Long-term Use Of NSAIDs Research Articles

Therapy of gout in 2024

The treatment of gout includes anti-inflammatory therapy and prophylaxis of flare-ups on the one hand and measures for long-term uric acid reduction on the other. Acute arthritis urica is best relieved by intra-articular steroids; systemic steroids, NSAIDs and, in exceptional cases, colchicine are also suitable. For the prophylaxis of relapses, long-term use of colchicine, NSAIDs or low-dose steroids is an option. However, the main pillar of gout therapy is pharmacological reduction of uric acid. The xanthine oxidase inhibitors allopurinol and febuxostat are best suited. The goal is a serum uric acid below 360 µmol/l ("treat to target"). The «start low, go slow» strategy reduces the risk of relapses and, in the case of allopurinol, the occurrence of hypersensitivity syndrome. Allopurinol is started at a maximum of 100 mg/d (less in renal insufficiency), followed by a slow upward titration to the required maintenance dose, which may largely exceed 300 mg/d (also in renal insufficiency). Febuxostat is started at a maximum of 40 mg/d and also titrated upwards. The most common cause of insufficient uric acid reduction is unreliable medication intake. In the management of gout, its comorbidities should also be sought and addressed.

Dendrimers as Drug Delivery Platforms of the Mechanisms, Benefits, and Use in Anti-Pain: Systematice Literature Review

Background: Efforts to reduce the side effects of long-term NSAID use have prompted exploration of transdermal drug delivery, which offers advantages such as avoiding first-pass metabolism, reducing pain, allowing sustained drug release, and improving patient compliance. Dendrimers, specifically polyamidoamine (PAMAM), are attracting attention for their potential in drug delivery. PAMAM has a three-dimensional structure of monodisperses with high amino group density and internal voids suitable for drug encapsulation. Methods: This research method uses the literature review method which begins with the collection of journals to be reviewed. The article search was conducted on the Pubmed database. Researchers searched with the keyword dendrimer. The two main synthesis methods are convergent and divergent dendrimers. Results: : Drug molecules can be trapped in dendrimers through hydrogen, hydrophobic, or electrostatic bonds. The advantages of dendrimers include improved solubility, permeability, and targeted drug delivery, while the disadvantages are high cost, toxicity and aggregation. This system has been used in several pain medications. Conclusions: Dendrimers are macrostructures with unique characteristics such as nanoscopic size, multifunctional surface, and high branching, making them ideal as drug delivery systems. Ketoprofen with PAMAM-type dendrimers showed that PAMAM dendrimers could significantly increase the accumulative amount of permeation of both drugs after 24 hours, compared with the drug suspension without PAMAM dendrimers. Dendrimers are multi-branched monodisperse macrostructures, derived from Greek.

Nonsteroidal anti-inflammatory drug-induced small bowel strictures (diaphragm disease) – an under-recognized cause of small bowel obstruction

BackgroundSmall bowel obstruction is a major source of morbidity and mortality that carries a significant economic burden. Recurrent small bowel obstruction may be secondary to circumferential strictures (small bowel diaphragm disease), an under-recognized entity secondary to long-term NSAID use. We aim to describe the sensitivity of preoperative CT enterography in patients with surgically treated small bowel diaphragm disease. MethodsWe retrospectively reviewed adult patients who underwent elective small bowel resection for small bowel obstruction performed by a single minimally-invasive surgeon between 2010-2023. Patient history, radiographic, endoscopic, operative, and pathology reports were reviewed for reference to NSAID use, small bowel strictures, diaphragms, and enteropathy. Exclusion criteria were prior radiation, inflammatory bowel disease, malignancy, adhesive disease, and anastomotic strictures. ResultsA total of 225 patients were identified; of those, 22 patients (10%) met inclusion criteria. The mean age was 60.7 years (range 29-78), with 15 women (68%). All patients underwent minimally invasive small bowel resection for obstruction with histopathologic evidence of stricture without evidence of transmural inflammation, granuloma, or dysplasia and confirmed NSAID use (n=22; 100%). Anemia was present in 36% (n=8). Preoperative CT or MR enterography was performed in 18 patients (82%) and stricturing was reported in 13 patients (72%). Intraoperatively, palpation identified strictures in all patients. ConclusionNSAID-induced small bowel injury is an under-recognized condition that, in severe cases, can present as small bowel obstruction. Surgeons should consider diaphragm disease in patients with obstruction and NSAID use, in which preoperative CT or MR enterography may be useful but cannot rule out disease.

