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Acta Dermato-venereologica Jan 2021A systematic literature review was conducted to identify and qualitatively assess randomized controlled trials in immunocompetent patients ≥ 18 years with head-... (Meta-Analysis)
Meta-Analysis
A systematic literature review was conducted to identify and qualitatively assess randomized controlled trials in immunocompetent patients ≥ 18 years with head- region lesions of actinic keratoses who were treated with field-directed, lesion-directed and other therapies. Network meta-analysis was used to quantitatively evaluate field-directed therapies (5-fluorouracil formulations, diclofenac sodium, imiquimod, ingenol mebutate, 5-aminolevulinic acid or methyl aminolevulinate plus photodynamic therapy) using complete clearance or partial clearance of actinic keratoses lesions, and adverse event-related withdrawals as a proxy of acceptability. Of 2,863 references identified, 75 trials reported in 151 publications were included. In summary, comparative network meta-analysis evaluation showed that 5-fluorouracil formulations were the most efficacious interventions examined. 5-fluorouracil 4%, which was recently approved, showed a comparable efficacy profile to 5-fluorouracil 5%, and had satisfactory acceptability outcomes.
Topics: Diterpenes; Humans; Imiquimod; Keratosis, Actinic; Network Meta-Analysis; Photochemotherapy; Treatment Outcome
PubMed: 33170301
DOI: 10.2340/00015555-3690 -
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 -
BMJ Open Sep 2020To assess the comparative efficacy of traditional non-steroidal anti-inflammatory drugs (NSAIDs) and selective cyclo-oxygenase-2 inhibitors in patients with acute gout. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To assess the comparative efficacy of traditional non-steroidal anti-inflammatory drugs (NSAIDs) and selective cyclo-oxygenase-2 inhibitors in patients with acute gout.
DESIGN
Systematic review and meta-analysis.
DATA SOURCES
Medline, Web of Science, China National Knowledge Infrastructure and Wanfang Data published as of 4 April 2020.
METHODS
We performed meta-analysis of randomised controlled trials (RCTs) of traditional non-selective NSAIDs versus cyclo-oxygenase-2 inhibitors and RCTs of various cyclo-oxygenase-2 inhibitors in patients with acute gout. The main outcome measures were mean change in pain Visual Analogue Scale (VAS) score and 5-point Likert scale score on days 2-8.
RESULTS
Twenty-four trials involving five drugs were evaluated. For pain Likert scale, etoricoxib was comparable to indomethacin (standardised mean difference (SMD): -0.09, 95% CI: -0.27 to 0.08) but better than diclofenac 50 mg three times a day (SMD: -0.53, 95% CI: -0.98 to 0.09). Regarding pain VAS score, etoricoxib was comparable to diclofenac 75 mg two times per day (SMD: -1.63, 95% CI: -4.60 to 1.34) and diclofenac 75 mg four times a day (SMD: -1.82, 95% CI: -5.18 to 1.53), while celecoxib was comparable to diclofenac 100 mg four times a day (SMD: -2.41, 95% CI: -5.91 to 1.09). Etoricoxib showed similar patients' global assessment of response (SMD: -0.10, 95% CI: -0.27 to 0.07) and swollen joint count (SMD: -0.25, 95% CI: -0.74 to 0.24), but better investigator's global assessment of response (SMD: -0.29, 95% CI: -0.46 to 0.11) compared with indomethacin. Etoricoxib showed more favourable pain VAS score than celecoxib (SMD: -2.36, 95% CI: -3.36 to 1.37), but was comparable to meloxicam (SMD: -4.02, 95% CI: -10.28 to 2.24). Etoricoxib showed more favourable pain Likert scale than meloxicam (SMD: -0.56, 95% CI: -1.10 to 0.02). Etoricoxib 120 mg four times a day was more likely to achieve clinical improvement than celecoxib 200 mg two times per day (OR: 4.84, 95% CI: 2.19 to 10.72).
