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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 <6 weeks prior, performance score (PS) 0 or 1, no significant physical or psychological comorbidity. Cox proportional hazards models were derived to examine for relationships with survival. Free text was assessed using content analysis, looking for common themes and words., 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.

Objective: To estimate normal ranges for postpartum maternal vital signs., Methods: We conducted a multicenter prospective longitudinal cohort study in the United Kingdom. We recruited women before 20 weeks of gestation without significant comorbidities and with accurately dated singleton pregnancies. Women recorded their own blood pressure, heart rate, oxygen saturation and temperature daily for 2 weeks postpartum. Trained midwives measured participants' vital signs including respiratory rate around postpartum days 1, 7, and 14., Results: From August 2012 to September 2016, we screened 4,279 pregnant women; 1,054 met eligibility criteria and chose to take part. Postpartum vital sign data were available for 909 women (86.2%). Median, or 50th centile (3rd-97th centile), systolic and diastolic blood pressures increased from the day of birth: 116 mm Hg (88-147) and 74 mm Hg (59-93) to a maximum median of 121 mm Hg (102-143) and 79 mm Hg (63-94) on days 5 and 6 postpartum, respectively, an increase of 5 mm Hg (95% CI 3-7) and 5 mm Hg (95% CI 4-6), respectively. Median (3rd-97th centile) systolic and diastolic blood pressure returned to 116 mm Hg (98-137) and 75 mm Hg (61-91) by day 14 postpartum. The median (3rd-97th centile) heart rate was highest on the day of birth, 84 beats per minute (bpm) (59-110) decreasing to a minimum of 75 bpm (55-101) 14 days postpartum. Oxygen saturation, respiratory rate, and temperature did not change in the 2 weeks postbirth. Median (3rd-97th centile) day-of-birth oxygen saturation was 96% (93-98). Median (3rd-97th centile) day-of-birth respiratory rate was 15 breaths per minute (10-22). Median (3rd-97th centile) day-of-birth temperature was 36.7°C (35.6-37.6)., Conclusion: We present widely relevant, postpartum, day-specific reference ranges which may facilitate early detection of abnormal blood pressure, heart rate, respiratory rate, oxygen saturation and temperature during the puerperium. Our findings could inform construction of an evidence-based modified obstetric early warning system to better identify unwell postpartum women., Clinical Trial Registration: ISRCTN, 10838017., Competing Interests: Financial Disclosure Peter J. Watkinson and Lionel Tarassenko, Lucy Chappell and Marian Knight hold grants from the National Institute for Health Research (NIHR). Marian Knight is an NIHR Senior Investigator. Lucy Chappell is an NIHR Research Professor. Lauren J. Green, Lucy H. Mackillop, Lionel Tarassenko, Peter J. Watkinson, Jude Mossop, Clare Edwards, Jacqueline Birks and Dario Salvi receive funding from NIHR Biomedical Research Centre, Oxford. Lucy H. Mackillop works part-time for Sensyne Health. Peter J. Watkinson worked for Sensyne Health. Both have share options in Sensyne Health. Lise Loerup is currently an employee of Boston Consulting Group. Lionel Tarassenko is a nonexecutive Director of Sensyne Health and holds share options in the company, and he is a nonexecutive Director of Oxehealth and holds shares in the company. Sensyne Health markets the System for Electronic Notification and Documentation, which allows recording of adult vital signs and early warning score calculation. It also markets an application for gestational diabetes management. Oxehealth markets a system to provide contact-free heart and breathing rate monitoring. Neither company had any role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The other authors did not report any potential conflicts of interest., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The association of age with the outcomes of bilateral internal thoracic arteries (BITAs) versus single internal thoracic arteries (SITAs) for coronary bypass grafting (CABG) remains to be determined., Objectives: The purpose of this study was to evaluate the association between age and BITA versus SITA outcomes in the Arterial Revascularization Trial., Methods: The primary endpoints were all-cause mortality and a composite of major adverse events, including all-cause mortality, myocardial infarction, or stroke. Secondary endpoints were bleeding complications and sternal wound complications up to 6 months after surgery. Multivariable fractional polynomials analysis and log-rank tests were used., Results: Age did not affect any of the explored outcomes in the overall BITA versus SITA comparison in the intention-to-treat analysis and in the analysis based on the number of arterial grafts received. However, when the intention-to-treat analysis was restricted to the populations of patients between age 50 and 70 years, younger patients in the BITA arm had a significantly lower incidence of major adverse events (p = 0.03)., Conclusions: Our results suggest that BITA may improve long-term outcome in younger patients, although more randomized data are needed to confirm this hypothesis., Competing Interests: Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Coronavirus disease 2019 (COVID-19) includes the cardiovascular complications in addition to respiratory disease. SARS-CoV-2 infection impairs endothelial function and induces vascular inflammation, leading to endotheliitis. SARS-CoV-2 infection relies on the binding of Spike glycoprotein (S protein) to angiotensin converting enzyme 2 (ACE2) in the host cells. We show here that S protein alone can damage vascular endothelial cells (ECs) in vitro and in vivo, manifested by impaired mitochondrial function, decreased ACE2 expression and eNOS activity, and increased glycolysis. The underlying mechanism involves S protein downregulation of AMPK and upregulation of MDM2, causing ACE2 destabilization. Thus, the S protein-exerted vascular endothelial damage via ACE2 downregulation overrides the decreased virus infectivity.

