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Background Patients with diabetes and/or obesity are at higher risk of adverse outcomes following coronary artery bypass grafting (CABG). The use of bilateral internal thoracic arteries (BITA) can potentially offer survival benefit in higher risk patients compared to single internal thoracic artery (SITA) in patients undergoing CABG, but the overall evidence base for BITA has not influenced guidelines, and there are concerns over increased risk of sternal wound complications. Methods We conducted a systematic review of the literature to identify observational studies and randomised controlled trials (RCT) comparing the efficacy (mortality) and safety (sternal wound infection) of BITA and SITA in diabetic and obese patients. Results We identified 18 observational studies and one RCT to obtain data comparing BITA and SITA in 19,589 diabetic patients, and two observational studies and one RCT comparing BITA and SITA in 6972 obese patients. Pooled analysis demonstrated significant mortality benefit of BITA compared to SITA in diabetic patients (risk ratio [RR] 0.79; 95% confidence interval [CI] 0.70, 0.90; Z=3.62, p=0.0003; I2=88%) (Figure 1a). Pooled analysis in obese patients found no significant difference in mortality rates between BITA and SITA (RR 0.73, 95% CI 0.47, 1.12; Z=1.43, p=0.15; I2=78%) (Figure 1b). A significantly higher rate of sternal wound complications following BITA was observed in diabetic (RR 1.53, 95% CI 1.23, 1.90; Z=3.86, p=0.0001; I2=4%) and obese patients (RR 2.24, 95% CI 1.63, 3.07; Z=5.00, p Conclusions BITA is associated with better long-term survival in diabetic patients, but most of the supportive data comes from observational studies. The effects of BITA grafting in patients who are obese is uncertain due to low numbers. BITA is associated with higher rates of sternal wound complications than SITA in both diabetic and obese patients. Further research is needed to understand if BITA has a role in higher risk patients undergoing CABG. Figure 1. Pooled all-cause mortality Funding Acknowledgement Type of funding source: None

Background: Postoperative atrial fibrillation (pAF) after coronary artery bypass grafting is a common complication. Whether pAF is associated with an increased risk of cerebrovascular accident (CVA) remains uncertain. We investigated the association between pAF and long-term risk of CVA by performing a post hoc analysis of 10-year outcomes of the ART (Arterial Revascularization Trial). Methods: For the present analysis, among patients enrolled in the ART (n=3102), we excluded those who did not undergo surgery (n=25), had a history of atrial fibrillation (n=45), or had no information on the incidence of pAF (n=9). The final population consisted of 3023 patients, of whom 734 (24.3%) developed pAF with the remaining 2289 maintaining sinus rhythm. Competing risk and Cox regression analyses were used to investigate the association between pAF and the risk of CVA. Results: At 10 years, the cumulative incidence of CVA was 6.3% (4.6%–8.1%) versus 3.7% (2.9%–4.5%) in patients with pAF and sinus rhythm, respectively. pAF was an independent predictor of CVA at 10 years (hazard ratio, 1.53 [95% CI, 1.06–2.23]; P =0.025) even when CVAs that occurred during the index admission were excluded from the analysis (hazard ratio, 1.47 [95% 1.02–2.11]; P =0.04). Conclusions: Patients with pAF after coronary artery bypass grafting are at higher risk of CVA. These findings challenge the notion that pAF is a benign complication.

Objectives The Arterial Revascularization Trial (ART) was designed to compare 10-year survival in bilateral versus single internal thoracic artery grafts. The intention-to-treat analysis has showed comparable outcomes between the 2 groups but an explanatory analysis suggested that those receiving 2 or more arterial grafts had better survival. Whether the exclusive use of arterial grafts provide further benefit is unclear. Methods We performed an exploratory analysis of the ART based on conduits actually received (as-treated principle). From ART cohort, only patients receiving at least 3 grafts were included. The final population consisted of 1084, 1010, and 390 patients in the single arterial graft (SAG) group, in the multiple arterial graft (MAG) group (2 or more arterial grafts with additional saphenous veins) and total arterial graft (TAG) group (3 or more arterial grafts only) respectively. Inverse probability of treatment weighting was used for comparison. Results When compared with the SAG group, there was a significant trend toward a reduction of 10-year mortality in the MAG and TAG group (test for trend P = .02). The TAG group was associated with the lowest risk of late mortality (hazard ratio, 0.68; 95% confidence interval, 0.48-0.96; P = .03) and with a significant risk reduction of the composite of death/myocardial infarction/stroke and repeat revascularization (hazard ratio, 0.71; 95% confidence interval, 0.53-0.94; P = .02). Conclusions When compared with SAG, both MAG and TAG represent valuable strategies to improve clinical outcomes following coronary artery bypass grafting but TAG can potentially provide further benefit.

Objective: Malignant Pleural Mesothelioma (MPM) has a poor prognosis and high symptom burden. RESPECT-Meso was a multicenter randomized study examining the role of early specialist palliative care (SPC) on quality of life (QoL) with MPM. This is a post-hoc exploratory analysis of the symptom burden and unmet needs identified from RESPECT-Meso participants. Methods: Exploratory analysis from 174 participants using the General Health Status (GHS) measure (from the EORTC QLQ-C30 QoL questionnaire) and 87 participants using validated assessment questionnaires in those randomized to SPC. Eligibility for the study included confirmed MPM with diagnosis Results: Participants were predominantly male (79.9%), mean age 72.8 years, PS was 0 in 38%, 78% of MPM was epithelioid. At least 3 symptoms were reported in 69.8% of participants, including fatigue (81%), dyspnea (73.3%), pain (61.2%), weight loss (59.3%). Anxiety was reported by 54.7% of participants, 52.3% low mood and 48.8% anhedonia symptoms. After multivariable adjustment, only pain remained statistically significant with a hazard ratio (HR) 2.9 (95% CI 1.3-6.7; p = 0.01). For each 1 unit increase in GHS score, the HR for death was 0.987 (0.978-0.996; p = 0.006), indicating a worse reported QoL is related to shorter survival. Unmet needs were common: 25.9% wanted more information about their condition, 24.7% about their care and 21.2% about their treatment. 79.1% were concerned about the effect of their illness on family. Conclusion: There is a high symptom burden in mesothelioma despite good baseline performance status. A worse QoL is associated with a worse survival. Unmet needs are common, perhaps highlighting a need for improved communication and information sharing.

Background Diabetes is associated with higher risk of mortality in patients undergoing coronary artery bypass graft (CABG) but the effects of obesity, and the interactions between diabetes and obesity in the context of CABG, have not been fully explored. Methods The Arterial Revascularisation Trial (ART) randomised patients to single- or bilateral internal thoracic arterial graft plus other vein or arterial grafts as needed and followed them for 10 years to compare mortality, clinical outcomes and safety. In this analysis we explored the effects of diabetes and obesity on mortality and risk (sternal wound complications) . Diabetes was defined according to clinical history at baseline and combined insulin and non-insulin dependent patients, and obesity was defined as body mass index (BMI) ≥30kg/m2 at baseline. Results Data on diabetes, obesity and ten-year mortality were available for 3094 patients who were included in the analysis. Mean age was 64 years, 86% male, mean weight 82kg and BMI 28. Diabetes was documented in 24% and obesity in 30% and as expected obese patients were more likely to be diabetic. The hazard ratios (95% confidence intervals) for ten-year mortality using the no-diabetes, non-obese group as a reference were 1.33 (1.08, 1.64) (diabetes, non-obese), 0.93 (0.75, 1.16) (no diabetes, obese) and 1.18 (0.91, 1.54) (diabetes, obese) groups (Figure). Similar patterns of risk were observed whether patients were randomised to receive single or bilateral internal thoracic arteries and diabetes appeared to be the main driver of elevated risk of early sternal wound complications following CABG. Conclusions Obesity and diabetes often occur in the same patients, but our analysis shows that patterns of risk of death after CABG are not additive for these characteristics, and obesity may actually be associated with lower death rates in patients with and without diabetes. Sternal wound complications appeared to be driven more by diabetes than obesity. Further analyses will be presented to explore the possible mechanisms for these observations. Conflict of Interest None

