Nonsteroidal Anti-inflammatory Drugs Users Research Articles

Identification of some novel amide conjugates as potent and gastric sparing anti-inflammatory agents: In vitro, in vivo, in silico studies and drug safety evaluation

Today, usage of NSAIDs (nonsteroidal anti-inflammatory drugs) is very common. However, it has been proven by many studies that NSAIDs with free carboxylic acid group damage the GI (gastrointestinal) system. Our aim was to mask the acidic groups of NSAIDs to prevent or reduce their side effects while preserving their pharmacological effects. In this study, new amide derivatives of known NSAIDs, compounds 11–20, were synthesized to investigate their analgesic and anti-inflammatory effects using in vivo models. While compound 11 showed the most remarkable anti-inflammatory activity by 60.9% inhibition value at 200 mg/kg dose, compounds 11, 12, 15 and 18 had almost the same analgesic activity to that of acetylsalicylic acid (100 mg/kg) and flurbiprofen (100 mg/kg). In addition, all test compounds used at high dose (200 mg/kg, p.o) did not show any acute toxicity. COX-1 and COX-2 inhibition properties of all compounds were measured by biochemical methods and the interaction of the most active compounds with COX enzymes is elucidated by computer-assisted virtual screening methods. It was determined by in vitro enzyme inhibition studies that compound 11 and 13, synthesized from selective COX-1 inhibitors dexketoprofen and flurbiprofen, are selective COX-2 inhibitors. Moreover, compounds 11–13 were found to be non-mutagenic according to the mutagenicity assay using Salmonella TA98 and TA100 strains with and without metabolic activation. Finally, the prediction of ADMET profile and drug-likeness properties of compounds 11–20 were examined and the obtained results were evaluated.

Proton pump inhibitors increase the risk of nonsteroidal anti-inflammatory drug-related small bowel injury: A Systematic Review with Meta-analysis.

Conflicting results exist on the association between proton-pump inhibitor (PPI) and nonsteroidal anti-inflammatory drug (NSAID)-related small bowel damage. Aims: To determine whether PPIs increased the risk of NSAID-related small bowel damage by meta-analysis. Methods: A systematic electronic search in PubMed, Embase, and Web of Science was conducted from the time the database was created until 31 March 2022 for studies reporting associations between PPI use and outcomes, including the endoscopy-verified prevalence of small bowel injury, mean number of small bowel injuries per patient, change in hemoglobin level, and risk of small bowel bleeding in subjects taking NSAIDs. Meta-analytical calculations for odds ratio (OR) and mean difference (MD) were performed with the random-effects model and interpreted with 95% confidence intervals (CIs). Results: Fourteen studies comprising 1996 subjects were included. Pooled analysis demonstrated that concomitant use of PPIs significantly increased the prevalence and number of endoscopy-verified small bowel injuries (prevalence: OR=3.00; 95% CI: 1.74-5.16; number: MD=2.30; 95% CI: 0.61-3.99) and decreased hemoglobin levels (MD=-0.50 g/dL; 95% CI: -0.88 to -0.12) in NSAID users but did not change the risk of small bowel bleeding (OR=1.24; 95% CI: 0.80-1.92). Subgroup analysis demonstrated that PPIs significantly increased the prevalence of small bowel injury in subjects taking nonselective NSAIDs (OR=7.05; 95% CI: 4.70-10.59, 4 studies, I2=0) and COX-2 inhibitors (OR=4.00; 95% CI: 1.18-13.60, 1 study, no calculated I2) when compared to COX-2 inhibitors alone.Conclusion: PPIs increased the risk of NSAID-related small bowel damage, and the clinical significance of higher prevalence of small bowel injuries should be studied in future.

Heart Failure Following Anti-Inflammatory Medications in Patients With Type 2 Diabetes Mellitus

BackgroundFluid retention and endothelial dysfunction have been related to use of nonsteroidal anti-inflammatory drugs (NSAIDs), and type 2 diabetes mellitus (T2DM) has been linked to both a decline in kidney function and subclinical cardiomyopathy. ObjectivesThe authors hypothesized that short-term use of NSAIDs could lead to subsequent development of incident heart failure (HF) in patients with T2DM. MethodsUsing nationwide Danish registers, we identified patients diagnosed with T2DM during 1998 to 2021 and included patients without previous HF, rheumatic disease, or use of NSAIDs 120 days before diagnosis. Associations between NSAIDs and first-time HF hospitalization were investigated using a case-crossover design with 28-day exposure windows, and ORs with 95% CIs were reported. ResultsIncluded were 331,189 patients with T2DM: 44.2% female, median age of 62 years (IQR: 52-71 years); 23,308 patients were hospitalized with HF during follow-up, and 16% of patients claimed at least 1 NSAID prescription within 1 year. Short-term use of NSAIDs was associated with increased risk of HF hospitalization (OR: 1.43; 95% CI: 1.27-1.63), most notably in subgroups with age ≥80 years (OR: 1.78; 95% CI: 1.39-2.28), elevated hemoglobin (Hb) A1c levels treated with 0 to 1 antidiabetic drug (OR: 1.68; 95% CI: 1.00-2.88), and without previous use of NSAIDs (OR: 2.71; 95% CI: 1.78-4.23). ConclusionsNSAIDs were widely used and were associated with an increased risk of first-time HF hospitalization in patients with T2DM. Patients with advanced age, elevated HbA1c levels, and new users of NSAID seemed more susceptible. These findings could guide physicians prescribing NSAIDs.

