deviation from average practice on patients’ risk-adjusted hospital mortality. Methods We conducted a retrospective multi-centre cohort study including all adult patients admitted after OHCA to UK ICUs between 2010 and 2017. We identified patient and ICU characteristics associated with early (within 72 h) and late (>72 h) WLST and quantified the between-ICU variation. We used the ICU-level observed-to-expected (O/E) ratios of early and late-WLST frequency as separate metrics of institutional deviation from average practice and calculated their association with patients’ hospital mortality. Results We included 28,438 patients across 204 ICUs. 10,775 (37.9%) had WLST and 6397 (59.4%) of them had early-WLST. Both WLST types were strongly associated with patient-level demographics and pre-existing conditions but weakly with ICU-level characteristics. After adjustment, we found unexplained between-ICU variation for both early-WLST (Median Odds Ratio 1.59, 95%CrI 1.49–1.71) and late-WLST (MOR 1.39, 95%CrI 1.31–1.50). Importantly, patients’ hospital mortality was higher in ICUs with higher O/E ratio of early-WLST (OR 1.29, 95%CI 1.21–1.38, p < 0.001) or late-WLST (OR 1.39, 95%CI 1.31–1.48, p < 0.001). Conclusions Significant variability exists between UK ICUs in WLST frequency and timing. This matters because unexplained higher-than-expected WLST frequency is associated with higher hospital mortality independently of timing, potentially signalling prognostic pessimism and lower healthcare quality

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

Geometrical analysis of the inland topography to assess the likely response of wave-dominated coastline to sea level: application to Great Britain

The need for quantitative assessments at a large spatial scale (103 km) and over time horizons of the order 101 to 102 years have been reinforced by the 2019 Special Report on the Ocean and Cryosphere in a Changing Climate, which concluded that adaptation to a sea-level rise will be needed no matter what emission scenario is followed. Here, we used a simple geometrical analysis of the backshore topography to assess the likely response of any wave-dominated coastline to a sea-level rise, and we applied it along the entire Great Britain (GB) coastline, which is ca. 17,820 km long. We illustrated how the backshore geometry can be linked to the shoreline response (rate of change and net response: erosion or accretion) to a sea-level rise by using a generalized shoreline Exner equation, which includes the effect of the backshore slope and differences in sediment fractions within the nearshore. To apply this to the whole of GB, we developed an automated delineation approach to extract the main geometrical attributes. Our analysis suggests that 71% of the coast of GB is best described as gentle coast, including estuarine coastline or open coasts where back-barrier beaches can form. The remaining 39% is best described as cliff-type coastlines, for which the majority (57%) of the backshore slope values are negative, suggesting that a non-equilibrium trajectory will most likely be followed as a response to a rise in sea level. For the remaining 43% of the cliffed coast, we have provided regional statistics showing where the potential sinks and sources of sediment are likely to be

Proteinase-activated receptor 2 modulates OA-related pain, cartilage and bone pathology

Objective Proteinase-activated receptor 2 (PAR2) deficiency protects against cartilage degradation in experimental osteoarthritis (OA). The wider impact of this pathway upon OA-associated pathologies such as osteophyte formation and pain is unknown. Herein, we investigated early temporal bone and cartilage changes in experimental OA in order to further elucidate the role of PAR2 in OA pathogenesis. Methods OA was induced in wild-type (WT) and PAR2-deficient (PAR2−/−) mice by destabilisation of the medial meniscus (DMM). Inflammation, cartilage degradation and bone changes were monitored using histology and microCT. In gene rescue experiments, PAR2−/− mice were intra-articularly injected with human PAR2 (hPAR2)-expressing adenovirus. Dynamic weight bearing was used as a surrogate of OA-related pain. Results Osteophytes formed within 7 days post-DMM in WT mice but osteosclerosis was only evident from 14 days post induction. Importantly, PAR2 was expressed in the proliferative/hypertrophic chondrocytes present within osteophytes. In PAR2−/− mice, osteophytes developed significantly less frequently but, when present, were smaller and of greater density; no osteosclerosis was observed in these mice up to day 28. The pattern of weight bearing was altered in PAR2−/− mice, suggesting reduced pain perception. The expression of hPAR2 in PAR2−/− mice recapitulated osteophyte formation and cartilage damage similar to that observed in WT mice. However, osteosclerosis was absent, consistent with lack of hPAR2 expression in subchondral bone. Conclusions This study clearly demonstrates PAR2 plays a critical role, via chondrocytes, in osteophyte development and subchondral bone changes, which occur prior to PAR2-mediated cartilage damage. The latter likely occurs independently of OA-related bone changes

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

Incidence and outcome of in-hospital cardiac arrest in the United Kingdom National Cardiac Arrest Audit

Objective To report the incidence, characteristics and outcome of adult in-hospital cardiac arrest in the United Kingdom (UK) National Cardiac Arrest Audit database. Methods A prospectively defined analysis of the UK National Cardiac Arrest Audit (NCAA) database. 144 acute hospitals contributed data relating to 22,628 patients aged 16 years or over receiving chest compressions and/or defibrillation and attended by a hospital-based resuscitation team in response to a 2222 call. The main outcome measures were incidence of adult in-hospital cardiac arrest and survival to hospital discharge. Results The overall incidence of adult in-hospital cardiac arrest was 1.6 per 1000 hospital admissions with a median across hospitals of 1.5 (interquartile range 1.2–2.2). Incidence varied seasonally, peaking in winter. Overall unadjusted survival to hospital discharge was 18.4%. The presenting rhythm was shockable (ventricular fibrillation or pulseless ventricular tachycardia) in 16.9% and non-shockable (asystole or pulseless electrical activity) in 72.3%; rates of survival to hospital discharge associated with these rhythms were 49.0% and 10.5%, respectively, but varied substantially across hospitals. Conclusions These first results from the NCAA database describing the current incidence and outcome of adult in-hospital cardiac arrest in UK hospitals will serve as a benchmark from which to assess the future impact of changes in service delivery, organisation and treatment for in-hospital cardiac arrest