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The Cochrane Database of Systematic... 2000Maintenance of optimal lung function is an important therapeutic goal in cystic fibrosis as it is lung damage that, in the long term, is responsible for most premature... (Review)
Review
BACKGROUND
Maintenance of optimal lung function is an important therapeutic goal in cystic fibrosis as it is lung damage that, in the long term, is responsible for most premature death among affected people. It has been hypothesised that lung damage results from inflammation and that prolonged use of non-steroidal anti-inflammatory drugs may prevent progressive pulmonary deterioration and respiratory morbidity in cystic fibrosis. It is thus important to establish the current level of evidence about the potential benefits and harms of treatment with non-steroidal anti-inflammatory drugs.
OBJECTIVES
The aim of this systematic review is to assess the effectiveness of treatment with non-steroidal anti-inflammatory agents in cystic fibrosis.
SEARCH STRATEGY
Trials were ascertained from the Cochrane Cystic Fibrosis and Genetic Disorders Specialised Register of Controlled Trials which includes published and unpublished trials identified through electronic databases such as Medline and Embase as well as those identified from handsearching of journals and conference proceedings. Pharmaceutical companies manufacturing non-steroidal anti-inflammatory drugs were also contacted to identify any trials of non-steroidal anti-inflammatory drugs in cystic fibrosis. Date of the most recent search of the Group's specialised register: November 1999.
SELECTION CRITERIA
All randomised or pseudorandomised controlled trials, published and unpublished, comparing non-steroidal anti-inflammatory drugs, administered orally at any dose for a period of at least two months, to placebo in patients with cystic fibrosis.
DATA COLLECTION AND ANALYSIS
The following outcomes were assessed: objective measures of lung function, nutritional status, radiological assessment of pulmonary involvement, use of intravenous antibiotics, hospital admissions, survival, frequency of major and minor adverse effects and compliance with therapy.
MAIN RESULTS
Three trials involving 145 patients aged from five to 39 years with a maximum follow up of four years met the inclusion criteria. Methodological quality was deemed good or adequate in two. Two trials, both reporting effectiveness of ibuprofen in subjects with mild lung disease, were from the same centre and included some patients in common, while the third assessed piroxicam in subjects with more severe impairment of respiratory function. Variation in outcomes reported and their summary measures precluded calculation of pooled treatment estimates. Only one trial reported within-subject changes in pulmonary function and the findings of this trial suggested that there was a greater absolute annual decline in percentage predicted forced expiratory volume in one second among controls than among those treated with ibuprofen. In a post-hoc sub-group analysis this effect was confined to children aged five to 13 years. In addition, in this one trial long term use of high dose ibuprofen was associated with reduced intravenous antibiotic usage, improved nutritional and radiological pulmonary status. No major adverse effects were reported but the power of the trials to identify clinically important differences in the incidence of adverse effects was low.
REVIEWER'S CONCLUSIONS
While there is preliminary evidence to suggest that non-steroidal anti-inflammatory drugs may prevent pulmonary deterioration in subjects with mild lung disease due to cystic fibrosis, currently their routine use cannot be recommended. Further trials are required to confirm that their use prevents pulmonary deterioration and is associated with improved nutritional status. Such trials should also address the age group of subjects most likely to benefit, the prevalence of important adverse effects and the optimal dosage schedule as well as any reduction in concomitant therapy. Multi-centre trials will add to the validity of findings by enhancing their generalisability. The question of whether anti-inflammatory treatment prevents lung damage in pre-symptomatic
Topics: Anti-Inflammatory Agents, Non-Steroidal; Cystic Fibrosis; Humans
PubMed: 10796797
DOI: 10.1002/14651858.CD001505 -
The Pharmacogenomics Journal Dec 2021Variable responses to medications complicates perioperative care. As a potential solution, we evaluated and synthesized pharmacogenomic evidence that may inform...
