Use Of Nonsteroidal Anti-inflammatory Drugs Research Articles

NSAID use in orthopedic surgery:A review of current evidence and clinical practice guidelines.

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.

P365 Incidental terminal ileitis in asymptomatic patients. Is it Crohn’s disease?

Abstract Background Inflammation of the terminal ileum is a common finding during colonoscopy, even in patients without symptoms as an accidental finding. Nevertheless, there are no guidelines or wide consensus about the indications for treatment or follow-up, since the clinical importance and natural history of this entity has not yet been fully investigated. Methods This was a retrospective cohort study, where the electronic database of the Gastroenterology Department of University Hospital of Heraklion, Greece was searched through using the term "inflammation of terminal ileum" and "ulcers of terminal ileum", through the years 2012-2023. All cases with terminal ileitis as an accidental finding in asymptomatic patients, where colonoscopies performed for miscellaneous reasons (e.g. screening colonoscopy, follow-up colonoscopy after polypectomy) were identified. Patients with symptoms, or known Crohn’s Disease (CD) were excluded. Patients’ demographics, endoscopic and clinical follow-up data, as well as treatment and final diagnosis of CD were registered. Possible risk factors for terminal ileitis [smoking, use non-steroidal anti-inflammatory drugs (NSAIDs)] were also recorded. Univariate and multivariate analysis of the data was performed with SpSS v22 software. Results In a total of 465 cases with terminal ileitis 205 had known CD, 153 underwent colonoscopy for symptoms whereas 107 patients (62 females) underwent colonoscopy with no associated symptoms and constituted the study population. Among these 107 patients [median age 50, interquartile range (IQR) 39-64years, median BMI 25kg/m2, IQR 23.2-27.1kg/m2, median follow-up 4years) 27 (25%) patients were current smokers, 32 (30%) ex-smokers and 22 (20%) reported recent use of NSAIDS (Table 1). During follow-up, 88 (82%) patients had a new colonoscopy with persistence of terminal ileitis in 66 (62%) of them, 68 (64%) developed symptoms, 37 (35%) were diagnosed with CD,39 (36%) received treatment, and 18 (17%) required hospitalization. In the group of the patients that required treatment, only 8 (7.4% of the study population) eventually required systemic immunosuppression (corticosteroids, thiopurines, biologic agents. In multivariate analysis, there was no statistically significant correlation between the persistent terminal ileitis on follow-up colonoscopy and BMI, the use of NSAIDs, or ex-smoking. Nevertheless, there was a significant correlation between active smoking and the persistence of terminal ileitis (p=.005). Conclusion Most of the patients with incidental, asymptomatic terminal ileitis remain asymptomatic and don’t require treatment. Close monitoring is required since diagnosis of Crohn’s disease is established in one third of them.

P1228 The EISER Study: Identifying Microbial Factors Associated with Subclinical Gut Inflammation in Psoriatic Arthritis Patients Who Develop Inflammatory Bowel Disease

Abstract Background Nearly 8% of patients with spondyloarthritis (SpA) manifest symptoms that are compatible with active inflammatory bowel disease (IBD). It is well established that microbial dysbiosis is associated with different immune-mediated diseases. We therefore hypothesized that the gut microbiome could be a modulator of intestinal inflammation and factor in the pathogenesis of IBD in SpA patients. Methods As part of the EISER study, we selected a subset of 193 subjects diagnosed with psoriatic arthritis (PsA), a form of SpA, who had no prior diagnosis of IBD. The presence of subclinical symptoms compatible with IBD was evaluated at time of enrollment. For patients with fCAL levels of 80 µg/g or higher, colonoscopy was performed and histological analysis of biopsies collected during the procedure were used to diagnose IBD. Capsule endoscopy was performed on those patients with a negative colonoscopy result. Stool samples were collected from all participants, and microbial DNA was extracted for shotgun metagenomic sequencing using the Illumina HiSeq platform. Sequenced data was processed using MetaPhlAn 4 to estimate taxonomic composition, MMEDS for overall microbiome analysis, and R for additional statistical analyses. Results Twenty-five out of 193 subjects in our cohort (12.95%) had symptoms that were compatible with subclinical IBD (sIBD) and five patients (2.6% of total) were confirmed to have clinical IBD (cIBD). The use of nonsteroidal anti-inflammatory drugs (NSAIDs) resulted in significant differences in overall alpha (Shannon entropy, p=0.03) and beta microbial diversity (PERMANOVA, p=0.043), while the use of proton-pump inhibitors (PPI) resulted in significant differences in beta diversity (PERMANOVA, p= 0.036). Patients with cIBD had significantly higher abundance of taxa including Prevotella copri and Prevotella stercorea. P. copri, P. stercorea and fCAL were all significantly elevated in cIBD patients (Wilcoxon’s p=0.0278, 0.0007, 0.0161), although with a larger effect size in P. copri and P. stercorea (Cohen’s D: P. copri = 1.074; P. stercorea = 1.269; fCAL= 0.629). fCAL was also significantly elevated in patients who used PPIs (p= 4.456e-11), while P. copri and P. stercorea abundances were not impacted (Wilcoxon’s p: P. copri = 0.2394; P. stercorea = 0.0643). Conclusion Microbiome composition was impacted by the use of NSAIDs and PPI. We identified taxa differentially enriched in cIBD patients, including Prevotella copri and P. stercorea. Importantly, while fCAL was significantly higher in cIBD patients, its discriminatory power was not as strong as that of P. copri and P. stercorea, suggesting that these taxa could be potentially used as biomarkers of co-morbid IBD in patients with PsA.

