Small-study Effects Research Articles

Long-term outcomes after different treatments for gastric cancer with synchronous liver metastasis: A PRISMA systematic review and network meta-analysis.

Background:The treatment of gastric cancer (GC) with synchronous liver metastasis is still controversial. This systematic review and network meta-analysis was designed to evaluate the long-term outcomes after different treatments of GC with synchronous liver metastasis.Methods:Several electronic databases were searched to identify eligible studies updated on May 1, 2021. Studies assessing the overall survival (OS) after different treatments (including chemotherapy, interventional therapy, surgical therapy alone and adjunctive therapy after surgery) of GC with synchronous liver metastasis were included. Odds ratios with 95% confidence interval (CI) were calculated for survival variables.Results:A total of 15 studies including 4312 patients were included in this network meta-analysis. Adjunctive therapy after surgery performed better than surgery therapy alone (hazard ratio [HR] = 1.23, 95% credible interval [CrI]: 0.69–2.17), chemotherapy (HR = 1.18, 95%CrI: 0.71–1.95), and interventional therapy in terms of 1-year OS (HR = 2.03, 95%CrI: 1.22–3.37). In terms of 3-OS, adjunctive therapy after surgery showed better efficacy than surgery therapy alone (HR = 1.48, 95%CrI: 0.40–5.47), chemotherapy (HR = 1.27, 95%CrI: 0.37–4.35), and interventional therapy (HR = 3.16, 95%CrI: 0.73–13.63). For 5-OS, adjunctive therapy after surgery was superior to surgery therapy alone (HR = 1.74, 95%CrI: 0.08–37.76), chemotherapy (HR = 1.44, 95%CrI: 0.66–3.14), and interventional therapy (HR = 1.46, 95%CrI: 0.06–34.36). There were no statistical inconsistency and small-study effect existed in our network meta-analysis for 1-year, 3-year, or 5-year OS. Cluster ranking analysis performed with surface under the cumulative ranking showed adjuvant therapies after surgery (99.9, 96.7, 90.2) ranking higher than surgery therapy alone, chemotherapy, and interventional therapy for 1-year, 3-year, 5-year OS.Conclusion:The OS of adjuvant therapy after surgery was better than that of surgery therapy alone, chemotherapy, and interventional therapy. Adjuvant therapy after surgery is the most recommended therapy for people with GC with synchronous liver metastasis.

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.

Diet and gastric cancer risk: an umbrella review of systematic reviews and meta-analyses of prospective cohort studies.

Several systematic reviews and meta-analyses evaluated the associations between dietary factors and the incidence of gastric cancer (GC). To evaluate the strength and validity of existing evidence, we conducted an umbrella review of published systematic reviews and meta-analyses that investigated the association between diets and GC incidence. We searched the PubMed, Embase, and Cochrane databases for systematic reviews and meta-analyses of prospective cohort studies investigating the association between dietary factors and GC risk. For each association, we recalculated the adjusted summary estimates with their 95% confidence interval (CI) and 95% prediction interval (PI) using a random-effects model. We used the I2 statistic and Egger's test to assess heterogeneity and small-study effects, respectively. We also assessed the methodological quality of each study and the quality of evidence. Finally, we identified 16 meta-analyses that described 57 associations in this umbrella review. Of the 57 associations, eight were statistically significant using random-effects, thirteen demonstrated substantial heterogeneity between studies (I2 > 50%), and three found small-study effects. The methodological quality of meta-analyses was classified as critically low for two (13%), low for thirteen (81%), and only one (6%) was rated as high confidence. Quality of evidence was rated high for a positive association for GC incidence with a higher intake of total alcohol (RR = 1.19, 95% CI 1.06-1.34) and moderate-quality evidence to support that increased processed meat consumption can increase GC incidence. Three associations (total fruit, vitamin E, and carotenoids) were determined to be supported by low-quality evidence, and two (pickled vegetables/foods and citrus fruit) were supported by very low-quality. Our findings support the dietary recommendations for preventative GC, emphasizing lower intake of alcohol and foods preserved by salting. New evidence suggests a possible role for total fruit, citrus fruit, carotenoids, and vitamin E. More research is needed on diets with lower quality evidence. CRD42021255115.