Role of Helicobacter Pylori Infection and Nonsteroidal Anti-Inflammatory Drug Use in Bleeding Peptic Ulcers

Most peptic ulcers and their complications are caused by Helicobacter pylori and nonsteroidal anti-inflammatory drugs (NSAIDs). Objective: To characterize the bleeding peptic ulcers features. Methods: This prospective study was carried out on 124 cases in the Department of Gastroenterology, Lady Reading Hospital in collaboration with Pharmacology Unit of Khyber Medical University, Peshawar from July 2018 to June 2020. All the patients were categorized into four groups: Positive H. pylori and no NSAID history (Group I), Positive H. pylori and NSAID use (Group-II), Negative H. pylori and NSAID user (Group-III), and Negative H. pylori and no NSAID history (Group-IV). Data analysis was carried out in SPSS version 26. Results: Of the total 124 cases, the prevalence of positive and negative H. pylori infection was 77.4% (n=96) and 22.6% (n=28) respectively. The number of patients in group I, II, III, and IV patients were 80 (64.5%), 16 (12.9%), 17 (13.7%), and 11 (8.9%) respectively. The incidence of NSAID users were 33 (26.6%) patients, out of which 18 used on daily basis and 15 on demand. Those in groups I and IV were substantially younger than groups II and III and they had less comorbid disorders than patients in group I. Conclusion: The present study concluded that about 26.6% of patients with bleeding ulcers took NSAIDs, meaning that low-dose aspirin will cause bleeding ulcers as will NSAID use on-demand.

Sustained Release of Dicumarol via Novel Grafted Polymer in Electrospun Nanofiber Membrane for Treatment of Peritendinous Adhesion.

The prevention and treatment of post-traumatic peritendinous adhesion (PA) have always been a great difficulty for orthopedic surgeons. Current treatments include resecting surgery, non-steroidal anti-inflammatory drugs (NSAIDs) usage and implantable membranes, often target single disease pathogenic processes, resulting in unfavorable therapeutic outcomes. Here a polylactic acid (PLA)-dicumarol conjugates-electrospun nanofiber membrane (ENM) (PCD) is generated, which can achieve spatial accuracy and temporal sustainability in drug release. It is further demonstrated that PCD possesses a significantly higher and more sustainable drug release profile than traditional drug-loading ENM. By providing a physical barrier and continuous releasing of dicumarol, PCD implantation significantly reduces tissue adhesion by 25%, decreases fibroblasts activity and inhibits key fibrogenic cytokine transforming growth factor beta (TGFβ) production by 30%, and improves the biomechanical tendon property by 14.69%. Mechanistically, PCD potently inhibits the connexin43 (Cx43) and thereby tunes down the fibroblastic TGFβ/Smad3 signaling pathway. Thus, this approach leverages the anti-adhesion effect of dicumarol and drug release properties of grafted copolymer ENM by esters to provide a promising therapeutic strategy for patients who suffer from PA.

Derivation and validation of a risk prediction score for nonsteroidal anti-inflammatory drug-related serious gastrointestinal complications in the elderly.

Few studies have quantified the impact of risk factors on GI complications in elderly nonsteroidal anti-inflammatory drug (NSAID) users. This study aimed to develop and validate a risk prediction score for severe GI complications to identify high-risk elderly patients using NSAID. We used the following two Korean claims datasets: customized data with an enrolment period 2016-2017 for model development, and the sample data in 2019 for external validation. We conducted a nested case-control study for model development and validation. NSAID users were identified as the elderly (≥65 years) who received NSAIDs for more than 30 days. Serious GI complications were defined as hospitalizations or emergency department visits, with a main diagnosis of GI bleeding or perforation. We applied the logistic least absolute shrinkage and selection operator (LASSO) regression model for variable selection and model fitting. We identified 8176 cases and 81 760 controls with a 1:10 matched follow-up period in the derivation cohort. In the external validation cohort, we identified 372 cases from 254 551 patients. The risk predictors were high-dose NSAIDs, nonselective NSAID, complicated GI ulcer history, male sex, concomitant gastroprotective agents, relevant co-medications, severe renal disease and cirrhosis. Area under the receiver operating characteristic curve was 0.79 (95% confidence interval, 0.77-0.81) in the external validation dataset. The prediction model may be a useful tool for reducing the risk of serious GI complications by identifying high-risk elderly patients.

