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Biomedical subjects

Kenneth G Saag

Publications and source records attributed to Kenneth G Saag.

At least 19 recordsLinked to original sources

Treatment of rheumatoid arthritis.

PURPOSE: Current and investigational treatments of rheumatoid arthritis (RA) are described. SUMMARY: The current therapies used to treat RA include nonsteroidal antiinflammatory drugs (NSAIDs), used for the management of pain and inflammation; disease-modifying antirheumatic drugs (DMARDs), used as first-line therapy for all newly diagnosed cases of RA; and biological-response modifiers, targeted agents that selectively inhibit specific molecules of the immune system. Glucocorticoids and other antirheumatic drugs are also used to treat RA. DMARDs include methotrexate, hydroxychloroquine, sulfasalazine, and leflunomide. NSAIDs and glucocorticoids are effective in controlling the pain, inflammation, and stiffness related to RA. Unlike NSAIDs, they slow clinical and radiographic progression of RA. The biological-response modifiers include infliximab, etanercept, and adalimumab (inhibitors of tumor necrosis factor [TNF]-alpha); anakinra, a recombinant inhibitor of interleukin-1; abatacept, the first costimulation blocker; and rituximab, a chimeric anti-CD20 monoclonal antibody. Investigational therapies for RA include anti-interleukin-6-receptor monoclonal antibodies, new TNF-alpha inhibitors (including one for oral administration), and antibodies against proteins critical for B-cell function and survival. Data accumulated in the past decade favor early aggressive therapy for patients suspected of having RA, including early referral to a rheumatologist, new diagnostic techniques, and aggressive therapy with DMARDs, glucocorticoids, and biological agents. The benefits of this approach have been demonstrated in clinical trials. CONCLUSION: Pharmacologic treatments of RA include NSAIDs, glucocorticoids, DMARDs, and biological agents. With an improved understanding of the pathophysiology of RA and the evidence from various clinical trials with the agents, early aggressive therapy with a combination of drugs or biological agents may be warranted for the effective treatment of RA.

Anti-Inflammatory Agents, Non-Steroidal↗

Using a modified nominal group technique to elicit director of nursing input for an osteoporosis intervention.

BACKGROUND: Barriers prevent osteoporosis care in nursing homes. Successful interventions designed to circumvent these barriers benefit from target recipient input during development. OBJECTIVE: To elicit suggestions for an osteoporosis quality improvement intervention designed for use by nursing home health care professionals. DESIGN: Modified nominal group technique. SETTING: Convenience sample of Alabama nursing home directors. PARTICIPANTS: Fifteen Alabama nursing home directors of nursing were recruited by mailing. Sixty percent of respondents participated (n = 9). MEASUREMENTS: In the first phase conducted via teleconference, an experienced moderator used a preformulated question and elicited 41 suggestions to improve osteoporosis care in nursing homes. Substantively similar suggestions were combined and idiosyncratic suggestions were discarded resulting in the retention of 20 suggestions. In the second phase conducted by mail, the same participants rated the 20 suggestions based on perceived practicality and helpfulness. Elements were grouped into tertiles based on the ranking of the mean ratings of the 2 attributes and then cross-tabulated. RESULTS: All director of nursing (n = 9) participants completed both phases. The most practical, most helpful suggestions were information on fall prevention program implementation, osteoporosis treatment protocols, and osteoporosis medication information. CONCLUSIONS: A modified nominal group technique provided useful information from nursing home directors of nursing for an osteoporosis intervention. The technique proved efficient and facile to perform.

Absorptiometry, Photon↗

Population-based assessment of adverse events associated with long-term glucocorticoid use.

OBJECTIVE: The frequency of many adverse events (AEs) associated with low-dose glucocorticoid use is unclear. We sought to determine the prevalence of glucocorticoid-associated AEs in a large US managed care population. METHODS: Using linked administrative and pharmacy claims, adults receiving >or=60 days of glucocorticoids were identified. These individuals were surveyed about glucocorticoid use and symptoms of 8 AEs commonly attributed to glucocorticoid use. RESULTS: Of the 6,517 eligible glucocorticoid users identified, 2,446 (38%) returned the mailed survey. Respondents were 29% men with a mean +/- SD age of 53 +/- 14 years; 79% were white and 13% were African American. Respondents had a mean +/- SD of 7 +/- 3 comorbid conditions and were prescribed a mean +/- SD prednisone-equivalent dosage of 16 +/- 14 mg/day. More than 90% of individuals reported at least 1 AE associated with glucocorticoid use; 55% reported that at least 1 AE was very bothersome. Weight gain was the most common self-reported AE (70% of the individuals), cataracts (15%) and fractures (12%) were among the most serious. After multivariable adjustment, all AEs demonstrated a strong dose-dependent association with cumulative glucocorticoid use. Among users of low-dose therapy (<or=7.5 mg of prednisone per day), increasing duration of use was significantly associated with acne, skin bruising, weight gain, and cataracts. CONCLUSION: The prevalence of 8 commonly attributed self-reported glucocorticoid-associated AEs was significantly associated with cumulative and average glucocorticoid dose in a dose-dependent fashion. Physicians should be vigilant for glucocorticoid-related AEs and should counsel patients about possible risks, even among low-dose long-term users.

