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Association Between Circulating Zinc and Risk for Childhood Asthma and Wheezing: A Meta-analysis on 21 Articles and 2205 Children.
Xue, M, Wang, Q, Pang, B, Zhang, X, Zhang, Y, Deng, X, Zhang, Z, Niu, W
Biological trace element research. 2024;(2):442-453
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Abstract
Asthma is one of the most frequent chronic diseases in children, and growing focus is placed on the exploration of attributable risk factors. Currently, no consensus has been reached on the implication of circulating zinc in the development of asthma. We aimed to conduct a meta-analysis to examine the association between circulating zinc and risk for childhood asthma and wheezing. We searched PubMed, Web of Science, EMBASE, and Google Scholar from inception until December 1, 2022. All procedures were performed independently and in duplicate. Random-effects model was adopted to derive standardized mean difference (SMD) and 95% confidence interval (95% CI). Statistical analyses were completed using the STATA software. Twenty-one articles and 2205 children were meta-analyzed. Overall, there was a statistically significant association between circulating zinc and risk for childhood asthma and wheezing (SMD: -0.38; 95% CI: -0.60 to -0.17; I2=82.6%, p<0.001), without evidence of publication bias as revealed by Begg's (p=0.608) and Egger (p=0.408) tests. Subgroup analyses showed that children with asthma or wheezing in Middle Eastern countries had significantly lower circulating zinc levels than controls (SMD: -0.42; 95% CI: -0.69 to -0.14; p<0.001; I2=87.1%). Additionally, average circulating zinc levels in asthma children were 0.41 μg/dl lower than that in controls, and the difference was statistically significant (SMD: -0.41; 95% CI: -0.65 to -0.16; p<0.001; I2=83.7%). By contrast, children with wheezing were 0.20 μg/dl lower than that in controls, and no between-group difference was noted (SMD=-0.20; 95% CI: -0.58 to 0.17; p=0.072; I2=69.1%). Our findings indicated that circulating zinc was associated with a significant risk for childhood asthma and its related symptom wheezing.
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Effectiveness of an intermittent fasting diet versus regular diet on fat loss in overweight and obese middle-aged and elderly people without metabolic disease: a systematic review and meta-analysis of randomized controlled trials.
Yao, K, Su, H, Cui, K, Gao, Y, Xu, D, Wang, Q, Ha, Z, Zhang, T, Chen, S, Liu, T
The journal of nutrition, health & aging. 2024;(3):100165
Abstract
OBJECTIVE As the number of adults aged over 40 with obesity increases dramatically, intermittent fasting interventions (IF) may help them to lose fat and weight. This systematic review investigated the most recent research on the effects of intermittent fasting and a regular diet on body composition and lipids in adults aged over 40 with obesity without the metabolic disease. DATA SOURCES Randomized controlled trials (RCTs) on IF on adults aged over 40 with obesity were retrieved from PubMed, Web of Science, EBSCO, China Knowledge Network (CNKI), VIP database, Wanfang database with the experimental group using IF and the control group using a regular diet. Revman was used for meta-analysis. Effect sizes are expressed as weighted mean differences (WMD) and 95% confidence intervals (CI). STUDY SELECTION A total of 9 articles of randomised controlled trials that met the requirements were screened for inclusion. Studies typically lasted 2-6 weeks. The experimental population was aged 42-66 years, with a BMI range of 25.7-35 kg/m2. SYNTHESIS A total of 9 RCTs were included. meta-analysis showed that body weight (MD: -2.05 kg; 95% CI (-3.84, -0.27); p = 0.02), BMI (MD: -0.73 kg/m2; 95% CI (-1.05, -0.41); p < 0.001), fat mass (MD: -2.14 kg; 95% CI (-3.81, 0.47); p = 0.01), and TG (MD = -0.32 mmol/L, 95% CI (-0.50, -0.15, p < 0.001) were significantly lower in the experimental group than in the control group. No significant reduction in lean body mass (MD: -0.31 kg; 95% CI (-0.96, 0.34); p = 0.35). CONCLUSION IF had a reduction in body weight, BMI, fat mass, and TG in adults aged over 40 with obesity without metabolic disease compared to RD, and IF did not cause a significant decrease in lean body mass, which suggests healthy and effective fat loss. However, more long-term and high-quality trials are needed to reach definitive conclusions.