Purpose: New onset atrial fibrillation (NOAF) in critically ill patients has been associated with increased short-term mortality. Analyses that do not take into account the time-varying nature of NOAF can underestimate its association with hospital outcomes. We investigated the prognostic association of NOAF with hospital outcomes using competing risks methods., Materials and Methods: We undertook a retrospective cohort study in three general adult intensive care units (ICUs) in the UK from June 2008 to December 2015. We excluded patients with known prior atrial fibrillation or an arrhythmia within four hours of ICU admission. To account for the effect of NOAF on the rate of death per unit time and the rate of discharge alive per unit time we calculated subdistribution hazard ratios (SDHRs)., Results: Of 7541 patients that fulfilled our inclusion criteria, 831 (11.0%) developed NOAF during their ICU admission. NOAF was associated with an increased duration of hospital stay (CSHR 0.68 (95% CI 0.63-0.73)) and an increased rate of in-hospital death per unit time (CSHR 1.57 (95% CI 1.37-1.1.81)). This resulted in a strong prognostic association with dying in hospital (adjusted SDHR 2.04 (1.79-2.32)). NOAF lasting over 30 min was associated with increased hospital mortality., Conclusions: Using robust methods we demonstrate a stronger prognostic association between NOAF and hospital outcomes than previously reported., Competing Interests: Declaration of Competing Interest Prof. Young's institution received funding from Health Innovation Challenge Fund (joint venture of Wellcome Trust and U.K. Department of Health. Prof. Watkinson's institution received funding from Drayson Health and National Institute for Health Research (NIHR) Biomedical Research Centre, Oxford. Prof. Watkinson has developed an electronic observations application for which Drayson Health (now Sensyne Health) has purchased a sole license. The company has a research agreement with the University of Oxford and pay personal fees. Prof. Watkinson owns shares in Drayson Health. No organisations played a role in the study process. No other authors have financial relationships with any organisations that might have an interest in the submitted work in the previous 3 years, nor other relationships or activities that could appear to have influenced the submitted work. Dr. Hatch, Dr. Bedford, Dr. Rechner and Mr. Gerry have declared they do not have any potential conflicts of interest., (Copyright © 2020. Published by Elsevier Inc.)

Background: Over 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., Objectives: To prospectively assess a previously described risk score (the RAPID (Renal (urea), Age, fluid Purulence, Infection source, Dietary (albumin)) score) in adults with pleural infection., Methods: Prospective 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., Results: Mortality 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., Conclusions: The 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., Competing Interests: Conflict of interest: J.P. Corcoran reports grants from the UK Medical Research Council (MRC; grant number G1001128), during the conduct of the study. Conflict of interest: I. Psallidas reports grants from the UK MRC (grant number G1001128), during the conduct of the study, as well as grants and personal fees from the European Respiratory Society (ERS), outside the submitted work. Conflict of interest: S. Gerry has nothing to disclose. Conflict of interest: F. Piccolo has nothing to disclose. Conflict of interest: C.F. Koegelenberg has nothing to disclose. Conflict of interest: T. Saba has nothing to disclose. Conflict of interest: C. Daneshvar has nothing to disclose. Conflict of interest: I. Fairbairn has nothing to disclose. Conflict of interest: R. Heinink has nothing to disclose. Conflict of interest: A. West has nothing to disclose. Conflict of interest: A.E. Stanton has nothing to disclose. Conflict of interest: J. Holme has nothing to disclose. Conflict of interest: J.A. Kastelik has nothing to disclose. Conflict of interest: H. Steer has nothing to disclose. Conflict of interest: N.J. Downer has nothing to disclose. Conflict of interest: M. Haris has nothing to disclose. Conflict of interest: E.H. Baker has nothing to disclose. Conflict of interest: C.F. Everett has nothing to disclose. Conflict of interest: J. Pepperell has nothing to disclose. Conflict of interest: T. Bewick has nothing to disclose. Conflict of interest: L. Yarmus has nothing to disclose. Conflict of interest: F. Maldonado has nothing to disclose. Conflict of interest: B. Khan has nothing to disclose. Conflict of interest: A. Hart-Thomas has nothing to disclose. Conflict of interest: G. Hands has nothing to disclose. Conflict of interest: G. Warwick has nothing to disclose. Conflict of interest: D. De Fonseka has nothing to disclose. Conflict of interest: M. Hassan reports grants from the UK MRC (grant number G1001128), during the conduct of the study. Conflict of interest: M. Munavvar has nothing to disclose. Conflict of interest: A. Guhan has nothing to disclose. Conflict of interest: M. Shahidi has nothing to disclose. Conflict of interest: Z. Pogson has nothing to disclose. Conflict of interest: L. Dowson has nothing to disclose. Conflict of interest: N.D. Popowicz has nothing to disclose. Conflict of interest: J. Saba has nothing to disclose. Conflict of interest: N.R. Ward has nothing to disclose. Conflict of interest: R.J. Hallifax reports grants from the UK MRC (grant number G1001128), during the conduct of the study. Conflict of interest: M. Dobson reports grants from the UK MRC (grant number G1001128), during the conduct of the study. Conflict of interest: R. Shaw reports grants from the UK MRC (grant number G1001128), during the conduct of the study. Conflict of interest: E.L. Hedley reports grants from the UK MRC (grant number G1001128), during the conduct of the study. Conflict of interest: A. Sabia reports grants from the UK MRC (grant number G1001128), during the conduct of the study. Conflict of interest: B. Robinson reports grants from the UK MRC (grant number G1001128), during the conduct of the study. Conflict of interest: G.S. Collins has nothing to disclose. Conflict of interest: H.E. Davies has nothing to disclose. Conflict of interest: L-M. Yu has nothing to disclose. Conflict of interest: R.F. Miller has nothing to disclose. Conflict of interest: N.A. Maskell has nothing to disclose. Conflict of interest: N.M. Rahman reports grants from the UK MRC (grant number G1001128), during the conduct of the study, as well as personal fees from the UK National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, outside the submitted work., (Copyright ©ERS 2020.)

