Nonsteroidal Anti-inflammatory Drugs Regimen Research Articles

Novel combined pharmacological strategy to alleviate acute phase response following zoledronic acid treatment.

Osteoporosis is a common condition associated with high morbidity rates, often requiring treatment with bisphosphonates such as zoledronic acid. However, the persistence to zoledronic acid infusion is commonly limited by acute phase response (APR). This retrospective study aimed to evaluate the efficacy of a novel combination therapy in preventing APR symptoms. A retrospective case-control study was conducted on 931 patients who received their first zoledronic acid infusion between 2011 and 2021. We evaluated the efficacy of combination therapy comprising a single dose of hydrocortisone prior to the infusion and a 3-d oral regimen of non-steroidal anti-inflammatory drugs, acetaminophen, and prednisolone following the infusion. Patients were divided into protocol (receiving combination therapy) and control groups (without treatment). Baseline characteristics, APR incidence, and the efficacy of symptom control were compared between groups using Fisher's exact test and Student's t-test. There was no difference in APR incidence between the protocol (n = 507) and control group (n = 407; p = 0.1442). However, the protocol group exhibited lower intolerable APR levels (3.72% vs. 16.71%; p < 0.0001) and complete symptom relief in 96.28% of cases. The combination therapy protocol effectively reduced intolerable APR and relieved symptoms in most patients following zoledronic acid infusion. This study highlights the importance of proactive management strategies for APR and emphasizes the potential of combination therapy in alleviating APR symptoms and reducing the occurrence of severe APR in patients undergoing osteoporosis management.

Does the Use of a Visual Cognitive Aid Improve Patient Compliance With a Postoperative Analgesic Regimen? A Randomized Controlled Trial

The use of scheduled non-steroidal anti-inflammatory drugs (NSAIDs) and acetaminophen in the postoperative setting has been shown to reduce the need for prescription narcotic pain medications. Our objective is to determine if the implementation of a visual cognitive aid will improve patient compliance with a scheduled NSAID and acetaminophen regimen, thereby decreasing the use of narcotic pain medications. We conducted a single-blind randomized controlled trial in patients receiving outpatient oral surgery procedures from a single office.

Duration of Symptom Relief and Early Trajectory of Adverse Events for Oral Nonsteroidal Antiinflammatory Drugs in Knee Osteoarthritis: A Systematic Review and Meta-Analysis.

Despite an extensive body of research on nonsteroidal antiinflammatory drugs (NSAIDs) in osteoarthritis, the duration of their efficacy and timeline of adverse event (AE) onset have been understudied. We conducted a systematic review and meta-analyses from 2 to 26 weeks to characterize the efficacy and AE trajectories of oral NSAIDs in knee osteoarthritis. We searched MEDLINE, Embase, Web of Science, Google Scholar, and the Cochrane Database from inception to May 2018. Randomized controlled trials assessing the efficacy and/or safety of Federal Drug Administration-approved NSAIDs in knee osteoarthritis patients were included. Two independent reviewers assessed quality and extracted data. We calculated standardized mean differences (SMDs) and risk ratios (RRs) with 95% confidence intervals (95% CIs). We included 72 randomized controlled trials (26,424 participants). NSAIDs demonstrated moderate, statistically significant effects on pain that peaked at 2 weeks (SMD -0.43 [95% CI -0.48, -0.38]), but the magnitude of the effects decreased over time. The results for function were similar. The incidence of gastrointestinal (GI) AEs was significantly higher in NSAID users than placebo users as early as 4 weeks (RR 1.38 [95% CI 1.21, 1.57]). The incidence of cardiovascular (CV) AEs in NSAID users was not significantly different from placebo. Most GI and CV AEs were transient and of minor severity. NSAIDs produced significant pain and function improvements that peaked at 2 weeks but decreased over time. The incidence of minor GI and CV AEs consistently rose, reaching significance as early as 4 weeks. Clinicians should weigh the durability of efficacy with the early onset of minor AEs along with patient tolerability and preferences when formulating an NSAID regimen.

