scholarly journals Systematic review and meta-analysis determining the benefits of in vivo genetic therapy in spinal muscular atrophy rodent models

Gene Therapy ◽  
2021 ◽  
Author(s):  
Ellie M. Chilcott ◽  
Evalyne W. Muiruri ◽  
Theodore C. Hirst ◽  
Rafael J. Yáñez-Muñoz
Keyword(s):  
Systematic Review ◽  
Experimental Design ◽  
Spinal Muscular Atrophy ◽  
Publication Bias ◽  
Median Survival ◽  
Muscular Atrophy ◽  
Meta Analysis ◽  
Significant Heterogeneity ◽  
Rodent Models ◽  
Genetic Therapy

AbstractSpinal muscular atrophy (SMA) is a severe childhood neuromuscular disease for which two genetic therapies, Nusinersen (Spinraza, an antisense oligonucleotide), and AVXS-101 (Zolgensma, an adeno-associated viral vector of serotype 9 AAV9), have recently been approved. We investigated the pre-clinical development of SMA genetic therapies in rodent models and whether this can predict clinical efficacy. We have performed a systematic review of relevant publications and extracted median survival and details of experimental design. A random effects meta-analysis was used to estimate and compare efficacy. We stratified by experimental design (type of genetic therapy, mouse model, route and time of administration) and sought any evidence of publication bias. 51 publications were identified containing 155 individual comparisons, comprising 2573 animals in total. Genetic therapies prolonged survival in SMA mouse models by 3.23-fold (95% CI 2.75–3.79) compared to controls. Study design characteristics accounted for significant heterogeneity between studies and greatly affected observed median survival ratios. Some evidence of publication bias was found. These data are consistent with the extended average lifespan of Spinraza- and Zolgensma-treated children in the clinic. Together, these results support that SMA has been particularly amenable to genetic therapy approaches and highlight SMA as a trailblazer for therapeutic development.

Efficacy and Safety of Valproic Acid for Spinal Muscular Atrophy: A Systematic Review and Meta-Analysis

CNS Drugs ◽  
2019 ◽  
Vol 33 (3) ◽  
pp. 239-250
Author(s):  
Abdelrahman Elshafay ◽  
Truong Hong Hieu ◽  
Mohamed Fahmy Doheim ◽  
Mahmoud Attia Mohamed Kassem ◽  
Mohammed Fathi ELdoadoa ◽  
...  
Keyword(s):  
Systematic Review ◽  
Valproic Acid ◽  
Spinal Muscular Atrophy ◽  
Muscular Atrophy ◽  
Meta Analysis ◽  
Efficacy And Safety

Efficacy and security of onasemnogene abeparvovec-XIOI in spinal muscular atrophy: a systematic review and meta-analysis

2021 ◽  
Vol 429 ◽  
pp. 118887
Author(s):  
Aaron Rodriguez-Calienes ◽  
Sandra Chavez-Malpartida ◽  
Giancarlo Alvarado-Gamarra ◽  
Niels Pacheco-Barrios ◽  
Peggy Martinez-Esteban ◽  
...  
Keyword(s):  
Systematic Review ◽  
Spinal Muscular Atrophy ◽  
Muscular Atrophy ◽  
Meta Analysis

scholarly journals The association between lithium in drinking water and neuropsychiatric outcomes: A systematic review and meta-analysis from across 2678 regions containing 113 million

2020 ◽  
pp. 000486742096374 ◽  
Author(s):  
Brenton Eyre-Watt ◽  
Eesharnan Mahendran ◽  
Shuichi Suetani ◽  
Joseph Firth ◽  
Steve Kisely ◽  
...  
Keyword(s):  
Systematic Review ◽  
Drinking Water ◽  
Confidence Interval ◽  
Publication Bias ◽  
Hospital Admissions ◽  
Meta Analysis ◽  
Significant Heterogeneity ◽  
Suicide Rates ◽  
Registration Number ◽  
Trim And Fill

