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Objective: Patient-physician discordance in health status ratings may arise because patients use temporal comparisons (comparing their current status with their previous status), while clinicians use social comparisons (comparing this patient's status to that of other patients, or to the full range of disease severity possible) to guide their assessments. We compared discordance between patients with rheumatoid arthritis (RA) and clinicians using either the conventional patient global assessment (PGA) or a rating scale with five anchors describing different health states. We hypothesized that discordance would be smaller with the rating scale because clinicians likely used similar social comparisons when making global assessments. Methods: We prospectively studied 206 patients with active RA, and assessed the PGA (0 – 100), rating scale (0 – 100), and evaluator global assessment (EGA; 0 – 100)) on each of two visits (total 401 visits). We compared the PGA/EGA discordance and the rating scale/EGA discordance at each visit. Results: The mean (± standard deviation) PGA/EGA discordance was 8.5 ± 22.4, and the mean rating scale/EGA discordance was 2.3 ± 24.0. The intraclass correlation, measuring agreement, was higher between the rating scale and EGA than between the PGA and EGA (0.39 versus 0.31). Agreement was larger at low levels of RA activity on both pairs of measures. Conclusion: Discordance between patients' global assessments and evaluators' global assessments was smaller when patients used a social standard of comparison than when they marked the PGA, suggesting that differences in standards of comparison contribute to patient-clinician discordance when the PGA is used. This article is protected by copyright. All rights reserved.

ObjectiveTo identify genetic associations with severity of radiographic damage in ankylosing spondylitis (AS).MethodWe studied 1537 AS cases of European descent; all fulfilled the modified New York Criteria. Radiographic severity was assessed from digitised lateral radiographs of the cervical and lumbar spine using the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). A two-phase genotyping design was used. In phase 1, 498 single nucleotide polymorphisms (SNPs) were genotyped in 688 cases; these were selected to capture >90% of the common haplotypic variation in the exons, exon–intron boundaries, and 5 kb flanking DNA in the 5′ and 3′ UTR of 74 genes involved in anabolic or catabolic bone pathways. In phase 2, 15 SNPs exhibiting pResultsExperiment-wise association was observed with the SNP rs8092336 (combined OR 0.32, p=1.2×10−5), which lies within RANK (receptor activator of NFκB), a gene involved in osteoclastogenesis, and in the interaction between T cells and dendritic cells. Association was also found with the SNP rs1236913 in PTGS1 (prostaglandin-endoperoxide synthase 1, cyclooxygenase 1), giving an OR of 0.53 (p=2.6×10−3). There was no observed association between radiographic severity and HLA-B*27.ConclusionsThese findings support roles for bone resorption and prostaglandins pathways in the osteoproliferative changes in AS.

Objective To analyze the minimum clinically important improvement (MCII) of disease activity measures in rheumatoid arthritis (RA) using patient-derived anchors, and to assess whether criteria for improvement differ with baseline disease activity. Methods We used data from a Norwegian observational database comprising 1,050 patients (73% women, 65% rheumatoid factor-positive, mean duration of RA 7.7 years). At 3 months after initiation of therapy, patients indicated whether their condition had improved, had considerably improved, was unchanged, had worsened, or had considerably worsened. We used receiver operating characteristic curve analysis to determine the MCII for the Disease Activity Score based on the assessment of 28 joints (DAS28), the Simplified Disease Activity Index (SDAI), and the Clinical Disease Activity Index (CDAI), and analyzed the effects of different levels of baseline disease activity on the MCII. Results On average, patients started with high disease activity and improved significantly during treatment (American College of Rheumatology 20%, 50%, and 70% improvement criteria responses were 37%, 17%, and 5%, respectively). The overall mean (95% confidence interval [95% CI]) thresholds for MCII after 3 months for the DAS28, SDAI, and CDAI were 1.20 (95% CI 1.18–1.22), 10.95 (95% CI 10.69–11.20), and 10.76 (95% CI 10.49–11.04), respectively, and the mean (95% CI) thresholds for major responses were 1.82 (95% CI 1.80–1.83), 15.82 (95% CI 15.65–16.00), and 15.00 (95% CI 14.82–15.18), respectively. With increasing disease activity, much higher changes in disease activity were needed to achieve MCII according to patient judgment. Conclusion The perception of improvement of disease activity of patients with RA is considerably different depending on the disease activity level at which they start.

Background: Physical function in rheumatoid arthritis (RA) has reversible and irreversible components, and is typically assessed by the Health Assessment Questionnaire Disability Index (HAQ). Since irreversible components are expected to increase with longer duration of RA and reduce the ability for improvement in physical function, we analysed responsiveness of HAQ scores in patient populations with differing RA durations in randomised controlled trials (RCTs). Methods: Data from all RCTs published between 1980 and 2005 that reported changes from baseline in HAQ at 6 and/or 12 months were analysed. Treatments were grouped as “biologics”, or “traditional” disease modifying antirheumatic drugs (DMARDs), and “placebo”. We computed effect sizes of HAQ in each trial, and contrasted the association between these effects and duration of RA among treatment groups using regression models. Results: We identified 42 RCTs with complete data for the statistical models. The models indicate that discrimination of functional improvement between active drug groups and placebo is reduced in patients with a longer duration of RA (p = 0.02 for the change in discrimination over time). The placebo-adjusted HAQ responses decreased on average by 0.37 per year of RA duration. Conclusion: Responsiveness in HAQ scores is inversely associated with mean disease duration in RA. This impacts assessment of physical function, a key outcome measure in RCTs and practice, and impacts the ability to discriminate active treatment from placebo.

