The cost-effectiveness of procalcitonin for guiding antibiotic prescribing in individuals hospitalized with COVID-19: part of the PEACH study.

BACKGROUND: Many hospitals introduced procalcitonin (PCT) testing to help diagnose bacterial coinfection in individuals with COVID-19, and guide antibiotic decision-making during the COVID-19 pandemic in the UK. OBJECTIVES: Evaluating cost-effectiveness of using PCT to guide antibiotic decisions in individuals hospitalized with COVID-19, as part of a wider research programme. METHODS: Retrospective individual-level data on patients hospitalized with COVID-19 were collected from 11 NHS acute hospital Trusts and Health Boards from England and Wales, which varied in their use of baseline PCT testing during the first COVID-19 pandemic wave. A matched analysis (part of a wider analysis reported elsewhere) created groups of patients whose PCT was/was not tested at baseline. A model was created with combined decision tree/Markov phases, parameterized with quality-of-life/unit cost estimates from the literature, and used to estimate costs and quality-adjusted life years (QALYs). Cost-effectiveness was judged at a £20 000/QALY threshold. Uncertainty was characterized using bootstrapping. RESULTS: People who had baseline PCT testing had shorter general ward/ICU stays and spent less time on antibiotics, though with overlap between the groups' 95% CIs. Those with baseline PCT testing accrued more QALYs (8.76 versus 8.62) and lower costs (£9830 versus £10 700). The point estimate was baseline PCT testing being dominant over no baseline testing, though with uncertainty: the probability of cost-effectiveness was 0.579 with a 1 year horizon and 0.872 with a lifetime horizon. CONCLUSIONS: Using PCT to guide antibiotic therapy in individuals hospitalized with COVID-19 is more likely to be cost-effective than not, albeit with uncertainty.

Modifiable risk factors for post-operative delirium in older adults undergoing major non-cardiac elective surgery: a multi-centre, trainee delivered observational cohort feasibility study and trainee survey.

BACKGROUND: Post-operative delirium (POD) is an acute brain failure which may occur following major surgery, with serious implications for participants and caregivers. Evidence regarding optimal anaesthetic management for older participants at higher risk of POD is conflicting. We conducted a feasibility study of our protocol in 5 centres to guide sample size estimation and inform future recruitment strategies for a larger cohort study. METHODS: Participants aged over 65 and scheduled for major surgery were recruited. They were assessed pre-operatively for delirium, cognitive impairment, depression, comorbidity, activity levels and alcohol use. Details of management during surgery, all medications and complications were recorded by a trainee-led research team. Participants were assessed for delirium in the immediate recovery period and then on post-operative days 1-4 using the 4 question attention test (4AT) with complications assessed at day 4 using the post-operative morbidity survey (POMS). Primary outcomes were the incident rates of POD. Secondary outcomes were number of eligible patients, recruitment rates and retention rates throughout the study, time required for data collection, preoperative risk factors assessment and daily postoperative delirium assessments. Also to assess the added value of employing the regional trainee research network (INCARNNET) to deliver the study. Specifically, what proportion of patient consent, data collection and post-operative testing is performed by anaesthesia trainees from this group, especially the success of weekend delirium assessment by trainees? A survey was completed at the end of the study by the trainees involved regarding their involvement in the study. RESULTS: Ninety-five participants were recruited, of whom 93 completed the study. Overall, POD occurred in 9 patients. Of these, three were detected in recovery and six on post-op days 1-4. Median length of stay was 6 days. Recruitment rates were high in all but one site. 59 (62%) participants were consented by trainees and 189 (63%) of post op delirium assessments were performed by trainees. A total of six patients declined the study (in a follow up survey of trainees). Pre-existing cognitive impairment, depression and problem drinking were detected in 4(4.3%), 3(3.2%) and 5(5.37%) participants, respectively. Co-morbidity was common with 55(59%) in class three or four of the geriatric index of morbidity. Overall, from a total of 641 data points, levels of missing data were as follows, site A = 9.3%, B = 13.5%, C = 15.4%, D = 10.9%, E = 11.1% (data could not be completed retrospectively). CONCLUSIONS: A multi-centre observational cohort study of delirium carried out by UK trainee anaesthetists is feasible. Patients are content to undergo day of surgery consent and multiple short questionnaires pre-operatively. Proposed data, especially pharmacological, should be carefully considered for their relevance to modifiable mechanisms that can lead to POD. Future research to enable prognostic modelling of POD should involve large scale cohort studies of enriched populations to capture a higher POD incidence. POD remains a common complication in older persons undergoing major surgery in the UK and studies of interventions are urgently needed. TRIAL REGISTRATION: All methods were carried out in accordance with relevant guidelines and regulations. The study was retrospectively registered with ISRCTN94663125 on 07/02/2018.