Administration, Oral↗

Comparison of weekly treatment of postmenopausal osteoporosis with alendronate versus risedronate over two years.

OBJECTIVE: A 1-yr extension of the Fosamax Actonel Comparison Trial was completed to compare changes in bone mineral density (BMD), bone turnover, and upper gastrointestinal tolerability over 2 yr of treatment. DESIGN: This was a randomized, double-blind extension conducted at 72 U.S. sites. PATIENTS AND METHODS: Of the 1053 women who completed yr 1, 833 postmenopausal women with low BMD entered the extension, continuing their same treatment allocation [once-weekly (OW) alendronate 70 mg or OW risedronate 35 mg]. Changes in BMD at the hip trochanter, total hip, femoral neck, and lumbar spine and in markers of bone turnover were compared at 24 months. Tolerability was assessed by adverse experience reporting. RESULTS: Alendronate produced greater increases from baseline in BMD at 24 months than did risedronate at the trochanter (alendronate, 4.6%; risedronate, 2.5%, P < 0.001) as well as at all other BMD sites. Significantly more alendronate than risedronate patients had measured BMD increases of 0% or more and 3% or more at all BMD sites (P < 0.001), and fewer alendronate patients had measured decreases of 3% or more at all BMD sites. Significantly greater reductions in all biochemical markers of bone turnover occurred with alendronate, compared with risedronate. No differences were seen in occurrence or discontinuations due to upper gastrointestinal adverse experiences. CONCLUSIONS: Patients receiving 70 mg OW alendronate had greater gains in BMD, were more likely to maintain or gain BMD, and had greater reductions in bone turnover markers than patients receiving 35 mg OW risedronate after 24 months, with no differences in upper gastrointestinal tolerability.

Aged↗

Epidemiology, risk factors, and lifestyle modifications for gout.

Gout affects more than 1% of adults in the USA, and it is the most common form of inflammatory arthritis among men. Accumulating data support an increase in the prevalence of gout that is potentially attributable to recent shifts in diet and lifestyle, improved medical care, and increased longevity. There are both nonmodifiable and modifiable risk factors for hyperuricemia and gout. Nonmodifiable risk factors include age and sex. Gout prevalence increases in direct association with age; the increased longevity of populations in industrialized nations may contribute to a higher prevalence of gout through the disorder's association with aging-related diseases such as metabolic syndrome and hypertension, and treatments for these diseases such as thiazide diuretics for hypertension. Although gout is considered to be primarily a male disease, there is a more equal sex distribution among elderly patients. Modifiable risk factors for gout include obesity, the use of certain medications, high purine intake, and consumption of purine-rich alcoholic beverages. The increasing prevalence of gout worldwide indicates that there is an urgent need for improved efforts to identify patients with hyperuricemia early in the disease process, before the clinical manifestations of gout become apparent.

Aged↗

Medication errors with the use of allopurinol and colchicine: a retrospective study of a national, anonymous Internet-accessible error reporting system.

OBJECTIVE: To more closely assess medication errors in gout care, we examined data from a national, Internet-accessible error reporting program over a 5-year reporting period. METHODS: We examined data from the MEDMARX database, covering the period from January 1, 1999 through December 31, 2003. For allopurinol and colchicine, we examined error severity, source, type, contributing factors, and healthcare personnel involved in errors, and we detailed errors resulting in patient harm. Causes of error and the frequency of other error characteristics were compared for gout medications versus other musculoskeletal treatments using the chi-square statistic. RESULTS: Gout medication errors occurred in 39% (n = 273) of facilities participating in the MEDMARX program. Reported errors were predominantly from the inpatient hospital setting and related to the use of allopurinol (n = 524), followed by colchicine (n = 315), probenecid (n = 50), and sulfinpyrazone (n = 2). Compared to errors involving other musculoskeletal treatments, allopurinol and colchicine errors were more often ascribed to problems with physician prescribing (7% for other therapies versus 23-39% for allopurinol and colchicine, p < 0.0001) and less often due to problems with drug administration or nursing error (50% vs 23-27%, p < 0.0001). CONCLUSION: Our results suggest that inappropriate prescribing practices are characteristic of errors occurring with the use of allopurinol and colchicine. Physician prescribing practices are a potential target for quality improvement interventions in gout care.

Adverse Drug Reaction Reporting Systems↗

Documented tuberculin skin testing among infliximab users following a multi-modal risk communication interventions.

