NSAID-induced corneal melt as the first presentation of Sjögren's syndrome.

A non-diabetic woman in her 80s presented 1 week following uncomplicated left eye cataract surgery complaining of decreased vision, gritty sensation and photophobia in the same eye. Postoperative treatment included G. Acular (Ketorolac Tromethamine 0.5%, NSAID: non-steroidal anti-inflammatory drug) and G. Tobradex (Tobramycin 0.3% and Dexamethasone 0.1%, antibiotic and steroid, respectively) each prescribed four times a day for 2 weeks. On examination, the patient had a corneal epithelial defect which progressed to a full-thickness perforation despite ceasing the NSAID drops. Cyanoacrylate glue application with a plastic drape patch failed to seal the perforation, and a full-thickness tectonic corneal transplant was performed. On investigation, the patient had positive anti-RO and anti-LA antibodies, suggesting a diagnosis of Sjögren's syndrome. We advocate for careful preoperative assessment prior to cataract surgery, patient education, close follow-up and cautious medication use postoperatively including avoiding NSAID drops in patients with risk factors for postoperative dry eye disease.

Perimyocarditis in a Patient with Ulcerative Colitis Treated with 5-Aminosalicylic Acid.

5-Aminosalicylic acid (5-ASA) is recommended for managing ulcerative colitis. Common adverse effects associated with 5-ASA include gastrointestinal disorders, headaches, and skin rashes. Perimyocarditis induced by 5-ASA is a rare adverse effect, with only a limited number of cases reported. This paper presents a case of 5-ASA-induced perimyocarditis in a 29-year-old female who had been taking 5-ASA for three weeks. The patient was admitted to the emergency department with dyspnea, chest discomfort, and fever. She subsequently underwent laboratory investigations, including electrocardiography, transthoracic echocardiography, chest computed tomographic angiography, cardiac magnetic resonance imaging, and heart biopsy. Intravenous steroid was administered, and 5-ASA was discontinued. The patient's signs and symptoms improved significantly within a few days of discontinuing 5-ASA, leading to her subsequent discharge. This case highlights the importance of considering perimyocarditis in patients exhibiting cardiac symptoms during 5-ASA therapy, despite it being a rare adverse effect. Drug withdrawal in such cases may lead to rapid clinical improvement.

Effectiveness of the pharmacological therapy to prevent post ERCP acute pancreatitis: a network meta-analysis.

OBJECTIVE: To determine the effectiveness of the different pharmacological agents in preventing post-ERCP acute pancreatitis. METHODS: We included clinical trials of pharmacological interventions for prophylaxis of acute post-ERCP pancreatitis. The event evaluated was acute pancreatitis. We conducted a search strategy in MEDLINE (OVID), EMBASE, and Cochrane Central Register of Controlled Trials from inception to nowadays. We reported the information in terms of relative risks (RR) with a 95% confidence interval. We assessed the heterogeneity using the I2 test. RESULTS: We included 84 studies for analysis (30,463 patients). The mean age was 59.3 years (SD ± 7.01). Heterogeneity between studies was low (I2 = 34.4%) with no inconsistencies (p = 0.2567). Post ERCP pancreatitis was less in prophylaxis with NSAIDs (RR 0.65 95% CI [0.52 to 0.80]), aggressive hydration with Lactate Ringer (RR 0.32 95% CI [0.12-0.86]), NSAIDs + isosorbide dinitrate (RR 0.28 95% CI [0.11-0.71]) and somatostatin and analogues (RR 0.54 [0.43 to 0.68]) compared with placebo. CONCLUSIONS: NSAIDs, the Combination of NSAIDs + isosorbide dinitrate, somatostatin and analogues, and aggressive hydration with lactate ringer are pharmacological strategies that can prevent post-ERCP pancreatitis when compared to placebo. More clinical trials are required to determine the effectiveness of these drugs.

Alarming Incidence of Gastric Outlet Obstruction Related to NSAIDS and Synthetic Opioid in North West India.

