Cyclooxygenase-2 Inhibitor Treatment Research Articles

Transcription factor Ets-1 inhibits glucose-stimulated insulin secretion of pancreatic β-cells partly through up-regulation of COX-2 gene expression

Increased cyclooxygenase-2 (COX-2) expression is associated with pancreatic β-cell dysfunction. We previously demonstrated that the transcription factor Ets-1 significantly up-regulated COX-2 gene promoter activity. In this report, we used the pancreatic β-cell line INS-1 and isolated rat islets to investigate whether Ets-1 could induce β-cell dysfunction through up-regulating COX-2 gene expression. We investigated the effects of ETS-1 overexpression and the effects of ETS-1 RNA interference on endogenous COX-2 expression in INS-1 cells. We used site-directed mutagenesis and a dual luciferase reporter assay to study putative Ets-1 binding sites in the COX-2 promoter. The effect of ETS-1 1 overexpression on the insulin secretion function of INS-1 cells and rat islets and the potential reversal of these effects by a COX-2 inhibitor were determined in a glucose-stimulated insulin secretion (GSIS) assay. ETS-1 overexpression significantly induces endogenous COX-2 expression, but ETS-1 RNA interference has no effect on basal COX-2 expression in INS-1 cells. Ets-1 protein significantly increases COX-2 promoter activity through the binding site located in the -195/-186 region of the COX-2 promoter. ETS-1 overexpression significantly inhibited the GSIS function of INS-1 cells and islet cells and COX-2 inhibitor treatment partly reversed this effect. These findings indicated that ETS-1 overexpression induces β-cell dysfunction partly through up-regulation of COX-2 gene expression. Moreover, Ets-1, the transcriptional regulator of COX-2 expression, may be a potential target for the prevention of β-cell dysfunction mediated by COX-2.

Patent Ductus Arteriosus, Low Platelets, Cyclooxygenase Inhibitors, and Intraventricular Hemorrhage in Very Low Birth Weight Preterm Infants

To assess the risk for intraventricular hemorrhage (IVH) in very low birth weight preterm infants with patent ductus arteriosus (PDA) and low platelet count with treatment with cyclooxygenase (COX) inhibitors. Diagnosis and treatment of PDA, as well as risk factors for IVH, were assessed using prospectively collected data of all infants born at a gestational age <32 weeks and with a birth weight ≤ 1500 g at Innsbruck University Hospital (January 2003-December 2009). Infants with severe thrombocytopenia (<50 × 10(9)/L) were excluded from analysis. Sixty-five (20%) of the 325 infants had IVH, and 149 (45.9%) of the 325 were treated with COX inhibitors. Treatment of PDA with COX inhibitors was not an independent risk predictor for IVH in preterm infants with platelets ≥ 100 × 10(9)/L. However, COX inhibitors amplified the risk of bleeding in the presence of moderately decreased platelets (50-99 × 10(9)/L) on days of life 2-7. Multivariable OR for IVH were 0.89 [95% CI 0.43-1.87] for patients with platelets ≥ 100 × 10(9)/L and treatment with COX inhibitors, 3.40 [95% CI 1.13-10.29] for those with moderately decreased platelets without treatment, and 53.3 [95% CI 5.9-484] for patients with both moderately decreased platelets and COX inhibitor treatment compared with those with platelets ≥ 100 × 10(9)/L and no treatment (reference group) (P < .001). In very low birth weight infants with moderate thrombocytopenia treatment with COX inhibitors increased the risk for intracerebral bleeding. Any benefits of this therapy should be carefully balanced against this potential hazard.

Randomized Trial of Cisplatin versus Firocoxib versus Cisplatin/Firocoxib in Dogs with Transitional Cell Carcinoma of the Urinary Bladder

