scholarly journals A survey of methodologies on causal inference methods in meta-analyses of randomized controlled trials

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Georgios Markozannes ◽  
Georgia Vourli ◽  
Evangelia Ntzani
Keyword(s):  
Causal Inference ◽  
Randomized Controlled Trials ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Generation Process ◽  
Data Generation ◽  
Randomized Controlled ◽  
Data Generation Process ◽  
Meta Analyses ◽  
Inference Methods

Abstract Background Meta-analyses of randomized controlled trials (RCTs) have been considered as the highest level of evidence in the pyramid of the evidence-based medicine. However, the causal interpretation of such results is seldom studied. Methods We systematically searched for methodologies pertaining to the implementation of a causally explicit framework for meta-analysis of randomized controlled trials and discussed the interpretation and scientific relevance of such causal estimands. We performed a systematic search in four databases to identify relevant methodologies, supplemented with hand-search. We included methodologies that described causality under counterfactuals and potential outcomes framework. Results We only identified three efforts explicitly describing a causal framework on meta-analysis of RCTs. Two approaches required individual participant data, while for the last one, only summary data were required. All three approaches presented a sufficient framework under which a meta-analytical estimate is identifiable and estimable. However, several conceptual limitations remain, mainly in regard to the data generation process under which the selected RCTs rise. Conclusions We undertook a review of methodologies on causal inference methods in meta-analyses. Although all identified methodologies provide valid causal estimates, there are limitations in the assumptions regarding the data generation process and sampling of the potential RCTs to be included in the meta-analysis which pose challenges to the interpretation and scientific relevance of the identified causal effects. Despite both causal inference and meta-analysis being extensively studied in the literature, limited effort exists of combining those two frameworks.

scholarly journals Pre-Procedural Lumbar Neuraxial Ultrasound—A Systematic Review of Randomized Controlled Trials and Meta-Analysis

Healthcare ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 479
Author(s):  
Tatiana Sidiropoulou ◽  
Kalliopi Christodoulaki ◽  
Charalampos Siristatidis
Keyword(s):  
Systematic Review ◽  
Lumbar Spine ◽  
Randomized Controlled Trials ◽  
Success Rate ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Technical Failure ◽  
Obese Patients ◽  
Randomized Controlled ◽  
Meta Analyses

A pre-procedural ultrasound of the lumbar spine is frequently used to facilitate neuraxial procedures. The aim of this review is to examine the evidence sustaining the utilization of pre-procedural neuraxial ultrasound compared to conventional methods. We perform a systematic review of randomized controlled trials with meta-analyses. We search the electronic databases Medline, Cochrane Central, Science Direct and Scopus up to 1 June 2019. We include trials comparing a pre-procedural lumbar spine ultrasound to a non-ultrasound-assisted method. The primary endpoints are technical failure rate, first-attempt success rate, number of needle redirections and procedure time. We retrieve 32 trials (3439 patients) comparing pre-procedural lumbar ultrasounds to palpations for neuraxial procedures in various clinical settings. Pre-procedural ultrasounds decrease the overall risk of technical failure (Risk Ratio (RR) 0.69 (99% CI, 0.43 to 1.10), p = 0.04) but not in obese and difficult spinal patients (RR 0.53, p = 0.06) and increase the first-attempt success rate (RR 1.5 (99% CI, 1.22 to 1.86), p < 0.0001, NNT = 5). In difficult spines and obese patients, the RR is 1.84 (99% CI, 1.44 to 2.3; p < 0.0001, NNT = 3). The number of needle redirections is lower with pre-procedural ultrasounds (SMD = −0.55 (99% CI, −0.81 to −0.29), p < 0.0001), as is the case in difficult spines and obese patients (SMD = −0.85 (99% CI, −1.08 to −0.61), p < 0.0001). No differences are observed in procedural times. Ιn conclusion, a pre-procedural ultrasound provides significant benefit in terms of technical failure, number of needle redirections and first attempt-success rate. Τhe effect of pre-procedural ultrasound scanning of the lumbar spine is more significant in a subgroup analysis of difficult spines and obese patients.