Background Obesity and diabetes put patients are at higher risk of mortality and other adverse outcomes following coronary artery bypass grafting (CABG) and are becoming more common. The use of bilateral internal thoracic arteries (BITA) can potentially offer survival benefit in higher risk patients compared to single internal thoracic artery (SITA) in patients undergoing CABG. Current evidence does not support the routine use of BITA and this approach is associated with a higher risk of sternal wound complications. Methods We conducted a systematic review of the literature to identify observational studies and randomised controlled trials (RCT) comparing efficacy (mortality) and safety (sternal wound infection) of BITA and SITA in diabetic and obese patients. Results Eighteen observational studies and one RCT (subgroup analysis) were identified comparing BITA and SITA in 19,589 patients with diabetes. In contrast there were just two observational studies and one RCT (subgroup analysis) comparing BITA and SITA in 6972 obese patients. Pooled analysis demonstrated significant mortality benefit of BITA compared to SITA in diabetic patients (risk ratio [RR] 0.79; 95% confidence interval [CI] 0.70, 0.90; Z=3.62, p=0.0003; I2=88%) (Figure 1b). Pooled analysis in obese patients found no significant difference in mortality rates between BITA and SITA (RR 0.73, 95% CI 0.47, 1.12; Z=1.43, p=0.15; I2=78%), although the overall effect was for a beneficial trend for BITA (Figure 1a). A significantly higher rate of sternal wound complications following BITA was observed in diabetic (RR 1.53, 95% CI 1.23, 1.90; Z=3.86, p=0.0001; I2=4%) and obese patients (RR 2.24, 95% CI 1.63, 3.07; Z=5.00, p Conclusions In a pooled analysis, BITA is associated with better long-term survival in diabetic patients, but most of the supportive data comes from observational studies. The effects of BITA grafting in patients who are obese is uncertain due to low numbers of patients available for analysis. BITA is associated with higher rates of sternal wound complications than SITA in both diabetic and obese patients. Further studies are needed to understand the benefits and risks of multiple arterial grafting in patients with diabetes and/or obesity. Conflict of Interest None

ObjectiveTo provide an overview and critical appraisal of early warning scores for adult hospital patients.DesignSystematic review.Data sourcesMedline, CINAHL, PsycInfo, and Embase until June 2019.Eligibility criteria for study selectionStudies describing the development or external validation of an early warning score for adult hospital inpatients.Results13 171 references were screened and 95 articles were included in the review. 11 studies were development only, 23 were development and external validation, and 61 were external validation only. Most early warning scores were developed for use in the United States (n=13/34, 38%) and the United Kingdom (n=10/34, 29%). Death was the most frequent prediction outcome for development studies (n=10/23, 44%) and validation studies (n=66/84, 79%), with different time horizons (the most frequent was 24 hours). The most common predictors were respiratory rate (n=30/34, 88%), heart rate (n=28/34, 83%), oxygen saturation, temperature, and systolic blood pressure (all n=24/34, 71%). Age (n=13/34, 38%) and sex (n=3/34, 9%) were less frequently included. Key details of the analysis populations were often not reported in development studies (n=12/29, 41%) or validation studies (n=33/84, 39%). Small sample sizes and insufficient numbers of event patients were common in model development and external validation studies. Missing data were often discarded, with just one study using multiple imputation. Only nine of the early warning scores that were developed were presented in sufficient detail to allow individualised risk prediction. Internal validation was carried out in 19 studies, but recommended approaches such as bootstrapping or cross validation were rarely used (n=4/19, 22%). Model performance was frequently assessed using discrimination (development n=18/22, 82%; validation n=69/84, 82%), while calibration was seldom assessed (validation n=13/84, 15%). All included studies were rated at high risk of bias.ConclusionsEarly warning scores are widely used prediction models that are often mandated in daily clinical practice to identify early clinical deterioration in hospital patients. However, many early warning scores in clinical use were found to have methodological weaknesses. Early warning scores might not perform as well as expected and therefore they could have a detrimental effect on patient care. Future work should focus on following recommended approaches for developing and evaluating early warning scores, and investigating the impact and safety of using these scores in clinical practice.Systematic review registrationPROSPERO CRD42017053324.

Thoracic electrical bioimpedance (TEB) and transthoracic echocardiography (TTE) are non-invasive methods to estimate stroke volume (SV) and cardiac output (CO). Thoracic electrical bioimpedance is not in widespread clinical use with reports of inaccurate cardiac output estimation compared to invasive monitors, particularly in non-healthy populations. We explore its use as a trend monitor by comparing it against thoracic echocardiography in fifteen healthy volunteers undergoing two physical challenges designed to vary cardiac output. Of all paired values, 54.6% showed gross trend agreement and only 1.9% showed direct disagreement between the two monitors. Our results show thoracic bioimpedance may have a role as a non-invasive cardiac output trend monitor in healthy volunteer studies.

Background: This study evaluated whether clinical and economic outcomes from CBT for child anxiety disorders in the context of maternal anxiety disorders are improved by adding treatment focused on (i) maternal anxiety disorders, or (ii) mother-child interactions. Methods: 211 children (7 – 12 years, 85% White British, 52% female) with a primary anxiety disorder, whose mothers also had a current anxiety disorder, were randomised to receive (i) child-focused CBT with non-specific control interventions (CCBT+Con), (ii) CCBT with CBT for the maternal anxiety disorder (CCBT+MCBT), or (iii) CCBT with an intervention targeting the mother-child interaction (CCBT+MCI). A cost-utility analysis from a societal perspective was conducted using mother/child combined Quality Adjusted Life Years (QALYs). [Trial registration: https://doi.org/10.1186/ISRCTN19762288]. Results: MCBT was associated with immediate reductions in maternal anxiety compared to the non-specific control; however, after children had also received CCBT, maternal outcomes in the CCBT+MCI and CCBT+Con arms improved and CCBT+MCBT was no longer superior. Neither CCBT+MCBT nor CCBT+MCI conferred a benefit over CCBT+Con in terms of child anxiety disorder diagnoses post-treatment [primary outcome] (adj RR: 1.22 (95% CI 0.88, 1.67), p = .23; adj RR: 1.21 (95% CI 0.88, 1.65), p = .24 respectively) or global improvement ratings (adj RR 1.25 (95% CI 0.99, 1.57), p = .06; adj RR 1.18 (95% CI 0.93, 1.50), p = .17) or six and 12 months later. No significant differences between the groups were found on the main economic outcome measures (child/mother combined QALY mean difference: CCBT+MCBT vs CCBT+Con: -0.04 (95% CI -0.12, 0.04), p = 0.29; CCBT+MCI vs CCBT+Con: 0.02 (95% CI -0.05, -0.09), p = 0.54). CCBT+MCI was associated with non-significantly higher costs than CCBT (mean difference: £154 (95% CI -£1239, £1547), p = 0.83) but, when taking into account sampling uncertainty, it may be cost-effective compared with CCBT alone. Conclusions: Good outcomes were achieved for children and their mothers across treatment arms. There was no evidence of significant clinical benefit from supplementing CCBT with either CBT for the maternal anxiety disorder or treatment focussed on mother-child interactions, but the addition of MCI (and not MCBT) may be cost-effective. Keywords: Child; anxiety; mother; parent-child interaction; CBT.

Background Primary spontaneous pneumothorax occurs in otherwise healthy young patients. Optimal management is not defined and often results in prolonged hospitalisation. Data on efficacy of ambulatory options are poor. We aimed to describe the duration of hospitalisation and safety of ambulatory management compared with standard care. Methods In this open-label, randomised controlled trial, adults (aged 16–55 years) with symptomatic primary spontaneous pneumothorax were recruited from 24 UK hospitals during a period of 3 years. Patients were randomly assigned (1:1) to treatment with either an ambulatory device or standard guideline-based management (aspiration, standard chest tube insertion, or both). The primary outcome was total length of hospital stay including re-admission up to 30 days after randomisation. Patients with available data were included in the primary analysis and all assigned patients were included in the safety analysis. The trial was prospectively registered with the International Standard Randomised Clinical Trials Number, ISRCTN79151659. Findings Of 776 patients screened between July, 2015, and March, 2019, 236 (30%) were randomly assigned to ambulatory care (n=117) and standard care (n=119). At day 30, the median hospitalisation was significantly shorter in the 114 patients with available data who received ambulatory treatment (0 days [IQR 0–3]) than in the 113 with available data who received standard care (4 days [IQR 0–8]; p Interpretation Ambulatory management of primary spontaneous pneumothorax significantly reduced the duration of hospitalisation including re-admissions in the first 30 days, but at the expense of increased adverse events. This data suggests that primary spontaneous pneumothorax can be managed for outpatients, using ambulatory devices in those who require intervention. Funding UK National Institute for Health Research.

