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The association of cryoprecipitate transfusion with patient outcomes after cardiac surgery is unclear. We aimed to investigate the predictors of, and outcomes associated with postoperative cryoprecipitate transfusion in cardiac surgery patients.We used the Medical Information Mart for Intensive Care III and IV databases. We included adults undergoing cardiac surgery, and propensity score matched cryoprecipitate-treated patients to controls. Using the matched cohort, we investigated the association of cryoprecipitate use with clinical outcomes. The primary outcome was in-hospital mortality. Secondary outcomes were infection, acute kidney injury, intensive care unit length of stay, hospital length of stay, and chest tube output at 2-hour intervals.Of 12,043 eligible patients, 283 (2.35%) patients received cryoprecipitate. The median dose was 5.83 units (IQR 4.17-7.24) given at a median first transfusion time of 1.75 hours (IQR 0.73-4.46) after intensive care unit admission. After propensity scoring, we matched 195 cryoprecipitate recipients to 743 controls. Postoperative cryoprecipitate transfusion was not significantly associated with in-hospital mortality (odds ratio [OR] 1.10; 99% confidence interval [CI] 0.43-2.84; p=0.791), infection (OR 0.77; 99% CI 0.45-1.34; p=0.220), acute kidney injury (OR 1.03; 99% CI 0.65-1.62; p=0.876) or cumulative chest tube output (adjusted mean difference 8 hrs post transfusion, 11 ml; 99% CI -104 to 125; p=0.804).Although cryoprecipitate was typically given to sicker patients with more bleeding, its administration was not associated with worse outcomes. Large, multicentred studies are warranted to further elucidate cryoprecipitate's safety profile and patterns of use in cardiac surgery.

Patients undergoing cardiac surgery are at significant risk of developing postoperative acute kidney injury (AKI). Neutrophil-lymphocyte ratio (NLR) is a widely available inflammatory biomarker which may be of prognostic value in this setting.We conducted a systematic review and meta-analysis of studies reporting associations between perioperative NLR with postoperative AKI. We searched Medline, Embase and the Cochrane Library, without language restriction, from inception to May 2022 for relevant studies. We meta-analysed the reported odds ratios (ORs) with 95% confidence intervals (CIs) for both elevated preoperative and postoperative NLR with risk of postoperative AKI and need for renal replacement therapy (RRT). We conducted a meta-regression to explore inter-study statistical heterogeneity.Twelve studies involving 10,724 participants undergoing cardiac surgery were included, with eight studies being deemed at high risk of bias using PROBAST modelling. We found statistically significant associations between elevated preoperative NLR and postoperative AKI (OR 1.45, 95% CI 1.18-1.77), as well as postoperative need for RRT (OR 2.37, 95% CI 1.50-3.72). Postoperative NLR measurements were not of prognostic significance.Elevated preoperative NLR is a reliable inflammatory biomarker for predicting AKI following cardiac surgery.

Cardiac troponin is a highly specific biomarker of myocardial injury that is of prognostic significance in a range of cardiovascular diseases. However, the prognostic value of elevated troponin in cardiac transplant recipients is uncertain. We aimed to evaluate the prognostic value of elevated cardiac troponin in predicting adverse recipient outcomes following heart transplant.We searched MEDLINE (Ovid), Embase (Ovid), and the Cochrane Library from inception until December 2020 and included studies reporting associations between elevated recipient troponin and outcomes after cardiac transplant. We generated summary odds ratios for associations with short- and long-term adverse events and used descriptive analyses where meta-analyses were inappropriate.We included 15 studies involving 1830 patients undergoing cardiac transplant. The risk of primary graft failure was greater in recipients with elevated troponin than in those without (odds ratio = 3.09; 95% CI, 1.08-8.87). Considerable interstudy heterogeneity (I2 statistic 98%) was partially explained by variations in study design, troponin subtype, and overall risk of bias. Descriptive analyses suggested associations between elevated recipient troponin and long-term adverse cardiac events, coronary artery disease, and mortality.Elevated cardiac troponin in cardiac transplant recipients may be prognostic for primary graft failure, adverse cardiac events, coronary artery disease, and mortality. Further high-quality, prospective, and multicenter research is needed to demonstrate the clinical applicability of these findings.

OBJECTIVES Neutrophil-lymphocyte ratio (NLR) is an inflammatory biomarker that has been evaluated across a variety of surgical disciplines and is widely predictive of poor postoperative outcome, but its value in cardiac surgery is unclear. The authors did this systematic review and meta-analysis to determine the impact of elevated perioperative NLR on survival after cardiac surgery. DESIGN Systematic review and meta-analysis of study-level data. SETTING Multiple hospitals involved in an international pool of studies. PARTICIPANTS Adults undergoing cardiac surgery. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS The authors searched multiple databases from inception until November 2020. They generated summary hazard ratios (HR) and odds ratios (OR) for the association of elevated preoperative NLR with long-term and short-term mortality following cardiac surgery. They separately reported on elevated postoperative NLR. Between-study heterogeneity was explored using metaregression. The authors included 12 studies involving 13,262 patients undergoing cardiac surgery. Elevated preoperative NLR was associated with worse long-term (>30 days) (hazard ratio [HR] 1.56; 95% CI [confidence interval], 1.18-2.06; 8 studies) and short-term (

Pseudoaneurysms are false aneurysms that consist of turbulent blood flow between the outside layers of the arterial wall, the tunica media and tunica adventitia. Typically, pseudoaneurysms develop after injury to an artery, most often as a result of blunt trauma. Femoral pseudoaneurysms can also develop after catheter-based vascular interventions due to laceration of the artery from access needles, insufficient time or pressure held at the access site after the procedure, amongst other causes. Rarely, arterial injury during orthopedic pinning procedures has been known to cause pseudoaneurysms. There are only two documented cases within the literature in which a patient underwent closed intermedullary nailing of a proximal tibia fracture after trauma and developed an anterior tibial artery pseudoaneurysm. There are few reports of pseudoaneurysm development as the result of external fixation device placement presumably caused by the inability to directly visualize internal anatomy.

Background Appendicitis is the most frequent aetiology of acute abdominal pain requiring surgical treatment, with an estimated lifetime risk between 7% and 8%. Antibiotics play a substantial role in treatment, and there is considerable debate regarding the duration of antibiotics in treating appendicitis. Methods We searched multiple databases from inception until June 2019 for peer-reviewed studies that compared different durations of antibiotic treatment after appendicectomy for acute complicated appendicitis in adults. We dichotomized reported data into short- and extended-term antibiotic use and controlled for different definitional thresholds in the meta-analysis. We generated risk ratios using restricted maximum likelihood methods and mixed effects modelling for each outcome of interest. Results Four observational studies involving 847 participants were included in the meta-analysis. For the primary outcomes of intra-abdominal infection, we did not find a statistically significant difference between extended- and short-term antibiotic strategies for intra-abdominal infection (Risk ratio 0.92, 95% confidence interval (CI) 0.49-1.74). Three randomized controlled trials involving 291 participants were included in a separate meta-analysis. We found that extended antibiotic usage was not associated with a statistically significant reduced risk for intra-abdominal infection (RR 0.52, 95% CI 0.21-1.29) or surgical site skin infection (RR 1.44, 95% CI 0.43-4.81). Conclusion This systematic review and meta-analysis found that extended post-operative antibiotic treatment may not be associated with a reduced risk of intra-abdominal infection; however, meta-analysis was significantly limited by heterogeneity between studies and underpowered trials. Further large randomized controlled trials are needed to confirm these findings.

