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Drug-induced pseudoporphyria is commonly linked to nonsteroidal anti-inflammatory drugs (NSAIDs) such as naproxen, oxaprozin, ketoprofen, and ibuprofen. The NSAID meloxicam is not a commonly reported inciting agent. We report a case of meloxicam-induced pseudoporphyria in a 55-year-old woman with a past medical history of hypertension, hyperlipidemia, gastroesophageal reflux disease, and osteoarthritis. She presented to the clinic with tense and denuded bullae on her dorsal feet, which was diagnosed as pseudoporphyria after further workup. Upon evaluating the patient's medication history, meloxicam was identified as the most likely inciting agent. The patient's condition resolved with the discontinuation of this medication. Our findings can help dermatologists effectively diagnose and treat meloxicam-induced pseudoporphyria in patients with similar cases.

Fluoroquinolones (FQs) are highly potent bactericidal antibiotics with broad-spectrum activity against Gram-negative/positive bacteria. The Food and Drug Administration (FDA) anticipated the presence of a long-lasting incapacity of Fluoroquinolone Associated Toxicity (FQAT), which is not officially documented yet. This review aimed to précis the existing information on FQA long-term toxicity, such as cardiotoxicity, aortic aneurysm, tendon rupture, nephrotoxicity, hepatotoxicity, peripheral neuropathy, vagus nervous dysfunction, reactive oxygen species (ROS), phototoxicity, glucose hemostasis, and central nervous system (CNS) toxicity. We are focused on the CNS toxicity of FQs, either due to the direct action of the FQs on CNS receptors or by other drug co-administration, including nonsteroidal anti-inflammatory disease (NSAIDs) and theophylline. Due to the nature of the R7 side chain, FQs containing unsubstituted 7-piperazine and 7-pyrrolidine have the most significant effect. The gamma-aminobutyric acid-A (GABAA) receptor and CNS effects are inhibited through at least three possible mechanisms. Firstly, by the pharmacological action of the quinolone directly. Secondly, FQ-NSAIDs interact pharmacodynamically in which the interaction between the FQ and a receptor is significantly altered by the presence of another drug that interacts with the same receptor. An example may be the interaction between NSAIDs and some FQs. Thirdly, a pharmacokinetic drug-drug interaction leads to a higher concentration of quinolone or the other drug. An example may be the interaction between theophylline and benzodiazepines with some FQs. [ABSTRACT FROM AUTHOR]

Objective: The objective of this systematic review and meta-analysis was to determine whether patients with episodic (EM) or chronic migraine (CM), who were treated with anti-CGRP antibodies, showed a reversal from medication overuse (MO) or medication overuse headache (MOH) status at their baseline to non-overuse status. Furthermore, this study aimed to establish which acute headache medication (AHM) categories responded more effectively to anti-CGRP antibodies. Methods: A systematic search was conducted in the PubMed database for relevant studies from January 2013 to September 2023. We included phase three randomized controlled trials to examine the role of anti-CGRP antibodies in patients with EM or CM and their MO status. A meta-analysis was conducted to find the association between anti-CGRP antibodies and the number of EM and CM patients with MO or MOH at baseline that reverted to non-MO status or below the MOH threshold. Results: The initial search yielded a total of 345 studies. After removing duplicates and screening with inclusion criteria, 5 studies fulfilled our conditions. Each study reviewed the response to changes in the MO status of patients after receiving anti-CGRP antibodies, including eptinezumab, fremanezumab, galcanezumab, and erenumab, compared to placebo. Our study analyzed three AHM categories: triptans, simple analgesics, and multiple drugs. The overall relative risk (RR) was 1.44 (95% CI, 1.31 to 1.59; p < 0.001). The RRs for triptans, simple analgesics, and multi-drug groups were 1.71 (95% CI, 1.53 to 1.91; p < 0.001), 1.10 (95% CI, 0.83 to 1.47; p = 0.5), and 1.29 (95%CI 1.14 to 1.46; p < 0.001) respectively. Conclusion: The meta-analysis has shown that anti-CGRP antibodies were statistically significant in transitioning from MO or MOH status to non-MO status or below the MOH threshold (RR = 1.44) for all included studies and all AHM categories except for simple analgesics. Patients from the triptan group had the highest RR of 1.71 with a p-value < 0.001, while the simple analgesics group had an RR of 1.10, however, with a p-value > 0.05. Interestingly, this analysis can be interpreted as that anti-CGRP antibodies might not be effective in reducing simple analgesics use in EM or CM patients. Further studies are needed to investigate these matters. [ABSTRACT FROM AUTHOR]

Aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) usage has been associated with pancreatic ductal adenocarcinoma (PDAC) prevention, though epidemiological data have not reliably demonstrated this. The aim of this study is to identify if aspirin and other NSAIDs are effective in the primary prevention of PDAC in a large UK prospective cohort. A nested case-control study was conducted using the UK Biobank cohort. Incident PDAC cases (n = 1129 of whom 239 (21.2 %) were using aspirin) were age and sex-matched with cancer-free controls (n = 8822 of whom 1752 (19.9 %) were using aspirin). Conditional logistic regression models were used to generate odds ratios (ORs) and 95 % confidence intervals (CI) for risk of PDAC with and without regular use of aspirin, non-aspirin NSAIDs and all NSAIDs respectively. Exploratory analyses were carried out assessing interactions with diabetes mellitus (DM) as a condition with increased pancreatic cancer risk. Regular aspirin use at initial recruitment was independently associated with a decreased risk of PDAC (OR [95 % CI] = 0.80 [0.68–0.95] P = 0.01). Regular non-aspirin NSAID use was not associated with a risk reduction of PDAC (OR [95 % CI] = 1.01 [0.84–1.23] P = 0.88). Exploratory analyses showed that in those with DM; regular aspirin use reduced risk of PDAC (OR [95 % CI] = 0.60 [0.42–0.85] P = 0.004) compared to non-use. Regular aspirin use is associated with a reduction in risk of PDAC. The reduced risk is more apparent in participants with DM. [ABSTRACT FROM AUTHOR]

Low back pain (LBP) may profoundly impact the quality of life across the globe, and intervertebral disc degeneration (IVDD) is the major cause of LBP; however, targeted pharmaceutical interventions for IVDD are still lacking. Ferroptosis is a novel form of iron-dependent programmed cell death. Studies have showed that ferroptosis may closely associate with IVDD; thus, targeting ferroptosis may have great potential for IVDD therapy. Non-steroidal anti-inflammatory drugs (NSAIDs) are the first-line medications for LBP, while nuclear factor-erythroid 2-related factor-2 (Nrf2) is a key inhibitory protein for ferroptosis. In the current study, we conducted a molecular docking screening between NSAIDs library and Nrf2 protein. Tinoridine was shown to have a high binding affinity to Nrf2. The in vitro study in nucleus pulposus (NP) cells showed that Tinoridine may promote the expression and activity of Nrf2, it may also rescue RSL3-induced ferroptosis in NP cells. Knockdown of Nrf2 reverses the protective effect of Tinoridine on RSL3-induced ferroptosis in NP cells, suggesting that the inhibitory effect of Tinoridine on ferroptosis is through Nrf2. In vivo study demonstrated that Tinoridine may attenuate the progression of IVDD in rats. As NSAIDs are already clinically used for LBP therapy, the current study supports Tinoridine's application from the view of ferroptosis inhibition. • Ferroptosis plays a critical role in intervertebral disc degeneration (IVDD), contributing significantly to its pathological progression. • Tinoridine, as an NSAID, can treat IVDD by inhibiting ferroptosis both in vitro and in vivo. • These findings highlight the therapeutic promise of Tinoridine in IVDD therapy. [ABSTRACT FROM AUTHOR]

