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PloS One 2021To assess whether in adults with dyslipidemia, statins reduce cardiovascular events, mortality, and adverse effects when compared to fibrates. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To assess whether in adults with dyslipidemia, statins reduce cardiovascular events, mortality, and adverse effects when compared to fibrates.
METHODS
Systematic review and meta-analysis of head-to-head randomized trials of statin and fibrate monotherapy. MEDLINE, EMBASE, Cochrane, WHO International Controlled Trials Registry Platform, and ClinicalTrials.gov were searched through October 30, 2019. Trials that had a follow-up of at least 28 days, and reported mortality or a cardiovascular outcome of interest were eligible for inclusion. Efficacy outcomes were cardiovascular mortality and major cardiovascular events. Safety outcomes included myalgia, serious adverse effects, elevated serum creatinine, and elevated serum alanine aminotransferase. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using the Mantel-Haenszel fixed-effect model, and heterogeneity was assessed using the I2 statistic.
RESULTS
We included 19 eligible trials that directly compared statin and fibrate monotherapy and reported mortality or a cardiovascular event. Studies had a limited duration of follow-up (range 10 weeks to 2 years). We did not find any evidence of a difference between statins and fibrates for cardiovascular mortality (OR 2.35, 95% CI 0.94-5.86, I2 = 0%; ten studies, n = 2657; low certainty), major cardiovascular events (OR 1.15, 95% CI 0.80-1.65, I2 = 13%; 19 studies, n = 7619; low certainty), and myalgia (OR 1.32, 95% CI 0.95-1.83, I2 = 0%; ten studies, n = 6090; low certainty). Statins had less serious adverse effects (OR 0.57, 95% CI 0.36-0.91, I2 = 0%; nine studies, n = 3749; moderate certainty), less elevations in serum creatinine (OR 0.17, 95% CI 0.08-0.36, I2 = 0%; six studies, n = 2553; high certainty), and more elevations in alanine aminotransferase (OR 1.43, 95% CI 1.03-1.99, I2 = 44%; seven studies, n = 5225; low certainty).
CONCLUSIONS
The eligible randomized trials of statins versus fibrates were designed to assess short-term lipid outcomes, making it difficult to have certainty about the direct comparative effect on cardiovascular outcomes and mortality. With the exception of myalgia, use of a statin appeared to have a lower incidence of adverse effects compared to use of a fibrate.
Topics: Animals; Fibric Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Randomized Controlled Trials as Topic
PubMed: 33561179
DOI: 10.1371/journal.pone.0246480 -
Cureus Jul 2019Severe alcoholic hepatitis (SAH) is associated with significant morbidity and mortality, yet the treatment options available are very limited. Past studies have... (Review)
Review
Severe alcoholic hepatitis (SAH) is associated with significant morbidity and mortality, yet the treatment options available are very limited. Past studies have evaluated the efficacy of infliximab in such patients; however, they were limited by sample size. Our aim was to perform a systematic review of these studies to assess the role of infliximab in patients with SAH. We conducted a literature search using electronic database engines including Ovid, PubMed, Scopus, MEDLINE and Cochrane Library from inception to October 2018 to identify published articles addressing outcomes in patients treated for alcoholic hepatitis with infliximab. The primary outcome reviewed was one-month mortality. Secondary outcomes included rate and type of infection; cause of mortality; levels of aspartate aminotransferase, alanine aminotransferase, bilirubin and tumor necrosis factor-α; and Maddrey discriminant function. Five studies including two randomized controlled trials and three case series were included in our analysis with a total sample size of 70 patients. One-month mortality ranged from 10% to 17% in patients who received a single dose of infliximab with or without prednisone compared to 38% in patients who received three doses of infliximab in combination with prednisone. A single dose of infliximab was associated with an infection rate of 10% to 26% in contrast to an 89% rate with three doses of infliximab. Infliximab, when used in a single dose, could potentially be an alternative agent for the management of SAH in a large group of patients who have contraindications such as gastrointestinal bleeding, uncontrolled diabetes or an active hepatitis infection. It might also have a role in the prevention of hepatorenal syndrome. There is a need for larger trials to evaluate the role of infliximab in a cohort of patients who are not candidates for prednisolone therapy.