BACKGROUND: In recent years, there has been an alarming increase in cases of gastric outlet obstruction (GOO) at our center due to drug abuse. So, we conducted this study to know the incidence of nonsteroidal anti-inflammatory drugs (NSAIDs) and synthetic opioid abuse in cases of GOO. METHODS: This was an observational study involving consecutive cases of GOO diagnosed from September 2017 to February 2019. A detailed history, including drug addiction history and clinical examination, was done. Investigations included routine biochemical and hematological tests, upper gastrointestinal endoscopy (UGIE), ultrasonography, rapid urease test (RUT), and histopathology of the diseased area. RESULTS: Among the 102 cases diagnosed with GOO, 62 (60.78%) cases had a history of drug addiction. The drug addiction history was as follows: NSAIDs and opioids in 56, opioids alone in four, and NSAIDs alone in two cases. The most common site of stricture was the second part of the duodenum. The features on histopathology were ulcerations of the mucosa infiltrated by eosinophils, plasma cells, and lymphocytes. CONCLUSION: There is an alarming increase in the incidence of GOO due to NSAIDs and opioid abuse at our center. Efforts should be made to control the indiscriminate use of these over-the-counter drugs to prevent dreaded complications.

Imrecoxib: Advances in Pharmacology and Therapeutics.

Imrecoxib, a cyclooxygenase-2 (COX-2) selective non-steroidal anti-inflammatory drug (NSAID), was discovered via the balanced inhibition strategy of COX-1/COX-2. It is indicated for the relief of painful symptoms of osteoarthritis. There have been some pharmacological and therapeutic advances since the approval of imrecoxib in 2011. However, an update review in this aspect is not yet available. Relevant literature until January 2024 was identified by search of PubMed, Web of science, Embase and CNKI. From the perspective of efficacy, imrecoxib provides relief of osteoarthritis symptoms, and potential off-label use for treatment of idiopathic pulmonary fibrosis, perioperative pain, hand-foot syndrome, axial spondyloarthritis, COVID-19, cartilage injury, and malignancies such as lung and colon cancer. From a safety point of view, imrecoxib showed adverse effects common to NSAIDs; however, it has lower incidence of new-onset hypertension than other types of selective COX-2 inhibitors, less gastrointestinal toxicities than non-selective NSAIDs, weaker risk of drug interaction than celecoxib, and more suitable for elderly patients due to balanced inhibition of COX-1/COX-2. From a pharmacoeconomic perspective, imrecoxib is more cost-effective than celecoxib and diclofenac for osteoarthritis patients. With the deepening of the disease pathophysiology study of osteoarthritis, new therapeutic schemes and pharmacological mechanisms are constantly discovered. In the field of osteoarthritis treatment, mechanisms other than the analgesic and anti-inflammatory effects of COX-2 inhibitors are also being explored. Taken together, imrecoxib is a moderate selective COX-2 inhibitor with some advantages, and there would be more clinical applications and research opportunities in the future.

Cardiovascular safety of using non-steroidal anti-inflammatory drugs for gout: a Danish nationwide case-crossover study.

Gout attacks are treated with uric-lowering and anti-inflammatory drugs. In patients with gout, non-steroidal anti-inflammatory drugs (NSAIDs) could be both cardiovascular beneficial, due to their anti-inflammatory actions, and cardiovascular hazardous, due to their prothrombotic, hypertensive, and proarrhythmic side effects. We, therefore, examined the risk of cardiovascular events associated with NSAID use in patients with gout. 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 cardiovascular event (myocardial infarction, ischemic stroke, congestive heart failure, atrial fibrillation/flutter, or cardiovascular death) (n = 59,150). The exposure was use of NSAIDs, overall and according to type (ibuprofen, naproxen, or diclofenac). We used the dates 300, 240, 180, and 120 before the outcome date as reference dates. We used the Mantel-Haenszel method to calculate odds ratios (ORs) with 95% confidence intervals (CIs) of the association between NSAID use and cardiovascular events. NSAID use was overall associated with 12% decreased odds of a cardiovascular event (OR = 0.88, 95% CI: 0.85-0.91). This decreased odds ratio was observed for the use of ibuprofen (OR = 0.92, 95% CI: 0.88-0.97) and naproxen (OR = 0.85, 95% CI: 0.74-0.97), but not for the use of diclofenac (OR = 0.97, 95% CI: 0.90-1.05). Overall, use of NSAIDs was associated with decreased odds of all the individual components of the composite outcome. NSAIDs were not associated with an increased cardiovascular event rate when used in gout patients. Ibuprofen and naproxen appeared to have better cardiovascular risk profiles than diclofenac.