Incidence of cystoid macular edema following routine cataract surgery using NSAIDs alone or with corticosteroids

To evaluate the rate of cystoid macular edema development among cataract surgery patients on four different therapeutic regimens. The present study is a retrospective analysis of 5,380 eyes following uncomplicated phacoemulsification at Wake Forest University. The study period went from July 2007 to December 2012. Patients received one of four regimens, as follows: postoperative generic ketorolac 0.4% and prednisolone 1%, postoperative name-brand ketorolac 0.45% and prednisolone 1%, postoperative bromfenac 0.09% and prednisolone 1%, preoperative and postoperative bromfenac 0.09% alone. A statistical analysis was performed to assess the differences in rate of cystoid macular edema development among the four different therapeutic regimens. The diagnosis of cystoid macular edema required worsening of vision and evidence of increased macular thickness on optical coherence tomography. The overall rate of cystoid macular edema was 0.82%. Treatment by postoperative generic ketorolac 0.45% and prednisolone 1% demonstrated the highest rate of cystoid macular edema development (2.20% of the cases). Postoperative name-brand ketorolac 0.45% and prednisolone 1% exhibited intermediate rates of cystoid macular edema development (0.90% of the cases). Postoperative administration of bromfenac 0.09% and prednisolone 1% exhibited intermediate rates of cystoid macular edema development (0.44% of the cases). Preoperative and postoperative bromfenac 0.09% alone resulted in the lowest rate of cystoid macular edema development (0.09% of the cases). The rate of cystoid macular edema was significantly lower when bromfenac was used alone vs. either regimen where ketorolac and prednisolone were used (OR 0.043, 95% CI 0.002 to 0.312; p<0.001). Post-cataract surgery cystoid macular edema developed less frequently following topical non-steroidal anti-inflammatory drugs regimen compared to the other therapies evaluated. Bromfenac, without corticosteroids, achieved lower rates of cystoid macular edema vs. various combinations of non-ste-roidal anti-inflammatory drugs with corticosteroids.

Improving NSAIDs Prescription in Emergency Services Unit by a Point-of-Care-Based Renal Function Evaluation.

Patients evaluated in our emergency department (ED) often receive nonsteroidal anti-inflammatory drugs (NSAIDs) without any determination of their renal function, despite the known nephrotoxicity of NSAIDs. Guidelines recommend NSAID avoidance in patients with estimated glomerular filtration rate (eGFR)<30mL/min/1.73m2, and long-lasting therapy is not recommended in people with chronic kidney disease. We aimed to highlight the influence of a rapid measurement of the eGFR on NSAID prescriptions in patients at risk of impaired renal function using a point-of-care (POC) device. Our goal was to prevent the potential nephrotoxicity of NSAIDs by allowing the physicians to modify their treatments after eGFR determination, while avoiding a standard blood test for patients that would extend the duration of stay in the ED. We included 192 patients evaluated in the ED for minor trauma or injury, with an indication of treatment with NSAIDs and no known contraindication to NSAIDs. Emergency physicians were asked to register their intention to actually prescribe NSAIDs based on their clinical gestalt with specific regard to kidney function. Immediately after, the creatinine level was measured in capillary blood and eGFR was calculated using the POC device (StatSensor Creatinine; Nova Biomedical, Waltham, MA). Our physicians avoided NSAID prescriptions when eGFR was < 30mL/min/1.73m2, and prescribed a shorter NSAID regimen therapy in patient with eGFR < 45mL/min/1.73m2, with a reminder to assure hydration. The decision based on eGFR was compared with original clinician intention. The clinicians intended to treat 164 patients with NSAIDs (group 1) and defer NSAIDs in 28 patients (group 2). In the first group, eGFR results supported no change in intended NSAID use in 144 patients, highlighted the need for a short regimen in 17 patients, and indicated contraindication to NSAIDs in 3 patients. In group 2, eGFR determination allowed prescription of NSAIDs in 21 patients, allowed utilization of NSAIDs with a short course in 5 patients, and supported the clinician decision to avoid NSAIDs in 2 patients. POC measurement of creatinine with eGFR estimation changed the prescription of NSAIDs in almost 25% of patients with previously unknown renal function.

