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BACKGROUND Traumatic brain injury (TBI) is a leading cause of injury-related deaths and neurological disability globally. Considering the widespread anticoagulant use among the aging population, we aimed to perform a systematic review and meta-analysis to evaluate the prognostic significance of preinjury anticoagulation in TBI patients. METHODS This systematic review was conducted according to a predefined protocol (International Prospective Register of Systematic Reviews CRD42020192323). In compliance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-Analysis of Observational Studies in Epidemiology standards, a structured electronic database search was undertaken to identify all observational studies comparing preinjury anticoagulation with no preinjury anticoagulation in TBI patients. The primary outcome measure was overall mortality. The secondary outcome measures comprised in-hospital mortality, length of hospital stay, length of intensive care unit stay, need for neurosurgical procedure, and number of patients discharged home. All outcome data were analyzed using random effects modeling. RESULTS Twelve comparative studies enrolling a total of 4,417 patients were included. Preinjury anticoagulation was associated with higher risk of overall mortality (odds ratio [OR], 2.39; 95% confidence interval [CI], 1.63-3.50, p < 0.00001), in-hospital mortality (OR, 2.47; 95% CI, 1.56-3.93, p = 0.0001), and longer length of intensive care unit stay (mean difference, 1.06; 95% CI, 0.54-1.57; p < 0.0001) compared with no preinjury anticoagulation. No statistical difference was observed in length of hospital stay (mean difference, -2.15; 95% CI, -5.36 to 1.05, p = 0.19), need for neurosurgical procedure (OR, 1.30; 95% CI, 0.70-2.44; p = 0.41), and discharged home (OR, 0.76; 95% CI, 0.55-1.04; p = 0.09) between the two groups. CONCLUSION Preinjury anticoagulation is a powerful prognosticator of mortality in TBI patients. This highlights the need for dedicated triage and trauma team activation protocols considering earlier intervention and more aggressive imaging in all anticoagulated patients. Future studies should focus on strategies that can potentially reduce the risk of mortality in this population. The prognostic significance of direct oral anticoagulants versus warfarin remains unanswered. LEVEL OF EVIDENCE Systematic review and meta-analysis of observational studies, level III.

Background Studies have reported that general anesthesia (GA), especially volatile agents were associated with higher cancer recurrence rate after cancer resection surgery. However, the effect of supplementary regional anesthesia (RA) in reducing the use of anesthetic agents on oncological outcomes remains unclear. The primary aim of this meta-analysis was to examine the effect of adjunctive use of RA on the cancer recurrence rate in adults undergoing cancer resection surgery. Methods MEDLINE, EMBASE and CENTRAL were systematically searched for randomized control trials (RCTs) from its inception until April 2020. Results Six RCTs (n = 3139 patients) were included. In comparison to the GA alone, our meta-analysis demonstrated no significant difference in the cancer recurrence rate in patients who received the adjunctive use of RA in the routine care of GA (3 studies, n = 2380 patients; odds ratio 0.93, 95%CI 0.63–1.39, ρ = 0.73, certainty of evidence = very low). Our review also showed no significant difference in cancer-related mortality (2 studies, n = 545; odds ratio 1.20, 95%CI 0.83–1.74, ρ = 0.33, certainty of evidence = low), all-cause mortality (3 studies, n = 2653; odds ratio 0.98, 95%CI 0.69–1.39, ρ = 0.89, certainty of evidence = low) and duration of cancer-free survival (2 studies, n = 659; mean difference 0.00 years, 95%CI -0.25-0.25, ρ = 1.00, certainty of evidence = high). Conclusion This meta-analysis concluded that the adjunctive use of RA in the routine care of GA did not reduce cancer recurrence rate in cancer resection surgery. However, this finding needs to be interpreted with caution due to low level of evidence, substantial heterogeneity and potential risk of bias across the included studies. Study registration number CRD42020171368.

