Use Of Nonsteroidal Anti-inflammatory Drugs Research Articles

Investigation of risk factors in the development of recurrent urethral stricture after internal urethrotomy

BACKGROUND Urethral stricture is a condition that often develops with trauma and results in narrowing of the urethral lumen. Although endoscopic methods are mostly used in its treatment, it has high recurrence rates. Therefore, open urethroplasty is recommended after unsuccessful endoscopic treatments. AIM To investigate the risk factors associated with urethral stricture recurrence. METHODS The data of male patients who underwent internal urethrotomy for urethral stricture between January 2017 and January 2023 were retrospectively analyzed. Demographic data, comorbidities, preoperative haemogram, and biochemical values obtained from peripheral blood and operative data were recorded. Patients were divided into two groups in terms of recurrence development; recurrence and non-recurrence. Initially recorded data were compared between the two groups. RESULTS A total of 303 patients were included in the study. The mean age of the patients was 66.6 ± 13.6 years. The mean duration of recurrence development was 9.63 ± 9.84 (min-max: 1-39) months in the recurrence group. Recurrence did not occur in non-recurrence group throughout the follow-up period with an average time of 44.15 ± 24.07 (min-max: 12-84) months. In the comparison of both groups, the presence of diabetes mellitus (DM), hypertension (HT), and multiple comorbidities were significantly higher in the recurrence (+) group (P = 0.038, P = 0.012, P = 0.013). Blood group, postoperative use of non-steroidal anti-inflammatory drugs, preoperative cystostomy, cause of stricture, iatrogenic cause of stricture, location and length of stricture, indwelling urinary cathater size and day of catheter removal did not differ between the two groups. No statistically significant difference was observed between the two groups in terms of age, uroflowmetric maximum flow rate value, hemogram parameters, aspartate aminotransferase (AST), alanine aminotransferase (ALT), fasting blood sugar, creatinine, glomerular filtration rate, neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, lymphocyte-monocyte ratio, monocyte-lymphocyte ratio and AST/ALT ratios. CONCLUSION In patients with urethral stricture recurrence, only the frequency of DM and HT was high, while inflammation marker levels and stricture-related parameters were similar between the groups.

Low back pain: justification of treatment standards (literature review)

The American Association of Neurological Surgeons reported that approximately 75–85 % of Americans experience low back pain (LBP) during their lifetime. There is considerable heterogeneity among epidemiologic studies of LBP, which limits the ability to compare and generalize the data. One-year incidence of the first episode of LBP ranges from 6.3 to 15.4 %, while 1-year incidence of any episode of low back pain is from 1.5 to 36 %. In hospital-based studies, episode remission after one year ranges from 54 to 90 %. Experts from Europe, Australia and Latin America identified 15 clinical practice guidelines for the treatment of low back pain in primary care settings. The authors pay attention to the fact that the data on the use of nonsteroidal anti-inflammatory drugs (NSAIDs) in the mentioned guidelines are contradictory. Enzymatic oxidation of arachidonic acid has been shown to lead to the formation of potent pathological agents by two main pathways. Those in the prostaglandin (PG) pathway, particularly PGE2, have been considered inflammatory mediators for many years. The discovery of the biological activity of thromboxane A2 and prostacyclin, as well as the destructive oxygen-centered radical as additional products of this biosynthetic pathway now require their consideration as potential inflammatory mediators. Like PGE2, their biosynthesis is inhibited by nonsteroidal anti-inflammatory drugs. There is also an alternative lipoxygenase pathway that yields arachidonic acid oxygenation products called leukotrienes and eicosanoids, which have also been shown to be important inflammatory mediators resistant to NSAIDs. It was shown that dexamethasone suppresses the release of arachidonate from human epithelial cells by inducing the synthesis of the p11 protein and inhibiting the activity of phospholipase A2, that is, it affects the pathological mechanisms of inflammation that are lacking in NSAIDs, namely, it blocks the release of arachidonic acid salts. Dexamethasone has been shown to affect both exudative and proliferative phases of inflammation. Inflammatory mediators block active sulfhydryl groups of proteins, enzymes, receptors, and ion channels. The positive role of donors of such groups in the treatment of LBP is shown in the literature. In the treatment of allodynia, bisphosphonates, which normalize calcium metabolism and reduce calcification of cartilage and ligaments, have proven themselves to be the best: they cause a decrease in the intensity of pain and swelling and improve nerve function. Racetams have been shown to be useful for the treatment of not only neuropathic pain, but also cognitive impairment. Racetams are especially active in combination with choline donors. Peripheral neuropathy (PN) is a common disease with an incidence of approximately 8 % in the elderly. Neuropathic pain has a high prevalence in the general population and affects more than half of all patients with PN. The pathophysiology of PN is characterized by damage to myelin-producing Schwann cells in peripheral nerves. Regeneration/protection of the myelin sheath after nerve injury is a fundamental element of recovery in PN. Nucleotides such as uridine monophosphate have been shown to be effective in treating the cause of myelin damage in several experimental and clinical models. B vitamins such as В12, В6, В3, В1 are essential for nerve health. These vitamins can aid in the healing of damaged nerves and relieve symptoms of nerve damage like numbness and tingling, that is why they are called neurotropic vitamins. In confirmation of the clinical value of these arguments, a clinical case is presented, when the patient was managed with a combination of the discussed drugs and felt significantly better.