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.

Multiple Sclerosis (MS) is a common cause of neurological disability among young adults and has a high economic burden. Currently there are 18 disease modifying agents for relapsing MS, which were tested in clinical trials versus placebo or an active comparator in a pairwise manner. However, there is currently no consensus on the fundamental principles of treatment approach and initial therapy selection. These factors result in variable use of disease modifying therapies. Here we describe the study protocol for Determining the Effectiveness of earLy Intensive Versus Escalation approaches for the Treatment of Relapsing-remitting Multiple Sclerosis (DELIVER-MS). The main objective of the study is to determine whether an early highly effective treatment approach, defined as use of one of four monoclonal antibodies as initial therapy, is more effective than an escalation treatment approach (any other approved medication as initial therapy with subsequent escalation to higher efficacy treatments guided by radiological and clinical evaluation). The primary endpoint of the study is reduction in normalized brain volume loss from baseline visit to month 36 visit using MRI. Brain volume loss was selected as the best short-term predictor of long-term clinical disability. A total of 400 participants will be randomized 1:1 using minimization to account for age and sex by site, and 400 will be enrolled into a parallel observational cohort. The study results will help guide overall treatment philosophy and will have important implications for patient choice, clinical practice, and treatment access., (Copyright © 2020 Elsevier Inc. All rights reserved.)

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<0·0001; median difference 2 days [95% CI 1-3]). 110 (47%) of 236 patients had adverse events, including 64 (55%) of 117 patients in the ambulatory care arm and 46 (39%) of 119 in the standard care arm. All 14 serious adverse events occurred in patients who received ambulatory care, eight (57%) of which were related to the intervention, including an enlarging pneumothorax, asymptomatic pulmonary oedema, and the device malfunctioning, leaking, or dislodging., 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., (Copyright © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objectives: National guidelines for identifying physiological deterioration and sepsis in hospitals depend on thresholds for blood pressure that do not account for age or sex. In populations outside hospital, differences in blood pressure are known to occur with both variables. Whether these differences remain in the hospitalised population is unknown. This database analysis study aims to generate representative centiles to quantify variations in blood pressure by age and sex in hospitalised patients., Design: Retrospective cross-sectional observational database analysis., Setting: Four near-sea-level hospitals between April 2015 and April 2017 PARTICIPANTS: 75 342 adult patients who were admitted to the hospitals and had at least one set of documented vital sign observations within 24 hours before discharge were eligible for inclusion. Patients were excluded if they died in hospital, had no vital signs 24 hours prior to discharge, were readmitted within 7 days of discharge, had missing age or sex or had no blood pressure recorded., Results: Systolic blood pressure (SBP) for hospitalised patients increases with age for both sexes. Median SBP increases from 122 (CI: 121.1 to 122.1) mm Hg to 132 (CI: 130.9 to 132.2) mm Hg in men, and 114 (CI: 113.1 to 114.4) mm Hg to 135 (CI: 134.5 to 136.2) mm Hg in women, between the ages of 20 and 90 years. Diastolic blood pressure peaked around 50 years for men 76 (CI: 75.5 to 75.9) mm Hg and women 69 (CI: 69.0 to 69.4) mm Hg. The blood pressure criterion for sepsis, systolic <100 mm Hg, was met by 2.3% of younger (20-30 years) men and 3.5% of older men (81-90 years). In comparison, the criterion was met by 9.7% of younger women and 2.6% of older women., Conclusion: We have quantified variations in blood pressure by age and sex in hospitalised patients that have implications for recognition of deterioration. Nearly 10% of younger women met the blood pressure criterion for sepsis at hospital discharge., Competing Interests: Competing interests: DW and PJW co-developed the SEND e-Obs system (for which Sensyne Health has purchased sole license) from which the study database was collected. The company has a research agreement with the University of Oxford and royalty agreements with Oxford University Hospitals NHS Trust and the University of Oxford. DAC is Research Director of Sensyne Health. PJW is employed part-time and holds shares in Sensyne Health. DW undertakes consultancy for Sensyne Health., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Objective: To estimate normal ranges for maternal vital signs throughout pregnancy, which have not been well defined in a large contemporary population., Methods: We conducted a three-center, prospective, longitudinal cohort study in the United Kingdom from August 2012 to September 2017. We recruited women at less than 20 weeks of gestation without significant comorbidities with accurately dated singleton pregnancies. We measured participants' blood pressure (BP), heart rate, respiratory rate, oxygen saturation and temperature following standardized operating procedures at 4-6 weekly intervals throughout pregnancy., Results: We screened 4,279 pregnant women, 1,041 met eligibility criteria and chose to take part. Systolic and diastolic BP decreased slightly from 12 weeks of gestation: median or 50th centile (3rd-97th centile) 114 (95-138); 70 (56-87) mm Hg to reach minimums of 113 (95-136); 69 (55-86) mm Hg at 18.6 and 19.2 weeks of gestation, respectively, a change (95% CI) of -1.0 (-2 to 0); -1 (-2 to -1) mm Hg. Systolic and diastolic BP then rose to a maximum median (3rd-97th centile) of 121 (102-144); 78 (62-95) mm Hg at 40 weeks of gestation, a difference (95% CI) of 7 (6-9) and9 (8-10) mm Hg, respectively. The median (3rd-97th centile) heart rate was lowest at 12 weeks of gestation: 82 (63-105) beats per minute (bpm), rising progressively to a maximum of 91 (68-115) bpm at 34.1 weeks. SpO2 decreased from 12 weeks of gestation: median (3-97 centile) 98% (94-99%) to 97% (93-99%) at 40 weeks. The median (3-97 centile) respiratory rate at 12 weeks of gestation was 15 (9-22), which did not change with gestation. The median (3-97 centile) temperature at 12 weeks of gestation was 36.7 (35.6-37.5)°C, decreasing to a minimum of 36.5 (35.3-37.3)°C at 33.4 weeks., Conclusion: We present widely relevant, gestation-specific reference ranges for detecting abnormal BP, heart rate, respiratory rate, oxygen saturation and temperature during pregnancy. Our findings refute the existence of a clinically significant BP drop from 12 weeks of gestation., Clinical Trial Registration: ISRCTN, ISRCTN10838017.

