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Introduction: Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used for pain disorders and exert pharmacological effects by inhibiting cyclooxygenase (COX). Although previous studies have evaluated the COX inhibitory activity and selectivity of NSAIDs, none has compared COX inhibitory concentrations with the plasma concentrations of clinical doses or investigated the efficacy and adverse effects of different dosage forms. Therefore, in this study we evaluated the COX inhibitory activities and inhibition rates of clinical doses of the various NSAID formulations, especially diclofenac sodium. Methods: Human blood and the drug (diclofenac sodium, celecoxib, ibuprofen, flurbiprofen, or etodolac) were mixed and incubated, and the supernatant was collected and quantified the COX inhibitory activity of each drug by ELISA. Logistic regression analyses were used to calculate the inhibition rates at maximum plasma drug concentration (Cmax) of clinical doses of marketed formulations. For diclofenac sodium, we also calculated the concentrations at which COX inhibition rates were 50% and 80% (IC50 and IC80). Results: COX-2 inhibition rate at Cmax of clinical doses exceeded 50% except celecoxib 100 mg. For diclofenac sodium, the Cmax at the clinical doses of the oral and suppository formulations showed almost complete inhibition of COX-2 and an inhibition rate exceeding IC80 for COX-1. The Cmax at repeated doses of the transdermal formulation showed an inhibition rate above IC80 for COX-2 but below IC80 for COX-1. Discussion: This result explains why gastrointestinal disorders frequently occur with oral and suppository formulations of diclofenac sodium despite its relatively high COX-2 selectivity. Although the plasma drug concentration of the transdermal formulation is lower than oral and suppository formulations, it has an inhibition rate above IC50 for COX-2, which is required for analgesic efficacy, and has a lower COX-1 inhibition rate than these formulations. Conclusion: The findings explain why the transdermal formulation exerts an analgesic effect despite having a lower Cmax than other diclofenac sodium formulations. [ABSTRACT FROM AUTHOR]

Background: Kidney stone-related pain often presents significant challenges in clinical practice, mainly due to the adverse effects by NSAIDs, which are the current first-line treatment for urolithiasis. Patients presenting with gastrointestinal tract disorders and contraindications toward NSAIDs are particularly susceptible. Intradermal sterile water injection (SWI) has evidently become apparent as one of the promising alternatives, offering rapid pain relief with minimal adverse effects. This purpose of this study to assess the safety and efficacy of SWI in comparison to NSAIDs particularly Natrium Diclofenac in the management of kidney-stone related pain. Main Body: A systematic review and meta-analysis was performed on papers published up to January 2024 obtained from scientific databases, guided by the PRISMA flowchart. The Cochrane risk of bias 2.0 tool was used to assess quality of the included studies. Statistical analyses were then performed using Review Manager 5.4.1 on studies that provide the baseline and complete follow-up numerical outcomes (e.g. mean and standard deviation) required. After screening was done, 3 retrievable studies met the inclusion and exclusion criteria with a total of 770 participants with kidney stone related pain. The result revealed no significant difference in pain reduction between SWI and Natrium diclofenac at 30 min (MD −0.12, 95% CI −0.68 to 0.44) and 60 min (MD −0.23, 95% CI −0.65 to 0.18). Furthermore, patients treated with SWI display a reduced need for rescue analgesia compared to Natrium Diclofenac (OR 0.73, 95% CI 0.36 to 1.49). Adverse events result was more superior in SWI, having lower occurrence when compared to Natrium Diclofenac, although not significant (OR 0.14, 95% CI 0.05 to 0.39). Conclusions: Intradermal sterile water injection (SWI) appears to be a promising alternative to NSAIDs for kidney stone related pain management, offering comparable efficacy in pain reduction, reduced need for rescue analgesia while maintaining a favorable safety profile. However, further research with larger sample sizes and standardized treatment protocols are required to further validate its safety and efficacy. [ABSTRACT FROM AUTHOR]

Intravenously administered nonsteroidal anti-inflammatory drugs (NSAIDs) constitute a crucial component of multimodal analgesia strategies in surgical settings. This narrative review aims to provide an up-to-date evaluation of the efficacy, safety, and clinical use of intravenous (IV) NSAIDs for perioperative pain management in adults and children. The NSAIDs and selective COX-2 inhibitors (coxibs) approved in Europe for the short-term symptomatic treatment of acute, moderate perioperative pain via IV infusion in adults and/or children have been influenced by US and global guidelines and practice: the drugs primarily reviewed here are ibuprofen, ketorolac, ketoprofen, naproxen, paracetamol, and acetylsalicylic acid. Furthermore, intravenous ibuprofen is authorized for the short-term symptomatic treatment of fever. In contrast to intravenous ketoprofen, intravenous ibuprofen is authorized for administration to children over 6 years of age or weighing more than 20 kg. Overall, IV ibuprofen had a more favorable profile with regard to peri- and postoperative opioid sparing and pain relief. Oral ibuprofen and IV ibuprofen have similar levels of efficacy, although IV ibuprofen has a shorter onset of action and is required in patients who are unable to take oral medications. The frequency of significant adverse events appears to be similar for ibuprofen and paracetamol. Systematic reviews and meta-analyses report that intravenous NSAIDs reduce postoperative opioid consumption by approximately 20–60%, improving pain management with fewer opioid-related side effects. In indications in infants, the choice of medication is limited, and the oral route is not always feasible; IV formulations of ibuprofen are preferred in this setting. Topics for further research should include head-to-head trials of IV NSAIDs. [ABSTRACT FROM AUTHOR]