Heart valve replacement surgeries account for 20% of all cardiac procedures. In-hospital mortality rates are approximately 6% for aortic valve replacements and 10% for mitral valve replacements. The objectives of the study are to provide nationally representative estimates of complications following aortic and mitral valve replacements and to quantify the impact of different types of complications on in-hospital outcomes.The Nationwide Inpatient Sample was analyzed for years 2000-2003. The effect of complications on in-hospital mortality, length of stay (LOS), and hospital charges were examined using bivariate and multivariable logistic and linear regression analyses. The confounding effects of age, sex, primary diagnosis, type of valve replacement, type of admission, comorbid conditions, and hospital characteristics were adjusted.A total of 43,909 patients underwent aortic valve replacement as the primary procedure during the study period and 16,516 patients underwent mitral valve replacement. Complications occurred in 35.2% of those undergoing aortic valve replacements and in 36.4% of those undergoing mitral valve replacements. Almost half of these are cardiac complications and a quarter involve hemorrhage/hematoma/seroma. Complications were significantly associated with in-hospital mortality, LOS, and hospital charges even after adjusting for patient and hospital characteristics.Complications are prevalent and exert a considerable influence on outcomes following aortic and mitral valve replacements. Quality initiatives should focus on minimizing complications and improving processes of care that would enable complications to be better resolved if they occur.

In each of two experiments, 924 pigs (4.99 kg BW; 16 to 18 d of age) were assigned to 1 of 42 pens based on BW and gender. Pens were allotted randomly to dietary copper (Cu) treatments that consisted of control (10 ppm Cu as cupric sulfate, CuSO4 x 5H2O) and supplemental dietary Cu concentrations of 15, 31, 62, or 125 ppm as cupric citrate (CuCit), or 62 (Exp. 2 only), 125 (Exp. 1 only), or 250 ppm as CuSO4. Live animal performance was determined at the end of the 45-d nursery phase in each experiment. On d 40 of Exp. 2, blood and fecal samples were collected from two randomly selected pigs per pen for evaluation of plasma and fecal Cu concentrations and fecal odor characteristics. In Exp. 1, ADG, ADFI, and G:F were increased (P0.05), relative to controls, when pigs were fed diets containing 250 ppm Cu as CuSO4. Pigs fed diets containing 125 ppm Cu as CuCit had increased (P0.05) ADG compared with pigs fed diets supplemented with 15 or 62 ppm Cu as CuCit. The ADG, ADFI, and G:F did not differ among pigs fed diets containing 125 and 250 ppm Cu as CuSO4 or 125 ppm Cu as CuCit. In Exp. 2, pigs fed diets containing 250 ppm Cu as CuSO4 had improved (P0.05) ADG, ADFI, and G:F compared with controls. In addition, ADG, ADFI, and G:F were similar when pigs were fed diets containing either 250 ppm Cu as CuSO4 or 125 ppm Cu as CuCit. Pigs fed diets containing 62 ppm Cu as CuSO4 or CuCit had similar ADG, ADFI, and G:F. Plasma Cu concentrations were not affected by dietary Cu source or concentration, but fecal Cu concentrations were increased (P0.05) as the dietary concentration of Cu increased. Pigs consuming diets supplemented with 125 ppm Cu as CuCit had fecal Cu concentrations that were lower (P0.05) than pigs consuming diets supplemented with 250 ppm Cu as CuSO4. Fecal Cu did not differ in pigs receiving diets supplemented with 62 ppm Cu as CuSO4 or CuCit. Odor characteristics of feces were not affected by Cu supplementation or source. These data indicate that 125 and 250 ppm Cu gave similar responses in growth, and that CuCit and CuSO4 were equally effective at stimulating growth and improving G:F in weanling pigs. Fecal Cu excretion was decreased when 125 ppm Cu as CuCit was fed compared with 250 ppm Cu as CuSO4. Therefore, 125 ppm of dietary Cu, regardless of source, may provide an effective environmental alternative to 250 ppm Cu as CuSO4 in weanling pigs.

Patients whose perspectiveis oriented to the future more than to the present may have better long-term health outcomes. We examined if time perspective predicted future organ damage in patients with systemic lupus erythematosus(SLE). We assessed the time perspectivesof 87 patients with SLE using a questionnaire at a baseline visit. Permanent organ damage was assessed by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index during the same visit, and reassessed after a median of 4.6 years. Patients who were oriented more to the futurewere less likely to have an increasein the Damage Index than those oriented more to the present. In a multivariate analysis, each 1-point increase in the degree of orientation to the future (on a scale of 1-6) was associatedwith a 22% decreasein the likelihood that the Damage Index would increase over time (odds ratio 0.78; 95% confidence interval 0.64-0.94; P 0.009). Other measures that predicted an increase in the Damage Index were lower education levels, greater health locus of control attributed to chance and greater health locus of control attributed to powerful others. In conclusion, time perspective is a significant predictor of future organ damage in SLE. Patients who have a greater orientation to the future are less likely to develop permanent organ damage.

Objective To determine if changes in depressive symptoms or anxiety lead to changes in the activity of systemic lupus erythematosus (SLE). Methods Twenty-three patients with SLE were examined prospectively every 2 weeks for up to 40 weeks. At each assessment, patients completed the Centers for Epidemiologic Studies--Depression scale (CES-D), the State subscale of the State-Trait Anxiety Inventory and a global assessment of the activity of their SLE by visual analogue scale. SLE activity was also assessed at each visit by physician global assessment, the Systemic Lupus Activity Measure (SLAM), the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and the European Consensus Lupus Activity Measure (ECLAM). Results Changes in depression and anxiety were positively correlated with simultaneous changes in the patient global assessment of SLE activity and in the SLAM, but not with changes in the physician global assessment, SLEDAI or ECLAM. Depression and anxiety scores were also correlated with patient global assessments and SLAM scores 2 weeks later, but lagged scores were not significantly associated with the patient global assessment or SLAM after controlling for current depression and anxiety scores. The associations between depression and anxiety scores and the SLAM were not present when SLAM scores were modified to exclude ratings of depression and fatigue. No measure of SLE activity increased in the 2 weeks immediately after a large increase in CES-D or State Anxiety scores. Conclusions Depression and anxiety scores parallel changes in patients' assessments of the activity of their SLE. We found no evidence to support the hypothesis that psychological distress causes increased SLE activity.

We present the first documented case of Kearns-Sayre syndrome presenting with a vocal fold palsy.

This paper describes a clinical situation where it was impossible to obtain a biopsy of a lesion at the anterior commissure in a patient with progressive hoarseness of voice using standard microlaryngoscopy techniques. Due to anatomical difficulties and a histological suggestion of laryngeal papillomatosis the incisor teeth were deliberately removed to allow an adequate view of the larynx and to facilitate further access.

