Social & psychological factors associated with oral analgesic use in knee osteoarthritis management.

OBJECTIVE: Determine modifiable social and psychological health factors that are associated with use of oral opioid and non-opioid medications for OA. METHODS: Patients were categorized based on use of the following oral medications: opioids (with/without other oral analgesic treatments), non-opioid analgesics, and no oral analgesic treatment. We used multinomial logistic regression models to estimate adjusted relative risk ratios (RRRs) of using an opioid or a non-opioid analgesic (vs. no oral analgesic treatment), comparing patients by levels of social support (Medical Outcomes Study scale), health literacy ("How confident are you filling out medical forms by yourself?"), and depressive symptoms (Patient Health Questionnaire-8). Models were adjusted for demographic and clinical characteristics. RESULTS: In this sample (mean age 64.2 years, 23.6% women), 30.6% (n = 110) reported taking opioid analgesics for OA, 54.2% (n = 195) reported non-opioid use, and 15.3% (n = 55) reported no oral analgesic use. Opioid users had lower mean social support scores (10.0 vs 10.5 vs 11.9, P = 0.007) and were more likely to have moderate-severe depressive symptoms (42.7% vs 24.1% vs 14.5%, P < 0.001). Health literacy did not differ by treatment group type. Having moderate-severe depression was associated with higher risk of opioid analgesic use compared to no oral analgesic use (RRR 2.96, 95%CI 1.08-8.07) when adjusted for sociodemographic and clinical factors. Neither social support nor health literacy was associated with opioid or non-opioid oral analgesic use in fully adjusted models. CONCLUSIONS: Knee OA patients with more severe depression symptoms, compared to those without, were more likely to report using opioid analgesics for OA.

Natural history of pain and disability among African-Americans and Whites with or at risk for knee osteoarthritis: A longitudinal study.

OBJECTIVE: Compare knee pain and disability between African Americans (AAs) and Whites (WHs), with or at risk of knee osteoarthritis (KOA), over 9 years, and evaluate racial disparities in KOA-related symptoms across socioeconomic and clinical characteristics. DESIGN: Osteoarthritis Initiative (OAI) participants were evaluated annually over 9 years for pain and disability, assessed by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and a numerical rating scale (NRS) for knee pain severity. Mean annual WOMAC pain, NRS pain, and WOMAC disability levels were estimated by race using mixed effects models, adjusted for age, sex, education, marital status, body mass index (BMI), depression, and baseline Kellgren-Lawrence grade score. Race-specific mean WOMAC pain scores were also estimated in analyses stratified by socioeconomic and clinical characteristics. RESULTS: AAs reported worse mean WOMAC pain compared to WHs at baseline (3.69 vs 2.20; P ≤ 0.0001) and over 9 years of follow-up, with similar disparities reflected in NRS pain severity and WOMAC disability. Radiographic severity did not account for the differences in pain and disability, as substantial and significant racial disparities were observed after stratification by Kellgren-Lawrence grade. Depression and low income exacerbated differences in WOMAC pain between AAs and WHs by a substantial and significant magnitude. CONCLUSIONS: Over 9 years of follow-up, AAs reported persistently greater KOA symptoms than WHs. Socioeconomically and clinically disadvantaged AAs reported the most pronounced disparities in pain and disability.

Healthcare resource utilization and costs associated with long-term corticosteroid exposure in patients with systemic lupus erythematosus.

Objective To evaluate the association between exposure to oral corticosteroids and future healthcare resource utilization and costs for patients with systemic lupus erythematosus. Methods Adults diagnosed with systemic lupus erythematosus (index date) between 1 January 2008 and 30 June 2013 and naive to oral corticosteroids with continuous health plan enrollment for ≥6 months pre- and ≥5 years post-index were identified from a large health plan claims database. Per-patient monthly average daily dose of oral corticosteroids (prednisone or its equivalent) was calculated for the first 2 years post-index to categorize patients into four steroid exposure cohorts: low (≤5 mg/day), medium (6-20 mg/day), high (>20 mg/day) and no steroids. Differences in healthcare resource utilization and total healthcare costs during the third year post-index across corticosteroid exposure cohorts were modeled with adjustment for baseline characteristics. Results The study included 18,618 systemic lupus erythematosus patients (163 high dose, 1127 medium dose, 6717 low dose and 10,611 no steroids). Compared to low-dose corticosteroid users, high-dose corticosteroid users were more likely to have emergency room visits (39.3% vs. 29.7%; p = 0.0085) and to be hospitalized (21.5% vs. 12.3%; p = 0.0005). After adjustment for baseline characteristics, they also had significantly greater average annual total healthcare costs (US$60,366 vs. US$18,777; p < 0.0001). A 1 mg increase in corticosteroid average daily dose was associated with 1.07 times the average annual costs after adjusting for baseline characteristics ( p < 0.0001). Conclusion Long-term high-dose oral corticosteroid use was associated with significantly greater future healthcare resource utilization and costs. Judicious reduction in daily steroid dose may decrease the imminent economic burden associated with high-dose steroid use in systemic lupus erythematosus.