Classification and Incidence of Heterotopic Ossifications in Relation to NSAID Prophylaxis after Elbow Trauma

Heterotopic ossification (HO) after elbow trauma can be responsible for significant motion restrictions. The study’s primary aim was to develop a new X-ray-based classification for HO of the elbow. This retrospective study analyzed elbow injury radiographs from 138 patients aged 6–85 years (mean 45.9 ± 18) who underwent operative treatment. The new classification was applied at 6 weeks, 12 weeks, and 6 months postoperatively. The severity of HO was graded from 0 to 4 and localization was defined as r (radial), p (posterior), u (ulnar) or a (anterior) by two observers. The patients were categorized based on injury location and use of non-steroidal anti-inflammatory drugs (NSAIDs) for HO prophylaxis. The correlations between the generated data sets were analyzed using Chi-square tests (χ2) with a significance level of p < 0.05. The inter- and intraobserver reliability was assessed using Cohen’s Kappa. In 50.7% of the evaluated X-rays, the formation of HO could be detected after 12 weeks, and in 60% after 6 months. The analysis showed a significant correlation between the injury’s location and the HO’s location after 12 weeks (p = 0.003). The use of an NSAID prophylaxis did not show a significant correlation with the severity of HO. The classification showed nearly perfect inter- (κ = 0.951, p < 0.001) and intrareliability (κ = 0.946, p < 0.001) according to the criteria of Landis and Koch. Based on the presented classification, the dimension and localization of HO in the X-ray image can be described in more detail compared to previously established classifications and, thus, can increase the comparability of results across studies.

Comparison of the Efficacy of Two-Week Vonoprazan Versus Lansoprazole-Based Quadruple Sequential Antibiotic Therapy in Eradicating Helicobacter pylori Infection: A Non-randomized Clinical Trial.

The prevalence of Helicobacter pylori is escalating in developing countries, exacerbated by unjustified antibiotic usage, which leads to increased resistance. This trend has been notably amplified since the COVID-19 pandemic. Consequently, the effectiveness of existing eradication regimens has been compromised. This study aimed to compare the efficacy of two weeks of vonoprazan-based quadruple sequential therapy and lansoprazole-based quadruple sequential therapy in treating H. pylori infection. Methods: A non-randomized clinical trial was conducted over 18 months at the Department of Gastroenterology, Lahore General Hospital, Lahore, Pakistan. It included patients presenting with dyspepsia, as defined by the Rome IV criteria, and who tested positive on the urea breath test. Patients were divided into two groups, i.e., Group A and Group B. Group A patients received lansoprazole 30 mg + amoxicillin + tinidazole + tab. colloidal bismuth subcitrate for the first seven days, followed by lansoprazole + levofloxacin + azithromycin + colloidal bismuth subcitrate. Group B patients received vonoprazan + amoxicillin + tinidazole + colloidal bismuth subcitrate for the first seven days, followed by vonoprazan + levofloxacin + azithromycin + colloidal bismuth subcitrate. Both regimes continued for 14 days. Four weeks after 14 days of the treatment, an early morning urea breath test was conducted to evaluate the efficacy of the treatment. Patients were scheduled for follow-up visits at seven and 14 days post-treatment initiation to record adverse events and assess compliance with the treatment regimen. Patients who lost the follow-up and remained non-compliant to the medications were excluded from the final data analysis as per standard protocols of the per-protocol analysis. Results: A total of 252 patients were included. In Group A and Group B, 6/126 (4.76%) and 8/126 (6.35%) of the patients were lost to follow-up, respectively. The non-compliance rate in Group A was 5/126 (3.97%), compared to Group B with 3/126 (2.38%). Finally, the per-protocol analysis of the resultsincluded 115 patients in each group. Baseline characteristics, including demographics, lifestyle, and clinical factors, were comparable between groups with p-values of 0.138 for age, 0.356 for gender, 0.126 for BMI, 0.495 for residence, 0.500 for water source, 0.866 for meal habit, 0.863 for smoking, 0.188 for nonsteroidal anti-inflammatory drug(NSAID) use, 0.145 for proton pump inhibitor(PPI) use, 0.213 for antibiotics, and 0.456 for treatment history. Both treatments effectively eradicated H. pylori, as determined by a negative urea breath test at four weeks post-treatment, with Group B showing a higher eradication rate of 96.5% compared to 92.2% in Group A, although the difference was not statistically significant (p = 0.153).There was no difference in adverse effects in both treatment groups (p-value > 0.05). Conclusion: The study found that while the vonoprazan-based regime exhibited a slightly higher eradication rate of H. pylori compared to lansoprazole, the difference was not statistically significant. It was concluded that both regimens demonstrated comparable efficacy and similar profiles of adverse effects in treating H. pylori infection.

