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Pain and Therapy Dec 2020Nonsteroidal anti-inflammatory drugs (NSAIDs) are, in general, the cornerstone of musculoskeletal pain management; however, systemic adverse events with oral... (Review)
Review
INTRODUCTION
Nonsteroidal anti-inflammatory drugs (NSAIDs) are, in general, the cornerstone of musculoskeletal pain management; however, systemic adverse events with oral formulations of NSAIDs are common. To address this problem and limit systemic exposure, topical formulations of some NSAIDs have been developed. The aim of this systematic review was to assess the available evidence on the efficacy and safety of the topical formulations of the NSAID etofenamate in patients with musculoskeletal disorders.
METHODS
A systematic search of PubMed and Web of Science was conducted using the key words "topical etofenamate efficacy" OR "topical etofenamate safety" OR "topical etofenamate effectiveness" to identify studies of etofenamate published from inception to November 2018. Some published manuscripts of interest known by the authors but not identified in the PubMed search were also included to ensure the review article was as comprehensive as possible.
RESULTS
Overall, 12 studies were identified. These studies demonstrate that topical etofenamate [administered either in gel (5 or 10%), cream (10%) or lotion (10%) formulations)] can improve pain and reduce inflammation in patients with musculoskeletal disorders, including blunt injuries and rheumatic diseases. Etofenamate was shown to have an overall efficacy that was superior to other topical NSAIDs, such as 1% indomethacin and 1% diclofenac, and to be as effective as topical formulations of 2.5% ketoprofen gel and 2% ketorolac gel (although ketorolac showed better elimination of pain at some time points). Also, clinical evidence indicates that etofenamate is generally well tolerated in these indications.
CONCLUSIONS
The clinical evidence currently available suggests that etofenamate is an effective therapeutic option for the management of musculoskeletal disorders, such as blunt traumas, lumbago or osteoarthrosis. However, larger and well-controlled clinical trials comparing the efficacy and safety of etofenamate with other newer topical NSAIDs are warranted.
PubMed: 32562238
DOI: 10.1007/s40122-020-00177-1 -
Evidence-based Complementary and... 2020Lumbar disc herniation (LDH) is based on the degenerative changes of the intervertebral disc. Many drugs are used to treat and prevent LDH, including Western medicine...
OBJECTIVE
Lumbar disc herniation (LDH) is based on the degenerative changes of the intervertebral disc. Many drugs are used to treat and prevent LDH, including Western medicine and Chinese medicine. Duhuo Jisheng Decoction (DHJSD) is one of the most classic Chinese medicine prescriptions. The purpose of our meta-analysis is to evaluate the efficacy and safety of modified DHJSD in the treatment of LDH.
METHODS
We searched multiple databases including PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI) databases, Wanfang Database, and Chinese Scientific Journal Database (VIP) to identify studies that met the inclusion criteria. This meta-analysis was registered at INPLASY with reference number ID: INPLASY202060053.
RESULTS
Fourteen randomized controlled trials (RCTs) were identified, including 1560 patients. This meta-analysis showed that the total effective rate and cure rate of modified DHJSD are higher than those of diclofenac sodium enteric-coated tablets (total effective rate: RR = 1.18, 95% CI: 1.12 to 1.25, < 0.0001, = 0%; cure rate: RR = 1.60, 95% CI: 1.30 to 1.97, < 0.00001, = 2%), diclofenac sodium enteric-coated tablets plus ibuprofen and indomethacin (total effective rate: RR = 1.23, 95% CI: 1.11 to 1.37, =0.0001, = 0%; cure rate: RR = 1.58, 95% CI: 1.22 to 2.04, =0.0005, = 0%), and diclofenac sodium sustained-release capsule (total effective rate: RR = 1.49, 95% CI: 1.27 to 1.74, < 0.00001, = 0%; cure rate: RR = 10.07, 95% CI: 3.29 to 30.88, < 0.00001, = 5%). Modified DHJSD was also better than Western medicine (MD = -1.56, 95% CI: -2.42 to -0.70, =0.0004, = 74%) in terms of visual analogue scale (VAS) scores. Three RCTs showed no adverse events in the modified DHJSD group, but adverse events existed in the Western medicine group.
CONCLUSION
This meta-analysis showed that modified DHJSD had a more favorable effect on the treatment of LDH than Western medicine, and there were no obvious adverse events. More high-quality RCTs are needed to complement existing conclusions.
