Improving clinical prediction rules in acute kidney injury with the use of biomarkers of cell cycle arrest: a pilot study.

INTRODUCTION: Early recognition of patients developing acute kidney injury (AKI) is of considerable interest, we report the first use of a combination of a clinical prediction rule with a biomarker in emergent adult medical patients to improve AKI recognition. METHODS: Single-centre prospective pilot study of medical admissions without AKI identified as high risk by a clinical prediction rule. Urine samples were obtained and tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor binding protein 7 (IGFBP7) - biomarkers associated with cell cycle arrest, were measured. OUTCOME: Creatinine-based KDIGO hospital-acquired AKI (HA-AKI). RESULTS: Of 69 patients recruited, HA-AKI developed in 13% (n = 9), in whom biomarker values were higher (median 0.43 (interquartile range (IQR) 0.21-1.25) vs. 0.07 (0.03-0.16) in cases without (p = 0.008). Peak rise in creatinine was higher in biomarker positive cases (median 30 µmol/L (7-72) vs. 1 µmol/L (0-16), p = 0.002). AUROC was 0.78 (95% CI 0.57-0.98). At the suggested cut-off (0.3) sensitivity for predicting AKI was 78% (95% CI 40-97%), specificity 89% (78-95%), positive predictive value 50% (31-69%) and negative predictive value 96% (89-99%). DISCUSSION: Addition of a urinary biomarker allows exclusion of a significant number of patients identified to be at higher risk of AKI by a clinical prediction rule.

A validation of the National Early Warning Score to predict outcome in patients with COPD exacerbation.

BACKGROUND: The National Early Warning Score (NEWS), proposed as a standardised track and trigger system, may perform less well in acute exacerbation of COPD (AECOPD). This study externally validated NEWS and modifications (Chronic Respiratory Early Warning Score (CREWS) and Salford-NEWS) in AECOPD. METHODS: An observational cohort study (2012-2014, two UK acute medical units (AMUs)), compared AECOPD (2361 admissions, 942 individuals, International Statistical Classification of Diseases and Related Health Problems-10 J40-J44 codes) with AMU patients (37 109 admissions, 20 415 individuals). OUTCOME: In-hospital mortality prediction was done by admission NEWS, CREWS and Salford-NEWS assessed by discrimination (area under receiver operating characteristic curves (AUROCs)) and calibration (plots and Hosmer-Lemeshow (H-L) goodness-of-fit). RESULTS: Median admission NEWS in AECOPD was 4 (IQR 2-6) versus 1 (0-3) in AMUs (p≤0.001), despite mortality of 4.5% in both. AECOPD AUROCs were NEWS 0.74 (95% CI 0.66 to 0.82), CREWS 0.72 (0.63 to 0.80) and Salford-NEWS 0.62 (0.53 to 0.70). AMU NEWS AUROC was 0.77 (0.75 to 0.78). At threshold NEWS=5 for AECOPD (44% of admissions), positive predictive value (PPV) of death was 8% (5 to 11) and negative predictive value (NPV) was 98% (97 to 99) versus AMU patients PPV of 17% (16 to 19) and NPV of 97% (97 to 97). For NEWS in AECOPD H-L p value=0.202. CONCLUSION: This first validation of the NEWS in AECOPD found modest discrimination to predict mortality. Lower specificity of NEWS in patients with AECOPD versus other AMU patients reflects acute and chronic respiratory physiological disturbance (including hypoxia), with resultant low PPV at NEWS=5. CREWS and Salford-NEWS, adjusting for chronic hypoxia, increased the specificity and PPV but there was no gain in discrimination.

The Hospital to Home study (H2H): smartwatch technology-enabled rehabilitation following hip fracture in older adults, a feasibility non-randomised trial.

Introduction: Hip fractures are associated with significant morbidity and mortality. This study assessed the feasibility of smartwatches supporting rehabilitation post-surgical fixation. Methods: This UK-based non-randomised intervention study recruited patients who had sustained a hip fracture (age ≥65 and Abbreviated Mental Test Score ≥8/10), following surgical fixation, at one hospital to the intervention group, and at a second hospital to a usual care group. The intervention group received a smartwatch (Fitbit Charge 4) and app (CUSH Health©). Feasibility measures included retention and completion of outcome measures. Results: Between November 2020 and November 21, 66 participants were recruited (median age 78 (IQR 74-84)). The intervention cohort were younger, with no significant differences in frailty or multi-morbidity between the cohorts. Hospital stay was shorter in the intervention cohort (10 days (7-16) versus 12 (10-18), p=0.05). There were 15 falls-related readmissions in the control cohort, including 11 fractures, with none in the intervention cohort (p=0.016). In the intervention group, median daily step counts increased from 477 (320-697) in hospital, to 931 (505-1238) 1 week post-discharge, to 5,352 (3,552-7,944) at 12-weeks (p=0.001). Of the intervention cohort, 12 withdrew. Conclusion: This study found that smartwatch-supported rehabilitation was feasible in this cohort. A significant proportion of patients either chose not to participate or withdrew; such a decrease in participants must be addressed to avoid digital exclusion. Falls and fracture-related readmissions were more frequent at the control site compared with the intervention site.