Variable responses to medications complicates perioperative care. As a potential solution, we evaluated and synthesized pharmacogenomic evidence that may inform anesthesia and pain prescribing to identify clinically actionable drug/gene pairs. Clinical decision-support (CDS) summaries were developed and were evaluated using Appraisal of Guidelines for Research and Evaluation (AGREE) II. We found that 93/180 (51%) of commonly-used perioperative medications had some published pharmacogenomic information, with 18 having actionable evidence: celecoxib/diclofenac/flurbiprofen/ibuprofen/piroxicam/CYP2C9, codeine/oxycodone/tramadol CYP2D6, desflurane/enflurane/halothane/isoflurane/sevoflurane/succinylcholine/RYR1/CACNA1S, diazepam/CYP2C19, phenytoin/CYP2C9, succinylcholine/mivacurium/BCHE, and morphine/OPRM1. Novel CDS summaries were developed for these 18 medications. AGREE II mean ± standard deviation scores were high for Scope and Purpose (95.0 ± 2.8), Rigor of Development (93.2 ± 2.8), Clarity of Presentation (87.3 ± 3.0), and Applicability (86.5 ± 3.7) (maximum score = 100). Overall mean guideline quality score was 6.7 ± 0.2 (maximum score = 7). All summaries were recommended for clinical implementation. A critical mass of pharmacogenomic evidence exists for select medications commonly used in the perioperative setting, warranting prospective examination for clinical utility.
Topics: Analgesics; Anesthetics; Clinical Decision-Making; Decision Support Techniques; Evidence-Based Medicine; Humans; Perioperative Care; Pharmacogenetics; Pharmacogenomic Testing; Pharmacogenomic Variants; Predictive Value of Tests; Risk Assessment; Risk Factors
PubMed: 34376788
DOI: 10.1038/s41397-021-00248-2 -
Arthritis and Rheumatism Jun 2010Traditional nonsteroidal antiinflammatory drugs (NSAIDs) increase the risk of upper gastrointestinal (GI) bleeding/perforation, but the magnitude of this effect for... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Traditional nonsteroidal antiinflammatory drugs (NSAIDs) increase the risk of upper gastrointestinal (GI) bleeding/perforation, but the magnitude of this effect for coxibs in the general population and the degree of variability between individual NSAIDs is still under debate. This study was undertaken to assess the risk of upper GI bleeding/perforation among users of individual NSAIDs and to analyze the correlation between this risk and the degree of inhibition of whole blood cyclooxygenase 1 (COX-1) and COX-2 in vitro.
METHODS
We conducted a systematic review of observational studies on NSAIDs and upper GI bleeding/perforation published between 2000 and 2008. We calculated pooled relative risk (RR) estimates of upper GI bleeding/perforation for individual NSAIDs. Additionally, we verified whether the degree of inhibition of whole blood COX-1 and COX-2 in vitro by average circulating concentrations predicted the RR of upper GI bleeding/perforation.
RESULTS
The RR of upper GI bleeding/perforation was 4.50 (95% confidence interval [95% CI] 3.82-5.31) for traditional NSAIDs and 1.88 (95% CI 0.96-3.71) for coxibs. RRs lower than that for NSAIDs overall were observed for ibuprofen (2.69 [95% CI 2.17-3.33]), rofecoxib (2.12 [95% CI 1.59-2.84]), aceclofenac (1.44 [95% CI 0.65-3.2]), and celecoxib (1.42 [95% CI 0.85-2.37]), while higher RRs were observed for ketorolac (14.54 [95% CI 5.87-36.04]) and piroxicam (9.94 [95% CI 5.99-16.50). Estimated RRs were 5.63 (95% CI 3.83-8.28) for naproxen, 5.57 (95% CI 3.94-7.87) for ketoprofen, 5.40 (95% CI 4.16-7.00) for indomethacin, 4.15 (95% CI 2.59-6.64) for meloxicam, and 3.98 (95% CI 3.36-4.72) for diclofenac. The degree of inhibition of whole blood COX-1 did not significantly correlate with RR of upper GI bleeding/perforation associated with individual NSAIDs (r(2) = 0.34, P = 0.058), but a profound and coincident inhibition (>80%) of both COX isozymes was associated with higher risk. NSAIDs with a long plasma half-life and with a slow-release formulation were associated with a greater risk than NSAIDs with a short half-life.