To identify risk factors for work disability in patients with ankylosing spondylitis (AS).Risk factors for permanent work disability and for receipt of disability payments were assessed using Cox regression models in a retrospective cohort study of 234 patients with AS. Candidate risk factors included age at onset of AS, sex, race, education level, marital status, the presence of comorbid conditions, smoking and drinking history, recreational activity, occupation, and physical activity at work. Risk factors for changes in the type of work performed, decrease in number of hours worked, long sick leave, and the need for help at work were assessed using logistic regression models in a prospective study of the subset of 144 patients who reported working for pay during the study. Candidate risk factors for these aspects of work disability were age, sex, race, education level, levels of functional disability, pain and stiffness, changes in functional disability, pain or stiffness over the preceding 6 months, minutes/week of recreational exercise, back exercises, freedom of movement at work, control over the pace of work, and physical activity at work.In a cohort of 234 patients with a median duration of AS of 21.4 years, 31 patients (13.2%) developed permanent work disability and 57 patients (24.3%) had received disability payments. Older age at onset of AS, less formal education, and having had jobs that were more physically active were significant risk factors for permanent work disability. These factors, along with the presence of a comorbid condition and being female, were also significantly associated with the receipt of disability payments. In a prospective study of 144 patients followed for a median of 4 years, higher levels of functional disability and pain were associated with increased risks of decreased work hours, long sick leaves, and needing help at work, while higher levels of pain were also associated with an increased risk of changing the type of work performed. Women were significantly more likely than men to change their type of work or decrease their work hours. Patients whose jobs were more physically demanding were more likely to change their type of work or need help at work.Patients with AS who have physically demanding jobs are more likely to experience permanent or temporary work disability, or need to change the type of work done or receive help at work, than those with jobs that are less physically demanding.

Preference measures may be useful tools to assess patients' overall health-related quality of life. We studied the validity and sensitivity to change of the rating scale preference measure in patients with systemic lupus erythematosus (SLE), and compared its properties with those of the patient global assessment of SLE activity, in a prospective longitudinal observational study of changes in the symptoms and clinical disease activity of 23 patients. Patients were assessed every two weeks for up to 40 weeks. Construct validity was assessed by the strength of correlations between changes over time in the rating scale preference measure and patient global assessment and changes in the physician global assessment, Systemic Lupus Activity Measure (SLAM), European Consensus Lupus Activity Measure (ECLAM), the British Isles Lupus Assessment Group index (BILAG), and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Changes in the rating scale were more highly correlated with changes in each of these standards than were changes in the patient global assessment, demonstrating the construct validity of this measure. Sensitivity to change was measured using the two-week interval of greatest change in either the physician global assessment or the SLE activity measures as standards. The rating scale preference measure was less sensitive to change than the patient global assessment when tested against four different standards. The sensitivity to change of the rating scale was less than one-half that of the patient global assessment when either the SLAM or ECLAM was used as the standard. Although these results support the validity of the rating scale as a measure of health-related quality of life in patients with SLE, its limited sensitivity to change may make it less attractive as an endpoint measure in clinical trials.

To determine whether a hospital's experience in treating patients with systemic lupus erythematosus (SLE) is associated with the risk of in-hospital mortality among these patients.The California Hospital Discharge Database, which contains information on all discharges from acute care hospitals in California, was used to identify patients with SLE hospitalized on an emergent or urgent basis from 1991 to 1994 (n = 9,989). For each of the 413 hospitals at which these patients were hospitalized, expected mortality risks were computed based on a model that included patient demographic and clinical characteristics, and differences between the observed and expected numbers of deaths were calculated. This difference was then associated with the average annual number of patients with SLE admitted to each hospital on an emergent or urgent basis. Similar analyses were performed for the subset of 2,372 patients hospitalized on an emergent basis (at 293 hospitals), and the subset of 405 patients hospitalized on an emergent basis due to SLE (at 122 hospitals).In all 3 patient subsets, there was an inverse association between the average annual number of patients with SLE hospitalized on an urgent or emergent basis at a hospital and the difference between the observed and expected number of deaths at that hospital. Highly experienced hospitals had fewer than expected deaths, while there was little association between the difference between the observed and expected number of deaths among less experienced hospitals.Hospitals that treat larger numbers of patients with SLE have fewer than the expected number of deaths among such patients.

To compare the construct validity and sensitivity to change of the Systemic Lupus Activity Measure (SLAM), Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), Lupus Activity Index (LAI), British Isles Lupus Assessment Group index (BILAG), and the European Consensus Lupus Activity Measure (ECLAM).Twenty-three patients with systemic lupus erythematosus (SLE) were examined prospectively every 2 weeks for up to 40 weeks. Nineteen patients completed all 20 assessments. At each assessment, each of the 5 activity indices was scored, along with physicians' and patients' global assessments of SLE activity. Construct validity was determined by the strength of correlations between changes over time in each activity index and changes in physician and patient global assessments. Sensitivity to change was determined by the magnitude of change in each index over the 2 week interval of greatest change in the physician or patient global assessments, and calculated as standardized response means (SRM; mean change/standard deviation of change). Thirteen patients were also examined monthly by a second physician who was blinded to previous scores on the activity indices and to the patient global assessments.Patients had substantial changes in SLE activity during the study. Changes in each activity index were correlated with changes in the physician global assessment (SLAM r = 0.54; SLEDAI r = 0.52; LAI r = 0.75; BILAG r = 0.61; ECLAM r = 0.65; all p0.0001). Correlations were somewhat lower with the blinded physician assessment (SLAM r = 0.42; SLEDAI r = 0.12; LAI r = 0.30; BILAG r = 0.28; ECLAM r = 0.32). The SLAM was the only index that was positively correlated with changes in the patient global assessment (r = 0.22; p0.0001). Sensitivity to change was greatest for the LAI (SRM = 0.74) and the ECLAM (SRM = 0.75) and smallest for the SLEDAI (SRM = 0.48) when the physician global assessment was used as the standard. Sensitivity to change was greatest for the SLAM (SRM = 0.61) and the BILAG (SRM = 0.57) and smallest for the SLEDAI (SRM = -0.01) when the patient global assessment was used as the standard.Each index is a valid measure of SLE activity. The SLAM captures patients' assessments better than the other indices, perhaps because it assesses the patients' subjective complaints to a greater extent. Estimates of sensitivity to change varied with the standard used, but the SLEDAI was least sensitive to change. Larger studies are indicated to further compare the sensitivity to change of these indices.