PURPOSE: Platelet count, mean platelet volume, platelet distribution width, and plateletcrit are standard indices of platelet activation that have been studied in retinal vein occlusion (RVO) and its subtypes: branch retinal vein occlusion and central retinal vein occlusion. This systematic review and meta-analysis aimed to assess the association between these platelet parameters and RVO. METHODS: We searched for studies investigating the association between these platelet indices and RVO in multiple online databases from inception to August 2020. Mean differences and the associated confidence intervals were obtained and calculated for each included study and pooled using random-effects inverse variance modeling. Meta-regression was used to explore interstudy and intrastudy heterogeneity. RESULTS: Thousand three hundred and twenty-five unique studies were screened, from which 24 studies encompassing 2,718 patients were included. Mean platelet volume and platelet distribution width were significantly elevated in RVO, with pooled mean differences of 0.45 fL (95% CI 0.24-0.66, P < 0.0001) and 1.43% (95% CI 0.57-2.29, P = 0.0011), respectively. Platelet count and plateletcrit were not significantly associated with RVO. Mean platelet volume was also independently elevated in branch retinal vein occlusion and central retinal vein occlusion. CONCLUSION: Mean platelet volume and platelet distribution width are significantly elevated in RVO. Further research is required to explore the independence and potential prognostic significance of these associations.

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the effects of early versus late surgical start times for on‐pump cardiac surgery on mortality, cardiac outcomes, and quality of life.

Objective: The global burden of surgical vascular disease is increasing and with it, the need for cost-effective, accessible prognostic biomarkers to aid optimization of peri-operative outcomes. The neutrophil-lymphocyte ratio (NLR) is emerging as a potential candidate biomarker for perioperative risk stratification. We therefore performed this systematic review and meta-analysis on the prognostic value of elevated preoperative NLR in vascular surgery. Methods: We searched Embase (Ovid), Medline (Ovid), and the Cochrane Library database from inception to June 2019. Screening was performed, and included all peer-reviewed original research studies reporting preoperative NLR in adult emergent and elective vascular surgical patients. Studies were assessed for bias and quality of evidence using a standardized tool. Meta-analysis was performed by general linear (mixed-effects) modelling where possible, and otherwise a narrative review was conducted. Between-study heterogeneity was estimated using the Chi-squared statistic and explored qualitatively. Results: Fourteen studies involving 5,652 patients were included. The overall methodological quality was good. Elevated preoperative NLR was associated with increased risk of long-term mortality (HR 1.40 [95%CI: 1.13-1.74], Chi-squared 60.3%, 7 studies, 3,637 people) and short-term mortality (OR: 3.08; 95%CI: 1.91-4.95), Chi-squared 66.59%, 4 studies, 945 people). Outcome measures used by fewer studies such as graft patency and amputation free survival were assessed via narrative review. Conclusions: NLR is a promising, readily obtainable, prognostic biomarker for mortality outcomes following vascular surgery. Heterogeneity in patient factors, severity of vascular disease, and type of vascular surgery performed renders direct comparison of outcomes from the current literature challenging. This systematic review supports further investigation for NLR measurement in pre-vascular surgical risk stratification. In particular, the establishment of a universally accepted NLR cut-off value is of importance in real-world implementation of this biomarker.

Pseudobulbar affect is a debilitating condition that significantly reduces quality of life for many individuals following traumatic brain injury (TBI). It is characterized by embarrassing and often uncontrollable episodes of crying or laughter. The aim of this systematic review was to evaluate the effectiveness of pharmacotherapy as compared to all other comparators for the management of pseudobulbar affect in adults who have sustained TBI. Six databases were searched, with additional hand searching of journals, clinical trials registries and international drug regulators to identify published and unpublished studies in English up to June 2018. Studies were eligible for this review if they included adults who had sustained a medically confirmed TBI and presented with pseudobulbar affect. All pharmacotherapy and comparator interventions were considered for inclusion, and study design was not limited to randomised controlled trials. Evidence quality was assessed using Joanna Briggs Institute Critical Appraisal Instruments. Two quasi-experimental studies examining the effectiveness of dextrometamorphan/quinidine (DM/Q) were identified. These studies reported that DM/Q was effective in reducing symptoms of pseudobulbar affect and had a positive safety profile, over follow-up periods of 3 months (n = 87) and 12 months (n = 23). However, both studies were limited by lack of a control group and a high dropout rate. The findings of twelve case reports examining the effectiveness of DM/Q (n = 6) and anti-depressants (n = 6) are also discussed. Further research is required to determine which pharmacological interventions provide the best outcomes for individuals with pseudobulbar affect following TBI, with consideration given to side effect profiles and financial costs.

The epidemiology of persistent postoperative opioid use at least 3 months after cardiac surgery is poorly characterised despite its potential public health importance.We searched MEDLINE, Embase, and Google Scholar from inception to December 2021 and included studies reporting the rate and risk factors of persistent postoperative opioid use after cardiac surgery in opioid-naive and opioid-exposed patients. We recorded incidence rates and odds ratios (ORs) with 95% confidence intervals (CIs) for risk factors from individual studies and used random-effects inverse variance modelling to generate pooled estimates.From 10 studies involving 112 298 patients, the pooled rate of persistent postoperative opioid use in opioid-naive patients was 5.7% (95% CI: 4.2-7.2%). Risk factors included female sex (OR 1.18; 95% CI: 1.09-1.29), smoking (OR 1.34; 95% CI: 1.06-1.69), alcohol use (OR 1.43; 95% CI: 1.17-1.76), congestive cardiac failure (OR 1.17; 95% CI: 1.08-1.27), diabetes mellitus (OR 1.21; 95% CI: 1.07-1.37), chronic lung disease (OR 1.42; 95% CI: 1.16-1.75), chronic kidney disease (OR 1.35; 95% CI: 1.08-1.68), and length of hospital stay (per day) (OR 1.03; 95% CI: 1.02-1.04).Persistent postoperative opioid use after cardiac surgery affects at least one in 20 patients. The identification of risk factors, such as female sex, smoking, alcohol use, congestive cardiac failure, diabetes mellitus, chronic lung disease, chronic kidney disease, and length of hospital stay, should help target interventions aimed at decreasing its prevalence.

