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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]

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]

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]

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]

Copyright of Medicina Pro Praxi is the property of SOLEN sro 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.)

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]

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]

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]

Mares enrolled in assisted reproductive technologies (ARTs) programs are often treated with non-steroidal anti-inflammatory drugs (NSAIDs), particularly phenylbutazone (Bute), due to chronic lameness. The current study was performed to determine the effect of Bute administration on the developmental competence of in vitro -matured equine oocytes subjected to Intracytoplasmic Sperm Injection (ICSI). In a Preliminary Study, immature cumulus-oocyte complexes (COCs) recovered by post-mortem ovary harvested from two healthy mares (n = 2) treated for 10 days with Bute (4.4 mg/kg, PO, BID), and four non-treated healthy mares (n = 4), were matured in vitro and subjected to Piezo-driven ICSI. Lower oocyte in vitro maturation [Bute: 25% (3/12) vs. Control: 61% (28/46)] and blastocyst rates [Bute: 0% (0/12) vs. Control: 18% (5/28)] were observed in the Bute-treated when compared to the Control mares (P < 0.05). In the Main Experiment, a group of healthy mares (n = 9) received a daily dose of Bute (4.4 mg/kg, orally, SID) for 10 days. A control group of mares (n = 10) was treated with an equal volume of placebo. Mares in both groups were subjected to ultrasound-guided transvaginal oocyte aspiration (TVA) on days 3, 33, and 77 following the last dose of Bute (PT). Recovered COCs from both mare groups were matured in vitro and subjected to Piezo-driven ICSI. By day-3 PT, oocyte in vitro maturation rate was similar between mare groups [Bute: 65% (36/55) vs. Control: 67% (78/116); P > 0.05], while oocyte recovery [Bute: 53% (55/103) vs. Control: 70% (116/166)], cleavage [Bute: 31% (11/36) vs. Control: 62% (48/78)] and blastocyst rates [Bute: [0%] (0/36) vs. Control: 28% (22/78)] were significantly different (P < 0.05). By day 33 PT and 77 PT, differences on oocyte recovery, in vitro maturation, cleavage, and blastocyst rates were not observed between mare groups. In summary, the administration of Bute for 10 consecutive days (4.4 mg/kg, PO, SID, or BID) is associated with a decrease in the ability of immature equine oocytes to undergo in vitro -maturation (Preliminary Study) and develop to the blastocyst stage following ICSI (Preliminary Study and Main Experiment). This negative effect appeared to be transient, as 30- and 77-days post-treatment, no differences on in vitro maturation, cleavage or blastocyst rates were observed. • Oral phenylbutazone impaired in vitro competence of equine oocytes. • Highest dose of phenylbutazone resulted in no blastocyst production after ICSI. • Recommended dose of phenylbutazone had a transient negative effect on blastocyst production after ICSI. • Embryo production was similar to non-treated mares after one month post-treatment with phenylbutazone. [ABSTRACT FROM AUTHOR]

Purpose: In 2005, the Food and Drug Administration (FDA) issued a decision memorandum regarding nonsteroidal anti-inflammatory drugs (NSAIDs). The memorandum recommended the withdrawal of certain NSAIDs due to potential cardiovascular adverse effects. It highlighted the issue of cardiovascular risk associated with NSAIDs as a class. The NSAID medication guide includes a wide range of adverse drug reactions (ADRs), such as increased blood pressure, liver failure, allergic reactions, heart attack, and intestinal bleeding. Although both sexes have an increased risk of ADRs with NSAID use, females have a greater risk than males due to differences in pharmacodynamics and higher medication concentrations (mg/kg). In particular, females with high blood pressure, coronary heart, kidney, and liver disease are at an additional risk of harm from NSAID ADRs. This study quantifies sex-specific differences and other factors associated with prescription NSAID use. Method: The data for this study were obtained from the National Health and Nutrition Examination Survey (NHANES), a complex survey conducted by the Centers for Disease Control and Prevention (CDC) in two-year cycles. A survey-weighted logistic regression model was utilized to investigate potential sex differences with prescription NSAIDs in the context of other factors, including kidney disease, hypertension, liver disease, insurance status, coronary heart disease, and age, within the 2011–2018 NHANES survey data. Results: Females reported a slightly higher percentage of high blood pressure and kidney disease than males, while males reported a slightly higher percentage of coronary heart and liver disease than females. Last, the model indicated that females were 58% more likely to have used a prescription NSAID than males. Conclusion: The results confirm that women and people with medical conditions, who would potentially suffer greater harm from NSAID ADRs, are more likely to use a prescription NSAID than individuals without these conditions. [ABSTRACT FROM AUTHOR]

Objective: To determine the effectiveness of oral Theophyline compared to Non-Steroidal Anti-Inflammatory Drugs in the management of postdural puncture headache in obstetric patients. Study Design: Quasi-experimental Study. Place and Duration of Study: Anaesthesia Department, Combined Military Hospital, Kharian Pakistan, from Apr to Sep 2018. Methodology: Our study enroled 60 pregnant women suffering from postdural puncture headache. The were divided in to two groups, NSAID-Group (Group-A) who received 30mg of Ketorolac in three divided doses in 24 hours and Theophyline-Group (Group-B) who received 750mg of oral Theophyline in three divided doses in 24 hours after which effects of both drugs were noted. Results: Pregnant women were enroled in NSAID-Group and in Theophyline Group. Mean baseline Visual Analogue Scale score was 7.500±0.97 in NSAID-Group and 7.33±0.92 in Theophyline Group. Mean weight was 66.86±5.25 kg in NSAID-Group and 67.16±7.01 Kg in Theophyline-Group. In NSAID-Group efficacy was noted in 7(23.3%) patients as compared to 25(83.3%) patients in Theophyline-Group, (p<0.001). Conclusion: Theophyline when given oraly in the management of postdural puncture headache proved to be a superior alternative to NSAID medication. [ABSTRACT FROM AUTHOR]

Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to manage pain, fever, and inflammation. Although most are usually classified as prescription-only medicines, in many countries they are frequently purchased for self-medication purposes. This study explores NSAID-usage patterns in Kosovo, aiming for a safer and more effective medicinal use. The study employed a dual approach to collect data. First, NSAID sales were analyzed in a convenience sample of ten community pharmacies across diverse regions in Kosovo in 2023. Second, data on NSAID-usage patterns and patient awareness were systematically gathered from 410 patients during routine pharmacist–patient interactions. The four most commonly purchased NSAIDs according to sales analysis were diclofenac (33.1%), ketoprofen (27.6%), ibuprofen (17.0%) and nimesulide (12.7%). A significant 74.8% of NSAIDs were bought without prescriptions, particularly among younger adults (20–39 years), who accounted for 82.8% of such purchases. The predominant reason for NSAID use was headache (43.8%). Although many of the patients suffered from occasional (33.7%) or frequent (12.6%) stomachaches and took acid-lowering medicines, the majority (85.9%) could not recall any NSAID adverse reactions. This study exposes widespread self-medication and a significant lack of awareness regarding potential risks of NSAIDs, particularly among young adults. To address these issues, it is critical to improve dispensing practices through increased pharmacist awareness and stricter law enforcement. [ABSTRACT FROM AUTHOR]

