Intensive treatment of hyperglycemia in the acute phase of myocardial infarction: the tenuous balance between effectiveness and safety – a systematic review and meta-analysis of randomized clinical trials

SUMMARY INTRODUCTION In acute myocardial infarction (AMI), each 18 mg/dl (1 mmol/L) increment is associated with a 3% increase in mortality rates. All strategies applied for reducing blood glucose to this date, however, have not presented encouraging results. METHODOLOGY We searched the Medline (PubMed) and Cochrane Library databases for randomized clinical trials (RCTs) from 1995 to 2017 that used the intensive strategy or GIK therapy for blood glucose control during the acute stage of the AMI. We included eight studies. In order to identify the effects of GIK or insulin therapy, we calculated a overall risk ratio (RR) with meta-analysis of fixed and random effects models. A two-tail p-value of < 0.05 was considered statistically significant. RESULTS A total of 28,151 patients were included: 1,379 intensively treated with insulin, 13,031 in GIK group, and 13,741 in the control group. The total mortality was 10.5% (n=2,961) and the RR of 1.03 [95%CI 0.96–1.10]; I2 = 31%; p = 0.41 for the combined intensive insulin plus GIK groups in comparison with the control group. In meta-regression analyses, intense reductions in blood glucose (> 36 mg/dL) in relation to the estimated average blood glucose (estimated by HbA1c) were associated with higher mortality, whereas lower reductions in blood glucose (< 36 mg/dL) were not associated with mortality. The lowering of blood glucose in the acute phase of MI compared with the average blood glucose was more effective around 18 mg/dL. CONCLUSION This meta-analysis suggests that there may be a tenuous line between the effectiveness and safety of reducing blood glucose in the acute phase of MI. The targets must not exceed a reduction greater than 36 mg/dL in relation to estimated average blood glucose.

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The efficacy and safety of bamlanivimab treatment against COVID-19: A meta-analysis

10.1101/2021.08.24.21262580 ◽

2021 ◽

Author(s):

Huairong Xiang ◽

Bei He ◽

Yun Li ◽

Xuan Cheng ◽

Qizhi Zhang ◽

...

Keyword(s):

Clinical Trials ◽

Observational Studies ◽

Randomized Clinical Trials ◽

Web Of Science ◽

Meta Analysis ◽

Cochrane Library ◽

Control Group ◽

Efficacy And Safety ◽

Positive Treatment ◽

The Cochrane Library

Background: Bamlanivimab is routinely used in the treatment of coronavirus disease 2019 (COVID-19) in worldwide. We performed a meta-analysis to investigate the efficacy and safety of bamlanivimab treatment in patients with COVID-19. Methods: We searched articles from Web of Science, PubMed, Embase, the Cochrane Library and MedRxiv between 30 January 2020 and August 5, 2021. We selected randomized clinical trials (RCTs) and observational studies with a control group to assess the efficiency of bamlanivimab in treating patients with COVID-19. Results: Our meta-analysis retrieved 3 RCTs and 7 cohort studies including 14461 patients. Bmlanivimab may help outpatients to prevent hospitalization or emergency department visit (RR 0.41 95%CI 0.29 to 0.58), reduce ICU admission (RR 0.47 95%CI 0.23 to 0.92) and mortality (RR 0.32 95%CI 0.13 to 0.77) from the disease. The combination of bamlanivimab and etesevimab may had a greater potential for positive treatment outcome. Conclusion: Bamlanivimab has demonstrated clinical efficacy on mild or moderate ill patients with COVID-19 to prevent hospitalization, reduce severity and mortality from the disease. Combinations of two or more monoclonal antibody increase the effect. Well-designed clinical trials to identify the clinical and biochemical characteristics in COVID-19 patients'population that could benefit from bamlanivimab are warranted in the future.

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The Effects of Aromatherapy on Premenstrual Syndrome Symptoms: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/6667078 ◽

2020 ◽

Vol 2020 ◽

pp. 1-13

Author(s):

Somayeh Es-haghee ◽

Fatemeh Shabani ◽

Jessie Hawkins ◽

Mohammad Ali Zareian ◽

Fatemeh Nejatbakhsh ◽

...

