Nonselective Nonsteroidal Anti-inflammatory Drugs Research Articles

Acute back pain: Diagnostic and therapeutic algorithms

The problem of diagnosis and treatment of acute back pain is discussed. Information concerning the etiology, pathogenesis, classification, clinic, diagnostic methods and principles of treatment of this pathology is presented. Special attention is paid to non-selective non-steroidal antiinflammatory drugs acting on both types of cyclooxygenase, which are the drug of choice for the treatment of vertebrogenic pain syndromes.

A Study of Prescribing Patterns for Non-Steroidal Anti-Inflammatory Drugs in a Tertiary Care Teaching Hospital

Analgesics, including nonsteroidal anti-inflammatory drugs, are a commonly prescribed group of drugs in clinical practice for the management of pain and inflammation. This study was carried out to evaluate the prescribing pattern for nonsteroidal anti-inflammatory drugs in the tertiary care teaching hospital. A prospective cross sectional study was conducted in the orthopaedic department of a tertiary care teaching hospital from February to December 2017. The institutional ethical committee approved the study. Patients of both genders were included in the study. Patients treated with at least one nonsteroidal anti-inflammatory drug in the outpatient department of orthopaedics were included. The prescription was compared with World Health Organization drug prescribing indicators to compare selective and nonselective nonsteroidal anti-inflammatory drugs associated with the treatment also concurrent prescription of gastro protective agents. The data collected was analysed by descriptive statistics. Chi-Square test was used to compare the difference between the two groups. A p value of <0.05 was considered significant. Out of 500 prescriptions included in the study, the total number of drugs prescribed was 1098, of which were nonsteroidal anti-inflammatory drugs. Based on the World Health Organization’s drug use indicators, the average number of drugs per encounter was 2.19 % and the average number of nonsteroidal antiinflammatory drugs per encounter was 1.38 %. Out of all the nonsteroidal anti-inflammatory drugs prescribed, 428 (62.20 %) were from National List of Essential Medicine India 2015 and 678 (98.5 %) nonsteroidal anti-inflammatory drugs were prescribed by generic name. Among the study population, only 40 % of patients were prescribed Proton Pump Inhibitors along with nonsteroidal anti-inflammatory drugs. Proton Pump Inhibitors are effective in ulcer prophylaxis in their standard dose. The present study concluded that among cyclooxygenase-1 inhibitors, Diclofenac was the most commonly prescribed nonsteroidal anti-inflammatory drugs from the national list of essential medicine. The most frequently prescribed cyclooxygenase-2 inhibitor in this study was Etoricoxib. The percentage of analgesic prescribed by generic name was excellent. However, the average number of drugs per prescription deviated from the World Health Organization’s rational drug use indicator. The use of gastro protective agents needs to be rationalised with nonsteroidal anti-inflammatory drugsy

A Machine Learning Approach to Identify Predictors of Potentially Inappropriate Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) Use in Older Adults with Osteoarthritis.

Evidence from some studies suggest that osteoarthritis (OA) patients are often prescribed non-steroidal anti-inflammatory drugs (NSAIDs) that are not in accordance with their cardiovascular (CV) or gastrointestinal (GI) risk profiles. However, no such study has been carried out in the United States. Therefore, we sought to examine the prevalence and predictors of potentially inappropriate NSAIDs use in older adults (age > 65) with OA using machine learning with real-world data from Optum De-identified Clinformatics® Data Mart. We identified a retrospective cohort of eligible individuals using data from 2015 (baseline) and 2016 (follow-up). Potentially inappropriate NSAIDs use was identified using the type (COX-2 selective vs. non-selective) and length of NSAIDs use and an individual’s CV and GI risk. Predictors of potentially inappropriate NSAIDs use were identified using eXtreme Gradient Boosting. Our study cohort comprised of 44,990 individuals (mean age 75.9 years). We found that 12.8% individuals had potentially inappropriate NSAIDs use, but the rate was disproportionately higher (44.5%) in individuals at low CV/high GI risk. Longer duration of NSAIDs use during baseline (AOR 1.02; 95% CI:1.02–1.02 for both non-selective and selective NSAIDs) was associated with a higher risk of potentially inappropriate NSAIDs use. Additionally, individuals with low CV/high GI (AOR 1.34; 95% CI:1.20–1.50) and high CV/low GI risk (AOR 1.61; 95% CI:1.34–1.93) were also more likely to have potentially inappropriate NSAIDs use. Heightened surveillance of older adults with OA requiring NSAIDs is warranted.

