Molecular Investigation of miRNA Biomarkers as Chemoresistance Regulators in Melanoma: A Protocol for Systematic Review and Meta-Analysis

Introduction: Melanoma is a global disease that is predominant in Western countries. However, reliable data resources and comprehensive studies on the theragnostic efficiency of miRNAs in melanoma are scarce. Hence, a decisive study or comprehensive review is required to collate the evidence for profiling miRNAs as a theragnostic marker. This protocol details a comprehensive systematic review and meta-analysis on the impact of miRNAs on chemoresistance and their association with theragnosis in melanoma. Methods and analysis: The articles will be retrieved from online bibliographic databases, including Cochrane Review, EMBASE, MEDLINE, PubMed, Scopus, Science Direct, and Web of Science, with different permutations of ‘keywords’. To obtain full-text papers of relevant research, a stated search method will be used, along with selection criteria. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis for Protocols 2015 (PRISMA-P) standards were used to create this study protocol. The hazard ratio (HR) with a 95% confidence interval will be analyzed using Comprehensive Meta-Analysis (CMA) software 3.0. (CI). The pooled effect size will be calculated using a random or fixed-effects meta-analysis model. Cochran’s Q test and the I2 statistic will be used to determine heterogeneity. Egger’s bias indicator test, Orwin’s and the classic fail-safe N tests, the Begg and Mazumdar rank collection test, and Duval and Tweedie’s trim and fill calculation will all be used to determine publication bias. The overall standard deviation will be evaluated using Z-statistics. Subgroup analyses will be performed according to the melanoma participants’ clinicopathological and biological characteristics and methodological factors if sufficient studies and retrieved data are identified and available. The source of heterogeneity will be assessed using a meta-regression analysis. A pairwise matrix could be developed using either a pairwise correlation or expression associations of miRNA with patients’ survival for the same studies.

The Effect of miRNA-Modified Exosomes in Animal Models of Spinal Cord Injury: A meta-Analysis

Background: Spinal cord injury (SCI) is currently not completely curable. Exosomes have been widely used in preclinical studies of spinal cord injury. Here, in this meta-analysis, we focused on evaluating the overall efficacy of therapies based on miRNA-modified exosomes on functional recovery in animal models of SCI.Methods: PubMed, embase and Web of Science library databases were searched. Relevant literature was included, and the random effects model was used to assess the overall effect of the intervention, with outcomes expressed as SMD. The primary outcome included motor function scores. Risk of bias (ROB) was assessed using the ROB tool of the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE). R version 4.1.1software and Review Manager software were used for meta-analysis.Results: A total of 11 preclinical studies were included. The meta-analysis revealed that miRNA-modified exosome therapy was effective in improving motor function scores compared with exosomes alone or control therapy (standardized mean difference: 4.21; 95% confidence interval: 3.39–5.04). There was significant asymmetry in the funnel plot, and trim-and-fill analysis revealed four unpublished studies of motor scores. The quality of all included studies was evaluated with SYRCLE’s ROB tool. The SCI model, administration time and dose had an impact on the effect of the treatment.Conclusion: MiRNA-modified exosomes have shown great potential in the treatment of SCI. Moreover, the efficacy of miRNA-modified exosomes was superior to that of exosomes alone.

Estimated incidence and case fatality rate of traumatic brain injury among children (0–18 years) in Sub-Saharan Africa. A systematic review and meta-analysis

Introduction Studies from Sub-Saharan Africa (SSA) countries have reported on the incidence and case fatality rate of children with Traumatic Brain Injury (TBI). However, there is lack of a general epidemiologic description of the phenomenon in this sub-region underpinning the need for an accurate and reliable estimate of incidence and outcome of children (0–18 years) with TBI. This study therefore, extensively reviewed data to reliably estimate incidence, case fatality rate of children with TBI and its mechanism of injury in SSA. Methods Electronic databases were systematically searched in English via Medline (PubMed), Google Scholar, and Africa Journal Online (AJOL). Two independent authors performed an initial screening of studies based on the details found in their titles and abstracts. Studies were assessed for quality/risk of bias using the modified Newcastle-Ottawa Scale (NOS). The pooled case fatality rate and incidence were estimated using DerSimonian and Laird random-effects model (REM). A sub-group and sensitivity analyses were performed. Publication bias was checked by the funnel plot and Egger’s test. Furthermore, trim and fill analysis was used to adjust for publication bias using Duval and Tweedie’s method. Results Thirteen (13) hospital-based articles involving a total of 40685 participants met the inclusion criteria. The pooled case fatality rate for all the included studies in SSA was 8.0%; [95% CI: 3.0%-13.0%], and the approximate case fatality rate was adjusted to 8.2%, [95% CI:3.4%-13.0%], after the trim-and-fill analysis was used to correct for publication bias. A sub-group analysis of sub-region revealed that case fatality rate was 8% [95% CI: 2.0%-13.0%] in East Africa, 1.0% [95% CI: 0.1% -3.0%] in Southern Africa and 18.0% [95% CI: 6.0%-29.0%] in west Africa. The pooled incidence proportion of TBI was 18% [95% CI: 2.0%-33.0%]. The current review showed that Road Traffic Accident (RTA) was the predominant cause of children’s TBI in SSA. It ranged from 19.1% in South Africa to 79.1% in Togo. Conclusion TBI affects 18% of children aged 0 to 18 years, with almost one-tenth dying in SSA. The most common causes of TBI among this population in SSA were RTA and falls. TBI incidence and case fatality rate of people aged 0–18 years could be significantly reduced if novel policies focusing on reducing RTA and falls are introduced and implemented in SSA.

