-
Journal of Clinical Medicine Mar 2022Actinic keratosis (AK) is a chronic skin condition that may progress to cutaneous squamous cell carcinoma. We conducted a systematic review of efficacy and safety for...
Comparative Efficacy and Safety of Tirbanibulin for Actinic Keratosis of the Face and Scalp in Europe: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.
Actinic keratosis (AK) is a chronic skin condition that may progress to cutaneous squamous cell carcinoma. We conducted a systematic review of efficacy and safety for key treatments for AK of the face and scalp, including the novel 5-day tirbanibulin 1% ointment. MEDLINE, PubMed, Embase, Cochrane Library, clinical trial registries and regulatory body websites were searched. The review included 46 studies, of which 35 studies included interventions commonly used in Europe and were sufficiently homogenous to inform a Bayesian network meta-analysis of complete clearance against topical placebo or vehicle. The network meta-analysis revealed the following odds ratios and 95% credible intervals: cryosurgery 13.4 (6.2-30.3); diclofenac 3% 2.9 (1.9-4.3); fluorouracil 0.5% + salicylic acid 7.6 (4.6-13.5); fluorouracil 4% 30.3 (9.1-144.7); fluorouracil 5% 35.0 (10.2-164.4); imiquimod 3.75% 8.5 (3.5-22.4); imiquimod 5% 17.9 (9.1-36.6); ingenol mebutate 0.015% 12.5 (8.1-19.9); photodynamic therapy with aminolevulinic acid 24.1 (10.9-52.8); photodynamic therapy with methyl aminolevulinate 11.7 (6.0-21.9); tirbanibulin 1% 11.1 (6.2-20.9). Four sensitivity analyses, from studies assessing efficacy after one treatment cycle only, for ≤25 cm treatment area, after 8 weeks post-treatment, and with single placebo/vehicle node confirmed the findings from the base case. Safety outcomes were assessed qualitatively. These results suggest that tirbanibulin 1% offers a novel treatment for AK, with a single short treatment period, favourable safety profile and efficacy, in line with existing topical treatments available in Europe.
PubMed: 35329979
DOI: 10.3390/jcm11061654 -
Pain Medicine (Malden, Mass.) Apr 2020Cumulative evidence suggests an analgesic effect of thiamine, pyridoxine, and cyanocobalamin (TPC) in monotherapy, and also when combined with nonsteroidal... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Cumulative evidence suggests an analgesic effect of thiamine, pyridoxine, and cyanocobalamin (TPC) in monotherapy, and also when combined with nonsteroidal anti-inflammatory drugs (NSAIDs), particularly diclofenac, in a synergistic manner. The aim of this review was to determine the effects of diclofenac combined with TPC compared with diclofenac monotherapy for low back pain (LBP) management.
METHODS
We searched for randomized clinical trials on the MEDLINE, EMBASE, LILACS, and Cochrane databases of records of clinical trials, among other sources. We evaluated the risk of bias regarding randomization, allocation concealment, blinding, incomplete outcome data, selective reporting, and other biases. A random-effects meta-analysis to examine patients with acute LBP (N = 1,108 adults) was performed, along with a subsequent sensitivity analysis.
RESULTS
Five studies in patients with LBP were included in the qualitative synthesis. Four of these studies in acute LBP were included in the first meta-analysis. A sensitivity test based on risk of bias (three moderate- to high-quality studies) found that the combination therapy of diclofenac plus TPC was associated with a significant reduction in the duration of treatment (around 50%) compared with diclofenac monotherapy (odds ratio = 2.23, 95% confidence interval = 1.59 to 3.13, P < 0.00001). We found no differences in the safety profile and patient satisfaction.
CONCLUSIONS
This meta-analysis demonstrated that combination therapy of diclofenac with TPC might have an analgesic superiority compared with diclofenac monotherapy in acute LBP. However, there is not enough evidence to recommend this therapy in other types of pain due to the scarcity of high-quality studies.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Diclofenac; Drug Therapy, Combination; Humans; Low Back Pain; Pain Measurement; Pyridoxine; Thiamine; Vitamin B 12; Vitamin B Complex
PubMed: 31529101
DOI: 10.1093/pm/pnz216 -
Journal of Cosmetic Dermatology Feb 2022Several treatments have been used to reduce inflammation and to reverse epithelial alterations in actinic cheilitis (AC).
INTRODUCTION
Several treatments have been used to reduce inflammation and to reverse epithelial alterations in actinic cheilitis (AC).
AIM
A systematic review was conducted to analyze the potential of topical treatments for remission and clinical improvement of AC as well as patient acceptability.