To identify aspects of health-related quality of life that are most commonly affected in patients with ankylosing spondylitis (AS).One hundred seventy-five participants in a longitudinal study of health status in AS completed a cross-sectional survey that asked them to rate the presence and importance of problems in 23 aspects of quality of life, including symptoms, disability, mood, relations with others, and concerns about treatments and the future. Participants also completed the Medical Outcomes Study Short Form 36 Health Survey (SF-36).The mean age of the participants was 51.1 years, and the mean duration of AS was 23.7 years; 119 (68%) were men. The most prevalent quality of life concerns included stiffness (90.2%), pain (83.1%), fatigue (62.4%), poor sleep (54.1%), concerns about appearance (50.6%), worry about the future (50.3%), and medication side effects (41%). Compared with those who had some college education, participants with 12 years of education or less were 2 to 4 times more likely to have problems or concerns with medication side effects, mobility, housework and self-care tasks, coping with illness, anxiety, payment for treatment, and relationships with spouses, family, and friends. Mean scores on the 8 domains of the SF-36 (range 0-100; higher scores indicate better function) ranged from 49 (energy/fatigue) to 77 (role limitations due to emotional problems). Patients with 12 years of education or less had significantly lower scores than those with some college on all domains except general health.In addition to pain and stiffness, fatigue and sleep problems are important concerns in patients with AS, while few reported problems with mood or social relationships. Less educated patients had lower quality of life in many different aspects.

To determine if a hospital's experience in treating patients with systemic lupus erythematosus (SLE) is associated with in-hospital mortality among patients with this condition.The California Hospital Discharge Database, which contains information on all discharges from acute-care hospitals in California, was used to identify patients with SLE hospitalized from 1991 to 1994 (n = 9,989). The risks of in-hospital mortality were compared between patients admitted to hospitals in which there was a high degree of experience (those with an average of50 urgent or emergency SLE admissions per year) and those in which there was less experience.Patients admitted on an urgent or emergency basis to hospitals in which there was a high degree of experience had a slightly lower risk of in-hospital mortality than patients admitted to hospitals in which there was less experience (mortality 3.8% versus 5.3%; adjusted odds ratio [OR] 0.72, 95% confidence interval [95% CI] 0.50-1.04). In the subset of 2,372 patients hospitalized on an emergency basis, those admitted to hospitals in which there was a high degree of experience had a risk of in-hospital mortality that was 66% lower than that of patients admitted to hospitals in which there was less experience (mortality 4.2% versus 11.3%; adjusted OR 0.34, 95% CI 0.19-0.58). In the subset of 405 patients hospitalized on an emergency basis due to SLE, those admitted to hospitals in which there was a high degree of experience had a risk of in-hospital mortality that was 95% lower than that of patients admitted to hospitals in which there was less experience (mortality 1.7% versus 10.0%; adjusted OR 0.05, 95% CI 0.006-0.34). Among those with emergency hospitalizations for any reason or emergency hospitalizations due to SLE, lengths of stay and total costs did not differ between patients hospitalized at hospitals in which there was a high degree of experience and hospitals in which there was less experience.In-hospital mortality among patients with SLE is lower at hospitals in which there is more experience in caring for patients with SLE. This association is strongest among patients hospitalized on an emergency basis due to SLE.

Pneumonia due to Pneumocystis carinii has been increasingly reported in patients with connective tissue diseases, but the frequency of this complication is not known. We sought to determine the frequency of P carinii pneumonia (PCP) in patients with connective tissue diseases, and to determine the role that a hospital's acquired immunodeficiency syndrome (AIDS)-related experience may have in the diagnosis of PCP in these patients.We used a state hospitalization registry to identify all patients with PCP and either rheumatoid arthritis, systemic lupus erythematosus, Wegener's granulomatosis, polymyositis, dermatomyositis, polyarteritis nodosa, or scleroderma who had an emergent or urgent hospitalization in California from 1983 to 1994. We compared patient and hospital characteristics between these patients and patients with connective tissue diseases hospitalized with other types of pneumonia.Two hundred twenty-three patients with connective tissue diseases were diagnosed with PCP in the 12-year study period. The frequency of PCP ranged from 89 cases/10,000 hospitalizations/year in patients with Wegener's granulomatosis to 2 cases/10,000 hospitalizations/year in patients with rheumatoid arthritis. Compared with 5,457 patients with connective tissue diseases and pneumonia due to other organisms, patients with PCP were more likely to be younger, to be male, to have private medical insurance, and to have systemic lupus erythematosus, Wegener's granulomatosis, inflammatory myopathy, or polyarteritis nodosa rather than rheumatoid arthritis, and were less likely to be African American. Hospital size, teaching status, urban/rural location, proportion of admissions due to AIDS or PCP, and proportion of patients with pneumonia undergoing bronchoscopy were each associated with the likelihood of diagnosis of PCP in univariate analyses, but only the number of patients with PCP being treated at a hospital (odds ratio [OR] 1.03 for each additional 10 cases/year, 95% confidence interval [95% CI] 1.01-1.05) was associated with the likelihood of diagnosis of PCP in multivariate analyses. Patients were also somewhat more likely to be diagnosed with PCP if there had previously been a case of PCP in a patient with a connective tissue disease at the same hospital (OR 135, 95% CI 0.98-1.85). In-hospital mortality was 45.7%, and was unrelated to hospital characteristics.PCP is an uncommon, but often fatal, occurrence in patients with connective tissue disease. A hospital's prior experience with patients with PCP is associated with the likelihood that this condition is diagnosed in patients with connective tissue diseases who present with pneumonia, suggesting that diagnostic suspicion is an important factor in the correct identification of affected patients.

