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Objective Estimates of minimal clinically important improvements (MCIIs) are larger among patients with higher values at baseline, suggesting that these patients require larger changes to appreciate improvements. We examined if baseline dependency of MCIIs was associated with specific patients across three measures, or was owing to floor and ceiling effects. Study Design and Setting We prospectively examined 250 outpatients with active rheumatoid arthritis (RA). We used an anchor-based approach to estimate MCIIs for three measures of RA activity (patient global assessment, swollen joint count, and walking time). We examined if the same patients constituted the baseline subgroups with high MCIIs across measures. Results The MCIIs were greater for those with higher baseline values of all three measures. At the ceiling, there was little opportunity to improve, and judgments were unrelated to measured changes. At midrange, improvements were balanced by worsenings, including some judged as improvements. At the floor, improvements were not similarly balanced. Patients in subgroups with high MCII for patient global assessment were not also predominantly in subgroups with high MCII for the swollen joint count or walking time, and vice versa. Conclusion Variation in MCII by baseline values is because of floor and ceiling effects rather than expectations of particular patients.

Ankylosing Spondylitis, an inflammatory disease affecting mainly the spine, can be characterized by abnormal bone formation (syndesmophytes) along the margins of the intervertebral disk. Monitoring syndesmophytes evolution is challenging because of their slow growth rate, a problem compounded by the use of radiography and qualitative rating systems. To improve sensitivity to change, we designed a computer algorithm that fully quantifies syndesmophyte volume using the 3D imaging capabilities of computed tomography. The reliability of the algorithm was assessed by comparing the results obtained from 2 scans performed on the same day in 9 patients. A longitudinal study on 20 patients suggests that the method will benefit longitudinal clinical studies of syndesmophyte development and growth. After one year, the 3D algorithm showed an increase in syndesmophyte volume in 75 % of patients, while radiography showed an increase in only 15 % of patients.

Identifying disparities in health among persons of different ethnic or socioeconomic groups, investigating the causes of these disparities, and implementing reme- dies for them have become priorities in national health care research. Among rheumatic diseases, systemic lu- pus erythematosus (SLE) shows marked health dispari- ties that have been the subject of many investigations. Survival rates of patients with SLE have been reported to vary by socioeconomic status (SES) (1-3) and, in some studies, to differ among ethnic groups (4,5). Mor- bidity, as assessed by measures of lupus activity (6,7), permanent organ damage (8-12), functional ability (11), and health status (10,13), has also been found to vary by SES in some, but not all (14,15), studies. In this issue of Arthritis & Rheumatism, Alarcon and colleagues add to this growing literature by report- ing their observations on the development of permanent organ damage in patients enrolled in the LUMINA (lupus in minority populations, nature versus nurture) cohort (16). Over a mean of 5 years, scores on the Systemic Lupus International Collaborating Clinics Damage Index (SDI) increased by 0.4 points among Caucasian and African American patients, but increased by 1 point among Hispanic patients. In multivariate analyses, the most important predictors of an increase in the SDI score were older age and greater lupus activity at study entry, but both Hispanic ethnicity and one measure of SES (household income under the federal poverty level) also predicted greater increases in the SDI score over 5 years. These findings indicate that ethnicity and SES, or factors associated with them, influence the development of organ damage in patients with SLE. Health disparities among persons of different socioeconomic groups are not the result of SES itself, but rather, are due to psychosocial factors that vary with SES and may more directly influence health (17). Ethnic differences in health outcomes also probably have their origin in psychosocial differences, but a contribution from biologic differences must also be considered. Psy- chosocial factors that vary by SES or ethnicity and that might influence health outcomes include health habits, environmental stressors, coping resources, social sup- port, compliance, and access to care, among others. SES and ethnicity are surrogate measures for these psycho- social processes.

Cohort studies of survival in systemic lupus erythematosus (SLE) often have been limited by methodologic problems. In studies of inception cohorts of patients followed since 1980, survival at 5 years has exceeded 90%. These estimates are generally higher than survival estimates from earlier studies, suggesting that short-term survival in SLE has improved. There is less evidence to support major improvements over time in survival after 10 years or more of SLE. Infections, atherosclerotic disease, and active systemic lupus erythematosus or organ damage caused by SLE are the main causes of death in patients with SLE, but the proportion of early deaths caused by active SLE has decreased over time.

