Use Of Nonsteroidal Anti-inflammatory Drugs Research Articles

Mitochondrial Stress Links Environmental Triggers with Pro-Inflammatory Signaling in Crohn's Disease.

Inflammatory Bowel Diseases (IBD) are a group of chronic, inflammatory disorders of the gut. The incidence and activity of IBD are determined by both genetic and environmental factors. Among these factors, polymorphisms in genes related to autophagy and the consumption of non-steroidal anti-inflammatory drugs (NSAIDs) have been consistently associated with IBD. We show that NSAIDs induce mitochondrial stress and mitophagy in intestinal epithelial cells. In an altered mitophagy context simulating that observed in IBD patients, NSAID-induced mitochondrial stress leads to the release of mitochondrial components, which act as Danger Associated Molecular Patterns with pro-inflammatory potential. Furthermore, colonic organoids from Crohn's disease patients and healthy donors show activation of the mitochondrial Unfolded Protein Response (UPRmt) upon treatment with ibuprofen. Finally, colon biopsies from Crohn's disease patients in remission or with low-to-moderate activity also show expression of genes involved in UPRmt, while patients with severe activity show no increase compared to healthy donors. Our results suggest the involvement of mitochondria in the mechanisms triggering inflammation in IBD after NSAID use. Moreover, our results highlight the clinical relevance of mitochondrial stress and activation of the UPRmt pathway in the pathophysiology of Crohn's disease.

Investigation of the association of long-term NSAID use with radiographic hip osteoarthritis over four to five years: Data from the OAI and CHECK studies

ObjectiveTo examine the relationship between long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) and the incidence and progression of radiographic hip osteoarthritis (RHOA), as well as the degeneration of individual radiographic features. MethodsWe analyzed data from the Osteoarthritis Initiative (OAI) and the Cohort Hip and Cohort Knee (CHECK) study. Our exposure was the number of years of NSAID use over a 4-to-5-year follow-up period. Our outcomes were the incidence and progression of RHOA over a 4-to-5-year follow-up as assessed using a modified Croft grade in OAI and the Kellgren-Lawrence (K/L) grade in CHECK. The incidence of RHOA was defined as having RHOA (grade ≥2) at follow-up and investigated in “incidence cohorts” of hips without RHOA at baseline (grade <2). The progression of RHOA was defined as an increase of ≥1 grade at follow-up from baseline and investigated in “progression cohorts” of hips with RHOA at baseline (grade ≥2). Additionally, we assessed the degeneration of nine specific radiographic features, such as joint space narrowing and osteophytes, defined by a grade increase of ≥1 ​at follow-up from baseline, in all cohorts. ResultsIn the incidence cohorts, there were 5153 hips in OAI and 1011 in CHECK; in the progression cohorts, there were 285 and 106 hips, respectively. There was no association between NSAID use and the outcomes investigated. ConclusionOver 4-to-5 years, long-term NSAID use showed no association with the incidence or progression of RHOA, or with the degeneration of individual radiographic features.

Causal effect of gut microbiota on Gastroduodenal ulcer: a two-sample Mendelian randomization study.

Gastroduodenal ulcers are associated with Helicobacter pylori infection and the use of nonsteroidal anti-inflammatory drugs (NSAIDs). However, the causal relationship between gastroduodenal ulcers and gut microbiota, especially specific gut microbiota, remains unclear. We conducted an analysis of published data on the gut microbiota and Gastroduodenal ulcer using genome-wide association studies (GWAS). Two-sample Mendelian randomization (MR) analysis was performed to determine the causal relationship between gut microbiota and Gastroduodenal ulcer. Sensitivity, heterogeneity, and pleiotropy analyses were conducted to confirm the accuracy of the research findings. Our study showed that the abundance of Enterobacteriaceae, Butyricicoccus, Candidatus Soleaferrea, Lachnospiraceae NC2004 group, Peptococcus, and Enterobacteriales was negatively correlated with the risk of Gastroduodenal ulcer. Conversely, the abundance of Streptococcaceae, Lachnospiraceae UCG010, Marvinbryantia, Roseburia, Streptococcus, Mollicutes RF9, and NB1n was positively correlated with the risk of Gastroduodenal ulcer. MR analysis revealed causal relationships between 13 bacterial genera and Gastroduodenal ulcer. This study represents a groundbreaking endeavor by furnishing preliminary evidence regarding the potentially advantageous or detrimental causal link between the gut microbiota and Gastroduodenal ulcer, employing Mendelian Randomization (MR) analysis for the first time. These discoveries have the potential to yield fresh perspectives on the prevention and therapeutic approaches concerning Gastroduodenal ulcer, with a specific focus on the modulation of the gut microbiota.

Use of non-steroidal anti-inflammatory drugs in renal transplant patients: A retrospective study.