The transdermal delivery of non-steroidal anti-inflammatory drugs (NSAIDs) has the potential to overcome some of the major disadvantages relating to oral NSAID usage, such as gastrointestinal adverse events and compliance. However, the poor solubility of many of the newer NSAIDs creates challenges in incorporating the drugs into formulations suitable for application to skin and may limit transdermal permeation, particularly if the goal is therapeutic systemic drug concentrations. This review is an overview of the various strategies used to increase the solubility of poorly soluble NSAIDs and enhance their permeation through skin, such as the modification of the vehicle, the modification of or bypassing the barrier function of the skin, and using advanced nano-sized formulations. Furthermore, the simple yet highly versatile microemulsion system has been found to be a cost-effective and highly successful technology to deliver poorly water-soluble NSAIDs. [ABSTRACT FROM AUTHOR]

The use of non-steroidal anti-inflammatory drugs (NSAID) in patients undergoing pleurodesis remains controversial. Although many surgeons are comfortable prescribing NSAIDs post-operatively, some oppose this practice due to concerns of suppressing the inflammatory response and quality of pleurodesis. Only a small body of inconsistent publications exists with respect to guiding therapy in this common clinical scenario. A retrospective cohort study was undertaken assessing effect of NSAID exposure on pleurodesis outcomes. An institutional thoracic surgery database was reviewed yielding 147 patients who underwent pleurodesis for pneumothorax between 2010 and 2018. Medical records and imaging were reviewed for patient characteristics, NSAID exposure, recurrent pneumothorax and other adverse events. There was no overall difference between rates of recurrence and procedural failure of pleurodesis (Relative Risk [RR] 1.67 [95% CI 0.74-3.77]). However, NSAID exposure of >48 hours was associated with increased risk of recurrent pneumothorax (RR 2.16 [95% CI 1.05-4.45]). There was no increased rate of other adverse events related to NSAID usage. NSAID exposure does not increase failure rates or other adverse events following pleurodesis for pneumothorax. However, prolonged NSAID exposure post-pleurodesis may increase procedural failure rates. Further large volume randomised control trials are required. [ABSTRACT FROM AUTHOR]

Background: We assessed the incidence of and risk factors for acute kidney injury (AKI) in very low birthweight infants (VLBW) in a center with a specific neonatal management protocol focusing on avoidance of early mechanical ventilation (MV). Methods: This retrospective single center analysis includes 128 infants born in 2020 with a gestational age ≥ 22 weeks who were screened for AKI using the nKDIGO criteria. Results: AKI was identified in 25/128 patients (19.5%) with eight of them (6.3%) presenting with severe AKI. Low gestational age, birthweight and 10-minute Apgar score as well as high CRIB-1 score were all associated with incidence of AKI. Forty-five percent of the infants with MV developed AKI vs. 8.9% of those without MV (p < 0.001). Early onset of MV and administration of more than 3 dosages of NSAIDs for patent duct were identified as independent risk factors for AKI in a logistic regression analysis. Conclusions: We report a substantially lower frequency of AKI in VLBW infants as compared to previous studies, along with a very low rate of MV. A neonatal protocol focusing on avoidance of MV within the first days of life may be a key factor to decrease the risk of AKI in immature infants. [ABSTRACT FROM AUTHOR]

Nonsteroidal anti‐inflammatory drugs (NSAIDs) are a valuable class of medications for orthopedic surgeons and often play a pivotal role in pain control. However, there are many common stipulations resulting in avoidance of its use in the treatment of musculoskeletal disease. This review summarizes the mechanism of action of NSAIDs as well as provides an overview of commonly used NSAIDs and the differences between them. It provides a concise summary on the osseous effects of NSAIDs with regard to bone healing and heterotopic ossification. Most of all, it serves as a guide or reference for orthopedic providers when counseling patients on the risks and benefits of NSAID use, as it addresses the common stipulations encountered: "It irritates my stomach," "I have a history of bariatric surgery," "I'm already on a blood thinner," "I've had a heart attack," and "I've got kidney problems" and synthesizes both current research and society recommendations regarding safe use and avoidance of NSAIDs. [ABSTRACT FROM AUTHOR]

Amides containing methyl esters of γ-aminobutyric acid (GABA), L-proline and L-tyrosine, and esters containing 3-(pyridin-3-yl)propan-1-ol were synthesized by conjugation with 3,5-di-tert-butyl-4-hydroxybenzoic, an NSAID (tolfenamic acid), or 3-phenylacrylic (cinnamic, (E)-3-(3,4-dimethoxyphenyl)acrylic and caffeic) acids. The rationale for the conjugation of such moieties was based on the design of structures with two or more molecular characteristics. The novel compounds were tested for their antioxidant, anti-inflammatory and hypolipidemic properties. Several compounds were potent antioxidants, comparable to the well-known antioxidant, Trolox. In addition, the radical scavenging activity of compound 6 reached levels that were slightly better than that of Trolox. All the tested compounds demonstrated remarkable activity in the reduction in carrageenan-induced rat paw edema, up to 59% (compound 2, a dual antioxidant and anti-inflammatory molecule, with almost 2.5-times higher activity in this experiment than the parent NSAID). Additionally, the compounds caused a significant decrease in the plasma lipidemic indices in Triton-induced hyperlipidemic rats. Compound 2 decreased total cholesterol by 75.1% and compound 3 decreased triglycerides by 79.3% at 150 μmol/kg (i.p.). The hypocholesterolemic effect of the compounds was comparable to that of simvastatin, a well-known hypocholesterolemic drug. Additionally, all compounds lowered blood triglycerides. The synthesized compounds with multiple activities, as designed, may be useful as potential candidates for conditions involving inflammation, lipidemic deregulation and oxygen toxicity. [ABSTRACT FROM AUTHOR]

The purpose of this study is to identify the risk factors with cardiovascular events among NSAID users. Methods: This study is a retrospective, nested case–control study, within the DAVINCI database, among active-duty service members and veterans with at least one NSAID pharmacy claim between fiscal year (FY) 2015-FY2020. Inclusion criteria individuals ≥ 18 years of age received a prescription NSAID for ≥ 7-day supply and a duration ≥ 1 month overall. Cases experienced nonfatal myocardial infarction, nonfatal stroke, or new onset heart failure. Ten controls were selected per case. Risk factors were identified through logistic regression modeling. Results: The risk factors with strongest association to the primary outcome included age starting at 45 up to 75 and older, the first 90 days of NSAID exposure, cerebrovascular disease, cardiomyopathy, and history of myocardial infarction. Cox-selectivity and dose did not appear to be clinically significant in their association with cardiovascular events. Conclusion: The results of this study indicate that age, initial NSAID exposure, and comorbidities are more predictive than NSAID-specific factors such as COX-selectivity and dose. The results provide the framework for development of a risk score to improve prediction of NSAID-associated cardiovascular events. [ABSTRACT FROM AUTHOR]

