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Objectives: Chronic kidney disease (CKD) is a comorbidity in psoriatic arthritis (PsA). We aimed to define the prevalence of CKD in patients with PsA, describe their long-term renal outcomes and identify risk factors for CKD development., Methods: We included patients with PsA followed by our prospective observational cohort. We defined CKD as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m 2 for at least 3 months. We characterised long-term renal outcomes of CKD cases identified following clinic entry. We used time-dependent Cox regression models to identify factors associated with CKD development., Results: Of 1336 patients included in the study, 123 (9.2%) had CKD. Of these, 25 (20.3%) were observed to have CKD at clinic entry and 98 (79.7%) developed CKD during follow-up at a median (IQR) of 8.2 (2.8-14.0) years from baseline. Doubling of baseline creatinine was observed in 18 of 98 (18.3%) new patients with CKD. 49 (50%) patients developed a sustained ≥40% reduction in baseline eGFR. Two patients developed eGFR <15 mL/min/1.73 m 2 . In the multivariate Cox regression model adjusted for age at study entry, sex and baseline eGFR, factors independently associated with the development of CKD included diabetes mellitus (HR 2.58, p<0.001), kidney stones (HR 2.14, p=0.01), radiographic damaged joint count (HR 1.02, p=0.02), uric acid (HR 1.21, p<0.001; 50-unit increase), daily use of non-steroidal anti-inflammatory drugs (NSAIDs) (HR 1.77, p=0.02) and methotrexate use (HR 0.51, p=0.01)., Conclusion: CKD is not infrequent in PsA. Its development is associated with related comorbidities, joint damage and NSAID use. Methotrexate seems to be protective., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Oligoarticular psoriatic arthritis (PsA) is frequent but rarely studied. The objective was to assess the efficacy of apremilast in early oligoarticular PsA., Methods: FOREMOST (NCT03747939) was a phase 4 multicentre, randomised, double-blind, placebo-controlled trial. Patients had early (symptom duration ≤5 years) oligoarticular PsA (>1 but ≤4 swollen and >1 but ≤4 tender joints; 2-8 total active joints). Patients were randomised 2:1 to apremilast 30 mg two times per day or placebo for 24 weeks, with an early escape at week 16. The primary endpoint was the proportion of patients at week 16 who achieved minimal disease activity (MDA)-Joints (modification of MDA mandating ≤1 swollen joint and ≤1 tender joint) based on sentinel joints (those affected at baseline) with a combination of non-responder imputation and multiple imputations. Exploratory analysis assessed all joints., Results: Of 308 patients randomised (apremilast: n=203; placebo: n=105), mean (SD) PsA duration was 9.9 (10.2) months, mean (SD) age was 50.9 (12.5) years and 39.9% of patients were using a conventional synthetic disease-modifying antirheumatic drug. MDA-Joints (sentinel joints (primary endpoint) and all joints) were achieved by significantly more patients with apremilast (33.9% and 21.3%) vs placebo (16.0% and 7.9%) at week 16 (p=0.0008 and nominal p=0.0028, respectively). Greater improvements in patient-reported outcomes, clinical disease activity and skin involvement were also seen with apremilast versus placebo., Conclusions: FOREMOST is the first randomised controlled trial designed for early oligoarticular PsA and showed apremilast improves clinical and patient-reported outcomes. This trial may inform the optimal management of PsA in these patients., Trial Registration Number: NCT03747939., Competing Interests: Competing interests: LG has received medical writing support and honoraria as part of advisory boards for this study. Outside this work: grants or contracts from AbbVie, Biogen, Lilly, Novartis and UCB; consulting fees from AbbVie, BMS, Celltrion, Janssen, Novartis, Pfizer and UCB; honoraria for lectures from AbbVie, Amgen, BMS, Celltrion, Janssen, Lilly, MSD, Novartis, Pfizer and UCB; support for attending meetings and/or travel from MSD, Novartis and Pfizer; and medical writing support from AbbVie, Janssen, Galapagos, and UCB. LCC: AbbVie, Amgen, Biogen, Bristol Myers Squibb, Celgene Corporation, Eli Lilly, Galapagos, Gilead, GSK, Janssen, Medac, MoonLake, Novartis, Pfizer, UCB–grant/research support, consulting fees, and/or speaker honoraria. LCC was supported by the National Institute for Health and Care Research (NIHR) Oxford Biomedical Research Centre (BRC). DDG: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, UCB–grant/research support or consulting fees. JAA: AbbVie, Amgen–speakers bureau; AbbVie, Ardea Biosciences, AstraZeneca, Bristol Myers Squibb, Celgene, Centocor, Eli Lilly, Galapagos, Genentech, GlaxoSmithKline, Human Genome Sciences, Janssen, Merck, Mesoblast, Novartis, Novo Nordisk, Pfizer, Roche, Sanofi-Aventis, Takeda, UCB, Vertex–grant/research support. JV: Nothing to disclose. AP: AbbVie, Almirall-Hermal, Amgen, Biogen Idec, Boehringer Ingelheim, Celgene, GSK, Eli Lilly, Galderma, Hexal, Janssen, LEO-Pharma, Medac, Merck Serono, Mitsubishi, MSD, Novartis, Pfizer, Tigercat Pharma, Regeneron, Roche, Sandoz Biopharmaceuticals, Schering-Plough, UCB Pharma–investigator/speaker/advisor. JFM: AbbVie, Arena, Avotres, Biogen, Bristol Myers Squibb, Dermavant, Eli Lilly, EMD, Janssen, LEO Pharma, Merck, Novartis, Pfizer, Regeneron, Sanofi, Serono, Sun, UCB–consultant and/or investigator. AK: Amgen, AbbVie, BMS, Janssen, Novartis, Pfizer, Eli Lilly–grant/research support and consultant. JR, RW, MB, YK and CD: Employment by and stock ownership in Amgen. PJM: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, Sun, UCB–grant/research support and consultant; Boehringer Ingelheim, GlaxoSmithKline–consultant; AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, UCB–speakers bureau., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ on behalf of EULAR.)