Pure total flavonoids from Citrus ameliorate NSAIDs-induced intestinal mucosal injury via regulation of exosomal LncRNA H19 and protective autophagy

IntroductionNon-steroid anti-inflammatory drugs (NSAIDs) are a class of prescription drugs with antipyretic, analgesic, anti-inflammatory, and antiplatelet effects. However, long-term use of NSAIDs will disrupt the intestinal mucosal barrier, causing erosion, ulcers, bleeding, and even perforation. Pure total flavonoids from Citrus (PTFC) is extracted from the dried peel of Citrus, showing a protective effect on intestinal mucosal barrier with unclear mechanisms. MethodsIn the present study, we used diclofenac (7.5 mg kg−1, i.g.) to induce a rat model of NSAIDs-related intestinal lesions. PTFC (50, 75, 100 mg·kg−1 d−1, i.g.) was administered 9 days before the initial diclofenac administration, followed by co-administration on the last 5 days. Exosomes were identified by western blotting and transmission electron microscopy (TEM), and then co-cultured with IEC-6 cells. The expression of long non-coding RNA (lncRNA) H19, autophagy-related 5 (Atg5), ZO-1, Occludin, and Claudin-1 were detected by quantitative real-time PCR (qRT-PCR). The expression of light chain 3 (LC3)-I, LC3-II, ZO-1, Occludin and Claudin-1 proteins was tested by western blotting. The localization of both exosomes and autophagosomes was examined by immunofluorescent technique. ResultsThe treatment of PTFC attenuated intestinal mucosal mechanical barrier function disturbance in diclofenac-induced NSAIDs rats. IEC-6 cells co-cultured with NSAIDs rats-derived exosomes possessed the lowest levels of protective autophagy, and severe intestinal barrier injuries. Cells co-cultured with the exosomes extracted from rats administrated PTFC exhibited an improvement of autophagy and intestinal mucosal mechanical barrier function. The prevention effect was proportional to the concentration of PTFC administered. ConclusionPTFC ameliorated NSAIDs-induced intestinal mucosal injury by down-regulating exosomal lncRNA H19 and promoting autophagy.

Gastrointestinal perforations induced by long-term non-steroidal anti-inflammatory drugs use: a case series analysis and discussion

Non-steroidal anti-inflammatory drugs (NSAIDS) are used in a wide range but may cause harm to the gastrointestinal mucosa, which leads to various complications. This study shows the impact of long term NSAID use on small and large intestine and presents 2 cases of patients with NSAID induced perforations. The first case involves a 62-year-old male patient with RA on long term Ibuprofen use, presented with abdominal pain, vomiting, and lower limbs pain. Laparotomy revealed a 5 mm perforation in the proximal jejunum. The second case, a male patient of 65 years of age using diclofenac without a prescription, which lead to a 4×4 cm sigmoid colon perforation. The comparison of both the cases presents a difference in examination and laboratory findings. Long-term NSAID use has been associated with various GI complications, including perforations. The case presents the importance of considering NSAID related complications, mainly in older patients and the persons with ulcers. Combining NSAIDS with other drugs, like misoprostol may minimize the risk of the GI complications. NSAIDs are also linked with cardiovascular events, and heart related issues. This study shows the need of careful NSAID prescription, with their association with preventable adverse effects. 30% of hospitalizations for adverse drug reactions are only by the NSAIDs. PPIs and H2 receptor antagonist are commonly used to protect the gastrointestinal mucosa which minimizes the occurrence of ulcers. Healthcare professionals should be careful particularly in case of high risk patients to minimize the NSAID related complications.