PubMed: 31516791
DOI: 10.7759/cureus.5082 -
PloS One 2016Sodium-glucose co-transporter 2 inhibitors (SGLT2-i) are a novel drug class for the treatment of diabetes. We aimed at describing the maximal benefits and risks... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Sodium-glucose co-transporter 2 inhibitors (SGLT2-i) are a novel drug class for the treatment of diabetes. We aimed at describing the maximal benefits and risks associated with SGLT2-i for patients with type 2 diabetes.
DESIGN
Systematic review and meta-analysis.
DATA SOURCES AND STUDY SELECTION
We included double-blinded, randomised controlled trials (RCTs) evaluating SGLT2-i administered in the highest approved therapeutic doses (canagliflozin 300 mg/day, dapagliflozin 10 mg/day, and empagliflozin 25 mg/day) for ≥12 weeks. Comparison groups could receive placebo or oral antidiabetic drugs (OAD) including metformin, sulphonylureas (SU), or dipeptidyl peptidase 4 inhibitors (DPP-4-i). Trials were identified through electronic databases and extensive manual searches. Primary outcomes were glycated haemoglobin A1c (HbA1c) levels, serious adverse events, death, severe hypoglycaemia, ketoacidosis and CVD. Secondary outcomes were fasting plasma glucose, body weight, blood pressure, heart rate, lipids, liver function tests, creatinine and adverse events including infections. The quality of the evidence was assessed using GRADE.
RESULTS
Meta-analysis of 34 RCTs with 9,154 patients showed that SGLT2-i reduced HbA1c compared with placebo (mean difference -0.69%, 95% confidence interval -0.75 to -0.62%). We downgraded the evidence to 'low quality' due to variability and evidence of publication bias (P = 0.015). Canagliflozin was associated with the largest reduction in HbA1c (-0.85%, -0.99% to -0.71%). There were no differences between SGLT2-i and placebo for serious adverse events. SGLT2-i increased the risk of urinary and genital tract infections and increased serum creatinine, and exerted beneficial effects on bodyweight, blood pressure, lipids and alanine aminotransferase (moderate to low quality evidence). Analysis of 12 RCTs found a beneficial effect of SGLT2-i on HbA1c compared with OAD (-0.20%, -0.28 to -0.13%; moderate quality evidence).
CONCLUSION
This review includes a large number of patients with type 2 diabetes and found that SGLT2-i reduces HbA1c with a notable increased risk in non-serious adverse events. The analyses may overestimate the intervention benefit due bias.
Topics: Benzhydryl Compounds; Canagliflozin; Diabetes Mellitus, Type 2; Glucosides; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Randomized Controlled Trials as Topic; Sodium-Glucose Transporter 2; Sodium-Glucose Transporter 2 Inhibitors; Treatment Outcome
PubMed: 27835680
DOI: 10.1371/journal.pone.0166125 -
Journal of the Chinese Medical... Jul 2016Antituberculosis drug-induced liver injury (ATDILI) is a major safety concern for the treatment of tuberculosis (TB). The impact of chronic hepatitis B infection (CHBI)... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Antituberculosis drug-induced liver injury (ATDILI) is a major safety concern for the treatment of tuberculosis (TB). The impact of chronic hepatitis B infection (CHBI) on the risk of ATDILI is still controversial. In this study, we aimed to assess systematically the influence of CHBI on the susceptibility to ATDILI.
METHODS
We reviewed all English-language medical literature with the medical subject search headings hepatitis B and antitubercular agents from the major medical databases. Thereafter, a systematic review and meta-analysis was performed on those publications that qualified.
RESULTS
A total of 938 citations were retrieved on the initial major database search, from which 15 studies were determined to be eligible for analysis. While undergoing anti-TB treatment, 575 cases with drug-induced liver injury (DILI) and 4128 controls without DILI were enrolled into this analysis. The pooled odds ratio of all studies for the CHBI to ATDILI was 2.18 (95% confidence interval, 1.41-3.37). Among the studies with a strict definition of DILI (alanine aminotransferase > 5 × upper limit of normal value) and combination anti-TB regimen, the impact of CHBI on ATDILI was significant only in the prospective studies (odds ratio, 3.41; 95% confidence interval, 1.77-6.59), but not in the case-control studies. However, in the studies with a strict definition of DILI and isoniazid only treatment, the association between CHBI and ATDILI was not statistically significant.
