scholarly journals Assessing the Association between the Methylenetetrahydrofolate Reductase (MTHFR) 677C->T Polymorphism on Blood Folate Concentrations: A Systematic Review and Meta-analysis of Trials and Observational Studies

Author(s):  
Becky Tsang ◽  
Amy Cordero ◽  
Claire Marchetta ◽  
Joseph Mulinare ◽  
Patricia Mersereau ◽  
...  

Objectives: The methylenetetrahydrofolate reductase (MTHFR) 677C->T polymorphism is a risk factor for neural tube birth defects (NTDs). The T allele produces an enzyme with reduced folate processing capacity, which has been shown to produce lower blood folate concentrations in some studies. Our objective was to assess the association between MTHFR C677T genotypes (CC, CT, TT) and blood folate concentrations among women aged 12-49 years. Methods: We conducted a systematic review of literature published between 1/1992-7/2013 to identify controlled trials and observational studies that reported serum, plasma, or red blood cell (RBC) folate concentrations and MTHFR C677T genotype. We applied a Bayesian random-effects model to predict differences in blood folate concentrations between MTHFR C677T genotypes, stratified by folate assay. Results: Thirty-eight studies met criteria for inclusion. Serum/plasma folate concentrations showed a consistent genotype trend with the highest concentrations for CC (CC > CT > TT) regardless of assay type. RBC folate concentrations measured by microbiologic assay also demonstrated this trend; however, this trend was reversed (CC < CT < TT) in studies using protein-binding assays. Conclusions: Meta-analyses results showed blood folate concentrations differed by assay type and genotype. Previous evidence has shown that RBC folate concentrations measured with a radioimmunoassay requires adjustment for genotype-dependent folate recovery; our results suggest that other protein-binding assays could have similar limitations. Compared to CC individuals, TT individuals have lower blood folate concentrations, which may increase a woman's risk for an NTD-affected pregnancy.

2015 ◽  
Vol 101 (6) ◽  
pp. 1286-1294 ◽  
Author(s):  
Becky L Tsang ◽  
Owen J Devine ◽  
Amy M Cordero ◽  
Claire M Marchetta ◽  
Joseph Mulinare ◽  
...  

ABSTRACTBackground: The methylenetetrahydrofolate reductase (MTHFR) 677C>T polymorphism is a risk factor for neural tube defects. The T allele produces an enzyme with reduced folate-processing capacity, which has been associated with lower blood folate concentrations.Objective: We assessed the association between MTHFR C677T genotypes and blood folate concentrations among healthy women aged 12–49 y.Design: We conducted a systematic review of the literature published from January 1992 to March 2014 to identify trials and observational studies that reported serum, plasma, or red blood cell (RBC) folate concentrations and MTHFR C677T genotype. We conducted a meta-analysis for estimates of percentage differences in blood folate concentrations between genotypes.Results: Forty studies met the inclusion criteria. Of the 6 studies that used the microbiologic assay (MA) to measure serum or plasma (S/P) and RBC folate concentrations, the percentage difference between genotypes showed a clear pattern of CC > CT > TT. The percentage difference was greatest for CC > TT [S/P: 13%; 95% credible interval (CrI): 7%, 18%; RBC: 16%; 95% CrI: 12%, 20%] followed by CC > CT (S/P: 7%; 95% CrI: 1%, 12%; RBC: 8%; 95% CrI: 4%, 12%) and CT > TT (S/P: 6%; 95% CrI: 1%, 11%; RBC: 9%; 95% CrI: 5%, 13%). S/P folate concentrations measured by using protein-binding assays (PBAs) also showed this pattern but to a greater extent (e.g., CC > TT: 20%; 95% CrI: 17%, 22%). In contrast, RBC folate concentrations measured by using PBAs did not show the same pattern and are presented in the Supplemental Material only.Conclusions: Meta-analysis results (limited to the MA, the recommended population assessment method) indicated a consistent percentage difference in S/P and RBC folate concentrations across MTHFR C677T genotypes. Lower blood folate concentrations associated with this polymorphism could have implications for a population-level risk of neural tube defects.


QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Ossama Abdelraoof El Shazly ◽  
Mohamed Mokhtar Abdellah ◽  
Mostafa Abdelnabee Abouzaid

Abstract Background With continued loss of dorsiflexion of the 1st MTP, degenerative changes occur within the joint with severe restriction of movement and increase in pain, which leads to the condition known as hallux rigidus. The amount of dorsiflexion may be reduced to 0-10 degrees with pain on both active and passive motion. Objectives Systematically reviewing available evidence from published articles to assess the effectiveness of arthrodesis of first metatarsophalangeal joint by plate and screws in hallux rigidus. The assessment also would encompass safety, side effects, and complications of this mode of treatment. Materials and Methods We performed this systematic review and meta-analysis in accordance to the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and Meta-analysis Of Observational Studies in Epidemiology (MOOSE) statement. PRISMA and MOOSE are reporting checklists for Authors, Editors, and Reviewers of Meta-analyses of interventional and observational studies. According to International committee of medical journal association (ICJME), reviewers must report their findings according to each of the items listed in those checklists. Results Previous results for arthrodesis have been favourable with a union rate of almost 96%. In the present systematic review and meta-analysis, the overall effect estimates showed that the union rates after plate and screw arthrodesis for 1st MTPJ was 96.2% (95% CI 94 – 98.4%). In addition, the overall effect estimates showed that the non-union rates after plate and screw arthrodesis for 1st MTPJ was 4.2% (95% CI 2.4 – 6.1%). Moreover, the overall effect estimates showed that the satisfaction rates after plate and screw arthrodesis for 1st MTPJ was 94.5% (95% CI 90 – 99%). In the present study, the overall effect estimates showed that the overall complications rate after plate and screw arthrodesis for 1st MTPJ was 7.2% (95% CI 2.5 – 12%). The overall effect estimates showed that the malunion rates after plate and screw arthrodesis for 1st MTPJ was 2.7% (95% CI 0 – 6.4%). Additionally, the overall effect estimates showed that the hardware removal and superficial infection rates after plate and screw arthrodesis for 1st MTPJ were 2% and 2.9%, respectively. Conclusion Our analysis showed that plate and screws fixation is effective techniques that can be used for first MTPJ arthrodesis in patients with hallux rigidus. We found that the screw and plate fixation has a significantly lower rate of nonunion compared with the screw alone, as reported by the literature. However, owing to the small group sizes and methodologic shortcomings, we were unable to identify the clinically superior fixation technique for first MTPJ arthrodesis arthrodesis.


2021 ◽  
Vol 12 ◽  
Author(s):  
Hao Meng ◽  
Shaoyan Huang ◽  
Yali Yang ◽  
Xiaofeng He ◽  
Liping Fei ◽  
...  

