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Biomedical subjects

Lee S Simon

Publications and source records attributed to Lee S Simon.

At least 19 recordsLinked to original sources
PubMed2006

Cardiovascular effects of selective COX-2 inhibition: is there a class effect? The International COX-2 Study Group.

The International COX-2 Study Group, a panel of independent physicians and scientists, convened January 28-30, 2005, in Washington, DC, to discuss the issues concerning the cardiovascular (CV) profile of coxibs. The purpose of the meeting was to review potential mechanisms by which inhibition of COX-2 by selective and nonselective NSAID could increase risk of CV events, to evaluate the similarities and differences between drugs based on mechanism and pharmacology, and to propose potential trial methodology to more definitively answer questions regarding cardiovascular risk.

Arthritis, Rheumatoid↗
PubMed2006

Patients, their doctors, nonsteroidal anti-inflammatory drugs and the perception of risk.

This article is about risk. Risk is probably the most misunderstood component in determining therapeutic intervention; however, it is probably the most relevant issue to consider in the context of expected benefit. The rarity of quantitative risk-benefit assessment and the lack of comparative risk-benefit when alternative therapies exist for a given condition leads to inadequate decisions. Without some quantitation of the risks associated with specific therapies, doctors and patients cannot make optimal risk-benefit calculations. Patients may abandon effective therapies for which benefits may still outweigh risks, or opt for therapies with less well-publicized potential adverse events of even greater frequency or severity. When only small incremental benefits accrue to patients from the use of a given therapy, on the other hand, even very rare serious events may play a role in decision-making by patients, by their health care providers and by regulatory authorities.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2006

Risedronate decreases biochemical markers of cartilage degradation but does not decrease symptoms or slow radiographic progression in patients with medial compartment osteoarthritis of the knee: results of the two-year multinational knee osteoarthritis structural arthritis study.

OBJECTIVE: Bisphosphonates have slowed the progression of osteoarthritis (OA) in animal models and have decreased pain in states of high bone turnover. The Knee OA Structural Arthritis (KOSTAR) study, which is the largest study to date investigating a potential structure-modifying OA drug, tested the efficacy of risedronate in providing symptom relief and slowing disease progression in patients with knee OA. METHODS: The study group comprised 2,483 patients with medial compartment knee OA and 2-4 mm of joint space width (JSW), as determined using fluoroscopically positioned, semiflexed-view radiography. Patients were enrolled in 2 parallel 2-year studies in North America and the European Union. These studies evaluated the efficacy of risedronate at dosages of 5 mg/day, 15 mg/day, 35 mg/week (in Europe), and 50 mg/week (in North America) compared with placebo in reducing signs and symptoms, as measured by the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index and patient global assessment (PGA) scores, and in slowing radiographic progression. RESULTS: A reduction of approximately 20% in signs and symptoms, as measured by WOMAC subscales and PGA scores, was observed in all groups, with no treatment effect of risedronate demonstrated. Risedronate did not significantly reduce radiographic progression as measured by decreased JSW or using a dichotomous definition of progression (joint space loss of >or=0.6 mm). Thirteen percent of patients receiving placebo demonstrated significant disease progression over 2 years. A dose-dependent reduction in the level of C-terminal crosslinking telopeptide of type II collagen, a cartilage degradation marker associated with progressive OA, was seen in patients who received risedronate. No increase in the number of adverse events was demonstrated for risedronate compared with placebo. CONCLUSION: Although risedronate (compared with placebo) did not improve signs or symptoms of OA, nor did it alter progression of OA, a reduction in the level of a marker of cartilage degradation was observed. A sustained clinically relevant improvement in signs and symptoms was observed in all treatment and placebo groups.

Adult↗
PubMed2005

Cardiovascular and gastrointestinal effects of COX-2 inhibitors and NSAIDs: achieving a balance.