Depression and anxiety prevalence in people with cystic fibrosis and their caregivers: a systematic review and meta-analysis

BackgroundPrevalence of depression and anxiety in people with cystic fibrosis (PwCF) and their caregivers is high, however, results have been inconsistent. This systematic review and meta-analysis aimed to estimate the prevalence of depression and anxiety in PwCF and their caregivers and explore sources of heterogeneity.MethodMEDLINE, EMBASE, CINAHL plus and PsychINFO databases were searched from inception to January 2021. Studies were included if a specific psychometric tool (PT) to assess depression or anxiety (rather than quality of life) was used and did not involve a transitory patient state. Random-effects models were applied due to high anticipated heterogeneity and I2 estimates were calculated. Sources of heterogeneity were explored through subgroup comparisons. The presence of small-study effects was investigated visually using funnel plots and statistically using the Egger test.ResultsA total of 94 articles (48 full-text publications, 46 abstracts) were included. Depression prevalence in adolescents aged 12–18 years (n = 2386), adults (n = 9206) and caregivers (n = 6617) were 18.7% (95% CI 12.8–25.3%, I2 = 89.2%), 27.2% (95% CI 23.6–31%, I2 = 90.4%), and 32.8% (95% CI 27.9–37.9%, I2 = 90.3%), respectively. Anxiety prevalence in adolescents aged 12–18 years (n = 2142) was 26% (95% CI 19.6–33%, I2 = 86.4%), 28.4% (95% CI 25–31.9%, I2 = 85%) for adults (n = 8175), and 38.4% (95% CI 30.8–46.2%, I2 = 94.6%) for caregivers (n = 5931). Prevalence differed by the PT used and study location.DiscussionThis comprehensive analysis found the prevalence of depression and anxiety in PwCF and their caregivers to be high, supporting recommendations for regular screening. Choice of PT significantly influenced prevalence, indicating a need for future studies to identify the optimal PT for each CF population to identify those most at risk.

Modifiable predictive factors and all-cause mortality in the non-hospitalized elderly population: An umbrella review of meta-analyses.

This umbrella review aimed to summarize the association between modifiable predictive factors and all-cause mortality in the non-hospitalized elderly population, and estimated the credibility and strength of the current evidence. PubMed, Embase, Web of science, and EBSCOhost were searched up to February 28, 2022. Random-effect summary effect sizes and 95% confidence intervals (CIs), heterogeneity, small-study effect, excess significance bias, as well as 95% prediction intervals (PIs) were calculated. Methodological quality was assessed with the Assessment of Multiple Systematic Reviews 2 (AMSTAR-2) tool. The credibility of the included meta-analyses was graded from convincing to weak using established criteria. This umbrella review was registered with PROSPERO, CRD 42021282183. In total, 32 predictive factors involving 49 associations extracted from 35 meta-analyses were analyzed. Forty-three of the 49 (87.8%) associations presented nominal significant effects by the random-effect model (P<0.05), of which 34 had harmful associations and nine had beneficial associations with all-cause mortality. Frailty (FRAIL scale), low short physical performance battery (SPPB) score, and fewer daily steps carried a more than three-fold risk for all-cause mortality. Convincing evidence showed that weight fluctuation, prefrailty and frailty status, sarcopenia, low SPPB score, fewer daily steps, and fatigue increased the risk of all-cause mortality, while daily moderate-to-vigorous physical activity (MVPA) duration and total physical activity participation reduced the risk of death. There were twenty, nine, five, and six associations that yielded highly suggestive, suggestive, weak, and non-significant grades of evidence. Thirty-four (69.4%) of the associations exhibited significant heterogeneity. Twenty-two associations presented 95% PIs excluding the null value, two indicated small-study effects, and three had evidence for excess significance bias, respectively. The methodological quality of most meta-analyses was rated as low (37.1%) or critically low (42.9%). A summary of the currently available meta-analyses suggests that a broad range of modifiable predictive factors are significantly associated with all-cause mortality risk in the non-hospitalized elderly population. The most credible evidence indicates that physical function represented by frailty and sarcopenia, as well as physical activity, are significant predictors for all-cause mortality. This umbrella review may provide prognostic information to direct appropriate diagnostic evaluation and treatment goals in the future. More solid evidence is still needed coming from moderate-to-high quality meta-analyses.