Patients With IBD Receiving Methotrexate Are at Higher Risk of Liver Injury Compared With Patients With Non-IBD Diseases: A Meta-Analysis and Systematic Review

Background: Methotrexate is well-known in treating inflammatory bowel disease (IBD), rheumatoid arthritis (RA), psoriasis (Ps), and psoriatic arthritis (PsA). Several reports have indicated a higher incidence of methotrexate (MTX)-related liver adverse events in patients with IBD. We aim to investigate the risk of liver injury in patients with IBD and those with non-IBD diseases treated with MTX.Methods: We searched PubMed, Embase, and the Cochrane Library for articles that reported liver adverse events in patients with IBD, RA, and Ps/PsA, receiving MTX therapy. Additional articles were obtained by screening the references of recent meta-analysis and reviews. Raw data from included articles were pooled to calculate the cumulative incidence of total liver injury (TLI), MTX discontinuation (MTX-D), and liver fibrosis (LF). RR (relative risk) was calculated to compare the difference between patients with IBD and those with non-IBD diseases.Results: A total of 326 articles with 128,876 patients were included. The patients with IBD had higher incidence of TLI [11.2 vs. 9.2%; relative risk (RR) = 1.22; P = 0.224] and MTX-D (2.6 vs. 1.8%; RR, 1.48; P = 0.089) than patients with non-IBD diseases. Due to the publication bias, trim-and-fill was performed. Afterwards, the patients with IBD showed significantly higher risk of TLI (11.2 vs. 3%; RR = 3.76; p < 0.001), MTX-D (3.3 vs. 0.7%; RR = 5; p < 0.001) and LF (3.1 vs. 0.1%; RR = 38.62; P = 0.001) compared with patients with non-IBD diseases.Conclusion: IBD is associated with a higher risk of MTX-related liver injury. The mechanism of MTX-induced hepatotoxicity might be different in IBD and non-IBD diseases, and needs to be verified in future research.

The Relationship Between Gambling Problems and the Five-Factor Model of Personality: A Systematic Review and Meta-Analysis

Objectives: The aim of the present meta-analysis was to synthesize results from the association between problem gambling (PG) and dimensions of the five factor model of personality and to identify potential moderators (gambling diagnosis: yes/no, comorbidity: yes/no and trait assessment: four or fewer items vs. five items or more) of these associations in meta-regressions.Methods: Searches were conducted in six databases; Medline, Web of Science, PsychInfo, Google Scholar, OpenGrey, and Cochrane Library (conducted on February, 22, 2021). Included studies: (1) reported a relationship between PG and at least one of the personality traits in the five-factor model, (2) contained information of zero-order correlations or sufficient data for such calculations, and (3) were original articles published in any European language. Case-studies, qualitative studies, and reviews were excluded. All articles were independently screened by two authors. Final agreement was reached through discussion or by consulting a third author. Risk of bias of the included studies was assessed by the Newcastle-Ottawa Scale. Data were synthesized using a random effects model.Results: In total 28 studies, comprising 20,587 participants, were included. The correlations between PG and the traits were as follows: Neuroticism: 0.273 (95% CI = 0.182, 0.358), conscientiousness −0.296 (95% CI = −0.400, −0.185), agreeableness −0.163 (95% CI = −0.223, −0.101), openness −0.219 (95% CI = −0.308, −0.127), and extroversion −0.083 (95% CI = −0.120, −0.046). For all meta-analyses the between study heterogeneity was significant. Presence of gambling diagnosis was the only moderator that significantly explained between-study variance showing a more negative correlation to extroversion when participants had a gambling diagnosis compared to when this was not the case.Discussion: The results indicated some publication bias. Correcting for this by a trim-and-fill procedure showed however that the findings were consistent. Clinicians and researchers should be aware of the associations between personality traits and PG. Previous studies have for example showed neuroticism to be related to treatment relapse, low scores on conscientiousness to predict treatment drop-out and agreeableness to reduce risk of treatment drop-out.Systematic Review Registration: PROSPERO (CRD42021237225).

