Preventing copper intrauterine device removals due to side effects among first-time users: randomized trial to study the effect of prophylactic ibuprofen. Control of IUD-induced bleeding by three non-steroidal anti-inflammatory drugs. Nonsteroidal anti-inflammatory drugs and the risk of Parkinson disease. The impact of reference pricing of nonsteroidal anti-inflammatory agents on the use and costs of analgesic drugs. A study of co-treatment of nonsteroidal anti-inflammatory drugs (NSAIDs) with misoprostol for cervical priming before suction termination of first trimester pregnancy. Effect of clinical pharmacists on drug prescribing in a primary-care clinic. Misoprostol prevents NSAID-induced gastroduodenal lesions in patients with osteoarthritis and rheumatoid arthritis. Cimetidine therapy in nonsteroidal anti-inflammatory drug gastropathy. Double-blind long-term evaluation. Misoprostol reduces serious gastrointestinal complications in patients with rheumatoid arthritis receiving nonsteroidal anti-inflammatory drugs. A randomized, double-blind, placebo-controlled trial. Misoprostol compared with sucralfate in the prevention of nonsteroidal anti-inflammatory drug-induced gastric ulcer. A randomized, controlled trial. Nonsteroidal anti-inflammatory drugs and risk of Parkinson's disease. Indomethacin suppositories versus intravenously titrated morphine for the treatment of ureteral colic. Characterization of rofecoxib as a cyclooxygenase-2 isoform inhibitor and demonstration of analgesia in the dental pain model. The therapeutic effectiveness of ibuprofen on the symptoms of naturally acquired common colds.
Increased menstrual bleeding and pain are the primary side effects that lead to early removal of the copper intrauterine device (IUD). Ibuprofen and other non-steroidal anti-inflammatory drugs (NSAIDs) are proven treatments for such IUD-induced problems, but their effect on early IUD removal is unknown.
                A total of 2019 first-time IUD users were recruited in Chile for this double-blind, randomized, placebo-controlled trial. Half of the participants were given ibuprofen and instructions to take 1200 mg daily during menses (for up to 5 days each cycle) for the first 6 months of IUD use. The other half were asked to take an identical appearing placebo in the same manner. The primary outcome was IUD removal within 12 months of insertion.
                A total of 1011 and 1008 women were randomly assigned to ibuprofen and placebo, respectively. During 12 months of observation, 190 had the device removed because of dysmenorrhoea and/or increased menstrual bleeding: 85 in the placebo group and 105 in the ibuprofen group. For ibuprofen users, the hazard ratio for removal for these IUD-induced side effects was 1.0 and 1.2 at 6 and 12 months, respectively (both not significant).
                Although increased menstrual bleeding and pain are common reasons for early IUD removal, prophylactic use of ibuprofen, at the dosage used here, does not reduce removal rates. Administration of nonsteroidal anti-inflammatory drugs (NSAIDs) reduced excessive IUD-induced bleeding. The effect of 3 different oral NSAIDs, namely indomethacin, Alclofenac, and flufenamic acid, on menstrual blood loss (MBL) and pain among women fitted with copper IUDs was studied and compared with a placebo on a randomized single blind basis. Each drug was given to 6 subjects (18 cases) over 2 consescutive cycles and was either preceded or followed by placebo for 2 more cycles. 1/2 of the cases on each drug started placebo medication in the 1st 2 months while the other 1/2 started by the drug. The oral treatment was begun on the 1st day of menstrual bleeding or spotting. Estimation of the daily MBL was done by the alkaline hematin method with mechanical extraction of sanitary pads. The 3 drugs tested in this study induced a significant reduction in MBL: maximum reduction by flufenamic acid medication, less with Alclofenac, and least with indomethacin medication. However, these reductions were not statistically different, and marked improvement in IUD-induced pain was observed under the effect of the 3 drugs. Several lines of evidence suggest a role of inflammatory processes in Parkinson disease, although it is still unclear whether inflammation is a cause or rather a consequence of neurodegeneration.