Commercial cyclodextrins (CDs) are commonly used to form inclusion complexes (ICs) with different molecules in order to enhance their water solubility, stability, and bioavailability. Nowadays, there is strong, convincing evidence of the anticancer effect of selenium (Se)-containing compounds. However, pharmaceutical limitations, such as an unpleasant taste or poor aqueous solubility, impede their further evaluation and clinical use. In this work, we study the enhancement of solubility with CD complexes for a set of different nonsteroidal anti-inflammatory drug (NSAID) derivatives with Se as selenoester or diacyl diselenide chemical forms, with demonstrated antitumoral activity. The CD complexes were analyzed via nuclear magnetic resonance (NMR) spectroscopic techniques. In order to obtain additional data that could help explain the experimental results obtained, 3D models of the theoretical CD-compound complexes were constructed using molecular modeling techniques. Among all the compounds, I.3e and II.5 showed a remarkable increase in their water solubility, which could be ascribed to the formation of the most stable interactions with the CDs used, in agreement with the in silico studies performed. Thus, the preliminary results obtained in this work led us to confirm the selection of β and γ-CD as the most suitable for overcoming the pharmaceutical drawbacks of these Se derivatives. [ABSTRACT FROM AUTHOR]

Stability, thermal characterization, and identification of possible polymorphism are relevant in the development of novel therapeutic drugs. In this context, thirty new nonsteroidal anti-inflammatory drug (NSAID) derivatives containing selenium (Se) as selenoesters or diacyl diselenides with demonstrated anticancer activity were thermally characterized in order to establish thermal stability criteria and detect possible polymorphic forms. Compounds were analyzed by a combination of thermogravimetry, differential scanning calorimetry, and X-ray diffraction techniques, and five different calorimetric behaviors were identified. Two compounds based on naproxen (I.3d and I.3e) and an indomethacin-containing derivative (II.2) presented two crystalline forms. The stability under acid, alkaline and oxidative conditions of selected polymorphs was also assessed using high-performance liquid chromatography. In addition, the cytotoxic activity of Se-NSAID crystalline polymorphs was studied in several cancer cell lines in vitro. Remarkably, no significant differences were found among the polymorphic forms tested, thus proving that these compounds are thermally qualified for further drug development. [ABSTRACT FROM AUTHOR]

The aim of the present study was to prepare and evaluate Ketoprofen loaded microspheres fabricated with sodium alginate and Carbopol 934 by ion gelation method which enhances the drug residence time into the stomach by adhering to the mucus layer of and control the rate of drug release for longer period of time. Ketoprofen is a nonsteroidal anti-inflammatory drug (NSAID) that is commonly used for its analgesic, anti-inflammatory, and antipyretic (fever-reducing) properties. It belongs to the propionic acid class of NSAIDs and is available in various formulations, including oral tablets, capsules, topical gels, creams, and as an injectable solution. In present study ketoprofen incorporates in mucoadhesive drug delivery system for utilizing its controlled drug delivery up to 12 hrs. In present study prepared microspheres were evaluated for- particle size, entrapment efficiency, percentage yield, morphology, mucoadhesive property, in-vitro drug release property. [ABSTRACT FROM AUTHOR]

Simple Summary: Prostate cancer is a serious health problem for men around the world, and it is often caused by inflammation in the prostate gland. The authors of this article explore how a group of drugs called nonsteroidal anti-inflammatory drugs (NSAIDs) can help prevent and treat this disease by reducing inflammation and interfering with the growth and survival of cancer cells. We describe the various mechanisms by which NSAIDs can affect prostate cancer, such as triggering cell death, halting cell division, and cutting off blood supply. We also discuss the evidence from previous studies that support the use of NSAIDs as anti-cancer agents, either alone or in combination with other treatments. NSAIDs have a lot of promise as potential drugs for prostate cancer, but more research to understand their optimal dosage, timing, and safety is needed. Prostate cancer (PC) is the second most common type of cancer and the leading cause of death among men worldwide. Preventing the progression of cancer after treatments such as radical prostatectomy, radiation therapy, and hormone therapy is a major concern faced by prostate cancer patients. Inflammation, which can be caused by various factors such as infections, the microbiome, obesity and a high-fat diet, is considered to be the main cause of PC. Inflammatory cells are believed to play a crucial role in tumor progression. Therefore, nonsteroidal anti-inflammatory drugs along with their effects on the treatment of inflammation-related diseases, can prevent cancer and its progression by suppressing various inflammatory pathways. Recent evidence shows that nonsteroidal anti-inflammatory drugs are effective in the prevention and treatment of prostate cancer. In this review, we discuss the different pathways through which these drugs exert their potential preventive and therapeutic effects on prostate cancer. [ABSTRACT FROM AUTHOR]

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most commonly used over-the-counter medications for the treatment of pain, fever, and inflammation. Gastrointestinal problems and renal complications are the most frequently observed adverse effects associated with NSAID usage. Therefore, this study aims to evaluate the levels of knowledge, attitude, and practice regarding the adverse effects of non-prescription NSAIDs among community pharmacists in Egypt. Methods: A 4-month cross-sectional survey, including licenced community pharmacists in Egypt, was conducted. The anonymous Google Forms survey was accompanied by a cover letter explaining its purpose. The survey link was sent to 2000 verified community pharmacist email addresses with clear instructions to complete and submit the questionnaire within 3 weeks. Descriptive and inferential statistical analyses were conducted using IBM-SPSS version 26. The means of variables were compared using analysis of variance test. Pearson correlation was employed to assess the level of linear association between the overall knowledge, practice, and attitude scores. P-value ≤ 0.05 was considered statistically significant. Results: Approximately 80% of community pharmacists in Egypt exhibit moderate-to-good knowledge regarding the adverse effects of NSAIDs. Additionally, 60.6% of them demonstrated a positive attitude and 80.9% showed moderate-to-good practice scores towards preventing such adverse effects. The education level was the only demographic factor with significant effects on the NSAIDs-related knowledge, practice, and attitude scores. Community pharmacists primarily rely on internet sources for knowledge updates. Additionally, there was a significant positive linear correlation between knowledge and attitude (r = 0.384, P < 0.001), knowledge and practice (r = 0.178, P < 0.001), and between attitude and practice (r = 0.311, P < 0.001) among the participants. Conclusion: Community pharmacists have a vital responsibility to perform screenings, assess patient risk elements, and share knowledge to guarantee the appropriate and safe utilisation of NSAIDs. Given that internet sources are presently the most accessible and used sources of information, governmental directions should prioritise the establishment and enhancement of freely accessible drug information sources for community pharmacists. Further research is necessary to assess the effectiveness of counselling and appropriate guidance provided by community pharmacies in promoting safe and proper drug usage. [ABSTRACT FROM AUTHOR]

Copyright of SEMS-Journal is the property of Schwiez Zschr Sportmed Sporttraumatologie 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.)

