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Graefe's Archive For Clinical and... Apr 2017Non-steroidal anti-inflammatory drugs (NSAIDs) are a class of anti-inflammatory drugs that are used in ophthalmologic surgery. These drugs do not have a steroid... (Meta-Analysis)
Meta-Analysis Review
The comparative efficacy and safety of topical non-steroidal anti-inflammatory drugs for the treatment of anterior chamber inflammation after cataract surgery: a systematic review and network meta-analysis.
PURPOSE
Non-steroidal anti-inflammatory drugs (NSAIDs) are a class of anti-inflammatory drugs that are used in ophthalmologic surgery. These drugs do not have a steroid structure, but can inhibit surgery-induced miosis, anterior chamber inflammation, and cystoid macular edema (CME). However, the application of NSAIDs remains controversial. Therefore, we performed a meta-analysis to assess the efficacy and safety of NSAIDs for the treatment of anterior chamber inflammation after cataract surgery.
METHODS
Relevant articles were identified from the PubMed, Embase, and Cochrane databases up to October 2016. The therapeutic effect of NSAIDs on anterior chamber inflammation was evaluated. The important outcomes of overall anterior chamber inflammation, freedom from ocular pain, and treatment-related/serious ocular adverse events were analyzed by using a random-effects network meta-analysis. The quality of evidence was assessed via the Grading of Recommendation Assessment, Development, and Evaluation (GRADE) approach.
RESULTS
A total of 19 trials assessing 7,234 patients were included in our meta-analysis. Diclofenac was the most likely to improve anterior chamber inflammation after cataract surgery, followed by nepafenac, ketorolac, bromfenac, and flurbiprofen. Nepafenac was most likely to improve postoperative ocular pain relief, followed by bromfenac and ketorolac. Our analysis of treatment-related/serious ocular adverse events revealed that piroxicam was most likely to have the fewest related adverse events, but the robustness of this finding was low. Diclofenac was another near-ideal drug, followed by nepafenac, bromfenac, and ketorolac.
CONCLUSIONS
NSAIDs are effective drugs compared to placebos for the relief of anterior chamber inflammation. Furthermore, diclofenac, nepafenac, ketorolac, and bromfenac demonstrated relatively greater significant effects than those of other NSAIDs.
Topics: Administration, Topical; Anterior Chamber; Anti-Inflammatory Agents, Non-Steroidal; Cataract Extraction; Endophthalmitis; Humans; Surgical Wound Infection; Treatment Outcome
PubMed: 28130595
DOI: 10.1007/s00417-017-3599-8 -
The Cochrane Database of Systematic... Apr 2016Progressive lung damage causes most deaths in cystic fibrosis. Non-steroidal anti-inflammatory drugs (such as ibuprofen) may prevent progressive pulmonary deterioration... (Meta-Analysis)
Meta-Analysis Review
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.
OBJECTIVES
To assess the effectiveness of treatment with 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.Latest search of the Group's Trials Register: 04 February 2016.
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.
MAIN RESULTS
The searches identified 10 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. Three trials compared ibuprofen to placebo (two from the same centre 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 significantly lower annual rate of decline for lung function, percent predicted forced expiratory volume in one second mean difference 1.32 (95% confidence interval 0.21 to 2.42); forced vital capacity mean difference 1.27 (95% confidence interval 0.26 to 2.28); forced expiratory flow (25-75%) mean difference 1.80 (95% confidence interval 0.15 to 3.45). The post-hoc analysis of data from two trials split by age showed a statistically significant slower rate of annual decline of percent predicted forced expiratory volume in one second and forced vital capacity in the ibuprofen group in younger children, mean difference 1.41% (95% confidence interval 0.03 to 2.80) and mean difference 1.32% (95% confidence interval 0.04 to 2.60) respectively. 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 analyse 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 analysable 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-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Child; Child, Preschool; Cystic Fibrosis; Humans; Ibuprofen; Lung; Piroxicam; Randomized Controlled Trials as Topic
PubMed: 27055154
DOI: 10.1002/14651858.CD001505.pub4 -
The Cochrane Database of Systematic... Feb 2016Chronic back pain is an important health problem. Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to treat people with low back pain, especially people... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Chronic back pain is an important health problem. Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to treat people with low back pain, especially people with acute back pain. Short term NSAID use is also recommended for pain relief in people with chronic back pain. Two types of NSAIDs are available and used to treat back pain: non-selective NSAIDs and selective COX-2 NSAIDs. In 2008, a Cochrane review identified a small but significant effect from NSAIDs compared to placebo in people with chronic back pain. This is an update of the Cochrane review published in 2008 and focuses on people with chronic low back pain.