METHODS
A systematic review of clinical trials was conducted following the PICO strategy to answer the following question: Are topical anti-inflammatory and antineoplastic agents effective in the treatment of actinic cheilitis? The quality of the studies was assessed by ROB-2, and the certainty of evidence was rated by GRADE guidelines.
RESULTS
Eight clinical trials were selected, including four that investigated the use of anti-inflammatory drugs and four use of antineoplastic agents. The use of 3% diclofenac sodium was associated with partial remission of AC, while 5% imiquimod and ingenol mebutate promoted complete remission. Furthermore, 5% fluorouracil was the drug most associated with complications during treatment. Diclofenac sodium (3%) and fludroxycortide showed the best acceptance by the patients, especially in terms of symptom relief and comfort provided.
CONCLUSION
The anti-inflammatory and antineoplastic agents analyzed largely provided good clinical outcomes, with evidence of remission of AC lesions, development of few local adverse reactions during treatment, and good patient adherence.
Topics: Aged; Anti-Inflammatory Agents; Antineoplastic Agents; Cheilitis; Humans; Treatment Outcome
PubMed: 33786961
DOI: 10.1111/jocd.14118 -
Journal of the American Academy of... Oct 2021Actinic keratoses (AK) are rough scaly patches that arise on chronically ultraviolet-exposed skin and can progress to keratinocyte carcinoma. Treatment options for AK...
BACKGROUND
Actinic keratoses (AK) are rough scaly patches that arise on chronically ultraviolet-exposed skin and can progress to keratinocyte carcinoma. Treatment options for AK include topical medications, photodynamic therapy, cryosurgery, and laser ablation.
OBJECTIVE
This executive summary provides a synopsis of the 18 evidence-based recommendations for the treatment of AK detailed in the Guidelines of Care for the Management of Actinic Keratosis.
METHODS
A multidisciplinary workgroup conducted a systematic review to address 5 clinical questions on the management of AKs and applied the Grading of Recommendations Assessment, Development and Evaluation approach for assessing the certainty of the evidence and formulating and grading clinical recommendations. Graded recommendations were voted on to achieve consensus.
RESULTS
Analysis of the evidence resulted in 18 recommendations, suggesting there are several effective treatments available for AK.
LIMITATIONS
The analysis informing the recommendations was based on the best available evidence at the time it was conducted. The results of future studies may necessitate a revision of current recommendations.
CONCLUSIONS
Strong recommendations are presented for using ultraviolet protection, topical imiquimod, topical 5-fluorouracil, and cryosurgery. Conditional recommendations are presented for the use of photodynamic therapy and diclofenac for the treatment of AK, both individually and as part of combination therapy regimens.
Topics: Cryosurgery; Fluorouracil; Humans; Imiquimod; Keratosis, Actinic; Photochemotherapy; Practice Guidelines as Topic
PubMed: 34111497
DOI: 10.1016/j.jaad.2021.05.056 -
Global Spine Journal May 2023Systematic review.
STUDY DESIGN
Systematic review.
OBJECTIVE
To investigate the efficacy of nonsurgical interventional treatments for chronic low back pain (LBP) caused by facet joint syndrome (FJS).
METHODS
A systematic review of the literature was conducted to identify studies that compared interventional treatments for LBP due to FJS among them, with usual care or sham procedures. Studies were evaluated for pain, physical function, disability, quality of life and employment status. The RoB-2 and MINORS tools were utilized to assess the risk of bias in included studies.
RESULTS
Eighteen studies published between January 2000 and December 2021 were included (1496 patients, mean age: 54.31 years old). Intraarticular (IA) facet joint (FJ) injection of hyaluronic acid (HA) did not show significant difference compared to IA corticosteroids (CCS) in terms of pain and satisfaction. FJ denervation using radiofrequency (RF) displayed slightly superior or similar outcomes compared to IA CCS, physical therapy, or sham procedure. IA CCS showed better outcomes when combined with oral diclofenac compared to IA CCS or oral diclofenac alone but was not superior to IA local anesthetic and Sarapin. IA platelet-rich plasma (PRP) led to an improvement of pain, disability and satisfaction in the long term compared to IA CCS.
CONCLUSION
FJS is a common cause of LBP that can be managed with several different strategies, including nonsurgical minimally invasive approaches such as IA HA, CCS, PRP and FJ denervation. However, available evidence showed mixed results, with overall little short-term or no benefits on pain, disability, and other investigated outcomes.