Exploring the association between microscopic colitis and celiac disease: A comprehensive analysis using the national in-patient data (2016-2019).

Several investigations suggested correlation between microscopic colitis (MC) and celiac disease (CD). This study aimed to examine this relationship using large-sized, population-based data with adequate control for confounding factors. This study employed the National Inpatient Sample (NIS) database over 4 years (2016-2019). Patients with/without MC in the presence/absence of CD were identified through ICD-10 codes. Univariate and multi-variate analyses involving odds ratios (OR) and 95% confidence intervals (CI) were performed. Overall, 26,836,118 patients were analyzed. Of whom, 6,836 patients had MC (n = 179 with CD and n = 6,657 without CD). The mean hospital stay was not significantly different between both groups (5.42 ± 5.44 days vs. 4.95 ± 4.66 days, P = 0.202). The univariate analysis revealed a significant association between MC and CD (OR = 22.69, 95% [19.55, 26.33], P < 0.0001). In the multi-variate analysis, which adjusted for potential confounders including age, race, hospital region, hospital teaching status, ZIP income, smoking status, alcohol overuse, hypertension, diabetes mellitus, lipidemia-related disorders, non-steroidal anti-inflammatory drug use, and selected auto-immune diseases, the association remained significant (OR = 15.71, 95% CI [13.52, 18.25], P < 0.0001). Moreover, in patients with MC, the presence of CD emerged as a significant, independent variable of in-hospital mortality in univariate (OR = 2.87, 95% [1.14, 7.21], P = 0.025) and multi-variate (OR = 3.37, 95% CI [1.32, 8.60], P = 0.011) analyses. This study establishes a probable link between MC and CD, backed by both univariate and multi-variate analyses, while also identifying CD as an independent risk factor for increased mortality among MC patients. These findings need to be validated in real-world clinical studies.

Analysis of the Consumption of Medicinal Products Associated with a High Risk of Drug-Induced Liver Injury in Patients with COVID-19