Background: Lithium in drinking water may have significant mental health benefits. We investigated the evidence on the association between lithium concentrations in drinking water and their neuropsychiatric outcomes. Methods: We conducted a systematic review and meta-analysis and searched Pubmed, Embase, Web of Science, PsycINFO and CINAHL up to 19 January 2020, for peer-reviewed research examining the association between lithium concentrations in drinking water and neuropsychiatric outcomes. We used a pairwise analysis and a random effects model to meta-analyse suicide rates and psychiatric hospital admissions. We assessed for publication bias using Egger’s test and Duval and Tweedie’s Trim and Fill analysis. Results: Twenty-seven studies including 113 million subjects were included in this systematic review. Meta-analysis of 14 studies including 94 million people found higher lithium concentrations were associated with reduced suicide rates ( r = −0.191, 95% confidence interval = [−0.287, −0.090], p < 0.001) and meta-analysis of two studies including 5 million people found higher lithium concentrations were associated with fewer hospital admissions ( r = −0.413, 95% confidence interval = [−0.689, −0.031], p = 0.035). We found significant heterogeneity between studies ( Q = 67.4, p < 0.001, I2 = 80.7%) and the presence of publication bias (Egger’s test; t value = 2.90, p = 0.013). Other included studies did not provide sufficient data to analyse other neuropsychiatric outcomes quantitatively. Conclusion: Higher lithium concentrations in drinking water may be associated with reduced suicide rates and inpatient psychiatric admissions. The relationship with other neuropsychiatric outcomes and complications remains unclear. Further research is required before any public health recommendations can be made. Trial registration number: The study was registered with PROSPERO, number CRD42018090145.

The impact of time to adjuvant chemotherapy (AC) on survival in colorectal cancer (CRC): A systematic review and meta-analysis.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 364-364 ◽  
Author(s):  
J. J. Biagi ◽  
M. Raphael ◽  
W. D. King ◽  
W. Kong ◽  
W. J. Mackillop ◽  
...  
Keyword(s):  
Systematic Review ◽  
Prognostic Factors ◽  
Adjuvant Chemotherapy ◽  
Publication Bias ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Significant Heterogeneity ◽  
Risk Of Death ◽  
The Impact ◽  
The Relationship

364 Background: The optimal timing from CRC surgery to initiation of AC is unknown. We report a systematic review and meta-analysis to determine the relationship between time to adjuvant chemotherapy (TTAC) and survival. Methods: A systematic review of literature was done to identify studies that described the relationship between TTAC and survival. Studies were only included if the distribution of relevant prognostic factors was adequately described, and either comparative groups were balanced or results adjusted for the prognostic factors. Hazard ratio (HR) and TTAC for overall survival (OS) and disease free survival (DFS) from each study were converted to a regression coefficient (β) and standard error (SE) corresponding to a continuous representation per 4 weeks of TTAC. The adjusted β from individual studies were combined using a fixed-effect model. Inverse-variance (1/SE2) was used to weight individual studies. The possible effect of publication bias was investigated using the trim and fill approach. Results: We identified 9 eligible studies involving 14,357 patients (4 published articles, 5 abstracts). Two studies were randomized trials and 7 were cohort studies. Six studies reported TTAC as a binary variable and 3 reported TTAC as ≥3 categories. An estimate of HR for OS was derived from all 9 studies and estimate for DFS was derived from 5 studies. Meta-analysis demonstrated that a 4-week increase in TTAC was associated with a significant decrease in both OS (HR = 1.12, 95% CI 1.09-1.15), and DFS (HR = 1.15, 95% CI 1.11-1.20). The analysis showed no significant heterogeneity among studies. These TTAC associations remained significant after analysis for potential publication bias, and when the analysis was repeated excluding the two studies of largest weight. Conclusions: This study demonstrates a 12% increase in the risk of death for each 4 week of delay in the start of AC for CRC. These findings indicate the need for clinicians and health systems managers to take the steps necessary to keep TTAC as short as reasonably achievable. In addition, our results suggest there may be some benefit to AC after a 3-month TTAC delay. No significant financial relationships to disclose.