The Medicare Prescription Drug Improvement and Modernization Act of 2003 (MMA) represented the most important change in the way the federal government supports medical care for the elderly since the inception of Medicare in 1965. Among its most significant provisions was the establishment for the first time of a benefit program, known as Part D, for outpatient prescription drugs. Despite its deductibles, doughnut holes, and dizzying differences among formularies, Part D has been lauded for redressing a major omission in health insurance coverage for the elderly (1, 2). As of January 1, 2006, when Part D was implemented, Medicare patients with rheumatoid arthritis (RA) could enroll in plans to cover part of the costs of outpatient medications, including the self-injectable biologic agents etanercept and adalimumab. Prior to January 1, 2006, Medicare patients had two primary means to access biologics: buy supplemental private insurance that would cover part of the cost of self-injectable biologic agents, or receive infliximab at their physician's office or hospital outpatient department, with the costs largely paid by Medicare. Medicare Part B traditionally has covered the medication and administration costs of treatments given by infusion, including chemotherapy, and with the advent of biologic agents, medications such as infliximab (3). Prior to 2004, Medicare reimbursements were based on the average wholesale price of the drug (the list price), which was often substantially higher than the costs to physicians and hospitals of acquiring the drug. Audits by the US Government Accountability Office reported that differences between the average wholesale price and the acquisition costs (i.e., the spread) for infused medications in 2001 were commonly between 15% and 30%, a difference that the physician or hospital could keep (4). The spread for infliximab was 32% in 1999 and 2001 (5). In many ways, this was a win-win-win situation. Patients had access to a valuably effective but expensive medication, which for many would not otherwise be available; physicians and hospitals could provide needed treatment and increase their incomes; and companies could sell more without the worry of price controls. Surveys between 1998 and 2003 confirmed that Medicare patients preferentially used infliximab (6, 7). The losers in this scenario were US taxpayers and businesses who, through Medicare, were paying the bill. Recognizing that each actor was responding to incentives that it had put in place, the federal government sought to reduce these incentives to help control Medicare spending and exert better stewardship of the public's money. Provisions were included in the MMA that from 2004 to 2006 sequentially changed the standard by which physicians and hospitals were reimbursed for infusion treatments. These changes had the effect of reducing the spread to 6–8%, which was a lower mark-up, but a mark-up nonetheless (8). Although the MMA also increased reimbursements for drug administration, there were concerns, primarily among hematologists and oncologists, that reductions in payments would cause practices to close or to stop providing infusion treatments, that hospital outpatient departments would be overwhelmed with patients not able to receive treatment at physician offices, and that access to treatments would be reduced (9). The American College of Rheumatology also presented these concerns in Congressional hearings (10). Limited evidence to date suggests that these potential problems have largely not been realized among patients with cancer (11, 12). However, the impact of the MMA on the use of biologic agents among patients with RA has not been explored. Four key questions arise to determine if the MMA has had its intended, or any unintended consequences, and if it has been a wise policy. Has the MMA reduced Medicare spending on infliximab? Has the MMA made it easier for patients with RA to access biologic agents or has it limited access to biologics? Has the MMA induced a shift in the type of biologic agent prescribed toward those that are more cost-effective? Has the MMA promoted optimal care of patients with RA? In this issue of Arthritis Care & Research, Doshi et al report the first analysis of changes in the use of, and expenditures for, infliximab among Medicare beneficiaries with RA before and after the MMA went into effect (13). The authors abstracted data on a 5% random sample of Medicare beneficiaries over the transition period of 2002–2006, and examined trends in the number of infliximab users, the number of units of infliximab dispensed (1 unit of infliximab in Medicare's accounting system = 10 mg), and total payments for infliximab, including and excluding the costs of drug administration. Doshi et al reported that the number of patients who were treated with infliximab increased sharply from 2002 to 2003, before the MMA took effect, and total payments for infliximab increased by 39%. The number of patients treated with infliximab increased at a much slower pace in subsequent years, and total payments leveled off in 2005–2006. Rather than decreasing, total payments remained stable because the decreases in payments for the medication imposed by the MMA were largely offset by higher payments for drug administration and increases in dose among those receiving infliximab. Introduction of the Part D outpatient prescription drug benefit in 2006 did not have a demonstrable effect on the overall use of infliximab or total payments. In a longitudinal analysis, the proportions of patients who discontinued infliximab in 2006 or who started infliximab in 2006 were similar to the proportions in previous years, suggesting that the new benefits for coverage of self-injectable biologics in Part D did not induce many patients to switch treatments or alter their initial choice of tumor necrosis factor α (TNFα) inhibitor. These results convincingly demonstrate that the MMA was successful in limiting the rise in Medicare spending on infliximab. The analysis by quarter-year demonstrates that the reductions in payment were implemented as designed. If payments had remained at the 2002 rate, total payments for infliximab by Medicare in 2006 would have been more than $708 million, rather than the $537 million that was paid. Although this represents a 31% decrease from projected expenditures, total payments still increased over time. Payments per patient with RA also increased over time, but payments per patient treated with infliximab remained stable ($13,218 in 2002 versus $13,543 in 2006), despite an increase in the average dose of infliximab from 338 mg/infusion to 401 mg/infusion. Although critics might argue that the MMA did not succeed in reducing Medicare spending on infliximab, it is clear that it held spending in check. Has the MMA limited or facilitated access to biologics? Although the analysis of Doshi et al indicates that the number of Medicare beneficiaries treated with infliximab increased from 2002 to 2006, the rate of increase slowed dramatically after 2003. Was this a consequence of changes in reimbursement stipulated by the MMA, or was this a natural settling in the rate of use of a new medication after introduction to the market? Although the data cannot answer this question definitively, the circumstantial evidence suggests natural causes. The prevalence represents the balance between patients entering treatment and leaving treatment (through either discontinuation or death). Patients who died were excluded from these analyses, so mortality was not responsible for the slowdown in growth of infliximab use, and the longitudinal analyses suggested that large numbers of patients were not discontinuing infliximab. Although the incentives might have been reduced by the MMA, infliximab remained a win-win situation for patients and physicians, so there is little reason to suspect that the MMA would have directly limited access to infliximab for patients with RA who needed it. Unfortunately, data on the use of etanercept and adalimumab by Medicare beneficiaries under Part D were not available, so this analysis could not determine if the expanded benefits in 2006 increased the access of patients with RA to these biologic agents. Without data on the use of other TNFα inhibitors, and without data after 2006, the analysis of Doshi and colleagues cannot address the important question of whether the MMA has induced a shift in the type of biologic agent that is prescribed for patients with RA. Several studies have concluded that infliximab is the least cost-effective TNFα inhibitor (14, 15). If the MMA resulted in a change toward the use of more cost-effective medications, this would further enhance Medicare's protection of the public good by emphasizing value for money. However, despite coverage under Part D, the self-injectable biologic agents have high out-of-pocket expenses, and financial incentives for many patients still favor infliximab (16). This leaves open the question of whether further changes in reimbursement policy guided by cost-effectiveness will be forthcoming. Ultimately, the most important question regarding any policy change is whether it improves patients' lives. To know if the MMA helped to promote optimal care for patients with RA will require not only data on access to biologic agents but information on whether access to other antirheumatic medications increased, whether comorbid conditions were better controlled, and whether health outcomes improved.

Accurate measurement of syndesmophyte development and growth in ankylosing spondylitis (AS) is needed for studies of biomarkers and of treatments to slow spinal fusion. We tested the longitudinal validity and sensitivity to change of quantitative measurement of syndesmophytes using CT.We performed lumbar spine CT scans on 33 patients with AS at baseline, 1 year and 2 years. Volumes and heights of syndesmophytes were computed in four intervertebral disk spaces. We compared the computed changes to a physician's ratings of change based on CT scan inspection. Sensitivity to change of the computed measures was compared with that of the modified Stoke AS Spinal Score (radiography) and a scoring method based on MRI.At years 1 and 2, respectively 24 (73%) and 26 (79%) patients had syndesmophyte volume increases by CT. At years 1 and 2, the mean (SD) computed volume increases per patient were, respectively 87 (186) and 201 (366) mm(3). Computed volume changes were strongly associated with the physician's visual ratings of change (p0.0002 and p0.0001 for changes at years 1 and 2, respectively). The sensitivity to change over 1 year was higher for the CT volume measure (1.84) and the CT height measure (1.22) than either the MRI measure (0.50) or radiography (0.29).CT-based syndesmophytes measurements had very good longitudinal validity and better sensitivity to change than radiography or MRI. This method shows promise for longitudinal clinical studies of syndesmophyte development and growth.

Purpose. Time perspective, a psychological construct denoting subjective orientation to either present or future concerns, has been inconsistently associated with healthy behaviors in adults. We hypothesized that associations would be stronger in young adults, who are first developing independent attitudes, than in older adults. Design. Cross-sectional survey. Setting. The study was conducted in three cities in the Mid-Atlantic region. Subjects. Subjects were 790 patrons of barber and beauty shops. Measures. Measures used were the Zimbardo Time Perspective Inventory future, present-fatalistic, and present-hedonistic subscales and current smoking, days per week of recreational exercise, and height and weight, by self-report. Analysis. We tested if associations between time perspective and exercise, obesity, and current smoking differed by age group (18–24 years, 25–34 years, and 35 years and older) using analysis of variance and logistic regression. Results. Higher future time perspective scores, indicating greater focus on future events, was associated with more frequent exercise, whereas higher present-fatalistic time perspective scores, indicating more hopelessness, was associated with less frequent exercise in 18- to 24-year-olds, but not in older individuals. Lower future time perspective scores, and higher present-hedonistic time perspective scores, indicating interest in pleasure-seeking, were also associated with obesity only in 18- to 24-year-olds. Current smoking was not related to time perspective in any age group. Conclusion. Time perspective has age-specific associations with exercise and obesity, suggesting stages when time perspective may influence health behavior decision making.