INTRODUCTION. The risk of liver damage correlates with the severity of COVID-19. However, a growing number of studies have shown an association between liver function impairment and combinations of medicinal products used to treat COVID-19.AIM. The study aimed to analyse the annual consumption of medicinal products associated with a high risk of drug-induced liver injury (DILI) used as part of combination therapy in COVID-19 patients and to review a number of medication administration records in order to develop measures to prevent DILI.MATERIALS AND METHODS. The study used the ATC/DDD methodology to study consumption data for 2020, 2021, and 2022 and analysed a sample of 1250 inpatient medical records and medication administration records of COVID-19 patients treated in a Volgograd region hospital converted into a COVID-19 care centre. For genetically engineered biologicals and cyclophosphamide, which were lacking DDDs, the authors calculated the volume of consumption using the average dose per treatment course. The authors identified medicines capable of causing clinically apparent liver damage (according to the LiverTox database and Russian clinical practice guidelines) and/or elevated liver enzymes in ≥1% of patients (according to safety reports).RESULTS. The study found that 28% of the medicinal products used in combination for inpatient treatment of COVID-19 were associated with a high risk of DILI. In 2020, 2021, and 2022, the total consumption of medicinal products associated with a high risk of DILI was 342.3, 425.3, and 402.3 DDDs per 100 bed days, and the total consumption of genetically engineered biologicals (administered as a single dose) and cyclophosphamide was 3.5, 16.9, and 29.7 average course doses per 100 patients, respectively. According to the selective analysis of medical records, 19.8% (247/1250) reported concomitant use of 5 or more medicinal products associated with a high risk of DILI, which increased the risk of adverse drug interactions leading to DILI. In 2022, the most prescribed medicinal products with a high risk of DILI were omeprazole (188.7 DDDs per 100 bed days), non-steroidal anti-inflammatory drugs and paracetamol (54.4 DDDs per 100 bed days), atorvastatin (46.2 DDDs per 100 bed days), levofloxacin (26.4 DDDs per 100 bed days), ceftriaxone (20.5 DDDs per 100 bed days), favipiravir (17.3 DDDs per 100 bed days), and genetically engineered biologicals (24.0 DDDs per 100 bed days).CONCLUSIONS. To reduce the risk of DILI in COVID-19 patients admitted to infectious disease units, including the risk of DILI due to drug interactions, it is necessary to limit the use of hepatotoxic antibacterial agents, proton-pump inhibitors, and non-steroidal anti-inflammatory drugs, or consider alternative medicinal products with a lower risk of hepatotoxicity.

Recent clinical practice guidelines for the management of low back pain: a global comparison.

Low back pain (LBP) is a significant health problem worldwide, with a lifetime prevalence of 84% in the general adult population. To rationalise the management of LBP, clinical practice guidelines (CPGs) have been issued in various countries around the world. This study aims to identify and compare the recommendations of recent CPGs for the management of LBP across the world. MEDLINE, EMBASE, CINAHL, PEDro, and major guideline databases were searched from 2017 to 2022 to identify CPGs. CPGs focusing on information regarding the management and/or treatment of non-specific LBP were considered eligible. The quality of included guidelines was evaluated using the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument. Our analysis identified a total of 22 CPGs that met the inclusion criteria, and were of middle and high methodological quality as assessed by the AGREE II tool. The guidelines exhibited heterogeneity in their recommendations, particularly in the approach to different stages of LBP. For acute LBP, the guidelines recommended the use of non-steroidal anti-inflammatory drugs (NSAIDs), therapeutic exercise, staying active, and spinal manipulation. For subacute LBP, the guidelines recommended the use of NSAIDs, therapeutic exercise, staying active, and spinal manipulation. For chronic LBP, the guidelines recommended therapeutic exercise, the use of NSAIDs, spinal manipulation, and acupuncture. Current CPGs provide recommendations for almost all major aspects of the management of LBP, but there is marked heterogeneity between them. Some recommendations lack clarity and overlap with other treatments within the guidelines.

A Contemporary Review on the Critical Role of Nonsteroidal Anti-inflammatory Agents in Colorectal Cancer Therapy.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) are widely recognized as effective pain relievers and function by inhibiting the cyclooxygenase enzyme (COXs). Moreover, they have been found to participate in various cellular processes through different signaling pathways, such as WNT, MAPK, NF-KB, and PI3K/AKT/mTOR. This makes them potential candidates for chemoprevention of several malignancies, particularly colorectal cancer (CRC). However, the use of NSAIDs in cancer prevention and treatment is a complex issue due to their adverse effects and gastrointestinal toxicity. Therefore, it is crucial to explore combination therapies that can minimize side effects while maximizing synergistic effects with other agents and to evaluate the success rate of such approaches in both pre-clinical and clinical studies. In this review, we aim to provide an overview of the effects of NSAIDs in the prevention and treatment of CRC. We will focus on elucidating the possible mechanisms of action of these drugs, the signaling pathways involved in CRC, and the potential synergistic effects when combined with other therapeutic agents.