PubMed: 32714400
DOI: 10.1155/2020/2381462 -
The Cochrane Database of Systematic... May 2021Postoperative pain is common and may be severe. Postoperative administration of non-steroidal anti-inflammatory drugs (NSAIDs) reduces patient opioid requirements and,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Postoperative pain is common and may be severe. Postoperative administration of non-steroidal anti-inflammatory drugs (NSAIDs) reduces patient opioid requirements and, in turn, may reduce the incidence and severity of opioid-induced adverse events (AEs).
OBJECTIVES
To assess the analgesic efficacy and adverse effects of single-dose intravenous ketorolac, compared with placebo or an active comparator, for moderate to severe postoperative pain in adults.
SEARCH METHODS
We searched the following databases without language restrictions: CENTRAL, MEDLINE, Embase and LILACS on 20 April 2020. We checked clinical trials registers and reference lists of retrieved articles for additional studies.
SELECTION CRITERIA
Randomized double-blind trials that compared a single postoperative dose of intravenous ketorolac with placebo or another active treatment, for treating acute postoperative pain in adults following any surgery.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. Our primary outcome was the number of participants in each arm achieving at least 50% pain relief over a four- and six-hour period. Our secondary outcomes were time to and number of participants using rescue medication; withdrawals due to lack of efficacy, adverse events (AEs), and for any other cause; and number of participants experiencing any AE, serious AEs (SAEs), and NSAID-related or opioid-related AEs. For subgroup analysis, we planned to analyze different doses of parenteral ketorolac separately and to analyze results based on the type of surgery performed. We assessed the certainty of evidence using GRADE.
MAIN RESULTS
We included 12 studies, involving 1905 participants undergoing various surgeries (pelvic/abdominal, dental, and orthopedic), with 17 to 83 participants receiving intravenous ketorolac in each study. Mean study population ages ranged from 22.5 years to 67.4 years. Most studies administered a dose of ketorolac of 30 mg; one study assessed 15 mg, and another administered 60 mg. Most studies had an unclear risk of bias for some domains, particularly allocation concealment and blinding, and a high risk of bias due to small sample size. The overall certainty of evidence for each outcome ranged from very low to moderate. Reasons for downgrading certainty included serious study limitations, inconsistency and imprecision. Ketorolac versus placebo Very low-certainty evidence from eight studies (658 participants) suggests that ketorolac results in a large increase in the number of participants achieving at least 50% pain relief over four hours compared to placebo, but the evidence is very uncertain (risk ratio (RR) 2.81, 95% confidence interval (CI) 1.80 to 4.37). The number needed to treat for one additional participant to benefit (NNTB) was 2.4 (95% CI 1.8 to 3.7). Low-certainty evidence from 10 studies (914 participants) demonstrates that ketorolac may result in a large increase in the number of participants achieving at least 50% pain relief over six hours compared to placebo (RR 3.26, 95% CI 1.93 to 5.51). The NNTB was 2.5 (95% CI 1.9 to 3.7). Among secondary outcomes, for time to rescue medication, moderate-certainty evidence comparing intravenous ketorolac versus placebo demonstrated a mean median of 271 minutes for ketorolac versus 104 minutes for placebo (6 studies, 633 participants). For the number of participants using rescue medication, very low-certainty evidence from five studies (417 participants) compared ketorolac with placebo. The RR was 0.60 (95% CI 0.36 to 1.00), that is, it did not demonstrate a difference between groups. Ketorolac probably results in a slight increase in total adverse event rates compared with placebo (74% versus 65%; 8 studies, 810 participants; RR 1.09, 95% CI 1.00 to 1.19; number needed to treat for an additional harmful event (NNTH) 16.7, 95% CI 8.3 to infinite, moderate-certainty evidence). Serious AEs were rare. Low-certainty evidence from eight studies (703 participants) did not demonstrate a difference in rates between ketorolac and placebo (RR 0.62, 95% CI 0.13 to 3.03). Ketorolac versus NSAIDs Ketorolac was compared to parecoxib in four studies and diclofenac in two studies. For our primary outcome, over both four and six hours there was no evidence of a difference between intravenous ketorolac and another NSAID (low-certainty and moderate-certainty evidence, respectively). Over four hours, four studies (337 participants) produced an RR of 1.04 (95% CI 0.89 to 1.21) and over six hours, six studies (603 participants) produced an RR of 1.06 (95% CI 0.95 to 1.19). For time to rescue medication, low-certainty evidence from four studies (427 participants) suggested that participants receiving ketorolac waited an extra 35 minutes (mean median 331 minutes versus 296 minutes). For the number of participants using rescue medication, very low-certainty evidence from three studies (260 participants) compared ketorolac with another NSAID. The RR was 0.90 (95% CI 0.58 to 1.40), that is, there may be little or no difference between groups. Ketorolac probably results in a slight increase in total adverse event rates compared with another NSAID (76% versus 68%, 5 studies, 516 participants; RR 1.11, 95% CI 1.00 to 1.23; NNTH 12.5, 95% CI 6.7 to infinite, moderate-certainty evidence). Serious AEs were rare. Low-certainty evidence from five studies (530 participants) did not demonstrate a difference in rates between ketorolac and another NSAID (RR 3.18, 95% CI 0.13 to 76.99). Only one of the five studies reported a single serious AE.
