TSHR Gene (rs179247) Polymorphism and Susceptibility to Autoimmune Thyroid Disease: A Systematic Review and Meta-Analysis.

Background: Both Graves' disease (GD) and Hashimoto's thyroiditis (HT) are classified as autoimmune thyroid diseases (AITDs). It has been hypothesized that changes in the thyroid-stimulating hormone receptor (TSHR) gene may contribute to the development of these conditions. This study aimed to analyze the correlation between the TSHR rs179247 gene polymorphism and susceptibility to AITD. Methods: We conducted a thorough search of the Google Scholar, Scopus, Medline, and Cochrane Library databases up until March 2, 2024, utilizing a combination of relevant keywords. This review examines data on the association between TSHR rs179247 and susceptibility to AITD. Random-effect models were employed to assess the odds ratio (OR), and the findings are presented along with their respective 95% confidence intervals (CIs). Results: The meta-analysis included 12 studies. All genetic models of the TSHR rs179247 gene polymorphism were associated with an increased risk of developing GD. Specifically, the associations were observed in the dominant model (OR, 1.65; P<0.00001), recessive model (OR, 1.65; P<0.00001), as well as for the AA genotype (OR, 2.09; P<0.00001), AG genotype (OR, 1.39; P<0.00001), and A allele (OR, 1.44; P<0.00001). Further regression analysis revealed that these associations were consistent regardless of the country of origin, sample size, age, and sex distribution. However, no association was found between TSHR rs179247 and the risk of HT across all genetic models. Conclusion: This study suggests that the TSHR rs179247 gene polymorphism is associated with an increased risk of GD, but not with HT, and may therefore serve as a potential biomarker.

Glucagon-like peptide-1 receptor agonist and new-onset diabetes in overweight/obese individuals with prediabetes: A systematic review and meta-analysis of randomized trials.

BACKGROUND: Glucagon-like peptide-1 receptor agonist (GLP-1RA) is incretin-based therapy that possessed significant glucose lowering and weight loss properties. The present study aims to analyze the efficacy of GLP-1RA in the management of overweight/obese individuals with prediabetes. METHODS: A thorough search was carried out on the Cochrane Library, ClinicalTrials.gov, Scopus, and Medline databases until April 3rd, 2024, using a mix of pertinent keywords. This review incorporates randomized clinical trials (RCTs) concerning the efficacy of GLP-1RA for prediabetes. The primary outcome was regression to normoglycemia and/or progression to type 2 diabetes (T2D). We used random-effect models to examine the odds ratio (OR) and mean difference (MD). RESULTS: A total of eight RCTs were incorporated. The results of our meta-analysis indicated that GLP-1RA therapy was associated with higher odds of regression to normoglycemia (OR 4.80; 95%CI: 3.40-6.77, p < 0.00001, I2 = 67 %) and lower risk of progression into T2D (OR 0.27; 95%CI: 0.18-0.42, p < 0.00001, I2 = 0 %) in overweight/obese individuals with prediabetes. Administration of GLP-1RA was also associated with higher reduction in HbA1c (MD -0.28 %; p < 0.00001), fasting glucose (MD -0.45 mmol/L; p < 0.00001), and BMI (MD -1.71 kg/m2; p < 0.00001) in comparison to placebo. However, the administration of GLP-1RA was associated with higher incidence of total adverse events (TAEs), treatment discontinuation due to AEs, hypoglycemia, and gastrointestinal AEs. CONCLUSIONS: This study indicates that while GLP-1RA is a potent therapeutic agent for prediabetes, its adverse effects are concerning, thereby precluding its recommendation as a prediabetes therapy.

Risk of Dementia in Patients with Diabetes Using Sodium-Glucose Transporter 2 Inhibitors (SGLT2i): A Systematic Review, Meta-Analysis, and Meta-Regression.