Current treatment of rheumatoid arthritis (RA) emphasizes the early and consistent use of disease modifying antirheumatic drugs (DMARD). We studied how often these medications were used to treat patients with RA, and whether use of these medications has increased over time.We used the National Ambulatory Medical Care Surveys to determine national probability estimates of the use of DMARD [hydroxychloroquine, intramuscular gold, auranofin, methotrexate (MTX), sulfasalazine, azathioprine, D-penicillamine, and cyclosporine] by patients with RA. The National Ambulatory Medical Care Surveys record information about treatments provided in outpatient settings by a nationally representative cross sectional sample of physicians. Estimates of the use of DMARD were based on the treatments reported on 502 visits by patients with RA in 1980-81, 339 visits by patients with RA in 1985, 386 visits by patients with RA in 1989-91, and 383 visits by patients with RA in 1993-95.DMARD were used in 30.3% of visits in 1980-81, 36.3% of visits in 1985, 24.9% of visits in 1989-91, and 43.6% of visits in 1993-95 (p for trend0.0001). Increased use of MTX accounted for most of the increased prevalence of DMARD use; MTX was used in 27.3% of visits in 1993-95. Use of DMARD increased in 1993-95 in all age, sex, and racial subgroups, and among visits reported by rheumatologists, but did not increase over time among visits reported by physicians other than rheumatologists.Use of DMARD in RA has increased in the recent past, but DMARD are currently used by fewer than 44% of patients with RA. Use of DMARD has not increased over time among patients of physicians other than rheumatologists.

To determine the extent to which office-based rheumatologists provide primary care to patients without rheumatic diseases or provide principal care to patients with rheumatoid arthritis (RA).The National Ambulatory Medical Care Survey was used to determine national probability estimates of the nature and types of conditions treated by office-based rheumatologists in 1991-1995. At each of 1,074 patient visits, the rheumatologists recorded up to 3 diagnoses and 3 patient-reported reasons for the visit, as well as information on the treatments provided at the visit.In only 9.8% of new consultations and 11.9% of return visits was neither a rheumatic disease diagnosis nor a musculoskeletal complaint recorded, indicating that the rheumatologist was likely acting as a primary care provider at a minority of patient visits. Among continuing patients with RA, the patient's primary reason for the visit was something other than a musculoskeletal complaint in only 9.9% of visits, and any nonrheumatic complaint was recorded in 30.4% of visits, indicating that at only some visits was the rheumatologist acting as the principal caregiver. In addition, only 31.1% of visits included the provision of medication for a nonrheumatic condition.In 1991-1995, most visits to rheumatologists involved the provision of specialized or consultative care to patients with rheumatic diseases or musculoskeletal complaints, and few visits were made by patients without either indication. Provision of principal care by rheumatologists to patients with RA is not currently widespread.

To describe changes in antirheumatic medication use by patients with rheumatoid arthritis (RA) over the 15 years 1981 to 1996.Medication use was ascertained every 6 months by mailed Health Assessment Questionnaire in a cohort of patients recruited from the local community (n = 305; mean duration of RA at study entry 14.2 yrs). Patients were treated by 53 rheumatologists and over 200 other physicians during the study. The proportions of patients treated with nonsteroidal antiinflammatory drugs (NSAID), disease modifying antirheumatic drugs (DMARD), prednisone, intraarticular corticosteroids, and analgesics were determined in serial cross sectional analyses, and trends in medication use over time were analyzed using linear regression.From 1981 to 1996, the proportion of patients treated with DMARD increased from 32 to 47% (average increase 1.06% each year; p0.0001), while the proportion treated with NSAID decreased from 86 to 76% (average decrease 0.57% each year; p0.0001). The proportion of patients treated with prednisone remained between 30 and 40%, with a trend toward increasing use over time (average increase 0.2% each year; p = 0.05). In contrast, the proportion treated with intraarticular corticosteroids decreased from 14.4 to 6.7% (average decrease 0.46% each year; p0.0001). In 1996, the most prevalent patterns of medication use were the use of NSAID alone (24.4%), use of an NSAID and DMARD (16.3%), and use of an NSAID, DMARD, and prednisone (12.2%). Use of an NSAID as the only antirheumatic medication decreased over time, and the use of DMARD in combination with other medications increased.The proportion of patients with RA treated with DMARD increased substantially from 1981 to 1996. This change in practice occurred during the time in which the concept of inverting the traditional therapeutic pyramid became popular, and may reflect a translation among clinicians of the philosophy of "early DMARD use" to "consistent DMARD use," even among patients with RA of moderate or longstanding duration.

To identify subgroups of smokers with different success rates, we applied "tree-structured survival analysis" (TSSA) to data from a previously published trial of transdermal nicotine. The subjects who received active treatment (14 mg patch, n = 275, or the 21 mg patch, n = 262) constituted the sample for this analysis. Using age, gender, the Fagerstrom Tolerance Questionnaire (FTQ), motivation to quit, number of cigarettes smoked at baseline, and body mass index (BMI) as classification variables, TSSA identified two subgroups within the 14 mg patch group and four subgroups of smokers within the 21 mg patch group. Among those receiving the 14 mg patch, individuals with a BMI greater than 26.4 kg/m2 relapsed sooner than did those with a BMI less than or equal to this value. Within the 21 mg patch group, the survival curve for males was significantly different from that observed in females, with males experiencing a longer time to relapse after treatment than did females. Among females, those with a higher motivation to quit relapsed more slowly than did those women with less motivation to quit. This information may be helpful to clinicians seeking to match specific patients to specific treatments with traditional nicotine in order to maximize treatment outcomes.

