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Calcium supplementation for the prevention of colorectal adenomas: A systematic review and meta-analysis of randomized controlled trials.

ABSTRACT: To determine the efficacy of calcium supplementation in reducing the recurrence of colorectal adenomas.We conducted a systematic review and meta-analysis of published studies. We searched PubMed, Scopus, the Cochrane Library, the WHO International Clinical Trials Registry Platform, and the ClinicalTrials.gov website, through December 2015. Randomized, placebo-controlled trials assessing supplemental calcium intake for the prevention of recurrence of adenomas were eligible for inclusion. Two reviewers independently selected studies based on predefined criteria, extracted data and outcomes (recurrence of colorectal adenomas, and advanced or "high-risk" adenomas), and rated each trial's risk-of-bias. Between-study heterogeneity was assessed, and pooled risk ratio (RR) estimates with their 95% confidence intervals (95%CI) were calculated using fixed- and random-effects models. To express the treatment effect in clinical terms, we calculated the number needed to treat (NNT) to prevent one adenoma recurrence. We also assessed the quality of evidence using GRADE.Four randomized, placebo-controlled trials met the eligibility criteria and were included. Daily doses of elemental calcium ranged from 1200 to 2000 mg, while the duration of treatment and follow-up of participants ranged from 36 to 60 mo. Synthesis of intention-to-treat data, for participants who had undergone follow-up colonoscopies, indicated a modest protective effect of calcium in prevention of adenomas (fixed-effects, RR = 0.89, 95%CI: 0.82-0.96; random-effects, RR = 0.87, 95%CI: 0.77-0.98; high quality of evidence). The NNT was 20 (95%CI: 12-61) to prevent one colorectal adenoma recurrence within a period of 3 to 5 years. On the other hand, the association between calcium treatment and advanced adenomas did not reach statistical significance (fixed-effects, RR = 0.92, 95%CI: 0.75-1.13; random-effects, RR = 0.92, 95%CI: 0.71-1.18; moderate quality of evidence).Our results suggest a modest chemopreventive effect of calcium supplements against recurrent colorectal adenomas over a period of 36 to 60 mo. Further research is warranted.

SUBMITTER: Bonovas S

PROVIDER: S-EPMC4858641 | biostudies-other | 2016 May

REPOSITORIES: biostudies-other

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Calcium supplementation for the prevention of colorectal adenomas: A systematic review and meta-analysis of randomized controlled trials.

Bonovas Stefanos S Fiorino Gionata G Lytras Theodore T Malesci Alberto A Danese Silvio S

World journal of gastroenterology 20160501 18

<h4>Aim</h4>To determine the efficacy of calcium supplementation in reducing the recurrence of colorectal adenomas.<h4>Methods</h4>We conducted a systematic review and meta-analysis of published studies. We searched PubMed, Scopus, the Cochrane Library, the WHO International Clinical Trials Registry Platform, and the ClinicalTrials.gov website, through December 2015. Randomized, placebo-controlled trials assessing supplemental calcium intake for the prevention of recurrence of adenomas were elig ...[more]

PMID: 27182169

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Project description:BackgroundProtective effects of calcium supplementation against colorectal adenomas have been documented in systematic reviews; however, the results have not been conclusive. Our objective was to update and systematically evaluate the evidence for calcium supplementation taking into consideration the risks of systematic and random error and to GRADE the evidence.MethodsThe study comprised a systematic review with meta-analysis and trial sequential analysis (TSA) of randomized controlled trials (RCTs). We searched for RCTs published up until September 2016. Retrieved trials were evaluated using risk of bias. Primary outcome measures were the incidences of any recurrent adenomas and of advanced adenomas. Meta-analytic estimates were calculated with the random-effects model and random errors were evaluated with trial sequential analyses (TSAs).ResultsFive randomized trials (2234 patients with a history of adenomas) were included. Two of the 5 trials showed either unclear or high risks of bias in most criteria. Meta-analysis of good quality RCTs suggest a moderate protective effect of calcium supplementation on recurrence of adenomas (relative risk [RR], 0.88 [95% CI 0.79-0.99]); however, its effects on advanced adenomas did not show statistical significance (RR, 1.02 [95% CI 0.67-1.55]). Subgroup analyses demonstrated a greater protective effect on recurrence of adenomas with elemental calcium dose ?1600?mg/day (RR, 0.74 [95% CI 0.56-0.97]) compared to ?1200?mg/day (RR, 0.84 [95% CI 0.73-0.97]). No major serious adverse events were associated with the use of calcium, but there was an increase in the incidence of hypercalcemia (P?=?.0095). TSA indicated a lack of firm evidence for a beneficial effect. Concerns with directness and imprecision rated down the quality of the evidence to "low."ConclusionThe available good quality RCTs suggests a possible beneficial effect of calcium supplementation on the recurrence of adenomas; however, TSA indicated that the accumulated evidence is still inconclusive. Using GRADE-methodology, we conclude that the quality of evidence is low. Large well-designed randomized trials with low risk of bias are needed.