CONCLUSION
The results of our analysis demonstrate that risk of upper GI bleeding/perforation varies between individual NSAIDs at the doses commonly used in the general population. Drugs that have a long half-life or slow-release formulation and/or are associated with profound and coincident inhibition of both COX isozymes are associated with a greater risk of upper GI bleeding/perforation.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Dose-Response Relationship, Drug; Gastrointestinal Hemorrhage; Half-Life; Humans; Regression Analysis; Risk; Risk Factors
PubMed: 20178131
DOI: 10.1002/art.27412 -
International Journal of Clinical... Oct 2020Intramuscular or, more rarely, local drug injection is occasionally followed by immediate local pain, livedoid skin lesions and, some days later, the development of...
AIM
Intramuscular or, more rarely, local drug injection is occasionally followed by immediate local pain, livedoid skin lesions and, some days later, the development of ischemic lesions. This very uncommon but potentially severe reaction, termed Nicolau syndrome, is traditionally associated with bismuth and β-lactam antimicrobials. The aim of this report was to review the literature associating Nicolau syndrome with the administration of non-steroidal anti-inflammatory drugs.
METHODS
The National Library, Excerpta Medica, Web of Science and Cochrane library databases were used.
RESULTS
Sixty-two cases (40 females and 22 males aged from 13 to 81, median 57 years) of Nicolau syndrome were published after 1992. Fifty-three cases occurred after diclofenac. The remaining nine cases were associated with ketoprofen (N = 2), ketorolac (N = 2), phenylbutazone (N = 2), etofenamate (N = 1), ibuprofen (N = 1) and piroxicam (N = 1).
CONCLUSION
Although Nicolau syndrome is extremely uncommon, physicians must be aware of this complication after intramuscular administration of non-steroidal anti-inflammatory drugs and should avoid unnecessary injections.
Topics: Adolescent; Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Diclofenac; Drug Eruptions; Female; Humans; Injections, Intramuscular; Male; Middle Aged; Nicolau Syndrome; Young Adult
PubMed: 32479658
DOI: 10.1111/ijcp.13567 -
JMIR Public Health and Surveillance Jan 2024Drug-induced suicide (DIS) is a severe adverse drug reaction (ADR). Although clinical trials have provided evidence on DIS, limited investigations have been performed on... (Review)
Review
BACKGROUND
Drug-induced suicide (DIS) is a severe adverse drug reaction (ADR). Although clinical trials have provided evidence on DIS, limited investigations have been performed on rare ADRs, such as suicide.
OBJECTIVE
We aimed to systematically review case reports on DIS to provide evidence-based drug information.
METHODS
We searched PubMed to obtain case reports regarding DIS published until July 2021. Cases resulting from drugs that are no longer used or are nonapproved, substance use, and suicidal intentions were excluded. The quality of each case report was assessed using the CASE (Case Reports) checklist. We extracted data regarding demographics, medication history, suicide symptoms, and symptom improvement and evaluated the causality of DIS using the Naranjo score. Furthermore, to identify the potential suicidal risk of the unknown drugs, we compared the results of the causality assessment with those of the approved drug labels.
RESULTS
In 83 articles, we identified 152 cases involving 61 drugs. Antidepressants were reported as the most frequent causative drugs of DIS followed by immunostimulants. The causality assessment revealed 61 cases having possible, 89 cases having probable, and 2 cases having definite relationships with DIS. For approximately 85% of suspected drugs, the risk of suicidal ADRs was indicated on the approved label; however, the approved labels for 9 drugs, including lumacaftor/ivacaftor, doxycycline, clozapine, dextromethorphan, adalimumab, infliximab, piroxicam, paclitaxel, and formoterol, did not provide information about these risks.
CONCLUSIONS
We found several case reports involving drugs without suicide risk information on the drug label. Our findings might provide valuable insights into drugs that may cause suicidal ADRs.