Serious Clinical Outcomes of COVID-19 Related to Acetaminophen or NSAIDs from a Nationwide Population-Based Cohort Study

Acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs) have been widely prescribed to infected patients; however, the safety of them has not been investigated in patients with serious acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Our objective was to evaluate the association between the previous use of acetaminophen or NSAIDs and the clinical outcomes of SARS-CoV-2 infection. A nationwide population-based cohort study was conducted using the Korean Health Insurance Review and Assessment Database through propensity score matching (PSM). A total of 25,739 patients aged 20 years and older who tested for SARS-CoV-2 were included from 1 January 2015 to 15 May 2020. The primary endpoint was a positive result for a SARS-CoV-2 test, and the secondary endpoint was serious clinical outcomes of SARS-CoV-2 infection, such as conventional oxygen therapy, admission to the intensive care unit, need for invasive ventilation care, or death. Of 1058 patients, after propensity score matching, 176 acetaminophen users and 162 NSAIDs users were diagnosed with coronavirus disease 2019. After PSM, 162 paired data sets were generated, and the clinical outcomes of the acetaminophen group were not significantly different from those of the NSAIDs group. This suggests that acetaminophen and NSAIDs can be used safely to control symptoms in patients suspected of having SARS-CoV-2.

Osteopathic manipulative treatment of patients with chronic low back pain in the United States: a retrospective cohort study.

The practice of osteopathic manipulative treatment (OMT) varies substantially across nations. Much of this variability may be attributed to disparate international educational, licensing, and regulatory environments that govern the practice of osteopathy by nonphysicians. This is in contrast with the United States, where osteopathic physicians are trained to integrate OMT as part of comprehensive patient management. This study will analyze the factors associated with OMT use and its outcomes when integrated within the overall medical care for chronic low back pain (CLBP) provided by osteopathic physicians in the United States. A retrospective cohort study was conducted within the Pain Registry for Epidemiological, Clinical, and Interventional Studies and Innovation (PRECISION) from April 2016 through April 2022 to study the effectiveness of OMT integrated within medical care provided by osteopathic physicians. The outcome measures, which included pain intensity, pain impact, physical function, and health-related quality of life, were assessed with the National Institutes of Health Minimum Dataset, Patient-Reported Outcomes Measurement Information System, and Roland-Morris Disability Questionnaire. A total of 1,358 adults with CLBP entered the cohort (mean age, 53.2 years; 74.4% female), 913 completed the finalquarterly encounter, 348 were in various stages of follow-up, and 97 had withdrawn. Blacks (odds ratio [OR], 0.36; 95% confidence interval [CI], 0.21-0.63; p<0.001), cigarette smokers (OR, 0.56; 95% CI, 0.33-0.93; p=0.02), and nonsteroidal anti-inflammatory drug users (OR, 0.59; 95% CI, 0.43-0.81; p=0.001) were less likely to have utilized OMT in the multivariable analysis. Mean between-group differences among 753 participants with no OMT crossover and complete follow-up favored OMT: 1.02 (95% CI, 0.63-1.42; p<0.001) for pain intensity; 5.12 (95% CI, 3.09-7.16; p<0.001) for pain impact; 3.59 (95% CI, 2.23-4.95; p<0.001) for physical function, and 2.73 (95% CI, 1.19-4.27; p<0.001) for health-related quality of life. Analyses involving propensity-score adjustment and inclusion of participants with missing data yielded similar conclusions. None of 12 prespecified participant characteristics demonstrated an OMT interaction effect. OMT integrated within medical care provided by osteopathic physicians for CLBP was associated with improved pain and related outcomes. Its use may be facilitated by the growing osteopathic physician workforce in the United States and adherence to relevant clinical practice guidelines.

Nephrolithiasis-Associated Renal Cell Carcinoma in Patients Who Underwent Nephrectomy: A Single-Center Experience.