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...

Risk Factors for Ovarian Cancer: An Umbrella Review of the Literature.

Simple SummaryOvarian cancer is the most lethal cancer of the female genital tract despite major advances in both surgical and oncological treatments. This is in part due to difficulties in identifying those most at risk of developing ovarian cancer, and that there are currently no effective screening strategies. Whilst 20% of cases have a genetic component, the majority have no obvious cause. Many risk factors have been associated with ovarian cancer, although the strength of this evidence remains unclear. This umbrella review attempts to review the validity of associations between non-genetic risk factors and the risk of developing or dying from ovarian cancer. There were six associations that were supported by strong evidence. Greater height, BMI and use of HRT increased the risk, whilst the use of oral contraceptive pill reduced that risk. This review will enable further research into these areas and may promote identification of individuals at high risk.Several non-genetic factors have been associated with ovarian cancer incidence or mortality. To evaluate the strength and validity of the evidence we conducted an umbrella review of the literature that included systematic reviews/meta-analyses that evaluated the link between non-genetic risk factors and ovarian cancer incidence and mortality. We searched PubMed, EMBASE, Cochrane Database of Systematic Reviews and performed a manual screening of references. Evidence was graded into strong, highly suggestive, suggestive or weak based on statistical significance of the random effects summary estimate and the largest study in a meta-analysis, the number of cases, between-study heterogeneity, 95% prediction intervals, small study effects, and presence of excess significance bias. We identified 212 meta-analyses, investigating 55 non-genetic risk factors for ovarian cancer. Risk factors were grouped in eight broad categories: anthropometric indices, dietary intake, physical activity, pre-existing medical conditions, past drug history, biochemical markers, past gynaecological history and smoking. Of the 174 meta-analyses of cohort studies assessing 44 factors, six associations were graded with strong evidence. Greater height (RR per 10 cm 1.16, 95% confidence interval (CI) 1.11–1.20), body mass index (BMI) (RR ≥ 30 kg/m2 versus normal 1.27, 95% CI 1.17–1.38) and three exposures of varying preparations and usage related to hormone replacement therapy (HRT) use increased the risk of developing ovarian cancer. Use of oral contraceptive pill reduced the risk (RR 0.74, 95% CI 0.69–0.80). Refining the significance of genuine risk factors for the development of ovarian cancer may potentially increase awareness in women at risk, aid prevention and early detection.

Risk of Cancer in Inflammatory Bowel Diseases: Umbrella Review and Reanalysis of Meta-analyses

To summarize the epidemiologic evidence and assess the validity of claimed associations of inflammatory bowel diseases (IBDs) with overall and site-specific cancer risk. We systematically searched PubMed, Embase, and Scopus from inception to May 10, 2021, to identify and comprehensively reanalyze the data of meta-analyses on associations between IBDs (ie, Crohn's disease [CD] and ulcerative colitis [UC]) and subsequent risk of cancer. The strength of epidemiologic evidence was graded as high, moderate, or weak, by applying prespecified criteria that included the random effects estimate, its 95% confidence interval, and P value, estimates of heterogeneity, small-study effects, and robustness to unmeasured confounding. This study critically appraised 277 estimates derived from 24 published meta-analyses and our own meta-analyses. The association between pediatric-onset IBDs and overall risk of cancer showed high epidemiologic evidence. Twenty associations (15 cancer types) demonstrated moderate evidence: any cancer (pediatric-onset UC), mouth to terminal ileum (CD), small bowel (CD/UC), colon (CD), rectum (CD/UC), colon-rectum (IBDs, pediatric-onset CD/UC), bile ducts and liver (CD/UC), liver (CD), intrahepatic cholangiocarcinoma (IBDs), bile ducts (CD), skin (CD), squamous cell carcinoma of the skin (CD), nonmelanoma skin cancer (UC), kidney (CD), and thyroid cancer (IBDs). Another 40 associations (23 cancer types) showed statistical significance; however, our confidence in these effect estimates was weak. No statistical significance was found regarding further 47 associations. Associations between IBDs and different types of malignancy showed varying levels of evidence and magnitude of risk. Further primary research investigating the impact of a consistent set of risk factors that are known to affect cancer risk is warranted. PROSPERO CRD42021254996.