Background: Since the 1990s, there have been a lot of research on single-nucleotide polymorphism (SNP) and different diseases, including many studies on 5,10-methylenetetrahydrofolate reductase (MTHFR) polymorphism and essential hypertension (EH). Nevertheless, their conclusions were controversial. So far, six previous meta-analyses discussed the internal relationship between the MTHFR polymorphism and EH, respectively. However, they did not evaluate the credibility of the positive associations. To build on previous meta-analyses, we updated the literature by including previously included papers as well as nine new articles, improved the inclusion criteria by also considering the quality of the papers, and applied new statistical techniques to assess the observed associations. Objectives: This study aims to explore the degree of risk correlation between two MTHFR polymorphisms and EH. Methods: PubMed, EMBASE, the Cochrane Library, CNKI, and Wan Fang electronic databases were searched to identify relevant studies. We evaluated the relation between the MTHFR C677T (rs1801133) and A1298C (rs1801131) polymorphisms and EH by calculating the odds ratios (OR) as well as 95% confidence intervals (CI). Here we used subgroup analysis, sensitivity analysis, cumulative meta-analysis, assessment of publication bias, meta-regression meta, False-positive report probability (FPRP), Bayesian false discovery probability (BFDP), and Venice criterion. Results: Overall, harboring the variant of MTHFR C677T was associated with an increased risk of EH in the overall populations, East Asians, Southeast Asians, South Asians, Caucasians/Europeans, and Africans. After the sensitivity analysis, positive results were found only in the overall population (TT vs. CC: OR = 1.14, 95% CI: 1.00–1.30, Ph = 0.032, I2 = 39.8%; TT + TC vs. CC: OR = 1.15, 95% CI: 1.01–1.29, Ph = 0.040, I2 = 38.1%; T vs. C: OR = 1.14, 95% CI: 1.04–1.25, Ph = 0.005, I2 = 50.2%) and Asian population (TC vs. CC: OR = 1.14, 95% CI: 1.01–1.28, Ph = 0.265, I2 = 16.8%; TT + TC vs. CC: OR = 1.17, 95% CI: 1.04–1.30, Ph = 0.105, I2 = 32.9%; T vs. C: OR = 1.10, 95% CI: 1.02–1.19, Ph = 0.018, I2 = 48.6%). However, after further statistical assessment by FPRP, BFDP, and Venice criteria, the positive associations reported here could be deemed to be false-positives and present only weak evidence for a causal relationship. In addition, when we performed pooled analysis and sensitivity analysis on MTHFR A1298C; all the results were negative. Conclusion: The positive relationships between MTHFR C677T and A1298C polymorphisms with the susceptibility to present with hypertension were not robust enough to withstand statistical interrogation by FPRP, BFDP, and Venice criteria. Therefore, these SNPs are probably not important in EH etiology.


2019 ◽  
Author(s):  
Amanual Getnet Mersha ◽  
Tadesse Melaku Abegaz ◽  
Mohammed Assen Seid ◽  
Eyob Alemayehu Gebreyohannes ◽  
Akshaya Srikanth Bhagavath ◽  
...  

Abstract Background Global data on stroke mortality remained to be sparse. In light of this, we aimed to conduct a Meta-analysis and systematic review of observational studies to estimate the mortality of stroke and to identify risk factors that predispose patients for stroke-related death.Methods This study was conducted based on the Meta-Analyses of Observational Studies in Epidemiology (MOOSE) guidelines. Overall mortality, in-hospital and 30- day mortality due to stroke were the primary outcome measures of the study. The meta-analysis was performed using Stata (Version 14, Stata Corp, College Station, Texas). Random-effect models were used for estimating pooled effects.Findings Overall, thirty two studies assessed overall mortality due to stroke. A total number of 2,885, 126 patients were recruited for the study. Pooled estimate indicated that the overall mortality of stroke was reported to be 20% (19%-22%). Whereas, the 30-day and In-hospital mortality were found to be 18% (16%-20%) and 16% (16%-19%), respectively. A subgroup analysis revealed that Africa registered the highest stroke-related death 29% (23%-36%). Hypertension was found to be an important risk factor for mortality secondary to stroke 61.9% (52.8%-71.1%).Conclusion Overall mortality of stroke was estimated to be twenty percent. The burden of stroke mortality was prominent in Africa region. Hypertension remained to be an independent risk factor for stroke mortality. Mortality of stroke can be minimized by establishing stroke centers that promptly deliver emergency management of stroke event.