Reducing the incidence of pressure ulcers in critical care units: a 4-year quality improvement.

QUALITY PROBLEM: Critical care patients often have several risk factors for pressure ulceration and implementing prevention interventions have been shown to decrease risk. INITIAL ASSESSMENT: We identified a high incidence of pressure ulcers in the four adult critical care units in our organization. Therefore, avoiding pressure ulceration was an important quality priority. CHOICE OF SOLUTION: We undertook a quality improvement programme aimed at reducing the incidence of pressure ulceration using an evidence-based bundle approach. IMPLEMENTATION: A bundle of technical and non-technical interventions were implemented supported by clinical leadership on each unit. Important components were evidence appraisals; changes to mattresses; focussed risk assessment alongside mandating patients at very high risk to be repositioned two hourly; and staff training to increase awareness of how to prevent pressure ulcers. EVALUATION: Pressure ulcer numbers, incidence and categories were collected continuously and monitored monthly by unit staff. Pressure ulcer rates reduced significantly from 8.08/100 patient admissions to 2.97/100 patient admissions, an overall relative rate reduction of 63% over 4 years. The greatest reduction was seen in the most severe category of pressure ulceration. The average estimated cost saving was £2.6 million (range £2.1-£3.1). LESSONS LEARNED: A quality improvement programme including technical and non-technical interventions, data feedback to staff and clinical leadership was associated with a sustained reduction in the incidence of pressure ulceration in the critically ill. Strategies used in this programme may be transferable to other critical care units to bring more widespread patient benefit.

Daily sedation interruption versus no daily sedation interruption for critically ill adult patients requiring invasive mechanical ventilation.

BACKGROUND: Daily sedation interruption (DSI) is thought to limit drug bioaccumulation, promote a more awake state, and thereby reduce the duration of mechanical ventilation. Available evidence has shown DSI to either reduce, not alter, or prolong the duration of mechanical ventilation. OBJECTIVES: The primary objective of this review was to compare the total duration of invasive mechanical ventilation for critically ill adult patients requiring intravenous sedation who were managed with DSI versus those with no DSI. Our other objectives were to determine whether DSI influenced mortality, intensive care unit (ICU) and hospital lengths of stay, adverse events, the total doses of sedative drug administered, and quality of life. SEARCH METHODS: We searched, from database inception to February 2014, the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2014, Issue 1); MEDLINE (OvidSP); EMBASE (OvidSP); CINAHL (EBSCOhost); Latin American and Caribbean Health Sciences Literature (LILACS); Web of Science Science Citation Index; Database of Abstracts of Reviews of Effects (DARE); the Health Technology Assessment Database (HTA Database); trial registration websites, and reference lists of relevant articles. We did not apply language restrictions. The reference lists of all retrieved articles were reviewed for additional, potentially relevant studies. SELECTION CRITERIA: We included randomized controlled trials that compared DSI with sedation strategies that did not include DSI in mechanically ventilated, critically ill adults. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and three authors assessed risk of bias. We contacted study authors for additional information as required. We combined data in forest plots using random-effects modelling. A priori subgroups and sensitivity analyses were performed. MAIN RESULTS: Nine trials were used in the analysis (n = 1282 patients). These trials were found to be predominantly at low risk of bias. We did not find strong evidence of an effect of DSI on the total duration of ventilation. Pooled data from nine trials demonstrated a 13% reduction in the geometric mean, with relatively wide confidence intervals (CI) indicating imprecision (95% CI 26% reduction to 2% increase, moderate quality evidence). Similarly, we did not find strong evidence of an effect on ICU length of stay (-10%, 95% CI -20% to 3%, n = 9 trials, moderate quality evidence) or hospital length of stay (-6%, 95% CI -18% to 8%, n = 8 trials, moderate quality evidence). Heterogeneity for these three outcomes was moderate and statistically significant. The risk ratio for ICU mortality was 0.96 (95% CI 0.77 to 1.21, n = 7 trials, moderate quality evidence), for rate of accidental endotracheal tube removal 1.07 (95% CI 0.55 to 2.12, n = 6 trials, moderate quality evidence), for catheter removal 1.48 (95% CI 0.76 to 2.90, n = 4 trials), and for incidence of new onset delirium 1.02 (95% CI 0.91 to 1.13, n = 3 trials, moderate quality evidence). Differences in the doses of any drug used or quality of life score (Short Form (SF)-36) did not reach statistical significance. Tracheostomy was performed less frequently in the DSI group (RR 0.73, 95% CI 0.57 to 0.92, n = 6 trials, moderate quality evidence). Sensitivity analysis of unlogged data resulted in similar findings. Post hoc analysis to further explain heterogeneity, based on study country of origin, showed that studies conducted in North America resulted in a reduction in the duration of mechanical ventilation (-21%, 95% CI -33% to -5%, n = 5 trials). AUTHORS' CONCLUSIONS: We have not found strong evidence that DSI alters the duration of mechanical ventilation, mortality, length of ICU or hospital stay, adverse event rates, drug consumption, or quality of life for critically ill adults receiving mechanical ventilation compared to sedation strategies that do not include DSI. We advise that caution should be applied when interpreting and applying the findings as the overall effect of treatment is always < 1 and the upper limit of the CI is only marginally higher than the no-effect line. These results should be considered unstable rather than negative for DSI given the statistical and clinical heterogeneity identified in the included trials.