The annonalide diterpene extracted from Casimirella ampla (Miers) reduces inflammatory and antinociceptive events in general models of inflammation

Ethnopharmacological relevanceThe plants of the genus Casimirella ampla (Miers) (C. ampla) are extensively used in folk medicine. For a long time, rural communities have been using extracts from its roots for food and therapeutic purposes. The extract is rich in diterpenoid annonalide (Annona), which has antiophidic, anti-inflammatory and antinociceptive properties. Inflammation is the body's primary defense mechanism against cell damage and invasion by pathogens, which can trigger acute and chronic inflammatory processes. The first line of treatment for this condition consists of the use of non-steroidal anti-inflammatory drugs, but these have numerous associated collateral damages, based on scientific knowledge about diterpenoids from C. ampla, as well as their already reported antinociceptive and anti-inflammatory properties. Aims of the studyEvaluate the effect of Annona in classic models of inflammation and pain. Materials and methodsAnimals were pretreated with Annona (0.1, 1.0 and 10 mg/kg), or Tween 80 (2%), or indomethacin (Indo) (10 mg/kg) orally in the paw edema tests induced by carrageenan (Cg), serotonin (5-HT), histamine, bradykinin, 48/80 and, prostaglandin E2 (PGE2), evaluating microscopic lesion scores, migration of leukocytes to the peritoneal cavity, concentration of myeloperoxide (MPO), malonyldialdehyde (MDA) and glutathione (GSH), abdominal contortion test by acetic acid and formalin test. ResultsTreatment with Annona compound at a dose of 0.1 mg/kg was more effective in reducing inflammatory, oxidant and nociceptive parameters, as it reduced paw edema induced by carrageenan, through different mediators and migration of inflammatory cells. Furthermore, it worked by reducing the concentration of MPO, MDA, preserving GSH levels and reducing nociception caused by formalin and acetic acid.

Peri-onset non-steroidal anti-inflammatory drugs use and organ failure in acute pancreatitis: A multicenter retrospective analysis

Organ failure (OF) of acute pancreatitis (AP) significantly contributes to AP-related mortality. Non-steroidal anti-inflammatory drugs (NSAIDs) have been associated with reduced complications of AP. We aimed to investigate whether NSAIDs ameliorates SIRS and OF in patients with AP. Eligible patients with AP were retrospectively identified in 4 hospitals between January 2015 and December 2018. Associations between peri-onset NSAIDs use (day -3 to day 3) and OF, persistent OF (POF), and SIRS within the first week were analyzed. Propensity score-matched (PSM) analysis and inverse probability of treatment-weighted (IPTW) analysis were used to estimate risk ratios. Among 1,528 patients with AP (97 [6.3%] with NSAIDs use), 242 (15.8%) developed organ failure, 89 (5.8%) progressed to POF, and 27 (1.8%) died within 3 months. PSM analysis showed no association between peri-onset NSAIDs and OF (risk ratio [RR], 1.00; 95% confidence interval [CI], 0.46 to 2.15) and POF (RR, 0.80; 95% CI, 0.21 to 2.98). IPTW analysis yielded similar results. Patients with and without peri-onset NSAIDs use were comparable with respect to OF, POF, and SIRS across subgroups defined by COX-2 selectivity and dose. Peri-onset NSAIDs use was not significantly associated with reduced OF.