Renal transplanted patients are often prescribed non-steroidal anti-inflammatory drugs (NSAIDs) for analgesic purposes. Considering the dearth of data, we carried out the present study to evaluate the use of various NSAIDs and the incidence of acute kidney injury (AKI) in transplant patients. A retrospective study amongst renal transplant patients prescribed at least one dose of NSAID was carried between January and December 2020 at the Department of Nephrology, Salmaniya Medical Complex, Kingdom of Bahrain. The patients' demographic details, serum creatinine values, and drug-related details were obtained. The Kidney Disease Improving Global Outcomes (KDIGO) criteria were used for defining AKI. Eighty-seven patients were included. Forty-three patients were prescribed diclofenac, 60 received ibuprofen, six received indomethacin, 10 were administered mefenamic acid, and 11 received naproxen. Due to multiple courses of NSAID prescription, a total of 70 prescriptions were identified for diclofenac, 80 for ibuprofen, six for indomethacin, 11 for mefenamic acid, and 16 for naproxen. No significant differences were observed in the absolute (p =0.08) and percent changes in serum creatinine (p =0.1) between the NSAIDs. Twenty-eight (15.2%) courses of NSAID therapy met the KDIGO criteria for AKI. Age (OR: 1.1, 95% CI: 1.007, 1.2; p =0.02), concomitant everolimus (OR: 483, 95% CI: 4.3, 54407; p =0.01), and mycophenolate + cyclosporine + azathioprine (OR: 63.4E+006, 95% CI: 203.2157 to 19.8E+012; p =0.005) administration were observed with significant risk of NSAID-induced AKI. We observed possible NSAID-induced AKI to an extent of around 15.2% in our renal transplant patients. No significant differences were observed in the incidence of AKI between various NSAIDs and none of them had either graft failure or death.

Phenotypic and metabolic adaptations of Rhodococcus cerastii strain IEGM 1243 to separate and combined effects of diclofenac and ibuprofen.

The increasing use of non-steroidal anti-inflammatory drugs (NSAIDs) has raised concerns regarding their environmental impact. To address this, understanding the effects of NSAIDs on bacteria is crucial for bioremediation efforts in pharmaceutical-contaminated environments. The primary challenge in breaking down persistent compounds lies not in the biochemical pathways but in capacity of bacteria to surmount stressors. In this study, we examined the biodegradative activity, morphological and physiological changes, and ultrastructural adaptations of Rhodococcus cerastii strain IEGM 1243 when exposed to ibuprofen, diclofenac, and their mixture. Our findings revealed that R. cerastii IEGM 1243 exhibited moderate biodegradative activity towards the tested NSAIDs. Cellular respiration assay showed higher metabolic activity in the presence of NSAIDs, indicating their influence on bacterial metabolism. Furthermore, catalase activity in R. cerastii IEGM 1243 exposed to NSAIDs showed an initial decrease followed by fluctuations, with the most significant changes observed in the presence of DCF and the NSAID mixture, likely influenced by bacterial growth phases, active NSAID degradation, and the formation of multicellular aggregates, suggesting potential intercellular synergy and task distribution within the bacterial community. Morphometric analysis demonstrated alterations in size, shape, and surface roughness of cells exposed to NSAIDs, with a decrease in surface area and volume, and an increase in surface area-to-volume ratio (SA/V). Moreover, for the first time, transmission electron microscopy confirmed the presence of lipid inclusions, polyphosphates, and intracellular membrane-like structures in the ibuprofen-treated cells. These results provide valuable insights into the adaptive responses of R. cerastii IEGM 1243 to NSAIDs, shedding light on the possible interaction between bacteria and pharmaceutical compounds in the environment.

Randomized Comparative Study of Analgesic Effects of Ilioinguinal and Iliohypogastric Nerve Block with Levobupivacaine (0.25%) versus Diclofenac Suppository in Pediatric Patients Undergoing Inguinal Herniotomy under General Anesthesia

