Are Early Warning Scores Useful Predictors for Mortality and Morbidity in Hospitalised Acutely Unwell Older Patients? : A Systematic Review

Funding: No funding was gained to directly support the conduct of this study. Toby Smith is supported by funding from the National Institute for Health Research (NIHR) Oxford Health Biomedical Research Centre. The views expressed are those of the author(s) and not necessarily those of the NIHR. Acknowledgments: We thank Samuel Ronald Neal who proofread the manuscript.Peer reviewedPublisher PD

Shock index predicts outcome in patients with suspected sepsis or community acquired pneumonia : a systematic review

Supplementary Materials: The following are available online at www.mdpi.com/xxx/s1, Table S1: Medline search strategy, Table S2: Downs and Black quality assessment for included studies. Table S3: CURASI score as a predictor of mortality in CAP.Peer reviewedPublisher PD

Has primary care antimicrobial use really been increasing? Comparison of changes in different prescribing measures for a complete geographic population 1995-2014

Objectives To elucidate how population trends in total antimicrobials dispensed in the community translate into individual exposure. Methods Retrospective, population-based observational study of all antimicrobial prescribing in a Scottish region in financial years 1995, 2000 and 2005–14. Analysis of temporal changes in all antimicrobials and specific antimicrobials measured in: WHO DDD per 1000 population; prescriptions per 1000 population; proportion of population with ≥1 prescription; mean number of prescriptions per person receiving any; mean DDD per prescription. Results Antimicrobial DDD increased between 1995 and 2014, from 5651 to 6987 per 1000 population [difference 1336 (95% CI 1309–1363)]. Prescriptions per 1000 fell (from 821 to 667, difference –154, –151 to –157), as did the proportion prescribed any antimicrobial [from 39.3% to 30.8% (–8.5, –8.4 to –8.6)]. Rising mean DDD per prescription, from 6.88 in 1995 to 10.47 in 2014 (3.59, 3.55–3.63), drove rising total DDD. In the under-5s, every measure fell over time (68.2% fall in DDD per 1000; 60.7% fall in prescriptions per 1000). Among 5–64 year olds, prescriptions per 1000 were lowest in 2014 but among older people, despite a reduction since 2010, the 2014 rate was still higher than in 2000. Trends in individual antimicrobials provide some explanation for overall trends. Conclusions Rising antimicrobial volumes up to 2011 were mainly due to rising DDD per prescription. Trends in dispensed drug volumes do not readily translate into information on individual exposure, which is more relevant for adverse consequences including emergence of resistance.PostprintPeer reviewe

Mesothelioma Evolution following a Diagnosis of Benign Pleural Inflammation: A Systematic Review and Meta-Analysis

Introduction Pleural Mesothelioma (PM) may be presaged by benign pleural inflammation, typically labelled non-specific pleuritis (NSP). NSP is common and presents a clinical challenge given divergent rates of subsequent PM in previous studies. Greater clarity on cohorts at highest risk would inform clinical decision-making and ongoing precision PM prevention research. Methods A systematic review and meta-analysis were performed (CRD42021290792). Studies post-2000 were identified via PubMed and conference proceedings. Data extracted included number of NSP cases and subsequent PM evolutions, NSP biopsy type, asbestos exposure, median follow-up, study design and setting. Between-study heterogeneity was described by Q test and I2(%). A random effects model was constructed for PM evolution rate (%) with subsequent stratification by significant heterogeneity sources. Risk of bias was assessed using the Quality in Prognosis Studies (QUIPS) tool, Funnel plot and rank correlation test. Results 17/265 identified studies were included, describing 2607 NSP cases and 146 PM evolutions. The summary point estimate of PM evolution was 5.44%(95% CI 3.37–7.51), with significant heterogeneity (p < 0.001, I2 82.7%). Asbestos exposure, study setting and NSP biopsy type were significant sources of heterogeneity. Follow-up and study design were non-significant. Higher PM evolution rate was associated with ≥50% asbestos exposure by cohort and high PM incidence settings. Lower evolution rate was associated with surgical NSP biopsies. Most studies demonstrated moderate/high risk of bias. There was evidence of publication bias

Extracellular fluid volume and glomerular filtration rate in 1,878 healthy potential renal transplant donors. Effects of age, gender, obesity and scaling.