Studies of the costs associated with rheumatic diseases, the referral of patients to rheumatology subspecialty care, rheumatology practice patterns, and the relation between medical care and patient outcomes are reviewed. Direct medical costs in patients with rheumatoid arthritis (RA) are higher among those with more functional disability. Direct medical costs in patients with systemic lupus erythematosus (SLE) did not differ among Canadian, American, and British patients, despite substantial differences in the mechanisms by which medical care is financed and delivered in these three countries. The diagnostic accuracy of rheumatic complaints by primary care physicians may be low, and concomitant psychiatric disorders may not be uncommon among patients referred to rheumatologists. Most patient visits to rheumatologists involve patients with rheumatic diseases or musculoskeletal complaints, and few visits involve primary care. Fewer than half of elderly patients with RA or SLE are seen by a rheumatologist in a given year; access is particularly limited among black women. Early access to rheumatology subspecialty care may be associated with improved health status in patients with RA, and mortality among patients with SLE varies with the experience a hospital has in treating patients with SLE.

The prevalence rate and disease manifestations of systemic lupus erythematosus (SLE) have been noted to vary among different ethnic groups. There has been no description in the English literature of SLE in the Vietnamese population. This is the first report, which details the clinical and laboratory features as well as an estimation of the prevalence of SLE in patients with a Vietnamese ancestry living in the United States. We performed a retrospective chart review of clinical and laboratory features of patients of Vietnamese descent with SLE. The case finding was performed by a review of the rheumatology clinic records at two large teaching hospitals in Santa Clara County searching for patients with SLE with a Vietnamese surname. In addition, we recruited patients by contacting all of the rheumatologists practicing in the county. Twenty-three patients of Vietnamese descent were identified with SLE in Santa Clara County. The estimated prevalence of SLE in the patients of Vietnamese descent was 42 cases per 100 000 persons. Eighty-seven per cent of the cases were born in Vietnam. The clinical and laboratory features of SLE were similar to prior published reviews except for a relatively high prevalence of anti-RNP antibody (54%). The patients with anti-RNP antibody exhibited features of overlap syndrome. There was a high rate of exposure to tuberculosis (TB). Fifty-eight per cent of patients had a positive purified protein derivative (PPD) skin test and 27% of patients had a history of clinical TB. Forty-four per cent of patients had evidence of hepatitis B exposure. The prevalence of SLE in the Vietnamese population in Santa Clara County is similar to that of other Asian populations. There was a relatively high prevalence of anti-RNP antibody in our patient group which was associated with overlap features. As expected in an immigrant population from Southeast Asia, there was a high rate of prior exposure to tuberculosis and hepatitis B. Clinicians should diligently screen for these infections and appropriately prophylaxe and treat patients.

Objective To identify aspects of health-related quality of life that are most commonly affected in patients with ankylosing spondylitis (AS). Methods 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). Results 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. Conclusions 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.

Objective. 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. Methods. 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 of >50 urgent or emergency SLE admissions per year) and those in which there was less experience. Results. 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. Conclusion. 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.

Objective 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. Methods 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. Results 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 1.35, 95% CI 0.98–1.85). In-hospital mortality was 45.7%, and was unrelated to hospital characteristics. Conclusion 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.

Objective. 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). Methods. 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. Results. 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. Conclusion. 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.

Objective To determine rates of morbidity due to cardiovascular and cerebrovascular diseases among women with systemic lupus erythematosus (SLE). Methods I used the California Hospital Discharge Database, which contains information on all discharges from acute care hospitals in California, to identify women with SLE who had been hospitalized for treatment of either acute myocardial infarction (AMI), congestive heart failure (CHF), or cerebrovascular accident (CVA) from 1991 to 1994. I compared the proportions of hospitalizations for each cause among women with SLE with those in a group of women without SLE, for 3 age strata (18–44 years, 45–64 years, and ≥65 years). Results Compared with young women without SLE, young women with SLE were 2.27 times more likely to be hospitalized because of AMI (95% confidence interval [95% CI] 1.08–3.46), 3.80 times more likely to be hospitalized because of CHF (95% CI 2.41–5.19), and 2.05 times more likely to be hospitalized because of CVA (95% CI 1.17–2.93). Among middle-aged women with SLE, the frequencies of hospitalization for AMI and CVA did not differ from those of the comparison group, but the risk of hospitalization for CHF was higher (odds ratio [OR] 1.39, 95% CI 1.05–1.73). Among elderly women with SLE, the risk of hospitalization for AMI was significantly lower (OR 0.70, 95% CI 0.51–0.89), the risk of hospitalization for CHF was higher (OR 1.25, 95% CI 1.01–1.49), and the risk of hospitalization for CVA was not significantly different from those in the comparison group. Conclusion Young women with SLE are at substantially increased risk of AMI, CHF, and CVA. The relative odds of these conditions decrease with age among women with SLE.