Context: Pain management intraoperatively and postoperatively in the pediatric age group is a matter of concern. On the one hand, children are poorer at precisely conveying the extent of pain all the while being more susceptible to pain-related complications such as laryngospasm. On the other hand, children are less suited to use of potent opioids due to associated complications which can often lead to catastrophe. Therefore, a multimodal approach is desirable to optimize pain management in children. A nerve block is a highly effective and popular modality nowadays. In this single-blinded, parallel group, monocentric, and randomized protocol study, we have compared the efficacy of pain control achieved in the use of nonsteroidal anti-inflammatory drugs as analgesic versus iliohypogastric ilioinguinal (IIIH) nerve block in herniotomy in pediatric age group. Materials and Method: The parallel-group prospective study recruited 104 participants who were randomly allocated into two groups of 52 each, such that both groups received 1 mcg/kg fentanyl and sevoflurane during induction of GA. For analgesia, Group 2 was given diclofenac suppository intraoperative after induction of GA. Group 1 was given IIIH nerve block under nerve stimulator guidance for perioperative analgesia. Both groups were studied for the following parameters which included: time to get the 1st dose of rescue analgesic, total dose of rescue analgesic, visual analog scale (VAS) score, and hemodynamic parameters. Results: We observed that Group 1 showed a statistically significant difference in the form of longer duration of analgesia after surgery (9.67 ± 1.80 h vs. 6.35 ± 0.84 h) and lower total dose of rescue analgesic requirement (69.23 ± 2 [22.77] vs. 106.23 ± 2 [21.49]) while having a better hemodynamic profile and lower cumulative VAS score (7.71 ± 1.39 vs. 12.04 ± 1.72). Conclusion: Based on the above findings, we deduce that preincisional nerve stimulator-guided IIIH block by levobupivacaine (0.25%, 0.3 ml/kg) and rectal diclofenac (2 mg/kg) is both safe approaches to provide postoperative analgesia in pediatric inguinal herniotomy under general anesthesia. However, nerve stimulator-guided IIIH nerve block by levobupivacaine is a safe and better choice as it provides more intense analgesia for a longer duration compared to diclofenac suppository in the immediate postoperative period.

Novel sulindac derivatives for colorectal cancer chemoprevention that target cGMP phosphodiesterases to suppress Wnt/β-catenin transcriptional activity

&lt;p class="MsoNormal" style="margin-top: 6pt; line-height: 13pt; text-align: justify;"&gt;&lt;span lang="EN-US" style="font-size: 10pt; font-family: arial, helvetica, sans-serif;"&gt;Approximately 28 million individuals in the United States face the risk of developing precancerous colonic adenomas (polyps) and potentially progressing to colorectal cancer (CRC). While a promising strategy for CRC prevention involves pharmacological intervention, such as cancer chemoprevention or interception, currently, there are no FDA-approved drugs capable of preventing the formation or progression of adenomas to adenocarcinoma. Numerous clinical, epidemiological, and preclinical studies have offered compelling evidence supporting the efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) in CRC chemoprevention. However, the prolonged use of NSAIDs is not FDA-approved due to potential life-threatening toxicities resulting from cyclooxygenase (COX) inhibition and the depletion of physiological prostaglandins. Despite indications that the COX inhibitory activity of NSAIDs may not be essential for their antineoplastic effects, the absence of a well-defined target impeded the development of derivatives that do not inhibit COX. Earlier research suggests that the inhibition of cyclic guanosine monophosphate phosphodiesterase (cGMP PDE) may be responsible, at least in part, for the antineoplastic activity of the NSAID sulindac. This could potentially offer a novel target for CRC chemoprevention. To identify the cGMP PDE isozyme(s) contributing to the antineoplastic activity of sulindac, we synthesized a chemically diverse library of over 1500 compounds, all sharing the indene scaffold of sulindac. Subsequently, we screened these compounds for their impact on cancer cell growth and PDE inhibitory activity. From this screening, a series of lead compounds emerged. These compounds lacked COX-1 and COX-2 inhibitory activity, surpassing sulindac in potency to inhibit CRC cell growth. Importantly, they demonstrated greater selectivity by not affecting normal cell growth. Through chemical optimization, we identified several development candidates that selectively inhibit PDE5 and/or PDE10. These compounds activate cGMP/PKG signaling, suppressing Wnt/&amp;beta;-catenin transcription. This action counters the growth advantages resulting from APC or CTNNB1 mutations, which are responsible for most human CRCs. This review delves into the scientific literature supporting PDE5 and/or PDE10 as potential targets for CRC chemoprevention or interception. Our findings suggest a promising avenue for developing drugs that may effectively intervene in the progression of colorectal cancer, offering hope for improved preventive strategies in the future.&lt;/span&gt;&lt;/p&gt;

Novel sulindac derivatives for colorectal cancer chemoprevention that target cGMP phosphodiesterases to suppress Wnt/β-catenin transcriptional activity