The drug-induced injury of the upper gastrointestinal tract: prophylaxis and treatment

It is well established that non-steroidal anti-inflammatory drugs (NSAIDs) are the causal factor of mucosa damage not only of in the stomach and duodenum, but also in esophagus, triggering the development of gastroesophageal reflux disease (GERD). It is known that NSAIDs’ intake (including low doses of aspirin) can significantly increase the likelihood of developing of the peptic esophagitis with the risk of ulceration, bleeding, or stricture formation. Recent years, there is an increasing number of papers, devoted to the investigation of esophageal lesions and mechanisms of GERD development, occurring during the NSAIDs’ administration (including low doses of acetylsalicylic acid) and other drugs. The structure of drug-induced lesions of the upper gastrointestinal tract in patients taking NSAIDs has been analyzed. The investigation has been performed to study the frequency and characteristics of esophageal lesions in patients with osteoarthrosis of large joints, receiving NSAID treatment, as well as to determine factors that increase risk of developing this pathology. With account of the considered risk factors, the most rational approach to the diagnosis and primary prevention of NSAID-induced esophagitis has been chosen, which in most cases should reduce the incidence of side effects of NSAID-associated lesions of the esophagus. The main directions in the treatment of NSAID-associated injuries of the esophagus, namely, lifestyle change, balanced diet, changing the dose and regimen of NSAIDs or switching to selective NSAIDs, modern pharmacotherapy and surgical treatment have been elucidated. Clinical examples of patients with esophagus and stomach injuries associated with the long-term administration of NSAIDs and antiplatelet drugs were used to discuss the prevention and treatment of this category of patients, using proton pump inhibitors and bismuth-containing drugs.

Effects of a cyclic NSAID regimen on levels of gingival crevicular fluid prostaglandin E2and Interleukin-1β: A 6-month randomized controlled clinical trial.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for inflammation control and pain relief. However, while the adjunct use of NSAIDs is avoided for periodontal therapy because of related side effects, cyclic administration of NSAIDs may reduce or eliminate these effects. We evaluated the effect of a cyclic diclofenac potassium (DP) regimen on clinical parameters and levels of prostaglandin E2 (PGE2) and interleukin-1β (IL-1β) in the gingival crevicular fluid (GCF) of individuals with periodontitis. The study protocol was approved by the Ethics Committee (2000/071). Forty-one individuals with chronic periodontitis (33 men, 8 women) were divided into two groups (test and control) after initial periodontal therapy. During this 6-month, randomized, double-blind, placebo-controlled study, test (n = 28) and control (n = 13) groups were administered a cyclic regimen of DP (50 mg, twice daily) or placebo. Clinical measurements and GCF sample collections were made at baseline, 2, 4, and 6 months. GCF levels of PGE2and IL-1β were determined using enzyme immunoassay and enzyme-linked immunoassay kits, respectively. At baseline, no significant differences existed between groups for plaque indices, gingival indices, bleeding on probing, probing depth (PD), or attachment levels (P > 0.05). Compared with the control group, cyclic regimen in the test group suppressed increased levels of PGE2found in GCF at the end of the study (P < 0.05). Significant differences for PD and relative attachment gain were also noted in favor of the test group (P < 0.05). These results suggest that a cyclic regimen of DP may be efficacious in the management of chronic periodontitis in adults.

Visual outcomes, efficacy, and surgical complications associated with intracameral phenylephrine 1.0%/ketorolac 0.3% administered during cataract surgery.

AimThe purpose of this study was to compare visual outcomes, surgical time, and perioperative surgical complications after intracameral use of either phenylephrine/ketorolac (P/K) or epinephrine (Epi) during cataract surgery.MethodsThis was a single-center, retrospective case review of patients undergoing cataract surgery from August to November 2015. Of the 641 eyes of 389 patients who underwent cataract surgery, 260 eyes were administered phenylephrine 1.0%/ketorolac 0.3% and 381 eyes received Epi in the irrigation solution intraoperatively. All patients received a topical nonsteroidal anti-inflammatory drug regimen (bromfenac 0.07%, nepafenac 0.3%, or ketorolac 0.5%) for 3 days before surgery and topical tropicamide 1.0%, cyclopentolate 1.0%, and phenylephrine 2.5% on the day of surgery.ResultsMean length of surgery (LOS) was 15.4±0.6 minutes. Although a positive correlation was noted between patient age and LOS (p<0.001), P/K was associated with a decrease in the LOS, when controlled for age quartiles. A statistically significant lower incidence of complications (1.1%) was observed with P/K use than Epi (4.5%; p=0.018). Among surgeons who used mydriatic-assist devices more frequently, P/K use was associated with a reduction in the use of these devices (p<0.001). When controlling for age quartile, patients of age groups 69–76 and 76–92 years who received P/K had significantly better uncorrected visual acuity at postoperative day 1 than those receiving Epi (p=0.003).ConclusionIntracameral use of phenylephrine 1.0%/ketorolac 0.3% during cataract surgery may be effective in maintaining mydriasis. It appears to be superior to intracameral Epi at reducing intraoperative and postoperative complications, need for pupillary dilating devices, and surgical time.

