Multivariable prediction models for atrial fibrillation after cardiac surgery: a systematic review protocol.

INTRODUCTION: Dozens of multivariable prediction models for atrial fibrillation after cardiac surgery (AFACS) have been published, but none have been incorporated into regular clinical practice. One of the reasons for this lack of adoption is poor model performance due to methodological weaknesses in model development. In addition, there has been little external validation of these existing models to evaluate their reproducibility and transportability. The aim of this systematic review is to critically appraise the methodology and risk of bias of papers presenting the development and/or validation of models for AFACS. METHODS: We will identify studies that present the development and/or validation of a multivariable prediction model for AFACS through searches of PubMed, Embase and Web of Science from inception to 31 December 2021. Pairs of reviewers will independently extract model performance measures, assess methodological quality and assess risk of bias of included studies using extraction forms adapted from a combination of the Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies checklist and the Prediction Model Risk of Bias Assessment Tool. Extracted information will be reported by narrative synthesis and descriptive statistics. ETHICS AND DISSEMINATION: This systemic review will only include published aggregate data, so no protected health information will be used. Study findings will be disseminated through peer-reviewed publications and scientific conference presentations. Further, this review will identify weaknesses in past AFACS prediction model development and validation methodology so that subsequent studies can improve upon prior practices and produce a clinically useful risk estimation tool. PROSPERO REGISTRATION NUMBER: CRD42019127329.

Comparison of the Asleep-Awake-Asleep Technique and Monitored Anesthesia Care During Awake Craniotomy: A Systematic Review and Meta-analysis.

Awake craniotomy (AC) is the preferred surgical option for intractable epilepsy and resection of tumors adjacent to or within eloquent cortical areas. Monitored anesthesia care (MAC) or an asleep-awake-asleep (SAS) technique is most widely used during AC. We used a random-effects modeled meta-analysis to synthesize the most recent evidence to determine whether MAC or SAS is safer and more effective for AC. We included randomized controlled trials and observational studies that explored the incidence of AC failure, duration of surgery, and hospital length of stay in adult patients undergoing AC. Eighteen studies were included in the final analysis. MAC was associated with a lower risk of AC failure when compared with SAS (global pooled proportion MAC vs. SAS 1% vs. 4%; odds ratio [ORs]: 0.28; 95% confidence interval [CI]: 0.11-0.71; P=0.007) and shorter surgical procedure time (global pooled mean MAC vs. SAS 224.44 vs. 327.94 min; mean difference, -48.76 min; 95% CI: -61.55 to -35.97; P<0.00001). SAS was associated with fewer intraoperative seizures (global pooled proportion MAC vs. SAS 10% vs. 4%; OR: 2.38; 95% CI: 1.05-5.39; P=0.04). There were no differences in intraoperative nausea and vomiting between the techniques (global pooled proportion MAC vs. SAS: 4% vs. 8%; OR: 0.86; 95% CI: 0.30-2.45; P=0.78). Length of stay was shorter in the MAC group (MAC vs. SAS 3.96 vs. 6.75 days; mean difference, -1.30; 95% CI: -2.69 to 0.10; P=0.07). In summary, MAC was associated with lower AC failure rates and shorter procedure time compared with SAS, whereas SAS was associated with a lower incidence of intraoperative seizures. However, there was a high risk of bias and other limitations in the studies included in this review, so the superiority of 1 technique over the other needs to be confirmed in larger randomized studies.

Global Landscape of Glioblastoma Multiforme Management in the Stupp Protocol Era: Systematic Review Protocol.

