Visual Inspection Of Funnel Plots Research Articles

Unraveling the role of computed tomography derived body composition metrics on anastomotic leakages rates in rectal cancer surgery: A protocol for a systematic review and meta-analysis.

Anastomotic leakage is a major concern following total mesorectal excision for rectal cancer, affecting oncological outcomes, morbidity an treatment costs. Body composition has been suggested to influence anastomotic leakage rates. However, literature on how body composition impact anastomotic leakage rates is conflicting. This systematic review aims to evaluate the role of computed tomography derived body composition metrics on anastomotic leakage rates in rectal cancer patients. Databases PubMed/MEDLINE, Cochrane Library, web of science, and EMBASE, will be systematically searched for papers from January 2010 onwards. Study selection, data collection and quality assessment will be independently performed by three research fellows. Outcomes described in three or more studies will be included in the meta-analysis. The Q-test and I2 statistic will be used to assess statistical heterogeneity between studies. Publication bias will be examined by visual inspection of funnel plots and quantified by Egger's test. Sensitivity analyses will be conducted to examine the robustness of the meta-analysis. Reporting of the findings will be in line with the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. This systematic review will synthesize the current evidence and will identify knowledge gaps. Results of the systematic review will aid health care professional in pre-operative decision making and will be distributed through a peer-reviewed publication and presentation of results at international meetings. PROSPERO protocol number: CRD42023471537.

Prevalence, incidence, and trends of epilepsy among children and adolescents in Africa: a systematic review and meta-analysis

BackgroundEpilepsy contributes to a significant disease burden in children and adolescents worldwide. The incidence of childhood epilepsy is threefold higher in low and middle income countries compared in high-income countries. Epilepsy is a serious neurological condition associated with stigma and discrimination, an impaired quality of life, and other mental health related problems.ObjectiveThis study is aimed to synthesize existing evidence and estimate the pooled prevalence and incidence of epilepsy in children and adolescents in Africa.MethodsA comprehensive and systematic search of relevant databases was conducted. The quality of each study was assessed using the Newcastle-Ottawa Quality Assessment Scale adapted for meta-analysis. Two reviewers screened retrieved articles, conducted critical appraisals, and extracted the data. Heterogeneity between studies was assessed by visual inspection of forest plots and statistically using Cochran’s Q statistics and the I2 test. Publication bias was checked by visual inspection of funnel plots as well as statistically using Egger’s correlation and Begg’s regression tests. Finally, the pooled prevalence and incidence of childhood epilepsy were computed with 95% confidence intervals.ResultIn this review and meta-analysis 42 studies with 56 findings were included to compute the pooled prevalence of childhood epilepsy. On the other hand, 6 studies were included to estimate the combined incidence. The pooled prevalence of cumulative epilepsy was 17.3 per 1000 children. Whereas the pooled prevalence of active and lifetime epilepsy was 6.8 and 18.6 per 1000 children respectively. The pooled incidence of childhood epilepsy was 2.5 per 1000 children.ConclusionNearly 1 in 50 children are suffering from epilepsy in Africa. However, little attention has been paid to the prevention and treatment of childhood epilepsy. Mass epilepsy screening, scaling up treatment coverage, and designing strict treatment follow up and monitoring mechanisms are recommended.

The effects of low-dose aspirin on preterm birth: a systematic review and meta-analysis of randomized controlled trials.

To conduct a systematic review and meta-analysis of all randomized controlled trials (RCTs) that evaluated the efficacy of low-dose aspirin (LDA, ≤ 160mg/day) on preventing preterm birth (PB). Five databases were screened from inception until June 25, 2023. The RCTs were assessed for quality according to Cochrane's risk of bias tool. The endpoints were summarized as risk ratio (RR) with 95% confidence interval (CI). Overall, 40 RCTs were analyzed. LDA significantly decreased the risk of PB < 37weeks (RR: 0.91, 95% CI 0.87, 0.96, p < 0.001, moderate certainty of evidence) with low between-study heterogeneity (I2 = 23.2%, p = 0.11), and PB < 34weeks (RR: 0.78, 95% CI 0.61, 0.99, p = 0.04, low certainty of evidence) with high between-study heterogeneity (I2 = 58.3%, p = 0.01). There were no significant differences between both groups regarding the risk of spontaneous (RR: 0.94, 95% CI 0.83, 1.07, p = 0.37) and medically indicated (RR: 1.28, 95% CI 0.87, 1.88, p = 0.21) BP < 37weeks. Sensitivity analysis revealed robustness for all outcomes, except for the risk of PB < 34weeks. For PB < 37weeks and PB < 34weeks, publication bias was detected based on visual inspection of funnel plots for asymmetry and statistical significance for Egger's test (p = 0.009 and p = 0.0012, respectively). LDA can significantly reduce the risk of PB < 37 and < 34weeks. Nevertheless, further high-quality RCTs conducted in diverse populations, while accounting for potential confounding factors, are imperative to elucidate the optimal aspirin dosage, timing of initiation, and treatment duration for preventing preterm birth and to arrive at definitive conclusions.

Glucometabolic outcomes of GLP-1 receptor agonist-based therapies in patients with type 2 diabetes: a systematic review and network meta-analysis

