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Background: Ventilator-associated pneumonia is the most common intensive care unit (ICU)-acquired infection, yet accurate diagnosis remains difficult, leading to overuse of antibiotics. Low concentrations of IL-1β and IL-8 in bronchoalveolar lavage fluid have been validated as effective markers for exclusion of ventilator-associated pneumonia. The VAPrapid2 trial aimed to determine whether measurement of bronchoalveolar lavage fluid IL-1β and IL-8 could effectively and safely improve antibiotic stewardship in patients with clinically suspected ventilator-associated pneumonia.Methods: VAPrapid2 was a multicentre, randomised controlled trial in patients admitted to 24 ICUs from 17 National Health Service hospital trusts across England, Scotland, and Northern Ireland. Patients were screened for eligibility and included if they were 18 years or older, intubated and mechanically ventilated for at least 48 h, and had suspected ventilator-associated pneumonia. Patients were randomly assigned (1:1) to biomarker-guided recommendation on antibiotics (intervention group) or routine use of antibiotics (control group) using a web-based randomisation service hosted by Newcastle Clinical Trials Unit. Patients were randomised using randomly permuted blocks of size four and six and stratified by site, with allocation concealment. Clinicians were masked to patient assignment for an initial period until biomarker results were reported. Bronchoalveolar lavage was done in all patients, with concentrations of IL-1β and IL-8 rapidly determined in bronchoalveolar lavage fluid from patients randomised to the biomarker-based antibiotic recommendation group. If concentrations were below a previously validated cutoff, clinicians were advised that ventilator-associated pneumonia was unlikely and to consider discontinuing antibiotics. Patients in the routine use of antibiotics group received antibiotics according to usual practice at sites. Microbiology was done on bronchoalveolar lavage fluid from all patients and ventilator-associated pneumonia was confirmed by at least 104 colony forming units per mL of bronchoalveolar lavage fluid. The primary outcome was the distribution of antibiotic-free days in the 7 days following bronchoalveolar lavage. Data were analysed on an intention-to-treat basis, with an additional per-protocol analysis that excluded patients randomly assigned to the intervention group who defaulted to routine use of antibiotics because of failure to return an adequate biomarker result. An embedded process evaluation assessed factors influencing trial adoption, recruitment, and decision making. This study is registered with ISRCTN, ISRCTN65937227, and ClinicalTrials.gov, NCT01972425.Findings: Between Nov 6, 2013, and Sept 13, 2016, 360 patients were screened for inclusion in the study. 146 patients were ineligible, leaving 214 who were recruited to the study. Four patients were excluded before randomisation, meaning that 210 patients were randomly assigned to biomarker-guided recommendation on antibiotics (n=104) or routine use of antibiotics (n=106). One patient in the biomarker-guided recommendation group was withdrawn by the clinical team before bronchoscopy and so was excluded from the intention-to-treat analysis. We found no significant difference in the primary outcome of the distribution of antibiotic-free days in the 7 days following bronchoalveolar lavage in the intention-to-treat analysis (p=0·58). Bronchoalveolar lavage was associated with a small and transient increase in oxygen requirements. Established prescribing practices, reluctance for bronchoalveolar lavage, and dependence on a chain of trial-related procedures emerged as factors that impaired trial processes.Interpretation: Antibiotic use remains high in patients with suspected ventilator-associated pneumonia. Antibiotic stewardship was not improved by a rapid, highly sensitive rule-out test. Prescribing culture, rather than poor test performance, might explain this absence of effect.Funding: UK Department of Health and the Wellcome Trust.

Background: Percutaneous tracheosotmies are commonly performed in intensive care to expedite weaning from mechanical ventilation especially following major trauma, acquired brain injury or severe respiratory failure. Often patients are discharged from the intensive care unit (ICU) to a ward environment with no specialist follow up Aim: To evaluate the effectiveness of a multi-disciplinary tracheostomy team (MDT) at reducing the total length of hospital stay and improving decannulation rates in tracheostomy patients once discharged from ICU Method: The team consisted of a Consultant, Physiotherapist, Speech and Language Therapist, a Head & Neck Specialist Nurse and a Critical Care Outreach Nurse. The team met weekly on the neurosurgery and respiratory wards and may prescribe treatments or therapies, offer advice to ward staff or carry out interventions. Audit data was gathered for 6 months preceding the establishment of the team and during the 6 month pilot period. Result: Based on around 62 patients being discharged to neurosurgical and respiratory wards per year, the permanent introduction of a Trust Tracheostomy MDT has the potential to reduce the time patients spend with a temporary tracheostomy in situ by 50% and in patient bed use by 911 days per year. Conclusion: A Tracheostomy MDT is an essential service to ensure timely decannulation as well as reducing hospital length of stay and improving overall outcome.

