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International Journal of Hepatology 2018Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most widely used medication in several countries, including Thailand. NSAIDs have been associated with hepatic side... (Review)
Review
BACKGROUND
Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most widely used medication in several countries, including Thailand. NSAIDs have been associated with hepatic side effects; however, the frequency of these side effects is uncertain.
AIM OF THE REVIEW
To systematically review published literature on randomized, controlled trials that assessed the risk of clinically significant hepatotoxicity associated with NSAIDs.
METHODS
Searches of bibliographic databases EMBASE, PubMed, and the Cochrane Library were conducted up to July 30, 2016, to identify randomized controlled trials of ibuprofen, naproxen, diclofenac, piroxicam, meloxicam, mefenamic acid, indomethacin, celecoxib, and etoricoxib in adults with any disease that provide information on hepatotoxicity outcomes.
RESULTS
Among the 698 studies, 18 studies met the selection criteria. However, only 8 studies regarding three NSAIDs (celecoxib, etoricoxib, and diclofenac) demonstrated clinically significant hepatotoxic evidence based on hepatotoxicity justification criteria. Of all the hepatotoxicity events found from the above-mentioned three NSAIDs, diclofenac had the highest proportion, which ranged from 0.015 to 4.3 (×10), followed by celecoxib, which ranged from 0.13 to 0.38 (×10), and etoricoxib, which ranged from 0.005 to 0.930 (×10).
CONCLUSION
Diclofenac had higher rates of hepatotoxic evidence compared to other NSAIDs. Hepatotoxic evidence is mostly demonstrated as aminotransferase elevation, while liver-related hospitalization or discontinuation was very low.
PubMed: 29568654
DOI: 10.1155/2018/5253623 -
Indian Pediatrics Feb 2021We conducted a systematic review and network meta-analysis to compare the efficacy and safety of nine non-steroidal anti-inflammatory drugs (NSAIDs) in treating patients... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
We conducted a systematic review and network meta-analysis to compare the efficacy and safety of nine non-steroidal anti-inflammatory drugs (NSAIDs) in treating patients with juvenile idiopathic arthritis (JIA).
METHODS
Randomized controlled trials (RCTs) of NSAIDs for the treatment in children with JIA were searched systematically by using MEDLINE, EMBASE, and the Cochrane Library for available literature up to January 1, 2019. Bayesian network meta-analysis was used to combine direct and indirect evidence on treatment effectiveness and safety.
RESULTS
Eight eligible RCTs involving 1112 patients with JIA were identified, addressing 9 interventions. The ranking probability plot based on the surface under the cumulative ranking curve (SUCRA) indicated that celecoxib (6 mg/kg twice-a-day) had the highest probability of being most effective (SUCRA = 76.4%) among four NSAIDs (celecoxib, rofecoxib, meloxicam, and naproxen). Also, rofecoxib (0.3 mg/kg once-a-day) and piroxicam demonstrated a higher probability of safety in treating children with JIA (SUCRA = 33.0% and 35.5%, respectively), compared with other interventions.
CONCLUSIONS
The quality of available evidence limits the formation of powerful conclusions regarding the comparative efficacy or safety of NSAIDs used to treat JIA.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Juvenile; Child; Humans; Network Meta-Analysis; Pharmaceutical Preparations; Treatment Outcome
PubMed: 33632948
DOI: No ID Found -
The Cochrane Database of Systematic... Jun 2015Renal colic is acute pain caused by urinary stones. The prevalence of urinary stones is between 10% and 15% in the United States, making renal colic one of the common... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Renal colic is acute pain caused by urinary stones. The prevalence of urinary stones is between 10% and 15% in the United States, making renal colic one of the common reasons for urgent urological care. The pain is usually severe and the first step in the management is adequate analgesia. Many different classes of medications have been used in this regard including non-steroidal anti-inflammatory drugs and narcotics.
OBJECTIVES
The aim of this review was to assess benefits and harms of different NSAIDs and non-opioids in the treatment of adult patients with acute renal colic and if possible to determine which medication (or class of medications) are more appropriate for this purpose. Clinically relevant outcomes such as efficacy of pain relief, time to pain relief, recurrence of pain, need for rescue medication and side effects were explored.
SEARCH METHODS
We searched the Cochrane Renal Group's Specialised Register (to 27 November 2014) through contact with the Trials' Search Co-ordinator using search terms relevant to this review.
