scholarly journals 1112. Vancomycin Nephrotoxicity Relative to Alternative Antibiotic Treatments: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S647-S648
Author(s):  
Nayle Ibragimova ◽  
Katherine Huynh ◽  
Vanessa Ng ◽  
Vionna Wong ◽  
Evan J Zasowski
Keyword(s):  
Confidence Intervals ◽  
Meta Analysis ◽  
Kidney Injury ◽  
Pooled Analysis ◽  
Fixed Dose ◽  
Therapeutic Drug ◽  
Forest Plot ◽  
Odds Ratios ◽  
Randomized Controlled ◽  
Vancomycin Group

Abstract Background Vancomycin is one of the most frequently prescribed antibiotics. Existing clinical evidence on vancomycin nephrotoxicity is limited to observational studies which are prone to confounding and bias. The purpose of this systematic review and meta-analysis is to compare acute kidney injury between vancomycin and comparator anti-methicillin resistant Staphylococcus aureus (MRSA) antibiotics using randomized controlled trial (RCT) data. Methods PubMed and Embase were searched for RCTs comparing intravenous vancomycin to other anti-MRSA antibiotics in adult patients, published from 1990 to January 2021. Studies were included if they reported comparative data on renal outcomes. The primary outcome was change in renal function, referred to as ‘nephrotoxicity’ in this study. Studies where another known nephrotoxic medication was part of study therapy in any treatment group were excluded. Eighteen studies met the inclusion criteria, and two independent reviewers assessed the risk of bias. Data on nephrotoxicity definition, comparator drug, infection type, vancomycin dosing strategy, duration of treatment, and concurrent gram-negative coverage were extracted. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Figure 1. Flow chart of article selection. Results Of 1,426 studies identified, 18 encompassing 8,966 patients were included. Treatment with vancomycin was associated with significantly increased odds of nephrotoxicity (OR, 2.41; 95% CI, 1.71 to 3.40; P< 0.00001) relative to its alternatives. A subgroup analysis grouping studies by reported vancomycin dosing approach revealed a stronger association between vancomycin and nephrotoxicity in studies with fixed-dose vancomycin regimens (OR 5.31; 95% CI 1.93 to 14.56; P=0.001) relative to studies with vancomycin therapeutic drug monitoring (TDM) (OR 2.17; 95% CI 1.51 to 3.13; P< 0.0001). Figure 2. Forest plot indicating the risk of nephrotoxicity associated with vancomycin vs. comparators. Odds ratios (ORs) and 95% confidence intervals (95% CIs) are shown for each study and the pooled analysis using a random effects model and the Mantel-Haenszel method. OR>1 means that the risk of kidney injury in the vancomycin group is greater than that in the comparator group. Figure 3. Forest plot indicating a strong association between vancomycin and nephrotoxicity in studies with fixed-dose vancomycin regimens relative to studies with vancomycin therapeutic drug monitoring (TDM). Odds ratios (ORs) and 95% confidence intervals (95% CIs) are shown for each study and the pooled analysis using a random effects model and the Mantel-Haenszel method. OR>1 means that the risk of kidney injury in the vancomycin group is greater than that in the comparator group. Table 1. Summary of included studies. Conclusion This analysis shows that intravenous vancomycin is associated with greater odds of renal toxicity relative to alternative antibiotics. This effect was not as pronounced in studies where vancomycin TDM was used potentially indicating benefit of TDM although further study is required to confirm this. Disclosures All Authors: No reported disclosures

scholarly journals Hydroxyethyl starch 130/0.4 for volume replacement therapy in surgical patients: a systematic review and meta-analysis of randomized controlled trials

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Yi Xu ◽  
Siying Wang ◽  
Leilei He ◽  
Hong Yu ◽  
Hai Yu
Keyword(s):  
Replacement Therapy ◽  
Meta Analysis ◽  
Postoperative Mortality ◽  
Kidney Injury ◽  
Volume Replacement ◽  
Surgical Patients ◽  
Controlled Trials ◽  
Randomized Controlled ◽  
Volume Replacement Therapy ◽  
Type Of Surgery

