Evidence Of Small-study Effects Research Articles

An Umbrella Review for Assessment of Treatment Effectiveness of Clear Aligners Compared to Conventional Fixed Appliances in Orthodontic Patients

Introduction Orthodontic improvements, mainly through the previous decade, have led to a substantial rise in patients’ esthetic needs. Traditional orthodontic procedures have been linked with a compromise in facial appearance, which increases concern among patients pursuing orthodontic treatment. Methods PubMed, MEDLINE, Google Scholar, and Cochrane Library of Systematic Reviews databases were searched using appropriate entry terms and Boolean operators. Search strategy was conducted till June 2022 for systematic reviews and meta-analyses. Publications were systematically assessed for eligibility, and two observers independently graded the methodologic quality using AMSTAR-2 tool. For each meta-analysis, we estimated the summary effect size by the use of random-effects and fixed-effects models and the 95% confidence interval. We estimated the between-study heterogeneity expressed by I 2 (defined as large for I 2 ≥50%), evidence of small-study effects (i.e., large studies had significantly more conservative results than smaller studies), and evidence of excess significance bias (i.e., more studies than expected with significant results). Results Overall, 16 unique systematic reviews and meta-analyses following the eligibility criteria were selected for umbrella review. The results of qualitative analysis of studies revealed that 4 studies had a critically low risk of bias, 11 showed low risk, and 1 study had moderate risk. The results of the meta-analysis favored clear aligners with respect to oral hygiene and root resorption parameters. When tooth movements were considered, the results favored conventional orthodontic treatment. Conclusion Clear aligner therapy (CAT) has significant advantages with regard to efficiency (treatment time, chair time) in mild-moderate malocclusion cases. The overall accuracy of CAT when compared to fixed orthodontic treatment was found to be 55-82%.

Ultra-processed foods and human health: An umbrella review and updated meta-analyses of observational evidence

Background & aimsUltra-processed food (UPF) intake has increased sharply over the last few decades and has been consistently asserted to be implicated in the development of non-communicable diseases. We aimed to evaluate and update the existing observational evidence for associations between ultra-processed food (UPF) consumption and human health. MethodsWe searched Medline and Embase from inception to March 2023 to identify and update meta-analyses of observational studies examining the associations between UPF consumption, as defined by the NOVA classification, and a wide spectrum of health outcomes. For each health outcome, we estimated the summary effect size, 95% confidence interval (CI), between-study heterogeneity, evidence of small-study effects, and evidence of excess-significance bias. These metrics were used to evaluate evidence credibility of the identified associations. ResultsThis umbrella review identified 39 meta-analyses on the associations between UPF consumption and health outcomes. We updated all meta-analyses by including 122 individual articles on 49 unique health outcomes. The majority of the included studies divided UPF consumption into quartiles, with the lowest quartile being the reference group. We identified 25 health outcomes associated with UPF consumption. For observational studies, 2 health outcomes, including renal function decline (OR: 1.25; 95% CI: 1.18, 1.33) and wheezing in children and adolescents (OR: 1.42; 95% CI: 1.34, 1.49), showed convincing evidence (Class I); and five outcomes were reported with highly suggestive evidence (Class II), including diabetes mellitus, overweight, obesity, depression, and common mental disorders. ConclusionsHigh UPF consumption is associated with an increased risk of a variety of chronic diseases and mental health disorders. At present, not a single study reported an association between UPF intake and a beneficial health outcome. These findings suggest that dietary patterns with low consumption of UPFs may render broad public health benefits.

Risk factors for preterm birth: an umbrella review of meta-analyses of observational studies