Effects of nonpharmacological interventions on the psychological health of high-risk pregnant women: a systematic review and meta-analysis

Purpose: This study aimed to summarize the current evidence on the effects of nonpharmacological interventions on psychological health outcomes for women with high-risk pregnancies due to conditions such as preeclampsia, gestational diabetes, or preterm labor.Methods: The following databases were searched from January 2000 to December 2020: PubMed, Ovid Embase, CINAHL, Web of Science, DBpia, RISS, and KISS. Two investigators independently reviewed and selected articles according to the inclusion/exclusion criteria. RoB 2 and the ROBINS-I checklist were used to evaluate study quality.Results: Twenty-nine studies with a combined total of 1,806 pregnant women were included in the systematic review and meta-analysis. Psychological health improvements were found in women with preeclampsia (Hedges’ g=–0.67; 95% confidence interval [CI], –0.91 to –0.44), gestational diabetes (Hedges’ g=–0.38; 95% CI, –0.54 to –0.12), and preterm labor (Hedges’ g=–0.73; 95% CI, –1.00 to –0.46). The funnel plot was slightly asymmetrical, but the fail-safe N value and the trim-and-fill method showed no publication bias.Conclusion: Nonpharmacological interventions for women with high-risk pregnancies due to conditions such as preeclampsia, gestational diabetes, and preterm labor can improve psychological parameters such as anxiety, stress, and depression. Nurses can play a pivotal role in the nursing management of pregnant women with high-risk conditions and apply various types of nonpharmacological interventions to meet their needs in uncertain and anxious times during pregnancy.

Mental Health in COVID-19 Pandemic: A Meta-Review of Prevalence Meta-Analyses

Background: Mental health burden has been massively reported during the COVID-19 pandemic period. Aiming to summarise these data, we present a meta-review of meta-analyses that evaluated the impact of COVID-19 pandemic on anxiety, depressive and stress symptoms, psychological distress, post-traumatic stress disorder/symptoms (PTSD), and sleep disturbance, reporting its prevalence on general public (GP) and health care workers (HCW).Methods: A search was performed in the PubMed, EMBASE, and the Web of Science. Sleep disturbances, psychological distress, stress, and burnout were grouped as “Psychophysiological stress,” and anxiety, depression, and PTSD were grouped as “Psychopathology.” A random-effects model, calculating the pooled prevalence together with 95% confidence interval was performed for each domain. Subgroup analyses were performed for each population type (GP and HCW) and for each mental health outcome. For anxiety and depression, subgroup analysis for population type was performed. Heterogeneity is reported as I2. Publication bias was assessed through visual inspection of the funnel plot, and further tested by Egger's test and trim and fill analyses.Results: A total of 18 meta-analyses were included. The prevalence of psychophysiological stress was 31.99% (CI: 26.88–37.58, I2 = 99.9%). HCW showed a higher prevalence (37.74%, CI: 33.26–42.45, I2 = 99.7%) than the GP (20.67%, 15.07–27.66, I2 = 99.9%). The overall prevalence of insomnia, psychological distress, and stress were, respectively, 32.34% (CI: 25.65–39.84), 28.25% (CI: 18.12–41.20), and 36% (CI: 29.31–43.54). Psychopathology was present at 26.45% (CI: 24.22–28.79, I2 = 99.9%) of the sample, with similar estimates for population (HCW 26.14%, CI: 23.37–29.12, I2 = 99.9%; GP: 26.99%, CI: 23.41–30.9, I2 = 99.9%). The prevalence of anxiety, depression, and PTSD was 27.77% (CI: 24.47–31.32), 26.93% (CI: 23.92–30.17), and 20% (CI: 15.54–24.37), respectively. Similar proportions between populations were found for anxiety (HCW = 27.5%, CI: 23.78–31.55; GP = 28.33%, CI: 22.1–35.5) and depression (HCW = 27.05%, CI: 23.14–31.36; GP = 26.7%, CI: 22.32–31.59). Asymmetry in the funnel plot was found, and a slight increase in the estimate of overall psychopathology (29.08%, CI: 26.42–31.89) was found after the trim and fill analysis.Conclusions: The prevalence of mental health problems ranged from 20 to 36%. HCW presented a higher prevalence of psychophysiological stress than the general population.Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=252221, identifier: CRD42021252221.