Abstract Background The safety of perioperative intravenous hydroxyethyl starch (HES) products, specifically HES 130/0.4, continues to be the source of much debate. The aim of this meta-analysis was to update the existing evidence and gain further insight into the clinical effects of HES 130/0.4 on postoperative outcomes for volume replacement therapy in surgical patients. Methods MEDLINE, EMBASE, and Cochrane Library databases were searched from inception to March 2020 for relevant randomized controlled trials (RCTs) on perioperative use of HES 130/0.4 in adult surgical patients. The primary outcome was postoperative mortality and secondary outcomes were the incidence of acute kidney injury (AKI) and requirement for renal replacement therapy (RRT). The analysis was performed using the random-effects method and the risk ratio (RR) with a 95% confidence interval (CI). We performed the risk-of-bias assessment of eligible studies and assessed the overall quality of evidence for each outcome. Results Twenty-five RCTs with 4111 participants were finally included. There were no statistical differences between HES 130/0.4 and other fluids in mortality at 30 days (RR 1.28, 95% CI 0.88 to 1.86, p = 0.20), the incidence of AKI (RR 1.23, 95% CI 0.99 to 1.53, p = 0.07), or requirement for RRT (RR 0.75, 95% CI 0.37 to 1.53, p = 0.43). Overall, there was a moderate certainty of evidence for all the outcomes. There was no subgroup difference related to the type of surgery (p = 0.17) in the incidence of AKI. As for the type of comparator fluids, however, there was a trend that was not statistically significant (p = 0.06) towards the increased incidence of AKI in the HES 130/0.4 group (RR 1.22, 95% CI 0.97 to 1.54) compared with the crystalloid group (RR 1.21, 95% CI 0.27 to 3.91). Subgroup analyses according to the type of surgery demonstrated consistent findings. Conclusions This systematic review and meta-analysis suggests that the use of HES 130/0.4 for volume replacement therapy compared with other fluids resulted in no significant difference in postoperative mortality or kidney dysfunction among surgical patients. Given the absent evidence of confirmed benefit and the potential trend of increased kidney injury, we cannot recommend the routine clinical use of HES 130/0.4 for volume replacement therapy in surgical patients from the perspective of benefit/risk profile. However, the results need to be interpreted with caution due to the limited sample size, and further well-powered RCTs are warranted. Trial registration PROSPERO registry reference: CRD42020173058

scholarly journals A Meta-Analysis of Nutritional Supplementation for Management of Hospitalized Alcoholic Hepatitis

2012 ◽  
Vol 26 (7) ◽  
pp. 463-467 ◽  
Author(s):  
Ramy Antar ◽  
Phil Wong ◽  
Peter Ghali
Keyword(s):  
Biochemical Parameters ◽  
Meta Analysis ◽  
Nutritional Therapy ◽  
Pooled Analysis ◽  
Nutritional Supplementation ◽  
Mortality Benefit ◽  
Randomized Controlled ◽  
Balanced Diet ◽  
Randomized Controlled Studies ◽  
Diet Versus

BACKGROUND: Alcoholic liver disease (ALD) is associated with a high risk of morbidity and mortality. Malnutrition accompanies this condition and may be both a consequence of and contributor to the pathology. Many trials have investigated the benefits of providing supplemental nutrition in the management of patients with ALD. The present study is a meta-analysis of the available evidence.METHOD: A meta-analysis of randomized controlled studies comparing nutritional supplementation plus a normal hospital diet versus diet alone.RESULTS: Seven randomized controlled studies including 262 patients with ALD were identified. Pooled analysis revealed no statistical difference in mortality between groups given special nutritional therapy versus a normal balanced diet (OR 0.80 [95% CI 0.42 to 1.52]). In addition, nutrition did not significantly improve ascites (OR 1.29 [95% CI 0.52 to 3.20]) or any biochemical parameters. However, encephalopathy showed a significant improvement or resolution (OR 0.24 [95% CI 0.06 to 0.93]).CONCLUSION: Nutritional supplementation provided no mortality benefit in patients with ALD, and neither ascites nor biochemical parameters significantly improved. However, encephalopathy was significantly ameliorated and, therefore, nutritional supplementation should be encouraged in that setting.

Abstract 3789: Nessun Dorma : Have the Risks of Rosiglitazone been Exaggerated?