scholarly journals The Efficacy of Mesenchymal Stem Cell Therapies in Rodent Models of Multiple Sclerosis: An Updated Systematic Review and Meta-Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Jialin He ◽  
Yan Huang ◽  
Jianyang Liu ◽  
Ziwei Lan ◽  
Xiangqi Tang ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Systematic Review ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Functional Outcome ◽  
Functional Recovery ◽  
Meta Analysis ◽  
Therapeutic Effects ◽  
Significant Heterogeneity ◽  
Rodent Models

Studies have demonstrated the potential of mesenchymal stem cell (MSC) administration to promote functional recovery in preclinical studies of multiple sclerosis (MS), yet the effects of MSCs on remyelination are poorly understood. We wished to evaluate the therapeutic effects of MSCs on functional and histopathological outcomes in MS; therefore, we undertook an updated systematic review and meta-analysis of preclinical data on MSC therapy for MS. We searched mainstream databases from inception to July 15, 2021. Interventional studies of therapy using naïve MSCs in in vivo rodent models of MS were included. From each study, the clinical score was extracted as the functional outcome, and remyelination was measured as the histopathological outcome. Eighty-eight studies published from 2005 to 2021 met the inclusion criteria. Our results revealed an overall positive effect of MSCs on the functional outcome with a standardized mean difference (SMD) of −1.99 (95% confidence interval (CI): −2.32, −1.65; p = 0.000). MSCs promoted remyelination by an SMD of −2.31 (95% CI: −2.84, −1.79; p = 0.000). Significant heterogeneity among studies was observed. Altogether, our meta-analysis indicated that MSC administration improved functional recovery and promoted remyelination prominently in rodent models of MS.

scholarly journals Inverse Association of Coffee with Liver Cancer Development: An Updated Systematic Review and Meta-analysis

2020 ◽  
Author(s):  
Abhishek Bhurwal ◽  
Puru Ratta ◽  
Sho Yoshitake ◽  
Lauren Pioppo ◽  
Debashish Reja ◽  
...  
Keyword(s):  
Systematic Review ◽  
Liver Cancer ◽  
Publication Bias ◽  
Meta Analysis ◽  
Coffee Consumption ◽  
Cancer Development ◽  
Significant Heterogeneity ◽  
Inverse Association ◽  
Coffee Drinking ◽  
Higher Doses

Background and Aims: Coffee consumption has been suggested to reduce the risk for hepatocellular carcinoma (HCC). While several studies report inverse correlation with coffee drinking, others have suggested more than 2 cups of coffee every day decrease the risk of liver cancer or HCC. However, controversy exists about the exact dose that would provide protective benefit. Therefore, we aimed to carry out a systematic review and meta-analysis of all studies that investigated the association of coffee consumption and risk of HCC and/or liver cancer. Our outcomes were the evaluation of the association of coffee with HCC or liver cancer development along with the amount of coffee needed to prevent HCC or liver cancer. Methods: We performed a PubMed/MEDLINE/EMBASE/Ovid/Google Scholar search of original articles published in English from 1996 to June 2019, on case-control or cohort or prospective studies that associated coffee with liver cancer or HCC. We calculated the relative risk (RR) of the two conditions for coffee drinking and then stratified this into increments of one cup of coffee per day. Twenty studies were identified. The analysis was performed using random effects models from the methods of DerSimonian and Laird with inverse variance weighting. The Cochrane Q and the I 2 statistics were calculated to assess heterogeneity between studies. A p<0.10 value for chi-square test and I 2 <20% were interpreted as low-level heterogeneity. Probability of publication bias was assessed using funnel plots and with the Egger’s test. Results: The overall RR was 0.69 (95%CI 0.56-0.85; p<0.001) with significant heterogeneity between the studies. We performed subgroup analysis over the increments of 1 cup of coffee. Higher doses of coffee consumption were associated with a significant decrease in the risks of developing HCC or liver cancer. The funnel plot did not show significant publication bias. Conclusions: Our systematic review and meta-analysis suggests that drinking coffee provides benefits with a reduction in the risk of HCC or liver cancer. Higher doses of coffee have higher benefits in terms of risk reduction. However, further biological and epidemiological studies are required to determine the exact mechanism and to study specific subgroups such as viral hepatitis B or C related HCC.