Study of the Dynamics of Diflunisal Release from a Polymer Matrix

Introduction. The effectiveness of diflunisal in the treatment of cardiac amyloidosis has been clinically proven. Currently, only tablet forms of diflunisal are registered in the world, however, long-term use of NSAIDs leads to characteristic side effects. Therefore, delivery systems for diflunisal (including a form for external use) are now being actively developed to reduce side effects and improve its bioavailability.Aim. Research of the dynamics of release of the active substance diflunisal from the polymer matrix of hyaluronic acid.Materials and methods. The objects of the study are diflunisal gels in hyaluronic acid with a concentration of the main substance of 0.093, 0.14, 0.19 and 0.25 %. Quantitative determination was carried out by reverse-phase HPLC using a Prontosil C18, 120-5, 75 × 2 mm chromatographic column, thermostatically controlled at 40 °C. Eluent: phosphate buffer solution (PBS) with pH 3.0 and acetonitrile (30 : 70), flow rate 0.1 ml/min. Eluates were detected at wavelengths of 230, 270, 310 nm.Results and discussion. During the work, a method (HPLC) was selected and a method for determining diflunisal in a HA matrix was developed. The delivery system under study significantly increases the solubility of diflunisal in an aqueous solution compared to the dissolution of the substance. The release of the active substance from the matrices was carried out in a phosphate buffer solution with pH 7.6. The release rate for all samples exceeded 90 % after 3 hours after the start of the experiment, with most of the active substance released within an hour.Conclusion. The data obtained suggest that the release profile is characteristic of biodegradable matrices and diffusion-controlled delivery systems. Complete extraction of diflunisal from HA was achieved using PBS with pH 7.6 as a dissolution medium.

Post-Operative Complications Associated with Long-Term NSAID or Long-Term Opioid Use Prior to Lumbar Spinal Fusion Surgery

ObjectiveLower back pain (LBP) has been implicated as a significant cause of chronic pain in the United States, often requiring analgesic use. In this study, we investigate the trends in long-term preoperative NSAID (LTN) and Opioid (LTO) use in patients with low back pain in the United States, and the resultant postoperative complications following lumbar fusion. MethodsIn this retrospective cohort study of patients with lumbar pathologies, multivariate population-based regression models were developed using the 2010–2017 National Readmission Database. Short-term complications (30-, 90-day) and long-term complications (180-, 300-day) were analyzed at readmission. ResultsOf patients diagnosed with LBP (N = 1427,190) we found a rise in LTO users and a fall in LTN users following 2015. We identified 654,264 individuals who received a lumbar spine fusion, of which 22,975 were LTN users and 11,213 were LTO users. LTO users had significantly higher total inpatient charges (p-value<0.0001) and LOS (p-value<0.0001), while LTN users had lower rates of acute infection (OR: 0.993, 95% CI: 0.987–0.999, p = 0.017) and acute posthemorrhagic anemia (OR: 0.957, 95% CI: 0.935–0.979, p < 0.001) at primary admission. Readmission analysis showed that LTN use had significantly lower odds of readmission compared to LTO use at all time points (p < 0.01 for all). LTN use had significantly higher odds of hardware failure (OR: 1.134, 95% CI: 1.039–1.237, p = 0.005) within 300-days of receiving a lumbar fusion. ConclusionsLTO users had significantly higher readmission rates compared to LTN. In addition, we found that LTN use was associated with significantly higher odds of hardware failure at long-term follow-up in patients receiving lumbar fusion surgery.

