-
Drug Safety Dec 2012The risk of upper gastrointestinal (GI) complications associated with the use of NSAIDs is a serious public health concern. The risk varies between individual NSAIDs;... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The risk of upper gastrointestinal (GI) complications associated with the use of NSAIDs is a serious public health concern. The risk varies between individual NSAIDs; however, there is little information on the risk associated with some NSAIDs and on the impact of risk factors. These data are necessary to evaluate the benefit-risk of individual NSAIDs for clinical and health policy decision making. Within the European Community's Seventh Framework Programme, the Safety Of non-Steroidal anti-inflammatory drugs (NSAIDs) [SOS] project aims to develop decision models for regulatory and clinical use of individual NSAIDs according to their GI and cardiovascular safety.
OBJECTIVE
The aim of this study was to conduct a systematic review and meta-analysis of observational studies to provide summary relative risks (RR) of upper GI complications (UGIC) associated with the use of individual NSAIDs, including selective cyclooxygenase-2 inhibitors.
METHODS
We used the MEDLINE database to identify cohort and case-control studies published between 1 January 1980 and 31 May 2011, providing adjusted effect estimates for UGIC comparing individual NSAIDs with non-use of NSAIDs. We estimated pooled RR and 95% CIs of UGIC for individual NSAIDs overall and by dose using fixed- and random-effects methods. Subgroup analyses were conducted to evaluate methodological and clinical heterogeneity between studies.
RESULTS
A total of 2984 articles were identified and 59 were selected for data abstraction. After review of the abstracted information, 28 studies met the meta-analysis inclusion criteria. Pooled RR ranged from 1.43 (95% CI 0.65, 3.15) for aceclofenac to 18.45 (95% CI 10.99, 30.97) for azapropazone. RR was less than 2 for aceclofenac, celecoxib (RR 1.45; 95% CI 1.17, 1.81) and ibuprofen (RR 1.84; 95% CI 1.54, 2.20); 2 to less than 4 for rofecoxib (RR 2.32; 95% CI 1.89, 2.86), sulindac (RR 2.89; 95% CI 1.90, 4.42), diclofenac (RR 3.34; 95% CI 2.79, 3.99), meloxicam (RR 3.47; 95% CI 2.19, 5.50), nimesulide (RR 3.83; 95% CI 3.20, 4.60) and ketoprofen (RR 3.92; 95% CI 2.70, 5.69); 4-5 for tenoxicam (RR 4.10; 95% CI 2.16, 7.79), naproxen (RR 4.10; 95% CI 3.22, 5.23), indometacin (RR 4.14; 95% CI 2.91, 5.90) and diflunisal (RR 4.37; 95% CI 1.07, 17.81); and greater than 5 for piroxicam (RR 7.43; 95% CI 5.19, 10.63), ketorolac (RR 11.50; 95% CI 5.56, 23.78) and azapropazone. RRs for the use of high daily doses of NSAIDs versus non-use were 2-3 times higher than those associated with low daily doses.
CONCLUSIONS
We confirmed variability in the risk of UGIC among individual NSAIDs as used in clinical practice. Factors influencing findings across studies (e.g. definition and validation of UGIC, exposure assessment, analysis of new vs prevalent users) and the scarce data on the effect of dose and duration of use of NSAIDs and on concurrent use of other medications need to be addressed in future studies, including SOS.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Case-Control Studies; Dose-Response Relationship, Drug; Gastrointestinal Hemorrhage; Humans; Risk Factors
PubMed: 23137151
DOI: 10.2165/11633470-000000000-00000 -
European Journal of Internal Medicine May 2015The association between acute kidney injury (AKI) and use of non-steroidal anti-inflammatory drugs (NSAIDs) is well established. However, little is known about the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The association between acute kidney injury (AKI) and use of non-steroidal anti-inflammatory drugs (NSAIDs) is well established. However, little is known about the comparative risk of individual NSAIDs, including specific COX-2 inhibitors.