Background: RCTs (randomized controlled trials) are the preferred source of evidence to support professional societies’ guidelines. The fragility index (FI), defined as the minimum number of patients whose status would need to switch from nonevent to event to render a statistically significant result nonsignificant, quantitatively estimates the robustness of RCT results. We evaluate RCTs supporting current guidelines on myocardial revascularization using the FI and FI minus number of patients lost to follow-up. Methods and Results: The FI and FI minus number of patients lost to follow-up of RCTs supporting the 2012 American College of Cardiology/American Heart Association Guideline for the Diagnosis and Management of Patients with Stable Ischemic Heart Disease, the 2014 Focused Update of the American College of Cardiology/American Heart Association Guideline for the Diagnosis and Management of Patients with Stable Ischemic Heart Disease, and the 2018 European Society of Cardiology/European Association for Cardio-Thoracic Surgery Guidelines for Myocardial Revascularization were calculated. Of 414 RCTs identified, 160 were eligible for FI calculation. The median FI was 8.0 (95% CI, 5.0–9.0) and the median FI minus number of patients lost to follow-up was 1.0 (95% CI, 0.0–3.0). FI was ≤3, indicating very limited robustness, in 44 (27.5%) RCTs, and was lower than the number LTF, indicating limited robustness, in 68 (42.5%) RCTs. FI was significantly (all P P -value level. Conclusions: More than a quarter of RCTs that support current guidelines on myocardial revascularization have a FI of 3 or lower, and over 40% of trials reveal a FI that is lower than the number of patients lost to follow-up. These findings suggest that the robustness of the findings that support current myocardial revascularization guidelines is tenuous and vulnerable to change as new evidence from RCTs appears.

Background Pleural infection (PI) is a common and complicated disease, bearing a heavy healthcare burden worldwide. Definitive pathogen identification based on current methods occurs in only 40% of cases, mainly due to prior antibiotic administration and special bacterial nutritional culture requirements. To this end PI microbiology knowledge remains incomplete. Novel deep sequencing techniques could increase the rate of reliable pathogen identification and shed light on the complex polymicrobial patterns of PI. Aim To investigate and further characterise the microbial nature of PI using next generation sequencing (NGS). Methods Pleural fluid samples from the ‘Pleural Infection Longitudinal Outcome Study’ (PILOT, ISRCTN50236700, n=243) underwent bacterial DNA extraction followed by 16S rRNA NGS using Illumina MiSeq. Data were analysed with DADA2 and Phyloseq R packages. Results Bacterial DNA from pleural fluid samples was successfully extracted and sequenced. NGS detected 391 diverse pathogens up to the genus level and analysis showed that PI is a polymicrobial disease. 131 (54%) samples had one pathogen with relative abundance over 50% and 89 (36%) samples had at least 3 pathogens with relative abundance over 10%. Streptococcus Pneumoniae was detected in 40 (16%) and Staphylococcus Aureus in 20 (8%) samples. Discussion It is feasible to extract and sequence bacterial DNA from pleural fluid samples from patients with PI. 16S rRNA NGS is a robust method for investigating the total bacteriology of pleural fluid samples. Funding National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC).

Summary Background The prevalence of malignant pleural effusion is increasing worldwide, but prognostic biomarkers to plan treatment and to understand the underlying mechanisms of disease progression remain unidentified. The PROMISE study was designed with the objectives to discover, validate, and prospectively assess biomarkers of survival and pleurodesis response in malignant pleural effusion and build a score that predicts survival. Methods In this multicohort study, we used five separate and independent datasets from randomised controlled trials to investigate potential biomarkers of survival and pleurodesis. Mass spectrometry-based discovery was used to investigate pleural fluid samples for differential protein expression in patients from the discovery group with different survival and pleurodesis outcomes. Clinical, radiological, and biological variables were entered into least absolute shrinkage and selection operator regression to build a model that predicts 3-month mortality. We evaluated the model using internal and external validation. Findings 17 biomarker candidates of survival and seven of pleurodesis were identified in the discovery dataset. Three independent datasets (n=502) were used for biomarker validation. All pleurodesis biomarkers failed, and gelsolin, macrophage migration inhibitory factor, versican, and tissue inhibitor of metalloproteinases 1 (TIMP1) emerged as accurate predictors of survival. Eight variables (haemoglobin, C-reactive protein, white blood cell count, Eastern Cooperative Oncology Group performance status, cancer type, pleural fluid TIMP1 concentrations, and previous chemotherapy or radiotherapy) were validated and used to develop a survival score. Internal validation with bootstrap resampling and external validation with 162 patients from two independent datasets showed good discrimination (C statistic values of 0·78 [95% CI 0·72–0·83] for internal validation and 0·89 [0·84–0·93] for external validation of the clinical PROMISE score). Interpretation To our knowledge, the PROMISE score is the first prospectively validated prognostic model for malignant pleural effusion that combines biological and clinical parameters to accurately estimate 3-month mortality. It is a robust, clinically relevant prognostic score that can be applied immediately, provide important information on patient prognosis, and guide the selection of appropriate management strategies. Funding European Respiratory Society, Medical Research Funding-University of Oxford, Slater & Gordon Research Fund, and Oxfordshire Health Services Research Committee Research Grants.

BackgroundChest drain displacement is a common clinical problem that occurs in 9–42% of cases and results in treatment failure or additional pleural procedures conferring unnecessary risk. A novel chest drain with an integrated intrapleural balloon may reduce the risk of displacement.MethodsA prospective randomised controlled trial comparing the balloon drain to standard care (12 F chest drain with no balloon) with the primary outcome of objectively defined unintentional or accidental chest drain displacement.Results267 patients were randomised (primary outcome data available in 257, 96.2%). Displacement occurred less frequently using the balloon drain (displacement 5 of 128, 3.9%; standard care displacement 13 of 129, 10.1%) but this was not statistically significant (OR for drain displacement 0.36, 95% CI 0.13–1.0, Chi-squared 1 degree of freedom (df)=2.87, p=0.09). Adjusted analysis to account for minimisation factors and use of drain sutures demonstrated balloon drains were independently associated with reduced drain fall-out rate (adjusted OR 0.27, 95% CI 0.08–0.87, p=0.028). Adverse events were higher in the balloon arm than the standard care arm (balloon drain 59 of 131, 45.0%; standard care 18 of 132, 13.6%; Chi-squared 1 df=31.3, pConclusionBalloon drains reduce displacement compared with standard drains independent of the use of sutures but are associated with increased adverse events specifically during drain removal. The potential benefits of the novel drain should be weighed against the risks, but may be considered in practices where sutures are not routinely used.

IntroductionMonitoring vital signs in hospital is an important part of safe patient care. However, there are no robust estimates of the workload it generates for nursing staff. This makes it difficult to plan adequate staffing to ensure current monitoring protocols can be delivered.ObjectiveTo estimate the time taken to measure and record one set of patient’s vital signs observations; and to identify factors associated with time to measure and record one set of patient’s vital signs observations.MethodsWe undertook a time-and-motion study of 16 acute medical or surgical wards across four hospitals in England. One hospital recorded vital signs on paper, while three recorded measurements on electronic devices. Two trained observers followed a standard operating procedure to record the time taken to measure and record vital sign observations. We used mixed-effects models to estimate the mean time using whole observation rounds, which included preparation time, or time spent taking observations at the bedside. We tested whether our estimates were influenced by nurse, ward and hospital factors.ResultsAfter excluding non-vital signs related interruptions, dividing the length of an observation round by the number of observations in that round yielded an estimated time per observation set of 5 minutes and 1 second (95% Confidence Interval (CI) = 4:39-5:24). If interruptions within the round were included, the estimated time was 6:26 (95% CI = 6:01-6:50). If only time taking each patient’s observations at the bedside was considered, after excluding non-vital signs related interruptions the estimated time was 3:45 (95% CI = 3:32-3:58). We found no substantial differences by hospital, ward or nurse characteristics, despite different systems for recording observations being used across the hospitals.DiscussionThe time taken to observe and record a patient’s vital signs is considerable, so changes to recommended observation frequency could have major workload implications. Variation in estimates derived from previous studies may, in part, arise from a lack of clarity about what was included in the reported times. We found no evidence that nurses save time when using electronic vital signs recording, or that the grade of staff taking the observation influenced the time taken.ConclusionsTaking and recording vital signs observations is time consuming and the impact of interruptions and preparation away from the bedside is considerable. When considering the nursing workload around vital signs observations, no assumption of relative efficiency should be made if different technologies or staff groups are deployed.