Cisplatin combined with a nonselective cyclooxygenase (cox) inhibitor has potent antitumor activity against transitional cell carcinoma (TCC) in dogs, but this treatment is limited by renal toxicosis. Cox-2 is expressed in TCC, but only in limited sites within the kidney. A cox-2 inhibitor could enhance the antitumor activity of cisplatin with potentially fewer adverse effects on the kidney. Cisplatin/cox-2 inhibitor treatment will have greater antitumor activity but no more renal toxicosis than cisplatin alone in dogs with TCC. Forty-four dogs with naturally occurring urinary bladder TCC. Dogs were randomized to receive cisplatin (60 mg/m(2) IV q21d), firocoxib (5 mg/kg PO q24h), or the combination. Tumor measurements were determined before and at 6-week intervals during treatment. Renal function was monitored by serum creatinine concentration, iohexol clearance, and urine specific gravity. Toxicoses were graded according to Veterinary Co-Operative Oncology Group (VCOG) criteria. The remission rate with cisplatin/firocoxib (57%) was significantly (P = .021) higher than that with cisplatin alone (13%). Renal and gastrointestinal toxicoses were common in dogs receiving cisplatin, but there were no significant differences between dogs receiving cisplatin or cisplatin/firocoxib. Firocoxib alone induced partial remission or stable disease in 20 and 33% of dogs, respectively. Firocoxib significantly enhanced the antitumor activity of cisplatin resulting in partial remission in more than half of the cases. The toxicoses inherent to cisplatin, however, were noted in dogs receiving this combination. Firocoxib had antitumor effects as a single agent and can be considered a palliative treatment for dogs with TCC.

Effectiveness of Cyclooxygenase-2 Inhibition in Limiting Abdominal Aortic Aneurysm Progression in Mice Correlates With a Differentiated Smooth Muscle Cell Phenotype

Abdominal aortic aneurysms (AAAs) are a chronic condition that often progress over years to produce a weakened aorta with increased susceptibility for rupture, and currently, there are no pharmacological treatments available to slow disease progression. AAA development has been characterized by increased expression of cyclooxygenase-2 (COX-2), and inactivation of COX-2 before disease initiation reduces AAA incidence in a mouse model of the disease. The current study determined the effectiveness of COX-2 inhibition on AAA progression when treatment was begun after initiation of the disease. COX-2 inhibitor treatment with celecoxib was initiated after angiotensin II-induced AAA formation in a strain of nonhyperlipidemic mice that we have previously identified as highly susceptible to AAA development. When analyzed at different time points during progression of the disease, celecoxib treatment significantly reduced the incidence and severity of AAAs. The celecoxib treatment also protected the mice from aortic rupture and death. The aneurysmal lesion displayed an altered smooth muscle cell (SMC) phenotype, whereas celecoxib treatment was associated with increased expression of differentiated SMC markers and reduced dedifferentiation marker expression during AAA progression. Maintenance of a differentiated SMC phenotype is associated with the effectiveness of COX-2 inhibition for limiting AAA progression in nonhyperlipidemic mice.

Cyclooxygenase-2 Inhibition Attenuates Abdominal Aortic Aneurysm Progression in Hyperlipidemic Mice

Abdominal aortic aneurysms (AAAs) are a chronic inflammatory disease that increase the risk of life-threatening aortic rupture. In humans, AAAs have been characterized by increased expression of cyclooxygenase-2 and the inactivation of COX-2 prior to disease initiation reduces AAA incidence in a mouse model of the disease. The current study examined the effectiveness of selective cyclooxygenase-2 (COX-2) inhibition on reducing AAA progression when administered after the initiation of AAA formation. AAAs were induced in hyperlipidemic apolipoprotein E-deficient mice by chronic angiotensin II (AngII) infusion and the effect of treatment with the COX-2 inhibitor celecoxib was examined when initiated at different stages of the disease. Celecoxib treatment that was started 1 week after initiating AngII infusion reduced AAA incidence by 61% and significantly decreased AAA severity. Mice treated with celecoxib also showed significantly reduced aortic rupture and mortality. Treatment with celecoxib that was started at a late stage of AAA development also significantly reduced AAA incidence and severity. Celecoxib treatment significantly increased smooth muscle alpha-actin expression in the abdominal aorta and did not reduce expression of markers of macrophage-dependent inflammation. These findings indicate that COX-2 inhibitor treatment initiated after formation of AngII-induced AAAs effectively reduces progression of the disease in hyperlipidemic mice.

Cyclooxygenase Inhibition in Sepsis: Is There Life after Death?

Prostaglandins are important mediators and modulators of the inflammatory response to infection. The prostaglandins participate in the pathogenesis of hemodynamic collapse, organ failure, and overwhelming inflammation that characterize severe sepsis and shock. In light of this, cyclooxygenase (COX) inhibiting pharmacological agents have been extensively studied for their capacity to ameliorate the aberrant physiological and immune responses during severe sepsis. Animal models of sepsis, using the systemic administration of pathogen-associated molecular patterns (PAMPs) or live pathogens, have been used to examine the effectiveness of COX inhibition as a treatment for severe sepsis. These studies have largely shown beneficial effects on mortality. However, human studies have failed to show clinical utility of COX inhibitor treatment in severely septic patients. Why this approach “worked” in animals but not in humans might reflect differences in the controlled nature of animal investigations compared to human studies. This paper contrasts the impact of COX inhibitors on mortality in animal models of sepsis and human studies of sepsis and examines potential reasons for differences between these two settings.