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The effect of exercise training intervention for patients with abdominal aortic aneurysm on cardiovascular and cardiorespiratory variables: an updated meta-analysis of randomized controlled trials.
Han, Q, Qiao, L, Yin, L, Sui, X, Shao, W, Wang, Q
BMC cardiovascular disorders. 2024;(1):80
Abstract
OBJECTIVE The purpose of this meta-analysis was to evaluate the effect of exercise training intervention in patients with abdominal aortic aneurysm (AAA). METHODS Eight randomized controlled trials (RCTs) that recruited 588 AAA patients were extracted using 4 databases (PubMed, Embase, Wanfang Data, and Cochrane Library). Physiological and biochemistry parameters that included in this study are high-sensitivity C-reactive protein (hs-CRP), respiratory peak oxygen uptake rate (VO2peak), triglyceride (TG), total cholesterol (TC), anaerobic threshold (AT), the diameter of AAA, high density lipoprotein cholesterol (HDL), low density lipoprotein cholesterol (LDL), and matrix metalloproteinase-9 (MMP-9). Standard mean difference (SMD) was used to assess the between group effect. RESULTS This meta-analysis was synthesized with findings from RCTs and found that hs-CRP (SMD, - 0.56 mg/dL; 95% CI: - 0.90 to 0.22; P = 0.001), VO2peak (SMD, 0.4 mL/kg/min; 95% CI, 0.21 to 0.60; P < 0.001), TG (SMD, - 0.39 mg/dL; 95% CI: - 0.02 to 0.77; P = 0.04), and AT (SMD, 0.75 mL/kg/min; 95% CI, 0.54 to 0.96; P < 0.001) were significantly improved in the exercise groups, while the size of AAA (SMD, - 0.15; 95% CI: - 0.36 to 0.06; P = 0.15), TC (SMD, 0.16 mg/dL; 95% CI: - 0.10 to 0.42; P = 0.23), HDL/LDL ratio (SMD, - 0.06; 95% CI: - 0.32 to 0.20; P = 0.64), HDL (SMD, - 0.09; 95% CI: - 0.39 to 0.20; P = 0.54), LDL (SMD, 0.08; 95% CI: - 0.21 to 0.38; P = 0.59), and MMP-9 (SMD, - 0.23 mg/dL; 95% CI: - 0.53 to 0.06; P = 0.12) did not differ in the exercise groups compared with the controls. CONCLUSION Exercise intervention improved some of the CVD risk factors but not all, hs-CRP, VO2peak and AT were significantly improved after exercise intervention, while, changes of MMP-9, the size of AAA, and the overall lipids profile were not. Exercise intervention provides an additional solution for improving cardiorespiratory capacity and health status among AAA patients, and might lead to a delay of AAA progression.
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Association of soft drinks and 100% fruit juice consumption with risk of cancer: a systematic review and dose-response meta-analysis of prospective cohort studies.
Pan, B, Lai, H, Ma, N, Li, D, Deng, X, Wang, X, Zhang, Q, Yang, Q, Wang, Q, Zhu, H, et al
The international journal of behavioral nutrition and physical activity. 2023;(1):58
Abstract
BACKGROUND Studies of the associations between soft drinks and the risk of cancer showed inconsistent results. No previous published systematic reviews and meta-analysis has investigated a dose-response association between exposure dose and cancer risk or assessed the certainty of currently available evidence. Therefore, we aim to demonstrate the associations and assessed the certainty of the evidence to show our confidence in the associations. METHODS We searched Embase, PubMed, Web of Science, and the Cochrane Library from inception to Jun 2022, to include relevant prospective cohort studies. We used a restricted cubic spline model to conduct a dose-response meta-analysis and calculated the absolute effect estimates to present the results. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess the certainty of the evidence. RESULTS Forty-two articles including on 37 cohorts enrolled 4,518,547 participants were included. With low certainty evidence, increased consumption of sugar-sweetened beverages (SSBs) per 250 mL/day was significantly associated with a 17% greater risk of breast cancer, a 10% greater risk of colorectal cancer, a 30% greater risk of biliary tract cancer, and a 10% greater risk of prostate cancer; increased consumption of artificially sweetened beverages (ASBs)re per 250 mL/day was significantly associated with a 16% greater risk of leukemia; increased consumption of 100% fruit juice per 250 mL/day was significantly associated with a 31% greater risk of overall cancer, 22% greater risk of melanoma, 2% greater risk of squamous cell carcinoma, and 29% greater risk of thyroid cancer. The associations with other specific cancer were no significant. We found linear dose-response associations between consumption of SSBs and the risk of breast and kidney cancer, and between consumption of ASBs and 100% fruit juices and the risk of pancreatic cancer. CONCLUSIONS An increment in consumption of SSBs of 250 mL/day was positively associated with increased risk of breast, colorectal, and biliary tract cancer. Fruit juices consumption was also positively associated with the risk of overall cancer, thyroid cancer, and melanoma. The magnitude of absolute effects, however, was small and mainly based on low or very low certainty of evidence. The association of ASBs consumption with specific cancer risk was uncertain. TRIAL REGISTRATION PROSPERO CRD42020152223.