Cardiac troponin is well known as a highly specific marker of cardiomyocyte damage, and has significant diagnostic accuracy in many cardiac conditions. However, the value of elevated recipient troponin in diagnosing adverse outcomes in heart transplant recipients is uncertain. We searched MEDLINE (Ovid), Embase (Ovid), and the Cochrane Library from inception until December 2020. We generated summary sensitivity, specificity, and Bayesian areas under the curve (BAUC) using bivariate Bayesian modelling, and standardised mean differences (SMDs) to quantify the diagnostic relationship of recipient troponin and adverse outcomes following cardiac transplant. We included 27 studies with 1,684 cardiac transplant recipients. Patients with acute rejection had a statistically significant late elevation in standardised troponin measurements taken at least 1 month postoperatively (SMD 0.98, 95% CI 0.33–1.64). However, pooled diagnostic accuracy was poor (sensitivity 0.414, 95% CrI 0.174–0.696; specificity 0.785, 95% CrI 0.567–0.912; BAUC 0.607, 95% CrI 0.469–0.723). In summary, late troponin elevation in heart transplant recipients is associated with acute cellular rejection in adults, but its stand-alone diagnostic accuracy is poor. Further research is needed to assess its performance in predictive modelling of adverse outcomes following cardiac transplant.Systematic Review Registration: identifier CRD42021227861

Background: The management of post-operative pain and high levels of acute and chronic opioid use following total knee arthroplasty (TKA) and total hip arthroplasty (THA) remain challenges to the perioperative team. We performed a systematic review and meta-analysis to determine the opioid sparing effects, analgesic effects, and safety profile of perioperative gabapentinoid usage in lower limb arthroplasty. Methods: We searched multiple databases from inception until May 2019 and included randomized controlled trials (RCT) on perioperative gabapentinoids in lower limb arthroplasty. The primary outcome was cumulative opioid consumption (oral morphine equivalents) at 24 and 48 hours, and the secondary outcomes were pain scores, time to hospital discharge, and adverse events including nausea, vomiting, pruritus, and sedation. Methodological quality was assessed using the Cochrane tool. The grading of recommendations assessment, development, and evaluation methodology for the certainty of evidence was also used. Results: We included 19 RCT involving 2,455 patients undergoing lower limb arthroplasty. The overall methodological quality of included studies was good. Gabapentinoid use was associated with a significant reduction in opioid consumption at 24 hour (mean difference (MD) 22.81 mg [95 percent Confidence Interval (CI) 13.64-31.98]) and 48 hour (MD 44.03 mg [95 percent CI 16.92-71.14]). We found no meaningful difference in pain scores at rest between gabapentinoid and placebo groups at 24 or 48 hours. Gabapentinoid use reduced the risk of postoperative nausea (risk ratio (RR) 0.69 [95 percent CI 0.57-0.82]), vomiting (RR 0.65 [95 percent CI 0.47-0.91]), and pruritus (RR 0.60 [0.37-0.98]), but not sedation (RR 1.25 [0.76-2.06]). There was no effect on time to discharge from hospital (MD—0.05 days [95 percent CI − 0.31 to 0.20]. Conclusions: The addition of gabapentinoids to perioperative multimodal analgesia decreases opioid consumption following lower limb arthroplasty, while also lowering rates of nausea, vomiting, and pruritus. Further study is required to evaluate the effect of gabapentinoid use on long-term opioid use and dependence.

Depression is a common psychiatric problem following traumatic brain injury (TBI) with reported prevalence rates of 30-77% in the first year post-TBI. Given the negative influence of post-TBI depression on cognition and interpersonal, social, physical, and occupational functioning, early initiation of pharmacotherapy to prevent post-TBI depression has been considered. This systematic review will synthesize the available evidence from published studies on the effectiveness and harms of pharmacotherapy for the secondary prevention of post-TBI depression. Studies published prior to October 2018 were eligible for inclusion. Six databases were searched, with additional searching of key additional documents. Studies meeting inclusion criteria were evaluated for methodological quality. Six articles addressing five studies met inclusion criteria. Study designs included three randomized controlled trials (RCTs), two retrospective cohorts, and one case-control. Prophylactic pharmacotherapy included antidepressants, beta-blockers and statins. In one RCT, the number needed to treat with sertraline to prevent one case of depression post-TBI at 24 weeks was 5.9 (95% confidence interval [CI]: 3.1-71.1). In a second RCT affected by significant attrition, sertraline had no effect. Prescribing beta-blockers prior to TBI reduced the depression risk regardless of the specific brain trauma. TBI patients with pre-existing hyperlipidemia not treated with statins had an increased risk for depression compared with those without hyperlipidemia. Overall, this systematic review yielded mixed evidence of prophylactic efficacy and insufficient evidence of harm. In the absence of tolerability data, existing data are insufficient to recommend sertraline prophylaxis. Optimal timing and treatment duration with identification of patients most likely to benefit from prophylaxis require further consideration. Dedicated prospective studies assessing the effects of beta-blockers and statins on post-TBI depression are required.

Background Hyperbilirubinemia following cardiac surgery is a common phenomenon and is of emerging interest in prognostic factor research. This systematic review and meta-analysis evaluated the association between post-operative hyperbilirubinemia (PH) and mortality and morbidity in cardiac surgery patients. Methods Ovid Medline and Ovid Embase were searched from inception to July 2020 for studies evaluating the prognostic significance of PH following cardiac surgery. Maximally adjusted odds ratios (OR) with associated confidence intervals were obtained from each study and pooled using random effects inverse variance modelling to assess in-hospital mortality. Standardised mean differences were pooled to assess Intensive Care Unit (ICU) and hospital length of stay (LOS). Qualitative analysis was performed to assess ventilation requirements and long-term mortality. Meta-regression was used to assess inter- and intra-study heterogeneity. Results 3251 studies satisfied the selection criteria, from which 12 studies incorporating 3876 participants were included. PH significantly predicted in-hospital mortality with a pooled OR of 7.29 (95% CI 3.53, 15.09). Multiple pre-defined covariates contributed to the prognostic significance of PH, however only aortic cross-clamp time (p p = 0.0001) were significant effect modifiers. PH significantly predicted both ICU LOS (Mean difference 1.32 [95% CI 0.04–2.6]) and hospital LOS (Mean difference 1.79 [95% CI 0.36–3.21]). Qualitative analysis suggested PH is associated with increased post-operative ventilation requirements and reduced long-term survival rates. Conclusions Hyperbilirubinemia is a cost-effective, widely available prognostic marker of adverse outcomes following cardiac surgery, albeit with residual sources of heterogeneity.