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
George A Diamond ◽  
Sanjay Kaul
Keyword(s):  
Confidence Intervals ◽  
Effect Size ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Cardiovascular Death ◽  
Sensitivity Analyses ◽  
Odds Ratios ◽  
True Effect Size ◽  
Index Study ◽  
The Stability

Background A highly publicized meta-analysis of 42 clinical trials comprising 27,844 diabetics ignited a firestorm of controversy by charging that treatment with rosiglitazone was associated with a “…worrisome…” 43% greater risk of myocardial infarction ( p =0.03) and a 64% greater risk of cardiovascular death ( p =0.06). Objective The investigators excluded 4 trials from the infarction analysis and 19 trials from the mortality analysis in which no events were observed. We sought to determine if these exclusions biased the results. Methods We compared the index study to a Bayesian meta-analysis of the entire 42 trials (using odds ratio as the measure of effect size) and to fixed-effects and random-effects analyses with and without a continuity correction that adjusts for values of zero. Results The odds ratios and confidence intervals for the analyses are summarized in the Table . Odds ratios for infarction ranged from 1.43 to 1.22 and for death from 1.64 to 1.13. Corrected models resulted in substantially smaller odds ratios and narrower confidence intervals than did uncorrected models. Although corrected risks remain elevated, none are statistically significant (*p<0.05). Conclusions Given the fragility of the effect sizes and confidence intervals, the charge that roziglitazone increases the risk of adverse events is not supported by these additional analyses. The exaggerated values observed in the index study are likely the result of excluding the zero-event trials from analysis. Continuity adjustments mitigate this error and provide more consistent and reliable assessments of true effect size. Transparent sensitivity analyses should therefore be performed over a realistic range of the operative assumptions to verify the stability of such assessments especially when outcome events are rare. Given the relatively wide confidence intervals, additional data will be required to adjudicate these inconclusive results.

Abstract P209: Dose-Response Relationship Between Dietary Intake of Alpha-linolenic Acid and Risk of Coronary Heart Disease: A Meta-analysis of Prospective Studies

Circulation ◽  
2017 ◽  
Vol 135 (suppl_1) ◽  
Author(s):  
Jingkai Wei ◽  
Yuzhi Xi ◽  
Ruixue Hou ◽  
Alysse Kowalski ◽  
Hao Sun ◽  
...  
Keyword(s):  
Dose Response ◽  
Meta Analysis ◽  
Pooled Analysis ◽  
Controlled Trials ◽  
Response Relationship ◽  
Alpha Linolenic Acid ◽  
Dose Response Relationship ◽  
Randomized Controlled ◽  
Chd Risk ◽  
Reduced Risk

Introduction: Previous studies show that alpha-linolenic acid (ALA) is associated with reduced risk of coronary heart disease (CHD). However, it remains unclear whether and how dietary ALA doses are related to CHD. Hypothesis: We hypothesized that higher dietary ALA intake is associated with a greater reduction in risk of CHD. Methods: We searched PubMed, EMBASE, and Web of Science for prospective studies examining the association between dietary ALA intake and CHD risk. Dietary ALA intake was assigned or measured by self-report. Outcomes were reported as total and fatal CHD and/or myocardial infarction, which were obtained from blinded endpoint assessments or medical records. Two-stage fixed-effects dose-response meta-analyses were conducted to estimate the association between increasing ALA intake (relative to study-specific referents) and CHD. Results: Fifteen published articles were identified and included in the meta-analysis (13 cohort studies and 2 randomized controlled trials). The pooled analysis was based on 310,768 individuals with 12,049 events with a mean length of follow-up of 9.6 years. The analysis showed a J-shaped curve between ALA intake and relative risk of total CHD (Chi-square=21.08, p<0.001). ALA intake from 0.3-1.4g/day showed reduced risk of total CHD, while intake ≥2.5g/day was associated with increased risk of CHD, compared to people without ALA intake (Figure 1A). Approximately 1g/day of ALA intake was associated with the lowest risk of total CHD. ALA intake was linearly associated with fatal CHD - every 1g/day increase in ALA intake was associated with an 11% decrease in fatal CHD risk (95% CI: -0.16, -0.05) (Figure 1B). Conclusion: The J-shaped dose-response relationship based on our pooled analysis suggests that 1g/day of dietary ALA may be optimal for total CHD prevention. Though a higher dietary ALA intake was associated with reduced risk of fatal CHD, the excess total CHD risk at higher ALA intakes warrants further investigation, especially through randomized controlled trials.

scholarly journals Remote Ischemic Preconditioning to Prevent Acute Kidney Injury After Cardiac Surgery: A Meta-Analysis of Randomized Controlled Trials

2021 ◽  
Vol 8 ◽  
Author(s):  
Zigang Liu ◽  
Yongmei Zhao ◽  
Ming Lei ◽  
Guancong Zhao ◽  
Dongcheng Li ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Cardiac Surgery ◽  
Randomized Controlled Trials ◽  
Ischemic Preconditioning ◽  
Meta Analysis ◽  
Kidney Injury ◽  
Controlled Trials ◽  
Randomized Controlled ◽  
Subgroup Analyses ◽  
Meta Regression