BackgroundPreterm birth defined as delivery before 37 gestational weeks is a leading cause of neonatal and infant morbidity and mortality. The aim of this study is to summarize the evidence from meta-analyses of observational studies on risk factors associated with PTB, evaluate whether there are indications of biases in this literature, and identify which of the previously reported associations are supported by robust evidence.MethodsWe searched PubMed and Scopus until February 2021, in order to identify meta-analyses examining associations between risk factors and PTB. For each meta-analysis, we estimated the summary effect size, the 95% confidence interval, the 95% prediction interval, the between-study heterogeneity, evidence of small-study effects, and evidence of excess-significance bias. Evidence was graded as robust, highly suggestive, suggestive, and weak.ResultsEighty-five eligible meta-analyses were identified, which included 1480 primary studies providing data on 166 associations, covering a wide range of comorbid diseases, obstetric and medical history, drugs, exposure to environmental agents, infections, and vaccines. Ninety-nine (59.3%) associations were significant at P < 0.05, while 41 (24.7%) were significant at P < 10−6. Ninety-one (54.8%) associations had large or very large heterogeneity. Evidence for small-study effects and excess significance bias was found in 37 (22.3%) and 12 (7.2%) associations, respectively. We evaluated all associations according to prespecified criteria. Seven risk factors provided robust evidence: amphetamine exposure, isolated single umbilical artery, maternal personality disorder, sleep-disordered breathing (SDB), prior induced termination of pregnancy with vacuum aspiration (I-TOP with VA), low gestational weight gain (GWG), and interpregnancy interval (IPI) following miscarriage < 6 months.ConclusionsThe results from the synthesis of observational studies suggest that seven risk factors for PTB are supported by robust evidence. Routine screening for sleep quality and mental health is currently lacking from prenatal visits and should be introduced. This assessment can promote the development and training of prediction models using robust risk factors that could improve risk stratification and guide cost-effective preventive strategies.Trial registrationPROSPERO 2021 CRD42021227296.

The Effects of Exercise-Based Injury Prevention Programmes on Injury Risk in Adult Recreational Athletes: A Systematic Review and Meta-Analysis.

Injuries are common in adult recreational athletes. Exercise-based injury prevention programmes offer the potential to reduce the risk of injury and have been a popular research topic. Yet, syntheses and meta-analyses on the effects of exercise-based injury prevention programmes for adult recreational athletes are lacking. We aimed to synthesise and quantify the pooled intervention effects of exercise-based injury prevention programmes delivered to adults who participate in recreation sports. Studies were eligible for inclusion if they included adult recreational athletes (aged > 16years), an exercise-based intervention and used a randomised controlled trial design. Exclusion criteria were studies without a control group, studies using a non-randomised design and studies including participants who were undertaking activity mandatory for their occupation. Eleven literature databases were searched from earliest record, up to 9 June, 2022. The Physiotherapy Evidence Database (PEDro) scale was used to assess the risk of bias in all included studies. Reported risk statistics were synthesised in a random-effects meta-analysis to quantify pooled treatment effects and associated 95% confidence intervals and prediction intervals. Sixteen studies met the criteria. Risk statistics were reported as risk ratios [RRs] (n = 12) or hazard ratios [HRs] (n = 4). Pooled estimates of RRs and HRs were 0.94 (95% confidence interval 0.80-1.09) and 0.65 (95% confidence interval 0.39-1.08), respectively. Prediction intervals were 0.80-1.09 and 0.16-2.70 for RR and HR, respectively. Heterogeneity was very low for RR studies, but high for HR studies (tau = 0.29, I2 = 81%). There was evidence of small study effects for RR studies, evidenced by funnel plot asymmetry and Egger's test for small study bias: - 0.99 (CI - 2.08 to 0.10, p = 0.07). Pooled point estimates were suggestive of a reduced risk of injury in intervention groups. Nevertheless, these risk estimates were insufficiently precise, too heterogeneous and potentially compromised by small study effects to arrive at any robust conclusion. More large-scale studies are required to clarify whether exercise-based injury prevention programmes are effective in adult recreational athletes. The protocol for this review was prospectively registered in the PROSPERO database (CRD42021232697).

Individual-level risk factors for suicide mortality in the general population: an umbrella review