Niacin inhibits skin dendritic cell mobilization in a GPR109A independent manner but has no impact on monocyte trafficking in atherosclerosis

High-dose niacin therapy in humans reduces mortality from cardiovascular disease and may also protect against death from other causes, with benefits apparent more than a decade beyond the therapeutic period. Niacin therapy modulates circulating lipids, raising HDL and lowering LDL, but has the unwanted side effect of inducing skin flushing in response to treatment. Skin flushing results from niacin-induced activation of GPR109A and subsequent release of prostaglandins that promote vasodilation. GPR109A may also mediate HDL elevation. Recent data suggest that high-dose niacin may have benefits beyond improved lipid profiles, such as quelling inflammation, suggesting a potential role in immune cell trafficking. To explore effects of niacin on immune cell trafficking independently of its effects on lipid profiles, we took advantage of the fact that niacin therapy does not raise HDL in wild-type or apoE−/− mouse strains. Wild-type and apoE−/− C57BL/6 mice were fed standard chow or high-fat diets supplemented or not with 1% niacin. Against our predictions, this treatment did not modulate monocyte recruitment to or retention within atherosclerotic plaques. By contrast, stimulating the skin of niacin-treated mice with a contact sensitizer revealed impaired dendritic cell accumulation in draining lymph nodes and associated impaired adaptive immunity. Surprisingly, niacin-mediated impaired dendritic cell mobilization could not be reversed by cyclooxygenase inhibitor treatment nor deletion of the niacin receptor GPR109A, suggesting that the effects of niacin on modulating the migration of dendritic cells are not directly linked to skin flushing. Overall, these data suggest the existence of novel pathways triggered by niacin that, through suppression of dendritic cell migration, might impact adaptive immune responses that participate in sustained therapeutic benefits independent of niacin's cardioprotective capabilities.

A cyclooxygenase-2 inhibitor reduces serum prostatic-specific antigen levels in men with benign prostatic hyperplasia and lower urinary tract symptoms and helps differentiate chronic inflammation from prostate cancer

Emerging evidence indicates that prostatic inflammation may contribute to prostatic growth in benign prostatic hyperplasia (BPH) and neoplastic changes (prostate cancer). The Medical Therapy of Prostatic Symptoms study showed that men with inflammation had a significantly higher risk of BPH progression and acute urinary retention. Evidence also shows that a cyclooxygenase-2 (COX-2) inhibitor can increase apoptotic activity in human BPH tissue. COX-2 inhibitors in combination with alpha-adrenergic blockers may increase the effectiveness of therapy for lower urinary tract symptoms (LUTS) secondary to BPH without significant side effects. COX-2 inhibitors may decrease the serum prostatic-specific antigen level and act as a biomarker to differentiate chronic inflammation from prostate cancer in patients with LUTS suggestive of BPH who do not have a palpable prostate nodule but have a serum prostatic-specific antigen level higher than 4 ng/mL. The results might provide a simple way to initially differentiate chronic inflammation from prostatic cancer. If chronic inflammation of the prostate can be reduced by COX-2 inhibitor treatment, bothersome LUTS as well as voiding conditions might be improved.

Ultrasound Stimulation Induces PGE 2 Synthesis Promoting Cementoblastic Differentiation Through EP2/EP4 Receptor Pathway

The present study aims to provide insights into how ultrasound treatment (US) can affect the regenerative response of cementum by evaluating the role of prostaglandin E 2 induced by ultrasound stimulation on cementoblastic differentiation. The mouse cementoblast cell line OCCM-30 was exposed to low-intensity ultrasound and the cyclooxygenase-2 (COX-2) mRNA expression and prostaglandin E 2 (PGE 2) production were quantified. The role of the US-induced PGE 2 in mineralization was examined using COX-2 inhibitor and prostaglandin receptors (EP-receptors) agonists and antagonists. In addition, gene expression of differentiation markers related to mineral metabolism was evaluated. Ultrasound significantly enhanced COX-2 mRNA expression and PGE 2 production. PGE 2 induced by US mediated mineral nodule formation, whereas COX-2 inhibitor treatment eliminated the enhancement of mineralization induced by US stimulation. Mineral deposition was also inhibited by treatment with EP2 or EP4 antagonist. Moreover, up-regulation of differentiation markers induced by US was suppressed by treatment with COX-2 inhibitor. The present findings provide evidence that US stimulation has a positive effect on mineralization ability of cementoblasts through the activation of EP2/EP4 pathway, suggesting that US can be a promising therapeutic tool for cementum repair. (E-mail: emanuelbraga@hiroshima-u.ac.jp)