&lt;p class="MsoNormal" style="margin-top: 6pt; line-height: 13pt; text-align: justify;"&gt;&lt;span lang="EN-US" style="font-size: 10pt; font-family: arial, helvetica, sans-serif;"&gt;Approximately 28 million individuals in the United States face the risk of developing precancerous colonic adenomas (polyps) and potentially progressing to colorectal cancer (CRC). While a promising strategy for CRC prevention involves pharmacological intervention, such as cancer chemoprevention or interception, currently, there are no FDA-approved drugs capable of preventing the formation or progression of adenomas to adenocarcinoma. Numerous clinical, epidemiological, and preclinical studies have offered compelling evidence supporting the efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) in CRC chemoprevention. However, the prolonged use of NSAIDs is not FDA-approved due to potential life-threatening toxicities resulting from cyclooxygenase (COX) inhibition and the depletion of physiological prostaglandins. Despite indications that the COX inhibitory activity of NSAIDs may not be essential for their antineoplastic effects, the absence of a well-defined target impeded the development of derivatives that do not inhibit COX. Earlier research suggests that the inhibition of cyclic guanosine monophosphate phosphodiesterase (cGMP PDE) may be responsible, at least in part, for the antineoplastic activity of the NSAID sulindac. This could potentially offer a novel target for CRC chemoprevention. To identify the cGMP PDE isozyme(s) contributing to the antineoplastic activity of sulindac, we synthesized a chemically diverse library of over 1500 compounds, all sharing the indene scaffold of sulindac. Subsequently, we screened these compounds for their impact on cancer cell growth and PDE inhibitory activity. From this screening, a series of lead compounds emerged. These compounds lacked COX-1 and COX-2 inhibitory activity, surpassing sulindac in potency to inhibit CRC cell growth. Importantly, they demonstrated greater selectivity by not affecting normal cell growth. Through chemical optimization, we identified several development candidates that selectively inhibit PDE5 and/or PDE10. These compounds activate cGMP/PKG signaling, suppressing Wnt/&amp;beta;-catenin transcription. This action counters the growth advantages resulting from APC or CTNNB1 mutations, which are responsible for most human CRCs. This review delves into the scientific literature supporting PDE5 and/or PDE10 as potential targets for CRC chemoprevention or interception. Our findings suggest a promising avenue for developing drugs that may effectively intervene in the progression of colorectal cancer, offering hope for improved preventive strategies in the future.&lt;/span&gt;&lt;/p&gt;

All-cause and immune checkpoint inhibitor-associated acute kidney injury in immune checkpoint inhibitor users: a meta-analysis of occurrence rate, risk factors and mortality.

Immune checkpoint inhibitors (ICIs) have been associated with acute kidney injury (AKI). However, the occurrence rate of ICI-related AKI has not been systematically examined. Additionally, exposure to proton pump inhibitors (PPIs) and non-steroidal anti-inflammatory drugs (NSAIDs) were considered as risk factors for AKI, but with inconclusive results in ICI-related AKI. Our aim was to analyse the occurrence rate of all-cause AKI and ICI-related AKI and the occurrence rates of severe AKI and dialysis-requiring AKI, and to determine whether exposure to PPIs and NSAIDs poses a risk for all-cause and ICI-related AKI. This study population was adult ICI recipients. A systematic review was conducted by searching MEDLINE, Embase and PubMed through October 2023. We included prospective trials and observational studies that reported any of the following outcomes: the occurrence rate of all-cause or ICI-related AKI, the relationship between PPI or NSAID exposure and AKI development or the mortality rate in the AKI or non-AKI group. Proportional meta-analysis and pairwise meta-analysis were performed. The evidence certainty was assessed using the Grading of Recommendations Assessment, Development and Evaluation framework. A total of 120 studies comprising 46417 patients were included. The occurrence rates of all-cause AKI were 7.4% (14.6% from retrospective studies and 1.2% from prospective clinical trials). The occurrence rate of ICI-related AKI was 3.2%. The use of PPIs was associated with an odds ratio (OR) of 1.77 [95% confidence interval (CI) 1.43-2.18] for all-cause AKI and an OR of 2.42 (95% CI 1.96-2.97) for ICI-related AKI. The use of NSAIDs was associated with an OR of 1.77 (95% CI 1.10-2.83) for all-cause AKI and an OR of 2.57 (95% CI 1.68-3.93) for ICI-related AKI. Our analysis revealed that approximately 1 in 13 adult ICI recipients may experience all-cause AKI, while 1 in 33 adult ICI recipients may experience ICI-related AKI. Exposure to PPIs and NSAIDs was associated with an increased OR risk for AKI in the current meta-analysis.

Associations between the use of common nonsteroidal anti-inflammatory drugs, genetic susceptibility and dementia in participants with chronic pain: A prospective study based on 194,758 participants from the UK Biobank

ObjectiveTo investigate the potential relationship between common nonsteroidal anti-inflammatory drugs (NSAIDs), genetic susceptibility and all-cause dementia (ACD), Alzheimer's disease (AD), and vascular dementia (VD) among individuals experiencing chronic pain. MethodsThis study was based on 194,758 chronic pain participants form UK biobank with a median follow-up of 13.7 years. Participants were categorized into different NSAIDs painkiller regimen groups: No NSAIDs group, Aspirin group, Ibuprofen group, Paracetamol group, and 2–3 NSAIDs group. Cox proportional risk models were used to examine the correlation between regular NSAIDs usage and the risk of ACD, AD, and VD. In addition, we further performed subgroup analyses and sensitivity analyses. Results1) Compared to the No NSAIDs group, the aspirin group (HR = 1.12, 95% CI:1.01–1.24, P < 0.05), the paracetamol group (HR = 1.15, 95% CI:1.05–1.27, P < 0.01), and the 2–3 NSAIDs group (HR = 1.2, 95% CI:1.08–1.33, P < 0.05) showed a higher risk of ACD. Furthermore, the 2–3 NSAIDs group was also associated with a higher risk of VD (HR = 1.39, 95% CI: 1.08–1.33, P < 0.05). 2) At high dementia GRS participants with chronic pain, the paracetamol group (HR = 1.2, 95% CI: 1.03–1.43, P < 0.05) and the NSAIDs group (HR = 1.3, 95% CI: 1.07–1.59, P < 0.05) were associated with a higher risk of ACD compared to the no painkiller group. 3) There was no significant association between ibuprofen use and higher risk of dementia. ConclusionIn individuals with chronic pain, the use of aspirin and paracetamol was associated with a higher risk of ACD, whereas the use of ibuprofen was not significantly associated with a higher risk of ACD.