Deaths by suicide remain a major public health challenge worldwide. Identifying and targeting risk factors for suicide mortality is a potential approach to prevention. We aimed to summarise current knowledge on the range and magnitude of individual-level risk factors for suicide mortality in the general population and evaluate the quality of the evidence. In this umbrella review, five bibliographic databases were systematically searched for articles published from database inception to Aug 31, 2022. We included meta-analyses of observational studies on individual-level risk factors for suicide mortality in the general population. Biological, genetic, perinatal, and ecological risk factors were beyond the scope of this study. Effect sizes were synthesised and compared across domains. To test robustness and consistency of the findings, evidence for small-study effects and excess significance bias (ie, the ratio between the overall meta-analysis effect size and that of its largest included study) was examined, and prediction intervals were calculated. Risk of bias was assessed by the Risk of Bias in Systematic Reviews instrument. The protocol was pre-registered with PROSPERO (CRD42021230119). We identified 33 meta-analyses on 38 risk factors for suicide mortality in the general population. 422 (93%) of the 454 primary studies included in the meta-analyses were from high-income countries. A previous suicide attempt and suicidal ideation emerged as strong risk factors (with effect sizes ranging from 6 to 16). Psychiatric disorders were associated with a greatly elevated risk of suicide mortality, with risk ratios in the range of 4-13. Suicide risk for physical illnesses (such as cancer and epilepsy) and sociodemographic factors (including unemployment and low education) were typically increased two-fold. Contact with the criminal justice system, state care in childhood, access to firearms, and parental death by suicide also increased the risk of suicide mortality. Among risk factors for which sex-stratified analyses were available, associations were generally similar for males and females. However, the quality of the evidence was limited by excess significance and high heterogeneity, and prediction intervals suggested poor replicability for almost two-thirds of identified risk factors. A wide range of risk factors were identified across various domains, which underscores suicide mortality as a multifactorial phenomenon. Prevention strategies that span individual and population approaches should account for the identified factors and their relative strengths. Despite the large number of risk factors investigated, few associations were supported by robust evidence. Evidence of causal inference will need to be tested in high-quality study designs. Wellcome Trust.

Individual-level exposures and risk of COVID-19: an umbrella review

Abstract As of April 2023, over 650 million people have been confirmed to have contracted COVID-19. The risk of transmission of COVID-19 might be influenced by various factors, including immunity from vaccination or previous infection, the use of personal protective equipment (PPE), indoors vs. outdoors environments, the degree of ventilation in indoor environments, and distance from the source of the infection. This review aims to assess the credibility of research conducted on individual risk factor epidemiology and prevention of COVID-19. A search was conducted on PubMed to identify systematic reviews and meta-analyses of studies examining the association between individual-level exposures and COVID-19. The study estimated the summary effect size and its 95% CI using both fixed-effect and random-effects models, and the 95% prediction interval was used to evaluate uncertainty. The study also examined heterogeneity among the studies and the presence of biases. We identified 141 meta-analyses examining 84 types of exposures or treatments. These were categorized into eight macro-groups: demographic factors, behavioural factors, dietary nutrient intake, comorbidities, drugs, PPE, contact types, and vaccination. Interventional studies comprised 5.7% of the total, contact tracing studies were 9.8%, and the remaining studies (84.5%) were other types of observational comparative studies. In these preliminary findings, the heterogeneity index (I2) ranged from large to very large, and there was evidence of small study effect and excess significance bias in many meta-analyses. Preliminary findings suggest that, apart from vaccines, for which abundant randomized evidence exists, the evidence base for COVID-19 prevention consists largely of studies of low or uncertain epidemiological credibility. Key messages • Overall epidemiological credibility of COVID-19 association studies might be low. • Rigorous methodological practices are recommended when conducting epidemiological studies.

Physical activity and risk of chronic kidney disease: systematic review and meta-analysis of 12 cohort studies involving 1,281,727 participants

The role of regular physical activity in preventing vascular and non-vascular disease is well established. Chronic kidney disease (CKD) is a major cause of global morbidity and mortality and largely preventable, but it is uncertain if regular physical activity can reduce the risk of CKD. Using a systematic review and meta-analysis of published observational cohort studies in the general population, we sought to assess the association between physical activity and CKD risk. Relevant studies with at least one-year of follow-up were sought from inception until 02 May 2022 in MEDLINE, Embase, Web of Science, and manual search of relevant articles. Relative risks (RRs) with 95% confidence intervals (CIs) for the maximum versus the minimal amount of physical activity groups were pooled using random effects meta-analysis. The quality of the evidence was evaluated using the GRADE tool. A total of 12 observational cohort studies comprising 1,281,727 participants and 66,217 CKD events were eligible for the analysis. The pooled multivariable-adjusted RR (95% CI) of CKD comparing the most versus the least physically active groups was 0.91 (0.85–0.97). The association was consistent across several study level subgroups. Exclusion of any single study at a time from the meta-analysis did not change the direction or significance of the association. There was no evidence of small study effects among contributing studies. The GRADE quality of the evidence was low. In the general population, individuals who are most physically active have a lowered risk of CKD compared to those who are not or least physically active. CRD42022327640.