IntroductionAmbulatory monitoring systems (AMS) can facilitate early detection of clinical deterioration, and have the potential to improve hospitalised patient outcomes. The objective of this systematic review is to assess the impact of vital signs monitoring on detection of deterioration and related outcomes in hospitalised patients using AMS, in comparison with standard care.Methods and analysisA systematic search was conducted on 27 August 2020 in MEDLINE, Embase, CINAHL, Cochrane Database of Systematic Reviews, CENTRAL and Health Technology Assessment databases, as well as grey literature. Search results will be reviewed in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis checklist for systematic reviews. Studies comparing the use of ambulatory monitoring devices against standard care for deterioration detection and related clinical outcomes in hospitalised patients will be included and further clinical and other outcomes will also be explored. Deterioration-related outcomes may include (but not limited to) unplanned intensive care admissions, rapid response team activation and unscheduled emergency interventions, as defined by the included studies. Two reviewers will independently extract study data and assess the quality and risk of bias of included studies. Where possible, a meta-analysis will be conducted and quantitative results presented. Alternatively, a narrative synthesis will be reported.Ethics and disseminationEthical approval is not required for this study as no primary data will be collected. This study is part of our virtual High Dependency Unit project and will be disseminated through peer-reviewed publications, public and scientific conference presentations.PROSPERO registration numberCRD42020188633.

Background: Respiratory complications are common after cardiac surgery and the use of extracorporeal circulation is one of the main causes of lung injury. We hypothesized a better postoperative respiratory function in off-pump coronary artery bypass grafting (OPCABG) as compared with “on-pump coronary artery bypass grafting” (ONCABG). Methods: This is a retrospective, single-center study at a cardiothoracic intensive care unit (ICU) in a tertiary university hospital. Consecutive data on 339 patients undergoing elective CABG (n = 215 ONCABG, n = 124 OPCABG) were collected for 1 year from the ICU electronic medical records. We compared respiratory variables (Pao2, Pao2/Fio2 ratio, Sao2, and Paco2) at 7 predefined time points (ICU admission, postoperative hours 1, 3, 6, 12, 18, and 24). We also evaluated time to extubation, rates of reintubation, and use of noninvasive ventilation (NIV). We used mixed-effects linear regression models (with time as random effect for clustering of repeated measures) adjusted for a predetermined set of covariates. Results: The values of Pao2 and Pao2/Fio2 were significantly higher in the OPCABG group only at ICU admission (mean differences: 9.7 mm Hg, 95% confidence interval [CI] 3.1-16.2; and 27, 95% CI 6.1-47.7, respectively). The OPCABG group showed higher Paco2, overall ( P = .02) and at ICU admission (mean difference 1.8 mm Hg, 95% CI: 0.6-3), although mean values were always within normal range in both groups. No differences were seen in Sao2 values, time to extubation, rate of reintubation rate, and use of postoperative NIV. Extubation rate was higher in OPCABG only at postoperative hour 12 (92% vs ONCABG 82%, P = .02). Conclusion: The OPCABG showed only marginal improvements of unlikely clinical meaning in oxygenation as compared to ONCABG in elective low-risk patients.

BackgroundThe use of bilateral internal thoracic (mammary) arteries for coronary-artery bypass grafting (CABG) may improve long-term outcomes as compared with the use of a single internal-thoracic-artery plus vein grafts.MethodsWe randomly assigned patients scheduled for CABG to undergo single or bilateral internal-thoracic-artery grafting in 28 cardiac surgical centers in seven countries. The primary outcome was death from any cause at 10 years. The composite of death from any cause, myocardial infarction, or stroke was a secondary outcome. Interim analyses were prespecified at 5 years of follow-up.ResultsA total of 3102 patients were enrolled; 1554 were randomly assigned to undergo single internal-thoracic-artery grafting (the single-graft group) and 1548 to undergo bilateral internal-thoracic-artery grafting (the bilateral-graft group). At 5 years of follow-up, the rate of death was 8.7% in the bilateral-graft group and 8.4% in the single-graft group (hazard ratio, 1.04; 95% confidence interval [CI], 0.81 to 1.32; P=0.77), and the rate of the composite of death from any cause, myocardial infarction, or stroke was 12.2% and 12.7%, respectively (hazard ratio, 0.96; 95% CI, 0.79 to 1.17; P=0.69). The rate of sternal wound complication was 3.5% in the bilateral-graft group versus 1.9% in the single-graft group (P=0.005), and the rate of sternal reconstruction was 1.9% versus 0.6% (P=0.002).ConclusionsAmong patients undergoing CABG, there was no significant difference between those receiving single internal-thoracic-artery grafts and those receiving bilateral internal-thoracic-artery grafts with regard to mortality or the rates of cardiovascular events at 5 years of follow-up. There were more sternal wound complications with bilateral internal-thoracic-artery grafting than with single internal-thoracic-artery grafting. Ten-year follow-up is ongoing. (Funded by the British Heart Foundation and others; ART Current Controlled Trials number, ISRCTN46552265.)

Background and purpose We investigated whether automated and reader-based ASPECTS in acute stroke patients are affected by different CT image reconstruction algorithms. Methods ASPECTS were assessed by commercial software and four independent blinded readers (two residents and two consultants) from different CT reconstructions (filtered back projection and two different iterative reconstruction [IR] levels) in 43 acute stroke patients with proximal middle cerebral artery occlusion. Ground truth was provided by an expert with unrestricted data access. Results The residents showed significant variations between IR levels and had a significantly lower internal consistency across different reconstructions compared to the software, which performed similarly to the consultants. The consultant as well as the software also showed different deviations from ground truth with different IR levels, which were least at IR strength level 2. Conclusions CT image postprocessing affects either automated or human ASPECTS in acute stroke patients. This effect was most pronounced in the less experienced readers, while the software had the most robust performance.

BackgroundThe use of bilateral internal thoracic arteries (BITA) for coronary artery bypass grafting (CABG) may improve survival compared with CABG using single internal thoracic arteries (SITA). We assessed the long-term costs of BITA compared with SITA.MethodsBetween June 2004 and December 2007, 3102 patients from 28 hospitals in seven countries were randomised to CABG surgery using BITA (n=1548) or SITA (n=1554). Detailed resource use data were collected from the initial hospital episode and annually up to 5 years. The associated costs of this resource use were assessed from a UK perspective with 5 year totals calculated for each trial arm and pre-selected patient subgroups.ResultsTotal costs increased by approximately £1000 annually in each arm, with no significant annual difference between trial arms. Cumulative costs per patient at 5-year follow-up remained significantly higher in the BITA group (£18 629) compared with the SITA group (£17 480; mean cost difference £1149, 95% CI £330 to £1968, p=0.006) due to the higher costs of the initial procedure. There were no significant differences between the trial arms in the cost associated with healthcare contacts, medication use or serious adverse events.ConclusionsHigher index costs for BITA were still present at 5-year follow-up mainly driven by the higher initial cost with no subsequent difference emerging between 1 year and 5 years of follow-up. The overall cost-effectiveness of the two procedures, to be assessed at the primary endpoint of the 10-year follow-up, will depend on composite differences in costs and quality-adjusted survival.Trial registration numberISRCTN46552265

Background Current reference ranges for blood pressure and heart rate throughout pregnancy have a poor evidence base. Methods This is a systematic review and meta-analysis. We included studies measuring blood pressure or heart rate from healthy pregnant women within defined gestational periods of 16 weeks or less. We analysed systolic blood pressure, diastolic blood pressure and heart rate by gestational age. We assessed effects of measurement year and method. Results We included 39 studies undertaken in 1967–2017, containing 124,349 systolic measurements from 36,239 women, 124,291 diastolic measurements from 36,181 women and 10,948 heart rate measurements from 8317 women. Mean (95% CI) systolic blood pressure was lowest at 10 weeks gestation, 110.4 (108.5, 112.3) mmHg, rising to 116.0 (113.6, 118.4) mmHg at 40 weeks, mean (95% CI) change 5.6 (4.0, 7.2) mmHg. Mean (95% CI) diastolic blood pressure was lowest at 21 weeks gestation, 65.9 (64.2, 67.7) mmHg; rising to 72.8 (71.0, 74.6) mmHg at 40 weeks, mean (95% CI) change 6.9 (6.2, 7.5) mmHg. Mean (95% CI) heart rate rose from 79.3 (75.5, 83.1) beats/min at 10 weeks to 86.9 (82.2, 91.6) beats/min at 40 weeks gestation, mean (95% CI) change 7.6 (1.8, 13.4) beats/min. Studies using manual measurement reported higher diastolic blood pressures than studies using automated measurement, mean (95 CI) difference 4.9 (0.8, 8.9) mmHg. Diastolic blood pressure increased by 0.26 (95% CI 0.10–0.43) mmHg/year. Including only higher-quality studies had little effect on findings, with heterogeneity remaining high (I2 statistic > 50%). Conclusions Significant gestational blood pressure and heart rate changes occur that should be taken into account when assessing pregnant women. Commonly taught substantial decreases in blood pressure mid-pregnancy were not seen and heart rate increases were lower than previously thought. Manual and automated blood pressure measurement cannot be used interchangeably. Increases in diastolic blood pressure over the last half-century and differences between published studies show contemporary data are required to define current normal ranges. Study registration PROSPERO CRD42014009673