Cardiovascular disease (CVD) is the major cause of death of patients with rheumatoid arthritis (RA) (1). In this issue of Arthritis Care & Research, Avina-Zubieta and colleagues examine whether the risk of CVD mortality is increased in patients with RA, compared with that in age-and sex-matched groups in the general population (2). In a meta-analysis of published English-language studies, the authors found that the risk of CVD mortality was, on average, 50% higher among patients with RA. When component causes of death were examined, risks of death from ischemic heart disease and cerebrovascular disease were elevated to similar degrees. The authors provided not only a pooled summary estimate of risk, but in a thorough analysis examined how the estimates varied among the primary studies. Risks were lower, and rates of CVD mortality were closer to those of the general population, in studies rated to be of higher methodologic quality, as indicated by the study of community-based and inception cohorts (in contrast to clinic-based or prevalence cohorts), use of validated case definitions and confirmation of the cause of death in medical records, control for CVD risk factors, and having few patients lost to followup. In these studies, the risk of CVD mortality was estimated to be 21% higher among patients with RA. As a meta-analysis, the study by Avina-Zubieta et al succeeds in its goal of quantitatively summarizing the results of studies of CVD mortality in RA. The literature search was carefully performed and the statistical analysis was state-of-the-science. The authors examined their results for publication bias and for potential impact of outliers. However, the authors were sensibly cautious in their consideration that the 50% higher risk of CVD mortality among patients with RA was the true estimate, given the nature of the primary studies included in the meta-analysis. By contrasting results across primary studies, their article provides insight into factors that affect estimates of the relative risk of CVD mortality in RA that single studies cannot provide. In particular, 3 issues of timing deserve consideration, because they affect the interpretation of the results. These 3 issues are the duration of RA among patients at the time of their entry into the primary study, the timing of onset of RA relative to CVD death, and the time of study entry relative to historical time. The duration of RA at the time patients enter a study of outcomes can have an important influence on the results. Studies of inception cohorts assemble and follow patients from a uniform and early point in the course of their RA, e.g., prospectively enrolling all patients newly diagnosed in a particular clinic for 1 year. By doing so, inception cohorts are likely to include patients with mild RA as well as those with more severe RA. In contrast, studies of prevalence cohorts assemble a cross-section of patients, regardless of RA duration, and follow them over time. Because less severely ill patients, and those who are in remission, tend to migrate out of clinics or are seen less frequently, prevalence cohorts typically have a higher number of patients with more severe RA. If the outcome occurs more often in patients with severe disease, as is the case for mortality in RA (3– 8), risks will be falsely inflated in studies of prevalence cohorts. Because the spectrum of disease severity tends to be less skewed in inception cohorts, studies using these cohorts are considered to provide less biased estimates of mortality risk. In this meta-analysis, the risk of CVD mortality in patients with RA compared with the general population was substantially lower in studies of inception cohorts than in studies of prevalence cohorts (standardized mortality ratios of 1.19 and 1.56, respectively), and the risk of CVD mortality for inception cohorts was not significantly different from the null. This difference may be due in part to the inclusion of patients with milder RA in these studies. The study of inception cohorts versus prevalence cohorts also relates to the second issue of how timing may influence the interpretation of these results, that of the relationship between the onset of RA and the time of CVD death. Studies of inception cohorts are able to capture deaths that occur soon after the onset of disease, and guard against underestimating mortality risks in conditions that are rapidly fatal. In these circumstances, prevalence cohorts represent survivors, and may convey falsely low mortality rates. Conversely, if any increase in the risk of mortality associated with a disease is typically delayed years or decades after its onset, studies of inception cohorts may underestimate risks unless the followup period is sufficiently long. Unfortunately, the hazard rate of death among patients with early, mid-duration, and late RA, relative to the general population, has not been reported, so the degree to which short-term studies of inception cohorts may underestimate the risk of mortality in RA is not precisely known. Studies have suggested that overall mortality risk begins to increase only after approximately 7 years of RA (9,10). However, inception cohort studies with followup periods of 10 to 14 years have reported risks of overall mortality that were 28 – 84% higher than expected, and were therefore of sufficient length to be able to detect increased risks of this magnitude (10 –13). Inception cohort studies of CVD mortality in this meta-analysis had median durations of followup that ranged from 6.9 to 25 years, suggesting that they might have been long enough to capture any increased risk. It is unknown whether the pooled standardized mortality ratio estimate of 1.19 would increase with the inclusion of studies with longer followup. CVD mortality may occur earlier in the course of RA than other causes of death, so inception cohorts may be less susceptible to this timing issue in studies of CVD mortality than in studies of overall mortality (14). The third issue of timing is the relationship of these studies to historical time. Avina-Zubieta et al compared results among studies that enrolled patients before or after 1987, using this date to distinguish studies that used different classification criteria for RA. No difference in standardized mortality ratios was found between early and more recent studies. Perhaps more important than distinguishing studies by classification criteria, the similarity in risks between early and more recent studies may seem to suggest that changes in RA treatment strategies over time have not resulted in improvements in CVD mortality. Plotting the standardized mortality ratios by calendar year of enrollment also indicated no temporal trend (Figure 1). Differences among studies in patient characteristics and designs may have masked changes over time (15,16). It may also be that CVD mortality is influenced by too many factors other than RA activity or severity to expect to see a decrease in rates with more aggressive antirheumatic therapy, although studies suggest, some more convincingly than others, that treatment with methotrexate, other conventional disease-modifying medications, and biologic agents is associated with fewer CVD events and lower CVD mortality in patients with RA (17–21). The more recent cohorts included in this meta-analysis may not have had long enough exposure to more aggressive antirheumatic treatment to experience a difference in CVD mortality, or too few patients in these cohorts may have received aggressive treatment (14). Because of these factors, the lack of temporal trend in CVD mortality should not be interpreted as a failure of treatment effectiveness. To examine this question, studies should report the prevalence and types of antirheumatic treatment, ideally as person-years or percentage of time on treatment, whenever possible. Figure 1 Standardized mortality ratio (SMR) for cardiovascular disease mortality in patients with rheumatoid arthritis, compared with the general population in individual studies, by calendar year of the midpoint of the enrollment period. The risk of CVD mortality is most certainly higher in patients with RA than in the general population, and attention to CVD risk factor modification and educating patients about this risk is critically important (1). However, these issues of timing suggest that the true risk may be lower than the 50% increase estimated in this analysis.

Tumour necrosis factor (TNF)-α is thought to play a central role in promoting and perpetuating inflammation in sarcoidosis, and treatment with TNF-α inhibitors has been reported to be successful.1–3 We present a patient with quiescent sarcoidosis who relapsed shortly after beginning treatment with a TNF-α inhibitor for an unrelated medical condition. A 35-year-old woman with a history of sarcoidosis, in remission while on no treatment, and ankylosing spondylitis experienced a severe flare of inflammatory back pain that was not responsive to non-steroidal anti-inflammatory drugs. Treatment with etanercept 50 mg subcutaneously weekly was begun with marked symptomatic improvement in her back pain. Three weeks after starting etanercept, she developed dry cough, exertional dyspnoea, blurred vision …

Objective Several laboratory tests can be used to monitor disease activity in patients with rheumatic diseases. We sought to learn how rheumatologists use evaluative laboratory tests in the care of patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Methods We surveyed United States rheumatologists by mailed questionnaire. Of the 976 rheumatologists who received the questionnaire, 575 responded, for a response rate of 59%. Results Eighty-six percent of the respondents reported using either the erythrocyte sedimentation rate (ESR) or C-reactive protein level to monitor patients with RA, 92% used either the anti-DNA antibody level or complement C3 level to monitor patients with SLE, and 95% used either the ESR or ANCA levels to monitor patients with ANCA-associated vasculitis. The frequency of testing was distributed over a broad range, but testing was common. Testing on 50% of the visits or more was reported by 52% of respondents for RA, 59% of respondents for SLE, and 64% of respondents for ANCA-associated vasculitis. Between 7% and 11% of respondents reported testing patients on every visit, regardless of clinical disease activity. The majority of respondents reported not altering the treatment of clinically stable patients based on these test results. Conclusion Evaluative laboratory testing is common and is rarely used as an independent guide for treatment.

A number of tests are available for diagnosis and follow-up evaluation of systemic rheumatic diseases. How accurate are they and when should they be used? Dr Ward discusses the specificity, sensitivity, and predictive values of various tests and explains which are most helpful for specific situations.

Professors Baker and Krueger ignore some costs associated with workers' compensation. Because of these costs, the contention that physicians willfully exploit the workers' compensation system for their own gain is questioned.