Innovative GLP-1 receptor agonist (GLP-1RA)-based treatment strategies-such as tirzepatide, GLP-1RA plus basal insulin fixed-ratio combinations [FRC], GLP-1RA plus sodium glucose cotransporter-2 inhibitors [SGLT-2i] combinations, and high-dose GLP-1RA-have been listed among the most efficacious options for type 2 diabetes management. However, differences in their glucometabolic effects have not been assessed in dedicated head-to-head trials. In the absence of such trials, we aimed to provide a useful comparison among these treatment strategies to guide clinical practice. In this network meta-analysis, we searched PubMed, MEDLINE, and Web of Science (from database inception to June 24, 2023) for randomised controlled studies, published in English, that enrolled individuals with type 2 diabetes treated with tirzepatide, iGlarLixi, iDegLira, GLP-1RA plus SGLT-2i combination, or high-dose GLP-1RA (dulaglutide 3mg and 4.5mg, semaglutide 2mg) compared with placebo or active comparators. Eligible studies reported change from baseline in HbA1c as an outcome, which was the primary outcome of this analysis. Secondary outcomes were changes in fasting and post-prandial glucose, bodyweight, LDL-cholesterol, blood pressure and risk of hypoglycaemia. We assessed risk of bias through the Cochrane Collaboration's tool (RoB2 tool), publication bias through visual inspection of funnel plots and Egger's test, and heterogeneity by comparing the magnitude of the common between-study variance (τ2) for each outcome with empirical distributions of heterogeneity variances. This network meta-analysis was registered in PROSPERO (CRD42022329878). 40 trials were included. Tirzepatide 15 mg ranked first in terms of HbA1c reduction compared to other GLP-1RA-based strategies, even those including insulin (vs. iDegLira MD -0.40%, 95% CI [-0.66; -0.14], low certainty; vs. iGlarLixi MD -0.48%, 95% CI [-0.75; -0.21], low certainty), without increasing the risk of hypoglycaemia (vs. iDegLira OR 0.35, 95% CI [0.16; 0.79], high certainty; vs. iGlarLixi OR 0.31, 95% CI [0.20; 0.48], high certainty). Tirzepatide 15 mg was also the most efficacious on weight lowering, even compared to high-dose GLP-1RA (eg, semaglutide 2 mg MD -6.56 kg, 95% CI [-7.38; -5.73], low certainty) and GLP-1RA plus SGLT-2i combination (MD -4.61 kg, 95% CI [-5.29; -3.93], low certainty). Risk of bias and publication bias were generally low throughout studies, while high levels of heterogeneity were detected for most outcomes. Aiming to support clinicians in tailoring treatment to patients' needs, we suggest that a hierarchy among treatment strategies be devised considering the best options for type 2 diabetes. Tirzepatide, followed by GLP-1RA plus basal insulin FRC and GLP-1RA plus SGLT-2i combination, was associated with greater benefit on HbA1c than high-dose GLP-1RA. Fondazione per la Ricerca Biomedica "Saverio e Isabella Cianciola" and Next Generation EU, in the context of the National Recovery and Resilience Plan, Investment PE8-Project Age-It: Ageing Well in an Ageing Society.

Prospective observational studies on nutrition intake and the incidence of cognitive impairment in middle-aged and older adults: A protocol for systematic review and meta-analysis.

According to several studies, a specific dietary pattern can reduce the risk of dementia and cognitive impairment. However, the robustness of these results has not been tested. The study intends to investigate the association between nutrition intake and cognitive impairment in middle-aged and older adults (≥45-years) and provide reliable, evidence-based references for healthcare decision-makers, researchers, and policymakers. Are the dietary characteristics of community-dwelling adults (≥45-years) associated with the occurrence of cognitive impairment? The primary objective of this protocol is to synthesize the longitudinal observational evidence on the relationship between nutrition intake patterns and the incidence of cognitive impairment in middle-aged and older adults (≥45-years), and to provide detailed dietary recommendations for the prevention of cognitive impairment in this population. Cohort studies conducted among adults (≥45-years) will be included. The following electronic databases will be searched for relevant records published by July 2023, with a restriction on language to English: Pubmed, Medline, Embase, Web of science, Cochrane Library. The studies will be selected, the data will be extracted, and the bias risk will be assessed by two independent investigators. The Meta-analysis of Observational Studies in Epidemiology guidelines will be followed to summarize observational studies, and the protocol will adhere to the recommendations from the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols 2015 statement. Endnote X9 will be used to manage data screening. We will use Review Manager 5.4 and Stata 16.0 to conduct data analysis, and a random-effects model will be applied to pool clinically homogenous studies. The results will be presented based on the form of nutrition intake. For assessing publication bias, Egger's test and visual inspection of funnel plots will be utilized. As this study does not involve primary data, ethical approval is not required. The final report will be published in a peer-reviewed journal. A registration number of DOI 10.17605/OSF.IO/NAKC3 was assigned to it on October 15, 2022 on Prospero.

Opening the black box: why do euploid blastocysts fail to implant? A systematic review and meta-analysis.