Objective: Over the last 15 years, developments in camera technology have coincided with increased availability and affordability. This has led to an increasing interest in using these technologies in healthcare settings. Image-based monitoring methods potentially allow multiple vital signs to be measured concurrently using a non-contact sensor. We have undertaken a systematic review of the current availability and performance of these monitoring methods. Approach: A multiple database search was conducted using MEDLINE, Embase, CINAHL, Cochrane Library, OpenGrey, IEEE Xplore Library and ACM Digital Library to July 2018. We included studies comparing image-based heart rate, respiratory rate, oxygen saturation and blood pressure monitoring methods against one or more validated reference device(s). Each included study was assessed using the modified GRRAS criteria for reporting bias. Main results: Of 30 279 identified studies, 161 were included in the final analysis. Twenty studies (20/161, 12%) were carried out on patients in clinical settings, while the remainder were conducted in academic settings using healthy volunteer populations. The 18–40 age group was best represented across the identified studies. One hundred and twenty studies (120/161, 75%) estimated heart rate, followed by 62 studies (62/161, 39%) estimating respiratory rate. Fewer studies focused on oxygen saturation (11/161, 7%) or blood pressure (6/161, 4%) estimation. Fifty-one heart rate studies (51/120, 43%) and 24 respiratory rate studies (24/62, 39%) used Bland–Altman analysis to report their results. Of the heart rate studies, 28 studies (28/51, 55%) showed agreement within industry standards of 5 beats per minute. Only two studies achieved this within clinical settings. Of the respiratory rate studies, 13 studies (13/24, 54%) showed agreement within industry standards of 3 breaths per minute, but only one study achieved this in a clinical setting. Statistical analysis was heterogeneous across studies with frequent inappropriate use of correlation. The majority of studies (99/161, 61%) monitored subjects for under 5 min. Three studies (3/161, 2%) monitored subjects for over 60 min, all of which were conducted in hospital settings. Significance: Heart rate and respiratory rate monitoring using video images is currently possible and performs within clinically acceptable limits under experimental conditions. Camera-derived estimates were less accurate in the proportion of studies conducted in clinical settings. We would encourage thorough reporting of the population studied, details of clinically relevant aspects of methodology, and the use of appropriate statistical methods in future studies. Systematic review registration: PROSPERO CRD42016029167 Protocol: https://systematicreviewsjournal.biomedcentral.com/articles/10.1186/s13643-017-0615-3

Background: Malignant pleural effusion (MPE) is a common condition that indicates advanced malignancy as it signals incurability, shortened life expectancy, and severely compromised quality of life. While MPE incidence is increasing worldwide, the discovery of prognostic biomarkers remains an unmet clinical need. Objective: To address that clinical call we designed a study to discover, validate and prospectively assess prognostic and therapeutic biomarkers for MPE and develop score that combines pleural fluid biology with clinical and radiological data. Methods: Five separate and independent patient cohorts (TIME-1, TIME-2, TIME-3, SIMPLE and Pleural Biobank), from previous clinical trials, have been used in order to establish a prognostic and therapeutic score for MPE. We considered clinical, radiological and biological factors as candidate variables. We assessed performance using both internal and external validation. Results: A high throughput mass spectrometry was applied to screen samples of the TIME-2 database for differential protein expression between the groups with differences in survival and pleurodesis outcome. Three databases (TIME1,2,3) were used for the validation of the protein expression. Data from 435 patients was used to develop the PROMISE score, which includes eight variables. Internal validation using bootstrap resampling and external validation using 161 patients (SIMPLE and biobank) both suggested good discrimination (c-index 0.78 and 0.89 respectively). In addition, external validation shows the model is well calibrated. Conclusions: We managed to develop and prospectively validate a prognostic score for MPE patients to estimate risk of 3-month mortality.

Thoracic electrical bioimpedance (TEB) and transthoracic echocardiography (TTE) are non-invasive methods to estimate stroke volume (SV) and cardiac output (CO). Thoracic electrical bioimpedance is not in widespread clinical use with reports of inaccurate cardiac output estimation compared to invasive monitors, particularly in non-healthy populations. We explore its use as a trend monitor by comparing it against thoracic echocardiography in fifteen healthy volunteers undergoing two physical challenges designed to vary cardiac output. Of all paired values, 54.6% showed gross trend agreement and only 1.9% showed direct disagreement between the two monitors. Our results show thoracic bioimpedance may have a role as a non-invasive cardiac output trend monitor in healthy volunteer studies.

We sought to establish whether continuous positive airway pressure (CPAP) for obstructive sleep apnoea (OSA) in people with type 2 diabetes and diabetic macular oedema (DMO) improved visual acuity. We randomly assigned 131 eligible patients aged 30–85 years from 23 UK centres with significant DMO causing visual impairment (LogMAR letters identified ≥39 and ≤78, score 0.92–0.14) plus severe OSA on screening to either usual ophthalmology care (n=67) or usual ophthalmology care plus CPAP (n=64) for 12 months. Mean age of participants was 64 years, 73% male, mean body mass index 35.0 kg·m−2. Mean 4% oxygen desaturation index was 36 events·h−1. There was no significant difference in the visual acuity at 12 months between the CPAP group and the control group (mean LogMAR 0.33 (95% CI 0.29–0.37) versus 0.31 (95% CI 0.27–0.35); p=0.39), and no significant correlation between change in LogMAR and average CPAP use. The median±sd (range) daily CPAP use was 3.33±2.25 (0–7.93) h at 3 months, 3.19±2.54 (0–8.07) h at 6 months and 3.21±2.70 (0–7.98) h at 12 months. CPAP therapy for OSA did not improve visual acuity in people with type 2 diabetes and DMO compared with usual care alone over 12 months., UK ROSA RCT shows 1 year of CPAP for OSA in people with type 2 diabetes and macular oedema does not improve visual acuity http://ow.ly/bw8H30lrAX8

BackgroundOver 30% of adult patients with pleural infection either die and/or require surgery. There is no robust means of predicting at baseline presentation which patients will suffer a poor clinical outcome. A validated risk prediction score would allow early identification of high-risk patients, potentially directing more aggressive treatment thereafter.ObjectivesTo prospectively assess a previously described risk score (the RAPID (Renal (urea), Age, fluid Purulence, Infection source, Dietary (albumin)) score) in adults with pleural infection.MethodsProspective observational cohort study that recruited patients undergoing treatment for pleural infection. RAPID score and risk category were calculated at baseline presentation. The primary outcome was mortality at 3 months; secondary outcomes were mortality at 12 months, length of hospital stay, need for thoracic surgery, failure of medical treatment and lung function at 3 months.ResultsMortality data were available in 542 out of 546 patients recruited (99.3%). Overall mortality was 10% at 3 months (54 out of 542) and 19% at 12 months (102 out of 542). The RAPID risk category predicted mortality at 3 months. Low-risk mortality (RAPID score 0–2): five out of 222 (2.3%, 95% CI 0.9 to 5.7%); medium-risk mortality (RAPID score 3–4): 21 out of 228 (9.2%, 95% CI 6.0 to 13.7%); and high-risk mortality (RAPID score 5–7): 27 out of 92 (29.3%, 95% CI 21.0 to 39.2%). C-statistics for the scores at 3 months and 12 months were 0.78 (95% CI 0.71–0.83) and 0.77 (95% CI 0.72–0.82), respectively.ConclusionsThe RAPID score stratifies adults with pleural infection according to increasing risk of mortality and should inform future research directed at improving outcomes in this patient population.