Keyword(s):

Clinical Trials ◽

Premenstrual Syndrome ◽

Randomized Clinical Trials ◽

Weighted Mean Difference ◽

Meta Analysis ◽

Random Effect ◽

Random Effect Model ◽

Cochrane Library ◽

Control Group ◽

Childbearing Age

ObjectivesPremenstrual syndrome (PMS) is a common disturbance among women of childbearing age. Aromatherapy is a commonly used form of complementary and alternative medicine (CAM) to treat PMS. The purpose of this study is to quantify and summarize the effects of aromatherapy on premenstrual syndrome symptoms. Methods. PubMed, Scopus, and Cochrane Library databases were searched through relevant search terms until October 2020. The effect sizes were pooled as weighted mean difference (WMD) and 95% confidence interval (CI) using the random effect model. Egger tests and visual inspection of the funnel plot were performed to identify the existence of publication bias. The I-squared (I2) test was applied to measure heterogeneity. Results. Eight studies (n = 8) were included in this analysis. The quantitative synthesis of evidence found that aromatherapy decreases PMS scores (WMD –13.83; 95% CI (−22.04, −5.63), I2 = 94.5%), total psychological symptoms of PMS (WMD –3.51; 95% CI (−4.84, −2.18), I2 = 82.6%), anxiety of PMS (WMD–1.78; 95% CI (−3.17, −0.38), I2 = 94.2%), depression of PMS (WMD–2.0; 95% CI (−3.65, −0.34), I2 = 93.7%), and fatigue of PMS (WMD – 1.44; 95% CI (−2.44, −0.44), I2 = 89.7%) compared to the control group. Conclusion. Aromatherapy is an effective tool for the relief of PMS symptoms. Additional randomized controlled clinical trials with different durations and essential oils should be conducted to confirm our findings.

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The Effectiveness of the Cold Therapy (cryotherapy) in the Management of Inflammatory Parameters after Removal of Mandibular Third Molars: A Meta-Analysis

International Archives of Otorhinolaryngology ◽

10.1055/s-0039-1677755 ◽

2019 ◽

Vol 23 (02) ◽

pp. 221-228 ◽

Cited By ~ 2

Author(s):

Ighor Andrade Fernandes ◽

Anna Catharina Vieira Armond ◽

Saulo Gabriel Moreira Falci

Keyword(s):

Clinical Trials ◽

Randomized Clinical Trials ◽

Meta Analysis ◽

Third Molar ◽

Cochrane Library ◽

Control Group ◽

Surgical Removal ◽

Third Molars ◽

Cold Therapy ◽

Mandibular Third Molar

Introduction Cold therapy (cryotherapy) is a common procedure recommended by dental surgeons after surgical removal of third molars, which is an invasive intervention that often deals with an expressive inflammatory response. Objective To investigate whether cryotherapy interferes with clinical outcomes such as pain, edema, and trismus in the postoperative period of mandibular third molar surgeries. Data Synthesis An electronic search was conducted in the OVID, PubMed, VHL, Science Direct, Cochrane Library, and Web of Science databases, through March 2018. The eligibility criteria included clinical trials that evaluated the effect of cryotherapy in at least one of the following variables: pain, swelling, and trismus.Two independent reviewers assessed the studies. The methodological quality of each article was analyzed. The search strategy resulted in 1,088 articles. Following the selection process, 11 studies were included in the systematic review and 4 of them in the meta-analysis. High risk of bias was found in most of the studies according to the Cochrane Handbook assessment. Patients receiving cryotherapy had less edema than patients in the control group at second day follow-up (mean difference [MD]: -0.94; 95%CI [-1.49; -0.39]). There were no statistically significant results when comparing trismus between experimental and control group (MD: 0.43; 95%CI [-0.34;1.20]). There were insufficient available data to support influences in postoperative pain. Conclusions Cryotherapy applied on the first day after mandibular third molar removal can manage edema in the patients. Well-designed randomized clinical trials to test the efficacy of cryotherapy after surgical removal of third molars are needed to justify its indication.