A normal chromosomal constitution defined through PGT-A assessing all chromosomes on trophectoderm (TE) biopsies represents the strongest predictor of embryo implantation. Yet, its positive predictive value is not higher than 50-60%. This gap of knowledge on the causes of euploid blastocysts' reproductive failure is known as 'the black box of implantation'. Several embryonic, maternal, paternal, clinical, and IVF laboratory features were scrutinized for their putative association with reproductive success or implantation failure of euploid blastocysts. A systematic bibliographical search was conducted without temporal limits up to August 2021. The keywords were '(blastocyst OR day5 embryo OR day6 embryo OR day7 embryo) AND (euploid OR chromosomally normal OR preimplantation genetic testing) AND (implantation OR implantation failure OR miscarriage OR abortion OR live birth OR biochemical pregnancy OR recurrent implantation failure)'. Overall, 1608 items were identified and screened. We included all prospective or retrospective clinical studies and randomized-controlled-trials (RCTs) that assessed any feature associated with live-birth rates (LBR) and/or miscarriage rates (MR) among non-mosaic euploid blastocyst transfer after TE biopsy and PGT-A. In total, 41 reviews and 372 papers were selected, clustered according to a common focus, and thoroughly reviewed. The PRISMA guideline was followed, the PICO model was adopted, and ROBINS-I and ROB 2.0 scoring were used to assess putative bias. Bias across studies regarding the LBR was also assessed using visual inspection of funnel plots and the trim and fill method. Categorical data were combined with a pooled-OR. The random-effect model was used to conduct the meta-analysis. Between-study heterogeneity was addressed using I2. Whenever not suitable for the meta-analysis, the included studies were simply described for their results. The study protocol was registered at http://www.crd.york.ac.uk/PROSPERO/ (registration number CRD42021275329). We included 372 original papers (335 retrospective studies, 30 prospective studies and 7 RCTs) and 41 reviews. However, most of the studies were retrospective, or characterized by small sample sizes, thus prone to bias, which reduces the quality of the evidence to low or very low. Reduced inner cell mass (7 studies, OR: 0.37, 95% CI: 0.27-0.52, I2 = 53%), or TE quality (9 studies, OR: 0.53, 95% CI: 0.43-0.67, I2 = 70%), overall blastocyst quality worse than Gardner's BB-grade (8 studies, OR: 0.40, 95% CI: 0.24-0.67, I2 = 83%), developmental delay (18 studies, OR: 0.56, 95% CI: 0.49-0.63, I2 = 47%), and (by qualitative analysis) some morphodynamic abnormalities pinpointed through time-lapse microscopy (abnormal cleavage patterns, spontaneous blastocyst collapse, longer time of morula formation I, time of blastulation (tB), and duration of blastulation) were all associated with poorer reproductive outcomes. Slightly lower LBR, even in the context of PGT-A, was reported among women ≥38 years (7 studies, OR: 0.87, 95% CI: 0.75-1.00, I2 = 31%), while obesity was associated with both lower LBR (2 studies, OR: 0.66, 95% CI: 0.55-0.79, I2 = 0%) and higher MR (2 studies, OR: 1.8, 95% CI: 1.08-2.99, I2 = 52%). The experience of previous repeated implantation failures (RIF) was also associated with lower LBR (3 studies, OR: 0.72, 95% CI: 0.55-0.93, I2 = 0%). By qualitative analysis, among hormonal assessments, only abnormal progesterone levels prior to transfer were associated with LBR and MR after PGT-A. Among the clinical protocols used, vitrified-warmed embryo transfer was more effective than fresh transfer (2 studies, OR: 1.56, 95% CI: 1.05-2.33, I2 = 23%) after PGT-A. Lastly, multiple vitrification-warming cycles (2 studies, OR: 0.41, 95% CI: 0.22-0.77, I2 = 50%) or (by qualitative analysis) a high number of cells biopsied may slightly reduce the LBR, while simultaneous zona-pellucida opening and TE biopsy allowed better results than the Day 3 hatching-based protocol (3 studies, OR: 1.41, 95% CI: 1.18-1.69, I2 = 0%). Embryo selection aims at shortening the time-to-pregnancy, while minimizing the reproductive risks. Knowing which features are associated with the reproductive competence of euploid blastocysts is therefore critical to define, implement, and validate safer and more efficient clinical workflows. Future research should be directed towards: (i) systematic investigations of the mechanisms involved in reproductive aging beyond de novo chromosomal abnormalities, and how lifestyle and nutrition may accelerate or exacerbate their consequences; (ii) improved evaluation of the uterine and blastocyst-endometrial dialogue, both of which represent black boxes themselves; (iii) standardization/automation of embryo assessment and IVF protocols; (iv) additional invasive or preferably non-invasive tools for embryo selection. Only by filling these gaps we may finally crack the riddle behind 'the black box of implantation'.

Effects of virtual reality-based intervention on depression in stroke patients: a meta-analysis

As one of the most common neuropsychiatric complications after stroke, post-stroke depression can significantly affect the initiative of rehabilitation exercise and the rehabilitation of neurological function of patients. Virtual reality (VR) has been widely used in health-related fields in recent years. There is some evidence that VR-based interventions have benefits for depression. The aim of this study was to assess the effectiveness of VR-based intervention on depression in stroke patients. A total of 752 patients with stroke from 11 randomized controlled trials (RCTs) studies were included in this meta-analysis and the studies derived from seven electronic databases searched from database inception to August 2021. Different tools were used to measure depression. For continuous results, the standardized mean differences (SMDs) and 95% confidence intervals (CIs) were calculated to synthesize the effects. We assessed the risk of bias by using the Cochrane Collaboration criteria. The results showed that compared to the control group, VR-based interventions significantly decreased the depression scale score (SMD = − 0.75, 95% CI − 1.35, − 0.15). The meta-analysis indicated that VR-based intervention had a moderate effect on depression in stroke patients compared to control group. There was no evidence of potential publication bias as assessed by visual inspection of funnel plots in Egger and Begg tests. Substantial heterogeneity between studies was observed, meta-regression analysis showed that mean age might be the source of heterogeneity.

Obesity as a risk factor for severe influenza infection in children and adolescents: a systematic review and meta-analysis.

The findings of our meta-analysis suggest that obesity in children with influenza is associated with a worse prognosis, both hospitalization and ICU admission/death. • Obesity has been identified as a risk factor for non-communicable as well as communicable diseases. • A previous meta-analysis failed to demonstrate a statistically significant association between obesity and influenza infection severity. • Children with high BMI and influenza infection are more likely to get hospitalized. • Pediatric inpatients with increased BMI and influenza infection may have a worse prognosis.

Effects of Special Therapeutic Footwear on the Prevention of Diabetic Foot Ulcers: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Objective To reduce diabetic foot ulcer (DFU) occurrence or recurrence, diabetic therapeutic footwear is widely recommended in clinical practice for at-risk patients. However, the effectiveness of therapeutic footwear is controversial. Thus, we performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to examine whether special therapeutic footwear could reduce the incidence of DFU. Method We systematically searched multiple electronic databases (Medline, EMBASE, and EMB databases) to identify eligible studies published from inception to June 11, 2021. The database search, quality assessment, and data extraction were independently performed by two reviewers. Efficacy (i.e., incidence of DFU) was explored using the R'meta' package (version 4.15-1). To obtain more robust results, the random-effects model and the Hartung-Knapp-Sidik-Jonkman method were selected to assess pooled data. Metaregression analysis and sensitivity analysis were performed to explore heterogeneity, and publication bias was assessed by a visual inspection of funnel plots and the AS-Thompson test. Results Eight RCTs with a total of 1,587 participants were identified from the search strategy. Compared with conventional footwear, special therapeutic footwear significantly reduced the incidence of DFU (RR 0.49; 95% CI, 0.28-0.84), with no evidence of publication bias (P = 0.69). Unexpectedly, the effectiveness of special therapeutic footwear had a reverse correlation with the intervention time (coefficient = 0.085, P < 0.05) in the metaregression analysis. Conclusion Special therapeutic footwear with offloading properties is effective in reducing the incidence of DFU. However, the effect may decrease gradually over time. Despite undefined reasons, the optimal utility time and renewal frequency of special therapeutic footwear should be considered.