Effect of Distraction Intervention for Needle-Related Pain and Distress in Children: A Systematic Review and Meta-Analysis

A systematic review and meta-analysis conducted to evaluate the combined effect of distraction intervention for needle-related pain in order to provide the basis for developing an effective nursing intervention for children. We searched three electronic databases, PubMed, Embase, and CINAHL, for original articles published in the period from 1 January 2011 to 31 July 2019. In addition, a manual search was performed on the basis of references in the literature and the references of the articles in pursuit of comprehensive data until 10 December 2019. Meta-analysis was performed by the synthesis of the effect size, homogeneity, heterogeneity, and trim-and-fill method using MIX 2.0 Pro. Well-planned RCTs, single-center studies, high-quality studies, participants older than 10 years of age, and visual and clown distraction interventions were effective for needle-related pain and distress management among children. The results showed evidence supporting the effect of distraction interventions for children’s needle-related pain and distress. Through this review, strategies were identified to design better interventions to improve the outcomes.

Using Selection Models to Assess Sensitivity to Publication Bias: A Tutorial and Call for More Routine Use

In meta-analyses, it is critical to assess the extent to which publication bias might have compromised the results. Classical methods based on the funnel plot, including Egger’s test and Trim-and-Fill, have become the de facto default methods to do so, with a large majority of recent meta-analyses in top medical journals (85%) assessing for publication bias exclusively using these methods. However, these classical funnel plot methods have important limitations when used as the sole means of assessing publication bias: they essentially assume that the publication process favors large point estimates for small studies and does not affect the largest studies, and they can perform poorly when effects are heterogeneous. In light of these limitations, we recommend that meta-analyses routinely apply other publication bias methods in addition to or instead of classical funnel plot methods. To this end, we describe how to use and interpret selection models. These methods make the often more realistic assumption that publication bias favors ``statistically significant'' results and that also directly accommodate effect heterogeneity. Selection models are well-established in the statistics literature and are supported by user-friendly software, yet remain rarely reported in many disciplines. We use previously published meta-analyses to demonstrate that selection models can yield insights that extend beyond those provided by funnel plot methods, suggesting the importance of establishing more comprehensive reporting practices for publication bias assessment.

Effects of Prior Antiplatelet Therapy on Mortality, Functional Outcome, and Hematoma Expansion in Intracerebral Hemorrhage: An Updated Systematic Review and Meta-Analysis of Cohort Studies

Background and Objective: Antiplatelet therapy (APT) is widely used and believed to be associated with increased poor prognosis by promoting bleeding in patients with intracerebral hemorrhage (ICH). We performed a systematic review and meta-analysis to determine whether prior APT is associated with mortality, functional outcome, and hematoma expansion in ICH patients.Methods: The PubMed, Embase, and Web of Science databases were searched for relevant published studies up to December 11, 2020. Univariate and multivariable adjusted odds ratios (ORs) were pooled using a random effects model. Cochran's chi-squared test (Cochran's Q), the I2 statistic, and meta-regression analysis were used to evaluate the heterogeneity. Meta-regression models were developed to explore sources of heterogeneity. Funnel plots were used to detect publication bias. A trim-and-fill method was performed to identify possible asymmetry and assess the robustness of the conclusions.Results: Thirty-one studies fulfilled the inclusion criteria and exhibited a moderate risk of bias. Prior APT users with intracerebral hemorrhage (ICH) had a slightly increased mortality in both univariate analyses [odds ratio (OR) 1.39, 95% CI 1.24–1.56] and multivariable adjusted analyses (OR 1.41, 95% CI 1.21–1.64). The meta-regression indicated that for each additional day of assessment time, the adjusted OR for the mortality of APT patients decreased by 0.0089 (95% CI: −0.0164 to −0.0015; P = 0.0192) compared to that of non-APT patients. However, prior APT had no effects on poor function outcome (pooled univariate OR: 0.99, 95% CI 0.59–1.66; pooled multivariable adjusted OR: 0.93, 95% CI 0.87–1.07) or hematoma growth (pooled univariate OR: 1.23, 95% CI 0.40–3.74, pooled multivariable adjusted OR: 0.94, 95% CI 0.24–3.60).Conclusions: Prior APT was not associated with hematoma expansion or functional outcomes, but there was modestly increased mortality in prior APT patients. Higher mortality of prior APT patients was related to the strong influence of prior APT use on early mortality.Systematic Review Registration:PROSPERO Identifier [CRD42020215243].