Topics: Humans; Doxycycline; Drug Labeling; Drug-Related Side Effects and Adverse Reactions; Suicidal Ideation; Suicide; Case Reports as Topic
PubMed: 38289650
DOI: 10.2196/49755 -
The Cochrane Database of Systematic... Nov 2011Methotrexate is routinely used in the treatment of inflammatory arthritis. There have been concerns regarding the safety of using concurrent non-steroidal... (Meta-Analysis)
Meta-Analysis Review
Safety of non-steroidal anti-inflammatory drugs, including aspirin and paracetamol (acetaminophen) in people receiving methotrexate for inflammatory arthritis (rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, other spondyloarthritis).
BACKGROUND
Methotrexate is routinely used in the treatment of inflammatory arthritis. There have been concerns regarding the safety of using concurrent non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin, or paracetamol (acetaminophen), or both, in these people.
OBJECTIVES
To systematically appraise and summarise the scientific evidence on the safety of using NSAIDs, including aspirin, or paracetamol, or both, with methotrexate in inflammatory arthritis; and to identify gaps in the current evidence, assess the implications of those gaps and to make recommendations for future research to address these deficiencies.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, second quarter 2010); MEDLINE (from 1950); EMBASE (from 1980); the Cochrane Database of Systematic Reviews (CDSR) and the Database of Abstracts of Reviews of Effects (DARE). We also handsearched the conference proceedings for the American College of Rheumatology (ACR) and European League against Rheumatism (EULAR) (2008 to 2009) and checked the websites of regulatory agencies for reported adverse events, labels and warnings.
SELECTION CRITERIA
Randomised controlled trials and non-randomised studies comparing the safety of methotrexate alone to methotrexate with concurrent NSAIDs, including aspirin, or paracetamol, or both, in people with inflammatory arthritis.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed the search results, extracted data and assessed the risk of bias of the included studies.
MAIN RESULTS
Seventeen publications out of 8681 identified studies were included in the review, all of which included people with rheumatoid arthritis using various NSAIDs, including aspirin. There were no identified studies for other forms of inflammatory arthritis.For NSAIDs, 13 studies were included that used concurrent NSAIDs, of which nine studies examined unspecified NSAIDs. The mean number of participants was 150.4 (range 19 to 315), mean duration 2182.9 (range 183 to 5490) days, although the study duration was not always clearly defined, and the studies were mainly of low to moderate quality. Two of these studies reported no evidence for increased risk of methotrexate-induced pulmonary disease; one study assessed the effect of concurrent NSAIDs on renal function and found no adverse effect; one study identified no adverse effect on liver function; three studies demonstrated no increase in methotrexate withdrawal; and one study showed no increase in all adverse events, including major toxic reactions. However, transient thrombocytopenia was demonstrated in one study, specifically when NSAIDs were taken on the same week day as methotrexate. This study was a retrospective review that involved small numbers only and was of moderate quality; these finding have not been replicated since.Four studies looked at specific NSAIDs (etodolac, piroxicam, celecoxib and etoricoxib), with a mean number of participants of 25.8 (range 14 to 50) and mean study duration of 16.8 (range 14 to 23) days. These studies were mainly of moderate quality. The studies were primarily pharmacokinetic studies but also reported adverse events as secondary outcomes. There were no clinically significant adverse effects with concomitant piroxicam or etodolac; and only mild adverse events with celecoxib or etoricoxib, such as nausea and vomiting, and headaches.For aspirin, seven studies provided data on adverse events with the use of aspirin and methotrexate. These studies included a mean number of participants of 100 (range 11 to 232), had a mean duration of 1325 (range 8 to 2928) days and were mainly of low to moderate quality. Two of the studies reported no evidence for increased risk of methotrexate-induced pulmonary disease and two studies showed no increase in all adverse events including major toxic reactions; however, none of these studies specified the dose of aspirin that was used. One study demonstrated that concurrent aspirin adversely affected liver function at a mean dose of 6.84 tablets of aspirin per day, which is a possible daily dose of 2.1 g presuming that 300 mg aspirin tablets were given. A further study described a partially reversible decline in renal function with 2 g daily of aspirin. One study reported no increase in adverse events with 975 g aspirin daily, however the study duration was only one week.For paracetamol, no studies were identified for inclusion.
