Systematic Reviews Of Observational Studies Research Articles

Resveratrol and male infertility: a systematic review of the literature.

The aim of this study is to provide an updated and comprehensive systematic review on the effects of resveratrol (RSV) in male infertility and sperm preservation. This systematic review followed the MOOSE guidelines for Meta-analyses and Systematic Reviews of Observational Studies and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P). Only original articles evaluating the effect of RSV on human spermatozoa in vivo or in vitro were included. Of the 1806 abstracts evaluated for eligibility, only 12 studies were included in the qualitative synthesis, of which three were prospective in-vivo studies and nine were in-vitro studies. Out of three human studies on RSV, only two studies administered RSV alone, one of them reported a positive impact and the other reported no significant impact on semen parameters. Overall, the in-vitro studies have reported the ability of RSV to protect spermatozoa against damage due to freeze-thaw cycles during cryopreservation. Other in-vitro studies have reported positive effects of RSV in fresh samples and protective effects in cell lines. Available in-vivo studies are controversial with regard to the effect of RSV in improving semen parameters. In-vitro studies support the use of RSV before sperm cryopreservation. Further well-designed prospective studies on large sample sizes are needed to fully understand the role of RSV in the treatment of male infertility in vivo.

Does Sperm SNRPN Methylation Change with Fertility Status and Age? A Systematic Review and Meta-Regression Analysis.

Background: The Small Nuclear Ribonucleoprotein Polypeptide N (SNRPN) gene is a paternally expressed imprinted gene, whose abnormal methylation appears to be associated with syndromes associated with the use of assisted reproductive techniques (ART), such as Angelman and Prader-Willi. Data present in the literature suggest the association between aberrant sperm SNRPN gene methylation and abnormal sperm parameters. The latest meta-analysis on the methylation pattern of this gene in spermatozoa of infertile patients published in 2017 reported a higher degree of methylation in the spermatozoa of infertile patients compared to fertile controls. Objectives: Here we provide an updated and comprehensive systematic review and meta-analysis of the sperm methylation pattern of the SNRPN gene in patients with abnormal sperm parameters/infertility compared to men with normal sperm parameters/fertile. For the first time in the literature, we performed a meta-regression analysis to evaluate whether age or sperm concentration could influence the methylation status of this gene at the sperm level. Methods: This meta-analysis was registered in PROSPERO (n. CRD42023397056). The Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P) and the MOOSE guidelines for meta-analyses and systematic reviews of observational studies were strictly followed in our meta-analysis. According to our Population Exposure Comparison Outcome (PECO) question, we included data from original articles assessing the levels of SNRPN gene methylation at the sperm level in infertile patients or patients with abnormalities in one or more sperm parameters compared to fertile or normozoospermic men. Results: Only six of 354 screened studies were included in the quantitative synthesis. Our analysis showed significantly higher levels of SNRPN gene methylation in patients compared to controls. However, significant heterogeneity was found between studies. In sensitivity analysis, no studies were sensitive enough to skew the results. The Egger test showed no publication bias. In the meta-regression analysis, the results were independent of age and sperm concentration in the overall population. The same results were found in the control group. However, when analyzing the patient group, a direct correlation was found between SNRPN methylation and age, indicating that the degree of methylation of the SNRPN gene increases with advancing age. Conclusions: Fertility status or abnormality of sperm parameters is associated with a change in the methylation pattern of the SNRPN gene, with higher levels found in infertile patients or those with abnormal sperm parameters compared to fertile men or men with normal sperm parameters. In the group of infertile patients/patients with abnormal sperm parameters, age was directly correlated to the degree of SNRPN methylation, highlighting the presence of a mechanism that explains the age-related altered sperm quality and the risk of ART. Despite some limitations present in the analyzed studies, our results support the inclusion of SNRPN methylation in the genetic panel of prospective studies aimed at identifying the most representative and cost-effective genes to analyze in couples who want to undergo ART.