Background: Pleural infection is common and associated with significant morbidity and mortality. Previous retrospective data have suggested the sonographic presence of pleural fluid septation at diagnosis may be a prognostic indicator [1]. Method The Pleural Infection Longitudinal Outcome Study (PILOT) was a multinational prospective observational cohort study (n = 551 patients) powered to validate a previously described clinical risk score (RAPID) [2]. The primary outcome was 3-month mortality from pleural infection. Secondary outcomes included surgical referral; failure of initial medical therapy; and length of hospital stay. Data collected included the sonographic extent of pleural fluid septation at diagnosis, as determined by the responsible clinician sonographer. The study was funded by the UK Medical Research Council, and registered with ClinicalTrials.gov (ISRCTN 50236700). Results: The presence of pleural fluid septation did not have a significant impact on the study’s primary outcome (figure 1); although it did reduce the performance of the clinical risk score. Conclusion: Pleural fluid septation does not have an independent impact on mortality from pleural infection, although it may have an influence on other relevant clinical outcomes. References 1. Ultrasound Med Biol 2009; 35(9):1468-74 2. Chest 2014; 145(4):848-55

PurposeMalignant pleural mesothelioma (MPM) has a high symptom burden and poor survival. Evidence from other cancer types suggests some benefit in health-related quality of life (HRQoL) with early specialist palliative care (SPC) integrated with oncological services, but the certainty of evidence is low.MethodsWe performed a multicentre, randomised, parallel group controlled trial comparing early referral to SPC versus standard care across 19 hospital sites in the UK and one large site in Western Australia. Participants had newly diagnosed MPM; main carers were additionally recruited. Intervention: review by SPC within 3 weeks of allocation and every 4 weeks throughout the study. HRQoL was assessed at baseline and every 4 weeks with the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30. Primary outcome: change in EORTC C30 Global Health Status 12 weeks after randomisation.ResultsBetween April 2014 and October 2016, 174 participants were randomised. There was no significant between group difference in HRQoL score at 12 weeks (mean difference 1.8 (95% CI −4.9 to 8.5; p=0.59)). HRQoL did not differ at 24 weeks (mean difference −2.0 (95% CI −8.6 to 4.6; p=0.54)). There was no difference in depression/anxiety scores at 12 weeks or 24 weeks. In carers, there was no difference in HRQoL or mood at 12 weeks or 24 weeks, although there was a consistent preference for care, favouring the intervention arm.ConclusionThere is no role for routine referral to SPC soon after diagnosis of MPM for patients who are cared for in centres with good access to SPC when required.Trial registration numberISRCTN18955704.

We investigated whether automated and reader-based ASPECTS in acute stroke patients are affected by different CT image reconstruction algorithms.ASPECTS were assessed by commercial software and four independent blinded readers (two residents and two consultants) from different CT reconstructions (filtered back projection and two different iterative reconstruction [IR] levels) in 43 acute stroke patients with proximal middle cerebral artery occlusion. Ground truth was provided by an expert with unrestricted data access.The residents showed significant variations between IR levels and had a significantly lower internal consistency across different reconstructions compared to the software, which performed similarly to the consultants. The consultant as well as the software also showed different deviations from ground truth with different IR levels, which were least at IR strength level 2.CT image postprocessing affects either automated or human ASPECTS in acute stroke patients. This effect was most pronounced in the less experienced readers, while the software had the most robust performance.

Background: Data smoothing of vital signs has been reported in the anesthesia literature, suggesting that clinical staff are biased toward measurements of normal physiology. However, these findings may be partially explained by clinicians interpolating spurious values from noisy signals and by the undersampling of physiological changes by infrequent manual observations. We explored the phenomenon of data smoothing using a method robust to these effects in a large postoperative dataset including respiratory rate, heart rate, and oxygen saturation (SpO2). We also assessed whether the presence of the vital sign taker creates an arousal effect. Methods: Study data came from a UK upper gastrointestinal postoperative ward (May 2009 to December 2013). We compared manually recorded vital sign data with contemporaneous continuous data recorded from monitoring equipment. We proposed that data smoothing increases differences between vital sign sources as vital sign abnormality increases. The primary assessment method was a mixed-effects model relating continuous-manual differences to vital sign values, adjusting for repeated measurements. We tested the regression slope significance and predicted the continuous-manual difference at clinically important vital sign values. We calculated limits of agreement (LoA) between vital sign sources using the Bland–Altman method, adjusting for repeated measures. Similarly, we assessed whether the vital sign taker affected vital signs, comparing continuous data before and during manual recording. Results: From 407 study patients, 271 had contemporaneous continuous and manual recordings, allowing 3740 respiratory rate, 3844 heart rate, and 3896 SpO2 paired measurements for analysis. For the model relating continuous-manual differences to continuous-manual average vital sign values, the regression slope (95% confidence interval) was 0.04 (−0.01 to 0.10; P = .11) for respiratory rate, 0.04 (−0.01 to 0.09; P = .11) for heart rate, and 0.10 (0.07–0.14; P < .001) for SpO2. For SpO2 measurements of 91%, the model predicted a continuous-manual difference (95% confidence interval) of −0.88% (−1.17% to −0.60%). The bias (LoA) between measurement sources was −0.74 (−7.80 to 6.32) breaths/min for respiratory rate, −1.13 (−17.4 to 15.1) beats/min for heart rate, and −0.25% (−3.35% to 2.84%) for SpO2. The bias (LoA) between continuous data before and during manual observation was −0.57 (−5.63 to 4.48) breaths/min for respiratory rate, −0.71 (−10.2 to 8.73) beats/min for heart rate, and −0.07% (−2.67% to 2.54%) for SpO2. Conclusions: We found no evidence of data smoothing for heart rate and respiratory rate measurements. Although an effect exists for SpO2 measurements, it was not clinically significant. The wide LoAs between continuous and manually recorded vital signs would commonly result in different early warning scores, impacting clinical care. There was no evidence of an arousal effect caused by the vital sign taker.

BackgroundThe Arterial Revascularization Trial has been designed to answer the question whether the use of bilateral internal thoracic arteries can improve 10-year outcomes when compared with single internal thoracic arteries. In the Arterial Revascularization Trial, a significant proportion of patients initially allocated to bilateral internal thoracic arteries received other conduit strategies. We sought to investigate the incidence and clinical implication of bilateral internal thoracic artery graft conversion in the Arterial Revascularization Trial.MethodsAmong patients enrolled in the Arterial Revascularization Trial (n = 3102), we excluded those allocated to single internal thoracic arteries (n = 1554), those who did not undergo surgery (n = 16), and those who underwent operation but withdrew after randomization (n = 7). Propensity score matching was used to compare converted versus nonconverted bilateral internal thoracic artery groups.ResultsA total of 1525 patients were operated with the intention to receive bilateral internal thoracic artery grafting. Of those, 233 (15.3%) were converted to other conduit selection strategies. Incidence of conversion largely varied across 131 participating surgeons (from 0% to 100%). The most common reason for bilateral internal thoracic artery graft conversion was the evidence of at least 1 internal thoracic artery that was not suitable, which was reported in 77 cases. Patients with intraoperative bilateral internal thoracic artery graft conversion received a lower number of grafts (2.95 ± 0.84 vs 3.21 ± 0.74; P ConclusionsThe incidence of intraoperative bilateral internal thoracic artery graft conversion is not infrequent. Bilateral internal thoracic artery graft conversion is not associated with increased operative morbidity, but its effect on late outcomes remains uncertain.

IntroductionEarly warning scores (EWSs) are used extensively to identify patients at risk of deterioration in hospital. Previous systematic reviews suggest that studies which develop EWSs suffer methodological shortcomings and consequently may fail to perform well. The reviews have also identified that few validation studies exist to test whether the scores work in other settings. We will aim to systematically review papers describing the development or validation of EWSs, focusing on methodology, generalisability and reporting.MethodsWe will identify studies that describe the development or validation of EWSs for adult hospital inpatients. Each study will be assessed for risk of bias using the Prediction model Risk of Bias ASsessment Tool (PROBAST). Two reviewers will independently extract information. A narrative synthesis and descriptive statistics will be used to answer the main aims of the study which are to assess and critically appraise the methodological quality of the EWS, to describe the predictors included in the EWSs and to describe the reported performance of EWSs in external validation.Ethics and disseminationThis systematic review will only investigate published studies and therefore will not directly involve patient data. The review will help to establish whether EWSs are fit for purpose and make recommendations to improve the quality of future research in this area.PROSPERO registration numberCRD42017053324.