OBJECTIVES
To determine if NSAIDs are more efficacious than various comparison treatments for non-specific chronic low back pain and if so, which type of NSAID is most efficacious.
SEARCH METHODS
We searched CENTRAL, MEDLINE, EMBASE, PubMed and two clinical trials registry databases up to 24 June 2015 for randomized controlled trials (RCTs) published in English, German or Dutch. We also screened references cited in relevant reviews.
SELECTION CRITERIA
We included RCTs (double-blind and single-blind) of NSAIDs used to treat people with chronic low back pain.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened trials for inclusion in this Cochrane review according to the inclusion criteria. One review author extracted the data, and a second review author checked the data. Two review authors independently evaluated the risk of bias of all included trials. If data were clinically homogeneous, we performed a meta-analysis and assessed the quality of evidence using the GRADE approach.
MAIN RESULTS
We included 13 trials in this Cochrane review. Ten studies were at 'low' risk of bias. Six studies compared NSAIDs with placebo, and included 1354 participants in total. There is low quality evidence that NSAIDs are more effective than placebo, with a mean difference in pain intensity score from baseline of -3.30 (95% CI -5.33 to -1.27) on a 0 to 100 visual analogue scale (VAS) with a median follow-up of 56 days (interquartile range (IQR) 13 to 91 days). Four studies measured disability using the Roland Morris Disability Questionnaire. There is low quality evidence that NSAIDs are more effective than placebo on disability, with a mean difference from baseline of -0.85 (95% CI -1.30 to -0.40) on a scale from 0 to 24 with a median follow-up of 84 days (IQR 42 to 105 days). All six placebo controlled studies also reported adverse events, and suggested that adverse events are not statistically significant more frequent in participants using NSAIDs compared to placebo (RR 1.04, 95% CI 0.92 to 1.17). Due to the relatively small sample size and relatively short follow-up in most included trials, it is likely that the proportion of patients experiencing an adverse event is underestimated.Two studies compared different types of non-selective NSAIDs, namely ibuprofen versus diclofenac and piroxicam versus indomethacin. The trials did not find any differences between these NSAID types, but both trials had small sample sizes. One trial reported no differences in pain intensity between treatment groups that used selective or non-selective NSAIDs. One other trial compared diflunisal with paracetamol and showed no difference in improvement from baseline on pain intensity score. One trial showed a better global improvement in favour of celecoxib versus tramadol.One included trial compared NSAIDs with 'home-based exercise'. Disability improved more in participants who did exercises versus participants receiving NSAIDs, but pain scores were similar.
AUTHORS' CONCLUSIONS
Six of the 13 included RCTs showed that NSAIDs are more effective than placebo regarding pain intensity. NSAIDs are slightly more effective than placebo regarding disability. However, the magnitude of the effects is small, and the level of evidence was low. When we only included RCTs at low risk of bias, differences in effect between NSAIDs and placebo were reduced. We identified no difference in efficacy between different NSAID types, including selective versus non-selective NSAIDs. Due to inclusion of RCTs only, the relatively small sample sizes and relatively short follow-up in most included trials, we cannot make firm statements about the occurrence of adverse events or whether NSAIDs are safe for long-term use.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Chronic Pain; Diclofenac; Disability Evaluation; Humans; Ibuprofen; Indomethacin; Low Back Pain; Pain Measurement; Piroxicam; Randomized Controlled Trials as Topic
PubMed: 26863524
DOI: 10.1002/14651858.CD012087 -
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 -
International Urogynecology Journal May 2016Bladder pain syndrome/interstitial cystitis (BPS/IC) has various treatments; however, no standardized treatment has been established. The aim was to analyze different... (Review)
Review
INTRODUCTION AND HYPOTHESIS
Bladder pain syndrome/interstitial cystitis (BPS/IC) has various treatments; however, no standardized treatment has been established. The aim was to analyze different types of treatment of BPS/IC and their effectiveness.
METHODS
A literature review with a search strategy for articles related to BPS/IC published between 1990 and 2014 was conducted on MEDLINE, PUBMED, and SCOPUS. Only randomized controlled trials in women were included in the meta-analysis, while other experimental studies were used as bases for a systematic review of the topic. Clinical trial quality was defined according to the Jadad scale.
RESULTS
Of 356 articles, 13 were included in the analysis. The intervention methods were as follows: instillation of hyaluronic acid, botulinum toxin A, intravesical lidocaine, hyperbaric chamber, massage, physiotherapy, phosphate-buffered saline, piroxicam in combination with doxepin, and others. We did not find any treatment with at least two randomized controlled trials for meta-analysis. Among the assessment tools for symptoms of BPS/IC, the most frequently used were the visual analogue scale, voiding record, and the O'Leary-Sant questionnaire.