Assessing risk of bias in the meta-analysis of round 1 of the Health Care Innovation Awards

BackgroundSystematic reviews of observational studies can be affected by biases that lead to under- or over-estimates of true intervention effects. Several tools have been reported in the literature that attempt to characterize potential bias. Our objective in this study was to determine the extent to which study-specific bias may have influenced intervention impacts on total costs of care (TCOC) in round 1 of the Health Care Innovation Awards.MethodsWe reviewed 82 statistical evaluations of innovation impacts on Medicare TCOC. We developed five risk-of-bias measures and assessed their influence on TCOC impacts using meta-regression.ResultsThe majority of evaluations used propensity score matching to create their comparison groups. One third of the non-randomized interventions were judged to have some risk of biased effects due largely to the way they recruited their treatment groups, and 35% had some degree of covariate imbalance remaining after propensity score adjustments. However, in the multivariable analysis of TCOC effects, none of the bias threats we examined (comparison group construction method, risk of bias, or degree of covariate imbalance) had a major impact on the magnitude of HCIA1 innovation effects. Evaluations using propensity score weighting produced larger but imprecise savings effects compared to propensity score matching.DiscussionOur results suggest that it is unlikely that HCIA1 TCOC effect sizes were systematically affected by the types of bias we considered. Assessing the risk of bias based on specific study design features is likely to be more useful for identifying problematic characteristics than the subjective quality ratings used by existing risk tools.

GUIA PARA REVISÃO SISTEMATICA DE ESTUDOS OBSERVACIONAIS

ABSTRACT Objective: to describe a guide for the development of systematic reviews of observational studies and systematization of international guidelines and tools, focusing on diverse evidence for innovation and clinical practice. Method: this theoretical-conceptual study was initiated during the development of a systematic review with meta-analysis of observational studies, using international guidelines and tools. Results: a guide was constructed to develop systematic reviews of observational studies. Diverse information about several stages and requirements for conducting a systematic review based on international guidelines and tools was systematized, aiming to ensure scientific rigor in manuscripts written by professionals from the health area. Conclusion: this study contributes to research in the health area by innovatively synthesizing guidance on the systematic review method and approaches. The references herein used serve as a starting point for understanding the procedures and international tools necessary for a systematic review of observational studies.

Sperm Mesoderm Specific Transcript Gene Methylation Status in Infertile Patients: A Systematic Review and Meta-Analysis.

The mesoderm specific transcription (MEST) gene is a paternally expressed imprinted gene that appears to play a role in embryo survival. The latest meta-analysis on MEST methylation pattern in spermatozoa of infertile patients found higher methylation in spermatozoa from infertile patients than fertile controls. To provide an updated and comprehensive systematic review and meta-analysis on the MEST gene methylation pattern in patients with abnormal sperm parameters compared to men with normal parameters. This meta-analysis was registered in PROSPERO (CRD42023397056) and performed following the MOOSE guidelines for Meta-analyses and Systematic Reviews of Observational Studies and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P). Only original articles evaluating MEST gene methylation in spermatozoa from patients with infertility or abnormalities in one or more sperm parameters compared to fertile or normozoospermic men were included. Of 354 abstracts evaluated for eligibility, only 6 studies were included in the quantitative synthesis, involving a total of 301 patients and 163 controls. Our analysis showed significantly higher levels of MEST gene methylation in patients compared with controls (standard mean difference [SMD] 2.150, 95% confidence interval [CI] 0.377, 3.922; p=0.017), although there was significant heterogeneity between studies (Q-value=239.90, p<0.001; I²=97.91%). No significant evidence of publication bias was found, although one study was sensitive enough to skew the results, leading to a loss of significance (SMD 1.543, 95% CI -0.300, 3.387; p=0.101). In meta-regression analysis, we found that the results were independent of both ages (p=0.6519) and sperm concentration (p=0.2360). Sperm DNA methylation may be associated with epigenetic risk in assisted reproductive techniques (ART). The MEST gene could be included in the genetic panel of prospective studies aimed at identifying the most representative and cost-effective genes to be analyzed in couples undergoing ART.

Signal of harm in morphine use in adults with acute pulmonary oedema: A rapid systematic review.