Rotational Bed Therapy to Prevent and Treat Respiratory Complications: A Review and Meta-Analysis

2007 ◽  
Vol 16 (1) ◽  
pp. 50-61 ◽  
Author(s):  
David R. Goldhill ◽  
Michael Imhoff ◽  
Barbara McLean ◽  
Carl Waldmann
Keyword(s):  
Mechanical Ventilation ◽  
Randomized Controlled Trials ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Meta Analysis ◽  
Convincing Evidence ◽  
Controlled Trials ◽  
Respiratory Complications ◽  
Randomized Controlled ◽  
Meta Analyses

• Background Immobility is associated with complications involving many body systems. • Objective To review the effect of rotational therapy (use of therapeutic surfaces that turn on their longitudinal axes) on prevention and/or treatment of respiratory complications in critically ill patients. • Methods Published articles evaluating prophylaxis and/or treatment were reviewed. Prospective randomized controlled trials were assessed for quality and included in meta-analyses. • Results A literature search yielded 15 nonrandomized, uncontrolled, or retrospective studies. Twenty prospective randomized controlled trials on rotational therapy were published between 1987 and 2004. Various types of beds were studied, but few details on the rotational parameters were reported. The usual control was manual turning of patients by nurses every 2 hours. One animal investigation and 12 clinical trials addressed the effectiveness of rotational therapy in preventing respiratory complications. Significant benefits were reported in the animal study and 4 of the trials. Significant benefits to patients were reported in 2 of another 4 studies focused on treatment of established complications. Researchers have examined the effects of rotational therapy on mucus transport, intrapulmonary shunt, hemodynamic effects, urine output, and intracranial pressure. Little convincing evidence is available, however, on the most effective rotation parameters (eg, degree, pause time, and amount of time per day). Meta-analysis suggests that rotational therapy decreases the incidence of pneumonia but has no effect on duration of mechanical ventilation, number of days in intensive care, or hospital mortality. • Conclusions Rotational therapy may be useful for preventing and treating respiratory complications in selected critically ill patients receiving mechanical ventilation.

scholarly journals Effect of folate supplementation on insulin sensitivity and type 2 diabetes: a meta-analysis of randomized controlled trials

2019 ◽  
Vol 109 (1) ◽  
pp. 29-42 ◽  
Author(s):  
Mads Vendelbo Lind ◽  
Lotte Lauritzen ◽  
Mette Kristensen ◽  
Alastair B Ross ◽  
Jane Nygaard Eriksen
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Randomized Controlled Trials ◽  
Fasting Glucose ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Folate Supplementation ◽  
Randomized Controlled ◽  
Meta Analyses

ABSTRACT Background Various mechanisms link higher total homocysteine to higher insulin resistance (IR) and risk of type 2 diabetes (T2D). Folate supplementation is recognized as a way to lower homocysteine. However, randomized controlled trials (RCTs) show inconsistent results on IR and T2D outcomes. Objective The aim of this study was to examine the effect of folate supplementation on IR and T2D outcomes. Design We conducted a systematic literature search in PubMed, Web of Science, and EMBASE and prior systematic reviews and meta-analyses and identified 29 RCTs (22,250 participants) that assessed the effect of placebo-controlled folate supplementation alone or in combination with other B vitamins on fasting glucose, insulin, homeostasis model assessment for insulin resistance (HOMA-IR), glycated hemoglobin (HbA1c), or risk of T2D. The meta-analysis was conducted using both random- and fixed-effects models to calculate weighted mean differences (WMDs) or risk ratios with 95% CIs. Subgroup analyses were conducted based on intervention type (folate alone or in combination with other B vitamins), as well as analysis based on population characteristics, duration, dose, and change in homocysteine. Results When compared with placebo, folate supplementation lowered fasting insulin (WMD: −13.47 pmol/L; 95% CI: −21.41, −5.53 pmol/L; P &lt; 0.001) and HOMA-IR (WMD: −0.57 units; 95% CI: −0.76, −0.37 units; P &lt; 0.0001), but no overall effects were observed for fasting glucose or HbA1c. Heterogeneity was low in all meta-analyses, and subgroup analysis showed no signs of effect modification except for change in homocysteine, with the most pronounced effects in trials with a change of &gt;2.5 µmol/L. Changes in homocysteine after folate supplementation correlated with changes in fasting glucose (β = 0.07; 95% CI: 0.01, 0.14; P = 0.025) and HbA1c (β = 0.46; 95% CI: 0.06, 0.85; P = 0.02). Only 2 studies examined folate supplementation on risk of T2D, and they found no change in RR (pooled RR: 0.91; 95% CI: 0.80, 1.04; P = 0.16). Conclusion Folate supplementation might be beneficial for glucose homeostasis and lowering IR, but at present there are insufficient data to conclusively determine the effect on development of T2D. This trial was registered on the Prospero database as CRD42016048254.