BACKGROUND: Glioblastoma multiforme is the most common and aggressive primary adult brain neoplasm. The current standard of care is maximal safe surgical resection, radiotherapy with concomitant temozolomide, followed by adjuvant temozolomide according to the Stupp protocol. Although the protocol is well adopted in high-income countries (HICs), little is known about its adoption in low- and middle-income countries (LMICs). The aim of this study is to describe a protocol design for a systematic review of published studies outlining the differences in GBM management between HICs and LMICs. METHODS: A systematic review will be conducted. MedLine via Ovid, Embase and Global Index Medicus will be searched from inception to date in order to identify the relevant studies. Adult patients (>18 years) with histologically confirmed primary unifocal GBM will be included. Surgical and chemoradiation management of GBM tumours will be considered. Commentaries, original research, non-peer reviewed pieces, opinion pieces, editorials and case reports will be included. RESULTS: Primary outcomes will include rates of complications, disability-adjusted life years (DALYs), prognosis, progression-free survival (PFS), overall survival (OS) as well as rate of care abandonment and delay. Secondary outcomes will include the presence of neuro-oncology subspecialty training programs. DISCUSSION: This systematic review will be the first to compare the current landscape of GBM management in HICs and LMICs, highlighting pertinent themes that may be used to optimise treatment in both financial brackets. SYSTEMATIC REVIEW REGISTRATION: The protocol has been registered on the International Prospective Register of Systematic Reviews (PROSPERO; registration number: CRD42020215843). HIGHLIGHTS: Glioblastoma multiforme (GBM) remains the most common primary adult cerebral neoplasm, with an age-adjusted incidence rate of 3.22 per 100,000 population and a 5-year survival rate of 6.8%Despite the well-evidenced efficacy of Stupp protocol, the implementation of this approach bears an institutional and individual financial burden that is particularly notable in low- and middle-income countries (LMICs)This systematic review will be the first to compare the current landscape of GBM management in HICs and LMICs, highlighting pertinent themes that may be used to optimise treatment in both financial brackets.

Treatment strategies for new onset atrial fibrillation in patients treated on an intensive care unit: a systematic scoping review.

BACKGROUND: New-onset atrial fibrillation (NOAF) in patients treated on an intensive care unit (ICU) is common and associated with significant morbidity and mortality. We undertook a systematic scoping review to summarise comparative evidence to inform NOAF management for patients admitted to ICU. METHODS: We searched MEDLINE, EMBASE, CINAHL, Web of Science, OpenGrey, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effects, ISRCTN, ClinicalTrials.gov, EU Clinical Trials register, additional WHO ICTRP trial databases, and NIHR Clinical Trials Gateway in March 2019. We included studies evaluating treatment or prevention strategies for NOAF or acute anticoagulation in general medical, surgical or mixed adult ICUs. We extracted study details, population characteristics, intervention and comparator(s), methods addressing confounding, results, and recommendations for future research onto study-specific forms. RESULTS: Of 3,651 citations, 42 articles were eligible: 25 primary studies, 12 review articles and 5 surveys/opinion papers. Definitions of NOAF varied between NOAF lasting 30 s to NOAF lasting > 24 h. Only one comparative study investigated effects of anticoagulation. Evidence from small RCTs suggests calcium channel blockers (CCBs) result in slower rhythm control than beta blockers (1 study), and more cardiovascular instability than amiodarone (1 study). Evidence from 4 non-randomised studies suggests beta blocker and amiodarone therapy may be equivalent in respect to rhythm control. Beta blockers may be associated with improved survival compared to amiodarone, CCBs, and digoxin, though supporting evidence is subject to confounding. Currently, the limited evidence does not support therapeutic anticoagulation during ICU admission. CONCLUSIONS: From the limited evidence available beta blockers or amiodarone may be superior to CCBs as first line therapy in undifferentiated patients in ICU. The little evidence available does not support therapeutic anticoagulation for NOAF whilst patients are critically ill. Consensus definitions for NOAF, rate and rhythm control are needed.

Traumatic Brain Injury-Related Pediatric Mortality and Morbidity in Low- and Middle-Income Countries: A Systematic Review.