Heart failure affects nearly 65million people globally, resulting in recurrent hospital admissions and substantial healthcare expenditure. The use of morphine in the management of acute pulmonary oedema remains controversial, with conflicting guidance and significant variation in practice. Synthesised evidence is needed to inform standard treatment guidelines and clinical practice. To determine whether morphine should be used in the treatment of acute pulmonary oedema (APE) in adults. A rapid review of systematic reviews of randomised controlled trials or observational studies, and then randomised controlled trials, was conducted searching three electronic databases (PubMed, Embase, Cochrane Library) and one clinical trial registry on 12February 2022. We used a prespecified protocol following Cochrane rapid review methods and aligned to the National Standard Treatment Guidelines and Essential Medicines List methodology. We first considered relevant high-quality systematic reviews of randomised controlled trials or observational studies, then (if required) randomised controlled trials to inform time-sensitive or urgent evidence requests, clinical practice, policy, or standard treatment guidelines. We identified four systematic reviews of observational studies. The two most relevant, up-to-date, and highest-quality reviews were used to inform evidence for critical outcomes. Morphine may increase in-hospital mortality (odds ratio (OR) 1.78; 95% confidence interval (CI) 1.01 - 3.13; low certainty of evidence; six observational studies, n=151735 participants), resulting in 15 more per 1000 hospital deaths, ranging from 0 to 40 more hospital deaths. Morphine may result in a large increase in invasive mechanical ventilation (OR 2.72; 95% CI 1.09- 6.80; low certainty of evidence; four observational studies, n=167847 participants), resulting in 45 more per1000 ventilations, ranging from 2 more to 136 more. Adverse events and hospital length of stay were not measured across reviews ortrials. Based on the most recent, relevant and best-available quality evidence, morphine use in adults with APE may increase in-hospital and all-cause mortality and may result in a large increase in the need for invasive mechanical ventilation compared to not using morphine. Recommending against the use of morphine in pulmonary oedema may improve patient outcomes. Disinvesting in morphine for this indication may result in cost savings, noting the possible accrued benefits of fewer patients requiring invasive ventilation and management of morphine-related side-effects.

P11-064-23 Environmental Elements and Cardiovascular Diseases: A Series of Systematic Reviews of Observational Studies and Meta-Analysis

P11-064-23 Environmental Elements and Cardiovascular Diseases: A Series of Systematic Reviews of Observational Studies and Meta-Analysis

H19 Sperm Methylation in Male Infertility: A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis summarize the difference in the methylation of the H19 gene in patients with abnormal versus normal conventional sperm parameters. It also evaluates the effects of age and sperm concentration on H19 methylation in spermatozoa using meta-regression analysis. It was performed according to the MOOSE guidelines for meta-analyses and Systematic Reviews of Observational Studies and the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P). The quality of the evidence reported in the studies included was assessed using the Cambridge Quality Checklists. A total of 11 articles met our inclusion criteria. Quantitative analysis showed that H19 methylation levels were significantly lower in the group of infertile patients than in fertile controls. The reduction in methylation was much more pronounced in patients with oligozoospermia (alone or associated with other sperm parameter abnormalities) and in those with recurrent pregnancy loss. Meta-regression analysis showed the results to be independent of both patient age and sperm concentration. Therefore, the H19 methylation pattern should be evaluated among couples accessing assisted reproductive techniques (ART), in order to gain prognostic information on ART outcome and offspring health.

The Effectiveness and Safety of Metformin Compared to Sulfonylureas in Diabetic Nephropathy: A Systematic Review.

Metformin and sulphonylureas are the most commonly used first-line anti-diabetic agents. However, medical practice guidelines and clinical experience caution against using these drugs in severe diabetic kidney disease. Consequently, the choice of anti-diabetic medicine in various stages of diabetic nephropathy should balance the benefits and risks to the patient. We aim to synthesize available evidence on the effectiveness and safety of metformin concerning sulfonylureas in patients with diabetic renal disease. The COSMOS-E (Guidance on conducting systematic reviews and meta-analyses of observational studies of etiology) and MOOSE (Meta-Analyses and Systematic Reviews of Observational Studies in Epidemiology) guidelines were followed when designing the systematic review. The present study assessed the effectiveness of metformin and sulphonylurea monotherapy regarding renal function. Studies published from 2001 to 2022 were included. We have identified 570 records from PubMed, BioMed Central, LILACS (Literatura Latino-Americana e do Caribe em Ciências da Saúde), ScienceDirect, and PLoS (The Public Library of Science) Medicine databases. Eight cohort studies met the inclusion criteria. All studies reported adjusted hazard ratios with confidence limits. Metformin was found to be more effective in the following events: all-cause mortality, GFR (glomerular filtration rate), ESRD (end-stage renal disease) or death events, one-year risk of death or end-stage renal disease, cardiovascular events, heart failure hospitalization, and hypoglycemic episodes. However, metformin was less effective in acute renal replacement therapy, end-stage renal disease, and/or death, with a one-year risk of acute dialysis. Lactic acidosis was not significant with metformin. The present study recommends that metformin therapy is safe compared to sulfonylurea therapy in diabetic nephropathy patients, provided that the contraindications given in the guidelines are strictly adhered to.

