Contour-enhanced Funnel Plots Research Articles

Assessment of inverse publication bias in safety outcomes: an empirical analysis

BackgroundThe aims of this study were to assess the presence of inverse publication bias (IPB) in adverse events, evaluate the performance of visual examination, and explore the impact of considering effect direction in statistical tests for such assessments.MethodsWe conducted a cross-sectional study using the SMART Safety, the largest dataset for evidence synthesis of adverse events. The visual assessment was performed using contour-enhanced funnel plots, trim-and-fill funnel plots, and sample-size-based funnel plots. Two authors conducted visual assessments of these plots independently, and their agreements were quantified by the kappa statistics. Additionally, IPB was quantitatively assessed using both the one- and two-sided Egger’s and Peters’ tests.ResultsIn the SMART Safety dataset, we identified 277 main meta-analyses of safety outcomes with at least 10 individual estimates after dropping missing data. We found that about 13.7–16.2% of meta-analyses exhibited IPB according to the one-sided test results. The kappa statistics for the visual assessments roughly ranged from 0.3 to 0.5, indicating fair to moderate agreement. Using the one-sided Egger’s test, 57 out of 72 (79.2%) meta-analyses that initially showed significant IPB in the two-sided test changed to non-significant, while the remaining 15 (20.8%) meta-analyses changed from non-significant to significant.ConclusionsOur findings provide supporting evidence of IPB in the SMART Safety dataset of adverse events. They also suggest the importance of researchers carefully accounting for the direction of statistical tests for IPB, as well as the challenges of assessing IPB using statistical methods, especially considering that the number of studies is typically small. Qualitative assessments may be a necessary supplement to gain a more comprehensive understanding of IPB.

Methods for assessing inverse publication bias of adverse events

In medical research, publication bias (PB) poses great challenges to the conclusions from systematic reviews and meta-analyses. The majority of efforts in methodological research related to classic PB have focused on examining the potential suppression of studies reporting effects close to the null or statistically non-significant results. Such suppression is common, particularly when the study outcome concerns the effectiveness of a new intervention. On the other hand, attention has recently been drawn to the so-called inverse publication bias (IPB) within the evidence synthesis community. It can occur when assessing adverse events because researchers may favor evidence showing a similar safety profile regarding an adverse event between a new intervention and a control group. In comparison to the classic PB, IPB is much less recognized in the current literature; methods designed for classic PB may be inaccurately applied to address IPB, potentially leading to entirely incorrect conclusions. This article aims to provide a collection of accessible methods to assess IPB for adverse events. Specifically, we discuss the relevance and differences between classic PB and IPB. We also demonstrate visual assessment through contour-enhanced funnel plots tailored to adverse events and popular quantitative methods, including Egger's regression test, Peters' regression test, and the trim-and-fill method for such cases. Three real-world examples are presented to illustrate the bias in various scenarios, and the implementations are illustrated with statistical code. We hope this article offers valuable insights for evaluating IPB in future systematic reviews of adverse events.

Association Between Immunoparesis and Treatment Outcomes of Patients With Newly Diagnosed Multiple Myeloma: A Systematic Review and Meta-Analysis

BackgroundImmunoparesis, defined as suppression of uninvolved polyclonal immunoglobulins, occurs in up to 80% of patients with newly diagnosed multiple myeloma (NDMM). Infections are the second most common cause of mortality in this population, yet evidence regarding prognostic impact of immunoparesis in NDMM remains unclear. Materials and MethodsUsing a prepublished protocol (CRD42022308687), we searched seven bibliographic databases from inception to February 2023 for studies reporting the impact of immunoparesis on clinical outcomes among adults with NDMM. The primary outcome of interest was overall survival (OS) and secondary outcomes were progression free survival (PFS) and infection risk. Effect sizes were quantified in terms of hazards ratio (HR) and pooled across studies using a random effects restricted maximum likelihood method. Heterogeneity was assessed using Cochran Q and the I2 statistic. Publication bias was assessed using contour enhanced funnel plots. ResultsOf 5175 studies screened, 7 studies involving 6091 patients met our search criteria. Immunoparesis was not associated with worse OS (pooled hazard ratio 1.30; 95% CI, 0.91-1.84; P-value .11), with significant heterogeneity among the studies (I2 = 72.9%; Cochran's Q P-value .003). However, immunoparesis was associated with a significantly worse PFS (pooled hazard ratio 1.42; 95% CI 1.11-1.82; p value 0.013), with moderate heterogeneity (I2 statistic = 51%; Cochran's Q P-value .056). Infection rates were not uniformly reported precluding meta-analysis. Visual examination of funnel plot revealed the possibility of publication bias. ConclusionOverall, our findings suggest that immunoparesis did not have a detrimental impact on OS, but was associated with a significantly shorter PFS. Further studies are needed to understand the complexity of immune system perturbations in NDMM.