CONCLUSION
This meta-analysis suggests that CHBI may increase the risk of ATDILI in the standard combination therapy for active TB. Close follow-up and regular liver test monitoring are mandatory to treat TB in chronic hepatitis B carriers.
Topics: Antitubercular Agents; Chemical and Drug Induced Liver Injury; Hepatitis B, Chronic; Humans; Risk
PubMed: 27032895
DOI: 10.1016/j.jcma.2015.12.006 -
Systematic Review with Meta-Analysis: The Effects of Probiotics in Nonalcoholic Fatty Liver Disease.Gastroenterology Research and Practice 2019Probiotics was considered as a potential therapy for nonalcoholic fatty liver disease (NAFLD) without approval and comprehensive assessment in recent years, which call... (Review)
Review
BACKGROUND AND AIMS
Probiotics was considered as a potential therapy for nonalcoholic fatty liver disease (NAFLD) without approval and comprehensive assessment in recent years, which call for a meta-analysis.
METHODS
We performed electronic and manual searches including English and Chinese databases published before April 2019, with the use of mesh term and free text of "nonalcoholic fatty liver disease" and "probiotics." Clinical trials evaluating the efficacy of probiotic therapy in NAFLD patients were included according to the eligibility criteria. With the use of random effects models, clinical outcomes were presented as weighted mean difference (WMD) with 95% confidence interval (CI), while heterogeneity and meta-regression were also assessed.
RESULTS
28 clinical trials enrolling 1555 criterion proven NAFLD patients with the use of probiotics from 4 to 28 weeks were included. Overall, probiotic therapy had beneficial effects on body mass index (WMD: -1.46, 95% CI: [-2.44, -0.48]), alanine aminotransferase (WMD: -13.40, 95% CI: [-17.03, -9.77]), aspartate transaminase (WMD: -13.54, 95% CI: [-17.86, -9.22]), gamma-glutamyl transpeptidase (WMD: -9.88, 95% CI: [-17.77, -1.99]), insulin (WMD: -1.32, 95% CI: [-2.43, -0.21]), homeostasis model assessment-insulin resistance (WMD: -0.42, 95% CI: [-0.73, -0.12]), and total cholesterol (WMD: -15.38, 95% CI: [-26.50, -4.25]), but not in fasting blood sugar, lipid profiles, or tumor necrosis factor-alpha.
CONCLUSION
The systematic review and meta-analysis support that probiotics are superior to placebo in NAFLD patients and could be utilized as a common complementary therapeutic approach.
PubMed: 31885541
DOI: 10.1155/2019/1484598 -
The Cochrane Database of Systematic... Mar 2017Hepatocellular carcinoma is the most common liver neoplasm, the sixth most common cancer worldwide, and the third most common cause of cancer mortality. Moreover, its... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Hepatocellular carcinoma is the most common liver neoplasm, the sixth most common cancer worldwide, and the third most common cause of cancer mortality. Moreover, its incidence has increased dramatically in the past decade. While surgical resection and liver transplantation are the main curative treatments, only around 20% of people with early hepatocellular carcinoma may benefit from these therapies. Current treatment options for unresectable hepatocellular carcinoma include various ablative and transarterial therapies in addition to the drug sorafenib.
OBJECTIVES
To assess the benefits and harms of external beam radiotherapy in the management of localised unresectable hepatocellular carcinoma.
SEARCH METHODS
We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE (OvidSP), Embase (OvidSP), Science Citation Index Expanded (Web of Science), and clinicaltrials.gov registry. We also checked reference lists of primary original studies and review articles manually for further related articles (cross-references) up to October 6, 2016.