The introduction of selenium (Se) into organic scaffolds has been demonstrated to be a promising framework in the field of medicinal chemistry. A novel design of nonsteroidal anti-inflammatory drug (NSAID) derivatives based on a bioisosteric replacement via the incorporation of Se as diacyl diselenide is reported. The antioxidant activity was assessed using the DPPH radical scavenging assay. The new Se-NSAID derivatives bearing this unique combination showed antioxidant activity in a time- and dose-dependent manner, and also displayed different antiproliferative profiles in a panel of eight cancer cell lines as determined by the MTT assay. Ibuprofen derivative 5 was not only the most antioxidant agent, but also selectively induced toxicity in all the cancer cell lines tested (IC50 < 10 µM) while sparing nonmalignant cells, and induced apoptosis partially without enhancing the caspase 3/7 activity. Furthermore, NSAID derivative 5 significantly suppressed tumor growth in a subcutaneous colon cancer xenograft mouse model (10 mg/kg, TGI = 72%, and T/C = 38%) without exhibiting any apparent toxicity. To our knowledge, this work constitutes the first report on in vitro and in vivo anticancer activity of an unprecedented Se-NSAID hybrid derivative and its rational use for developing precursors for bioisosteric selenocompounds with appealing therapeutic applications. [ABSTRACT FROM AUTHOR]

Objective: Patients diagnosed with drug allergy should be carefully instructed to avoid using the culprit drug and provided with drug allergy passports to alert healthcare providers. However, accidental re-exposure to the offending drug may occur. To determine the rate of re-exposure to culprit drugs in patients diagnosed with drug allergy and the characteristics of reactions they experienced. Materials and Methods: Patients who were diagnosed with drug allergy confirmed with diagnostic tests in the Pediatric Allergy Clinic between 2010 and 2020 were contacted by phone to obtain information on re-exposure to the offending drug after diagnosis and to determine whether the drug reuse was associated with any reaction. Results: A total of 92 patients with confirmed drug allergy who were contacted by phone were included in the study. The mean age of the study patients was 152 months (range, 108-204) and 54.3% (n=50) of the patients were female. Culprit drugs were antibiotics in 68.5% (n=63), NSAIDs in 23.9% (n=22), antiepileptics in 4.3% (n=4), and other drugs in 3.3% (n=3) of the patients. All of the patients reported that they carry a drug allergy passport at all times and informed the physician about their drug allergy during an examination. Three of the study patients were re-exposed to the culprit drug and two of them had developed a reaction. One had urticaria and the other experienced anaphylaxis after re-exposure. Conclusion: Patients with confirmed drug allergy should be advised to avoid re-exposure to the culprit drug and to carry their drug allergy passports at all times to alert physicians when they are prescribing a drug treatment. [ABSTRACT FROM AUTHOR]

Background: Predicting disease severity can be informative for management of HUS. Dialysis requirement, volume depletion, elevated white blood cell counts, very young age, and use of antimotility agents are known factors associated with severe HUS. Methods: A retrospective cohort analysis was performed to identify factors associated with dialysis duration using electronic medical record and chart review of 76 children ≤ 18 years of age at presentation with STEC-HUS identified through billing data from July 2008 to April 2020 at James Whitcomb Riley Hospital for Children, Indiana University, Indiana. Results: Novel findings associated with prolonged dialysis duration were age ≥ 6 years old at presentation (p = 0.041) and lack of drop in platelets below 60,000/mm3 anytime during the illness (p = 0.015). In addition, children with NSAID exposure trended longer on dialysis: 15 days with vs. 10 days without (p = 0.117). Known risk factors for severe disease including elevated peak white blood cell (WBC) count and higher hematocrit at presentation were also associated with longer dialysis duration: children with peak WBC > 20,000/mm3 were on dialysis for 15 vs. 9.5 days (p = 0.002) and in children on dialysis ≥ 14 days hematocrit at presentation was 29.6% vs. 24.2% (p = 0.03). Children requiring dialysis for 20 days or longer were more likely to be on anti-hypertensive medications (p = 0.025) and have chronic kidney disease at 12-month follow up (p = 0.044). Conclusions: Age ≥ 6, elevated WBC count > 20,000/mm3, higher hematocrit at presentation, lack of drop in platelets to < 60,000/mm3, and possibly NSAID exposure during illness are associated with longer dialysis duration in STEC-HUS. [ABSTRACT FROM AUTHOR]

The combination of non-steroidal anti-inflammatory drugs (NSAIDs) with non-opioid analgesics is common in clinical practice for the treatment of acute painful conditions like post-operative and post-traumatic pain. Despite the satisfactory results achieved by oral analgesics, parenteral analgesia remains a key tool in the treatment of painful conditions when the enteral routes of administration are inconvenient. Parenteral ready-to-use fixed-dose combinations of non-opioid analgesics combinations, including NSAIDs and paracetamol or metamizole, could play a central role in the treatment of painful conditions by combining the advantages of multimodal and parenteral analgesia in a single formulation. Surprisingly, only in 2020, a parenteral ready-to-use fixed-dose combination of ibuprofen/paracetamol was launched to the market. This review aims to investigate the current availability of combinations of NSAIDs with paracetamol or metamizole in both European and American markets, and how the combination of such drugs could play a central role in a multimodal analgesia strategy. Also, we explored how the parenteral formulations of NSAIDs, paracetamol, and metamizole could serve as starting elements for the development of new parenteral ready-to-use fixed-dose combinations. We concluded that, despite the well-recognized utility of combining NSAIDs with paracetamol or metamizole, several randomized clinical trial studies demonstrate no clear advantages concerning their efficacy and safety. Future clinical trials specifically designed to assess the efficacy and safety of pre-formulated fixed-dose combinations are required to generate solid evidence about their clinical advantages. [ABSTRACT FROM AUTHOR]

Objective To investigate the effect of pharmacological treatment of SpA on depressive symptoms and explore whether this effect differs between drug classes. Methods Data from the observational Assessment of SpondyloArthritis international Society Health Index Validation Study were used. Patients were assessed at baseline and after initiation of NSAIDs/conventional synthetic DMARDs (csDMARDs)/TNF inhibitors (TNFis). Depressive symptoms were assessed with the Hospital Anxiety and Depression Scale depression subscale [HADS-D; 0–21 (best–worst)]. Covariables included demographics and disease characteristics, including disease activity [Ankylosing Spondylitis Disease Activity Score (ASDAS)/BASDAI]. The change in HADS-D from baseline was compared between treatments (NSAIDs/csDMARDs/TNFis) with analysis of variance and multivariable regression analysis. Results A total of 304 patients were included; 102/45/157 initiated NSAIDs/csDMARDs/TNFis and 260 (85%) / 44 (15%) had axial/peripheral SpA. At baseline, the mean HADS-D was 6.9 (s. d. 4.2); 126 (42%) were possibly depressed (HADS-D ≥8) and 66 (22%) were probably depressed (HADS-D ≥11). At follow-up, depressive symptoms significantly improved in all treatment groups. In multivariable regression without disease activity measures, initiating TNFis compared with NSAIDs was associated with greater improvement in depressive symptoms [β = −1.27 (95% CI −2.23, −0.32)] and lower odds of possible depression at follow-up [odds ratio 0.47 (95% CI 0.23, 0.94)]. This association was attenuated after additional adjustment for disease activity (ASDAS/BASDAI) but not CRP. csDMARDs did not differ from NSAIDs regarding their effect on HADS-D. Between-drug class results were confirmed in axial SpA (axSpA), although less clear in peripheral SpA. Conclusion Treatment of active SpA also improves depressive symptoms. Especially in axSpA, TNFis have a greater effect than NSAIDs, which is mainly explained by a stronger effect on disease activity. We found no evidence for a direct link between CRP-mediated inflammation and depressive symptoms in SpA. [ABSTRACT FROM AUTHOR]