The use of non-steroid anti-inflammatory drugs during radical resection correlated with the outcome in non-small cell lung cancer

AimsThe use of non-steroid anti-inflammatory drugs (NSAIDs) is conventional in management of postoperative pain in cancer patients, and further investigations have reported that some of these drugs correlated with the outcome in cancers. However, the prognostic value of the use of NSAIDs during surgery in non-small cell lung cancer (NSCLC) patients has been less addressed.MethodsNSCLC patients staged I–III are retrospectively enrolled, and the data of the use of NSAIDs during surgery are collected. Patients are divided into two subgroups according to the use intensity (UI) (low or high) of the NSAIDs, which was calculated by the accumulate dosage of all the NSAIDs divided by the length of hospitalization. The differences of the clinical features among these groups were checked. And the disease-free survival (DFS) and overall survival (OS) differences in these groups were compared by Kaplan–Meier analysis; risk factors for survival were validated by using a Cox proportional hazards model.ResultsThe UI was significant in predicting the DFS (AUC = 0.65, 95% CI: 0.57–0.73, P = 0.001) and OS (AUC = 0.70, 95% CI: 0.59–0.81, P = 0.001). Clinical features including type of resection (P = 0.001), N stages (P < 0.001), and TNM stages (P = 0.004) were significantly different in UI low (< 74.55 mg/day) or high (≥ 74.55 mg/day) subgroups. Patients in UI-high subgroups displayed significant superior DFS (log rank = 11.46, P = 0.001) and OS (log rank = 7.63, P = 0.006) than the UI-low ones. At last, the UI was found to be an independent risk factor for DFS (HR: 0.52, 95% CI: 0.28–0.95, P = 0.034).ConclusionsThe use of NSAIDs during radical resection in NSCLC patients correlated with the outcome and patients with a relative high UI has better outcome.

Trends of Antihypertensive, Antidiabetic, and Nonsteroidal Anti-Inflammatory Drugs Use among the Health Workers Cohort Study, Mexico 2004 to 2018.

Hypertension and type 2 diabetes (T2D) are the most prevalent noncommunicable diseases in Mexico and worldwide. According to international practice management guidelines, the principal chronic management therapy is daily oral medication. We aim to describe the trends of antihypertensive, antidiabetic, and nonsteroidal anti-inflammatory (NSAID) drugs use among the Mexican adult population from 2004-2018. We analyzed data from the Health Workers Cohort Study (HWCS) for males and females aged >18 years. We calculated the prevalence of chronic diseases and utilization for every kind of antihypertensive, antidiabetic, and NSAIDs (measured by self-reported utilization) at baseline and two follow-ups (2004, 2010, and 2017). Trends were analyzed using Fisher's exact test. Hypertension prevalence increased from 19.8 to 30.3%, higher than T2D prevalence from 7.0 to 12.8% through fourteen years of follow-up. Like the self-reported dual therapy, the proportion of patients using beta-blockers and angiotensin II receptor blockers increased. Regarding T2D, the prevalence of metformin utilization increased to 83.9%. The utilization of common NSAIDs, mainly for muscular pain, remained around 13 to 16%. Our findings showed a changing prevalence of drug utilization for hypertension and T2D between 2004 and 2018 and consistent use of NSAIDs in the adult Mexican population.