Predictors of adherence to direct oral anticoagulants after cardiovascular or bleeding events in Medicare Advantage Plan enrollees with atrial fibrillation.

Direct oral anticoagulants (DOACs) are recommended for patients with atrial fibrillation (AF) given their improved safety profile. Suboptimal adherence to DOACs remains a significant concern among individuals with AF. However, the extent of adherence to DOACs following a cardiovascular or bleeding event has not been fully evaluated. To evaluate the pattern of adherence trajectories of DOACs after a cardiovascular or bleeding event and to investigate the sociodemographic and clinical predictors associated with each adherence trajectory by using claims-based data. This retrospective study was conducted among patients with AF prescribed with DOACs (dabigatran/apixaban/rivaroxaban) between July 2016 and December 2017 and who were continuously enrolled in the Texas-based Medicare Advantage Plan. Patients who experienced a cardiovascular or bleeding event while using the DOACs were further included in the analysis. The sample was limited to patients who experienced a clinical event such as a cardiovascular or bleeding event while using the DOACs. The clinical events considered in this study were cardiovascular (stroke, congestive heart failure, myocardial infarction, systemic embolism) and bleeding events. To assess adherence patterns, each patient with a DOAC prescription was followed up for a year after experiencing a clinical event. The monthly adherence to DOACs after these events was evaluated using the proportion of days covered (PDC). A group-based trajectory model incorporated the monthly PDC to classify groups of patients based on their distinct patterns of adherence. Predictors associated with each trajectory were assessed using a multinomial logistic regression model, with the adherent trajectory serving as the reference group in the outcome variable. Among the 694 patients with AF who experienced clinical events after the initiation of DOACs, 3 distinct adherence trajectories were identified: intermediate nonadherent (30.50%), adherent (37.7%), and low adherent (31.8%); the mean PDC was 0.47 for the intermediate nonadherent trajectory, 0.93 for the adherent trajectory, and 0.01 for low adherent trajectory. The low-income subsidy was significantly associated with lower adherence trajectories (odds ratio [OR] = 4.81; 95% CI = 3.07-7.51) and with intermediate nonadherent trajectories (OR = 1.57; 95% CI = 1.06-2.34). Also, nonsteroidal anti-inflammatory drug use was significantly associated with lower adherence trajectories (OR = 5.10; 95% CI = 1.95-13.36) and intermediate nonadherent trajectories (OR = 3.17; 95% CI = 1.26-7.93). Other predictors significantly associated with both nonadherent trajectories are type of DOACs (OR = 0.53; 95% CI = 0.35-0.79), presence of coronary artery disease (OR = 1.89; 95% CI = 1.01-3.55), and having 2 or more clinical events (OR = 1.65; 95% CI = 1.09-2.50). Predictors identified provide valuable insights into the suboptimal adherence of DOACs among Medicare Advantage Plan enrollees with AF, which can guide the development of targeted interventions to enhance adherence in this high-risk patient population.

Characteristics of Nonunion Fractures in Patients with Antebrachial Fractures at dr. Mohamad Soewandhie General Hospital Surabaya 2021-2022: A Retrospective Study

Background: Nonunion, a complication of fracture healing, can lead to patient morbidity. Contributing factors include age, gender, fracture type, multiple fractures, infection, prolonged nonsteroidal anti-inflammatory drug (NSAID) use, smoking, nutritional status, and history of chronic disease. This study aims to determine the prevalence and characteristics of nonunion antebrachial fractures at dr. Mohamad Soewandhie General Hospital Surabaya. Methods: This retrospective descriptive study involved 111 patients. Data was gathered from medical records treated at dr. Mohamad Soewandhie General Hospital Surabaya for antebrachial fracture during 2021-2022. The study protocol obtained approvals from two local ethical committees. Data included demographics, fracture characteristics, fracture type, multiple fractures, infection, NSAID use, hypertension and diabetes history, smoking habits, and nutritional status by BMI calculation. Results: This study found a 24.3% prevalence of antebrachial nonunion fractures at dr. Mohamad Soewandhie General Hospital Surabaya in 2021-2022, mostly in males (66.7%) aged 17-25 years (22.2%). Nonunion in antebrachial fractures is marked by high rates in closed (92.6%) and single fractures (92.6%). Notably, infections (22.2%), smoking (7.4%), and hypertension history (7.4%) are common contributors. Despite ideal BMI in many cases (44.4%), nonunion still occurred. Conclusions: The study conducted at Dr. Mohamad Soewandhie General Hospital in Surabaya revealed a high prevalence of antebrachial nonunion fractures at 24.3%, particularly among young males. It was found that closed, single fractures were the most common type, with infections, smoking, and a history of hypertension being significant contributing factors. Interestingly, even individuals with an ideal BMI were still at risk for nonunion.