Introduction: Arterial graft physiology influences the long-term outcome of coronary artery bypass grafting (CABG). We studied factors that can affect the overall resistance to flow using internal mammary artery grafting to the left anterior descending artery., Methods: This was a prospective, nonrandomized observational study of 100 consecutive patients who underwent elective on-pump isolated or combined valve surgery and CABG. Coronary stenoses were assessed using conventional and quantitative coronary angiography assessment. The flow and pulsatility index (PI) of the grafts were assessed by transit-time flowmetry during cardioplegic arrest and at the end of the operation. Fractional polynomials were used to explore linearity, followed by multivariable regression analysis., Results: Univariate analysis demonstrated higher flows at the end of the operation in patients who had higher flows with the cross-clamp on (P < .001), in males (P = .004), in patients with a low PI at the end of the operation (P = .04), and in patients with a larger size of the recipient artery (P = .005). Multivariable regression analysis showed that the graft flow at the end of the operation was significantly associated with the mean flow with the cross-clamp on (P < .001), sex (P = .003), and PI at the end of the operation (P = .003). Concomitant valve surgery did not influence flows. Male patients had 18 mL/min higher flow., Conclusions: The graft flow at the end of the operation can be determined by the flow with the cross-clamp on, the PI with the cross-clamp off and coronary artery. We reported differences in the graft flows between sexes, and for first the time, we introduced the concepts of "adequate flow" and "resistance-to-forward-flow" for patent coronary grafts., (© 2019 Wiley Periodicals, Inc.)

Background: Acute stroke patients are usually transported to the nearest hospital regardless of their required level of care. This can lead to increased pressure on emergency departments and treatment delay., Objective: The aim of the study was to explore the benefit of a mobile stroke unit (MSU) in the UK National Health Service (NHS) for reduction of hospital admissions., Methods: Prospective cohort audit observation with dispatch of the MSU in the East of England Ambulance Service area in Southend-on-Sea was conducted. Emergency patients categorized as code stroke and headache were included from June 5, 2018, to December 18, 2018. Rate of avoided admission to the accident and emergency (A&E) department, rate of admission directly to target ward, and stroke management metrics were assessed., Results: In 116 MSU-treated patients, the following diagnoses were made: acute stroke, n = 33 (28.4%); transient ischaemic attacks, n = 13 (11.2%); stroke mimics, n = 32 (27.6%); and other conditions, n = 38 (32.8%). Pre-hospital thrombolysis was administered to 8 of 28 (28.6%) ischaemic stroke patients. Pre-hospital diagnosis avoided hospital admission for 29 (25.0%) patients. As hospital treatment was indicated, 35 (30.2%) patients were directly triaged to the stroke unit, 1 patient (0.9%) even directly to the catheter laboratory. Thus, only 50 (43.1%) patients required transfer to the A&E department. Moreover, the MSU enabled thrombolysis with a median dispatch-to-needle time of 42 min (interquartile range, 40-60)., Conclusion: This first deployment of an MSU in the UK NHS demonstrated improved triage decision-making for or against hospital admission and admission to the appropriate target ward, thereby reducing pressure on strained A&E departments., (© 2020 The Author(s) Published by S. Karger AG, Basel.)

