Regulatory T Cells in Pregnancy Adverse Outcomes: A Systematic Review and Meta-Analysis

BackgroundSeveral studies report the role of Regulatory T-cells (Tregs) in the pathophysiology of pregnancy adverse outcomes.ObjectiveThe aim of this systematic review and meta-analysis was to determine whether there is an association between regulatory T cell levels and pregnancy adverse outcomes (PAOs), including pre-eclampsia and preterm birth (PTB).MethodLiterature searches were conducted in PubMed/MEDLINE, Embase, and Cochrane CENTRAL databases. Inclusion criteria were original articles (clinical trials, case-control studies and cohort studies) comparing Tregs, sampled from the decidua or maternal blood, in healthy pregnant women versus women with pre-eclampsia or PTB. The outcome was standardised mean difference (SMD) in Treg numbers. The tau-squared (Tau²), inconsistency index (I²), and chi-squared (χ²) test quantified heterogeneity among different studies. Analyses were performed in RevMan software V.5.4.0 for Mac using a random-effects model with outcome data reported with 95% confidence intervals (CI). This study was prospectively registered with PROSPERO (CRD42020205469). PRISMA guidelines were followed.ResultsFrom 4,085 unique studies identified, 36 were included in qualitative synthesis, and 34 were included in quantitative synthesis (meta-analysis). In total, there were 1,783 participants in these studies: healthy controls=964, pre-eclampsia=759, PTB=60. Thirty-two studies compared Tregs in healthy pregnant women and women with pre-eclampsia, and 30 of these sampled Tregs from peripheral blood showing significantly higher Treg numbers in healthy pregnancies (SMD; 1.46; 95% CI, 1.03–1.88; I²=92%). Four studies sampled Tregs from the maternal decidua showing higher Tregs in healthy pregnancies (SMD, 0.76; 95% CI, -0.13–1.65; I²=84%). No difference was found in the number of Tregs between early versus late pre-eclampsia (SMD,-1.17; 95% CI, -2.79–0.44; I²=94%). For PTB, two studies compared Tregs sampled from the peripheral blood with a tendency for higher Tregs in healthy pregnancies but this did not reach significance (SMD, 2.18; 95% CI, -1.34–5.70; I²=96%). Subcohort analysis using Treg analysis (flow cytometry vs. qPCR vs. immunofluorescence tissue staining) showed similar associations.ConclusionLower Tregs in pregnancy, sampled from the maternal peripheral blood, are associated with pre-eclampsia. There is a need for further studies to confirm a relationship between low Tregs and PTB. As the precise mechanisms by which Tregs may mediate pre-eclampsia and PTB remain unclear, further fundamental research is necessary to elucidate the underlying processes and highlight the causative link.Systematic Review RegistrationPROSPERO, identifier CRD42020205469.

Prevalence and impact of frailty in patients with atrial fibrillation: a systematic review and meta-analysis

Background Frailty is a clinical syndrome characterized by a reduced physiologic function, increased vulnerability to stressors, and an increased risk of adverse outcomes. Patients with Atrial Fibrillation (AF) are often burdened with a high number of comorbidities and prone to frailty. The prevalence of frailty, its management and association with major outcomes in patients with AF are still unclear. Purpose To estimate the pooled prevalence of frailty in patients with AF, as well as its association with AF-related risk factors and comorbidities, oral anticoagulants (OAC) prescription, and major outcomes. Methods We systematically searched PubMed and EMBASE, from inception to 31st January 2021, for studies reporting the prevalence of frailty (irrespective of the tool used for assessment). Pooled prevalence, odds ratio (OR), and 95% Confidence Intervals (CI) were computed using random-effect models; heterogeneity was assessed through the inconsistency index (I2). This study was registered in PROSPERO: CRD42021235854. Results A total of 1,116 studies were retrieved from the literature search, and 31 were finally included in the systematic review (n=842,521 patients). The frailty pooled prevalence was 39.6% (95% CI=29.2%-51.0%, I2=100%; Figure 1). Significant subgroup differences were observed according to geographical location (higher prevalence found in European-based cohorts; p=0.003) and type of tool used for the assessment (higher prevalence in studies using the Clinical Frailty Scale and Tilburg Frailty Index tools; p<0.001). Meta-regressions showed that study-level mean age and prevalence of hypertension, diabetes, and history of stroke were directly associated with frailty prevalence. Frailty was significantly associated with a 29% reduced probability of OAC prescription in observational studies (OR=0.71, 95% CI=0.62–0.81). Frail patients with AF were at higher risk of all-cause death (OR=4.12, 95% CI=3.15–5.41), ischemic stroke (OR=1.55, 95% CI=1.01–2.38), and bleeding (OR=1.55, 95% CI=1.12–2.14), compared to non-frail patients with AF. Conclusions In this systematic review and meta-analysis analysis, the prevalence of frailty was high in patients with AF, and associated with study-level mean age and prevalence of several stroke risk factors. Frailty may influence the management of patients, and worsening the prognosis for all major AF-related outcomes. FUNDunding Acknowledgement Type of funding sources: None. Prevalence of Frailty among AF patients