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Is Intracanal Cryotherapy Effective in Reducing Postoperative Endodontic Pain? An Updated Systematic Review and Meta-Analysis of Randomized Clinical Trials

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph182211750 ◽

2021 ◽

Vol 18 (22) ◽

pp. 11750

Author(s):

Amal Almohaimede ◽

Ebtissam Al-Madi

Keyword(s):

Clinical Trials ◽

Postoperative Pain ◽

Randomized Clinical Trials ◽

Meta Analysis ◽

Grey Literature ◽

Cochrane Library ◽

Control Group ◽

Randomized Controlled Clinical Trials ◽

Cold Therapy ◽

Quality Evidence

This research aimed to assess the potency of intracanal cold therapy in diminishing postoperative endodontic pain. PubMed, Scopus, the Cochrane Library, EMBASE, the Web of Science, grey literature, and endodontic journals were used to identify randomized controlled clinical trials evaluating postoperative pain after a final irrigation with a cold irrigant (as an experimental group) and a room temperature irrigant (as a control group). The risk of bias was rated according to the Cochrane Collaboration’s tool and the Grading Recommendation Assessment, Development, and Evaluation (GRADE) system was used to estimate the evidence quality. For the meta-analysis, a random effects model was utilized. The qualitative analysis contained 16 studies and the quantitative analysis contained 9 studies. The experimental groups showed a reduction in postoperative pain at 6 h (mean difference (MD) = −1.11; p = 0.0004; I2 = 72%; low quality evidence), 24 h (MD = −1.08; p = 0.003; I2 = 92%; low quality evidence), 48 h (MD = −0.38; p = 0.04; I2 = 81%; low quality evidence), and 72 h (MD = −0.69; p = 0.04; I2 = 90%; low quality evidence). A higher quality of evidence from more clinical trials is needed.

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Complete revascularization reduces cardiovascular death in patients with ST-segment elevation myocardial infarction and multivessel disease: systematic review and meta-analysis of randomized clinical trials

European Heart Journal ◽

10.1093/eurheartj/ehz896 ◽

2019 ◽

Vol 41 (42) ◽

pp. 4103-4110 ◽

Cited By ~ 13

Author(s):

Rita Pavasini ◽

Simone Biscaglia ◽

Emanuele Barbato ◽

Matteo Tebaldi ◽

Dariusz Dudek ◽

...

Keyword(s):

Myocardial Infarction ◽

Clinical Trials ◽

Randomized Clinical Trials ◽

Meta Analysis ◽

Cardiovascular Death ◽

Multivessel Disease ◽

Complete Revascularization ◽

St Segment Elevation ◽

Segment Elevation Myocardial Infarction ◽

St Segment

Abstract Aims The aim of this work was to investigate the prognostic impact of revascularization of non-culprit lesions in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease by performing a meta-analysis of available randomized clinical trials (RCTs). Methods and results Data from six RCTs comparing complete vs. culprit-only revascularization in STEMI patients with multivessel disease were analysed with random effect generic inverse variance method meta-analysis. The endpoints were expressed as hazard ratio (HR) with 95% confidence interval (CI). The primary outcome was cardiovascular death. Main secondary outcomes of interest were all-cause death, myocardial infarction (MI), and repeated coronary revascularization. Overall, 6528 patients were included (3139 complete group, 3389 culprit-only group). After a follow-up ranging between 1 and 3 years (median 2 years), cardiovascular death was significantly reduced in the group receiving complete revascularization (HR 0.62, 95% CI 0.39–0.97, I2 = 29%). The number needed to treat to prevent one cardiovascular death was 70 (95% CI 36–150). The secondary endpoints MI and revascularization were also significantly reduced (HR 0.68, 95% CI 0.55–0.84, I2 = 0% and HR 0.29, 95% CI 0.22–0.38, I2 = 36%, respectively). Needed to treats were 45 (95% CI 37–55) for MI and 8 (95% CI 5–13) for revascularization. All-cause death (HR 0.81, 95% CI 0.56–1.16, I2 = 27%) was not affected by the revascularization strategy. Conclusion In a selected study population of STEMI patients with multivessel disease, a complete revascularization strategy is associated with a reduction in cardiovascular death. This reduction is concomitant with that of MI and the need of repeated revascularization.