Low back pain is a common reason for presentation to the Emergency Department (ED). However, there are limited large-scale, recent data on the epidemiology, disposition, and medication administration for this condition. The objective of this was to assess the incidence, admission rates, medication administrations, and discharge prescriptions among ED visits for low back pain in the United States. This was a cross-sectional study of ED presentations for low back pain from 1/1/2016 to 12/31/2023 using the Epic Cosmos database. All ED visits for adults with low back pain identified by ICD-10 codes were included. Outcomes included admission rates, distribution of opioid, benzodiazepine, (non-benzodiazepine) muscle relaxant, acetaminophen, NSAID, and corticosteroid medications administered in the ED, and distribution of opioid, benzodiazepine, muscle relaxant, and corticosteroid medications given upon discharge. Subgroup analyses were performed by specific medication. Of 207,154,419 ED encounters, 12,241,240 (5.9%) were due to back pain with 1,957,299 of these (16.0%) admitted. The admission rate increased over time from 12.8% to 17.1%. The most common medication given in the ED was opioids (40.7%), followed by acetaminophen (37.8%), NSAIDs (22.6%), muscle relaxants (18.4%) benzodiazepines (12.8%), and corticosteroids (5.5%). The most common medications prescribed upon discharge were muscle relaxants (32.1%), followed by opioids (23.2%), corticosteroids (12.2%), and benzodiazepines (3.0%). Low back pain represents a common reason for presentation to the ED, and admissions have been increasing over time. Opioids remain the most common ED medication, whereas muscle relaxants have arisen as the most common discharge prescription. These findings can help inform health policy decisions, resource allocation, and evidence-based interventions for medication administration. [ABSTRACT FROM AUTHOR]

Non-steroidal anti-inflammatory drugs (NSAIDs) are largely used for controlling various pain conditions and are widely available in community pharmacies, with and without prescription. Despite their effectiveness, NSAIDs can pose significant risks due to potential side effects and drug interactions, particularly in polypharmacy and comorbidity contexts and for vulnerable users. This study investigated whether and how NSAIDs deprescribing can be conducted at the community pharmacy level by assessing pharmacists' confidence, attitudes, and potential barriers and facilitators. Additionally, we aimed to identify any deprescribing guidelines that pharmacists could use. A literature search and a cross-sectional digital questionnaire targeting community pharmacists in Norway were conducted. Results showed that study participants (N = 73) feel confident in identifying needs for deprescribing NSAIDs but barriers such as time constraints, lack of financial compensation, and communication challenges were noted. Participants reported positive attitudes toward deprescribing but highlighted a need for better guidelines and training. This study highlights a gap in specific guidelines for deprescribing NSAIDs and a potential for enhancing pharmacists' roles in the deprescribing process, for example, through training and improved financial incentives. Further research is encouraged to develop concrete strategies for an effective implementation where community pharmacists can be involved in the deprescribing of NSAIDs. [ABSTRACT FROM AUTHOR]

Phenylbutazone (PBZ) is a widely used nonsteroidal anti-inflammatory drug for horses. However, because of its gastrointestinal side effects, its administration requires careful attention in veterinary practice. Malondialdehyde (MDA) is a serum biomarker associated with increased damage to the equine gastrointestinal system. This study investigated the hematological effects and alterations in the gastrointestinal tract and assessed serum MDA concentrations following repeated oral PBZ administration at clinical doses. Fourteen horses were randomly divided into control and treatment groups. All horses in the treatment group were administered 4.4 milligrams per kilogram of body weight of PBZ syrup orally twice a day for 7 days, whereas the control group received syrup as a placebo. The development of gastrointestinal side effects was investigated using gastroscopy, abdominal ultrasound, and fecal pH; serum MDA concentrations were assessed using a commercially available enzyme-linked immunosorbent assay kit. Data were compared between PBZ-treated and control horses before and after the treatment period. The treatment group exhibited decreased albumin and total protein concentrations. Moreover, this group exhibited a higher thickness of the right dorsal colon wall (p = 0.03) and had higher scores for squamous gastric ulcers (p = 0.01). Fecal pH was lower in the treatment group than in the control group after PBZ administration (p < 0.01). Although MDA concentrations were higher in the treatment group after PBZ administration, they did not differ significantly from those of the control group. This study highlighted the changes in hematological and gastrointestinal lesions resulting from PBZ administration in horses at clinical doses, even without clinical signs. However, MDA may not be an optimal biomarker for the early detection of gastrointestinal damage due to PBZ treatment in horses. [ABSTRACT FROM AUTHOR]

As the most common cause of dementia, Alzheimer's disease (AD) is characterized by neurodegeneration and synaptic loss with an increasing prevalence in the elderly. Increased inflammatory responses triggers brain cells to produce pro-inflammatory cytokines and accelerates the Aβ accumulation, tau protein hyper-phosphorylation leading to neurodegeneration. Therefore, in this paper, we discuss the current understanding of how inflammation affects brain activity to induce AD pathology, the inflammatory biomarkers and possible therapies that combat inflammation for AD. [ABSTRACT FROM AUTHOR]

Our study focuses on creating hybrid compounds and assessing their suitability for use in skincare products. The synergistic combination of Kojic acid, NSAIDs, and Palmitic acid proved to be an effective approach in inhibiting melanin production, making it a promising solution for individuals with hyperpigmentation concerns with Kojic acid (KA) Ibuprofen monoester (IBUM) and Ibuprofen-Kojic acid-Palmitic acid diester (IBUD) exhibiting a potential tyrosinase (38 % and 49 % inhibition at 200 µM) and anti-melanogenesis activity (77 % and 79 % inhibition at 100 µM). Furthermore, these compounds exhibited potent anti-inflammatory effects, Kojic acid-Diclofenac monoester (DICM) and Diclofenac-Kojic acid-Palmitic acid diester (DICD) offering potential benefits for inflammation by lowering the paw volume. A stability study under chemical conditions and enzymatic conditions was also performed, wherein DICM and DICD showed a better half-life of 515, 593 h under chemical stability and 6.3, 7.5 h under enzymatic stability studies respectively. The diester hybrids IBUD, DICD, Naproxen-Kojic acid-Palmitic acid diester (NAPD) showed a better permeation and penetration profiles compared to their parent drugs. In-vitro cell line studies were conducted to assess the safety and efficacy of these hybrid esters, with promising results. The dual inhibitor demonstrated minimal cytotoxicity and remarkable anti-melanogenic and anti-inflammatory activities, showing its potential as a versatile agent in addressing both melanogenesis and inflammation. [ABSTRACT FROM AUTHOR]

NSAIDs and paracetamol are commonly used as antipyretic treatments, which may impair renal and hepatic function, respectively. Both organ systems are also negatively affected by COVID-19. In two retrospective case–control studies, we investigated whether COVID-19 is a risk factor for the development of renal or hepatic function impairment after NSAID and paracetamol use, respectively. In the NSAID study, we defined cases as patients with a decrease of ≥15% in the estimated glomerular filtration rate (eGFR). We matched them using a 1:2 ratio with controls who did not show a decrease in the eGFR. For the paracetamol study, we matched patients with ALT or ALP ≥ 3x, the upper limits of normal, using a 1:3 ratio with controls whose liver enzymes did not increase. In both studies, we selected demographic data, comorbidities, drug doses, and laboratory values as predictors in addition to SARS-CoV-2 test status. We applied different machine learning models to predict renal and hepatic function impairment. From the cohort of 12,263 unique adult inpatients, we found 288 cases of renal function impairment, which were matched with 576 controls, and 213 cases of liver function impairment, which were matched with 639 controls. In both case–control studies, testing positive for SARS-CoV-2 was not an independent risk factor for the studied adverse drug effects. [ABSTRACT FROM AUTHOR]

Chagas disease is a parasitic disease caused by the protozoan Trypanosoma cruzi with an acute, detectable blood parasites phase and a chronic phase, in which the parasitemia is not observable, but cardiac and gastrointestinal consequences are possible. Mice are the principal host used in experimental Chagas disease but reproduce the human infection depending on the animal and parasite strain, besides dose and route of administration. Lipidic mediators are tremendously involved in the pathogenesis of T. cruzi infection, meaning the prostaglandins and thromboxane, which participate in the immunosuppression characteristic of the acute phase. Thus, the eicosanoids inhibition caused by the nonsteroidal anti‐inflammatory drugs (NSAIDs) alters the dynamic of the disease in the experimental models, both in vitro and in vivo, which can explain the participation of the different mediators in infection. However, marked differences are founded in the various NSAIDs existing because of the varied routes blocked by the drugs. So, knowing the results in the experimental models of Chagas disease with or without the NSAIDs helps comprehend the pathogenesis of this infection, which still needs a better understanding. [ABSTRACT FROM AUTHOR]