Therapeutic Vaccines for Follicular Lymphoma: A Systematic Review.

(1) Background: We aimed to estimate the pooled effectiveness and safety of vaccination in follicular lymphoma (FL) and discuss implications for immunotherapy development. (2) Methods: We included randomized trials (RCTs) of therapeutic vaccines in patients with FL. Progression-free survival (PFS) was the primary outcome. We searched databases (PubMed, Embase, Scopus, Web of Science Core, medRxiv) and registries (PROSPERO, CENTRAL, ClinicalTrials.gov, EuCTR, WHO ICTRP) and conducted online, citation, and manual searches. We assessed risks of bias across outcomes using RoB 2.0 and across studies using ROB-ME and a contour-enhanced funnel plot. (3) Results: Three RCTs were included (813 patients, both previously treated and untreated). Patients with a complete or partial response after chemotherapy were randomized to either a patient-specific recombinant idiotype keyhole limpet hemocyanin (Id-KLH) vaccine plus granulocyte-macrophage colony-stimulating factor (GM-CSF) or placebo immunotherapy (KLH + GM-CSF). Meta-analyses showed that PFS was worse with the vaccine, but not significantly: hazard ratio, 1.09 (95% CI 0.91-1.30). The GRADE certainty of evidence was moderate. Adverse event data were mixed. (4) Conclusions: We are moderately certain that Id-KLH results in little to no difference in PFS in FL. (5) Funding: Russian Science Foundation grant #22-25-00516. (6) Registration: PROSPERO CRD42023457528.

Predictability of Neutrophile to Lymphocyte Ratio and Platelet to Lymphocyte Ratio on the Effectiveness of Immune Checkpoint Inhibitors in Non-small Cell Lung Cancer patients: A Meta-Analysis.

The associations between the neutrophil-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) with the responses of non-small cell lung cancer (NSCLC) patients receiving immune checkpoint inhibitors (ICI) and the NLR/PLR predictive potential were evaluated via meta-analysis. A systematic review was conducted using the PubMed, Embase, and The Cochrane Library databases until October 2021. The relationship between NLR/PLR and overall survival (OS) and progression-free survival (PFS) was evaluated using pooled hazard ratios (HR). The relationship between NLR/PLR and overall response rate (ORR) and disease control rate (DCR) was assessed via pooled odds ratios (OR). Heterogeneity between studies, publication bias, subgroup and sensitivity analyses, trim and fill meta-analysis, and the contour-enhanced funnel plot were performed using the R software. A total of 44 (out of 875) studies met the eligibility criteria, providing a sample size of 4597 patients. Patients with a high NLR were statistically significantly associated with worse outcomes, including OS (pooled HR = 2.44; P < 0.001), PFS (pooled HR = 2.06; P < 0.001), DCR (pooled OR = 0.71; P < 0.001), and ORR (pooled OR = 0.33; P < 0.001). Similarly, a high PLR was associated with poorer outcomes in response to ICI drugs, including OS (pooled HR = 2.13; P < 0.001) and PFS (pooled HR = 1.61; P < 0.001). High NLR and PLR were associated with a statistically significant reduction in the efficacy of ICI drugs in NSCLC patients. Thereby, it is possible to use NLR and PLR as potential and available biomarkers in the clinical practice to predict the outcome of ICI treatment in NSCLC patients.

Healthcare Waste Management Practices and Its Associated Factors Among Healthcare Workers in Health Facilities in Ethiopia: A Systematic Review and Meta-analysis

Introduction: Waste Management Practices have garnered growing interest in hospitals, research facilities, and laboratories over the past few years. However, there seems to be noticeable absence of a comprehensive understanding regarding research on waste management practices in health facilities among healthcare workers. Objective: This study aimed to determine the prevalence and factors associated with healthcare waste management practices among healthcare workers in Ethiopia. Methods: The search was performed by using the Web of Science (WoS) database, PubMed, and the Cochrane Library. To assess the presence of publication bias, by using funnel plots, contour-enhanced funnel plots, trim and fill analysis, and Begg and Egger regression test. A significance level of P ⩽ .05 was used to indicate potential publication bias. Heterogeneity between studies was assessed using the I2 statistics. Results: From retrieved original studies, 15 studies were included in the meta-analysis with a total of n = 5260 healthcare workers. The pooled prevalence of waste management practices in Ethiopia was 52.86% (95% CI = 51.57, 54.15), with significant heterogeneity observed between studies ( I2 = 97.0%; P ⩽ .001). Sub-group analysis based on regional distribution in Ethiopia revealed that the highest prevalence of waste management practices was observed in Southern Nation and Nationalities and People’s Region with 61.9% (95% CI = 52.953, 64.449). Conclusions: This systematic review and meta-analysis revealed that the pooled prevalence of waste management practices among healthcare workers in Ethiopia was notably low. Training and the presence of guidelines were significantly associated with waste management practices. The healthcare facilities have improved access to and availability of policies related to waste management and the Ministry of Health promotes their use through various means, including training for healthcare professionals.