BACKGROUND: The burden of pediatric traumatic brain injury (pTBI) in low- and middle-income countries (LMICs) is unknown. To fill this gap, we conducted a review that aimed to characterize the causes of pTBI in LMICs, and their reported associated mortality and morbidity. METHODS: A systematic review was conducted. MEDLINE, Embase, Global Health, and Global Index Medicus were searched from January 2000 to May 2020. Observational or experimental studies on pTBI of individuals aged between 0 and 16 years in LMICs were included. The causes of pTBI and morbidity data were descriptively analyzed, and case fatality rates were calculated. PROSPERO ID: CRD42020171276. RESULTS: A total of 136 studies were included. Fifty-seven studies were at high risk of bias. Of the remaining studies, 170,224 cases of pTBI were reported in 32 LMICs. The odds of having a pTBI were 1.8 times higher (95% confidence interval, 1.6-2.0) in males. The odds of a pTBI being mild were 4.4 times higher (95% confidence interval, 1.9-6.8) than a pTBI being moderate or severe. Road traffic accidents were the most common cause (n = 16,275/41,979; 39%) of pTBIs. On discharge, 24% of patients (n = 4385/17,930) had a reduction in their normal mental or physical function. The median case fatality rate was 7.3 (interquartile range, 2.1-7.7). CONCLUSIONS: Less than a quarter (n = 32) of all LMICs have published high-quality data on the volume and burden of pTBI. From the limited data available, young male children are at a high risk of pTBIs in LMICs, particularly after road traffic accidents.

Systematic review of applied usability metrics within usability evaluation methods for hospital electronic healthcare record systems: Metrics and Evaluation Methods for eHealth Systems.

BACKGROUND AND OBJECTIVES: Electronic healthcare records have become central to patient care. Evaluation of new systems include a variety of usability evaluation methods or usability metrics (often referred to interchangeably as usability components or usability attributes). This study reviews the breadth of usability evaluation methods, metrics, and associated measurement techniques that have been reported to assess systems designed for hospital staff to assess inpatient clinical condition. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology, we searched Medline, EMBASE, CINAHL, Cochrane Database of Systematic Reviews, and Open Grey from 1986 to 2019. For included studies, we recorded usability evaluation methods or usability metrics as appropriate, and any measurement techniques applied to illustrate these. We classified and described all usability evaluation methods, usability metrics, and measurement techniques. Study quality was evaluated using a modified Downs and Black checklist. RESULTS: The search identified 1336 studies. After abstract screening, 130 full texts were reviewed. In the 51 included studies 11 distinct usability evaluation methods were identified. Within these usability evaluation methods, seven usability metrics were reported. The most common metrics were ISO9241-11 and Nielsen's components. An additional "usefulness" metric was reported in almost 40% of included studies. We identified 70 measurement techniques used to evaluate systems. Overall study quality was reflected in a mean modified Downs and Black checklist score of 6.8/10 (range 1-9) 33% studies classified as "high-quality" (scoring eight or higher), 51% studies "moderate-quality" (scoring 6-7), and the remaining 16% (scoring below five) were "low-quality." CONCLUSION: There is little consistency within the field of electronic health record systems evaluation. This review highlights the variability within usability methods, metrics, and reporting. Standardized processes may improve evaluation and comparison electronic health record systems and improve their development and implementation.

Human factors in escalating acute ward care: a qualitative evidence synthesis.

BACKGROUND: Identifying how human factors affect clinical staff recognition and managment of the deteriorating ward patient may inform process improvements. We systematically reviewed the literature to identify (1) how human factors affect ward care escalation (2) gaps in the current literature and (3) critique literature methodologies. METHODS: We undertook a Qualitative Evidence Synthesis of care escalation studies. We searched MEDLINE, EMBASE and CINHAL from inception to September 2019. We used the Critical Appraisal Skills Programme and the Grading of Recommendations Assessment-Development and Evaluation and Confidence in Evidence from Reviews of Qualitative Research tool to assess study quality. RESULTS: Our search identified 24 studies meeting the inclusion criteria. Confidence in findings was moderate (20 studies) to high (4 studies). In 16 studies, the ability to recognise changes in the patient's condition (soft signals), including skin colour/temperature, respiratory pattern, blood loss, personality change, patient complaint and fatigue, improved the ability to escalate patients. Soft signals were detected through patient assessment (looking/listening/feeling) and not Early Warning Scores (eight studies). In contrast, 13 studies found a high workload and low staffing levels reduced staff's ability to detect patient deterioration and escalate care. In eight studies quantifiable deterioration evidence (Early Warning Scores) facilitated escalation communication, particularly when referrer/referee were unfamiliar. Conversely, escalating concerning non-triggering patients was challenging but achieved by some clinical staff (three studies). Team decision making facilitated the clinical escalation (six studies). CONCLUSIONS: Early Warning Scores have clinical benefits but can sometimes impede escalation in patients not meeting the threshold. Staff use other factors (soft signals) not captured in Early Warning Scores to escalate care. The literature supports strategies that improve the escalation process such as good patient assessment skills. PROSPERO REGISTRATION NUMBER: CRD42018104745.