Pharmaceuticals are emerging contaminants given their increasing use worldwide due to intensive food production and population growth. These compounds reach the environment through different pathways with potential negative consequences for wildlife. One dramatic example occurred in Asia, where three native vulture populations collapsed almost to extinction due to acute intoxication with diclofenac, a veterinary use non-steroidal anti-inflammatory drug (NSAID). As seen with diclofenac, avian scavengers are useful sentinels to monitor for the presence of pharmaceuticals in the environment given their position at the top of the trophic chain, and in the case of obligate avian scavengers (vultures), their intimate link to domestic animal carcasses. Unfortunately, little is known about the wider exposure and potential health and population risks of pharmaceuticals to birds of prey. Here we compile literature data regarding relevant toxicological aspects of the most important pharmaceutical groups for birds of prey in terms of toxicity: NSAIDs, antibiotics, external antiparasitics and barbiturates. This work also includes critical information for future risk assessments, including concentrations of drug residues that can remain in animal tissues after treatment, or specific pharmaceutical features that might influence their toxicity in avian scavengers and other birds of prey. We also consider future research needs in this field and provide management recommendations to prevent potential intoxication events with pharmaceuticals in these species. This review highlights the need to consider specific risk assessments regarding exposure to pharmaceuticals, especially those used in veterinary medicine, for birds of prey., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Aim: To examine the risk of non-steroidal anti-inflammatory drug-induced heart failure in patients with chronic kidney disease. Methods: Embase, Medline, CENTRAL, Web of Science, and Google Scholar were searched for papers published in English between 1st January 1999 and 31st May 2020. Papers were included if some participants had chronic kidney disease, were exposed to non-steroidal anti-inflammatory drugs, and where heart failure was measured as an outcome. Papers were assessed for risk of bias using the Cochrane Risk of Bias 2 tool for randomised controlled trials, and ROBINS-I for observational studies. Results: A total of 2480 independent papers were retrieved. Following abstract screening, 165 full texts were reviewed to identify seven eligible papers: two randomised controlled trials, four cohort studies, and one case-control study. For chronic kidney disease (stage 3–5), relative risk for heart failure ranged from 0.3 to 1.9 with 95% confidence interval 0.04 to 15.1. Results were not pooled due to study heterogeneity. We attributed bias to heterogenous populations studied, probable confounding due to partially adjusted risk estimates, and heterogenous measurement of the heart failure outcome. Conclusion: Overall, there are only a few studies to refute or support an increased risk of heart failure associated with taking non-steroidal anti-inflammatory drugs in patients with chronic kidney disease, and therefore no robust evidence was available. [ABSTRACT FROM AUTHOR]

Background As nonsteroidal anti-inflammatory drugs (NSAIDs) and steroids have similar effects, steroids can be avoided to reduce adverse effects. This study aimed to compare the differences in symptom improvement after subacromial injection of steroids or NSAIDs. Methods Sixty patients with rotator cuff syndrome for at least 3 months were enrolled and divided into steroid and NSAID groups. The steroid group received a mixture of 1 mL of triamcinolone acetonide (40 mg/mL) and 1 mL of lidocaine hydrochloride 2%, while the NSAID group received a mixture of 1 mL of Ketorolac Tromethamine (30 mg/mL) and 1 mL of lidocaine hydrochloride 2%. The patients were assessed before and at 3, 6, and 12 weeks after the procedure. Shoulder scores from visual analog scale (VAS), American Shoulder and Elbow Surgeons (ASES), and University of California Los Angeles (UCLA) were used for evaluation. Results Both groups showed improvements in the clinical outcomes. Overall VAS, ASES, and UCLA scores improved from 6.9, 32.7, and 16.0 before the procedure to 2.0, 1.2, and 1.1; 81.5, 87.6, and 88.5; and 29.7, 31.8, and 32.0 at weeks 3, 6, and 12 weeks after the procedure, respectively. Twenty-six patients (86.7%) in the steroid group and 28 (93.3%) in the NSAID group reported satisfactory treatment outcomes. There were no significant differences in the outcomes between the two groups (p=0.671). Conclusions Subacromial injection of NSAIDs for rotator cuff tendinitis with shoulder pain had equivalent outcomes with those of steroid injection at the 12-week follow-up.