A rare case of phenobarbital-induced leukocytoclastic vasculitis.

Drug hypersensitivity reactions (DHRs) manifested as vasculitis are rare. Antibiotics, non-steroidal anti-inflammatory drugs (NSAIDs), sulphonamides, diuretics, immunosupressants and anticonvulsants are the most common culprits for drug-induced leukocytoclastic vasculitis (LCV) but there is scarce information about barbiturates. We present a case of 53-year-old female with severe vasculitis after phenobarbital- and NSAIDs-containing medications use. The preliminary diagnosis of drug-induced vasculitis was made based on anamnestic and clinical data. Further examinations confirmed the diagnosis of LCV and excluded other more common causes of vasculitis. The causative significance of used medications was assessed by long-term observation of the patient after the reaction, including the drug challenge series and Naranjo's Adverse Drug Reaction Probability Scale. It was concluded that phenobarbital is the most probable culprit drug. The patient's data were included in the Armenian Registry of Patients with Severe DHRs. Since then, the patient has avoided only barbiturate-containing drugs and no reactions were noted. Thus, the case indicates that even with limited diagnostic capabilities, the final diagnosis of rare drug-induced LCV and even rarer culprit drug can be established by comparing the available data. Awareness about phenobarbital and proper recording of the case are important in the management and prevention of DHRs manifested as vasculitis.

Effect of perioperative ketorolac on postoperative bleeding after pediatric tonsillectomy.

INTRODUCTION: Ketorolac is a frequently used anesthetic pain agent which is traditionally avoided during tonsillectomy due to concern for postoperative hemorrhage. Our goal was to assess the degree of risk associated with the use of Ketorolac following pediatric tonsillectomy. METHODS: The TriNetX electronic health records research database was queried in January 2024 for patients undergoing tonsillectomy with or without adenoidectomy under the age of 18 years and without a diagnosed bleeding disorder. Patients were separated into two cohorts either having received or not having received ketorolac the same day as surgery. Propensity score matching was performed for age at the time of surgery, sex, race, ethnicity, and preoperative diagnoses. The outcomes assessed were postoperative hemorrhage requiring operative control within the first day (primary hemorrhage) and within the first month after surgery (secondary hemorrhage). RESULTS: 17,434 patients were identified who had undergone pediatric tonsillectomy with or without adenoidectomy and had received ketorolac the same day as surgery. 290,373 patients were identified who had undergone pediatric tonsillectomy with or without adenoidectomy and had not received ketorolac the same day as surgery. 1:1 propensity score matching resulted in 17,434 patients within each cohort. Receipt of ketorolac the same day as surgery resulted in an increased risk of primary hemorrhage OR 2.158 (95 % CI 1.354, 3.437) and secondary hemorrhage OR 1.374 (95 % CI 1.057, 1.787) requiring operative control. CONCLUSION: Ketorolac use during pediatric tonsillectomy with or without adenoidectomy was associated with an increased risk of postoperative primary and secondary bleeding requiring surgery.