Association between perioperative non-steroidal anti-inflammatory drug use and cardiovascular complications after non-cardiac surgery in older adult patients.

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. We retrospectively extracted the information for patients with age ≥ 65years who had inpatient non-cardiac surgery with a duration of ≥ 1h 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 30days 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. 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). 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 30days after surgery, or length of postoperative hospital stay.

Changes in analgesic prescribing among older adults hospitalised for osteoarthritis or joint replacements

Abstract Introduction Osteoarthritis is a chronic, progressive joint disease, associated with frequent pain, and functional decline. The primary risk factor for developing osteoarthritis is advanced age. Older patients are more susceptible to the adverse effects of commonly prescribed analgesics such as opioids and non-steroidal anti-inflammatory drugs (NSAIDs), owing to a greater prevalence of comorbidities and age-related changes in this cohort. The analgesic burden and prescribing trends in this cohort are largely unknown in the Irish context despite their increased susceptibility to adverse effects. Aim This study aims to evaluate analgesic prescribing patterns before and after an osteoarthritis or joint arthroplasty related hospital admission in patients aged ≥65 years and to identify factors associated with long-term prescribing of opioids and oral NSAIDs post-discharge. Methods This was an observational study of older adults with an osteoarthritis or joint arthroplasty hospitalisation. Data were collected for a larger study from 44 general practices in Ireland from 2012-2018 and included general practice records (12 months pre/post-index hospitalisation) and hospital discharge summaries, which was extracted as anonymous data from the practice software system. The analysis described prevalence of use of analgesics in the 12 months pre and post their hospitalisation. To assess long-term prescribing, multivariable analysis assessed discharge prescription and patient characteristics associated with opioid and oral NSAID use 3-12 months post-discharge. Results Overall, 738 individuals were included (52.9% female, mean age 78.1 years). Compared to 12 months pre-hospitalisation, patients were less likely to be prescribed a weak opioid or oral NSAID from discharge to 3 months post-discharge, or in the 3-12 months post-discharge. For strong opioids, prescribing was significantly less likely in the 3-12 months post-discharge compared to pre-discharge (odds ratio (OR) 0.54, 95%CI 0.40-0.74). Female sex (OR 1.61, 95%CI 1.10-2.36), strong opioid prescribing at discharge (OR 2.47, 95%CI 1.56-3.90) and pregabalin discharge prescribing (OR 2.21, 95%CI 1.12-4.33) were significantly associated with long-term strong opioid prescribing 3-12 months post-discharge. For oral NSAID prescribing, lower age (OR 0.97, 95%CI 0.95-1.00), female sex (OR 1.56, 95%CI 1.08-2.25), and discharge prescribing of strong opioids (OR 1.94, 95%CI 1.23-3.04) were significantly associated. Conclusion The use of opioids and oral NSAIDs is typically reduced for patients post-discharge from an osteoarthritis or joint arthroplasty hospitalisation. Female sex and strong opioids at discharge are associated with the prescribing of strong opioids and oral NSAIDs. Although our study was limited by use of prescription records which may not accurately represent what was dispensed or utilised by patients, it is the first to examine changing patterns of analgesic prescribing among osteoarthritis/joint arthroplasty patients. This contributes knowledge on modifiable characteristics which could reduce long-term use of these medications where appropriate.

Pouchitis: pathophysiology and management.