Objective The human major histocompatibility complex class I chain-related gene A ( MICA ) controls the immune process by balancing activities of natural killer cells, γδ T cells and αβ CD8 T cells, and immunosuppressive CD4 T cells. MICA is located near HLA-B on chromosome 6. Recent genomewide association studies indicate that genes most strongly linked to ankylosing spondylitis (AS) susceptibility come from the region containing HLA-B and MICA . While HLA-B27 is a well-known risk genetic marker for AS, the potential effect of linkage disequilibrium (LD) shields any associations of genes around HLA-B with AS. The aim of this study was to investigate a novel independent genetic association of MICA to AS. Methods We examined 1543 AS patients and 1539 controls from two ethnic populations by sequencing MICA and genotyping HLA-B alleles. Initially, 1070 AS patients and 1003 controls of European ancestry were used as a discovery cohort, followed by a confirmation cohort of 473 Han Chinese AS patients and 536 controls. We performed a stratified analysis based on HLA-B27 carrier status. We also conducted logistic regression with a formal interaction term. Results Sequencing of MICA identified that MICA *007:01 is a significant risk allele for AS in both Caucasian and Han Chinese populations, and that MICA *019 is a major risk allele in Chinese AS patients. Conditional analysis of MICA alleles on HLA-B27 that unshielded LD effect confirmed associations of the MICA alleles with AS. Conclusions Parallel with HLA-B27 , MICA confers strong susceptibility to AS in US white and Han Chinese populations.

Objective To study the effect of tumor necrosis factor α (TNFα) inhibitors on progressive spinal damage in patients with ankylosing spondylitis (AS). Methods All AS patients meeting the modified New York criteria who had been monitored prospectively and had at least 2 sets of spinal radiographs a minimum of 1.5 years apart were included in the study (n = 334). The patients received standard therapy, which included nonsteroidal antiinflammatory drugs and TNFα inhibitors. Radiographic severity was assessed by the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). Patients with a rate of AS progression that was ≥1 mSASSS unit/year were considered progressors. Univariable and multivariable regression analyses were done. Propensity score matching and sensitivity analysis were performed. A zero-inflated negative binomial (ZINB) model was used to analyze the effect of TNFα inhibitors on the change in the mSASSS with varying followup periods. Potential confounders, such as disease activity (as assessed by the Bath Ankylosing Spondylitis Disease Activity Index), the erythrocyte sedimentation rate, C-reactive protein level, HLA–B27 positivity, sex, age at onset, smoking burden (number of pack-years), and baseline damage, were included in the model. Results TNFα inhibitor treatment was associated with a 50% reduction in the odds of progression, with an odds ratio (OR) of 0.52 (95% confidence interval [95% CI] 0.30–0.88, P = 0.02). Patients with a delay of >10 years in starting therapy were more likely to experience progression as compared to those who started earlier (OR 2.4 [95% CI 1.09–5.3], P = 0.03). In the ZINB model, the use of TNFα inhibitors significantly reduced disease progression when the gap between radiographs was >3.9 years. The protective effect of TNFα inhibitors was stronger after propensity score matching. Conclusion Treatment with TNFα inhibitors appears to reduce radiographic progression in AS patients, especially with early initiation and with longer duration of followup.

To study the effect of tumor necrosis factor α (TNFα) inhibitors on progressive spinal damage in patients with ankylosing spondylitis (AS).All AS patients meeting the modified New York criteria who had been monitored prospectively and had at least 2 sets of spinal radiographs a minimum of 1.5 years apart were included in the study (n=334). The patients received standard therapy, which included nonsteroidal antiinflammatory drugs and TNFα inhibitors. Radiographic severity was assessed by the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). Patients with a rate of AS progression that was ≥1 mSASSS unit/year were considered progressors. Univariable and multivariable regression analyses were done. Propensity score matching and sensitivity analysis were performed. A zero-inflated negative binomial (ZINB) model was used to analyze the effect of TNFα inhibitors on the change in the mSASSS with varying followup periods. Potential confounders, such as disease activity (as assessed by the Bath Ankylosing Spondylitis Disease Activity Index), the erythrocyte sedimentation rate, C-reactive protein level, HLA-B27 positivity, sex, age at onset, smoking burden (number of pack-years), and baseline damage, were included in the model.TNFα inhibitor treatment was associated with a 50% reduction in the odds of progression, with an odds ratio (OR) of 0.52 (95% confidence interval [95% CI] 0.30-0.88, P=0.02). Patients with a delay of10 years in starting therapy were more likely to experience progression as compared to those who started earlier (OR 2.4 [95% CI 1.09-5.3], P=0.03). In the ZINB model, the use of TNFα inhibitors significantly reduced disease progression when the gap between radiographs was3.9 years. The protective effect of TNFα inhibitors was stronger after propensity score matching.Treatment with TNFα inhibitors appears to reduce radiographic progression in AS patients, especially with early initiation and with longer duration of followup.

ObjectiveSyndesmophyte growth in ankylosing spondylitis can be difficult to measure using radiographs because of poor visualisation and semiquantitative scoring methods. We developed and tested the reliability and validity of a new computer-based method that fully quantifies syndesmophyte volumes and heights on CT scans.MethodsIn this developmental study, we performed lumbar spine CT scans on 38 patients and used our algorithm to compute syndesmophyte volume and height in four intervertebral disk spaces. To assess reliability, we compared results between two scans performed on the same day in nine patients. To assess validity, we compared computed measures to visual ratings of syndesmophyte volume and height on both CT scans and radiographs by two physician readers.ResultsCoefficients of variation for syndesmophyte volume and height, based on repeat scans, were 2.05% and 2.40%, respectively. Based on Bland–Altman analysis, an increase in syndesmophyte volume of more than 4% or in height of more than 0.20 mm represented a change greater than measurement error. Computed volumes and heights were strongly associated with physician ratings of syndesmophyte volume and height on visual examination of both the CT scans (pConclusionsThis new CT-based method that fully quantifies syndesmophytes in three-dimensional space had excellent reliability and face and construct validity. Given its high precision, this method shows promise for longitudinal clinical studies of syndesmophyte development and growth.

Evaluation of treatments of many spine disorders requires precise measurement of the heights of vertebral bodies and disk spaces. The authors present a semiautomated computer algorithm measuring those heights from spine computed tomography (CT) scans and evaluate its precision.Eight patients underwent two spine CT scans in the same day. In each scan, five thoracolumbar vertebral heights and four disk heights were estimated using the algorithm. To assess precision, the authors computed the differences between the height measurements in the two scans, coefficients of variation (CV), and 95% limits of agreement. Intraoperator and interoperator precisions were evaluated. For local vertebral and disk height measurement (anterior, middle, posterior) the algorithm was compared to a manual mid-sagittal plane method.The mean (standard deviation) interscan difference was as low as 0.043 (0.031) mm for disk heights and 0.044 (0.043) mm for vertebral heights. The corresponding 95% limits of agreement were [-0.085, 0.11] and [-0.10, 0.12] mm, respectively. Intraoperator and interoperator precision was high, with a maximal CV of 0.30%. For local vertebral and disk heights, the algorithm improved upon the precision of the manual mid-sagittal plane measurement by as much as a factor of 6 and 4, respectively.The authors evaluated the precision of a novel computer algorithm for measuring vertebral body heights and disk heights using short term repeat CT scans of patients. The 95% limits of agreement indicate that the algorithm can detect small height changes of the order of 0.1 mm.