Introduction: Intravenous non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used in healthcare settings, but their comparative safety and resource utilization impacts remain understudied. This study aimed to compare adverse drug reactions (ADRs) and healthcare resource utilization (HCRU) between patients receiving IV-ibuprofen versus IV/IM ketorolac. Methods: A retrospective, longitudinal analysis was conducted using an all-payer database, examining records from January 1, 2014, to June 3, 2023. The study included both adult (≥18 years) and pediatric (<18 years) populations who received one or more doses of either medication. Propensity score matching was applied to both populations, and HCRU was tracked for 29 days post-final dose. The adult cohort included 31,046 IV-ibuprofen and 124,184 ketorolac records, while the pediatric cohort had 5,579 patients per treatment arm. Results: Both adult and pediatric patients receiving IV-ibuprofen demonstrated lower ADR incidence and reduced HCRU compared to those receiving ketorolac. Discussion: The findings suggest IV-ibuprofen may be a safer alternative to ketorolac, potentially improving patient care outcomes while reducing healthcare system burden. These results have implications for clinical practice and healthcare resource management. [ABSTRACT FROM AUTHOR]

Tonsillectomy is one of the most common operations. Tonsillectomy is also one of the most painful surgical procedures. However, there is still no satisfactory standard for postoperative pain management. Four databases (Cochrane Library, Ovid Technologies, PubMed, Web of Science) were searched for the period from 1908 to 2019. The systematic literature review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data were pooled using random-effects and fixed-effects models. Randomized controlled trials, reviews and meta-analyses were included. Primary outcomes were quantitative pain intensity in the first 24 h after tonsillectomy and on days 1, 3, and 7 postoperatively. The search yielded 1594 publications, of which 111 publications with 7566 patients, both children and adults, could be included. Intraoperative medication with intravenous dexamethasone significantly reduced pain (mean difference [MD] -0.42; 95% confidence interval [CI]: -0.61- -0.24). Among the local anesthetics, only the preoperative injection of levobupivacaine into the tonsillar compartment was able to provide sufficient pain reduction up to three days after tonsillectomy (MD: -1.92; 95% CI: -2.73 - -1.11). Preoperative or intraoperative administration of non-steroidal anti-inflammatory drugs (NSAIDs) significantly reduced pain (MD: -0.75; 95% CI: -0.87- -0.63). Steroids and NSAIDs are an important part of pain management after tonsillectomy. [ABSTRACT FROM AUTHOR]

Background: Drug delivery systems based on microballoons are one of the promising approaches for gastric retention, especially useful for drugs with site-specific absorption in the stomach. The microballoons are hollow, spherical particles under 200 micrometers, designed to float in the gastric environment. The Aceclofenac formulation of an NSAID is helpful with a half-life of 4-4.3 hours; this delivery form gives a sustained release and maintains constant plasma levels with enhanced bioavailability and decrease in dosing frequency. Methodology: Microballoons of Aceclofenac were prepared using Eudragit RS 100 and Hydroxy Propyl Methyl Cellulose as polymers from the emulsion-solvent diffusion method. In this, the polymers impart stability along with a profile of controlled release. Here, the microballoons was evaluated for physical parameter and the release profile regarding average particle size, floatation percentage, entrapment efficiency, true tapped density, and percentage yield, and FTIR will be carried out on complexes of drug and polymer. Results and Discussion: The prepared microballoons exhibit excellent floating properties and uniformity in size, which aided in long gastric retention. High entrapment efficiency with controlled and sustained release of the drug for an extended period was obtained. FTIR studies indicated that Aceclofenac remained stable in the polymer matrix with no considerable chemical interaction between the drug and the polymers. Conclusion: This research shows promise in microballoons-based delivery systems that could maintain the release for a longer duration from the delivery device with respect to Aceclofenac, which enhances bioavailability and reduces dosing frequencies. [ABSTRACT FROM AUTHOR]

Abstract Objective Osteoarthritis (OA) causes significant musculoskeletal pain. This study assessed the efficacy and safety of fasinumab, an investigational nerve growth factor inhibitor, in patients with moderate-to-severe OA pain of the knee/hip. Methods In this Phase 3, randomized, double-blind, placebo- and non-steroidal anti-inflammatory drug (NSAID)-controlled study, patients with OA (Kellgren-Lawrence grade ≥ 2; Western Ontario and McMaster Universities Arthritis Index [WOMAC] pain score ≥ 4) received (2:1:1:1) fasinumab 1 mg every 4 weeks, diclofenac 75 mg twice daily, celecoxib 200 mg daily, or placebo for 24 weeks. Co‑primary endpoints were change in WOMAC pain and physical function scores to Week 24 versus placebo. For safety, joints were imaged in all patients at pre‑specified times, regardless of symptoms. Results Of 4531 patients screened, 1650 were randomized. At Week 24, greater improvements were observed for fasinumab versus placebo; least-squares mean difference: –0.63 (p = 0.0003) for WOMAC pain and –0.64 (p = 0.0003) for physical function. Improvements were numerically greater for fasinumab versus NSAIDs for physical function (–0.64 versus –0.31; nominal p