Factors Affecting Gastric Perforation Patient Outcome with History of Arthritis and Long Term Use of NSAIDs in Dr. Kariadi Semarang Period 2020 – 2022

Background: The incidence of gastric perforation gives a high mortality outcome. The second most common cause of gastric perforation is long-term use of NSAIDs. In cases of arthritis during the COVID-19 pandemic, a conservative therapeutic approach and administration of NSAIDs are preferred. Due to this, researchers want to know the factors affecting gastric perforation cause by NSAIDs. Method: An analytic descriptive study with a retrospective cohort study design, using electronic medical records of patients at RSUP Dr. Kariadi Semarang from January 2020 - December 2022. Data collected was in the form of demographics, diagnoses, procedures, preoperative conditions, scoring system, and outcome. Results: PULP score, one of prognostic factor, has a good level of significance compared to other scoring systems in determining the prognostic mortality of patients with gastric perforation. The combination of variables between the type of NSAIDs and the type of arthritis has a direct correlation with a positive inter-variable power of 86.7% and a significance of 0.049 on patient outcome. Conclusion: NSAIDs pose a risk of gastric perforation in long-term use. tNSAIDs carry a higher risk inducing gastric perforation than selective NSAIDs.

Novel ibuprofen prodrug: A possible promising agent for the management of complications of Alzheimer’s disease

BackgroundAlzheimer’s disease (AD) is a severe, varied, and complex brain condition that gradually impairs memory and cognitive function. Epidemiological studies have shown that patients who have a history of long-term NSAID use have a decreased risk of developing AD. The objective of this study is to conduct the structural analysis of a novel ibuprofen prodrug and test its anti-Alzheimer’s properties. MethodsComputational and docking studies were conducted using AMBER 18 package. The in-vivo studies were performed using aluminum chloride-induced experimental AD in rats. Adult Wistar rats of either sex were used and treated with aluminum chloride (32.5 mg/kg, p.o) and ibuprofen prodrug (50 mg/kg, p.o) daily for 30 days. The hole-board test and elevated plus maze were conducted on 10th, 20th and 30th day. Further, on 31st day, animals were euthanized and the brain tissue was used for histopathology. The results obtained were subjected to statistical analysis by one-way ANOVA and Dunnet’s test, p < 0.05 was considered to indicate the significance. ResultsThe structural configuration of the novel compound indicated the presence of several structures such as aliphatic, aromatic, and asymmetry in the compound. The geometrical analysis indicated that the ibuprofen conjugate has dreiding energy of 51.22 kcal/mol with a van der waals radius of 62.56 A. The Huckel analysis confirmed the presence of aromatic rings in the compound. The molecular docking studies suggested affinity towards beta-secretase and acetylcholinesterase, besides indicating that the compound has ideal characteristics for the oral route (Log P = 2.33), cellular absorption (TPSA = 95.50), and oral bioavailability (number of rotatable bonds = 10). The toxicity profile indicated devoid of major systemic toxicity with mild possibility of cytotoxicity. The in-vivo analysis showed that the Ibu-prodrug significantly (P < 0.001) reversed the changes induced by aluminum chloride and restored histomorphological features in brain tissue. ConclusionThe findings suggested that the ibuprofen conjugate might possess the potential to manage the complications of AD. The action appears to be mediated through inhibition of beta-secretase and acetylcholinesterase activities. More studies might aid in identifying a specific therapeutic intervention that is still lacking in the treatment of AD.

Pyridazine derivatives as selective COX-2 inhibitors: A review on recent updates.

Selective cyclooxygenase (COX)-2 inhibitors have several advantages over nonselective COX inhibitors (nonsteroidal anti-inflammatory drugs[NSAIDs]), including the absence of adverse effects (renal and hepatic disorders) associated with the long-term use of standard NSAIDs, as well as an improved gastrointestinal profile. The pyridazine nucleus is regarded as a promising scaffold for the development of powerful COX-2 inhibitors, particularly when selectively functionalized. This article summarizes some methods for the synthesis of pyridazine derivatives. Furthermore, it covers all of the pyridazine derivatives that have appeared as selective COX-2 inhibitors, making it useful as a reference for the rational design of novel selective COX-2 inhibitors.