Patterns of polysomnography parameters in 27 neuropsychiatric diseases: an umbrella review.

We provide an umbrella review of the reported polysomnographic changes in patients with neuropsychiatric diseases compared with healthy controls. An electronic literature search was conducted in EMBASE, MEDLINE, All EBM databases, CINAHL, and PsycINFO. Meta-analyses of case-control studies investigating the polysomnographic changes in patients with neuropsychiatric diseases were included. For each meta-analysis, we estimated the summary effect size using random effects models, the 95% confidence interval, and the 95% prediction interval. We also estimated between-study heterogeneity, evidence of excess significance bias, and evidence of small-study effects. The levels of evidence of polysomnographic changes in neuropsychiatric diseases were ranked as follows: not significant, weak, suggestive, highly suggestive, or convincing. We identified 27 articles, including 465 case-control studies in 27 neuropsychiatric diseases. The levels of evidence of polysomnographic changes in neuropsychiatric diseases were highly suggestive for increased sleep latency and decreased sleep efficiency (SE) in major depressive disorder (MDD), increased N1 percentage, and decreased N2 percentage, SL and REML in narcolepsy, and decreased rapid eye movement (REM) sleep percentage in Parkinson's disease (PD). The suggestive evidence decreased REM latency in MDD, decreased total sleep time and SE in PD, and decreased SE in posttraumatic stress disorder and in narcolepsy. The credibility of evidence for sleep characteristics in 27 neuropsychiatric diseases varied across polysomnographic variables and diseases. When considering the patterns of altered PSG variables, no two diseases had the same pattern of alterations, suggesting that specific sleep profiles might be important dimensions for defining distinct neuropsychiatric disorders.

Effectiveness of exercise intervention during pregnancy on high-risk women for gestational diabetes mellitus prevention: A meta-analysis of published RCTs.

We aimed at investigating the preventive role of exercise intervention during pregnancy, in high-risk women for gestational diabetes mellitus (GDM). We searched PubMed, CENTRAL, and Scopus for randomized controlled trials (RCTs) that evaluated exercise interventions during pregnancy on women at high risk for GDM. Data were combined with random effects models. Between study heterogeneity (Cochran's Q statistic) and the extent of study effects variability [I2 with 95% confidence interval (CI)] were estimated. Sensitivity analyses examined the effect of population, intervention, and study characteristics. We also evaluated the potential for publication bias. Among the 1,508 high-risk women who were analyzed in 9 RCTs, 374 (24.8%) [160 (21.4%) in intervention, and 214 (28.1%) in control group] developed GDM. Women who received exercise intervention during pregnancy were less likely to develop GDM compared to those who followed the standard prenatal care (OR 0.70, 95%CI 0.52, 0.93; P-value 0.02) [Q 10.08, P-value 0.26; I2 21% (95%CI 0, 62%]. Studies with low attrition bias also showed a similar result (OR 0.70, 95%CI 0.51, 0.97; P-value 0.03). A protective effect was also supported when analysis was limited to studies including women with low education level (OR 0.55; 95%CI 0.40, 0.74; P-value 0.0001); studies with exercise intervention duration more than 20 weeks (OR 0.54; 95%CI 0.40, 0.74; P-value 0.0007); and studies with a motivation component in the intervention (OR 0.69, 95%CI 0.50, 0.96; P-value 0.03). We could not exclude large variability in study effects because the upper limit of I2 confidence interval was higher than 50% for all analyses. There was no conclusive evidence for small study effects (P-value 0.31). Our study might support a protective effect of exercise intervention during pregnancy for high-risk women to prevent GDM. The protective result should be corroborated by large, high quality RCTs.