Inappropriate Methods May Lead to Misleading Conclusions From the Meta-analysis of Observational Studies.

To the Editors: We read the article by Renko and colleagues with the outmost interest.1 This article discusses an important and relevant aspect of urinary tract infection (UTI) for pediatricians. The authors in this article systematically reviewed and synthesized data on risk factors for UTI in children. Twenty-four studies were included in the meta-analysis. Authors found that circumcision and breastfeeding reduce the risk of UTI, and poor fluid intake, infrequent voiding, and being overweight or obese increase the risk of UTI recurrence in children. More importantly, the authors also observed that obstipation and high-grade vesicoureteric reflux do not increase the risk of recurrent UTIs. Overall, this article addresses an important issue for clinicians, but we came across a few methodological concerns, which may affect the validity of the findings of this meta-analysis. It is usually recommended that the literature search be comprehensive (at least 2–3 bibliographic electronic databases) before conducting a meta-analysis. Systematic reviews of observational studies require an even more robust literature search.2,3 Authors performed a literature search only in 1 database (PubMed); hence, the likely possibility that few studies may have been missed putting this systematic review at higher risk of publication bias. In this article, authors did not report publication bias, which was not discussed under limitations. A few missed studies (Gondim et al. 2018, Shaikh et al. 2016, Conway et al. 2007, and Cho et al. 2005) that assess risk factors for UTI are missed. High-grade VUR and bladder-bowel dysfunction (BBD) are 2 widely recognized and reported risk factors for UTI. Still, the present meta-analysis failed to demonstrate these risk factors for recurrence of UTI, as the literature search was not extensive and missed studies. The authors state that they have followed the checklist of the Meta-analysis of Observational Studies in Epidemiology group (MOOSE) but failed to report the search strategy for literature search, which is an essential component per this MOOSE guidance. In the current risk-stratification model for recurrence of UTI, age, sex, VUR severity, BBD, and circumcision status are considered important factors.4 However, the authors in this meta-analysis did not assess age and sex as risk factors and failed to show the other 2 factors (BBD and VUR) as risk predictors for recurrent UTI in children. Similarly, some studies (Ellison et al. 2018, Dubrovsky et al. 2015, Braga et al. 2015, Alsaywid et al. 2010, Nayir et al. 2001) assessing the circumcision status as a risk factor for UTI are also missed.5 These findings are likely caused by a suboptimal literature search and an inappropriate study selection process. The authors mention low heterogeneity in the text, but it has not been reported for most risk factors except I2 –7.5% for circumcision status. Furthermore, the authors do not explicitly report what was considered severe congenital renal abnormalities as they used it as one of the exclusion criteria. Although they included studies with VUR grade IV and V, we feel that these limitations could have been better discussed in the limitation section because these may have had a significant impact on this meta-analysis’s finding.

Diet quality indices and their associations with all-cause mortality, CVD and type 2 diabetes mellitus: an umbrella review.

Numerous observational studies have investigated associations between diet indices and health outcomes. Our aim was to systematically synthesise data that was previously summarised separately for each diet index in one umbrella review of all diet indices with sufficient evidence gained in systematic reviews and to assess the quality and strength of evidence for selected health outcomes. The MEDLINE, EMBASE and Scopus databases were systematically searched following the PRISMA guidelines through October 2021 for systematic reviews of observational studies investigating associations between adherence to diet indices and selected health outcomes (all-cause mortality, CVD incidence or mortality, type 2 diabetes mellitus incidence or mortality). Methodological quality and quality of evidence were assessed using the AMSTAR 2 and NutriGrade tools. The inclusion criteria were met by seven systematic reviews, entirely based on prospective cohort studies and reviewing five different diet indices - alternate healthy eating index (AHEI), dietary approaches to stop hypertension (DASH), dietary inflammatory index (DII), healthy eating index (HEI) and Mediterranean diet (MedDiet). All seven included systematic reviews showed that greater adherence to these diet indices reduces the risks of all-cause mortality, CVD incidence and mortality and type 2 diabetes mellitus incidence. Moderate meta-evidence was presented for AHEI and DASH for all outcomes, also for DII for all-cause mortality, CVD mortality and incidence, MedDiet for all-cause mortality and for HEI for CVD incidence and mortality. Our umbrella review provides further evidence for AHEI, DASH, DII and HEI diet indices to be used as predictors of selected health outcomes.

