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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 -
Efficacy of tramadol for postoperative pain management in dogs: systematic review and meta-analysis.Veterinary Anaesthesia and Analgesia May 2021To evaluate the evidence of analgesic efficacy of tramadol for the management of postoperative pain and the presence of associated adverse events in dogs. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To evaluate the evidence of analgesic efficacy of tramadol for the management of postoperative pain and the presence of associated adverse events in dogs.
DATABASES USED
A comprehensive search using PubMed/MEDLINE, LILACS, Google Scholar and CAB databases with no restrictions on language and following a prespecified protocol was performed from June 2019 to July 2020. Included were randomized controlled trials (RCTs) performed in dogs that had undergone general anesthesia for any type of surgery. Two authors independently classified the studies, extracted data and assessed their risk of bias using Cochrane's tool. RevMan and GRADE methods were used to rate the certainty of evidence (CoE).
CONCLUSIONS
Overall 26 RCTs involving 848 dogs were included. Tramadol administration probably results in a lower need for rescue analgesia versus no treatment or placebo [moderate CoE; relative risk (RR): 0.47; 95% confidence interval (CI): 0.26-0.85; I = 0%], and may result in a lower need for rescue analgesia versus buprenorphine (low CoE; RR: 0.50; 95% CI: 0.20-1.24), codeine (low CoE; RR: 0.75; 95% CI: 0.16-3.41) and nalbuphine (low CoE; RR: 0.05; 95% CI: 0.00-0.72). However, tramadol administration may result in an increased requirement for rescue analgesia versus methadone (low CoE; RR: 3.45; 95% CI: 0.66-18.08; I = 43%) and COX inhibitors (low CoE; RR: 2.27; 95% CI: 0.68-7.60; I = 45%). Compared with multimodal therapy, tramadol administration may make minimal to no difference in the requirement for rescue analgesia (low CoE; RR: 1.12; 95% CI: 0.48-2.60; I = 0%). Adverse events were inconsistently reported and the CoE was very low. The overall CoE of the analgesic efficacy of tramadol for postoperative pain management in dogs was low or very low, and the main reasons for downgrading the evidence were risk of bias and imprecision.
Topics: Analgesia; Animals; Dog Diseases; Dogs; Nalbuphine; Pain Management; Pain, Postoperative; Tramadol
PubMed: 33745825
DOI: 10.1016/j.vaa.2021.01.003 -
Pharmaceutics Jun 2022This systematic review summarizes the impact of pharmacogenetics on the effect and safety of non-steroidal anti-inflammatory drugs (NSAIDs) and antidepressants when used... (Review)
Review
BACKGROUND
This systematic review summarizes the impact of pharmacogenetics on the effect and safety of non-steroidal anti-inflammatory drugs (NSAIDs) and antidepressants when used for pain treatment.
METHODS
A systematic literature search was performed according to the preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines regarding the human in vivo efficacy and safety of NSAIDs and antidepressants in pain treatment that take pharmacogenetic parameters into consideration. Studies were collected from PubMed, Scopus, and Web of Science up to the cutoff date 18 October 2021.
RESULTS
Twenty-five articles out of the 6547 initially detected publications were identified. Relevant medication-gene interactions were noted for drug safety. Interactions important for pain management were detected for (1) ibuprofen/; (2) celecoxib/; (3) piroxicam/, ; (4) diclofenac/, , , ; (5) meloxicam/; (6) aspirin/, , and ; (7) amitriptyline/ and ; (8) imipramine/; (9) nortriptyline/, , ; and (10) escitalopram/, , and .
CONCLUSIONS
Overall, a lack of well powered human in vivo studies assessing the pharmacogenetics in pain patients treated with NSAIDs or antidepressants is noted. Studies indicate a higher risk for partly severe side effects for the poor metabolizers and NSAIDs. Further in vivo studies are needed to consolidate the relevant polymorphisms in NSAID safety as well as in the efficacy of NSAIDs and antidepressants in pain management.
PubMed: 35745763
DOI: 10.3390/pharmaceutics14061190 -
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 -
Inflammopharmacology Feb 2015Non-steroidal anti-inflammatory drugs (NSAIDs) are known to increase the risk of cardiovascular (CV) and renal incidences, especially at higher doses and upon long term... (Review)
Review
PURPOSE
Non-steroidal anti-inflammatory drugs (NSAIDs) are known to increase the risk of cardiovascular (CV) and renal incidences, especially at higher doses and upon long term use. However, the available reports are criticized for lack of specificity, grouping of vastly different outcomes together and ignoring the heterogeneity among NSAIDs. In this systematic review, we are reporting CV/renal risks associated with meloxicam, stratified into myocardial, vascular, renal risk categories, to address the differential nature of NSAIDs effects on different body systems. We are also reporting composite CV/renal risk to present overall risk associated with various covariates.