Abstract IA11: Chemoprevention in hereditary GI cancer syndromes

Abstract IA11: Chemoprevention in hereditary GI cancer syndromes

The Effect of NSAID Prophylaxis and Operative Variables on Heterotopic Ossification After Hip Arthroscopy

Background: Heterotopic ossification (HO) is a known complication of hip arthroscopy. Little is known about the factors that lead to HO after hip arthroscopy. Purpose: The aim of this study was to evaluate the effect of nonsteroidal anti-inflammatory drugs (NSAIDs) and other operative variables on the development of HO. Study Design: Cohort study; Level of evidence, 3. Methods: A total of 357 consecutive cases of hip arthroscopy were retrospectively reviewed over a 3-year period. Routine NSAID prophylaxis was not performed for the first 117 cases. Prophylaxis with naproxen for 3 weeks was then routinely prescribed for the remaining 240 cases. Complete follow-up was available for 288 of the original 357 cases. The presence of HO and its characteristics were recorded for each patient, along with baseline demographic and surgical variables. Odds ratios and logistic regression were used to identify causal factors for HO. Results: The incidence of HO in cases in which the patient did not receive NSAID prophylaxis was 25.0% (23/92) versus 5.6% (11/196) of cases in which the patient received NSAIDs. Patients who received no NSAID prophylaxis were 13.6 times more likely to develop HO postoperatively (95% confidence interval, 2.44-75.5; P = .003). Comparing just mixed-type femoroacetabular impingement resections, patients who received no NSAID prophylaxis were 16.6 times more likely to develop HO postoperatively (95% confidence interval, 2.2-126.0; P = .006). Multivariate logistic regression identified the performance of a mixed-type femoroacetabular impingement resection (P = .011) and the absence of NSAID prophylaxis (P = .003) as predictors of HO development. The majority of HO cases (29/34) occurred in patients with mixed-type femoroacetabular impingement who had both osteochondroplasty and acetabuloplasty. Complications of NSAID therapy in this study population included acute renal failure, hematochezia from acute colitis, and gastritis. Conclusion: Routine NSAID prophylaxis reduces but does not eliminate the incidence of HO in patients undergoing hip arthroscopy. Heterotopic ossification was more likely to develop in patients undergoing acetabuloplasty along with osteochondroplasty and in those who did not receive prophylactic postoperative NSAIDs. Side effects from the investigated NSAID regimen can be serious and should be weighed against the potential benefits in preventing the formation of HO.

Managing Surgical Pain in Long-Term Opioid Patients

ABSTRACTThe number of patients taking long-term opioid therapy for pain is increasing, with opioid use no longer being confined to advanced cancer patients. Challenges to peri- and postoperative pain management in chronic pain patients include complex existing drug regimens and problems arising from tolerance to opioid analgesia. Postoperatively, individualized, multimodal pain therapy involving a round-the-clock regimen of nonsteroidal anti-inflammatory drugs (NSAIDs), cyclooxygenase-2 (COX-2) inhibitors, paracetamol, and regional blocks should be used. Other considerations may include patients receiving opioids by intrathecal drug delivery systems, spinal cord stimulator (SCS), and potential substance abusers.

Topical steroidal and nonsteroidal antiinflammatory drugs for the treatment of cystoid macular edema in retinitis pigmentosa.