CONCLUSION
Although cyclo-oxygenase-2 inhibitors and traditional non-selective NSAIDs may be equally beneficial in terms of pain relief, cyclo-oxygenase-2 inhibitors (especially etoricoxib) may confer a greater benefit.
Topics: Anti-Inflammatory Agents, Non-Steroidal; China; Diclofenac; Etoricoxib; Gout; Humans
PubMed: 32912981
DOI: 10.1136/bmjopen-2019-036748 -
Annals of Internal Medicine Nov 2020Patients and clinicians can choose from several treatment options to address acute pain from non-low back, musculoskeletal injuries. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Patients and clinicians can choose from several treatment options to address acute pain from non-low back, musculoskeletal injuries.
PURPOSE
To assess the comparative effectiveness of outpatient treatments for acute pain from non-low back, musculoskeletal injuries by performing a network meta-analysis of randomized clinical trials (RCTs).
DATA SOURCES
MEDLINE, EMBASE, CINAHL, PEDro (Physiotherapy Evidence Database), and Cochrane Central Register of Controlled Trials to 2 January 2020.
STUDY SELECTION
Pairs of reviewers independently identified interventional RCTs that enrolled patients presenting with pain of up to 4 weeks' duration from non-low back, musculoskeletal injuries.
DATA EXTRACTION
Pairs of reviewers independently extracted data. Certainty of evidence was evaluated by using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach.
DATA SYNTHESIS
The 207 eligible studies included 32 959 participants and evaluated 45 therapies. Ninety-nine trials (48%) enrolled populations with diverse musculoskeletal injuries, 59 (29%) included patients with sprains, 13 (6%) with whiplash, and 11 (5%) with muscle strains; the remaining trials included various injuries ranging from nonsurgical fractures to contusions. Topical nonsteroidal anti-inflammatory agents (NSAIDs) proved to have the greatest net benefit, followed by oral NSAIDs and acetaminophen with or without diclofenac. Effects of these agents on pain were modest (around 1 cm on a 10-cm visual analogue scale, approximating the minimal important difference). Regarding opioids, compared with placebo, acetaminophen plus an opioid improved intermediate pain (1 to 7 days) but not immediate pain (≤2 hours), tramadol was ineffective, and opioids increased the risk for gastrointestinal and neurologic harms (all moderate-certainty evidence).
LIMITATIONS
Only English-language studies were included. The number of head-to-head comparisons was limited.
CONCLUSION
Topical NSAIDs, followed by oral NSAIDs and acetaminophen with or without diclofenac, showed the most convincing and attractive benefit-harm ratio for patients with acute pain from non-low back, musculoskeletal injuries. No opioid achieved benefit greater than that of NSAIDs, and opioids caused the most harms.
PRIMARY FUNDING SOURCE
National Safety Council. (PROSPERO: CRD42018094412).
Topics: Acetaminophen; Acute Pain; Administration, Oral; Administration, Topical; Analgesics, Opioid; Anti-Inflammatory Agents, Non-Steroidal; Comparative Effectiveness Research; Diclofenac; Drug Eruptions; Gastrointestinal Diseases; Humans; Musculoskeletal System; Nervous System Diseases; Network Meta-Analysis; Patient Satisfaction; Physical Functional Performance; Randomized Controlled Trials as Topic
PubMed: 32805127
DOI: 10.7326/M19-3601 -
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 -
Critical Care Explorations Jul 2020This systematic review and meta-analysis addresses the efficacy and safety of nonopioid adjunctive analgesics for patients in the ICU.
UNLABELLED
This systematic review and meta-analysis addresses the efficacy and safety of nonopioid adjunctive analgesics for patients in the ICU.
DATA SOURCES
We searched PubMed, Embase, the Cochrane Library, CINAHL Plus, and Web of Science.
STUDY SELECTION
Two independent reviewers screened citations. Eligible studies included randomized controlled trials comparing efficacy and safety of an adjuvant-plus-opioid regimen to opioids alone in adult ICU patients.
