Sanford H. Roth

Interpersonal Stress, Depression, and Disease Activity in Rheumatoid Arthritis and Osteoarthritis Patients

The relationships among interpersonal stressors, depression, coping inefficiency, hormones (prolactin, cortisol, and estradiol), and disease activity were examined. The sample comprised 33 women with rheumatoid arthritis (RAs; age 37-78) and 37 women with osteoarthritis (OAs; age 47-91), who served as controls. In a regression analysis, interpersonal conflict events accounted for more than twice as much variance in depression in RAs than in OAs. In the RA patients, the immune-stimulating hormones prolactin and estradiol were significantly positively correlated with interpersonal conflicts, depression, coping inefficacy, and clinician ratings of disease activity, suggesting that RAs are more reactive to interpersonal stressors than are OAs, both psychologically and physiologically.

Life stress and lymphocyte alterations among patients with rheumatoid arthritis.

The relation between life stress and immune parameters was investigated for 33 female rheumatoid arthritis (RA) patients interviewed during three routine monthly clinic checkups. Life stress from major and minor events, coping efficacy, and self-reported psychological distress were assessed, and immunofluorescence of T-cells and B-cells was performed on the blood drawn during each visit. Small stressful events were positively related to the proportion of circulating B-cells, psychological distress was inversely related to proportion of circulating T-cells, and major life events were associated with lower T-helper/T-suppressor cell ratios.

Coming to Terms with Nonsteroidal Anti-Inflammatory Drug Gastropathy

Despite well known complications, oral nonsteroidal anti-inflammatory drugs (NSAIDs) remain the most commonly prescribed medications in the US for musculoskeletal disorders such as osteoarthritis. Although there has been a recent focus on the cardiovascular and renal complications associated with these agents, NSAID gastropathy continues to be a particular concern in many patients, especially those at increased risk for serious adverse events, including the elderly. Complicating the diagnosis of NSAID gastropathy is its silent course, which, up to half of the time, is asymptomatic. Several strategies are currently employed by physicians to mitigate the risk of serious gastrointestinal events. These include either addition of a proton pump inhibitor to current nonselective NSAID therapy or the use of a cyclo-oxygenase-2—selective NSAID. Although these agents are effective at mitigating the overall risk of gastrointestinal adverse events, they fail to address NSAID-related cardiovascular and renal risks. Due to their reduced systemic absorption, topical NSAIDs may present a viable option for patients at increased risk for serious NSAID-related adverse events, including gastropathy.

A New Role for Opioids in the Treatment of Arthritis

Arthritis, rheumatic diseases, spinal and peripheral joint disorders share in common a legacy of chronic pain. At the turn of the millennium, nonsteroidal anti-inflammatories (NSAIDs) had replaced aspirin as the agents most commonly used to deal with rheumatic symptoms, including pain. Paracetamol (acetaminophen) was the most common alternative analgesic for minor pain. Opioids were most commonly used on an ad-lib basis, usually for ‘breakthrough’ pain. However, neurobiological research has confirmed the basis for 24-hour around-the-clock complete suppression of chronic nonmalignant pain. This avoids the ‘wind up’ that leads to intractable pain progression. Proper monitoring, in the absence of the end organ toxicity seen with NSAIDs, allows a change in direction to opioids for arthritis for more severe pain. This requires understanding the responsibilities of maintaining opioids, in properly selected patients, based upon host response and informed consent. Under such circumstances, evidence-based trials support the use of stronger opioids in recalcitrant chronic pain of arthritis. Thus, we endeavour to better fulfill our Oath of Hippocrates: ‘to relieve pain and suffering’.

The NSAID Dilemma: Managing Osteoarthritis in High-Risk Patients

Abstract For decades, evidence-based data and reported experience have warned that the common chronic oral nonsteroidal anti-inflammatory drug (NSAID) therapy for osteoarthritis (OA) in elderly patients is ultimately dangerous. Elderly patients with OA are at heightened risk for developing serious gastrointestional and cardiovascular adverse events, including gastrointestinal bleeding, myocardial infarction, and stroke. Prescribing NSAIDs, especially in an elderly population, continues to be discouraged because of these significant risks. A dilemma exists for individuals who need the established efficacy associated with oral NSAIDs but who are at increased risk for serious adverse events associated with these agents. The goal of this clinical review was to evaluate the risks versus benefits of current options in the treatment of OA. This review found that topical NSAIDs seem to be the safest choice among all options to mitigate gastrointestinal and cardiovascular risks and should be considered prior to the intitation of oral nonselective or cyclooxygenase (COX)-2–selective NSAIDs for individuals presenting with a localized expression of OA. Further research is needed to evaluate and compare these therapies in treating both pain and inflammation effectively while mitigating safety risks in high-risk populations.