To assess the effect of preinjury anticoagulation on mortality in trauma patients.A search of electronic information sources was conducted to identify all observational studies comparing preinjury anticoagulation with no preinjury anticoagulation in trauma patients. The primary outcome measure was overall mortality (overall mortality, in-hospital mortality and 30-day mortality). The secondary outcome measures included the length of hospital stay, length of intensive care unit (ICU) stay, incidence of intracranial haemorrhage (ICH), and need for operation. Fixed effect or random effects modelling was applied as appropriate to calculate pooled outcome data.Nineteen comparative studies enrolling a total of 1,365,446 patients were included. Preinjury anticoagulation was associated with higher risk of overall mortality (OR 2.12, 95%CI 1.79 - 2.51, p0.00001), in-hospital mortality (OR 2.04, 95%CI 1.66 - 2.52, p0.00001), ICH (OD 1.99, 95%CI 1.61 - 2.45, p0.00001), and shorter length of hospital stay (MD 0.50, 95%CI 0.03 - 0.97, p = 0.04) in comparison to no preinjury anticoagulation. We found no difference between the two groups in 30-day mortality (OR 1.61, 95%CI 0.91 - 2.85, p = 0.10), length of ICU stay (MD 0.62, 95%CI -0.13 - 1.36, p = 0.11), and need for operation (OR 1.73, 95%CI 0.71 - 4.20, p = 0.23). The quality of the available evidence was moderate.Preinjury anticoagulation is a significant predictor of mortality in trauma patients. Future studies should focus on strategies required to reduce such a significant risk of mortality in these high-risk patients. This may include adaptation of primary, secondary and tertiary trauma surveys for patients on preinjury anticoagulation.

Supplemental Digital Content is available in the text., OBJECTIVES: To compare the performance of Sequential Organ Failure Assessment, systemic inflammatory response syndrome, Red Flag Sepsis, and National Institute of Clinical Excellence sepsis risk stratification tools in the identification of patients at greatest risk of mortality from sepsis in nonintensive care environments. DESIGN: Secondary analysis of three annual 24-hour point-prevalence study periods. SETTING: The general wards and emergency departments of 14 acute hospitals across Wales. Studies were conducted on the third Wednesday of October in 2017, 2018, and 2019. PATIENTS: We screened all patients presenting to the emergency department and on the general wards. MEASUREMENTS AND MAIN RESULTS: We recruited 1,271 patients, of which 724 (56.9%) had systemic inflammatory response syndrome greater than or equal to 2, 679 (53.4%) had Sequential Organ Failure Assessment greater than or equal to 2, and 977 (76.9%) had Red Flag Sepsis. When stratified according to National Institute of Clinical Excellence guidelines, 450 patients (35.4%) were in the “High risk” category in comparison with 665 (52.3%) in “Moderate to High risk” and 156 (12.3%) in “Low risk” category. In a planned sensitivity analysis, we found that none of the tools accurately predicted mortality at 90 days, and Sequential Organ Failure Assessment and National Institute of Clinical Excellence tools showed only moderate discriminatory power for mortality at 7 and 14 days. Furthermore, we could not find any significant correlation with any of the tools at any of the mortality time points. CONCLUSIONS: Our data suggest that the sepsis risk stratification tools currently utilized in emergency departments and on the general wards do not predict mortality adequately. This is illustrated by the disparity in mortality risk of the populations captured by each instrument, as well as the weak concordance between them. We propose that future studies on the development of sepsis identification tools should focus on identifying predicator values of both the short- and long-term outcomes of sepsis.