Objective. To compare the effects of education interventions and nonsteroidal antiinflammatory drug (NSAID) treatment on pain and functional disability in patients with osteoarthritis (OA), and on pain, functional disability, and tender joint counts in patients with rheumatoid arthritis (RA). Methods. Two meta-analyses were performed: one of controlled trials of patient education interventions and one of placebo-controlled trials of NSAID treatments. Results. Nineteen patient education trials comprised of 32 treatment arms and 28 NSAID trials comprised of 46 treatment arms were included. The weighted average effect size for pain was 0.17 in the education trials and 0.66 in the NSAID trials. The average effect size for functional disability was 0.03 in the education trials and 0.34 in the NSAID trials; effects of education were much larger in RA studies than in OA studies. In RA studies, the average effect size for the tender joint count was 0.34 in the education trials and 0.43 in the NSAID trials. Because most patients in the education trials were being treated with medications, the effect sizes of these trials represent the additional, or marginal, effects of patient education interventions beyond those achieved by medication. Conclusions. Based on this meta-analysis, patient education interventions provide additional benefits that are 20–30% as great as the effects of NSAID treatment for pain relief in OA and RA, 40% as great as NSAID treatment for improvement in functional ability in RA, and 60–80% as great as NSAID treatment in reduction in tender joint counts in RA.

Objective. To investigate the associations of age, sex, race, and socioeconomic status with long-term survival in patients with systemic lupus erythematosus (SLE). Methods. We examined survival in an inception cohort of 408 patients with SLE. The cohort included 177 black females, 162 white females, 49 white males, and 20 black males. The median duration of followup was 11 years (range 0.1-22 years). Results. One hundred forty-four patients died during the study. The 5-, 10-, and 15-year survival estimates for the entire cohort were 82%, 71%, and 63%, respectively. In univariate analyses, mortality rates increased with age and were higher among males, blacks, those without private medical insurance, and those living in census tracts with lower household incomes. In multivariate analyses, age, sex, and both socioeconomic indicators were associated with total mortality (mortality from any cause), while race was not. Lower socioeconomic status and increased age were also associated with higher rates of death from SLE. Conclusion. Socioeconomic status, but not race, is associated with mortality in SLE. SLE-related mortality also tends to increase with age, which suggests that SLE may not be less severe when it occurs later in life.

Whether a person engages in a particular behavior depends in part on the anticipated consequences of the behavior. Outcome expectancies are a major component of social learning theories of behavior, and are shaped by appraisals of both the likelihood of the outcome and of how rewarding or beneficial the outcome is expected to be1,2. For many health behaviors, such as exercising or eating a healthy diet, some benefits may occur only far in the future, with lower likelihoods of heart disease and cancer. At the same time, these behaviors may involve short-term sacrifices, inconveniences, or disappointments. How a person values future benefits versus present enjoyment (or disengagement from health-promoting behaviors) may influence their outcome expectancies3,4. Some individuals may have a long time horizon and highly value their future health, engaging in whatever behaviors possible to safeguard it. Others may discount the value of future health, believing they are either not susceptible to or can escape any harmful consequences of present behaviors, or that they have time to remediate before consequences develop. Expectancies may differ for near compared to far-off outcomes. Because much of health education involves motivating people to engage in behaviors that provide future health benefits, understanding peoples’ perspectives on time may be important for shaping, delivering, or targeting health promotion interventions. Psychological time perspective is a construct that represents a person’s orientation of the past, present, and future and how it shapes their decision-making5,6. Time perspective is theorized as a subconscious cognitive framework used when making decisions about short-term and long-term goals. In some circumstances, the primary orientation favors consideration of the future, while in other circumstances, the primary orientation may favor the present or the past. Time perspective may be conceived as multidimensional, with different time frames influencing motivations for different decisions and in different domains simultaneously, or as unidimensional, with people having a time perspective that is predominantly future-, present-, or past-oriented6. Time perspective affects the perception and resonance of health-promoting messages, suggesting this construct is actively accessed when decisions regarding health are considered7. Psychological time perspective has been associated with the likelihood of engagement in several risky health behaviors, including substance abuse8–15, gambling16, risky driving11,16,17, and unsafe sexual practices11,14,18–20. However, whether time perspective is associated with more common health behaviors, such as smoking, diet, and recreational exercise, is less clear. Greater future orientation on the Consideration of Future Consequences (CFC) scale was associated with lower body mass indexes (N.B. with obesity considered a result of several different health behaviors), but was not associated with current smoking, in a large community sample in England21. Among volunteers who responded to an online survey in the United States, greater future orientation on the CFC scale was associated with lower body mass indexes and a lower likelihood of current smoking, but was not associated with regular exercise22. Among adolescents, future orientation has been associated with more physical activity and eating a healthy diet23. However, among a small sample of patients undergoing cardiac rehabilitation, scores on the future subscale of the Zimbardo Time Perspective Inventory (ZTPI) were not associated with either exercise or diet, while higher scores on the present-fatalistic subscale were associated with more (rather than less) exercise24. Lastly, in a national sample in Great Britain, associations were found between future orientation and both not smoking and eating more vegetables, but not with recreational activity25. In a previous study, we found no associations between the future and present subscales of the ZTPI and smoking, obesity, or exercise in a community sample26. Although the sample was representative of the local population, participants were highly-educated and had low prevalences of smoking and physical inactivity. Both of these factors may have limited our ability to detect associations between time perspective and health behaviors. More highly-educated individuals tend to be more future-oriented than less well-educated persons and those of lower socioeconomic status21,25–28. Therefore, the association between time perspective and health behaviors may have been affected by the socioeconomic composition of the sample. The purpose of the current study was to examine associations between time perspective and smoking, obesity, and recreational exercise in a diverse community-based sample of lower socioeconomic status than our previous study. We hypothesized that persons with higher future-orientation would be less likely to be smokers or to be obese, and more likely to exercise. In addition, we hypothesized that those with higher present-orientation would be more likely to be smokers or obese, and less likely to exercise. Also, future time perspective and health share similar socioeconomic gradients. Because time perspective provides a scheme for motivations of investments in future health, time perspective has been theorized to be a mediator of socioeconomic disparities in health21,25,26,29–31. An additional aim of this study was to test if time perspective mediated the association between socioeconomic status and health behaviors.

The measurement of vertebral heights is necessary for the evaluation of many disorders affecting the spine. High precision is particularly important for longitudinal studies where subtle changes are to be detected. Computed tomography (CT) is the modality of choice for high precision studies. Radiography and dual emission X-ray absorptiometry (DXA) use 2D images to assess 3D structures, which can result in poor visualization due to the superimposition of extraneous anatomical objects on the same 2D space. We present a semi-automated computer algorithm to measure vertebral heights in the 3D space of a CT scan. The algorithm segments the vertebral bodies, extracts their end plates and computes vertebral heights as the mean distance between end plates. We evaluated the precision of our algorithm using repeat scans of an anthropomorphic vertebral phantom. Our method has high precision, with a coefficient of variation of only 0.197% and Bland-Altmann 95% limits of agreement of [-0.11, 0.13] mm. For local heights (anterior, middle, posterior) the algorithm was up to 4.2 times more precise than a manual mid-sagittal plane method.