AUTHORS' CONCLUSIONS
In the management of rheumatoid arthritis, the concurrent use of NSAIDs with methotrexate appears to be safe provided appropriate monitoring is performed. The use of anti-inflammatory doses of aspirin should be avoided.
Topics: Acetaminophen; Anti-Inflammatory Agents, Non-Steroidal; Antirheumatic Agents; Arthritis, Psoriatic; Arthritis, Rheumatoid; Aspirin; Drug Interactions; Drug Therapy, Combination; Humans; Methotrexate; Randomized Controlled Trials as Topic; Spondylarthritis; Spondylitis, Ankylosing
PubMed: 22071858
DOI: 10.1002/14651858.CD008872.pub2 -
The Cochrane Database of Systematic... 2000To determine whether there is a difference in the relative efficacy of individual non-steroidal anti-inflammatory drugs (NSAIDs) when used in the management of... (Review)
Review
OBJECTIVES
To determine whether there is a difference in the relative efficacy of individual non-steroidal anti-inflammatory drugs (NSAIDs) when used in the management of osteoarthritis (OA) of the knee.
SEARCH STRATEGY
We searched Medline (1966-1995) and Bids Embase (Jan-Dec, 1980-1995). The searches were limited to publications in the English language, and were last perfomed in November 1996. We used modified Cochrane Collaboration search strategy to identify all randomised controlled trials. The MeSH heading osteoarthritis was combined with the generic names of the 17 non-aspirin NSAIDs licensed in the UK for the management of OA in general practice. The search of Embase used the term "osteoarthritis" if present in the abstract, title or keywords, and was combined with the generic names of the 17 non-aspirin NSAIDs, only if they were mentioned in the title, abstract or keywords.
SELECTION CRITERIA
All double blind, randomised controlled trials, in the English language, comparing the efficacy of two non-aspirin NSAIDs in the management of osteoarthritis of the knee, were selected. Only trials with subjects aged 16 years and over, with clinical and/or radiological confirmation of the diagnosis of OA knee were included. Studies which compared one "trial" NSAID with one "reference" NSAID were included provided they were non-aspirin NSAIDs available in the UK and were licensed for the treatment of OA by general practitioners. Trials which were placebo-controlled and which also involved the comparison of two NSAIDs were also included.
DATA COLLECTION AND ANALYSIS
The methodological design of each study was scored according to a pre-determined system. The three main outcome measures of pain, physical function and patient global assessment were chosen based on the core set agreed upon by OMERACT (Outcome Measures in Rheumatology Clinical Trials). These were used to determine the power of each trial. The equivalency of NSAID doses was calculated using the percentage of the recommended maximum daily dose. Sample size estimates for the detection of clinically relevant changes in outcome measures used in the assessment of OA knee were used for power calculations. These calculations were performed to determine whether the trials were of a sufficient size to detect clinically relevant differences which were statistically significant. The calculations incorporate estimates of standard deviation, and minimum, median and maximum differences (delta) between drugs which are deemed to be clinically important. The number of "withdrawals due to lack of efficacy" was also selected as an outcome measure for this review. The Peto odds ratio and 95% confidence intervals were calculated where possible. The results of studies which compared the same trial and reference NSAIDs were combined where possible.