Key Clinical Message: The history of any allergy to the medications should be asked by physicians before administration of the medication. The coincidence of allergic and ACS symptoms after a short time of drug administration might be an indicator of Kounis syndrome. Allergic and coronary symptoms should be considered and treated. Ischemic heart disease is still the leading cause of death worldwide. Some medications, including NSAIDS and antibiotics, can cause allergic reactions with cardiac manifestations due to spasms of the coronary arteries. In this case, we present a patient with chest pain syndrome due to a hypersensitivity reaction caused by an intramuscular (IM) diclofenac injection. The patient was a 51‐year‐old male who presented to the emergency department complaining of retrosternal chest pain, breathlessness, and pruritis that started half an hour after an IM diclofenac injection he had because of low back pain. The allergic symptoms subsided with an antihistamine injection, but chest pain and dyspnea remained stable. He was admitted due to the presence of ST‐segment depression in leads II, III, and AVF and underwent percutaneous coronary angiography, which was normal. The patient was discharged with the diagnosis of Kounis syndrome, and he had an uneventful follow‐up 1 year later. Kounis hypersensitivity‐associated acute coronary syndrome, especially type I variant coronary spasm due to endothelial dysfunction is a type of acute myocardial syndrome. The following report describes an uncommon case of anaphylaxis‐associated Kounis type I syndrome manifesting ST‐segment changes in a male patient following an intramuscular injection of diclofenac. [ABSTRACT FROM AUTHOR]

Non-steroidal anti-inflammatory drugs (NSAIDs) may cause drug-induced liver injury (DILI). However, the molecular mechanisms underlying NSAIDs hepatotoxicity remain elusive. Dysregulations of bile acids (BAs) have been implicated in various DILI. In this study, we systematically investigated the effects of ibuprofen, the most commonly used NSAID, on BA metabolism and signaling in adult male C57/BL6 mice after oral administration of ibuprofen (IBU) at clinically relevant doses (30, 100, and 200 mg/kg) for one week. Notably, IBU significantly decreased BA concentrations in the liver in a dose-dependent manner, with a concomitant increase in both mRNA and protein expression of cholesterol 7alpha-hydoxylase (CYP7A1), the rate-limiting enzyme for BA synthesis. Mechanically, IBU altered the composition of gut microbiota and increased cecal BAs, leading to reduced intestinal absorption of BAs and thus deactivated ileal farnesoid X receptor-fibroblast growth factor 15 (FXR-FGF15) signaling. Additionally, diclofenac and indomethacin also induced hepatic Cyp7a1 expression in mice via their effects on gut microbiota and intestinal BA signaling. To conclude, the current findings suggest that NSAIDs-induced liver injury could be at least partially attributable to the dysregulation of BA metabolism and signaling. • Ibuprofen decreased hepatic bile acids in mice. • Ibuprofen induced hepatic Cyp7a1 expression in mice. • Ibuprofen did not alter hepatic FXR-SHP signaling in mice. • Ibuprofen suppressed intestinal FXR-FGF15 signaling in mice. • NSAIDs altered gut microbiota in mice. [ABSTRACT FROM AUTHOR]

Introduction: Alzheimer's disease (AD), the main cause of dementia, is characterized by synaptic loss and neurodegeneration. Amyloid‐β (Aβ) accumulation, hyperphosphorylation of tau protein, and neurofibrillary tangles (NFTs) in the brain are considered to be the initiating factors of AD. However, this hypothesis falls short of explaining many aspects of AD pathogenesis. Recently, there has been mounting evidence that neuroinflammation plays a key role in the pathophysiology of AD and causes neurodegeneration by over‐activating microglia and releasing inflammatory mediators. Methods: PubMed, Web of Science, EMBASE, and MEDLINE were used for searching and summarizing all the recent publications related to inflammation and its association with Alzheimer's disease. Results: Our review shows how inflammatory dysregulation influences AD pathology as well as the roles of microglia in neuroinflammation, the possible microglia‐associated therapeutic targets, top neuroinflammatory biomarkers, and anti‐inflammatory drugs that combat inflammation. Conclusion: In conclusion, microglial inflammatory reactions are important factors in AD pathogenesis and need to be discussed in more detail for promising therapeutic strategies. [ABSTRACT FROM AUTHOR]

Mefenamic acid, renowned for its analgesic properties, stands as a reliable choice for alleviating mild to moderate pain. However, its versatility extends beyond pain relief, with ongoing research unveiling its promising therapeutic potential across diverse domains. A straightforward, environmentally friendly, and sensitive spectrofluorometric technique has been developed for the precise quantification of the analgesic medication, mefenamic acid. This method relies on the immediate reduction of fluorescence emitted by a probe upon interaction with varying concentrations of the drug. The fluorescent probe utilized, N‐phenyl‐1‐naphthylamine (NPNA), was synthesized in a single step, and the fluorescence intensities were measured at 480 nm using synchronous fluorescence spectroscopy with a wavelength difference of 200 nm. Temperature variations and lifetime studies indicated that the quenching process was static. The calibration curve exhibited linearity within the concentration range of 0.50–9.00 μg/mL, with a detection limit of 60.00 ng/mL. Various experimental parameters affecting the quenching process were meticulously examined and optimized. The proposed technique was successfully applied to determine mefenamic acid in pharmaceutical formulations, plasma, and urine, yielding excellent recoveries ranging from 98% to 100.5%. The greenness of the developed method was evaluated using three metrics: the Analytical Eco‐scale, AGREE, and the Green Analytical Procedure Index. [ABSTRACT FROM AUTHOR]

Nonsteroidal anti‐inflammatory drugs (NSAIDs) are among the most frequently used drugs that can cause liver toxicity. The aim of this study was to integrate bioanalytical and population pharmacokinetic (PopPK) assay to rapidly screen and quantify the concentrations of NSAIDs in plasma and monitor clinical safety. A liquid chromatography–tandem mass spectrometry (LC–MS/MS) method was developed for the simultaneous quantification of acetaminophen (APAP), flurbiprofen (FLB), aspirin (ASP), and ibuprofen (IBP), four commonly used NSAIDs. The PopPK model of the signature toxicant was analyzed based on the published literature. The LC–MS/MS method was successfully validated and applied to determine NSAID concentrations in patient plasma samples. APAP, ASP, and IBP data were best fitted using a one‐compartment model, and FLB data were best fitted using a two‐compartment model. Bootstrapping and visual predictive checks suggested that a robust and reliable pharmacokinetic model was developed. A fast, simple, and sensitive LC–MS/MS method was developed and validated for determining APAP, FLB, ASP, and IBP in human plasma. Combined with the PopPK model, this method was applied to rapidly analyze the concentrations of NSAIDs in clinical samples from patients presenting to the emergency department with acute liver dysfunction and monitored NSAIDs clinical safety. [ABSTRACT FROM AUTHOR]