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

OBJECTIVES: Potentially harmful non-steroidal anti-inflammatory drugs (NSAIDs) utilisation persists at undesirable rates worldwide. The purpose of this paper is to review the literature on interventions to de-implement potentially harmful NSAIDs in healthcare settings and to suggest directions for future research. DESIGN: Scoping review. DATA SOURCES: PubMed, CINAHL, Embase, Cochrane Central and Google Scholar (1 January 2000 to 31 May 2022). STUDY SELECTION: Studies reporting on the effectiveness of interventions to systematically reduce potentially harmful NSAID utilisation in healthcare settings. DATA EXTRACTION: Using Covidence systematic review software, we extracted study and intervention characteristics, including the effectiveness of interventions in reducing NSAID utilisation. RESULTS: From 7818 articles initially identified, 68 were included in the review. Most studies took place in European countries (45.6%) or the USA (35.3%), with randomised controlled trial as the most common design (55.9%). Interventions were largely clinician-facing (76.2%) and delivered in primary care (60.2%) but were rarely (14.9%) guided by an implementation model, framework or theory. Academic detailing, clinical decision support or electronic medical record interventions, performance reports and pharmacist review were frequent approaches employed. NSAID use was most commonly classified as potentially harmful based on patients' age (55.8%), history of gastrointestinal disorders (47.1%), or history of kidney disease (38.2%). Only 7.4% of interventions focused on over-the-counter (OTC) NSAIDs in addition to prescription. The majority of studies (76.2%) reported a reduction in the utilisation of potentially harmful NSAIDs. Few studies (5.9%) evaluated pain or quality of life following NSAIDs discontinuation. CONCLUSION: Many varied interventions to de-implement potentially harmful NSAIDs have been applied in healthcare settings worldwide. Based on these findings and identified knowledge gaps, further efforts to comprehensively evaluate the effectiveness of interventions and the combination of intervention characteristics associated with effective de-implementation are needed. In addition, future work should be guided by de-implementation theory, focus on OTC NSAIDs and incorporate patient-focused strategies and outcomes, including the evaluation of unintended consequences of the intervention.

2024 ISFM and AAFP consensus guidelines on the long-term use of NSAIDs in cats.

PRACTICAL RELEVANCE: Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used and are effective for the management of pain in cats. These Guidelines will support veterinarians in decision-making around prescribing NSAIDs in situations of chronic pain, to minimise adverse effects and optimise pain management. Information is provided on mechanism of action, indications for use, screening prior to prescription, use in the presence of comorbidities, monitoring of efficacy, and avoidance and management of adverse effects. CLINICAL CHALLENGES: The cat's unique metabolism should be considered when prescribing any medications, including NSAIDs. Chronic pain may be challenging to detect in this species and comorbidities, particularly chronic kidney disease, are common in senior cats. Management of chronic pain may be complicated by prescription of other drugs with the potential for interactions with NSAIDs. EVIDENCE BASE: These Guidelines have been created by a panel of experts brought together by the International Society of Feline Medicine (ISFM) and American Association of Feline Practitioners (AAFP). Information is based on the available literature, expert opinion and the panel members' experience.

Impact of Non-steroidal Anti-inflammatory Drugs, Glucocorticoids, and Disease-Modifying Anti-Rheumatic Drugs on Cancer Response to Immune Checkpoint Inhibitor Therapy.

Immune checkpoint inhibitor (ICI) therapy for advanced malignancies often leads to off-target adverse events. Rheumatic immune-related adverse events can often linger beyond the duration of ICI therapy and sometimes requires the use of immunomodulator therapy. A key question, therefore, is if the commonly used therapies affect cancer outcomes. In this review, the authors summarize the state of the data as it currently stands, taking into consideration the limitations of the various source studies. The most information is known about glucocorticoids, which appear to be harmful especially when used early and at high doses.

[Progress in application of aspirin desensitization and maintenance therapy in aspirin-exacerbated respiratory disease].

Aspirin-exacerbated respiratory disease (AERD) is a clinical syndrome characterized by chronic rhinosinusitis with nasal polyps, asthma and the development of significant airway symptoms following the ingestion of aspirin and other nonsteroid anti-inflammatory drugs (NSAIDs). At present, aspirin challenge is the gold standard for diagnosis. Aspirin desensitization and aspirin therapy after desensitization (ATAD) is one of the classical therapies. This paper described the application of aspirin desensitization and ATAD in AERD and provided the reference for the comprehensive treatment of AERD.

Prolonged Non-Steroidal Anti-Inflammatory Drug Exposure After Pleurodesis Increases Pneumothorax Recurrence: A Retrospective Cohort Study.