METHODS
We conducted a systematic review and meta-analysis of cohort studies that reported relative risk, hazard ratio or standardized incidence ratio with 95% confidence comparing AKI risk in NSAID users versus non-users. Pooled risk ratios and 95% confidence intervals for individual NSAIDs were calculated using random-effect, generic inverse variance methods.
RESULTS
Five studies were identified and included in our data analysis. Pooled risk ratios were calculated for seven traditional NSAIDs and two specific COX-2 inhibitors, including indomethacin, piroxicam, ibuprofen, naproxen, sulindac, diclofenac, meloxicam, rofecoxib and celecoxib that were evaluated in at least two studies. Our meta-analysis was able to demonstrate a statistically significant elevated AKI risk among most of the included traditional NSAIDs. The pooled risk ratios were fairly consistent among individual traditional NSAIDs, ranging from 1.58 to 2.11. Differences between pooled risk ratios did not reach statistical significance (p≥0.19 for each comparison). Elevated AKI risk was also observed in diclofenac, meloxicam, rofecoxib and celecoxib users, although did not achieve a statistical significance.
CONCLUSION
A statistically significant elevated AKI risk among traditional NSAID users has been demonstrated in this meta-analysis. The pooled risk ratios among individual traditional NSAIDs were not significantly different. The pooled risk ratios of specific COX-2 inhibitors and the two traditional NSAIDs with the most COX-2 selectivity (diclofenac and meloxicam) were also comparable with other traditional NSAIDs even though they did not achieve a statistical significance.
Topics: Acute Kidney Injury; Anti-Inflammatory Agents, Non-Steroidal; Cyclooxygenase 2 Inhibitors; Humans; Observational Studies as Topic; Odds Ratio; Risk Factors
PubMed: 25862494
DOI: 10.1016/j.ejim.2015.03.008 -
The Cochrane Database of Systematic... Sep 2015This is an updated version of the original Cochrane overview published in Issue 9, 2011. That overview considered both efficacy and adverse events, but adverse events... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This is an updated version of the original Cochrane overview published in Issue 9, 2011. That overview considered both efficacy and adverse events, but adverse events are now dealt with in a separate overview.Thirty-nine Cochrane reviews of randomised trials have examined the analgesic efficacy of individual drug interventions in acute postoperative pain. This overview brings together the results of those individual reviews and assesses the reliability of available data.
OBJECTIVES
To summarise the efficacy of pharmaceutical interventions for acute pain in adults with at least moderate pain following surgery who have been given a single dose of oral analgesic.
METHODS
We identified systematic reviews in the Cochrane Database of Systematic Reviews in The Cochrane Library through a simple search strategy. All reviews were overseen by a single review group, had a standard title, and had as their primary outcome the number of participants with at least 50% pain relief over four to six hours compared with placebo. For individual reviews, we extracted the number needed to treat for an additional beneficial outcome (NNT) for this outcome for each drug/dose combination, and also the percentage of participants achieving at least 50% maximum pain relief, the mean of mean or median time to remedication, and the percentage of participants remedicating by six, eight, 12, or 24 hours. Where there was adequate information for pairs of drug and dose (at least 200 participants, in at least two studies), we defined the addition of four comparisons of typical size (400 participants in total) with zero effect as making the result potentially subject to publication bias and therefore unreliable.