Psychological Intervention to Promote Resilience in Nurses: A Systematic Review and Meta-Analysis.

Nurses primarily focus on caring for others, but they also require care and support to enhance their own resilience. Thus, this study aims to determine the effects of psychological interventions on nurses' resilience support and to define the influence of moderating variables that can affect these effects. The literature search was conducted in 10 electronic databases, and 5 randomized controlled trials and 10 non-randomized controlled trials were finally selected for analysis (a total of 852 participants). Statistical analyses of the effect sizes and homogeneity of the intervention programs were conducted using RevMan 5.3 from the Cochrane Library and the R program. Publication bias in the retrieved studies was tested using contour-enhanced funnel plots. The meta-analysis found that psychological interventions were effective in improving nurses' resilience immediately after the intervention (SMD = 0.59, 95% CI 0.31 to 0.86, Z = 4.18, p < 0.001) and in the short term within three months (SMD = 1.52, 95% CI 0.74 to 2.31, Z = 3.80, p < 0.001). Interventions using emotion regulation, relaxation, and self-compassion were particularly effective, and the intervention period was effective in both a short period of 1 day and a long period of more than 12 weeks. In addition, the optimal one-session time was 121-150 min, and offline interventions were more effective than online interventions. Furthermore, the effect size was affected by the intervention time for one session (QB = 12.02, df = 3, p = 0.007) and the on/offline intervention method (QB = 5.85, df = 1, p = 0.015). These findings may inform the development of targeted interventions and resilience support systems for nurses. However, in the future, more rigorous studies, such as randomized controlled trials, should be conducted to ensure strict control over the variables and to establish a stronger evidence base for the effectiveness of these interventions.

Is There an Association Between Parkinson's Disease and Periodontitis? A Systematic Review and Meta-Analysis.

Multiple observational studies have yielded controversial results regarding the association between Parkinson's disease (PD) and periodontitis. This systematic review and meta-analysis was conducted to ascertain their bidirectional relationship. A literature search for relevant studies was performed in PubMed, EMBASE, the Cochrane Library, and Web of Science databases from inception to December 19, 2022. Effect sizes (ES) with 95% confidence intervals were pooled under the random-effects model. Then, leave-one-out sensitivity analysis and contour-enhanced funnel plot were applied to assess the stability of the results. A total of 34 studies and 24 studies were included for systematic review and quantitative meta-analysis, respectively. Pooled ES indicated that periodontitis was not significantly associated with PD risk (HR = 1.13, 95% CI 0.88-1.45, n = 3; OR = 1.94, 95% CI 0.55-6.90, n = 7), while the Mendelian randomization study revealed no association between PD and periodontitis risk (coefficient [B] = -0.0001, standard error = 0.0001, p = 0.19). Furthermore, PD patients exhibited higher levels of periodontal pocket depth (SMD = 1.10, 95% CI 0.53-1.67), clinical attachment level (SMD = 1.40, 95% CI 0.55-2.26), plaque index (SMD = 0.81, 95% CI 0.22-1.39), and Oral Health Impact Profile-14 score (SMD = 0.91, 95% CI 0.33-1.49) compared to healthy controls. Our meta-analysis identified no bidirectional association between PD risk and periodontitis risk, though the prevalence of periodontitis and poorer oral status was higher in PD patients.

Feeding styles and adiposity in children of 6 months- 5 years of age: Protocol for a systematic review and meta- analysis.

