Surviving severe COVID-19: Interviews with patients, informal carers and health professionals.

BACKGROUND: The COVID-19 pandemic has been associated with an unprecedented number of critical care survivors. Their experiences through illness and recovery are likely to be complex, but little is known about how best to support them. AIM: This study aimed to explore experiences of illness and recovery from the perspective of survivors, their relatives and professionals involved in their care. STUDY DESIGN: In-depth qualitative interviews were conducted with three stakeholder groups during the first wave of the pandemic. A total of 23 participants (12 professionals, 6 survivors and 5 relatives) were recruited from 5 acute hospitals in England and interviewed by telephone or video call. Data analysis followed the principles of Reflexive Thematic Analysis. FINDINGS: Three themes were generated from their interview data: (1) Deteriorating fast-a downhill journey from symptom onset to critical care; (2) Facing a new virus in a hospital-a remote place; and (3) Returning home as a survivor, maintaining normality and recovering slowly. CONCLUSIONS: Our findings highlight challenges in accessing care and communication between patients, hospital staff and relatives. Following hospital discharge, patients adopted a reframed 'survivor identity' to cope with their experience of illness and slow recovery process. The concept of survivorship in this patient group may be beneficial to promote and explore further. RELEVANCE TO CLINICAL PRACTICE: All efforts should be made to continue to improve communication between patients, relatives and health professionals during critical care admissions, particularly while hospital visits are restricted. Adapting to life after critical illness may be more challenging while health services are restricted by the impacts of the pandemic. It may be beneficial to promote the concept of survivorship, following admission to critical care due to severe COVID-19.

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.

An external validation study of a clinical prediction rule for medical patients with suspected bacteraemia.

OBJECTIVE: The objective of this study was to externally validate a clinical prediction rule (CPR)-the 'Shapiro criteria'-to predict bacteraemia in an acute medical unit (AMU). METHODS: Prospectively collected data, retrospectively evaluated over 11 months in an AMU in the UK. From 4810 admissions, 635 patients (13%) had blood cultures (BCs) performed. The 100 cases of true bacteraemia were compared with a randomly selected sample of 100 control cases where BCs were sterile. RESULTS: To predict bacteraemia (at a cut-off score of two points), the Shapiro criteria had a sensitivity of 97% (95% CIs 91% to 99%), specificity 37% (28% to 47%), positive likelihood ratio 1.54 (1.3 to 1.8) and a negative likelihood ratio of 0.08 (0.03 to 0.25). The area under the receiver operating curve was 0.80 (0.74 to 0.86), and the Hosmer-Lemeshow p value was 0.45. CONCLUSIONS: A cut-off score of two points on the Shapiro criteria had high sensitivity to predict bacteraemia in a study of acute general medical admissions. Application of the rule in patients being considered for a BC could identify those at low risk of bacteraemia. Though the model demonstrated good discrimination, the lengthy number of variables (13) and difficulty automating the CPR may limit its use.

Identifying the patient at risk of acute kidney injury: a predictive scoring system for the development of acute kidney injury in acute medical patients.

BACKGROUND: Acute kidney injury (AKI) in hospitalized patients has significant implications in terms of morbidity and mortality, length of hospital stay and associated costs. To date, no interventions are proven to prevent the development of AKI but this is hampered in part by the lack of early recognition of patients at risk. We aimed to determine whether a simple system could be devised from both physiological and demographic data in order to identify individuals at increased risk from the development of inpatient AKI. METHOD: Our observational, population-based single-centred study took place in an 870-bed associated university hospital. All patients admitted to the acute medical admissions unit on the Worthing site of the Western Sussex Hospitals Trust during the study period were included. RESULTS: Multivariate logistic regression analysis demonstrated that age, respiratory rate and disturbed consciousness together with a history of chronic kidney disease, diabetes mellitus, congestive cardiac failure and liver disease were associated with an increased risk of developing AKI within 7 days of admission. We derived a simple scoring system to identify acute medical patients at greater risk of developing AKI. CONCLUSIONS: The incidence of AKI complicating inpatient admissions remains high, however with the application of the derived AKI prediction score it is hoped that early recognition will translate to improved outcomes.

1-year outcomes of patients admitted to critical care with treatment limitations: A dual-centre observational study.

Intensivists are increasingly involved in the care of frail patients as our population ages. Careful person-orientated, individualised decision-making, weighing benefits and harms of critical care are required in such situations. Few studies have reported outcomes of patients with treatment limitations. This dual-centre observational study reports outcomes of 3781 patients (2018-20). At least one treatment limitation was set at admission in 13% (n = 486). Of this group 55% survived to hospital discharge, of whom 69% were discharged home; 39% remained alive at 1 year. These findings provide objective data to support clinicians, patients and relatives in shared decision-making. Future multi-centre work could explore how best to identify those most likely to benefit from critical care.