Patients with stroke due to spontaneous (non-traumatic) intracerebral haemorrhage (ICH) are at risk of recurrent ICH, ischaemic stroke, and other serious vascular events. We aimed to analyse these risks in population-based studies and compare them with the risks in RESTART, which assessed antiplatelet therapy after ICH.We pooled individual patient data from two prospective, population-based inception cohort studies of all patients with an incident firs-in-a-lifetime ICH in Oxfordshire, England (Oxford Vascular Study; April 1, 2002, to Sept 28, 2018) and Lothian, Scotland, UK (Lothian Audit of the Treatment of Cerebral Haemorrhage; June 1, 2010, to May 31, 2013). We quantified the absolute and relative risks of recurrent ICH, ischaemic stroke, or any serious vascular event (non-fatal stroke, non-fatal myocardial infarction, or vascular death), stratified by ICH location (lobar vs non-lobar) and comorbid atrial fibrillation (AF). We compared pooled event rates with those after allocation to avoid antiplatelet therapy in RESTART.Among 674 patients (mean age 74·7 years [SD 12·6], 320 [47%] men) with 1553 person-years of follow-up, 46 recurrent ICHs (event rate 3·2 per 100 patient-years, 95% CI 2·0-5·1) and 25 ischaemic strokes (1·7 per 100 patient-years, 0·8-3·3) were reported. Patients with lobar ICH (n=317) had higher risk of recurrent ICH (5·1 per 100 patient-years, 95% CI 3·6-7·2) than patients with non-lobar ICH (n=355; 1·8 per 100 patient-years, 1·0-3·3; hazard ratio [HR] 3·2, 95% CI 1·6-6·3; p=0·0010), but there was no evidence of a difference in the risk of ischaemic stroke (1·8 per 100 patient-years, 1·0-3·2, vs 1·6 per 100 patient-years, 0·6-4·4; HR 1·1, 95% CI 0·5-2·8). Conversely, there was no evidence of a difference in recurrent ICH rate in patients with AF (n=147; 3·3 per 100 patient-years, 95% CI 1·0-10·7) compared with those without (n=526; 3·2 per 100 patient-years, 2·2-4·7; HR 0·9, 95% CI 0·4-2·1), but the risk of ischaemic stroke was higher with AF (6·3 per 100 patient-years, 3·7-10·9, vs 0·7 per 100 patient-years, 0·1-5·6; HR 8·2, 3·3-20·3; p0·0001), resulting in patients with AF having a higher risk of all serious vascular events than patients without AF (15·5 per 100 patient-years, 10·0-24·1, vs 6·8 per 100 patient-years, 3·6-12·5; HR 1·78, 95% CI 1·16-2·74; p=0·0090). Only for patients with lobar ICH without comorbid AF was the risk of recurrent ICH greater than the risk of ischaemic stroke (5·2 per 100 patient-years, 95% CI 3·6-7·5, vs 0·9 per 100 patient-years, 0·2-4·8; p=0·00034). Comparing data from the pooled population-based studies with that from patients allocated to not receive antiplatelet therapy in RESTART, there was no evidence of a difference in the rate of recurrent ICH (3·5 per 100 patient-years, 95% CI 1·9-6·0, vs 4·4 per 100 patient-years, 2·6-6·1) or ischaemic stroke (3·4 per 100 patient-years, 1·9-5·9, vs 5·3 per 100 patient-years, 3·3-7·2).The risks of recurrent ICH, ischaemic stroke, and all serious vascular events after ICH differ by ICH location and comorbid AF. These data enable risk stratification of patients in clinical practice and ongoing randomised trials.UK Medical Research Council, Stroke Association, British Heart Foundation, Wellcome Trust, and the National Institute for Health Research Oxford Biomedical Research Centre.

Objective(s) Using the Medical Information Mart for Intensive Care III (MIMIC-III) database, we compared the performance of machine learning (ML) to the to the established gold standard scoring tool (POAF Score) in predicting postoperative atrial fibrillation (POAF) during intensive care unit (ICU) admission after cardiac surgery. Methods Random forest classifier (RF), decision tree classifier (DT), logistic regression (LR), K neighbours classifier (KNN), support vector machine (SVM), and gradient boosted machine (GBM) were compared to the POAF Score. Cross-validation was used to assess the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity of ML models. POAF Score performance confidence intervals were generated using 1,000 bootstraps. Risk profiles for GBM were generated using Shapley additive values. Results A total of 6,349 ICU admissions encompassing 6,040 patients were included. POAF occurred in 1,364 of the 6,349 admissions (21.5%). For predicting POAF during ICU admission after cardiac surgery, GBM, LR, RF, KNN, SVM and DT achieved an AUC of 0.74 (0.71–0.77), 0.73 (0.71–0.75), 0.72 (0.69–0.75), 0.68 (0.67–0.69), 0.67 (0.66–0.68) and 0.59 (0.55–0.63) respectively. The POAF Score AUC was 0.63 (0.62–0.64). Shapley additive values analysis of GBM generated patient level explanations for each prediction. Conclusion Machine learning models based on readily available preoperative data can outperform clinical scoring tools for predicting POAF during ICU admission after cardiac surgery. Explanatory models are shown to have potential in personalising POAF risk profiles for patients by illustrating probabilistic input variable contributions. Future research is required to evaluate the clinical utility and safety of implementing ML-driven tools for POAF prediction.

The neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) are emerging haematological inflammatory biomarkers. However, their significance in retinal vein occlusion (RVO) and its subtypes, branch and central RVO (BRVO and CRVO, respectively), is uncertain. This systematic review and meta-analysis aimed to clarify the association of NLR and PLR with RVO. We searched MEDLINE (Ovid), EMBASE (Ovid) and the Cochrane Library for studies investigating the association of NLR and PLR with RVO from inception to 2 December 2020. We used random-effects inverse-variance modelling to generate pooled effect measures. We used bivariate Bayesian modelling to meta-analyse the ability of NLR and PLR to differ between individuals with and without RVO and performed meta-regression and sensitivity analyses to explore inter-study heterogeneity. Eight studies published encompassing 1059 patients were included for analysis. Both NLR and PLR were significantly elevated in RVO, with pooled mean differences of 0.63 (95% confidence interval (CI) 0.31-0.95) and 21.49 (95% CI 10.03-32.95), respectively. The pooled sensitivity, specificity and area under the Bayesian summary receiver operating characteristic curve were, respectively, 0.629 (95% credible interval (CrI) 0.284-0.872), 0.731 (95% CrI 0.373-0.934) and 0.688 (95% CrI 0.358-0.872) for NLR; and 0.645 (95% CrI 0.456-0.779), 0.616 (95% CrI 0.428-0.761) and 0.621 (95% CrI 0.452-0.741) for PLR. Mean and variability of age and diabetes mellitus prevalence partially explained between-study heterogeneity. NLR and PLR are significantly elevated in RVO. Future research is needed to investigate the potential prognostic value and independence of these findings.

After a traumatic brain injury (TBI), many persons experience significant and debilitating problems with anxiety. The aim of this systematic review was to critically evaluate the evidence regarding efficacy of pharmacological interventions for anxiety after TBI. We reviewed studies published in English before July 2020 and included original research on pharmacological interventions for anxiety after TBI in adults ≥16 years of age. MEDLINE, PubMed, CINAHL, EMBASE, PsycINFO, and CENTRAL databases were searched, with additional searching of key journals, clinical trials registries, and international drug regulators. The primary outcomes of interest were reduction in symptoms of anxiety and occurrence of harms. The secondary outcomes of interest were changes in depression, cognition, quality of life, and participation. Data were summarized in a narrative synthesis, and evidence quality was assessed using the Cochrane Risk of Bias tool. Only a single non-peer-reviewed, randomized controlled trial of 19 male military service members with mild TBI met inclusion criteria. This study found no significant effect of citalopram on anxiety symptoms over a 12-week intervention. The trial was stopped early because of poor recruitment, and much of the study detail was not included in the report. The methodological quality of the study was difficult to assess because of the lack of detail. No recommendations could be drawn from this review. There is a critical need for adequately powered and controlled studies of pharmacological interventions for anxiety after TBI across all severities that examine side-effect profiles and consider issues of comorbidity and effects of long-term pharmacotherapy.