Biomarkers of disease progression in adolescents and adults with 5q spinal muscular atrophy: a systematic review and meta-analysis

2022 ◽  
Author(s):  
Maria Gavriilaki ◽  
Maria Moschou ◽  
Vasileios Papaliagkas ◽  
Konstantinos Notas ◽  
Evangelia Chatzikyriakou ◽  
...  
Keyword(s):  
Systematic Review ◽  
Spinal Muscular Atrophy ◽  
Disease Progression ◽  
Muscular Atrophy ◽  
Meta Analysis ◽  
Adolescents And Adults

scholarly journals Plasmodium vivax epidemiology in Ethiopia 2000-2020: A systematic review and meta-analysis

2021 ◽  
Vol 15 (9) ◽  
pp. e0009781
Author(s):  
Tsige Ketema ◽  
Ketema Bacha ◽  
Kefelegn Getahun ◽  
Hernando A. del Portillo ◽  
Quique Bassat
Keyword(s):  
Systematic Review ◽  
Plasmodium Vivax ◽  
Publication Bias ◽  
Systematic Reviews ◽  
Meta Analysis ◽  
Infection Prevalence ◽  
Clear Understanding ◽  
Significant Heterogeneity ◽  
Funnel Plot ◽  
Study Setting

Background Ethiopia is one of the scarce rare African countries where Plasmodium vivax and P. falciparum co-exist. There has been no attempt to derive a robust prevalence estimate of P. vivax in the country although a clear understanding of the epidemiology of this parasite is essential for informed decisions. This systematic review and meta-analysis, therefore, is aimed to synthesize the available evidences on the distribution of P. vivax infection by different locations/regions, study years, eco-epidemiological zones, and study settings in Ethiopia. Methods This study was conducted in accordance with Preferred Reposting Items for Systematic Reviews and Meta Analyses (PRISMA) guidelines. Studies conducted and published over the last two decades (2000 to 2020) that reported an estimate of P. vivax prevalence in Ethiopia were included. The Cochrane Q (χ2) and the I2 tests were used to assess heterogeneity, and the funnel plot and Egger’s test were used to examine publication bias. A p-value of the χ2 test <0.05 and an I2 value >75% were considered presence of considerable heterogeneity. Random effect models were used to obtain pooled estimate of P. vivax infection prevalence. This study is registered with PROSPERO (International Prospective Register of Systematic Reviews): ID CRD42020201761. Results We screened 4,932 records and included 79 studies that enrolled 1,676,659 confirmed malaria cases, from which 548,214 (32.69%) were P. vivax infections and 1,116,581 (66.59%) were due to P. falciparum. The rest (11,864 or 0.7%) were due to mixed infections. The pooled estimate of P. vivax prevalence rate was 8.93% (95% CI: 7.98–9.88%) with significant heterogeneity (I2 = 100%, p<0.0001). Regional differences showed significant effects (p<0.0001, and I2 = 99.4%) on the pooled prevalence of P. vivax, while study years (before and after the scaling up of interventional activities) did not show significant differences (p = 0.9, I2 = 0%). Eco-epidemiological zones considered in the analysis did show a significant statistical effect (p<0.001, I2 = 78.5%) on the overall pooled estimate prevalence. Also, the study setting showed significant differences (p = 0.001, and I2 = 90.3%) on the overall prevalence, where significant reduction of P. vivax prevalence (4.67%, 95%CI: 1.41–7.93%, p<0.0001) was observed in studies conducted at the community level. The studies included in the review demonstrated lack of publication bias qualitatively (symmetrical funnel plot) and quantitatively [Egger’s test (coefficient) = -2.97, 95% CI: -15.06–9.13, p = 0.62]. Conclusion The estimated prevalence of P. vivax malaria in Ethiopia was 8.93% with P. vivax prevailing in the central west region of Ethiopia, but steadily extending to the western part of the country. Its distribution across the nation varies according to geographical location, study setting and study years.

scholarly journals Incidence and Clinical Impacts of COVID-19 Infection in Patients with Hemodialysis: Systematic Review and Meta-Analysis of 396,062 Hemodialysis Patients