PURPOSE: Following its licensure, tuberculosis (TB) was reported as a potential adverse effect of infliximab. Subsequently, the product circular was changed to recommend tuberculin skin testing before patients received infliximab, which was reinforced by several risk communication efforts. The aim of this study was to evaluate patterns and predictors of documented tuberculin skin testing in patients before and after manufacturer, federal, and academic risk communications. METHODS: Patients administered infliximab were identified from 11 health plans located throughout the United States, and claims data were examined to determine whether the patients had received a tuberculin skin test. Patients were divided into three cohorts depending on the timing of their first infliximab treatment in relation to the risk communication efforts. RESULTS: The overall tuberculin skin testing rate doubled from 15.4% in the first cohort to 30.9% in the last cohort, while the rate of pre-infliximab treatment testing increased from 0 to 27.7% (Chi-squared test for trend, p < 0.0001 for both). Tuberculin skin testing rates were significantly higher in women, those with a diagnosis of rheumatoid or psoriatic arthritis, and those with a rheumatologist as prescriber. After multivariable analysis, only rheumatologist remained significantly associated with tuberculin skin testing. CONCLUSIONS: Although the tuberculin skin testing rate was relatively low overall, tuberculin skin testing doubled over 30 months of ongoing risk communication efforts and under ascertainment likely occurred. We also found variation in the tuberculin skin testing rate associated with physician specialty. This study demonstrates a significant change in patient care following risk communication efforts.

Adult↗

Agreement and validity of pharmacy data versus self-report for use of osteoporosis medications among chronic glucocorticoid users.

PURPOSE: Pharmacy and linked claims databases are commonly used to determine medication receipt as a measure of quality of care. However, these data sources have not been previously compared with self-reported data for receipt of medications used for glucocorticoid-induced osteoporosis (GIOP). METHODS: Using databases from a national managed care organization (MCO), we identified 6282 chronic glucocorticoid users (60+ days in 18 months). We compared self-reported current use of alendronate, risedronate, calcitonin, and raloxifene (reference standard) to different intervals of preceding pharmacy data to determine agreement, sensitivity, specificity, and positive and negative predictive values of the pharmacy data. RESULTS: Survey respondents (n = 2363) were mean +/- SD age 53 +/- 14 years old, 70% women, and 78% Caucasian. Agreement between self-reported and pharmacy data ranged from Kappa = 0.64 (95%CI 0.53-0.75) (calcitonin) to 0.80 (0.76-0.84) (alendronate). The positive predictive value of a filled prescription in the pharmacy database in the prior 6 months exceeded 90% compared to the reference standard of self-reported current bisphosphonate use. However, the 6-month interval of pharmacy data failed to capture >25% of self-reported current bisphosphonate users. The optimal interval of pharmacy data to distinguish between current and past bisphosphonate users was 120-180 days. CONCLUSIONS: Among chronic glucocorticoid users enrolled in managed care, underreporting of current osteoporosis medication use was uncommon, and agreement between self-report and pharmacy data was high. Use of pharmacy data alone is unlikely to underestimate quality of osteoporosis care, but different intervals of pharmacy data have important implications on the ability to identify current users of osteoporosis medications.

Alendronate↗

Health-related quality of life among self-reported arthritis sufferers: effects of race/ethnicity and residence.

OBJECTIVE: We evaluated differences in health-related quality of life (HRQoL) for African Americans and Caucasians with self-reported arthritis residing in rural and urban areas of a southern state. METHODS: 1,191 individuals completed a telephone survey, which included the 12-Item Short Form Health Survey (SF-12). Participants were stratified into groups: African American/rural, Caucasian/rural, African American/urban, and Caucasian/urban. We evaluated differences and associations in HRQoL for the four groups. RESULTS: Multivariable linear regression models revealed that being an African American rural resident was associated with worse self-reported mental health on the SF-12 even after adjusting for multiple confounding variables. In contrast, multivariable linear regression models revealed that being a Caucasian rural resident was associated with worse physical health SF-12 scores. CONCLUSIONS: The study revealed differences in HRQoL on the mental and physical health functioning scales of the SF-12 for African American rural and Caucasian rural residents. Researchers assessing HRQoL in arthritis patients should consider using a race/residence product term in their analyses.

Black or African American↗

Postmenopausal osteoporosis. What have we learned since the introduction of bisphosphonates?