Atrial fibrillation (AF) is associated with an increased risk of dementia. Studies have shown the beneficial effects of anticoagulants in preventing dementia in this population. However, evidence around the use of direct oral anticoagulants (DOACs) versus warfarin in AF-related dementia prevention remains sparse. This systematic review and meta-analysis aimed to evaluate the use of DOACs versus warfarin in dementia prevention in this population. MEDLINE, EMBASE, PsycINFO, and the CENTRAL databases were systematically searched from its inception until May 2020. Nine studies (n = 611,069) were included for quantitative meta-analysis. DOACs use was associated with a lower risk of composite dementia outcomes compared with warfarin use [odds ratio (OR) 0.56, 95% confidence interval (CI) 0.34-0.94, P = 0.03]. No significant difference was found in subtypes of dementia (vascular dementia, Alzheimer's disease, and cognitive disorder) between both groups. No significant difference in the risk of composite dementia outcomes between the dabigatran and warfarin groups (OR 0.97, 95% CI 0.88-1.08, P = 0.61). Apixaban (OR 0.58, 95% CI 0.50-0.67, P < 0.00001) and rivaroxaban (OR 0.67, 95% CI 0.61-0.75, P < 0.00001) use were both associated with a significantly lower risk of composite dementia outcomes compared with warfarin use. Findings need to be interpreted with caution because of low certainty of evidence. In conclusion, this systematic review and meta-analysis of 9 comparative studies demonstrated the superiority of DOACs over warfarin in prevention of dementia in AF. Future prospective trials with adequate follow-up period are warranted to ascertain its causal relationship.

Aim The aim of this study was to explore the value of the FRANCE-2 score in associating with clinical outcome in the medium and short-term after TAVI and to compare its relative merits with other risk score models. Methods 187 consecutive patients undergoing TAVI in a single UK centre were retrospectively studied. The FRANCE-2, logistic EuroSCORE, EuroSCORE II, German AV and STS/ACC TVT risk scores were calculated retrospectively and c-statistics associating with mortality were applied. Survival outcomes were compared between different risk groups according to the FRANCE-2 scores. Results Of the 187 patients, 57.2% were male and their mean age was 80.9 ± 6.9 years. The c-index of FRANCE-2 score for predicting 30-day mortality was 0.793 (p = 0.009), for 1-year mortality 0.679 (p = 0.016) and for 2-year mortality was 0.613 (p = 0.088). The mean survival time for patients with a high FRANCE-2 score (18.6 months) was significantly less than for patients with low and moderate scores (p = 0.0004). The logistic EuroSCORE and EuroSCORE II were poorly associated with 30-day and 1-year mortality. STS/ACC TVT score was best predictive of 1-year mortality and German AV score was moderately predictive of 30-day mortality. Conclusions The FRANCE-2 risk score is associated with differential short- and medium-term survival in patients undergoing TAVI. The presence of a high FRANCE-2 score (>5) is associated with poor survival. The FRANCE-2 scoring system could be considered as a useful additional tool by the Heart multidisciplinary team (MDT) in identifying patients who are likely to have limited survival benefit although this requires further prospective evaluation.

The repetitive hypoxic and hypercapnia events of obstructive sleep apnea (OSA) are believed to adversely affect cardiopulmonary function, which make them vulnerable to a higher incidence of postoperative complications. The primary aim of this systematic review and meta-analysis was to examine the association of OSA and the composite endpoints of postoperative cardiac or cerebrovascular complications in adult undergoing non-cardiac surgery.MEDLINE, EMBASE and CENTRAL were systematically searched from its inception until May 2019.All observational studies were included.Twenty-two studies (n = 3,033,814; 184,968 OSA vs 2,848,846 non-OSA) were included for quantitative meta-analysis. In non-cardiac surgery, OSA was significantly associated with a higher incidence of the composite endpoints of postoperative cardiac or cerebrovascular complications (odd ratio: 1.44, 95%CI: 1.17 to 1.78, ρ = 0.007, trial sequential analysis = conclusive; certainty of evidence = very low). In comparison to non-OSA, OSA patients were reported to have nearly 2.5-fold risk of developing pulmonary complications (odd ratio: 2.52, 95%CI: 1.92 to 3.31, ρ 0.001, certainty of evidence = very low), postoperative delirium (odd ratio: 2.45, 95%CI: 1.50 to 4.01, ρ 0.001, certainty of evidence = low) and acute kidney injury (odd ratio: 2.41, 95%CI: 1.93 to 3.02, ρ 0.001, certainty of evidence = very low).This meta-analysis of 22 comparative studies demonstrated that OSA is a potential risk factor to postoperative adverse complications in adults undergoing non-cardiac surgery. However, the conclusions need to be interpreted with caution due to the nature of included observational studies with significant heterogeneity and low quality of evidence.CRD42019136564.