Objective: Randomized controlled trials (RCTs) evaluating the influence of remote ischemic preconditioning (RIPC) on acute kidney injury (AKI) after cardiac surgery showed inconsistent results. We performed a meta-analysis to evaluate the efficacy of RIPC on AKI after cardiac surgery.Methods: Relevant studies were obtained by search of PubMed, Embase, and Cochrane's Library databases. A random-effect model was used to pool the results. Meta-regression and subgroup analyses were used to determine the source of heterogeneity.Results: Twenty-two RCTs with 5,389 patients who received cardiac surgery −2,702 patients in the RIPC group and 2,687 patients in the control group—were included. Moderate heterogeneity was detected (p for Cochrane's Q test = 0.03, I2 = 40%). Pooled results showed that RIPC significantly reduced the incidence of AKI compared with control [odds ratio (OR): 0.76, 95% confidence intervals (CI): 0.61–0.94, p = 0.01]. Results limited to on-pump surgery (OR: 0.78, 95% CI: 0.64–0.95, p = 0.01) or studies with acute RIPC (OR: 0.78, 95% CI: 0.63–0.97, p = 0.03) showed consistent results. Meta-regression and subgroup analyses indicated that study characteristics, including study design, country, age, gender, diabetic status, surgery type, use of propofol or volatile anesthetics, cross-clamp time, RIPC protocol, definition of AKI, and sample size did not significantly affect the outcome of AKI. Results of stratified analysis showed that RIPC significantly reduced the risk of mild-to-moderate AKI that did not require renal replacement therapy (RRT, OR: 0.76, 95% CI: 0.60–0.96, p = 0.02) but did not significantly reduce the risk of severe AKI that required RRT in patients after cardiac surgery (OR: 0.73, 95% CI: 0.50–1.07, p = 0.11).Conclusions: Current evidence supports RIPC as an effective strategy to prevent AKI after cardiac surgery, which seems to be mainly driven by the reduced mild-to-moderate AKI events that did not require RRT. Efforts are needed to determine the influences of patient characteristics, procedure, perioperative drugs, and RIPC protocol on the outcome.

scholarly journals Flunarizine as prophylaxis for episodic migraine: a systematic review with meta-analysis

Ból ◽  
2019 ◽  
Vol 20 (1) ◽  
pp. 25-38
Author(s):  
Anker Stubberud ◽  
Nikolai Melseth Flaaen ◽  
Douglas C. McCrory ◽  
Sindre Andre Pedersen ◽  
Mattias Linde
Keyword(s):  
Confidence Interval ◽  
Meta Analysis ◽  
Episodic Migraine ◽  
Pooled Analysis ◽  
Risk Of Bias ◽  
Current Guideline ◽  
Data Synthesis ◽  
Randomized Controlled ◽  
The Mean ◽  
Meta Analyses

Based on few clinical trials, flunarizine is considered a first-line prophylactic treatment for migraine in several guidelines. In this meta-analysis, we examined the pooled evidence for its effectiveness, tolerability, and safety. Prospective randomized controlled trials of flunarizine as a prophylaxis against migraine were identified from a systematic literature search, and risk of bias was assessed for all included studies. Reduction in mean attack frequency was estimated by calculating the mean difference (MD), and a series of secondary outcomes –including adverse events (AEs) – were also analyzed. The database search yielded 879 unique records. Twentyfive studies were included in data synthesis. We scored 31/175 risk of bias items as “high”, with attrition as the most frequent bias. A pooled analysis estimated that flunarizine reduces the headache frequency by 0.4 attacks per 4 weeks compared with placebo (5 trials, 249 participants: MD 20.44; 95% confidence interval 20.61 to 2 0.26). Analysis also revealed that the effectiveness of flunarizine prophylaxis is comparable with that of propranolol (7 trials, 1151 participants, MD 20.08; 95% confidence interval 20.34 to 0.18). Flunarizine also seems to be effective in children. The most frequent AEs were sedation and weight increase. Meta-analyses were robust and homogenous, although several of the included trials potentially suffered from high risk of bias. Unfortunately, reporting of AEs was inconsistent and limited. In conclusion, pooled analysis of data from partially outdated trials shows that 10- mg flunarizine per day is effective and well tolerated in treating episodic migraine – supporting current guideline recommendations.

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