Phytoconstituents of Kenyan stinging nettle (Urtica species) and their molecular docking interactions revealed anti-inflammatory potential as cyclooxygenase-2 inhibitors

Inflammation is a complex, natural protective response towards different stimuli characterized by the dilation and permeation of the blood vessels with a surge in leukocytes in the tissues. The current treatment involves the use of anti-inflammatory drugs, corticosteroids and non-steroidal anti-inflammatory drugs (NSAIDs), which have been associated with adverse side effects especially gastrointestinal ulcers. Therefore, there is a growing need to explore alternative sources from medicinal plants. In the present study we investigated anti-inflammatory activities of the leaves of the Kenyan stinging nettle using in vivo and in silico molecular docking. Molecular identification of plant sample was carried out based on DNA barcoding. Crude extracts were prepared using water and methanol: dichloromethane (1:1) and preliminary identification of total phenolic and flavonoids was carried out using Folin-Ciocalteu and aluminum chloride colorimetric methods, respectively. The classical model of Carrageenan- induced paw edema was used to test the in vivo anti-inflammatory activity of the extracts. The extract was screened using Laser Raman Spectroscopy and Liquid Chromatography Mass Spectroscopy (LC-MS) and the molecular interaction between the identified compounds within the binding site of Cyclooxygenase-2 (COX-2) performed through molecular docking as the confirmatory tool of in vivo experiments. Based on DNA barcoding analysis, the plant sample was identified as Urtica species. The total phenolic content of the aqueous and methanol: dichloromethane extracts were 3.75 mg gallic acid equivalents (GAE)/g dry sample and 6.26 mg GAE/g dry sample while total flavonoid content were 0.3872 mg quercetin/g dry sample and 1.76 mg quercetin/g dry sample, respectively. The aqueous extract significantly (p < 0.05) reduced the paw edema in the Carrageenan model of inflammation. LC-MS confirmed the presence of 19 phytochemicals, of which 10 and 9 were phenolic and flavonoid compounds, respectively. From these identified compounds quercetin attained the lowest binding energy when complexed with COX-2, followed by rhamnetin, quercetin rhamnoside, epigallocatechin gallate and chlorogenic acid. Molecular docking studies supported the in vivo findings and confirmed the anti-inflammatory potential of Urtica sp. These findings suggest Urtica sp. is a potential source of bioactive compounds that could be employed in the future development of anti-inflammation drugs. Further studies can attempt to assess the individual isolated active compound(s) for their anti-inflammatory activity.

Risk of cardiovascular disease associated with long-term use of non-steroidal anti-inflammatory drugs in ankylosing spondylitis.

To examine the risk of cardiovascular disease associated with long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) in a large real-world ankylosing spondylitis (AS) cohort. This nationwide population-based cohort study used data from the Korean National Health Insurance Database. Patients aged ≥18 years old who were newly diagnosed with AS without prior cardiovascular disease between January 2010 and December 2018 were included in this study. Controls without AS were randomly selected by age, sex, and index year. The primary outcome was cardiovascular disease, a composite outcome of ischemic heart disease, stroke, or congestive heart failure. Long-term use of NSAIDs was defined as use of NSAIDs for >365 cumulative defined daily doses. The association between long-term use of NSAIDs and incident cardiovascular disease was examined in both AS and non-AS populations. Among 19 775 patients with AS and 59 325 matched controls without AS, there were 1,663 and 4,308 incident cases of cardiovascular disease, showing an incidence of 16.9 and 13.8 per 1,000 person-years, respectively. Long-term use of NSAIDs was associated with increased risk of cardiovascular disease in non-AS controls (adjusted hazard ratio [aHR], 1.64; 95% CI, 1.48-1.82). In contrast, long-term use of NSAIDs did not increase the risk of cardiovascular disease in AS patients (aHR, 1.06; 95% CI, 0.94-1.20; adjusted for age, sex, socioeconomic status, body mass index, smoking status, hypertension, diabetes, hyperlipidemia, and tumor necrosis factor inhibitor use). Prolonged NSAID treatment in AS patients may not be as harmful as in the general population regarding cardiovascular risk.

Evaluation of Triple Whammy Prescriptions After the Implementation of a Drug Safety Algorithm.

The term triple whammy (TW) refers to the concomitant use of non-steroidal anti-inflammatory drugs, diuretics, and angiotensin system inhibitors; this combination significantly increases the risk of acute kidney injury (AKI). To prevent this serious complication, we developed an electronic algorithm that detects TW prescriptions in patients with additional risk factors such as old age and impaired kidney function. The algorithm alerts a clinical pharmacist who then evaluates and forwards the alert to the prescribing physician. We evaluated the performance of this algorithm in a retrospective observational study of clinical data from all adult patients admitted to the Cantonal Hospital of Aarau in Switzerland in 2021. We identified all patients who received a TW prescription, had a TW alert, or developed AKI during TW therapy. Algorithm performance was evaluated by calculating the sensitivity and specificity as a primary endpoint and determining the acceptance rate among clinical pharmacists and physicians as a secondary endpoint. Among 21,332 hospitalized patients, 290 patients had a TW prescription, of which 12 patients experienced AKI. Overall, 216 patients were detected by the alert algorithm, including 11 of 12 patients with AKI; the algorithm sensitivity is 88.3% with a specificity of 99.7%. Physician acceptance was high (77.7%), but clinical pharmacists were reluctant to forward the alerts to prescribers in some cases. The TW algorithm is highly sensitive and specific in identifying patients with TW therapy at risk for AKI. The algorithm may help to prevent AKI in TW patients in the future.