SELECTION CRITERIA
Eligible studies included all randomised clinical trials comparing external beam radiotherapy either as a monotherapy or in combination with other systemic or locoregional therapies versus placebo, no treatment, or other systemic or locoregional therapies for people with unresectable hepatocellular carcinoma.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. We used a random-effects model as well as a fixed-effect model meta-analysis but in case of discrepancy between the two models (e.g. one giving a significant intervention effect, the other no significant intervention effect), we reported both results; otherwise, we reported only the results from the fixed-effect model meta-analysis. We assessed risk of bias of the included trials using predefined risk of bias domains; assessed risks of random errors with Trial Sequential Analysis; and presented the review results incorporating the methodological quality of the trials using GRADE.
MAIN RESULTS
Nine randomised clinical trials with 879 participants fulfilled our inclusion criteria. All trials were at high risk of bias, and we rated the evidence as low to very low quality. All of the included trials compared combined external beam radiotherapy plus chemoembolisation versus chemoembolisation alone in people with unresectable hepatocellular carcinoma; moreover, three of the trials compared external beam radiotherapy alone versus chemoembolisation alone. All trials were conducted in China. The median age in most of the included trials was around 52 years, and most trial participants were male. The median follow-up duration ranged from one to three years. None of the trials reported data on cancer-related mortality, quality of life, serious adverse events, or time to progression of the tumour. For the comparison of radiotherapy plus chemoembolisation versus chemoembolisation alone, the risk ratio for one-year all-cause mortality was 0.51 (95% confidence interval (CI) 0.41 to 0.62; P < 0.001; 9 trials; low-quality evidence); for complete response rate was 2.14 (95% CI 1.47 to 3.13; P < 0.001; 7 trials; low-quality evidence); and for overall response rate defined as complete response plus partial response was 1.58 (95% CI 1.40 to 1.78; P < 0.001; 7 trials; low-quality evidence), all in favour of combined treatment with external beam radiotherapy plus transarterial chemoembolisation and seemingly supported by our Trial Sequential Analysis. Additionally, the combined treatment was associated with a higher risk of elevated total bilirubin and elevated alanine aminotransferase. The risk ratio for the risk of elevated alanine aminotransferase was 1.41 (95% CI 1.08 to 1.84; P = 0.01; very low-quality evidence), while for elevated total bilirubin it was 2.69 (95% CI 1.34 to 5.40; P = 0.005; very low-quality evidence). For the comparison of radiotherapy versus chemoembolisation, the risk ratio for one-year all-cause mortality was 1.21 (95% CI 0.97 to 1.50; 3 trials; I = 0%; very low-quality evidence) which was not supported by our Trial Sequential Analysis.In addition, we found seven ongoing randomised clinical trials evaluating different external beam radiotherapy techniques for people with unresectable hepatocellular carcinoma.
AUTHORS' CONCLUSIONS
We found very low- and low-quality evidence suggesting that combined external beam radiotherapy and chemoembolisation may be associated with lower mortality and increased complete and overall response rates, despite an increased toxicity as expressed by a higher rise of bilirubin and alanine aminotransferase. A high risk of systematic errors (bias) as well as imprecision and inconsistency suggest that these findings should be considered cautiously and that high-quality trials are needed to assess further the role of external beam radiotherapy for unresectable hepatocellular carcinoma.
Topics: Alanine Transaminase; Bilirubin; Carcinoma, Hepatocellular; Cause of Death; Chemoembolization, Therapeutic; Combined Modality Therapy; Female; Humans; Liver Neoplasms; Male; Middle Aged; Radiotherapy; Randomized Controlled Trials as Topic
PubMed: 28267205
DOI: 10.1002/14651858.CD011314.pub2 -
British Journal of Clinical Pharmacology Feb 2022Statin liver safety in non-alcoholic fatty liver disease (NAFLD) patients is not well defined. We analysed differences in liver function tests, including alanine... (Meta-Analysis)
Meta-Analysis Review
AIMS
Statin liver safety in non-alcoholic fatty liver disease (NAFLD) patients is not well defined. We analysed differences in liver function tests, including alanine transaminase aminotransferase (ALT), aspartate transaminase (AST) and gamma-glutamyl transpeptidase (GGT) in NAFLD patients treated or not treated with statins.