Methods PFAPA patients were prospectively recruited. All patients had genetic testing to exclude mutations in the known fever genes (MVK, MEFV, TNFRSF1A, NLRP3, and ELA2). These PFAPA patients have been classified as sporadic or familial cases based on family history. Familial cases included those with a family member having PFAPA or a family member having a feature of PFAPA (recurrent fever, oral ulcer, pharyngitis, or lymphadenopathy). The demographics, symptoms, response to therapies, and clinical characteristics were compared for sporadic and familial cases. Detailed histories were obtained from families with multiple members affected by PFAPA.

Physical therapy and orthopedic surgery are important components in the treatment of ankylosing spondylitis (AS). Supervised physical therapy is more effective than individual or unsupervised exercise in improving symptoms, but controlled trials suggest that combined inpatient and outpatient therapy provides the greatest improvement. Recommendations for exercise are universal, but the best types and sequence of therapies are not known. Total hip replacement is the surgery most commonly performed for AS, with good long-term implant survival. Heterotopic ossification may occur no more frequently after hip replacement in patients with AS than in patients with other diseases. Corrective spinal surgery is rarely performed and requires specialized centers and experienced surgeons.

The inflammatory arthritides are a diverse group of conditions characterised by joint inflammation which can lead to pain, deformity and disability. Of these diseases, rheumatoid arthritis (RA) and spondyloarthritis are two of the most common. While the clinical and demographic features of these diseases differ, the central role of inflammation in their pathogenesis has allowed the development of highly effective treatment strategies with wide applicability. These strategies include the use of biological agents which target the cytokine tumour necrosis factor (TNF), a key mediator of inflammation. With the advent of effective agents, therapy has become more aggressive, reducing disease activity and allowing, at least in RA, remission in many patients. While the array of available effective treatments is extensive, the use of objective measures of disease activity can guide treatment decisions (treat to target) and lead to improved outcomes.

Objective Both radiographic damage and functional limitations increase with the duration of ankylosing spondylitis (AS). We examined whether radiographic damage contributed more to functional limitations in late AS than in early AS, and if the strength of association varied with the anatomic region of damage. Methods In this cross-sectional study of 801 patients with AS, we examined associations of the lumbar modified Stoke Ankylosing Spondylitis Spine Score (mSASSS), the cervical mSASSS, lumbar posterior fusion, cervical posterior fusion, and hip arthritis with the Bath Ankylosing Spondylitis Functional Index (BASFI) and the Health Assessment Questionnaire modified for the spondyloarthritides (HAQ-S). Results Higher lumbar and cervical mSASSS scores were associated with more functional limitations, but there was an interaction between mSASSS scores and the duration of AS, such that the strength of their association with functional limitations decreased with increasing duration of AS. Cervical posterior fusion was associated with worse functioning independent of mSASSS scores. Hip arthritis was significantly associated with functional limitations independent of spinal damage measures. Among patients with AS duration ≥40 years, the number of comorbid conditions accounted for most of the variation in functioning. Results were similar for both the BASFI and the HAQ-S. Conclusion Although both radiographic damage and functional limitations increase over time in AS, the relative contribution of radiographic damage to functional limitations is lower among patients with longstanding AS than with early AS, suggesting patients may accommodate to limited flexibility. Damage in different skeletal regions impacts functioning over the duration of AS. Functional limitations due to comorbidity supervene in late AS.

Persons with systemic lupus erythematosus (SLE) are at an increased risk of cardiovascular disease (CVD) events, but this excess CVD burden in the perioperative setting is yet to be determined. We aimed to determine the risk of perioperative short-term all-cause mortality and CVD events among women with SLE compared to those without SLE.We conducted a cross-sectional analysis of pooled hospital discharge data of the Nationwide Inpatient Sample from 1998-2002. We abstracted diseases and procedures using International Classification of Diseases, Ninth Revision, Clinical Modification codes. The principal procedure was categorized into either a low, intermediate, or high risk level. Survey logistic regression adjusting for potential confounders provided estimates for stratum-specific odds of adverse events in women with SLE relative to those without SLE for each procedure risk level.All-cause mortality was significantly greater among women with SLE having a low- (odds ratio [OR] 1.54, 95% confidence interval [95% CI] 1.00-2.37) or a high-risk principal procedure (OR 2.52, 95% CI 1.34-4.75) relative to women without SLE, but did not differ significantly among persons with intermediate-risk procedures. Women with SLE with a low-risk procedure were also more likely to experience a composite CVD event relative to women without SLE (OR 1.40, 95% CI 1.04-1.87).Women with SLE are at an increased risk for short-term perioperative adverse events. These results highlight a need for greater scrutiny during perioperative evaluation and management of women with SLE.

Sense of control has been linked to improved health outcomes, but it is unclear if this association is independent of other psychosocial factors.The aim of this study is to test the strength of association between sense of control and self-reported health after adjustment for positive and negative affect, "Big 5" personality factors, and social support.Data on sense of control (measured by personal mastery, perceived constraints, and a health-specific rating of control), affect, personality, social support, and two measures of self-reported health (global rating of fair or poor health and presence of functional limitations) were obtained on 6,891 participants in the Health and Retirement Study, a population-based survey of older Americans. The cross-sectional association between sense of control measures and each measure of self-reported health was tested in hierarchical logistic regression models, before and after adjustment for affect, personality, and social support.Participants with higher personal mastery were less likely to report fair/poor health (odds ratio 0.76 per 1-point increase) while those with higher perceived constraints were more likely to report fair/poor health (odds ratio 1.37 per 1-point increase). Associations remained after adjustment for affect, but adjustment for affect attenuated the association of personal mastery by 37% and of perceived constraints by 67%. Further adjustment for personality and social support did not alter the strength of association. Findings were similar for the health-specific rating of control, and for associations with functional limitations.Sense of control is associated with self-reported health in older Americans, but this association is partly confounded by affect.

We thank Wei et al 1 for their comments on our paper on comparative efficacy of non-steroidal anti-inflammatory drugs (NSAIDs) in the treatment of ankylosing spondylitis.2 Here we address their questions regarding study heterogeneity, effect modification and the fit of our models. Wei et al questioned if heterogeneity among studies could have affected our results. In all meta-analyses, an assessment of study heterogeneity is important. Heterogeneity was first addressed by our inclusion criteria, which limited the types of primary studies that were eligible for inclusion in the meta-analysis to those of patients with the same diagnosis (ankylosing spondylitis), similar trial durations and no …

Stronger sense of control has been associated with improved health outcomes. This study tested whether the association between sense of control and self-reported health varied among demographic groups and whether sense of control attenuated sociodemographic differences in self-reported health.Data from 6,815 participants in the Health and Retirement Study were used to examine moderation between demographic characteristics and sense of control (measured by the personal mastery and perceived constraints scales of the midlife developmental inventory) in their associations with three self-reported health measures (global rating of fair/poor health, functional limitations, and number of comorbid conditions).Higher personal mastery and lower perceived constraints were associated with better self-reported health. There were no significant interactions between the sense of control measures and age, gender, education level, income, or marital status in their associations with either global self-rated health or functional limitations. Higher levels of mastery were associated with lower likelihood of functional limitations among blacks and whites, but not among those of other races. Perceived constraints were slightly more strongly associated with number of comorbid conditions among older than younger individuals.Sense of control measures were generally similarly associated with self-reported health across demographic groups and did not attenuate demographic differences in health.