An interpretive structural model for factors affecting the tax compliance of professional athletes: a case study of football players

PurposeTax revenues are becoming one of the crucial tax policy segments in developing countries. Governments intend to collect more funds in the budget. The study aimed to identify the dimensions and factors influencing tax compliance in Iranian professional football players.Design/methodology/approachBased on interpretive structural modelling (ISM), the required information was collected using a literature review and a pairwise comparison questionnaire from eleven sport academic and executive participants. Content validity index of the questionnaire was >0.7 and its inconsistency index was <0.1.FindingsThe influential factors put in six levels. Results showed “new technologies for implementing regulations” and “clear tax regulations” were the lowest level's most independent factors. Simultaneously, the “possibility of identifying violating taxpayers” and “transparency of the clubs' financial data” were the most dependent factors at the model's first level. Moreover, “legal” was the greatest, and “technological” dimensions had at least importance, and the “amount and manner of fines” was the influential factor. The findings can use for policymaking to improve the professional player's and society tax compliance.Originality/valueThe authors identified the most independent, dependent, influential and minor essential football players' tax compliance factors and the relations between these factors. Recognising each of the factors' role and level of importance can help governments and policymakers in tax legislation in sport.

Identifying Critical States of Complex Diseases by Single-Sample Jensen-Shannon Divergence

MotivationThe evolution of complex diseases can be modeled as a time-dependent nonlinear dynamic system, and its progression can be divided into three states, i.e., the normal state, the pre-disease state and the disease state. The sudden deterioration of the disease can be regarded as the state transition of the dynamic system at the critical state or pre-disease state. How to detect the critical state of an individual before the disease state based on single-sample data has attracted many researchers’ attention.MethodsIn this study, we proposed a novel approach, i.e., single-sample-based Jensen-Shannon Divergence (sJSD) method to detect the early-warning signals of complex diseases before critical transitions based on individual single-sample data. The method aims to construct score index based on sJSD, namely, inconsistency index (ICI).ResultsThis method is applied to five real datasets, including prostate cancer, bladder urothelial carcinoma, influenza virus infection, cervical squamous cell carcinoma and endocervical adenocarcinoma and pancreatic adenocarcinoma. The critical states of 5 datasets with their corresponding sJSD signal biomarkers are successfully identified to diagnose and predict each individual sample, and some “dark genes” that without differential expressions but are sensitive to ICI score were revealed. This method is a data-driven and model-free method, which can be applied to not only disease prediction on individuals but also targeted drug design of each disease. At the same time, the identification of sJSD signal biomarkers is also of great significance for studying the molecular mechanism of disease progression from a dynamic perspective.

Incidence of Immune-Mediated Pseudoprogression of Lymphoma Treated with Immune Checkpoint Inhibitors: Systematic Review and Meta-Analysis

We evaluated the incidence of pseudoprogression and indeterminate response (IR) in patients with lymphoma treated with immune checkpoint inhibitors (ICIs). A systematic search of PubMed and EMBASE was performed up to 6 February 2021, using the keywords “lymphoma,” “immunotherapy,” and “pseudoprogression.” Random-effects models were used to calculate both pooled incidence of pseudoprogression patients with lymphoma and an IR according to LYRIC criteria, while the Higgins inconsistency index (I2) test and Cochran’s Q test were used for heterogeneity. Eight original articles were included, in which the number of patients ranged from 7 to 243. Among the lymphoma patients with ICIs, the pooled incidence of pseudoprogression was 10% (95% confidence interval [CI]: 0.06–0.17). There was no publication bias in Begg’s test (p = 0.14). Three articles were analyzed to determine the pooled incidence of pseudoprogression in patients with IR according to LYRIC criteria in a subgroup analysis, which was shown to be 19% (95% CI: 0.08–0.40). A significant proportion (10%) of patients with lymphoma treated with ICIs showed pseudoprogression, and 19% of patients with an IR response showed pseudoprogression and a delayed response. Immune-related response criteria such as LYRIC may be used for patients with lymphoma treated with ICIs.