Oral carbonic anhydrase inhibitors have been the treatment of choice for managing cystoid macular edema (CMO) in retinitis pigmentosa. We report a case illustrating the effectiveness of topical steroidal and nonsteroidal antiinflammatory drugs (NSAIDs) in managing CMO in a patient with retinitis pigmentosa, who is unable to take oral carbonic anhydrase inhibitor because of chronic renal impairment. An 85-year-old woman with retinitis pigmentosa-related CMO in the left eye was prospectively followed up after treatment with a 4 times daily regimen consisting of a topical steroid (prednisolone acetate 1%) and an NSAID (ketorolac trometamol 0.5%). The right eye showed no evidence of CMO. Oral acetazolamide was avoided as the patient had chronic renal impairment. Three months after treatment, best-corrected visual acuity in the left eye improved from 20/200 to 20/60, and spectral domain optical coherence tomography showed complete resolution of CMO. Topical steroid and NSAID were therefore stopped. However, 6 months later, left best-corrected visual acuity was reduced to 20/120 and spectral domain optical coherence tomography showed recurrence of CMO. This was managed with the same treatment regimen of topical steroid and NSAID, which resulted in complete resolution of CMO with best-corrected visual acuity in the left eye improving to 20/80 after 3 months. To our knowledge, this is the first report that demonstrates the effectiveness of topical steroids or NSAIDs in managing CMO in a retinitis pigmentosa patient with chronic renal impairment who is unable to take a carbonic anhydrase inhibitor because of chronic renal impairment.

The Effect of Nonsteroidal Anti-Inflammatory Drug Administration on Acute Phase Fracture-Healing: A Review

The analgesic efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) is well established, and these agents often form an integral part of posttraumatic pain management. However, potentially deleterious effects of resulting prostaglandin suppression on fracture-healing have been suggested. A systematic literature review involving searches of electronic databases and online sources was performed to identify articles exploring the influence of NSAIDs on fracture-healing. A structured search approach identified 316 papers as potentially relevant to the topic, and these were manually reviewed. The majority described small-scale studies that were retrospective or observational in nature, with limited control of potentially confounding variables, or presented little key information that was not also present in other studies. Although increasing evidence from animal studies suggests that cyclooxygenase-2 (COX-2) inhibition suppresses early fracture-healing, in vivo studies involving human subjects have not provided convincing evidence to substantiate this concern. We found no robust evidence to attest to a significant and appreciable patient detriment resulting from the short-term use of NSAIDs following a fracture. The balance of evidence in the available literature appears to suggest that a short-duration NSAID regimen is a safe and effective supplement to other modes of post-fracture pain control, without a significantly increased risk of sequelae related to disrupted healing.

Comparison of bromfenac 0.09% QD to nepafenac 0.1% TID after cataract surgery: pilot evaluation of visual acuity, macular volume, and retinal thickness at a single site

PurposeThe purpose of this study was to investigate the clinical outcomes of bromfenac ophthalmic solution 0.09% once daily (QD) and nepafenac 0.1% ophthalmic suspension three times daily following cataract extraction with posterior chamber intraocular lens implantation, specifically looking at any differences in Early Treatment Diabetic Retinopathy Study visual acuities, macular volume, and/or retinal thickness changes.MethodsSubjects were randomly assigned to receive either bromfenac (n = 10) QD or nepafenac (n = 10) three times daily. Dosing began 3 days before cataract surgery, continuing to day 21 postsurgery. In addition to the investigated nonsteroidal antiinflammatory drug regimen, all subjects received antiinfective intraoperative and postoperative standard of care. Subjects were followed at 1 day and 1, 3, and 6 weeks postoperatively. Study visit assessments included best-corrected visual acuity, biomicroscopy, summed ocular inflammation score (anterior chamber cells and flare grading), intraocular pressure measurement, adverse event recording, and concomitant medication review. Optical coherence tomography was performed at 1, 3, and 6 weeks.ResultsBoth treatment groups had similar baseline measurements. Outcomes for mean letters read (P = 0.318), mean change in macular volume (P = 0.665), and retinal thickness (P = 0.552) were not statistically different between the groups from baseline through week six, although independently only the bromfenac group demonstrated a statistically significant improvement in letters gained from baseline to week six (P = 0.040). In the same time period, mean macular volume and retinal thickening worsened in the nepafenac group, demonstrating a statistically significant increase (P = 0.006) at week six for macular volume when compared to baseline. One subject in the nepafenac group experienced recurrent inflammation at week six, was unmasked, and then rescued with bromfenac 0.09% QD and difluprednate 0.05% QD.ConclusionBoth bromfenac and nepafenac resulted in positive clinical outcomes of Early Treatment Diabetic Retinopathy Study visual acuities. Postoperative measurements of macular volume and retinal thickness of bromfenac subjects showed a trend toward improved vision, less retinal thickening, and more stable macular volumes overall.