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Abstract P391: Marine N-3 Fatty Acids Reduce Atherosclerosis Cardiovascular Disease: A Systemic Review and Meta-analysis of Clinical Trials

Circulation ◽

10.1161/circ.127.suppl_12.ap391 ◽

2013 ◽

Vol 127 (suppl_12) ◽

Author(s):

Akira Sekikawa ◽

Nobutake Hirooka ◽

Abhishek Vishnu ◽

Vashudha Ahuja ◽

Emmanuel Sampene ◽

...

Keyword(s):

Cardiovascular Disease ◽

Fatty Acids ◽

Clinical Trials ◽

Randomized Clinical Trials ◽

Imaging Techniques ◽

Meta Analysis ◽

Quantitative Information ◽

Systemic Review ◽

Cochrane Library ◽

Cardiac Imaging Techniques

Introduction: Although marine n-3 fatty acids are believed to be cardioprotective through their anti-arrhythmic, anti-thrombotic, anti-atherogenic and other effects, results from recent meta-analyses of marine n-3 fatty acids on cardiovascular disease (CVD) are controversial. We performed a meta-analysis of marine n-3 fatty acids on CVD outcomes in randomized clinical trials (RCTs) to test the hypothesis that marine n-3 fatty acids are anti-atherogenic. We also tested the hypothesis that such benefit is dose-dependent. Methods: A systematic review of English language articles using PubMed, EMBASE and Cochrane Library through Aug 2012 was performed selecting RCTs evaluating the effect of marine n-3 fatty acids intake for 2 years or more on cardiovascular diseases, coronary disease, arteriosclerosis, cardiac imaging techniques, and carotid artery ultrasound. Descriptive and quantitative information was extracted. Odds ratios were calculated for cardiac event outcome. Correlation coefficients were obtained from studies of which outcome is intima-media thickness (IMT) and coronary lumen diameter (CD). We converted the estimates into a single effect size; the log odds ratio and its corresponding standard error. Results: Of 14,236 citations retrieved, 13 studies were selected, including studies reporting IMT (n=3) and CD (n=2) and major CVD events (n=8). Overall, marine n-3 fatty acids significantly reduced atherosclerotic CVD (RR 0.94: 95%CI 0.90 to 0.99, p<0.05). There was no evidence of heterogeneity (p=0.65) or publication bias (p=0.37, Begg’s test). A sub-analysis among 8 studies of major CVD events showed the similar results (RR 0.94: 95% CI 0.89 to 0.99, p<0.05). Another sub-analysis among 4 studies excluding sudden cardiac death as an outcome showed RR of 0.91 (95% CI 0.82 to 1.02, p=0.097). A meta-regression analysis shows that dose of marine n-3 fatty acids was inversely associated with CVD outcome, although the association was not statistically significant (p=0.06). Conclusions: The result of our meta-analysis supports a modest anti-atherogenic effect of marine n-3 fatty acids. This benefit may be proportional to the amount of marine n-3 fatty acids consumed.

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Clinical and Molecular Characteristics Associated with Survival in Advanced Melanoma Treated with Checkpoint Inhibitors

Journal of Oncology ◽

10.1155/2018/6279871 ◽

2018 ◽

Vol 2018 ◽

pp. 1-13 ◽

Cited By ~ 1

Author(s):

Sunil Badami ◽

Sunil Upadhaya ◽

Ravi Kanth Velagapudi ◽

Pushyami Mikkilineni ◽

Ranju Kunwor ◽

...

Keyword(s):