                In a prospective population-based cohort study among 6,512 participants aged >or=55 years, with repeated in-person examination, we evaluated the association between cumulative use of nonsteroidal anti-inflammatory drugs (NSAIDs) and the risk of Parkinson disease. Complete information on filled prescriptions was available from automated pharmacy records. Data were analyzed by means of Cox proportional hazards regression analysis, adjusted for age, sex, smoking habits and coffee consumption.
                After an average 9.4 years of follow-up, 88 new cases of Parkinson disease were detected. No association was found between use of NSAIDs and the risk of Parkinson disease (adjusted hazard ratio for any NSAID use, 1.50; 95% confidence interval, 0.95-2.37).
                Our findings do not support the hypothesis that NSAIDs might decrease the risk of Parkinson disease.
                (c) 2007 S. Karger AG, Basel. To estimate the effect of reference pricing (RP) of nonsteroidal anti-inflammatory drugs (NSAIDs) on drug subsidy program and beneficiary expenditures on analgesic drugs.
                Monthly claims data from Pharmacare, the public drug subsidy program for seniors in British Columbia, Canada, over the period of February 1993 to June 2001.
                RP limits drug plan reimbursement of interchangeable medicines to a reference price, which is typically equal to the price of the lowest cost interchangeable drug; any cost above that is borne by the patient. Pharmacare introduced two different forms of RP to the NSAIDs, Type 1 in April 1994 and Type 2 in November 1995. Under Type 1 RP, generic and brand versions of the same NSAID are considered interchangeable, whereas under Type 2 RP different NSAIDs are considered interchangeable. We extrapolated average reimbursement per day of NSAID therapy over the months before RP to estimate what expenditures would have been without the policies. These counterfactual predictions were compared with actual values to estimate the impact of the policies; the estimated impacts on reimbursement rates were multiplied by the postpolicy volume of NSAIDS dispensed, which appeared unaffected by the policies, to estimate expenditure changes.
                After Type 2 RP, program expenditures declined by $22.7 million (CAN), or $4 million (CAN), annually cutting expenditure by about half. Most savings accrued from the substitution of low-cost NSAIDs for more costly alternatives. About 20 percent of savings represented expenditures by seniors who elected to pay for partially reimbursed drugs. Type 1 RP produced one-quarter the savings of type 2 RP.
                Type 2 RP of NSAIDs achieved its goal of reducing drug expenditures and was more effective than Type 1 RP. The effects of RP on patient health and associated health care costs remain to be investigated. This double-blind randomized control study was conducted to evaluate whether a nonsteroidal anti-inflammatory drug (NSAID) could act as an effective pain control method during first trimester suction abortion, and whether co-treatment of NSAID with misoprostol will decrease the efficacy of the cervical ripening effect of misoprostol. Subjects were randomized to receive misoprostol alone or misoprostol together with diclofenac sodium. Both groups of subjects suffered from similar incidence of preoperative side effects. Co-treatment of NSAID with misoprostol did not attenuate the cervical ripening efficacy of misoprostol. There was no significant pain reduction in the group treated with NSAID, except that a marginal benefit was found in the subgroup of multiparous women. About two thirds of the subjects in both treatment groups found that this was a satisfactory pain relief method during the procedure. The effect of clinical pharmacy services on prescribing patterns and drug costs for nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates in a primary-care clinic operated by a health-maintenance organization (HMO) was studied. Two pharmacists provided clinical services to a randomly selected cluster of family practice physicians in the HMO for six months. A second family practice cluster served as a control group. The pharmacists alerted prescribers to the availability of low-cost alternatives (such as ibuprofen and salicylates) and reviewed the medication profiles of patients receiving high-cost NSAIDs. Data were collected for both physician clusters for nine months before and six months after the pharmacists' intervention. Changes in the mean numbers of prescriptions for ibuprofen and piroxicam per 1000 enrollees per physician in the baseline and evaluation periods were not significantly different between the two groups. Significantly more prescriptions for