Prolonged Postoperative Administration of a COX-2 Inhibitor Significantly Decreases Pain and Improves Function Following Knee Replacement Surgery

Perioperative administration of a COX-2 inhibitor has demonstrated decreased in-hospital narcotic requirements and improved knee range of motion after total knee arthroplasty (TKA). The purpose of this study was to determine what benefits resulted from an additional 6 weeks of COX-2 inhibitor treatment.

Correction: A Computer Simulation of Progesterone and Cox2 Inhibitor Treatment for Preterm Labor

The affiliations of the fifth author, Charles F. Simmons, are incorrect. He is affiliated only with #1, Department of Pediatrics, Steven Spielberg Pediatric Research Center, Burns and Allen Research Institute, Cedars-Sinai Medical Center, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, United States of America

Neurodevelopmental outcome after COX inhibitor treatment for patent ductus arteriosus

Aim To compare neurodevelopmental results in very low birth weight (VLBW) infants two years after successful or failed cyclooxygenase inhibitor treatment with either indomethacin or ibuprofen for a haemodynamically significant patent ductus arteriosus (hsPDA). Methods We retrospectively evaluated closure rates and outcome parameters of VLBW infants with hsPDA 89 of whom were treated with indomethacin and 93 with ibuprofen. Results Indomethacin and ibuprofen therapy groups did not differ in their baseline clinical profile (median gestational age 26.0 and 26.2 wks d) in early (median CRIB 6 and 5, respiratory distress > 2° in 36 and 34 infants) and late morbidities (intraventricular hemorrhage > 2° in 9 and 10 infants, bronchopulmonary dysplasia in 31 and 27 infants, 80 and 85 survivors), PDA closure rates (63 and 58%) or neurodevelopmental outcome. The therapy failure group (54 infants) was characterized by lower median gestational age (25.0 wks d) and higher mortality (17%). No differences were found in the neurodevelopmental outcome of the surviving infants with ligation as compared to the survivors with successful pharmacological closure of the PDA at 24 months corrected age. Conclusion Use of either ibuprofen or indomethacin for closure of a hsPDA did not influence two year neurodevelopmental outcomes in VLBW infants.

A Computer Simulation of Progesterone and Cox2 Inhibitor Treatment for Preterm Labor

BackgroundSufficient information from in vitro and in vivo studies has become available to permit computer modeling of the processes that occur in the myometrium during labor. This development allows the in silico investigation of pathological mechanisms and the trialing of potential treatments.Methods/ResultsBased on the human literature, we developed a computer model of the immune-endocrine environment of the myometrial cell. The interactions between molecules are represented by differential equations. The model is designed to simulate the estrogen and progesterone receptor changes during pregnancy and particularly the changes in the progesterone receptor (PR) isoforms A and B that are thought to mediate functional progesterone withdrawal in the human at labor. Parturition is represented by an increase in the PRA to PRB ratio to levels seen in women in labor. Infection is shown by inducing inflammation in the system by increasing phospho-IkB kinase concentration (IKK) levels; which lead to increased NF-κB activation, causing an increase in the PRA/PRB ratio. We examined the effects of progesterone or cyclo-oxygenase 2 (Cox2) inhibitor treatments on the PRA/PRB ratio in silico. The model predicted that high doses of progesterone and Cox2 inhibition would be effective in preventing an NF-κB-induced PRA/PRB ratio increase to the levels found during labor.ConclusionsOur data illustrate the use of dynamic biological computer simulations to test the effectiveness of therapeutic interventions. This may allow the early rejection of ineffective therapies prior to expensive field trials.