PPARγ, NF-κB and the UPR pathway as new molecular targets in the anti-inflammatory actions of NSAIDs: Novel applications in cancers and central nervous system diseases?

Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin, diclofenac, ibuprofen, or celecoxib have a well-established and unquestionable role in the human therapeutic arsenal, but still new perspectives are being discovered. This review presents new anti-inflammatory mechanisms of NSAIDs action, other than the classical one, i.e., the inhibition of cyclooxygenase (COX) isoforms leading to the prostanoids synthesis blockage. Literature data show that this group of drugs can activate anti-inflammatory peroxisome proliferator-activated receptor gamma (PPARγ), inhibit pro-inflammatory nuclear factor-κB (NF-κB) activation or modulate the components of the unfolded protein response (UPR) pathway. These alternative pathways induced by NSAIDs may not only enhance their basic anti-inflammatory mechanism of action but also promote other effects of the drugs such as anti-cancer. It was also proved that neuroinflammation, with the involvement of NF-κB, PPARγ and the components of the UPR pathway has an essential impact on the development of central nervous system (CNS) diseases. Thus, it seems possible that these new molecular targets may expand the use of NSAIDs, e.g., in the treatment of cancers and/or CNS disorders.

Bioavailability of Orally Administered Drugs After Bariatric Surgery.

Oral drug absorption after bariatric surgery is likely to be altered, but the impact of different bariatric surgery procedures on individual drugs is not uniform. The aim of this article is to describe factors influencing the bioavailability of orally administered drugs after bariatric surgery and to provide readers with practical recommendations for drug dosing. We also discuss the medications that may be harmful after bariatric surgery. The fundamental factors for enteral drug absorption are the production of gastric acid; the preserved length of the intestine, i.e., the size of the absorption surface and/or the preserved enterohepatic circulation; and the length of common loop where food and drugs are mixed with digestive enzymes and bile acids. Bypassing of metabolizing enzymes or efflux pumps and changes in intestinal motility can also play an important role. Significant changes of drug absorption early after the anatomic alteration may also be gradually ameliorated due to gradual intestinal adaptation. The most affected drugs are those with low or variable bioavailability and those undergoing enterohepatic circulation. Attention should also be paid to oral drug formulations, especially in the early postoperative period, when immediate-release and liquid formulations are preferred. The changes in oral bioavailability are especially clinically meaningful in patients treated with drugs possessing narrow therapeutic index (e.g., oral anticoagulants, levothyroxine, and anticonvulsants) or in acute conditions (e.g., anti-infectives); nevertheless, it may also influence the therapeutic value of chronic therapy (e.g., antidepressants. antihypertensives, antiplatelets, statins, PPIs, contraceptives, and analgesics); therapeutic effect of chronic therapy is further influenced by pharmacokinetic alterations resulting from weight loss. Therapeutic drug monitoring, periodical clinical evaluation, and adequate dose adjustments are necessary. Due to safety reasons, patients should avoid oral bisphosphonates, regular use of non-steroidal anti-inflammatory drugs, and, if possible, corticosteroids after bariatric surgery.

Higher risk of Achilles tendon ruptures at competition than training sites in female collegiate gymnasts.

Reportedly, 17.2% of collegiate female gymnasts experience Achilles tendon ruptures (ATRs). Cumulative microtraumas resulting in chronic tendinopathy/tendinitis may contribute to this high injury risk. We hypothesized that the risk of ATRs in female collegiate gymnasts increases with years of competitive gymnastics, that non-steroidal anti-inflammatory drug (NSAID) use is associated with less ATRs, and that the risk is larger during competition than training. Female gymnasts from 78 USA collegiate teams completed a survey assessing the prevalence of ATRs, NSAID use, age at which competitive gymnastics started and age at which ATR occurred, and whether ATRs occurred during training or competition. Twenty-one of 103 gymnasts (20.4%, 95% CI: 13.6% to 29.4%) experienced ATRs. Eighteen of 21 ruptures (85.7%, 95% CI: 61.3% to 95.8%) occurred after more than ten years of competitive gymnastics (mean: 14.0±2.6 years, 95% CI: 12.8 to 15.2 years). ATRs occurred 0.08±0.01 (95% CI: 0.06 to 0.11) times per 1000 hours at training versus 1.85±0.11 (95% CI: 1.60 to 2.10) times per 1000 hours at competition (P<0.05). Prevalence of NSAID use was 27.6% (95% CI: 18.6% to 39.0%) in gymnasts without ATR but only 5.5% (95% CI: 0.6% to 35.5%, P=0.09) in gymnasts with ATR. Multiple regression analysis demonstrated a negative association between NSAID use and incidence of ATRs (P<0.05). Female collegiate gymnasts are at high risk for ATRs, especially after more than ten years of competitive gymnastics and during competition.

