Methods: We performed a meta-analysis based on a systematic review of randomized controlled trials (RCTs) comparing celecoxib at various doses (400 mg once daily, 200 mg twice daily, and 400 mg twice daily) vs placebo in persons with history of colorectal adenomas. Several databases were searched from inception up to April 2018. Long-term follow-ups of RCTs were also included to evaluate posttreatment effect. Primary outcome was the incidence of recurrent colorectal adenomas. Various safety outcomes were evaluated, especially cardiovascular (CV) events. Risk-benefit integrated analyses were also performed.
Results: A total of three RCTs (4,420 patients) and three post-trial studies (2,159 patients) were included in the analysis. Use of celecoxib at any dose for 1-3 years significantly reduced the incidence of recurrent advanced adenomas (risk ratio, 0.42 [95% CI, 0.34-0.53]) and any adenomas (0.67 [95% CI, 0.62-0.72]) compared with placebo. Subgroup analysis on different dosing suggested a greater effect with 400 mg twice daily. However, celecoxib 400 mg twice daily significantly increased the risk of serious adverse (1.2 [95% CI, 1.0-1.5]) and CV events (3.42 [95% CI, 1.56-7.46]), while celecoxib at 400 mg/day, especially with once daily dosing, did not increase CV risk (1.01 [95% CI, 0.70-1.46]). Analysis of post-trial studies indicated that the treatment effect disappeared (1.15 [95% CI, 0.88-1.49]) after discontinuing celecoxib for >2 years.
Conclusion: Celecoxib 400 mg once daily dosing could potentially be considered as a viable chemopreventive option in patients with high risk of adenomas but with low CV risk. Long-term trials on celecoxib at a dose of ≤400 mg either once or twice daily are warranted.
METHODS: The review protocol was registered in the PROSPERO database (CRD42017071899). A literature search was performed in the MEDLINE and EBSCOhost databases until June 2017 with no language restriction. Randomized controlled trials evaluating the efficacy of oral premedications, whether given alone or in combination, compared with other agents, placebo, or no treatment in adult patients before NSRCT for postoperative pain were included. Nonintervention studies, nonendodontic studies, animal studies, and reviews were excluded. The quality of the studies was assessed using the revised Cochrane risk of bias tool. Pair-wise meta-analysis, network meta-analysis, and quality of evidence assessment using the Grading of Recommendations Assessment, Development and Evaluation criteria was performed.
RESULTS: Eleven studies comparing pharmacologic groups of medications were included in the primary analysis. Compared with placebo, corticosteroids (prednisolone 30-40 mg) was ranked best for reducing postoperative pain (median difference [MD] = -18.14 [95% confidence interval (CI), -32.90 to -3.37] for the pain score at 6 hours; MD = -22.17 [95% CI, -36.03 to -8.32] for the pain score at 12 hours; and MD = -21.50 [95% CI, -37.95 to -5.06] for the pain score at 24 hours). However, the evidence was very low (6 and 24 hours) to moderate quality (12 hours). Nonsteroidal anti-inflammatory drugs were ranked least among the medications, and the quality of this evidence was very low. Additional analysis based on the chemical name showed that sulindac, ketorolac, and ibuprofen significantly reduced pain at 6 hours, whereas piroxicam and prednisolone significantly reduced the pain at 12 and 24 hours. Etodolac was found to be least effective in reducing pain. Overall, the evidence was of moderate to very low quality.
CONCLUSIONS: Based on the limited and low-quality evidence, oral premedication with piroxicam or prednisolone could be recommended for controlling postoperative pain after NSRCT. However, more trials are warranted to confirm the results with a higher quality of evidence.
METHODS: PubMed, EBSCOhost, and Scopus databases were searched. Additional searching was performed in clinical trial registry, reference lists of systematic reviews, and textbooks. Randomized clinical trials (RCTs) published in the English language through October 2017 comparing the success of pulpotomies in vital primary molars with a follow-up of at least 6 months were selected. Study selection, data extraction, and risk of bias assessment were performed. MA by random effects model, TSA, and GRADE were performed.
RESULTS: Eight RCTs (n = 474) were included. Two RCTs had low risk of bias. No significant difference was observed between MTA and BD in clinical success at 6 months (risk ratio [RR], 1.00; 95% confidence interval [95% CI], 0.97-1.02; I2 = 0%), 12 months (RR, 1.00; 95% CI, 0.96-1.05; I2 = 0%), and 18 months (RR, 1.00; 95% CI, 0.93-1.08; I2 = 0%). No difference was observed in radiographic success at follow-up of 6 months (RR, 0.99; 95% CI, 0.96-1.02; I2 = 0%), 12 months (RR, 1.02; 95% CI, 0.47-2.21; I2 = 0%), and 18 months (RR, 1.02; 95% CI, 0.91-1.15; I2 = 0%). TSA indicated lack of firm evidence for the results of the meta-analytic outcomes on clinical and radiographic success. GRADE assessed the evidence from the MA comparing the effect of MTA and BD in pulpotomy to be of low quality.