Kidney stones (nephrolithiasis) affect around 5% of the world's population. Some medical disorders, like obesity or diabetes, have increased the incidence and prevalence of nephrolithiasis. In addition, chronic inflammation and infection are frequently linked to kidney stone formation. Urothelial cell proliferation may change as a result of chronic inflammation, tumors will therefore develop as a result of this. The correlation between nephrolithiasis and renal cell cancer can also be explained by shared risk factors. At Adam Malik General Hospital, we strive to identify the risk factor for stone-induced renal cell cancer. This study was carried out at Adam Malik General Hospital by collecting medical record reports from patients who had nephrectomy for nephrolithiasis between July 2014 and August 2020. A variety of information was obtained, including identification, smoking status, body mass index (BMI), hypertension, diabetes mellitus, and nephrolithiasis history. The histopathological examination of cancer patients was used to determine adjusted odds ratios (ORs) both separately and in combination with other variables. Age, smoking status, BMI, hypertension, and diabetes mellitus all influenced the OR. The single variable was examined using Chi-square test, and the multivariate analysis was carried out using linear regression. A total of 84 patients who underwent nephrectomy due to nephrolithiasis were included in the study, with an average age of 48.77 ± 7.23 years old; 48 (60%) of those were aged < 55 years old. In this study, 52 male patients (63.4%) and 16 patients (20%) were found to have renal cell carcinoma. Univariate analysis showed that the OR of patients with familial history of cancer was 4.5 (95% confidence interval (CI) 2.17 - 19.8), and the OR for smokers was 1.54 (95% CI 1.42 - 1.68). Similar results were shown in patients with hypertension and urinary tract infections due to stones. Nephrolithiasis patients with hypertension were 2.56 (95% CI 1.075 - 6.106) times more likely to develop a malignancy, while patients who had an infection due to a urinary tract stone were 2.85 (95% CI 1.37 - 5.92) times more likely to develop renal cell carcinoma compared to its counterpart. Both have a P-value of less than 0.05. Contrarily, alcoholism and frequent nonsteroidal anti-inflammatory drugs (NSAIDs) user results were different. Both have a P-value of 0.264 and 0.07, respectively. Furthermore, diabetes mellitus type 2 and BMI over 25 are not statistically significant, with a P-value of 0.341 and 0.12, respectively. In multivariable-adjusted analyses, participants with a family history of cancer and recurrent urinary tract infection due to urinary tract stones had a statistically significant increase in overall renal cell carcinoma risk (hazard ratio (HR): 1.39, 95% CI 1.05 - 1.84 and HR: 1.12, 95% CI 1.05 - 1.34). Kidney stone and renal cell carcinoma are significantly correlated due to recurrent urinary tract infection and familial history of cancer, which increases renal cell carcinoma risk.

The role of CYP2C9*2, CYP2C9*3 and VKORC1-1639 variants on the susceptibility of upper gastrointestinal bleeding: A full case-control study.

Purpose: To investigate whether interindividual variability in the CYP2C9 (*2 and *3 alleles) and VKORC1 (rs9923231) genes is associated with increased risk of upper gastrointestinal bleeding (UGIB) in users of non-steroidal anti-inflammatory drugs (NSAIDs) or low-dose aspirin (LDA). Methods: A full case-control study including 200 cases of patients diagnosed with UGIB and 706 controls was conducted in a Brazilian hospital complex. To perform an analysis of NSAIDs dose-effect, the defined daily dose (DDD) for NSAIDs was calculated in the 7-day etiologic window preceding the data index. Three categories of DDD, considering the genotypes of the genetic variants, were established: non-users of NSAIDs (DDD = 0), DDD ≤0.5, and DDD >0.5. Genetic variants and LDA or NSAIDs use synergism was estimated through Synergism Index (SI) and Relative Excess Risk Due To Interaction (RERI). Results: For DDDs of NSAIDs upward of 0.50, a risk of UGIB was identified in carriers of the *3 allele (OR: 15,650, 95% CI: 1.41-174.10) and in carriers of the variant homozygous genotype (TT) of rs9923231 (OR: 38,850, 95% CI: 2.70-556.00). In LDA users, the risk of UGIB was observed to be similar between carriers of the wild type homozygous genotype and carriers of the variant alleles for the CYP2C9 and VKORC1 genes. No synergism was identified. Conclusion: Our findings suggest an increased risk of UGIB in carriers of the variant allele of rs9923231 and in carriers of the *3 allele associated with doses of NSAIDs greater than 0.5. Hence, the assessment of these variants might reduce the incidence of NSAIDs-related UGIB and contribute to the safety of the NSAIDs user.

Development of Prediction Model Using Machine-Learning Algorithms for Nonsteroidal Anti-inflammatory Drug-Induced Gastric Ulcer in Osteoarthritis Patients: Retrospective Cohort Study of a Nationwide South Korean Cohort.