Role of diet in stroke incidence: an umbrella review of meta-analyses of prospective observational studies

BackgroundStroke is one of the major challenges for the global healthcare system, which makes it necessary to explore the relationship between various modifiable factors and stroke risk. Recently, numerous meta-analyses of prospective observational studies have reported that dietary factors played a key role in the occurrence of stroke. However, the conclusions of previous studies have remained controversial and unclear. Accordingly, we conducted an umbrella review synthesizing and recalculating available evidence to assess the certainty of the associations between dietary factors and stroke.MethodsRelevant meta-analyses examining the associations between dietary factors and stroke were searched in PubMed and Embase databases up to September 1, 2021. For each eligible meta-analysis, two independent reviewers appraised the methodologic quality using the AMSTAR 2 criteria and estimated the summary effect size, 95% confidence intervals, 95% prediction intervals, heterogeneity between studies, and small-study effects. Moreover, we further assessed the associations between dietary factors and ischemic stroke as well as hemorrhagic stroke. Lastly, a set of pre-specified criteria was applied to qualitatively evaluate the epidemiological credibility of each dietary factor.ResultsOverall, our umbrella review included 122 qualified meta-analyses for qualitative synthesis, involving 71 dietary factors related to food groups, foods, macronutrients, and micronutrients. Using the AMSTAR 2 criteria, 5 studies were assessed as high quality, 4 studies as moderate quality, and 113 studies as low or critically low quality. We identified 34 dietary factors associated with stroke occurrence, 25 dietary factors related to ischemic stroke, and 11 factors related to hemorrhagic stroke. Among them, high/moderate certainty epidemiological evidence demonstrated an inverse association between intake of fruits (RR: 0.90) and vegetables (RR: 0.92) and stroke incidence, but a detrimental association between red meat (RR: 1.12), especially processed red meat consumption (RR:1.17), and stroke incidence. Besides, the evidence of high/moderate certainty suggested that the intake of processed meat, fruits, coffee, tea, magnesium, and dietary fiber was associated with ischemic stroke risk, while consumption of tea, fruits, and vegetables was relevant to hemorrhagic stroke susceptibility.ConclusionsOur study has reported that several dietary factors have a significant impact on stroke risk and offered a new insight into the relationship between dietary modification and stroke occurrence. Our results may provide an effective strategy for stroke prevention.

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.

Alcohol and Health Outcomes: An Umbrella Review of Meta-Analyses Base on Prospective Cohort Studies.

An umbrella review of meta-analyses was performed to summarize the evidence of associations between alcohol consumption and health outcomes and to assess its credibility. Meta-analyses of prospective cohort studies reporting the associations of alcohol consumption with health outcomes were identified. We recalculated the random-effects summary effect size and 95% confidence interval, heterogeneity, and small-study effect for each meta-analysis and graded the evidence. Fifty-nine publications reporting 224 meta-analyses of prospective cohort studies with 140 unique health outcomes were included, in which there were 49 beneficial associations and 25 harmful associations with nominally statistically significant summary results. But quality of evidence was rated high only for seven beneficial associations (renal cell carcinoma risk, dementia risk, colorectal cancer mortality, and all-cause mortality in patients with hypertension for low alcohol consumption; renal cell carcinoma risk, cardiovascular disease (CVD) risk in patients with hypertension and all-cause mortality in patients with hypertension for moderate consumption) and four harmful associations (cutaneous basal cell carcinoma risk for low alcohol consumption; cutaneous basal cell carcinoma risk and cutaneous squamous cell carcinoma risk for moderate alcohol consumption; hemorrhagic stroke risk for high alcohol consumption). In this umbrella review, only 11 health outcomes (5 in low alcohol consumption, 5 in moderate alcohol consumption and 1 in high alcohol consumption) with statistically significant showed high quality of epidemiologic evidence. More robust and larger prospective studies are needed to verify our results.

Magnitude and predictors of HIV-Drug resistance in Africa: A protocol for systematic review and meta-analysis.