salicylates were written by physicians in the intervention group than in the control group during the evaluation period. Annualized mean drug ingredient costs per enrollee and per prescription for NSAIDS and salicylates decreased during the evaluation period in both groups, but these differences were not significant. In relatively unstructured interactions with physicians and nurses, clinical pharmacists were not able to reduce the costs associated with NSAIDs but did have a modest effect on altering salicylate prescribing patterns. This clinical pharmacy program was not economically self-sustaining during the first six months of operation, since operating costs exceeded anticipated savings. The clinical use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with significant adverse effects on the integrity of the gastrointestinal (GI) mucosa. A unique, double-blind, placebo-controlled, randomized, multicentre study investigated the prophylactic co-therapy with misoprostol, a novel PGE1 analog, for the prevention of the NSAID-induced gastric and duodenal mucosal lesions. The study also investigated whether the co-therapy with misoprostol could interfere with the anti-rheumatic action of the NSAIDs using detailed rheumatological assessments. Patients with osteoarthritis or rheumatoid arthritis had to be free of symptoms and significant erosive and/or haemorrhagic lesions of the upper GI tract. The patients were randomized to co-therapy with misoprostol or its matching placebo. Follow-up endoscopy and symptoms assessment were carried out within 4 weeks and compared to pre-study findings. Misoprostol significantly reduced (p less than 0.01) the incidence of erosive and/or haemorrhagic gastric and duodenal mucosal lesions. Misoprostol also reduced the proportion of patients with epigastric pain (p less than 0.01). Misoprostol was well tolerated and did not interfere with the anti-rheumatic activity of the administered NSAID. We conclude that misoprostol is safe and effective in the protection against NSAID-induced gastric and duodenal mucosal lesions and symptoms. To assess the efficacy of cimetidine in treating and preventing gastric mucosal lesions associated with nonsteroidal anti-inflammatory drug (NSAID) therapy (NSAID gastropathy), we endoscopically studied 104 patients taking NSAIDs for a variety of rheumatic diseases. Fifty-six percent (22/43) of patients randomized to cimetidine 300 mg four times a day and 52% (22/42) of those randomized to placebo showed progression of endoscopic lesions during the eight-week short-term phase. Thirty-nine patients whose endoscopic lesions improved were then randomized to a ten-month maintenance regimen of either cimetidine 400 mg at bedtime or placebo. Fifty percent (7/14) of placebo-treated and 42% (5/12) of cimetidine-treated patients showed progression of lesions during the maintenance phase. The failure of cimetidine to offer any significant benefit under these protocol conditions reflects the fundamental difference in pathophysiologic features between classic acid-mediated ulcer disease and NSAID gastropathy. To investigate whether concurrent administration of misoprostol reduces the occurrence of serious upper gastrointestinal complications, such as perforation, gastric outlet obstruction, or bleeding, in patients with rheumatoid arthritis who are receiving nonsteroidal anti-inflammatory drugs (NSAIDs).
                6-month randomized, double-blind, placebo-controlled trial.
                664 clinical practices of family medicine, internal medicine, or rheumatology in the United States and Canada.
                8843 men and women (mean age, 68 years) receiving continuous therapy with any of 10 specified NSAIDs for control of symptoms of rheumatoid arthritis. Patients were enrolled between July 1991 and August 1993.
                Patients were randomly assigned to receive 200 micrograms of misoprostol or placebo four times a day.
                Development of serious upper gastrointestinal complications detected by clinical symptoms or findings (not by scheduled endoscopy).
                Serious upper gastrointestinal complications were reduced by 40% (odds ratio, 0.598 [95% CI, 0.364 to 0.982; P = 0.049]) among patients receiving misoprostol (25 of 4404 patients) compared with those receiving placebo (42 of 4439 patients). During the first month, more patients receiving misoprostol (20%) than placebo (15%) withdrew from the study, primarily because of diarrhea and related problems (P < 0.001). Risk factors for serious upper gastrointestinal complications were increasing age, history of peptic ulcer or bleeding, and cardiovascular disease. Patients with all four risk factors would have a 9% risk for a major complication in 6 months.