MAIN RESULTS
The overview included 39 separate Cochrane Reviews with 41 analyses of single dose oral analgesics tested in acute postoperative pain models, with results from about 50,000 participants in approximately 460 individual studies. The individual reviews included only high-quality trials of standardised design, methods, and efficacy outcome reporting. No statistical comparison was undertaken.Reliable results (high quality information) were obtained for 53 pairs of drug and dose in painful postsurgical conditions; these included various fixed dose combinations, and fast acting formulations of some analgesics. NNTs varied from about 1.5 to 20 for at least 50% maximum pain relief over four to six hours compared with placebo. The proportion of participants achieving this level of benefit varied from about 30% to over 70%, and the time to remedication varied from two hours (placebo) to over 20 hours. Good (low) NNTs were obtained with ibuprofen 200 mg plus paracetamol (acetaminophen) 500 mg (NNT compared with placebo 1.6; 95% confidence interval 1.5 to 1.8), ibuprofen fast acting 200 mg (2.1; 1.9 to 2.3); ibuprofen 200 mg plus caffeine 100 mg (2.1; 1.9 to 3.1), diclofenac potassium 50 mg (2.1; 1.9 to 2.5), and etoricoxib 120 mg (1.8; 1.7 to 2.0). For comparison, ibuprofen acid 400 mg had an NNT of 2.5 (2.4 to 2.6). Not all participants had good pain relief and, for many pairs of drug and dose, 50% or more did not achieve at least 50% maximum pain relief over four to six hours.Long duration of action (eight hours or greater) was found for etoricoxib 120 mg, diflunisal 500 mg, paracetamol 650 mg plus oxycodone 10 mg, naproxen 500/550 mg, celecoxib 400 mg, and ibuprofen 400 mg plus paracetamol 1000 mg.There was no evidence of analgesic effect for aceclofenac 150 mg, aspirin 500 mg, and oxycodone 5 mg (low quality evidence). No trial data were available in reviews of acemetacin, meloxicam, nabumetone, nefopam, sulindac, tenoxicam, and tiaprofenic acid. Inadequate amounts of data were available for nine drugs and doses, and data potentially susceptible to publication bias for 13 drugs and doses (very low quality evidence).
AUTHORS' CONCLUSIONS
There is a wealth of reliable evidence on the analgesic efficacy of single dose oral analgesics. Fast acting formulations and fixed dose combinations of analgesics can produce good and often long-lasting analgesia at relatively low doses. There is also important information on drugs for which there are no data, inadequate data, or where results are unreliable due to susceptibility to publication bias. This should inform choices by professionals and consumers.
Topics: Acute Pain; Administration, Oral; Adult; Analgesics; Humans; Pain, Postoperative
PubMed: 26414123
DOI: 10.1002/14651858.CD008659.pub3 -
Preventive Medicine Sep 2022Colorectal cancer (CRC) is the fourth most common cancer and third leading cause of cancer-related death worldwide. Use of chemopreventive agents (CPAs) to reduce the... (Meta-Analysis)
Meta-Analysis Review
Colorectal cancer (CRC) is the fourth most common cancer and third leading cause of cancer-related death worldwide. Use of chemopreventive agents (CPAs) to reduce the incidence of precursor colorectal adenomas could lower the future burden of CRC. Many classes of potential CPAs have been investigated. To identify the most effective CPAs, we conducted a systematic review and a network meta-analysis (NMA). An electronic search was performed through August 2020 to identify all randomized controlled trials (RCTs) assessing the efficacy of CPAs in reducing the incidence of colorectal adenomas at the time of surveillance colonoscopy among patients who had previously undergone polypectomy during an index colonoscopy. In total, 33 RCTs were included in the NMA, which was conducted under a Bayesian inference framework. Random effects models were used with adjustment for follow-up length and control group event rates to yield relative risks (RRs) and 95% credible intervals (CrIs). Our full network consisted of 13 interventions in addition to a placebo arm. Of 20,925 included patients, 7766 had an adenoma. Compared to placebo, the combination of difluoromethylornithine (DFMO) + Sulindac (RR 0.24, CrI 0.10-0.55) demonstrated a protective effect, while aspirin had a RR of 0.77 (CrI 0.60-1.00), celecoxib 800 mg had a RR of 0.56 (CrI 0.31-1.01) and metformin had a RR of 0.56 (CrI 0.22-1.39). Our results suggest that select CPAs may be efficacious in preventing the development of adenomas. Further studies are needed to identify those patients most likely to benefit and the minimum effective dosages of CPAs.