The investigation of children presenting with infantile and childhood epileptic encephalopathies (ICEE) is challenging due to diverse aetiologies, overlapping phenotypes and the relatively low diagnostic yield of MRI, electroencephalography (EEG) and biochemical investigations. Careful history and thorough examination remain essential as these may identify an acquired cause or indicate more targeted investigation for a genetic disorder. Whole exome sequencing (WES) with analysis of a panel of candidate epilepsy genes has increased the diagnostic yield. Whole genome sequencing (WGS), particularly as a trio with both parents’ DNA, is likely to supersede WES. Modern genomic investigation impacts on the timing and necessity of other testing. We propose a structured approach for children presenting with ICEE where there is diagnostic uncertainty, emphasising the importance of WGS or, if unavailable, WES early in the investigative process. We note the importance of expert review of all investigations, including radiology, neurophysiology and biochemistry, to confirm the technique used was appropriate as well as the results. It is essential to counsel families on the risks associated with the procedures, the yield of the procedures, findings that are difficult to interpret and implication of ‘negative’ results. Where children remain without a diagnosis despite comprehensive investigation, we note the importance of ongoing multidisciplinary care.

ObjectivesTo investigate the effects of adding high-grade quantitative evidence of outcomes of treatments into relevant Wikipedia pages on further information-seeking behaviour by the use of routinely collected data.SettingWikipedia, Cochrane summary pages and the Cochrane Library.DesignRandomised trial.ParticipantsWikipedia pages which were highly relevant to up-to-date Cochrane Schizophrenia systematic reviews that contained a Summary of Findings table.InterventionsEligible Wikipedia pages in the intervention group were seeded with tables of best evidence of the effects of care and hyperlinks to the source Cochrane review. Eligible Wikipedia pages in the control group were left unchanged.Main outcome measuresRoutinely collected data on access to the full text and summary web page (after 12 months).ResultsWe randomised 70 Wikipedia pages (100% follow-up). Six of the 35 Wikipedia pages in the intervention group had the tabular format deleted during the study but all pages continued to report the same data within the text. There was no evidence of effect on either of the coprimary outcomes: full-text access adjusted ratio of geometric means 1.30, 95% CI: 0.71 to 2.38; page views 1.14, 95% CI: 0.6 to 2.13. Results were similar for all other outcomes, with exception of Altmetric score for which there was some evidence of clear effect (1.36, 95% CI: 1.05 to 1.78).ConclusionsThe pursuit of fair balance within Wikipedia healthcare pages is impressive and its reach unsurpassed. For every person who sought and clicked the reference on the ‘intervention’ Wikipedia page to seek more information (the primary outcome), many more are likely to have been informed by the page alone. Enriching Wikipedia content is, potentially, a powerful way to improve health literacy and it is possible to test the effects of seeding pages with evidence. This trial should be replicated, expanded and developed.Trial registration numberIRCT2017070330407N2.

Our study tested the diagnostic accuracy of increased signal intensity (SI) within FLAIR MR images of resection cavities in differentiating early progressive disease (ePD) from pseudoprogression (PsP) in patients with glioblastoma treated with radiotherapy with concomitant temozolomide therapy. In this retrospective study approved by our Institutional Review Board, we evaluated the records of 122 consecutive patients with partially or totally resected glioblastoma. Region of interest (ROI) analysis assessed 33 MR examinations from 11 subjects with histologically confirmed ePD and 37 MR examinations from 14 subjects with PsP (5 histologically confirmed, 9 clinically diagnosed). After applying an N4 bias correction algorithm to remove B0 field distortion and to standardize image intensities and then normalizing the intensities based on an ROI of uninvolved white matter from the contralateral hemisphere, the mean intensities of the ROI from within the resection cavities were calculated. Measures of diagnostic performance were calculated from the receiver operating characteristic (ROC) curve using the threshold intensity that maximized differentiation. Subgroup analysis explored differences between the patients with biopsy-confirmed disease. At an optimal threshold intensity of 2.9, the area under the ROC curve (AUROC) for FLAIR to differentiate ePD from PsP was 0.79 (95% confidence interval 0.686–0.873) with a sensitivity of 0.818 and specificity of 0.694. The AUROC increased to 0.86 when only the patients with biopsy-confirmed PsP were considered. Increased SI within the resection cavity of FLAIR images is not a highly specific sign of ePD in glioblastoma patients treated with the Stupp protocol.

Background The prognostic value of asymptomatic perioperative troponin rise in vascular surgery is unclear. We conducted this systematic review and meta-analysis to determine the significance of clinical and subclinical troponin elevation after vascular surgery. Methods We searched MEDLINE (Ovid), Embase (Ovid), and the Cochrane Library, without language restriction, from inception to May 2019 and included studies that reported associations between elevated postoperative troponin and short-term mortality, major adverse cardiac events (MACEs), or long-term mortality in a vascular surgery cohort. We synthesized study-level data on the maximally adjusted estimates using mixed effects modeling to generate summary odds ratios (ORs) for fixed-interval outcomes and summary hazard ratios for long-term mortality. Between-study heterogeneity was assessed with meta-regression. Methodologic quality and publication bias were formally assessed. Results We included 24 studies involving 11,657 participants. Postoperative troponin was found to have a strong, positive association with short-term mortality (OR, 4.95; 95% confidence interval [CI], 2.87-8.52; 7 studies; 2661 people) and MACEs (OR, 5.33; 95% CI, 1.59-17.82; 12 studies; 5047 people) independent of meeting the criteria for myocardial infarction. Subclinical postoperative troponin elevation was further demonstrated to be associated with greater long-term mortality (hazard ratio, 1.94; 95% CI, 1.56-2.42; 13 studies; 7630 people; median follow-up, 24 months). Time to troponin sampling, hypertension, and type of surgery partially accounted for between-study heterogeneity. The methodologic quality of included studies was variable, and publication bias was not detected. Conclusions Elevated postoperative troponin is strongly prognostic of worse survival and greater likelihood of MACEs after vascular surgery, regardless of whether symptoms of myocardial ischemia are present. These data support the benefit of postoperative troponin monitoring in identifying patients at increased risk of worse outcomes and who may be candidates for personalized preventive interventions.

Background The neutrophil-lymphocyte ratio (NLR) is an emerging inflammatory perioperative biomarker which has been studied to predict the incidence of postoperative atrial fibrillation (POAF) after cardiac surgery. This systematic review and meta-analysis aimed to evaluate the prognostic accuracy of elevated perioperative NLR in predicting POAF after cardiac surgery. Methods Multiple databases were searched from inception to May 2019 for prognostic studies on perioperative NLR and POAF following cardiac surgery. Maximally adjusted odds ratios (OR) with associated confidence intervals were obtained from each included study and pooled using random effects inverse variance modelling for preoperative NLR measurements, while standardised mean differences were pooled for postoperative NLR values. The significance of inter- and intra-study heterogeneity was explored using meta-regression. Results 1,799 unique studies satisfied selection criteria, from which 12 studies incorporating 9,262 participants were included. Elevated preoperative NLR significantly predicted POAF, with a pooled OR of 1.42 (95% CI 1.16–1.72). Multiple predefined covariates contributed to inter-study heterogeneity; however, only prevalence of hypertension (p=0.0055), history of congestive cardiac failure (p=0.0282) and average ejection fraction (p=0.0359) were significant effect modifiers. Elevated postoperative NLR was not a significant predictor of POAF (standardised mean difference 1.60 [95% CI -0.56–3.77] between POAF+ and POAF- groups). Conclusions Elevated preoperative NLR is a promising prognostic biomarker for POAF, but residual sources of heterogeneity remain. Larger scale validation studies are required to justify the integration of preoperative NLR testing into routine clinical practice.