A176 ASSOCIATIONS OF ANTIBIOTICS, HORMONAL THERAPIES, ORAL CONTRACEPTIVES, AND LONG-TERM NSAIDS WITH INFLAMMATORY BOWEL DISEASE: RESULTS FROM THE PROSPECTIVE URBAN RURAL EPIDEMIOLOGY (PURE) STUDY

A176 ASSOCIATIONS OF ANTIBIOTICS, HORMONAL THERAPIES, ORAL CONTRACEPTIVES, AND LONG-TERM NSAIDS WITH INFLAMMATORY BOWEL DISEASE: RESULTS FROM THE PROSPECTIVE URBAN RURAL EPIDEMIOLOGY (PURE) STUDY

P856 Associations of antibiotics, hormonal therapies, oral contraceptives, and long-term NSAIDs with Inflammatory Bowel Disease: results from the Prospective Urban Rural Epidemiology (PURE) study

Abstract Background Several medications have been considered to contribute to the aetiology of inflammatory bowel disease (IBD). This study assessed the association between medication use and risk of developing IBD using the Prospective Urban Rural Epidemiology (PURE) cohort. Methods This was a prospective cohort study of 133,137 individuals between the ages of 20-80 from 24 countries. Country-specific validated questionnaires documented baseline and follow-up medication use. Participants were followed prospectively at least every 3 years. The main outcome was development of IBD, including Crohn’s disease (CD) and ulcerative colitis (UC). Short-term (baseline but not follow-up use) and long-term use (baseline and subsequent follow-up use) was evaluated. Results are presented as adjusted odds ratios (aOR) with 95% confidence intervals (CI). Results During the median follow-up of 11.0 years [interquartile range (IQR) 9.2-12.2], we recorded 571 incident cases of IBD (143 CD and 428 UC). Higher risk of incident IBD was associated with baseline antibiotic use [aOR: 2.81 (95% CI: 1.67-4.73), p=0.0001] and hormonal medication use [aOR: 4.43 (95% CI: 1.78-11.01), p=0.001]. Among females, previous or current oral contraceptive use was also associated with IBD development [aOR: 2.17 (95% CI: 1.70-2.77), p=5.02E-10]. NSAID users were also observed to have increased risk of IBD [aOR: 1.80 (95% CI: 1.23-2.64), p=0.002], which was driven by long-term users [aOR: 5.58 (95% CI: 2.26-13.80), p&amp;lt;0.001]. All significant results were consistent in direction for CD and UC with low heterogeneity. Conclusion Antibiotics, hormonal medications, oral contraceptives, and long-term NSAID use were associated with increased odds of incident IBD after adjustment for covariates.

Evaluation of the England Community Pharmacy Quality Scheme (2018–2019 and 2019–2020) in reducing harm from NSAIDs in older patients

IntroductionNon-steroidal anti-inflammatory drugs (NSAIDs) are widely used for their analgesic and anti-inflammatory action, but the gastrointestinal (GI) adverse effects are a known cause of preventable harm. A medication safety audit...

Drug utilization, clinical and economic outcomes of patients with osteoarthritis of the hip and/or knee treated with long-term use of traditional NSAIDs, topical NSAIDs, and COX-2 inhibitors

Objectives To describe and compare baseline characteristics, healthcare and drug utilization, and negative clinical outcomes of commercially-insured patients diagnosed with OA of the hip and/or knee who initiated treatment on traditional oral NSAIDs (tNSAIDs), topical NSAIDs, or cyclooxygenase-2 inhibitors (COX-2s). Methods A commercial claims database (1/2012–3/2017) was used to identify patients ≥18 years old, with ≥2 diagnoses of hip and/or knee OA, and ≥90 days supply of NSAIDs. Patients were assigned to cohorts based on the type of NSAID initially prescribed and observed in the 6 months before (baseline) and 36 months after (follow-up) the date of their first NSAID prescription after the first OA diagnosis. Analyses estimated baseline demographic and clinical characteristics and follow-up period drug utilization. Logistic regressions assessed the risk of gastrointestinal (GI) and acute renal failure (ARF) events. Results tNSAIDs were the most frequently prescribed treatment. During the follow-up period, less than 15% of patients prescribed tNSAIDs switched to either COX-2s or topical NSAIDs and 37% of patients prescribed a COX-2 and 56% of patients prescribed a topical NSAID switched to tNSAIDs. GI and ARF events during the follow-up period ranged from 7.3–8.1% and 8.0–11.0%, respectively, across cohorts. The tNSAIDs and COX-2s cohorts had increased risk of both types of events relative to patients prescribed topical NSAIDs, controlling for other characteristics. Conclusions Analyses characterize the long-term real-world utilization of NSAIDs and associated outcomes for patients with OA of the hip and/or knee. Study results highlight the likelihood of switching and the risk of negative clinical outcomes associated with long-term use.