Cardiac abnormalities identified with echocardiography in anorexia nervosa: systematic review and meta-analysis.

BACKGROUND: Anorexia nervosa affects most organ systems, with 80% suffering from cardiovascular complications. AIMS: To define echocardiographic abnormalities in anorexia nervosa through systematic review and meta-analysis. METHOD: Two reviewers independently assessed eligibility of publications from Medline, EMBASE and Cochrane Database of Systematic Reviews registries. Studies were included if anorexia nervosa was the primary eating disorder and the main clinical association in described cardiac abnormalities. Data was extracted in duplicate and quality-assessed with a modified Newcastle-Ottawa scale. For continuous outcomes we calculated mean and standardised mean difference (SMD), and corresponding 95% confidence interval. For dichotomous outcomes we calculated proportion and corresponding 95% confidence interval. For qualitative data we summarised the studies. RESULTS: We identified 23 eligible studies totalling 960 patients, with a mean age of 17 years and mean body mass index of 15.2 kg/m2. Fourteen studies (469 participants) reported data suitable for meta-analysis. Cardiac abnormalities seen in anorexia nervosa compared with healthy controls were reduced left ventricular mass (SMD 1.82, 95% CI 1.32-2.31, P < 0.001), reduced cardiac output (SMD 1.92, 95% CI 1.38-2.45, P < 0.001), increased E/A ratio (SMD -1.10, 95% CI -1.67 to -0.54, P < 0.001), and increased incidence of pericardial effusions (25% of patients, P < 0.01, 95% CI 17-34%, I2 = 80%). Trends toward improvement were seen with weight restoration. CONCLUSIONS: Patients with anorexia nervosa have structural and functional cardiac changes, identifiable with echocardiography. Further work should determine whether echocardiography can help stratify severity and guide safe patient location, management and effectiveness of nutritional rehabilitation.

The PRICES statement: an ESICM expert consensus on methodology for conducting and reporting critical care echocardiography research studies.

PURPOSE: Echocardiography is a common tool for cardiac and hemodynamic assessments in critical care research. However, interpretation (and applications) of results and between-study comparisons are often difficult due to the lack of certain important details in the studies. PRICES (Preferred Reporting Items for Critical care Echocardiography Studies) is a project endorsed by the European Society of Intensive Care Medicine and conducted by the Echocardiography Working Group, aiming at producing recommendations for standardized reporting of critical care echocardiography (CCE) research studies. METHODS: The PRICE panel identified lists of clinical and echocardiographic parameters (the "items") deemed important in four main areas of CCE research: left ventricular systolic and diastolic functions, right ventricular function and fluid management. Each item was graded using a critical index (CI) that combined the relative importance of each item and the fraction of studies that did not report it, also taking experts' opinion into account. RESULTS: A list of items in each area that deemed essential for the proper interpretation and application of research results is recommended. Additional items which aid interpretation were also proposed. CONCLUSION: The PRICES recommendations reported in this document, as a checklist, represent an international consensus of experts as to which parameters and information should be included in the design of echocardiography research studies. PRICES recommendations provide guidance to scientists in the field of CCE with the objective of providing a recommended framework for reporting of CCE methodology and results.

The Diagnostic Accuracy of Mutant KRAS Detection from Pancreatic Secretions for the Diagnosis of Pancreatic Cancer: A Meta-Analysis.