Objectives: Prolonged admissions to an ICU are associated with high resource utilization and personal cost to the patient. Previous reports suggest increasing length of stay may be associated with poor outcomes. Conditional survival represents the probability of future survival after a defined period of treatment on an ICU providing a description of how prognosis evolves over time. Our objective was to describe conditional survival as length of ICU stay increased., Design: Retrospective observational cohort study of three large intensive care databases., Setting: Three intensive care databases, two in the United States (Medical Information Mart for Intensive Care III and electronic ICU) and one in United Kingdom (Post Intensive Care Risk-Adjusted Alerting and Monitoring)., Patients: Index admissions to intensive care for patients 18 years or older., Interventions: None., Measurements and Main Results: A total of 11,648, 38,532, and 165,125 index admissions were analyzed from Post Intensive Care Risk-Adjusted Alerting and Monitoring, Medical Information Mart for Intensive Care III and electronic ICU databases respectively. In all three cohorts, conditional survival declined over the first 5-10 days after ICU admission and changed little thereafter. In patients greater than or equal to 75 years old conditional survival continued to decline with increasing length of stay., Conclusions: After an initial period of 5-10 days, probability of future survival does not appear to decrease with increasing length of stay in unselected patients admitted to ICUs in United Kingdom and United States [corrected]. These findings were consistent between the three populations and suggest that a prolonged admission to an ICU is not a reason for a pessimism in younger patients but may indicate a poor prognosis in the older population.

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 (a) maternal anxiety disorders or (b) mother-child interactions., Methods: Two hundred and eleven 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 (a) child-focused CBT with nonspecific control interventions (CCBT+Con), (b) CCBT with CBT for the maternal anxiety disorder (CCBT+MCBT), or (c) 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 nonspecific 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 = .29; CCBT+MCI vs. CCBT+Con: 0.02 (95% CI: -0.05, -0.09), p = .54). CCBT+MCI was associated with nonsignificantly higher costs than CCBT (mean difference: £154 (95% CI: -£1,239, £1,547), p = .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., (© 2019 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

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 <0.05) correlated with the sample size, number of events, statistical power, journal impact factor, use of intention-to-treat analysis, and of composite end points and negatively correlated with the use of percutaneous interventions in the treatment arm and the 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: 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 (I 2 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.

Background: The 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., Methods: Between 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., Results: Total 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., Conclusions: Higher 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 Number: ISRCTN46552265., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.)

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 [Formula: see text]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 [Formula: see text]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.

Introduction: Pneumothorax 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 Analysis: 236 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 Dissemination: The trial has received ethical approval from the National Research Ethics Service Committee South-Central Oxford A (15/SC/0240)., Trial Registration Number: ISRCTN79151659., Competing Interests: Competing interests: NR has received consultancy fees from Rocket Medical. All other authors have no competing interests to declare.

Purpose: Malignant 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., Methods: We 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., Results: Between 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., Conclusion: There 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 Number: ISRCTN18955704., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

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 (Pao 2 , Pao 2 /Fio 2 ratio, Sao 2 , and Paco 2 ) 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 Pao 2 and Pao 2 /Fio 2 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 Paco 2 , 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 Sao 2 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.

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: Multiple arterial grafts may result in longer survival than single arterial grafts after coronary-artery bypass grafting (CABG) surgery. We evaluated the use of bilateral internal-thoracic-artery grafts for CABG., Methods: We randomly assigned patients scheduled for CABG to undergo bilateral or single internal-thoracic-artery grafting. Additional arterial or vein grafts were used as indicated. 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., Results: A total of 1548 patients were randomly assigned to undergo bilateral internal-thoracic-artery grafting (the bilateral-graft group) and 1554 to undergo single internal-thoracic-artery grafting (the single-graft group). In the bilateral-graft group, 13.9% of the patients received only a single internal-thoracic-artery graft, and in the single-graft group, 21.8% of the patients also received a radial-artery graft. Vital status was not known for 2.3% of the patients at 10 years. In the intention-to-treat analysis at 10 years, there were 315 deaths (20.3% of the patients) in the bilateral-graft group and 329 deaths (21.2%) in the single-graft group (hazard ratio, 0.96; 95% confidence interval [CI], 0.82 to 1.12; P=0.62). Regarding the composite outcome of death, myocardial infarction, or stroke, there were 385 patients (24.9%) with an event in the bilateral-graft group and 425 patients (27.3%) with an event in the single-graft group (hazard ratio, 0.90; 95% CI, 0.79 to 1.03)., Conclusions: Among patients who were scheduled for CABG and had been randomly assigned to undergo bilateral or single internal-thoracic-artery grafting, there was no significant between-group difference in the rate of death from any cause at 10 years in the intention-to-treat analysis. Further studies are needed to determine whether multiple arterial grafts provide better outcomes than a single internal-thoracic-artery graft. (Funded by the British Heath Foundation and others; 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., (© 2018 by the American Society of Neuroimaging.)

Aims: To compare the ability of the National Early Warning Score (NEWS) and the National Early Warning Score 2 (NEWS2) to identify patients at risk of in-hospital mortality and other adverse outcomes., Methods: We undertook a multi-centre retrospective observational study at five acute hospitals from two UK NHS Trusts. Data were obtained from completed adult admissions who were not fit enough to be discharged alive on the day of admission. Diagnostic coding and oxygen prescriptions were used to identify patients with type II respiratory failure (T2RF). The primary outcome was in-hospital mortality within 24 h of a vital signs observation. Secondary outcomes included unanticipated intensive care unit admission or cardiac arrest within 24 h of a vital signs observation. Discrimination was assessed using the c-statistic., Results: Among 251,266 adult admissions, 48,898 were identified to be at risk of T2RF by diagnostic coding. In this group, NEWS2 showed statistically significant lower discrimination (c-statistic, 95% CI) for identifying in-hospital mortality within 24 h (0.860, 0.857-0.864) than NEWS (0.881, 0.878-0.884). For 1394 admissions with documented T2RF, discrimination was similar for both systems: NEWS2 (0.841, 0.827-0.855), NEWS (0.862, 0.848-0.875). For all secondary endpoints, NEWS2 showed no improvements in discrimination., Conclusions: NEWS2 modifications to NEWS do not improve discrimination of adverse outcomes in patients with documented T2RF and decrease discrimination in patients at risk of T2RF. Further evaluation of the relationship between SpO 2 values, oxygen therapy and risk should be investigated further before wide-scale adoption of NEWS2., (Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.)