Conventional 'nonselective' nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for the treatment of pain and inflammation; however, the potential gastrointestinal risks associated with their use can be a cause for concern. In response to the adverse effects that can accompany nonselective NSAID use, selective cyclo-oxygenase (COX)-2 inhibitors were developed to target the COX-2 isoenzyme, thus providing anti-inflammatory and analgesic benefits while theoretically sparing the gastroprotective activity of the COX-1 isoenzyme. Data from large-scale clinical trials have confirmed that the COX-2 inhibitors are associated with substantial reductions in gastrointestinal risk in the majority of patients who do not receive aspirin. However, some or all of the gastrointestinal benefit of COX-2 inhibitors may be lost in patients who receive low, cardioprotective doses of aspirin, and recent evidence suggests that some of these agents, at some doses, may be associated with an increased risk for cardiovascular adverse events compared with no therapy. The risks and benefits of conventional NSAIDs and of COX-2 inhibitors must be weighed carefully; in clinical practice many patients who might benefit from NSAID or COX-2 therapy are likely to be elderly and at relatively high risk for gastrointestinal and cardiovascular adverse events. These patients are also more likely to be taking low-dose aspirin for cardiovascular prophylaxis and over-the-counter NSAIDs for pain. Identifying therapies that provide relief from arthritis related symptoms, confer optimum cardioprotection, and preserve the gastrointestinal mucosa is complex. Factors to consider include the interference of certain NSAIDs with the antiplatelet effects of aspirin, differences in the adverse gastrointestinal event rates among nonselective NSAIDs and selective COX-2 inhibitors, emerging data regarding the relative risks for cardiovascular events associated with these drugs, and the feasibility and cost of co-therapy with proton pump inhibitors.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2005

The COX-2 inhibitors: a reasoned review of the data.

The recent press coverage of the issues surrounding non steroidal anti-inflammatory drugs and the selective COX-2 inhibitors has not allowed for an informed debate to take place regarding the therapeutic risk to benefit ratio of these drugs. The overall discussions that have taken place within the context of the regulatory decision process has been mostly proprietary and thus not made public and the resultant decisions have not been prominently featured in the popular press so have not gotten the attention of the practicing clinician or the patients who use these drugs. This paper will review the evidence that has been accumulated and highlight the decisions that have been made by some of the regulatory groups to address the issues surrounding overall benefit to risk of the NSAIDs inclusive the COX-2 selective inhibitors.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2005

The Effects of cyclooxygenase-2 inhibitors and nonsteroidal anti-inflammatory therapy on 24-hour blood pressure in patients with hypertension, osteoarthritis, and type 2 diabetes mellitus.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase-2 (COX-2) inhibitors may attenuate the efficacy of antihypertensive agents in high-risk patients. Therefore, we conducted a double-blind, randomized trial to evaluate the effects of celecoxib, rofecoxib, and naproxen on 24-hour blood pressure (BP) in patients with type 2 diabetes, hypertension, and osteoarthritis. METHODS: Patients were randomly assigned to treatment with 200 mg of celecoxib once daily (n = 136), 25 mg of rofecoxib once daily (n = 138), or 500 mg of naproxen twice daily (n = 130) for 12 weeks. Twenty-four-hour ambulatory BP monitoring and validated arthritis efficacy assessments were conducted at randomization and at weeks 6 and 12 of treatment. The primary end point was the mean change from baseline in average 24-hour systolic BP at week 6. RESULTS: Reductions in osteoarthritis symptoms, including pain, mobility, and stiffness, were similar in all treatment groups. The mean +/- SE 24-hour systolic BP following 6 weeks of therapy was increased significantly by rofecoxib (from 130.3 +/- 1.2 to 134.5 +/- 1.4 mm Hg; P < .001) but not by celecoxib (132.0 +/- 1.3 to 131.9 +/- 1.3 mm Hg; P = .54) or naproxen (133.7 +/- 1.5 to 133.0 +/- 1.4 mm Hg; P = .74). The BP difference between rofecoxib and celecoxib was 3.78 mm Hg (95% confidence interval, 1.18-6.38; P = .005); between rofecoxib and naproxen, 3.85 mm Hg (95% confidence interval, 1.15-6.55; P = .005). The proportion of patients with controlled hypertension at baseline who developed ambulatory hypertension by week 6 (24-hour systolic BP>135 mm Hg) was significantly greater with rofecoxib (30%) than with celecoxib (16%) (P = .05) but not significantly greater than with naproxen (19%). CONCLUSIONS: At equally effective doses for osteoarthritis management, treatment with rofecoxib but not celecoxib or naproxen induced a significant increase in 24-hour systolic BP. However, destabilization of hypertension control occurred to some extent in all 3 treatment groups; this phenomenon was seen more often in patients treated with rofecoxib than with the other therapies.

Administration, Oral↗
PubMed2005

Osteoporosis.