Abstract A48: In vivo evaluation of Cox-2 inhibition to prevent the progression of invasive urinary bladder cancer

Abstract Background: Invasive transitional cell carcinoma (InvTCC) of the urinary bladder has a propensity to metastasize, is only partially responsive to chemotherapy, and causes &amp;gt; 14,000 deaths yearly in the United States. The development of effective means to prevent the development and progression of InvTCC is crucial. Cyclooxygenase-2 (Cox-2) is over-expressed in InvTCC in humans and animals. In a pilot study, a Cox-2 inhibitor induced apoptosis of InvTCC in humans. Cox-2 inhibitors may offer an avenue for prevention of InvTCC progression. The purpose of this study was to determine the effects of Cox-2 inhibitor treatment in preventing the progression of InvTCC in a highly relevant animal model, canine InvTCC. Naturally-occurring InvTCC in dogs closely mimics human InvTCC in cellular and molecular features (including Cox-2 expression), sites and frequency of metastasis, and response to therapy. Methods: Dogs with histologically confirmed InvTCC who failed or whose owner declined standard chemotherapy protocols, and with expected survival of &amp;gt; 6 weeks were prospectively enrolled. The Cox-2 inhibitor deracoxib (Novartis, Greensboro, NC) was given as a single agent with a planned dose of 3mg/kg/day orally. Dogs were evaluated prior to and during therapy with abdominal ultrasound including mapping of the urinary bladder masses, thoracic radiographs, complete blood count, serum biochemistry profiles and urinalyses. Toxicity was assessed by clinical signs and serial blood work. Tumor response was defined as: complete remission (CR), no evidence of disease detected; partial remission (PR) ≥ 50% reduction in tumor volume; stable disease (SD) &amp;lt;50% change in tumor volume; or progressive disease (PD) ≥ 50% increase in tumor volume or new lesions. A whole blood assay was used to confirm selective Cox-2 inhibition. Results: Thirty-nine dogs with InvTCC received deracoxib at a mean dose of 2.79 mg/kg/day (range 1.18 mg/kg/day to 4.08mg/kg/day). Of 39 dogs, 1 had nodal metastasis, and 3 had distant metastasis at diagnosis. Initial responses in 30 dogs with measurable disease included PR in 4 dogs (13%), SD in 17 dogs (57%), and PD in 3 dogs (10%); and in 6 dogs, response to therapy has not been determined. Mean time to subsequent PD (n=20) was 167 days (range 36 – 482 days). After PD was noted, 10 dogs went on to receive other therapy (leukeran, mitoxantrone, mitomycin-C, 5 azacitidine, carboplatin). Of the 39 dogs treated, 9 had microscopic residual disease after surgical intervention. Of these 9 dogs, 4 had relapse (median time to relapse, 221 days), and 3 had not relapsed at the time of death from other causes (median time to death 772 days). The median survival times for dogs with measurable disease and microscopic disease were 349 and 772 days, respectively. Conclusion: The results of this work help justify further study of the use of Cox-2 inhibitors in preventing the progression of InvTCC. Citation Information: Cancer Prev Res 2010;3(1 Suppl):A48.

Peran Siklooksigenase dalam Pertumbuhan Kanker Leher Rahim

Cyclooxygenase-2 (COX-2) expression and selective COX-2 inhibitor such as celecoxib, which widely used as antiinflamatory drug, is known to have role in cancer by reducing proliferation and growth of turnor cells, and increasing apoptosis. The research aims were to investigate the effect of selective COX-2 inhibitor and role of COX- 2 on tumor growth. This was an experimental study with pretest-posttestcontrol group design. This study was done at Hasan Sadikin Hospital Bandung, November 2007-0ctober 2008. Twenty patients received selective COX-2 inhibitor and chemoradiation, whereas 21 patients were treated by chemoradiation only, as control group. COX-2, K.i-67, and caspase-3 expression was analyzed by immunohistochemistry. Cervical size was measured by transabdominal ultrasonograpy. All variables obtained before and afterextemal chemoradiation. Data were analyzed using Wilcoxon and Pearson's correlation test. Selective COX-2 inhibitor significantly reduced COX-2 expression, 10% in control group and 42% in treated group (p=O.OO I) as well as Ki-67 expression as proliferation marker, -3% in the control group and 48% in the treated group (p~0.007). Caspase-3 expression as marker of apoptosis was increased after selective COX-2 inhibitor treatment, 59% whereas only 16% in the control group (p

Effects of cyclooxygenase inhibitor treatment on the renal toxicity of cisplatin in rats