Simple Summary: The disbudding of calves is undertaken as a routine management practice. It is known to be a painful procedure for calves, and it is a legal requirement that calves are disbudded under local anaesthesia. It is also recommended that calves receive pain-relieving drugs (NSAIDs, non-steroidal anti-inflammatory drugs) which improve welfare and performance as well as reducing the pain experienced. Calves were allocated to one of two groups prior to undergoing disbudding; both groups received the same local anaesthetic. One group received a subcutaneous injection of Meloxicam as a positive control, and the second group received oral sodium salicylate added into their milk. Behaviour changes were monitored between treatment groups using accelerometers, with no differences being found in activity, lying bouts or lying times. There were also no differences in weight gain between the groups. Sodium salicylate offers a cheaper option for farmers when compared to meloxicam and can be administered orally, which is a less invasive technique than injection. Despite anaesthetic and NSAID administration, all calves showed behaviour changes for 5 days post procedure. Disbudding calves using hot iron cautery is a routine management procedure to destroy the germinal cells around the horn bud in calves. It is recommended that NSAIDs are used in conjunction with local anaesthesia to reduce pain in calves during and after the procedure. In this study, two treatment groups were examined; calves in the positive control MEL group received subcutaneous meloxicam, and SAL calves received sodium salicylate orally for three days, both in addition to a local anaesthesia. Tri-axis accelerometers were attached to the calves, and DLWG (Daily Live Weight Gain) was measured. There was no significant difference between the treatment groups with regard to DLWG (p = 0.52), MI (motion index (p = 0.66)), lying bouts (p = 0.96) or lying times (p = 0.54). Given these findings, sodium salicylate may offer a lower-cost option for farmers when given at licensed doses compared to meloxicam, as well as providing a reduced-stress method of NSAID administration via an oral route. In addition, this study identified significant differences in activity in the time periods before and after disbudding, with MI (p < 0.01), lying bouts (p = 0.002) and lying times (p < 0.001) indicating changes in behaviour which extended to five days post disbudding. [ABSTRACT FROM AUTHOR]

Purpose: (i) To report the prevalence of participants to a first-line intervention for OA in Sweden using over-the-counter (OTC) and/or prescribed NSAIDs; (ii) To estimate the accuracy of dispensed prescriptions of NSAIDs recorded in a Swedish health-care register to capture the use of NSAID considering clinician-report as reference standard. Methods: Register-based study. We used data from OA individuals who participated in the Swedish first-line intervention recorded in the Swedish Osteoarthritis Register (SOAR). SOAR includes clinician-reported use of NSAIDs in the three months preceding the intervention. We used the Prescribed Drug Register to retrieve data on NSAID prescriptions dispensed in the same period. We estimated the prevalence of OTC users (individuals with clinicians-reported use of NSAID but no prescription dispensed), prescription users (individuals with clinicians-reported use of NSAID and a prescription dispensed) and non-users (neither of the previous). We calculated sensitivity, specificity, positive predictive value, and negative predictive value of dispensed prescriptions of NSAIDs vs clinician-report. Results: We included 116,162 individuals (mean age [Standard Deviation]: 66 [9.6] years, 79% women, 77% knee OA). Overall, 24.7% (95% Confidence Intervals [CI] 24.5%; 25.0%) used OTC NSAIDs only, 18.2% (18.0%; 18.5%) used prescribed NSAIDs, 6.6% (6– 4%; 6.7%) reported not using NSAIDs while having an NSAID prescription dispensed. Of the 49,913 individuals with clinician-reported use of NSAIDs, 21,190 had a prescription dispensed (sensitivity: 42.5% [95% CI 42.0%, 42.9%]; positive predictive value: 73.5% [73.0%, 74.0%]). Of the 66,249 individuals reporting not using NSAIDs, 58,617 did not have a prescription dispensed (specificity: 88.5% [88.2%, 88.7%]; negative predictive value: 67.1% [66.8%, 67.4%]). Conclusion: Overall, 24.7% of participants in a first-line intervention for OA used OTC NSAIDs only while 18.2% used prescribed NSAIDs. Dispensed prescriptions of NSAIDs have high specificity but low sensitivity and can correctly identify about 70% of both the non-users and users in this population. [ABSTRACT FROM AUTHOR]

A facile experimental protocol for the synthesis of poly(ethylene glycol)-modified (PEGylated) gold nanorods (AuNRs@PEG) is presented as well as an effective drug loading procedure using the non-steroidal anti-inflammatory drug (NSAID) naproxen (NAP). The interaction of AuNRs@PEG and drug-loaded AuNRs (AuNRs@PEG@NAP) with calf-thymus DNA was studied at a diverse temperature revealing different interaction modes; AuNRs@PEG may interact via groove-binding and AuNRs@PEG@NAP may intercalate to DNA-bases. The cleavage activity of the gold nanoparticles for supercoiled circular pBR322 plasmid DNA was studied by gel electrophoresis while their affinity for human and bovine serum albumins was also evaluated. Drug-release studies revealed a pH-sensitive behavior with a release up to a maximum of 24% and 33% NAP within the first 180 min at pH = 4.2 and 6.8, respectively. The cytotoxicity of AuNRs@PEG and AuNRs@PEG@NAP was evaluated against MCF-7 and MDA-MB-231 breast cancer cell lines. The development of AuNRs as an efficient non-steroidal anti-inflammatory drugs (NSAIDs) delivery system for chemotherapy is still in its infancy. The present work can shed light and inspire other research groups to work in this direction. [ABSTRACT FROM AUTHOR]