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Role of lifestyle factors in mediating the effect of educational attainment on bone mineral density: a Mendelian randomization study.
Liu, Q, Tooki, T, Di, D, Zhou, H, Cui, Z, Zhang, R, Zhang, J, Yuan, T, Zhou, T, Luo, X, et al
Archives of osteoporosis. 2023;(1):120
Abstract
UNLABELLED We performed two-step multivariable Mendelian randomization analysis to explore the mediating role of lifestyle factors in educational attainment (EA) and bone mineral density (BMD). Summary statistics from genome-wide association studies of European lineages were used. Coffee intake and processed-meat intake mediated the association between EA and BMD. PURPOSE This study aimed to explore the causal relationship between educational attainment (EA) and bone mineral density (BMD), as well as the potential mediating roles of lifestyle factors in the expected EA-BMD relationship. By identifying modifiable lifestyle factors, we hope to provide relevant information to prevent osteoporosis or low BMD in the less educated population. METHODS Using summary statistics from genome-wide association studies (GWAS) of major European lineages, one- and two-sample Mendelian randomization (MR) analyses were performed to estimate the association between EA (in the social sciences genetic association consortium (SSGAC) involving 766,345 individuals and in the UK Biobank (UKB) involving 293,723 individuals) and BMD (in the Genetic Factors for Osteoporosis Consortium involving 426,824 individuals selected from the UKB). The EA variable in both consortia were expressed by years of schooling completed. Two-step multivariable MR was used to assess the mediating roles of eight lifestyle-related factors (moderate-to-vigorous physical activity, watching television, computer using, smoking initiation, coffee intake, alcohol intake frequency, tea intake, and processed-meat intake) in the EA and BMD association, and the corresponding mediating proportion was calculated. Meta-analysis was used to present a pooled estimate. RESULTS A total of 317 and 73 independent single-nucleotide polymorphisms (SNPs) of GWAS significance (P < 5.0 × 10-8) were selected as instrumental variables (IVs) for EA in the SSGAC and UKB, respectively. A total of 513 SNPs were selected as IVs for the BMD. The results of one- and two-sample MR revealed that the genetically predicted BMD increased by 0.094 and 0.047 g/cm2, respectively, in response to each SD increment of genetically predicted schooling years. Among the eight candidate mediators, coffee intake and processed-meat intake were potential mediators revealed by the two-step multivariable MR analysis, mediating 26.87% and 23.92% of EA's effect on BMD, respectively. Meta-analysis showed consistent findings. Results of sensitivity analysis indicated the robustness of our findings. CONCLUSION We elucidated the causal protective effect of EA on BMD and the mediating roles of coffee intake and processed-meat intake. Intervening with these factors can potentially reduce the burden of bone density loss or osteoporotic fractures among the less educated population.
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Effect of polyphenol compounds on Helicobacter pylori eradication: a systematic review with meta-analysis.
Wang, Q, Yao, C, Li, Y, Luo, L, Xie, F, Xiong, Q, Feng, P
BMJ open. 2023;13(1):e062932
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Expert Review
Conflicts of interest:
None
Take Home Message:
- This is the first meta-analysis of polyphenol efficacy and safety in eradicating H. pylori.
- The results suggest that polyphenol compounds (curcumin, cranberry, garlic, liquorice and broccoli) can improve eradication rates.
- Furthermore, polyphenol compounds combined with standard triple therapy for H.pylori infection can significantly improve eradication (p=0.03).
- No evidence for an increased rate of side effects could be found.
- Due to the low quality of the included studies, these results should be interpreted with caution.
