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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 -
Frontiers in Oncology 2023To evaluate the efficacy of Difluoromethylornithine (DFMO) chemoprevention in the high-risk population for colorectal cancer (CRC).
OBJECTIVES
To evaluate the efficacy of Difluoromethylornithine (DFMO) chemoprevention in the high-risk population for colorectal cancer (CRC).
METHODS
Meta-analysis was conducted to assess the caliber of the included literature by searching five databases for randomized controlled trials of DFMO chemoprevention in the high-risk population of CRC, with RevMan 5.4, Stata 15.0 and TSA 0.9.5.10 employed to statistically analyze the extracted data. Grade profiler 3.6 was employed for grading the evidence for the outcome indicators (disease progression and adenoma incidence).
RESULTS
Six trials were finally included in this research, with the collective data indicating that the DFMO combination therapy was efficacious in lowering the incidence of recurrent adenomas in patients who had experienced advanced CRC [RR 0.34, 95% CI 0.14 - 0.83, P < 0.05]. Meta-analysis showed that DFMO combined therapy had no statistical difference in disease progression in patients with familial adenomatous polyposis[RR 0.52, 95% CI 0.14 - 1.86, P > 0.05]; Trial Sequential Analysis reveals that the combination therapy of DFMO effectively diminishes the occurrence of recurrent adenomas in patients with a history of advanced colorectal tumors, displaying a Risk Ratio (RR) of 0.33 with a 95% Confidence Interval (CI) of 0.12 - 0.90 and a significance level of P < 0.05. This combination exhibits a statistically significant difference. Subgroup analysis demonstrates that, depending on the drug treatment regimen (DFMO+ Aspirin/DFMO+ Sulindac), the combination of DFMO and aspirin exhibits an effect comparable to a placebo in diminishing the occurrence of new adenomas in patients with a history of advanced colorectal tumors. However, the combination of DFMO and sulindac significantly mitigates the incidence of recurrent adenomas in this patient population.
CONCLUSION
This meta-analysis indicates that the existing randomized controlled trials are adequate to ascertain the efficacy of DFMO combination therapy in diminishing the incidence of recurrent adenomas in patients who have previously encountered advanced colorectal tumors. However, further clinical trials need to be conducted to evaluate the optimum dosage and treatment course of prophylactic implementation of DFMO combination therapy in high-risk populations.
PubMed: 38033490
DOI: 10.3389/fonc.2023.1281844 -
European Journal of Gastroenterology &... Jan 2024The onset of colorectal adenomas (CRAs) is significantly associated with colorectal cancer. The preventive effects of chemical drugs on the recurrence of CRAs have been... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The onset of colorectal adenomas (CRAs) is significantly associated with colorectal cancer. The preventive effects of chemical drugs on the recurrence of CRAs have been evaluated in a large number of randomized controlled trials (RCTs). However, there are still uncertainties about the relative effectiveness of such chemical drugs.
METHODS
We searched relevant RCTs published in six databases up to February 2023. The quality of the included studies was assessed by using the Cochrane risk of bias assessment tool and Review Manager 5.4. Pairwise comparison and network meta-analysis (NMA) were conducted using RStudio to compare the effects of chemical drugs on the recurrence of CRAs.
RESULTS
Forty-five high-quality RCTs were included. A total of 35 590 (test group: 20 822; control group: 14 768) subjects with a history of CRAs have been enrolled and randomized to receive placebo treatment or one of 24 interventions. Based on surface under the cumulative ranking values and NMA results, difluoromethylornithine (DFMO) + Sulindac significantly reduced the recurrence of CRAs, followed by berberine and nonsteroidal antiinflammatory drugs.
CONCLUSION
DFMO + Sulindac is more effective in reducing the recurrence of CRAs but has a high risk of adverse events. Considering drug safety, tolerance, and compliance, berberine has a brighter prospect of clinical development. However, further studies are needed to verify our findings.
Topics: Humans; Sulindac; Network Meta-Analysis; Berberine; Colorectal Neoplasms; Adenoma; Randomized Controlled Trials as Topic
PubMed: 37942763
DOI: 10.1097/MEG.0000000000002676 -
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 -
Pharmacological Research Feb 2020To conduct a comprehensive systematic meta-analysis investigating the association of nonsteroidal anti-inflammatory drugs (NSAIDs) and their subtypes with skin cancer... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To conduct a comprehensive systematic meta-analysis investigating the association of nonsteroidal anti-inflammatory drugs (NSAIDs) and their subtypes with skin cancer (SC) and its subclasses (basal cell carcinoma BCC; squamous cell carcinoma SCC; melanoma; nonmelanoma skin cancer NMSC) in general, American and European populations.
METHODS
PubMed, Embase, the Cochrane Library, the China National Knowledge Infrastructure and ClinicalTrials.gov were searched up to 24 February 2019. Pooled effect sizes and 95% confidence intervals were used to estimate associations.
RESULTS
Results based on 26 original studies including 223,619 cases and 1,398,507 controls showed both NSAIDs and nonselective Cyclooxygenase (COX) inhibitors to be statistically significantly associated with a reduced risk of SC, BCC, SCC and NMSC but not with melanoma. Conversely, no association was observed between selective Cyclooxygenase 2 (COX-2) inhibitors and SC or its subclasses. Further subgroup analysis showed that the results analyzed for American populations were almost the same as those for the general population. For European populations, neither NSAIDs nor its subtypes correlated significantly with susceptibility to SC or its subclasses.
CONCLUSIONS
The use of NSAIDs might reduce the risk of SC, but many factors including study population, drug subtype, and disease subclass affect the significance of the association.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Europe; Humans; Randomized Controlled Trials as Topic; Skin Neoplasms; United States
PubMed: 31689521
DOI: 10.1016/j.phrs.2019.104499 -
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 -
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 -
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 -
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