Human Immunodeficiency Virus (HIV) is continued to be a major public health problem in low-income countries and more importantly in Africa. For the last decade, access to Antiretroviral Therapy (ART) and its impact in improving quality of life and reducing HIV-related morbidity and mortality has significantly been improved in Africa. Nevertheless, the emergency of HIV drug resistance (HIVDR) has posed challenges in achieving optimal ART treatment outcomes and is alarmingly increasing globally in general and in Africa in particular. Comprehensive epidemiological data on the magnitude of HIVDR and HIVDR mutations, and predictors of HIVDR are, however, limited in Africa. The main objective of this systematic review will be to estimate the pooled proportion of HIVDR and HIVDR mutations, and identify factors associated with HIVDR among people living with HIV/AIDS (PLWH) in Africa. Published Literature from 2000 until 30 October 2021 will be searched in PubMed/Medline Ovid, HINARI, SCOPUS, EMBASE, CINAHL, Web of Sciences, and Cochrane electronic databases. Initially, the literature will be screened based on title/abstract and followed by full-text appraisal for methodological quality using JBI critical appraisal tools. Data will be extracted from eligible articles after the full-text appraisal. Heterogeneity will be qualitatively assessed by a visual Funnel plot and quantitatively measured by an index of heterogeneity (I2 statistics). Random-effects model will be fitted to estimate the proportion of HIVDR and each HIVDR mutations. Sub-group and sensitivity analyses will be conducted to reduce heterogeneity. Meta-regression will be done by median year of sampling per study to observe the pattern of changes over time. Publication bias will be assessed by egger's statistics. In case of publication bias, Trim and Fill analysis will be conducted to overcome small-study effect. Data analysis will be performed using Stata version 14. As the data sources are published papers, the protocol will not require an ethical approval letter. The final report of the review will be published in a peer-reviewed journal.

Cardiac consequences of intermittent hypoxia: a matter of dose? A systematic review and meta-analysis in rodents.

AimIntermittent hypoxia (IH) is considered to be a major contributor to obstructive sleep apnoea-related cardiovascular consequences. The present meta-analysis aimed to assess the effects of IH on cardiac remodelling, function and infarct size after myocardial ischaemia across different rodent species and IH severities.Methods and resultsRelevant articles from PubMed, Embase and Web of Science were screened. We performed a random effect meta-analysis to assess the effect of IH on myocardium in rodents by using standardised mean difference (SMD). Studies using rodents exposed to IH and outcomes related to cardiac remodelling, contractile function and response to myocardial ischaemia–reperfusion were included. 5217 articles were screened and 92 were included, demonstrating that IH exposure induced cardiac remodelling, characterised by cardiomyocyte hypertrophy (cross-sectional area: SMD=2.90, CI (0.82–4.98), I2=94.2%), left ventricular (LV) dilation (LV diameter: SMD=0.64, CI (0.18–1.10), I2=88.04%), interstitial fibrosis (SMD=5.37, CI (3.22–7.53), I2=94.8) and apoptosis (terminal deoxynucleotidyl transferase dUTP nick end labelling: SMD=6.70, CI (2.96–10.44), I2=95.9). These structural changes were accompanied by a decrease in LV ejection fraction (SMD=−1.82, CI (−2.52–−1.12), I2=94.22%). Importantly, most of the utilised IH protocols mimicked extremely severe hypoxic disease. Concerning infarct size, meta-regression analyses highlighted an ambivalent role of IH, depending on its severity. Indeed, IH exposure with inspiratory oxygen fraction (FIO2) <7% was associated with an increase in infarct size, whereas a reduced infarct size was reported for FIO2 levels above 10%. Heterogeneity between studies, small study effect and poor reporting of methods in included articles limited the robustness of the meta-analysis findings.ConclusionThis meta-analysis demonstrated that severe IH systematically induces cardiac remodelling and contractile dysfunction in rodents, which might trigger or aggravate chronic heart failure. Interestingly, this meta-analysis showed that, depending on stimulus severity, IH exhibits both protective and aggravating effects on infarct size after experimental ischaemia–reperfusion procedures.