This meta-analysis aims to identify the diagnostic accuracy of mutations in the Kirsten Rat Sarcoma (KRAS) oncogene in the diagnosis of pancreatic ductal adenocarcinoma (PDAC). The survival of PDAC remains poor often due to the fact that disease is advanced at diagnosis. We analysed 22 studies, with a total of 2156 patients, to identify if the detection of KRAS mutations from pancreatic exocrine secretions yields sufficient specificity and sensitivity to detect patients with PDAC amongst healthy individuals. The majority of the studies were retrospective, samples were obtained endoscopically or surgically, and included comparator populations of patients with chronic pancreatitis and pre-malignant pancreatic lesions (PanIN) as well as healthy controls. We performed several analyses to identify the diagnostic accuracy for PDAC among these patient populations. Our results highlighted that the diagnostic accuracy of KRAS mutation for PDAC was of variable sensitivity and specificity when compared with PanINs and chronic pancreatitis, but had a higher specificity among healthy individuals. The sensitivity of this test must be improved to prevent missing early PDAC or PanINs. This could be achieved with rigorous prospective cohort studies, in which high-risk patients with normal cross-sectional imaging undergo surveillance following KRAS mutation testing.

Managing new-onset atrial fibrillation in critically ill patients: a systematic narrative review.

OBJECTIVES: The aim of this review is to summarise the latest evidence on efficacy and safety of treatments for new-onset atrial fibrillation (NOAF) in critical illness. PARTICIPANTS: Critically ill adult patients who developed NOAF during admission. PRIMARY AND SECONDARY OUTCOMES: Primary outcomes were efficacy in achieving rate or rhythm control, as defined in each study. Secondary outcomes included mortality, stroke, bleeding and adverse events. METHODS: We searched MEDLINE, EMBASE and Web of Knowledge on 11 March 2019 to identify randomised controlled trials (RCTs) and observational studies reporting treatment efficacy for NOAF in critically ill patients. Data were extracted, and quality assessment was performed using the Cochrane Risk of Bias Tool, and an adapted Newcastle-Ottawa Scale. RESULTS: Of 1406 studies identified, 16 remained after full-text screening including two RCTs. Study quality was generally low due to a lack of randomisation, absence of blinding and small cohorts. Amiodarone was the most commonly studied agent (10 studies), followed by beta-blockers (8), calcium channel blockers (6) and magnesium (3). Rates of successful rhythm control using amiodarone varied from 30.0% to 95.2%, beta-blockers from 31.8% to 92.3%, calcium channel blockers from 30.0% to 87.1% and magnesium from 55.2% to 77.8%. Adverse effects of treatment were rarely reported (five studies). CONCLUSION: The reported efficacy of beta-blockers, calcium channel blockers, magnesium and amiodarone for achieving rhythm control was highly varied. As there is currently significant variation in how NOAF is managed in critically ill patients, we recommend future research focuses on comparing the efficacy and safety of amiodarone, beta-blockers and magnesium. Further research is needed to inform the decision surrounding anticoagulant use in this patient group.

Transcatheter aortic valve implantation vs. surgical aortic valve replacement for treatment of symptomatic severe aortic stenosis: an updated meta-analysis.

AIMS: Owing to new evidence from randomized controlled trials (RCTs) in low-risk patients with severe aortic stenosis, we compared the collective safety and efficacy of transcatheter aortic valve implantation (TAVI) vs. surgical aortic valve replacement (SAVR) across the entire spectrum of surgical risk patients. METHODS AND RESULTS: The meta-analysis is registered with PROSPERO (CRD42016037273). We identified RCTs comparing TAVI with SAVR in patients with severe aortic stenosis reporting at different follow-up periods. We extracted trial, patient, intervention, and outcome characteristics following predefined criteria. The primary outcome was all-cause mortality up to 2 years for the main analysis. Seven trials that randomly assigned 8020 participants to TAVI (4014 patients) and SAVR (4006 patients) were included. The combined mean STS score in the TAVI arm was 9.4%, 5.1%, and 2.0% for high-, intermediate-, and low surgical risk trials, respectively. Transcatheter aortic valve implantation was associated with a significant reduction of all-cause mortality compared to SAVR {hazard ratio [HR] 0.88 [95% confidence interval (CI) 0.78-0.99], P = 0.030}; an effect that was consistent across the entire spectrum of surgical risk (P-for-interaction = 0.410) and irrespective of type of transcatheter heart valve (THV) system (P-for-interaction = 0.674). Transcatheter aortic valve implantation resulted in lower risk of strokes [HR 0.81 (95% CI 0.68-0.98), P = 0.028]. Surgical aortic valve replacement was associated with a lower risk of major vascular complications [HR 1.99 (95% CI 1.34-2.93), P = 0.001] and permanent pacemaker implantations [HR 2.27 (95% CI 1.47-3.64), P < 0.001] compared to TAVI. CONCLUSION: Compared with SAVR, TAVI is associated with reduction in all-cause mortality and stroke up to 2 years irrespective of baseline surgical risk and type of THV system.