Marathon running and cell-cycle arrest biomarkers of acute kidney injury.

OBJECTIVES: Endurance exercise is known to cause a rise in serum creatinine. It is not known to what extent this rise reflects renal stress and a potential acute kidney injury (AKI). Increases in Insulin Like Growth Factor Binding Protein 7 (IGFBP7) and Tissue Inhibitor of Metalloprotinases-2 (TIMP-2), urinary biomarkers of cell cycle arrest and renal stress, are associated with the development of AKI in clinical populations. DESIGN: Repeated measures study. METHODS: Runners were recruited at the 2019 Brighton Marathon (UK) and provided urine and blood samples at baseline, immediately post-race and 24 h post-race. Serum creatinine, urinary creatinine and urinary IGFBP7 and TIMP-2 were analysed from the samples. RESULTS: Seventy nine participants (23 females, 56 males), aged 43 ±â€¯10 yrs. (mean ±â€¯SD), finish time 243 ±â€¯40mins were included for analysis. Serum creatinine increased over the race by 40 ±â€¯26% (p < 0.001), TIMP-2 increased by 555 ±â€¯697% (p < 0.001) and IGFBP7 increased by 1094 ±â€¯1491% (p < 0.001) over the race. A subset of twenty-two participants supplied samples 24 h post-race, reporting values similar to baseline for all variables. CONCLUSIONS: This study is the first to report large rises in IGFBP7 and TIMP-2 following marathon running. This suggests that rises in creatinine are not fully explained by changes in production and clearance and marathon running induces a state of kidney stress and potential injury.

Agreement and validity of electronic patient self-triage (eTriage) with nurse triage in two UK emergency departments: a retrospective study.

BACKGROUND: Triage and redirection of patients to alternative care providers is one tool used to overcome the growing issue of crowding in emergency departments (EDs). Electronic patient self-triage (eTriage) may reduce waiting times and required face-to-face contact. There are limited studies into its efficacy, accuracy and validity in an ED setting. OBJECTIVES: The aim of this study was to assess the agreement and validity of eTriage with a reference standard of nurse face-to-face triage. A secondary aim was to assess the ability of both systems to predict high and low acuity outcomes. DESIGN: This was a retrospective study conducted over 8 months in two UK hospitals. Inclusion criteria were all ambulatory patients aged ≥18. All patients completed an eTriage and nurse-led triage using the Manchester Triage System (MTS). MAIN RESULTS: During the study period, 43 788 adult patients attended one of the two ED sites and 26 757 used eTriage. A total of 1424 patient episodes had no recorded MTS and were excluded from the study leaving 25 333 paired triages for the final cohort. Agreement between eTriage and nurse triage was low with a weighted Kappa coefficient of 0.14 (95% CI, 0.14-0.15) with an associated weak positive correlation (rs 0.321). Level of undertriage by eTriage compared with nurse triage was 10.1%, and overtriage was 59.2%. The sensitivity for prediction of high acuity outcomes was 88.5% (95% CI, 77.9-95.3%) for eTriage and 53.8% (95% CI 41.1-66.0%) for nurse MTS. The specificity for predicting low risk patients was 88.5% (95% CI, 87.4-89.5%) for eTriage and 80.6% (95% CI, 79.3-81.8%) for nurse MTS. CONCLUSION: Agreement and correlation of eTriage with the reference standard of nurse MTS was low; patients using eTriage tended to over triage when compared to the triage nurse. eTriage had a higher sensitivity for high acuity presentations and demonstrated similar specificity for low acuity presentations when compared to triage nurse MTS. Further work is necessary to validate eTriage as a potential tool for safe redirection of ED attenders to alternative care providers.

Virtual visiting and other technological adaptations for critical care.

Social distancing measures introduced in response to the COVID-19 pandemic resulted in an almost complete cessation of family bedside interaction, with negative effects on patients, families and staff. Here we report on measures introduced in response to this situation at the critical care unit in one hospital involving the use of videoconferencing technology. The solutions used also had the potential to be extended to clinical use, for example when seeking advice for colleagues, and to the provision of training.

COVID-19 recognition and digital risk stratification.