                In older patients with rheumatoid arthritis, misoprostol reduced serious NSAID-induced upper gastrointestinal complications by 40% compared with placebo. To compare the efficacy and frequency of adverse experiences of misoprostol and sucralfate in the prevention of gastric ulcers in patients receiving nonsteroidal anti-inflammatory drug (NSAID) therapy.
                A prospective, randomized, single-blind, multicenter trial.
                Patients with osteoarthritis receiving treatment with ibuprofen, piroxicam, or naproxen and experiencing abdominal pain were eligible.
                Patients who were expected to receive at least 3 months of NSAID therapy and who did not have a gastric ulcer at the time of the initial screening endoscopy were randomized to receive misoprostol, 200 micrograms four times a day, or sucralfate, 1 g four times a day. A gastric ulcer was defined as a lesion of the gastric mucosa 0.3 cm or greater in diameter. Patients were followed clinically, and repeat endoscopies were performed after 4, 8, and 12 weeks.
                The development of a gastric ulcer, which was regarded as a prophylaxis failure.
                Two hundred fifty-three patients were evaluable for efficacy analysis. A gastric ulcer developed in 2 of the 122 (1.6%, 95% CI, 0.3% to 6.4%) patients on misoprostol, compared with 21 of 131 patients on sucralfate (16%, CI, 10.4% to 23.7%). The difference in ulcer rates was 14.4% (CI, 10.4% to 19.5%; P less than 0.001).
                In patients receiving chronic NSAID therapy for osteoarthritis, treatment with misoprostol for 3 months was associated with a significantly lower frequency of gastric ulcer formation, compared with treatment with sucralfate (P less than 0.001). Inflammation and oxidative stress have been implicated as pathogenic mechanisms in Parkinson's disease (PD). Evidence from in vitro and animal studies suggests a possible protective role of nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin. We investigated the risk of PD associated with use of aspirin and nonaspirin NSAIDs in a population-based case-control study among enrollees of Group Health Cooperative, a health maintenance organization in the Seattle area. Subjects included 206 cases between ages 35 and 89 with a new diagnosis of idiopathic PD between 1992 and 2002, and 383 randomly selected controls frequency-matched by age, sex, duration of enrollment, and clinic. We obtained information on participants' age, smoking, and medical history from interview. Exposure to NSAIDs was ascertained from an automated pharmacy database. Medications filled within 5 years of the interview were excluded. After adjusting for age, sex, smoking, duration of enrollment, and clinic, the risk of PD among individuals who received nonaspirin NSAIDs between 1977 and 1992 was 0.90 (95% CI: 0.59-1.35) and 1.67 (95% CI: 0.60-4.60) between 1993 and 2002. Use of ibuprofen was not associated with PD (OR: 0.89; 95% CI: 0.60-1.32). The risk of PD associated with aspirin or aspirin-containing medications was 0.74 (95% CI: 0.49-1.12). We observed no trend in risk according to number of fills for these drugs. Our results provide only limited support for the hypothesis that use of aspirin may reduce the risk of this disease, and no indication of protection from other NSAIDs.
                (c) 2006 Movement Disorder Society. To develop a protocol for the blinded IV titration of morphine and to compare the analgesic efficacy and side effect profile of indomethacin suppositories versus IV morphine in the treatment of acute ureteral colic.
                Randomized, double-blind, double-dummy, two-period crossover study.
                Emergency department of a central-city, teaching hospital.
                Patients 18 to 75 years of age with pain suggestive of ureteral colic. Exclusions included pregnancy, adverse reactions to the study drugs, chronic nonsteroidal anti-inflammatory drug (NSAID) therapy, or any pain medicine taken within four hours of ED admission.
                Patients were randomized to one of two groups: indomethacin 100-mg rectal suppository or morphine by IV titration (5-mg loading dose and up to two additional 2.5-mg doses if needed). At the end of 30 minutes, if adequate pain relief had not been obtained, treatment was crossed over.
                Verbal analog scale (initial pain) and visual analog pain relief scale.