Obesity in children is a major public health concern due to the increased risk of developing adverse health outcomes in their future, and disability in adulthood. The existing systematic reviews on the topic are limited in scope, focusing solely on high-income countries and children aged 4-12 years. Hence, we propose to conduct a systematic review and meta-analysis to understand, how exposure to authoritative feeding style versus authoritarian, indulgent, uninvolved compare in terms of its association with adiposity in children aged 6 months to 5 years. Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) guidelines were followed for ensuring the completeness of the protocol. Case-control and cohort studies will be included. Searches will be done using electronic databases viz. PubMed, Ovid EMBASE, PsycINFO and Web of Science. Grey literature will be searched using OpenGrey and Grey Literature Report. We will only include quantitative studies using the developed search strategy. For categorical outcomes, relative risks, odds ratios, and hazard ratios with confidence intervals and for continuous outcomes mean difference with confidence intervals will be used. Risk of Bias In Non-randomized Studies- of Exposure (ROBINS-E) will be used for the evaluation of risk of bias in the individual observational studies. Considering the inherent variability in the observational studies, random effects meta-analysis will also be conducted. If between-study heterogeneity exists, a subgroup analysis based on low and middle-income countries vs. high income countries will be conducted. If the data is not suitable for combining quantitatively, a narrative synthesis will be undertaken. We propose to identify publication bias by using contour-enhanced funnel plots and "trim and fill" method. Outcome reporting bias will be ascertained by comparing the outcomes published in the protocol and the published report. The Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) system will be used to understand the confidence we can have on the effect estimates. Registration: This protocol has been registered in International Prospective Register of Systematic Reviews (PROSPERO) on 13 March 2023 with registration number CRD42023356014.

Economic recession, illicit drug use and the young population: a systematic literature review and meta-analysis.

Economic recessions impact on drug use through different channels, with potential conflicting outcomes. Previous studies have reached mixed outcomes, and a clear and comprehensive picture is difficult to depict. We use a systematic review of literature - conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines - and a hierarchical mixed-effects meta-analysis to provide a comprehensive quantitative assessment of the relationship between business cycle and the use of drugs by young populations. The heterogeneity of studies was assessed by the I2 statistic, and the publication bias was evaluated with contour-enhanced funnel plots. We identify 25 studies, published over the period 2008-2020. These articles carried out an empirical analysis of the impact of the business cycle on illegal drug consumption in Organisation for Economic Co-operation Development (OECD) countries. Most of the studies (17 studies) covered the 2007 financial crisis. Among the outcomes, 9 studies traced a countercyclical relationship between economic recessions and drug use, 3 showed a procyclical relationship and 13 studies found mixed results. Unemployment was the most widely used variable to assess macroeconomic conditions in most of the studies (21 studies). The meta-analysis shows a partial correlation of .03 (95% confidence interval (CI): .0147-.0453) between the unemployment rate and drug use among young individuals. Therefore, we conclude that, on average, recessions tend to boost drug use. This impact is more marked with cannabis use than it is with cocaine, opioids or other drugs. This study provides robust evidence that in periods of economic downturns, the young populations tend to increase the use of illegal drugs, with cannabis as their main preference. Therefore, in periods of economic severity, society may particularly benefit from implementing widely reaching public prevention programmes and demand reduction interventions, targeting this subgroup of the population.

P-629 Dietary and/or physical activity interventions in women with overweight or obesity prior to fertility treatment – an individual participant data meta-analysis (Venus-IPD)

Abstract Study question Do dietary and/or physical activity interventions prior to fertility treatment improve live birth rates in women with overweight or obesity? Summary answer Dietary and/or physical activity interventions prior to fertility treatment do not significantly increase live birth rates in women with overweight or obesity. What is known already Existing guidelines recommend lifestyle interventions based on dietary and/or physical activity targeting at a 5 to 10% reduction in body weight as an initial step prior to fertility treatment for women with infertility and overweight or obesity. However, the evidence underlying this recommendation is limited and findings from recent randomized controlled trials (RCTs) are inconsistent. Individual participant data meta-analysis (IPDMA) has been considered the “gold standard” for evidence synthesis. Study design, size, duration We performed an IPDMA of RCTs comparing dietary and/or physical activity interventions as core interventions prior to fertility treatment versus standard advice concerning a healthy diet and physical activity, routine care or no intervention. We searched MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials up to September 2022 to identify potential eligible RCTs. Participants/materials, setting, methods After identifying eligible RCTs in women with infertility and overweight or obesity (BMI ≥ 25 kg/m2), we contacted the investigators of eligible RCTs to share the deidentified IPD and established the Venus-IPD Collaboration. The primary outcome was live birth. Secondary outcomes included weight loss and other fertility outcomes. We performed a two-stage random-effects IPDMA as the primary analysis. Main results and the role of chance Of 14 eligible RCTs, as of January 2023 we obtained IPD of 9 RCTs with 1715 participants (916 in the intervention group and 799 in the control group). The mean female age was 30.7 years (standard deviation 4.5) and the median baseline BMI was 34.8 kg/m2 (Interquartile range 32.4 to 38.5). The duration of the diet/physical activity interventions ranged from 2.5 to 6 months. Physical activity and/or dietary interventions prior to fertility treatment resulted in more weight reduction compared to those in the control group (9 RCTs, 1715 participants, mean difference –5.71 kg, 95%CI –7.76 to –3.66). The intervention group did not have a significantly higher rate of live birth (8 RCTs, 1697 participants, OR 1.30, 95%CI 0.74 to 2.27, I2=60%) or clinical pregnancy (8 RCTs, 1697 participants, OR 1.22, 95%CI 0.81 to 1.83, I2=28%). The asymmetrical contour-enhanced funnel plot indicates possible small-study effects. Limitations, reasons for caution Blinding was not possible due to the nature of the intervention. IPD of three small RCTs are not obtained at this time. The heterogeneity in the type and period for lifestyle interventions and in the follow-up duration was moderate to high. Wider implications of the findings Dietary and/or physical activity interventions are effective in reducing body weight in women with overweight or obesity, but such a benefit in weight loss may not translate to improved live birth rates. Trial registration number CRD42021266201