Viscosupplementation for knee osteoarthritis: systematic review and meta-analysis

ObjectiveTo evaluate the effectiveness and safety of viscosupplementation for pain and function in patients with knee osteoarthritis.DesignSystematic review and meta-analysis of randomised trials.Data sourcesSearches were conducted of Medline, Embase, and...

Gut microbiota–derived metabolite trimethylamine-N-oxide and multiple health outcomes: an umbrella review and updated meta-analysis

ABSTRACTBackgroundTrimethylamine-N-oxide (TMAO) is a gut microbiota–derived metabolite produced from dietary nutrients. Many studies have discovered that circulating TMAO concentrations are linked to a wide range of health outcomes.ObjectivesThis study aimed to summarize health outcomes related to circulating TMAO concentrations.MethodsWe searched the Embase, Medline, Web of Science, and Scopus databases from inception to 15 February, 2022 to identify and update meta-analyses examining the associations between TMAO and multiple health outcomes. For each health outcome, we estimated the summary effect size, 95% prediction CI, between-study heterogeneity, evidence of small-study effects, and evidence of excess-significance bias. These metrics were used to evaluate the evidence credibility of the identified associations.ResultsThis umbrella review identified 24 meta-analyses that investigated the association between circulating TMAO concentrations and health outcomes including all-cause mortality, cardiovascular diseases (CVDs), diabetes mellitus (DM), cancer, and renal function. We updated these meta-analyses by including a total of 82 individual studies on 18 unique health outcomes. Among them, 14 associations were nominally significant. After evidence credibility assessment, we found 6 (33%) associations (i.e., all-cause mortality, CVD mortality, major adverse cardiovascular events, hypertension, DM, and glomerular filtration rate) to present highly suggestive evidence.ConclusionsTMAO might be a novel biomarker related to human health conditions including all-cause mortality, hypertension, CVD, DM, cancer, and kidney function. Further studies are needed to investigate whether circulating TMAO concentrations could be an intervention target for chronic disease.This review was registered at www.crd.york.ac.uk/prospero/ as CRD42021284730.

Incremental net monetary benefit of direct oral anticoagulants for the prevention of venous thromboembolism after total knee or hip replacement: A systematic review and meta-analysis

IntroductionThis meta-analysis was conducted to quantitatively pool the incremental net benefit (INB) of using direct oral anticoagulants (DOACs) for the prevention of venous thromboembolism (VTE) in patients undergoing total knee or hip replacements (TKR or THR). Materials and methodsWe performed a comprehensive search in several databases published before June 2021. Studies were included if they were cost-effectiveness analyses reporting cost per quality-adjusted life-year or life-year of DOACs compared to low molecular-weight heparins (LMWHs) or other anticoagulant agents for the prevention of VTE after TKR or THR. Risk of bias was also assessed using the biases in economic studies (ECOBIAS) checklist. Various monetary units were converted to purchasing power parity, adjusted to 2020 US dollars. The INBs were pooled across studies using a random-effects model, stratified by high-income countries (HICs) and low- and middle-income countries (LMICs). Heterogeneity was assessed using the I2 statistic. ResultsA total of 49 comparisons (TKR = 25 and THR = 24) from 16 studies was included. In HICs, DOACs were cost-effective compared to LMWHs from the health care system/payer perspective for the prevention of VTE after both TKR and THR with corresponding INBs (95 % CI; I2) of $231.91 ($178.71, $285.11; 0 %) and $254.99 ($159.20, $350.77; 27.79 %), respectively. In LMICs, DOACs were not cost-effective compared to LMWHs for both TKR and THR with the INBs of $94.13 (−$40.21, $228.47; 97.04 %) and $80.55 (−$157.37, $318.47; 99.78 %), respectively. No evidence of small-study effects was identified in any analyses. The cost-effectiveness of using DOACs for TKR and THR in HICs was robust across a series of sensitivity analyses. ConclusionsDOACs were cost-effective as compared to LMWHs for VTE prophylaxis following TKR and THR surgeries in HICs. Further studies from LMICs are warranted.