CONCLUSION
Existing studies were not able to define the best approach for the treatment of BPS/IC. The lack of standardized treatment may be related to the diversity of interventions used; therefore, further studies with better methodological quality are needed.
Topics: Acetylcholine Release Inhibitors; Adjuvants, Immunologic; Administration, Intravesical; Anesthetics, Local; Anti-Inflammatory Agents, Non-Steroidal; Antidepressive Agents; Botulinum Toxins, Type A; Cystitis, Interstitial; Drug Therapy, Combination; Female; Humans; Hyaluronic Acid; Hyperbaric Oxygenation; Lidocaine; Pentosan Sulfuric Polyester; Physical Therapy Modalities; Sodium Chloride
PubMed: 26272202
DOI: 10.1007/s00192-015-2815-5 -
The Cochrane Database of Systematic... Jul 2015Tension-type headache (TTH) affects about one person in five worldwide. It is divided into infrequent episodic TTH (fewer than one headache per month), frequent episodic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Tension-type headache (TTH) affects about one person in five worldwide. It is divided into infrequent episodic TTH (fewer than one headache per month), frequent episodic TTH (1 to 14 headaches per month), and chronic TTH (15 headaches a month or more). Ibuprofen is one of a number of analgesics suggested for acute treatment of headaches in frequent episodic TTH.
OBJECTIVES
To assess the efficacy and safety of oral ibuprofen for treatment of acute episodic TTH in adults.
SEARCH METHODS
We searched CENTRAL (The Cochrane Library), MEDLINE, EMBASE, and our own in-house database to January 2015. We sought unpublished studies by asking personal contacts and searching on-line clinical trial registers and manufacturers' websites.
SELECTION CRITERIA
We included randomised, placebo-controlled studies (parallel-group or cross-over) using oral ibuprofen for symptomatic relief of an acute episode of TTH. Studies had to be prospective and include at least 10 participants per treatment arm.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed studies for inclusion, and extracted data. Numbers of participants achieving each outcome were used to calculate risk ratio (RR) and number needed to treat for an additional beneficial outcome (NNT) or number needed to treat for an additional harmful outcome (NNH) of oral ibuprofen compared to placebo for a range of outcomes, predominantly those recommended by the International Headache Society (IHS).
MAIN RESULTS
We included 12 studies, all of which enrolled adult participants with frequent episodic TTH. Nine used the IHS diagnostic criteria, but two used the older classification of the Ad Hoc Committee, and one did not describe diagnostic criteria but excluded participants with migraines. While 3094 people with TTH participated in these studies, the numbers available for any form of analysis were lower than this; placebo was taken by 733, standard ibuprofen 200 mg by 127, standard ibuprofen 400 mg by 892, and fast-acting ibuprofen 400 mg by 230. Participants had moderate or severe pain at the start of treatment. Other participants were either in studies not reporting outcomes we could analyse, or were given one of several active comparators in single studies.For the IHS-preferred outcome of being pain free at 2 hours the NNT for ibuprofen 400 mg (all formulations) compared with placebo was 14 (95% confidence interval (CI), 8.4 to 47) in four studies, with no significant difference from placebo at 1 hour (moderate quality evidence). The NNT was 5.9 (4.2 to 9.5) for the global evaluation of 'very good' or 'excellent' in three studies (moderate quality evidence). No study reported the number of participants experiencing no worse than mild pain at 1 or 2 hours. The use of rescue medication was lower with ibuprofen 400 mg than with placebo, with the number needed to treat to prevent one event (NNTp) of 8.9 (5.6 to 21) in two studies (low quality evidence).Adverse events were not different between ibuprofen 400 mg and placebo; RR 1.1 (0.64 to 1.7) (high-quality evidence). No serious adverse events were reported.
AUTHORS' CONCLUSIONS
Ibuprofen 400 mg provides an important benefit in terms of being pain free at 2 hours for a small number of people with frequent episodic tension-type headache who have an acute headache with moderate or severe initial pain. There is no information about the lesser benefit of no worse than mild pain at 2 hours.