Cross-reactive hypersensitivity to NSAIDs: Experience of a Tunisian allergology center

BackgroundThe accurate diagnosis of cross-reactive reactions (CRR) to nonsteroidal anti-inflammatory drugs (NSAIDs) depends on a careful history and oral drug challenge. In this study, we report the result of a new procedure implemented in Tunisian allergology center to explore CRR to NASIDs in patients with immediate hypersensitivity (IHS) to NSAIDs. MethodsOur structured protocol using oral provocation tests (OPTs) was based on the latest advances in the literature. This protocol was tested in patients with a clinical history of IHS reactions to one or more NSAIDs and referred to the pharmacology department of Sfax (Tunisia) between 2012 and 2018. Patients were classified into 5 subgroups: an ASA subgroup, a multiple NSAIDs subgroup, a single non-selective NSAID subgroup, a paracetamol subgroup, and a celecoxib subgroup. ResultsA total of 34 patients were enrolled. Personal history of atopy was found in 26 (76.5%). A diagnosis of CRR to NSAIDs was made in 24 patients (70.6%): 6 patients in the ASA subgroup, 12 patients in the multiple NSAIDs subgroup, 4 patients in the single non-selective NSAID subgroup, 1 patient in the paracetamol subgroup and 1 patient in the celecoxib subgroup. Regarding safe alternatives in patients with CRR to NSAIDs (n=24), prevalence of cross-reactivity to paracetamol or celecoxib was found in 20% and 27.3% of patients with confirmed CRR to NSAIDs, respectively. ConclusionOur structured protocol based on standardized oral provocation tests helps physicians to prescribe a suitable drug in patients with a history of IHS reactions to NSAIDs.

Perioperative anesthesia. Features of anesthesia for patients with different surgeries and traumas

Background. Chronic postoperative and post-traumatic pain is included in the new edition of the International Classification of Diseases, which should become valid on 01.01.2022. Routine adherence to specialized differentiated evidence-based protocols for perioperative management of patients is the best way to optimize perioperative analgesia. The patient and his relatives should be informed about the possibility of postoperative pain (POP) and treatment options. It is advisable to use multimodal analgesia (MMA) with non-pharmacological methods to eliminate POP.&#x0D; Objective. To describe modern points of view on perioperative analgesia.&#x0D; Materials and methods. Analysis of literature data on this topic.&#x0D; Results and discussion. Analgesics are divided into antinociceptive drugs (hyperalgetics (morphine and μ-agonists) and antihyperalgetics – paracetamol, nonsteroidal anti-inflammatory drugs (NSAID), glucocorticoids, nefopam, tramadol) and non-antinociceptive antihyperalgetics (ketamine, gabapentine, topical anesthetics, clonidine, adenosine, neostigmine). Whenever possible, every anesthesiologist should take a multimodal approach. In the absence of contraindications, all patients should receive NSAID around the clock, including cyclooxygenase-2 inhibitors or acetaminophen (paracetamol). Intravenous paracetamol has a number of advantages over oral one. With the infusion of paracetamol (Infulgan, “Yuria-Pharm”), the time to achieve clinically significant analgesia is only 8 minutes, and to achieve maximum anesthesia – 15 minutes. Preoperative intravenous paracetamol has convincingly demonstrated an opioid-sparing effect in various surgical interventions (joint replacement, bariatric surgery, surgery for head and neck tumors) and delivery. The financial and economic feasibility of treatment with intravenous paracetamol has been proven. Additionally, the administration of regional blockades with topical anesthetics should be considered. It is also advisable to use pregabalin or gabapentin. The choice of drug, dose, route of administration and duration of therapy should be individualized. Intramuscular administration of analgesics should be avoided. In neuropathic POP, first-line drugs include tricyclic antidepressants, norepinephrine and serotonin reuptake inhibitors, antiepileptics, topical anesthetics (bupivacaine – Longocaine, “Yuria-Pharm”), second-line – opioids, tramadol, and third-line – mexiletine, NMDA-receptor antagonists, capsaicin. It should be noted that bupivacaine is 2-3 times more effective than lidocaine and 6-12 times more effective than novocaine. Local anesthetics can be used for infiltration anesthesia, blockade, intraperitoneal injection and direct infusion into the wound. Dexmedetomidine, which also provides sedation and additional analgesia, can be used to prolong sensory and motor anesthesia with bupivacaine. Analgesia in different interventions is slightly different. Thus, in total joint arthroplasty, a single blockade of the adductor canal is effective. When restoring the rotator cuff, it is advisable to use an arthroscopic approach, paracetamol (Infulgan), NSAID, dexamethasone and regional anesthesia. In spinal surgery, postoperative MMA involves the use of cold compresses, pregabalin, cyclobenzaprine, tramadol, if necessary – oxycodone. In total mastectomy, gabapentin and paracetamol should be prescribed before surgery, and opioids, ondansetron, and/or lorazepam on demand – after surgery. After abdominal hysterectomy, in severe pain opioids are used in combination with cyclooxygenase-2 inhibitors or non-selective NSAID, in mild pain – cyclooxygenase-2 inhibitors or non-selective NSAID in combination with paracetamol and, if necessary, weak opioids. Postoperative management of women after caesarean section involves the use of oral NSAID and paracetamol, opioids (rescue analgesia) and long-term infusions of local anesthetics into the wound.&#x0D; Conclusions. 1. Anesthesia plays a leading role in accelerated postoperative rehabilitation programs. 2. When choosing an approach to analgesia one should take into account the area of intervention. 3. Rational reduction in the opioids amount is achieved through balanced MMA. 4. The most basic components of MMA include NSAID, paracetamol and regional techniques.