Lifestyle as well as metabolic syndrome and non-alcoholic fatty liver disease: an umbrella review of evidence from observational studies and randomized controlled trials

Background & AimsRecent epidemiological studies have indicated that NAFLD is pathologically associated with a sedentary lifestyle, unhealthy dietary habits and metabolic syndrome. An umbrella review of meta-analyses was performed to summarize the quality of evidence regarding the epidemiologic associations between lifestyle, metabolic syndrome, and non-alcoholic fatty liver disease (NAFLD) in regards to risk and treatment.MethodsWe searched PubMed, Web of Science and Embase Database from inception until June 1, 2021. Meta-analyses of observational studies and randomized controlled trials (RCTs) examining the associations of lifestyle as well as metabolic syndrome with NAFLD risk or treatment were screened. We assessed meta-analyses of observational studies based on random-effect summary effect sizes and their P values, 95% prediction intervals, heterogeneity, and small-study effects. For meta-analyses of RCTs, outcomes with a random-effect P < 0.005 and a high-GRADE assessment were classified as strong evidence.ResultsA total of 37 publications were included in this review: twenty-two publications reporting 41 meta-analyses of observational studies (37 unique outcomes) and 15 publications reporting 81 meta-analyses of RCTs (63 unique outcomes) met the inclusion criteria. Methodological quality was high for 97% of the included meta-analyses. Quality of evidence was rated high only for the association of sugar-sweetened soda consumption with increased NAFLD risk in meta-analyses of observational studies. Only 3 therapeutic interventions (green tea improving ALT, TG, TC and LDL, omega-3 PUFAs improving HOMR-IR and plasma glucose, and exercise improving RT and ALT) from meta -analyses of RCTs with suggestive (change to high/low/etc) levels of evidence were identified.ConclusionDespite many meta-analyses exploring the associations of lifestyle as well as metabolic syndrome with the risk or treatment of NAFLD, robust clinical RCTs are needed to further investigate the associations between lifestyle modifications and incidence of NAFLD or therapeutic effects on disease progression.

Comparison of survival outcomes among patients with uterine carcinosarcoma and those with grade 3 uterine carcinoma: A systematic review of the literature

Introduction: Endometrial carcinosarcoma is an aggressive form of cancer that has been classified in type II endometrial carcinomas. However, survival outcomes seem to differ considerably compared to grade 3 endometrioid adenocarcinoma, the predominant form of cancer in this group of patients. The purpose of the present systematic review is to investigate overall and progression free survival in patients with endometrial carcinosarcoma to those of patients with grade 3 endometrioid adenocarcinoma. Methods: We used Medline, Scopus, EMBASE, Cochrane Central Register of Controlled Trials CENTRAL, Clinicaltrials.gov and Google Scholar databases. Statistical analysis was performed using the Sidik-Jonkman random effect model (REM) in Rstudio. Findings: Overall, 10.121 patients from 8 studies were investigated. The results of the present meta-analysis indicate that patients with Gr3EC had better overall survival rates HR 2.41 (95% CI 1.29, 4.51). However, this effect might be influenced by selection bias and underpowered studies as following adjustment of the aggregated estimate for small study effects we observed that it was not significant (HR 1.00, 95%CI 0.96, 1.05, p=.858). Although it was not possible to accumulate data concerning the progression free survival, individual studies reported worse outcomes in patients with carcinosarcoma. Conclusions: Carcinosarcoma is a particularly aggressive form of endometrial cancer and deserves further attention from researchers as current treatment alternatives do not seem to reach survival outcomes of patients suffering from grade 3 endometrioid adenocarcinoma.

Prevalence of intellectual disability in India: A meta-analysis.