Background: Recent basic and clinical evidence suggests amiloride may be neuroprotective in multiple sclerosis (MS) through the blockade of the acid sensing ion channel (ASIC). Objective: To examine the neuroprotective efficacy of amiloride in acute optic neuritis (ON). Methods: A total of 48 patients were recruited to a phase 2, double blind, single site, randomised controlled trial. Scanning laser polarimetry (GDx) at 6 months was the primary outcome measure and optical coherence tomography (OCT) and visual and electrophysiological measures were secondary outcome measures. Participants aged 18–55 years, ≤28 days of onset of first episode unilateral ON, were randomised to amiloride (10 mg daily for 5 months) or placebo ( clinicaltrials.gov , NCT 01802489). Results: Intention-to-treat (ITT) cohort consisted of 43 patients; 23 placebo and 20 amiloride. No significant drug-related adverse events occurred. No significant differences were found in GDx ( p = 0.840). Visual evoked potentials (VEP) were significantly prolonged in the amiloride group compared to placebo ( p = 0.004). All other secondary outcome measures showed no significant difference. Baseline analysis of OCT data demonstrated a significant pre-randomisation thinning of ganglion cell layer. Conclusion: Amiloride has not demonstrated any neuroprotective benefit within this trial paradigm, but future neuroprotective trials in ON should target the window of opportunity to maximise potential neuroprotective benefit.

Background For many vital signs, monitoring methods require contact with the patient and/or are invasive in nature. There is increasing interest in developing still and video image-guided monitoring methods that are non-contact and non-invasive. We will undertake a systematic review of still and video image-based monitoring methods. Methods We will perform searches in multiple databases which include MEDLINE, Embase, CINAHL, Cochrane library, IEEE Xplore and ACM Digital Library. We will use OpenGrey and Google searches to access unpublished or commercial data. We will not use language or publication date restrictions. The primary goal is to summarise current image-based vital signs monitoring methods, limited to heart rate, respiratory rate, oxygen saturations and blood pressure. Of particular interest will be the effectiveness of image-based methods compared to reference devices. Other outcomes of interest include the quality of the method comparison studies with respect to published reporting guidelines, any limitations of non-contact non-invasive technology and application in different populations. Discussion To the best of our knowledge, this is the first systematic review of image-based non-contact methods of vital signs monitoring. Synthesis of currently available technology will facilitate future research in this highly topical area. Systematic review registration PROSPERO CRD42016029167 Electronic supplementary material The online version of this article (10.1186/s13643-017-0615-3) contains supplementary material, which is available to authorized users.

BACKGROUND: The aim of this study was to describe the longevity and causes of mortality in 39 (12 males, 27 females) pedigree adult neutered Labrador retrievers with a median age of 6.5 years at the start of the study and kept under similar housing and management conditions. Body condition score was maintained between two and four on a 5-point scale by varying food allowances quarterly. The impact of change in body weight (BW) and body composition on longevity was analysed using linear mixed models with random slopes and intercepts. RESULTS: On 31 July 2014, 10 years after study start, dogs were classified into three lifespan groups: 13 (33 %) Expected (≥9 to ≤12.9 years), 15 (39 %) Long (≥13 to ≤15.5 years) and 11 (28 %) Exceptional (≥15.6 years) with five still alive. Gender and age at neutering were not associated with longevity (P ≥ 0.06). BW increased similarly for all lifespan groups up to age 9, thereafter, from 9 to 13 years, Exceptional dogs gained and Long-lifespan dogs lost weight (P = 0.007). Dual-energy x-ray absorptiometer scans revealed that absolute fat mass increase was slower to age 13 for Long compared with Expected lifespan dogs (P = 0.003) whilst all groups lost a similar amount of absolute lean mass (P > 0.05). Percent fat increase and percent lean loss were slower, whilst the change in fat:lean was smaller, in both the Exceptional and Long lifespan compared with Expected dogs to age 13 (P ≤ 0.02). Total bone mineral density was significantly lower for Expected compared to Exceptional and Long lifespan dogs (P

Objective: To investigate time differences in recording observations and an early warning score using traditional paper charts and a novel e-Obs system in clinical practice. Methods: Researchers observed the process of recording observations and early warning scores across 3 wards in 2 university teaching hospitals immediately before and after introduction of the e-Obs system. The process of recording observations included both measurement and documentation of vital signs. Interruptions were timed and subtracted from the measured process duration. Multilevel modeling was used to compensate for potential confounding factors. Results: In all, 577 nurse events were observed (281 paper, 296 e-Obs). The geometric mean time to take a complete set of vital signs was 215 s (95% confidence interval [CI], 177 s–262 s) on paper, and 150 s (95% CI, 130 s–172 s) electronically. The treatment effect ratio was 0.70 (95% CI, 0.57–0.85, P Discussion: Introduction of an e-Obs system was associated with a statistically significant reduction in overall time to measure and document vital signs electronically compared to paper documentation. The reductions in time varied among wards and were of clinical significance on only 1 of 3 wards studied. Conclusion: Our results suggest that introduction of an e-Obs system could lower nursing workload as well as increase documentation quality.

Background Neuropsychiatric symptoms in Alzheimer disease (AD) cause significant distress and present a complex clinical challenge for treatment. Pharmacological treatment options are limited to antipsychotics, which carry extensive safety issues. There is emerging evidence to support the potential benefits of memantine, currently licensed for moderate to severe AD, in the prophylaxis of neuropsychiatric symptoms. Methods The MAIN-AD study is a double-blind randomized placebo-controlled withdrawal trial comparing memantine with antipsychotics for the treatment of neuropsychiatric symptoms over 24 weeks. A total of 199 people with probable AD living in care homes already receiving an antipsychotic were randomized to receive either memantine or to continue an antipsychotic. The primary outcomes were function (Bristol Activities of Daily Living Scale [BADLS]) and agitation (Cohen-Mansfield Agitation Inventory [CMAI]). Secondary outcomes were Neuropsychiatric Inventory (NPI), Mini-Mental State Examination (MMSE), and mortality. Results There was no significant difference between groups on the BADLS or CMAI. At 24 weeks, there was a nonsignificant adjusted difference in favor of memantine on the BADLS of 0.23 (95% CI –1.80–2.27; P = .82) and in favor of antipsychotic on the CMAI of 0.09 (95% CI –0.35–8.53; P = .07). Although there were no significant differences in total NPI, there were 5.01 (95% CI –1.68–11.70; P = .05) and 3.63 (95% CI –1.40–8.67; P = .16) point advantages favoring antipsychotics at weeks 12 and 24, respectively. In addition, in an exploratory analysis, individuals allocated to antipsychotics were significantly less likely to experience relapse of neuropsychiatric symptoms at all time points. The group receiving memantine had a nonsignificant 1.3-point advantage on the MMSE at 24 weeks. Discussion This study indicates no benefits for memantine in the long-term treatment and prophylaxis of clinically significant neuropsychiatric symptoms. The results did indicate some benefits for antipsychotic medications in reducing the relapse of neuropsychiatric symptoms, but this must be balanced against increased mortality risk.

Aims Angiotensin-converting enzyme (ACE) inhibitors improve left ventricular (LV) remodelling and outcome in heart failure and hypertensive heart disease. They may be similarly beneficial in patients with aortic stenosis (AS), but historical safety concerns have limited their use, and no prospective clinical trials exist. Methods and results We conducted a prospective, randomized, double-blind, placebo-controlled trial in 100 patients with moderate or severe asymptomatic AS to examine the physiological effects of ramipril, particularly LV mass (LVM) regression. Subjects were randomized to ramipril 10 mg daily ( n = 50) or placebo ( n = 50) for 1 year, and underwent cardiac magnetic resonance, echocardiography, and exercise testing at 0, 6, and 12 months, with follow-up data available in 77 patients. There was a modest but progressive reduction in LVM (the primary end point) in the ramipril group vs. the placebo group (mean change −3.9 vs. +4.5 g, respectively, P = 0.0057). There were also trends towards improvements in myocardial physiology: the ramipril group showed preserved tissue Doppler systolic velocity compared with placebo (+0.0 vs. −0.5 cm/s, P = 0.04), and a slower rate of progression of the AS (valve area 0.0 cm2 in the ramipril group vs. −0.2 cm2 in the placebo arm, P = 0.067). There were no significant differences in major adverse cardiac events. Conclusion ACE inhibition leads to a modest, but progressive reduction in LVM in asymptomatic patients with moderate–severe AS compared with placebo, with trends towards improvements in myocardial physiology and slower progression of valvular stenosis. A larger clinical outcome trial to confirm these findings and explore their clinical relevance is required. [10.1093/ehjci/jev082][1] [1]: /lookup/doi/10.1093/ehjci/jev082