Effect of lateral wedged insole shoe in knee osteoarthritis: A 12 month randomized controlled trial

Introduction: Knee osteoarthritis (OA) is a chronic degenerative musculoskeletal condition that imposes a major healthcare burden due to considerable pain, disability and loss of quality of life especially among the older adults. Most knee OA researchers have focused on tertiary management strategies i.e pain relief with effective drug therapies (Non steroidal anti inflammatory drugs, chondroitin supplements etc). However, long-term use of NSAIDS have significant side effects and are expensive. With the exception of knee joint arthroplasty, typically reserved for end-stage disease, there is no definitive cure for osteoarthritis. Accordingly, there is an urgent need for conservative treatment modalities, that not only alleviate painful symptoms of OA, but also reduce the progression of the degenerative pathology over time. Patients with knee OA usually show major involvement in only one compartment; medial tibiofemoral compartment being more common than the lateral compartment. The lateral wedge shoe insole is an orthotic device, which is hypothesized to reduce the moment arm of the ground reaction force vector relative to the knee joint center during walking. They are an inexpensive and feasible treatment modality, that has shown to reduce medial knee load. Materials and Methods: 80 patients with bilateral medial compartment osteoarthritis of knee were included in the present study. They were randomly divided into two groups ; Group A (n = 40) included patients who were given lateral wedged insole shoes and Group B (n = 40) included those who were given normal flat soled shoes. All patients who fulfilled the inclusion and exclusion criteria were recruited for the study. The present study was carried between January 2020 to January 2021 in Krishna Institute Of Medical Sciences, “Deemed to be University” Karad. Severity of pain using WOMAC score, FTA using plain knee radiograph in AP view and frequency of intake of NSAIDS were calculated at the start of study, thereafter at each follow up every 2 months up to 12 months. Results: At the initial 2nd month follow up group A patients showed significant reduction in severity pain scale (66.74+/-19.44) as compared to group B (72.78+/-17.04), but neither of group A or group B showed any significant change in remaining variable characters (p>0.005). At the end of 12 months follow up assessment, Group A patients showed a marked reduction in severity of pain (average 46.8+/-16.24) as compared to Group B (mean 59.26+/-18.74). Patients in Group A showed significant decrease in the frequency of intake of NSAIDS for pain relief as compared to patients in Group B (p

In Vitro and In Silico Evaluation of New 1,3,4-Oxadiazole Derivatives of Pyrrolo[3,4-d]pyridazinone as Promising Cyclooxygenase Inhibitors

Since long-term use of classic NSAIDs can cause severe side effects related mainly to the gastroduodenal tract, discovery of novel cyclooxygenase inhibitors with a safe gastric profile still remains a crucial challenge. Based on the most recent literature data and previous own studies, we decided to modify the structure of already reported 1,3,4-oxadiazole based derivatives of pyrrolo[3,4-d]pyridazinone in order to obtain effective COX inhibitors. Herein we present the synthesis, biological evaluation and molecular docking studies of 12 novel compounds with disubstituted arylpiperazine pharmacophore linked in a different way with 1,3,4-oxadiazole ring. None of the obtained molecules show cytotoxicity on NHDF and THP-1 cell lines and, therefore, all were qualified for further investigation. In vitro cyclooxygenase inhibition assay revealed almost equal activity of new derivatives towards both COX-1 and COX-2 isoenzymes. Moreover, all compounds inhibit COX-2 isoform better than Meloxicam which was used as reference. Anti-inflammatory activity was confirmed in biological assays according to which title molecules are able to reduce induced inflammation within cells. Molecular docking studies were performed to describe the binding mode of new structures to cyclooxygenase. Investigated derivatives take place in the active site of COX, very similar to Meloxicam. For some compounds, promising druglikeness was calculated using in silico predictions.