Consumer awareness and knowledge regarding use of non-steroidal anti-inflammatory drugs (NSAIDs) in a metropolitan area.

Non-steroidal anti-inflammatory drugs (NSAIDs) have well-known adverse effects, and numerous studies have shown inappropriate behaviors regarding their use. The primary aim of this study was to analyze the knowledge, attitudes, and behaviors regarding the use of NSAIDs simultaneously in one of the largest and most populated areas of Italy, Naples. From 2021 December 14th to 2022 January 4th, a cross-sectional survey study was conducted among community centers, working places, and universities using a snowball sampling method. For inclusion in the study, the participants were required to be at least 18 years old and residents in the metropolitan area of Naples. Three multiple linear regression analysis (MLRA) models were developed by including variables that could potentially be associated with the following outcomes of interest: knowledge (Model I), attitudes (Model II), and behavior (Model III) regarding the use of NSAIDs. Data were acquired from 1,012 questionnaires administered to subjects evenly divided by gender with an average age of 36.8 years and revealed that only 7.9% of the participants self-admittedly did not take NSAIDs, while approximately half the participants (50%) admitted to occasionally using them. The results showed a statistically significant correlation between attitudes regarding the appropriate use of NSAIDs and less knowledge. The regression analyses indicated that behaviors regarding the appropriate use of NSAIDs were statistically significant in younger respondents, non-smokers, and those without children. These interesting results showed that behaviors regarding the appropriate use of NSAIDs were significantly higher among respondents with less knowledge and more positive attitudes. According to the collected data and statistical analysis results, it is possible to identify factors that can greatly affect inappropriate behaviors regarding the use of NSAIDs and establish targeted prevention programs.

Effects of early treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) on the bronchoalveolar lavage proteome and oxylipids during bovine respiratory syncytial virus (BRSV) infection.

Non-steroidal anti-inflammatory drugs (NSAID) are not recommended for use against pneumonia in humans, but are commonly utilised against bovine respiratory disease. This study aimed to determine if the use of NSAIDs in the early phase of bovine respiratory syncytial virus (BRSV)-infection limits pulmonary inflammation. Four to nine-week old calves were infected with BRSV by aerosol and were treated with either meloxicam intravenously on day (D)4 (n = 5, MEL), acetylsalicylat-DL-lysin intravenously on D4 and D5 (n = 5, ASA), or were left untreated as controls (n = 5, CTR). Clinical signs were monitored daily until necropsy on D7, BRSV-RNA was detected in nasal swabs and bronchoalveolar lavage (BAL) by RT-qPCR, inflammatory cells and proteins were identified in BAL by cytology and label-free quantitative mass spectrometry-based proteomics, respectively, and oxylipids were quantified in BAL and plasma by liquid chromatography tandem mass spectrometry with triple quadrupole mass detectors. The calves developed mild to moderate signs of respiratory disease and, with the exception of one MEL-treated and one ASA-treated calf, limited lung lesions. None of the treatments had a significant effect on virus replication, clinical signs or lung lesion extent. Relative to controls, both treatments initially induced a downregulation of proteins in BAL. Immunoglobulin (Ig)-related proteins, such as the Ig kappa and lambda locus and the joining chain of IgA and IgM, were downregulated in MEL-treated calves compared to controls. In addition, meloxicam induced an increased neutrophil influx in BAL in response to BRSV, possibly related to a reduction in plasma prostaglandin, and to a downregulation of The Liver X Receptor/ Retinoid X Receptor (LXR/RXR), the Farnesoid X Receptor (FXR)/RXR and the 24-Dehydrocholesterol Reductase (DHC24) signalling pathways in the lung. The risk of NSAIDs to increase neutrophil activity during stimulation with BRSV or other toll-like receptor 4 agonists needs to be investigated further. Since augmented neutrophil responses can be detrimental, the results of the present study do not support the use of NSAIDs to prevent the clinical expression of BRSV-infection.

Regular Nonsteroidal Anti-Inflammatory Drug Use Increases Stress Fracture Risk in the General Population: A Retrospective Case-Control Study.