SELECTION CRITERIA
Only randomised or quasi randomised studies were included. Other inclusion criteria included adult patients with a clinical diagnosis of renal colic due to urolithiasis, at least one treatment arm included a non-narcotic analgesic compared to placebo or another non-narcotic drug, and reporting of pain outcome or medication adverse effect. Patient-rated pain by a validated tool, time to relief, need for rescue medication and pain recurrence constituted the outcomes of interest. Any adverse effects (minor or major) reported in the studies were included.
DATA COLLECTION AND ANALYSIS
Abstracts were reviewed by at least two authors independently. Papers meeting the inclusion criteria were fully reviewed and relevant data were recorded in a standardized Cochrane Renal Group data collection form. For dichotomous outcomes relative risks and 95% confidence intervals were calculated. For continuous outcomes the weighted mean difference was estimated. Both fixed and random models were used for meta-analysis. We assessed the analgesic effects using four different outcome variables: patient-reported pain relief using a visual analogue scale (VAS); proportion of patients with at least 50% reduction in pain; need for rescue medication; and pain recurrence. Heterogeneity was assessed using the I² test.
MAIN RESULTS
A total of 50 studies (5734 participants) were included in this review and 37 studies (4483 participants) contributed to our meta-analyses. Selection bias was low in 34% of the studies or unclear in 66%; performance bias was low in 74%, high in 14% and unclear in 12%; attrition bias was low in 82% and high in 18%; selective reporting bias low in 92% of the studies; and other biases (industry funding) was high in 4%, unclear in 18% and low in 78%.Patient-reported pain (VAS) results varied widely with high heterogeneity observed. For those comparisons which could be pooled we observed the following: NSAIDs significantly reduced pain compared to antispasmodics (5 studies, 303 participants: MD -12.97, 95% CI -21.80 to - 4.14; I² = 74%) and combination therapy of NSAIDs plus antispasmodics was significantly more effective in pain control than NSAID alone (2 studies, 310 participants: MD -1.99, 95% CI -2.58 to -1.40; I² = 0%).NSAIDs were significantly more effective than placebo in reducing pain by 50% within the first hour (3 studies, 197 participants: RR 2.28, 95% CI 1.47 to 3.51; I² = 15%). Indomethacin was found to be less effective than other NSAIDs (4 studies, 412 participants: RR 1.27, 95% CI 1.01 to 1.60; I² = 55%). NSAIDs were significantly more effective than hyoscine in pain reduction (5 comparisons, 196 participants: RR 2.44, 95% CI 1.61 to 3.70; I² = 28%). The combination of NSAIDs and antispasmodics was not superior to NSAIDs only (9 comparisons, 906 participants: RR 1.00, 95% CI 0.89 to 1.13; I² = 59%). The results were mixed when NSAIDs were compared to other non-opioid medications.When the need for rescue medication was evaluated, Patients receiving NSAIDs were significantly less likely to require rescue medicine than those receiving placebo (4 comparisons, 180 participants: RR 0.35, 95% CI 0.20 to 0.60; I² = 24%) and NSAIDs were more effective than antispasmodics (4 studies, 299 participants: RR 0.34, 95% CI 0.14 to 0.84; I² = 65%). Combination of NSAIDs and antispasmodics was not superior to NSAIDs (7 comparisons, 589 participants: RR 0.99, 95% CI 0.62 to 1.57; I² = 10%). Indomethacin was less effective than other NSAIDs (4 studies, 517 participants: RR 1.36, 95% CI 0.96 to 1.94; I² = 14%) except for lysine acetyl salicylate (RR 0.15, 95% CI 0.04 to 0.65).Pain recurrence was reported by only three studies which could not be pooled: a higher proportion of patients treated with 75 mg diclofenac (IM) showed pain recurrence in the first 24 hours of follow-up compared to those treated with 40 mg piroxicam (IM) (60 participants: RR 0.05, 95% CI 0.00 to 0.81); no significant difference in pain recurrence at 72 hours was observed between piroxicam plus phloroglucinol and piroxicam plus placebo groups (253 participants: RR 2.52, 95% CI 0.15 to12.75); and there was no significant difference in pain recurrence within 72 hours of discharge between IM piroxicam and IV paracetamol (82 participants: RR 1.00, 95% CI 0.65 to 1.54).Side effects were presented inconsistently, but no major events were reported.
