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Journal of Clinical Oncology : Official... May 2024Hand-foot syndrome (HFS) is a dose-limiting side effect of capecitabine. Celecoxib prevents HFS by inhibiting cyclooxygenase-2 (COX-2) that is upregulated because of the... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
Hand-foot syndrome (HFS) is a dose-limiting side effect of capecitabine. Celecoxib prevents HFS by inhibiting cyclooxygenase-2 (COX-2) that is upregulated because of the underlying associated inflammation. However, systemic side effects of celecoxib have limited routine prescription. Topical diclofenac inhibits COX-2 locally with minimal risk of systemic adverse events. Therefore, we conducted this study to assess the efficacy of topical diclofenac in the prevention of capecitabine-induced HFS.
METHODS
In this single-site phase III randomized double-blind trial, we enrolled patients with breast or GI cancer who were planned to receive capecitabine-based treatment. Participants were randomly assigned in a 1:1 ratio to receive topical diclofenac or placebo gel for 12 weeks or until the development of HFS, whichever occurred earlier. The primary end point was the incidence of grade 2 or 3 HFS (Common Terminology Criteria for Adverse Events version 5), which was compared between the two groups using simple logistic regression.
RESULTS
In total, 264 patients were randomly assigned to receive topical diclofenac gel (n = 131) or placebo (n = 133). Grade 2 or 3 HFS was observed in 3.8% of participants in the diclofenac group compared with 15.0% in the placebo group (absolute difference, 11.2%; 95% CI, 4.3 to 18.1; = .003). Grade 1-3 HFS was lower in the diclofenac group than in the placebo group (6.1% 18.1%; absolute risk difference, 11.9%; 95% CI, 4.1 to 19.6). Capecitabine dose reductions because of HFS were less frequent in the diclofenac group (3.8%) than in the placebo group (13.5%; absolute risk difference, 9.7%; 95% CI, 3.0 to 16.4).
CONCLUSION
Topical diclofenac prevented HFS in patients receiving capecitabine. This trial supports the use of topical diclofenac to prevent capecitabine-associated HFS.
Topics: Humans; Capecitabine; Double-Blind Method; Hand-Foot Syndrome; Diclofenac; Female; Male; Middle Aged; Aged; Antimetabolites, Antineoplastic; Breast Neoplasms; Administration, Topical; Adult; Gastrointestinal Neoplasms; Anti-Inflammatory Agents, Non-Steroidal
PubMed: 38412399
DOI: 10.1200/JCO.23.01730 -
ACS Nano Dec 2023Meniscus injuries are associated with the degeneration of cartilage and development of osteoarthritis (OA). It is challenging to protect articular cartilage and improve...
Meniscus injuries are associated with the degeneration of cartilage and development of osteoarthritis (OA). It is challenging to protect articular cartilage and improve exercise when a meniscus injury occurs. Herein, inspired by the components and functions of the meniscus, we developed a self-lubricating and friction-responsive hydrogel that contains nanoliposomes loaded with diclofenac sodium (DS) and Kartogenin (KGN) for anti-inflammation and cartilage regeneration. When the hydrogel was injected into the meniscus injury site, the drug-loaded nanoliposomes were released from the hydrogel in a friction-responsive manner and reassembled to form hydration layers that lubricate joints during movement. Meanwhile, DS and KNG were constantly released from the nanoliposomes to mitigate inflammation and promote cartilage regeneration. Additionally, this hydrogel exhibited favorable injectability, mechanical properties, fatigue resistance, and prolonged degradation. experiments demonstrated that injection of the hydrogel effectively improved exercise performance and protected the articular cartilage of rats, suggesting it as a potential therapeutic approach for meniscal injuries.
Topics: Rats; Animals; Cartilage, Articular; Hydrogels; Friction; Meniscus; Injections; Diclofenac
PubMed: 37975685
DOI: 10.1021/acsnano.3c10139 -
The Science of the Total Environment Nov 2023Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most frequently used pharmaceuticals for human therapy, pet therapeutics, and veterinary feeds, enabling... (Review)
Review
Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most frequently used pharmaceuticals for human therapy, pet therapeutics, and veterinary feeds, enabling them to enter into water sources such as wastewater, soil and sediment, and seawater. The control of NSAIDs has led to the advent of the novel materials for treatment techniques. Herein, we review the occurrence, impact and toxicity of NSAIDs against aquatic microorganisms, plants and humans. Typical NSAIDs, e.g., ibuprofen, ketoprofen, diclofenac, naproxen and aspirin were detected at high concentrations in wastewater up to 2,747,000 ng L. NSAIDs in water could cause genotoxicity, endocrine disruption, locomotive disorders, body deformations, organs damage, and photosynthetic corruption. Considering treatment methods, among adsorbents for removal of NSAIDs from water, metal-organic frameworks (10.7-638 mg g) and advanced porous carbons (7.4-400 mg g) were the most robust. Therefore, these carbon-based adsorbents showed promise in efficiency for the treatment of NSAIDs.