Nonsteroidal anti-inflammatory drugs (NSAID) are currently among the most prescribed medications worldwide to relieve pain and reduce inflammation, especially in patients suffering osteoarthritis (OA). However, NSAIDs are known to have adverse effects on the gastrointestinal system. If a gastric ulcer occurs, planned OA treatment needs to be changed, incurring additional treatment costs and causing discomfort for both patients and clinicians. Therefore, it is necessary to create a gastric ulcer prediction model that can reflect the detailed health status of each individual and to use it when making treatment plans. Using sample cohort data from 2008 to 2013 from the National Health Insurance Service in South Korea, we developed a prediction model for NSAID-induced gastric ulcers using machine-learning algorithms and investigated new risk factors associated with medication and comorbidities. The population of the study consisted of 30,808 patients with OA who were treated with NSAIDs between 2008 and 2013. After a 2-year follow-up, these patients were divided into two groups: without gastric ulcer (n=29,579) and with gastric ulcer (n=1,229). Five machine-learning algorithms were used to develop the prediction model, and a gradient boosting machine (GBM) was selected as the model with the best performance (area under the curve, 0.896; 95% confidence interval, 0.883-0.909). The GBM identified 5 medications (loxoprofen, aceclofenac, talniflumate, meloxicam, and dexibuprofen) and 2 comorbidities (acute upper respiratory tract infection [AURI] and gastroesophageal reflux disease) as important features. AURI did not have a dose-response relationship, so it could not be interpreted as a significant risk factor even though it was initially detected as an important feature and improved the prediction performance. We obtained a prediction model for NSAID-induced gastric ulcers using the GBM method. Since personal prescription period and the severity of comorbidities were considered numerically, individual patients' risk could be well reflected. The prediction model showed high performance and interpretability, so it is meaningful to both clinicians and NSAID users.

Population-Based Analysis of Nonsteroidal Anti-inflammatory Drug Prescription in Subjects With Chronic Kidney Disease

Pain is a prevalent symptom experienced by patients with chronic kidney disease (CKD) and appropriate management of pain is an important element of comprehensive care. Nonsteroidal anti-inflammatory drugs (NSAID) are known to be nephrotoxic in persons with CKD. This study examined the pattern of NSAID prescribing practices in a population based-cohort of patients with CKD. Retrospective cohort study using linked population-based health care data. Entire province of Alberta, Canada. All adults in Alberta with eGFR defined CKD G3 or greater between 2009 and 2017 were included. CKD was defined using at least 2 outpatient serum creatinine (SCr) greater than 90 days apart; the date of second SCr measurement was used as index date. We determined the incidence of hyperkalemia using the peak serum potassium. Prescription drug information was obtained from the Pharmaceutical Information Network (PIN) database. All patients were followed from the index date until March 31, 2019, with a minimum follow-up of 2 years. Prescription drug information and the follow-up laboratory testing of serum creatinine and serum potassium were obtained. Patients with kidney failure defined as eGFR < 15 mL/min per 1.73 m2, receiving chronic dialysis, or prior kidney transplant at baseline were excluded. A total of 170 574 adults (mean age 76.3; 44% male) with CKD were identified and followed for a median of 7 years; 27% were dispensed at least 1 NSAID prescription. While there was a trend toward fewer prescriptions in patients with more advanced CKD (P < .001), 16% of those with CKD G4 were prescribed an NSAID. Primary care providers provided 79% of the prescriptions. Among NSAID users, 21% had a follow-up serum creatinine (SCr) within 30 days of the index prescription. Data collected were from clinical and administrative databases not created for research purposes. The study cohort is limited to subjects who sought medical care and had a serum creatinine measurement obtained. Measurement of NSAID use is limited to those who were dispensed a prescription, over-the-counter NSAIDs use is not captured. Despite guidelines advocating cautious use of NSAIDs in patients with CKD, this study indicates that there is a discrepancy from best practice recommendations. Effective strategies to better support and educate prescribers, as well as patients, may help reduce inappropriate prescribing and adverse events.

Efficacy and Safety of Naproxen Gel in Musculoskeletal Pain Management: A Prospective Cohort Study