Risk of Intracranial Hemorrhage With Concomitant Use of Antidepressants and Nonsteroidal Anti-inflammatory Drugs: A Nested Case-Control Study.

Whereas previous studies found that concomitant antidepressant and nonsteroidal anti-inflammatory drug (NSAIDs) use may increase the risk of gastrointestinal bleeding, either drug alone increases the risk of intracranial hemorrhage (ICH). To assess the risk for ICH in patients on concomitant treatment with antidepressants and NSAIDs. This was a nested case-control study using national insurance claims data in Taiwan between 2005 and 2013. Drug exposure was measured and compared during 3 time windows: 1 to 30, 31 to 60, and 61 to 90 days before the index date, which is the date of the ICH event. Both traditional and newer-generation antidepressants were considered in this study. Patients exposed to both antidepressants and NSAIDs 1 to 30 days before the index date presented a 50% increased odds of developing ICH (OR: 1.53; 95% CI: 1.31-1.80) compared with patients receiving antidepressants alone. Specifically, the concomitant use of nonselective NSAIDs and antidepressants increased these odds compared with antidepressants alone (OR: 1.56; 95% CI: 1.31-1.84), but using a selective cyclooxygenase-2 inhibitor with antidepressant did not alter ICH risk. Regarding antidepressant class, newer-generation antidepressants generally increase the odds of developing ICH by 60% when used concomitantly with NSAIDs. Our results suggested that the concomitant use of antidepressants and NSAIDs was associated with an increased odds of developing ICH. NSAIDs, especially nonselective NSAIDs, and serotonergic antidepressants played an important role in this risk. Given the prevalent use of these 2 classes of drugs, this potential drug interaction deserves more attention.

Effects of atorvastatin and aspirin on post-stroke epilepsy and usage of levetiracetam.

Objective:Atorvastatin and aspirin have been used in treating different forms of epilepsy. However, their effect on post-stroke epilepsy (PSE) still needs to be validated by large-scale clinical studies. In addition, their impact on the use of the antiepileptic drug levetiracetam for post-stroke epilepsy remains to be explored. Thus, the aim of this study was to further evaluate the effect of atorvastatin and aspirin on PSE and their effect on the usage of the antiepileptic drug levetiracetam in PSE patients.Methods:Patients, aged 65 to 85 years, with newly diagnosed post-ischemic stroke epilepsy from August 30, 2014 to August 30, 2018 were included in the study, with the exclusion of those with coexisting conditions.Results:Initially, 1321 patients were included, and 780 remained in the study at the 1-year follow-up. During the study, atorvastatin treatment with or without aspirin reduced the number of clinical epileptic episodes in PSE patients. It also reduced the dosage of levetiracetam and achieved better control of epilepsy compared to levetiracetam mono-treatment. Aspirin co-treatment with levetiracetam did not result in a significant improvement. However, the combination of aspirin with atorvastatin significantly reduced the number of seizures compared to atorvastatin treatment alone.Conclusion:Atorvastatin and aspirin co-treatment with levetiracetam can reduce epilepsy in PSE patients and reduce the dosage of levetiracetam required for effective control of PSE.