Risk factors for new-onset atrial fibrillation on the general adult ICU: A systematic review.

PURPOSE: This study was performed to systematically review the available evidence for the risk factors for new-onset atrial fibrillation (NOAF) on the general adult intensive care unit (ICU) and provide a semi-quantitative evidence synthesis. METHODS: We searched the MEDLINE, EMBASE, Cochrane Database of Systematic Reviews and the CENTRAL databases from 1970 to 2018. We included studies of adults based in general ICUs that evaluated potential risk factors for NOAF. We excluded studies involving patients with a history of atrial fibrillation (AF). We semi-qualitatively evaluated the strength of evidence for each identified variable. RESULTS: We screened 1447 studies. Seventeen studies were included in the final analysis. We identified strong evidence for age, male sex, preceding cardiovascular disease, acute renal failure, acute respiratory failure, APACHE score and the use of vasopressors as risk factors for the development of NOAF on the ICU. Modifiable risk factors had not been studied in detail. CONCLUSIONS: We provide the first systematic review with evidence synthesis of risk factors for NOAF on the general adult ICU. Evidence for modifiable risk factors was limited. Further research is therefore required and may contribute towards the evidence-based prevention and management of this important condition.

How human factors affect escalation of care: a protocol for a qualitative evidence synthesis of studies.

INTRODUCTION: Failure to rescue is defined as mortality after complications during hospital care. Incidence ranges 10.9%-13.3% and several national reports such as National Confidential Enquiry into Patient Outcomes and Death and National Institute of Clinical Excellence CG 50 highlight failure to rescue as a significant problem for safe patient care.To avoid failure to rescue events, there must be successful escalation of care. Studies indicate that human factors such as situational awareness, team working, communication and a culture promoting safety contribute to avoidance of failure to rescue events. Understanding human factors is essential to developing work systems that mitigate barriers and facilitate prompt escalation of care. This qualitative evidence synthesis will identify and synthesise what is known about the human factors that affect escalation of care. METHODS AND ANALYSIS: We will search MEDLINE (Ovid), EMBASE (Ovid) and CINAHL, between database inception and 2018, for studies describing human factors affecting failure to rescue and/or care escalation. A search strategy was developed by two researchers and a medical librarian. Only studies exploring in-hospital (ward) populations using qualitative data collection methods will be included. Screening will be conducted by two researchers. We are likely to undertake a thematic synthesis, using the Thomas and Harden framework. Selected studies will be assessed for quality, rigour and limitations. Two researchers will extract and thematically synthesise codes using a piloted data extraction tool to develop analytical themes. ETHICS AND DISSEMINATION: The qualitative evidence synthesis will use available published literature and no ethical approval is required. This synthesis will be limited by the quality of studies, rigour and reproducibility of study findings. Results will be published in a peer-reviewed journal, publicised at conferences and on social media. PROSPERO REGISTRATION NUMBER: CRD42018104745.

Risk factors for new-onset atrial fibrillation on the general adult ICU: protocol for a systematic review.