Elayna Kirsch,1 Sadiq Rahman,2 Katrina Kerolus,2 Rabale Hasan,1 Dorota B Kowalska,1 Amruta Desai,2 Sergio D Bergese2 1Department of Obstetrics and Gynecology, Stony Brook University Hospital, Stony Brook, NY, USA; 2Department of Anesthesiology, Stony Brook University Hospital, Stony Brook, NY, USACorrespondence: Sergio D Bergese, School of Medicine, Stony Brook University, Health Science Center, Level 4, Room 060, Stony Brook, NY, 11794, USA, Tel +631444-2979, Fax +631444-2907, Email sergio.bergese@stonybrookmedicine.eduAbstract: Dysmenorrhea is the most common pathology women of childbearing age face. It is defined as painful uterine cramping associated with menstruation. Primary dysmenorrhea occurs in the absence of an organic cause, whereas secondary dysmenorrhea is pelvic pain associated with an underlying pelvic pathology. The purpose of this review is to discuss the pathophysiology of dysmenorrhea and provide a discussion of pharmacologic and non-pharmacologic treatment options. Prostaglandins play a large role in the pathophysiology of dysmenorrhea by causing myometrial contraction and vasoconstriction. The first-line treatment for dysmenorrhea is with nonsteroidal anti-inflammatory drugs due to the inhibition of cyclooxygenase enzymes, thereby blocking prostaglandin formation, as well as hormonal contraception. Other pharmacologic treatment options include Paracetamol, as well as Gonadotrophic Release Hormone Analogs, which are typically used in the treatment for endometriosis. Non-pharmacologic treatments with strong evidence include heat therapy and physical exercise. There are less evidence-based data behind other modalities for treating dysmenorrhea, such as dietary supplements, acupuncture, and transcutaneous nerve stimulation, and these methods should be used in conjunction with first-line therapy after a discussion of risks and benefits. Lastly, for women who fail medical management, surgical options include endometrial ablation, presacral neurectomy, and laparoscopic uterosacral nerve ablation. Further research is needed to measure the socioeconomic burden of dysmenorrhea on the healthcare system and to evaluate the efficacy of treatment combinations, as a multi-modal approach likely provides the most benefit for women who suffer from this condition.Keywords: dysmenorrhea, prostaglandin, NSAIDs, hormonal contraception, pelvic pain, pharmacologic management, behavioral interventions, surgical intervention

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for their analgesic, antipyretic, and anti-inflammatory properties. However, they are also associated with a broad spectrum of hypersensitivity reactions, ranging from mild cutaneous manifestations to severe systemic responses. The complex nature of these reactions and their underlying mechanisms pose challenges in diagnosis and management. We review the clinical evidence to six distinct clinical phenotypes of NSAID hypersensitivity, including: NSAID-induced urticaria/angioedema or anaphylaxis (SNIUAA), NSAID-exacerbated respiratory disease (NERD), NSAID-exacerbated cutaneous disease (NECD), NSAID-induced urticaria/angioedema (NIUA), food-dependent NSAID-induced hypersensitivity reactions (FDNIH), and selective NSAID-induced delayed reactions (SNIDR). This review aims to provide a comprehensive review of NSAID hypersensitivity reactions based on clinical phenotyping, which can aid in understanding and managing these adverse events.

Ankylosing spondylitis (AS), a common type of spondyloarthropathy, is a chronic inflammatory autoimmune disease that mainly affects spine joints, causing severe, chronic pain; additionally, in more advanced cases, it can cause spine fusion. Significant progress in its pathophysiology and treatment has been achieved in the last two decade. Management of ankylosing spondylitis (AS) is challenged by the progressive nature of the disease. Current drug treatment may perhaps induce a spurious state of “disease remission,” which is merely a low level of disease activity. Non-steroidal anti-inflammatory drugs are first line treatment, but over time, the disease often becomes refractory to these agents. For patients with AS, it is important and necessary to develop and implement in clinical practice therapeutic schemes that affect the pathogenesis of the disease, control the symptoms, reduce the progressive course of the disease, thereby increasing the quality of life of the patients. This is within the capabilities of biological therapies. [ABSTRACT FROM AUTHOR]

NSAIDs and paracetamol are commonly used as antipyretic treatments, which may impair renal and hepatic function, respectively. Both organ systems are also negatively affected by COVID-19. In two retrospective case–control studies, we investigated whether COVID-19 is a risk factor for the development of renal or hepatic function impairment after NSAID and paracetamol use, respectively. In the NSAID study, we defined cases as patients with a decrease of ≥15% in the estimated glomerular filtration rate (eGFR). We matched them using a 1:2 ratio with controls who did not show a decrease in the eGFR. For the paracetamol study, we matched patients with ALT or ALP ≥ 3x, the upper limits of normal, using a 1:3 ratio with controls whose liver enzymes did not increase. In both studies, we selected demographic data, comorbidities, drug doses, and laboratory values as predictors in addition to SARS-CoV-2 test status. We applied different machine learning models to predict renal and hepatic function impairment. From the cohort of 12,263 unique adult inpatients, we found 288 cases of renal function impairment, which were matched with 576 controls, and 213 cases of liver function impairment, which were matched with 639 controls. In both case–control studies, testing positive for SARS-CoV-2 was not an independent risk factor for the studied adverse drug effects.

Abstract Background There have been reports on the impact of concurrent drugs on the outcome of immunotherapy for non‐small cell lung carcinoma (NSCLC). However, the effect of some drugs, such as antibiotics and nonsteroidal anti‐inflammatory drugs (NSAIDs), has not been clarified in patients with NSCLC. In the present study, we aimed to assess the association between concurrent drugs and the outcomes of immune checkpoint inhibitors (ICIs) alone or in combination with chemotherapy for patients with advanced NSCLC. Methods We retrospectively assessed patients with advanced NSCLC who underwent ICI treatment between September 2017 and December 2021 at Kobe University Hospital. We evaluated the data regarding the use of antibiotics within 30 days before ICI initiation, as well as the use of proton pump inhibitors (PPIs) and NSAIDs during ICI initiation. Results A total of 127 patients were assessed, among whom 28 (22.0%) patients received antibiotics, 39 (30.7%) PPIs, and 36 (28.3%) NSAIDs. No significant differences were observed between the patients with and without antibiotic use. However, patients using NSAIDs had significantly worse objective response rates (ORR) and progression‐free survival (PFS) with ICI alone or in combination with chemotherapy compared to those who did not (ORR, 47.2% vs. 67.0%; p = 0.045. PFS, 6.3 months vs. 10.8 months; p = 0.02). Patients using PPIs demonstrated a worse ORR of ICI in combination with chemotherapy compared to those who did not (ORR, 45.2% vs. 72.6%; p = 0.013). Conclusions The unnecessary use of NSAIDs along with immunotherapy should be discouraged.

Chronic inflammation plays a crucial role in carcinogenesis. High levels of serum prostaglandin E2 and tissue overexpression of cyclooxygenase-2 (COX-2) have been described in breast, urinary, colorectal, prostate, and lung cancers as being involved in tumor initiation, promotion, progression, angiogenesis, and immunosuppression. Non-steroidal anti-inflammatory drugs (NSAIDs) are prescribed for several medical conditions to not only decrease pain and fever but also reduce inflammation by inhibiting COX and its product synthesis. To date, significant efforts have been made to better understand and clarify the interplay between cancer development, inflammation, and NSAIDs with a view toward addressing their potential for cancer management. This review provides readers with an overview of the potential use of NSAIDs and selective COX-2 inhibitors for breast cancer treatment, highlighting pre-clinical in vitro and in vivo studies employed to evaluate the efficacy of NSAIDs and their use in combination with other antineoplastic drugs.

Abstract Background We investigated in older adult non-cardiac surgical patients whether receipt of perioperative non-steroidal anti-inflammatory drugs (NSAIDs) is associated with increased incidence of postoperative cardiovascular complications. Methods We retrospectively extracted the information for patients with age ≥ 65 years who had inpatient non-cardiac surgery with a duration of ≥ 1 h from the American College of Surgeons-National Surgical Quality Improvement Program registry data acquired at the University of Washington Medical Center. We compared patients who received NSAIDs perioperatively to those who did not receive NSAIDs, on the two composite outcomes: (1) the incidence of postoperative cardiovascular complications within 30 days of the surgery, and (2) the incidence of combined postoperative gastrointestinal and renal complications, and length of postoperative hospital stay. We used separate multivariable logistic regression models to analyze the two composite outcomes and a Poisson regression model for the length of hospital stay. Results The receipt of perioperative NSAIDs was not associated with postoperative cardiovascular complications (estimated odds ratio (OR), 1.78; 95% confidence interval (CI), 0.97 to 3.25; P = 0.06), combined renal and gastrointestinal complications (estimated OR, 1.30; 95% CI, 0.53 to 3.20; P = 0.57), and length of postoperative hospital stay in days (incidence rate ratio, 1.06; 95% CI, 0.93 to 1.21; P = 0.39). Conclusions In older adult non-cardiac surgical patients, receipt of perioperative NSAIDs was not associated with increased incidences of postoperative cardiovascular complications, and renal and gastrointestinal complications within 30 days after surgery, or length of postoperative hospital stay.