To determine if the frequency of visits to rheumatologists by patients with rheumatoid arthritis (RA) is associated with either short term (6 month) or longterm (10 year) changes in functional disability or pain.Information on health care utilization and health status was obtained for up to 10 years by biannual mailed Health Assessment Questionnaires (HAQ) in a community based cohort of patients with RA. We studied the relationship between the frequency of visits to rheumatologists and changes in functional disability and pain among 127 patients who were treated by a rheumatologist at least once each year.The median visit frequency was 7.2 visits/year (range 2-17.5 visits/year). The number of rheumatology visits was significantly associated with short term changes in both functional disability and pain: each additional visit in a 6 month study interval was associated with a decrease in the pain score in the current interval by an average of 0.02 points (on a 3 point scale), and each additional visit was associated with a decrease in the HAQ Disability Index in the subsequent 6 month interval by an average of 0.007 points (on a 3 point scale). In analyses of longterm changes in health status, there was a U-shaped relationship between the frequency of rheumatology visits and the rate of progression of functional disability over time, with the lowest rates associated with average visit frequencies of between 7 and 11 visits/year. Average pain scores over time were positively correlated with the average annual frequency of rheumatology visits (r = 0.25).More frequent visits to rheumatologists were associated with greater improvements in pain and functional disability over periods of 6 and 12 months, respectively. Rates of progression of functional disability over time were also higher among patients with less than 7 visits/year than among those with 7-11 visits/year, suggesting that the outcomes of these patients might have been improved with more frequent visits.

Mortality in patients with systemic lupus erythematosus (SLE) is often related to disease in particular organ systems. We examined the risks of mortality associated with 8 clinical manifestations of SLE and determined whether these risks differed among patients with different sociodemographic characteristics.Using life table analysis, we determined the associations of hemolytic anemia, leukopenia, thrombocytopenia, arthritis, serositis, nephritis, psychosis, and seizures with both all-cause mortality and SLE-related mortality in a cohort of 408 patients.Over a median duration of follow-up of 11 years, 144 patients died; 78 deaths (54%) were SLE related. In univariate analyses, the presence of hemolytic anemia, serositis, nephritis, psychosis, and seizures was associated with greater all-cause mortality, while the presence of arthritis was protective. In multivariate analyses that controlled for patient demographic characteristics, nephritis (relative risk, 2.34) and seizures (relative risk, 1.77) were associated with poorer overall survival. Nephritis and seizures, along with thrombocytopenia, were also associated with greater SLE-related mortality, while leukopenia was protective. The risk of death in association with these clinical manifestations did not differ among patient age, sex, race, or socioeconomic subgroups.The presence of nephritis and seizures each increased the risk of death in patients with SLE approximately 2-fold. Thrombocytopenia also increased the risk of SLE-related mortality, while leukopenia was protective.

To identify factors associated with interruptions in care from rheumatologists among patients with rheumatoid arthritis (RA).A person-time analysis was used to examine the association of medical insurance status, income, health status, treatment by a primary care physician, and presence of comorbid conditions with interruptions in rheumatology subspecialty care in a cohort of 161 patients with RA followed prospectively for up to 10 years. An interruption was defined as a 6-month period during which a patient was not treated by a rheumatologist. Each patient had at least one interruption.Interruptions in rheumatology care occurred more commonly during periods when patients reported no medical insurance coverage than when they had medical insurance coverage (relative risk, RR = 1.49; 95% confidence interval, CI = 1.05, 2.11). Interruptions in care were more common during intervals in which patients reported at least a 40% improvement in functional disability (RR = 1.30; 95% CI = 1.03, 1.63), but interruptions were not associated with either absolute or relative changes in pain or global arthritis status. Interruptions in rheumatology care also occurred more commonly during periods when patients reported seeing a primary care physician (RR = 2.07; 95% CI = 1.71, 2.50), and when they reported having a comorbid condition (RR = 1.37; 95% CI = 1.06, 1.77). Income was not associated with interruptions in care.Lack of medical insurance and short term improvements in functional disability are associated with interruptions in rheumatology care among patients with RA. Patients also appear to substitute primary care for care from rheumatologists. These associations suggest that potential strategies for enhancing continuity in rheumatology care might include the promotion of universal insurance coverage and the development of informational programs for patients.

To determine the extent to which mood in general, and depression in particular, may confound self-report measures of functional disability, pain, and global arthritis status among patients with rheumatoid arthritis (RA).Twenty-four patients with RA were prospectively examined every 2 weeks for up to 60 weeks. At each examination, self-report measures of functional disability, pain, and global arthritis status were assessed using the Health Assessment Questionnaire, and the clinical measures of swollen and tender joint counts, duration of morning stiffness, grip strength, 50' walk time, and Westergren sedimentation rate were recorded. In addition, patients completed a questionnaire derived from the Profile of Mood States-B (POMS-B), which assessed positive and negative moods, and the Center for Epidemiologic Studies Depression Scale (CES-D) at each examination. The degree to which mood or depression confounded the self-report measures of functional disability, pain, and global arthritis status was estimated using pooled time series regression models that examined the relationship between changes in either mood or depression and changes in each self-report measure over the course of the study, while controlling for the effects of the clinical measures of arthritis activity.Mood, as measured by the POMS-B scale, explained 2.0% or less of the variation in longitudinal changes in each of the self-report measures, after controlling for the effects of the clinical measures of arthritis activity. Depression, as measured by the CES-D, explained less than 2.0% of the variation in changes in functional disability, but explained 6.0 and 8.0% of the variation in changes in pain and global arthritis status, respectively.Depression may confound self-reports of pain and global arthritis status somewhat, but appears to have minimal influence on self-reported functional disability.

To determine the relative accuracy and sensitivity to change of 14 measures commonly used to assess arthritis activity in patients with rheumatoid arthritis (RA).Twenty-four patients with RA were prospectively examined every 2 weeks for up to 60 weeks. At each examination, arthritis activity was assessed using 5 physician determined measures (global assessment, swollen joint count, weighted swollen joint count, tender count, weighted tender joint count), 3 patient determined measures (global assessment, pain score, duration of morning stiffness), 3 functional measures (Health Assessment Questionnaire Disability Index, grip strength, 50' walk time), and 3 laboratory measures [Westergren erythrocyte sedimentation rate (ESR), hemoglobin, platelet count]. Accuracy was determined by the degree to which changes in each measure over time were related to changes in other measures (i.e., correlational validity). Sensitivity to change was measured using standardized response means.Over the course of the study, each patient had at least 6 measures change more than 50% from their baseline values. The most highly intercorrelated measures were the physician global assessment (range of partial correlations r = 0.4-0.7), patient global assessment and pain scores (r = 0.2-0.7), the Disability Index (r = 0.3-0.7), and ESR (r = 0.2-0.4). Physician and patient global assessments, pain scores, and the Disability Index were more sensitive to change than other measures, while laboratory measures were generally less sensitive to change.Based on the relative accuracy and sensitivity to change of these 14 clinical measures, the physician global assessment, a functional status questionnaire, and the patient global assessment or pain score should be the principal measures used to assess arthritis activity in patients with RA. Recognizing its limitations, the ESR could be included if a laboratory measure is needed.