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Abstract Background Cancer patients have a highly increased risk of psychiatric disorders following diagnosis, compared with cancer-free individuals. Inflammation is involved in the development of both cancer and psychiatric disorders. The role of non-steroidal anti-inflammatory drugs (NSAIDs) in the subsequent risk of psychiatric disorders after cancer diagnosis is however unknown. Methods We performed a cohort study of all patients diagnosed with a first primary malignancy between July 2006 and December 2013 in Sweden. Cox proportional hazards models were used to assess the association of NSAID use during the year before cancer diagnosis with the risk of depression, anxiety, and stress-related disorders during the first year after cancer diagnosis. Results Among 316,904 patients identified, 5613 patients received a diagnosis of depression, anxiety, or stress-related disorders during the year after cancer diagnosis. Compared with no use of NSAIDs, the use of aspirin alone was associated with a lower rate of depression, anxiety, and stress-related disorders (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.81 to 0.97), whereas the use of non-aspirin NSAIDs alone was associated with a higher rate (HR, 1.24; 95% CI, 1.15 to 1.32), after adjustment for sociodemographic factors, comorbidity, indications for NSAID use, and cancer characteristics. The association of aspirin with reduced rate of depression, anxiety, and stress-related disorders was strongest for current use (HR, 0.84; 95% CI, 0.75 to 0.93), low-dose use (HR, 0.88; 95% CI, 0.80 to 0.98), long-term use (HR, 0.84; 95% CI, 0.76 to 0.94), and among patients with cardiovascular disease (HR, 0.81; 95% CI, 0.68 to 0.95) or breast cancer (HR, 0.74; 95% CI, 0.56 to 0.98). Conclusion Pre-diagnostic use of aspirin was associated with a decreased risk of depression, anxiety, and stress-related disorders during the first year following cancer diagnosis.

Acute pancreatitis is the most common and feared adverse event associated with performance of endoscopic retrograde cholangiopancreatography (ERCP). Unremitting effort has been made for over 40 years to minimize the frequency and severity of this complication. Recently, the use of rectal non-steroidal anti-inflammatory drugs (NSAIDs) have opened a new era for its prevention. This review focuses on the role of NSAIDs in pancreatitis, the pharmacokinetics of these agents, and summarizes the results of clinical trials with rectal NSAIDs alone and combination regimens in the prevention of post-ERCP pancreatitis.

Background: Safer prescribing in general practice may help to decrease preventable adverse drug events (ADE) and related hospitalisations. Aim: To test the effect of the Safer Prescribing and Care for the Elderly (SPACE) intervention on high-risk prescribing of non-steroidal anti-inflammatory drugs (NSAIDs) and/or antiplatelet medicines and related hospitalisations. Design & setting: A pragmatic cluster randomised controlled trial in general practice. Participants were patients at increased risk of ADEs from NSAIDs and/or antiplatelet medicines at baseline. SPACE comprises automated search to generate for each GP a list of patients with high-risk prescribing; pharmacist outreach to provide education and one-on-one review of list with GP; and automated letter inviting patients to seek medication review with their GP. Method: The primary outcome was the difference in high-risk prescribing of NSAIDs and/or antiplatelet medicines at 6 months. Secondary outcomes were high-risk prescribing for gastrointestinal, renal, or cardiac ADEs separately, 12-month outcomes, and related ADE hospitalisations. Results: Thirty-nine practices were recruited with 205 GPs and 191 593 patients, of which 21 877 (11.4%) were participants. Of the participants, 1479 (6.8%) had high-risk prescribing. High-risk prescribing improved in both groups at 6 and 12 months compared with baseline. At 6 months, there was no significant difference between groups (odds ratio [OR] 0.99; 95% confidence intervals [CI] = 0.87 to 1.13) although SPACE improved more for gastrointestinal ADEs (OR 0.81; 95% CI = 0.68 to 0.96). At 12 months, the control group improved more (OR 1.29; 95% CI = 1.11 to 1.49). There was no significant difference for related hospitalisations. Conclusion: Further work is needed to identify scalable interventions that support safer prescribing in general practice. The use of automated search and feedback plus letter to patient warrants further exploration.

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed for pain and inflammation. NSAID complications include acute kidney injury (AKI), causing burden to patients and health services through increased morbidity, mortality, and hospital admissions. Aim: To measure the extent of NSAID prescribing in an adult population, the degree to which patients with potential higher risk of AKI were exposed to NSAIDs, and to quantify their risk of AKI. Design & setting: Retrospective 2-year closed-cohort study. Method: A retrospective cohort of adults was identified from a pseudonymised electronic primary care database in Hampshire, UK. The cohort had clinical information, prescribing data, and complete GP- and hospital-ordered biochemistry data. NSAID exposure (minimum one prescription in a 2-month period) was categorised as never, intermittent, and continuous, and first AKI using the national AKI e-alert algorithm. Descriptive statistics and logistic regression were used to explore NSAID prescribing patterns and AKI risk. Results: The baseline population was 702 265. NSAID prescription fell from 19 364 (2.8%) to 16 251 (2.4%) over 2 years. NSAID prescribing was positively associated with older age, female sex, greater socioeconomic deprivation, and certain comorbidities (diabetes, hypertension, osteoarthritis, and rheumatoid arthritis) and negatively with cardiovascular disease (CVD) and heart failure. Among those prescribed NSAIDs, AKI was associated with older age, greater deprivation, chronic kidney disease (CKD), CVD, heart failure, diabetes, and hypertension. Conclusion: Despite generally good prescribing practice, NSAID prescribing was identified in some people at higher risk of AKI (for example, patients with CKD and older) for whom medication review and NSAID deprescribing should be considered.