Background: Osteoarthritis (OA), is a leading causes of disability. Herbal medications are often used as an alternative to allopathic drugs to manage symptoms of osteoarthritis. Objectives: This study was conducted to evaluate the efficacy of curcumin longa & fenugreek extracts in patients of KOA (knee osteoarthritis). Methods: Patients were randomized into four groups. Group 1 received placebo (glucose 500mg), Group 2 curcumin longa (CL 500mg), Group 3 Fenugreek (FE 500mg) and Group 4 combination (CL 500 mg + FE 500 mg). Also, aceclofenac 100 mg twice daily was given to all patients. Groups were compared using VAS & WOMAC scores, as well as, by changes seen in serum level of IL-1β and SOD at 0, 60 and 120 days. Results: VAS and WOMAC scores, IL - 1 β level significantly reduced, while SOD level significantly increased in CL, FE, and (CL+FE) groups as compared to placebo at 60 and 120 days. Though the effect in FE group is not significant in 60 days, significant improvement was seen at 120 days. Conclusion: Curcumin longa and Fenugreek may be effective in reducing progression and pain of OA, and can be combined with NSAIDs. They are not known to produce any side effects and have better tolerability.

Background In acute settings around the globe, renal/ureteric colic remains one of the most common diagnoses for patients presenting with loin-to-groin pain. Even though management spans from medical expulsive therapies to surgical options, pain as a significant component of a patient’s presentation must be dealt with quickly, decisively, and safely, as it can be excruciating and its effects on overall health are dire. This study aimed to explore compliance with the National Institute for Health and Care Excellence (NICE) guidelines for pain management in patients with suspected renal/ureteric colic. It includes the use of nonsteroidal anti-inflammatory drugs (NSAIDs), intravenous paracetamol, and opioids as first-, second-, and third-line analgesics, respectively, and does not offer antispasmodics. In the event of deviations from the standard, the aim was to put in corrective measures, followed by re-exploration of compliance with patient care. Methods This study involved a single healthcare facility with the study type being retrospective before interventions and prospective after interventions. In the first cycle, we retrieved and analysed 78 patients records whom had been suspected to have renal/ureteric colic between July and September 2022. The inclusion criteria were documented complaints of “flank/loin-to-groin pain” and diagnosis prior to performing diagnostic tests. We surveyed the first-, second-, and third-line painkillers issued, and whether an antispasmodic was given. We collected and entered data into a Microsoft Excel file and correlated it with NICE standards. Having found deviations from the standard, we conducted interventions, allowed time for clinicians to adapt, and re-explored compliance using patient case records [n=58] between February and May 2023. Results In the 1 st cycle, 78 patients were suspected of having renal/ureteric colic. M: F = 1.2:1. Non-contrast computerized tomography of the kidney ureters and bladder (NC-CTKUB) confirmed 87% of patients with stones and 3% had no stones. NC-CTKUB was not performed in 9% of patients because they were young, and urinalysis showed no microscopic hematuria. One patient had discharged against medical advise before the NC-CTKUB was performed. Compliance with the NICE pain management guidelines for suspected renal/ureteric colic was full in 23% of cases but unsatisfactory in 78% of cases. In the 2 nd cycle, M: F = 1.5:1, NC-CTKUB was not re-audited, as the first cycle study yielded excellent results, and our action plan resulted in an NICE pain management compliance rate of 56%. Although our interventions resulted in improvements of more than twice the initial results, work still needs to be performed. Conclusion Clinicians’ ability to correctly diagnose renal/ureteric colic is remarkable. However, the pain management compliance rate indicates room for improvement. This may be due to the limited awareness of the NICE guideline or the fact that the clinical team has an affinity for certain analgesics compared to others. We propose the need to consider select variables to existing standard guidelines to enhance compliance for improved patient care.

Background: Radiographic axial spondyloarthritis (r-axSpA), formerly known as ankylosing spondylitis (AS), is a chronic, inflammatory rheumatic disease associated with symptoms such as inflammatory back pain, morning stiffness, and arthritis. First-line recommendations for patients with AS include treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) for reducing pain and stiffness. Objectives: The objective of our study is to evaluate the efficacy and short-term NSAID-sparing effect of secukinumab in patients with AS currently treated with NSAIDs. Design: We assessed the clinical Assessment of SpondyloArthritis International Society (ASAS20) response to secukinumab and evaluated the extent to which the use of concomitant NSAID can be reduced between weeks 4 and 12 in r-axSpA patients treated with secukinumab 150 mg compared with placebo. Methods: ASTRUM was a prospective 24-week randomized controlled trial of adult patients with active r-axSpA [Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ⩾4] who had a documented inadequate response to ⩾2 NSAIDs. Patients were randomized (1:1:1) to initiate treatment with subcutaneous secukinumab 150 mg from either week 0 (group 1), week 4 (group 2), or week 16 (group 3). From week 4 onward, tapering of NSAIDs was allowed in all groups. Results: This study included 211 patients (n = 71, 70, and 70 in groups 1, 2, and 3, respectively). ASAS20 response at week 12 for pooled groups 1 and 2 versus group 3 was 51.1% versus 44.3% (p = 0.35). A higher proportion of patients in groups 1 and 2 achieved ASAS40 and BASDAI50 and showed improvements in other secondary clinical outcomes as compared to group 3 at week 16. More patients in groups 1 and 2 versus group 3 stopped their NSAID intake from baseline through week 16. Conclusion: Treatment with secukinumab improved clinical outcomes and showed a short-term NSAID-sparing effect in patients with r-axSpA, even though the primary endpoint was not met. Trial registration: ClinicalTrials.gov; NCT02763046, EudraCT 2015-004575-74. [ABSTRACT FROM AUTHOR]

Background: Numerous epidemiological studies have elucidated the intricate connection between inflammation and cancer, highlighting how sustained inflammatory responses can fuel carcinogenesis by fostering proliferation, angiogenesis, and metastasis, while dampening immune responses and sensitivity to chemotherapy. Previous clinical investigations have underscored the potential of anti-inflammatory medications in either preventing or mitigating tumor formation. Here, the causal relationship between anti-inflammatory drugs and cancer was further explored through Mendelian randomization studies. Methods: Employing Mendelian randomization, we scrutinized the causal links between three anti-inflammatory drugs--NSAIDs, Aspirin, and Anilide--and 37 types of cancer. We primarily utilized inverse variance weighting (IVW) as the primary analytical approach to delineate the causal association between these drugs and cancer types. Concurrently, sensitivity analyses were conducted to ascertain the absence of horizontal pleiotropy and heterogeneity. Results: Our investigation revealed a discernible causal relationship between certain anti-inflammatory drugs and a subset of cancers, albeit without a pervasive impact across all cancer types. Specifically, NSAIDs exhibited a riskreducing effect on non-small cell lung cancer (OR: 0.76, 95% CI: 0.59-0.97, p-value: 0.03) and gastric cancer (OR: 0.57, 95% CI: 0.34-0.98, p-value: 0.04). Conversely, aspirin was associated with an increased risk of oral malignant tumors (OR: 2.18, 95% CI: 1.13-4.21, p-value: 0.02). Notably, no statistically significant findings were observed for anilide drugs (p < 0.05). Conclusion: We identified several cancers with potential causal links to NSAIDs, including non-small cell lung cancer and gastric cancer. Despite our extensive analysis, we did not identify a substantial causal relationship between the use of anti-inflammatory drugs and the development of various cancers. [ABSTRACT FROM AUTHOR]