Topics: Adenoma; Colonoscopy; Colorectal Neoplasms; Humans; Incidence; Network Meta-Analysis
PubMed: 35878711
DOI: 10.1016/j.ypmed.2022.107169 -
Cureus Jan 2024Sulindac sulfone, an active metabolite of sulindac, a non-steroidal anti-inflammatory drug, has good anti-inflammatory potential. The antineoplastic effect of sulindac... (Review)
Review
Sulindac sulfone, an active metabolite of sulindac, a non-steroidal anti-inflammatory drug, has good anti-inflammatory potential. The antineoplastic effect of sulindac sulfone is mediated through a cyclooxygenase inhibitory mechanism, followed by apoptosis and inhibition of cell proliferation. Mounting studies have explored the anti-neoplastic effect of sulindac sulfone in various types of cancers in a dose-dependent manner. In this backdrop, we have conducted a systematic review to evaluate the efficacy and dose of sulindac sulfone as an anti-neoplastic agent in human head and neck squamous cell carcinoma cell lines (HNSCCs). In this study, we used a systematic literature review approach, and articles were searched in PubMed, and Medline with the keywords "sulindac sulfone," "anti-neoplastic activity," "chemopreventive," and "head and neck squamous cell carcinoma". A hand-search of journals was also performed. Articles were reviewed and analyzed. The analysis reveals that, based on the in vitro studies on various tumor models, the optimum concentration of sulindac sulfone which elicits anti-neoplastic effects is 200-800 µM. The anti-neoplastic effect is mediated through inhibition of cell proliferation and apoptosis. The results of our systematic review show that the anti-neoplastic activity of pharmacologic Sulindac sulfone is part of its dose-dependent activity, which can be safely employed in the therapy for human HNSCCs and would be responsible for a beneficial outcome of the treatment.
PubMed: 38313951
DOI: 10.7759/cureus.51692 -
Current Medical Research and Opinion Oct 2007To investigate the effects of continued use of non-selective NSAIDs (nsNSAIDs) on blood pressure and hypertension. (Review)
Review
OBJECTIVE
To investigate the effects of continued use of non-selective NSAIDs (nsNSAIDs) on blood pressure and hypertension.
RESEARCH DESIGN AND METHODS
This was a systematic review of randomized clinical trials of oral nsNSAIDs used for at least a 4-week duration. Searches were conducted of PubMed and the Cochrane Database of Systematic Reviews, using key terms for nsNSAIDs and blood pressure or hypertension, to identify articles published in the English language peer-reviewed literature through March 2007.
MAIN OUTCOME MEASURES
Change from baseline to end of study in systolic blood pressure (SBP) and diastolic blood pressure (DBP), and the incidence of hypertension. Pooled statistics were computed using fixed and random-effects analyses.
RESULTS
Thirty-two articles were included. The mean change (95% confidence interval [CI]) in blood pressure (in mmHg) from baseline to end of study for five trials of ibuprofen was 3.54 (2.70, 4.39) for SBP and 1.16 (0.68, 1.64) for DBP (p < 0.001 for both changes). Results of four trials of indomethacin were similar to those for ibuprofen: 2.90 (-0.28, 6.08) for SBP (p = 0.07) and 1.58 (0.29, 2.87) for DBP (p = 0.02). Mean changes from baseline for two trials of diclofenac were -0.46 (-1.48, 0.56) for SBP (p = 0.38) and -0.56 (-1.19, 0.07) for DBP (p = 0.08) and were similar to those for placebo. Changes from baseline in SBP were positive but not statistically significant for naproxen, sulindac, and nabumetone. Compared with placebo, the risk ratio (95% CI) for hypertension was 2.85 (1.44, 5.65; p = 0.003) in two ibuprofen trials.