METHODS
We searched the online healthcare databases for observational studies or randomized controlled trials, reporting myocardial or all-cause mortality outcome (>90 days exposure) and/or vascular/renal outcomes (any exposure) after meloxicam use, published until April 2014. The combined odd ratio values (OR'; 95% CI) were calculated using the random effect inverse variance model.
RESULTS
We found 19 eligible studies out of 2,422 reports. Meloxicam demonstrated a low increase in composite risk (OR' 1.14; CI 1.04-1.25) which was mainly vascular in nature (OR' 1.35; CI 1.18-1.55] as it did not elevate myocardial (OR' 1.13; CI 0.98-1.32) or renal (OR', 0.99; CI 0.72-1.35) risks. Relative to meloxicam, other NSAIDs increased the composite risk, in a dose-dependent fashion, in the following order: rofecoxib > indomethacin > diclofenac > celecoxib > naproxen > ibuprofen. OR' was also influenced by type of disease and the comparator used, and acetylsalicylic acid.
CONCLUSION
NSAIDs are heterogeneous in increasing CV/renal risks. The low increased risk associated with meloxicam is mainly vascular in origin.
Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cardiovascular Diseases; Case-Control Studies; Cyclooxygenase 2 Inhibitors; Humans; Kidney Diseases; Meloxicam; Randomized Controlled Trials as Topic; Risk Factors; Thiazines; Thiazoles; Vascular Diseases
PubMed: 25515365
DOI: 10.1007/s10787-014-0225-9 -
Veterinary Anaesthesia and Analgesia Jan 2016To systematically review published studies evaluating pain associated with onychectomy in cats, and to assess the efficacy of the analgesic therapies applied. (Review)
Review
OBJECTIVES
To systematically review published studies evaluating pain associated with onychectomy in cats, and to assess the efficacy of the analgesic therapies applied.
DATABASES USED
Four sources were used to identify manuscripts for review. Databases searched were those of the National Library of Medicine, EMBASE and CAB International. In addition, pertinent references in the bibliographies of included articles were retrieved.
RESULTS
Twenty manuscripts published in refereed journals were reviewed. These included papers reporting 18 clinical trials and two studies conducted in conditioned research cats. Twelve analgesics were evaluated, including seven opioids, four non-steroidal anti-inflammatory drugs and one local anesthetic. Nine studies involved a direct comparison of analgesic agents. Limb use was abnormal when measured at 2 and 12 days following onychectomy, and neither fentanyl patch nor butorphanol administration resulted in normal use of the surgical limb. In another study, cats evaluated at 6 months after this surgery were not lame. Differing surgical techniques were compared in six studies; the results indicated that pain scores were lower after laser surgery than after scalpel surgery. The difficulties associated with assessing pain in cats and the lack of sensitivity of the evaluation systems utilized were highlighted in many of the studies. Huge variations in dose and dosing strategies had significant impacts on drug efficacy. Statistically significant differences among treatments were found in most studies; however, no clearly superior analgesic treatment was identified. A combination of meloxicam or robenacoxib with an opioid may provide more effective analgesia and should be evaluated.
Topics: Analgesics; Animals; Cats; Female; Humans; Male; Orchiectomy; Ovariectomy; Pain Measurement; Pain, Postoperative; Randomized Controlled Trials as Topic
PubMed: 26457818
DOI: 10.1111/vaa.12314 -
Health Technology Assessment... Apr 2008To review the clinical effectiveness and cost-effectiveness of cyclooxygenase-2 (COX-2) selective non-steroidal anti-inflammatory drugs (NSAIDs) (etodolac, meloxicam,... (Meta-Analysis)
Meta-Analysis Review
Cyclooxygenase-2 selective non-steroidal anti-inflammatory drugs (etodolac, meloxicam, celecoxib, rofecoxib, etoricoxib, valdecoxib and lumiracoxib) for osteoarthritis and rheumatoid arthritis: a systematic review and economic evaluation.