Multidrug-resistant bacteria have become the predominant etiology in bovine female reproductive tract infections and thus require effective treatment approaches. The main goal of this study was the molecular detection of mecA, blaZ, tetK, and aacA-aphD genes in Staphylococcus aureus (S. aureus) responsible for methicillin, beta-lactam, tetracycline, and aminoglycoside resistance respectively. Phylogenetic analysis was conducted to check the homology of staphylococcal genes with NCBI sequences. The in-vitro efficacy of non-steroidal anti-inflammatory drugs (NSAIDs) in combination therapies against MDR S. aureus was evaluated using well diffusion assay and checkerboard method. Vaginal swab samples (n = 384) collected from bovines suffering from endometritis, pyometra, and retained placenta were tested for S. aureus. Results showed a 17.96% overall prevalence. Both phenotypic and genotypic resistance was observed among S. aureus isolates with 50.72% and 37.68% isolates being confirmed as methicillin-resistant (MRSA), 36.23% and 18.84% isolates exhibiting beta-lactam, 40.58%, and 27.54% isolates showing tetracycline, and 33.33% and 36.23% isolates showing aminoglycosides resistance based on disc diffusion and gene confirmation, respectively. Phylogenetic analysis indicated homology with previously reported Pakistani isolates suggesting the possibility of MDR S. aureus transmission within and between animals. Synergy testing indicated that combinations of ceftriaxone-ketoprofen (153.77%), ceftriaxone-meloxicam (149.55%), amoxiclav-flunixin meglumine (106.06%), and oxytetracycline-flunixin meglumine (104.47%) showed synergy on well diffusion assay. Based on the fractional inhibitory concentration index by checkerboard method, oxytetracycline-meloxicam and gentamicin-ketoprofen combinations exhibited synergistic interaction. In conclusion, MDR S. aureus resistance was mitigated in-vitro through the combination of antibiotics (oxytetracycline, gentamicin) with NSAIDs (meloxicam, ketoprofen) that could be used to create therapeutic strategies for bovine reproductive issues. [ABSTRACT FROM AUTHOR]

Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the most widely consumed drugs. These drugs often end up in our water systems because human bodies cannot fully metabolize them, and the residual amounts are excreted through urine or feces. Their ubiquitous presence in wastewater poses various degrees of risk to non-targeted species. Cognizant of the situation, this review encompasses and probes into the occurrence, sources, removal strategies, and legislations pertaining to NSAIDs in aqueous environments. A comprehensive and state-of-the-art overview of the utilization of multifunctional nanomaterials such as nanoadsorbent, metal–organic frameworks, semiconductor-based nanocatalysts, and biologically modified nanoparticles for the efficient removal of NSAIDs in water has been discussed. Furthermore, the review is an output of a conscientious effort to bring attention to the current global guidelines, policies, and directives. The review also entails recommendations for future studies toward managing pharmaceutical contaminants in the environment. We believe that the present study is useful for environmentalists, legislators and policymakers, scientists, industrialists, and organizations working toward sustainable development goals. [ABSTRACT FROM AUTHOR]

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Fast and straightforward incorporation of radionuclides into pharmaceutically relevant molecules is one of the main barriers to preclinical and clinical tracer research. Late‐stage direct incorporation of cyclotron‐produced [11C]CO2 to afford carbon‐11‐labeled radiopharmaceuticals has the potential to provide ready‐to‐inject positron emission tomography agents in less than an hour. The present work describes photocatalyzed carboxylation of alkylbenzene derivatives to afford 11C‐phenylacetic acids. Reaction conditions and scope are investigated followed by application of this methodology to the preparative radiosynthesis of [11C]fenoprofen, a nonsteroidal anti‐inflammatory drug. [ABSTRACT FROM AUTHOR]

Background: There have been reports on the impact of concurrent drugs on the outcome of immunotherapy for non‐small cell lung carcinoma (NSCLC). However, the effect of some drugs, such as antibiotics and nonsteroidal anti‐inflammatory drugs (NSAIDs), has not been clarified in patients with NSCLC. In the present study, we aimed to assess the association between concurrent drugs and the outcomes of immune checkpoint inhibitors (ICIs) alone or in combination with chemotherapy for patients with advanced NSCLC. Methods: We retrospectively assessed patients with advanced NSCLC who underwent ICI treatment between September 2017 and December 2021 at Kobe University Hospital. We evaluated the data regarding the use of antibiotics within 30 days before ICI initiation, as well as the use of proton pump inhibitors (PPIs) and NSAIDs during ICI initiation. Results: A total of 127 patients were assessed, among whom 28 (22.0%) patients received antibiotics, 39 (30.7%) PPIs, and 36 (28.3%) NSAIDs. No significant differences were observed between the patients with and without antibiotic use. However, patients using NSAIDs had significantly worse objective response rates (ORR) and progression‐free survival (PFS) with ICI alone or in combination with chemotherapy compared to those who did not (ORR, 47.2% vs. 67.0%; p = 0.045. PFS, 6.3 months vs. 10.8 months; p = 0.02). Patients using PPIs demonstrated a worse ORR of ICI in combination with chemotherapy compared to those who did not (ORR, 45.2% vs. 72.6%; p = 0.013). Conclusions: The unnecessary use of NSAIDs along with immunotherapy should be discouraged. [ABSTRACT FROM AUTHOR]

Background: Acetaminophen and ibuprofen are widely administered to babies due to their presumed safety as over‐the‐counter drugs. However, no reports exist on the effects of cyclooxygenase inhibitors on undifferentiated spermatogonia and spermatogonial stem cells. Infancy represents a critical period for spermatogonial stem cell formation and disrupting spermatogonial stem cells or their precursors may be associated with infertility and testicular cancer formation. Objectives: The goal of this study was to examine the molecular and functional impact of cyclooxygenase inhibition and silencing on early steps of undifferentiated spermatogonia (u spg) and spermatogonial stem cell development, to assess the potential reproductive risk of pharmaceutical cyclooxygenase inhibitors. Methods: The effects of cyclooxygenase inhibition were assessed using the mouse C18‐4 undifferentiated juvenile spermatogonial cell line model, previously shown to include cells with spermatogonial stem cell features, by measuring prostaglandins, cell proliferation, and differentiation, using cyclooxygenase 1‐ and cyclooxygenase 2‐selective inhibitors NS398, celecoxib, and FR122047, acetaminophen, and ibuprofen. Cyclooxygenase 1 gene silencing was achieved using a stable short‐hairpin RNA approach and clone selection, then assessing gene and protein expression in RNA sequencing, quantitative real‐time polymerase chain reaction, and immunofluorescence studies. Results: Cyclooxygenase 2 inhibitors NS398 and celecoxib, as well as acetaminophen, but not ibuprofen, dose‐dependently decreased retinoic acid‐induced expression of the spg differentiation gene Stra8, while NS398 decreased the spg differentiation marker Kit, suggesting that cyclooxygenase 2 is positively associated with spg differentiation. In contrast, short‐hairpin RNA‐based cyclooxygenase 1 silencing in C18‐4 cells altered cellular morphology and upregulated Stra8 and Kit, implying that cyclooxygenase 1 prevented spg differentiation. Furthermore, RNA sequencing analysis of cyclooxygenase 1 knockdown cells indicated the activation of several signaling pathways including the TGFb, Wnt, and Notch pathways, compared to control C18‐4 cells. Notch pathway genes were upregulated by selective cyclooxygenase inhibitors, acetaminophen and ibuprofen. Conclusion: We report that cyclooxygenase 1 and 2 differentially regulate undifferentiated spermatogonia/spermatogonial stem cell differentiation. Cyclooxygenases regulate Notch3 expression, with the Notch pathway targeted by PGD2. These data suggest an interaction between the eicosanoid and Notch signaling pathways that may be critical for the development of spermatogonial stem cells and subsequent spermatogenesis, cautioning about using cyclooxygenase inhibitors in infants. [ABSTRACT FROM AUTHOR]

Chronic inflammation plays a crucial role in carcinogenesis. High levels of serum prostaglandin E2 and tissue overexpression of cyclooxygenase-2 (COX-2) have been described in breast, urinary, colorectal, prostate, and lung cancers as being involved in tumor initiation, promotion, progression, angiogenesis, and immunosuppression. Nonsteroidal anti-inflammatory drugs (NSAIDs) are prescribed for several medical conditions to not only decrease pain and fever but also reduce inflammation by inhibiting COX and its product synthesis. To date, significant efforts have been made to better understand and clarify the interplay between cancer development, inflammation, and NSAIDs with a view toward addressing their potential for cancer management. This review provides readers with an overview of the potential use of NSAIDs and selective COX-2 inhibitors for breast cancer treatment, highlighting pre-clinical in vitro and in vivo studies employed to evaluate the efficacy of NSAIDs and their use in combination with other antineoplastic drugs. [ABSTRACT FROM AUTHOR]

Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely utilized pharmaceuticals worldwide. Besides their recognized anti-inflammatory effects, these drugs exhibit various other pleiotropic effects in several cells, including platelets. Within this article, the multifaceted properties of NSAIDs on platelet functions, activation and viability, as well as their interaction(s) with established antiplatelet medications, by hindering several platelet agonists' pathways and receptors, are thoroughly reviewed. The efficacy and safety of NSAIDs as adjunctive therapies for conditions involving inflammation and platelet activation are also discussed. Emphasis is given to the antiplatelet potential of commonly administered NSAIDs medications, such as ibuprofen, diclofenac, naproxen and ketoprofen, alongside non-opioid analgesic and antipyretic medications like paracetamol. This article delves into their mechanisms of action against different pathways of platelet activation, aggregation and overall platelet functions, highlighting additional health-promoting properties of these anti-inflammatory and analgesic agents, without neglecting the induced by these drugs' side-effects on platelets' functionality and thrombocytopenia. Environmental issues emerging from the ever-increased subscription of these drugs are also discussed, along with the need for novel water treatment methodologies for their appropriate elimination from water and wastewater samples. Despite being efficiently eliminated during wastewater treatment processes on occasion, NSAIDs remain prevalent and are found at significant concentrations in water bodies that receive effluents from wastewater treatment plants (WWTPs), since there is no one-size-fits-all solution for removing all contaminants from wastewater, depending on the specific characteristics of the wastewater. Several novel methods have been studied, with adsorption being proposed as a cost-effective and environmentally friendly method for wastewater purification from such drugs. This article also presents limitations and future prospects regarding the observed antiplatelet effects of NSAIDs, as well as the potential of novel derivatives of these compounds, with benefits in other important platelet functions. [ABSTRACT FROM AUTHOR]

Background: Knee osteoarthritis (OA) is a significant contributor to pain and disability globally, with the efficacy and safety of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) and opioids in managing this condition are still being debated. Objective: This study aimed to evaluate and compare the effects of NSAIDs and opioids on knee pain reduction and functional improvement in knee OA patients. Methods: A randomised controlled trial was conducted at the Orthopedics Department of Varun Arjun Medical College & Rohilkhand Hospital, involving 80 knee OA patients aged 40-60 years. Participants were randomly assigned to two groups: Group I (n=40) receiving NSAIDs and Group II (n=40) subjects receiving opioids Pain intensity was assessed using the Visual Analog Scale (VAS), and functional status was evaluated through the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at baseline and bi-weekly intervals over three months. Adverse events were also monitored. Results: Both NSAIDs and opioids significantly alleviated pain and enhanced functional status over a 3-month period, evidenced by reductions in mean VAS scores by -2.2 for Group-I and -1.7 for Group-II; (P=0.001) and mean WOMAC scores -16.2 for NSAIDs and -12.2 for opioids; (P=0.001). NSAIDs exhibited marginally better efficacy and a more favourable side effect profile, although opioids were linked to a significantly higher incidence of constipation (P=0.02). Conclusion: NSAIDs and opioids effectively manage knee OA pain, with NSAIDs slightly outperforming opioids in effectiveness and safety. These results underscore the necessity of tailored pain management strategies for knee OA patients. Further studies must validate these findings over larger populations and extended periods. [ABSTRACT FROM AUTHOR]

Background: Peritonitis caused by gastrointestinal tract perforations, a common occurrence in this country, requires rapid surgical intervention and is associated with high rates of morbidity and mortality. The most catastrophic outcome, a perforated duodenal ulcer, is estimated to have a high mortality rate. Previously, increased risk was linked to variables such as delayed patient presentation, surgical postponement, and poor antibiotic usage. Methods: All patients with duodenal ulcer perforation who were hospitalised and treated at DD MCH, Keonjhar between August 2021 and November 2022 were studied after providing written informed permission. The research was approved by the institutional ethics council prior to its initiation. Results: 110 individuals with duodenal ulcer perforation who had surgery were evaluated. 32 patients (29.09%) were older than 60 years. The male:female ratio was 6.85 to 1. Among the sociodemographic characteristics, older age (>60 years) was shown to have a significant connection with mortality after surgery. 37.27% of the study population had IHD, 40.90% utilised NSAIDs, 10.90% presented with shock, and 50% arrived at the health institution after 24 hours. Ischaemic heart disease, NSAID usage, the occurrence of shock upon admission, and late presentation were all linked with death. Conclusions: Increasing age, the presence of IHD, the use of NSAIDs, patients presenting in shock, and those arriving late to the health institution all predicted a bad outcome. [ABSTRACT FROM AUTHOR]

One of the most frequent problems that patients bring to a dental clinic is pain in the orofacial region or within the tooth. To identify and solve the issue, a proficient practitioner needs to be equipped with the necessary information and resources. Comprehending the history of pain control in dentistry can provide valuable understanding into the development of the present techniques. Newer and more effective pain management treatments have been created as dentistry continues to advance. Several modalities have been developed to reduce and eliminate this, including pharmacological and nonpharmacological treatment modalities. The goal of the present review of the literature's findings is to provide dentists with reliable information regarding the application of contemporary local anesthetics, alternative methods, and strategies to reduce pain during anesthesia administration, thereby improving patient comfort. [ABSTRACT FROM AUTHOR]

Aim and objectives: A prospective split mouth study was done to compare the efficacy of transdermal ketoprofen versus diclofenac patch after therapeutic orthodontic tooth extraction based on four parameters – pain intensity (VAS), number of rescue analgesia intakes, local allergic reactions and patient tolerability for immediate and 3 consecutive postoperative days. Materials and methods: In total, 33 (66 extraction sites) patients were divided into the ketoprofen patch group and the diclofenac patch group. A single ketoprofen patch (70 cm2 30 mg) was applied following extraction of premolars of the 1st and 4th quadrants and patients were recalled after 1 week for extractions of premolars of the 2nd and 3rd quadrants and diclofenac patch (50 cm2 100 mg) was applied on the deltoid region of the right arm, respectively. Patients were then evaluated under the above‐mentioned parameters. Results: Ketoprofen transdermal patch was found to be more effective in terms of controlling postoperative pain and the minimum number of rescue analgesia tablets taken as compared to diclofenac (statistically significant on 1st and 2nd day) though the former showed the incidence of a local allergic reaction (p‐value 0.002, 0.002 and 0.012), respectively, in few cases which were not seen in case of diclofenac. Conclusion: Overall, both the transdermal patches are effective in terms of safety and providing analgesia, though more research are needed in proving the safeness and efficiency of these transdermal patches with large sample size. [ABSTRACT FROM AUTHOR]

Background: We investigated in older adult non-cardiac surgical patients whether receipt of perioperative non-steroidal anti-inflammatory drugs (NSAIDs) is associated with increased incidence of postoperative cardiovascular complications. Methods: We retrospectively extracted the information for patients with age ≥ 65 years who had inpatient non-cardiac surgery with a duration of ≥ 1 h from the American College of Surgeons-National Surgical Quality Improvement Program registry data acquired at the University of Washington Medical Center. We compared patients who received NSAIDs perioperatively to those who did not receive NSAIDs, on the two composite outcomes: (1) the incidence of postoperative cardiovascular complications within 30 days of the surgery, and (2) the incidence of combined postoperative gastrointestinal and renal complications, and length of postoperative hospital stay. We used separate multivariable logistic regression models to analyze the two composite outcomes and a Poisson regression model for the length of hospital stay. Results: The receipt of perioperative NSAIDs was not associated with postoperative cardiovascular complications (estimated odds ratio (OR), 1.78; 95% confidence interval (CI), 0.97 to 3.25; P = 0.06), combined renal and gastrointestinal complications (estimated OR, 1.30; 95% CI, 0.53 to 3.20; P = 0.57), and length of postoperative hospital stay in days (incidence rate ratio, 1.06; 95% CI, 0.93 to 1.21; P = 0.39). Conclusions: In older adult non-cardiac surgical patients, receipt of perioperative NSAIDs was not associated with increased incidences of postoperative cardiovascular complications, and renal and gastrointestinal complications within 30 days after surgery, or length of postoperative hospital stay. [ABSTRACT FROM AUTHOR]