Background and Purpose- The frequency and prognostic implications of incident cerebral microbleeds (CMB), defined as development of one or more new CMB, after intracerebral hemorrhage (ICH) is unclear. Therefore, we performed a systematic review and meta-analysis to investigate the frequency and prognostic implications of incident CMB after ICH. Methods- We searched Ovid Medline and Embase in May 2018 for longitudinal studies of adults who underwent brain magnetic resonance imaging at 2 or more times after ICH. We calculated the pooled proportion of adults with incident CMB and sought associations between incident CMB and clinical outcomes (death, recurrent ICH, or new ischemic stroke). We planned subgroup analyses to investigate clinical variables associated with incident CMB. Results- We identified 2354 publications, of which we included 4 cohort studies involving 349 patients. The pooled proportion of adults with at least one new CMB during a mean 27 months follow-up (SD 20 months) was ≈40% (95% CI, 30%-50%). In one study, as the number of incident CMB increased (0 versus 1-3 new CMB versus ≥4 new CMB) the risk of recurrent symptomatic lobar ICH increased (hazard ratio 3.0; 95% CI, 1.2-7.3). No study reported on outcomes of incident ischemic stroke or death. Conclusions- Incident CMB occurs in ≈40% of adults after ICH. The association of incident CMB with recurrent lobar ICH needs confirmation and their association with death and ischemic stroke investigation.

Background and Purpose— The frequency and prognostic implications of incident cerebral microbleeds (CMB), defined as development of one or more new CMB, after intracerebral hemorrhage (ICH) is unclear. Therefore, we performed a systematic review and meta-analysis to investigate the frequency and prognostic implications of incident CMB after ICH. Methods— We searched Ovid Medline and Embase in May 2018 for longitudinal studies of adults who underwent brain magnetic resonance imaging at 2 or more times after ICH. We calculated the pooled proportion of adults with incident CMB and sought associations between incident CMB and clinical outcomes (death, recurrent ICH, or new ischemic stroke). We planned subgroup analyses to investigate clinical variables associated with incident CMB. Results— We identified 2354 publications, of which we included 4 cohort studies involving 349 patients. The pooled proportion of adults with at least one new CMB during a mean 27 months follow-up (SD 20 months) was ≈40% (95% CI, 30%–50%). In one study, as the number of incident CMB increased (0 versus 1–3 new CMB versus ≥4 new CMB) the risk of recurrent symptomatic lobar ICH increased (hazard ratio 3.0; 95% CI, 1.2–7.3). No study reported on outcomes of incident ischemic stroke or death. Conclusions— Incident CMB occurs in ≈40% of adults after ICH. The association of incident CMB with recurrent lobar ICH needs confirmation and their association with death and ischemic stroke investigation.

Background and aims Glial fibrillary acidic protein (GFAP) has shown promise in several studies for its ability to diagnose intracerebral hemorrhage (ICH). We evaluated the diagnostic accuracy of blood GFAP level to differentiate (ICH) from acute ischemic stroke (AIS) and stroke mimics, both overall, and in the first three hours after symptom onset. Methods We searched multiple databases, without language restriction, from inception until December 2017. Hierarchical summary receiver operating characteristic (HSROC) modeling was used to meta-analyze results. We conducted subgroup analyses restricted to blood samples collected within 0–60, 60–120, and 120–180 min time groups after symptom onset, to evaluate diagnostic accuracy in the early pre-hospital phase. Between and within study heterogeneity was explored using meta-regression. Results The search identified 199 potentially relevant citations from which 11 studies involving 1297 participants (350 ICH, 947 AIS, or mimic) were included. The pooled sensitivity, specificity, and area under the HSROC curve were 0.756 (95% CI 0.630–0.849), 0.945 (95% CI 0.858–0.980), and 0.904 (95% CI 0.878–0.931), respectively. Differences in assays used, but not the other covariates, partially explained between-study heterogeneity ( p = 0.034). The summary estimates for the 0–60, 60–120, and 120–180 min subgroups were comparable to the primary analysis and there was no statistically significant difference in diagnostic accuracy between subgroups. Conclusions GFAP is a promising diagnostic biomarker for ICH diagnosis in the early pre-hospital phase. Test accuracy is affected by assay subtype, but there are still unexplained sources of heterogeneity. High quality, international multi-center trials are warranted to develop and validate a point-of-care GFAP assay for the rapid triage and evaluation of acute stroke in the pre-hospital setting.

BACKGROUND/OBJECTIVE: Given the poor overall survival (OR) and progression-free survival (PFS) rates for lung cancers managed with surgical resection, there is a need to identify the prognostic markers that would improve the risk stratification of patients with operable lung cancer to inform treatment decisions. We investigate the prognostic utility of two established inflammation-based scores, the neutrophil–lymphocyte ratio (NLR) and the change in neutrophil–lymphocyte ratio (ΔNLR), throughout the operative period in a prospective cohort of patients with lung cancer who underwent surgical resection. METHODS: Demographic, clinical, and treatment details for 345 patients with lung cancer who underwent surgical resection between 2000 and 2019 at multiple centers across Melbourne, Victoria (Australia), were prospectively collected. Preoperative NLR and ΔNLR were calculated after which Cox univariate and multivariate analyses were conducted for OS and PFS against the known prognostic factors. RESULTS: Both univariate and multivariate analyses showed that preoperative NLR >4.54, as well as day 1 and day 2 postoperative NLR (P < 0.01), was associated with increased risk for postoperative mortality (hazard ratio 1.8; P < 0.01) and PFS (P < 0.05), whereas ΔNLR was not a significant predictor of OS or PFS. CONCLUSION: Elevated NLR among patients with lung cancer who underwent surgical resection was prognostic for poor OS and PFS, whereas ΔNLR was not found to be prognostic for either OS or PFS. Further research may yet reveal a prognostic value for ΔNLR when compared across a greater time period.

Background The role of perioperative erythropoietin (EPO) for preventing cardiac surgery associated acute kidney injury (CSA-AKI) remains uncertain with published trials producing conflicting results. Perspective into the factors at work is needed, due to ongoing uncertainty. Methods We undertook the systematic review and meta-analysis of randomised-controlled trials (RCTs) using random-effects modelling. The primary outcome was safety and efficacy of perioperative EPO to prevent CSA-AKI and the secondary outcomes were change in serum creatinine, urinary neutrophil gelatinase-associated lipocalin, time in ICU, rates of postoperative transfusions, haemodialysis, and mortality. Subgroup analysis explored the effect of the timing of the EPO dose in relation to surgery, the dose response, and the impact of the preoperative risk for CSA-AKI for the patient group. Results Six RCTs were included, which totalled 473 participants. Erythropoietin administration did not reduce the incidence of CSA-AKI compared with controls (OR: 0.69, 95% CI: 0.35 to 1.36, P=0.28; I 2 =64%, P=0.001), however, subgroup analysis suggested administrating EPO before anaesthesia was correlated with a reduction in CSA-AKI (OR: 0.27, 95% CI: 0.13 to 0.54, P=0.0002; I 2 =0%, P=0.98). Additionally, in low risk populations, perioperative EPO administration correlated with significant reduction in CSA-AKI when compared to controls (OR: 0.25, 95% CI: 0.11 to 0.56, P=0.0008; I 2 =0%, P=0.86). Conclusion Our findings suggest that administering EPO before anaesthesia is emerging as an important factor for efficacy. Erythropoietin may have a role in preventing CSA-AKI, however, additional high-quality prospective studies are warranted, particularly aimed at describing the methodological components, such as the timing and size of the dose, which potentiate the cytoprotective effect of EPO in the clinical setting.