Adi Nurmesa,1,2 Neily Zakiyah,1,3 Widya Norma Insani1,3 1Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Bandung, 40132, Indonesia; 2Department of Pharmacy, Dr Rivai Abdullah Regional General Hospital, Banyuasin, 30961, Indonesia; 3Center of Excellence for Pharmaceutical Care Innovation, Universitas Padjadjaran, Bandung, 40132, IndonesiaCorrespondence: Neily Zakiyah, Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Bandung, 40132, Indonesia, Email neily.zakiyah@unpad.ac.idAbstract: Non-steroidal anti-inflammatory drugs (NSAIDs) are widely administered in all age groups due to their effectiveness in reducing fever, relieving pain, and reducing inflammation. However, they have also been identified as the second most common cause of drug-induced hypersensitivity reactions, after beta-lactam antibiotics. Adverse reactions to NSAIDs can range from expected pharmacological side effects such as gastritis to severe allergies, including anaphylaxis. It is important to distinguish true hypersensitivity reactions from other side effects to ensure proper management and patient safety. Four patients aged 35– 60 years were treated with NSAIDs for pain management and subsequently developed hypersensitivity reactions to NSAIDs such as ketorolac, ketoprofen, and diclofenac sodium in the type of allergic reactions such as NSAIDs-induced urticaria/angioedema (NIUA). This case series provides valuable insights into the clinical presentations and potential mechanisms of NSAID hypersensitivity in the documented cases in one of the hospitals in Indonesia. It highlights important areas for future investigation, including the need for larger, controlled studies to better understand incidence, risk factors, and generalizability to broader populations.Keywords: hypersensitivity, NSAID, pain, analgesic, allergic reaction

INTRODUCTION: Overprescribing of acid suppressants is a common phenomenon in human and small animal patients, leading to potential deleterious gastrointestinal (GI) and non-GI consequences. The impact of consensus statements on veterinary prescribing habits in clinical practice have not been fully evaluated. This study aimed to compare the prescribing habits of the proton pump inhibitor (PPI), omeprazole, in dogs in an academic veterinary teaching hospital before and after the publication of the American College of Veterinary Internal Medicine (ACVIM) consensus statement on rational use of gastrointestinal protectants. METHODS: Evaluation of the prescribing habits of omeprazole in dogs during the years 2017 and 2021 was retrospectively compared. These years were selected to reflect a 12-month period prior to and following the publication of the consensus statement. One hundred dogs from each year were randomly selected. Dose, frequency of administration, duration of treatment, concurrent prescription of more than one gastroprotectant and indications for prescribing omeprazole were analyzed. RESULTS: A significant increase in the cases that received omeprazole q12h (p  0.0001) was detected after the publication of the 2018 ACVIM consensus statement. Considering the indications, there was also a significant increase in the appropriate prescription of omeprazole in the second compared to the first period of study (p

After dental caries, the most common multifactorial oral disease is periodontal disease. Periodontitis can result in biofilm and host dysbiosis, ultimately causing inflammation and destruction of periodontal tissues. This narrative review aimed to summarise and discuss the mechanism of action, categories and use of non-steroidal anti-inflammatory drugs (NSAIDs) in clinical practice in the treatment of periodontitis because of their analgesic, anti-inflammatory and reducing effects on platelet aggregation and thus bleeding. Also, this review illustrates the importance of studies demonstrating synergism between specialty drugs and their derivatives as valuable active substances. The eleven clinical trials conducted in small groups of adult volunteers (14-50) treated with various NSAIDs, e.g. aspirin, ibuprofen, diclofenac, ketoprofen and tenoxicam are discussed. The results of clinical trials have shown that the use of NSAIDs together with surgical intervention in the treatment of periodontal diseases produces beneficial effects as an adjunctive treatment. It is worth noting that these studies were conducted on small cohorts of adult volunteers, with variations in the duration of treatment and doses of administered drugs. Further research on the impact of NSAIDs administration on periodontal disease may provide in-depth knowledge of patient groups with different demographics, including age, gender and comorbidities. Additional research is necessary to explore the use of NSAIDs in combination with periodontitis treatment for different patient groups.

Our study aimed to evaluate the effect of different treatments for BRD on health and welfare in fattening bulls. A total of 264 bulls were enrolled. Welfare was assessed on day 2 (T0) and day 15 (T1) after arrival. A decrease in the welfare level was observed from T0 to T1. All bulls were inspected clinically at T0 and T1 revealing an increase of skin lesions and lameness in T1. In both periods, a high incidence of respiratory disease was observed. A prevalence of 79.55% and 95.45% of Mycoplasma bovis using RT-PCR and culture at T0 and T1 respectively was observed. Blood samples were collected for haematology at T0 and T1. At T0, 36 animals were individually treated for BRD with an antimicrobial (IT), 54 received a metaphylactic treatment with tulathromycin (M), 150 received a metaphylactic treatment with tulathromycin plus a second antimicrobial (M + IT) whereas 24 were considered healthy and therefore not treated (NT). Additionally, 128 were treated with a non-steroid anti-inflammatory (NSAID). Neutrophils of M + IT were significantly higher than groups NT and M and the lymphocytes of M + IT were significantly lower than that of IT. White blood cells, neutrophils and N/L ratio of animals treated with an NSAID was significantly higher than that not treated. Lung inspection of 172 bulls at the abattoir indicated that 92.43% presented at least one lung lesion. A statistically significant effect of the NSAID treatment on the lung lesions was observed. Our findings indicate that BRD was a major welfare and health concern and evidence the difficulties of antimicrobial treatment of M. bovis.