AUTHORS' CONCLUSIONS
The amount and certainty of evidence for the use of intravenous ketorolac as a treatment for postoperative pain varies across efficacy and safety outcomes and amongst comparators, from very low to moderate. The available evidence indicates that postoperative intravenous ketorolac administration may offer substantial pain relief for most patients, but further research may impact this estimate. Adverse events appear to occur at a slightly higher rate in comparison to placebo and to other NSAIDs. Insufficient information is available to assess whether intravenous ketorolac has a different rate of gastrointestinal or surgical-site bleeding, renal dysfunction, or cardiovascular events versus other NSAIDs. There was a lack of studies in cardiovascular surgeries and in elderly populations who may be at increased risk for adverse events.
Topics: Acute Pain; Adult; Analgesics, Opioid; Anti-Inflammatory Agents, Non-Steroidal; Bias; Diclofenac; Humans; Injections, Intravenous; Isoxazoles; Ketorolac; Middle Aged; Numbers Needed To Treat; Pain, Postoperative; Placebos; Randomized Controlled Trials as Topic; Time Factors; Young Adult
PubMed: 33998669
DOI: 10.1002/14651858.CD013263.pub2 -
Frontiers in Pharmacology 2023This review of systematic reviews evaluated the effectiveness and safety of the preemptive use of anti-inflammatory and analgesic drugs in the management of...
This review of systematic reviews evaluated the effectiveness and safety of the preemptive use of anti-inflammatory and analgesic drugs in the management of postoperative pain, edema, and trismus in oral surgery. The databases searched included the Cochrane Library, MEDLINE, EMBASE, Epistemonikos, Scopus, Web of Science, and Virtual Health Library, up to March 2023. Pairs of reviewers independently selected the studies, extracted the data, and rated their methodological quality using the AMSTAR-2 tool. All of the 19 studies reviewed had at least two critical methodological flaws. Third molar surgery was the most common procedure ( = 15) and the oral route the most frequent approach ( = 14). The use of betamethasone (10, 20, and 60 mg), dexamethasone (4 and 8 mg), methylprednisolone (16, 20, 40, 60, 80, and 125 mg), and prednisolone (10 and 20 mg) by different routes and likewise of celecoxib (200 mg), diclofenac (25, 30, 50, 75, and 100 mg), etoricoxib (120 mg), ibuprofen (400 and 600 mg), ketorolac (30 mg), meloxicam (7.5, 10, and 15 mg), nimesulide (100 mg), and rofecoxib (50 mg) administered by oral, intramuscular, and intravenous routes were found to reduce pain, edema, and trismus in patients undergoing third molar surgery. Data on adverse effects were poorly reported. Further randomized clinical trials should be conducted to confirm these findings, given the wide variety of drugs, doses, and routes of administration used.
PubMed: 38328575
DOI: 10.3389/fphar.2023.1303382 -
World Journal of Gastrointestinal... Nov 2020Endoscopic retrograde cholangiopancreatography (ERCP) is the primary therapeutic procedure for the treatment of diseases affecting the biliary tree and pancreatic duct....
BACKGROUND
Endoscopic retrograde cholangiopancreatography (ERCP) is the primary therapeutic procedure for the treatment of diseases affecting the biliary tree and pancreatic duct. Although the therapeutic success rate of ERCP is high, the procedure can cause complications, such as acute pancreatitis [post-ERCP pancreatitis (PEP)], bleeding and perforation.
AIM
To assess the efficacy of non-steroidal anti-inflammatory drugs (NSAIDs) in preventing PEP during follow-up.