Aim. The aim of this study was to investigate the influence of age, gender, obesity and scaling on glomerular filtration rate (GFR) and extracellular fluid volume (ECV) in healthy subjects. Methods. This is a retrospective multi-centre study of 1878 healthy prospective kidney transplant donors (819 men) from 15 centres. Age and body mass index (BMI) were not significantly different between men and women. Slope-intercept GFR was measured (using Cr-51-EDTA in 14 centres; Tc-99m-DTPA in one) and scaled to body surface area (BSA) and lean body mass (LBM), both estimated from height and weight. GFR was also expressed as the slope rate constant, with one-compartment correction (GFR/ECV). ECV was measured as the ratio, GFR to GFR/ECV. Results. ECV was age independent but GFR declined with age, at a significantly faster rate in women than men. GFR/BSA was higher in men but GFR/ECV and GFR/LBM were higher in women. Young women (65 years). There was no difference in GFR between obese (BMI > 30 kg/m2) and non-obese men. Obese women, however, had lower GFR than non-obese women and negative correlations were observed between GFR and both BMI and %fat. The decline in GFR with age was no faster in obese versus non-obese subjects. ECV/BSA was higher in men but ECV/LBM was higher in women. ECV/weight was almost gender independent, suggesting that fat-free mass in women contains more extracellular water. BSA is therefore a misleading scaling variable. Conclusion. There are several significant differences in GFR and ECV between healthy men and women

The reliability of glomerular filtration rate measured from plasma clearance: a multi-centre study of 1,878 healthy potential renal transplant donors

PURPOSE The objective of the study was to undertake a clinical audit of departmental performance in the measurement of glomerular filtration rate (GFR) using the coefficient of variation (CV) of extracellular fluid volume (ECFV) as the benchmark. ECFV is held within narrow limits in healthy subjects, narrower than GFR, and should therefore have a low CV. METHODS Fifteen departments participated in this retrospective study of healthy renal transplant donors. Data were analysed separately for men (n ranged from 28 to 115 per centre; total = 819) and women (n = 28-146; 1,059). All centres used the slope-intercept method with blood sample numbers ranging from two to five. Subjects did not fast prior to GFR measurement. GFR was scaled to body surface area (BSA) and corrected for the single compartment assumption. GFR scaled to ECFV was calculated as the terminal slope rate constant and corrected for the single compartment assumption. ECFV/BSA was calculated as the ratio of GFR/BSA to GFR/ECFV. RESULTS The departmental CVs of ECFV/BSA and GFR/BSA ranged from 8.3 to 25.8% and 12.8 to 21.9%, respectively, in men, and from 9.6 to 21.1% and 14.8 to 23.7%, respectively, in women. Both CVs correlated strongly between men and women from the same centre, suggesting department-specific systematic errors. GFR/BSA was higher in men in 14 of 15 centres, whereas GFR/ECFV was higher in women in 14 of 15 centres. Both correlated strongly between men and women, suggesting regional variation in GFR. CONCLUSION The CV of ECFV/BSA in normal subjects is a useful indicator of the technical robustness with which GFR is measured and, in this study, indicated a wide variation in departmental performance

Staging by Thoracoscopy in potentially radically treatable Lung Cancer associated with Minimal Pleural Effusion (STRATIFY): Protocol of a prospective, multicentre, observational study

