Browsing by Subject "Non-steroidal anti-inflammatory agents"

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    Chemopreventative celecoxib fails to prevent schwannoma formation or sensorineural hearing loss in genetically engineered murine model of neurofibromatosis type 2
    (Impact Journals, 2017-10-24) Wahle, Benjamin M.; Hawley, Eric T.; He, Yongzheng; Smith, Abbi E.; Yuan, Jin; Masters, Andi R.; Jones, David R.; Gehlhausen, Jeffrey R.; Park, Su-Jung; Conway, Simon J.; Clapp, D. Wade; Yates, Charles W.; Otolaryngology -- Head and Neck Surgery, School of Medicine
    Mutations in the tumor suppressor gene NF2 lead to Neurofibromatosis type 2 (NF2), a tumor predisposition syndrome characterized by the development of schwannomas, including bilateral vestibular schwannomas with complete penetrance. Recent work has implicated the importance of COX-2 in schwannoma growth. Using a genetically engineered murine model of NF2, we demonstrate that selective inhibition of COX-2 with celecoxib fails to prevent the spontaneous development of schwannomas or sensorineural hearing loss in vivo, despite elevated expression levels of COX-2 in Nf2-deficient tumor tissue. These results suggest that COX-2 is nonessential to schwannomagenesis and that the proposed tumor suppressive effects of NSAIDs on schwannomas may occur through COX-2 independent mechanisms.
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    Non-Steroidal Anti-Inflammatory Drug Hypersensitivity in a Pediatric Severe Asthmatic Population
    (Wiley, 2023) Hadley, Abigail; Slaven, James E.; Krupp, Nadia L.; Kloepfer, Kirstin M.; Pediatrics, School of Medicine
    Introduction: Asthma is a common pediatric disease. Identification of exacerbating factors is important to gain better asthma control. One potential exacerbation trigger is NSAID-hypersensitivity (NSAID-H). Studies regarding pediatric NSAID-H have varied demographics, methodologies, and conclusions. However, most studies find NSAID-H more prevalent in asthmatic patients. Methods: The objective was to determine the prevalence, symptoms, and factors associated with NSAID-H in a pediatric severe asthma population. One hundred children aged 6 to 18 years old from the Severe Asthma Clinic at Riley Hospital for Children in Indianapolis, IN, between 11/2020 and 5/2022 completed a survey about asthma triggers, allergies, co-morbid diagnoses, sinus symptoms, and NSAID reaction history. Results: Nineteen percent of participants reported a reaction to at least one NSAID. Ibuprofen (16%), aspirin (9%), and acetaminophen (9%) were the most implicated NSAIDs. Most common symptoms were dyspnea, wheezing, coughing, lightheadedness, and abdominal pain appearing within 30 minutes. Associated factors included history of a medication other than an NSAID triggering asthma (p = 0.02), nasal polyps (p = 0.01), ageusia (p = 0.01), cold-induced asthma (p = 0.02), and chronic sinusitis in immediate family member (p = 0.04). Conclusions: Prevalence of NSAID-H in a large children’s hospital pediatric severe asthma clinic was 19%. The most common drug was ibuprofen and the most common symptoms were respiratory and gastrointestinal. Associated factors included medication and cold triggered asthma, nasal polyps, ageusia, and family history of chronic sinusitis. This highlights the importance of a thorough history in severe asthma patients who may be at higher risk for NSAID-H. Future studies should focus on looking at the rate of NSAID-H in a larger severe asthma population and if social determinants of health play a role in the increased incidence of reacting.
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    Prevention of post-ERCP pancreatitis: the search continues
    (Elsevier, 2021-05) Easler, Jeffrey J.; Fogel, Evan L.; Medicine, School of Medicine
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    Rectal Indomethacin Dose Escalation (RIDE) for Prevention of Post-ERCP Pancreatitis in High-Risk Patients: a Randomized Trial
    (Elsevier, 2020) Fogel, Evan L.; Lehman, Glen A.; Tarnasky, Paul; Cote, Gregory A.; Schmidt, Suzette E.; Waljee, Akbar K.; Higgins, Peter D. R.; Watkins, James L.; Sherman, Stuart; Kwon, Richard S. Y.; Elta, Grace H.; Easler, Jeffrey J.; Pleskow, Douglas K.; Scheiman, James M.; El Hajj, Ihab I.; Guda, Nalini M.; Gromski, Mark A.; McHenry, Lee, Jr.; Arol, Seena; Korsnes, Sheryl; Suarez, Alejandro L.; Spitzer, Rebecca; Miller, Marilyn; Hofbauer, Maria; Elmunzer, B. Joseph; US Cooperative for Outcomes Research in Endoscopy (USCORE); Medicine, School of Medicine
    Background: Although rectal indometacin 100 mg is effective in reducing the frequency and severity of pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP) in high-risk patients, the optimal dose is unknown, and pancreatitis incidence remains high. The aim of this study was to compare the efficacy of two dose regimens of rectal indometacin on the frequency and severity of pancreatitis after ERCP in high-risk patients. Methods: In this randomised, double-blind, comparative effectiveness trial, we enrolled patients from six tertiary medical centres in the USA. Eligible patients were those at high risk for the development of pancreatitis after ERCP. We randomly assigned eligible patients (1:1) immediately after ERCP to receive either two 50 mg indometacin suppositories and a placebo suppository (standard-dose group) or three 50 mg indometacin suppositories (high-dose group). 4 h after the procedure, patients assigned to the high-dose group received an additional 50 mg indometacin suppository, whereas patients in the standard-dose group received an additional placebo suppository. The randomisation schedule, stratified according to study centre and with no other restrictions, was computer generated by an investigator who was uninvolved in the clinical care of any participants, distributed to the sites, and kept by personnel not directly involved with the study. These same personnel were responsible for packaging the drug and placebo in opaque envelopes. Patients, study personnel, and treating physicians were masked to study group assignment. The primary outcome of the study was the development of pancreatitis after ERCP. Analyses were done on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, number NCT01912716, and enrolment is complete. Findings: Between July 9, 2013, and March 22, 2018, 1037 eligible patients were enrolled and randomly assigned to receive either standard-dose (n=515) or high-dose indometacin (n=522). Pancreatitis after ERCP occurred in 141 (14%) of 1037 patients-76 (15%) of 515 patients in the standard-dose indometacin group and 65 (12%) of 522 patients in the high-dose indometacin group (risk ratio [RR] 1·19, 95% CI 0·87-1·61; p=0·32). We observed 19 adverse events that were potentially attributable to study drug. Clinically significant bleeding occurred in 14 (1%) of 1037 patients-six (1%) of 515 patients in the standard-dose indometacin group and eight (2%) of 522 patients in the high-dose indometacin group (p=0·79). Three (1%) of 522 patients in the high-dose indometacin group developed acute kidney injury versus none in the standard-dose group (p=0·25). A non-ST elevation myocardial infarction occurred in the standard-dose indometacin group 2 days after ERCP. A transient ischaemic attack occurred in the high-dose indometacin group 5 days after ERCP. All 19 adverse events, in addition to the 141 patients who developed pancreatitis after ERCP, were considered serious as all required admission to hospital. We observed no allergic reactions or deaths at 30 day follow-up. Interpretation: Dose escalation to rectal indometacin 200 mg did not confer any advantage compared with the standard 100 mg regimen, with pancreatitis incidence remaining high in high-risk patients. Current practice should continue unchanged. Further research should consider the pharmacokinetics of non-steroidal anti-inflammatory drugs to determine the optimal timing of their administration to prevent pancreatitis after ERCP.