Topics: Humans; Wastewater; Anti-Inflammatory Agents, Non-Steroidal; Naproxen; Ibuprofen; Diclofenac; Water; Water Pollutants, Chemical
PubMed: 37419350
DOI: 10.1016/j.scitotenv.2023.165317 -
BioRxiv : the Preprint Server For... May 2024causes life-threatening infections that are becoming difficult to treat due to increasing rates of multi-drug resistance (MDR) among clinical isolates. This has led the...
causes life-threatening infections that are becoming difficult to treat due to increasing rates of multi-drug resistance (MDR) among clinical isolates. This has led the World Health Organization and the CDC to categorize MDR as a top priority for the research and development of new antibiotics. Colistin is the last-resort antibiotic to treat carbapenem-resistant . Not surprisingly, reintroduction of colistin has resulted in the emergence of colistin-resistant strains. Diclofenac is a nonsteroidal anti-inflammatory drug used to treat pain and inflammation associated with arthritis. In this work, we show that diclofenac sensitizes colistin-resistant clinical strains to colistin, and in a murine model of pneumonia. Diclofenac also reduced the colistin MIC of and isolates. Transcriptomic and proteomic analyses revealed an upregulation of oxidative stress-related genes and downregulation of type IV pili induced by the combination treatment. Notably, the concentrations of colistin and diclofenac effective in the murine model were substantially lower than those determined , implying a stronger synergistic effect compared to . A mutant strain, lacking the primary component of the type IV pili, became sensitive to colistin in the absence of diclofenac. This suggest that the downregulation of type IV pili is key for the synergistic activity of these drugs and indicates that colistin and diclofenac exert an anti-virulence effect. Together, these results suggest that the diclofenac can be repurposed with colistin to treat MDR .
PubMed: 38798593
DOI: 10.1101/2024.05.17.594771 -
Journal of Environmental Health Science... Dec 2023The grafting of biopolymer gum ghatti (GG) over the PNIPAM and PAA was done and loaded with graphene oxide (GO). Aim of this work is carried out combine adsorption of...
UNLABELLED
The grafting of biopolymer gum ghatti (GG) over the PNIPAM and PAA was done and loaded with graphene oxide (GO). Aim of this work is carried out combine adsorption of sodium diclofenac (SD) and metformin (MF) by the prepared hydrogels under influence of various parameters. The adsorbent GG-P(NIPAM--PAA)/GO(3 mg) chosen for adsorption activity as it displayed highest swelling capacity. The effect of amount of both adsorbents GG-P(NIPAM--PAA and GG-P(NIPAM--PAA)/GO(3 mg) showed that highest adsorption capacity found at 40 mg of adsorbents for both drugs at conditions: 100 mg/L concentration, 30 °C, 24 h and pH 6 and subsequently became stable. Both the drugs were removed in greater amount at 25 mg/L concentration, 24 h of contact time, 30 °C, 40 mg amount of both adsorbents and pH 6. Effect of time revealed that as time elevated from 2 h to 12 (100 mg/L concentration,, 30 °C, 40 mg amount of both adsorbents and pH 6) led to increase adsorption efficiency and after that increase time did not much impact on adsorption activity. Adsorption activity of hydrogels declined with increase of temperature (100 mg/L concentration, 12 h, 40 mg amount of both adsorbents and pH 6). The acidic conditions favored adsorption of SD while MF adsorbed under the weak acidic(100 mg/L concentration, 30 °C, 12 h, 40 mg amount of both adsorbents). However, basic conditions did not much influence on adsorption of MF but effected on adsorption activity of SD. Adsorption isotherm and kinetic model suggested that adsorption is homogenous and chemical in nature. The maximum adsorption capacity (q) found to be 289.01 and 154.55 mg/g for SD and MF respectively.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s40201-023-00867-w.