To investigate the efficacy of etanercept in improving the symptoms and underlying inflammation in patients with tumor necrosis factor receptor-associated periodic syndrome (TRAPS).Fifteen patients with TRAPS were enrolled in a prospective, open-label, dose-escalation study. Patients recorded attacks, symptom severity, and use of ancillary medications in a daily diary. Blood samples were collected during each period and measured for levels of acute-phase reactants. Between 7 years and 9 years after the conclusion of the initial study, patients completed a followup survey and were evaluated to determine the long-term outcome of etanercept treatment.Etanercept treatment significantly attenuated the total symptom score and reduced the frequency of symptoms. Etanercept also reduced levels of acute-phase reactants, particularly during asymptomatic periods. During a 10-year followup period, patients continued to receive etanercept for a median of 3.3 years, with a number of patients switching to anti-interleukin-1β receptor therapy or not receiving biologic agents, most frequently citing injection site reactions and lack of efficacy as reasons for discontinuation. However, patients continuing to receive etanercept had reduced symptoms at followup.Etanercept reduces symptoms and serum levels of inflammatory markers of TRAPS in a dose-dependent manner, but does not completely normalize symptoms or acute-phase reactant levels. Although long-term adherence to etanercept is poor, continuing to receive etanercept may provide continued symptomatic benefit.

Objectives. To explore whether helplessness, internality and depression would mediate the relationship between disease activity and functional limitations in patients with AS in a 12-month longitudinal study. Methods. A total of 294 participants with AS meeting modified New York criteria completed clinical and psychological assessments at 6-month intervals. Psychological measures evaluated helplessness, depression and internality. Path analysis evaluated the direct and indirect effects of baseline disease activity on 12-month functional limitations via the psychological measures of helplessness, internality and depression at 6 months. Results. Baseline disease activity demonstrated direct and indirect effects on 12-month functional limitations. Helplessness and depression, but not internality, served as mediators of the relationship between disease activity and functional limitations. Conclusion. Higher baseline disease activity predicted greater functional limitations at 12 months through helplessness and depression. Our findings suggest that helplessness and depression may constitute future treatment targets in reducing functional limitations in patients with AS.

Throughout history, medical advances have been adopted first and preferentially by the well educated and economically advantaged groups. The development of personalized therapeutics holds promise to fundamentally alter the practice of clinical medicine, but if it also is used preferentially by economically advantaged groups, this advance will likely worsen socioeconomic disparities in health. Prospective development of strategies to ensure non- differential access to these therapies may help limit this unintended consequence of medical progress for economically disadvantaged groups.

Objective To evaluate the prevalence, correlates, and subgroups at highest risk for suicidal ideation among adults with arthritis. Methods We used data on US adults with arthritis, ages ≥40 years, participating in the 2007–2008 National Health and Nutrition Examination Survey. Suicidal ideation was assessed by item 9 of the Patient Health Questionnaire 9 (PHQ-9). Sociodemographic factors, health behaviors, and comorbid conditions were examined as potential correlates. Depression was measured by the PHQ-8 score (range 1–24). We used random forests to identify subgroups at highest risk for suicidal ideation. To determine if any correlates were unique to arthritis, we compared results to those for persons with diabetes mellitus and cancer. Results The prevalence ± SEM of suicidal ideation was 5.6% ± 0.8% among persons with arthritis and 2.4% ± 0.4% among those without. The most important correlates for suicidal ideation in adults with arthritis were depression, anxiety, duration of arthritis, age, income:poverty ratio, number of close friends, pain, alcohol, excessive daytime sleepiness, and comorbidities. Eleven of the 16 most important contributors for suicidal ideation among adults with arthritis were also important for people with diabetes mellitus and cancer. Among persons with arthritis, subgroups at highest risk for suicidal ideation were those with a PHQ-8 score between 18 and 24 and less than 4.5 years of arthritis (96.5%), and those with a PHQ-8 score between 7 and 17, ≥1.24 days of binges/month, and either an income of ≥$45,000/year (85.4%) or an income of 3 comorbidities (70.8%). Conclusion Depression, short duration of arthritis, binge drinking, income, and >3 comorbidities identified subgroups of adults with arthritis at greatest risk for suicidal ideation.

This study proposes an econometric technique to reduce attrition bias in panel data. In the simplest case, one estimates two regressions. The first is a probit regression based on sociodemographic and clinical characteristics measured at baseline. The probit regression estimates the probability that subjects stay or leave over the duration of the study. We insert the predicted probabilities from the probit regression into an inverse Mills ratio (IMR) or hazard rate to form an instrumental variable. We use this instrumental variable subsequently as an additional covariate in a second regression model that attempts to explain fluctuations in the dependent variable. The second regression, which is linear, includes only subjects who remained in the study. In alternative models, instrumental variables are created using predicted values from least squares and logit regressions estimating the probability that subjects stay or leave. The use of the instrumental variables reduces the effects of attrition bias in the linear regression model. We applied the technique to a panel of patients with rheumatoid arthritis (RA) enrolled in 1981 and followed through 1990. We attempted to predict values for a measure of functional disability recorded in 1990 with use of covariates measured in 1981. The dependent variable was an index of disability in 1990 and the independent variables (covariates) included the disability index from 1981, the years of duration of RA, gender, marital status, education, and age in 1981. The correction technique suggested that ignoring attrition bias would underestimate the strength of associations between being female and the subsequent disability index, and overestimate the strength of associations between being married spouse present, age, and the initial disability index on the one hand and the subsequent disability index on the other.

Objective. To determine if marital status is associated with differences in rates of progression of functional disability in patients with rheumatoid arthritis (RA). Methods. A community cohort of 282 persons with RA was followed prospectively for up to 9.5 years. The progression of functional disability over time was determined using the Health Assessment Questionnaire Disability Index, which was completed by study participants every 6 months. Results. At study entry, the Disability Index was 1.1 ± 0.8 (mean ± 1 SD) (possible range 0–3) among the 188 married participants and 1.3 ± 0.9 among the 94 unmarried participants. Over time, the rate of progression of functional disability was generally higher among unmarried participants. However, the extent of this difference varied somewhat over the disease course, with rates of progression higher among unmarried than among married participants during years 5–7 and years 17–29 of RA. Overall estimated rates of progression, adjusted for the effects of other sociodemographic factors, were 0.03 Disability Index units per year in unmarried participants and 0.01 Disability Index units per year in married participants (P < 0.0001). Conclusion. Marriage, possibly reflecting the influence of social support, is associated with a lower rate of progression of functional disability in persons with RA.