Introduction: Naproxen is effective for various musculoskeletal conditions and has a longer half-life, making it a favourable choice for sustained relief. Additionally, there is a potential unmet need for guidelines on the usage of topical Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) in the Asia-Pacific region. A study on naproxen 10% gel aims to address this need and increase awareness of its therapeutic potential in the region. Aim: To assess the efficacy and safety of naproxen 10% gel in relieving pain associated with lower back, knee, cervical, synovitis, bursitis, muscle sprain, and tendinitis. Materials and Methods: This prospective, cohort, observational, open-label, single-arm, multicentric study was conducted at 458 centres in India, including Ahmedabad, Bengaluru, Chandigarh, Chennai, Delhi, Guwahati, Hyderabad, Indore, Jaipur, Kolkata, Lucknow, Meerut, Mumbai, Patna, and Pune, between February 2023 and May 2023. The data was collected from outpatient settings/clinics of orthopaedicians and clinicians who have been prescribing topical naproxen 10% gel to their patients. The study included patients aged 18 to 60 years of either sex who were suffering from back pain, muscle pain, sprains, frozen shoulder, arthritis, acute low back ache (non-specific), or pain. The data was captured during the scheduled follow-up visits planned by the treating clinician, with data recorded at 3, 5, 10, and 15 days. At the baseline visit, demographic details (age, sex, weight, height, body mass index, and symptoms), Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain subscale score, pain intensity on movement score, Visual Analogue Scale (VAS), and overall pain score were obtained. Results: Out of 10,587 patients, 10,265 completed the present study. The majority of patients had lower back pain (n=3386, 32.99%) and knee pain (n=3184, 31.02%). The average pain intensity on movement score of patients with bursitis significantly decreased from the baseline to 15 days {mean change {95% Confidence Interval (CI)}: 6.04 (5.89, 6.20); p&lt;0.001}. Post-naproxen treatment, the average pain intensity, WOMAC pain score, VAS, and overall pain score significantly decreased from baseline to day 15 in patients with knee pain and lower back pain. A significant improvement in WOMAC, WOMAC pain (5.42 vs 17.98), WOMAC stiffness (1.49 vs 5.75), and WOMAC physical function score (18.93 vs 56.21) at day 15 was observed in patients with a muscle sprain. Adverse Events (AE) were reported in 173 (1.69%) patients overall, with dryness (n=125) being the most common, followed by erythema (n=20) and pruritus (n=17). Conclusion: Naproxen 10% gel is an effective topical treatment for lower back pain, knee pain, cervical pain, synovitis, bursitis, muscle sprain, and tendinitis. It could prove helpful in patients where the side-effects of oral NSAIDs are to be avoided.

Relationship of Nonsteroidal Anti-Inflammatory Drug Use During Pregnancy with Autism Spectrum Disorder and Intellectual Disability Among Offspring.

Objective: This study aimed to examine the association of nonsteroidal anti-inflammatory drug (NSAID) use by pregnant women during pregnancy with autism spectrum disorder (ASD) and intellectual disability (ID) in their children among Medicaid-insured mother-child dyads. Materials and Methods: We conducted a retrospective cohort study linking multiple datasets of South Carolina for the years between 2010 and 2017, in which the main exposure variable was NSAID use during pregnancy and outcome variables were ASD only, ID only, and ASD with ID. We conducted a multinomial logistic regression analysis, controlling for identified risk factors for ASD (mother's age, race, body-mass index, preeclampsia, and gestational diabetes). Results: NSAID use during pregnancy was found to be associated with ID only in both unadjusted and adjusted analyses. Children with mothers who had NSAID prescriptions were 26% more likely to have ID in comparison with children whose mothers did not have NSAID prescriptions (odds ratio: 1.26 [1.10-1.46]). The other risk factors identified for ASD were maternal age, race, preeclampsia, smoking, low birth weight, and obesity. For ID, the risk factors were maternal age, race, smoking, birth weight, overweight, and obesity, all of which were also associated with ASD with ID, except for overweight. Conclusions: NSAID usage during pregnancy was found to be associated with ID only and not with ASD. However, more research is needed to validate the effect of NSAIDs during pregnancy on ASD and ID among children.

Risk of Gastrointestinal Bleeding with Concurrent Use of NSAID and SSRI: A Systematic Review and Network Meta-Analysis.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used over-the-counter medications that can increase the risk of gastrointestinal (GI) bleeding through antiplatelet effects and loss of GI protection. Selective serotonin reuptake inhibitors (SSRIs), commonly used for mental and behavioral health, are another group of medications that can cause platelet dysfunction. Previous literature has shown a possible increased risk of GI bleeding with concurrent use of SSRIs and NSAIDs. We performed a network meta-analysis comparing NSAIDs, SSRIs, and combined SSRI/NSAIDs to assess the risk of GI bleeding. The following databases were searched: MEDLINE, Embase, Web of Science Core Collection, SciELO, KCI, and Cochrane database. All comparative studies, i.e., case-control, cohort, and randomized controlled trials were included. Direct and network meta-analysis was conducted using DerSimonian-Laird approach and random effect. For binary outcomes, odds ratio (OR) with 95% confidence interval (CI) and p value were calculated. After a comprehensive search through November 10th, 2021, 15 studies with 82,605 patients were identified. 11 studies reported higher rates of GI bleeds in SSRI/NSAID than SSRI users (36.9% vs 22.8%, OR 2.14, 95% CI 1.52-3.02, p < 0.001, I2 = 86.1%). 10 studies compared SSRI/NSAID to NSAID users with higher rates of bleeds in SSRI/NSAID group (40.9% vs 34.2%, OR 1.49, 95% CI 1.20-1.84, p < 0.001, I2 = 68.8%). The results were consistent using network meta-analysis as well. Given higher risk of bleeding with concurrent NSAIDs and SSRIs, prescribers should exercise caution when administering NSAIDs and SSRIs concurrently especially in patients with higher risks of GI bleeding.