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Background
The authors highlight that Helicobacter pylori (H. pylori) has been classified as a group 1 carcinogen and H. pylori infection is considered the leading cause of gastric cancer. More than half the world’s population is infected with H. pylori and recurrence rates have increased over the past decade. Several studies indicate that polyphenol compounds positively affect H. pylori eradication. However, experimental and clinical studies have shown different results.
Methods
- This is the first meta-analysis to assess the efficacy and safety of polyphenol compounds (curcumin, cranberry, garlic, liquorice and broccoli) in eradicating H. pylori.
- A total of 12 RCTs with 1251 adult participants were finally included. Two studies evaluated the efficacy of curcumin, four studies evaluated the efficacy of cranberry, four studies assessed the efficacy of liquorice, one study evaluated the efficacy of garlic, and one study assessed the efficacy of broccoli.
- Subgroup analysis of different treatment schemes on the eradication rate of H.pylori infection included: three studies which compared the effects of polyphenols with placebo; six studies compared the effects of polyphenols along with triple therapy; two studies compared the effects of polyphenol plus triple therapy with bismuth triple therapy; one study compared the effects of polyphenols plus quadruple regimen with quadruple regimen plus placebo.
Results
- The results indicate that polyphenols are conducive to H. pylori eradication. The total eradication rate of H.pylori in the polyphenol compounds group was significantly higher than in the group without polyphenol compounds (RR 1.19, 95% CI 1.03 to 1.38, p=0.02).
- In subgroup analyses, eradication rate with polyphenol therapy was superior to that without polyphenol therapy in the polyphenols versus placebo subgroup (RR 4.23, 95% CI 1.38 to 12.95, p=0.01) and in the polyphenols plus triple therapy versus triple therapy subgroup (RR 1.11, 95% CI 1.01 to 1.22, p=0.03).
- No significant differences existed between the five different polyphenol compounds analysed.
- The most frequent adverse effects of polyphenol compounds included diarrhoea, headache and vomiting. However, there were no differences regarding side effects between the polyphenol compounds and control groups (RR 1.47, 95% CI 0.83 to 2.58, p=0.18).
Limitations:
- Only the eradication rate of H. pylori infection according to different treatment schemes and polyphenol compounds was analysed, with no analysis of polyphenol dose.
- Visual inspection of the funnel plot suggested that publication bias existed. Most studies ignored possible adverse reactions, and safety observations could be improved.
- The number of cases included in this meta-analysis is small and the methodological quality of the included trials was generally poor.
- The results of subgroup analyses on different treatment schemes and polyphenol compound species seem more inconclusive due to the small number of studies that could be included.
- The polyphenol contents of each food before and after the eradication period from each study could not be determined which might work as a confounding factor. This confounding factor may have an impact on the final result.
Clinical practice applications:
- Infection with H.pylori is a major pathogenic factor for many gastrointestinal conditions such as chronic atrophic gastric ulcers and has been linked with several extra-digestive diseases such as atherosclerosis, Alzheimer’s disease and rosacea.
- The efficacy of standard 1-week triple therapy containing clarithromycin and either metronidazole or amoxicillin combined with a PPI has decreased dramatically, with eradication rates as low as 50%–70%. Antibiotic resistance and patient compliance are the major causes of this decline.
- Concomitant, sequential and hybrid therapies are also recommended for treating H. pylori infection. However, there are currently few, if any, regimens which consistently achieve eradication rates exceeding 90%. In this analysis H. pylori eradication rates ranged from 54.4% to 91.7% in the polyphenol treatment groups.
- The results of this analysis indicate that polyphenol compounds can significantly improve H. pylori eradication rates and might be more effective during polyphenol treatment combined with standard triple therapy.
- No evidence for an increased rate of side effects could be found.
- Due to the low quality of the included studies, these results should be interpreted with caution.
Considerations for future research:
- While a few included studies mention doses of these polyphenol compounds for eradicating H. pylori, it was not an outcome analysed in this meta-analysis and therefore future research on this would help to clarify appropriate dosages.
- Adverse reactions and safety observations warrant further study.
- More large-scale, high-quality clinical trials should be conducted to provide a stronger, evidence-based foundation for guiding clinical medication. In particular in relation to more studies on different treatment schemes and species.
- Finally, the polyphenol contents of each food before and after the eradication period from each manuscript included in the analysis could not be determined which could be a confounding factor. Future studies should address this.