Abstract Background Undifferentiated arthritis (UA) is a term used to describe patients with inflammatory arthritis that has not differentiated into a specific rheumatic disease. UA may be a pre-stage of rheumatoid arthritis (RA) or another inflammatory disease or remain undifferentiated, but a substantial proportion of patients may also achieve spontaneous remission. As UA may be an early presentation of RA, rheumatologists often start methotrexate (or another csDMARD) as early as possible. There are however very little data on the potential benefits of early DMARD treatment, and longitudinal data suggests that long-term outcomes such as physical functioning hardly improved in these patients in the past decades. In the I CEA trial, we investigate if it is beneficial to start early treatment with MTX or baricitinib, a more rapidly acting drug with a broader mechanism of action, compared to waiting for spontaneous remission with symptomatic therapy in patients with UA. Methods The I CEA is a multicenter single-blind (independent assessor) randomized clinical trial with a 3-month interventional and 9-month observational follow-up period. The study includes patients with early (

ABSTRACT: Our objectives were to compare the efficacy of ketoprofen or ceftiofur for treatment of metritis in dairy cows considering subsequent health, production, and reproduction. Cows from 2 commercial dairy farms in Ontario, Canada were examined with a Metricheck device 3 times per week from 2 to 14 DIM. Cows with metritis (fetid vaginal discharge; n = 193) were blocked by parity and fever (rectal temperature ≥39.5°C or

Abstract Background Pseudophakic cystoid macular edema (PCME) is a known complication of cataract surgery that contributes to decreased visual acuity. Mechanical manipulation associated with the release of inflammatory mediators is the leading hypothesis for PCME. To date, no standardized prophylactic protocol has been established to effectively reduce the incidence of PCME. This study assessed the efficacy and safety of nonsteroidal anti-inflammatory drops (NSAIDs) and corticosteroids for the prevention of PCME. Method We searched the following databases MEDLINE, EMBASE, and Cochrane Central. Register of Controlled Trials and included randomized controlled trials (RCTs) that studied the efficacy of NSAID vs. placebo, NSAID vs. steroid, or NSAID + steroid vs. placebo, reporting the incidence of PCME, macular thickness, and best-corrected visual acuity. The risk ratio (RR) with a 95% confidence interval (CI) and a random-effects model was used. The risk of bias was assessed using the revised Cochrane risk-of-bias tool. Results A total of 18 RCTs were included in this study (n = 2959). Nine RCT showed low risk of bias, 7 RCT showed unclear risk of bias, and 2 RCT had high risk of bias. The incidence of cystoid macular edema among patients treated with NSAIDs was significantly lower (RR = 0.33, P

After understanding the biological signaling roles of hydrogen sulfide and its involvement in various physiological processes, there has been enormous interest in exploring its therapeutic utility in areas such as cancer, inflammation, cardiovascular diseases, etc. There is also growing interest in using suitable H2S donors in combination with other drugs to improve the treatment outcome through the modulation of multiple pathways. The premature release of H2S from small molecule donors and the difficulty in controlling its spatio‐temporal distribution are the major challenges during these efforts. Hence the development of appropriate carriers that can release this gasotransmitter along with the therapeutic entity of interest in a controlled manner has high significance. In this regard, this report presents a novel drug delivery system from oxanorbornane‐based synthetic lipids that carries a H2S‐releasing 1,2‐dithiole‐3‐thione moiety as part of the head group. Nanoaggregates of the resulting conjugate are not only capable of efficiently entrapping a non‐steroidal anti‐inflammatory drug such as ibuprofen, but also release this drug and H2S in a controlled and sequential manner. [ABSTRACT FROM AUTHOR]

Copyright of Acta Stomatologica Croatica is the property of Acta Stomatologica Croatica and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Aspirin is one of the most frequently detected non-steroidal anti-inflammatory drugs in aquatic environments. Despite its prevalence, toxicity possessed by aspirin to non-target organisms like fish is poorly explored. In the present study, cell death induced by different concentrations of aspirin (1, 10, and 100 µg/L) has been investigated in the liver of fish, Labeo rohita exposed for 28 days. A significant increase (p < 0.05) in the density of caspase-3 positive cells in a dose and duration-dependent manner assessed through immunofluorescent staining indicates caspase-dependent pathway of cell death which may be either through intrinsic or extrinsic pathway. The flow cytometric analysis, in addition, revealed a significant (p < 0.05) decline in the live cells and an increase in apoptotic cells in the liver of fish exposed to aspirin. Cell death due to apoptosis is further indicated by a significant increase (p < 0.05) in the Kupffer cells and tumor necrosis factor-α. The decrease in the activity of cyclooxygenase (COX) enzyme significantly (p < 0.05) in all three exposure concentrations of aspirin suggests COX-dependent pathway of cell death. The present study provides in-depth insights into aspirin-induced cell death in the liver of fish at environmentally realistic concentrations. [ABSTRACT FROM AUTHOR]

Introduction: Nonsteroidal anti-inflammatory drugs (NSAIDs), which inhibit prostaglandin synthesis, are used in many clinical areas. Although they are advantageous because of their analgesic, anti-inflammatory, and antipyretic properties, their effects on tissue healing are controversial. Dexketoprofen and lornoxicam are widely used, new-generation NSAIDs. However, their effects on fibroblasts, which are important for healing, are unknown. Herein, we aimed to investigate the effects of these two drugs on fibroblast viability, migration, and collagen expression. Methods: L929 mouse fibroblasts were cultured in vitro. Viability assays, wound-healing assays, and gene expression analyses were performed after 24 hours of treatment with lornoxicam and dexketoprofen at a 0-1-mM dosage. The viability test, wound-healing test, and gene expression analysis were performed using the MTT method, by calculating the closed area, and by qRT-PCR, respectively. Results: Lornoxicam and dexketoprofen at doses of 0-1 mM dose-dependently decreased viability, and changes in cell morphology were observed. Lornoxicam 1 µM and dexketoprofen 10 µM doses significantly reduced the migration rate of L929 cells compared with the control group (****p<0.0001). After 24 hours, COL1A1 expression in L929 cells was 0.027 and 0.015 when 1 and 10 µM of lornoxicam and dexketoprofen were applied. Discussion and Conclusion: Lornoxicam and dexketoprofen have negative effects on the viability, migration, and type 1 collagen synthesis of fibroblasts. Considering these negative effects on fibroblasts is crucial while using these drugs. [ABSTRACT FROM AUTHOR]