Asthma is a chronic heterogeneous disease characterized by various symptoms and persistent airway inflammation, resulting in progressive lung function decline. Classifying asthma phenotypes/endotypes is crucial because the underlying mechanisms and long-term outcomes vary from patient to patient. Recent trials have identified several biomarkers for classifying asthma phenotypes/endotypes, and current treatments have been developed on the basis of these biomarkers. Conventional biomarkers, including immunoglobulin E, blood/sputum eosinophil counts, airway obstruction or reversibility, and fractional exhaled nitric oxide, are widely used to diagnose asthma. However, these markers have some limitations, necessitating the discovery of additional biomarkers. Therefore, this review summarizes recently suggested biomarkers for representing type 2-high (eosinophilic) vs. type 2-low (neutrophilic) asthma, non-steroidal anti-inflammatory drug-exacerbated respiratory disease, and severe asthma. Additionally, we discuss the potential benefits of these biomarkers in classifying specific phenotypes/endotypes and managing asthmatic patients., Competing Interests: There are no financial or other issues that might lead to conflict of interest., (Copyright © 2024 The Korean Academy of Asthma, Allergy and Clinical Immunology • The Korean Academy of Pediatric Allergy and Respiratory Disease.)

Background: Studies investigating the associations of self-reported aspirin use and mammographic breast density (MBD) have reported conflicting results. Therefore, we investigated the associations of aspirin metabolites with MBD in premenopausal women., Methods: We performed this study on 705 premenopausal women who had a fasting blood draw for metabolomic profiling. We performed covariate-adjusted linear regression models to calculate the least square means of volumetric measures of MBD [volumetric percent density (VPD), dense volume (DV), and nondense volume (NDV)] by quartiles of aspirin metabolites [salicyluric glucuronide, 2-hydroxyhippurate (salicylurate), salicylate, and 2,6-dihydroxybenzoic acid]., Results: Approximately 13% of participants reported taking aspirin in the past 12 months. Aspirin users had higher levels of 2-hydroxyhippurate (salicylurate), salicylate, and salicyluric glucuronide (peak area) than nonusers, but only the mean peak area of salicyluric glucuronide was increased by both dose (1-2 tablets per day = 1,140,663.7 and ≥3 tablets per day = 1,380,476.0) and frequency (days per week: 1 day = 888,129.3, 2-3 days = 1,199,897.9, and ≥4 days = 1,654,637.0). Aspirin metabolites were not monotonically associated with VPD, DV, or NDV., Conclusions: Given the null results, additional research investigating the associations of aspirin metabolites in breast tissue and MBD is necessary. Impact: Elucidating the determinants of MBD, a strong risk factor for breast cancer, can play an important role in breast cancer prevention. Future studies should determine the associations of nonaspirin NSAID metabolites with MBD., (©2024 American Association for Cancer Research.)

Diclofenac, a traditional non-steroidal anti-inflammatory drug, is commonly used for treating chronic pain and inflammation. Recently, a number of articles have highlighted the toxicities associated with diclofenac. The current study explores the molecular mechanism of diclofenac induced cardiac toxicity following oxidative stress. Diclofenac inhibits catalase, disrupts the redox balance in cardiac tissue, accelerates the monoamine oxidase induced hydroperoxide generation and eventually inhibits crucial mitochondrial enzyme, viz., aldehyde dehydrogenase, thereby causing myocardial injury. Melatonin, the pineal indoleamine with high antioxidative efficacy, is well known for its cardio-protective properties and its dietary consumption has profound impact on cardiac health. The present study demonstrates perhaps for the first time, that apart from ameliorating oxidative load in the cardiac tissue, melatonin also attenuates the inhibition of catalase and aldehyde dehydrogenase, and prevents stress mediated stimulation of monoamine oxidase. Moreover, favourable binding of diclofenac with melatonin may protect the myocardium from the deleterious effects of this drug. The results indicate toward a novel mechanism of protection by melatonin, having future therapeutic relevance., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Overprescribing of potentially harmful medication in UK general practice has a complex association with socioeconomic deprivation., Aim: To assess trends in general practice prescribing of five high-risk medications and their relationship with deprivation., Design & Setting: An observational study was conducted using general practice data from three English regions with varied sociodemographic factors: West Yorkshire and Harrogate (WY), Black Country and West Birmingham (BC), and Surrey and East Sussex (SE)., Method: Practice-level prescribing data were obtained from 2016-2021 for five drug classes: opioids, hypnotics, gabapentinoids, non-steroidal anti-inflammatory drugs (NSAIDs), and antibacterials. Prescribing trends were demonstrated using a linear model., Results: Reduction in NSAID, opioid, hypnotic and antibacterial prescriptions, and the increase in gabapentinoid prescriptions, were significant at each financial year time period. Index of Multiple Deprivation (IMD) was positively associated with all drug classes except antibacterials, which showed a positive association when incorporating the interaction term between IMD and age.When adjusting for IMD and population, region was independently associated with prescribing rate. Compared with WY, IMD had a smaller association with prescribing in BC for NSAIDs (coefficient = -0.01578, P = 0.004) and antibacterials (coefficient = -0.02769, P = 0.007), whereas IMD had a greater association with prescribing in SE for NSAIDs (coefficient = 0.02443, P <0.001), opioids (coefficient = 0.08919, P <0.001), hypnotics (coefficient = 0.09038, P <0.001), gabapentinoids (coefficient = 0.1095, P <0.001), and antibacterials (coefficient = 0.01601, P = 0.19)., Conclusion: The association of socioeconomic deprivation with overprescribing of high-risk medication in general practice varies by region and drug type. Geographical location is associated with overprescribing, independent of socioeconomic status., (Copyright © 2024, The Authors.)