Pouchitis is an acute or chronic inflammatory disease of the ileal reservoir. It is common after restorative proctocolectomy with ileal pouch-anal anastomosis, and treatment of chronic antibiotic-refractory pouchitis has proven challenging. Most cases of acute pouchitis evolve into chronic pouchitis. The aetiology of acute pouchitis is likely to be partly related to the gut microbiota, whereas the pathophysiology of chronic pouchitis involves abnormal interactions between genetic disposition, faecal stasis, the gut microbiota, dysregulated host immunity, surgical techniques, ischaemia and mesentery-related factors. Pouchoscopy with biopsy is the most valuable modality for diagnosis, disease monitoring, assessment of treatment response, dysplasia surveillance and delivery of endoscopic therapy. Triggering or risk factors, such as Clostridioides difficile infection and use of non-steroidal anti-inflammatory drugs, should be modified or eradicated. In terms of treatment, acute pouchitis usually responds to oral antibiotics, whereas chronic antibiotic-refractory pouchitis often requires induction and maintenance therapy with integrin, interleukin or tumour necrosis factor inhibitors. Chronic pouchitis with ischaemic features, fistulae or abscesses can be treated with hyperbaric oxygen therapy.

Oligohydramnios and Intrauterine Premature Closure of Ductus Arteriosus Associated with the Use of NSAIDs During Pregnancy – An Overview of Clinical Evidence

Background: Pregnant women may experience low back pain and other pain symptoms, fever, and inflammatory conditions that may harm the fetus and mother if left untreated. The most common uses of non-steroidal anti-inflammatory drugs (NSAIDs) are the treatment of inflammation, pain and pyrexia. However, after 20-30 weeks of gestation, using NSAIDs during pregnancy may cause oligohydramnios and premature ductus arteriosus closure, which could harm the developing fetus. Objective: The purpose of this review article is to critically examine the clinical evidence that is currently available for oligohydramnios and premature ductus arteriosus closure linked to NSAIDs. Methods: Online databases such as Medline/Pubmed/PMC, EBSCOhost, Scopus, Web of science, Embase, Science Direct, Google Scholar, and reference lists were searched to identify articles which dealt with NSAIDs-associated oligohydramnios and premature closure of ductus arteriosus. Results: Numerous regulatory agencies released warnings about oligohydramnios and premature closure of ductus arteriosus linked to NSAIDs. Furthermore, a number of case reports, case series, and some observational studies have also been published about the possibility of oligohydramnios and premature closure of ductus arteriosus linked to NSAIDs use. Conclusion: Women who are pregnant for 20 weeks or more should refrain from self-medicating with NSAIDs without consulting a pharmacist or a physician. The use of NSAIDs during pregnancy should carefully be considered due to potential risks to the mother and developing fetus, especially after 20-30 weeks of gestation. To guarantee the best possible health for the expectant mother and the unborn child, healthcare professionals should weigh the benefits and risks and look into alternate options. Pregnant women may opt for acetaminophen (paracetamol) to relieve pain and fever during pregnancy. Pregnant women should seek medical attention if there is persisting pain for more than three days.

A Minority of Childhood Disorders of Gut-Brain Interaction Persist Into Adulthood: A Risk-Factor Analysis.

Disorders of gut-brain interaction (DGBIs) may originate in childhood. There are currently limited data on persistence of DGBI into adulthood and risk factors for persistence. Furthermore, there are no data on this question from general practice, where the majority of DGBIs are diagnosed and managed. This study documents the proportion of childhood-diagnosed DGBIs that persisted into adulthood and what factors were associated with persistence. General practice records were obtained for more than 60,000 patients whose medical record spanned both childhood and adulthood years. Patients with diagnosed organic gastrointestinal disorder were excluded. Medical records were also interrogated for potential risk factors. Eleven percent of patients with irritable bowel syndrome (IBS) and 20% of patients with functional dyspepsia (FD) diagnosed in childhood had repeat diagnoses of the same condition in adulthood. Female sex (odds ratio [OR] 2.02) was associated with persistence for IBS, while a childhood diagnosis of gastritis (OR 0.46) was risk-protective. Childhood non-steroidal anti-inflammatory drug use (OR 1.31, 95% confidence interval [CI] 1.09-1.56) was a risk factor for persistence in IBS. For FD, a childhood diagnosis of asthma (OR 1.30, 95% CI 1.00-1.70) was a risk factor, as was anxiety for both IBS (OR 1.24, 95% CI 1.00-1.54) and FD (OR 1.48 95% CI 1.11-1.97) with a similar finding for depression for IBS (OR 1.34, 95% CI 1.11-1.62) and FD (OR 1.88 95% CI 1.47-2.42). Childhood DGBIs persist into adulthood in 10%-20% of patients, suggesting that management monitoring should continue into adulthood. Those diagnosed with anxiety or mood disorders in childhood should receive particular attention, and prescription of non-steroidal anti-inflammatory drugs in children should be made judiciously.