Efficacy of Repetitive Transcranial Magnetic Stimulation in Patients With Methamphetamine Use Disorder: A Systematic Review and Meta-Analysis of Double-Blind Randomized Controlled Trials.

BackgroundRepetitive transcranial magnetic stimulation (rTMS) has demonstrated therapeutic potential for treating patients with methamphetamine use disorder (MUD). However, the most effective target and stimulation frequency of rTMS for treating MUD remains unclear. This meta-analysis explored the effect of rTMS on MUD.MethodsIn this study, PubMed, Cochrane Systematic Reviews, and the Cochrane Collaboration Central Register of Controlled Clinical Trials were searched electronically for double-blind randomized controlled trials that used rTMS for treating MUD. We used published trials to investigate the efficacy of rTMS in MUD up to March 5, 2022, and pooled studies using a random-effect model to compare rTMS treatment effects. Patients who were diagnosed with MUD according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders were recruited. Clinical craving scores between baseline and after rTMS were compared using the standardized mean difference (SMD) with 95% confidence intervals (CIs). The heterogeneity of the included trials was evaluated through a visual inspection of funnel plots and the I2 statistic.ResultsWe identified seven trials with 462 participants with MUD that met the inclusion criteria. All the studies evaluated craving scores, with rTMS demonstrating a more significant effect than the sham treatment on reducing craving scores (SMD = 0.983, CI = 0.620–1.345, p ≤ 0.001). A subgroup meta-analysis revealed that intermittent theta-burst stimulation (iTBS) had a greater positive effect than 10-Hz rTMS. A metaregression revealed that the SMDs increased with the increase in baseline craving scores, whereas they decreased with the increase in the proportion of men and duration of abstinence.ConclusionThe meta-analysis suggests that rTMS may be associated with treatment effect on craving symptoms in patients with MUD. iTBS may have a greater positive effect on craving reduction than 10-z rTMS.

Hot balloon versus cryoballoon ablation in patients with atrial fibrillation: a systematic review and meta-analysis

Abstract Funding Acknowledgements Type of funding sources: None. Background Atrial fibrillation (AF) incidence is expected to increase more than 60% in the following 30 years. Catheter ablation is the treatment of choice for medically intractable AF with arrhythmia recurrence remaining an unsolved issue. Purpose We systematically reviewed existing literature to compare the efficacy of hot balloon (HBA) versus cryoballoon ablation (CBA). Methods PubMed, Scopus, ClinicalTrials.gov, medRxiv and Cochrane Library (according to PRISMA guidelines) were scrutinized for relevant articles up to 2 December 2021. Eligible studies had to compare clinical outcomes (arrhythmia recurrence rates or/and procedural data or/and safety outcomes) between patients undergoing HBA and CBA for AF. Quality assessment of studies was conducted via the Newcastle-Ottawa Scale (high quality≥ 7, moderate 4-6, poor &amp;lt;4). Statistical pooling was performed according to a random-effect model with generic inverse-variance weighting of odds ratios and mean differences computing risk estimates with 95% confidence intervals. The presence of heterogeneity among studies was evaluated under the Cochran Q chi-square test. I² values of 25%, 50% and 75% have been assigned adjectives of low, moderate, and high heterogeneity. Publication biases were assessed by visual inspection of funnel plots. Results PRISMA study search and individual study characteristics are presented in Figure 1. Literature search identified 131 studies, 5 of which (evaluating 513 patients) met inclusion criteria. Patients undergoing HBA demonstrated similar long term recurrence rate as compared to CBA treated controls (OR: 0.68; 95% CI: 0.38-1.22; p-value: 0.19; I2: 0%). Procedural aspects, such as touch-up radiofrequency ablation (per pulmonary vein), procedure time (min) and fluoroscopic time (min) did not differ among treatment arms (OR: 1.79; 95% CI: 0.84-3.83; p-value: 0.13, I2: 80%, MD: 9.69; 95% CI: -2.78-22.16; p-value: 0.13, I2: 63%, and OR: 1.03; 95% CI: -9.50-7.44; p-value: 0.81, I2: 87%, respectively). Regarding safety outcomes (Figure 1), the small number of the reported events precluded us from analyzing these data. Yet, tamponade and phrenic nerve injury were infrequent in both modalities; pulmonary vein stenosis of at least moderate severity (&amp;gt;50% luminal narrowing) was reported in 18 instances in the HBA arm as compared to zero events in the CBA arm. Of note, all events were asymptomatic. Quality assessment scores are shown in Figure 1. Four studies were of high quality and one study was of moderate quality. Funnel-plot distributions of the pre-specified outcomes indicated absence of publication bias for all outcomes. High statistical heterogeneity and the small number of patients included are the main limitations of this study. Conclusion Hotballoon ablation is a promising therapeutic option for patients suffering from AF, featuring comparable efficacy and procedural outcomes with cryoablation. Safety outcomes, especially PV stenosis, mandate further evaluation.

Surgical management in phyllodes tumors of the breast: a systematic review and meta-analysis.