MAIN RESULTS
Of the 1151 trials identified by the search strategy, 22 involved knee osteoarthritis only. Sixteen of these trials fulfilled the inclusion criteria and were entered in the review. Eight NSAIDs were represented in these trials. Etodolac was represented in 11 trials. The reference NSAID in these trials was piroxicam (n=3), naproxen(n=3), diclofenac (n=3), indomethacin (n=1), and, nabumetone (n=1). The reported methodological design of the trials was poor, with a median score of 3 (out of a maximum of 8). The results of the trials comparing the same trial and reference NSAIDs were pooled for the outcome "withdrawal due to lack of efficacy". For the comparison, etodolac vesus piroxicam, the odds ratio favoured etodolac i.e. patients receiving etodolac were less likely to withdraw due to lack of efficacy. The dose of etodolac used in each of these three studies, however, was greater than the corresponding dose of piroxicam (based on percentage maximum daily dose). The significance of these results is therefore questionable. For the comparisons etodolac versus diclofenac, and etodolac versus naproxen, there were no clear differences betw
Topics: Anti-Inflammatory Agents, Non-Steroidal; Humans; Osteoarthritis, Knee
PubMed: 10796306
DOI: 10.1002/14651858.CD000142 -
The Cochrane Database of Systematic... Jul 2007Osteoarthritis(OA) is the most common rheumatic disease. Simple analgesics are now accepted as the appropriate first line pharmacological treatment of uncomplicated OA.... (Review)
Review
BACKGROUND
Osteoarthritis(OA) is the most common rheumatic disease. Simple analgesics are now accepted as the appropriate first line pharmacological treatment of uncomplicated OA. Non-aspirin NSAIDs are licensed for the relief of pain and inflammation arising from rheumatic disease.
OBJECTIVES
To determine whether there is a difference in the relative efficacy of individual non-steroidal anti-inflammatory drugs (NSAIDs) when used in the management of osteoarthritis (OA) of the knee.
SEARCH STRATEGY
We searched Medline (1966-1995) and Bids Embase (Jan-Dec, 1980-1995). The searches were limited to publications in the English language, and were last performed in November 1996. We used modified Cochrane Collaboration search strategy to identify all randomised controlled trials. The MeSH heading "osteoarthritis" was combined with the generic names of the 17 non-aspirin NSAIDs licensed in the UK for the management of OA in general practice. The search of Embase used the term "osteoarthritis" if present in the abstract, title or keywords, and was combined with the generic names of the 17 non-aspirin NSAIDs, only if they were mentioned in the title, abstract or keywords.
SELECTION CRITERIA
All double blind, randomised controlled trials, in the English language, comparing the efficacy of two non-aspirin NSAIDs in the management of osteoarthritis of the knee, were selected. Only trials with subjects aged 16 years and over, with clinical and/or radiological confirmation of the diagnosis of OA knee were included. Studies which compared one "trial" NSAID with one "reference" NSAID were included provided they were non-aspirin NSAIDs available in the UK and were licensed for the treatment of OA by general practitioners. Trials which were placebo-controlled and which also involved the comparison of two NSAIDs were also included.
DATA COLLECTION AND ANALYSIS
The methodological design of each study was scored according to a pre-determined system. The three main outcome measures of pain, physical function and patient global assessment were chosen based on the core set agreed upon by OMERACT (Outcome Measures in Rheumatology Clinical Trials). These were used to determine the power of each trial. The equivalency of NSAID doses was calculated using the percentage of the recommended maximum daily dose. Sample size estimates for the detection of clinically relevant changes in outcome measures used in the assessment of OA knee were used for power calculations. These calculations were performed to determine whether the trials were of a sufficient size to detect clinically relevant differences which were statistically significant. The calculations incorporate estimates of standard deviation, and minimum, median and maximum differences (delta) between drugs which are deemed to be clinically important. The number of "withdrawals due to lack of efficacy" was also selected as an outcome measure for this review. The Peto odds ratio and 95% confidence intervals were calculated where possible. The results of studies which compared the same trial and reference NSAIDs were combined where possible.