The Association between Five Genetic Variants in MicroRNAs (rs2910164, rs11614913, rs3746444, rs11134527, and rs531564) and Cervical Cancer Risk: A Meta-Analysis

The objective of this study was to conduct a meta-analysis to systematically summarize and investigate the association of miRNA-124 rs531564, miRNA-218 rs11134527, miRNA-146a rs2910164, miRNA-196a2 rs11614913, and miRNA-499 rs3746444 polymorphisms with cervical cancer. A systematic review was performed to identify relevant studies using Embase and PubMed databases. A chi-square-based Q -test combined with the inconsistency index ( I 2 ) was used to check the heterogeneity between studies. A total of six case-control studies on rs2910164 and rs11614913, 4 studies on rs3746444 and rs11134527, and three studies on rs531564 were included. No evidence of association was found between miR-146a rs2910164, miR-196a2 rs11614913, miRNA-499 rs3746444, and miR-218 rs11134527 polymorphisms and cervical cancer risk in all the genetic models. The miR-124 rs531564 polymorphism was associated with a statistically increased risk of cervical cancer in a homozygote model (CC vs. GG: OR = 2.87 , 95% CI: 1.40-5.91, P H = 0.887 ), dominant model (GC/CC vs. GG: OR = 1.38 , 95% CI: 1.07-1.80, P H = 0.409 ), and recessive model (CC vs. GC/GG: OR = 2.26 , 95% CI: 1.58-3.23, P H = 0.979 ). However, this finding should be interpreted with caution for limited samples and heterogeneity. Large-scale and well-designed studies are needed to validate our result.

Diabetic Peripheral Neuropathy in Ethiopia: A Systematic Review and Meta-Analysis

Background. Currently, diabetic peripheral neuropathy (DPN) is one of the most severe complications of diabetes mellitus (DM). Despite the seriousness of this problem, limited evidence is available on the prevalence of diabetic peripheral neuropathy among patients with diabetes mellitus in Ethiopia. In Ethiopia, there were no updated studies that estimate the national prevalence of DPN. Hence, this systematic review and meta-analysis provided a national prevalence of diabetic peripheral neuropathy among patients with diabetes mellitus in Ethiopia. Methods. This study was submitted for registration with the International Prospective Register of Systematic Reviews (PROSPERO) in March 2020 and accepted with the registration number CRD42020173831. Different database searching engines were searched online to retrieve related articles, including PubMed, Scopus, Google Scholar, African Journals Online, World Health Organization (WHO) Afro Library, and Cochrane Review. The reviewers used the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guideline in the reviewing process. In this systematic review and meta-analysis, all published and unpublished articles were analyzed. The reviewers used the random effects model to estimate the pooled prevalence of diabetic peripheral neuropathy among diabetes mellitus patients. The reviewers conducted the statistical analysis using the R version 3.5.3 and RStudio version 1.2.5033 software for Windows. The reviewers evaluated the heterogeneity across the included studies by the inconsistency index ( I 2 ). The reviewers examined the publication bias by the funnel plot. Results. The search of the databases produced 245 papers. After checking the inclusion and exclusion criteria, 38 articles with 14029 total patients with diabetes mellitus were found suitable for the review. Except for three (retrospective cohort study), all studies were cross-sectional. The overall pooled prevalence of diabetic peripheral neuropathy was 22% (95% CI 18% to 26%). The subgroup analysis of diabetic peripheral neuropathy among patients with diabetes in the different regions was 23% (95% CI 17% to 29%) in Addis Ababa, 27% (95% CI 16% to 38%) in Oromia, 16% (95% CI 14% to 18%) in South nation and nationalities, and 15% (95% CI 6% to 24%) in Amhara. Conclusions. More than one-fifth of patients with diabetes have diabetic peripheral neuropathy. According to this study, the prevalence of diabetic peripheral neuropathy in Ethiopia is considerably high. This evidence suggests that attention should be given to patients with diabetes in monitoring patients’ blood glucose.