Introduction: Nonsteroidal antiinflammatory drugs (NSAIDs) are commonly used for pain disorders such as low back pain and exist in multiple formulations; however, no systemically acting transdermal formulations are available for low back pain. Transdermal formulations can be safely administered even to patients with trouble swallowing or at risk of aspiration, and without regard to the effect of food on drug absorption. Unlike locally acting formulations, systemically acting transdermal formulations need not be applied at the target site, so dosing is simple and the burden is not on one area of the skin. A patch with the systemically acting NSAID diclofenac sodium is approved in Japan for treatment of cancer-related pain, and we hypothesized that it would be useful for controlling low back pain. Methods: This randomized, double-blind, placebo-controlled study aimed to evaluate the efficacy and safety of diclofenac sodium patch in Japanese patients with low back pain. Eligible patients were randomized to receive diclofenac sodium patch 75 mg or 150 mg or placebo once daily for 2 weeks. The primary endpoint was pain intensity assessed on a visual analog scale (VAS). Results: Primary analysis of the primary endpoint showed that both doses of the diclofenac sodium patch (150 mg and 75 mg) were superior to placebo in terms of absolute change from baseline in mean 3-day VAS score after 2 weeks' treatment; the mean difference between the active and placebo treatments in this variable was −5.67 [95% confidence interval (CI) −9.34 to −2.00] mm in the 150 mg group and −5.68 (95% CI −9.34 to −2.01) mm in the 75 mg group. Most adverse events were mild. No serious adverse events occurred. Conclusion: In Japanese patients, diclofenac sodium patch is effective for the relief of low back pain and is well tolerated. Trial Registration: JPRN number, JPRN-JapicCTI-205134. [ABSTRACT FROM AUTHOR]

Nonsteroidal anti-inflammatory drugs (NSAIDs) are a class of analgesics that inhibit the activity of cyclooxygenase isoenzymes, which drive tissue inflammation pathways. Caution should be exercised when taking these drugs during pregnancy as they increase the risk of developmental defects. Due to the high rates of NSAID use by individuals, possibilities for in utero exposure to NSAIDs are high, and it is vital that we define the potential risks these drugs pose during embryonic development. In this review, we characterize the identified roles of the cyclooxygenase signaling pathway components throughout pregnancy and discuss the effects of cyclooxygenase pathway perturbation on developmental outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer cells that grow near adipose tissue inevitably exchange signals with adipocytes. The dynamic crosstalk between these two cell types facilitates the alteration of their cellular properties. The transformation of normal adipocytes into cancer-associated adipocytes (CAAs) provides a pro-tumorigenic niche for rapid tumor progression. However, the cancer-originated signals that mediate adipocyte transformation remain largely unknown. In this review, we discuss various inflammatory signals amplified in both obese and peritumoral adipose tissue. These inflammatory signals could mediate adipocyte transformation to phenotypes similar to CAAs by promoting adipocyte dedifferentiation and lipolysis. Epidemiological studies indicate a higher efficacy of nonsteroidal anti-inflammatory drugs in obese patients with cancer. Therefore, delivering anti-inflammatory agents can be a plausible therapeutic strategy to ameliorate the activation of tumor microenvironment components, especially adipocytes. Of the various cell types in the tumor microenvironment (TME), adipocytes undergo a dynamic transformation when activated by neighboring cancer cells. Although these adipocytes, known as cancer-associated adipocytes (CAAs), have been reported to play a crucial role in tumor progression, the factors that mediate their transformation remain elusive. In this review, we discuss the hypothesis that inflammatory signals involving NF-ĸB activation can induce lipolysis and adipocyte dedifferentiation. This provides a mechanistic understanding of CAA formation and introduces the concept of preventing adipocyte transformation via anti-inflammatory agents. Indeed, epidemiological studies indicate a higher efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) in obese patients with cancer, suggesting that NSAIDs can modulate the TME. Inhibition of cyclooxygenase-2 (COX-2) and prostaglandin production leads to the suppression of inflammatory signals such as NF-ĸB. Thus, we suggest the use of NSAIDs in cancer patients with metabolic disorders to prevent the transformation of TME components. Moreover, throughout this review, we attempt to expand our knowledge of CAA transformation to improve the clinical feasibility of targeting CAAs. [ABSTRACT FROM AUTHOR]

Through examining the incidence of cardiovascular diseases (CVDs) among nonsteroidal anti‐inflammatory drug (NSAID) users and nonusers, this study aims to compare the risks contributed by different NSAIDs in a Chinese population. The retrospective cohort including 4 298 368 adults without CVD from electronic health records between 2008 and 2017 in Hong Kong was adopted. A total of 4.5% of individuals received NSAIDs including celecoxib, etoricoxib, diclofenac, ibuprofen, indomethacin, mefenamic acid, or naproxen for ≥4 consecutive weeks at baseline. Cox regression, including NSAID use as a time‐dependent covariate and adjusted with patient's characteristics, was conducted to examine the association between NSAID exposure and incident CVD. After a median follow‐up of 6.9 years (30 million person‐years), a total of 258 601 cases of incident CVD was recorded. NSAID use was shown to be associated with a significantly higher risk of CVD (hazard ratio [HR], 1.32 [95%CI, 1.28–1.37]) compared to non‐NSAID use. Similar results in coronary heart disease (HR, 1.37 [95%CI, 1.31–1.43]), stroke (HR, 1.27 [95%CI, 1.21–1.33]), and heart failure (HR, 1.25 [95%CI, 1.16–1.34]) were obtained. Overall, similar CVD risk was observed across users of NSAIDs except for etoricoxib, which showed a higher risk (HR, 2.01 [95%CI, 1.63–2.48]). Considering that a higher CVD risk was consistently displayed among NSAID users, NSAIDs should be used cautiously, and the usage of etoricoxib in the Chinese population should be reviewed. [ABSTRACT FROM AUTHOR]

Lung inflammation is associated with elevated pro-inflammatory cytokines and chemokines. Treatment with FCBD:std (standard mix of cannabidiol [CBD], cannabigerol [CBG] and tetrahydrocannabivarin [THCV]) leads to a marked reduction in the inflammation of alveolar epithelial cells, but not in macrophages. In the present study, the combined anti-inflammatory effect of FCBD:std with two corticosteroids (dexamethasone and budesonide) and two non-steroidal anti-inflammatory drugs (NSAID; ibuprofen and diclofenac), was examined. Enzyme-linked immunosorbent assay (ELISA) was used to determine protein levels. Gene expression was determined by quantitative real-time PCR. Inhibition of cyclo-oxygenase (COX) activity was determined in vitro. FCBD:std and diclofenac act synergistically, reducing IL-8 levels in macrophages and lung epithelial cells. FCBD:std plus diclofenac also reduced IL-6, IL-8 and CCL2 expression levels in co-cultures of macrophages and lung epithelial cells, in 2D and 3D models. Treatment by FCBD:std and/or NSAID reduced COX-1 and COX-2 gene expression but not their enzymatic activity. FCBD:std and diclofenac exhibit synergistic anti-inflammatory effects on macrophages and lung epithelial cells, yet this combined activity needs to be examined in pre-clinical studies and clinical trials. [ABSTRACT FROM AUTHOR]