Salicylates revisited: are they still the hallmark of anti-inflammatory therapy?

Salicylates have enjoyed a curious , convoluted role in the management of pain and various diseases, which have been mainly rheumatic. Originally a herbal remedy, numerous cation-salicylate molecular mod ifications were synthesised before the current acetylated derivat ive emerged and predominated. So overwhelming was the popularity of acetylsalicylic acid that its original trade name , aspirin, ultimately became the generic name and by all accounts it is now the most widely used drug in the world. For rapid pain relief, no non-narcotic analgesic has surpassed aspir in, and it is also an effective antipyretic. Of central interest to this review, however, is the peculiar place of favour and disfavour of aspirin in the treatment of various rheumatic diseases. With aspirin included within the greater body of salicylate molecular modifications, formulations , and applications, this article aims to provide a perspective on the commanding presence and continually evolving impact of the salicylates on what is now over a

Diclofenac sodium topical solution 1.5% w/w with dimethyl sulfoxide compared with placebo for the treatment of osteoarthritis: pooled safety results.

US2 billion anti-inflammato ry therapy market that dwarfs most other important arenas of pharmacotherapy by comparison. Central to this theme is the role of antiinflammatory therapy in rheumatic disorders and, in part icular, the role of the salicylates in relation to the man y other non-salicylate ant i-inflammatory drugs now available. 1. Anti-Inflammatory Therapy: Recognition and Ramifications

NSAID Gastropathy: The Central Issue

Abstract Oral nonsteroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase-2-selective inhibitors are frequently recommended for management of osteoarthritis (OA). However, serious gastrointestinal and cardiovascular systemic adverse events (AEs) are associated with oral NSAIDs and can be treatment limiting. The efficacy of diclofenac sodium topical solution 1.5% w/w with dimethyl sulfoxide (TDiclo) has been established as superior to placebo and comparable with oral NSAIDs in the management of OA. This study characterizes the safety and tolerability profile of TDiclo compared with placebo through a pooled analysis of data from 1252 patients in 7 randomized controlled trials across 61 centers in the United States and 97 centers in Canada. Patients received TDiclo (n = 911) or placebo (n = 341) for 4 to 12 weeks for management of OA of the hand or knee. The most frequently reported AE was dry skin, occurring in 33.0% of patients receiving TDiclo and 5.0% of patients receiving placebo (P < 0.001). Dyspepsia was the most common gastrointestinal reaction, reported by 7.7% of patients receiving TDiclo and 2.9% of patients receiving placebo (P = 0.002). Changes in vital signs and laboratory assessments of hepatic and renal function were similar between the 2 groups; TDiclo did not increase mean blood pressure, nor was it associated with hypertension. The rate of serious AEs favored placebo in both groups (0.9% for TDiclo vs 1.5% for placebo; P = 0.358), as did the rate of severe AEs (4.4% vs 7.6%; P = 0.023). The most common reason for study discontinuation was dry skin (2.5% vs 0.3%). Results from this analysis suggest that TDiclo is well tolerated in a large population and may offer an alternative to oral NSAID therapy for OA of the knee or hand, particularly for patients at increased risk for serious systemic AEs. Larger head-to-head, long-term, multicenter trials would be beneficial to further evaluate safety data comparing both topical and oral NSAIDs.

The emerging new arthritis drugs: A clinician's opinion

SummaryNSAID gastropathy is a serious, iatrogenic problem of common NSAID usage of major public health dimensions. Since ulcer bleeding and perforations can be disastrous, the issue clearly requires prevention.Various gastroprotective therapies exist, but since symptoms do not predict the evolving pathophysiology in most cases, the problem continues to be underestimated in clinical care. Endoscopy is of definitive value, but not generally thought appropriate for screening purposes. Under these circumstances, not driven by putative symptomatology, a long term basis for compliance with gastroprotective therapies is potentially compromised and always expensive.NSAID treatment strategy based on reducing putative gastrotoxicity is a primary goal. Present encouraging postmarketing surveillance experience, clinical research, and most recently, endoscopy evaluation suggest nabumetone as a potential prototype for a new generation of gastro-sparing NSAID therapies based on desirable pharmacological features.

Role of Apheresis in Rheumatoid Arthritis

In the face of deficiencies in our present system of introducing new drugs, clinicians must be committed to monitoring patients carefully. They must not be caught up in the hyperbole and excitement of the latest new drug, but instead should allow the crucible of time to teach them and the rest of the medical community the ultimate truths about this drug in all situations. They must not let the package circular be their only guide to therapy, for it reflects only what has been accomplished under limited conditions. By knowing their patients well and by learning to proficiently use selected drugs that they have become familiar and comfortable with, conscientious practitioners will approach the present state of the art in meeting the needs of their patients.