Management of Mild-to-Moderate Osteoarthritis: A Study of the Primary Care Perspective

Objectives: Examine the knowledge, attitudes, and practice patterns of primary care clinicians regarding the management of mild-to-moderate osteoarthritis (OA). Design: Case vignette-based survey. Methods: A survey was distributed to 251 physicians, physician assistants (PAs), and nurse practitioners (NPs) in the primary care setting. The survey assessed practice patterns in the management of patients with mild-to-moderate OA, as well as attitudes toward guidelines and future educational topics that may be of benefit to the clinician. Results: We found that primary care clinicians are most likely to treat mild-to-moderate OA with an oral nonsteroidal anti-inflammatory drug regimen. Patients with initial or recurrent OA were “very likely” to be recommended to a physical therapy maintenance program. Two-thirds of respondents claimed to be unfamiliar with Osteoarthritis Research Society International guidelines for OA management. Conclusion: This study reflects the need for further education for primary care physicians, NPs, and PAs on the management of OA.

Safety and Utility of Scheduled Nonnarcotic Analgesic Medications in Children Undergoing Craniotomy for Brain Tumor

We have reported that a scheduled nonnarcotic analgesic regimen after dorsal lumbar rhizotomy and Chiari I malformation decompression is efficacious in managing postoperative pain in children. To date, this regimen has not been analyzed in children after brain tumor biopsy or resection. To elucidate the safety and utility of such an analgesic protocol in these patients. A database review was conducted to identify children who received a scheduled dose of alternating acetaminophen and ibuprofen after craniotomy for tumor biopsy or resection, and postoperative imaging was evaluated. Fifty-one children who met the inclusion criteria were identified. On postoperative imaging, 17.67% had routine, postoperative blood in the resection cavity according to both radiology and neurosurgical review. One patient had moderate postoperative bleeding in the tumor cavity. Overall, 44 of the 51 patients (86.3%) required no or minimal narcotic medication for pain. A scheduled regimen of nonsteroidal antiinflammatory drugs given in alternating doses immediately after craniotomy for tumor biopsy or resection and throughout hospitalization did not result in any significant postoperative hemorrhage in our patient series.

Effectiveness of administration of phenylbutazone alone or concurrent administration of phenylbutazone and flunixin meglumine to alleviate lameness in horses

To determine the effectiveness of administering multiple doses of phenylbutazone alone or a combination of phenylbutazone and flunixin meglumine to alleviate lameness in horses. 29 adult horses with naturally occurring forelimb and hind limb lameness. Lameness evaluations were performed by use of kinematic evaluation while horses were trotting on a treadmill. Lameness evaluations were performed before and 12 hours after administration of 2 nonsteroidal anti-inflammatory drug (NSAID) treatment regimens. Phenylbutazone paste was administered at approximately 2.2 mg/kg, PO, every 12 hours for 5 days, or phenylbutazone paste was administered at approximately 2.2 mg/kg, PO, every 12 hours for 5 days in combination with flunixin meglumine administered at 1.1 mg/kg, IV, every 12 hours for 5 days. Alleviation of lameness was greater after administration of the combination of NSAIDs than after oral administration of phenylbutazone alone. Improvement in horses after a combination of NSAIDs did not completely mask lameness. Five horses did not improve after either NSAID treatment regimen. All posttreatment plasma concentrations of NSAIDs were less than those currently allowed by the United States Equestrian Federation Inc for a single NSAID. One horse administered the combination NSAID regimen died of acute necrotizing colitis during the study. Administration of a combination of NSAIDs at the dosages and intervals used in the study reported here alleviated the lameness condition more effectively than did oral administration of phenylbutazone alone. This may attract use of combinations of NSAIDs to increase performance despite potential toxic adverse effects.