                Seventy-five patients were entered into the study. Only data from those patients with stone presence confirmed by IV pyelogram or stone passage were analyzed. Twenty-four could not be evaluated (23 who did not meet criteria for stone presence and one whose pain resolved spontaneously before study medications could be administered). Of the remaining 51 patients, 31 received indomethacin first and 20 received morphine first. Morphine recipients reported more pain relief at ten minutes (P = .02), but at 20 and 30 minutes, no significant difference (P = .17 and .74, respectively) existed between the two groups.
                IV morphine produced more rapid analgesia than rectally administered indomethacin. There were no significant differences in vital sign changes or number of side effects between the two treatment groups. This study is the first to compare an NSAID with morphine administered by IV titration, considered by many to be the "gold standard" for relief of acute, severe pain. Future studies could evaluate the simultaneous administration of an opioid combined with an NSAID or compare an IV titrated opioid with an IV NSAID. Nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin, ibuprofen, and indomethacin (INN, indometacin) inhibit both the constitutive (COX-1) and inducible (COX-2) isoforms of cyclooxygenase. The induction of COX-2 after inflammatory stimuli has led to the hypothesis that COX-2 inhibition primarily accounts for the therapeutic properties of NSAIDs.
                Chinese hamster ovary (CHO) cell lines that express each COX isoform were used to characterize the in vitro selectivity of rofecoxib. Single oral doses of rofecoxib and indomethacin were then assessed in subjects with use of ex vivo COX-isoform specific assays (serum thromboxane B2 [TXB2] and lipopolysaccharide [LPS]-stimulated whole blood prostaglandin E2 and assays of COX-1 and COX-2 activity, respectively). A double-blind, parallel-group study compared the analgesic efficacy of rofecoxib to placebo and ibuprofen in 102 patients with dental pain.
                Rofecoxib showed a >800-fold COX-2 selectivity with use of CHO cells that express human COX-1 and COX-2. In subjects, dose- and concentration-dependent inhibition of LPS-stimulated prostaglandin E2 was observed with both rofecoxib (IC50 [the concentration estimated to produce 50% inhibition], 0.77 micromol/L) and indomethacin (IC50, 0.33 micromol/L). Whereas indomethacin inhibited TXB2, (IC50, 0.14 micromol/L), no inhibition was observed with rofecoxib even at doses of up to 1000 mg. In the dental pain study, total pain relief (TOTPAR) over the 6 hours after dosing was similar between 50 mg and 500 mg rofecoxib and 400 mg ibuprofen (P > .20). All active treatments showed greater improvement than placebo (P < .001)
                Rofecoxib inhibited COX-2 without evidence of COX-1 inhibition, even at oral doses of up to 1000 mg. Nonetheless, rofecoxib showed analgesic activity indistinguishable from that observed with ibuprofen, a nonisoform-selective COX inhibitor. These results support the hypothesis that the analgesic effects of NSAIDs primarily derive from inhibition of COX-2. The pathogenesis of the common cold is associated with inflammation of the nasal mucous membrane with polymorphonuclear cells (PMNs)(1,2) and increased levels of inflammatory cytokines and mediators in nasal secretions.(3,4) We have investigated the effect of a nonsteroidal anti-inflammatory drug (NSAID) ibuprofen, 400 mg three times daily, in a placebo-controlled trial of 80 adults with naturally occurring common colds. Ibuprofen caused a significant reduction of headache (p = 0.008), earache (p = 0.01), muscle/joint pain (p = 0.045), and reduced body temperature (p = 0.02). There was a 40% reduction in the number of sneezes (p = 0.02) and a 33% reduction in the symptom score for sneezing (p = 0.04). This study did not detect any effect on other nasal symptoms.
Nonsteroidal anti-inflammatory drugs reduce bleeding and pain associated with IUD use. NSAIDs should be considered first-line therapy; if NSAIDs are ineffective, tranexamic acid may be considered as second-line therapy. Prophylactic ibuprofen administration with the first six menses after insertion appears unwarranted.