Objective: To investigate the risk of cardiovascular disease (CVD) associated with increasing dose of a non-steroidal anti-inflammatory drug (NSAID) in patients with ankylosing spondylitis (AS)., Methods: Using the Korean National Health Insurance database, patients newly diagnosed with AS without prior CVD between 2010 and 2018 were included in this nationwide cohort study. The primary outcome was CVD, a composite outcome of ischaemic heart disease, stroke or congestive heart failure. Exposure to NSAIDs was evaluated using a time-varying approach. The dose of NSAIDs was considered in each exposure period. Cox proportional hazard regression was used to investigate the risk of CVD associated with NSAID use., Results: Of the 19 775 patients (mean age, 36 years; 75% were male), 19 706 received NSAID treatment. During follow-up period of 98 290 person-years, 1663 cases of CVD occurred including 1157 cases of ischaemic heart disease, 301 cases of stroke and 613 cases of congestive heart failure. Increasing dose of NSAIDs was associated with incident CVD after adjusting for confounders (adjusted HR (aHR) 1.10; 95% CI 1.08 to 1.13). Specifically, increasing dose of NSAIDs was associated with incident ischaemic heart disease (aHR 1.08; 95% CI 1.05 to 1.11), stroke (aHR 1.09; 95% CI 1.04 to 1.15) and congestive heart failure (aHR 1.12; 95% CI 1.08 to 1.16). The association between NSAID dose and higher CVD risk was consistent in different subgroups., Conclusion: In a real-world AS cohort, higher dose of NSAID treatment was associated with a higher risk of CVD, including ischaemic heart disease, stroke and congestive heart failure., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ on behalf of EULAR.)

Non-steroidal anti-inflammatory drugs are intensively manufactured, used, and regulated. However, these compounds incur toxic effects on gastrointestinal, cardiovascular, and renal systems when administered in high doses for extended periods. Additionally, once these drugs reach the ecosystems through various pathways, they become environmental contaminants and raise ecological concerns. Traditional detection methods proposed for non-steroidal anti-inflammatory drugs detection encompass certain limitations. In this context, the need for simple, cost-effective, sensitive, and selective detection methods that could improve the quality of analysis led the attention of the scientific community toward electrochemical sensors. The lowest limit of detection of ibuprofen (33.33 × 10 -12  μmol L -1 ) was recorded for a sensor based on ibuprofen specific aptamer bound with nitrogen-doped graphene quantum dots and gold nanoparticles nanocomposite modified glassy carbon electrode using differential pulse voltammetry, while the lowest limit of detection reported for ketoprofen was 0.11 μmol L -1 when differential pulse voltammetry was used. This review focuses on the construction, analytical performances, and applicability of electrochemical sensors developed for ibuprofen and ketoprofen determination. This work covers 24 articles published between 2016 and 2022.

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Background/Aims: The incidence of peptic ulcer disease has decreased in past decades; however, the trends in peptic ulcer bleeding (PUB) are inconsistent among regions. This study aimed to investigate the trends in PUB incidence and the effect of risk factors on PUB in Korea. Methods: The records of patients hospitalized with PUB from 2006 to 2015 were retrieved from the Korean National Health Insurance Service Database. Standardized incidences of PUB were calculated, and the clinical characteristics such as age, sex, Helicobacter pylori infection, drug exposure, comorbidities, and mortality were obtained. Results: In total, 151,507 hospitalizations with PUB were identified. The overall annual hospitalization rate was 34.98 per 100,000 person-years. The incidence of PUB showed no significant change from 2006 to 2008 and decreased from 2008 to 2015, with an annual change of –2.7% (p<0.05); however, this change was only significant in men. The incidence of PUB was higher in men than in women between 40 and 70 years old and higher in women than in men older than 80 years. From 2006 to 2015, the H. pylori infection rate increased significantly in patients with PUB; however, there was no significant change in exposure to nonsteroidal anti-inflammatory drugs or other drugs that increase the risk of PUB. Conclusions: Over the past decade, the incidence of PUB has decreased in a sex-specific manner. There has been a decreasing trend in the H. pylori infection rate and no change in exposure to drugs that increase the risk of PUB in Korea. [ABSTRACT FROM AUTHOR]