DATA EXTRACTION
We conducted duplicate screening of citations and data abstraction.
DATA SYNTHESIS
Of 10,949 initial citations, we identified 34 eligible trials. These trials examined acetaminophen, carbamazepine, clonidine, dexmedetomidine, gabapentin, ketamine, magnesium sulfate, nefopam, nonsteroidal anti-inflammatory drugs (including diclofenac, indomethacin, and ketoprofen), pregabalin, and tramadol as adjunctive analgesics. Use of any adjuvant in addition to an opioid as compared to an opioid alone led to reductions in patient-reported pain scores at 24 hours (standard mean difference, -0.88; 95% CI, -1.29 to -0.47; low certainty) and decreased opioid consumption (in oral morphine equivalents over 24 hr; mean difference, 25.89 mg less; 95% CI, 19.97-31.81 mg less; low certainty). In terms of individual medications, reductions in opioid use were demonstrated with acetaminophen (mean difference, 36.17 mg less; 95% CI, 7.86-64.47 mg less; low certainty), carbamazepine (mean difference, 54.69 mg less; 95% CI, 40.39-to 68.99 mg less; moderate certainty), dexmedetomidine (mean difference, 10.21 mg less; 95% CI, 1.06-19.37 mg less; low certainty), ketamine (mean difference, 36.81 mg less; 95% CI, 27.32-46.30 mg less; low certainty), nefopam (mean difference, 70.89 mg less; 95% CI, 64.46-77.32 mg less; low certainty), nonsteroidal anti-inflammatory drugs (mean difference, 11.07 mg less; 95% CI, 2.7-19.44 mg less; low certainty), and tramadol (mean difference, 22.14 mg less; 95% CI, 6.67-37.61 mg less; moderate certainty).
CONCLUSIONS
Clinicians should consider using adjunct agents to limit opioid exposure and improve pain scores in critically ill patients.
PubMed: 32696016
DOI: 10.1097/CCE.0000000000000157 -
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 -
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 -
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 -
Therapeutic Advances in Drug Safety 2019Poor oral hygiene is strongly associated with oral and systemic diseases. Alongside mechanical tooth cleaning, the adjunctive use of mouthrinses has been widely... (Review)
Review
BACKGROUND
Poor oral hygiene is strongly associated with oral and systemic diseases. Alongside mechanical tooth cleaning, the adjunctive use of mouthrinses has been widely advocated. Although research on the efficacy of various mouthrinse formulations is very active, there are a lack of conclusive data regarding their adverse effects.
METHODS
We undertook a systematic review in accordance wih PRISMA guidelines of electronic databases of clinical trials of any duration with daily home use of mouthwashes, presenting clinical and subjective side effects (PROSPERO registration: CRD42016054037).
RESULTS
After evaluating 614 titles and abstracts, 154 studies were selected for full-text analysis; 85 final papers were included. Based on the active ingredient in the test product, nine categories were created: cetyl pyridinium chloride, essential oils, chlorhexidine, triclosan, natural products, diclofenac, fluorides, delmopinol, and miscellaneous active substances. Most of the studies were of short duration (less than 6 months) with a defective 'methods' description; the reporting of adverse events often being overlooked. Both local morphological (oral mucosa and dental-crown staining, mucosal lesions) and functional (taste modifications, abnormal oral sensation) alterations were reported. Tooth staining was the most commonly listed adverse event, but it was quantitatively assessed only in a very small number of papers; most studies relied on patient reports. Staining was time associated; the longer the study, the higher its reported incidence and severity.
CONCLUSIONS
The reduced report of side effects may partly be due to a lack of an objective measure and lack of general guidelines that demand studies report their adverse events. The most frequently reported adverse effect was teeth staining. As in most studies, the effect was associated with trial duration; clinical trials should be of sufficient duration. New investigations meeting the suggested criteria of a minimal duration of 6 months should be planned.
PubMed: 31579502
DOI: 10.1177/2042098619854881