INTRODUCTION: Dementia is quite prevalent and among the leading causes of death worldwide. According to earlier research, diabetes may increase the possibility of developing dementia. However, the association between antidiabetic agents and dementia is not yet clear. This investigation examines the association between the use of sodium-glucose transporter 2 inhibitors (SGLT2i) and the risk of dementia in patients with diabetes. METHODS: Up to April 18, 2023, four databases-Europe PMC, Medline, Scopus, and Cochrane Library-were searched for relevant literature. We included all studies that examine dementia risk in adults with diabetes who use SGLT2i. Random-effect models were used to compute the outcomes in this investigation, producing pooled odds ratios (OR) with 95% confidence intervals (CI). RESULTS: Pooled data from seven observational studies revealed that SGLT2i use was linked to a lower risk of dementia in people with diabetes (OR 0.45, 95% CI 0.34-0.61; p < 0.00001, I2 = 97%). The reduction in the risk of dementia due to SGLT2i's neuroprotective effect was only significantly affected by dyslipidemia (p = 0.0004), but not by sample size (p = 0.2954), study duration (p = 0.0908), age (p = 0.0805), sex (p = 0.5058), hypertension (p = 0.0609), cardiovascular disease (p = 0.1619), or stroke (p = 0.2734). CONCLUSIONS: According to this research, taking SGLT2i reduces the incidence of dementia in people with diabetes by having a beneficial neuroprotective impact. Randomized controlled trials (RCTs) are still required in order to verify the findings of our research.

Comparative Efficacy and Safety of Radiofrequency Ablation and Microwave Ablation in the Treatment of Benign Thyroid Nodules: A Systematic Review and Meta-Analysis.

OBJECTIVE: The current body of evidence lacks clarity regarding the comparative efficacy and safety of radiofrequency ablation (RFA) and microwave ablation (MWA) as minimally invasive treatments for benign thyroid nodules. The primary objective of this study is to clarify these concerns. MATERIALS AND METHODS: A comprehensive search was conducted using the Cochrane Library, Scopus, Europe PMC, and Medline databases until October 10th, 2023, using a combination of relevant keywords. This study incorporated literature that compared RFA and MWA for benign thyroid nodules. The primary outcome was the volume reduction ratio (VRR) from baseline to follow-up. Secondary outcomes were symptom score, cosmetic score, ablation time, major complications rate, hemorrhage, hoarseness, skin burn, cough, and sympathetic nerve injury. We used Risk of Bias in Non-randomized Studies - of Interventions (ROBINS-I) tool to assess the risk of bias in the included studies. We employed random effects models to analyze the standardized mean difference (SMD) and odds ratio for the presentation of outcomes. RESULTS: Nine studies with 2707 nodules were included. The results of our meta-analysis indicated similar efficacy between RFA and MWA in terms of VRR during the 1 (SMD 0.06; 95% confidence interval [CI]: -0.13 to 0.26; P = 0.52) and 3 (SMD 0.11; 95% CI: -0.03 to 0.25; P = 0.12) months of follow-up. VRR was significantly higher in RFA than in MWA at the 6 (SMD 0.25; 95% CI: 0.06-0.43; P = 0.008) and 12 month of follow-up (SMD 0.38; 95% CI: 0.17 to 0.59; P < 0.001). There were no significant differences between RFA and MWA in symptom scores, cosmetic scores, or the incidence of complications, including hemorrhage, hoarseness, skin burn, cough, and sympathetic nerve injury. CONCLUSION: RFA showed a higher VRR than MWA at 6 and 12-month follow-ups, with a comparable safety profile.

The role of nutrition-based index in predicting survival of breast cancer patients: A systematic review and meta-analysis.

Background: Prognostic nutritional index (PNI) and Controlling Nutritional Status (CONUT) are two model that incorporates the role of inflammation and nutrition factors to predict the progression of tumor. The primary objective of this investigation is to examine the ability of PNI and CONUT score for predicting the survival in breast cancer patients. Methods: A comprehensive search was conducted on the Cochrane Library, Scopus, Europe PMC, and Medline databases up until August 14th, 2023, utilizing a combination of relevant keywords. This review incorporates literature that examines the relationship between PNI, CONUT, and survival in breast cancer. We employed random-effect models to analyze the hazard ratio (HR) and present the outcomes together with their corresponding 95 % confidence intervals (CI). Results: A total of sixteen studies were incorporated. The results of our meta-analysis indicated that high PNI was associated with better overall survival (OS) (HR 0.38; 95%CI: 0.28-0.51, p < 0.00001, I2 = 32 %), but not disease-free survival (DFS) (HR 0.60; 95%CI: 0.33-1.10, p = 0.10, I2 = 78 %) than low PNI in breast cancer patients. Meta-analysis also indicated that high CONUT was associated with worse OS (HR 1.66; 95%CI: 1.21-2.28, p = 0.002, I2 = 78 %) and worse DFS (HR 2.09; 95%CI: 1.60-2.73, p < 0.00001, I2 = 41 %) in breast cancer patients. Conclusions: This study suggests the prognostic role of both PNI and CONUT score for predicting survival in breast cancer patients.