AUTHORS' CONCLUSIONS
Although due to variability in studies (inclusion criteria, outcome variables and interventions) and the evidence is not of highest quality, we still believe that NSAIDs are an effective treatment for renal colic when compared to placebo or antispasmodics. The addition of antispasmodics to NSAIDS does not result in better pain control. Data on other types of non-opioid, non-NSAID medication was scarce.Major adverse effects are not reported in the literature for the use of NSAIDs for treatment of renal colic.
Topics: Acute Disease; Analgesics, Non-Narcotic; Anti-Inflammatory Agents, Non-Steroidal; Diclofenac; Humans; Indomethacin; Parasympatholytics; Randomized Controlled Trials as Topic; Renal Colic; Scopolamine
PubMed: 26120804
DOI: 10.1002/14651858.CD006027.pub2 -
World Journal of Clinical Cases Apr 2024Various non-steroidal anti-inflammatory drugs (NSAIDs) have been used for juvenile idiopathic arthritis (JIA). However, the optimal method for JIA has not yet been...
BACKGROUND
Various non-steroidal anti-inflammatory drugs (NSAIDs) have been used for juvenile idiopathic arthritis (JIA). However, the optimal method for JIA has not yet been developed.
AIM
To perform a systematic review and network meta-analysis to determine the optimal instructions.
METHODS
We searched for randomized controlled trials (RCTs) from PubMed, EMBASE, Google Scholar, CNKI, and Wanfang without restriction for publication date or language at August, 2023. Any RCTs that comparing the effectiveness of NSAIDs with each other or placebo for JIA were included in this network meta-analysis. The surface under the cumulative ranking curve (SUCRA) analysis was used to rank the treatments. value less than 0.05 was identified as statistically significant.
RESULTS
We included 8 RCTs (1127 patients) comparing 8 different instructions including meloxicam (0.125 qd and 0.250 qd), Celecoxib (3 mg/kg bid and 6 mg/kg bid), piroxicam, Naproxen (5.0 mg/kg/d, 7.5 mg/kg/d and 12.5 mg/kg/d), inuprofen (30-40 mg/kg/d), Aspirin (60-80 mg/kg/d, 75 mg/kg/d, and 55 mg/kg/d), Tolmetin (15 mg/kg/d), Rofecoxib, and placebo. There were no significant differences between any two NSAIDs regarding ACR Pedi 30 response. The SUCRA shows that celecoxib (6 mg/kg bid) ranked first (SUCRA, 88.9%), rofecoxib ranked second (SUCRA, 68.1%), Celecoxib (3 mg/kg bid) ranked third (SUCRA, 51.0%). There were no significant differences between any two NSAIDs regarding adverse events. The SUCRA shows that placebo ranked first (SUCRA, 88.2%), piroxicam ranked second (SUCRA, 60.5%), rofecoxib (0.6 mg/kg qd) ranked third (SUCRA, 56.1%), meloxicam (0.125 mg/kg qd) ranked fourth (SUCRA, 56.1%), and rofecoxib (0.3 mg/kg qd) ranked fifth (SUCRA, 56.1%).
CONCLUSION
In summary, celecoxib (6 mg/kg bid) was found to be the most effective NSAID for treating JIA. Rofecoxib, piroxicam, and meloxicam may be safer options, but further research is needed to confirm these findings in larger trials with higher quality studies.
PubMed: 38680254
DOI: 10.12998/wjcc.v12.i12.2056 -
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 -
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 -
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 -
The Cochrane Database of Systematic... Sep 2019Progressive lung damage causes most deaths in cystic fibrosis. Non-steroidal anti-inflammatory drugs (such as ibuprofen) may prevent progressive pulmonary deterioration...
BACKGROUND
Progressive lung damage causes most deaths in cystic fibrosis. Non-steroidal anti-inflammatory drugs (such as ibuprofen) may prevent progressive pulmonary deterioration and morbidity in cystic fibrosis. This is an update of a previously published review.
OBJECTIVES
To assess the effectiveness of treatment with oral non-steroidal anti-inflammatory drugs in cystic fibrosis.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, hand searches of relevant journals and abstract books of conference proceedings. We contacted manufacturers of non-steroidal anti-inflammatory drugs and searched online trials registries.Latest search of the Group's Trials Register: 21 November 2018.