MAIN RESULTS
Of the 1151 trials identified by the search strategy, 22 involved knee osteoarthritis only. Sixteen of these trials fulfilled the inclusion criteria and were entered in the review. Eight NSAIDs were represented in these trials. Etodolac was represented in 11 trials. The reference NSAID in these trials was piroxicam (n=3), naproxen(n=3), diclofenac (n=3), indomethacin (n=1), and, nabumetone (n=1). The reported methodological design of the trials was poor, with a median score of 3 (out of a maximum of 8). The results of the trials comparing the same trial and reference NSAIDs were pooled for the outcome "withdrawal due to lack of efficacy". For the comparison, etodolac versus piroxicam, the odds ratio favoured etodolac i.e. patients receiving etodolac were less likely to withdraw due to lack of efficacy. The dose of etodolac used in each of these three studies, however, was greater than the corresponding dose of piroxicam (based on percentage maximum daily dose). The significance of these results is therefore questionable. For the comparisons etodolac versus diclofenac, and etodolac versus naproxen, there were no clear differences between treatments. In one study [Bellamy 1993], a statistically significant difference was detected between treatments with regard to withdrawals due to lack of efficacy. In this trial, which compared equivalent NSAID doses, diclofenac was the favoured NSAID compared to tenoxicam(p=0.04). Two studies showed a statistical difference in patient global assessment of condition, which favoured the trial NSAID. In both cases the trial NSAID was etodolac, used in doses approximately 25-44% greater than the reference NSAID. Two studies showed a statistically significant difference in pain relief between NSAIDs. The trial NSAID in both cases was again etodolac but the doses exceeded those of the reference NSAIDs.
AUTHORS' CONCLUSIONS
In spite of the large number of publications in this area, there are few randomized controlled trials. Furthermore, most trials comparing two or more NSAIDs suffer from substantial design errors. From the results of this review it is concluded that no substantial evidence is available related to efficacy, to distinguish between equivalent recommended doses of NSAIDs. Had studies employed appropriate doses of comparator drug, most would have been sufficiently powerful to detect clinically important differences in efficacy. As differences in efficacy between NSAIDs have not been recorded, the selection of an NSAID for prescription for OA knee should be based upon relative safety, patient acceptability and cost.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Humans; Osteoarthritis, Knee
PubMed: 17636601
DOI: 10.1002/14651858.CD000142.pub2 -
BMJ (Clinical Research Ed.) Jan 1998To review the effectiveness and safety of topical non-steroidal anti-inflammatory drugs in acute and chronic pain conditions. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To review the effectiveness and safety of topical non-steroidal anti-inflammatory drugs in acute and chronic pain conditions.
DESIGN
Quantitative systematic review of randomised controlled trials.
DATA SOURCES
86 trials involving 10,160 patients.
MAIN OUTCOME MEASURES
Measures of treatment success approximating at least 50% reduction in pain, local and systemic adverse effects. Analysis at 1 week for acute and 2 weeks for chronic conditions with relative benefit and number needed to treat.
RESULTS
In acute pain conditions (soft tissue trauma, strains, and sprains) placebo controlled trials had a relative benefit of 1.7 (1.5 to 1.9), the number needed to treat was 3.9 (3.4 to 4.4). With analysis by drug (at least three trials), ketoprofen (number needed to treat 2.6), felbinac (3.0), ibuprofen (3.5), and piroxicam (4.2) had significant efficacy. Benzydamine and indomethacin were no different from placebo. In chronic pain conditions (osteoarthritis, tendinitis) placebo controlled trials had a relative benefit of 2.0 (1.5 to 2.7); the number needed to treat was 3.1 (2.7 to 3.8). Small trials (< 40 treated patients) exaggerated effectiveness of topical non-steroidals by 33% in acute conditions but not in chronic conditions. There was no relation between trial quality and treatment effect. In both acute and chronic pain local and systemic adverse events and withdrawal from the study related to the drug had a low incidence and were no different from placebo.
CONCLUSION
Topical non-steroidal anti-inflammatory drugs are effective in relieving pain in acute and chronic conditions.
Topics: Acute Disease; Administration, Topical; Anti-Inflammatory Agents, Non-Steroidal; Chronic Disease; Drug Combinations; Humans; Pain; Randomized Controlled Trials as Topic; Sprains and Strains; Treatment Outcome
PubMed: 9487165
DOI: 10.1136/bmj.316.7128.333 -
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