Introduction There is a high prevalence of patent foramen ovale (PFO) in patients with cryptogenic stroke; paradoxical embolism may be implicated in some but not all of these. Percutaneous device PFO closure reduces the risk of recurrent emboli but the success of this treatment is dependent on appropriate patient selection. The work-up of patients with cryptogenic stroke and PFO is best undertaken by a multi-disciplinary team (MDT). Aim The aim was to evaluate the impact of a methodical approach to MDT investigation and work-up of patients with cryptogenic stroke and PFO on the final diagnosis and selection of patients for device PFO closure in a UK centre. Methods The study was done in a single tertiary cardiac centre providing a PFO device closure service to a population of 1.3 million. Consecutive patients referred to the service between March 2011 and January 2017 were studied. Assessment included clinical consultation and expert review of all cardiac imaging (TOE and bubble contrast TTE), brain imaging (CT, DWI MRI, CT angiography), thrombophilia and arrhythmia investigations. Information about the MDT conclusions was obtained from meeting minutes, electronic and paper patient records. Results 171 patients [51% female, mean age of 42 years (SD: ±16)] were assessed. The median number of MDT discussions was 1 per patient (range 1–5). Referral was with a cerebral infarct in 82%, transient cerebral ischaemia in 12% and peripheral emboli in 6%. Brain imaging confirmed the presence of cerebral infarction in 74% of patients. Cardiac imaging confirmed the presence of a PFO in 88%, an ASD in 5% and both in 4%; the intra-atrial septum was intact in 3%. One ‘high risk’ echo marker for paradoxical embolism was present in 44% of patients; an atrial septal aneurysm (23%), large right-to-left shunt (20%) or spontaneous shunt (43%). Clinically significant atrial arrhythmia was detected in 5% and thrombophilia testing was abnormal in 5% with lupus anticoagulant being positive in 62% of this subgroup. The final diagnoses are summarized in the figure 1. Paradoxical embolism was proposed if there was cerebral infarction typical of thrombo-embolism in the absence of vascular disease or arrhythmia and in the presence of PFO or ASD with a ’high-risk’ ECHO marker. Based on these criteria, device closure was recommended in 41% of patients. The remainder received treatment appropriate to their diagnosis: antiplatelet therapy in 36%, anti-coagulants in 10% and no treatment in 15%. Conclusion In patients with cryptogenic stroke who have a PFO, paradoxical embolism is implicated in the minority. Methodical work-up of patients by an MDT results in a range of diagnoses most of which are unrelated to the PFO. While clinical follow-up is required in all patients included in this study, we conclude that PFO device closure should be offered cautiously and only after careful multi-disciplinary assessment. Conflict of Interest None to declare

Objective To systematically review contemporary data on the safety of clopidogrel and newer antiplatelet agents in pregnant women, with particular attention to maternal and neonatal complications. Methods The review protocol was published via PROSPERO (ID 42020165235) and conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). Databases were searched using MeSH and free text terms encompassing the included antiplatelets, relevant indications, and pregnancy. Included studies reported the drug dose, the stage of pregnancy at which it was administered, and at least one primary or secondary outcome relating to pregnancy. The primary outcome was reporting of complications associated with antiplatelet use in pregnancy. Results The search yielded 5271 results. 39 publications were included, incorporating 42 live births. The mean age of women was 34.6 years. Seven different antiplatelet agents were described, clopidogrel being most frequent (n = 37). 14 women received antiplatelet therapy in the first trimester. 14 women had regional anaesthesia (12 while taking clopidogrel), all without complication. Two women developed bleeding post caesarean section. There were no recorded neonatal delivery complications. Two neonates had congenital anomalies not felt to be related to maternal antiplatelet use. Conclusions This systematic review describes outcomes for both mothers and neonates when exposed to clopidogrel at varying durations throughout gestation, and does not suggest higher than acceptable risk, with a congenital anomaly rate comparable to background risk. Evidence for other antiplatelet agents remains limited. Regional anaesthesia should be offered, with recommendation to stop prior to delivery in line with national guidance and in the context of individualised decision making.