Topics: Acetaminophen; Administration, Oral; Adult; Analgesics, Non-Narcotic; Cyclooxygenase Inhibitors; Diclofenac; Humans; Ibuprofen; Ketoprofen; Naproxen; Numbers Needed To Treat; Pain Measurement; Piroxicam; Randomized Controlled Trials as Topic; Tension-Type Headache; Time Factors
PubMed: 26230487
DOI: 10.1002/14651858.CD011474.pub2 -
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 -
The Cochrane Database of Systematic... Jun 2015Use of topical NSAIDs to treat acute musculoskeletal conditions has become widely accepted because they can provide pain relief without associated systemic adverse... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Use of topical NSAIDs to treat acute musculoskeletal conditions has become widely accepted because they can provide pain relief without associated systemic adverse events. This review is an update of 'Topical NSAIDs for acute pain in adults' originally published in Issue 6, 2010.
OBJECTIVES
To determine the efficacy and safety of topically applied NSAIDs in acute musculoskeletal pain in adults.
SEARCH METHODS
We searched the Cochrane Register of Studies Online, MEDLINE, and EMBASE to February 2015. We sought unpublished studies by asking personal contacts and searching online clinical trial registers and manufacturers websites. For the earlier review, we also searched our own in-house database and contacted manufacturers.
SELECTION CRITERIA
We included randomised, double-blind, active or placebo (inert carrier)-controlled trials in which treatments were administered to adults with acute pain resulting from strains, sprains or sports or overuse-type injuries (twisted ankle, for instance). There had to be at least 10 participants in each treatment arm, with application of treatment at least once daily.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed studies for inclusion, and extracted data. We used numbers of participants achieving each outcome to calculate the risk ratio and numbers needed to treat for an additional beneficial outcome (NNT) or additional harmful outcome (NNH) compared with placebo or other active treatment. We reported 95% confidence intervals (CI). We were particularly interested to compare different formulations (gel, cream, plaster) of individual NSAIDs.
MAIN RESULTS
For this update we added 14 new included studies (3489 participants), and excluded four studies. We also identified 20 additional reports of completed or ongoing studies that have not been published in full. The earlier review included 47 studies.This update included 61 studies. Most compared topical NSAIDs in the form of a gel, spray, or cream with a similar topical placebo; 5311 participants were treated with a topical NSAID, 3470 with placebo, and 220 with an oral NSAID. This was a 63% increase in the number of included participants over the previous version of this review. We also identified a number of studies in clinical trial registries with unavailable results amounting to about 5900 participants for efficacy and 5300 for adverse events.Formulations of topical diclofenac, ibuprofen, ketoprofen, piroxicam, and indomethacin demonstrated significantly higher rates of clinical success (more participants with at least 50% pain relief) than matching topical placebo (moderate or high quality data). Benzydamine did not. Three drug and formulation combinations had NNTs for clinical success below 4. For diclofenac, the Emulgel® formulation had the lowest NNT of 1.8 (95% CI 1.5 to 2.1) in two studies using at least 50% pain intensity reduction as the outcome. Diclofenac plasters other than Flector® also had a low NNT of 3.2 (2.6 to 4.2) based on good or excellent responses in some studies. Ketoprofen gel had an NNT of 2.5 (2.0 to 3.4), from five studies in the 1980s, some with less well defined outcomes. Ibuprofen gel had an NNT of 3.9 (2.7 to 6.7) from two studies with outcomes of marked improvement or complete remission. All other drug and formulation combinations had NNT values above 4, indicating lesser efficacy.There were insufficient data to compare reliably individual topical NSAIDs with each other or the same oral NSAID.Local skin reactions were generally mild and transient, and did not differ from placebo (high quality data). There were very few systemic adverse events (high quality data) or withdrawals due to adverse events (low quality data).
AUTHORS' CONCLUSIONS
Topical NSAIDs provided good levels of pain relief in acute conditions such as sprains, strains and overuse injuries, probably similar to that provided by oral NSAIDs. Gel formulations of diclofenac (as Emugel®), ibuprofen, and ketoprofen, and some diclofenac patches, provided the best effects. Adverse events were usually minimal.Since the last version of this review, the new included studies have provided additional information. In particular, information on topical diclofenac is greatly expanded. The present review supports the previous review in concluding that topical NSAIDs are effective in providing pain relief, and goes further to demonstrate that certain formulations, mainly gel formulations of diclofenac, ibuprofen, and ketoprofen, provide the best results. Large amounts of unpublished data have been identified, and this could influence results in updates of this review.