Information is still controversial in the studies regarding the current optimal surgical management of phyllodes tumors (PTs) of the breast. Local recurrence (LR) may occur with an upgraded in the pathological grade, influencing the prognosis of patients with PT. This systematic review and meta-analysis aimed to investigate the association of LR risk with margin status and margin width which could have significant implications on the surgical management of PT. Independent and comprehensive searches were performed by two authors through five databases including PubMed, Medline, Embase, ScienceDirect and Cochrane Library from January 1990 to October 2021. Studies investigating the association between margin width, margin status and LR rates were considered for inclusion. Study quality was evaluated using the Newcastle-Ottawa Scale (NOS). Meta-analysis was performed using RevMan5.3 software, and statistical heterogeneity was assessed using the Chi-square test and quantified using the I2 statistic. Visual inspection of funnel plots was used to judge publication bias. A total of 34 articles were included in this article, all of which with NOS scores above 5. Regardless of the PT grade, positive margin significantly increased the risk of LR [odds ratio (OR) 3.64, 95% confidence interval (CI): 2.60-5.12]. No significant difference was found in the risk of LR between the margins <1 and ≥1 cm (OR 1.39, 95% CI: 0.67-2.92). For benign and borderline PTs, there were no significant differences of the LR risk between breast-conserving surgery (BCS) and mastectomy (benign OR 0.68, 95% CI: 0.12-3.78; borderline OR 1.14, 95% CI: 0.29-4.51). While the LR risk was significantly increased by BCS for malignant PT (OR 2.77, 95% CI: 1.33-5.74). Different surgical management strategies should be considered for different PT grades. BCS was a feasible option and margins <1 cm was not significantly associated with LR risk for all grade of PT. After BCS, benign PT with positive margin could adopt the "wait and watch" strategy with regular follow-up, while borderline and malignant PTs were expected to underwent re-excision to ensure negative margins. More studies are still needed to clarify and update the existing conclusions and improve the prognosis of PT patients.

Systematic Analysis of Publication Bias in Neurosurgery Meta-Analyses.

Statistically significant positive results are more likely to be published than negative or insignificant outcomes. This phenomenon, also termed publication bias, can skew the interpretation of meta-analyses. The widespread presence of publication bias in the biomedical literature has led to the development of various statistical approaches, such as the visual inspection of funnel plots, Begg test, and Egger test, to assess and account for it. To determine how well publication bias is assessed for in meta-analyses of the neurosurgical literature. A systematic search for meta-analyses from the top neurosurgery journals was conducted. Data relevant to the presence, assessment, and adjustments for publication bias were extracted. The search yielded 190 articles. Most of the articles (n = 108, 56.8%) were assessed for publication bias, of which 40 (37.0%) found evidence for publication bias whereas 61 (56.5%) did not. In the former case, only 11 (27.5%) made corrections for the bias using the trim-and-fill method, whereas 29 (72.5%) made no correction. Thus, 111 meta-analyses (58.4%) either did not assess for publication bias or, if assessed to be present, did not adjust for it. Taken together, these results indicate that publication bias remains largely unaccounted for in neurosurgical meta-analyses.

Direct Oral Anticoagulant Versus Low Molecular Weight Heparin for the Treatment of Cancer-Associated Thromboembolism: 2021 Updated Meta-Analysis of Randomized Controlled Trials

Introduction: International clinical practice guidelines (ITAC, ASCO, NCCN and ASH) have progressively endorsed direct factor Xa inhibitors (edoxaban, rivaroxaban and apixaban) as an alternative to monotherapy with low-molecular-weight heparin (LMWH) for the treatment of venous thromboembolism (VTE) in cancer patients. The results from new randomized controlled trials (RCT) which assessed the efficacy and the safety of direct oral anticoagulants (DOAC) compared to LMWH for the treatment of cancer-associated thrombosis (CAT) were released during the past months. We therefore performed an updated meta-analysis of all publicly available data from RCT comparing DOAC with LMWH for the treatment of CAT.Methods: Embase, MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL) and conference proceedings from all languages were searched up to August 2, 2021. Search strategy, study selection, data extraction and statistical analysis were performed in accordance with the Preferred Reporting Items for Meta-Analyses (PRISMA) guidelines. The primary efficacy outcome was recurrent VTE, and the primary safety outcome was major bleeding. Secondary outcomes included clinically relevant nonmajor bleeding (CRNMB), and all-cause mortality. Risk of bias was assessed by using the Cochrane risk-of-bias tool in randomized controlled trials version 2.0. Pooled relative risk (RR) and 95% confidence intervals (CIs) were estimated using the Mantel-Haenszel method of Der Simonian and Laird within a random-effect model. Heterogeneity of effect size across studies was assessed using the I 2 statistic. Publication bias was assessed by visual inspection of funnel plots. All the statistical analyses were performed with the RevMan 5.3 software.Results: Six RCT comparing the efficacy and safety of DOAC versus LMWH, which enrolled a total of 3,690 cancer patients with acute VTE (1850 randomized to the DOAC arms and 1840 randomized to the LMWH arms), were included in the pooled analysis. Main study characteristics are summarized in Table 1. During a follow-up of 3 to 6 months under anticoagulant treatment, recurrent VTE occurred in 99 of 1,850 (5.3%) patients receiving DOACs versus 152 of 1,840 (8.3%) patients receiving LMWH. The risk of recurrent VTE was significantly lower with DOAC than with LMWH (RR 0.67, 95% CI 0.52-0.85, p = 0.001, I 2 = 0%, Figure 1A). Major bleeding occurred in 78 (4.2%) patients with CAT treated with DOAC versus 65 (3.5%) patients treated with LMWH. The risk of major bleeding was non significantly higher with DOAC (RR 1.20, 95% CI 0.85-1.70, p = 0.31, I 2= 7%, Figure 1B). CRNMB was more frequent in cancer patients receiving DOAC compared to those receiving LMWH (10.3% versus 6.3%, RR 1.63, 95% CI 1.25-2.11, p = 0.0003, I²= 6%, Figure 1C). The rates of all-cause mortality did not differ between the two groups (23.6% in the DOAC arms versus 23.3% in the LMWH arms, RR 1.02, 95% CI 0.89-1.16, p = 0.80, I² = 13%, Figure 1D).Conclusions: In this August 2021 meta-analysis of 3,690 patients treated for CAT, DOAC significantly reduced the risk of recurrent VTE compared with LMWH, without increasing the risk of major bleeding. However, as previously highlighted, the use of DOAC was associated with an increased risk of CRNMB. Our results provide additional evidence for the use of DOAC as a safe and effective first-line option for the treatment of CAT in patients who are not at high risk of bleeding. These findings may increase the level of certainty for the evidence used in the national or international clinical practice guidelines supporting the use of DOAC in cancer patients with CAT. [Display omitted] DisclosuresConnors: CSL Behring: Research Funding; Pfizer: Honoraria; Alnylam: Consultancy; takeda: Honoraria; Bristol-Myers Squibb: Honoraria; Abbott: Consultancy.