Factors Influencing the Serum Uric Acid in Gout with Cerebral Infarction.

Background Although the relationship between gout and cardiovascular has been well demonstrated, there is little information about the difference between gout with cerebrovascular disease and cardiovascular disease. In this study, the differences between gout with cerebral infarction (gout+CI) and gout with coronary heart disease (gout+CHD) and related factors that affect serum uric acid (sUA) levels in gout+CI were investigated by a cross-sectional study. Method The patients from Jiangxi Provincial People's Hospital with gout+CHD, gout+CI, and gout with coronary heart disease and cerebral infarction (gout+CHD+CI) between 2016 and 2020 were included in this study, and the medical record data were collected and analyzed. Results We observed significant differences in age, drinking, hypertension, long-term use of diuretics and NSAIDs, sUA, CRE, and blood glucose in patients with gout+CHD and gout+CI. The sUA level was significantly positively correlated with smoking, CRE, and TG in the gout+CI group and was only positively correlated with CRE in the gout+CHD group and the gout+CHD+CI group (p < 0.05). Interestingly, the sUA level was only negatively correlated with the age and gender in the gout+CI group (p < 0.05). After excluding factors with no significant statistical effect, only age, gender, smoking, CRE, and TG were included in the multiple linear regression model. It suggested that smoking, CRE, and TG are positively correlated with the sUA level, while age was negatively correlated with the sUA level. Conclusions There are many discrepancies in clinical characteristics between gout+CHD patients and gout+CI patients, especially that the factors that affect UA levels are significantly different. The data also suggested that uric acid-lowering therapy may need to be strengthened in the young gout+CI patients with a history of smoking.

Basic Pharmacological Characterization of EV-34, a New H2S-Releasing Ibuprofen Derivative.

Background: Cardioprotective effects of H2S are being suggested by numerous studies. Furthermore, H2S plays a role in relaxation of vascular smooth muscle, protects against oxidative stress, and modulates inflammation. Long-term high-dose use of NSAIDs, such as ibuprofen, have been associated with enhanced cardiovascular risk. The goal of the present work is the synthesis and basic pharmacological characterization of a newly designed H2S-releasing ibuprofen derivative. Methods: Following the synthesis of EV-34, a new H2S-releasing derivative of ibuprofen, oxidative stability assays were performed (Fenton and porphyrin assays). Furthermore, stability of the molecule was studied in rat serum and liver lysates. H2S-releasing ability of the EC-34 was studied with a hydrogen sulfide sensor. MTT (3-(4,5-dimethylthiazol 2-yl)-2,5-(diphenyltetrazolium bromide)) assay was carried out to monitor the possible cytotoxic effect of the compound. Cyclooxygenase (COX) inhibitory property of EV-34 was also evaluated. Carrageenan assay was carried out to compare the anti-inflammatory effect of EV-34 to ibuprofen in rat paws. Results: The results revealed that the molecule is stable under oxidative condition of Fenton reaction. However, EV-34 undergoes biodegradation in rat serum and liver lysates. In cell culture medium H2S is being released from EV-34. No cytotoxic effect was observed at concentrations of 10, 100, 500 µM. The COX-1 and COX-2 inhibitory effects of the molecule are comparable to those of ibuprofen. Furthermore, based on the carrageenan assay, EV-34 exhibits the same anti-inflammatory effect to that of equimolar amount of ibuprofen (100 mg/bwkg). Conclusion: The results indicate that EV-34 is a safe H2S releasing ibuprofen derivative bearing anti-inflammatory properties.

Medication use among participants in a clinical trial of massage for chronic neck pain.