CONCLUSIONS
Continued use of ibuprofen increases blood pressure and raises the incidence of hypertension. There appears to be heterogeneity in such effects with continued use of other nsNSAIDs but, due to limitations in the data, results for naproxen, sulindac, and nabumetone are inconclusive.
Topics: Administration, Oral; Anti-Inflammatory Agents, Non-Steroidal; Blood Pressure; Humans; Hypertension; Placebos; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 17714606
DOI: 10.1185/030079907X219553 -
Otolaryngology--head and Neck Surgery :... Mar 2015To perform a systematic review evaluating the association between sensorineural hearing loss and (1) nonsteroidal anti-inflammatory drugs (NSAIDs) as a class, (2) NSAIDs... (Review)
Review
OBJECTIVE
To perform a systematic review evaluating the association between sensorineural hearing loss and (1) nonsteroidal anti-inflammatory drugs (NSAIDs) as a class, (2) NSAIDs available over the counter, (3) NSAIDs in short intravenous courses, (4) prescription NSAIDs utilized by patients without systemic inflammatory conditions, (5) prescription NSAIDs in patients with arthritides, and (6) acetaminophen with and without concomitant narcotic usage.
DATA SOURCES
Computerized searches of PubMed, EMBASE, and the Cochrane Library were updated through May 2014, along with manual searches and inquiries to topic experts.
REVIEW METHODS
The systematic review was performed according to an a priori protocol. Data extraction was performed by 2 independent investigators, and it focused on relevant audiologic measurements, methodological elements related to risk of bias, and potential confounders.
RESULTS
The 23 criterion-meeting studies included a total of 92,532 participants, with mixed results. Sulindac was the only specific agent to have been studied with formal audiometry in a randomized double-blind placebo-controlled trial in which hearing was the reported primary outcome: Although an effect was seen in the unadjusted analysis (pure tone threshold>15 dB, 9.3% vs 2.9%; relative risk [RR], 3.2; confidence interval [CI], 1.09-9.55; P=.02), the effect dissipated in the adjusted analysis (P=.09). There was a significant effect on self-reported hearing loss from NSAIDs as a class (RR, 1.21; CI, 1.11-1.33), ibuprofen (RR, 1.13; CI, 1.06-1.19), and acetaminophen (RR, 1.21; CI, 1.11-1.33), but no formal audiometric data confirm or refute this suggested effect. Audiometry has demonstrated profound loss in some instances of acetaminophen-narcotic combination ingestions.
CONCLUSIONS
Data are varied regarding the impact of NSAIDs and acetaminophen on population hearing health.
Topics: Acetaminophen; Analgesics, Non-Narcotic; Anti-Inflammatory Agents, Non-Steroidal; Audiometry; Hearing; Hearing Loss, Sensorineural; Humans; Risk Factors
PubMed: 25560405
DOI: 10.1177/0194599814564533 -
Diseases of the Colon and Rectum May 2004A systematic review was conducted to determine the effect of nonsteroidal anti-inflammatory drugs for the prevention or regression of colorectal adenomas and cancer. (Review)
Review
PURPOSE
A systematic review was conducted to determine the effect of nonsteroidal anti-inflammatory drugs for the prevention or regression of colorectal adenomas and cancer.
METHODS
Randomized, controlled trials through September 2003 were identified. Nonsteroidal anti-inflammatory drugs were the interventions. The primary outcomes were the number of patients with at least one colorectal adenoma, a change in polyp burden, or colorectal cancer. The secondary outcome was adverse events. Two reviewers independently extracted data and assessed trial quality. Dichotomous outcomes were reported as relative risks with 95 percent confidence intervals. The data were combined if clinically and statistically reasonable.