9033Background: Immune checkpoint inhibitors are active in the treatment of NSCLC. Expression of PDL1 is being studied as a predictive biomarker. This study aimed to evaluate the cost-effectiveness...

Pseudobulbar affect is a debilitating condition that significantly reduces quality of life for many individuals following traumatic brain injury (TBI). It is characterized by embarrassing and often uncontrollable episodes of crying or laughter. The aim of this systematic review was to evaluate the effectiveness of pharmacotherapy as compared to all other comparators for the management of pseudobulbar affect in adults who have sustained TBI. Six databases were searched, with additional hand searching of journals, clinical trials registries and international drug regulators to identify published and unpublished studies in English up to June 2018. Studies were eligible for this review if they included adults who had sustained a medically confirmed TBI and presented with pseudobulbar affect. All pharmacotherapy and comparator interventions were considered for inclusion, and study design was not limited to randomised controlled trials. Evidence quality was assessed using Joanna Briggs Institute Critical Appraisal Instruments. Two quasi-experimental studies examining the effectiveness of dextrometamorphan/quinidine (DM/Q) were identified. These studies reported that DM/Q was effective in reducing symptoms of pseudobulbar affect and had a positive safety profile, over follow-up periods of 3 months (n = 87) and 12 months (n = 23). However, both studies were limited by lack of a control group and a high dropout rate. The findings of twelve case reports examining the effectiveness of DM/Q (n = 6) and anti-depressants (n = 6) are also discussed. Further research is required to determine which pharmacological interventions provide the best outcomes for individuals with pseudobulbar affect following TBI, with consideration given to side effect profiles and financial costs.

Aim: Immune checkpoint inhibitors revolutionized the treatment of non-small-cell lung cancer, although their costs are a limitation. Methods: The number of patients with non-small-cell lung cancer eligible for immunotherapy was estimated using local epidemiology data. We extracted survival data from RCTs to estimate the life-years saved in a 5-year time horizon. All costs were in local prices converted to US dollars. Results: In the first-line, the budget impact of pembrolizumab decreased by 35% through risk-sharing. In the second-line, patient selection by programmed-death receptor ligand 1 expression decreased the budgetary impact by 45%, and improved cost–effectiveness. Immunotherapy was more cost-effective in the first-line. Conclusion: Given current pricing, Immune checkpoint inhibitors are cost-prohibitive in the majority of South American health services. Nevertheless, several strategies should improve access to immunotherapy.

Many individuals in post-traumatic amnesia (PTA) following traumatic brain injury (TBI) experience neurobehavioral symptoms (NBS) in addition to disorientation and amnesia. These symptoms are associated with low rehabilitation engagement, self-inflicted harm, and risk of violence. The aim of this systematic review was to evaluate the efficacy and harms of pharmacological interventions for NBS in PTA following TBI in adults. Studies in English published before December 2017 were reviewed. Six databases were searched, with additional hand searching of key journals, clinical trials registries, and international drug regulators. Evidence quality was assessed using Joanna Briggs Institute Critical Appraisal Instruments. Thirteen studies were identified: three randomized controlled trials (RCTs), three cohort studies, and seven case series. In the RCTs, neither amantadine nor sertraline reduced NBS. Less rigorous studies reported reduced NBS in patients administered haloperidol, ziprasidone, carbamazepine, amitriptyline, desipramine, and varied neuroleptics. There is a paucity of well-designed, adequately powered and controlled studies of pharmacological interventions for NBS in PTA. More research is needed to provide evidence-based treatment recommendations and improve care.

BACKGROUND: Many individuals who have a diagnosis of schizophrenia experience a range of distressing and debilitating symptoms. These can include positive symptoms (such as delusions, hallucinations, disorganised speech), cognitive symptoms (such as trouble focusing or paying attention or using information to make decisions), and negative symptoms (such as diminished emotional expression, avolition, alogia, and anhedonia). Antipsychotic drugs are often only partially effective, particularly in treating negative symptoms, indicating the need for additional treatment. Mirtazapine is an antidepressant drug that when taken in addition to an antipsychotic may offer some benefit for negative symptoms. OBJECTIVES: To systematically assess the effects of mirtazapine as adjunct treatment for people with schizophrenia. SEARCH METHODS: The Information Specialist of Cochrane Schizophrenia searched the Cochrane Schizophrenia Group’s Study‐Based Register of Trials (including registries of clinical trials) up to May 2018. SELECTION CRITERIA: All randomised‐controlled trials (RCTs) with useable data focusing on mirtazapine adjunct for people with schizophrenia. DATA COLLECTION AND ANALYSIS: We extracted data independently. For binary outcomes, we calculated risk ratio (RR) and its 95% confidence interval (CI), on an intention‐to‐treat (ITT) basis. For continuous data, we estimated the mean difference (MD) between groups and its 95% CI. We employed a fixed‐effect model for analyses. For included studies we assessed risk of bias and created 'Summary of findings' table using GRADE. MAIN RESULTS: We included nine RCTs with a total of 310 participants. All studies compared mirtazapine adjunct with placebo adjunct and were of short‐term duration. We considered five studies to have a high risk of bias for either incomplete outcome data, selective reporting, or other bias. Our main outcomes of interest were clinically important change in mental state (negative and positive symptoms), leaving the study early for any reason, clinically important change in global state, clinically important change in quality of life, number of days in hospital and incidence of serious adverse events. One trial defined a reduction in the Scale for the Assessment of Negative Symptoms (SANS) overall score from baseline of at least 20% as no important response for negative symptoms. There was no evidence of a clear difference between the two treatments with similar numbers of participants from each group showing no important response to treatment (RR 0.81, 95% CI 0.57 to 1.14, 1 RCT, n = 20, very low‐quality evidence). Clinically important change in positive symptoms was not reported, however, clinically important change in overall mental state was reported by two trials and data for this outcome showed a favourable effect for mirtazapine (RR 0.69, 95% CI 0.51 to 0.92; I(2) = 75%, 2 RCTs, n = 77, very low‐quality evidence). There was no evidence of a clear difference for numbers of participants leaving the study early (RR 1.03, 95% CI 0.64 to 1.66, 9 RCTs, n = 310, moderate‐quality evidence), and no evidence of a clear difference in global state Clinical Global Impressions Scale (CGI) severity scores (MD ‐0.10, 95% CI ‐0.68 to 0.48, 1 RCT, n = 39, very low‐quality evidence). A favourable effect for mirtazapine adjunct was found for the outcome clinically important change in akathisia (RR 0.33, 95% CI 0.20 to 0.52, 2 RCTs, n = 86, low‐quality evidence; I(2) = 61%I). No data were reported for quality life or number of days in hospital. In addition to the main outcomes of interest, there was evidence relating to adverse events that the mirtazapine adjunct groups were associated with an increased risk of weight gain (RR 3.19, 95% CI 1.17 to 8.65, 4 RCTs, n = 127) and sedation/drowsiness (RR 1.64, 95% CI 1.01 to 2.68, 7 RCTs, n = 223). AUTHORS' CONCLUSIONS: The available evidence is primarily of very low quality and indicates that mirtazapine adjunct is not clearly associated with an effect for negative symptoms, but there is some indication of a positive effect on overall mental state and akathisia. No effect was found for global state or leaving the study early and data were not available for quality of life or service use. Due to limitations of the quality and applicability of the evidence it is not possible to make any firm conclusions, the role of mirtazapine adjunct in routine clinical practice remains unclear. This underscores the need for new high‐quality evidence to further evaluate mirtazapine adjunct for schizophrenia.