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.

Computed tomography angiography (CTA) collateral scoring can identify patients most likely to benefit from mechanical thrombectomy and those more likely to have good outcomes and ranges from 0 (no collaterals) to 3 (complete collaterals). In this study, we used a machine learning approach to categorise the degree of collateral flow in 98 patients who were eligible for mechanical thrombectomy and generate an e-CTA collateral score (CTA-CS) for each patient (e-STROKE SUITE, Brainomix Ltd., Oxford, UK). Three experienced neuroradiologists (NRs) independently estimated the CTA-CS, first without and then with knowledge of the e-CTA output, before finally agreeing on a consensus score. Addition of the e-CTA improved the intraclass correlation coefficient (ICC) between NRs from 0.58 (0.46-0.67) to 0.77 (0.66-0.85, p = 0.003). Automated e-CTA, without NR input, agreed with the consensus score in 90% of scans with the remaining 10% within 1 point of the consensus (ICC 0.93, 0.90-0.95). Sensitivity and specificity for identifying favourable collateral flow (collateral score 2-3) were 0.99 (0.93-1.00) and 0.94 (0.70-1.00), respectively. e-CTA correlated with the Alberta Stroke Programme Early CT Score (Spearman correlation 0.46, p < 0.001) highlighting the value of good collateral flow in maintaining tissue viability prior to reperfusion. In conclusion, -e-CTA provides a real-time and fully automated approach to collateral scoring with the potential to improve consistency of image interpretation and to independently quantify collateral scores even without expert rater input., (© 2019 The Author(s). Published by S. Karger AG, Basel.)

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., Competing Interests: Conflict of interest: S.D. West has nothing to disclose. Conflict of interest: B. Prudon reports grants (paid to institution) and supply of equipment for the project from ResMed UK, during the conduct of the study. Conflict of interest: J. Hughes has nothing to disclose. Conflict of interest: R. Gupta reports travel support from Bayer and Novartis, and personal fees from Bayer, outside the submitted work. Conflict of interest: S.B. Mohammed has nothing to disclose. Conflict of interest: S. Gerry has nothing to disclose. Conflict of interest: J.R. Stradling reports grants from ResMed Foundation, during the conduct of the study; personal fees for consultancy work from ResMed UK and Bayer Germany, outside the submitted work., (Copyright ©ERS 2018.)

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.