Non-steroidal Anti-inflammatory Drugs and Cyclooxygenase-2 Inhibitors Do Not Affect Healing After Rotator Cuff Repair: A Systematic Review and Meta-analysis

To determine whether non-steroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase-2 (COX-2) inhibitors affect healing rate, functional outcomes, and patient satisfaction after rotator cuff repair. Medline, EMBASE, PsychINFO and the Cochrane Library were searched for randomized controlled trials (RCTs) investigating the use of NSAIDs and COX-2 inhibitors after arthroscopic rotator cuff repair. Primary outcomes included healing and retear rate, determined by radiological imaging. Secondary outcomes included shoulder-specific outcome measures and the visual analog scale (VAS). Risk of bias was graded using the Cochrane risk-of-bias v2.0 tool. The GRADE framework was used to assess certainty of findings. Seven RCTs with a total of 507 patients were included (298 randomized to NSAID/COX-2 vs 209 randomized to control). NSAIDs use did not yield a difference in retear rate (P= .77). NSAIDs were shown to significantly reduce pain in the perioperative period (P= .01); however, no significant difference was present at a minimum of 6 months (P= .11). COX-2 inhibitors did not significantly reduce pain (P= .15). Quantitative analysis of ASES and UCLA scores showed NSAIDs significantly improved functional outcomes versus control (P= .004). COX-2 inhibitors did not significantly improve functional outcomes (P= .15). Two trials were deemed "low" risk of bias, four trials were graded to have "some concerns", and one trial was graded to have "high" risk of bias. Retear rate and functional PROMs were deemed to have "low" certainty. VAS pain scale was graded to have "moderate" certainty. This systematic review and meta-analysis indicates that NSAIDs do not affect healing rate after arthroscopic rotator cuff repair, but they do significantly improve postoperative pain and functional outcomes. No significant difference was seen in pain or functional outcomes with the use of COX-2 inhibitors. Level I, meta-analysis of randomized controlled trials.

Prevalence, awareness, and patterns of non-steroidal anti-inflammatory drug use among health science students in Palestine: a cross-sectional study

Despite the widespread use of nonsteroidal anti-inflammatory drugs (NSAIDs), many people lack sufficient awareness regarding their side effects and proper usage. Consequently, this study aimed to assess the knowledge, behavior, and usage patterns of NSAIDs among students enrolled in Palestinian health colleges. The study was conducted in December 2020 using a cross-sectional design, and a convenience sampling method was employed to enroll a total of 206 students. The questionnaire comprised seven sections, each containing approximately 5 to 10 closed-ended questions. Data were analyzed using version 21 of the Statistical Package for the Social Sciences (IBM-SPSS Statistics 21). The percentage of respondents who admitted that NSAIDs were used several times in the year was 35.9%. More than half of the students believed that NSAIDs were generally safe. Seventy-two percent of the students were aware that more than one type of NSAID at the same time increased the side effects. The median knowledge score of NSAID side effects was 9 [6.25–11] out of 13. The knowledge score increased significantly with age (p < 0.001), higher academic year (p < 0.001), and pharmacy and medicine specialties (p = 0.002). The college students surveyed in this study possess a general awareness of NSAIDs. Nonetheless, there remains a necessity to enhance their behavior and practices concerning the utilization of NSAIDs through the implementation of programmed educational strategies.

Assessing causality between osteoarthritis and gastrointestinal disorders: a Mendelian randomization study

The association between osteoarthritis (OA) and gastrointestinal disorders was found in observational studies. However, the causality is still elusive. A bidirectional Mendelian randomization (MR) analysis using genome wide association studies data was conducted to assess the causal association between OA and gastrointestinal diseases [including peptic ulcer disease (PUD), gastroesophageal reflux disease (GORD), and inflammatory bowel disease (IBD)]. A two-step MR (TSMR) was conducted between OA, gastrointestinal diseases and drugs to explore the mediating effects of non-steroidal anti-inflammatory drugs (NSAIDs) and opioids use. We used multivariable MR (MVMR) analysis to further validate the impact of prescription history on diseases. Results had statistical significance at a Bonferroni corrected P-value below 0.008. We observed that genetically predicted OA had a significant positive association with GORD [odds ratio (OR) = 1.26, P = 5e−05], but not with PUD or IBD. Regarding the other direction, gastrointestinal disorders as exposure had a null association with OA. Using TSMR, OA patients tended to increase the use of NSAIDs (OR = 1.45, P = 0.001) and opioids (OR = 1.77, P = 2e−05), but only the use of opioids increased the risk of GORD (OR = 1.43, P = 5e−09). Further MVMR analysis showed that the adverse effect of OA on GORD was significantly reduced after adjusting for opioids use (OR = 1.20, P = 0.038). This study provides evidence for the causal association between OA and increased risk of GORD, which is partly attributed to opioids use in OA patients but not NSAIDs.