Dietary protein and multiple health outcomes: An umbrella review of systematic reviews and meta-analyses of observational studies

Numerous studies have evaluated the effects of dietary protein on specific health outcomes. The aim of our umbrella review was to summarize the existing evidence between the intake of dietary proteins and multiple health outcomes, and assess their strength and validity. Our study was registered at PROSPERO (No. CRD42021255938). We systematically searched PubMed, Embase, and Web of Science databases from inception to May 18, 2021, to identify relevant systematic reviews and meta-analyses of observational studies. The validated "A Measurement Tool to Assess Systematic Reviews" for assessing the methodological quality of included systematic reviews was utilized. For each association, we estimated the summary effect size using fixed and random effects methods, and the 95% confidence and prediction intervals. We also evaluated heterogeneity, evidence of small-study effects, and excess significance bias. Overall, 16 articles with 58 meta-analyses were included. All studies were categorized as over moderate quality. On employing the random-effects model, fourteen (24.1%) meta-analyses were found to be significant at P<0.05, whereas only one (1.7%) remained significant at P<10-6. Twenty-two (37.9%) meta-analyses had large or very large heterogeneity. Evidence of small-study effects and excess significance bias was found for three (5.2%) meta-analyses, respectively. One meta-analysis was supported by highly suggestive evidence, indicating that a 5% increase in energy intake from animal protein was associated with 12% higher risk of type 2 diabetes (95% confidence interval [CI]: 1.08-1.17). Of note, the intake of animal and plant proteins had different health effects on type 2 diabetes, all-cause mortality, and risk of cardiovascular disease mortality. Although the intake of dietary protein was associated with certain health outcomes, the strength of evidence was limited for most outcomes. Moreover, the source of dietary protein is an important factor that requires better consideration in future studies.

Environmental risk factors for non-Hodgkin's lymphoma: umbrella review and comparison of meta-analyses of summary and individual participant data

ObjectivesTo summarise the range, strength, and validity of reported associations between environmental risk factors and non-Hodgkin's lymphoma, and to evaluate the concordance between associations reported in meta-analyses of summary level...

P185 META–ANALYSIS OF PLACEBO–CONTROLLED TRIALS OF LEVOSIMENDAN IN ACUTE MYOCARDIAL INFARCTION

Abstract Introduction Despite the potential beneficial effects in the acute phase of myocardial infarction, the use of Levosimendan in recent guidelines is currently limited to patients with heart failure and a severe reduction in cardiac output not responding to standard therapy. In spite of everything, the haemodynamic effects of the drug that reduces afterload, the beneficial pleiotropic effects on myocardial stunning and the improvement of microcirculatory indices make Levosimendan still an interesting therapeutic prospect in AMI. Purpose of the Study The study aimed to analyse the available data of the use of Levosimendan in the acute setting of myocardial infarction Materials and Methods This review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) and was conducted and presented according to best practice recommendations, including the Preferred Reporting Items for Systematic Reviews and Meta–Analyses (PRISMA) reporting guidelines. Seven selected studies were included in the meta–analysis. Meta–Analysis Levosimendan treatment was associated with a reduction in one year mortality and adverse event rates, without inconsistency. A trend of the increase of cardiac index and reduction of wedge pressure was evident, with an inconsistent effect on blood pressure and heart rate. No evidence of small study effects was found upon the inspection of funnel plots or regression tests. Finally, possibly given the limited number of included studies, metaregression analysis did not identify any major effect modifier. Discussion A clearly significant mortality reduction in the acute phase and long–term mortality induced by Levosimendan in AMI is evident. In the acute ischemic field, the haemodynamic properties of Levosimendan may explain part of the benefits. Levosimendan, over an inotropic effect, has a positive effect on ventriculo–arterial coupling, peripheral vasodilation consequently increasing tissue perfusion, anti–stunning effects and anti–inflammatory effects. Conclusions Our data support the idea that Levosimendan may already have a role in the treatment of acute ischemic heart disease. Further studies, specifically designed to investigate the early role in the treatment of ischemic heart failure are needed.

Effect of statins on risk and mortality of urologic malignancies: Protocol of an umbrella review.