Different doses of imeglimin for management of type 2 diabetes mellitus: a systematic review, meta-analysis, and meta-regression of randomized clinical trials.

BACKGROUND: A new medication for type 2 diabetes mellitus (T2DM) called imeglimin can target all three organs involved in the pathogenesis of DM, namely the liver, skeletal muscles, and pancreas. This research seeks to examine the most efficacious and safe dose of imeglimin for the management of T2DM. RESEARCH DESIGN AND METHODS: Using particular keywords, we searched the CENTRAL, Medline, Scopus, and ClinicalTrials.gov databases for pertinent literature. The results of continuous variables were pooled into the mean difference (MD) and dichotomous variables into odds ratio (OR) along with their 95% confidence intervals (95% CI) using fixed-effect models. RESULTS: Our pooled analysis revealed that imeglimin 1000 mg twice daily [MD -0.90% p < 0.00001] and 1500 mg twice daily [MD -0.84% p = 0.0003] as monotherapy was associated with a higher reduction in the HbA1c compared to placebo. This superiority was still maintained when given as combination therapy. Regrettably, there was an observed escalation in gastrointestinal AEs as the dosage of imeglimin was raised, despite the absence of a corresponding improvement in its efficacy in decreasing HbA1c levels. CONCLUSIONS: Our study suggests that imeglimin 1000 mg twice daily may offer the most optimum therapeutic effects for glycemic control without compromising its safety profiles.

The efficacy of thymosin alpha-1 therapy in moderate to critical COVID-19 patients: a systematic review, meta-analysis, and meta-regression.

BACKGROUND: Effort to search for the optimal COVID-19 treatment has continuously been attempted. Thymosin alpha-1 have immunomodulatory properties which may be beneficial in case of viral infection. This study's goal is to determine whether thymosin alpha-1 is effective in treating people with moderate-to-severe COVID-19. METHODS: We searched for literature in 4 database: Scopus, Europe PMC, Medline, ClinicalTrials.gov, and Cochrane Library until March 25th, 2023. If those articles have data on the efficacy of thymosin alpha-1 therapy on COVID-19, they would be included. Risk ratio (RR) and Mean Difference (MD) along with their 95% confidence intervals were used to pool the results of dichotomous and continuous variables, respectively. RESULTS: Pooled data from 8 studies indicated that moderate to critical Covid-19 patients who were receiving thymosin alpha-1 therapy had significantly lower mortality from COVID-19 (RR 0.59; 95% CI 0.37-0.93, p = 0.02, I2 = 84%), but without any difference in the needs for mechanical ventilation (RR 0.83; 95% CI 0.48-1.44, p = 0.51, I2 = 74%) and hospital length of stay (MD 2.32; 95% CI - 0.93, 5.58, p = 0.16, I2 = 94%) compared to placebo. The benefits of thymosin alpha-1 on the mortality rate were significantly affected only by sample size (p = 0.0000) and sex (p = 0.0117). CONCLUSION: Our study suggests that treatment with thymosin alpha-1 may reduce mortality rate in moderate to critical COVID-19 patients. Randomized clinical trials (RCTs) are still required to verify the findings of our study.

Relationship between Phenotype Models Based on Waist Circumference and Triglyceride Levels and the Risk of Chronic Kidney Disease: A Systematic Review and Meta-analysis.

Background: Chronic kidney disease (CKD) is a leading cause of death worldwide and has a high cost of treatment. Studies have indicated that a combination of waist circumference (WC) and triglyceride (TG) levels can be used to determine the risk of CKD. This study analyzes the risk of CKD using four phenotype models based on WC and TG. Methods: This meta-analysis analyzes 113,019 participants from 13 studies. We conducted relevant literature searches in the Europe PMC, Medline, and Scopus databases using specific keywords. The results obtained were pooled into odds ratios (ORs) with 95% confidence intervals (CIs) using random-effects models. Results: Our pooled analysis revealed that the highest significant independent association was between CKD and the high WC-high TG phenotype (adjusted OR, 1.61; 95% CI, 1.39 to 1.88; P<0.00001; I2=59%), followed by the high WC-normal TG phenotype (adjusted OR, 1.33; 95% CI, 1.12 to 1.57; P=0.001; I2=67%), and the normal WC-high TG phenotype (adjusted OR, 1.20; 95% CI, 1.06 to 1.37; P=0.005; I2=29%) when the normal WC-normal TG phenotype was taken as the reference. Conclusion: Our study suggests that phenotype models based on WC and TG can be used as screening tools to predict the risk of CKD. Our results also indicate that WC plays a larger role than TG in the CKD risk. Further prospective studies are needed to confirm the results of our study.