Diagnostic test accuracy of novel biomarkers for lupus nephritis-An overview of systematic reviews.

IntroductionSystemic lupus erythematosus (SLE) is a chronic autoimmune disease with multiorgan inflammatory involvement and a mortality rate that is 2.6-fold higher than individuals of the same age and sex in the general population. Approximately 50% of patients with SLE develop renal impairment (lupus nephritis). Delayed diagnosis of lupus nephritis is associated with a higher risk of progression to end-stage renal disease, the need for replacement therapy, and mortality. The initial clinical manifestations of lupus nephritis are often discrete or absent and are usually detected through complementary tests. Although widely used in clinical practice, their accuracy is limited. A great scientific effort has been exerted towards searching for new, more sensitive, and specific biomarkers in recent years. Some systematic reviews have individually evaluated new serum and urinary biomarkers tested in patients with lupus nephritis. This overview aimed to summarize systematic reviews on the accuracy of novel serum and urinary biomarkers for diagnosing lupus nephritis in patients with SLE, discussing how our results can guide the clinical management of the disease and the direction of research in this area.MethodsThe research question is “What is the accuracy of the new serum and urinary biomarkers studied for the diagnosis of LN in patients with SLE?”. We searched for systematic reviews of observational studies evaluating the diagnostic accuracy of new serum or urinary biomarkers of lupus nephritis. The following databases were included: PubMed, EMBASE, BIREME/LILACS, Scopus, Web of Science, and Cochrane, including gray literature found via Google Scholar and PROQUEST. Two authors assessed the reviews for inclusion, data extraction, and assessment of the risk of bias (ROBIS tool).ResultsTen SRs on the diagnostic accuracy of new serum and urinary BMs in LN were selected. The SRs evaluated 7 distinct BMs: (a) antibodies (anti-Sm, anti-RNP, and anti-C1q), (b) cytokines (TWEAK and MCP-1), (c) a chemokine (IP-10), and (d) an acute phase glycoprotein (NGAL), in a total of 20 review arms (9 that analyzed serum BMs, and 12 that analyzed BMs in urine). The population evaluated in the primary studies was predominantly adults. Two SRs included strictly adults, 5 reviews also included studies in the paediatric population, and 4 did not report the age groups. The results of the evaluation with the ROBIS tool showed that most of the reviews had a low overall risk of bias.ConclusionsThere are 10 SRs of evidence relating to the diagnostic accuracy of serum and urinary biomarkers for lupus nephritis. Among the BMs evaluated, anti-C1q, urinary MCP-1, TWEAK, and NGAL stood out, highlighting the need for additional research, especially on LN diagnostic panels, and attempting to address methodological issues within diagnostic accuracy research. This would allow for a better understanding of their usefulness and possibly validate their clinical use in the future.RegistrationThis project is registered on the International Prospective Registry of Systematic Reviews (PROSPERO) database (CRD42020196693).

Quality of systematic reviews of COVID-19 in people with diabetes: A systematic review

ObjectiveTo investigate the methodological quality of published systematic reviews of factors associated with COVID-19 in people with diabetes. MethodSystematic review with registration protocol in PROSPERO, under the number CRD42020222418. Searches were carried out from October to November 2020 in the databases of the MedLine, Web of Science, Scopus, Lilacs, Embase and Cochrane libraries, in addition to searching the reference list of the selected studies. Systematic review studies with or without meta-analysis and without date and language restrictions were included. Data were extracted in a standardized way and the quality of the studies was assessed using the Assessment of Multiple Systematic Reviews scale. ResultsTwelve reviews, published between 2020 and 2021, with a predominance of the English language, systematic reviews of observational studies with meta-analysis with a sample ranging from six to 83 studies, were included. Regarding financing, most of the study reported did not receive this type of support. Regarding to the assessment of the methodological quality of the studies, three were of moderate quality, five were classified as low quality and three with critically low quality. ConclusionsThe analyzed articles presented a bias in the preparation of reports on their studies, suggesting the need to use mechanisms to improve adherence to the established reporting guidelines and methodological evaluation tools.

Reversible Cerebral Vasoconstriction Syndrome in the Postpartum Period: A Systematic Review and Meta-Analysis.