INTRODUCTION: The use of non-steroidal anti-inflammatory drugs (NSAID) in patients undergoing pleurodesis remains controversial. Although many surgeons are comfortable prescribing NSAIDs post-operatively, some oppose this practice due to concerns of suppressing the inflammatory response and quality of pleurodesis. Only a small body of inconsistent publications exists with respect to guiding therapy in this common clinical scenario. METHODS: A retrospective cohort study was undertaken assessing effect of NSAID exposure on pleurodesis outcomes. An institutional thoracic surgery database was reviewed yielding 147 patients who underwent pleurodesis for pneumothorax between 2010 and 2018. Medical records and imaging were reviewed for patient characteristics, NSAID exposure, recurrent pneumothorax and other adverse events. RESULTS: There was no overall difference between rates of recurrence and procedural failure of pleurodesis (Relative Risk [RR] 1.67 [95% CI 0.74-3.77]). However, NSAID exposure of >48 hours was associated with increased risk of recurrent pneumothorax (RR 2.16 [95% CI 1.05-4.45]). There was no increased rate of other adverse events related to NSAID usage. CONCLUSIONS: NSAID exposure does not increase failure rates or other adverse events following pleurodesis for pneumothorax. However, prolonged NSAID exposure post-pleurodesis may increase procedural failure rates. Further large volume randomised control trials are required.

Clinical pharmacokinetics and pharmacodynamics of topical non-biological therapies for psoriasis patients.

INTRODUCTION: Psoriasis is a chronic inflammatory cutaneous disease that causes patients psychosocial distress. Topical therapies are utilized for mild-to-moderate disease and for more severe disease in conjunction with systemic therapies. Topical corticosteroids are a cornerstone of treatment for psoriasis, but long-term use can cause stria and cutaneous atrophy and as well as systemic side effects such as topical steroid withdrawal. Non-steroidal topical therapies tend to be safer than topical corticosteroids for long-term use. AREAS COVERED: We conducted a literature review on the pharmacokinetic (PK) and pharmacodynamic (PD) properties of topical therapies for psoriasis. We discuss how the PK and PD characteristics of these therapies inform clinicians on efficacy and toxicity when prescribing for patients. EXPERT OPINION: Topical corticosteroids, used intermittently, are very safe and effective. Long-term, continuous use of topical corticosteroids can cause systemic side effects. Several generic and newly approved non-steroidal options are available, but no head-to-head studies compare the effectiveness of the generics (vitamin D analogs, tacrolimus, pimecrolimus) against the newer therapies (roflumilast, tapinarof). Patients often do not respond to topical therapies due to poor adherence to treatment regimens. For patients resistant to topical treatment, phototherapy or systemic therapy may be an option.

Low-Dose Aspirin Use Does Not Increase Disease Activity in Pregnant Patients with Inflammatory Bowel Disease.

BACKGROUND: The adverse effects of non-steroidal anti-inflammatory (NSAID) drugs on the gastrointestinal system are well recognized, but the effect of NSAID use on disease activity patients with inflammatory bowel disease (IBD) remains unresolved. Low-dose aspirin (LDA) is recommended for all pregnant patients with risk factors for developing preeclampsia, including autoimmune conditions. As recognition of risk factors for preeclampsia improves, the preventative use of LDA is likely to increase. AIMS: To investigate if LDA use for prevention of preeclampsia increases the risk of disease activity in pregnant women with IBD. METHODS: Single-center retrospective cohort study of pregnant patients with IBD who delivered from 2012 to 2020, comparing those with and without LDA use. Primary outcome was odds of clinical IBD activity in patients in remission at time of conception. Secondary outcomes were rate of elevated inflammatory biomarkers, defined as C-reactive protein > 5 ug/mL or fecal calprotectin > 250 ug/g, and rate of preeclampsia. Univariate analyses tested for associations. RESULTS: Patients taking LDA were older (p = 0.003) and more likely to have chronic hypertension (p = 0.002), to have undergone in vitro fertilization (p < 0.001), and to be on biologics (p = 0.03). Among patients in remission at conception, there was no difference in clinical disease activity or biomarker elevation during pregnancy based on LDA use (OR 1.27, 95% CI [0.55-2.94], p = 0.6). Rates of preeclampsia were similar between groups. CONCLUSION: LDA use for preeclampsia prevention did not increase the incidence of disease activity in pregnant patients with IBD.