Dietary saturated fat and heart disease: a narrative review

2019 ◽  
Vol 78 (6) ◽  
pp. 474-485 ◽  
Author(s):  
Jeffery L Heileson
Keyword(s):  
Heart Disease ◽  
Randomized Controlled Trials ◽  
Observational Studies ◽  
Meta Analysis ◽  
Saturated Fat ◽  
Heart Association ◽  
Controlled Trials ◽  
Randomized Controlled ◽  
Disease Outcomes ◽  
Meta Analyses

Abstract The American Heart Association (AHA) recently published a meta-analysis that confirmed their 60-year-old recommendation to limit saturated fat (SFA, saturated fatty acid) and replace it with polyunsaturated fat to reduce the risk of heart disease based on the strength of 4 Core Trials. To assess the evidence for this recommendation, meta-analyses on the effect of SFA consumption on heart disease outcomes were reviewed. Nineteen meta-analyses addressing this topic were identified: 9 observational studies and 10 randomized controlled trials. Meta-analyses of observational studies found no association between SFA intake and heart disease, while meta-analyses of randomized controlled trials were inconsistent but tended to show a lack of an association. The inconsistency seems to have been mediated by the differing clinical trials included. For example, the AHA meta-analysis only included 4 trials (the Core Trials), and those trials contained design and methodological flaws and did not meet all the predefined inclusion criteria. The AHA stance regarding the strength of the evidence for the recommendation to limit SFAs for heart disease prevention may be overstated and in need of reevaluation.

scholarly journals Almond Consumption and Risk Factors for Cardiovascular Disease: A Systematic Review and Meta-analysis of Randomized Controlled Trials

2019 ◽  
Vol 10 (6) ◽  
pp. 1076-1088 ◽  
Author(s):  
Michelle A Lee-Bravatti ◽  
Jifan Wang ◽  
Esther E Avendano ◽  
Ligaya King ◽  
Elizabeth J Johnson ◽  
...  
Keyword(s):  
Risk Factors ◽  
Systematic Review ◽  
Blood Pressure ◽  
Cardiovascular Disease ◽  
Body Weight ◽  
Randomized Controlled Trials ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Randomized Controlled ◽  
Meta Analyses

ABSTRACT Evidence suggests that eating nuts may reduce the risk of cardiovascular disease (CVD). We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating almond consumption and risk factors for CVD. MEDLINE, Cochrane Central, Commonwealth Agricultural Bureau, and previous systematic reviews were searched from 1990 through June 2017 for RCTs of ≥3 wk duration that evaluated almond compared with no almond consumption in adults who were either healthy or at risk for CVD. The most appropriate stratum was selected with an almond dose closer to 42.5 g, with a control most closely matched for macronutrient composition, energy intake, and similar intervention duration. The outcomes included risk factors for CVD. Random-effects model meta-analyses and subgroup meta-analyses were performed. Fifteen eligible trials analyzed a total of 534 subjects. Almond intervention significantly decreased total cholesterol (summary net change: −10.69 mg/dL; 95% CI: −16.75, −4.63 mg/dL), LDL cholesterol (summary net change: −5.83 mg/dL; 95% CI: −9.91, −1.75 mg/dL); body weight (summary net change: −1.39 kg; 95% CI: −2.49, −0.30 kg), HDL cholesterol (summary net change: −1.26 mg/dL; 95% CI: −2.47, −0.05 mg/dL), and apolipoprotein B (apoB) (summary net change: −6.67 mg/dL; 95% CI: −12.63, −0.72 mg/dL). Triglycerides, systolic blood pressure, apolipoprotein A1, high-sensitivity C-reactive protein, and lipoprotein (a) showed no difference between almond and control in the main and subgroup analyses. Fasting blood glucose, diastolic blood pressure, and body mass index significantly decreased with almond consumption of >42.5 g compared with ≤42.5 g. Almond consumption may reduce the risk of CVD by improving blood lipids and by decreasing body weight and apoB. Substantial heterogeneity in eligible studies regarding almond interventions and dosages precludes firmer conclusions.

scholarly journals Lidocaine vs. Other Local Anesthetics in the Development of Transient Neurologic Symptoms (TNS) Following Spinal Anesthesia: A Meta-Analysis of Randomized Controlled Trials