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., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: The 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., Methods: Among 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., Results: A 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 < .001). However, the hospital mortality rate was comparable to that of those who did not require bilateral internal thoracic artery graft conversion (0% vs 1.6%; P = .1), as well as the incidence of major complications. At 5 years, we found a nonsignificant excess of deaths (11.9% vs 8.4%; P = .1) and major adverse events (17.1% 13.2%; P = .1) mainly driven by an excess of revascularization in patients requiring conversion., Conclusions: The 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., (Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: The long-term effects of off-pump coronary artery bypass continue to be controversial because some studies have reported increased adverse event rates with off-pump coronary artery bypass when compared with on-pump coronary artery bypass. The Arterial Revascularization Trial compared survival after bilateral versus single internal thoracic artery grafting. The choice of off-pump coronary artery bypass versus on-pump coronary artery bypass was based on the surgeon's discretion. We performed a post hoc analysis of the Arterial Revascularization Trial to compare 5-year outcomes with 2 strategies., Methods: Among 3102 patients enrolled in the Arterial Revascularization Trial, we selected 1260 patients who underwent off-pump coronary artery bypass versus 1700 patients who underwent on-pump coronary artery bypass with cardioplegic arrest for the present comparison. Primary outcomes were 5-year mortality and incidence of major cardiac and cerebrovascular events, including cardiovascular death, myocardial infarction, cerebrovascular accident, and revascularization after index procedure. Propensity score matching selected 1260 pairs for final comparison. Stratified Cox models were used for treatment effect estimate., Results: Hospital mortality was comparable between off-pump coronary artery bypass and on-pump coronary artery bypass groups (12 [1.0%] vs 15 [1.2%]; P = .7). Conversion rate to on-pump during off-pump coronary artery bypass was 29 of 1260 (2.3%). When compared with off-pump coronary artery bypass not converted, off-pump coronary artery bypass converted to on-pump presented a remarkably higher hospital mortality (10.3% vs 0.7%; P < .001). At 5 years, the mortality rate was 110 (8.9%) versus 102 (8.3%) in the off-pump coronary artery bypass and on-pump coronary artery bypass groups, respectively, with no significant difference (hazard ratio, 1.14; 95% confidence interval, 0.86-1.52; P = .35). Incidence of major cardiac and cerebrovascular events was 175 (14.3) versus 169 (13.8) in the off-pump coronary artery bypass and on-pump coronary artery bypass groups, respectively, with no significant difference (hazard ratio, 1.05; 95% confidence interval, 0.84-1.31; P = .65)., Conclusions: The present post hoc Arterial Revascularization Trial analysis supports the hypothesis that both off-pump coronary artery bypass and on-pump coronary artery bypass are equally effective and safe., (Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: There is still uncertainty about the safety of aprotinin for coronary artery bypass graft surgery. The ART (Arterial Revascularization Trial) was designed to compare survival after bilateral versus single internal thoracic artery grafting. Many of the ART patients (≈30%) received perioperative aprotinin. We investigated the association between perioperative aprotinin administration and short-term (in-hospital) and long-term outcomes by performing a post hoc analysis of the ART., Methods and Results: Among patients enrolled in the ART (n=3102) from 2004 to 2007, we excluded those who did not undergo surgery (n=18) and those with no information about use of perioperative aprotinin (n=9). Finally, 836 of 3076 patients (27%) received aprotinin. Propensity matching was used to select 536 pairs for final comparison. Aprotinin was also associated with an increased risk of hospital mortality (9 [1.7%] versus 1 [0.2%]; odds ratio, 9.12; 95% confidence interval [CI], 1.15-72.2; P =0.03), intra-aortic balloon pump insertion (37 [6.9%] versus 17 [3.2%]; odds ratio, 2.26; 95% CI, 1.26-4.07; P =0.006), and acute kidney injury (102 [19.0%] versus 76 [14.2%]; odds ratio, 1.42; 95% CI, 1.03-1.97; P =0.03). Aprotinin was not associated with a lower incidence of transfusion (37 [6.9%] versus 28 [5.2%]; odds ratio, 1.34; 95% CI, 0.81-2.23; P =0.25) and reexploration (26 [4.9%] versus 19 [3.5%]; hazard ratio, 1.39; 95% CI, 0.76-2.53; P =0.28). At 5 years, all-cause mortality was significantly increased in the aprotinin group (56 [10.6%] versus 38 [7.3%]; hazard ratio, 1.51; 95% CI, 1.0-2.28; P =0.045)., Conclusions: In the present post hoc ART analysis, aprotinin was associated with a significantly increased risk of early and late mortality., Clinical Trial Registration: URL: http://www.isrctn.com. Unique identifier: ISRCTN46552265., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Introduction: Early 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., Methods: We 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 Dissemination: This 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 Number: CRD42017053324., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Heterologous prime-boost vaccination with chimpanzee adenovirus 63 (ChAd63) and modified vaccinia virus Ankara (MVA) encoding multiple epitope string thrombospondin-related adhesion protein (ME-TRAP) has shown acceptable safety and promising immunogenicity in African adult and pediatric populations. If licensed, this vaccine could be given to infants receiving routine childhood immunizations. We therefore evaluated responses to ChAd63 MVA ME-TRAP when co-administered with routine Expanded Program on Immunization (EPI) vaccines., Methods: We enrolled 65 Gambian infants and neonates, aged 16, 8, or 1 week at first vaccination and randomized them to receive either ME-TRAP and EPI vaccines or EPI vaccines only. Safety was assessed by the description of vaccine-related adverse events (AEs). Immunogenicity was evaluated using IFNγ enzyme-linked immunospot, whole-blood flow cytometry, and anti-TRAP IgG ELISA. Serology was performed to confirm all infants achieved protective titers to EPI vaccines., Results: The vaccines were well tolerated in all age groups with no vaccine-related serious AEs. High-level TRAP-specific IgG and T cell responses were generated after boosting with MVA. CD8 + T cell responses, previously found to correlate with protection, were induced in all groups. Antibody responses to EPI vaccines were not altered significantly., Conclusion: Malaria vectored prime-boost vaccines co-administered with routine childhood immunizations were well tolerated. Potent humoral and cellular immunity induced by ChAd63 MVA ME-TRAP did not reduce the immunogenicity of co-administered EPI vaccines, supporting further evaluation of this regimen in infant populations., Clinical Trial Registration: The clinical trial was registered on http://Clinicaltrials.gov (NCT02083887) and the Pan-African Clinical Trials Registry (PACTR201402000749217).

Objective: Coronary artery bypass grafting (CABG) using bilateral internal mammary arteries (BIMA) may improve survival over CABG using single internal mammary arteries (SIMA), but may be surgically more complex (and therefore costly) and associated with impaired sternal wound healing. We report, for the first time, a detailed comparison of healthcare resource use and costs over 12 months, as part of the Arterial Revascularisation (ART) Trial., Methods: 3102 patients in 28 hospitals in seven countries were randomised to CABG surgery using BIMA (n=1548) or SIMA (n=1554). Detailed resource use data were collected covering surgery, the initial hospital episode, and for 12 months post randomisation. Using UK unit costs, total costs were calculated and compared between trial arms and for subgroups., Results: Patients randomised to BIMA spent 20 min longer in theatre (95% CI 15 to 25, p<0.001) and also required more treatment for sternal wound problems. Mean (SD) total costs per patient at 12 months were £13 839 (£10 534) for BIMA and £12 717 (£9719) for SIMA (mean cost difference £1122, 95% CI £407 to £1838, p=0.002). No tests for interaction between subgroups and treatment allocation were significant., Conclusions: At 12 months from randomisation, mean costs were approximately 9% higher in BIMA than SIMA patients, primarily due to longer time in theatre and in-hospital stay, and slightly higher costs related to sternal wound problems during follow-up. Follow-up to the primary trial endpoint of 10 years will reveal whether longer-term differences emerge in graft patency or in overall survival., Trial Registration Number: Controlled-trials.com (ISRCTN46552265)., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

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.