Background/Aims Irsogladine maleate, an enhancer of gastric mucosal protective factors, has demonstrated its efficacy for various gastric mucosal injuries. The aim of this study was to evaluate the efficacy and safety of irsogladine for prevention of nonsteroidal anti-inflammatory drugs (NSAIDs) or aspirin-induced peptic ulcer and gastritis. Methods In this multicenter, randomized, double-blind, exploratory clinical trial, 100 patients over 50 years of age who needed continuous NSAIDs or aspirin for more than 8 weeks were randomly assigned to either test group (irsogladine maleate 2 mg, twice daily, 39 patients for full analysis) or placebo group (37 patients for full analysis). Primary outcomes were incidence of peptic ulcer and ratio of modified Lanza score (MLS) 2 to 4. Secondary outcome was the number of acute erosions confirmed by endoscopy at 8 weeks. Adverse effects were also compared. Results There were no significant differences in gastric protective effects between test and placebo groups. However, two cases of peptic ulcer in the placebo group but none in the test group were observed. These two cases of peptic ulcer were Helicobacter pylori-negative. In addition, H. pylori-negative group showed significant changes in MLS score (p = 0.0247) and edema score (p = 0.0154) after the treatment compared to those before treatment in the test group. There was no significant difference in adverse events between the two groups. Conclusions The efficacy of irsogladine maleate was found in H. pylori-negative group, suggesting its potential as a protective agent against NSAIDs or aspirin-induced peptic ulcer and gastritis.

The article highlights the current data on the prevalence and pathogenesis of osteoarthritis (OA), presents a new definition of the disease, research results on the heterogeneity of OA, its relationship with obesity and metabolic syndrome. Obesity is one of the main factors in the development and more rapid progression of OA, and the presence of metabolic syndrome not only increases the risk of developing the disease, but also determines its severity. It is noted that with an increase of the components of the metabolic syndrome, the severity of OA increases. Therefore, hyperuricemia is associated with the presence of osteophytes and the progression of osteoarthritis, hyperglycemia - with the severity of the clinical manifestations and radiological progression. Much attention is given to the treatment of patients with OA and The European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) recommendations for the treatment of knee joints OA updated in 2019. In which for the first time a symptomatic slow-acting drugs for osteoarthritis (SYSADOAs) are assigned as the basis in the treatment of OA. The data on the effectiveness of some drugs from this group are presented. The glycosaminoglycan-peptide complex, which contains pharmacologically high-quality chondroitin sulfate when administered intramuscularly, has a significant effect on the symptoms, and in case of continued use, slows the progression of OA. The multicenter open-label prospective study of diacerein in patients with knee-joint OA combined with metabolic syndrome showed that during therapy pain syndrome and stiffness are reduced, and functional condition of the joints and quality of life of patients improves quickly and significantly. In addition, the positive effect of the drug on some components of the metabolic syndrome was demonstrated: a significant decrease in body mass index, low density lipoproteins, triglycerides, glucose and uric acid.

Gut microbiota have been known to play an essential role in host immunity and metabolism. Dysbiosis is associated with various gastrointestinal (GI) and other diseases such as cancers, metabolic diseases, allergies, and immunological disorders. So far, the role of gut microbiota has been studied mainly in lower GI disease but has recently been reported in upper GI diseases other than Helicobacter pylori infection, including Barrett’s esophagus, esophageal carcinoma, gastric cancer, functional dyspepsia, and nonsteroidal anti-inflammatory drug-induced small intestinal mucosal injury. Probiotics have some beneficial effect on these diseases, but the effects are strain specific.

The eradication of Helicobacter pylori and the widespread use of effective antisecretory therapies, including proton pump inhibitors, have improved the management of peptic ulcer disease. However, in some patients, peptic ulcer disease is refractory to 8 to 12 weeks of standard antisecretory drug treatment. For refractory peptic ulcer disease, further evaluation of the risk factors and causes of refractory peptic ulcer disease, including patient risk factors and noncompliance (smoking, nonsteroidal anti-inflammatory drug use, and noncompliance with medical treatment), persistent H. pylori infection, and non-H. pylori-related factors (giant ulcer, gastrinoma, infections other thanH. pylori, and malignancy), is essential. The treatment should focus on the cause of the refractory peptic ulcer disease, avoiding smoking and nonsteroidal anti-inflammatory drug, the treatment of persistent H. pylori, use of high-dose proton pump inhibitors, or surgical excision of gastrinomas. Surgery should be considered in patients who are at high risk for complications and recurrent peptic ulcer disease despite medical treatment. In this review, I describe the diagnosis and treatment of refractory peptic ulcer disease.