Surgical site infection and its association with rupture of membrane following cesarean section in Africa: a systematic review and meta-analysis of published studies

Introduction Surgical site infection occurs within 30 days after a surgical procedure and involves the skin, subcutaneous tissue, and soft tissue. Surgical site infection following cesarean section is a common postoperative complication and is associated with maternal morbidity and mortality in resource-limited settings. Even though the proportion of surgical site infection and some risk factors were reported by kinds of literature, varying results were stated across studies. There is also limited knowledge on the association between postpartum surgical site infection and the rupture of membrane. Hence, this systematic review and meta-analysis was designed to estimate the pooled proportion of surgical site infection and its association with rupture of membrane following cesarean section in Africa. Methods Studies published from January 01, 2000 to January 30, 2020 were searched from MEDLINE via PubMed, Scopus, Medscape, Web-science and CINAHL databases to search relevant published articles. We also performed a manual search of reference lists of key articles to retrieve additional relevant articles. Initially, 559 records were identified and 15 studies included in the analysis. The statistical analysis was performed using STATA 11. Heterogeneity between-study was explored by forest plot and inconsistency index (I2). The publication bias was checked by a funnel plot and Egger’s test. Pooled estimates of proportion and odds ratio were calculated by a random-effects model with a 95% confidence interval (CI). Results The overall pooled proportion of surgical site infection following cesarean section was 10.21% (I2 = 86.8, p < 0.000; 95% CI = 8.36, 12.06). The odds of developing surgical site infection among women who had the rupture of membrane before delivery were nearly 6 times higher than those who had not a rupture of the membrane (AOR = 5.65, 95% CI: 3.95–8.07). Conclusions The proportion of surgical site infections following the cesarean section is relatively high. Women who had rupture of the membrane before delivery were more likely to develop surgical site infections following the cesarean section. Due attention should be given to the provision of prophylactic antibiotics that can reduce surgical site infection after cesarean delivery.

Reducing inconsistency in AHP by combining Delphi and Nudge theory and network analysis of the judgements: an application to future scenarios

The Analytic Hierarchy Process (AHP) is a Multi-Criteria method in which a number of decision factors (typically criteria and alternatives) are compared pairwise by one or more experts, using the Saaty scale, with the goal of sorting the alternatives (Saaty, 1977; 1980). For group AHP the Delphi method can be used in parallel with the AHP (Di Zio and Maretti, 2014), and this allows the search for a consensus on each pairwise judgement. A big issue of the AHP regards the inconsistency of the pairwise comparison matrices and here we propose a new method to reduce the inconsistency. As a solution we exploit the Nudge theory (Thaler and Sunstein, 2008) and from the second round of the Delphi survey, we calculate and circulate a Nudge to “gentle push” the experts towards more consistent evaluations. Furthermore, we propose the representation of the AHP matrices through graphs. In a direct graph two nodes are linked with two direct and weighted edges (or one edge with the direction based on the weights), where the weights indicate the evaluation given by an expert or, for a group, the geometric mean of the judgements. This type of visualization facilitates the reading of the results and could also be used as real-time feedback in the Delphi process, by displaying on the edges also a measure of variability. An application is proposed, on the evaluation of four future scenarios on the regulation of genetic modification experiments, assessed by a panel of 27 experts according to different criteria (plausibility, consistency and simplicity). The application demonstrated that it is possible to: a) reduce the inconsistency; b) collect useful textual material which enrich the AHP itself; c) use the inconsistency index as a stopping criterion for the Delphi rounds; d) display the pairwise comparison matrices with graphs.

Effects of Quran Recitation on the Reduction of Preoperative Anxiety in Elective Surgery: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background: Anxiety is a common reaction among patients undergoing surgery. This study aim to assess effectiveness of Quran recitation on reducing the preoperative anxiety.Methods: A systematic review of the citations in the Medline, EMBASE, Cochrane Library, PsycInfo, Arab World Research Source and other relevant databases was performed to collect the data. Randomized clinical trials about the effect of Quran recitation on the reduction of preoperative anxiety in elective surgery were included without any Language and date restriction. Interventions with self-reading/self-recitation were excluded. The Cochran’s Q statistic and the (I2) with 50 percent threshold was used for calculation of the heterogeneity and inconsistency index. Subgroup analysis was conducted based on the type of surgery. The funnel plot has been used to evaluate the possibility of the publication bias.Results:Twelve studies were included in the qualitative synthesis and nine studies included in the quantitative synthesis. Our meta-analysis showed a significant reduction in the anxiety level with Quran recitation. The heterogeneity of the included studies was statistically significant (Q=23.05, I2=65.29, P=0.003). The pooled effect size of the anxiety was d=−8.893; 95% CI=[−10.763 to −7.022] (P < 0.001). The subgroup analysis showed that Quran recitation has a beneficial effect on reducing anxiety in both major and minor surgeries.There was no publication bias (t=0.907, P=0.39) in the studies.Conclusion: Quran recitation can be considered as a non-invasive and peaceful intervention to reduce preoperative anxiety in elective surgery.