Background and Objectives: Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to control pain and fever. However, their effect on COVID-19 infected patients has not been fully studied. In this study, we investigated the effect of the duration of NSAIDs use on COVID-19 infection and clinical outcomes. Materials and Methods: In South Korea, 25,739 eligible patients who received COVID-19 testing between 1 January and 31 July 2020, were included in this retrospective observational cohort analysis. Based on the date of the first COVID-19 test for each patient, NSAID prescription dates were used to separate patients into two groups (short-term group: <2 weeks; long-term group: 8–12 weeks). COVID-19 infectivity and clinical outcomes were analyzed. We used the propensity score-matching (PSM) method. Results: Of the 580 patients who had taken NSAIDs before the date of COVID-19 test, 534 and 46 patients were grouped in the short- and long-term NSAID-use groups, respectively. We did not find a statistically significant increased risk of COVID-19 infection (adjustment for age and sex, p = 0.413; adjustment for age, sex, region of residence, comorbidity, Charlson Comorbidity Index, and current use of medication, p = 0.259) or change in clinical outcomes, including conventional oxygen therapy, admission of intensive care unit, artificial ventilation, or death, between the two groups in which the PSM method was applied. Conclusions: The duration of NSAIDs use did not have a statistically significant effect on COVID-19 infectivity or clinical outcomes. However, further studies looking at clinical presentation and laboratory test results in a large number of people should be performed. [ABSTRACT FROM AUTHOR]

Preeclampsia (PE) is often associated with multiple organ damage that remains noticeable postnatally. Here, we tested the hypotheses that antenatal therapy with nonsteroidal antiinflammatory drugs (NSAIDs) refashions liver damage induced by PE in weaning rats and that the high mobility group box 1 (HMGB1) signaling modulates this interaction. PE was induced by pharmacologic nitric oxide deprivation during the last week of gestation (Nω-nitro-L-arginine methyl ester, L-NAME, 50 mg/kg/day, oral gavage). Compared with control rats, weaning PE rats revealed substantial rises in serum transaminases together with histopathological signs of hepatic cytoplasmic changes, portal inflammation, and central vein dilation. While gestational NSAIDs reversed the elevated transaminases, they had no effects (celecoxib, naproxen) or even worsened (diclofenac) the structural damage. Molecularly, celecoxib was the most effective NSAID in (i) reversing PE-evoked upregulation of hepatic HMGB1 gene expression and concomitant increments and decrements in mitogen-activated protein kinases MAPK ERK and MAPK p38 expression, respectively, and (ii) elevating and suppressing serum interleukin-10 and tumor necrosis factor-α, respectively. Alternatively, rises in serum interleukin-1β and shifts in macrophage polarization towards an inflammatory phenotype caused by PE were comparably diminished by all NSAIDs. The data disclose an advantageous therapeutic potential for gestational celecoxib over diclofenac or naproxen in controlling hepatic dysfunction and HMGB1-interrelated inflammatory and oxidative sequels of PE. • Prenatal NSAIDs reduce PE rises in blood transaminases, but not hepatic damage. • Celecoxib is more potent than diclofenac/naproxen in reversing PE-HMGB1 inflammation. • Celecoxib upregulates hepatic antioxidant machinery. [ABSTRACT FROM AUTHOR]

The discovery of next-generation non-steroidal anti-inflammatory drugs (NSAIDs) remains an active area of research as over a billion people suffer from pain and inflammation. A strategic approach in this endeavor is establishing a quantitative relationship between the anti-inflammatory activity and the molecular descriptors of inhibitors of cyclooxygenase-2 (COX-2) that will streamline and expedite the discovery and the subsequent development of novel NSAIDs devoid of side effects associated with COX-1 inhibition. In this work, Random Forest (RF) technique was implemented to formulate a robust quantitative model that predicts the inhibitory activity of compounds on COX-2. The model established in this work displayed excellent predictive performance on compound classification with 93% accuracy and 0.98 AUC. Upon application to two external sets, 759 newly designed derivatives of COX-2 inhibitors and 188 structurally similar compounds were predicted active; 19 of them were found to be promising leads as COX-2-acting anti-inflammatory drugs. The top 2 hits with the highest probability of being active were also found to have the strongest binding affinity with COX-2 and are superior to the known COX-2 selective inhibitors. The RF model is likewise conservative in identifying compounds as active making it all the more beneficial as it helps avoid costly failures at the later stages of the drug discovery phase. [ABSTRACT FROM AUTHOR]

Background: Osteoarthritis (OA) is a common joint disorder. Oal non-steroidal anti-inflammatory drugs (NSAIDs), including selective cyclooxygenase-2 (COX-2) inhibitors, are the mainstay of pharmacotherapy but it can not be used for long time due to their adverse effects. Diacerein is SYSADOAs, an advantage of using diacerein in OA treatment is, that Diacerein does not affect the synthesis of prostaglandins, and does thereby not have a deleterious effect on the upper gastro-intestinal mucosa. This is an important advantage compared to NSAID treatment. But still there is still no consensus on the place of Diacerein in OA because there is lack of pragmatic trials those have evaluated the effectiveness of Diacerein in real life situations. Objective: So this study was planned to evaluate the effectiveness of Diacerein in symptomatic treatment of knee OA. Methods: All the Patients were given Diacerein 50 mg BD. The evaluation of effectiveness will be in terms of improvements in symptoms and physical functions of patients. Results: Diacerein is not as effective in controlling clinical symptoms of knee Osteoarthritis as it claimed to be. It also takes long time to show a clinically relevant & appreciable effect. Conclusion: Diacerein is a overrated drug in Osteoarthritis which is mainly due to lack of pragmatic trials of this drug. Pragmatic clinical trials should must be done to know the real place of a drug in management of any condition. [ABSTRACT FROM AUTHOR]

Nonsteroidal anti-inflammatory drugs (NSAIDs) and analgesics are the most commonly used drugs worldwide and their availability over-the-counter is increasing. The aim of this study was to examine the frequency of their use as well as the awareness of the associated risk of side effects in patients with chronic kidney disease (CKD) compared to the patients at general practice (GP) offices. We found that 88.5% of the CKD and 97.1% of the GP group used NSAIDs and/or analgesics (p < 0.0001). Paracetamol was chosen the most often by both study groups, but the proportion of patients taking paracetamol was significantly higher in the CKD group (p < 0.006). On the contrary, the proportion of patients taking ibuprofen was significantly higher in GP group (p < 0.0001). Furthermore, almost 37% of CKD and 60% of GP patients never consult with their doctor before taking NSAIDs or analgesics. The influence of advertisements on the decision to take these drugs was found to be marginal in both groups. In conclusion, the NSAIDs and/or analgesics use is very common. The differences between the studied cohorts in self-decision making and the type of drugs used between the studied cohorts warrant tailored educational approaches. [ABSTRACT FROM AUTHOR]

Direct and atom‐economical amidation of nonsteroidal anti‐inflammatory drugs naproxen ibuprofen and ketoprofen with a variety of secondary amines was effected using commercially available DCC under mild and open‐air conditions. These prodrug amides were obtained in good to moderate yields ranging between 30–90 %. [ABSTRACT FROM AUTHOR]