2020 ◽  
Author(s):  
Chun-Yu Chen ◽  
Shih-Chieh Shao ◽  
Yih-Ting Chen ◽  
Cheng-Kai Hsu ◽  
Heng-Jung Hsu ◽  
...  
Keyword(s):  
Systematic Review ◽  
Mortality Rate ◽  
Clinical Outcomes ◽  
Publication Bias ◽  
Meta Analysis ◽  
Healthcare Providers ◽  
Geographic Area ◽  
Epidemiologic Studies ◽  
Significant Heterogeneity ◽  
Incidence And Mortality

Abstract Background: Better understanding of incidence and clinical outcomes of COVID-19 infection in hemodialysis (HD) patients could assist healthcare providers to develop proper preventive strategies and optimal management. However, no published systematic review summarizes current epidemiological evidence regarding COVID-19 infection in HD patients.Methods: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We systematically searched PUBMED and EMBASE for articles published on incidence or mortality of COVID-19 infection in maintenance HD patients until September 2020, and conducted meta-analysis of proportions for incidence and mortality rate. Heterogeneity was measured by Cochran’s Q and I2 statistic. Publication bias was evaluated by Egger’s test. The study protocol was registered in the PROSPERO database (CRD42020209134).Results: In total, 29 articles with 3,261 confirmed COVID-19 cases from pooled 396,062 HD patients were identified. Overall COVID-19 incidence in these HD patients was 7.7% (95% CI: 5.0-10.9%), with significant heterogeneity among the studies (I2 = 99.7%, p<0.001) and risk of publication bias (Egger’s test, p<0.001). Overall mortality rate was 22.4% (95% CI: 17.9-27.1%) in HD patients with COVID-19, with significant heterogeneity among the studies (I2 = 87.1%, p<0.001). Reported incidence and mortality varied by geographic area, being higher in non-Asian- than Asian countries.Conclusions: Both incidence and mortality of COVID-19 infection were higher in HD patients. Available data may underestimate the real incidence of infection because screening and diagnosis differ between countries. International collaboration and standardized reporting of future epidemiologic studies is encouraged to improve clinical outcomes of COVID-19 infection in HD patients.

scholarly journals The Magnitude of Medication Administration Errors among Nurses in Ethiopia: a Systematic Review and Meta-analysis

2020 ◽  
Vol 9 (1) ◽  
pp. 1-8
Author(s):  
Berhanu Boru Bifftu ◽  
Bezenaw Yimer Mekonnen
Keyword(s):  
Systematic Review ◽  
Publication Bias ◽  
Meta Analysis ◽  
Medication Administration ◽  
Significant Heterogeneity ◽  
Random Effects Model ◽  
Time Error ◽  
Medication Administration Errors ◽  
Pooled Prevalence

Introduction: Nurses are the final safety check in the process of medication administration process to prevent errors that adversely affect life; yet death of comprehensive evidences in Ethiopia. The present study aimed to assess the pooled magnitude of MAEs (Medication Administration Errors) in Ethiopia. Methods: Systematic literature search in the databases of Pub-Med, Cochrane, and Google Scholar for gray literature were performed until December 3, 2018. The quality of study was assessed using criteria adopted from similar studies. Heterogeneity test and evidence of publication bias were assessed. Moreover, sensitivity analysis was also performed. Pooled prevalence of MAE was calculated using the random effects model. Results: A total of 2142 medication administrations were from observational and 681from selfreported studies were included in this systematic review and meta-analysis. The most prevalent and frequently reported type of MAEs was documentation error (52% to 87.5%) and time error (25.5% to 58.5%) respectively. Overall, the pooled magnitude of MAE was found to be 39.3% (95% CI, 29.1%-49.5%).It has no evidence of significant heterogeneity (I2 = 0%, P = 0.57) and publication bias Egger’s test (P = 0.40). Conclusion: Overall, more than one in four observed/perceived medication administrations had errors. Documentation error is the most prevalent type of error. Nurses are suggested to strengthen their focus on the rights of medication administration guide particularly, documentation of their activities need special attention.

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