GASTROPROTECTIVE EFFECT OF ONION PEEL (Allium Cepa L. Var Ascalonicum) EXTRACT ON WISTAR RATS INDUCED BY MEFENAMIC ACID

Non Steroidal Anti-inflammatory Drugs (NSAID) have been implicated in the etiology of gastritis. Mefenamic acid is a non-selective NSAID used to treat mild to moderate pain and inflammation. Mefenamic acid induces gastritis through its inhibition of prostaglandin that results in increased HCl secretion, decreased mucin, and bicarbonate ion production. This study aimed to investigate the gastroprotective effect of onion peel extract (OPE) against mefenamic acid-induced gastritis. In this study, the gastroprotective effect of OPE was examined through mucosal integrity scoring. A total of 28 male Wistar rats were divided into 4 groups, normal (Group 1), mefenamic acid+NaCMC 0,5% (Group 2), mefenamic acid+OPE 600mg/kg body weight (Group 3), and mefenamic acid+OPE 1200mg/kg body weight (Group 4). All rats were sacrificed on day 15 then all gasters were collected. Histopathological examination was done under a microscope with 100X magnification. Administration of mefenamic acid without OPE at all significantly increased gastric mucosal damage (p&lt;0,05). Administration of OPE 1200mg/kg body weight significantly decreased gastric mucosal damage (p&lt;0,05). Group 4 shows no significant difference (p=0,66) with the normal group (Group 1). This indicates that administration of OPE 1200mg/kg body weight per oral ameliorates mefenamic acid-induced gastritis.

Effects of Therapies on Cardiovascular Events in Ankylosing Spondylitis: A Systematic Review and Meta-Analysis.

IntroductionNon-steroidal anti-inflammatory drugs (NSAIDs) and tumor necrosis factor inhibitors (TNFi) are the most common therapies used in AS, however, the associated long-term cardiovascular risk is unclear. We performed a systematic review and meta-analysis on the association of therapies used for ankylosing spondylitis (AS) such as NSAIDs and TNFi on cardiovascular events (CVE) in AS.MethodsA comprehensive search was performed from database inception to May 29, 2020 to include controlled studies of AS treated with NSAIDs, oral small molecules, or biologics reporting CVE. Study-specific risk ratios (RR) were pooled using a random effects model.ResultsNine non-randomized studies from 1570 studies screened fulfilled inclusion criteria. Among NSAID users as a whole versus no NSAIDs, no increased risk of CVE (composite outcome) was observed; however, the risk of cerebrovascular accident was significantly lower (RR 0.58, 95% CI 0.37–0.93, I2 = 66%). Cox-2 inhibitor use was associated with reduced risk of all CVE (RR 0.48, 95% CI 0.33–0.70, I2 = 0%). Non-selective NSAIDs were not associated with any increased/decreased risk of any CVE. Meta-analysis of three studies of MI did not show a significant association with TNFi (RR 0.88, 95% CI 0.57–1.35, I2 = 76%).ConclusionsIn this meta-analysis of non-randomized studies, NSAID users as a whole and users of non-selective NSAIDs did not seem to have a higher risk of any CVE. Limited data suggest a lower risk of composite CVE outcome with Cox-2 inhibitors, unlike the increased risk reported in the general population. No significant association between TNFi and MI was observed. The certainty in evidence was very low due to all studies being observational. More studies are needed to study the association between TNFi use and CVE in general to evaluate a possible protective role in AS.Electronic Supplementary MaterialThe online version of this article (10.1007/s40744-020-00248-x) contains supplementary material, which is available to authorized users.