IntroductionUrologic malignancies are the major causes of morbidity and mortality in men over 40 years old, accounting for more than 20% of all malignant tumors. Several meta-analyses are shown that statin exposure can reduce the morbidity and mortality of various urologic cancers. The adjuvant roles of statin in tumor prevention and anti-tumor activity are now being gradually recognized and have gained attention. Nevertheless, to date, multiple clinical studies and meta-analyses found inconsistent results of their anti-cancer effects. This study aims to evaluate the credibility of the published systematic reviews and meta-analyses that assessed the effects of statin exposure for the incidence and mortality of urologic cancers through an umbrella review.Methods and analysisThe guidance of overviews of systematic reviews reported in the Cochrane Handbook for Systematic Reviews of interventions will be followed while performing and reporting this umbrella review. This project was registered in PROSPERO with the registration number of CRD42020208854. PubMed, Embase and Cochrane Library will be searched for systematic reviews to identify and appraise systematic reviews or meta-analyses of interventional and observational studies examining statin use and the risks of urologic cancer incidence and mortality without language restriction. The search will be carried out on 10 February 2022. Systematic reviews based on qualitative, quantitative or mixed-methods studies will be involved and critically evaluated by two authors using the Assessment of Multiple Systematic Reviews 2 (AMSTAR2, an updated version of AMSTAR) tool. We will determine the level of evidence using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) tool. The summary effect estimates will be calculated using random-effects models. Between- study heterogeneity will be assessed using the I2 statistic. Furthermore, we will also assess the evidence of excess significance bias and evidence of small study effects.Ethics and disseminationEthics approval is not required as we will search and gather data based on the published systematic reviews and meta-analyses. We plan to publish the results of this umbrella review in a peer-reviewed journal and will be presented at a urological disease conference. All the relevant additional data will also be uploaded to the online open access databases.PROSPERO registration numberCRD42020208854.

Associations of Nutritional, Lifestyle, and Metabolic Factors With Non-alcoholic Fatty Liver Disease: An Umbrella Review With More Than 380,000 Participants.

Background & Aims: Nonalcoholic fatty liver disease (NAFLD) is the most common liver injury. We performed this umbrella review of meta-analyses to summarize the evidence on the associations of nutritional, lifestyle, and metabolic factors with NAFLD.Methods: We searched the PubMed, Embase, and Web of Science databases from inception until July 2, 2020, to identify meta-analyses of observational studies which explored the associations of nutritional, lifestyle, and metabolic factors with NAFLD. Evidence levels were assessed using summary effect sizes, 95% prediction intervals, between-study heterogeneity, evidence of small-study effects, and evidence of excess significance bias for each meta-analysis. (No. of PROSPERO, CRD42020200124).Results: Twenty two risk or protective factors from 10 published meta-analyses were included and studied. Three risk factors (sugar-sweetened beverage consumption, serum fetuin-A, and waist circumference) with highly suggestive levels of evidence and three risk factors (soft drink consumption, former smoking, and body mass index) with suggestive levels of evidence were identified. Only two protective factors (physical activity and serum vitamin D level [among adults in Western countries]) with suggestive levels of evidence were identified. Furthermore, other six risk factors and two protective factors with weak levels of evidence were identified.Conclusions: We found varying levels of evidence of associations of nutritional, lifestyle, and metabolic factors and NAFLD. The results suggest that nutritional and lifestyle management should be considered as a major primary preventive strategy for NAFLD. Moreover, considering the low quality of included meta-analyses and limited area of research topics, future high-quality original studies and meta-analyses should be performed to study these associations.

Shift work and health outcomes: an umbrella review of systematic reviews and meta-analyses of epidemiological studies.

Shift work is commonly increasing, and some physiological changes occur as workers sleep less and their circadian rhythms are disrupted. This umbrella review not only summarizes the evidence but also evaluates the validity of the associations of shift work with different health outcomes. We searched the MEDLINE, Web of Science, and Embase databases from their inception to April 25, 2020. For each systematic review and/or meta-analysis, we estimated the summary effect size, the 95% confidence interval, the 95% prediction interval, the between-study heterogeneity, evidence of small-study effects, and evidence of excess-significance bias. Eight eligible systematic reviews and meta-analyses were identified, providing data on 16 associations. We observed highly suggestive evidence for associations between shift work and myocardial infarction (having ever vs having never done shift work) and diabetes mellitus incidence (per 5-year increment in shift work). Furthermore, we observed suggestive evidence for an association between shift work and diabetes mellitus incidence (having ever vs having never done shift work). Two health outcomes, including prostate cancer incidence (having ever vs having never done shift work and rotating night shift work vs daytime work) and colorectal cancer incidence (longest vs shortest shift work time), were only supported by weak evidence. This umbrella review found that shift work was associated with several health outcomes with different levels of evidence. Associations for myocardial infarction and diabetes mellitus incidence were supported by highly suggestive evidence. Registry: PROSPERO; Identifier: CRD42020188537. Wu Q-J, Sun H, Wen Z-Y, etal. Shift work and health outcomes: an umbrella review of systematic reviews and meta-analyses of epidemiological studies. J Clin Sleep Med. 2022;18(2):653-662.