PubMed: 36458366
DOI: 10.1177/21925682221142264 -
Pain Physician Nov 2020Postherpetic neuralgia (PHN) is a neuropathic pain that causes a reduction in patients' quality of life. There are many topical drugs for PHN, including topical... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Postherpetic neuralgia (PHN) is a neuropathic pain that causes a reduction in patients' quality of life. There are many topical drugs for PHN, including topical lidocaine patch, topical application of capsaicin, and others.
OBJECTIVES
This study aims to compare the efficacy and safety of topical drugs for PHN.
STUDY DESIGN
Relevant studies were found by systemically searching for terms including "topical" and "Postherpetic neuralgia" in PubMed, Cochrane library, MEDLINE, and EMBASE databases (inception through June 12, 2019). The primary outcome was the percentage of change in the Numeric Rating Scale or the Visual Analog Scale scores from baseline. The secondary outcome was the number of adverse events.
METHODS
The efficacy and safety of topical drugs for PHN was investigated by the pairwise meta-analysis and Bayesian network meta-analysis, applying Revman 5.3, the Stata 14.0 software, and GeMTC 0.14.3.
RESULTS
Twelve studies met the inclusion criteria, and eligible studies were selected for the ultimate meta-analysis. Our meta-analysis displayed 6 topical drugs for PHN. Lidocaine, high-concentration capsaicin, and aspirin/diethyl ether (ADE) had a higher possibility of bringing pain relief than placebo. Among them, lidocaine had the highest possibility of being the most effective drug for PHN and had the statistical significances compared with diclofenac, high-concentration capsaicin, indomethacin, low-concentration capsaicin, and placebo, and lidocaine was significantly preferable than other effective drugs in the aspect of safety.
LIMITATIONS
(1) The small number of included studies; (2) a small number of patients and short-term trials in progress, including lidocaine and ADE; (3) both randomized controlled trial and crossover randomized trial were included in our network meta-analysis; (4) only studies published in English were evaluated; (5) lack of head-to-head comparisons of some treatments; (6) different measurement methods were used in different trial, which may cause deviation; and (7) with the lack of cycles in the included trials, the inconsistency factors cannot be calculated, and node-splitting method cannot be performed in our network meta-analysis to check the inconsistency.
CONCLUSIONS
Compared with other topical drugs, lidocaine was the most effective and most tolerable drug to be recommended for PHN.
Topics: Bayes Theorem; Capsaicin; Humans; Lidocaine; Network Meta-Analysis; Neuralgia, Postherpetic; Pharmaceutical Preparations; Quality of Life
PubMed: 33185370
DOI: No ID Found -
Journal of Gastroenterology and... Jun 2021Rectally administered non-steroidal anti-inflammatory drugs (NSAIDs) are effective but suboptimal in the prevention of post-endoscopic retrograde... (Meta-Analysis)
Meta-Analysis
Prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis with a combination of pharmacological agents based on rectal non-steroidal anti-inflammatory drugs: A systematic review and network meta-analysis.
BACKGROUND AND AIMS
Rectally administered non-steroidal anti-inflammatory drugs (NSAIDs) are effective but suboptimal in the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis or PEP. New trials with the combination of rectal NSAIDs and other pharmacological agents have been conducted. This network meta-analysis (NMA) aimed to determine the relative efficacy of combination regimens and identify an optimal regimen for preventing PEP.
METHODS
We performed a systematic and comprehensive search to identify and analyze all the randomized controlled studies published until October 15, 2019, examining rectal NSAIDs and their combination with other pharmacological agents for the prevention of PEP. The primary outcome was the frequency of PEP. We conducted an NMA to combine the direct and indirect comparisons of rectal NSAIDs and their combination with other pharmacological agents.
RESULTS
The NMA included 24 studies evaluating 14 regimens in 11 321 patients. According to predictive interval plot and surface under the cumulative ranking curve values, indomethacin + lactated Ringer's solution, followed by diclofenac + nitrate and indomethacin + normal saline, is the most efficacious combination of pharmacological agents for the overall prevention of PEP. Rectal indomethacin alone is the most efficacious agent for prevention of moderate to severe PEP, and rectal diclofenac is the most useful agent for prevention of PEP among the high-risk group.
CONCLUSIONS
Rectal indomethacin with intravenous hydration and rectal diclofenac with sublingual nitrate are the most efficacious combination regimens for the overall prevention of PEP.
Topics: Administration, Rectal; Anti-Inflammatory Agents, Non-Steroidal; Cholangiopancreatography, Endoscopic Retrograde; Diclofenac; Drug Therapy, Combination; Female; Humans; Indomethacin; Male; Nitrates; Pancreatitis; Postoperative Complications; Ringer's Lactate; Treatment Outcome
PubMed: 33068012
DOI: 10.1111/jgh.15303 -
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 -
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 -
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