Venous thromboembolism in users of hormonal contraception and non-steroidal anti-inflammatory drugs: a nationwide cohort study

Abstract Objective To study the influence of concomitant use of hormonal contraception and non-steroidal anti-inflammatory drugs (NSAIDs) on the risk of venous thromboembolism. Design: Nationwide cohort study. Setting: Denmark through national registries. Participants: All 15-49-year-old women living in Denmark between the years 1996-2017 with no medical history of any venous or arterial thrombotic event, cancer, thrombophilia, hysterectomy, bilateral oophorectomy, sterilisation, or infertility treatment. Main outcome measure: A first-time discharge diagnosis of lower-limb deep venous thrombosis or pulmonary embolism. Results Among 2.0 million women followed for 21.0 million person-years, 8710 venous thromboembolic events occurred. Compared to non-use of NSAIDs, use of NSAIDs was associated with an adjusted incidence rate ratio of venous thromboembolism of 8.1 (95% confidence interval (CI) 6.9 to 9.6) in women not using hormonal contraception, 12.1 (10.6 to 13.9) in women using high-risk hormonal contraception, 8.7 (6.5 to 11.6) in users of medium-risk hormonal contraception, and 5.1 (2.9 to 9.1) with low/no-risk hormonal contraception. Compared to non-use of NSAIDs, the number of extra venous thromboembolic events per 100,000 one-week NSAID treatments was 4 in women not using hormonal contraception, 18 in women using high-risk hormonal contraception, 9 in users of medium-risk hormonal contraception, and 2 in women using low/no-risk hormonal contraception. Conclusions NSAID use was positively associated with the development of venous thromboembolism. The association was stronger in women concomitantly using high-risk hormonal contraceptives and weaker in women using low/no-risk hormonal contraception. Women requiring both hormonal contraception and regular use of NSAIDs should be advised accordingly.

Influence of cholesterol levels on NSAID-associated risks after myocardial infarction: a nationwide population-based cohort study

Abstract Introduction Non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat pain, fever, and inflammation, but they can increase the risk of recurrent myocardial infarction (MI), ischemic stroke, atrial fibrillation, and death in patients with MI. Consequently, the European Society of Cardiology warns against using NSAIDs in patients with manifest cardiovascular disease and in high-risk individuals, such as those with dyslipidemia. However, no study has investigated whether NSAID-associated cardiovascular risks differ according to patients’ low-density lipoprotein cholesterol (LDL-C) levels. Purpose To examine whether LDL-C levels influence the cardiovascular risk associated with NSAID use after first-time MI. Methods Using Danish health registries, we conducted a population-based cohort study of all adult patients with a first-time MI hospitalization during 2010–2020 with an LDL-C value before discharge. Based on the latest LDL-C value, we categorized patients into a low and high LDL-C group (&amp;lt;3 vs. ≥3 mmol/L). We used multivariate Cox regression to compute adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for the association between NSAID use (modelled in time-varying manner) and a major adverse cardiovascular event (MACE), defined as a composite of recurrent MI, ischemic stroke, and all-cause death. We repeated the analysis by changing the cut-off value for LDL-C to 1.8 and 1.4 mmol/L. Results We followed 50,573 patient with a first-time MI for a mean of 3.5 years (66% males, median age of 68 years. During NSAID use, 521 patients experienced a MACE: 312 in the low LDL-C group and 209 in the high LDL-C group. The HRs for MACE comparing NSAID use with non-use were 1.21 (1.11–1.32) overall, 1.19 (1.06–1.33) in the low LDL-C group, and 1.23 (1.07–1.41) in the high LDL-group. The HRs in the low and high LDL-C groups were 1.09 (0.88–1.34) vs. 0.94 (0.74–1.19) for recurrent MI, 0.97 (0.66–1.41) vs. 1.27 (0.86–1.87) for ischemic stroke, and 1.22 (1.07–1.39) vs. 1.54 (1.30–1.83) for all-cause death. Changing the cut-off value for LDL-C to 1.8 and 1.4 mmol/L showed consistent results. Conclusion In patients with a first-time MI, NSAID use was associated with an increased risk of MACE. The LDL-C level did not influence the association between NSAID use and MACE, but it might influence the association between NSAID use and all-cause death. Thus, healthcare providers should be mindful of the increased cardiovascular risk associated with NSAID use in patients with previous MI, regardless of LDL-C values.

Cardiovascular safety of non-steroidal anti-inflammatory drug use for gout: A Danish nationwide case-crossover study