OBJECTIVES
To review the clinical effectiveness and cost-effectiveness of cyclooxygenase-2 (COX-2) selective non-steroidal anti-inflammatory drugs (NSAIDs) (etodolac, meloxicam, celecoxib, rofecoxib, etoricoxib, valdecoxib and lumiracoxib) for osteoarthritis (OA) and rheumatoid arthritis (RA).
DATA SOURCES
Electronic databases were searched up to November 2003. Industry submissions to the National Institute for Health and Clinical Excellence (NICE) in 2003 were also reviewed.
REVIEW METHODS
Systematic reviews of randomised controlled trials (RCTs) and a model-based economic evaluation were undertaken. Meta-analyses were undertaken for each COX-2 selective NSAID compared with placebo and non-selective NSAIDs. The model was designed to run in two forms: the 'full Assessment Group Model (AGM)', which includes an initial drug switching cycle, and the 'simpler AGM', where there is no initial cycle and no opportunity for the patient to switch NSAID.
RESULTS
Compared with non-selective NSAIDs, the COX-2 selective NSAIDs were found to be equally as efficacious as the non-selective NSAIDs (although meloxicam was found to be of inferior or equivalent efficacy) and also to be associated with significantly fewer clinical upper gastrointestinal (UGI) events (although relatively small numbers of clinical gastrointestinal (GI) and myocardial infarction (MI) events were reported across trials). Subgroup analyses of clinical and complicated UGI events and MI events in relation to aspirin use, steroid use, prior GI history and Helicobacter pylori status were based on relatively small numbers and were inconclusive. In the RCTs that included direct COX-2 comparisons, the drugs were equally tolerated and of equal efficacy. Trials were of insufficient size and duration to allow comparison of risk of clinical UGI events, complicated UGI events and MIs. One RCT compared COX-2 (celecoxib) with a non-selective NSAID combined with a gastroprotective agent (diclofenac combined with omeprazole); this included arthritis patients who had recently suffered a GI haemorrhage. Although no significant difference in clinical GI events was reported, the number of events was small and more such studies, where patients genuinely need NSAIDs, are required to confirm these data. A second trial showed that rofecoxib was associated with fewer diarrhoea events than a combination of diclofenac and misoprostol (Arthrotec). Previously published cost-effectiveness analyses indicated a wide of range of possible incremental cost per quality-adjusted life-year (QALY) gained estimates. Using the simpler AGM, with ibuprofen or diclofenac alone as the comparator, all of the COX-2 products are associated with higher costs (i.e. positive incremental costs) and small increases in effectiveness (i.e. positive incremental effectiveness), measured in terms of QALYs. The magnitude of the incremental costs and the incremental effects, and therefore the incremental cost-effectiveness ratios, vary considerably across all COX-2 selective NSAIDs. The base-case incremental cost per QALY results for COX-2 selective NSAIDs compared with diclofenac for the simpler model are: celecoxib (low dose) 68,400 pounds; celecoxib (high dose) 151,000 pounds; etodolac (branded) 42,400 pounds; etodolac (generic) 17,700 pounds; etoricoxib 31,300 pounds; lumiracoxib 70,400 pounds; meloxicam (low dose) 10,300 pounds; meloxicam (high dose) 17,800 pounds; rofecoxib 97,400 pounds; and valdecoxib 35,500 pounds. When the simpler AGM was run using ibuprofen or diclofenac combined with proton pump inhibitor (PPI) as the comparator, the results change substantially, with the COX-2 selective NSAIDs looking generally unattractive from a cost-effectiveness point of view (COX-2 selective NSAIDs were dominated by ibuprofen or diclofenac combined with PPI in most cases). This applies both to 'standard' and 'high-risk' arthritis patients defined in terms of previous GI ulcers. The full AGM produced results broadly in line with the simpler model.
CONCLUSIONS
The COX-2 selective NSAIDs examined were found to be similar to non-selective NSAIDs for the symptomatic relief of RA and OA and to provide superior GI tolerability (the majority of evidence is in patients with OA). Although COX-2 selective NSAIDs offer protection against serious GI events, the amount of evidence for this protective effect varied considerably across individual drugs. The volume of trial evidence with regard to cardiovascular safety also varied substantially between COX-2 selective NSAIDs. Increased risk of MI compared to non-selective NSAIDs was observed among those drugs with greater volume of evidence in terms of exposure in patient-years. Economic modelling shows a wide range of possible costs per QALY gained in patients with OA and RA. Costs per QALY also varied if individual drugs were used in 'standard' or 'high'-risk patients, the choice of non-selective NSAID comparator and whether that NSAID was combined with a PPI. With reduced costs of PPIs, future primary research needs to compare the effectiveness and cost-effectiveness of COX-2 selective NSAIDs relative to non-selective NSAIDs with a PPI. Direct comparisons of different COX-2 selective NSAIDs, using equivalent doses, that compare GI and MI risk are needed. Pragmatic studies that include a wider range of people, including the older age groups with a greater burden of arthritis, are also necessary to inform clinical practice.