In the acute hospital setting the COVID-19 pandemic presents some unique challenges to acute patient care. These include accurate recognition of cases, confirmation of both testing requests and results, establishing patient acuity and alerting to deterioration. We report our experience introducing a digital COVID-19 assessment tool with an associated live dashboard at two acute NHS hospitals, enabling accurate hospital-level reporting alongside risk stratification.

The Role of Risk Prediction Models in Prevention and Management of AKI.

Acute kidney injury is a major health care problem. Improving recognition of those at risk and highlighting those who have developed AKI at an earlier stage remains a priority for research and clinical practice. Prediction models to risk-stratify patients and electronic alerts for AKI are two approaches that could address previously highlighted shortcomings in management and facilitate timely intervention. We describe and critique available prediction models and the effects of the use of AKI alerts on patient outcomes are reviewed. Finally, the potential for prediction models to enrich population subsets for other diagnostic approaches and potential research, including biomarkers of AKI, are discussed.

NEWS 2 - too little evidence to implement?

The Royal College of Physicians (RCP) recently published the National Early Warning Score 2 (NEWS2), aiming to improve safety for patients with hypercapnic respiratory failure by suggesting a separate oxygen saturation (SpO2) parameter scoring system for such patients. A previously published study of patients (n=2,361 admissions) with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) demonstrated alternative scoring systems at admission did not outperform the original NEWS. Applying NEWS2 SpO2 parameters to this previously described cohort would have resulted in 44% (n=27/62) of patients who scored ≥7 points on the original NEWS and subsequently died being placed in a lower call-out threshold. NEWS2 loses the benefits of a unified, standardised scoring system and we suggest prospective research in this area before applying this adjustment.

The ICE-AKI study: Impact analysis of a Clinical prediction rule and Electronic AKI alert in general medical patients.

BACKGROUND: Acute kidney injury (AKI) is assoicated with high mortality and measures to improve risk stratification and early identification have been urgently called for. This study investigated whether an electronic clinical prediction rule (CPR) combined with an AKI e-alert could reduce hospital-acquired AKI (HA-AKI) and improve associated outcomes. METHODS AND FINDINGS: A controlled before-and-after study included 30,295 acute medical admissions to two adult non-specialist hospital sites in the South of England (two ten-month time periods, 2014-16); all included patients stayed at least one night and had at least two serum creatinine tests. In the second period at the intervention site a CPR flagged those at risk of AKI and an alert was generated for those with AKI; both alerts incorporated care bundles. Patients were followed-up until death or hospital discharge. Primary outcome was change in incident HA-AKI. Secondary outcomes in those developing HA-AKI included: in-hospital mortality, AKI progression and escalation of care. On difference-in-differences analysis incidence of HA-AKI reduced (odds ratio [OR] 0.990, 95% CI 0.981-1.000, P = 0.049). In-hospital mortality in HA-AKI cases reduced on difference-in-differences analysis (OR 0.924, 95% CI 0.858-0.996, P = 0.038) and unadjusted analysis (27.46% pre vs 21.67% post, OR 0.731, 95% CI 0.560-0.954, P = 0.021). Mortality in those flagged by the CPR significantly reduced (14% pre vs 11% post intervention, P = 0.008). Outcomes for community-acquired AKI (CA-AKI) cases did not change. A number of process measures significantly improved at the intervention site. Limitations include lack of randomization, and generalizability will require future investigation. CONCLUSIONS: In acute medical admissions a multi-modal intervention, including an electronically integrated CPR alongside an e-alert for those developing HA-AKI improved in-hospital outcomes. CA-AKI outcomes were not affected. The study provides a template for investigations utilising electronically generated prediction modelling. Further studies should assess generalisability and cost effectiveness. TRIAL REGISTRATION: Clinicaltrials.org NCT03047382.

Correction: The ICE-AKI study: Impact analysis of a Clinical prediction rule and Electronic AKI alert in general medical patients.

[This corrects the article DOI: 10.1371/journal.pone.0200584.].

The use of veno-venous extracorporeal membrane oxygenation following thrombolysis for massive pulmonary embolism.

A 59-year-old man was diagnosed with a massive pulmonary embolism. Despite thrombolysis there were two episodes of cardiac arrest and following recovery of spontaneous circulation profound cardiorespiratory failure ensued. An extracorporeal membrane oxygenation retrieval team initiated veno-venous extracorporeal membrane oxygenation on site to facilitate transfer to the extracorporeal membrane oxygenation centre. An excellent outcome is reported in the short term. This represents one of the few published cases of veno-venous extracorporeal membrane oxygenation for a massive pulmonary embolism following thrombolysis.

Update on clinical trials in home mechanical ventilation.