Aims The Standard care vs. Celecoxib Outcome Trial (SCOT) found similar risk of cardiovascular events with traditional non-steroidal anti-inflammatory drugs (NSAIDs) and the cyclooxygenase-2-selective drug celecoxib. While pre-clinical work has suggested roles for vascular and renal dysfunction in NSAID cardiovascular toxicity, our understanding of these mechanisms remains incomplete. A post hoc analysis of the SCOT cohort was performed to identify clinical risk factors and circulating biomarkers of cardiovascular events in NSAID users. Methods and results Within SCOT (7295 NSAID users with osteoarthritis or rheumatoid arthritis), clinical risk factors associated with cardiovascular events were identified using least absolute shrinkage and selection operator regression. A nested case–control study of serum biomarkers including targeted proteomics was performed in individuals who experienced a cardiovascular event within 1 year (n = 49), matched 2:1 with controls who did not (n = 97). Risk factors significantly associated with cardiovascular events included increasing age, male sex, smoking, total cholesterol:HDL ratio ≥5, and aspirin use. Statin use was cardioprotective [odds ratio (OR) 0.68; 95% confidence interval (CI) 0.46–0.98]. There was significantly higher immunoglobulin (Ig)G anti-malondialdehyde-modified LDL (MDA-LDL), asymmetric dimethylarginine (ADMA), and lower arginine/ADMA. Targeted proteomic analysis identified serum growth differentiation factor 15 (GDF-15) as a candidate biomarker [area under the curve of 0.715 (95% CI 0.63–0.81)]. Conclusion Growth differentiation factor 15 has been identified as a candidate biomarker and should be explored for its mechanistic contribution to NSAID cardiovascular toxicity, particularly given the remarkable providence that GDF-15 was originally described as NSAID-activated gene-1. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus is a bacterial pathogen of considerable significance in public health, capable of inducing a diverse range of infectious diseases. One of the most notorious mechanisms used by S. aureus to survive and colonize the site of infection is its ability to form biofilms. Diflunisal, a non-steroidal antiinflammatory drug (NSAID), is a known inhibitor of the Agr system in S. aureus, which is key in regulating biofilm formation. This study evaluated the effect of broad-spectrum antibiotics in combination with diflunisal on S. aureus biofilm density. Eight antibiotics were tested independently at different concentrations and in combination with diflunisal to assess their effect on S. aureus biofilm formation. When using the antibiotics alone and with diflunisal, a significant control effect on biofilm formation was observed (p < 0.05), irrespective of diflunisal presence, but did not achieve a complete biofilm growth inhibition. Over time, diflunisal influenced biofilm formation; however, such an effect was correlated with antibiotic concentration and exposure time. With amikacin treatments, biofilm density increased with extended exposure time. In the case of imipenem, doripenem, levofloxacin, and ciprofloxacin, lower doses and absence of diflunisal showed higher control over biofilm growth with longer exposure. However, in all cases, diflunisal did not significantly affect the treatment effect on biofilm formation. In the absence of antibiotics, diflunisal significantly reduced biofilm formation by 53.12% (p < 0.05). This study suggests that diflunisal could be a potential treatment to control S. aureus biofilms, but it does not enhance biofilm inhibition when combined with antibiotics. [ABSTRACT FROM AUTHOR]

Copyright of Equine Veterinary Journal is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction: With little to no regulation of the supplement markets and a paucity of quality information regarding clinical utility of individual marketed supplements, it is difficult for veterinarians to provide any evidence-based recommendations to owners. The current study aimed to provide clinically useful comparative efficacy data on certain marketed supplements. Methods: Using a prospective, block-randomized, double-blinded, placebo-controlled design, one hundred and one pet dogs with clinical hip OA-associated pain with one side worse than the other (index limb) were randomly assigned to one of four treatment groups: Green lipped Mussel plus Krill oil extracts (Antinol® Rapid, EAB-277); Biota orientalis extracts (4CYTE™ Epiitalis® Forte); an NSAID (meloxicam); or placebo (sunflower oil). Peak vertical force (PVF, expressed as a percentage of bodyweight) of the index limb, orthopedic assessment score (OAS) and hematology and blood chemistry values were evaluated before treatment (week 0), at 2, 4 and 6 weeks during treatment. Results: At 6 weeks, the changes from baseline in PVF of the index limb in the EAB-277 and meloxicam groups were significantly greater than the change in the placebo and 4CYTE™ groups, and the placebo and 4CYTE groups were not different from each other. At 6 weeks, there were significant differences between the groups for overall OAS scores with the lowest scores (least impairment) in the EAB-277 and meloxicam groups, followed by the 4CYTE group and then the placebo group. Discussion: Results of this study indicate that meloxicam and EAB-277 have significant objectively measured benefits in managing OA-related pain in dogs compared to placebo, but 4CYTE does not differ from placebo. [ABSTRACT FROM AUTHOR]