Abstract
OBJECTIVES Polyphenol compounds are classified as organic compounds with phenolic units exhibiting a variety of biological functions. This meta-analysis aims to assess the efficacy and safety of polyphenol compounds (curcumin, cranberry, garlic, liquorice and broccoli) in eradicating Helicobacter pylori. DESIGN Systematic review and meta-analysis. METHODS Literature searches were conducted on PubMed, Embase, The Cochrane Library, Web of Science, Medline, Chinese National Knowledge Infrastructure database, Chinese Scientific Journal Database and Wan Fang database from inception to January 2022. All randomised controlled trials comparing polyphenol compounds with the placebo or used as an adjunct treatment are included in this meta-analysis.The treatment effect for dichotomous outcomes was assessed using risk ratio (RR), while for continuous outcomes, mean differences both with 95% CIs, were used. Subgroup analyses were carried out for different treatment schemes and polyphenol compound species. RESULTS 12 trials were included in the meta-analysis. The total eradication rate of H.pylori in the polyphenol compounds group was higher than in the group without polyphenol compounds. Statistical significance was also observed (RR 1.19, 95% CI 1.03 to 1.38, p=0.02). The most frequent adverse effects of polyphenol compounds included diarrhoea, headache and vomiting. However, there were no differences regarding side effects between the two groups (RR 1.47, 95% CI 0.83 to 2.58, p=0.18). In subgroup analyses, the H.pylori eradication rate regimens with polyphenols therapy was superior to that of regimens without polyphenols therapy in the polyphenols versus placebo subgroup (RR 4.23, 95% CI 1.38 to 12.95, p=0.01), polyphenols plus triple therapy versus triple therapy subgroup (RR 1.11, 95% CI 1.01 to 1.22, p=0.03). CONCLUSION Polyphenol compounds can improve H.pylori eradication rates. Polyphenol compounds plus standard triple therapy can significantly improve the eradication. However, no evidence of a higher incidence of side effects could be found. PROSPERO REGISTRATION NUMBER CRD42022307477.
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Evaluation of improvement of cognitive impairment in older adults with probiotic supplementation: A systematic review and meta-analysis.
Kou, J, Kang, H, Hu, L, Wang, D, Wang, S, Wang, Q, Yang, Z
Geriatric nursing (New York, N.Y.). 2023;:155-162
Abstract
OBJECTIVE This study aimed to evaluate the improvement of cognitive impairment in older adults through probiotic supplementation. METHODS A literature review on probiotic supplementation for treating cognitive impairment in older adults was conducted using English and Chinese databases from 1984 to 2023. Two researchers extracted relevant data independently, and a meta-analysis was performed with RevMan software. RESULTS A comprehensive analysis of ten pertinent papers was conducted, involving a sample of 702 old adults with cognitive impairment. The findings from this study revealed that probiotic supplementation exhibited a positive impact on cognitive symptoms, specifically memory (MD = 0.14, 95% CI :0.05~0.22, P = 0.001) and overall cognitive function (SMD = 0.73, 95% CI: 0.25~1.21, P=0.003), as well as oxidative stress levels, including total antioxidant capacity (MD=52.54, 95% CI:39.52~65.56, P < 0.01), malondialdehyde (MD=-0.11, 95% CI:-0.15~-0.07, P < 0.01), and glutathione (MD=17.08, 95% CI:8.65~25.5, P < 0.01). However, probiotic supplementation failed to enhance patients' psychological symptoms (SMD =0.18, 95% CI:-0.56~0.92, P = 0.64). CONCLUSIONS Probiotic supplementation can enhance cognitive symptoms and decrease oxidative stress in older adults with cognitive impairment. However, it does not improve psychological symptoms. More research is needed to determine the effects of probiotic supplementation on gastrointestinal symptoms and sleep quality in this population. Further supplementation and improvement will be necessary once high-quality literature becomes available.
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Exercise modalities for type 2 diabetes: A systematic review and network meta-analysis of randomized trials.
