A national survey of the diagnosis and management of suspected ventilator-associated pneumonia.

BACKGROUND: Ventilator-associated pneumonia (VAP) affects up to 20% of patients admitted to intensive care units (ICU). It is associated with increased morbidity, mortality and healthcare costs. Despite published guidelines, variability in diagnosis and management exists, the extent of which remains unclear. We sought to characterise consultant opinions surrounding diagnostic and management practice for VAP in the UK. METHODS: An online survey was sent to all consultant members of the UK Intensive Care Society (n=∼1500). Data were collected regarding respondents' individual practice in the investigation and management of suspected VAP including use of diagnostic criteria, microbiological sampling, chest X-ray (CXR), bronchoscopy and antibiotic treatments. RESULTS: 339 (23%) responses were received from a broadly representative spectrum of ICU consultants. All respondents indicated that microbiological confirmation should be sought, the majority (57.8%) stating they would take an endotracheal aspirate prior to starting empirical antibiotics. Microbiology reporting services were described as qualitative only by 29.7%. Only 17% of respondents had access to routine reporting of CXRs by a radiologist. Little consensus exists regarding technique for bronchoalveolar lavage (BAL) with the reported volume of saline used ranging from 5 to 500 mL. 24.5% of consultants felt inadequately trained in bronchoscopy. CONCLUSIONS: There is wide variability in the approach to diagnosis and management of VAP among UK consultants. Such variability challenges the reliability of the diagnosis of VAP and its reported incidence as a performance indicator in healthcare systems. The data presented suggest increased radiological and microbiological support, and standardisation of BAL technique, might improve this situation

Why honey is effective as a medicine. 1. Its use in modern medicine

Honey has been used as a medicine for thousands of years and its curative properties are well documented. However, modern medicine turned its back on honey and it is only now, with the advent of multi-resistant bacteria, that the antibiotic properties of honey are being rediscovered

Randomised controlled trial of GM-CSF in critically ill patients with impaired neutrophil phagocytosis

Background. Critically ill patients with impaired neutrophil phagocytosis have significantly increased risk of nosocomial infection. Granulocyte-macrophage colony-stimulating factor (GM-CSF) improves phagocytosis by neutrophils ex vivo. This study tested the hypothesis that GM-CSF improves neutrophil phagocytosis in critically ill patients in whom phagocytosis is known to be impaired Methods. This was a multi-centre, phase 2a randomised, placebo-controlled clinical trial Using a personalised medicine approach, only critically ill patients with impaired neutrophil phagocytosis were included. Patients were randomised 1:1 to subcutaneous GM-CSF (3 microgrammws/kg/day) or placebo, once daily for 4 days. The primary outcome measure was neutrophil phagocytosis 2 days after initiation of GM-CSF. Secondary outcomes included neutrophil phagocytosis over time, neutrophil functions other than phagocytosis, monocyte HLA-DR expression, and safety. Results. Thirty-eight patients were recruited from 5 intensive care units (17 randomised to GM-CSF). Mean neutrophil phagocytosis at day 2 was 57.2% (SD 13.2%) in the GM-CSF group and 49.8% (13.4%) in the placebo group, p=0.73. The proportion of patients with neutrophil phagocytosis >50% at day 2, and monocyte HLA-DR, appeared significantly higher in the GM-CSF group. Neutrophil functions other than phagocytosis did not appear significantly different between the groups. The most common adverse event associated with GM-CSF was pyrexia. Conclusions. GM-CSF did not improve mean neutrophil phagocytosis at day 2, but was safe and appeared to increase the proportion of patients with adequate phagocytosis. The study suggests proof of principle for a pharmacological effect on neutrophil function in a subset of critically ill patients.This work was funded by a grant from the Medical Research Council (G1100233), with additional support from the National Institute for Health Research (NIHR) Newcastle Biomedical Research Centre. It was sponsored by Newcastle Universit

The prevalence of dental erosion and associated risk factors in 12-13-year-old school children in Southern China