The critical role of piperamide derivative D4 in the regulation of inflammatory response by the microglia and astrocytic glial cells

Acute and chronic inflammation in the central nervous system plays a critical role in the development of neurodegenerative disorders. Various pro-inflammatory cytokines, chemokines, and enzymes such as TNF-α, IL1-β, IL-6, COX-1, COX-2, iNOS, IKK, and inducible nitric oxide are expressed in several signalling pathways, and mediate the neuroinflammatory process. ROS and NF-kB nuclear translocation are the two fundamental pathways involved in neuroinflammatory pathogenesis in neuronal and glial cells. In recent years several compoundswere designed to affect the neuroinflammation and suppress neurodegenerative process. Derivatives of natural products (NPs) attract the most attention of drug developers and industries due to their safety and lesser side effects in comparison with generic drugs. One of the most well-known NP is piperine, which is a yellow crystalline alkaloid extracted from black and white pepper. Recently, we developed a novel piperine derivative (((2E,4E)-5-(benzo[d][1,3]dioxol-5-yl)-N-(4-(hydroxymethyl)phenyl)penta-2,4-dienamide, D4) to enhance the specificity and efficacy of the base molecule. Next, we evaluated the potential anti-inflammatory properities of D4 in CHME3 and SVG cell-lines corresponding to human microglia and astrocytes, respectively. Our results indicated that D4 inhibited NF-kB translocation pathway, and significantly reduced transcript and protein levels of pro-inflammatory cytokines in comparison with Aspirin, as a well-known non-selective NSAID. Furthermore, in silico study showed excellent D4 bioavailability in oral administration. The results of the present study suggest a novel molecule with high anti-neuroinflammatory potency for further pre-clinical tests and pharmacological drug investigation.

NSAIDs-dependent adaption of the mitochondria-proteasome system in immortalized human cardiomyocytes

The progressive consumption growth of non-steroidal anti-inflammatory drugs (NSAIDs) has progressively raised the attention toward the gastrointestinal, renal, and cardiovascular toxicity. Increased risk of cardiovascular diseases was strictly associated with the usage of COX-2 selective NSAIDs. Other studies allowed to clarify that the cardiovascular risk is not limited to COX-2 selective but also extended to non-selective NSAIDs, such as Diclofenac and Ketoprofen. To date, although a less favorable cardiovascular risk profile for Diclofenac as compared to Ketoprofen is reported, the mechanisms through which NSAIDs cause adverse cardiovascular events are not entirely understood. The present study aimed to evaluate the effects of Ketoprofen in comparison with Diclofenac in immortalized human cardiomyocytes. The results obtained highlight the dose-dependent cardiotoxicity of Diclofenac compared to Ketoprofen. Despite both drugs induce the increase in ROS production, decrease of mitochondrial membrane potential, and proteasome activity modulation, only Diclofenac exposure shows a marked alteration of these intracellular parameters, leading to cell death. Noteworthy, Diclofenac decreases the proteasome 26S DC and this scenario may be dependent on the intracellular overload of oxidized proteins. The data support the hypothesis that immortalized human cardiomyocytes exposed to Ketoprofen are subjected to tolerable stress events, conversely Diclofenac exposition triggers cell death.

Synthesis and Biological Evaluation of Benzodioxol Derivatives as Cyclooxygenase Inhibitors

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely used therapeutics; they are competitive inhibitors of cyclooxygenase (COX), the enzyme which mediates the conversion of arachidonic acid to inflammatory prostaglandins. Objective: In this study, new benzodioxol derivatives with different core cycles and functional groups (i.e., aryl acetate, aryl acetic acid and diazepine) were designed, synthesized, identified and evaluated for their analgesic and anti-inflammatory activity, as a preliminary screening study to identify the most potent and more selective groups. Methods: The synthesized compounds were identified using FTIR, HRMS, 1H-NMR and 13C-NMR, and evaluated for their inhibitory activity against ovine COX-1 and COX-2 using an in vitro cyclooxygenase (COX) inhibition assay kit. Results: Six compounds were synthesized as a preliminary screening study to identify which was the most potent and more selective group towards COX-2 versus COX-1, compared to ketoprofen as non-selective NSAIDs. The compounds have three different groups: aryl acetate, aryl acetic acid and diazepine. The results showed that the most potent compound against the COX- 1 enzyme was 4b (which has diazepine and 2-chlorophenyl) with IC50 = 0.363 μM, and the selectivity ratio of 4b was found to be better than ketoprofen. In contrast, compound 4a (which has diazepine and 3-chlorophenyl) was the most selective with a COX-1/COX-2 ratio value of 0.85 in comparison with a ketoprofen ratio value of 0.20. Conclusion: In general, the synthesized library has moderate activity against both enzymes (i.e., COX-1 and COX-2). Moreover, all six compounds have better COX-2 inhibition selectivity compared to the commercial drug ketoprofen.