In April 2016, the National Institute of Social Services for Retirees and Pensioners discontinued its policy of 100% coverage for 159 drugs (the “social subsidy”), including symptomatic slow-acting drugs for osteoarthritis (SYSADOAs), due to insufficient evidence of significant clinical benefit. We evaluated the effect of this measure on the use of SYSADOAs as well as non-steroidal anti-inflammatory drugs (NSAIDs), which were unaffected by this policy change. We compared outpatient dispensations of SYSADOAs and NSAIDs from 2015 to 2017, measuring dispensed units, retail price, and out-of-pocket expenses for beneficiaries each month. After the change in coverage, there was a 61.6% total decrease in SYSADOA units dispensed, and a 63.4% decrease in the final sales price to the public, measured in constant values. Dispensation was not reoriented towards NSAIDs, which fell by 6.1%. The incidence of new treatments decreased (from 6.4 to 3.3 treatments per 1,000 beneficiaries per month), as did their continuity. Beneficiaries’ out-ofpocket spending on SYSADOAs increased by 75.8% (at constant values). Disinvestment in interventions with questionable therapeutic value is an important tool in working toward the sustainability of health systems. [ABSTRACT FROM AUTHOR]

The objective of this study was to describe dental prescriptions of non-steroidal anti-inflammatory drugs (NSAID), opioids, and analgesics dispensed by the Brazilian National Health System (BNHS, SUS in Portuguese) of a Southeastern state from January to December 2017, and to analyze their association with socioeconomic and oral health care services' characteristics at municipal level. Data were collected from the Brazilian Integrated Pharmaceutical Care Management System. Medicines were grouped according to the Anatomical Therapeutic Chemical Classification System. The total number of Defined Daily Doses (DDD) and DDD per 1,000 inhabitants (inhab.) per year were presented and compared between groups of municipalities. Data analysis used the Classification and Regression Tree model performed with IBM SPSS 25.0. The total number of NSAID, opioids, and analgesics prescriptions was 70,747 and accounted for 354,221.13 DDD. The most frequently prescribed medicine was ibuprofen (n = 24,676; 34.88%). The number of dental practitioners in the BNHS per 1,000 inhab. (p < 0.001), first dental appointment coverage (p = 0.010), oral health teams per 1,000 inhab. (p=0.022), and the proportion of rural population (p = 0.014) were variables positively associated with the number of DDD of NSAID per 1,000 inhab. per year. Bolsa Família program coverage per 1,000 inhab. (p = 0.022) was negatively associated with NSAID prescription. Regarding analgesics, first dental appointment coverage (p=0.002) and Bolsa Família program coverage per 1,000 inhab. (p = 0.012) were positively associated with DDD per 1,000 inhab. per year. In conclusion, dental prescriptions of analgesics and NSAID in the BNHS were associated with socioeconomic and oral health care services' characteristics. [ABSTRACT FROM AUTHOR]

Competing Interests: Competing interests: None declared.

Purpose: In competitive sport, classic methods of measuring drug prevalence, such as doping controls or questionnaires, are challenging. Here we describe a novel urine sampling method to measure drug use in athletes. We hypothesize that the prevalence of drug use in ultramarathon runners is measured more accurately with our sampling method than randomized-response questionnaires., Methods: Urine samples and associated demographic data were collected from male participants using blind, automated urinals at the start of ultramarathon races. Various nonprohibited and prohibited substances were subsequently screened. Concomitantly, 2931 male and female runners participating in the same ultramarathons completed an anonymized, randomized-response questionnaire regarding drug use., Results: Among 412 individual urine samples, 205 (49.8%) contained at least one substance, and 16.3% of the samples contained one or more prohibited substances. Substances detected in urine included nonsteroid anti-inflammatory drugs (NSAID) (22.1%), acetaminophen (15.5%), opioids (6.6%), diuretics (4.9%), hypnotics (4.4%), glucocorticoids (2.7%), beta-2 agonists (2.2%), cannabinoids (1.9%), and stimulants (1.2%). None of the samples contained erythropoietin-receptor agonists or suspicious testosterone. Drug use was not associated with the participants' characteristics or ranking. Respondents to the questionnaire reported using acetaminophen (13.6%) and NSAID (12.9%); however, no prohibited substances were declared., Conclusions: There was a high prevalence of drug use among male ultramarathon runners, in particular, NSAID and painkillers; however, performance-enhancing drugs were marginally used. Blind urine sampling highlighted prohibited drug use not declared in questionnaires, and it is useful to assess the prevalence of drug use and/or doping in competitive athletes., (Copyright © 2024 by the American College of Sports Medicine.)