METHODS
We performed a systematic review of MEDLINE via PubMed and EMBASE databases and metanalysis of clinical studies investigating levels of ALT, AST and GGT in NAFLD according to statin treatment. Mean difference (MD) and percentage MD were calculated between the two groups.
RESULTS
We included 22 studies with 2345 NAFLD patients. Overall, 16 were before-after interventional, five were cross-sectional and one was combined cross-sectional/interventional study. In all interventional studies, except one, patients had raised ALT, AST and GGT at baseline. Interventional studies showed reduced ALT values with an MD reduction of -27.2 U/L (95% CI -35.25/-19.15) and a percentage MD reduction of -35.41% (95% CI -44.78/-26.04). Also, AST values were reduced after statin treatment in interventional studies with an MD of -18.82 U/L (95% CI -25.63/-12.02) (percentage -31.78%, 95% CI -41.45/-22.11). Similarly, GGT levels were reduced after statin treatment with an MD of -19.93 U/L (95% CI -27.10/-12.77) (percentage -25.57%, 95% CI -35.18/-15.97). Cross-sectional studies showed no difference in AST and GGT values between patients treated with and without statins.
CONCLUSION
In interventional studies, ALT, AST and GGT were reduced after statin treatment with a percentage mean difference of -35.41%, -31.78% and -25.57%, respectively, while observational studies showed a null effect, suggesting liver safety of statins in NAFLD patients.
Topics: Alanine Transaminase; Aspartate Aminotransferases; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Liver; Non-alcoholic Fatty Liver Disease; gamma-Glutamyltransferase
PubMed: 34133035
DOI: 10.1111/bcp.14943 -
Journal of Hepatology Apr 2012Non-alcoholic fatty liver disease (NAFLD) is a frequent accompaniment of obesity and insulin resistance. With the prevalence approaching 85% in obese populations, new... (Meta-Analysis)
Meta-Analysis Review
Non-alcoholic fatty liver disease (NAFLD) is a frequent accompaniment of obesity and insulin resistance. With the prevalence approaching 85% in obese populations, new therapeutic approaches to manage NAFLD are warranted. A systematic search of the literature was conducted for studies pertaining to the effect of omega-3 polyunsaturated fatty acid (PUFA) supplementation on NAFLD in humans. Primary outcome measures were liver fat and liver function tests: alanine aminotransferase (ALT) and aspartate aminotransferase [1]. Data were pooled and meta-analyses conducted using a random effects model. Nine eligible studies, involving 355 individuals given either omega-3 PUFA or control treatment were included. Beneficial changes in liver fat favoured PUFA treatment (effect size=-0.97, 95% CI: -0.58 to -1.35, p<0.001). A benefit of PUFA vs. control was also observed for AST (effect size=-0.97, 95% CI: -0.13 to -1.82, p=0.02). There was a trend towards favouring PUFA treatment on ALT but this was not significant (effect size=-0.56, 95% CI: -1.16 to 0.03, p=0.06). Sub-analyses of only randomised control trials (RCTs) showed a significant benefit for PUFA vs. control on liver fat (effect size=-0.96, 95% CI: -0.43 to -1.48, p<0.001), but not for ALT (p=0.74) or AST (p=0.28). There was significant heterogeneity between studies. The pooled data suggest that omega-3 PUFA supplementation may decrease liver fat, however, the optimal dose is currently not known. Well designed RCTs which quantify the magnitude of effect of omega-3 PUFA supplementation on liver fat are needed.
Topics: Adult; Alanine Transaminase; Aspartate Aminotransferases; Dietary Supplements; Fatty Acids, Omega-3; Fatty Liver; Female; Humans; Lipid Metabolism; Liver; Male; Non-alcoholic Fatty Liver Disease; Treatment Outcome
PubMed: 22023985
DOI: 10.1016/j.jhep.2011.08.018 -
Infection Feb 2022This review was aimed to synthesise the best available evidence on the effectiveness and safety of remdesivir in the treatment of moderate to severe COVID-19. (Meta-Analysis)
Meta-Analysis Review
PURPOSE
This review was aimed to synthesise the best available evidence on the effectiveness and safety of remdesivir in the treatment of moderate to severe COVID-19.