Hou, L, Wang, Q, Pan, B, Li, R, Li, Y, He, J, Qin, T, Cao, L, Zhang, N, Cao, C, et al
Diabetes/metabolism research and reviews. 2023;(1):e3591
Abstract
AIMS: We aimed to determine the effects of different exercise modalities in patients with type 2 diabetes mellitus (T2DM). METHODS We searched PubMed, Embase, and the Cochrane Library from their inception until July 2020 to identify randomised controlled trials (RCTs) on exercise in adults with T2DM. Paired reviewers independently performed study selection, data extraction, and risk of bias assessment. The certainty of the evidence was assessed using the Confidence in Network Meta-Analysis (CINeMA) framework. RESULTS A total of 106 RCTs that enroled eight exercise modalities with 7438 patients were included. Six exercise modalities, except unsupervised aerobic/resistance exercise, significantly reduced glycosylated haemoglobin (HbA1c), with mean differences (MDs) ranging from 0.71 (95% confidence interval [CI]: 0.34-1.08) to 0.34 (95% CI: 0.17-0.52), low to high certainty, in comparison with no exercise. The evidence of low to moderate certainty showed that supervised aerobic/resistance exercise improved glycaemic control, body weight, blood pressure, and blood lipid profiles compared with no exercise. Flexibility exercise may be associated with glycaemic control (HbA1c: MD = 0.71, 95% CI: 0.34-1.08); fasting plasma glucose (MD = 1.48, 95% CI: 0.78-2.17), and weight loss (MD = 1.80, 95% CI: 0.85-2.75) compared with controls, but not blood pressure and lipid profiles. Balance exercise showed the largest benefit in improving total cholesterol (MD = 52.81, 95% CI: 28.47-77.16) and low certainty. We found no significant differences between exercises and the triacylglycerol (TG) level. CONCLUSIONS Overall, our network meta-analyses support the recommendation for exercise in patients with T2DM, especially supervised exercises. Limited evidence supports the benefits of flexibility and balance exercises. The effectiveness of exercise modalities for TG reduction remains unclear.
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9.
Interactive Association Between Gut Microbiota and Thyroid Cancer.
Hou, T, Wang, Q, Dai, H, Hou, Y, Zheng, J, Wang, T, Lin, H, Wang, S, Li, M, Zhao, Z, et al
Endocrinology. 2023;(1)
Abstract
CONTEXT The association between the gut microbiota and thyroid cancer remains controversial. OBJECTIVE We aimed to systematically investigate the interactive causal relationships between the abundance and metabolism pathways of gut microbiota and thyroid cancer. METHODS We leveraged genome-wide association studies for the abundance of 211 microbiota taxa from the MiBioGen study (N = 18 340), 205 microbiota metabolism pathways from the Dutch Microbiome Project (N = 7738), and thyroid cancer from the Global Biobank Meta-analysis Initiative (N cases = 6699 and N participants = 1 620 354). We performed a bidirectional Mendelian randomization (MR) to investigate the causality from microbiota taxa and metabolism pathways to thyroid cancer and vice versa. We performed a systematic review of previous observational studies and compared MR results with observational findings. RESULTS Eight taxa and 12 metabolism pathways had causal effects on thyroid cancer, where RuminococcaceaeUCG004 genus (P = .001), Streptococcaceae family (P = .016), Olsenella genus (P = .029), ketogluconate metabolism pathway (P = .003), pentose phosphate pathway (P = .016), and L-arginine degradation II in the AST pathway (P = .0007) were supported by sensitivity analyses. Conversely, thyroid cancer had causal effects on 3 taxa and 2 metabolism pathways, where the Holdemanella genus (P = .015) was supported by sensitivity analyses. The Proteobacteria phylum, Streptococcaceae family, Ruminococcus2 genus, and Holdemanella genus were significantly associated with thyroid cancer in both the systematic review and MR, whereas the other 121 significant taxa in observational results were not supported by MR. DISCUSSIONS These findings implicated the potential role of host-microbiota crosstalk in thyroid cancer, while the discrepancy among observational studies calls for further investigations.
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10.
Oral direct thrombin inhibitors or oral factor Xa inhibitors versus conventional anticoagulants for the treatment of deep vein thrombosis.