Cardiac Arrhythmias and Mortality after Hematopoietic Stem Cell Transplant (HSCT): A Systematic Review and Meta-Analysis

IntroductionHematopoietic stem cell transplant (HSCT) is commonly performed for the treatment of advanced hematological malignancies. Emerging data suggest non-relapse related events, including cardiac arrhythmias, increasingly limit anticancer outcomes and non-relapse mortality after initially successful HSCT. Yet, the relationship between HSCT and increased risk of arrhythmias after transplant remains controversial and unclear. Our aim was to evaluate the incidence and effect on mortality risk of arrhythmia development after HSCT.Materials and methodsLeveraging the PubMed, Embase, Cochrane, Scopus and Clinicaltrials.gov databases, we identified all published studies evaluating the incidence and impacts of early arrhythmias after HSCT from January 1995 to July 2021 using PRISMA guidelines. We included all available observational studies (case-control, and cohort) and clinical trials without restriction of language or country of publication. The primary outcome was incidence of atrial fibrillation (AF) at 1 year of follow-up after HSCT. Secondary outcomes included the incidence of any arrhythmia across follow-up, the incidence of left atrium (LA) dilation, and non-relapse mortality associated with HSCT induced AF. Subgroup analysis based on type of HSCT treatment employed, allogenic (Allo-HSCT) or autologous (Auto-HSCT), was also performed. Variance weighted random effects modeling (DerSimonian and Laird) was used to define the associations between HSCT and AF and mortality events. Outcomes were reported as event rates, and relative risks (RR). Medians were reported with corresponding standard errors (SE). Heterogeneity was assessed using Cochrane Q-statistic which was quantified with I 2test (>75% was considered high heterogeneity). Publication bias was assessed using Eager's test where applicable. Further, the quality of included studies was assessed using the New-Castle Ottawa scale.ResultsOverall, from 769 articles, 12 cohort studies inclusive of 6,371 patients meeting study-criteria were identified. The mean incidence of AF was 8.8% (I 2:97%, P<0.001), including 5.2% (I 2:65%, P=0.05) within 1-year of any HSCT. The overall incidence of any type of arrhythmia was 11.2% (I 2 =95%, P≤0.001); Figure. Median time to AF onset was 10.3 days (SE= 1.2), but was longer in those treated with Allo-HSCT, at 71 days (SE=68.4); P<0.05. Among those treated with Allo-HSCT, 8.2% (I 2:73%, P<0.001) developed AF, including 6.5% (I 2:72%, P<0.01) at 1 year; the event rate for any type of arrhythmia was 8.3% (I 2:52%, P<0.001). In those treated with Auto-HSCT, the rate of AF was 8.7% (I 2=97%, P≤0.001) across follow-up. Among those with AF following HSCT therapy, LA dilatation was observed in 37.2% (I 2 =61.5%, P=0.1) among available studies. Similarly, mortality was higher among patients who developed AF vs. those without AF after HSCT (RR: 7.4, P=0.008, I 2 = 92.87). There was low risk of publication bias as assessed by visual inspection of funnel plot and Egger's regression test (P= 0.21); and low risk of bias within the included studies.ConclusionAtrial fibrillation is increasingly common after HSCT therapy, and associates with increased mortality. The presence of LA remodeling, reflected by atrial dilation, appears to portend AF risk. Further research into the mechanisms and predictors of AF after HSCT are needed. [Display omitted] DisclosuresVasu: Kiadis, Inc.: Research Funding; Boehringer Ingelheim: Other: Travel support; Seattle Genetics: Other: travel support; Omeros, Inc.: Membership on an entity's Board of Directors or advisory committees. Saad: Incyte Pharmaceuticals: Consultancy; careDx: Consultancy; Amgen: Research Funding; Kadmon: Research Funding; OrcaBio: Research Funding; Magenta Therapeutics: Consultancy. de Lima: Miltenyi Biotec: Research Funding; BMS: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees. Jaglowski: Juno: Consultancy; Novartis: Consultancy, Research Funding; Kite, a Gilead Company: Consultancy, Research Funding; Takeda: Consultancy; CRISPR Therapeutics: Consultancy.

Mental disorders and risk of COVID-19-related mortality, hospitalisation, and intensive care unit admission: a systematic review and meta-analysis