Hearing impairment and diverse health outcomes : An umbrella review of meta-analyses of observational studies.

Globally, it is estimated that approximately 1.3billion people live with some form of hearing impairment. Major causes of hearing loss include infection/disease, age-related factors, and occupational factors. Numerous systematic reviews and meta-analyses have attempted to synthesise literature on these topics. To date there has not been asystematic evaluation of the relationships between hearing impairment and diverse physical, mental, and social outcomes. We performed an umbrella review of systematic reviews of observational studies with meta-analyses for any physical disease, biomarkers of disease, mental health or cognitive outcomes, and/or modifiable risk factors associated with hearing impairment. For each meta-analytic association, random effects summary effect size, 95% confidence intervals, heterogeneity, evidence for small-study effect, excess significance bias and 95% prediction intervals were calculated, and risk of bias was assessed via the AMSTAR2 tool. These were used to grade significant evidence (p < 0.05) fromI toIV, using the recommendations from the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) criteria. From 3747studies, 21 were included covering 54outcomes. Overall, 44/54 outcomes (82%) yielded significant results. Of the highest quality evidence, age-related hearing loss and non-specific hearing impairment were negatively associated with several types of cognitive impairments; pediatric bilateral hearing loss was negatively associated with quality of life, sensorineural hearing loss was positively associated with rheumatoid arthritis and tinnitus was positively associated with temporomandibular disorders. Results show moderate quality evidence for associations between several types of hearing impairments and cognitive difficulties, quality of life and systemic diseases such as rheumatoid arthritis. Practitioners and public health policies should note these findings when developing relevant healthcare policies.

Systemic Corticosteroid Administration in Coronavirus Disease 2019 Outcomes: An Umbrella Meta-Analysis Incorporating Both Mild and Pulmonary Fibrosis-Manifested Severe Disease.

Background: Effective treatments for coronavirus disease 2019 (COVID-19) are urgently needed. The real role of corticosteroid use in COVID-19 has long been of interest and is disputable. Methods: We aimed to quantitatively reevaluate the efficacy of corticosteroids on COVID-19. Databases were searched for eligible meta-analyses/systematic reviews with available outcome data. For each association, we estimated the summary effect size with fixed- and random-effects models, 95% confidence intervals, and 95% prediction intervals. Heterogeneity, Egger’s test, evidence of small-study effects and excess significance bias, and subgroup analyses were rigorously evaluated. Results: Intended outcomes of 12 eligible studies were mortality, clinical improvement, hospitalization, mechanical ventilation (MV), adverse events (AEs), intensive care unit (ICU) stay, hospital stay, virus clearance time (VCT), and negative conversion. Corticosteroid administration was associated with a 27% risk reduction in MV [hazard ratio (HR): 0.73 (0.64–0.83)] and a 20% reduction in mortality of critically ill/severe COVID-19 patients [HR: 0.80 (0.65–0.98)]. Interestingly, shorter ICU stays and, conversely, potentially longer hospital stays, a longer VCT, and a longer time to negative conversion were associated with corticosteroid use. There was no significant impact of different corticosteroid doses on mortality. Only one study showed slightly excess significant bias. Caution should be applied given the weak nature of the evidence, and it has been confirmed by sensitivity analyses too. Conclusion: This umbrella study found benefits from corticosteroids on MV and especially the mortality of critically ill/severe patients with shorter ICU stays but prolonged hospital stays and VCT. The benefits and harms should be reevaluated and balanced before corticosteroids are cautiously prescribed in clinical practice.