CONCLUSION: BD and MTA have similar clinical and radiographic success rates based on limited and low-quality evidence. Future high-quality RCTs between MTA and BD is required to confirm the evidence.
METHODS: We did a network meta-analysis based on a systematic review of randomised controlled trials comparing fibrinolytic drugs in patients with STEMI. Several databases were searched from inception up to Feb 28, 2017. We included only randomised controlled trials that compared fibrinolytic agents as a reperfusion therapy in adult patients with STEMI, whether given alone or in combination with adjunctive antithrombotic therapy, against other fibrinolytic agents, a placebo, or no treatment. Only trials investigating agents with an approved indication of reperfusion therapy in STEMI (streptokinase, tenecteplase, alteplase, and reteplase) were included. The primary efficacy outcome was all-cause mortality within 30-35 days and the primary safety outcome was major bleeding. This study is registered with PROSPERO (CRD42016042131).
FINDINGS: A total of 40 eligible studies involving 128 071 patients treated with 12 different fibrinolytic regimens were assessed. Compared with accelerated infusion of alteplase with parenteral anticoagulants as background therapy, streptokinase and non-accelerated infusion of alteplase were significantly associated with an increased risk of all-cause mortality (risk ratio [RR] 1·14 [95% CI 1·05-1·24] for streptokinase plus parenteral anticoagulants; RR 1·26 [1·10-1·45] for non-accelerated alteplase plus parenteral anticoagulants). No significant difference in mortality risk was recorded between accelerated infusion of alteplase, tenecteplase, and reteplase with parenteral anticoagulants as background therapy. For major bleeding, a tenecteplase-based regimen tended to be associated with lower risk of bleeding compared with other regimens (RR 0·79 [95% CI 0·63-1·00]). The addition of glycoprotein IIb or IIIa inhibitors to fibrinolytic therapy increased the risk of major bleeding by 1·27-8·82-times compared with accelerated infusion alteplase plus parenteral anticoagulants (RR 1·47 [95% CI 1·10-1·98] for tenecteplase plus parenteral anticoagulants plus glycoprotein inhibitors; RR 1·88 [1·24-2·86] for reteplase plus parenteral anticoagulants plus glycoprotein inhibitors).
INTERPRETATION: Significant differences exist among various fibrinolytic regimens as reperfusion therapy in STEMI and alteplase (accelerated infusion), tenecteplase, and reteplase should be considered over streptokinase and non-accelerated infusion of alteplase. The addition of glycoprotein IIb or IIIa inhibitors to fibrinolytic therapy should be discouraged.
FUNDING: None.
Methods: We did a network meta-analysis based on a systematic review of randomized controlled trials (RCTs) that compared at least one CPA (aspirin, antioxidants, folic acid, vitamin B6, vitamin B12, calcium, vitamin D, alone or in combination) to placebo or other CPA in persons without history of CRC. Several databases were searched from inception up to March 2017. Primary outcomes were early and long-term CRC incidence and mortality.
Results: Twenty-one RCTs comprising 281,063 participants, 9 RCTS comprising 160,101 participants, and 7 RCTs comprising 24,001 participants were included in the network meta-analysis for early risk of CRC incidence, long-term risk of CRC incidence and mortality, respectively. For early CRC incidence, no CPAs were found to be effective. For long-term CRC incidence and mortality, aspirin was the only intervention that showed protective effects with potential dose-dependent effects (risk ratio [RR], 0.74 [95% CI, 0.57-0.97] for high-dose [≥325 mg/day] and RR, 0.81 [95% CI, 0.67-0.98] for very-low-dose [≤100 mg/day]). Similar trend was found for mortality (RR, 0.43 [95% CI, 0.23-0.81] for low-dose [>100-325 mg/day] and RR, 0.65 [95% CI, 0.45-0.94] for very-low-dose). However, in net clinical benefit analysis, when combining risk estimates on mortality from CRC, cardiovascular disease, and pooled risk estimates of major gastrointestinal bleeding, low-dose aspirin provided the highest net survival gain (%) of 1.736 [95% CI, 1.010-2.434].
Conclusion: Aspirin at the dose range of 75-325 mg/day is a safe and effective primary prevention for long-term CRC among people at average risk. None of the other CPAs were found to be effective. There may potentially be differential effects among various doses of aspirin that needs further investigation.