INTRODUCTION: Atrial fibrillation (AF) is a common arrhythmia in the critical care environment. New-onset AF is associated with increased mortality and intensive care unit (ICU) length of stay. Observational studies have identified several epidemiological and disease severity-related factors associated with developing new-onset AF on the ICU. However, there are limited data on the modifiable risk factors in the general adult ICU population.We describe a protocol for a systematic review of modifiable and non-modifiable risk factors for new-onset AF in the general adult ICU population. The results of this review will aid the development of risk prediction tools and inform future research into AF prevention on the ICU. METHODS AND ANALYSIS: Medical Literature Analysis and Retrieval System Online, Excerpta Medica database and the Cochrane Library, including Cochrane Database of Systematic Reviews and the Cochrane Central Register of Controlled Trials will be searched for studies that assess the association of patient variables, investigation results, interventions and diagnoses associated with subsequent new-onset AF on the ICU.Only studies involving adult patients admitted to non-service-specific ICUs will be included. We will extract data relating to the statistical association between reversible and non-reversible factors and AF, the quality of the studies and the generalisability of the results. This systematic review will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. ETHICS AND DISSEMINATION: This proposed systematic review will be based on published data, and therefore ethical approval is not required. The findings of this study will be disseminated through publication in a peer reviewed journal and will be presented at conferences. PROSPERO REGISTRATION NUMBER: CRD42017074221.

Out-of-hours discharge from intensive care, in-hospital mortality and intensive care readmission rates: a systematic review and meta-analysis.

PURPOSE: Discharge from an intensive care unit (ICU) out of hours is common. We undertook a systematic review and meta-analysis to explore the association between time of discharge and mortality/ICU readmission. METHODS: We searched Medline, Embase, Web of Knowledge, CINAHL, the Cochrane Library and OpenGrey to June 2017. We included studies reporting in-hospital mortality and/or ICU readmission rates by ICU discharge "out-of-hours" and "in-hours". Inclusion was limited to patients aged ≥ 16 years discharged alive from a non-specialist ICU to a lower level of hospital care. Studies restricted to specific diseases were excluded. We assessed study quality using the Newcastle Ottowa Scale. We extracted published data, summarising using a random-effects meta-analysis. RESULTS: Our searches identified 1961 studies. We included unadjusted data from 1,191,178 patients from 18 cohort studies (presenting data from 1994 to 2014). "Out of hours" had multiple definitions, beginning between 16:00 and 22:00 and ending between 05:59 and 09:00. Patients discharged out of hours had higher in-hospital mortality [relative risk (95% CI) 1.39 (1.24, 1.57) p < 0.0001] and readmission rates [1·30 (1.19, 1.42), p < 0.001] than patients discharged in hours. Heterogeneity was high (I2 90.1% for mortality and 90.2% for readmission), resulting from differences in effect size rather than the presence of an effect. CONCLUSIONS: Out-of-hours discharge from an ICU is strongly associated with both in-hospital death and ICU readmission. These effects persisted across all definitions of "out of hours" and across healthcare systems in different geographical locations. Whether these increases in mortality and readmission result from patient differences, differences in care, or a combination remains unclear.

Progress in clinical research in surgery and IDEAL.

The quality of clinical research in surgery has long attracted criticism. High-quality randomised trials have proved difficult to undertake in surgery, and many surgical treatments have therefore been adopted without adequate supporting evidence of efficacy and safety. This evidence deficit can adversely affect research funding and reimbursement decisions, lead to slow adoption of innovations, and permit widespread adoption of procedures that offer no benefit, or cause harm. Improvement in the quality of surgical evidence would therefore be valuable. The Idea, Development, Exploration, Assessment, and Long-term Follow-up (IDEAL) Framework and Recommendations specify desirable qualities for surgical studies, and outline an integrated evaluation pathway for surgery, and similar complex interventions. We used the IDEAL Recommendations to assess methodological progress in surgical research over time, assessed the uptake and influence of IDEAL, and identified the challenges to further methodological progress. Comparing studies from the periods 2000-04 and 2010-14, we noted apparent improvement in the use of standard outcome measures, adoption of Consolidated Standards of Reporting Trials (CONSORT) standards, and assessment of the quality of surgery and of learning curves, but no progress in the use of qualitative research or reporting of modifications during procedure development. Better education about research, integration of rigorous evaluation into routine practice and training, and linkage of such work to awards systems could foster further improvements in surgical evidence. IDEAL has probably contributed only slightly to the improvements described to date, but its uptake is accelerating rapidly. The need for the integrated evaluation template IDEAL offers for surgery and other complex treatments is becoming more widely accepted.