(1) Background: Reversible cerebral vasoconstriction syndrome (RCVS) encompasses a clinical and radiological diagnosis characterized by recurrent thunderclap headache, with or without focal deficits due to multifocal arterial vasoconstriction and dilation. RCVS can be correlated to pregnancy and exposure to certain drugs. Currently, the data on prevalence of RCVS in the postpartum period is lacking. We aim to investigate the prevalence of RCVS in the postpartum period and the rate of hemorrhagic complications of RCVS among the same group of patients; (2) Methods: We conducted the metanalysis by using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), and Meta-Analyses and Systematic Reviews of Observational Studies in Epidemiology (MOOSE) protocol. To analyze the Bias, we used the Ottawa Newcastle scale tool. We included only full-text observational studies conducted on humans and written in English. We excluded Literature Reviews, Systematic Reviews, and Metanalysis. Additionally, we excluded articles that did not document the prevalence of RCVS in the postpartum period (3). Results: According to our analysis, the Prevalence of RCVS in the postpartum period was 129/1083 (11.9%). Of these, 51/100 (52.7%) patients had hemorrhagic RCVS vs. 49/101 (49.5%) with non-hemorrhagic RCVS. The rates of Intracerebral Hemorrhage (ICH) and Subarachnoid Hemorrhage (SAH) were (51.6% and 10.7%, respectively. ICH seems to be more common than.; (4) Conclusions: Among patients with RCVS, the prevalence in PP patients is relativity high. Pregnant women with RCVS have a higher recurrence of hemorrhagic vs. non-hemorrhagic RCVS. Regarding the type of Hemorrhagic RCVS, ICH is more common than SAH among patients in the postpartum period. Female Sex, history of migraine, and older age group (above 45) seem to be risk factors for H-RCVS. Furthermore, recurrence of RCVS is associated with a higher age group (above 45). Recurrence of RCVS is more commonly idiopathic than being triggered by vasoactive drugs in the postpartum period.

The role of donor-recipient gender matching in lung transplantation: a systematic review.

Donor to recipient (D-R) matching in lung transplantation (LTx) is firstly directed by blood group (identity or compatibility), immunological status and morphological criteria. Sex matching is ignored and impact on outcome less investigated. Systematic review of English literature using PubMed (1990-2019) was performed to evaluate the potential role of D-R matching in determining long-term outcome in patients after LTx. Search terms included (LTx) AND (sex) OR (gender) OR (matching) OR (mismatch) OR (donor characteristics) and were restricted to articles' title. Only articles directly reporting LTx survival outcome according to gender match/mismatch and D-R gender combination in LTx were included. Two authors independently extracted articles using predefined data fields, including study quality indicators. MOOSE Guidelines for Meta-Analyses and Systematic Reviews of Observational Studies applied. Nine articles were analyzed and included into this study. All studies analyzed the effect of the different D-R gender combinations on survival while seven of them investigated exclusively the role of sex matching on LTx outcome. In this latter group two out of seven showed a trend towards an overall survival advantage for sex matching LTx combination. The worst survival results were reported for F to M gender combination in 3 studies and for M to F gender combination by 1 study. No differences were reported in remaining 4 studies. This systematic review suggests that sex matching and several gender combinations could play a role in determining overall survival rate after LTx. Data deriving from unbiased studies supported that matching female-female (F-F) and male-male (M-M) could improve LTx outcome while FD-MR combination should be avoided. Unfortunately, a good part of the analyzed data are affected by bias due to confounding factors. Up-to-date immunological, hormonal and morphological factors could explain the gender-based difference in LTx outcome. Further investigations should clarify their role and importance to define the effects of gender combinations on survival.

Occurrence rate and risk factors for long-term central line-associated bloodstream infections in patients with cancer: A systematic review.