This study examined the role of psychophysiological reactivity to general stressors measured before smoking cessation as a predictor of relapse in individuals who quit for a minimum of 12 hr and were then followed for a 12-month interval. The study group consisted of 132 (56.9%) female and 100 (43.1%) male participants in a formal smoking cessation program. The reactivity measures were taken while the Ss were still smoking. Heart rate and blood pressure measurements were taken while Ss were resting, performing mental arithmetic, and delivering a speech and after Ss had been standing for 2 min. In the sample as a whole and for women, a higher level of systolic blood pressure reactivity to the cognitive challenge was associated with a shorter time to relapse (p.05). In men, greater systolic blood pressure decline to standing was significantly associated with a shorter time to relapse (p.05).

To determine whether patients with rheumatoid arthritis and their physicians make appropriate decisions regarding referral to rheumatologists and the need for continuing rheumatology care, we examined the relationship between the progression of functional disability in these patients and their use of rheumatology subspecialty care over time.A cohort of 282 patients with rheumatoid arthritis was followed prospectively for up to 10 years. Participants were categorized into three subgroups based on the pattern of care received from rheumatologists over the study period: patients who were never treated by a rheumatologist; patients treated by a rheumatologist only intermittently; and patients treated by a rheumatologist at least once during each 6-month study period. The outcome was the rate of progression of functional disability, measured using the Health Assessment Questionnaire Disability Index.Among the 52 patients who had not been referred to a rheumatologist, 30 (58%) had rates of progression of functional disability that were stable or improving over time (rate0.01 Disability Index units per year), while 22 (42%) had rates that were worsening (rateor = 0.01 Disability Index units per year). Among patients treated by rheumatologists, the average rate of progression was substantially lower among the 69 patients who were treated regularly by a rheumatologist than among 161 patients treated by rheumatologists intermittently (0.008 Disability Index units per year vs 0.020 Disability Index units per year). This difference was associated with more intensive use of second-line antirheumatic medications, and more frequent joint surgeries, among patients treated by rheumatologists on a regular basis.Most patients with rheumatoid arthritis in this community cohort were treated by a rheumatologist, but 42% of those not referred had progressively increasing functional disability. Among patients treated by rheumatologists, those who had continuing care from rheumatologists experienced lower rates of progression of functional disability than those who had only intermittent care. These results suggest that use of rheumatology subspecialty care is associated with better health outcomes in rheumatoid arthritis.

Pain and functional disability are 2 major factors influencing the health status of patients with rheumatoid arthritis (RA). To determine the relative importance ascribed to these factors by patients, we examined the relationship of levels of both pain and functional disability to self-reported global arthritis status in patients with RA.Pain, disability and global arthritis status were measured prospectively in 305 patients with RA using the Health Assessment Questionnaire, which was completed by patients every 6 months for up to 9.5 years. The relative importance of pain and functional disability was determined by the relative magnitude of their association with global arthritis status, as estimated by pooled time series regression analysis.At study entry, median levels of pain, functional disability, and global arthritis status for the cohort were 1.1 (possible range: 0-3.0), 1.25 (possible range: 0-3.0), and 35 (possible range: 0-100), respectively, indicating moderate arthritis severity. Both pain (p0.0001) and functional disability (p0.0001) were significantly related to changes in global arthritis status over time. The standardized regression coefficient of pain was 1.2 times larger than that of disability, indicating that patients' ratings of their arthritis status was only slightly more heavily weighted by changes in pain than by changes in functional disability. Pain was a more important feature than disability among nonwhites (pain/disability standardized coefficient ratio = 2.7), while disability appeared to be more important for males (ratio = 0.8). The duration of RA did not influence the relative importance of pain and disability.Pain and functional disability were of similar importance to this group of patients with RA, and the relative importance of pain and disability did not vary with the duration of RA.

Many previous studies of the influence of sociodemographic and clinical factors on the development of renal failure in patients with lupus nephritis have been based on selected subgroups of patients and have yielded conflicting results. We sought to determine the prognostic importance of patient demographic characteristics (age, gender, race, and socioeconomic status), smoking status, and hypertension in the development of end-stage renal disease (ESRD) among patients with lupus nephritis.This retrospective cohort study followed an inception cohort of 160 adults with lupus nephritis. The outcome measure was the development of ESRD, defined as the institution of maintenance dialysis or measurement of a creatinine clearance of 10 mL/min or less. Life-table analysis was used to determine differences between patient subgroups in the time to development of ESRD.End-stage renal disease developed in 41 (26%) of 160 patients followed up for a median of 6.4 years. Hypertension and smoking status at the onset of nephritis were strongly associated with differences in the time to development of ESRD. The median time to ESRD among patients with moderate to severe hypertension (diastolic blood pressure, greater than or equal to 105 mm Hg) was 7 months, among patients with mild hypertension (diastolic blood pressure, 90 to 104 mm Hg) it was 146 months, and among normotensive patients it was greater than 273 months. The median time to ESRD among smokers was 145 months and among nonsmokers it was greater than 273 months. These effects persisted in multivariable analyses adjusting for differences among patients in age, gender, socioeconomic status, renal histology, and immunosuppressive treatment. The independent effects of hypertension and smoking resulted in shorter times to renal failure among patients who were both hypertensive and smoking, compared with nonsmoking hypertensive patients. The development of ESRD did not differ among patient demographic subgroups.Patient demographic characteristics had no detectable impact on the rate of progression to ESRD in this cohort. Hypertension and smoking appear to be important, potentially modifiable, factors influencing the prognosis of patients with lupus nephritis.