Occupational arsenic exposure and genitourinary cancer: systematic review and meta-analysis.

Existing evidence suggests that ingestion of high doses of arsenic through drinking water is associated with an increased risk of genitourinary cancers, while systematic evidence on workers exposed to arsenic is lacking. The aim of this study is to systematically review the evidence on the association between occupational exposure to arsenic and genitourinary cancer risk and mortality. A systematic literature search was carried out on Pubmed, Web of Science and Embase by including cohort and case-control studies. Study-specific relative risks (RRs) and the corresponding 95% confidence intervals (CIs) were pooled using Mandel-Paule random-effects model. Contour-enhanced funnel plot and Egger's test were used to assess the occurrence of publication bias. A total of 17 studies were included in the meta-analysis, 7 on cancer incidence (n = 161,244 individuals) and 10 on cancer mortality (n = 91,868). Most of them were cohort (71%) and industry-based studies (59%). The meta-analysis failed to detect an increased risk of genitourinary cancers among workers exposed to arsenic, except for a suggestive but not significant positive association for bladder cancer incidence (RR: 1.26, 95% CI: 0.89, 1.80), although this estimate was based on only three studies. No compelling evidence of publication bias was found (P = 0.885). Our findings did not show an association between occupational exposure to arsenic and genitourinary cancers, although further high-quality studies with detailed exposure assessment at the individual level are needed to clarify this relationship.

Efficacy, safety and methodological quality of light therapy and sleep improvement interventions for people with attention deficit hyperactivity disorder (ADHD)

IntroductionLarge proportion of patients with ADHD experience sleep problems. Well conducted, good quality clinical research could identify non-pharmacological sleep improvement interventions that would benefit patients with ADHD and would inform evidence based guidelines for sleep management in ADHD.ObjectivesTo conduct a novel meta-research assessment of available clinical trials in the field of light therapy and non‑pharmacological sleep improvement interventions for people with ADHD.MethodsPeer-reviewed publications of clinical trials were analysed. An advanced literature search strategy was performed in major medical databases, including EMBASE, MEDLINE, the Cochrane Central Register of Controlled Trials and PsycINFO. Available data at WHO-approved clinical trial registries were searched and linked to the published literature. Detailed methodological assessment of results was conducted using the Cochrane Risk of Bias Tool version 2.0 (ROB2), conflict of interest, spin and favourability of findings. Reduction in ADHD symptom severity and improvement of sleep quality served as primary outcomes for the efficacy analysis. Any adverse events were recorded. Statistical analysis of the primary outcomes was conducted by calculating standardised mean difference and transformed as necessary. Publication bias was evaluated with contour enhanced funnel plots and the trim-and-fill procedure, and by summarising unpublished trials.ResultsAnalysed clinical trials often had a high risk of bias (evaluated by the ROB2). The primary outcome interpretation and overall trial conclusions frequently favoured the trial intervention. Clinical trials showed an association between primary outcome effect size and interpretation, and risk of bias. Clinical research in this field faces many of the same challenges identified for complex interventions in mental health, such as small sample size, lack of funding and difficulties with blinding.ConclusionsClinical research regarding light therapy and non‑pharmacological sleep improvement interventions for ADHD patients indicates safety and effectiveness but studies often lack methodological rigour.Disclosure of InterestNone Declared

Association of several loci of SMAD7 with colorectal cancer: A meta-analysis based on case–control studies