2020 ◽  
Vol 9 (2) ◽  
pp. 493 ◽  
Author(s):  
Chang-Hoon Koo ◽  
Hyun-Jung Shin ◽  
Sung-Hee Han ◽  
Jung-Hee Ryu
Keyword(s):  
Randomized Controlled Trials ◽  
Spinal Anesthesia ◽  
Local Anesthetics ◽  
Meta Analysis ◽  
Control Group ◽  
Controlled Trials ◽  
Control Groups ◽  
Lidocaine Group ◽  
Randomized Controlled ◽  
Meta Analyses

The use of lidocaine in spinal anesthesia may increase the risk of transient neurological symptoms (TNS) according to previous meta-analyses. However, the previous meta-analyses lacked data on some other local anesthetics and thus, more evaluations are still needed to compare the effect of lidocaine on the development of TNS. The objective of this study was to compare the risk of TNS according to lidocaine versus other local anesthetics in patients undergoing spinal anesthesia. A total of 39 randomized controlled trials with 4733 patients were analyzed. The incidence of TNS was 10.8% in the lidocaine group and was 2.2% in the control groups (risk ratio (RR) 4.12, 95% confidence interval (CI) 3.13 to 5.43, p < 0.001). In subgroup analysis, lidocaine increased the incidence of TNS compared with other local anesthetics except mepivacaine, ropivacaine or sameridine. The risk of TNS was higher in the hyperbaric (p < 0.001) or isobaric lidocaine (p < 0.001) group compared with the control group, but there were no differences found between the two groups when hypobaric lidocaine was administered (p = 1.00). This study confirmed that lidocaine for spinal anesthesia still causes TNS more frequently than most other local anesthetics, especially when hyperbaric or isobaric lidocaine was used.

scholarly journals Second-line treatments for Advanced Hepatocellular Carcinoma: A Systematic Review and Bayesian Network Meta-analysis

2021 ◽  
Author(s):  
Antonio Giovanni Solimando ◽  
Nicola Susca ◽  
Antonella Argentiero ◽  
Oronzo Brunetti ◽  
Patrizia Leone ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Randomized Controlled Trials ◽  
Meta Analysis ◽  
Performance Status ◽  
Progression Free Survival ◽  
Controlled Trials ◽  
Advanced Hepatocellular Carcinoma ◽  
Second Line ◽  
Randomized Controlled ◽  
Meta Analyses

Abstract Background & Aims A plethora of second-line therapies have been recently introduced for hepatocellular carcinoma (HCC) treatment with promising results. A meta-analysis of second-line treatments for HCC has been performed to better tailor their use based on improved patient stratification and to identify the best available option. Methods Pubmed, Scopus, Web of Science, and ClinicalTrials.gov were searched for randomized controlled trials evaluating second-line treatment for advanced HCC in patients already treated with sorafenib. The primary outcome was overall survival (OS). Secondary outcomes were progression-free survival (PFS) and drug withdrawal due to adverse events. Network meta-analyses were performed considering placebo as the basis for comparison in efficacy and safety analyses. Subgroup stratification considered gender, age, sorafenib-responsiveness and drug tolerability, viral infection, macrovascular invasion, HCC extrahepatic spread, performance status, and alpha-fetoprotein levels. Results Fourteen phase II or III randomized controlled trials, involving 5,488 patients and 12 regimens, were included in the analysis. Regorafenib (hazard ratio (HR) = 0.63, 95% confidence interval (CI) = 0.50–0.79), cabozantinib (HR = 0.76, 95% CI = 0.63–0.92), and ramucirumab (HR = 0.82, 95% CI = 0.70–0.76) significantly prolonged OS compared with placebo. Cabozantinib (HR = 0.44, 95% CI = 0.36–0.52), regorafenib (HR = 0.46, 95% CI = 0.37–0.56), ramucirumab (HR = 0.54, 95% CI = 0.43–0.68), brivanib (HR = 0.56, 95% CI = 0.42–0.76), S-1 (HR = 0.60, 95% CI = 0.46–0.77), axitinib (HR = 0.62, 95% CI = 0.44–0.87), and pembrolizumab (HR = 0.72, 95% CI = 0.57–0.90) significantly improved PFS compared with placebo. None of the compared drugs deemed undoubtedly superior after having performed a patients’ stratification. Conclusions The results of this network meta-analysis suggest the use of regorafenib and cabozantinib as second-line treatments in HCC.

scholarly journals Colistin Nephrotoxicity: Meta-Analysis of Randomized Controlled Trials