Previous studies have shown that the use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with increased stress fracture risk. This phenomenon has been studied predominantly in high-activity individuals, so data regarding the general population are limited despite the substantial economic and resource burden of stress fracture injuries within the general US population. Furthermore, our preclinical studies demonstrate that regular use of NSAIDs also diminishes the intrinsic ability of bone to resist fracture. To determine the association of regular NSAID use with stress fractures in the general population, we surveyed subjects presenting with either stress fracture or uncomplicated ankle sprain to assess their use of NSAIDs over the three months before their injury. We hypothesized that subjects with stress fractures would have increased regular NSAID usage as compared to controls. Subjects diagnosed with a stress fracture (n = 56) and subjects with uncomplicated ankle sprains (n = 51; control) were surveyed about their NSAID use at the time of their diagnosis and in the previous three months using a questionnaire based on the National Health and Nutrition Examination Survey (NHANES). Subjects were surveyed in person on the day of their injury diagnosis or by phone within 30 days of their diagnosis. Fisher's exact test was used to determine significant differences in NSAID usage between stress fracture and control subjects. Subjects diagnosed with stress fractures had a statistically significant increase in both current use (p=0.03) and regular use (p=0.04) of ibuprofen/naproxen/celecoxib as compared to control subjects. There were no significant differences in the use of aspirin, acetaminophen, or prescription medications containing acetaminophen between groups. Consistent with previous clinical reports, we observed a strong correlation between regular ibuprofen/naproxen/celecoxib use and stress fracture incidence in the general population. These results indicate that patients at high risk of stress fracture should avoid regular use of ibuprofen, naproxen, or celecoxib.

НПВП-гастропатия — скрытая угроза при лечении боли

INTRODUCTION. NSAID gastropathy is one of the possible negative consequences of taking non-steroidal anti-inflammatory drugs (NSAIDs), characterized by pathological changes in the gastrointestinal tract. The disease is often asymptomatic, which is the reason for its low detectability during outpatient appointments. The risks of developing serious complications from the gastrointestinal tract (ulcers, bleeding, perforations) increase 3-fold already in the first days of NSAID use. Even a short course of NSAID therapy lasting 3–5 days carries a risk of gastrointestinal complications similar to that of long-term treatment. As a consequence, prevention strategies should be implemented regardless of the duration of therapy, especially in patients with more than one risk factor. CONCLUSION. The risks of complications when taking this group of drugs can be significantly reduced by drug prophylaxis in patients with risk factors for the development of NSAID-gastropathy. Proton pump inhibitors are the main means of preventing possible adverse drug reactions of NSAIDs from the upper gastrointestinal tract. Physicians should consider the need for prophylactic use of proton pump inhibitors throughout the duration of NSAID use. Omez® 20 mg has indications for both prevention and treatment of NSAID-associated gastropathy and can be recommended to such patients from the first day of NSAID intake regardless of the course duration of NSAID intake. KEYWORDS: pain, gastroenterology, geriatrics, gastrointestinal bleeding, gastrointestinal tract, proton pump inhibitors, neurology, adverse events, nonsteroidal anti-inflammatory drugs, NSAIDs, NSAID-associated complications, NSAID gastropathies, general surgery, prevention, therapy, risk factor, chronic pain

Recent trends in populations of Critically Endangered Gyps vultures in India

Summary This paper reports results from the eighth of a series of road transect surveys of Gyps vultures conducted across northern, central, western, and north-eastern India since the early 1990s. Populations of the White-rumped Vulture Gyps bengalensis, Indian Vulture G. indicus, and Slender-billed Vulture G. tenuirostris declined rapidly, beginning in the mid-1990s. The principal cause of the declines was poisoning due to widespread veterinary use of the non-steroidal anti-inflammatory drug (NSAID) diclofenac on cattle. The results of the current survey suggest that, while populations of all three species of vulture remain at a low level with no signs of recovery, they appear to have been approximately stable since veterinary use of diclofenac was banned in the mid-2000s. Population trends in India, where the illegal use of diclofenac and legal use of other toxic NSAIDs continues, are compared with more positive trends in Nepal, where the veterinary use of toxic NSAIDs appears to have been reduced to a low level.