Central line-associated bloodstream infection (CLABSI) is a public health problem that harms patients' outcomes and healthcare costs, especially in susceptible populations such as patients with cancer. Overall, systematic queries about etiology, risks, and epidemiology are explained by data from observational studies, which better underline the relationship between factors and incidence of disease. However, no recent systematic reviews of observational studies on adult patients with cancer have been conducted on this topic, considering the wide range of all potential factors which can contribute to the increase in infection rate in the hospitalized adults with cancer. This study systematically reviewed observational studies investigating the occurrence rate of CLABSI and its risk factors for long-term inserted central catheter-related infections in hospitalized adult cancer patients. A systematic review was performed on four databases from the earliest available date until December 2020. Retrospective and prospective cohort studies focused on the occurrence rate of CLABSI and its risk factors in hospitalized adult cancer patients. The pooled occurrence rate of CLABSI (95% CI) was calculated by applying a random-effects model. Of 1712studies, 8 were eligible, and the data of device-related infection rate were meta-analyzed. The pooled occurrence rate of CLABSI was roughly 8% (95% CI [4%, 14%]). The device characteristics, device's management aspects, therapies administration, and select patients' clinical conditions represent the main risk factors for long-term catheter-related infection in cancer patients. Considering the substantial infection rate among cancer patients, identifying risk rate factors is pivotal to support evidence-grounded preventive strategies and maximize cancer patient safety. This study's results could guide policymakers and healthcare leaders and future research studies to disseminate appropriate risk-reducing management culture and implement standardized research and clinical approach to the investigated phenomenon as an infection surveillance strategy.

Potential importance of residual confounding in systematic reviews of observational studies: Answer to Mathur and VanderTweele.

Potential importance of residual confounding in systematic reviews of observational studies: Answer to Mathur and VanderTweele.

The confounder matrix: A tool to assess confounding bias in systematic reviews of observational studies of etiology.

Systematic reviews and meta-analyses are essential for drawing conclusions regarding etiologic associations between exposures or interventions and health outcomes. Observational studies comprise a substantive source of the evidence base. One major threat to their validity is residual confounding, which may occur when component studies adjust for different sets of confounders, fail to control for important confounders, or have classification errors resulting in only partial control of measured confounders. We present the confounder matrix-an approach for defining and summarizing adequate confounding control in systematic reviews of observational studies and incorporating this assessment into meta-analyses. First, an expert group reaches consensus regarding the core confounders that should be controlled and the best available method for their measurement. Second, a matrix graphically depicts how each component study accounted for each confounder. Third, the assessment of control adequacy informs quantitative synthesis. We illustrate the approach with studies of the association between short interpregnancy intervals and preterm birth. Our findings suggest that uncontrolled confounding, notably by reproductive history and sociodemographics, resulted in exaggerated estimates. Moreover, no studies adequately controlled for all core confounders, so we suspect residual confounding is present, even among studies with better control. The confounder matrix serves as an extension of previously published methodological guidance for observational research synthesis, enabling transparent reporting of confounding control and directly informing meta-analysis so that conclusions are drawn from the best available evidence. Widespread application could raise awareness about gaps across a body of work and allow for more valid inference with respect to confounder control.

Teaching and learning in the content of International Mobility: An overview of the existing evidence

Universities and educational organizations aim to bring an innovative approach to internationalization in higher education in the digital environment. They focus on enhancing and cultivating the students' communication and intercultural competencies and building self-confidence in an international environment. This study presents an overview of the existing educative strategies and innovative interventions used for integrating/developing International Mobility (IM hereafter) competencies in higher education. For this purpose, we searched various databases following the MOOSE Guidelines for Meta-Analyses and Systematic Reviews of Observational Studies in the last five years. Our findings reveal the literature gap regarding teaching and learning in the content of International Mobility and extend the possibilities for future research directions.

An approach to quantifying the potential importance of residual confounding in systematic reviews of observational studies: A GRADE concept paper.

Small relative effect sizes are common in observational studies of exposure in environmental and public health. However, such effects can still have considerable policy importance when the baseline rate of the health outcome is high, and many persons are exposed. Assessing the certainty of the evidence based on these effect sizes is challenging because they can be prone to residual confounding due to the non-randomized nature of the evidence. When applying GRADE, a precise relative risk >2.0 increases the certainty in an existing effect because residual confounding is unlikely to explain the association. GRADE also suggests rating up when opposing plausible residual confounding exists for other effect sizes. In this concept paper, we propose using the E-value, defined as the smallest effect size of a confounder that still can reduce an observed RR to the null value, and a reference confounder to assess the likelihood of residual confounding. We propose a 4-step approach. 1. Assess the association of interest for relevant exposure levels. 2. Calculate the E-value for this observed association. 3. Choose a reference confounder with sufficient strength and information and assess its effect on the observed association using the E-value. 4. Assess how likely it is that residual confounding will still bias the observed RR. We present three case studies and discuss the feasibility of the approach.