Bone is a complex organ which contains an organic matrix which serves as scaffolding, includes mineral as calcium distributed in a pattern providing structure and serves as an ion reservoir for the body. Throughout life it dynamically changes in response to changes in activity, body mass, and weight bearing. It is important to define patients at risk for bone loss, since accrued bone loss leading to osteoporosis in the older population of both men and women is unacceptable. There are many different therapies including biphosphonates which can decrease loss of bone and decrease fracture risk in patients who already have had sustained a fracture. Newer therapies such as parathyroid hormone may improve the fracture risk even more than biphosphonates over a shorter period of time.

Alkaline Phosphatase↗
PubMed2005

Minimal disease activity for rheumatoid arthritis: a preliminary definition.

Agreement on response criteria in rheumatoid arthritis (RA) has allowed better standardization and interpretation of clinical trial reports. With recent advances in therapy, the proportion of patients achieving a satisfactory state of minimal disease activity (MDA) is becoming a more important measure with which to compare different treatment strategies. The threshold for MDA is between high disease activity and remission and, by definition, anyone in remission will also be in MDA. True remission is still rare in RA; in addition, the American College of Rheumatology definition is difficult to apply in the context of trials. Participants at OMERACT 6 in 2002 agreed on a conceptual definition of minimal disease activity (MDA): "that state of disease activity deemed a useful target of treatment by both the patient and the physician, given current treatment possibilities and limitations." To prepare for a preliminary operational definition of MDA for use in clinical trials, we asked rheumatologists to assess 60 patient profiles describing real RA patients seen in routine clinical practice. Based on their responses, several candidate definitions for MDA were designed and discussed at the OMERACT 7 in 2004. Feedback from participants and additional on-site analyses in a cross-sectional database allowed the formulation of 2 preliminary, equivalent definitions of MDA: one based on the Disease Activity Score 28 (DAS28) index, and one based on meeting cutpoints in 5 out the 7 WHO/ILAR core set measures. Researchers applying these definitions first need to choose whether to use the DAS28 or the core set definition, because although each selects a similar proportion in a population, these are not always the same patients. In both MDA definitions, an initial decision node places all patients in MDA who have a tender joint count of 0 and a swollen joint count of 0, and an erythrocyte sedimentation rate (ESR) no greater than 10 mm. If this condition is not met: * The DAS28 definition places patients in MDA when DAS28 < or = 2.85; * The core set definition places patients in MDA when they meet 5 of 7 criteria: (1) Pain (0-10) < or = 2; (2) Swollen joint count (0-28) < or = 1; (3) Tender joint count (0-28) < or = 1; (4) Health Assessment Questionnaire (HAQ, 0-3) < or = 0.5; (5) Physician global assessment of disease activity (0-10) < or = 1.5; (6) Patient global assessment of disease activity (0-10) < or = 2; (7) ESR < or = 20. This set of 2 definitions gained approval of 73% of the attendees. These (and other) definitions will now be subject to further validation in other databases.

Arthritis, Rheumatoid↗
PubMed2005

Fibromyalgia syndrome.

The objectives of the first OMERACT Fibromyalgia Syndrome (FM) Workshop were to identify and prioritize symptom domains that should be consistently evaluated in FM clinical trials, and to identify aspects of domains and outcome measures that should be part of a concerted research agenda of FM researchers. Such an effort will help standardize and improve the quality of outcomes research in FM. A principal assumption in this workshop has been that there exists a clinical syndrome, generally known as FM, characterized by chronic widespread pain typically associated with fatigue, sleep disturbance, mood disturbance, and other symptoms and signs, and considered to be related to central neuromodulatory dysregulation. FM can be diagnosed using 1990 American College of Rheumatology criteria. In preparation for the workshop a Delphi exercise involving 23 FM researchers was conducted to establish a preliminary prioritization of domains of inquiry. At the OMERACT meeting, the workshop included presentation of the Delphi results; a review of placebo-controlled trials of FM treatment, with a focus on the outcome measures used and their performance; a panel discussion of the key issues in FM trials, from both an investigator and regulatory agency perspective; and a voting process by the workshop attendees. The results of the workshop were presented in the plenary session on the final day of the meeting. A prioritized list of domains of FM to be investigated was thus developed, key issues and controversies in the field were debated, and consensus on a research agenda on outcome measure development was reached.

Delphi Technique↗
PubMed2004

Analysis of aspirin-associated risks in healthy individuals.