Introduction: Recurrence rate following radical therapy for lung cancer remains high, potentially reflecting occult metastatic disease, and better staging tools are required. Minimal pleural effusion (mini-PE) is associated with particularly high recurrence risk and is defined as an ipsilateral pleural collection (<1/3 hemithorax on chest radiograph), which is either too small to safely aspirate fluid for cytology using a needle, or from which fluid cytology is negative. Thoracoscopy (local anaesthetic thoracoscopy (LAT) or video-assisted thoracoscopic surgery (VATS)) is the gold-standard diagnostic test for pleural malignancy in patients with larger symptomatic effusions. Staging by Thoracoscopy in potentially radically treatable Lung Cancer associated with Minimal Pleural Effusion (STRATIFY) will prospectively evaluate thoracoscopic staging in lung cancer associated-mini-PE for the first time. Methods and analysis: STRATIFY is a prospective multicentre observational study. Recruitment opened in January 2020. The primary objective is to determine the prevalence of detectable occult pleural metastases (OPM). Secondary objectives include assessment of technical feasibility and safety, and the impact of thoracoscopy results on treatment plans, overall survival and recurrence free survival. Inclusion criteria are (1) suspected/confirmed stages I–III lung cancer, (2) mini-PE, (3) Performance Status 0–2 (4), radical treatment feasible if OPM excluded, (5) ≥16 years old and (6) informed consent. Exclusion criteria are any metastatic disease or contraindication to the chosen thoracoscopy method (LAT/VATS). All patients have LAT or VATS within 7 (±5) days of registration, with results returned to lung cancer teams for treatment planning. Following an interim analysis, the sample size was reduced from 96 to 50, based on a lower-than-expected OPM rate. An MRI substudy was removed in November 2022 due to pandemic-related site setup/recruitment delays. These also necessitated a no-cost recruitment extension until October 2023

Staging by Thoracoscopy in potentially radically treatable Lung Cancer associated with Minimal Pleural Effusion (STRATIFY): protocol of a prospective, multicentre, observational study

Introduction Recurrence rate following radical therapy for lung cancer remains high, potentially reflecting occult metastatic disease, and better staging tools are required. Minimal pleural effusion (mini-PE) is associated with particularly high recurrence risk and is defined as an ipsilateral pleural collection (<1/3 hemithorax on chest radiograph), which is either too small to safely aspirate fluid for cytology using a needle, or from which fluid cytology is negative. Thoracoscopy (local anaesthetic thoracoscopy (LAT) or video-assisted thoracoscopic surgery (VATS)) is the gold-standard diagnostic test for pleural malignancy in patients with larger symptomatic effusions. Staging by Thoracoscopy in potentially radically treatable Lung Cancer associated with Minimal Pleural Effusion (STRATIFY) will prospectively evaluate thoracoscopic staging in lung cancer associated-mini-PE for the first time.Methods and analysis STRATIFY is a prospective multicentre observational study. Recruitment opened in January 2020. The primary objective is to determine the prevalence of detectable occult pleural metastases (OPM). Secondary objectives include assessment of technical feasibility and safety, and the impact of thoracoscopy results on treatment plans, overall survival and recurrence free survival. Inclusion criteria are (1) suspected/confirmed stages I–III lung cancer, (2) mini-PE, (3) Performance Status 0–2 (4), radical treatment feasible if OPM excluded, (5) ≥16 years old and (6) informed consent. Exclusion criteria are any metastatic disease or contraindication to the chosen thoracoscopy method (LAT/VATS). All patients have LAT or VATS within 7 (±5) days of registration, with results returned to lung cancer teams for treatment planning. Following an interim analysis, the sample size was reduced from 96 to 50, based on a lower-than-expected OPM rate. An MRI substudy was removed in November 2022 due to pandemic-related site setup/recruitment delays. These also necessitated a no-cost recruitment extension until October 2023.Ethics and dissemination Protocol approved by the West of Scotland Research Ethics Committee (Ref: 19/WS/0093). Results will be published in peer-reviewed journals and presented at international meetings.Trial registration number ISRCTN13584097