PubMed: 37869591
DOI: 10.1007/s40201-023-00867-w -
Diclofenac Versus Corticosteroids Following Strabismus Surgery: Systematic Review and Meta-analysis.Journal of Pediatric Ophthalmology and... 2023The purpose of the current study was to compare outcomes of diclofenac versus corticosteroids following strabismus surgery. A systematic review and meta-analysis were... (Review)
Review
The purpose of the current study was to compare outcomes of diclofenac versus corticosteroids following strabismus surgery. A systematic review and meta-analysis were performed in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. An electronic search was performed to include comparative studies of diclofenac versus corticosteroids following strabismus surgery. The analysis was based on fixed and random effect models. Primary outcomes included discomfort, chemosis, inflammation, conjunctival gap, intraocular pressure, and conjunctival injection. Secondary outcomes were conjunctival congestion, discharge, and drop intolerance. Eight studies with a sample of 469 eyes were included. At weeks 1 and 4 postoperatively, there were no statistically significant differences between the diclofenac and corticosteroid groups, except for conjunctival injection at week 1 (mean difference [MD] = -0.21, = .04) favoring diclofenac. Interestingly, all primary outcomes significantly favored diclofenac at week 2: discomfort (MD = -0.34, = .03), conjunctival chemosis (MD = -0.16, = .04), conjunctival inflammation (MD = -0.16, = .02), conjunctival gap (MD = -0.17, = .002), intraocular pressure (MD = -2.53, < .00001), and conjunctival injection (MD = -0.30, = .03). Moreover, conjunctival congestion was significantly improved for dexamethasone, whereas discharge and drop intolerance was not statistically different. Diclofenac is comparable to various corticosteroids when used following strabismus surgery. However, it is important to note that diclofenac yielded significant improvements in discomfort, conjunctival chemosis, inflammation, conjunctival gap, intraocular pressure, and conjunctival injection, mainly at 2 weeks postoperatively. .
PubMed: 36441127
DOI: 10.3928/01913913-20221011-01 -
Iranian Journal of Microbiology Apr 2024is an opportunistic pathogen causing nosocomial infections. Diclofenac is an anti-inflammatory drug that is considered a non-antibiotic drug. This study assessed the...
BACKGROUND AND OBJECTIVES
is an opportunistic pathogen causing nosocomial infections. Diclofenac is an anti-inflammatory drug that is considered a non-antibiotic drug. This study assessed the antibacterial and antibiofilm effects of diclofenac and levofloxacin/diclofenac combination against levofloxacin resistant isolates.
MATERIALS AND METHODS
Minimum inhibitory concentration was determined using broth microdilution method for levofloxacin, diclofenac, and levofloxacin/diclofenac combination. Biofilm forming capacity and biofilm inhibition assay were determined. Relative gene expression was measured for efflux pump genes; , and genes and biofilm related genes , and without and with diclofenac and the combination.
RESULTS
Diclofenac demonstrated MIC of 1 mg/ml. The combination-with ½ MIC diclofenac-showed synergism where levofloxacin MIC undergone 16-32 fold decrease. All the isolates that overexpressed and showed a significant decrease in gene expression in presence of diclofenac or the combination. The mean percentage inhibition of biofilm formation with diclofenac and the combination was 40.59% and 46.49%, respectively. This agreed with biofilm related genes expression investigations.
CONCLUSION
Diclofenac showed an antibacterial effect against The combination showed synergism, significant reduction in biofilm formation and in the relative level of gene expression. Furthermore, it can potentiate the levofloxacin activity or revert its resistance.
PubMed: 38854979
DOI: 10.18502/ijm.v16i2.15349 -
Clinical Gastroenterology and... Mar 2024Although both nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids are used for analgesia in acute pancreatitis (AP), the analgesic of choice is not known. We... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Although both nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids are used for analgesia in acute pancreatitis (AP), the analgesic of choice is not known. We compared buprenorphine, an opioid, and diclofenac, an NSAID, for analgesia in AP.
METHODS
In a double-blind randomized controlled trial, AP patients were randomized to receive intravenous diclofenac or intravenous buprenorphine. Fentanyl was used as rescue analgesia, delivered through a patient-controlled analgesia pump. Primary outcome was the difference in the dose of rescue fentanyl required. Secondary outcomes were the number of effective and ineffective demands of rescue fentanyl, pain-free interval, reduction in visual analogue scale (VAS) score, adverse events, and organ failure development.
RESULTS
Twenty-four patients were randomized to diclofenac and 24 to buprenorphine. The 2 groups were matched at baseline. The total amount of rescue fentanyl required was significantly lower in the buprenorphine group:130 μg, interquartile range (IQR), 80-255 vs 520 μg, IQR, 380-1065 (P < .001). The number of total demands was 32 (IQR, 21-69) in the diclofenac arm vs 8 (IQR, 4-15) in the buprenorphine arm (P < .001). The buprenorphine group had more prolonged pain-free interval (20 vs 4 hours; P < .001), with greater reduction in the VAS score at 24, 48, and 72 hours compared with the diclofenac group. These findings were confirmed in the subgroup of moderately severe/severe pancreatitis. Adverse events profile was similar in the 2 groups.
CONCLUSIONS
Compared with diclofenac, buprenorphine appears to be more effective and equally safe for pain management in AP patients, even in the subcohort of moderately severe or severe pancreatitis (Trial Registration number: CTRI/2020/07/026914).
Topics: Humans; Diclofenac; Buprenorphine; Pain Management; Acute Disease; Pancreatitis; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Opioid; Pain; Fentanyl; Double-Blind Method
PubMed: 37924855
DOI: 10.1016/j.cgh.2023.10.021