Sma-and mad-related protein 7 (SMAD7) can affect tumor progression by closing transforming growth factor-beta intracellular signaling channels. Despite the extensive research on the correlation between SMAD7 polymorphisms and colorectal cancer (CRC), the conclusions of studies are still contradictory. We conducted a study focusing on the association of SMAD7 polymorphisms rs4939827, rs4464148, and rs12953717 with CRC. We searched through 5 databases for articles and used odd ratios (ORs) and 95% confidence intervals (CIs) to discuss the correlation of SMAD7 polymorphisms with CRC risk. The heterogeneity will be appraised by subgroup analysis and meta-regression. Contour-enhanced funnel plot, Begg test and Egger test were utilized to estimate publication bias, and the sensitivity analysis illustrates the reliability of the outcomes. We performed False-positive report probability and trial sequential analysis methods to verify results. We also used public databases for bioinformatics analysis. We conclusively included 34 studies totaling 173251 subjects in this study. The minor allele (C) of rs4939827 is a protective factor of CRC (dominant, OR/[95% CI] = 0.89/[0.83-0.97]; recessive, OR/[95% CI] = 0.89/[0.83-0.96]; homozygous, OR/[95% CI] = 0.84/[0.76-0.93]; heterozygous, OR/[95% CI] = 0.91/[0.85-0.97]; additive, OR/[95% CI] = 0.91/[0.87-0.96]). the T allele of rs12953717 (recessive, OR/[95% CI] = 1.22/[1.15-1.28]; homozygous, OR/[95% CI] = 1.25/[1.13-1.38]; additive, OR/[95% CI] = 1.11/[1.05-1.17]) and the C allele of rs4464148 (heterozygous, OR/[95% CI] = 1.13/[1.04-1.24]) can enhance the risk of CRC. Rs4939827 (T > C) can decrease the susceptibility to CRC. However, the rs4464148 (T > C) and rs12953717 (C > T) variants were connected with an enhanced risk of CRC.

An updated systematic review of the association between the TLR4 polymorphism rs4986790 and cancers risk.

Background:Toll-like receptor 4 (TLR4) is a lipopolysaccharide receptor that may influence tumor progression through inflammatory response and immune response. This complex process mainly occurs within cells. The correlation between TLR4 and neoplasms has been of great interest, but discrepancies remain.Methods:We analyze the literature retrieved from five databases (Web of Science, PubMed, Embase, CNKI, and Wan Fang) to assess the intensity of association using odds ratio (ORs) and 95% confidence intervals (95% CI). Meta-regression and subgroup analysis were utilized to find sources of heterogeneity. Publication bias is estimated using contour-enhanced funnel plots, Begg’s test, and Egger’s test, and we implemented sensitivity analysis to clarify the reliability of the outcomes. We also conducted an evaluation of the sample size using trial sequential analysis (TSA) method.Results:We found a significant association between rs4986790 and tumors (dominant model: OR [95% CI] = 1.25 [1.11–1.42]; heterozygous model OR [95% CI] = 1.25 [1.11–1.41]; and additive model: OR [95% CI] = 1.25 [1.10–1.41]. Specifically, the rs4986790 minor allele G may increase the risk of gastric cancer (dominant model: OR [95% CI] = 1.62 [1.3–2.03]; heterozygous model: OR [95% CI] = 1.57 [1.24–1.97]; additive model: OR [95% CI] = 1.64 [1.31–2.05] and other tumors (dominant model: OR [95% CI] = 1.36 [1.17–1.57]; heterozygous model: OR [95% CI] = 1.43 [1.25–1.63]; additive model: OR [95% CI] = 1.35 [1.18–1.55]. Further subgroup analysis showed that this association are both present in Caucasian and Asian.Conclusion:The outcomes of our systemic review proved that the TLR4 polymorphism rs4986790 is associated with cancer, especially with gastric cancer, and this strong correlation are evident in Caucasians and Asian.

Aberrantly expressed long noncoding RNAs as potential prognostic biomarkers in newly diagnosed multiple myeloma: A systemic review and meta-analysis.