BackgroundMental disorders might be a risk factor for severe COVID-19. We aimed to assess the specific risks of COVID-19-related mortality, hospitalisation, and intensive care unit (ICU) admission associated with any pre-existing mental disorder, and specific diagnostic categories of mental disorders, and exposure to psychopharmacological drug classes.MethodsIn this systematic review and meta-analysis, we searched Web of Science, Cochrane, PubMed, and PsycINFO databases between Jan 1, 2020, and March 5, 2021, for original studies reporting data on COVID-19 outcomes in patients with psychiatric disorders compared with controls. We excluded studies with overlapping samples, studies that were not peer-reviewed, and studies written in languages other than English, Danish, Dutch, French, German, Italian, and Portuguese. We modelled random-effects meta-analyses to estimate crude odds ratios (OR) for mortality after SARS-CoV-2 infection as the primary outcome, and hospitalisation and ICU admission as secondary outcomes. We calculated adjusted ORs for available data. Heterogeneity was assessed using the I2 statistic, and publication bias was tested with Egger regression and visual inspection of funnel plots. We used the GRADE approach to assess the overall strength of the evidence and the Newcastle Ottawa Scale to assess study quality. We also did subgroup analyses and meta-regressions to assess the effects of baseline COVID-19 treatment setting, patient age, country, pandemic phase, quality assessment score, sample sizes, and adjustment for confounders. This study is registered with PROSPERO, CRD42021233984.Findings841 studies were identified by the systematic search, of which 33 studies were included in the systematic review and 23 studies in the meta-analysis, comprising 1 469 731 patients with COVID-19, of whom 43 938 had mental disorders. The sample included 130 807 females (8·9% of the whole sample) and 130 373 males (8·8%). Nine studies provided data on patient race and ethnicity, and 22 studies were rated as high quality. The presence of any mental disorder was associated with an increased risk of COVID-19 mortality (OR 2·00 [95% CI 1·58–2·54]; I2=92·66%). This association was also observed for psychotic disorders (2·05 [1·37–3·06]; I2=80·81%), mood disorders (1·99 [1·46–2·71]; I2=68·32%), substance use disorders (1·76 [1·27–2·44]; I2=47·90%), and intellectual disabilities and developmental disorders (1·73 [1·29–2·31]; I2=90·15%) but not for anxiety disorders (1·07 [0·73–1·56]; I2=11·05%). COVID-19 mortality was associated with exposure to antipsychotics (3·71 [1·74–7·91]; I2=90·31%), anxiolytics (2·58 [1·22–5·44]; I2=96·42%), and antidepressants (2·23 [1·06–4·71]; I2=95·45%). For psychotic disorders, mood disorders, antipsychotics, and anxiolytics, the association remained significant after adjustment for age, sex, and other confounders. Mental disorders were associated with increased risk of hospitalisation (2·24 [1·70–2·94]; I2=88·80%). No significant associations with mortality were identified for ICU admission. Subgroup analyses and meta-regressions showed significant associations of baseline COVID-19 treatment setting (p=0·013) and country (p<0·0001) with mortality. No significant associations with mortality were identified for other covariates. No evidence of publication bias was found. GRADE assessment indicated high certainty for crude mortality and hospitalisation, and moderate certainty for crude ICU admission.InterpretationPre-existing mental disorders, in particular psychotic and mood disorders, and exposure to antipsychotics and anxiolytics were associated with COVID-19 mortality in both crude and adjusted models. Although further research is required to determine the underlying mechanisms, our findings highlight the need for targeted approaches to manage and prevent COVID-19 in at-risk patient groups identified in this study.FundingNone.TranslationsFor the Italian, French and Portuguese translations of the abstract see Supplementary Materials section.

Diurnal preference and depressive symptomatology: a meta-analysis

Eveningness, a preference for later sleep and rise times, has been associated with a number of negative outcomes in terms of both physical and mental health. A large body of evidence links eveningness to Major Depressive Disorder (MDD). However, to date, evidence quantifying this association is limited. The current meta-analysis included 43 effect sizes from a total 27,996 participants. Using a random-effects model it was demonstrated that eveningness is associated with a small effect size (Fisher’s Z = − 2.4, 95% CI [− 0.27. − 0.21], p < 0.001). Substantial heterogeneity between studies was observed, with meta-regression analyses demonstrating a significant effect of mean age on the association between diurnal preference and depression. There was also evidence of potential publication bias as assessed by visual inspection of funnel plots and Egger’s test. The association between diurnal preference and depression is small in magnitude and heterogenous. A better understanding of the mechanistic underpinnings linking diurnal preference to depression and suitably powered prospective studies that allow causal inference are required.

Mental Disorders and Risk of Covid-19 Related Mortality, Hospitalization and Intensive Care Unit Admission: A Systematic Review and Meta-Analysis