METHODS
Databases such as MEDLINE, EMBASE and Cochrane Central Library were searched. Only randomized controlled trials (RCTs) comparing the efficacy of NSAIDs and placebo for the prevention of PEP were included. Outcomes evaluated included the incidence of PEP, severity of pancreatitis, route of administration, types, dose, and timing of administration of NSAIDs.
RESULTS
Twenty-six RCTs were considered eligible with a total of 8143 patients analyzed. Overall, 4020 patients used NSAIDs before ERCP and 4123 did not use NSAIDs (control group). Ultimately, 298 cases of post-ERCP acute pancreatitis were diagnosed in the NSAID group and 484 cases in the placebo group. The risk of PEP was lower in the NSAID group risk difference (RD): -0.04; 95% confidence interval (CI): -0.07 to - 0.03; number needed to treat (NNT), 25; < 0.05. NSAID use effectively prevented mild pancreatitis compared to placebo use (2.5% 4.1%; 95%CI: -0.05 to -0.01; NNT, 33; < 0.05), but information on moderate PEP and severe PEP could not be fully elucidated. Only rectal administration reduced the incidence of PEP with RD: -0.06; 95%CI: -0.08 to -0.04; NNT, 17; < 0.05). Furthermore, only the use of diclofenac or indomethacin was effective in preventing PEP, at a dose of 100 mg, which must be administered before performing ERCP.
CONCLUSION
Rectal administration of diclofenac and indomethacin significantly reduced the risk of developing mild PEP. Additional RCTs are needed to compare the efficacy between NSAID routes of administration in preventing PEP.
PubMed: 33269056
DOI: 10.4253/wjge.v12.i11.469 -
Journal of Clinical Medicine Jul 2020Multiple interventions are available for the treatment of actinic keratosis (AK) showing high efficacy in pivotal trials. However, data from post-marketing surveillance...
Multiple interventions are available for the treatment of actinic keratosis (AK) showing high efficacy in pivotal trials. However, data from post-marketing surveillance studies have received little attention until now. Here, we systematically investigate interventions for AK from post-marketing surveillance trials as a proxy for real-world efficacy and tolerability. A systematic literature search was conducted in Medline, Embase, and CENTRAL. Pertinent trial registers were hand-searched until 25 March 2020. Results were pooled using a random-effects model to calculate pooled proportions and relative risks (RR) or were described qualitatively. Eleven records with a total sample size of = 4109 were included. Three of the studies had an active-controlled design, while seven were single-armed. Participant complete clearance ranged from 23.1% for diclofenac sodium 3% gel to 88.9% for ingenol mebutate 0.05% gel. The lesion-specific clearance rate for photodynamic therapy (PDT) was 74% (95% confidence interval (CI) 56-87%). The recurrence rate was significantly higher for diclofenac sodium 3% in comparison to imiquimod 5% cream (RR 1.10, 95% CI 1.02-1.1.8) and ranged from 10.6% for ingenol mebutate 0.015% gel to 23.5% for PDT. Few patients discontinued the trials due to adverse events. The results from the majority of the post-marketing surveillance studies deviated from those of pivotal trials.
PubMed: 32679902
DOI: 10.3390/jcm9072253 -
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 -
Journal of Dental Anesthesia and Pain... Feb 2021This study aimed to evaluate and compare the pre-emptive analgesic efficacy of injected ketorolac to that of other agents for impacted third molar surgical removal in a... (Review)
Review
This study aimed to evaluate and compare the pre-emptive analgesic efficacy of injected ketorolac to that of other agents for impacted third molar surgical removal in a healthy population. PubMed, Ovid SP, Cochrane databases were filtered from 1980 to July 2020 for potential papers using relevant MeSH terms and pre-specified inclusion and exclusion criteria independently by reviewers. Studies that compared pre-emptive intramuscular or intravenous administration of ketorolac to other agents were evaluated. The outcomes sought were self-reported postoperative pain (patient-perceived pain), median duration for rescue analgesic medication, total number of analgesics consumed in the recovery period, and global assessment (overall patient satisfaction) after the recovery period. Six studies were included in the final evaluation. The outcome of pain perception and the number of analgesics taken were significantly lower in the ketorolac group (intramuscular or intravenous) in most of the studies (n=5) than in the group of other drugs. The mean time for rescue analgesia intake was higher for the ketorolac group, and global assessment scores were also better in the ketorolac group. Although the included studies show significantly better outcomes such as postoperative pain, median time taken for rescue medication, total number of analgesics taken, and overall patient satisfaction with injected ketorolac group in comparison to injected diclofenac, dexamethasone, and tramadol, definitive conclusions cannot be made regarding the superiority of injected Ketorolac as a pre-emptive agent. A greater number of randomized control trials with a proper protocol are needed to make definitive conclusions.