Wang, X, Ma, Y, Hui, X, Li, M, Li, J, Tian, J, Wang, Q, Yan, P, Li, J, Xie, P, et al
The Cochrane database of systematic reviews. 2023;(4):CD010956
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Abstract
BACKGROUND Deep vein thrombosis (DVT) is a condition in which a clot forms in the deep veins, most commonly of the leg. It occurs in approximately one in 1000 people. If left untreated, the clot can travel up to the lungs and cause a potentially life-threatening pulmonary embolism (PE). Previously, a DVT was treated with the anticoagulants heparin and vitamin K antagonists. However, two forms of direct oral anticoagulants (DOACs) have been developed: oral direct thrombin inhibitors (DTIs) and oral factor Xa inhibitors, which have characteristics that may be favourable compared to conventional treatment, including oral administration, a predictable effect, lack of frequent monitoring or dose adjustment and few known drug interactions. DOACs are now commonly being used for treating DVT: recent guidelines recommended DOACs over conventional anticoagulants for both DVT and PE treatment. This Cochrane Review was first published in 2015. It was the first systematic review to measure the effectiveness and safety of these drugs in the treatment of DVT. This is an update of the 2015 review. OBJECTIVES To assess the effectiveness and safety of oral DTIs and oral factor Xa inhibitors versus conventional anticoagulants for the long-term treatment of DVT. SEARCH METHODS The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase and CINAHL databases and the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 1 March 2022. SELECTION CRITERIA We included randomised controlled trials (RCTs) in which people with a DVT, confirmed by standard imaging techniques, were allocated to receive an oral DTI or an oral factor Xa inhibitor compared with conventional anticoagulation or compared with each other for the treatment of DVT. DATA COLLECTION AND ANALYSIS We used standard Cochrane methods. Our primary outcomes were recurrent venous thromboembolism (VTE), recurrent DVT and PE. Secondary outcomes included all-cause mortality, major bleeding, post-thrombotic syndrome (PTS) and quality of life (QoL). We used GRADE to assess the certainty of evidence for each outcome. MAIN RESULTS We identified 10 new studies with 2950 participants for this update. In total, we included 21 RCTs involving 30,895 participants. Three studies investigated oral DTIs (two dabigatran and one ximelagatran), 17 investigated oral factor Xa inhibitors (eight rivaroxaban, five apixaban and four edoxaban) and one three-arm trial investigated both a DTI (dabigatran) and factor Xa inhibitor (rivaroxaban). Overall, the studies were of good methodological quality. Meta-analysis comparing DTIs to conventional anticoagulation showed no clear difference in the rate of recurrent VTE (odds ratio (OR) 1.17, 95% confidence interval (CI) 0.83 to 1.65; 3 studies, 5994 participants; moderate-certainty evidence), recurrent DVT (OR 1.11, 95% CI 0.74 to 1.66; 3 studies, 5994 participants; moderate-certainty evidence), fatal PE (OR 1.32, 95% CI 0.29 to 6.02; 3 studies, 5994 participants; moderate-certainty evidence), non-fatal PE (OR 1.29, 95% CI 0.64 to 2.59; 3 studies, 5994 participants; moderate-certainty evidence) or all-cause mortality (OR 0.66, 95% CI 0.41 to 1.08; 1 study, 2489 participants; moderate-certainty evidence). DTIs reduced the rate of major bleeding (OR 0.58, 95% CI 0.38 to 0.89; 3 studies, 5994 participants; high-certainty evidence). For oral factor Xa inhibitors compared with conventional anticoagulation, meta-analysis demonstrated no clear difference in recurrent VTE (OR 0.85, 95% CI 0.71 to 1.01; 13 studies, 17,505 participants; moderate-certainty evidence), recurrent DVT (OR 0.70, 95% CI 0.49 to 1.01; 9 studies, 16,439 participants; moderate-certainty evidence), fatal PE (OR 1.18, 95% CI 0.69 to 2.02; 6 studies, 15,082 participants; moderate-certainty evidence), non-fatal PE (OR 0.93, 95% CI 0.68 to 1.27; 7 studies, 15,166 participants; moderate-certainty evidence) or all-cause mortality (OR 0.87, 95% CI 0.67 to 1.14; 9 studies, 10,770 participants; moderate-certainty evidence). Meta-analysis showed a reduced rate of major bleeding with oral factor Xa inhibitors compared with conventional anticoagulation (OR 0.63, 95% CI 0.45 to 0.89; 17 studies, 18,066 participants; high-certainty evidence). AUTHORS' CONCLUSIONS The current review suggests that DOACs may be superior to conventional therapy in terms of safety (major bleeding), and are probably equivalent in terms of efficacy. There is probably little or no difference between DOACs and conventional anticoagulation in the prevention of recurrent VTE, recurrent DVT, pulmonary embolism and all-cause mortality. DOACs reduced the rate of major bleeding compared to conventional anticoagulation. The certainty of evidence was moderate or high.