Perioperative blood transfusion in major abdominal cancer surgery: a multi-centre service evaluation and national survey.

Background: Anaemia is associated with complications and death after surgery. Perioperative red-cell transfusion triggers are not well defined in patients having oncological surgery, or with cardiovascular disease. Methods: We carried out a prospective multicentre cohort study and a clinician survey of UK transfusion practice in adult patients undergoing surgery for abdominal malignancy. The primary outcome was red cell transfusion. Secondary outcomes were transfusion trigger haemoglobin, incidence of complications, length of hospital stay, and acute hospital mortality. Results: In this prospective cohort study, data were collected on 412 patients undergoing surgery for intrabdominal malignancy in 14 NHS hospitals. Twenty-two (5.2%) patients received preoperative, 42 (10.2%) intraoperative, and 52 (12.2%) postoperative red blood cell transfusion. The mean postoperative transfusion trigger was 75.3 g L-1, and the mean number of units of red blood cells transfused was 1.5 (standard deviation, 1.1). Seventeen (4.0%) patients had a documented postoperative troponin elevation. Five (1.2%) patients died within 30 days of surgery. In the survey, 117 clinicians submitted complete responses, of whom 62 (53%) indicated that a transfusion threshold of 70 g L-1 was appropriate: however, this decreased to six (5.1%) if there was evidence of recent cardiac ischaemia. There were 100 (86%) respondents who indicated equipoise for a trial of restrictive vs liberal transfusion, decreasing to 56% if there was coexisting cardiovascular disease. Conclusions: Many patients having oncological surgery receive red cell transfusion, the majority being given postoperatively. Restrictive transfusion practice is generally followed; however, variability exists especially in cardiovascular disease. Equipoise exists for a study of transfusion thresholds in this group.

Role of immunosuppression in an antibiotic stewardship intervention and its association with clinical outcomes and antibiotic use: protocol for an observational study (RISC-sepsis).

INTRODUCTION: Sepsis is characterised by a dysregulated immune response to infection, with exaggerated pro-inflammatory and anti-inflammatory responses. A predominant immunosuppressive profile affecting both innate and adaptive immune responses is associated with increased hospital-acquired infection and reduced infection-free survival. While hospital-acquired infection leads to additional antibiotic use, the role of the immunosuppressive phenotype in guiding complex decisions, such as those affecting antibiotic stewardship, is uncertain. This study is a mechanistic substudy embedded within a multicentre clinical and cost-effectiveness trial of biomarker-guided antibiotic stewardship. This mechanistic study aims to determine the effect of sepsis-associated immunosuppression on the trial outcome measures. METHODS AND ANALYSIS: RISC-sepsis is a prospective, multicentre, exploratory, observational study embedded within the ADAPT-sepsis trial. A subgroup of 180 participants with antibiotics commenced for suspected sepsis, enrolled in the ADAPT-sepsis trial, will be recruited. Blood samples will be collected on alternate days until day 7. At each time point, blood will be collected for flow cytometric analysis into cell preservation tubes. Immunophenotyping will be performed at a central testing hub by flow cytometry. The primary outcome measures are monocyte human leucocyte antigen-DR; neutrophil CD88; programmed cell death-1 on monocytes, neutrophils and T lymphocytes and the percentage of regulatory T cells. Secondary outcome measures will link to trial outcomes from the ADAPT-sepsis trial including antibiotic days; occurrence of hospital-acquired infection and length of ICU-stay and hospital-stay. ETHICS AND DISSEMINATION: Ethical approval has been granted (IRAS 209815) and RISC-sepsis is registered with the ISRCTN (86837685). Study results will be disseminated by peer-reviewed publications, presentations at scientific meetings and via patient and public participation groups and social media.