Usability evaluation methods employed to assess information visualisations of electronically stored patient data for clinical use: a protocol for a systematic review.

BACKGROUND: The use of electronic records in healthcare is increasing. To avoid errors, it is essential that the data displays used by these systems are usable: efficient, effective and satisfying. A wide variety of display techniques are used to present clinical data, but the best methods to assess the usability of these techniques have not been determined. This systematic review will answer the question: What methods are employed to assess the usability of electronic visualisations of patient data for clinical use? The results of this systematic review will then be used to inform best assessment and design practice. METHODS: MEDLINE, EMBASE, CINAHL, OpenGrey, and the Cochrane Database of Systematic Reviews will be searched for original studies related to the usability of electronic information visualisations of patient data for clinical use. Reference lists of eligible studies and relevant reviews will be explored to identify further eligible studies. DISCUSSION: This systematic review will identify methods used to assess the usability of electronic information visualisations of patient data for clinical use. We will summarise the similarities and differences between the methods found. Our results will inform best practice when developing new user interfaces to display electronic patient data for clinical use. TRIAL REGISTRATION: PROSPERO CRD42016041604.

A meta-analysis of CXCL12 expression for cancer prognosis.

BACKGROUND: CXCL12 (SDF1) is reported to promote cancer progression in several preclinical models and this is corroborated by the analysis of human tissue specimens. However, the relationship between CXCL12 expression and cancer survival has not been systematically assessed. METHODS: We conducted a systematic review and meta-analysis of studies that evaluated the association between CXCL12 expression and cancer survival. RESULTS: Thirty-eight studies inclusive of 5807 patients were included in the analysis of overall, recurrence-free or cancer-specific survival, the majority of which were retrospective. The pooled hazard ratios (HRs) for overall and recurrence-free survival in patients with high CXCL12 expression were 1.39 (95% CI: 1.17-1.65, P=0.0002) and 1.12 (95% CI: 0.82-1.53, P=0.48) respectively, but with significant heterogeneity between studies. On subgroup analysis by cancer type, high CXCL12 expression was associated with reduced overall survival in patients with oesophagogastric (HR 2.08; 95% CI: 1.31-3.33, P=0.002), pancreatic (HR 1.54; 95% CI: 1.21-1.97, P=0.0005) and lung cancer (HR 1.37; 95% CI: 1.08-1.75, P=0.01), whereas in breast cancer patients high CXCL12 expression conferred an overall survival advantage (HR 0.5; 95% CI: 0.38-0.66, P<0.00001). CONCLUSIONS: Determination of CXCL12 expression has the potential to be of use as a cancer biomarker and adds prognostic information in various cancer types. Prospective or prospective-retrospective analyses of CXCL12 expression in clearly defined cancer cohorts are now required to advance our understanding of the relationship between CXCL12 expression and cancer outcome.

Variables associated with unplanned general adult ICU admission in hospitalised patients: protocol for a systematic review.

BACKGROUND: Failure to promptly identify deterioration in hospitalised patients is associated with delayed admission to intensive care units (ICUs) and poor outcomes. Existing vital sign-based Early Warning Score (EWS) algorithms do not have a sufficiently high positive predictive value to be used for automated activation of an ICU outreach team. Incorporating additional patient data might improve the predictive power of EWS algorithms; however, it is currently not known which patient data (or variables) are most predictive of ICU admission. We describe the protocol for a systematic review of variables associated with ICU admission. METHODS/DESIGN: MEDLINE, EMBASE, CINAHL and the Cochrane Library, including Cochrane Database of Systematic Reviews and the Cochrane Central Register of Controlled Trials (CENTRAL) will be searched for studies that assess the association of routinely recorded variables associated with subsequent unplanned ICU admission. Only studies involving adult patients admitted to general ICUs will be included. We will extract data relating to the statistical association between ICU admission and predictor variables, the quality of the studies and the generalisability of the findings. DISCUSSION: The results of this review will aid the development of future models which predict the risk of unplanned ICU admission. SYSTEMATIC REVIEW REGISTRATION: PROSPERO: CRD42015029617.