Introduction: With rapidly growing interest in the use of cannabidiol (CBD) in the management of pain and other conditions, more information is needed on the safety and efficacy of this supplement, particularly its co-administration with commonly used pharmaceuticals such as non-steroidal anti-inflammatory drugs (NSAIDs). This study sought to assess the effect of CBD in dogs with mobility impairments, as well as evaluate the clinical tolerance of CBD used together with NSAIDs. Materials and methods: Forty-two client-owned dogs with diagnosed mobility impairments were enrolled in this prospective, double-blind, crossover, placebo-controlled study. Baseline data were collected for 10-14 days followed by random allocation to either placebo or CBD oil for 45 days with a 30-day washout period in between. CBD was dosed at 5 mg/kg orally every 12 h with masked placebo administered at equal volume. Outcome measures included objective gait analysis, accelerometry, and clinical metrology instruments. CBD plasma levels and serum biochemistry were also collected along with hepatic ultrasound if warranted. Results: Thirty-eight dogs finished the study with thirty-nine included for at least partial analysis. Compared to baseline, dogs receiving CBD showed evidence of improved outcomes based on blinded veterinary assessments and accelerometer data. Compared to placebo, dogs receiving CBD showed some evidence of improved outcomes on CBPI, CSOM, and blinded veterinary assessments, but not for objective outcome measures. There was evidence of increased ALP when CBD was co-administered with NSAIDs compared to CBD administration alone. Additionally, there was evidence of ALT elevations with CBD and NSAID co-administration, but this elevation did not show evidence of an increase over CBD use alone. Discussion: These results suggest a potential therapeutic benefit in the administration of CBD for the management of mobility impairments, but greater ALP elevations were seen when administered with NSAIDs. While the sample size of dogs that received further hepatic work-up for liver enzyme elevations is small, chosen diagnostics varied, and liver biopsies were not performed, there did not appear to be clinically apparent liver damage. Further research is needed to better understand the efficacy of CBD in a larger population of dogs and patient tolerance and safety when administered with NSAIDs or other medications long term. [ABSTRACT FROM AUTHOR]

Background: Pseudophakic cystoid macular edema (PCME) is a known complication of cataract surgery that contributes to decreased visual acuity. Mechanical manipulation associated with the release of inflammatory mediators is the leading hypothesis for PCME. To date, no standardized prophylactic protocol has been established to effectively reduce the incidence of PCME. This study assessed the efficacy and safety of nonsteroidal anti-inflammatory drops (NSAIDs) and corticosteroids for the prevention of PCME. Method: We searched the following databases MEDLINE, EMBASE, and Cochrane Central. Register of Controlled Trials and included randomized controlled trials (RCTs) that studied the efficacy of NSAID vs. placebo, NSAID vs. steroid, or NSAID + steroid vs. placebo, reporting the incidence of PCME, macular thickness, and best-corrected visual acuity. The risk ratio (RR) with a 95% confidence interval (CI) and a random-effects model was used. The risk of bias was assessed using the revised Cochrane risk-of-bias tool. Results: A total of 18 RCTs were included in this study (n = 2959). Nine RCT showed low risk of bias, 7 RCT showed unclear risk of bias, and 2 RCT had high risk of bias. The incidence of cystoid macular edema among patients treated with NSAIDs was significantly lower (RR = 0.33, P < 0.001). Subgroup analysis revealed a statistically significant low risk of edema among patients treated with NSAIDs alone (P < 0.001) compared to others. NSAIDs were associated with significantly low mean corrected visual acuity values using LogMar (P < 0.001). Conclusion: NSAID alone or in combination with steroids showed its efficacy in reducing the incidence of PCME post-operatively. Future double-blind randomized controlled trials are required to standardize the protocol for different patient population. [ABSTRACT FROM AUTHOR]

Diclofenac is a hepatotoxic non-steroidal anti-inflammatory drug (NSAID) that affects liver histology and its protein expression levels. Here, we studied the effect of diclofenac on rat liver when co-administrated with either Yersinia enterocolitica strain 8081 serotype O:8 biovar 1B (D*Y) or Lactobacillus fermentum strain 9338 (D*L). Spectroscopic analysis of stool samples showed biotransformation of diclofenac. When compared with each other, D*Y rats lack peaks at 1709 and 1198 cm−1, while D*L rats lack peaks at 1411 cm−1. However, when compared to control, both groups lack peaks at 1379 and 1170 cm−1. Assessment of serum biomarkers of hepatotoxicity indicated significantly altered activities of AST (D*Y: 185.65 ± 8.575 vs Control: 61.9 ± 2.607, D*L: 247.5 ± 5.717 vs Control: 61.9 ± 2.607), ALT (D*Y: 229.8 ± 6.920 vs Control: 70.7 ± 3.109, D*L: 123.75 ± 6.068 vs Control: 70.7 ± 3.109), and ALP (D*Y: 276.4 ± 18.154 vs Control: 320.6 ± 9.829, D*L: 298.5 ± 12.336 vs Control: 320.6 ± 9.829) in IU/L. The analysis of histological alterations showed hepatic sinusoidal dilation with vein congestion and cell infiltration exclusively in D*Y rats along with other histological changes that are common to both test groups, thereby suggesting more pronounced alterations in D*Y rats. Further, LC–MS/MS based label-free quantitation of proteins from liver tissues revealed 74.75% up-regulated, 25.25% down-regulated in D*Y rats and 51.16% up-regulated, 48.84% down-regulated in D*L experiments. The proteomics-identified proteins majorly belonged to metabolism, apoptosis, stress response and redox homeostasis, and detoxification and antioxidant defence that demonstrated the potential damage of rat liver, more pronounced in D*Y rats. Altogether the results are in favor that the administration of lactobacilli somewhat protected the rat hepatic cells against the diclofenac-induced toxicity. [ABSTRACT FROM AUTHOR]