Rheumatoid arthritis (RA) is an autoimmune disease suffered by millions of people worldwide. It can significantly affect the patient's quality of life by damaging not only the joints but also organs such as the lungs and the heart. RA is normally treated using nonsteroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, disease-modifying antirheumatic drugs (DMARDs), and biologics. These active agents often cause side effects and offer low efficacy due to their lack of specificity and limited retention time. In an attempt to improve RA treatments, hydrogel-based systems have been proposed as drug delivery carriers. Due to their exceptional adaptability and biocompatibility, hydrogels have the potential of enhancing the delivery of RA therapy through different administration routes in an efficient and effective manner. In this review, we explore the application of hydrogel systems as potential carriers in RA treatment. Additionally, we discuss recent work in the field and highlight the required hydrogel properties, depending on the administration route. The outstanding potential of hydrogel systems as carriers for RA was demonstrated; however, there is extensive research yet to be done to improve available treatments for RA., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Phenylbutazone (PBZ) is the most commonly used drug to treat symptoms of lameness in horses; however, it is associated with adverse effects such as gastric ulcer syndrome (EGUS). Interestingly, many practitioners prescribe omeprazole (OME) concurrently with PBZ to prevent the development of EGUS. However, the efficacy and safety of this practice in Mongolian horses with chronic lameness remain unknown., Objectives: To evaluate the clinical effects of a combination of PBZ and OME on chronic lameness in Mongolian horses., Study Design: Randomised block experimental design., Methods: Eighteen Mongolian horses with lameness score was ≥3 points, were divided into three treatment groups, with six horses in each group: placebo (CON), PBZ (4.4 mg/kg PO q. 24 h), or PBZ plus OME (4 mg/kg PO q. 24 h; PBZ + OME) in a randomised block design based on the initial lameness score. The horses were treated for 15 days. During this period, weekly gastroscopy, and physiological and biochemical tests were performed., Results: Both PBZ (median 1.0, interquartile range [IQR]: 0.8-1.3; p = 0.01) and PBZ + OME (median 1.0, IQR: 1.0-1.0; p = 0.01) significantly decreased the lameness score compared with before administration. In addition, PBZ significantly increased the equine glandular gastric disease (EGGD) score (3.0 ± 0.6, p < 0.001), GT-17 content (293.4 ± 21.8 pg/mL, p < 0.001), and pepsinogen-1 (PG1) content (295.3 ± 38.3 ng/mL, p < 0.001) compared with CON or PBZ + OME. However, it significantly reduced the total protein (53.6 ± 1.5 g/L, p < 0.05) and albumin (25.5 ± 1.8 g/L, p < 0.05) contents. Nevertheless, compared with PBZ, PBZ + OME significantly decreased the EGGD score (0.3 ± 0.5, p < 0.001) and significantly increased the gastric fluid pH (7.3 ± 0.5, p < 0.001), total protein content (62.5 ± 4.6 g/L, p = 0.009), and albumin content (29.4 ± 1.1 g/L, p = 0.004). Meanwhile, they significantly diminished the gastrin 17 (GT-17) (162.0 ± 21.0 pg/mL, p < 0.001) and PG1 (182.4 ± 22.5 ng/mL, p < 0.001) contents., Main Limitations: Individual differences in horses were larger, but the sample size was small. There was larger interval between observations for each index., Conclusions: Compared with PBZ alone, PBZ + OME had no therapeutic effect on chronic lameness; however, it reduced the occurrence of EGGD in Mongolian horses. Horses may be protected against chronic lameness and PBZ-induced EGGD by increasing the pH value, decreasing serum PG1 and GT-17 content, and preventing the reduction of myeloperoxidase content., (© 2023 EVJ Ltd.)

Arthritis causes inflammatory damage to joints and connective tissues. In the treatment of arthritis, precise and controlled drug delivery to the target site is among the frontline research approaches. In the present research work, celecoxib drug and bioactive glass incorporated chitosan hydrogels were fabricated by the freeze gelation method. Fourier transform infrared spectroscopy, scanning electron microscopy, and thermogravimetric analysis/differential scanning calorimetry techniques were used to characterize the hydrogels. Different kinetic models were applied to study the drug release kinetics. The celecoxib release was mainly controlled by a Fickian diffusion process followed by the Higuchi model. Maximum 86.2% drug entrapment was observed in 20 mg drug-loaded hydrogel and its swelling ratio was 115.5% in 28 d. Good hydrophilicity, good drug entrapment efficiency, and moderate drug release patterns of hydrogels can make them suitable for sustained drug release. The cytocompatibility of hydrogels was established by performing an MTT assay on the BHK-21 fibroblast cell line. The promising results have proved that hydrogels can be considered potential material for the slow release of anti-inflammatory drug at the target site in arthritis., (© 2024 IOP Publishing Ltd.)

In the crystals of alkaline earth metal compounds strontium and barium with the non-steroidal anti-inflammatory drug nimesulide, the strontium cation is nine-coordinated with a distorted tricapped trigonal prismatic geometry TCTPR-9, whereas the ten-coordinated barium ion exhibits a distorted tetracapped trigonal prismatic geometry TCTPR-10.

A variety of novel indole-derived γ-hydroxy propiolate esters were designed, synthesized, and evaluated for their anti-inflammatory activity in-vitro and in-vivo. According to the nitric oxide (NO) inhibitory analysis, all compounds showed potent NO inhibitory ability in a dose-dependent manner, with no apparent cytotoxicity. The model compound, L-37, also exhibited significant potency in PGE 2 inhibition. In addition, compounds L-37 and L-39 can downregulate the expression of COX-2 enzyme at 5 μM via ELISA experiment. Compound L-37 (1 μM) also inhibited the PGF 1 production as well as the expression of COX-1, but displayed weak inhibition activity towards the Leukotrienes (LT) and Thromboxane-B2 (TXB-2) production. However, the expression of 5-LOX was significantly inhibited by compound L-39 at 5 μM. Xylene-induced ear edema model was explored for in-vivo anti-inflammatory evaluation, compound L-37 showed similar inhibitory activity compared with celecoxib, approximately 80% at 50 mg/kg dosage. Every outcome showed that the newly synthesized compounds can effectively inhibit inflammation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)