Abstract Background Gout is associated with increased cardiovascular risk through inflammation and shared risk factors. Gout attacks are treated with a uric-lowering drug, such as allopurinol, and an anti-inflammatory drug, such as a non-steroidal anti-inflammatory drug (NSAID). Thus, NSAIDs could be both cardiovascular beneficial, due to their anti-inflammatory actions, and cardiovascular hazardous, due to their prothrombotic, hypertensive, and proarrhythmic actions. Yet, no study has examined the cardiovascular safety of NSAIDs for the treatment of gout. Purpose To examine the risk of major adverse cardiovascular events (MACEs) associated with NSAID use in gout patients. Methods We conducted a nationwide, population-based case-crossover study of all Danes ≥18 years of age with first-time gout during 1997–2020, who experienced a MACE (myocardial infarction, ischemic stroke, congestive heart failure, atrial fibrillation or flutter, or all-cause death) (n=103,522). The patients were identified either via a hospital diagnosis for gout (12%) or via a filling of an allopurinol prescription (88%). The exposures were use of NSAIDs overall and according to subtype (ibuprofen, naproxen, or diclofenac). An individual was considered exposed from the time of a filled prescription until the end of a use period, estimated from average use of two tablets per day. In the case-crossover design, we used four reference dates at 120, 180, 240, and 300 days before the outcome. An individual was considered exposed if the use period covered a reference date or the outcome date. We used the Mantel-Haenszel method to calculate odds ratios (ORs) with 95% confidence intervals (CIs) of the association between NSAID use and MACE. Results NSAID use was overall associated with a 15% decreased risk of MACE (OR=0.85, 95% CI: 0.83–0.87). The ORs of the association between NSAID use and the individual cardiovascular events were 0.91 (95% CI: 0.84–0.99) for myocardial infarction, 0.88 (95% CI: 0.81–0.95) for ischemic stroke, 0.89 (95% CI: 0.83–0.94) for congestive heart failure, 0.80 (95% CI: 0.75–0.85) for atrial fibrillation or flutter, and 0.77 (95% CI: 0.75–0.80) for all-cause death. The decreased risk of MACE was observed for use of ibuprofen (OR=0.91, 95% CI: 0.88–0.95) and naproxen (OR=0.78, CI: 0.70–0.86), but not for use of diclofenac (OR=1.03, 95% CI: 0.97–1.09). Conclusions In patients with first-time gout, use of ibuprofen and naproxen was associated with a slightly decreased cardiovascular risk, whereas diclofenac was not.

The effectiveness of direct oral anticoagulant therapy on stroke severity and functional prognosis for very elderly cardioembolic stroke patients at high bleeding risk

Abstract Background The All Nippon AF In the Elderly (ANAFIE) Registry showed that taking any DOACs was associated with reduced stroke/systemic embolisms and was not associated with increased major bleeding in very elderly (≥80 years) patients with nonvalvular atrial fibrillation (NVAF) at high bleeding risk (1). However, the relationship between very elderly (≥80 years) cardioembolic stroke (CES) patients with NVAF at high bleeding risk and direct oral anticoagulant (DOAC) therapy before stroke onset remains unknown. Methods During a 10-year period from April 2011 to March 2021, 364 CES patients (≥80 years) with NVAF admitted to our hospital within 48 hours after stroke onset and with a modified Rankin Scale (mRS) score of 0 or 1 before onset were studied. High bleeding risk was defined as having any following factors; a bleeding history, renal dysfunction (creatinine clearance &amp;lt;30 ml/min), low body weight (≤45 kg), use of antiplatelet or nonsteroidal anti-inflammatory drugs. They were divided into two groups: high bleeding risk group (H group) (n=214; median 85 years [82-88]; 144 women [67%]) and non-high bleeding risk group (Non-H group) (n=150; median 84 years [82-87]; 69 women [46%]). We compared stroke severity between the two groups and evaluated effect of DOAC treatment on stroke severity and functional outcome. Results CHADS₂ score was significantly higher in the H group than in the Non-H group (median 4 [3-4] versus 3 [2-4], p=0.002). NIHSS (National Institutes of Health Stroke Scale) score on admission and proportion of mortality (mRS:6) were relatively higher in H group than in Non-H group, but there were no significant differences among the two groups. However, mRS score at discharge was worse in the H group than in the Non-H group (median 4 [2-5] versus 3 [1-4], p=0.002). The patients in the H group were further divided into three groups based on the treatment with OAC before stroke onset: DOAC therapy (n=20), no-OAC (n=148) and warfarin therapy (n=46). The number of patients with NIHSS (≥8) on admission and mRS (≥5) at discharge were 8 (40%), 104 (70%), and 30 (65%) (p=0.03) and 3 (15%), 60 (41%) and 23 (50%) (p=0.03), respectively. Multivariate analysis confirmed that DOAC therapy had a lower odds ratio (OR) for severe stroke (NIHSS ≥8) on admission (OR to no-OAC=0.22; 95% confidence interval [CI]=0.08-0.62; p=0.005) and poor functional outcome (mRS ≥5) at discharge (OR=0.20; 95% CI=0.05-0.80; p=0.02), when no-OAC was used as a reference after adjusting for confounders. Conclusion Very elderly (≥80 years) CES patients with NVAF at high bleeding risk have severe CES than those at non-high bleeding risk. However, DOAC therapy before stroke onset may be associated with reduced stroke severity on admission and poor functional outcome at discharge in very elderly (≥80 years) CES patients with NVAF at high bleeding risk.

Knowledge About and the Use of Oral Nonsteroidal Anti-inflammatory Drugs Among Patients With Rheumatic Disorders in Saudi Arabia: A Cross-Sectional Study

Knowledge About and the Use of Oral Nonsteroidal Anti-inflammatory Drugs Among Patients With Rheumatic Disorders in Saudi Arabia: A Cross-Sectional Study