2008 ◽  
Vol 5;12 (5;9) ◽  
pp. 819-850
Author(s):  
Laxmaiah Manchikanti

Observational studies provide an important source of information when randomized controlled trials (RCTs) cannot or should not be undertaken, provided that the data are analyzed and interpreted with special attention to bias. Evidence-based medicine (EBM) stresses the examination of evidence from clinical research and describes it as a shift in medical paradigm, in contrast to intuition, unsystematic clinical experience, and pathophysiologic rationale. While the importance of randomized trials has been created by the concept of the hierarchy of evidence in guiding therapy, much of the medical research is observational. The reporting of observational research is often not detailed and clear enough with insufficient quality and poor reporting, which hampers the assessment of strengths and weaknesses of the study and the generalizability of the mixed results. Thus, in recent years, progress and innovations in health care are measured by systematic reviews and meta-analyses. A systematic review is defined as, “the application of scientific strategies that limit bias by the systematic assembly, clinical appraisal, and synthesis of all relevant studies on a specific topic.” Meta-analysis usually is the final step in a systematic review. Systematic reviews and meta-analyses are labor intensive, requiring expertise in both the subject matter and review methodology, and also must follow the rules of EBM which suggests that a formal set of rules must complement medical training and common sense for clinicians to integrate the results of clinical research effectively. While expertise in the review methods is important, the expertise in the subject matter and technical components is also crucial. Even though, systematic reviews and meta-analyses, specifically of RCTs, have exploded, the quality of the systematic reviews is highly variable and consequently, the opinions reached of the same studies are quite divergent. Numerous deficiencies have been described in methodologic assessment of the quality of the individual articles. Consequently, observational studies can provide an important complementary source of information, provided that the data are analyzed and interpreted in the context of confounding bias to which they are prone. Appropriate systematic reviews of observational studies, in conjunction with RCTs, may provide the basis for elimination of a dangerous discrepancy between the experts and the evidence. Steps in conducting systematic reviews of observational studies include planning, conducting, reporting, and disseminating the results. MOOSE, or Meta-analysis of Observational Studies in Epidemiology, a proposal for reporting contains specifications including background, search strategy, methods, results, discussion, and conclusion. Use of the MOOSE checklist should improve the usefulness of meta-analysis for authors, reviewers, editors, readers, and decision-makers. This manuscript describes systematic reviews and meta-analyses of observational studies. Authors frequently utilize RCTs and observational studies in one systematic review; thus, they should also follow the reporting standards of the Quality of Reporting of Meta-analysis (QUOROM) statement, which also provides a checklist. A combined approach of QUOROM and MOOSE will improve reporting of systematic reviews and lead to progress and innovations in health care. Key words: Observational studies, evidence-based medicine, systematic reviews, metaanalysis, randomized trials, case-control studies, cross-sectional studies, cohort studies, confounding bias, QUOROM, MOOSE


2021 ◽  
Vol 11 (6) ◽  
pp. 777
Author(s):  
Woon-Man Kung ◽  
Sheng-Po Yuan ◽  
Muh-Shi Lin ◽  
Chieh-Chen Wu ◽  
Md. Mohaimenul Islam ◽  
...  

Background: Cognitive impairment is one of the most common, burdensome, and costly disorders in the elderly worldwide. The magnitude of the association between anemia and overall cognitive impairment (OCI) has not been established. Objective: We aimed to update and expand previous evidence of the association between anemia and the risk of OCI. Methods: We conducted an updated systematic review and meta-analysis. We searched electronic databases, including EMBASE, PubMed, and Web of Science for published observational studies and clinical trials between 1 January 1990 and 1 June 2020. We excluded articles that were in the form of a review, letter to editors, short reports, and studies with less than 50 participants. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed. We estimated summary risk ratios (RRs) with random effects. Results: A total of 20 studies, involving 6558 OCI patients were included. Anemia was significantly associated with an increased risk of OCI (adjusted RR (aRR) 1.39 (95% CI, 1.25–1.55; p < 0.001)). In subgroup analysis, anemia was also associated with an increased risk of all-cause dementia (adjusted RR (aRR), 1.39 (95% CI, 1.23–1.56; p < 0.001)), Alzheimer’s disease [aRR, 1.59 (95% CI, 1.18–2.13; p = 0.002)], and mild cognitive impairment (aRR, 1.36 (95% CI, 1.04–1.78; p = 0.02)). Conclusion: This updated meta-analysis shows that patients with anemia appear to have a nearly 1.39-fold risk of developing OCI than those without anemia. The magnitude of this risk underscores the importance of improving anemia patients’ health outcomes, particularly in elderly patients.


QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Atef Mohamed Fathy Elbeltagy ◽  
Mostafa Mamdouh Abdelrahman Ashoub ◽  
Shady Saleh Mohammed Ahmed

Abstract Background Acute ankle sprain is a very common injury which comprises 80% of all ankle injuries. Acute ankle sprain affects almost exclusively the lateral ligamentous complex including ATFL followed by CFL, while PTFL is rarely of clinical significance. Objective To study the clinical trials in a Meta-analytical form, in order to compare surgical versus conservative treatments for the management of acute injuries of the lateral ligament complex of the ankle. Materials and Methods We performed this systematic review and meta-analysis in accordance to the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Meta-analyses Of Observational Studies in Epidemiology (MOOSE) statements. PRISMA and MOOSE are reporting checklists for Authors, Editors, and Reviewers of Meta-analyses of interventional and observational studies. Results In the present study, we searched Medline via PubMed, SCOPUS, Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL) from their inception till April 2019. The search retrieved 702 unique records. We then retained 48 potentially eligible records for full-texts screening. Finally, 14 studies (Total No. of patients=1896) were included in the present systematic review and meta-analysis Conclusion: Starting a physiotherapy programme as early as possible is essential to control pain and swelling, to improve and maintain the range of motion, and to minimize the risk of stiffness and muscle wasting, which are the two decisive factors which delay patients from returning to their normal activities. Regardless of severity, surgery for acute ankle sprain is not recommended anymore.


2020 ◽  
Vol 9 (6) ◽  
pp. 1845 ◽  
Author(s):  
Irene Sanz-Corbalán ◽  
Aroa Tardáguila-García ◽  
Josep M. García-Alamino ◽  
Yolanda García-Álvarez ◽  
Francisco Javier Álvaro-Afonso ◽  
...  

A systematic review and proportional meta-analysis were carried out to investigate the complications that occur after surgical metatarsal head resection in diabetic foot patients. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) checklist recommendations were applied, and the selected studies were evaluated using a Strengthening the Reporting of Observational studies in Epidemiology (STROBE) checklist. PubMed (Medline) and Embase (Elsevier) were searched in December 2019 to find clinical trials, cohort studies, or case series assessing the efficacy of the metatarsal head resection technique in diabetic foot patients. The systematic review covered 21 studies that satisfied the inclusion criteria and included 483 subjects. The outcomes evaluated were the time to heal, recurrence, reulceration, amputation, and other complications. The proportion of recurrence was 7.2% [confidence interval (CI) 4.0–10.4, p < 0.001], that of reulceration was 20.7% (CI 11.6–29.8, p < 0.001), and that of amputation was 7.6% (CI 3.4–11.8, p < 0.001). A heterogeneity test indicated I2 = 72.6% (p < 0.001) for recurrences, I2 = 94% (p < 0.001) for reulcerations, and I2 = 79% (p < 0.001) for amputations. We conclude that metatarsal head resections in diabetic foot patients are correlated with significant complications, especially reulceration.


2021 ◽  
Author(s):  
Lin Wang ◽  
Qinguang Xu ◽  
Yan Chen ◽  
Yan Xue ◽  
Ding Jiang ◽  
...  

Abstract Background Osteoarthritis (OA) is the most common form of arthritis, causing by multiple factors. It has long been a belief that arthritis pain is influenced by the weather. However, scientific studies have documented inconsistent results. To date, neither systematic review nor meta-analysis of existing findings has comprehensively considered their relations. The present study will critically appraise and synthesize the existing evidence from observational studies that examined the relationship between certain climate conditions and OA. Methods and design: This protocol will be conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) guidelines. There are no restrictions on the study date or publication status for searches in the Cochrane Library, EMBASE, Web of Science, PubMed, and other relative databases. All eligible observational studies will be included, with weather conditions as effect factors and OA symptom or imaging abnormality as outcomes. Two reviewers will be responsible for data extraction and analysis. Risk of bias and quality appraisal will be performed for the included studies using Newcastle-Ottawa Scale (NOS). Meta-analysis will be conducted using Rev Man V.5.3 with the associations between weather conditions and OA presented by odds ratios (ORs), relative risks (RRs), hazard ratios (HRs) and the 95% confidence intervals (CIs). Results This systematic review and meta-analysis will present the overall association between weather conditions and OA. The association of climate factors influencing OA incidence or progression would be further illustrated in subgroup analysis depending on whether that has been extensively described in the literature. Discussion This study will provide the analysis evidence on the effect of meteorological factors on OA. In an approach of dealing with weather conditions, the results will benefit the daily management of OA.


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