Acute psychotic manifestations in systemic lupus erythematosus (SLE) have been considered usually to occur early in the course of illness, although these findings are primarily based on studies with few patients and limited lengths of observation. To further investigate the chronology of acute psychiatric disturbances in SLE, the time course of these episodes was examined in 36 patients over a median duration of observation of 72 months. Twenty-two of 36 (61.1%) initial psychiatric episodes occurred within the first year of diagnosis of SLE, although several patients experienced the initial onset of psychiatric manifestations several years after the onset of SLE. Recurrent episodes occurred in 10 of 36 patients at a median of 8 months after the initial episode. Although tending to occur early in SLE, primary acute psychiatric events may first occur in patients with long durations of illness, and the time of onset of these episodes does not appear helpful in their differential diagnosis.

To determine whether factors other than disease activity influence immunoglobulin levels in patients with systemic lupus erythematosus (SLE), the effect of age, sex, race, and duration of disease on serum IgG and IgM levels in 170 patients with SLE were investigated. Serum IgM and IgG levels did not differ between men and women, while IgM levels were higher in whites. Serum IgG levels did not vary with age or duration of SLE. In contrast, serum IgM levels were negatively correlated with both age (r = -0.236; p = 0.002) and duration of SLE (r = 0.248; p = 0.001), and demonstrated a U-shaped age relationship, being higher in children and older patients. These patterns of immunoglobulin expression in patients with SLE contrast with those exhibited in populations of healthy individuals, suggesting that the immunoregulatory disturbances of SLE predominate over the normal mechanisms regulating levels of IgM and IgG.

Levels of soluble interleukin 2 receptors (IL-2R) have been found to be elevated in the serum of patients with systemic lupus erythematosus (SLE) and are considered an indication of immune system activation in this disease. To assess the relationship between soluble IL-2R levels and other serological markers, we compared levels of soluble IL-2R and anti-double stranded DNA (anti-dsDNA) antibodies in SLE sera. In a cross sectional study of 34 patients with SLE, soluble IL-2R levels were elevated compared with healthy individuals (1126 U/ml vs 235 U/ml, p less than 0.0001), and a significant correlation between levels of soluble IL-2R and anti-dsDNA antibodies was present (r = 0.543, p = 0.0009). In a longitudinal study of 10 additional patients, the time courses of soluble IL-2R levels and anti-dsDNA antibody measurements were similar in 3 patients. In 7 patients, substantial differences in the levels of soluble IL-2R and anti-dsDNA antibodies over time were observed, including marked changes in anti-dsDNA antibody levels that were accompanied by only minor changes in soluble IL-2R levels, and soluble IL-2R measurements that were persistently elevated despite generally low anti-dsDNA antibody levels. Our results indicate that soluble IL-2R levels may not always parallel other serological markers of SLE, suggesting measurement of different facets of immune system activation by various assays.

The influence of age on the prevalence of individual clinical manifestations of systemic lupus erythematosus (SLE) has not been adequately distinguished from racial or gender influences. Therefore, we examined variations in the clinical manifestations of SLE with age in a group of 361 patients. Multivariate regression techniques, including logistic regression and analysis of covariance, were used to identify clinical features associated with age, while controlling for important confounding factors, including race, gender, duration of followup, and treatment effects. Lymphopenia was found more frequently with increasing age, while malar rash, seizures, false-positive VDRL, thrombocytopenia (in whites), proteinuria (0.5-3.5 g/day), elevated antidouble stranded DNA antibodies, and hypocomplementemia were found less frequently. No age relationship was found for the prevalence of 16 of 24 clinical features examined, including the important disease manifestations of arthritis, serositis, psychosis, nephrotic-range proteinuria, renal failure, autoimmune hemolytic anemia, and leukopenia. The use of regression analysis allows the recognition of similarities and differences in cumulative clinical features of SLE due to age in isolation from the effects of other demographic factors.

The marked gender influence on the occurrence of systemic lupus erythematosus (SLE) indicates that genetic and hormonal factors may be important in the etiology of this illness. However, few differences in clinical manifestations between males and females have been reported. To further investigate gender differences in SLE, the prevalence of 23 clinical manifestations of SLE were compared in a cohort of 62 men and 299 women. After adjusting for differences in age, race, and duration of followup, men were found to more commonly have seizures (odds ratio = 1.65; 95% confidence interval = 1.09, 2.49), and showed a trend to progress to renal failure more often (odds ratio = 1.40; 95% confidence interval = 0.96, 2.03) than women. Gender differences were not evident for the remaining 21 clinical features. The clinical similarity between men and women with SLE represents a circumstance in which the use of clinically defined patient subsets does not appear to facilitate the investigation of potential pathogenetic or etiologic factors.

In a historical cohort study, acute renal failure developed in 16.5% of 157 patients with rhabdomyolysis over a two-year study period. Underlying clinical, laboratory, and causative factors associated with the development of acute renal failure were examined. Factors predictive of renal failure in this setting, determined by multiple logistic regression analysis, included the degree of serum creatine kinase, serum potassium, and serum phosphorus level elevation; the degree of depression of serum albumin level; and the presence of dehydration at presentation or sepsis as the underlying cause. The predictive model that was developed correctly classified 93% of subjects and was statistically validated.

Relationships to CHD risk factors of work environment variables, of the Type A behavior pattern, and of their interaction were studied in 384 male salaried workers. Except for an association between physical comfort in the work environment and systolic blood pressure, no significant independent relationships were found between any of the work environment variables or the Type A behavior pattern and coronary heart disease (CHD) risk factors. Type A workers who described their work environments as encouraging autonomy or being high in peer cohesion had lower blood pressures than those who did not. The reverse was found for Type Bs. Type Bs who described their environments as low in physical comfort had higher systolic blood pressure than those who did not. These significant interactions are discussed from the perspective of person-environment fit. Future directions for research and implications for CHD risk reduction are presented.

Cardiovascular (CV) responses to laboratory stressors were measured in 12 pairs of identical and 21 pairs of fraternal adult male twins. For this study, blood pressure and heart rate were measured during a mental arithmetic task and the Cold Pressor Test. The analyses of cardiovascular responses to these stressors were designed to test for the presence of a genetic component in cardiovascular reactivity in an adult sample of twins aged 54-64 years. The results suggest that certain measures of cardiovascular reactivity to laboratory stressors may be heritable for both physical and psychological stressors. The possible role of this genetic component in the etiology and course of coronary heart disease is discussed.