METHOD
Randomised controlled trials (RCTs) and observational studies reporting the effectiveness and safety of remdesivir were searched via databases and other sources from December 2019 to December 2020. Two independent reviewers performed literature screening, data extraction and assessment of risk bias. Seven studies involving 3686 patients were included.
RESULTS
Treatment with remdesivir was associated with an increase in clinical recovery rate by 21% (RR 1.21; 95% CI 1.08-1.35) on day 7 and 29% (RR 1.29; 95% CI 1.22-1.37) on day 14. The likelihoods of requiring high-flow supplemental oxygen and invasive mechanical ventilation in the remdesivir group were lower than in the placebo group by 27% (RR 0.73; 95% CI 0.54-0.99) and 47% (RR 0.53; 95% CI 0.39-0.72), respectively. Remdesivir-treated patients showed a 39% (RR 0.61; 95% CI 0.46-0.79) reduction in the risk of mortality on day 14 compared to the control group; however, there was no significant difference on day 28. Serious adverse effects (SAEs) were significantly less common in patients treated with remdesivir, with an absolute risk difference of 6% (RD -0.06; 95% CI -0.09 to -0.03).
CONCLUSION
Despite conditional recommendation against its use, remdesivir could still be effective in early clinical improvement; reduction of early mortality and avoiding high-flow supplemental oxygen and invasive mechanical ventilation among hospitalised COVID-19 patients. Remdesivir was also well tolerated without significant SAEs compared to placebo, yet available evidence from clinical studies support the need to conduct close monitoring.
Topics: Adenosine Monophosphate; Alanine; Humans; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 34331674
DOI: 10.1007/s15010-021-01671-0 -
Complementary Therapies in Medicine Aug 2021Several studies reported beneficial effects of chromium supplementation for management of type 2 diabetes mellitus (T2DM). The present study aimed to provide a... (Meta-Analysis)
Meta-Analysis Review
Effects of chromium supplementation on blood pressure, body mass index, liver function enzymes and malondialdehyde in patients with type 2 diabetes: A systematic review and dose-response meta-analysis of randomized controlled trials.
BACKGROUND
Several studies reported beneficial effects of chromium supplementation for management of type 2 diabetes mellitus (T2DM). The present study aimed to provide a systematic review and meta-analysis of randomized controlled trials (RCTs) examining the effects of chromium supplementation on blood pressure, body mass index (BMI), liver function enzymes and malondialdehyde (MDA) in patients with T2DM.
METHODS
PubMed, Scopus, and Embase were searched up to 15 November 2020 with no language and time restriction. RCTs that reported the effects of chromium supplementation on blood pressure, BMI, liver function enzymes and MDA in patients with T2DM were included. A random-effects model was used to compute weighted mean differences (WMDs) with 95 % confidence intervals (CIs). Between-study heterogeneity was assessed by Cochran's Q test and quantified by I statistic.
RESULTS
Of 3586 publications, 15 RCTs were included for the meta-analysis. Pooled effect sizes indicated that chromium significantly reduced diastolic blood pressure (DBP) (WMD): -2.36 mmHg, 95 % CI: -4.14, -0.60; P = 0.008), and MDA (WMD: -0.55 umol/l, 95 % CI: -0.96, -0.14; P = 0.008). However, chromium supplementation did not significantly affect BMI, systolic blood pressure (SBP), alanine aminotransferase (ALT), aspartate aminotransferase (AST). Meta-regression analysis did not show significant linear relationship between dose of chromium and change in BMI (p = 0.412), SBP (p = 0. 319), DBP (p = 0.102), ALT (p = 0.923), AST (p = 0.986) and MDA (p = 0.055).
CONCLUSION
The present systematic review and meta-analysis shows that supplementation with chromium at dose of 200-1000 μg/day may reduce DBP and MDA in T2DM patients.
Topics: Blood Pressure; Body Mass Index; Chromium; Diabetes Mellitus, Type 2; Dietary Supplements; Humans; Liver; Malondialdehyde; Randomized Controlled Trials as Topic
PubMed: 34237387
DOI: 10.1016/j.ctim.2021.102755