Feasibility of an electronic fluid balance chart to detect and understand the significance of oliguric acute kidney injury in a general ward setting: a prospective observational cohort study.

Background: Outside critical care environments, few studies have assessed the significance of oliguric acute kidney injury (AKI). This study investigated the feasibility of an electronic fluid balance chart to diagnose oliguric AKI. Data were used to determine if oliguric AKI was met earlier than creatinine AKI and to establish outcomes of those who developed AKI. Methods: A single-centre prospective cohort study investigated Kidney Disease Improving Global Outcomes oliguric and creatinine AKI criteria on general surgical wards. Results: 2,149 cases were included in the analysis. Incidence of oliguric AKI was significantly higher than creatinine criteria (73 versus 10.1%) and detection occurred earlier (2.1 versus 6.1 days, p<0.05). In cases with oliguric AKI, 8.1% also developed AKI by creatinine criteria. In cases not meeting oliguric AKI criteria, fewer cases developed creatinine AKI, as compared to those meeting oliguric AKI criteria (7.9% versus 11%, p=0.043). There was a high incidence of missing data. Conclusions: Oliguric AKI was met in a high proportion of cases and occurred earlier than by changes in creatinine. Barriers to consistency of recording must be addressed before oliguric criteria could be implemented in clinical practice.

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.

Responding to the deteriorating patient: The rationale for treatment escalation plans.

A Treatment Escalation Plan (TEP) is a communication tool designed to improve quality of care in hospital, particularly if patients deteriorate. The aims are to reduce variation caused by discontinuity of care; avoid harms caused by inappropriate treatment and promote patients' priorities and preferences. The TEP is based on the goals of treatment - 'What are we trying to achieve?' The goals take account of the context of acute illness, the consequences of interventions and discussion with the patient. They should reflect a shift away from 'fix-it' medicine to what is realistic and pragmatic. A TEP has three escalation categories: full escalation, selected appropriate treatments and palliative/supportive care. Other appropriate/inappropriate treatments are also recorded. Treatment Escalation Plans are associated with significant reductions in intensive care unit (ICU) admissions, non-beneficial interventions, harms and complaints. Treatment Escalation Plans contribute to staff well-being by reducing uncertainty. Successful implementation requires training and education in medical decision-making and communication skills.

Clinical decision-making in older adults following emergency admission to hospital. Derivation and validation of a risk stratification score: OPERA.

OBJECTIVES OF THE STUDY: Demographic changes alongside medical advances have resulted in older adults accounting for an increasing proportion of emergency hospital admissions. Current measures of illness severity, limited to physiological parameters, have shortcomings in this cohort, partly due to patient complexity. This study aimed to derive and validate a risk score for acutely unwell older adults which may enhance risk stratification and support clinical decision-making. METHODS: Data was collected from emergency admissions in patients ≥65 years from two UK general hospitals (April 2017- April 2018). Variables underwent regression analysis for in-hospital mortality and independent predictors were used to create a risk score. Performance was assessed on external validation. Secondary outcomes included seven-day mortality and extended hospital stay. RESULTS: Derivation (n = 8,974) and validation (n = 8,391) cohorts were analysed. The model included the National Early Warning Score 2 (NEWS2), clinical frailty scale (CFS), acute kidney injury, age, sex, and Malnutrition Universal Screening Tool. For mortality, area under the curve for the model was 0.79 (95% CI 0.78-0.80), superior to NEWS2 0.65 (0.62-0.67) and CFS 0.76 (0.74-0.77) (P<0.0001). Risk groups predicted prolonged hospital stay: the highest risk group had an odds ratio of 9.7 (5.8-16.1) to stay >30 days. CONCLUSIONS: Our simple validated model (Older Persons' Emergency Risk Assessment [OPERA] score) predicts in-hospital mortality and prolonged length of stay and could be easily integrated into electronic hospital systems, enabling automatic digital generation of risk stratification within hours of admission. Future studies may validate the OPERA score in external populations and consider an impact analysis.

Analgesia requirements after interscalene block for shoulder arthroscopy: the 5 days following surgery.

INTRODUCTION: Excellent initial post-operative analgesia for patients undergoing arthroscopic shoulder surgery can be provided with a single-shot interscalene brachial plexus block. However there have been concerns that when the block wears off, patients may experience pain and this may occur at home. Some investigators have advocated the use of continuous ambulatory local anaesthetic infusions following hospital discharge. We prospectively studied pain scores, analgesic requirements and satisfaction of patients at home in the first 5 days following arthroscopic shoulder surgery to see whether continuous infusion would be of benefit. RESULTS: Fifteen percent of patients experienced severe pain at some time over the first 3 days, and this percentage decreased to 7% by day 5. However 97% of our patients were satisfied with their post-operative oral analgesia management and less than 5% contacted their GP for further analgesia issues. Over 80% of our patients required only simple analgesics following hospital discharge. CONCLUSION: Post-operative continuous ambulatory local anaesthetic infusions may not be justified following this intermediate magnitude of surgery.