The Role of Knowledge and Attitudes About Nonsteroidal Anti-inflammatory Drugs in Determining Treatment Use.

OBJECTIVE: The objective of this study was to evaluate how patient knowledge and beliefs regarding nonsteroidal anti-inflammatory drugs (NSAIDs) may influence the use of NSAIDs for osteoarthritis (OA). METHODS: Surveys of 334 adults with knee and/or hip OA were analyzed in this cross-sectional study. Familiarity with and perceptions of benefits/risks of NSAID use were measured to assess associations with the use of prescription and nonprescription oral NSAIDs. Multinomial logistic regression models were adjusted for sociodemographic and clinical variables. RESULTS: In this sample, 35.9% and 35.6% reported use of oral prescription and nonprescription-only NSAIDs, respectively. Hispanic participants, compared with non-Hispanic White participants, had lower perceived benefit (P = 0.005) and risk (P = 0.001) of prescription NSAIDs. The following were associated with prescription NSAID use instead of no NSAID use: having family/friends who used prescription (relative risk ratio [RRR] 3.91; 95% confidence interval [CI] 2.05-7.47) and over-the-counter (OTC) (RRR 3.10; 95% CI 1.65-5.83) NSAIDs for OA, understanding the consequences of using both prescription (RRR 3.50; 95% CI 1.79-6.86) and OTC (RRR 2.80; 95% CI 1.39-5.65) NSAIDs, higher perceived benefit of both prescription (RRR 2.51; 95% CI 1.71-3.66) and OTC (RRR 1.44; 95% CI 1.01-2.06) NSAIDs, and lower perceived risk of both types of NSAIDs (prescription: RRR 0.63 [95% CI 0.46-0.87]; OTC: RRR 0.53 [95% CI 0.37-0.75]). Similar results were found when we assessed the relationship between these variables and OTC NSAID use versus no oral NSAID use. CONCLUSION: Adults with knee and/or hip OA were more likely to use NSAIDs if they were more familiar with, had an increased perceived benefit of, and had a decreased perceived risk of these drugs. Patients' perceptions and beliefs about NSAIDs should be evaluated when considering them for treatment.

The effect of aspirin and two nitric oxide donors on the infarcted heart in situ.

Nitric oxide (NO) donors are heterogeneous substances which release NO, a biologically active compound. NO released by nitric oxide donors has important effects on the circulation by causing vasodilation, diminishing myocardial contractile force, inhibiting platelet aggregation, and counteracting the effects of thromboxane A2. In the infarcted heart, activation of the inducible form of nitric oxide synthase (iNOS) and the formation of prostacyclin and thromboxane A2 by cyclooxygenase (COX) were increased. Myocardial infarction also resulted in increased myocardial NO production. Aspirin (acetylsalicylic acid. ASA) at low concentration (35 mg/kg/day) fails to change iNOS production, in contrast to higher dose (150 mg/kg/day) which, as previously shown, inhibits iNOS activity. ASA at all doses also suppresses myocardial prostanoid formation because of inhibition of COX. Recently, two NO donors have been synthesized: NCX 4016 and Diethylenetriamine/NO (DETA/NO). NCX 4016 combines an NO-releasing moiety with a carboxylic residue via an esteric bond. We describe here that NCX 4016 (65 mg/kg/day) increased prostacyclin and thromboxane A2 production in the infarcted heart muscle, overcoming the inhibitory effects of ASA. As a result of nitric oxide release, oxidation products of NO (NO2- and NO3-; NOx) in arterial blood rose following administration of NCX 4016. On oral administration, NCX 4016 did not change systemic arterial pressure. The effects of a single NO donor, DETA/NO (1.0 mg/kg/day) on the infarcted heart were also investigated On intravenous administration, the compound increased NO concentration in arterial blood slightly but to a lesser degree than NCX 4016. Like NCX 4016, it raised myocardial production of prostacyclin and thromboxane A2 in the infarcted heart. However, it caused a severe fall in blood pressure. These findings demonstrate that newly-synthesized NO donors release nitric oxide in situ and increase myocardial production of prostanoids. NCX 4016 has therapeutic potential because it can be orally administered, lacks hypotensive effects, increases blood levels of nitric oxide and myocardial prostacyclin production.

Effect of cyclooxygenase-2 inhibitor (celecoxib) on the infarcted heart in situ.

Several attempts have been made to replace aspirin with compounds without gastric toxicity; a cyclooxygenase-2 (COX-2) inhibitor, celecoxib, and a nitric oxide-aspirin, NCX-4016, have been developed for this purpose. This paper compares effects of celecoxib, NCX-4016 and aspirin on production of prostacyclin (PGI2) and thromboxane A2 (TXA2) and activation of the inducible form of nitric oxide synthase (iNOS) in infarcted heart in situ. Aspirin was most effective in reducing myocardial PGI2 synthesis and formation of TXA2. Myocardial effects of celecoxib resemble those of NCX-4016, although the two compounds have different modes of action.