Background In September 2016, three acutely jaundiced (AJS) pregnant women were admitted to Am Timan Hospital, eastern Chad. We described the outbreak and conducted a case test-negative study to identify risk factors for this genotype of HEV in an acute outbreak setting. Methods Active case finding using a community based surveillance network identified suspected AJS cases. Pregnant or visibly ill AJS cases presenting at hospital were tested with Assure® IgM HEV rapid diagnostic tests (RDTs) and some with Polymerase Chain Reaction (PCR) in Amsterdam; confirmed cases were RDT-positive and controls were RDT-negative. All answered questions around: demographics, household makeup, area of residence, handwashing practices, water collection behaviour and clinical presentation. We calculated unadjusted odds ratios (ORs) and 95% confidence intervals (95% CI). Results Between September and April 2017, 1443 AJS cases (1293 confirmed) were detected in the town(attack rate: 2%; estimated 65,000 population). PCR testing confirmed HEV genotype 1e. HEV RDTs were used for 250 AJS cases; 100 (40%) were confirmed. Risk factors for HEV infection, included: having at least two children under the age of 5 years (OR 2.1, 95%CI 1.1-4.3), having another household member with jaundice (OR 2.4, 95%CI 0.90-6.3) and, with borderline significance, living in the neighbourhoods of Riad (OR 3.8, 95%CI 1.0-1.8) or Ridina (OR 3.3, 95%CI 1.0-12.6). Cases were more likely to present with vomiting (OR 3.2, 9%CI 1.4-7.9) than controls; possibly due to selection bias. Cases were non-significantly less likely to report always washing hands before meals compared with controls (OR 0.33, 95%CI 0.1-1.1). Discussion Our study suggests household factors and area of residence (possibly linked to access to water and sanitation) play a role in HEV transmission; which could inform future outbreak responses. Ongoing sero-prevalence studies will elucidate more aspects of transmission dynamics of this virus with genotype 1e.

Despite taking every precaution while treating patients with Ebola in Guinea, Craig Spencer was hospitalized with Ebola last October. Rather than being welcomed home as a humanitarian, he was vilified even as his liver was failing and his fiancee was quarantined.

Background: Excessive use of empirical antibiotics is common in critically ill patients. Rapid biomarker-based exclusion of infection may improve antibiotic stewardship in ventilator-acquired pneumonia (VAP). However, successful validation of the usefulness of potential markers in this setting is exceptionally rare.Objectives: We sought to validate the capacity for specific host inflammatory mediators to exclude pneumonia in patients with suspected VAP. Methods: A prospective, multicentre, validation study of patients with suspected VAP was conducted in 12 intensive care units. VAP was confirmed following bronchoscopy by culture of a potential pathogen in bronchoalveolar lavage fluid (BALF) at >104 colony forming units per millilitre (cfu/mL). Interleukin-1 beta (IL-1β), IL-8, matrix metalloproteinase-8 (MMP-8), MMP-9 and human neutrophil elastase (HNE) were quantified in BALF. Diagnostic utility was determined for biomarkers individually and in combination. Results: Paired BALF culture and biomarker results were available for 150 patients. 53 patients (35%) had VAP and 97 (65%) patients formed the non-VAP group. All biomarkers were significantly higher in the VAP group (pConclusions: Low BALF IL-1β in combination with IL-8 confidently excludes VAP and could form a rapid biomarker-based rule-out test, with the potential to improve antibiotic stewardship.

We report the case of a 63-year-old man who suffered a witnessed pulseless electrical activity cardiac arrest on presentation to the emergency department. Despite a profound post-arrest acidosis (pH 6.48) he went on to make an unexpectedly good recovery. He was treated for metformin-associated lactic acidosis (MALA) and septic shock, although the origin of the sepsis was never confirmed. We discuss the growing evidence against the existence of MALA as a lone diagnosis and the aetiology of post-cardiac arrest metabolic acidosis.

This paper describes a 21-year-old man who presented to the emergency department with a knife wound to his buttock. He had a witnessed cardiac arrest with pulseless electrical activity in hospital as a result of further haemorrhage. His post-resuscitation arterial blood gas revealed a severe lactic acidosis (pH 6.61, lactate 22.0 mmol/l). Despite poor expectations he went on to make a full neurological recovery. To the authors' knowledge, he had the fourth-lowest pH for a cardiac arrest survivor with normal neurology. Severe lactic acidosis occurs post cardiac arrest due to imbalance between cellular oxygen supply and demand. Severe lactic acidosis is associated with hypoxic brain injury but has a low specificity in its prediction. The case illustrates that, especially in younger adults, severe lactic acidosis may be a poor predictor of outcome if it reflects a period of relative hypoperfusion preceding cardiac arrest.

Immunologic studies were performed on 5 patients with pigeon breeders' disease. Intradermal injection of pigeon serum produced an immediate wheal-and-flare reaction within 15 minutes and a secondary Arthus-type reaction within 4 to 8 hours. Immunofluorescent studies of the secondary reaction site showed IgG, C3, and C4 in 2 patients. Patients' sera produced multiple precipitin bands with pigeon serum when reacted by double diffusion in gel. IgG antibody isolated from each of the patients' serum formed precipitating immune complexes that fixed large amounts of complement (C4) when added to fresh human serum. Peripheral blood lymphocytes from 4 of the 5 patients produced macrophage migration inhibitory factor (MIF) when challenged with dilute pigeon serum. These studies are the first to show complement fixing antibodies and macrophage MIF production by lymphocytes from patients with hypersensitivity lung disease and suggest that both humoral and cellular immunity may be important in the pathogenesis of these disorders.