IntroductionSuccessive confidential enquiries into maternal deaths in the UK have identified an urgent need to develop a national early warning score (EWS) specifically for pregnant or recently pregnant women to aid more timely recognition, referral and treatment of women who are developing life-threatening complications in pregnancy or the puerperium. Although many local EWS are in use in obstetrics, most have been developed heuristically. No current obstetric EWS has defined the thresholds at which an alert should be triggered using evidence-based normal ranges, nor do they reflect the changing physiology that occurs with gestation during pregnancy.Methods and analysisAn observational cohort study involving 1000 participants across three UK sites in Oxford, London and Newcastle. Pregnant women will be recruited at approximately 14 weeks’ gestation and have their vital signs (heart rate, blood pressure, respiratory rate, oxygen saturation and temperature) measured at 4 to 6-week intervals during pregnancy. Vital signs recorded during labour and delivery will be extracted from hospital records. After delivery, participants will measure and record their own vital signs daily for 2 weeks. During the antenatal and postnatal periods, vital signs will be recorded on an Android tablet computer through a custom software application and transferred via mobile internet connection to a secure database. The data collected will be used to define reference ranges of vital signs across normal pregnancy, labour and the immediate postnatal period. This will inform the design of an evidence-based obstetric EWS.Ethics and disseminationThe study has been approved by the NRES committee South East Coast–Brighton and Sussex (14/LO/1312) and is registered with the ISRCTN (10838017). All participants will provide written informed consent and can withdraw from the study at any point. All data collected will be managed anonymously. The findings will be disseminated in international peer-reviewed journals and through research conferences.

Objectives: There is still little evidence to support routine dual antiplatelet therapy (DAPT) with P2Y12 antagonists following coronary artery bypass grafting (CABG). The Arterial Re-vascularization Trial (ART) was designed to compare 10-year survival after bilateral versus single internal thoracic artery grafting. We aimed to get insights into the effect of DAPT (with clopidogrel) following CABG on 1 year outcomes by performing a post-hoc ART anal-ysis. Methods: Among patients enrolled in the ART (n=3102), 609 (21%) and 2308 (79%) were discharged on DAPT or aspirin alone respectively. The primary endpoint was the incidence of major adverse cerebrovascular and cardiac events (MACCE) at 1 year including cardiac death, myocardial infarction, cerebrovascular accident and reintervention; safety endpoint was bleeding requiring hospitalization. Propensity score (PS) matching was used to create comparable groups. Results: Among 609-PS matched pairs, MACCE occurred in 34 (5.6%) and 34 (5.6%) in the DAPT and aspirin alone groups respectively with no significant difference between the two groups (HR 0.97; 95%CI 0.59-1.59; P=0.90). Only 188 (31%) subjects completed 1 year of DAPT and in this subgroup, MACCE rate was 5.8% (HR 1.11; 95%CI 0.53-2.30; P=0.78). In the overall sample, bleeding rate was higher in DAPT group (2.3% versus 1.1%; P=0.02) although this difference was no longer significant after matching (2.3% vs 1.8%; P=0.54). Conclusions: Based on these findings, when compared to aspirin alone, DAPT with clopidogrel prescribed at discharge was not associated with a significant reduction of adverse cardiac and cerebrovascular events at 1 year following CABG.

Background Temporal changes in the placebo arm of randomized controlled trials (RCTs) have not been thoroughly investigated, despite the fact that results of RCTs depend on the comparison between arms. Methods In this update of our earlier systematic review and meta-analysis, we set out to investigate the effect of assessment time and number of visits on the magnitude of change from baseline in the placebo arm of these trials. We used linear mixed-effects models to account for within-trial correlations. Results Across all 47 trials the magnitude of response in the placebo arm did not change with time (β = -0.0070, 95% CI -0.024, 0.010) or visit (β = -0.033, 95% CI -0.082, 0.017) and remained significantly different from baseline for at least 12 months or seven follow-up visits. Change in the placebo arm in trials with subjective outcomes was large (β0 = 0.68, 95% CI 0.53, 0.82) and relatively constant across time (β = -0.0042, 95% CI -0.024, 0.016) and visit (β = -0.029, 95% CI -0.089, 0.031), whereas in trials with objective outcomes the response was smaller (β0 = 0.28, 95% CI 0.11, 0.46) and diminished with time (β = -0.030, 95% CI -0.050, -0.010), but not with visit (β = -0.099, 95% CI -0.30, 0.11). For trials with assessed outcomes, there was no significant effect of time (β = -0.0071, 95% CI -0.026, 0.011) or visit (β = -0.032, 95% CI -0.33, 0.26); however, these results should be interpreted with caution due to the small number of studies, and high clinical heterogeneity between studies. In trials with pain as an outcome, the improvement was significant (β0 = 0.91, 95% CI 0.75, 1.07), but there was no effect of time (β = -0.013, 95% CI -0.06, 0.03) or visit (β = -0.045, 95% CI -0.16, 0.069), and pain ratings remained significantly different from baseline for 12 months or seven visits. Conclusions These results are consistent with our previous findings. In trials with subjective outcomes response in the placebo arm remains large and relatively constant for at least a year, which is interesting considering that this is an effect of a single application of an invasive procedure. The lack of effect of time and visit number on subjective outcomes raises further questions regarding whether the observed response is the result of placebo effect or the result of bias. Electronic supplementary material The online version of this article (doi:10.1186/s13063-017-2070-9) contains supplementary material, which is available to authorized users.

Background The Alberta Stroke Program Early Computed Tomography Score (ASPECTS) is an established 10-point quantitative topographic computed tomography scan score to assess early ischemic changes. We performed a non-inferiority trial between the e-ASPECTS software and neuroradiologists in scoring ASPECTS on non-contrast enhanced computed tomography images of acute ischemic stroke patients. Methods In this multicenter study, e-ASPECTS and three independent neuroradiologists retrospectively and blindly assessed baseline non-contrast enhanced computed tomography images of 132 patients with acute anterior circulation ischemic stroke. Follow-up scans served as ground truth to determine the definite area of infarction. Sensitivity, specificity, and accuracy for region- and score-based analysis, receiver-operating characteristic curves, Bland-Altman plots and Matthews correlation coefficients relative to the ground truth were calculated and comparisons were made between neuroradiologists and different pre-specified e-ASPECTS operating points. The non-inferiority margin was set to 10% for both sensitivity and specificity on region-based analysis. Results In total 2640 (132 patients × 20 regions per patient) ASPECTS regions were scored. Mean time from onset to baseline computed tomography was 146 ± 124 min and median NIH Stroke Scale (NIHSS) was 11 (6–17, interquartile range). Median ASPECTS for ground truth on follow-up imaging was 8 (6.5–9, interquartile range). In the region-based analysis, two e-ASPECTS operating points (sensitivity, specificity, and accuracy of 44%, 93%, 87% and 44%, 91%, 85%) were statistically non-inferior to all three neuroradiologists (all p-values Conclusions e-ASPECTS was non-inferior to three neuroradiologists in scoring ASPECTS on non-contrast enhanced computed tomography images of acute stroke patients.

IntroductionPneumothorax is a common clinical problem. Primary spontaneous pneumothorax (PSP) occurs in otherwise fit young patients, but optimal management is not clearly defined and often results in a long hospital stay. Ambulatory treatment options are available, but the existing data on their efficacy are poor. The Randomised Ambulatory Management of Primary Pneumothorax trial is a multicentre, randomised controlled trial comparing ambulatory management with standard care, specifically designed to safely and effectively reduce hospital stay.Methods and analysis236 patients with PSP will be recruited from UK hospitals. Patients will be randomised 1:1 to treatment to either the ‘Intervention’ arm (ambulatory device; Rocket Pleural Vent) or the ‘Control’ arm (aspiration ± standard chest drain insertion). Patients will be followed up for a total of 12 months to assess recurrence rates. The primary outcome is total length of stay in hospital (including readmissions) up to 30 days postrandomisation. The secondary outcomes are pain and breathlessness scores, air leak measurement and radiological evidence (on CT scanning) of emphysema-like changes, compared with short-term and long-term outcomes, respectively, and health economic analysis.Ethics and disseminationThe trial has received ethical approval from the National Research Ethics Service Committee South-Central Oxford A (15/SC/0240).Trial registration numberISRCTN79151659