SELECTION CRITERIA
Randomized controlled trials comparing oral non-steroidal anti-inflammatory drugs, at any dose for at least two months, to placebo in people with cystic fibrosis.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed trials for inclusion the review and their potential risk of bias. Two authors independently rated the quality of the evidence for each outcome using the GRADE guidelines.
MAIN RESULTS
The searches identified 17 trials; four are included (287 participants aged five to 39 years; maximum follow-up of four years) and one is currently awaiting classification pending publication of the full trial report and two are ongoing. Three trials compared ibuprofen to placebo (two from the same center with some of the same participants); one trial assessed piroxicam versus placebo.The three ibuprofen trials were deemed to have good or adequate methodological quality, but used various outcomes and summary measures. Reviewers considered measures of lung function, nutritional status, radiological assessment of pulmonary involvement, intravenous antibiotic usage, hospital admissions, survival and adverse effects. Combined data from the two largest ibuprofen trials showed a lower annual rate of decline for lung function, % predicted forced expiratory volume in one second (FEV), mean difference (MD) 1.32 (95% confidence interval (CI) 0.21 to 2.42) (moderate-quality evidence); forced vital capacity (FVC), MD 1.27 (95% CI 0.26 to 2.28) (moderate-quality evidence); forced expiratory flow (FEF), MD 1.80 (95% CI 0.15 to 3.45). The post hoc analysis of data from two trials split by age showed a slower rate of annual decline of FEV % predicted and FVC in the ibuprofen group in younger children, MD 1.41% (95% CI 0.03 to 2.80) (moderate-quality evidence) and MD 1.32% (95% CI 0.04 to 2.60) (moderate-quality evidence) respectively. Data from four trials demonstrated the proportion of participants with at least one hospitalization may be slightly lower in the ibuprofen group compared to placebo, Peto odds ratio 0.61 (95% CI 0.37 to 1.01) (moderate-quality evidence). In 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.We did not have any concerns with regards to risk of bias for the trial comparing piroxicam to placebo. However, the trial did not report many data in a form that we could analyze in this review. No data were available for the review's primary outcome of lung function; available data for hospital admissions showed no difference between the groups. No analyzable data were available for any other review outcome.
AUTHORS' CONCLUSIONS
High-dose ibuprofen can slow the progression of lung disease in people with cystic fibrosis, especially in children, which suggests that strategies to modulate lung inflammation can be beneficial for people with cystic fibrosis.
Topics: Administration, Oral; Adolescent; Adult; Anti-Inflammatory Agents, Non-Steroidal; Child; Cystic Fibrosis; Female; Humans; Ibuprofen; Male; Piroxicam; Randomized Controlled Trials as Topic; Young Adult
PubMed: 31499593
DOI: 10.1002/14651858.CD001505.pub5 -
European Journal of Clinical... Jan 2021Frailty and adverse drug effects are linked in the fact that polypharmacy is correlated with the severity of frailty; however, a causal relation has not been proven in...
Current evidence on the impact of medication optimization or pharmacological interventions on frailty or aspects of frailty: a systematic review of randomized controlled trials.
BACKGROUND
Frailty and adverse drug effects are linked in the fact that polypharmacy is correlated with the severity of frailty; however, a causal relation has not been proven in older people with clinically manifest frailty.
METHODS
A literature search was performed in Medline to detect prospective randomized controlled trials (RCTs) testing the effects of pharmacological interventions or medication optimization in older frail adults on comprehensive frailty scores or partial aspects of frailty that were published from January 1998 to October 2019.
RESULTS
Twenty-five studies were identified, 4 on comprehensive frailty scores and 21 on aspects of frailty. Two trials on comprehensive frailty scores showed positive results on frailty although the contribution of medication review in a multidimensional approach was unclear. In the studies on aspects related to frailty, ten individual drug interventions showed improvement in physical performance, muscle strength or body composition utilizing alfacalcidol, teriparatide, piroxicam, testosterone, recombinant human chorionic gonadotropin, or capromorelin. There were no studies examining negative effects of drugs on frailty.
CONCLUSION
So far, data on a causal relationship between drugs and frailty are inconclusive or related to single-drug interventions on partial aspects of frailty. There is a clear need for RCTs on this topic that should be based on a comprehensive, internationally consistent and thus reproducible concept of frailty assessment.
Topics: Aged; Frail Elderly; Frailty; Humans; Polypharmacy; Randomized Controlled Trials as Topic
PubMed: 32770278
DOI: 10.1007/s00228-020-02951-8