Introduction There is growing evidence on the influence of general anaesthesia (GA) in promoting the proliferation of cancer cells. RA comprised of epidural, spinal and nerve block, which can attenuate surgical stress response by reducing catecholamine levels and minimizing immunosuppression. The benefits of regional anaesthesia (RA) on cancer recurrence rate in cancer surgery remains unclear in the literature. Objectives To examine the effect of RA-only on the incidence of post-operative cancer recurrence rate in cancer resection surgery. Methods This review was conducted and reported in adherence to the Cochrane Handbook and PRISMA statement 2015. The protocol was registered and published on a public database, PROSPERO (CRD42020163780). Databases: MEDLINE, EMBASE and CENTRAL (its inception until April 2020) Inclusion criteria: Randomized clinical trials, observational studies (cohort or case-control)Exclusion criteria: Case reports, case series and editorials Primary outcome: Incidence of cancer recurrence rate Secondary outcomes: Overall survival rate, time to cancer recurrence and cancer-related mortality All the included observational studies were assessed for risk of bias using the Newcastle-Ottawa Scale. Results The titles and abstracts of 4477 non-duplicate articles were screened, of which 44 articles were retrieved. After applying inclusion and exclusion criteria, 10 observational studies with a total of 9708 patients (4567 GA vs 5141 RA-only) were included for qualitative and quantitative meta-analysis. In comparison to GA, RA-only was not significantly associated with a lower cancer recurrence rate in cancer resection surgery (p=0.95, certainty of evidence=very low, Fig 1). However, the trial sequential analysis for cancer recurrence rate was inconclusive (Fig 2). Our analysis demonstrated no significant difference between the RA-only and GA groups in the overall survival rate (odds ratio 1.51, 95% CI 0.65 to 3.51, p=0.34, certainty of evidence=very low), time to cancer recurrence (mean difference 1.45 months, 95% CI -8.69 to 11.59, p=0.78, certainty of evidence=very low) and cancer-related mortality (odds ratio 1.79, 95% CI 0.57 to 5.62, p=0.32, certainty of evidence=very low). DiscussionFirst meta-analysis of the effect of RA-only versus routine care GA in cancer resection surgery. At present, only 22.2% of required information size (16031 patients) available to detect significance difference of 20% reduction in incidence of cancer recurrence. Substantial heterogeneity non-RCT, inadequate sample size True effect of GA-only may be skewed by many small sample size observational studies with conflicting results and substantial heterogeneity. Confounding factors: types of GA (TIVA/ volatile), amount of opioids use, types of cancer surgery. Conclusions Given the low level of evidence and underpowered trial sequential analysis, our review neither support nor oppose that the use of RA-only was associated with lower incidence of cancer recurrence rate than GA in cancer resection surgery.

Flash glucose monitoring (FGM) is widely accepted as an alternative means to conventional finger prick test for measuring glucose level in individuals with diabetes mellitus. In this clinical review, we endeavour to draw all available clinical evidence on the usage and efficacy of FGM from research trials and observational studies in real-world settings. We aim to explore its clinical efficacy and impact on quality of life (QoL) in the diabetic population. In terms of clinical outcomes, use of FGM is associated with a significant reduction in glycated haemoglobin A1c (HbA1c) level, notably in patients with suboptimal glycaemic control prior to commencement of FGM and reduction in time spent in hypoglycaemia. FGM demonstrated non-inferiority in device accuracy when compared to other well-established CGMs available in the market. Patients have reported improved QoL and treatment satisfaction measured by validated objective scores after consistent use of FGM. This results in a positive impact on patient psychosocial wellbeing and ultimately enhances patient compliance and optimisation of glycaemic control. Evaluation of QoL and patient reported outcome measures (PROMs) will require a standardised approach to allow comparability of the results and evidence.

Transcatheter aortic valve implantation (TAVI) for severe, symptomatic aortic stenosis improves quality of life and survival in most patients. It is, however, important to identify patients who are unlikely to get these benefits from TAVI so that futile treatment can be avoided. Futility in this