Utility of non-invasive liver fibrosis markers to predict the incidence of chronic kidney disease (CKD): A systematic review, meta-analysis, and meta-regression.

BACKGROUND AND AIMS: Chronic kidney disease (CKD) and non-alcoholic fatty liver disease (NAFLD) share common risk factors and pathogenesis mechanisms. However, the association between the degree of liver fibrosis and the incidence of CKD remains unclear. This study aims to examine the utility of non-invasive fibrosis markers to predict the occurrence of CKD. METHODS: Cochrane Library, Scopus, and Medline were searched up to May 20th, 2023 using combined keywords. Literature that analyzes FIB-4, NFS, and APRI to predict CKD incidence was included in this review. We used random-effect models of odds ratio (OR) with 95% confidence intervals (CI) to express the outcomes in this review. RESULTS: Twenty-one studies were included. Our meta-analysis showed that high FIB-4 was associated with a higher incidence of CKD (OR 2.51; 95%CI: 1.87-3.37, p < 0.00001, I2 = 96%). Further regression analysis revealed that this association was significantly influenced by hypertension (p = 0.0241), NAFLD (p = 0.0029), and body mass index (BMI) (p = 0.0025). Our meta-analysis also showed that high NFS (OR 2.49; 95%CI: 1.89-3.30, p < 0.00001, I2 = 96%) and high APRI (OR 1.40; 95%CI: 1.14-1.72, p = 0.001, I2 = 26%) were associated with a higher incidence of CKD. CONCLUSIONS: This study suggests that these non-invasive liver fibrosis markers can be routinely measured both in NAFLD patients and the general population to enable better risk stratification and early detection of CKD.

Efficacy and Safety of Fluvoxamine as Outpatient Treatment for Patients With Covid-19: A Systematic Review and Meta-analysis of Clinical Trials.

BACKGROUND: Fluvoxamine may be beneficial for the management of coronavirus disease 2019 (Covid-19) because of its effect on the sigma-1 receptor. Available evidence from randomized clinical trials (RCTs) has shown conflicting results. OBJECTIVE: This study sought to analyze the efficacy and safety of fluvoxamine as an outpatient treatment for Covid-19. METHODS: Using specific keywords, we comprehensively go through the potential articles on PubMed, Scopus, Europe PMC, and ClinicalTrials.gov sources until February 1, 2023. We collected all published clinical trials on fluvoxamine and Covid-19. We were using Review Manager 5.4 to conduct statistical analysis. RESULTS: We include a total of 6 trials. Our pooled analysis revealed that fluvoxamine did not offer any significant benefit when compared with placebo in reducing the risk of clinical deterioration (risk ratio [RR] = 0.83; 95% CI: 0.65-1.06, P = 0.14, I2 = 29%), and hospitalization (RR = 0.80; 95% CI: 0.62-1.04, P = 0.09, I2 = 0%) of Covid-19 outpatients. The serious adverse events did not differ significantly between the 2 groups. CONCLUSIONS AND RELEVANCE: This study indicates that although safe, fluvoxamine was not effective for outpatient treatment of Covid-19. Until more evidence can be obtained from larger RCTs, our study did not encourage the use of fluvoxamine as routine management for patients with Covid-19.

Efficacy and safety of tixagevimab-cilgavimab as pre-exposure prophylaxis for COVID-19: A systematic review and meta-analysis.