The purpose of this study was to determine the effects of a nonselective cyclooxygenase (cox) inhibitor and of a selective cox-2 inhibitor on the renal toxicity of cisplatin. Cisplatin with or without a cox-1 inhibitor (SC560), a cox-2 inhibitor (SC236), or a nonselective cox inhibitor (piroxicam) was administered to Sprague-Dawley rats. Renal toxicity was assessed by serum creatinine concentration (SCR), urine specific gravity (USG), and histopathologic lesion score (HLS). Acutely, the SCR was significantly higher in rats receiving cisplatin/SC560 (1.62+/-0.34 mg/dl) or cisplatin/piroxicam (2.0+/-0.41 mg/dl) than in rats receiving cisplatin alone (1.09+/-0.40 mg/dl). The apparent increase in SCR in the rats receiving cisplatin/SC236 (1.58+/-0.31) was not significantly different from that of rats receiving cisplatin alone (1.09+/-0.40 mg/dl). No significant differences in USG or HLSs were noted between rats receiving cisplatin alone and cisplatin combined with any cox inhibitor. In a chronic study, no differences in renal toxicity were found between rats treated with cisplatin alone and cisplatin/SC236 or cisplatin/piroxicam. The acute rise in SCR following cisplatin treatment can be worsened by the addition of cox inhibitors, especially those that inhibit cox-1.

Improvement in docetaxel-induced nail changes associated with cyclooxygenase-2 inhibitor treatment

Improvement in docetaxel-induced nail changes associated with cyclooxygenase-2 inhibitor treatment

Total serum bilirubin levels during cyclooxygenase inhibitor treatment for patent ductus arteriosus in preterm infants

To determine whether ibuprofen use in VLBW infants is associated with increased serum bilirubin levels and impaired neurodevelopmental outcome at 2 years of age compared to indomethacin. We retrospectively evaluated bilirubin data and outcome parameters of 178 VLBW infants treated with COX inhibitors for a haemodynamically relevant patent ductus arteriosus (PDA) between 1998 and 2003 in a single institution. In our department ibuprofen replaced indomethacin for PDA treatment in 2001, while clinical and echocardiographic criteria for the indication of PDA invention have remained unchanged. Ibuprofen and indomethacin therapy groups did not differ in their baseline clinical profile. Peak serum bilirubin concentration was 10.2 mg/dL in the ibuprofen group and 8.6 mg/dL in the indomethacin group (p < 0.01), while phototherapy duration did not differ. At 2 years of age neurodevelopmental outcome was similar in both groups. In a single case analysis, four cases of adverse neurodevelopmental outcome despite inconspicuous clinical course were identified in the ibuprofen group. In VLBW infants with PDA, ibuprofen treatment was associated with higher bilirubin levels than indomethacin.

Nonselective and Cyclooxygenase-2-Selective NSAIDs and Acute Kidney Injury

Objective The association between nonsteroidal anti-inflammatory drugs (NSAIDs) and acute kidney injury is well established, but it is less clear whether this risk is focused with specific agents. We undertook a large pharmacoepidemiologic analysis of the risk of acute kidney injury among older adults using nonselective NSAIDs or cyclooxygenase (COX)-2 inhibitors. Methods Medicare beneficiaries from 2 large states with drug benefit were eligible for study. Patients were included if they filled a prescription for a nonselective NSAID or COX-2 inhibitor after more than 6 months without any such prescriptions and without a previous diagnosis of acute kidney injury. Incident acute kidney injury was ascertained from hospitalization claims within 45 days of initiating nonselective NSAID or COX-2 inhibitor therapy. Adjusted proportional hazards models estimated the relative risk of acute kidney injury associated with each agent compared with celecoxib. Results We included 183,446 patients whose mean age was 78 years; 80% were women. Acute kidney injury was identified in 870 (0.47%) of nonselective NSAID or COX-2 inhibitor users. The agents with significantly elevated risk compared with celecoxib were indomethacin (rate ratio [RR] = 2.23; 95% confidence interval [CI], 1.70-2.93), ibuprofen (RR = 1.73; 95% CI, 1.36-2.19), and rofecoxib (RR = 1.52; 95% CI, 1.26-1.83). These findings were robust in several subgroups. Conclusion Acute kidney injury requiring hospitalization is a relatively rare adverse event among older adults after initiation of nonselective NSAIDs or COX-2 inhibitor treatment, observed in approximately 1 in 200 new users within 45 days. There seems to be a marked gradient of risk for acute kidney injury across agents, specifically for indomethacin, ibuprofen, and rofecoxib.

Effectiveness of COX2 inhibitor treatment in patients with dysplastic oral leukoplakia

Effectiveness of COX2 inhibitor treatment in patients with dysplastic oral leukoplakia