Clinical Trials ◽

Randomized Clinical Trials ◽

Checkpoint Inhibitors ◽

Meta Analysis ◽

Random Effect ◽

Eastern Cooperative Oncology Group ◽

Advanced Melanoma ◽

Cochrane Library ◽

Molecular Characteristics ◽

Significant Heterogeneity

Background. We performed meta-analysis to gather more evidence regarding clinical-molecular subgroups associated with better overall survival (OS) in advanced melanoma treated with checkpoint inhibitors. Materials and Methods. We performed a systematic search of PubMed, Scopus, Cochrane Library, and clinical trial.gov. Randomized clinical trials that compared a checkpoint inhibitor (nivolumab or pembrolizumab) with investigator choice chemotherapy or ipilimumab were included in our study. Hazard ratios (HR) and confidence interval (CI) were calculated for progression-free survival (PFS) and OS for each subgroup using generic inverse model along with the random effect method. Results. A total of 6 clinical trials were eligible for the meta-analysis. OS was prolonged in wild BRAF subgroup (HR 0.65, 95% CI 0.49-0.85, p 0.002), Programmed cell death subgroup (PD-1+) (HR 0.57, 95% CI 0.41-0.80, p 0.001), and high lactate dehydrogenase (LDH) level subgroup (HR 0.60, 95% CI 0.38-0.95, p 0.03). Similarly, we found increased OS in eastern cooperative oncology group (ECOG) 1, males and age >65 years subgroups. Conclusions. Checkpoint inhibitors significantly increased OS in patients with wild BRAF, positive PD-1, and high LDH. However, results should be interpreted keeping in mind associated significant heterogeneity. The results of this study should help in designing future clinical trials.

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Nervous and Muscular Adverse Events after COVID-19 Vaccination: A Systematic Review and Meta-Analysis of Clinical Trials

Vaccines ◽

10.3390/vaccines9080939 ◽

2021 ◽

Vol 9 (8) ◽

pp. 939

Author(s):

Jiaxin Chen ◽

Yuangui Cai ◽

Yicong Chen ◽

Anthony P. Williams ◽

Yifang Gao ◽

...

Keyword(s):

Systematic Review ◽

Clinical Trials ◽

Adverse Events ◽

Fixed Effects ◽

Meta Analysis ◽

Phase 1 ◽

Cochrane Library ◽

Categorical Variables ◽

Control Group ◽

Open Label

Background: Nervous and muscular adverse events (NMAEs) have garnered considerable attention after the vaccination against coronavirus disease (COVID-19). However, the incidences of NMAEs remain unclear. We aimed to calculate the pooled event rate of NMAEs after COVID-19 vaccination. Methods: A systematic review and meta-analysis of clinical trials on the incidences of NMAEs after COVID-19 vaccination was conducted. The PubMed, Medline, Embase, Cochrane Library, and Chinese National Knowledge Infrastructure databases were searched from inception to 2 June 2021. Two independent reviewers selected the study and extracted the data. Categorical variables were analyzed using Pearson’s chi-square test. The pooled odds ratio (OR) with the corresponding 95% confidence intervals (CIs) were estimated and generated with random or fixed effects models. The protocol of the present study was registered on PROSPERO (CRD42021240450). Results: In 15 phase 1/2 trials, NMAEs occurred in 29.2% vs. 21.6% (p < 0.001) vaccinated participants and controls. Headache and myalgia accounted for 98.2% and 97.7%, and their incidences were 16.4% vs. 13.9% (OR = 1.97, 95% CI = 1.28–3.06, p = 0.002) and 16.0% vs. 7.9% (OR = 3.31, 95% CI = 2.05–5.35, p < 0.001) in the vaccine and control groups, respectively. Headache and myalgia were more frequent in the newly licensed vaccines (OR = 1.97, 95% CI = 1.28–3.06, p = 0.02 and OR = 3.31, 95% CI = 2.05–5.35, p < 0.001) and younger adults (OR = 1.40, 95% CI = 1.12–1.75, p = 0.003 and OR = 1.54, 95% CI = 1.20–1.96, p < 0.001). In four open-label trials, the incidences of headache, myalgia, and unsolicited NMAEs were 38.7%, 27.4%, and 1.5%. Following vaccination in phase 3 trials, headache and myalgia were still common with a rate of 29.5% and 19.2%, although the unsolicited NMAEs with incidence rates of ≤ 0.7% were not different from the control group in each study. Conclusions: Following the vaccination, NMAEs are common of which headache and myalgia comprised a considerable measure, although life-threatening unsolicited events are rare. NMAEs should be continuously monitored during the ongoing global COVID-19 vaccination program.

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Direct Anticoagulants and Risk of Myocardial Infarction, a Multiple Treatment Network Meta-Analysis

Angiology ◽

10.1177/0003319719874255 ◽

2019 ◽

Vol 71 (1) ◽

pp. 27-37 ◽

Cited By ~ 1

Author(s):

Péter Kupó ◽

Zsolt Szakács ◽

Margit Solymár ◽

Tamás Habon ◽

László Czopf ◽

...