Introduction: Successive 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 Analysis: An 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 Dissemination: The 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., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objectives: There is still little evidence to boldport routine dual antiplatelet therapy (DAPT) with P2Y12 antagonists following coronary artery bypass grafting (CABG). The Arterial Revascularization 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 analysis., Methods: Among patients enrolled in the ART (n = 3102), 609 (21%) and 2308 (79%) were discharged on DAPT or aspirin alone, respectively. The primary end-point was the incidence of major adverse cerebrovascular and cardiac events (MACCE) at 1 year including cardiac death, myocardial infarction, cerebrovascular accident and reintervention; safety end-point 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 2 groups [hazard ratio (HR) 0.97, 95% confidence interval (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% vs 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 with 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., (© The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

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 <0.003). Both Matthews correlation coefficients for e-ASPECTS were higher (0.36 and 0.34) than those of all neuroradiologists (0.32, 0.31, and 0.3). Conclusions e-ASPECTS was non-inferior to three neuroradiologists in scoring ASPECTS on non-contrast enhanced computed tomography images of acute stroke patients.

Background: Whether the use of the radial artery (RA) can improve clinical outcomes in coronary artery bypass graft surgery remains unclear. The ART (Arterial Revascularization Trial) was designed to compare survival after bilateral internal thoracic artery (BITA) over single left internal thoracic artery (SITA). In the ART, a large proportion of patients (≈20%) also received an RA graft instead of a saphenous vein graft (SVG). We aimed to investigate the associations between using the RA instead of an SVG to supplement SITA or BITA grafts and outcomes by performing a post hoc analysis of the ART., Methods: Patients enrolled in the ART (n=3102) were classified on the basis of conduits actually received (as treated). The analysis included 2737 patients who received an RA graft (RA group; n=632) or SVG only (SVG group; n=2105) in addition to SITA or BITA grafts. The primary end point was the composite of myocardial infarction, cardiovascular death, and repeat revascularization at 5 years. Propensity score matching and stratified Cox regression were used to compare the 2 strategies., Results: Myocardial infarction, cardiovascular death, and repeat revascularization cumulative incidence was 2.3% (95% confidence interval [CI], 1.1-3.4), 3.5% (95% CI, 2.1-5.0), and 4.4% (95% CI, 2.8-6.0) in the RA group and 3.4% (95% CI, 2.0-4.8), 4.0% (95% CI, 2.5-5.6), and 7.6% (95% CI, 5.5-9.7) in the SVG group, respectively. The composite end point was significantly lower in the RA group (8.8%; 95% CI, 6.5-11.0) compared with the SVG group (13.6%; 95% CI, 10.8-16.3; P =0.005). This association was present when an RA graft was used to supplement both SITA and BITA grafts (interaction P =0.62)., Conclusions: This post hoc ART analysis showed that an additional RA was associated with lower risk for midterm major adverse cardiac events when used to supplement SITA or BITA grafts., Clinical Trial Registration: URL: https://www.situ.ox.ac.uk/surgical-trials/art. Unique identifier: ISRCTN46552265., (© 2017 American Heart Association, Inc.)

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 (β 0  = 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 (β 0  = 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 (β 0  = 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.

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  < .001). The treatment effect ratio in ward 1 was 0.37 (95% CI, 0.26-0.53), in ward 2 was 0.98 (95% CI, 0.70-1.38), and in ward 3 was 0.93 (95% CI, 0.66-1.33)., 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., (© The Author 2017. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com)

Exposure to airborne toxins can trigger headaches, but the mechanisms are not well understood. Some environmental toxins, such as acrolein, activate transient receptor potential ankyrin 1 (TRPA1), a receptor involved in pain sensation that is highly expressed in the trigeminovascular system. It has been shown in rat models that repeated exposure to acrolein induces trigeminovascular sensitization to both TRPA1 and TRP vanilloid 1 (TRPV1) agonists, a phenomenon linked to headache. In this study, we test the hypothesis that the sensitization of trigeminovascular responses in rats after acrolein exposure via inhalation is associated with changes in levels of endogenous lipids, including TRPV1 agonists, in the trigeminal ganglia, trigeminal nucleus, and cerebellum. Lipidomics analysis of 80 lipids was performed on each tissue after acute acrolein, chronic acrolein, or room air control. Both acute and chronic acrolein exposure drove widespread alterations in lipid levels. After chronic acrolein exposure, levels of all 6 N -acyl ethanolamines in the screening library, including the endogenous cannabinoid and TRPV1 agonist, N -arachidonoyl ethanolamine, were elevated in trigeminal tissue and in the cerebellum. This increase in TRPV1 ligands by acrolein exposure may indicate further downstream signaling, in that we also show here that a combination of these TRPV1 endogenous agonists increases the potency of the individual ligands in TRPV1-HEK cells. In addition to these TRPV1 agonists, 3 TRPV3 antagonists, 4 TRPV4 agonists, and 25 orphan lipids were up and down regulated after acrolein exposure. These data support the hypothesis that lipid signaling may represent a mechanism by which repeated exposure to the TRPA1 agonist and environmental toxin, acrolein, drives trigeminovascular sensitization.