Some proportions of populations, such as immunocompromised patients and organ transplant recipients might have inadequate immune responses to the vaccine for coronavirus disease 2019 (COVID-19). For these groups of populations, administering monoclonal antibodies might offer some additional protection. This review sought to analyze the effectiveness and safety of tixagevimab-cilgavimab (Evusheld) as pre-exposure prophylaxis against COVID-19. We used specific keywords to comprehensively search for potential studies on PubMed, Scopus, Europe PMC, and ClinicalTrials.gov sources until 3 September 2022. We collected all published articles that analyzed tixagevimab-cilgavimab on the course of COVID-19. Review Manager 5.4 was utilized for statistical analysis. Six studies were included. Our pooled analysis revealed that tixagevimab-cilgavimab prophylaxis may decrease the rate of SARS-CoV-2 infection (OR: 0.24; 95% CI: 0.15-0.40, p < 0.00001, I2  = 75%), lower COVID-19 hospitalization rate (OR: 0.13; 95% CI: 0.07-0.24, p < 0.00001, I2  = 0%), decrease the severity risk (OR: 0.13; 95% CI: 0.07-0.24, p < 0.00001, I2  = 0%), and lower COVID-19 deaths (OR: 0.17; 95% CI: 0.03-0.99, p = 0.05, I2  = 72%). In the included studies, no major adverse events were reported. This study proposes that tixagevimab-cilgavimab was effective and safe for preventing COVID-19. Tixagevimab-cilgavimab may be offered to those who cannot be vaccinated or have inadequate immune response from the COVID-19 vaccine to give additional protection.

Efficacy and Safety of Near-Infrared Florescence Cholangiography Using Indocyanine Green in Laparoscopic Cholecystectomy: A Systematic Review and Meta-Analysis.

Background: Achieving critical view of safety is a key for a successful laparoscopic cholecystectomy (LC) procedure. Near-infrared fluorescence cholangiography using indocyanine green (NIF-ICG) in LC has been extensively used and accepted as beneficial auxiliary tool to visualize extrahepatic biliary structures intraoperatively. This study aimed to analyze its safety and efficacy. Materials and Methods: Searching for potential articles up to March 25, 2022 were conducted on PubMed, Europe PMC, and ClinicalTrials.gov databases. Articles on the near infrared fluorescence during laparoscopy cholecystectomy were collected. Review Manager 5.4 software was utilized to perform the statistical analysis. Results: Twenty-two studies with a total of 3457 patients undergo LC for the analysis. Our meta-analysis revealed that NIF-ICG technique during LC was associated with shorter operative time (Std. Mean Difference -0.86 [95% confidence interval (CI) -1.49 to -0.23], P = .007, I2 = 97%), lower conversion rate (risk ratio [RR] 0.28 [95% CI 0.16-0.50], P < .0001, I2 = 0%), higher success in identification of cystic duct (CD) (RR 1.24 [95% CI 1.07-1.43], P = .003, I2 = 94%), higher success in identification of common bile duct (CBD) (RR 1.31 [95% CI 1.07-1.60], P = .009, I2 = 90%), and shorter time to identify biliary structures (Std. Mean Difference -0.52 [95% CI -0.78 to -0.26], P < .0001, I2 = 0%) compared with not using NIF-ICG. Conclusions: NIF-ICG technique beneficial for early real-time visualization of biliary structure, shorter operative time, and lower risk of conversion during LC. Larger randomized clinical trials are still needed to confirm the results of our study.

Utility of botulinum toxin injection for post-operative pain management after conventional hemorrhoidectomy: a systematic review and meta-analysis of clinical trials.

BACKGROUND: Botulinum Toxin (BTX) has been found to have anti-spasm and analgesic effects. The utility of BTX after conventional hemorrhoidectomy remains unclear. Thus, a systematic review and meta-analysis are required to find out its utility after conventional hemorrhoidectomy. METHODS: Using specific keywords, we comprehensively go through the potential articles on PubMed, ClinicalTrials.gov, and Europe PMC sources until March 27th, 2022. All published studies on botulinum toxin anal sphincter injection after conventional hemorrhoidectomy were collected. We were using Review Manager 5.4 software to conduct statistical analysis. RESULTS: Five clinical trial studies with a total of 260 patients undergoing hemorrhoidectomy were included in the analysis Our pooled analysis revealed that BTX injection after hemorrhoidectomy was associated with lower VAS at 24 h post-operative [Mean Difference -1.35 (95% CI -1.90, -0.80), p < 0.00001, I2 = 0%] and shorter time to return work [Mean Difference -8.94 days (95% CI -12.57, -5.30), p < 0.00001, I2 = 0%]. However, BTX injection did not differ significantly from placebo in terms of time to first defecation (p = 0.22), fecal incontinence (p = 0.91) and urinary retention incidence (p = 0.18). CONCLUSION: BTX sphincter injection may offer some benefit after conventional hemorrhoidectomy in reducing pain from the first day after the procedure and promoting wound healing without complication. Further randomized clinical trials are still needed to confirm the results of our study.