<p>Abstract</p> <p>Background</p> <p>Dental erosion has been investigated in developed and developing countries and the prevalence varies considerably in different countries, geographic locations, and age groups. With the lifestyle of the Chinese people changing significantly over the decades, dental erosion has begun to receive more attention. However, the information about dental erosion in China is scarce. The purpose of this study was to explore the prevalence of dental erosion and associated risk factors in 12-13-year-old school children in Guangzhou, Southern China.</p> <p>Methods</p> <p>This cross-sectional survey was performed by two trained, calibrated examiners. A stratified random sample of 12-13-year-old children (774 boys and 725 girls) from 10 schools was examined for dental erosion using the diagnostic criteria of Eccles and the index of O'Sullivan was applied to record the distribution, severity, and amount of the lesions. Data on the socio-economic status, health behaviours, and general health involved in the etiology of dental erosion were obtained from a self-completed questionnaire. The analyses were performed using SPSS software.</p> <p>Results</p> <p>At least one tooth surface with signs of erosion was found in 416 children (27.3%). The most frequently affected teeth were the central incisors (upper central incisors, 16.3% and 15.9%; lower central incisors, 17.4% and 14.8%). The most frequently affected surface was the incisal or occlusal edge (43.2%). The loss of enamel contour was present in 54.6% of the tooth surfaces with erosion. Of the affected tooth surfaces, 69.3% had greater than one-half of the tooth surface was affected. The results from logistic regression analysis demonstrated that the children who were female, consumed carbonated drinks once a week or more, and those whose mothers were educated to the primary level tended to have more dental erosion.</p> <p>Conclusions</p> <p>Dental erosion in 12-13-year-old Chinese school children is becoming a significant problem. A strategy of offering preventive care, including more campaigns promoting a healthier lifestyle for those at risk of dental erosion should be conducted in Chinese children and their parents.</p

Biomarker-guided antibiotic stewardship in suspected ventilator-associated pneumonia (VAPrapid2) : a randomised controlled trial and process evaluation

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

Methodological considerations concerning the development of oral dental erosion indexes: literature survey, validity and reliability

Within the context of preventing non-communicable diseases, the World Health Report (2002) and the WHO Global Oral Health Program (2003) put forward a new strategy of disease prevention and health promotion. Greater emphasis is placed on developing global policies in oral health promotion and oral disease prevention. The Decayed, Missing, Filled Teeth (DMFT) index does not meet new challenges in the field of oral health. Dental erosion seems to be a growing problem, and in some countries, an increase in erosion of teeth is associated with an increase in the consumption of beverages containing acids. Therefore, within a revision of the WHO Oral Health Surveys Basic Methods, new oral disease patterns, e.g. dental erosion, have to be taken into account. Within the last 20 years, many studies on dental erosion have been carried out and published. There has been a rapid growth in the number of indexes quantifying dental erosion process in different age groups. However, these indexes are not comparable. This article discusses quality criteria which an index intended for assessing tooth erosion should possess

Risk of adverse outcomes in patients with underlying respiratory conditions admitted to hospital with COVID-19:a national, multicentre prospective cohort study using the ISARIC WHO Clinical Characterisation Protocol UK