Topics: Anti-Ulcer Agents; Arthritis, Rheumatoid; Cost-Benefit Analysis; Cyclooxygenase 2 Inhibitors; Gastrointestinal Diseases; Humans; Markov Chains; Models, Econometric; Omeprazole; Osteoarthritis; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Risk Factors; Technology Assessment, Biomedical; Thrombosis
PubMed: 18405470
DOI: 10.3310/hta12110 -
Veterinary Research Communications Feb 2022Although laboratory animals experience pain as a necessary component of the objectives of experimental protocols, the level of pain should be minimized through use of an... (Review)
Review
Although laboratory animals experience pain as a necessary component of the objectives of experimental protocols, the level of pain should be minimized through use of an adequate analgesic regimen. The non-steroidal anti-inflammatory drug meloxicam may be beneficial in alleviating post-operative pain in mice, although no regimen has been demonstrated as universally efficacious owing to differences in experimental protocols, strain, sex, and incomplete descriptions of methodology in the literature. The aim of this systematic literature review was to identify potential applications of meloxicam for pain management in experimental mice and to evaluate the general quality of study design. Searches of MEDLINE, Scopus and CAB Direct databases elicited 94 articles published between January 2000 and April 2020 that focused on the analgesic efficacy of meloxicam in the management of momentary or persistent pain in mice. The extracted data showed that most articles were deficient in descriptions of housing, husbandry, group size calculation and humane endpoint criteria, while few described adverse effects of the drug. A wide range of dosages of meloxicam was identified with analgesic efficiencies that varied considerably according to the different models or procedures studied. It was impossible to correlate the extracted data into a single meta-analysis because of the differences in experimental protocols and strains employed, the low representation of female mice in the studies, and incomplete descriptions of the methodology applied. We conclude that meloxicam has potential application for pain management in mice but that the dosage must be adjusted carefully according to the experimental procedures. Moreover, authors must take more care in designing their studies and in describing the methodology employed.
Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Female; Meloxicam; Mice; Pain
PubMed: 34988874
DOI: 10.1007/s11259-021-09868-2 -
Stroke Feb 2016The association between hemorrhagic stroke and use of nonsteroidal anti-inflammatory drugs (NSAIDs) is not well established. We conducted a systematic review and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND PURPOSE
The association between hemorrhagic stroke and use of nonsteroidal anti-inflammatory drugs (NSAIDs) is not well established. We conducted a systematic review and meta-analysis of observation studies to further characterize this possible association.
METHODS
Case-control and cohort studies that reported odds ratio, relative risk, hazard ratio, or standardized incidence ratio comparing risk of hemorrhagic stroke among NSAIDs users versus nonusers were systematically searched. Point estimates from each study were extracted. Pooled risk ratios (RR) and 95% confidence intervals (CI) for all NSAIDs and individual NSAIDs were calculated using random-effect, generic inverse variance method.
RESULTS
Ten studies were identified and included in our data analysis. As a single group, NSAIDs use was associated with a small but insignificant risk of hemorrhagic stroke with the pooled RR of 1.09 (95% CI, 0.98-1.22). Individual NSAIDs analysis revealed a significantly increased risk among diclofenac and meloxicam users (RR 1.27; 95% CI, 1.02-1.59 and RR 1.27; 95% CI, 1.08-1.50, respectively). The risk estimate for rofecoxib users was higher, but statistically nonsignificant (RR 1.35; 95% CI, 0.88-2.06).
CONCLUSIONS
Overall, the use of NSAIDs is not associated with an increased risk of hemorrhagic stroke, although this risk was modestly significantly elevated in diclofenac and meloxicam users.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Celecoxib; Cerebral Hemorrhage; Diclofenac; Humans; Ibuprofen; Incidence; Indomethacin; Lactones; Meloxicam; Naproxen; Observational Studies as Topic; Odds Ratio; Piroxicam; Proportional Hazards Models; Stroke; Sulfones; Thiazines; Thiazoles
PubMed: 26670086
DOI: 10.1161/STROKEAHA.115.011678