Comparative efficacy of traditional non-selective NSAIDs and selective cyclo-oxygenase-2 inhibitors in patients with acute gout: a systematic review and meta-analysis

ObjectiveTo assess the comparative efficacy of traditional non-steroidal anti-inflammatory drugs (NSAIDs) and selective cyclo-oxygenase-2 inhibitors in patients with acute gout.DesignSystematic review and meta-analysis.Data sourcesMedline, Web of Science, China National Knowledge...

Practice Advisory on the Appropriate Use of NSAIDs in Primary Care.

Cyclo-oxygenase (COX)-2 selective and nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) are important in managing acute and chronic pain secondary to inflammation. As a greater understanding of the risks of gastrointestinal (GI), cardiovascular (CV) and renal events with NSAIDs use has emerged, guidelines have evolved to reflect differences in risks among NSAIDs. Updated guidelines have yet to reflect new evidence from recent trials which showed similar CV event rates with celecoxib compared to naproxen and ibuprofen, and significantly better GI tolerability for celecoxib. This practice advisory paper aims to present consensus statements and associated guidance regarding appropriate NSAID use based on a review of current evidence by a multidisciplinary group of expert clinicians. This paper is especially intended to guide primary care practitioners within Asia in the appropriate use of NSAIDs in primary care. Following a literature review, group members used a modified Delphi consensus process to determine agreement with selected recommendations. Agreement with a statement by 75% of total voting members was defined a priori as consensus. For low GI risk patients, any nonselective NSAID plus proton pump inhibitor (PPI) or celecoxib alone is acceptable treatment when CV risk is low; for high CV risk patients, low-dose celecoxib or naproxen plus PPI is appropriate. For high GI risk patients, celecoxib plus PPI is acceptable for low CV risk patients; low-dose celecoxib plus PPI is appropriate for high CV risk patients, with the alternative to avoid NSAIDs and consider opioids instead. Appropriate NSAID prescription assumes that the patient has normal renal function at commencement, with ongoing monitoring recommended. In conclusion, appropriate NSAID use requires consideration of all risks.

Risk of Major Adverse Cardiovascular Events Associated with Concomitant Use of Antidepressants and Non-steroidal Anti-inflammatory Drugs: A Retrospective Cohort Study.

Both antidepressants and non-steroidal anti-inflammatory drugs (NSAIDs) have been reported to affect platelet aggregation, blood pressure and heart rate. Despite the high prevalence of the combined use of antidepressants and NSAIDs, there is limited evidence on the potential risk of major adverse cardiovascular events (MACE) associated with their use. The objective of this study was to assess the association between concomitant antidepressant and NSAID use and MACE. We conducted a retrospective cohort study using South Korea's nationwide healthcare database. The study cohort was defined as those with new prescriptions for antidepressants and NSAIDs between 2004 and 2015. Exposure was assessed as time varying into four discrete periods: non-use, antidepressant use, NSAID use and concomitant use. Our primary outcome was MACE, a composite of haemorrhagic and thromboembolic events; secondary outcomes were the individual events of MACE. A multivariable Cox proportional hazards model was used to estimate hazards ratios with 95% confidence intervals. We also performed subgroup analyses by class of antidepressant/type of NSAIDs, age and sex. From 240,982 patients, 235,080, 4393 and 1509 patients were users of NSAIDs, antidepressants or both drugs at cohort entry, respectively. The cohort generated 2.1 million person-years of follow-up with 22,453 events of MACE (incidence rate 1.07 per 100 person-years). Compared with non-use, concomitant use (hazard ratio 1.13, 95% confidence interval 1.01-1.26) and NSAID-only use (1.05, 1.001-1.10) were positively associated with MACE, while antidepressant-only use showed a negative association (0.91, 0.83-0.99). Concomitant use increased the individual risk of haemorrhagic stroke (1.46, 1.06-2.00), ischaemic stroke (1.22, 1.07-1.38) and heart failure (1.19, 1.02-1.38), but showed a protective effect on cardiovascular deaths (0.36, 0.21-0.62). Of the six possible combinations of antidepressants and NSAIDs by their classes, only concomitant use of tricyclic antidepressants and non-selective NSAIDs was positively associated with MACE (1.26, 1.09-1.47). The risk of MACE remained elevated with concomitant use among those aged ≥ 45years (1.14, 1.01-1.29) and male patients (1.19, 1.01-1.42). Concomitant use of antidepressants and NSAIDs moderately elevated the risk of MACE, of which the observed risk appears to be driven by the concomitant use of tricyclic antidepressants and non-selective NSAIDs. Thus, healthcare providers should take precaution when co-prescribing these drugs, weighing the potential benefits and risks associated with their use.