PubMed: 33585680
DOI: 10.17245/jdapm.2021.21.1.1 -
Turkish Journal of Urology Jul 2021Extracorporeal Shock Wave Lithotripsy (ESWL) is one of the treatment options for patients with renal and ureteral calculi. Even though the procedure is less invasive...
Extracorporeal Shock Wave Lithotripsy (ESWL) is one of the treatment options for patients with renal and ureteral calculi. Even though the procedure is less invasive compared to others, pain caused by the procedure is a major concern. Several studies recommended the use of either local or systemic analgesia with varying results. We aimed to compare the use of local anesthetics and systemic analgesics from randomized controlled trials evaluating pain management during ESWL. A systematic search adhering to the Preferred Reporting Items for Systematic Review and Meta-Analysis protocol was performed in theMedline, ScienceDirect, and Cochrane library databases. The bias was evaluated using the Cochrane risk of bias tool. Mean difference (MD) was used to analyze continuous outcomes. A total of seven studies were obtained. The topical anesthesia used was eutectic mixture of local anesthetic cream and xylocaine gel. In contrast, the local injection anesthesia used was subcutaneous prilocaine and intracutaneous sterile water injection. The systemic analgesics used were intramuscular and oral forms of sodium diclofenac. There is no significant difference between the visual analogue scale results between the local and systemic groups (P> .05). The differences in ESWL frequency were also insignificant (P > .05). Additional analgesics supplementation (MD 8.44, 95% CI 2.28-14.61, P¼ .007) and the duration of the procedure (MD 1.39, 95% CI 0.21-2.56, P¼ .02) were significantly lower in the local group. Local anesthesia in ESWL shows a similar degree of pain and frequency but has a shorter duration and fewer analgesics supplementation than systemic analgesics.
PubMed: 35118950
DOI: 10.5152/tju.2021.21143 -
PloS One 2020This study aimed to review previous articles and evaluate the influence of topical non-steroidal anti-inflammatory drugs (NSAIDs) on intraocular pressure (IOP) in... (Meta-Analysis)
Meta-Analysis Review
The influence of topical non-steroidal anti-inflammatory drugs on the intraocular pressure lowering effect of topical prostaglandin analogues-A systemic review and meta-analysis.
PURPOSE
This study aimed to review previous articles and evaluate the influence of topical non-steroidal anti-inflammatory drugs (NSAIDs) on intraocular pressure (IOP) in glaucoma patients who were treated with prostaglandin analogues (PGs).
METHOD
The presenting study was designed as a meta-analysis of previous research. Databases include PubMed, Web of science, Cochrane library, and Embase were searched with keywords of "intraocular pressure, prostaglandin analogues, NSAIDs, latanoprost, travoprost, bimatoprost, tafluprost, unoprostone, latanoprostene bunod, ketorolac, diclofenac, nepafenac, bromfenac, flurbiprofen". Inclusion criteria were: 1. Study population were glaucoma patients; 2. Comparison between PGs monotherapy and PGs in combination with topical NSAIDs; 3. Changes of IOP as final outcomes. Studies with non-randomized design, treatments combining other anti-glaucomatous drugs, or unavailable absolute IOP were excluded from the analysis. Estimated difference in IOP were calculated using STATA 14.0.
RESULT
Seven studies were retrieved for this meta-analysis. Since there is a significant heterogeneity (I2 = 94%) in these studies, random-effect model was used to calculate pooled standardized mean differences (SMD). Our results showed a significantly favorable IOP lowering effect in glaucoma patients treated with combination of topical NSAIDs and PGEs (SMD: 1.3 and -0.03, 95% CI: 0.29 to 2.38 and -0.32 to 0.26, Z = 2.50 and 0.23, p = 0.013 and 0.820, respectively).
CONCLUSION
Results of our meta-analysis suggested that topical NSAIDs may enhance the IOP lowering effect of topical PGs in glaucoma patients.
Topics: Administration, Topical; Anti-Inflammatory Agents, Non-Steroidal; Glaucoma; Humans; Intraocular Pressure; Prostaglandins, Synthetic; Tonometry, Ocular
PubMed: 32925955
DOI: 10.1371/journal.pone.0239233