BACKGROUND: Aspirin therapy is widely accepted for patients with documented cardiovascular disease, but there is a growing trend among healthy individuals to use aspirin as primary prevention for both cardiovascular disease and cancer. OBJECTIVE: To determine the impact of the complications of aspirin therapy on quality-adjusted life-years (QALYs) in healthy individuals. METHODS: A computer-based decision-analytic model was constructed. In this model, healthy individuals taking aspirin were assumed to receive no advantages from the aspirin, but were at risk of developing its associated complications. Individuals took 325 mg of enteric-coated aspirin every day until death, discontinuing therapy only if an aspirin-induced complication occurred. The analysis was performed from a societal perspective, starting at age 50 years. Extensive sensitivity analyses were performed. RESULTS: In the absence of any beneficial effect, aspirin reduced QALYs by 0.03 per individual. Unadjusted life expectancy was decreased by 0.04 years (2 wk). Lifetime aspirin use cost an average of $460/healthy person. The total complication rate over a lifetime of aspirin therapy was 6.79%, with a mortality rate of 0.18%. Alternatively stated, there was one complication for every 15 individuals treated and one death for every 556 individuals treated. Extensive sensitivity analysis showed the range of results possible when varying age, gender, length of follow-up, and other key parameters. CONCLUSIONS: Assuming no benefits, aspirin therapy in healthy individuals leads to a small reduction in QALYs at an overall low cost per person. However, approximately 1 in 15 individuals will experience an aspirin-induced complication and 1 in 556 individuals will die.

Adult↗
PubMed2004

The cost-effectiveness of aspirin versus cyclooxygenase-2-selective inhibitors for colorectal carcinoma chemoprevention in healthy individuals.

BACKGROUND: Aspirin therapy is accepted widely for secondary prevention in patients with documented cardiovascular disease, but there is a growing trend among healthy individuals to use aspirin as primary chemoprevention for both cardiovascular and oncologic diseases. Accruing evidence suggests that cyclooxygenase-2-selective inhibitors (coxibs) may be effective for colorectal carcinoma (CRC) chemoprevention but would not provide the primary cardiac benefit of aspirin. METHODS: A computer-based Markov model simulated hypothetical cohorts of healthy men age 50 years who took either 325 mg of enteric-coated aspirin daily or celecoxib at a dose of 400 mg twice a day. Patients in both cohorts could develop drug-related complications that would lead to its discontinuation. The aspirin group also was modeled to have a decreased rate of coronary ischemic events; however, decreased CRC mortality was not modeled in either group based on the assumption that the two treatments were effective equally in this regard. Data sources included published literature and the Centers for Medicare and Medicaid Services. Endpoints used to compare the two strategies included quality-adjusted life years (QALYs), mortality and complication rates, and cost. The analysis was from a societal perspective with a time horizon of 10 years from age 50 years. Extensive sensitivity analyses were performed. RESULTS: Aspirin therapy resulted in 0.03 more QALYs and cost $23,000 less than coxib therapy over a 10-year period. Compared with the aspirin group, the coxib group had 3.877% more complications and 0.17% more deaths. Alternatively stated, coxib therapy resulted in 1 patient complication or death for every 26 or 588 patients treated with coxibs, respectively. CONCLUSIONS: Assuming equal efficacy in CRC prevention over a 10-year period, aspirin was both more effective and less costly than coxib therapy when used for primary chemoprevention of CRC.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2004

The treatment of rheumatoid arthritis.

The treatment of rheumatoid arthritis has changed dramatically in the last 10 years and in parallel the definition and expectations of patients and clinicians of the effects of disease-modifying anti-rheumatic agents has changed as well. Current expectations of efficacy now include improvement of signs and symptoms of disease activity as well as slowing, if not complete inhibition, of disease progression as measured by X-ray progression along with significant improvement in patient physical function. In addition, clinicians assess the safety profile of these agents more critically in an attempt to improve the risk:benefit profile. Drugs, such as methotrexate, sulfasalazine and leflunomide have provided patients with substantial relief of symptoms and improvement in terms of X-ray progression, but they have been hampered by the occurrence of significant adverse events along with the inability to maintain benefit for prolonged periods of time. With the increased understanding of the basic biological mechanisms of the disease process, there has been the introduction of four biological disease modifying therapies and other drugs into clinical practice, which have altered aspects of the risk:benefit ratio for patients with various rheumatic diseases.

Antirheumatic Agents↗