Project description:BackgroundMultiple lines of evidence indicate that aspirin has an antineoplastic effect in the large bowel. Randomized clinical trials have been conducted to evaluate the effectiveness of aspirin for reducing the risk of colorectal adenomas. A meta-analysis of these trials will provide more precise estimates of the aspirin effect, both overall and in subgroups.MethodsWe combined data from all randomized double-blind placebo-controlled trials that evaluated aspirin for the prevention of colorectal adenomas. We used random-effects meta-analysis to estimate risk ratios and 95% confidence intervals (CIs) for the effect of aspirin on the occurrence of adenomas and of advanced lesions (ie, tubulovillous adenomas, villous adenomas, adenomas >or=1 cm in diameter, adenomas with high-grade dysplasia, or invasive cancer). All statistical tests were two-sided.ResultsWe identified four clinical trials with 2967 randomly assigned participants. Each trial evaluated aspirin for the secondary prevention of colorectal adenomas. Doses of aspirin tested ranged from 81 to 325 mg/d. The average age of participants at baseline was 58 years, and 60% were male. Median follow-up was 33 months. A total of 2698 participants underwent colonoscopic follow-up and were included in the analysis of adenoma occurrence and advanced-lesion occurrence after randomization. Among these participants, adenomas were found in 424 (37%) of the 1156 participants allocated to placebo and in 507 (33%) of the 1542 participants allocated to any dose of aspirin. Advanced lesions were found in 12% of participants in the placebo group and in 9% of participants allocated to any dose of aspirin. The pooled risk ratio of any adenoma for any dose of aspirin vs placebo was 0.83 (95% CI = 0.72 to 0.96). This corresponded to an absolute risk reduction of 6.7% (95% CI = 3.2% to 10.2%). For any advanced lesion, the pooled risk ratio was 0.72 (95% CI = 0.57 to 0.90). We found no statistically significant effect modification for any of the baseline factors studied.ConclusionAspirin is effective for the prevention of colorectal adenomas in individuals with a history of these lesions.

Project description:BackgroundThe high prevalence of delirium among postoperative patients has increased morbidity and mortality. The kind of drug that can effectively reduce the incidence of delirium has become the focus of discussion in recent years. However, a consensus in this respect has yet to be reached.MethodsRandomized controlled trials (RCTs) were retrieved from the PubMed, Cochrane Library, ClinicalTrials.gov, and Embase databases from their inception through October 12, 2018. We included RCTs of pharmacological prevention for postoperative delirium in adults (at least 18 years), and the Cochrane risk of bias tool was used to evaluate the methodological quality of trials. The primary outcomes were the risk ratios (RRs) of incidence of postoperative delirium, and the secondary outcomes were the RRs of mortality and adverse events in the intervention and control groups.ResultsThirty-eight trials, which comprised 20302 patients and 18 different drugs, were included in the analysis. Of the 38 studies, 17 were rated as low risk with respect to methodological quality. Dexmedetomidine administration (RR 0.58, 95%CI 0.44-0.76, P<0.01) was associated with a significantly lower incidence of postoperative delirium than the control conditions. However, the findings from the studies with a low risk of bias did not show a significant difference in this beneficial effect (RR 0.64, 95%CI 0.39-1.04, P=0.07). The antipsychotic drugs olanzapine (RR 0.44, 95%CI 0.30- 0.65, P<0.01) and risperidone (RR 0.42, 95%CI 0.19-0.92, P=0.03) had promising effects, but there was a lack of sufficient evidence to obtain a definitive conclusion. The beneficial effect of other drugs, including haloperidol, methylprednisolone, dexamethasone, gabapentin, ketamine, cyproheptadine, donepezil, hypertonic saline, melatonin, nimodipine, ondansetron, pregabalin, rivastigmine, TJ-54, and tryptophan, was not proven on the basis of present evidence.ConclusionAmong the pharmacological prophylactic measures for postoperative delirium, dexmedetomidine, olanzapine, and risperidone showed higher efficacy than other drugs. However, more high-quality evidence is needed to confirm these results.

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Calcium supplementation for the prevention of colorectal adenomas: A systematic review and meta-analysis of randomized controlled trials.

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Calcium supplementation for the prevention of colorectal adenomas: A systematic review and meta-analysis of randomized controlled trials.

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