2021 ◽  
Vol 8 (2) ◽  
Author(s):  
Khalid Eljaaly ◽  
Monique R Bidell ◽  
Ronak G Gandhi ◽  
Samah Alshehri ◽  
Mushira A Enani ◽  
...  
Keyword(s):  
Randomized Controlled Trials ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Controlled Trials ◽  
Random Effects Models ◽  
Randomized Controlled ◽  
Colistimethate Sodium ◽  
Meta Analyses ◽  
Risk Ratios ◽  
Number Needed To Harm

Abstract Background Nephrotoxicity is a known adverse effect of polymyxin antibiotics, including colistin. Although previous meta-analyses have aimed to characterize colistin-associated nephrotoxicity risk relative to other antibiotics, included studies were observational in nature with high risk of confounding and heterogeneity. We conducted this systematic review and meta-analysis of exclusively randomized controlled trials (RCTs) to evaluate the incidence of nephrotoxicity associated with colistin versus minimally nephrotoxic antibiotics. Methods We searched PubMed, EMBASE, Cochrane Library, and 3 trial registries for RCTs comparing the nephrotoxicity of colistin to nonpolymyxin antibiotics. Randomized controlled trials that used aminoglycosides were excluded. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using random-effects models. The study outcome was the rate of nephrotoxicity. Results Five RCTs with a total of 377 patients were included. Most patients received colistin for pneumonia in the intensive care unit, and the comparators were β-lactam-based regimens. Colistimethate sodium was dosed at 9 million units/day (300 mg/day of colistin base activity), with administration of a loading dose in 4 studies. The nephrotoxicity incidence in patients who received colistin was 36.2% (95% CI, 23.3% to 51.3%). The nephrotoxicity rate was significantly higher in the colistin arm than comparators (RR, 2.40; 95% CI, 1.47 to 3.91; P ≤ .001; I2 = 0%), and the number needed to harm was 5. Findings persisted upon one-study-removed-analysis. Conclusions This meta-analysis of RCTs found a colistin-associated nephrotoxicity rate of 36.2% and an increase in this risk compared with β-lactam-based regimens by 140%. Colistin should be regarded as a last-line agent and safer alternatives should be considered when possible.

scholarly journals Efficacy of Photobiomodulation in the Treatment of Cancer Chemotherapy-Induced Oral Mucositis: A Meta-Analysis with Trial Sequential Analysis

2021 ◽  
Vol 18 (14) ◽  
pp. 7418
Author(s):  
Ali Hatem Manfi Al-Rudayni ◽  
Divya Gopinath ◽  
Mari Kannan Maharajan ◽  
Sajesh K. Veettil ◽  
Rohit Kunnath Menon
Keyword(s):  
Randomized Controlled Trials ◽  
Cancer Chemotherapy ◽  
Oral Mucositis ◽  
Sequential Analysis ◽  
Meta Analysis ◽  
Trial Sequential Analysis ◽  
Controlled Trials ◽  
Random Errors ◽  
Randomized Controlled ◽  
Meta Analyses

Oral mucositis is a debilitating complication of chemotherapy, characterized by erythema, ulcers and oedema of the oral mucosa. This review aimed to evaluate the efficacy of Photobiomodulation in the treatment of oral mucositis using meta-analysis and trial sequential analysis, and also to assess the quality of the results by Grading of Recommendations, Assessment, Development and Evaluation (GRADE). A comprehensive search of three databases, including Embase, Medline and Central, was performed to identify randomized controlled trials studying the efficacy of Photobiomodulation in the treatment of cancer chemotherapy-induced oral mucositis. The primary outcome was reduction in the severity of oral mucositis. Secondary outcomes were pain relief, duration of oral mucositis and adverse effects. The meta-analysis was performed using the random-effects model, and random errors of the meta-analyses were detected by trial sequential analysis. A total of 6 randomized controlled trials with 398 participants were included in our analysis. Photobiomodulation significantly reduced the severity of oral mucositis when compared to sham radiation (RR 0.43, 95% CI 0.20 to 0.93; p < 0.05). Sensitivity analysis by excluding trials with high risk of bias reiterated the robustness of our results (RR 0.28, 95% CI 0.16 to 0.48). Trial sequential analysis illustrated that the evidence from the meta-analysis was conclusive. The result of the meta-analyses with trial sequential analysis illustrated that Photobiomodulation is an effective therapeutic intervention for the treatment of oral mucositis, and the evidence gathered can be considered conclusive with a moderate level of certainty according to GRADE. Further trials are recommended to standardize the laser parameters required for the optimal effect.

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