Background: Mental disorders may represent a risk factor for severe COVID-19. This study evaluated the risk of COVID-19 mortality, hospitalization, and intensive care unit (ICU) admission in patients with pre-existing mental disorders or exposure to psychopharmacological treatments. Methods: In this PRISMA-compliant systematic review and meta-analysis (PROSPERO-CRD42021233984), we searched Web of Science, PsycINFO, Cochrane, PubMed, and Ovid/PsycINFO databases through March 5, 2021 for studies reporting data on COVID-19 outcomes in psychiatric patients compared to controls. Risk of COVID-19 mortality was defined as the primary outcome, with hospitalization and ICU admission as secondary outcomes. We modeled random-effects meta-analyses to estimate crude (OR) and adjusted (aOR) odds ratios for these three outcomes. Heterogeneity was assessed using the I2 statistic, publication bias was tested with Egger regression and visual inspection of funnel plots. Newcastle Ottawa Scale was used to explore study quality. We estimated effect sizes associated with any pre-existing mental disorder as well as specific categories of mental disorders (psychotic disorders, mood disorders, substance use disorders, anxiety disorders, intellectual disabilities and developmental disorders), and exposure to psychopharmacological drug classes (antidepressants, antipsychotics, and anxiolytics). Severe mental illness was compared with other mental disorders. We also conducted subgroup analyses and meta-regressions to assess the effects of baseline COVID-19 treatment setting, patient age, country, pandemic phase, quality assessment score and adjustment for confounders. Findings: A total of 32 studies were included in the systematic review and 23 in the meta-analysis, representing 658,702 patients with COVID-19 (41,944 with mental disorders). The presence of any mental disorder was associated with increased risk of COVID-19 mortality (Crude OR 1·99, 95% CI 1·56-2·54; aOR 1·34, 95% CI 1·15-1·56). This association was confirmed in psychotic disorders (Crude OR 2·11, 95% CI 1·47-3·03; aOR 1·77, 95% CI 1·34-2·33), and mood disorders (Crude OR 1·98, 95% CI 1·48-2·64; aOR 1·44, 95% CI 1·14-1·82). An increased mortality risk with substance use disorders (Crude OR 1·76, 95% CI 1·30- 2·38; aOR 1·12, 95% CI 0·89-1·39) and intellectual disabilities and developmental disorders (Crude OR 1·47, 95% CI 1·08-2·01) was only established in unadjusted estimates. We detected no effect for anxiety disorders (Crude OR 1·06, 95% CI 0·75-1·51; aOR 1·01, 95% CI 0·76-1·34). COVID-19 mortality was also associated with exposure to antipsychotics (Crude OR 3·71, 95% CI 1·74-7·91; aOR 2·43, 95% CI 1·81-3·25) and anxiolytics (Crude OR 2·58, 95% CI 1·22-5·44; aOR 1·47, 95% CI 1·15-1·88), but with antidepressant exposure only in unadjusted models (Crude OR 2·23, 95% CI 1·06-4·71; aOR 1·18, 95% CI 0·93-1·50). Overall, mental disorders were consistently associated with increased risk of hospitalization (Crude OR: 2·24, 95% CI 1·70-2·94; aOR: 1·77, 95% CI 1·29-2·42), but not ICU admission (Crude OR 1·71, 95% CI 1-2·93; aOR 1·26, 95% CI 0·78-2·05). Increased rates of hospital and ICU admission were found in substance use disorders (Hospitalization - Crude OR: 2·66, 95% CI 1·79-3·95; aOR: 1·87, 95% CI 1·16-3·03; ICU - Crude OR 2·59, 95% CI 1·54-4·38) and for unadjusted estimates in mood disorders (Hospitalization Crude OR 2·26, 95% CI 1·33-3·86; aOR 1·26, 95% CI 0·64-2·50; ICU - Crude OR 2·39, 95% CI 1·15-5·00; aOR 1·13, 95% CI 0·70-1·84). Psychotic disorders were not associated with an increased risk of hospitalization (Crude OR 1·68, 95% CI 0·86-3·29; aOR: 1·34, 95% CI 0·61-2·94), and even showed a decreased risk of ICU admission in adjusted estimates (Crude OR 0·77, 95% CI 0·42- 1·42; aOR 0·75, 95% CI 0·62-0·91). Adjusted effect sizes were significantly higher for mortality (p=0·005) and lower for ICU admission (pInterpretation: Pre-existing mental disorders, in particular psychotic and mood disorders, as well as exposure to antipsychotics and anxiolytics, were associated with COVID-19 mortality. Substance use disorders were associated with COVID-19 hospitalization. These findings support the need for targeted approaches for the management and prevention of COVID-19 in patients with mental disorders. Funding: NoneDeclaration of Interest: LDP reports grants from Boehringer-Ingelheim and Janssen R&D, outside the submitted work. PFP reports grants from Lundbeck, personal fees from Angelini, personal fees from Menarini, non-financial support from Boehringer Ingelheim, outside the submitted work. BV, FB, AB, RT, ML, MEB, IB, PFP and LDP are members of the ECNP Immunopsychiatry Thematic Working Group. All other authors have nothing to disclose.

Poor vitamin D status and the risk of maternal depression: a dose-response meta-analysis of observational studies.

The association between 25-hydroxyvitamin D (25(OH)D) and maternal depression (MD) is deemed to be inconclusive. The current analysis aimed to quantify the relationship between 25(OH)D serum concentrations, the main indicator of vitamin D nutritional status, and MD. Dose-response meta-analysis. A systematic search in PubMed, Embase and Web of Science from inception to June 2019. Relevant observational studies reporting risk estimates and 95 % CI of random effects for 25(OH)D concentration on MD were identified. Twelve observational studies with thirteen independent reports involving 10 317 pregnant women were included. Compared with the lowest category of 25(OH)D, the pooled OR for the highest category of MD was 0·49 (95 % CI 0·35, 0·63); a high heterogeneity was observed (P = 0·001, I2 = 82·1 %). A non-linear association between 25(OH)D and MD was found (P for non-linearity = 0·001); the dose-response analysis indicated that the lowest pooled OR was at blood 25(OH)D concentrations of 90-110 nmol/l. Subgroup analyses suggested a stronger association between 25(OH)D and MD in summer time (OR 0·25, 95 % CI 0·08, 0·43) than in other seasons (OR 0·68, 95 % CI 0·52, 0·83) (P for interaction = 0·008). A visual inspection of funnel plot and Begg's and Egger's tests did not indicate any evidence of publication bias. Low circulating 25(OH)D is associated with MD, and our analysis suggests that they influence each other. Further randomised controlled trials would be needed to determine the direction of causation.

Abstract 14670: A Meta-analysis of Survival Outcomes Between Two Uncommon Mechanical Circulatory Support Device Combinations

Introduction: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and Impella devices are being used in increasing frequency for cardiogenic shock. Left ventricular unloading strategies are often used in VA-ECMO. The combination of simultaneous left- and right-sided Impellas, colloquially called “BIPELLA”, also offers biventricular support. There is a paucity of data regarding these combinations of platforms. We performed a systematic review of the literature to assess clinical outcomes in patients treated with ECPELLA and BIPELLA for cardiogenic shock. Methods: A systematic search of PubMed using the terms “ECMO”, “ECPELLA”, “BIPELLA”, and “Impella” was performed. Included studies evaluated mortality and complications associated with use of ECPELLA and/or BiPELLA. Reference lists of eligible studies helped identify additional publications meeting inclusion criteria. Case reports and conference abstracts were excluded. Heterogeneity among eligible studies was assessed using the I2 statistic. Publication bias was assessed using Egger’s regression and visual inspection of funnel plots. The primary outcome was in-hospital or 30-day mortality. Secondary outcomes assessed complications. Results: The results of publication bias assessment are provided in Figure 1A. Egger’s test was not significant (p = 0.56). A total of 139 patients underwent ECPELLA implantation and 20 underwent BIPELLA implantation. Mortality for the overall cohort was 51% with no significant difference between groups (p = 0.93) (Figure 1B). There was no significant difference between the groups with bleeding (p = 0.74), hemolysis (p = 0.34), and limb ischemia (p = 0.58). Conclusion: These data suggest no differences in short-term mortality and certain complications between ECPELLA and BIPELLA strategies. However, the available literature is sparse, with small sample sizes and suffers from a paucity of significant hemodynamic data. Further prospective data are needed.