Associations of Antibiotics, Hormonal Therapies, Oral Contraceptives, and Long-Term NSAIDS With Inflammatory Bowel Disease: Results From the Prospective Urban Rural Epidemiology (PURE) Study

Several medications have been suspected to contribute to the etiology of inflammatory bowel disease (IBD). This study assessed the association between medication use and the risk of developing IBD using the Prospective Urban Rural Epidemiology cohort. This was a prospective cohort study of 133,137 individuals between the ages of 20 and 80 from 24 countries. Country-specific validated questionnaires documented baseline and follow-up medication use. Participants were followed up prospectively at least every 3 years. The main outcome was the 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) were evaluated. Results are presented as adjusted odds ratios (aORs) with 95% CIs. During a median follow-up period of 11.0 years (interquartile range, 9.2-12.2 y), there were 571 incident IBD cases (143 CD and 428 UC). Incident IBD was associated significantly with baseline antibiotic (aOR, 2.81; 95% CI, 1.67-4.73; P= .0001) and hormonal medication use (aOR, 4.43; 95% CI, 1.78-11.01; P= .001). Among females, previous or current oral contraceptive use also was associated with IBD development (aOR, 2.17; 95% CI, 1.70-2.77; P < .001). Nonsteroidal anti-inflammatory drug users also were observed to have increased odds of IBD (aOR, 1.80; 95% CI, 1.23-2.64; P= .002), which was driven by long-term use (aOR, 5.58; 95% CI, 2.26-13.80; P < .001). All significant results were consistent in direction for CD and UC with low heterogeneity. Antibiotics, hormonal medications, oral contraceptives, and long-term nonsteroidal anti-inflammatory drug use were associated with increased odds of incident IBD after adjustment for covariates.

Acute kidney injury in 18 cats after subcutaneous meloxicam and an update on non-steroidal anti-inflammatory drug usage in feline patients in Australia.

Acute kidney injury (AKI) is a well-known but poorly documented adverse effect of non-steroidal anti-inflammatory drugs (NSAIDs) in cats. We aimed to describe instances of NSAID-associated AKI in cats and survey Australian veterinarians on NSAID use in acute settings. Medical records of cats that developed an AKI subsequent to the administration of meloxicam were obtained by searching the databases of seven practices in Queensland, as well as by contemporaneously contacting select veterinary colleagues of the authors in both general and specialist small animal practice. An online questionnaire was created for the survey, and the URL distributed to Australian practitioners. A total of 18 cases were retrieved, all of which received injectable meloxicam. The indication(s) for its use and the dosage prescribed were within the manufacturer's recommendations for Australian veterinarians. The majority of cases (13/18 cats) received the label dose of 0.3 mg/kg subcutaneously (SC) on the day of the procedure. In 12/18 cats, the injection was given in association with general anaesthesia or sedation. Fourteen cats survived to hospital discharge. Of 187 survey respondees, 89% routinely administered NSAIDs for surgery-related analgesia, with 98% prescribing meloxicam and 84% of these giving it SC. Ninety percent of respondees routinely administered NSAIDs for non-surgical-related analgesia, with 99% prescribing meloxicam and 35% of those giving it SC. We strongly recommend that practitioners avoid prescribing meloxicam SC in cats. This recommendation is emphatic in situations where concurrent dehydration and/or hypotension are possible.

The burden of city's pain treatment – A longitudinal one year study of two cities via wastewater-based epidemiology