Perioperative management of chronic pain patients with opioid dependency

In this article, we discuss the perioperative anesthesia and pain management of patients with chronic pain receiving chronic opioid administration. In our practice we may expect to be confronted with opioid-dependent patients in routine anesthesia practice and should acquire specific knowledge and skills to effectively manage the perioperative and acute pain management issues that arise. The number of patients treated chronically with opioids has increased steadily over the past decade; currently about 10% of all chronic-pain patients are treated with opioids. As these patients are no longer confined to terminally ill cancer patients, growing numbers of these patients are facing surgical interventions. In our clinical practice, we should employ multimodal pain management therapy by using an around-the-clock regimen of nonsteroidal anti-inflammatory drugs, cyclooxygenase-2 inhibitors, acetaminophen, and regional blockade. Dosing regimens should be individualized to optimize efficacy while minimizing the risk of adverse events.

Electronically monitored adherence to medications by newly diagnosed patients with juvenile rheumatoid arthritis

To describe patterns of adherence to nonsteroidal antiinflammatory drugs (NSAIDs) in newly diagnosed patients with juvenile rheumatoid arthritis (JRA), and to examine demographic and disease-related variables as potential predictors of adherence. Adherence to NSAIDs was monitored in 48 children with JRA (mean age 8.6 years) over 28 consecutive days using an electronic monitoring device. Measures of disease activity (active joint counts, morning stiffness) and demographics (age, sex, ethnicity, socioeconomic status) were also obtained. Using an 80% adherence cut point, 25 (52%) patients were classified as adherent and 23 (48%) as nonadherent. There was considerable variability across patients, with full adherence (taking all doses on time) ranging from 0 to 100% of the monitored days. Logistic regression showed that active joint count and socioeconomic status were the only significant predictors. Both were positively related to adherence. The model correctly classified 70.5% of patients as either adherent or nonadherent (Cox and Snell R(2) = 0.295, P = 0.0005). Children newly diagnosed with JRA are more likely to adhere to an NSAID regimen if they have a greater number of active joints or their families have higher socioeconomic status. The former finding suggests that children's adherence is symptom-driven, while the latter suggests that families of lower socioeconomic status deserve special attention to address adherence issues.

Use of NSAIDs for the chemoprevention of colorectal cancer.

To discuss the role of nonsteroidal antiinflammatory drugs (NSAIDs) in the chemoprevention of colorectal cancer. A MEDLINE search (1966-May 2003) was performed to identify key literature. Search items included, but were not limited to, NSAIDs, colorectal cancer, chemoprevention, cyclooxygenase-2 (COX-2)-specific inhibitors, and familial adenomatous polyposis (FAP). The search included experimental (in vitro and animal models) and clinical studies evaluating the use of NSAIDs for the chemoprevention of colorectal cancer. The MEDLINE search was supplemented by references from selected articles. Numerous experimental, epidemiologic, and clinical studies suggest that NSAIDs have promise as anticancer agents. The mechanism by which NSAIDs lead to decreased colon carcinogenesis is not fully understood, but may involve restoration of apoptosis and inhibition of prostaglandin-mediated angiogenesis. Compelling evidence from many observational studies has consistently documented a 40-50% reduction in the risk of adenomatous polyps, colorectal cancer incidence, and mortality in patients using NSAIDs. Recent randomized, controlled trials have demonstrated a benefit with aspirin in reducing the rate of development of new or recurrent adenomas in high-risk patients. In addition, randomized studies using sulindac and celecoxib in patients with FAP have documented significant regression of existing adenomatous polyps. Inhibition of COX-2 is an example of a targeted approach to the chemoprevention of colorectal cancer. However, controversy exists about the safety, efficacy, and optimal treatment regimen of NSAIDs as long-term chemopreventive agents in the general population. Ongoing studies in high-risk patients with both selective and nonselective COX inhibitors will provide important information in the area of colorectal chemoprevention, but clinical trials' use of adenomas as surrogate markers for chemoprevention trials makes their application to the general population limited.