Home mechanical ventilation (HMV) is an increasingly common intervention and is initiated for a range of pathological processes, including neuromuscular disease (NMD), chronic obstructive pulmonary disease (COPD) and obesity related respiratory failure. There have been important recent data published in this area, which helps to guide practice by indicating which populations may benefit from this intervention and the optimum method of setting up and controlling sleep disordered breathing. Recent superficially conflicting data has been published regarding HMV in COPD, with a trial in post-exacerbation patients suggesting no benefit, but in stable chronic hypercapnic patients suggesting a clear and sustained mortality benefit. The two studies are critiqued and the potential reasons for the differing results are discussed. Early and small trial data is frequently contradicted with larger randomised controlled trials and this has been the case with diaphragm pacing being shown to be potentially harmful in the latest data, confirming the importance of non-invasive ventilation (NIV) in NMD such as motor neurone disease. Advances in ventilator technology have so far appeared quicker than the clinical data to support their use; although small and often unblinded, the current data suggests equivalence to standard modes of NIV, but with potential comfort benefits that may enhance adherence. The indications for NIV have expanded since its inception, with an effort to treat sleep disordered breathing as a result of chronic heart failure (HF). The SERVE-HF trial has recently demonstrated no clear advantage to this technology and furthermore detected a potentially deleterious effect, with a worsening of all cause and cardiovascular mortality in the treated group compared to controls. The review serves to provide the reader with a critical review of recent advances in the field of sleep disordered breathing and HMV.

A comparison of the non-invasive ultrasonic cardiac output monitor (USCOM) with the oesophageal Doppler monitor during major abdominal surgery.

BACKGROUND: Perioperative interventions, targeted to increase global blood flow defined by explicit measured goals, reduce postoperative complications. Consequently, reliable non-invasive estimation of the cardiac output could have far-reaching benefit. METHODS: This study compared a non-invasive Doppler device - the ultrasonic cardiac output monitor (USCOM) - with the oesophageal Doppler monitor (ODM), on 25 patients during major abdominal surgery. Stroke volume was determined by USCOM (SVUSCOM) and ODM (SVODM) pre and post fluid challenges. RESULTS: A ≥ 10% change (Δ) SVUSCOM had a sensitivity of 94% and specificity of 88% to detect a ≥ 10% Δ SVODM; the area under the receiver operating curve was 0.94 (95% CI 0.90-0.99). Concordance was 98%, using an exclusion zone of <10% Δ SVODM. 135 measurements gave median SVUSCOM 80 ml (interquartile range 65-93 ml) and SVODM 86 ml (69-100 ml); mean bias was 5.9 ml (limits of agreement -20 to +30 ml) and percentage error 30%. CONCLUSIONS: Following fluid challenges SVUSCOM showed good concordance and accurately discriminated a change ≥10% in SVODM.

Measuring the cardiac output in acute emergency admissions: use of the non-invasive ultrasonic cardiac output monitor (USCOM) with determination of the learning curve and inter-rater reliability.

Traditionally, assessment of the cardiac output has been limited to theatre or the intensive care unit. However, non-invasive cardiac output estimation is now readily available, and its application may have wider benefit in the emergency setting. The non-invasive ultrasonic cardiac output monitor (USCOM) was investigated to determine its learning curve and inter-rater reliability. Four trainee operators each performed stroke volume measurements on 25 volunteers, compared to an experienced operator pre- and post-passive leg raise. Inter-rater reliability was then assessed on 24 acute emergency in-patients. Mean percentage difference in stroke volume decreased from 19% (95% confidence intervals 14-23) across volunteers 1-5, to 6% (4-8) for the last 5 volunteers scanned. Consequently, on acute emergency in-patients, excellent inter-rater reliability (Lin's concordance correlation coefficient (ρc) 0.96 (0.92-0.98)) and agreement of a change ≥10% in stroke volume following passive leg raise on 23/24 cases were found. Following a training period of less than 5 h, USCOM stroke volume measurements demonstrated excellent inter-rater reliability.

Respiratory management of the obese patient undergoing surgery.

As a reflection of the increasing global incidence of obesity, there has been a corresponding rise in the proportion of obese patients undergoing major surgery. This review reports the physiological effect of these changes in body composition on the respiratory system and discusses the clinical approach required to maximize safety and minimize the risk to the patient. The changes in respiratory system compliance and lung volumes, which can adversely affect pulmonary gas exchange, combined with upper airways obstruction and sleep-disordered breathing need to be considered carefully in the peri-operative period. Indeed, these challenges in the obese patient have led to a clear focus on the clinical management strategy and development of peri-operative pathways, including pre-operative risk assessment, patient positioning at induction and under anesthesia, modified approach to intraoperative ventilation and the peri-operative use of non-invasive ventilation (NIV) and continuous positive airways pressure.