This paper explores Wastewater-Based Epidemiology (WBE) as a tool enabling understanding of city's pain treatment in an intercity longitudinal study. An intensive 13-month monitoring programme was undertaken in two adjacent urban areas in South-West England: a small commuter town Keynsham and the city of Bath (>180 samples collected). The study has shown a great potential of using triangulated WBE and National health Service (NHS) prescription data in understanding pain treatment in two contrasting communities with strong apparent seasonal patterns of short pain medications vs chronic pain treatment as well as the type of treatment used (e.g. oral vs topical). Community-wide usage of Non-Steroidal Anti-inflammatory Drugs (NSAIDs) and paracetamol in the intercity study is population size and season driven with the highest usage recorded in winter months. This contrasts with other pain pharmaceuticals, especially those used for chronic pain, where no/limited seasonal usage was recorded. Unmetabolized NSAIDs are, to a large extent, directly disposed of into the sewerage system bypassing metabolism due to their topical application. This is particularly apparent in winter months with naproxen showing the highest seasonal variability. Pharma/met (ratio of pharmaceutical and its metabolite concentration) analysis allows for tracking topical (non-metabolic) application/down-the-drain disposal of pharmaceuticals with frequent instances of direct disposal of NSAIDs into the sewerage system observed. Normalisation of pharma markers to population size shows comparable estimates of pharma usage in the two cities confirming population as the main driver of pharma loads in wastewater. Variable application patterns of pain pharmaceuticals make back-calculation of intake more convoluted. Intake calculated using percentage excretion of parent NSAIDs will likely lead to overestimation, as it is assumed that NSAIDs are subject to extensive metabolism (this is not the case for topical applications). Intake calculated using percentage excretion of metabolites (or parent compound) as consumption markers leads to underestimation of NSAIDs usage due to contributions from topical application not being accounted for. Prescription data indicates cumulative internal and topical usage, but the data ignores large proportion of over-the-counter usage. Therefore, we have proposed a combined approach allowing for estimation of total usage including, and differentiating between, topical application and oral administration.

A Review on Non-Steroidal Anti-Inflammatory Drugs Induced Kidney Diseases

Non-Steroidal Anti-inflammatory Drugs (NSAIDs) are used as over-the-counter drugs for Analgesic and Anti-inflammatory conditions. They inhibit prostaglandins synthesis by acting on Cyclooxygenase enzymes in the Arachidonic cascade which causes various abnormal effects like peptic ulcers, Gastrointestinal bleeding, sodium and water retention, hypertension, hemodynamic kidney injury, nephrotoxicity, stroke, and myocardial infarction when used for a longer duration, especially in older patients/comorbidities patients/ pre-existing renal disease patients. This is because in older patients decrease in glomerular filtration rate and comorbidity conditions increase the risk of NSAIDs and cause Acute Kidney injury, Tubulointerstitial nephritis, and chronic kidney injury. NSAIDs do not cause much risk in patients who are young, without pre-existing kidney disease and without comorbidities. Physicians should educate patients with caution on the usage of NSAIDs for longer periods and should prescribe drugs in a dose-dependent manner.

Association between metabolic syndrome and colorectal cancer incidence and all-cause mortality: a hospital-based observational study

BackgroundMetabolic syndrome (MetS) is a worldwide pandemic and complex disorder associated with colorectal cancer (CRC). This study aims to identify the influence of number of MetS components on CRC incidence and mortality, using a national, longitudinal dataset of hospital care in Taiwan.MethodsPatient data from the Taiwan National Health Insurance Research Database (NHIRD) from 2001 to 2008 were extracted. Individuals with at least one inpatient diagnosis or 2 outpatient visits with any MetS component found within one year were identified and included. Subjects died within 12 months after the presence of MetS components or had any prior cancer were excluded. The study cohort were then divided into two groups: subjects who had more (i.e., 3 to 4) MetS components and those who had fewer (i.e., 1 to 2) MetS components. An 2:1 propensity score (PS) matching were performed to balance the baseline characteristics between the groups. Cox regression analyses were conducted to compare the CRC incidence and all-cause mortality at follow-up between subjects with more MetS components versus fewer components.ResultsAfter matching, a total of 119,843 subjects (78,274 with 1–2 and 41,569 with 3–4 MetS components) were analyzed. After adjusting for confounders, subjects with 3–4 MetS components had a significantly higher risk of CRC [adjusted hazard ratio (aHR), 1.28; 95% confidence interval (CI), 1.15–1.43, p < 0.001) and all-cause mortality (aHR, 1.13; 95% CI, 1.08–1.17, p < 0.001) than those with only 1–2 MetS components. In stratified analyses, the greatest increased risk of CRC incidence that 3–4 MetS components posed as compared to 1–2 MetS components was seen in subjects without CHD history (aHR, 1.41, 95% CI, 1.23–1.62, p < 0.001). In addition, 3–4 MetS components (vs. 1–2) led to greater all-cause mortality among the subjects < 65y, both genders, with or without CHD, subjects without CKD hisotry, both aspirin users and non-users, users of nonsteroidal anti-inflammatory drugs (NSAIDs), and users of statin.ConclusionCompared with 1–2 components, subjects with 3–4 MetS components are at greater risk of CRC and death at follow-up. This study also demonstrates the risks for CRC and all-cause mortality in certain subgroups of individuals with 3–4 MetS components compared to 1–2 components. These findings may help clinicians on the CRC risk stratification according to individuals’ characteristics, as well as to optimize the strategy of MetS surveillance and control in order to prevent CRC.