Initial analgesic prescriptions for osteoarthritis in the United Kingdom, 2000-2016.

To examine trends in the initial prescription of commonly-prescribed analgesics and patient- as well as practice-level factors related to their selection in incident OA. Patients consulting with incident clinical OA between 2000-2016 were identified within The Health Improvement Network in the United Kingdom (UK) general practice. Excluded were patients who had history of cancer or were prescribed the analgesics of interest within 6 months before diagnosis of OA. Initial analgesic prescription included oral non-selective NSAID, oral selective cyclooxygenase-2 inhibitor, topical NSAID, paracetamol, topical salicylate or oral/transdermal opioid within 1 month after OA diagnosis. ∼44% of patients with incident OA (n = 125696) were prescribed one of these analgesics. Incidence of oral NSAID prescriptions decreased whereas other analgesic prescriptions, including oral opioid prescriptions, increased (all P-for-trend < 0.001). Patients with a history of gastrointestinal disease were more likely to receive topical NSAIDs, paracetamol or oral/transdermal opioids. Only 38% of patients with history of gastrointestinal disease and 21% of patients without it had co-prescription of gastroprotective agent with oral NSAIDs. Oral/transdermal opioid prescription was higher among the elderly (≥65 years), women, obesity, current smoker, and patients with gastrointestinal, cardiovascular or chronic kidney disease. Prescription of oral opioids increased with social deprivation (P-for-trend < 0.05) and was highest in Scotland, whereas transdermal opioid prescription was highest in Northern Ireland (all P-for-homogeneity-test < 0.05). The initial prescription pattern of analgesics for OA has changed over time in the UK. Co-prescription of gastroprotective agents with oral NSAIDs remains suboptimal, even among those with prior gastrointestinal disease.

The Efficacy and Safety of Nonsteroidal Anti-Inflammatory Drugs in Total Joint Arthroplasty: Systematic Review and Direct Meta-Analysis

BackgroundNonsteroidal anti-inflammatory drugs (NSAIDs) have become widely used to manage perioperative pain following total joint arthroplasty (TJA). The purpose of our study is to evaluate the efficacy and safety of NSAIDs in support of the combined clinical practice guidelines of the American Association of Hip and Knee Surgeons, American Academy of Orthopaedic Surgeons, Hip Society, Knee Society, and American Society of Regional Anesthesia and Pain Management. MethodsDatabases including MEDLINE, EMBASE, and the Cochrane Central Registry of Controlled Trials were searched for studies published prior to November 2018 on NSAIDs in TJA. Studies included after a systematic review evaluated through direct comparisons and/or meta-analysis, including qualitative and quantitative heterogeneity testing, to evaluate effectiveness and safety of NSAIDs. ResultsAfter critical appraisal of 2921 publications, 25 articles represented the best available evidence for inclusion in the analysis. Oral selective cyclooxygenase (COX)-2 and non-selective NSAIDs and intravenous ketorolac safely reduce postoperative pain and opioid consumption during the hospitalization for primary TJA. Administration of an oral selective COX-2 NSAID reduced postoperative opioid consumption after discharge from TKA. ConclusionStrong evidence supports the use of an oral selective COX-2 or non-selective NSAID and intravenous ketorolac as adjunctive medications to manage postoperative pain during the hospitalization for TJA. Although no safety concerns were observed, prescribers need to remain vigilant when prescribing NSAIDs.