RESULTS
Nine trials with 150 familial adenomatous polyposis and 24,143 population patients met the inclusion criteria. The interventions included sulindac, celecoxib, or aspirin. From the combined results of three trials, significantly fewer patients in the aspirin group developed recurrent sporadic colorectal adenomas (relative risk, 0.77 (95 percent confidence interval, 0.61, 0.96), number needed to treat 12.5 (95 percent confidence interval, 7.7, 25)) after one to three years. In another three trials, patients with familial adenomatous polyposis who received nonsteroidal anti-inflammatory drugs had a greater proportional reduction (range, 11.9-44 percent) in the number of colorectal adenomas compared with those in the control group (range, 4.5-10 percent). There was no significant difference for the outcomes of colorectal cancer or adverse events in any of the trials.
CONCLUSIONS
There is combined evidence from three randomized trials that aspirin significantly reduced the recurrence of sporadic adenomatous polyps. There was evidence from short-term trials to support regression, but not elimination or prevention, of colorectal polyps in familial adenomatous polyposis.
Topics: Adenoma; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Colorectal Neoplasms; Humans; Neoplastic Syndromes, Hereditary; Randomized Controlled Trials as Topic
PubMed: 15054679
DOI: 10.1007/s10350-003-0111-9 -
Cancer Epidemiology, Biomarkers &... May 2003The Apc(Min/+) mouse model and the azoxymethane (AOM) rat model are the main animal models used to study the effect of dietary agents on colorectal cancer. We reviewed... (Review)
Review
The Apc(Min/+) mouse model and the azoxymethane (AOM) rat model are the main animal models used to study the effect of dietary agents on colorectal cancer. We reviewed recently the potency of chemopreventive agents in the AOM rat model (D. E. Corpet and S. Tache, Nutr. Cancer, 43: 1-21, 2002). Here we add the results of a systematic review of the effect of dietary and chemopreventive agents on the tumor yield in Min mice. The review is based on the results of 179 studies from 71 articles and is displayed also on the internet http://corpet.net/min.(2) We compared the efficacy of agents in the Min mouse model and the AOM rat model, and found that they were correlated (r = 0.66; P < 0.001), although some agents that afford strong protection in the AOM rat and the Min mouse small bowel increase the tumor yield in the large bowel of mutant mice. The agents included piroxicam, sulindac, celecoxib, difluoromethylornithine, and polyethylene glycol. The reason for this discrepancy is not known. We also compare the results of rodent studies with those of clinical intervention studies of polyp recurrence. We found that the effect of most of the agents tested was consistent across the animal and clinical models. Our point is thus: rodent models can provide guidance in the selection of prevention approaches to human colon cancer, in particular they suggest that polyethylene glycol, hesperidin, protease inhibitor, sphingomyelin, physical exercise, epidermal growth factor receptor kinase inhibitor, (+)-catechin, resveratrol, fish oil, curcumin, caffeate, and thiosulfonate are likely important preventive agents.
Topics: Animals; Anticarcinogenic Agents; Azoxymethane; Chemoprevention; Colonic Neoplasms; Diet; Disease Models, Animal; Humans; Mice; Mice, Mutant Strains; Precancerous Conditions; Randomized Controlled Trials as Topic; Rats
PubMed: 12750232
DOI: No ID Found -
Journal of Endodontics Apr 2019This review aimed to find the most effective oral premedication in reducing pain in adults after nonsurgical root canal therapy (NSRCT) using network meta-analysis. (Meta-Analysis)
Meta-Analysis
INTRODUCTION
This review aimed to find the most effective oral premedication in reducing pain in adults after nonsurgical root canal therapy (NSRCT) using network meta-analysis.
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.
Topics: Administration, Oral; Adolescent; Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Databases, Bibliographic; Female; Humans; Ibuprofen; Ketorolac; Male; Middle Aged; Pain, Postoperative; Piroxicam; Prednisolone; Premedication; Randomized Controlled Trials as Topic; Root Canal Therapy; Sulindac; Treatment Outcome; Young Adult
PubMed: 30737050
DOI: 10.1016/j.joen.2018.10.016