The impact of non-steroidal anti-inflammatory drugs (NSAIDs) on rotator cuff repair is an ongoing area of study within orthopedics, with conflicting results in current literature. Despite concerns over the deleterious effects of NSAIDs on rotator cuff healing, they are becoming an integral part of a multimodal post-operative pain control regiment. The purpose of this study was to compare post-operative patient-reported outcomes (PROs), complications rates, and retear rates of arthroscopic rotator cuff repairs in patients using ibuprofen post-operatively to those who abstained from NSAIDs for six weeks after surgery. It was hypothesized that a short course of ibuprofen post-operatively would not lead to inferior PRO scores, increased retear rates, nor increased complication rates after arthroscopic rotator cuff repair. Patients of the primary surgeon who underwent arthroscopic rotator cuff repair between 2012 and 2022 were evaluated by retrospective chart review. In May 2017 the primary surgeon changed his protocol from avoiding NSAIDs for six weeks after surgery to routinely prescribing two weeks of Ibuprofen 800 mg TID post-operatively. Patients who avoided NSAIDs for six weeks were compared to patients who were prescribed NSAIDs post-operatively. Patient demographic data, pre-operative MRI results, pre-operative and post-operative PROs were collected from the EMR. Additionally, post-operative complications and repair failures requiring reoperation within one year were evaluated. 125 patients met inclusion criteria for this study with 36 patients in the NSAID group and 89 in the no NSAID group. When comparing improvement in PROs, the NSAID group reached MCID at one year in 83.8 % of patients and the no NSAID group reached MCID at one year in 73.9 % of patients. There was no significant difference between the groups in reaching MCID improvement at one year (p = 0.471). Five post-operative complications were reported in the no NSAID group and two in the NSAID group (5.7 % vs 5.4 %, respectively, p = 0.827). Finally, there was no significant difference in the percentage of post-operative rotator cuff repair failures requiring revision in the first year between the groups (2.3 % vs 2.7 %, p = 1.000). There was no difference in percent of patients improving their PRO by the MCID between the groups that used ibuprofen and the group that did not. There was also no difference in post-operative complication rates and rates of symptomatic retear requiring reoperation between the groups. This supports that a short course of NSAIDs post-operatively, specifically ibuprofen, after rotator cuff repair does not increase reoperation rates nor lead to a clinically significant decrease in PROs at one year. [ABSTRACT FROM AUTHOR]

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IntroductionIntravenous non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used in healthcare settings, but their comparative safety and resource utilization impacts remain understudied. This study aimed to compare adverse drug reactions (ADRs) and healthcare resource utilization (HCRU) between patients receiving IV-ibuprofen versus IV/IM ketorolac.MethodsA retrospective, longitudinal analysis was conducted using an all-payer database, examining records from January 1, 2014, to June 3, 2023. The study included both adult (≥18 years) and pediatric (

Birds use their legs and wings when transitioning from aerial to ground locomotion during landing. To improve our understanding of the effects of footpad dermatitis (FPD) and keel bone fracture (KBF) upon landing biomechanics in laying hens, we measured ground-reaction forces generated by hens (n = 37) as they landed on force plates (Bertec Corporation, Columbus, OH) from a 30 cm drop or 170 cm jump in a single-blinded placebo-controlled trial using a cross-over design where birds received an anti-inflammatory (meloxicam, 5 mg/kg body mass) or placebo treatment beforehand. We used generalized linear mixed models to test for effects of health status, treatment and their interaction on landing velocity (m/s), maximum resultant force (N), and impulse (force integrated with respect to time [N s]). Birds with FPD and KBF tended to show divergent alterations to their landing biomechanics when landing from a 30 cm drop, with a higher landing velocity and maximum force in KBF compared to FPD birds, potentially indicative of efforts to either reduce the use of their wings or impacts on inflamed footpads. In contrast, at 170 cm jumps fewer differences between birds of different health statuses were observed likely due to laying hens being poor flyers already at their maximum power output. Our results indicate that orthopedic injuries, apart from being welfare issues on their own, may have subtle influences on bird mobility through altered landing biomechanics that should be considered.

Introduction: Upper gastrointestinal bleeding (UGIB) is among the most common causes of morbidity and mortality worldwide, accounting for major resource allocation and increasing incidence. This study aimed to evaluate the severity of non-variceal bleeding in patients at risk of bleeding through the use of NSAIDs, oral anticoagulants, and antiplatelet therapy. Material and Method: The study included 296 patients admitted in the Gastroenterology Department of the Municipal County Emergency University Hospital, Timisoara, between 01.01.2018 and 01.04.2020, and diagnosed via gastroscopy with non-variceal gastrointestinal bleeding. The patients were divided among four groups based on their use of different drugs known to induce UGIB, i.e., aspirin and clopidogrel, NOACs, NSAIDs, and anti-vitamin K drugs, respectively. Statistical analyses were performed based on ANOVA one-way tests for continuous variables and Chi-square tests for categorical variables with pairwise comparisons based on Bonferroni adjusted significance tests. Results: The results showed several parameters having statistical significance among the different groups of patients. Patients on NOACs had statistically significant lower hemoglobin levels, lower hematocrit values, lower erythrocytes, lower RDW and higher fibrinogen levels compared to patients on VKA. Discussion: Surprisingly, the results from our study suggest that the use of NOACs was associated with a higher risk of bleeding when compared to VKA, which differs from the existing literature. Conclusions: One of the important factors causing upper non-variceal bleeding can be iatrogenic, either due to antiplatelet drugs or anticoagulants, to which NSAID treatment is additionally associated for various reasons. In our study, the use of NOACs seemed to have a more severe bleeding spectrum with higher morbidity compared to VKA. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To retrospectively evaluate safety and tolerance of leflunomide for long-term treatment of canine idiopathic immune-mediated polyarthritis (IMPA), ANIMALS: 27 dogs with clinical signs and synovial fluid cytology supportive of IMPA with 26 months' follow-up after starting leflunomide. METHODS: Medical records were reviewed to identify dogs prescribed leflunomide for treatment of IMPA from February 2012 to May 2022. Initial leflunomide doses of 2 to 4 mg/kg once daily were prescribed and were titrated to the lowest effective dose with concurrent anti-inflammatory therapy. Complete blood count, serum chemistry, and clinical signs were monitored throughout the course of treatment. RESULTS: Adverse effects potentially attributable to leflunomide noted in 9 of 27 dogs (33%) included vomiting, diarrhea, lethargy, decreased or absent appetite, polyuria and polydipsia, and secondary antibiotic responsive infection and were self-limiting or resolved with outpatient therapy. Alkaline phosphatase (ALP) and alanine aminotransferase (ALT) elevation were documented in all dogs prescribed leflunomide plus prednisone, with persistent liver enzyme elevation in 6 of 9 dogs (67%) and normalization after antibiotic therapy in 3 of 9 dogs (33%). The majority of dogs prescribed leflunomide plus NSAID (11/17 [65%] dogs) did not experience liver enzyme elevation; 2 of 17 (12%) dogs developed transient antibiotic-responsive liver enzyme elevations, and 4 of 17 (23%) dogs had persistent liver enzyme elevation. CLINICAL RELEVANCE: Leflunomide was well tolerated for long-term management of IMPA. A significant difference in liver enzyme elevation was identified between dogs prescribed prednisone versus NSAID in combination with leflunomide. Leflunomide with NSAID therapy resulted in less hepatotoxicity compared with leflunomide with prednisone. [ABSTRACT FROM AUTHOR]