Procalcitonin Evaluation of Antibiotic Use in COVID-19 Hospitalised Patients (PEACH): Protocol for a Retrospective Observational Study.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel virus responsible for the coronavirus disease 2019 (COVID-19) pandemic. Although COVID-19 is a viral illness, many patients admitted to hospital are prescribed antibiotics, based on concerns that COVID-19 patients may experience secondary bacterial infections, and the assumption that they may respond well to antibiotic therapy. This has led to an increase in antibiotic use for some hospitalised patients at a time when accumulating antibiotic resistance is a major global threat to health. Procalcitonin (PCT) is an inflammatory marker measured in blood samples and widely recommended to help diagnose bacterial infections and guide antibiotic treatment. The PEACH study will compare patient outcomes from English and Welsh hospitals that used PCT testing during the first wave of the COVID-19 pandemic with those from hospitals not using PCT. It will help to determine whether, and how, PCT testing should be used in the NHS in future waves of COVID-19 to protect patients from antibiotic overuse. PEACH is a retrospective observational cohort study using patient-level clinical data from acute hospital Trusts and Health Boards in England and Wales. The primary objective is to measure the difference in antibiotic use between COVID-19 patients who did or did not have PCT testing at the time of diagnosis. Secondary objectives include measuring differences in length of stay, mortality, intensive care unit admission, and resistant bacterial infections between these groups.

Are treatment effects consistent with hypothesized mechanisms of action proposed for postoperative delirium interventions? Reanalysis of systematic reviews.

Aim: Postoperative delirium (POD) is associated with increased morbidity and is poorly understood. The aim of this review was to identify putative mechanisms through re-analysis of randomized trials on treatment or prevention of POD. Materials & methods: A systematic review was performed to identify systematic reviews of treatments for POD. Constituent randomized controlled trials were identified, and interventions were grouped according to hypothesized mechanisms of action. Effects were meta-analyzed by hypothesized mechanism and timing of intervention. Results: A total of 116 randomized controlled trials described 47 individual interventions for POD, with nine mechanisms identified. The largest effects were observed for postoperative inflammation reduction, and preoperative reinforcement of sleep-wake cycle. Conclusion: This approach identifies treatments focused on mechanisms of action that may be front runners for future trials and interventions.

Use of Procalcitonin during the First Wave of COVID-19 in the Acute NHS Hospitals: A Retrospective Observational Study.

A minority of patients presenting to hospital with COVID-19 have bacterial co-infection. Procalcitonin testing may help identify patients for whom antibiotics should be prescribed or withheld. This study describes the use of procalcitonin in English and Welsh hospitals during the first wave of the COVID-19 pandemic. A web-based survey of antimicrobial leads gathered data about the use of procalcitonin testing. Responses were received from 148/151 (98%) eligible hospitals. During the first wave of the COVID-19 pandemic, there was widespread introduction and expansion of PCT use in NHS hospitals. The number of hospitals using PCT in emergency/acute admissions rose from 17 (11%) to 74/146 (50.7%) and use in Intensive Care Units (ICU) increased from 70 (47.6%) to 124/147 (84.4%). This increase happened predominantly in March and April 2020, preceding NICE guidance. Approximately half of hospitals used PCT as a single test to guide decisions to discontinue antibiotics and half used repeated measurements. There was marked variation in the thresholds used for empiric antibiotic cessation and guidance about interpretation of values. Procalcitonin testing has been widely adopted in the NHS during the COVID-19 pandemic in an unevidenced, heterogeneous way and in conflict with relevant NICE guidance. Further research is needed urgently that assesses the impact of this change on antibiotic prescribing and patient safety.