Vitamin D supplementation for improving sperm parameters in infertile men: A systematic review and meta-analysis of randomized clinical trials.

Objective: Vitamin D has been hypothesized to have a potential role in altering sperm motility and metabolism. However, experimental studies have demonstrated inconsistent results between vitamin D and sperm parameters. This study aims to investigate the role of vitamin D supplementation to improve sperm parameters in infertile men. Methods: This is a systematic review and meta-analysis study. We comprehensively conducted a search on ClinicalTrials.gov, IRCT.ir, Europe PMC, and PubMed and collected published studies on vitamin D supplementation and sperm parameters for infertile men. The risk of bias was assessed by using Risk of Bias version 2 (RoB v2) and the statistical analysis was performed by using Review Manager 5.4 software. Results: Five trials with a total of 648 infertile men were included. Our meta-analysis showed that supplementation with vitamin D may significantly improve total sperm motility [mean difference 4.96 (95% CI 0.38, 9.54), p = 0.03, I2 = 69%], progressive sperm motility [mean difference 4.14 (95% CI 0.25, 8.02), p = 0.04, I2 = 89%], and normal sperm morphology [mean difference 0.44 (95% CI 0.30, 0.57), p < 0.00001, I2 = 0%] better than placebo in infertile men. However, total sperm count (p = 0.15), sperm concentration (p = 0.82), and semen volume (p = 0.83) did not differ significantly between two groups. Conclusions: Vitamin D supplementation may improve sperm motility, progressive sperm motility, and morphology in infertile men. Vitamin D supplementation may be considered in managing male fertility issue.

Efficacy and safety of tirzepatide as novel treatment for type 2 diabetes: A systematic review and meta-analysis of randomized clinical trials.

BACKGROUND AND AIMS: This study aims to explore the efficacy and safety of tirzepatide for patients with type 2 diabetes (T2D). METHODS: Using specific keywords, we comprehensively go through the potential articles on Europe PMC, Scopus, PubMed, and ClinicalTrials.gov sources until July 12th, 2022. We collected all clinical trials that compare tirzepatide 5, 10, or 15 mg once-weekly with placebo or other glucose lowering agents in adult patients with T2D. RESULTS: Nine clinical trials were included. Our pooled analysis revealed the dose-dependent superiority of tirzepatide in reducing HbA1c, ranging from -1.50% with 5 mg to -1.80% with 15 mg when compared with placebo, -0.61% with 5 mg to -0.95% with 15 mg when compared with GLP-1 receptor agonist, and -0.70% with 5 mg to 1.09% with 15 mg when compared with basal insulin. The dose-dependent superiority of tirzepatide was also seen in the bodyweight reduction effect with all comparators. These superiorities were not accompanied by increased odds of hypoglycemia, but there is an increase in gastrointestinal adverse events incidence. CONCLUSIONS: Tirzepatide has shown superiority in glycemic control and bodyweight reduction with a good safety profile in patients with T2D. Tirzepatide may become a future potential drug in the management of T2D.

Efficacy and safety of eptinezumab as preventive treatment for episodic/chronic migraine: A systematic review and meta-analysis.