Parenteral ketorolac and intravenous (IV) acetaminophen have been used for prehospital analgesia, yet limited data exist on their comparative effectiveness. To evaluate the comparative effectiveness of IV acetaminophen and parenteral ketorolac for analgesia in the prehospital setting. We conducted a retrospective cross-sectional evaluation of patients receiving IV acetaminophen or parenteral ketorolac for pain management in a large suburban EMS system between 1/1/2019 and 11/30/2021. The primary outcome was change in first to last pain score. Subgroup analysis was performed on patients with traumatic pain. We used inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) to estimate the treatment effect of acetaminophen versus ketorolac among all patients and the subgroup of those with traumatic pain. Of 2178 patients included, 856 (39.3%) received IV acetaminophen and 1322 (60.7%) received parenteral ketorolac. The unadjusted mean change in pain score was −1.9 (SD 2.4) for acetaminophen group and −2.4 (SD 2.4) for ketorolac. In the propensity score analyses, there was no statistically significant difference in pain score change for the acetaminophen group versus ketorolac among all patients (mean difference, IPTW: 0.11, 95% confidence interval [CI] −0.16, 0.37; PSM: 0.15, 95% CI −0.13, 0.43) and among those with traumatic pain (unadjusted: 0.18, 95% CI −0.35, 0.72; IPTW: 0.23, 95% CI −0.25, 0.71; PSM: −0.03, 95% CI −0.61, 0.54). We found no statistically significant difference in mean pain reduction of IV acetaminophen and parenteral ketorolac for management of acute pain. [ABSTRACT FROM AUTHOR]

The aim of this paper was to present a rapid, simple, and straightforward high-performance liquid chromatography (HPLC) method for the determination of robenacoxib in plasma. Robenacoxib is a member of the COXIB group of nonsteroidal anti-inflammatory drugs developed for veterinary use. The method was validated based on the FDA Guidance for Industry: Bioanalytical Method Validation for selectivity, linearity, accuracy, precision, stability, and recovery. Methylene chloride was used in a liquid–liquid extraction that produced an average recovery of 97%. Chromatographic separation occurred on a Sunfire C18 column (4.6 × 150 mm) using an isocratic combination of 0.025% trifluoroacetic acid in water and acetonitrile (50:50, v/v). Ultraviolet absorbance was measured at 275 nm and the flow rate was 1.1 mL/min. The method was linear in the concentration range of 0.1 to 50 µg/mL. The assay variability ranged from 2.2% to 9.2% while the accuracy was 100%. The lower limit of quantification for a 0.1 mL sample size was 0.1 µg/mL. The method was used for the determination of robenacoxib in plasma samples. [ABSTRACT FROM AUTHOR]

This study aimed to assess the anti-inflammatory properties of a bioactive glutamic-alanine rich glycoprotein (GP) derived from Undaria pinnatifida on both LPS-stimulated RAW264.7 cells, peritoneal macrophages, and mouse models of carrageenan- and xylene-induced inflammation, investigating the underlying molecular mechanisms. In both in-vitro and in-vivo settings, GP was found to reduce the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) while also inhibiting the production of nitric oxide (NO) and prostaglandin E2 (PGE2) in response to lipopolysaccharide (LPS) stimulation. GP treatment significantly impeded the nuclear translocation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway by blocking the phosphorylation of IKKα and IκBα, leading to a reduction in proinflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). Additionally, GP effectively inhibited the activation of mitogen-activated protein kinases (MAPKs), with specific inhibitors of p38 and extra-cellular signal regulated kinase (ERK) enhancing GP's anti-inflammatory efficacy. Notably, GP administration at 10 mg/kg/day (p.o.) markedly reduced carrageenan-induced paw inflammation and xylene-induced ear edema by preventing the infiltration of inflammatory cells into targeted tissues. GP treatment also downregulated key inflammatory markers, including iNOS, COX-2, IκBα, and NF-κB, by suppressing the phosphorylation of p38 and ERK, thereby improving the inflammatory index in both carrageenan- and xylene-induced mouse models. These findings suggest that marine resources, particularly seaweeds like U. pinnatifida, could serve as valuable sources of natural anti-inflammatory proteins for the effective treatment of inflammation and related conditions. [ABSTRACT FROM AUTHOR]