Background Studies of patients admitted to hospital with COVID-19 have found varying mortality outcomes associated with underlying respiratory conditions and inhaled corticosteroid use. Using data from a national, multicentre, prospective cohort, we aimed to characterise people with COVID-19 admitted to hospital with underlying respiratory disease, assess the level of care received, measure in-hospital mortality, and examine the effect of inhaled corticosteroid use. Methods We analysed data from the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) WHO Clinical Characterisation Protocol UK (CCP-UK) study. All patients admitted to hospital with COVID-19 across England, Scotland, and Wales between Jan 17 and Aug 3, 2020, were eligible for inclusion in this analysis. Patients with asthma, chronic pulmonary disease, or both, were identified and stratified by age (<16 years, 16–49 years, and ≥50 years). In-hospital mortality was measured by use of multilevel Cox proportional hazards, adjusting for demographics, comorbidities, and medications (inhaled corticosteroids, short-acting β-agonists [SABAs], and long-acting β-agonists [LABAs]). Patients with asthma who were taking an inhaled corticosteroid plus LABA plus another maintenance asthma medication were considered to have severe asthma. Findings 75 463 patients from 258 participating health-care facilities were included in this analysis: 860 patients younger than 16 years (74 [8·6%] with asthma), 8950 patients aged 16–49 years (1867 [20·9%] with asthma), and 65 653 patients aged 50 years and older (5918 [9·0%] with asthma, 10 266 [15·6%] with chronic pulmonary disease, and 2071 [3·2%] with both asthma and chronic pulmonary disease). Patients with asthma were significantly more likely than those without asthma to receive critical care (patients aged 16–49 years: adjusted odds ratio [OR] 1·20 [95% CI 1·05–1·37]; p=0·0080; patients aged ≥50 years: adjusted OR 1·17 [1·08–1·27]; p<0·0001), and patients aged 50 years and older with chronic pulmonary disease (with or without asthma) were significantly less likely than those without a respiratory condition to receive critical care (adjusted OR 0·66 [0·60–0·72] for those without asthma and 0·74 [0·62–0·87] for those with asthma; p<0·0001 for both). In patients aged 16–49 years, only those with severe asthma had a significant increase in mortality compared to those with no asthma (adjusted hazard ratio [HR] 1·17 [95% CI 0·73–1·86] for those on no asthma therapy, 0·99 [0·61–1·58] for those on SABAs only, 0·94 [0·62–1·43] for those on inhaled corticosteroids only, 1·02 [0·67–1·54] for those on inhaled corticosteroids plus LABAs, and 1·96 [1·25–3·08] for those with severe asthma). Among patients aged 50 years and older, those with chronic pulmonary disease had a significantly increased mortality risk, regardless of inhaled corticosteroid use, compared to patients without an underlying respiratory condition (adjusted HR 1·16 [95% CI 1·12–1·22] for those not on inhaled corticosteroids, and 1·10 [1·04–1·16] for those on inhaled corticosteroids; p<0·0001). Patients aged 50 years and older with severe asthma also had an increased mortality risk compared to those not on asthma therapy (adjusted HR 1·24 [95% CI 1·04–1·49]). In patients aged 50 years and older, inhaled corticosteroid use within 2 weeks of hospital admission was associated with decreased mortality in those with asthma, compared to those without an underlying respiratory condition (adjusted HR 0·86 [95% CI 0·80−0·92]). Interpretation Underlying respiratory conditions are common in patients admitted to hospital with COVID-19. Regardless of the severity of symptoms at admission and comorbidities, patients with asthma were more likely, and those with chronic pulmonary disease less likely, to receive critical care than patients without an underlying respiratory condition. In patients aged 16 years and older, severe asthma was associated with increased mortality compared to non-severe asthma. In patients aged 50 years and older, inhaled corticosteroid use in those with asthma was associated with lower mortality than in patients without an underlying respiratory condition; patients with chronic pulmonary disease had significantly increased mortality compared to those with no underlying respiratory condition, regardless of inhaled corticosteroid use. Our results suggest that the use of inhaled corticosteroids, within 2 weeks of admission, improves survival for patients aged 50 years and older with asthma, but not for those with chronic pulmonary disease

Development and validation of the ISARIC 4C Deterioration model for adults hospitalised with COVID-19: a prospective cohort study.

BACKGROUND: Prognostic models to predict the risk of clinical deterioration in acute COVID-19 cases are urgently required to inform clinical management decisions. METHODS: We developed and validated a multivariable logistic regression model for in-hospital clinical deterioration (defined as any requirement of ventilatory support or critical care, or death) among consecutively hospitalised adults with highly suspected or confirmed COVID-19 who were prospectively recruited to the International Severe Acute Respiratory and Emerging Infections Consortium Coronavirus Clinical Characterisation Consortium (ISARIC4C) study across 260 hospitals in England, Scotland, and Wales. Candidate predictors that were specified a priori were considered for inclusion in the model on the basis of previous prognostic scores and emerging literature describing routinely measured biomarkers associated with COVID-19 prognosis. We used internal-external cross-validation to evaluate discrimination, calibration, and clinical utility across eight National Health Service (NHS) regions in the development cohort. We further validated the final model in held-out data from an additional NHS region (London). FINDINGS: 74 944 participants (recruited between Feb 6 and Aug 26, 2020) were included, of whom 31 924 (43·2%) of 73 948 with available outcomes met the composite clinical deterioration outcome. In internal-external cross-validation in the development cohort of 66 705 participants, the selected model (comprising 11 predictors routinely measured at the point of hospital admission) showed consistent discrimination, calibration, and clinical utility across all eight NHS regions. In held-out data from London (n=8239), the model showed a similarly consistent performance (C-statistic 0·77 [95% CI 0·76 to 0·78]; calibration-in-the-large 0·00 [-0·05 to 0·05]); calibration slope 0·96 [0·91 to 1·01]), and greater net benefit than any other reproducible prognostic model. INTERPRETATION: The 4C Deterioration model has strong potential for clinical utility and generalisability to predict clinical deterioration and inform decision making among adults hospitalised with COVID-19. FUNDING: National Institute for Health Research (NIHR), UK Medical Research Council, Wellcome Trust, Department for International Development, Bill & Melinda Gates Foundation, EU Platform for European Preparedness Against (Re-)emerging Epidemics, NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections at University of Liverpool, NIHR HPRU in Respiratory Infections at Imperial College London