Migraine, the third most common neurological disorders worldwide, can cause significant burden to the patients. Currently, it has been found that calcitonin gene-related peptide (CGRP) has a significant role in pathophysiology of migraine. This study sought to analyse the efficacy and safety of eptinezumab, one of the CGRP-monoclonal antibody as preventive treatment for episodic/chronic migraine. Specific keywords were used to comprehensively go through the potential articles on ClinicalTrials.gov, Europe PMC, Scopus and PubMed databases until April 2022. All published randomized clinical trials (RCTs) on eptinezumab and migraine were gathered. Statistical analysis was conducted by using Review Manager 5.4 and Comprehensive Meta-Analysis version 3 software. There were four RCTs with 2739 migraine patients in the meta-analysis. In terms of efficacy, our analysis revealed that eptinezumab corresponded with higher reduction in monthly migraine days from baseline to week 12 (standardized mean difference, -0.34 [95% confidence interval (CI), -0.41, -0.28], P < 0.00001; I2  = 0%), higher 75% and 50% migraine responder rate, reduction in rate of migraine on day-1 after dosing, lower headache impact test-6 score on week 4 and week 12. In terms of safety, eptinezumab has comparable adverse events when compared with placebo (risk ratio, 1.01 [95% CI 0.96-1.07], P = 0.63, I2  = 0%). Further regression analysis also revealed that the association between eptinezumab and each outcomes of interest were not influenced by age, gender, body mass index and duration of migraine. This study proposes that eptinezumab is generally effective and safe for the preventive treatment of episodic or chronic migraine.

Association between viral hepatitis and increased risk of severe coronavirus disease 2019 (COVID-19) outcome: a systematic review and meta-analysis.

Aim: The purpose of the current study is to analyze the potential association between viral hepatitis and the severity of COVID-19. Background: Coronavirus disease 2019 (COVID-19) is a worldwide concern that has created major issues with many aspects. It is important to identify the risk factors for severe outcomes of this disease. To date, no association between viral hepatitis and severe COVID-19 has not been established. Methods: Through November 5th, 2020, the databases of PubMed, Google Scholar, and medRxiv were systematically searched using specific keywords related to the focus of the study. All articles published on COVID-19 and viral hepatitis were retrieved. The Mantel-Haenszel formula with random-effects models was used to obtain the risk ratio (RR) along with its 95% confidence intervals (CIs) for dichotomous variables. The two-tailed p-value was set with a value ≤0.05 considered statistically significant. Restricted-maximum likelihood meta-regression was done for several variables, such as age, gender, hypertension, diabetes, and other liver disease. Results: Analysis results included a total of 16 studies with a total of 14,682 patients. Meta-analysis showed that viral hepatitis increases the risk of developing severe COVID-19 (RR 1.68 (95% CI 1.26 - 2.22), p = 0.0003, I 2 = 21%, random-effect modeling). According to the meta-regression analysis, the association between viral hepatitis and severe COVID-19 was not influenced by age (p = 0.067), diabetes (p = 0.057), or other liver disease (p = 0.646). Conclusion: An increase of severe COVID-19 risk is associated with viral hepatitis. To reduce the risk of COVID-19, patients with viral hepatitis should be monitored carefully.

Pre-Admission Beta-Blocker Therapy and Outcomes of Coronavirus Disease 2019 (COVID-19): A Systematic Review, Meta-Analysis, and Meta-Regression.

BACKGROUND: Hypertension and heart failure are known risk factors for coronavirus disease 2019 (COVID-19) severity and mortality outcomes. Beta-blocker is one of the drugs of choice to treat these conditions. The purpose of this study is to explore the relationship between preadmission beta-blocker use and COVID-19 outcomes. METHODS: PubMed and Europe PMC were used as the database for our search strategy by using combined keywords related to our aims until December 10th, 2020. All articles related to COVID- 19 and beta-blocker were retrieved. Review Manager 5.4 and Comprehensive Meta-Analysis 3 software were used to perform statistical analysis. RESULTS: A total of 43 studies consisting of 11,388,556 patients were included in our analysis. Our meta-analysis showed that the use of beta-blocker was associated with increased risk of COVID-19 [OR 1.32 (95% CI 1.02 - 1.70), p = 0.03, I2 = 99%, random-effect modelling], clinical progression [OR 1.37 (95% CI 1.01 - 1.88), p = 0.04, I2 = 89%, random-effect modelling], and mortality from COVID-19 [OR 1.64 (95% CI 1.22 - 2.19), p = 0.0009, I2 = 94%, random-effect modelling]. Metaregression showed that the association with mortality outcome were influenced by age (p = 0.018) and hypertension (p = 0.005). CONCLUSION: The risk and benefits of using beta-blocker as a drug of choice to treat hypertensive patients should be considered and reviewed individually, case by case, knowing their association with higher incidence and severity of COVID-19 infections. Other first-line antihypertensive drugs may be considered as an alternative therapy if the risk of administering beta blockers outweighs the benefits of COVID-19 infection. REGISTRATION DETAILS: PROSPERO (CRD42021260455).