P064 It’s a long time to wait: exploring the support needs of people with rheumatoid arthritis starting methotrexate

Abstract Background/Aims Methotrexate (MTX) is recommended as initial Disease Modifying Anti-Rheumatic Drug (DMARD) therapy for people with Rheumatoid Arthritis (RA) but often takes several months to become effective. Little is known about the support needs of people with RA whilst MTX takes effect. Methods 76 adults with RA referred for MTX counselling attending two rheumatology units in the West Midlands were invited to take part in qualitative semi-structured interviews (either by phone or video). Research partners with RA helped to develop interview topic guides. Interviews were digitally recorded, transcribed and analysed using reflexive thematic analysis. Results 19 participants, (11 male, 8 Female, White British, age 45-75 years, disease duration (6 weeks - 35 years) took part in telephone (n = 17) and video (n = 2) interviews (duration 34-82 minutes). Three themes were identified; Concerns regarding time to effect, Learning to cope with the impact of RA, A need for support to self-manage RA. Concerns regarding time to effect: most people expressed concerns about coping with active symptoms of RA whilst waiting for MTX to take effect. Few recalled receiving information about nonpharmacological symptom management. Many experienced initial benefit following intramuscular bridging steroids, often wearing off as MTX commenced, and did not recall plans for further steroids. Conflicting advice about the use of analgesia and non-steroidal anti-inflammatory drugs (NSAIDs) to manage pain and joint stiffness sometimes created confusion. A few recollected advice to stop taking analgesia or NSAIDs when starting MTX. Several reported difficulties accessing help with symptom control and obtaining analgesia and NSAIDs in primary care. Learning to cope with the impact of RA: Participants reported limitations to physical function, restricting their independence with daily living activities with an impact on social, relational and work roles. Most, however, reported finding ways to manage these limitations. Several described negative impacts on mental health. A need for support to self-manage RA: Most identified unmet needs regarding self-management whilst waiting for MTX to take effect. Few recalled receiving education or support regarding self-management for RA. Some received leaflets regarding managing flares of RA that were seen to provide practical advice and reassurance. Several reported not reading leaflets and coping with flares without education or support. Positive support was sometimes received from relatives and others with RA, whereas few used the internet to find additional help. Rheumatology advice lines were often perceived as a useful source of support, but some people were reticent to seek help and others had concerns about delayed responses. Conclusion Many people with RA report unmet needs to support self-management whilst waiting for MTX to take effect. Appropriate signposting and referral to support provided by RA patient associations may offer useful solutions for some. Disclosure S.J. Logan: None. S. Hider: None. J. Green: None. S. Ryan: None.

Evaluation of the efficacy of complex analgesic therapy, including a combination of B vitamins, in patients with combination of osteoarthritis and chronic non-specific low back pain (results of an open-label pilot clinical trial)