Over the past 12 years bisphosphonates have become a mainstay of treatment for postmenopausal osteoporosis. As a class, bisphosphonates significantly suppress bone turnover and increase BMD at the lumbar spine and other site through their direct inhibitory effects on osteoclasts. Alendronate and risedronate reduce the incidence of clinical vertebral and non-vertebral fractures. Etidronate and both oral and intravenous ibandronate reduce the incidence of clinical vertebral fractures, but data from primary analyses for reduction in non-vertebral fractures are currently less robust. Intravenous administration of zoledronate is under late-stage investigation for use in postmenopausal osteoporosis. Combinations of alendronate with estrogen or raloxifene provide a greater reduction in bone turnover markers and greater increases in BMD, but fracture risk reduction has not been determined. Overall, bisphosphonates are well tolerated. The most common side effects of oral bisphosphonates are upper gastrointestinal symptoms. Newer safety concerns about the use of bisphosphonates include osteonecrosis of the jaw and oversuppression of bone turnover. The optimal duration of bisphosphonate treatment has not been clearly established.

Bone Density Conservation Agents↗

Osteoporotic fractures in older adults.

Osteoporotic fractures are emerging as a major public health problem in the aging population. Fractures result in increased morbidity, mortality and health expenditures. This article reviews current evidence for the management of common issues following osteoporotic fractures in older adults including: (1) thromboembolism prevention; (2) delirium prevention; (3) pain management; (4) rehabilitation; (5) assessing the cause of fracture; and (6) prevention of subsequent fractures. Areas for practice improvement and further research are highlighted.

Aged↗

Ethnic variations in the prevalence of metabolic bone disease among HIV-positive patients with lipodystrophy.

A high prevalence of metabolic bone disease and osteonecrosis among HIV+ patients on highly active antiretroviral therapy (HAART) has been reported in predominantly white cohorts. We examined bone health in an ethnically diverse cohort of 23 African-Americans and 21 non-African-Americans who were mean (standard deviation) age 45 (7) years old, 66% male, and on HAART for 34 (28) months. Non-African-Americans were more likely to have osteopenia or osteoporosis (59%) compared to African-Americans (26%) (p = 0.09). The prevalence of vitamin D insufficiency (< 34 ng/ml) and elevated i-PTH (>65 pg/ml) was 79% and 20%, respectively. Higher mean urinary N-telopeptide levels were found in non-African-Americans [58 (34) nmol BCE/mmol] compared to African-Americans [41 (18) nmol BCE/mmol] (p = 0.09). Magnetic resonance imaging identified one African-American subject (3%) with bilateral asymptomatic hip osteonecrosis. Our findings suggest that the burden of metabolic bone disease in HIV+ patients with HAART-associated lipodystrophy may be greater in whites than in African-Americans. Studies to examine ethnic variations in bone metabolism are necessary to devise optimal interventions.

Absorptiometry, Photon↗

New insights into gout epidemiology.

PURPOSE OF REVIEW: The systematic study of gout dates to antiquity, to Hippocrates' initial descriptions of disease risk factors including advancing age, female menopause, and male sex. Although urate crystal diagnosis remains the gold standard for diagnosis it is impractical at a population level. Beyond crystal diagnosis, progress in gout epidemiology has been hampered by the lack of a standardized approach in defining case status. RECENT FINDINGS: Substantial progress has been made in furthering our understanding of gout over the last few decades. Taken together, epidemiologic investigations suggest that gout frequency is on the rise worldwide. Our understanding of gout risk factors continues to expand with the recent availability of well designed prospective cohort studies from both the USA and abroad. Moreover, recent investigations have shed important insight on the complex relationships of hyperuricemia, gout, and comorbid conditions, particularly the association of serum urate levels with cardiovascular morbidity and mortality. SUMMARY: Despite our growing understanding of the many facets of this age-old condition, current evidence continues to underscore the frequency with which gout is characterized by suboptimal care. Below we review our current knowledge of gout epidemiology with an emphasis on the association of hyperuricemia with cardiovascular comorbidity and evidence and determinants of continued suboptimal care in gout.

Cardiovascular Diseases↗

Pathophysiology, clinical presentation and treatment of gout.

Gout is a common form of inflammatory arthritis that has been managed primarily in general medical practices for centuries. It appears that there has been an increasing prevalence of gout over the past decades, implying a growing public health burden. Accurate diagnosis and recognition of the various stages and manifestations of gout enable realistic goal setting for management. Recent evidence suggests new risk factors and potentially refutes others. Management of gout requires characterising and modifying risk factors and associated disorders, and commonly initiating drug therapy. Pharmacotherapy of gout includes the management of acute flares with anti-inflammatory agents such as NSAIDs and glucocorticoids and long-term treatment with urate-lowering drugs. Although pharmacotherapy is generally safe and effective, there are caveats and limitations to all gout therapies. Patient non-adherence and errors with the use of drugs for gout treatment are important factors leading to medical failures. With early intervention, careful monitoring and patient education, gout is a condition that can be managed very effectively. The advent of new drugs (such as febuxostat and urate oxidase [uricase]) and enhanced understanding of the pathogenesis of gout continue to improve our therapeutic options, particularly in a subset of patients with refractory disease and those who are intolerant to currently available medications.

Acute Disease↗