BACKGROUNDBurden due to intellectual disability (ID) is only third to the depressive disorders and anxiety disorders in India. This national burden significantly contributes to the global burden of ID and hence one has to think globally and act locally to reduce this burden. At its best the collective prevalence of ID is in the form of narrative reviews. There is an urgent need to document the summary prevalence of ID to enhance further policymaking, national programs and resource allocation.AIMTo establish the summary prevalence of ID during the past 60 years in India. METHODSTwo researchers independently and electronically searched PubMed, Scopus, and the Cochrane library from January 1961 to December 2020 using appropriate search terms. Two other investigators extracted the study design, setting, participant characteristics, and measures used to identify ID. Two other researchers appraised the quality of the studies using the Joanna Briggs Institute critical appraisal format for Prevalence Studies. Funnel plot and Egger’s regression test were used to ascertain the publication and small study effect on the prevalence. To evaluate the summary prevalence of ID, we used the random effects model with arcsine square-root transformation. Heterogeneity of I2 ≥ 50% was considered substantial and we determined the heterogeneity with meta-regression. The analyses were performed using STATA (version 16). RESULTSNineteen studies were included in the meta-analysis. There was publication bias; the trim-and-fill method was used to further ascertain bias. Concerns with control of confounders and the reliable measure of outcome were noted in the critical appraisal. The summary prevalence of ID was 2% [(95%CI: 2%, 3%); I2 = 98%] and the adjusted summary prevalence was 1.4%. Meta-regression demonstrated that age of the participants was statistically significantly related to the prevalence; other factors did not influence the prevalence or heterogeneity.CONCLUSIONThe summary prevalence of ID in India was established to be 2% taking into consideration the individual prevalence studies over the last six decades. This knowledge should improve the existing disability and mental health policies, national programs and service delivery to reduce the national and global burden associated with ID.

Association of Admission Time and Mortality in STEMI Patients: A Systematic Review and Meta-analysis.

This systematic review and meta-analysis aimed to evaluate patients with acute ST-segment elevation myocardial infarction (STEMI) who were admitted during off-hours and treated with primary angioplasty associated with an increased risk of mortality compared with those admitted during regular working hours. We performed a systematic literature search using PubMed, SCOPUS, Europe PMC, and Cochrane CENTRAL databases that was finalized on March 15, 2021. The primary outcome was mortality comprising early (in-hospital), midterm (30 days to 1 year), and long-term mortality (>1 year). A total of 384,452 patients from 56 studies were included. The overall mortality of acute STEMI patients admitted during off-hours and regular hours were 6.1 and 6.7%, respectively. Patients admitted during off-hours had similar risk of early, midterm, and long-term mortality compared to those admitted during regular working hours ([relative risk or RR = 1.07, 95% confidence interval or CI, 1.00-1.14, p = 0.06; I 2 = 45%, p = 0.0009], [RR = 1.00, 95% CI, 0.95-1.05, p = 0.92; I 2 = 13%, p = 0.26], and [RR = 0.95, 95% CI, 0.86-1.04, p = 0.26; I 2 = 0%, p = 0.76], respectively). Subgroup analyses indicated that the results were consistent across all subgroups ([women vs. men], [age >65 years vs. ≤65 years], and [Killip classification II to IV vs. Killip I]). Funnel plot was asymmetrical. However, Egger's test suggests no significance of small-study effects ( p = 0.19). This meta-analysis showed that patients with acute STEMI who were admitted during off-hours and treated with primary angioplasty had similar risk of early, midterm, and long-term mortality compared with those admitted during regular working hours.

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.

Meta-analyzing enhanced expectancies on motor learning: positive effects but methodological concerns

ABSTRACT The OPTIMAL theory of motor learning predicts enhanced expectancies facilitate learning. This meta-analysis investigated this prediction by quantifying effect sizes from studies manipulating feedback after good trials, comparative feedback, perceived task difficulty, conceptions of ability, self-modeling, or extrinsic rewards, and assessing learning. After searching databases, 48 studies met inclusion criteria for quantitative analysis. Fifty-six effect sizes were calculated from performance differences between enhanced expectancies and neutral/diminished expectancies groups at delayed retention tests. Results revealed a Hedges’ g = 0.54 (95% CI [0.38, 0.69]) that may be overestimated due to small-study effects and underpowered studies. Moderator analyses revealed feedback after good trials, comparative feedback, perceived task difficulty, and conceptions of ability manipulations significantly improved learning. Few studies used other manipulations, precluding reliable estimates of their effects. Further, significant effects of enhanced expectancies were shown for children/adolescents, young adults, and older adults. Few studies examined special populations, preventing a reliable effect estimate. Finally, the effect of enhanced expectancies on learning was not affected by type of comparison group (neutral/diminished expectancies). Findings suggest enhanced expectancies may facilitate motor learning, consistent with OPTIMAL theory, but pre-registered/registered reports and more powerful studies should be conducted to confirm the effect and estimate its size more accurately.