Keyword(s):

Myocardial Infarction ◽

Relative Risk ◽

Randomized Clinical Trials ◽

Meta Analysis ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Credible Interval ◽

Control Group ◽

Cardiovascular Safety ◽

Coronary Syndrome

We assessed the cardiovascular safety of long-term direct-acting oral anticoagulant (DOAC) treatment. A search of the medical literature was performed from inception until May 31, 2019. Inclusion criteria were (1) randomized trial that assessed the clinical efficacy and/or safety of 1 or more DOAC, (2) control group including oral anticoagulation and/or antiplatelet and/or placebo treatment, and (3) the incidence of acute coronary syndrome during follow-up was reported. Fixed-effect and random-effects models were applied. The analyzed outcomes were myocardial infarction (MI), major bleeding, and mortality. Twenty-eight randomized clinical trials (196 761 patients) were included. Rivaroxaban was associated with a 21% reduction in the relative risk of MI when compared to placebo (relative risk [RR]: 0.79 [95% credible interval, CrI: 0.65-0.94]) and a 31% reduction (RR: 0.70 [95% CrI: 0.53-0.89]) when compared to dabigatran. Apixaban resulted in 24% (RR: 0.76 [95% CrI: 0.58-0.99]) and vitamin K antagonists anticoagulation resulted in 19% (RR: 0.81 [95% CrI: 0.65-0.98]) risk reduction compared to dabigatran. The computed probability of being the first best choice of treatment was 61.8% for rivaroxaban. Cardiovascular safety shows considerable heterogeneity among oral anticoagulants. Treatment with rivaroxaban is associated with reduced rate of MI.

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Systematic Review and Meta-Analysis of Randomized Clinical Trials on Chemomechanical Caries Removal

Operative Dentistry ◽

10.2341/14-021-lit ◽

2015 ◽

Vol 40 (4) ◽

pp. E167-E178 ◽

Cited By ~ 14

Author(s):

HHH Hamama ◽

CKY Yiu ◽

MF Burrow ◽

NM King

Keyword(s):

Systematic Review ◽

Clinical Trials ◽

Sodium Hypochlorite ◽

Randomized Clinical Trials ◽

Meta Analysis ◽

Assessment Process ◽

Cochrane Library ◽

Removal Method ◽

Caries Removal ◽

Caries Excavation

SUMMARY Objectives The aim of this review was to assess the methodologies used in previously published prospective randomized clinical trials on chemomechanical caries removal and to conduct a meta-analysis to quantify the differences in the excavation time between chemomechanical and conventional caries removal methods. Methods An electronic search was performed using Scopus, PubMed, EBSCO host, and Cochrane Library databases. The following categories were excluded during the assessment process: non-English studies published before 2000, animal studies, review articles, laboratory studies, case reports, and nonrandomized or retrospective clinical trials. The methodologies of the selected clinical trials were assessed. Furthermore, the reviewed clinical trials were subjected to meta-analysis for quantifying the differences in excavation time between the chemomechanical and the conventional caries removal techniques. Results Only 19 randomized clinical trials fit the inclusion criteria of this systematic review. None of the 19 reviewed trials completely fulfilled Delphi's ideal criteria for quality assessment of randomized clinical trials. The meta-analysis results revealed that the shortest mean excavation time was recorded for rotary caries excavation (2.99±0.001 minutes), followed by the enzyme-based chemomechanical caries removal method (6.36±0.08 minutes) and the the hand excavation method (atraumatic restorative technique; 6.98±0.17 minutes). The longest caries excavation time was recorded for the sodium hypochlorite-based chemomechanical caries removal method (8.12±0.02 minutes). Conclusions It was found that none of the current reviewed trials fulfilled all the ideal requirements of clinical trials. Furthermore, the current scientific evidence shows that the sodium hypochlorite-based (Carisolv) chemomechanical caries removal method was more time consuming when compared to the enzyme-based (Papacarie) chemomechanical and the conventional caries removal methods. Further prospective randomized controlled clinical trials evaluating the long-term follow-up of papain-treated permanent teeth are needed.

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