Numerous studies have manifested long noncoding RNAs (lncRNAs) as biomarkers to determine the prognosis of multiple myeloma (MM) patients. Nevertheless, the prognostic role of lncRNAs in MM is still ambiguous. Herein, we performed a meta-analysis to evaluate the predictive value of aberrantly expressed lncRNAs in MM. A systemic literature search was performed in PubMed, EMBASE, Cochrane, and Web of Science databases until October 9, 2021, and the protocol was registered in the PROSPERO database (CRD42021284364). Our study extracted the hazard ratios (HRs) and 95% confidence intervals (CIs) of overall survival (OS), progression-free survival (PFS), or event-free survival (EFS). Begg's and Egger's tests were employed to correct publication bias. Twenty-six individual studies containing 3501 MM patients were enrolled in this study. The results showed that aberrant expression of lncRNAs was associated with poor OS and PFS of MM patients. The pooled HRs for univariate OS and PFS were 1.48 (95% CI=1.17-1.88, p < 0.001) and 1.30 (95% CI=1.18-1.43, p< 0.001), respectively, whereas the pooled HRs for multivariate OS and PFS were 1.50 (95% CI=1.16-1.95, p < 0.001) and 1.59 (95% CI=1.22-2.07, p < 0.001), respectively. Subgroup analysis suggested that MALAT1, TCF7, NEAT1, and PVT1 upregulation were associated with poor OS (p< 0.05), PVT1, and TCF7 upregulation were implicated with worse PFS (p< 0.05), while only TCF7 overexpression was correlated with reduced EFS (p< 0.05). Moreover, the contour-enhanced funnel plot demonstrated the reliability of our current conclusion, which was not affected by publication bias. Aberrantly expressed particular lncRNAs are critical prognostic indicators in long-term survival as well as promising biomarkers in progression-free status. However, different cutoff values and dissimilar methods to assess lncRNA expression among studies may lead to heterogeneity.

Prevalence and Characteristics of Malaria and Influenza Co-Infection in Febrile Patients: A Systematic Review and Meta-Analysis.

Malaria and influenza are co-endemic in several geographical areas, and differentiation of their clinical features is difficult. The present study aimed to qualitatively and quantitatively analyze the prevalence and characteristics of malaria and influenza co-infection in febrile patients. The systematic review was registered at PROSPERO (CRD42021264525). Relevant literature that reported malaria and influenza co-infection in febrile patients were searched in PubMed, Web of Science, and Scopus from 20 June to 27 June 2021 and the risk of bias for each study was assessed. Quantitative analysis included pooled prevalence, and the odds of malaria and influenza virus co-infection among febrile patients were estimated using a random-effects model. Subgroup analyses were performed to summarize the effect estimate for each group. Funnel plot, Egger’s test, and contour-enhanced funnel plot were used to demonstrate any publication bias among outcomes of included studies. Among 4253 studies retrieved, 10 studies that enrolled 22,066 febrile patients with 650 co-infected patients were included for qualitative and quantitative syntheses. The pooled prevalence of malaria and influenza virus co-infection among febrile patients was 31.0% in Nigeria, 1.0% in Tanzania, 1.0% in Uganda, 1.0% in Malawi, 1.0% in Ghana, 0% in Cambodia, 7.0% in the Central African Republic, and 7.0% in Kenya. Meta-analysis also showed co-infection occurrence by chance (p = 0.097, odds ratio 0.54, 95% CI 0.26–1.12, I2 94.9%). The prevalence of malaria and influenza virus co-infection among febrile patients was heterogeneous by country, characteristics of febrile participants, and diagnostic tests for influenza virus. Further studies should investigate severe clinical manifestations or differentiate clinical outcomes between mono-infected or co-infected individuals, whether the co-infection leads to severe disease outcome.

Meta-analysis using Python: a hands-on tutorial

BackgroundMeta-analysis is a central method for quality evidence generation. In particular, meta-analysis is gaining speedy momentum in the growing world of quantitative information. There are several software applications to process and output expected results. Open-source software applications generating such results are receiving more attention. This paper uses Python’s capabilities to provide applicable instruction to perform a meta-analysis.MethodsWe used the PythonMeta package with several modifications to perform the meta-analysis on an open-access dataset from Cochrane. The analyses were complemented by employing Python’s zEpid package capable of creating forest plots. Also, we developed Python scripts for contour-enhanced funnel plots to assess funnel plots asymmetry. Finally, we ran the analyses in R and STATA to check the cross-validity of the results.ResultsA stepwise instruction on installing the software and packages and performing meta-analysis was provided. We shared the Python codes for meta-analysts to follow and generate the standard outputs. Our results were similar to those yielded by R and STATA.ConclusionWe successfully produced standard meta-analytic outputs using Python. This programming language has several flexibilities to improve the meta-analysis results even further.

The Effect of Cognitive Function Health Care Using Artificial Intelligence Robots for Older Adults: Systematic Review and Meta-analysis.