Cerebral amyloid angiopathy is a common hemorrhagic small vessel disease of the brain, often associated with high risk of spontaneous lobar intracerebral hemorrhage. When the suspicion of cerebral amyloid angiopathy is raised, clinicians are hesitant in prescribing oral anticoagulation in patients in whom it is otherwise indicated, including the case of non-valvular atrial fibrillation. This is one of the thorniest clinical dilemmas in the field currently. In this short Leading Opinion piece by an international panel of clinicians-researchers active in the field, we present our consistent approach and future outlook on oral anticoagulation post intracerebral hemorrhage and in the setting of clinical-radiologic evidence of cerebral amyloid angiopathy. We discuss recent advances and support a more balanced approach with implications for the wider neurological clinical community in regards to successful recruiting this patient population in ongoing and future randomized trials.

Review objective/question:The objective of this systematic review is to synthesize the current evidence on the effectiveness and harms of pharmacotherapy in the management of depression in adults who have sustained a traumatic brain injury.

Many survivors of stroke because of intracerebral hemorrhage (ICH) are at risk of ischemic vascular disease. Antithrombotic (antiplatelet or anticoagulant) treatments may lower the risk of ischemic events after ICH, but they may increase the risks of bleeding. To determine the overall effectiveness and safety of antithrombotic drugs for secondary prevention after ICH.1 ### Search Methods We searched the Cochrane Stroke Group Trials Register (March 24, 2017), the CENTRAL (Cochrane Central Register of Controlled Trials: the Cochrane Library 2017, Issue 3), Ovid Medline (from 1948 to March 2017), Ovid Embase (from …

Lung cancer is the leading cause of cancer-related deaths in the world. Immune checkpoint inhibitors (ICI) stimulate cytotoxic lymphocyte activity against tumour cells. These agents are available for the treatment of nonsmall cell lung cancer (NSCLC) after failure of platinumbased therapy. One recent study has demonstrated that ICI monotherapy was superior to platinum-based chemotherapy for first-line treatment. Nevertheless, this benefit was only for a minority of the population (30%) whose tumour programmed death receptor ligand-1 (PD-L1) expression was above 50%. Therefore, several strategies are under investigation. One option for patients with PD-L1 expression lower than 50% may be the combination of ICI with platinum-based chemotherapy or with ICIs against different targets. However, all of these combinations are at an early stage of investigation and may be very expensive or toxic, producing several harmful adverse events. info:eu-repo/semantics/publishedVersion

Background: Immune checkpoint inhibitors improve outcomes compared with chemotherapy in lung cancer. Tumor PD-L1 receptor expression is being studied as a predictive biomarker. The objective of this study was to assess the cost-effectiveness and economic impact of second-line treatment with nivolumab, pembrolizumab, and atezolizumab with and without the use of PD-L1 testing for patient selection. Design: We developed a decision-analytic model to determine the cost-effectiveness of PD-L1 assessment and second-line immunotherapy versus docetaxel. The model used outcomes data from randomized clinical trials (RCTs) and drug acquisition costs from the United States. Thereafter, we used epidemiologic data to estimate the economic impact of the treatment. Results: We included four RCTs (2 with nivolumab, 1 with pembrolizumab, and 1 with atezolizumab). The incremental quality-adjusted life year (QALY) for nivolumab was 0.417 among squamous tumors and 0.287 among non-squamous tumors and the incremental cost-effectiveness ratio (ICER) were $155 605 and $187 685, respectively. The QALY gain in the base case for atezolizumab was 0.354 and the ICER was $215 802. Compared with treating all patients, the selection of patients by PD-L1 expression improved incremental QALY by up to 183% and decreased the ICER by up to 65%. Pembrolizumab was studied only in patients whose tumors expressed PD-L1. The QALY gain was 0.346 and the ICER was $98 421. Patient selection also reduced the budget impact of immunotherapy. Conclusion: The use of PD-L1 expression as a biomarker increases cost-effectiveness of immunotherapy but also diminishes the number of potential life-years saved. info:eu-repo/semantics/publishedVersion

BACKGROUND: Survivors of stroke due to intracerebral haemorrhage (ICH) are at risk of thromboembolism. Antithrombotic (antiplatelet or anticoagulant) treatments may lower the risk of thromboembolism after ICH, but they may increase the risks of bleeding.OBJECTIVES: To determine the overall effectiveness and safety of antithrombotic drugs for people with ICH.SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (24 March 2017). We also searched the Cochrane Central Register of Controlled Trials (CENTRAL: the Cochrane Library 2017, Issue 3), MEDLINE Ovid (from 1948 to March 2017), Embase Ovid (from 1980 to March 2017), and online registries of clinical trials (8 March 2017). We also screened the reference lists of included trials for additional, potentially relevant studies.SELECTION CRITERIA: We selected all randomised controlled trials (RCTs) of any antithrombotic treatment after ICH.DATA COLLECTION AND ANALYSIS: Three review authors independently extracted data. We converted categorical estimates of effect to the risk ratio (RR) or odds ratio (OR), as appropriate. We divided our analyses into short- and long-term treatment, and used fixed-effect modelling for meta-analyses. Three review authors independently assessed the included RCTs for risks of bias and we created a 'Summary of findings' table using GRADE.MAIN RESULTS: We included two RCTs with a total of 121 participants. Both RCTs were of short-term parenteral anticoagulation early after ICH: one tested heparin and the other enoxaparin. The risk of bias in the included RCTs was generally unclear or low, with the exception of blinding of participants and personnel, which was not done. The included RCTs did not report our chosen primary outcome (a composite outcome of all serious vascular events including ischaemic stroke, myocardial infarction, other major ischaemic event, ICH, major extracerebral haemorrhage, and vascular death). Parenteral anticoagulation did not cause a statistically significant difference in case fatality (RR 1.25, 95% confidence interval (CI) 0.38 to 4.07 in one RCT involving 46 participants, low-quality evidence), ICH, or major extracerebral haemorrhage (no detected events in one RCT involving 75 participants, low-quality evidence), growth of ICH (RR 1.64, 95% CI 0.51 to 5.29 in two RCTs involving 121 participants, low-quality evidence), deep vein thrombosis (RR 0.99, 95% CI 0.49 to 1.96 in two RCTs involving 121 participants, low quality evidence), or major ischaemic events (RR 0.54, 95% CI 0.23 to 1.28 in two RCTs involving 121 participants, low quality evidence).AUTHORS' CONCLUSIONS: There is insufficient evidence from RCTs to support or discourage the use of antithrombotic treatment after ICH. RCTs comparing starting versus avoiding antiplatelet or anticoagulant drugs after ICH appear justified and are needed in clinical practice.