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.

Persistently elevated early warning scores and lactate identifies patients at high risk of mortality in suspected sepsis.

OBJECTIVE: In the UK, the National Early Warning Score (NEWS) is recommended as part of screening for suspicion of sepsis. Is a change in NEWS a better predictor of mortality than an isolated score when screening for suspicion of sepsis?. METHODS: A prospectively gathered cohort of 1233 adults brought in by ambulance to two UK nonspecialist hospitals, with suspicion of sepsis at emergency department (ED) triage (2015-2017) was analysed. Associations with 30-day mortality and ICU admission rate were compared between groups with an isolated NEWS ≥5 points prehospital and those with persistently elevated NEWS prehospital, in ED and at ward admission. The effect of adding the ED (venous or arterial) lactate was also assessed. RESULTS: Mortality increased if the NEWS persisted ≥5 at ED arrival 22.1% vs. 10.2% [odds ratio (OR) 2.5 (1.6-4.0); P < 0.001]. Adding an ED lactate ≥2 mmol/L was associated with an increase in mortality greater than for NEWS alone [32.2% vs. 13.3%, OR 3.1 (2.2-4.1); P < 0.001], and increased ICU admission [13.9% vs. 3.7%, OR 3.1 (2.2-4.3); P < 0.001]. If NEWS remained ≥5 at ward admission (predominantly within 4 h of ED arrival), mortality was 32.1% vs. 14.3%, [OR 2.8 (2.1-3.9); P < 0.001] and still higher if accompanied by an elevated ED lactate [42.1% vs. 16.4%, OR 3.7 (2.6-5.3); P < 0.001]. CONCLUSION: Persistently elevated NEWS, from prehospital through the ED to the time of ward admission, combined with an elevated ED lactate identifies patients with suspicion of sepsis at highest risk of in-hospital mortality.

Determination of a potent urokinase-type plasminogen activator, UK-356,202, in plasma at pg/mL levels using column-switching HPLC and fluorescence detection.

A rapid, sensitive and selective method using column-switching HPLC with fluorescence detection has been developed for the determination of UK-356,202, a potent urokinase-type plasminogen activator, in human plasma. A structural isomer of UK-356,202 is used as an internal standard. The lower limit of quantification is 20 pg/mL and the method is linear over a 100-fold concentration range. UK-356,202 is extracted from plasma simply through the removal of proteins by precipitation with acetonitrile. The HPLC system comprises three columns and the cycle time is 9.5 min per sample. The eluate from the extraction column is heart-cut onto a trace enrichment cartridge which is then back-flushed onto a narrow-bore Supelco ABZ+ Plus analytical column. The method has been used to analyze many thousands of samples from clinical and toxicological studies support. Its ruggedness is demonstrated by the use of a single extraction column for the analysis of over 1200 clinical samples.

Recently published papers: a series of negative results.

Studies with negative results rarely hit the headlines. But the results are often just as important as the positive ones. A number of 'negative headline' studies are looked at in this review: intensive insulin therapy regime, thrombolysis in cardiac arrest, the effects of nutritional guidelines and rapid response outreach teams.

Recently published papers: Renal replacement therapy: which route and how much? Intracerebral haematomas: does the size matter? Beta blockers and steroids: will we ever know?

Femoral access for renal replacement therapy appears to have a similar infection rate to jugular access. High-intensity renal support does not seem to improve mortality or length of hospital stay. Acute kidney injury as defined by Acute Kidney Injury Network predicts increased hospital mortality. Recombinant factor VIIa reduces growth of volume of intracerebral haematoma but does not affect clinical outcome. Sustained released metoprolol reduces perioperative cardiac events in non-cardiac surgery but leads to more deaths and strokes. Steroids are probably not beneficial in either children with non-Haemophilus influenzae type b bacterial meningitis, or in prophylaxis of acute respiratory distress syndrome (ARDS), but could be beneficial in the treatment of ARDS.

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.].

Recently published papers: predictors, pressors and poietins.

Simple, sensitive and specific predictors of mortality in the critically ill remain elusive goals, and brain natriuretic peptide and venous lactate are the subjects of recent studies. The role of vasopressin in sepsis continues to be the focus of much research interest. Dose ranging studies, potential adverse effects, and selective V1 agonists are discussed below in recent trials. Finally the use of erythropoietin in the critically ill continues to be studied but many continue to urge caution for widespread use outside of clinical trials.