Background and Hypothesis: &#x0D; Chronic neck pain is a common problem in veterans and is treated with NSAIDS and other analgesics. Massage is gaining traction due to patient demand, and concerns of long-term use of opioids and NSAIDS. We evaluated the use of analgesics and psychotropics among veterans in a clinical trial of massage for chronic neck pain. We hypothesized that analgesic use would be common and change over time. &#x0D; Project Methods: &#x0D; This is a retrospective chart review study of patients enrolled in the TOMCATT trial. The TOMCATT trial addressed biological, psychological, and social aspects to the treatment of chronic neck pain. Eligible patients were Veterans with chronic neck pain at the Richard L. Roudebush VA Medical Center in Indianapolis. The medications assessed by reviewing the pharmacy records embedded in the VA’s EMR were acetaminophen, NSAIDS, muscle relaxants, opioids, topical analgesics, antidepressants, benzodiazepines, and anxiolytics. Patient medication use was assessed for 9 months during the trial. &#x0D; Results: &#x0D; Of the 235 veterans reviewed 33 were female and 202 were male. 11% of the patients were not prescribed medication during their trial. At kickoff date, 24% were prescribed acetaminophen, 29% NSAIDS, 40% muscle relaxants, 20% opioids, and 34% topical analgesics. At 9 months, those prescribed analgesics changed only slightly. Also, at kickoff date 35% were on antidepressants, 6% on benzodiazepines, and 5% on anxiolytics. These medications did not change much by 9-months. &#x0D; Conclusion and Potential Impact &#x0D; Analgesics and antidepressants/anxiolytics were frequently prescribed among participants in this clinical trial. The most prescribed analgesics were muscle relaxants and topical analgesics. Overall, analgesic use did not change much over the course of the trial. In future work, we will monitor the continued use of meds to see if muscle relaxants and topicals remain the most used analgesics.

121. Effects of long-term opioid vs long-term NSAID use prior to lumbar spinal fusion

BACKGROUND CONTEXT Chronic low back pain continues to be the leading cause of pain and disability in the United States. There are diverse therapeutic interventions to ameliorate the pain, ranging from pharmaceuticals to surgery. Many patients have been using NSAIDs and opioid analgesics to initially manage their pain, but long-term use of both have been associated with many deleterious effects. PURPOSE The current study compares the associated costs and postoperative complications following lumbar spinal fusion between patients who are long-term current users of opioid analgesics and patients who are long-term current users of NSAIDs. STUDY DESIGN/SETTING Retrospective cohort analysis using the 2010-2016 National Readmission Database. PATIENT SAMPLE Using the 2010-2016 National Readmission Database, we conducted a retrospective cohort analysis of 31,670 patients who received a lumbar spinal fusion surgery and were either diagnosed as long-term current users of opioid analgesics (n=7,663) or long-term current users of NSAIDs (n=24,007). Comorbidities and demographics were controlled between the two groups. OUTCOME MEASURES Associated costs and postoperative complications. METHODS We then collected all of the individuals that had a nonelective readmission (Opioids, 13.5%, n=1,034; NSAIDs, 9.6%, n=2,302) and analyzed associated costs and postoperative complications including surgical site/wound infection, UTI, postoperative pain, osteomyelitis, thromboembolism, sepsis, pneumonia, pseudarthrosis, novel lumbar pathology, nervous system complications, need for revision surgery, and death. Statistical analysis was conducted in R. Tukey multiple comparisons of means and Welch two sample t-test were used to compare complications and costs by surgical approach. RESULTS Long-term current users of opioid analgesics had significantly higher total charges at their primary lumbar fusion surgery ($174,321.59±$149,861.10) compared to the long-term current NSAID users ($112,095.00±$83,212.89) (p CONCLUSIONS Long-term current users of opioid analgesics had significantly higher costs and longer lengths of stay at the primary lumbar fusion, and significantly more postoperative complications with higher costs at the nonelective readmissions compared to the long-term NSAID users. Long-term NSAID users had significantly higher rates of UTI and thromboembolic events, whereas long-term opioid analgesic users had significantly higher rates of infection and death following lumbar spinal fusion. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.