The vitamin B1, B6 and B12 complex (VBC) is frequently used to treat acute and chronic low back pain.Objective: to investigate the effect of a combination of a non-steroidal anti-inflammatory drug (NSAID) and a VBC on the main manifestations of nociceptive system dysfunction in patients with combination of osteoarthritis (OA) and chronic non-specific low back pain (NSLBP).Material and methods. The study group consisted of 99 patients (82% women, mean age 63.6±17.2 years) with OA of various localization andNSLBP who had moderate to severe pain (≥4 on a numerical rating scale, NRS 0–10). All patients received etoricoxib 60 mg/day (up to 14 days) and a course of intramuscular (IM) injections of VBC (a drug for parenteral administration containing solutions of thiamine 100 mg, pyridoxine 100 mg, cyanocobalamin 1.0 mg and lidocaine 20 mg) 2.0 ml №10. Treatment outcome was assessed after 14 days.Results and discussion. During treatment, the vast majority of patients showed a significant improvement: the median severity of pain on movement (NRS) decreased from 6.3 [5.0; 8.0] to 3.7 [3.0; 5.0], p=0.0001; functional impairment  –  from 3.8 [2.0; 6.0] to 2.2 [1.0; 3.0], p=0.001; fatigue – from 5.6 [4.0; 8.0] to 3.5 [0.0; 2.0], p=0.0001. 71.6% of patients rated the treatment results as good or excellent. Six patients had adverse reactions: 2 – local pain at the site of the intramuscular injections, 1 – arterial hypertension, 3 – epigastric pain. No serious adverse events were recorded.Conclusion. The combined use of NSAIDs and VBC can provide significant improvement in patients with a combination of OA and NSLBP.

Identifying Vulnerabilities to NSAID Adverse Events in the U.S. Population: An Analysis of Preexisting Conditions and Sex.

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

Celecoxib and sulindac sulfide elicit anticancer effects on PIK3CA-mutated head and neck cancer cells through endoplasmic reticulum stress, reactive oxygen species, and mitochondrial dysfunction

Gain-of-function mutation in the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) catalytic subunit alpha gene (PIK3CA) is a significant factor in head and neck cancer (HNC). Patients with HNC harboring PIK3CA mutations receive therapeutic benefits from the use of non-steroidal anti-inflammatory drugs (NSAIDs). However, the molecular mechanisms underlying these effects remain unknown. Here, we examined the Detroit562 and FaDu cell lines as HNC models with and without a hyperactive PIK3CA mutation (H1047R), respectively, regarding their possible distinct responses to the NSAIDs celecoxib and sulindac sulfide (SUS). Detroit562 cells exhibited relatively high PI3K/Akt pathway-dependent cyclooxygenase-2 (COX-2) expression, associated with cell proliferation. Celecoxib treatment restricted cell proliferation and upregulated endoplasmic reticulum (ER) stress-related markers, including GRP78, C/EBP-homologous protein, activating transcription factor 4, death receptor 5, and reactive oxygen species (ROS). These effects were much stronger in Detroit562 cells than in FaDu cells and were largely COX-2-independent. SUS treatment yielded similar results. Salubrinal (an ER stress inhibitor) and N-acetyl-L-cysteine (a ROS scavenger) prevented NSAID-induced ROS generation and ER stress, respectively, indicating crosstalk between ER and oxidative stress. In addition, celecoxib and/or SUS elevated cleaved caspase-3 levels, Bcl-2-associated X protein/Bcl-2-interacting mediator of cell death expression, and mitochondrial damage, which was more pronounced in Detroit562 than in FaDu cells. Salubrinal and N-acetyl-L-cysteine attenuated celecoxib-induced mitochondrial dysfunction. Collectively, our results suggest that celecoxib and SUS efficiently suppress activating PIK3CA mutation-harboring HNC progression by inducing ER and oxidative stress and mitochondrial dysfunction, leading to apoptotic cell death, further supporting NSAID treatment as a useful strategy for oncogenic PIK3CA-mutated HNC therapy.

Scoping review of interventions to de-implement potentially harmful non-steroidal anti-inflammatory drugs (NSAIDs) in healthcare settings

ObjectivesPotentially harmful non-steroidal anti-inflammatory drugs (NSAIDs) utilisation persists at undesirable rates worldwide. The purpose of this paper is to review the literature on interventions to de-implement potentially harmful NSAIDs in...

Impact of concurrent medications on the outcome of immunotherapy in non-small cell lung carcinoma.

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. 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. 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). The unnecessary use of NSAIDs along with immunotherapy should be discouraged.

Risk of cardiovascular disease with high-dose versus low-dose use of non-steroidal anti-inflammatory drugs in ankylosing spondylitis

ObjectiveTo 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).MethodsUsing the Korean National Health Insurance database,...