Background: Therapeutic plasma exchange (TPE) is gaining popularity for the management of nonsteroidal anti‐inflammatory drug (NSAID) overdose in dogs. Hypothesis/Objectives: Describe a population of dogs treated with TPE for NSAID overdose. Animals: Sixty‐two dogs with NSAID overdose treated with TPE. Methods: Multicenter retrospective study of dogs treated with TPE for ibuprofen, carprofen, or naproxen overdose. Results: The median dose of ibuprofen, carprofen or naproxen ingested was 533 mg/kg (range, 36‐4857 mg/kg), 217 mg/kg (range, 88‐625 mg/kg) and 138 mg/kg (range, 26‐3000 mg/kg), respectively. Based on previously established toxic ranges for each NSAID, 2 (3.2%), 14 (22.6%), and 46 (74.2%) dogs ingested a gastrointestinal, renal, and neurological toxic dose, respectively. The median time between ingestion and presentation was 4 hours (range, 1‐20 hours). The median number of plasma volumes processed was 1.6 (range, 0.4‐2.2). The median TPE session duration was 2 hours (range, 1‐4.5 hours). Circuit clotting developed during 8 (12.9%) sessions. Patient adverse events reported during 21 (33.8%) sessions consisted of urticaria (12.9%), asymptomatic hypocalcemia (9.6%), and hypotension (9.6%). The median duration of hospitalization was 2.25 days (range, 1‐11 days). Sixty‐one (98.4%) dogs survived to discharge, and none were rehospitalized. Thirty‐one (91.1%) of the 34 dogs with at least 1 follow‐up visit were not azotemic at the time of reevaluation. Conclusions and Clinical Importance: This population of dogs managed with TPE had excellent outcomes, even in cases of high NSAID dose ingestion. When TPE is available and the time frame is appropriate, this extracorporeal modality should be considered for the management of NSAID overdose. [ABSTRACT FROM AUTHOR]

This study performed population‐pharmacokinetic/pharmacodynamic (pop‐PK/PD) modeling of ketoprofen and flunixin in piglets undergoing routine castration and tail‐docking, utilizing previously published data. Six‐day‐old male piglets (8/group) received either ketoprofen (3.0 mg/kg) or flunixin (2.2 mg/kg) intramuscularly. Two hours post‐dose, piglets were castrated and tail docked. Inhibitory indirect response models were developed utilizing plasma cortisol or interstitial fluid prostaglandin E2 (PGE2) concentration data. Plasma IC50 for ketoprofen utilizing PGE2 as a biomarker was 1.2 μg/ml, and ED50 for was 5.83 mg/kg. The ED50 calculated using cortisol was 4.36 mg/kg; however, the IC50 was high, at 2.56 μg/ml. A large degree of inter‐individual variability (124.08%) was also associated with the cortisol IC50 following ketoprofen administration. IC50 for flunixin utilizing cortisol as a biomarker was 0.06 μg/ml, and ED50 was 0.51 mg/kg. The results show that the currently marketed doses of ketoprofen (3.0 mg/kg) and flunixin (2.2 mg/kg) correspond to drug responses of 33.97% (ketoprofen‐PGE2), 40.75% (ketoprofen‐cortisol), and 81.05% (flunixin‐cortisol) of the maximal possible responses. Given this information, flunixin may be the best NSAID to use in mitigating castration and tail‐docking pain at the current label dose. [ABSTRACT FROM AUTHOR]

Finger joint osteoarthritis (HOA) is a common joint disease that increases with age. The cause is polyethiological. The distal joints of the fingers are most frequently affected, followed by the carpometacarpal joint of the thumb, the proximal interphalangeal joints, and the metacarpophalangeal joints. The clinical symptoms of HOA are painful functional restrictions of the hand and fingers. In terms of therapy, lifestyle modifications and exercise are primarily recommended. Only when these measures are inadequate or not helpful drugs will be recommended be recommended. First-choice drugs are non-steroidal anti-inflammatory drugs applied topically or p.o. Pharmaceutically manufactured chondroitin preparations are also helpful. In severely painful or erosive forms of HOA, corticosteroids can be used intra-articularly. The status of laser therapy or fractionated radiation is (still) unclear. Classical disease-modifying drugs such as those used in inflammatory joint diseases have no therapeutic value. Surgical interventions should be considered if conservative treatments are not sufficiently helpful and hand function is significantly impaired. [ABSTRACT FROM AUTHOR]

Modulating the cyclooxygenase 2 (COX-2) pathway has improved responses to immune checkpoint inhibitors (ICIs) in certain solid tumors, such as melanoma. Little is known about COX-2 inhibition in response to ICIs in metastatic renal cell carcinoma (mRCC). In this retrospective cohort study, we examined the effect of COX-2 inhibitors on the long-term outcomes of mRCC patients undergoing ICI therapies. Among 211 patients with mRCC, 23 patients were excluded due to loss to follow-up. Among 188 included patients, 120 patients received either an NSAID or aspirin for at least three weeks during ICI therapies. Clear cell histology was present in 96% of cases. The median overall survival (OS) was similar regardless of the COX inhibitor (COXi) (i.e., NSAID or aspirin) use (27 months for COXi vs. 33 months for no-COXi groups; p = 0.73). The no-COXi group showed a trend toward longer median progression-free survival (8 months for COXi vs. 13 months for no-COXi groups; p = 0.13). When looking specifically at NSAID use in a multivariate analysis, NSAID use was associated with a higher risk of progression (HR = 1.52 [95% CI, 1.04–2.22]) and death (HR = 1.60 [95% CI, 1.02–2.52]). In summary, COXis did not improve disease control or survival among patients with mRCC who were undergoing ICI therapies. Instead, the concurrent use of NSAIDs was associated with worse outcomes. Larger studies are needed to validate our observation. [ABSTRACT FROM AUTHOR]

Corneal epithelium removal during photorefractive keratotomy (PRK), TransPRK, or corneal cross-linking (CXL) means that patients experience pain and inflammation after the procedure, which need to be carefully managed with topical drug regimens. One highly effective class of topical analgesics is non-steroidal anti-inflammatory drugs (NSAIDs), but these must be used carefully, as their use has been associated with delayed re-epithelialization and, in rare cases, corneal melting. However, our clinical experience has been that the concomitant use of topical corticosteroids obviates this risk. Here, we present a mechanistic explanation for our observations, our TransPRK and epithelium-off CXL protocols, and the postoperative medication regimens where topical NSAIDs are used in combination with topical steroid therapy during the first two postoperative days (where pain and inflammation levels are the highest). We detail the results of a single-center retrospective case analysis that examined eyes that underwent TransPRK (n = 301) or epithelium-off CXL (n = 576). Topical NSAID use in the first two postoperative days to control pain and inflammation after PRK/TransPRK or epithelium-off CXL, when used in combination with topical steroid therapy, does not appear to be associated with corneal melting or delayed epithelial healing. This approach may represent an improvement over current methods of handling post-surgical pain in procedures that require corneal epithelial debridement. [ABSTRACT FROM AUTHOR]