Risk of Nonunion with Nonselective NSAIDs, COX-2 Inhibitors, and Opioids.

Cyclooxygenase-2 (COX-2) has been found to be important for fracture-healing in animal models, raising concerns about use of nonsteroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 inhibitors after fractures. We evaluated associations of NSAIDs, COX-2 inhibitors, and opioids with nonunion after long-bone fracture. Using private health insurance claims data from Optum's de-identified Clinformatics Data Mart database from January 1, 2000, to September 30, 2015, we identified adults with a single long-bone fracture or commonly paired long-bone fractures who had 1 year of available follow-up data. Using multivariable logistic regression models, we examined associations between NSAID, COX-2-inhibitor, or opioid prescription fills after the fracture and the risk of nonunion within 1 year, defined as a nonunion diagnosis with a procedure to treat the nonunion. A nonunion diagnosis with a procedure to treat the nonunion was identified after 2,996 (0.9%) of the 339,864 fracture episodes, with rates varying by fracture site. The risk of that outcome was greater in patients who had filled COX-2-inhibitor prescriptions (adjusted odds ratio = 1.84 [95% confidence interval = 1.38 to 2.46]) or opioid prescriptions (1.69 [1.53 to 1.86]), but not in patients who had filled nonselective-NSAID prescriptions (1.07 [0.93 to 1.23]) after the fracture. Results were similar when the outcome definition was changed to just a nonunion diagnosis. COX-2 inhibitors, but not nonselective NSAIDs, were associated with a greater risk of nonunion after fracture. Opioids were also associated with nonunion risk, although patients filling prescriptions for opioids may have had more severe fractures. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

COMBINED NSAID-INDUCED LESIONS OF THE GASTROINTESTINAL TRACT: FREQUENCY, CLINICAL AND ENDOSCOPIC FEATURES, TREATMENT

Purpose: to study the frequency of lesions of the gastrointestinal tract in NSAIDs users with rheumatoid diseases, as well as to increase the effectiveness of therapeutic and preventivestrategies. Matherials and methods: 112 patients (50 men, 62 women) with various rheumatic diseases and long-term NSAIDs were examined. All patients underwent upper and lower endoscopy, in some patients video capsule endoscopy of the small intestine was also performed. Results: аccording to the data obtained, the most common NSAID-induced gastrointestinal damage was NSAID-gastropathy, observed in 43 % of all NSAID users. 68.6 % of patients with NSAID gastropathy during video capsule endoscopy were additionally diagnosed with NSAID enteropathy, and 9 % of patients with NSAID gastropathy were also diagnosed with NSAID colopathy, which were significantly more common in patients receiving non-selective NSAIDs. Combined lesions of all sections of the gastrointestinal tract, the gastroduodenal zone, small and large intestine, were observed in a significant number of patients — in 27 % of cases, most often in patients with rheumatic diseases who took non-selective NSAIDs. A generalization of the existing experience in the treatment of patients with NSAID-induced gastrointestinal lesions showed that in the case of a combination of NSAID-gastropathy and NSAID-enteropathy, the preferred preventive strategies should be H. pylori eradication, the use of rebamipide and the use of selective COX-2 inhibitors. With the combination of NSAIDs with concomitant excess bacterial growth syndrome and NSAIDs-colopathy, rifaximin, rebamipid and sulfalazine are effective. Conclusions: the data obtained confirm the high prevalence of combined lesions of the proximal and distal gastrointestinal tract in rheumatological patients, which may indicate a universal damaging effect of NSAIDs on the entire gastrointestinal tract.

PIH10 COST-EFFECTIVENESS ANALYSIS OF IMRECOXIB, CELECOXIB AND DICLOFENAC IN OSTEOARTHRITIS IN CHINA

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely prescribed to patients with osteoarthritis (OA), it was assumed that both cyclooxygenase-2 (COX-2) inhibitor and non-selective NSAIDs have similar efficacy but associated with different rates of adverse events. Imrecoxib was approved by the Chinese Food and Drug Administration (CFDA) in 2011, which is a COX-2 inhibitor. This study is aimed to access the cost-effectiveness of celecoxib, imrecoxib and diclofenac for managing OA in Chinese aged ≥55 years and ≥65 years based on the real-world data from China.