Acetaminophen (ACE) is a widely used analgesic and antipyretic drug with various applications, from pain relief to fever reduction. Recent studies have reported equivocal effects of habitual ACE intake on exercise performance, muscle growth, and risks to bone health. Thus, this study aimed to assess the impact of a 6‐week, low‐dose ACE regimen on muscle and bone adaptations in exercising and non‐exercising rats. Nine‐week‐old Wistar rats (n = 40) were randomized to an exercise or control (no exercise) condition with ACE or without (placebo). For the exercise condition, rats ran 5 days per week for 6 weeks at a 5% incline for 2 min at 15 cm/s, 2 min at 20 cm/s, and 26 min at 25 cm/s. A human equivalent dose of ACE was administered (379 mg/kg body weight) in drinking water and adjusted each week based on body weight. Food, water intake, and body weight were measured daily. At the beginning of week 6, animals in the exercise group completed a maximal treadmill test. At the end of week 6, rats were euthanized, and muscle cross‐sectional area (CSA), fiber type, and signaling pathways were measured. Additionally, three‐point bending and microcomputer tomography were measured in the femur. Follow‐up experiments in human primary muscle cells were used to explore supra‐physiological effects of ACE. Data were analyzed using a two‐way ANOVA for treatment (ACE or placebo) and condition (exercise or non‐exercise) for all animal outcomes. Data for cell culture experiments were analyzed via ANOVA. If omnibus significance was found in either ANOVA, a post hoc analysis was completed, and a Tukey's adjustment was used. ACE did not alter body weight, water intake, food intake, or treadmill performance (p >.05). There was a treatment‐by‐condition effect for Young's Modulus where placebo exercise was significantly lower than placebo control (p <.05). There was no treatment by condition effects for microCT measures, muscle CSA, fiber type, or mRNA expression. Phosphorylated‐AMPK was significantly increased with exercise (p <.05) and this was attenuated with ACE treatment. Furthermore, phospho‐4EBP1 was depressed in the exercise group compared to the control (p <.05) and increased in the ACE control and ACE exercise group compared to placebo exercise (p <.05). A low dose of ACE did not influence chronic musculoskeletal adaptations in exercising rodents but acutely attenuated AMPK phosphorylation and 4EBP1 dephosphorylation post‐exercise. [ABSTRACT FROM AUTHOR]

In this paper, we report the synthesis of a multi-template molecularly imprinted polymer (MIP) to target and extract naproxen, ibuprofen, diclofenac, emtricitabine, tenofovir disoproxil, and efavirenz from wastewater bodies. A bulk polymerization procedure was used to synthesize the MIP and non-imprinted polymer (NIP). The specific recognition sites for each target were obtained through the removal of the imprinted targeted compounds. The interaction of antiretroviral drugs (ARVs) and non-steroidal anti-inflammatory drugs (NSAIDs) compounds with the MIP was studied under various conditions such as pH, mass, concentration, and time factors. The results demonstrated the optimum conditions were 55 mg of MIP, pH 7.0, a concentration of 5 mg L−1, and a contact time of 10 min. For every compound studied, the extraction efficiencies for ARVs and NSAIDs in aqueous solutions was >96%. The adsorption capacity for the MIP was >0.91 mg·g−1. Adsorption obeys a second-order rate, and the Freundlich model explains the adsorption isotherm data. This study demonstrated that the synthesized multi-template MIP has huge potential to be employed for the removal of ARVs and NSAIDs from the environment as well as in drug purification or recovery processes. [ABSTRACT FROM AUTHOR]

Nonsteroidal anti-inflammatory drugs, which are used to treat numerous diseases, can cause a number of side effects. Therefore, the development of new molecules with anti-inflammatory and antimicrobial properties is an important task of modern medicine and veterinary medicine. A promising group of drugs with the above-described action are derivatives of 4-thiazolidinones. The thiazolidinone ring is a part of many existing potential antimicrobial and anti-inflammatory agents. The combination with a pharmacophore pyrazole moiety in the same structure, may result in enhanced therapeutic benefit. Aim. To assess the effects of the 4-thiazolidinone derivative Les-6490 and the conventional anti-inflammator y agent Nimesulide on hematological and biochemical parameters in rats within the context of an induced inflammatory process. Methods. The inflammatory process in animals was modeled with complete Freund's adjuvant. (CFA). The assessment of changes in the animal body was carried out by the biochemical indicators of blood serum: activity of transaminases and alkaline phosphatase, indicators of total protein and albumin content, creatinine and urea levels, indicators of lipid metabolism (total cholesterol and triglycerides), quantitative levels of phosphorus and calcium as markers of mineral exchange. The results. The compound Les-6490 slows down the development of the inflammatory process in the AF inflammation model. It was determined that the development of the СFA-induced inflammatory process was not accompanied by significant changes in the concentration of total protein and albumin. Nimesulide caused a significant 22.7 % (p < 0.001) decrease in the albumin concentration, whereas no changes were observed with the compound Les-6490 against the background of FA. The self action of Les-6490 was accompanied by a significant decrease of urea compared to the control. The introduction of Les-6490 against the background of the inflammatory process led to a 9.9 % (P < 0.001) increase in the level of creatinine in the blood and a decrease in the activity of transaminases. It was confirmed that the action of Nimesulide is accompanied by a decrease in the amount of phosphorus and calcium in the serum, whereas Les-6490 does not show such effect. Conclusions. The studied compound Les-6490 is not inferior to the level of anti-inflammatory activity of Nimesulide in markers of the inflammatory process; the research of influence of the compound Les-6490 on the markers of liver diseases in comparison with the action of Nimesulide did not reveal a significant hepatotoxic effect of the substance; the compound Les-6490 showed a hypolipidemic effect that was similar to the effects of Nimesulide, both under the conditions of self-administration and when modeling the inflammatory process; the investigated compound can be considered promising for further research as a substance with an anti-inflammatory effect. The compound Les-6490 slows down the development of the inflammatory process in the AF inflammation model. [ABSTRACT FROM AUTHOR]

Nonsteroidal anti-inflammatory drugs (NSAIDs) are well known to cause ulcers and bleeding in the upper gastrointestinal tract. Furthermore, several studies to date have demonstrated that NSAIDs may also cause ulcers in the lower gastrointestinal tract, or the bowel, resulting in small bowel bleeding. The diagnosis and management of bleeding in the small bowel region pose a significant challenge. Here, we present the case of a 30-year-old female who presented to the hospital with lower gastrointestinal bleeding after taking an NSAID for a prolonged period. The results of all investigations, including computed tomography angiography, esophagogastroduodenoscopy, colonoscopy, and digital subtraction angiography, were negative. The patient was transferred to the operating room for an on-table colonoscopy and surgical intervention because of continuous bleeding and hemodynamic instability. During the operation, a suspected bleeding site was located in the terminal ileum, leading to the resection of the small bowel, which revealed ulcerative lesions. NSAIDs are believed to have caused the ulcer in this patient, as evidenced by all the available information, including the pathological results. [ABSTRACT FROM AUTHOR]

Cadmium sulfide and zinc oxide nanoparticles were prepared, characterized and used as electrode modifiers for the sensing of two non-steroidal anti-inflammatory drugs (NSAIDs): naproxen and mobic. The structural and morphological characterization of the synthesized nanoparticles was carried out by XRD, UV-Vis spectroscopy, FTIR and scanning electron microscopy. The electrode's enhanced surface area facilitated the signal amplification of the selected NSAIDs. The CdS-modified glassy carbon electrode (GCE) enhanced the electro-oxidation signals of naproxen to four times that of the bare GCE, while the ZnO-modified GCE led to a two-fold enhancement in the electro-oxidation signals of mobic. The oxidation of both NSAIDs occurred in a pH-dependent manner, suggesting the involvement of protons in their electron transfer reactions. The experimental conditions for the sensing of naproxen and mobic were optimized and, under optimized conditions, the modified electrode surface demonstrated the qualities of sensitivity and selectivity, and a fast responsiveness to the target NSAIDs. [ABSTRACT FROM AUTHOR]