Topics: Acute Pain; Administration, Topical; Adult; Anti-Inflammatory Agents, Non-Steroidal; Athletic Injuries; Humans; Musculoskeletal Pain; Randomized Controlled Trials as Topic; Sprains and Strains
PubMed: 26068955
DOI: 10.1002/14651858.CD007402.pub3 -
European Journal of Internal Medicine May 2015The association between acute kidney injury (AKI) and use of non-steroidal anti-inflammatory drugs (NSAIDs) is well established. However, little is known about the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The association between acute kidney injury (AKI) and use of non-steroidal anti-inflammatory drugs (NSAIDs) is well established. However, little is known about the comparative risk of individual NSAIDs, including specific COX-2 inhibitors.
METHODS
We conducted a systematic review and meta-analysis of cohort studies that reported relative risk, hazard ratio or standardized incidence ratio with 95% confidence comparing AKI risk in NSAID users versus non-users. Pooled risk ratios and 95% confidence intervals for individual NSAIDs were calculated using random-effect, generic inverse variance methods.
RESULTS
Five studies were identified and included in our data analysis. Pooled risk ratios were calculated for seven traditional NSAIDs and two specific COX-2 inhibitors, including indomethacin, piroxicam, ibuprofen, naproxen, sulindac, diclofenac, meloxicam, rofecoxib and celecoxib that were evaluated in at least two studies. Our meta-analysis was able to demonstrate a statistically significant elevated AKI risk among most of the included traditional NSAIDs. The pooled risk ratios were fairly consistent among individual traditional NSAIDs, ranging from 1.58 to 2.11. Differences between pooled risk ratios did not reach statistical significance (p≥0.19 for each comparison). Elevated AKI risk was also observed in diclofenac, meloxicam, rofecoxib and celecoxib users, although did not achieve a statistical significance.
CONCLUSION
A statistically significant elevated AKI risk among traditional NSAID users has been demonstrated in this meta-analysis. The pooled risk ratios among individual traditional NSAIDs were not significantly different. The pooled risk ratios of specific COX-2 inhibitors and the two traditional NSAIDs with the most COX-2 selectivity (diclofenac and meloxicam) were also comparable with other traditional NSAIDs even though they did not achieve a statistical significance.
Topics: Acute Kidney Injury; Anti-Inflammatory Agents, Non-Steroidal; Cyclooxygenase 2 Inhibitors; Humans; Observational Studies as Topic; Odds Ratio; Risk Factors
PubMed: 25862494
DOI: 10.1016/j.ejim.2015.03.008 -
Otolaryngology--head and Neck Surgery :... Mar 2015To perform a systematic review evaluating the association between sensorineural hearing loss and (1) nonsteroidal anti-inflammatory drugs (NSAIDs) as a class, (2) NSAIDs... (Review)
Review
OBJECTIVE
To perform a systematic review evaluating the association between sensorineural hearing loss and (1) nonsteroidal anti-inflammatory drugs (NSAIDs) as a class, (2) NSAIDs available over the counter, (3) NSAIDs in short intravenous courses, (4) prescription NSAIDs utilized by patients without systemic inflammatory conditions, (5) prescription NSAIDs in patients with arthritides, and (6) acetaminophen with and without concomitant narcotic usage.
DATA SOURCES
Computerized searches of PubMed, EMBASE, and the Cochrane Library were updated through May 2014, along with manual searches and inquiries to topic experts.
REVIEW METHODS
The systematic review was performed according to an a priori protocol. Data extraction was performed by 2 independent investigators, and it focused on relevant audiologic measurements, methodological elements related to risk of bias, and potential confounders.
RESULTS
The 23 criterion-meeting studies included a total of 92,532 participants, with mixed results. Sulindac was the only specific agent to have been studied with formal audiometry in a randomized double-blind placebo-controlled trial in which hearing was the reported primary outcome: Although an effect was seen in the unadjusted analysis (pure tone threshold>15 dB, 9.3% vs 2.9%; relative risk [RR], 3.2; confidence interval [CI], 1.09-9.55; P=.02), the effect dissipated in the adjusted analysis (P=.09). There was a significant effect on self-reported hearing loss from NSAIDs as a class (RR, 1.21; CI, 1.11-1.33), ibuprofen (RR, 1.13; CI, 1.06-1.19), and acetaminophen (RR, 1.21; CI, 1.11-1.33), but no formal audiometric data confirm or refute this suggested effect. Audiometry has demonstrated profound loss in some instances of acetaminophen-narcotic combination ingestions.
CONCLUSIONS
Data are varied regarding the impact of NSAIDs and acetaminophen on population hearing health.
Topics: Acetaminophen; Analgesics, Non-Narcotic; Anti-Inflammatory Agents, Non-Steroidal; Audiometry; Hearing; Hearing Loss, Sensorineural; Humans; Risk Factors
PubMed: 25560405
DOI: 10.1177/0194599814564533