BackgroundWith rapidly aging populations in most parts of the world, it is only natural that the need for caregivers for older adults is going to increase in the near future. Therefore, most technologically proficient countries are in the process of using artificial intelligence (AI) to build socially assistive robots (SAR) to play the role of caregivers in enhancing interaction and social participation among older adults.ObjectiveThis study aimed to examine the effect of intervention through AI SAR on the cognitive function of older adults through a systematic literature review.MethodsWe conducted a meta-analysis of the various existing studies on the effect of AI SAR on the cognitive function of older adults to standardize the results and clarify the effect of each method and indicator. Cochrane collaboration and the systematic literature review flow of PRISMA (Preferred Reporting Item Systematic Reviews and Meta-Analyses) were used on original, peer-reviewed studies published from January 2010 to March 2022. The search words were derived by combining keywords including Population, Intervention, and Outcome—according to the Population, Intervention, Comparison, Outcome, Time, Setting, and Study Design principle—for the question “What is the effect of AI SAR on the cognitive function of older adults in comparison with a control group?” (Population: adults aged ≥65 years; Intervention: AI SAR; Comparison: comparison group; Outcome: popular function; and Study Design: prospective study). For any study, if one condition among subjects, intervention, comparison, or study design was different from those indicated, the study was excluded from the literature review.ResultsIn total, 9 studies were selected (6 randomized controlled trials and 3 quasi-experimental design studies) for the meta-analysis. Publication bias was examined using the contour-enhanced funnel plot method to confirm the reliability and validity of the 9 studies. The meta-analysis revealed that the average effect size of AI SAR was shown to be Hedges g=0.43 (95% CI –0.04 to 0.90), indicating that AI SAR are effective in reducing the Mini Mental State Examination scale, which reflects cognitive function.ConclusionsThe 9 studies that were analyzed used SAR in the form of animals, robots, and humans. Among them, AI SAR in anthropomorphic form were able to improve cognitive function more effectively. The development and expansion of AI SAR programs to various functions including health notification, play therapy, counseling service, conversation, and dementia prevention programs are expected to improve the quality of care for older adults and prevent the overload of caregivers. AI SAR can be considered a representative, digital, and social prescription program and a nonpharmacological intervention program that communicates with older adults 24 hours a day. Despite its effectiveness, ethical issues, the digital literacy needs of older adults, social awareness and reliability, and technological advancement pose challenges in implementing AI SAR. Future research should include bigger sample sizes, pre-post studies, as well as studies using an older adult control group.

Meta-Analysis and Systematic Review of Coagulation Disbalances in COVID-19: 41 Studies and 17,601 Patients.

IntroductionCoagulation parameters are important determinants for COVID-19 infection. We conducted meta-analysis to assess the association between early hemostatic parameters and infection severity.MethodsElectronic search was made for papers that addressed clinical characteristics of COVID-19 patients and disease severity. Results were filtered using exclusion and inclusion criteria and then pooled into a meta-analysis to estimate the standardized mean difference (SMD) with 95% confidence interval (CI) for D-dimers, fibrinogen, prothrombin time, platelet count (PLT), activated partial thromboplastin time. To explore the heterogeneity and robustness of our fundings, sensitivity and subgroup analyses were conducted. Publication bias was assessed with contour-enhanced funnel plots and Egger's test by linear regression. Coagulation parameters data from retrospective cohort study of 451 patients with COVID-19 at National Research Center for Cardiac Surgery were included in meta-analysis of published studies.ResultsOverall, 41 original studies (17,601 patients) on SARS-CoV-2 were included. For the two groups of patients, stratified by severity, we identified that D-dimers, fibrinogen, activated partial thromboplastin time, and prothrombin time were significantly higher in the severe group [SMD 0.6985 with 95%CI (0.5155; 0.8815); SMD 0.661 with 95%CI (0.3387; 0.9833); SMD 0.2683 with 95%CI (0.1357; 0.4009); SMD 0.284 with 95%CI (0.1472; 0.4208)]. In contrast, PLT was significantly lower in patients with more severe cases of COVID-19 [SMD −0.1684 with 95%CI (−0.2826; −0.0542)]. Neither the analysis by the leave-one-out method nor the influence diagnostic have identified studies that solely cause significant change in the effect size estimates. Subgroup analysis showed no significant difference between articles originated from different countries but revealed that severity assessment criteria might have influence over estimated effect sizes for platelets and D-dimers. Contour-enhanced funnel plots and the Egger's test for D-dimers and fibrinogen revealed significant asymmetry that might be a sign of publication bias.ConclusionsThe hemostatic laboratory parameters, with exception of platelets, are significantly elevated in patients with severe COVID-19. The two variables with strongest association to disease severity were D-dimers and fibrinogen levels. Future research should aim outside conventional coagulation tests and include analysis of clotting formation and platelet/platelet progenitors characteristics.