Pain relief after abdominal oncologic surgery. Evaluation of the effectiveness and safety of a fixed combination of diclofenac and orphenadrine

Evaluation of the analgesic, opioid-sparing, anti-inflammatory and adverse effects of the diclofenac and orphenadrine (Neodolpasse) fixed combination for analgesia in the postoperative period of surgical cancer patients. A randomized, single-center, prospective, comparative study evaluated two analgesic regimens in 40 cancer patients undergoing various open cavity surgeries, including extensive combined interventions associated with the resection of 3 or more organs. The study was conducted following the transfer from the ICU to the surgical department during the early activation period, within the first two postoperative days. In the first group N (n=20), "Neodolpasse" (a fixed combination of 75 mg Diclofenac and 30 mg Orphenadrine) was administered as an infusion, twice daily. In the second group K (n=20) analgesia was performed with ketoprofen as an intravenous infusion at a daily dose of 200 mg. Patients in both groups received scheduled prolonged epidural analgesia with 0.2% ropivacaine, and when the severity of pain in a visual analogue scale (VAS) increased to more than 40 mm, so an additional dose of 100 mg tramadol was administered intramuscularly. Daily measurments of blood creatinine level and C-reactive protein were taken, postoperative blood loss was accounted for, as well as postoperative complications according to the Clavien-Dindo classification. The comparative analysis of the indicators of pain syndrome severity showed that the patients in group N exhibited a more pronounced analgesic effect, so on the second postoperative day 30% of patients reported moderate pain (from 50 to 60 mm on the pain scale), on the third day - 15%, and by the fourth day - all 100% of patients experienced pain of low intensity. The additional analgesia with tramadol in group N was required twice less than in the comparison group, and such adverse effects as nausea, drowsiness, and weakness were significantly more common in the ketoprofen group. In both groups, the average blood creatinine level did not exceed permissible values, and the C-reactive protein was elevated at all stages of the study but tended to decrease by the fourth day. The analysis of postoperative complications according to the Clavien-Dindo scale at the time of discharge did not reveal a direct correlation between the occurred complications and the use of NSAIDs. Adverse effects such as anastomotic failure, gastrointestinal complications, or other hemorrhagic manifestations were not recorded. The inclusion of Neodolpasse into multimodal analgesic regimens resulted in the most pronounced analgesic and opioid-sparing effects in surgical cancer patients using laparotomy access. Additionally, the application of short courses of nonsteroidal anti-inflammatory drugs (NSAIDs) was associated with a favorable safety profile.

Characterizing NSAID Allergy and Strategies for Management in Patients with Rheumatological and Orthopaedic Conditions, in a Single Tertiary Hospital in Hong Kong

Background Non-steroidal anti-inflammatory drugs (NSAIDs) are amongst the most frequently prescribed medications, their associated hypersensitivity reactions can not only lead to potentially severe reactions, but also limit analgesic and anti-inflammation options. This is especially true for those who are ailed with rheumatological or orthopaedic diseases leading to chronic pain and inflammatory conditions. This highlights the importance of identifying different types of NSAID hypersensitivity, and to find safe alternatives, namely selective COX-2 inhibitors, to groups of patients that may benefit the most from its utility. Objective To assess and categorise patients with suspected NSAID hypersensitivity, and to successfully provide alternatives to those with chronic rheumatologic and orthopedic ailments. Methods 115 patients with suspected NSAID hypersensitivity were referred to Queen Mary Hospital for specialist evaluation between Jan 2023 and March 2024, those suitable were later challenged and delabelled. Remaining patients were assessed as clinically compatible with NSAID hypersensitivity, and later separated into whether they had background of orthopedic or rheumatological conditions, hence strong indications for NSAIDs, and without, to which selective COX-2 inhibitors tolerance tests were offered. Results Of 115 patients, 20% (23/115) were assessed as unlikely to have NSAID hypersensitivity, and later challenged. 18.2% (21/115) had negative challenges and were delabelled; only 2 patients had positive reactions, confirming NSAID hypersensitivity, of which symptoms were mild and did not require hospitalization. 82% of the remaining patients (94/115) were then later stratified into different NSAID hypersensitivity reactions according to European Academy of Allergy &amp; Clinical Immunology (EAACI) guidelines. 57.3% (66/115) of patients were able to resume use of NSAIDs either by finding an alternative NSAID, namely a selective COX2 inhibitor (45/115, 39.1%), or through a negative drug challenge (21/115, 18.2%). Overall there was no significant difference in the proportion of patients with successful COX2 inhibitor challenges between the group with rheumatological and orthopedic diagnoses against those without (62% vs 54% p=0.414). 29 patients are still pending workup, likely underestimating the amount of patients that are able to resume NSAIDs. Conclusion NSAID hypersensitivity is amongst the most commonly reported drug allergies, and may present with many different clinical phenotypes. Patients with suspected NSAID hypersensitivity require allergist evaluation, and if not clinically suggestive of allergy, would benefit from drug challenges, especially in cases with underlying rheumatological or orthopedic conditions, where NSAIDs are essential. In situations where NSAID hypersensitivity is considered likely, selective COX-2 inhibitors can often be considered as a suitable alternative.