Outpatient healthcare utilization among incident cases of systemic sclerosis: results from a population-based US cohort (1988-2016).

OBJECTIVE: Systemic sclerosis (SSc) is a complex, heterogeneous connective tissue disease with multiorgan dysfunction. This study aimed to compare healthcare utilization among incident cases of SSc versus age- and gender-matched comparators. METHOD: A population-based cohort of physician-diagnosed patients with SSc in Olmsted County, MN, USA, from 1 January 1988 to 31 December 2016 was assembled. A 2:1 cohort of age- and gender-matched non-SSc subjects was randomly selected for comparison. Patients were followed until death, migration from Olmsted County, or 31 December 2017. Outpatient utilization data were obtained beginning 12 months before the SSc incidence/index date and compared using negative binomial and multinomial models. Services were summarized as visit-days to avoid overestimation of services provided. RESULTS: The study included 69 incident SSc cases and 138 non-SSc comparators (mean ± sd age 57 ± 16 years at diagnosis/index, 90% female). Patients with SSc had higher utilization of outpatient physician, laboratory, and combined radiology visit-days annually for the year before and for each of the first 5 years after diagnosis than comparators. Among patients with SSc, healthcare utilization was highest during the year of SSc diagnosis. Rate ratios comparing utilization in patients with and without SSc ranged from 1.8 to 3.0 for all comparisons. CONCLUSION: Higher utilization of outpatient physician, laboratory, and radiology visit-days was observed among patients with SSc compared to non-SSc subjects throughout 5 years of disease duration, indicating high and continued care needs in this patient population. The highest utilization of services among SSc patients occurred during the year of SSc diagnosis.

Immunoglobulin A vasculitis associated with inflammatory bowel disease: a retrospective cohort study.

Objective: To describe the baseline characteristics and outcome of a series of patients with inflammatory bowel disease (IBD) and immunoglobulin A vasculitis (IgAV). Method: Patients with biopsy-proven IgAV with IBD were identified retrospectively. Data were abstracted from direct medical chart review. Each IBD-IgAV case was matched to two controls with IgAV but without IBD. Results: Nine patients were identified (seven Crohn's disease, two ulcerative colitis). Mean length of time between IBD diagnosis and IgAV onset was 17.3 ± 19.9 years. For patients on biologic treatment for IBD, mean length of time between biologic initiation and IgAV onset was 3.3 ± 3.8 years. Active IBD at IgAV onset was present in 56%. Tumour necrosis factor inhibitors (TNFi) were used for IBD in 89%. At IgAV onset, six patients were on treatment with TNFi; one subsequently discontinued, two switched to another TNFi, and three continued. At the last follow-up, three of five patients who remained on TNFi had full resolution of IgAV despite ongoing TNFi use. No differences were seen between cases with IBD IgAV and matched non-IBD-IgAV controls regarding development of end-stage renal disease, resolution of haematuria or proteinuria, and time to complete IgAV response. Conclusion: Baseline characteristics and outcomes of patients with IBD-IgAV are similar to those with IgAV without IBD. Development of IgAV is not limited to patients with clinically active IBD. Whether TNFi use is related to the pathogenesis of IgAV in some patients with IBD remains unclear. Further research into pathophysiological connections between IBD and IgAV is needed.

Incidence and predictors of thoracic aortic damage in biopsy-proven giant cell arteritis.

Objective: To describe the frequency and predisposing factors of aortic structural disease among patients with biopsy-proven giant cell arteritis (GCA).Method: A retrospective review identified all patients with biopsy-proven GCA from 1998 to 2013 with aortic imaging. Kaplan-Meier methods were used to estimate cumulative incidence and Cox models were used to examine potential predictors of development of aneurysm/dilatation of the thoracic aorta.Results: The cohort included 114 patients with aortic imaging performed within a median time of 1.8 months from GCA diagnosis. Fifty-seven patients (50%) had at least one additional follow-up imaging study. At the first imaging study, 8% had evidence of aneurysm/dilatation and 25% thickening of the thoracic aorta. Excluding prevalent cases, the cumulative incidence for aneurysm/dilatation of the thoracic aorta during follow-up was 0% at both 1 year and 2 years but increased to 10% at 5 years. The sole predictor for development of thoracic aortic aneurysm/dilatation was current smoking (hazard ratio 28.8, 95% confidence interval 1.62, 511.4; p = 0.02).Conclusion: Thoracic aortic aneurysm/dilatation was seen in 8% of patients at baseline. Among patients without aortic disease, the cumulative incidence of aortic disease was 10% at 5 years after diagnosis. Current smokers were at an increased risk for developing thoracic aortic damage. Surveillance for aortic damage should be pursued in patients with GCA, particularly those with a smoking history.

Risk of fragility fracture among patients with sarcoidosis: a population-based study 1976-2013-supplementary presentation.

Incidence of fragility fracture of a population-based cohort of 345 patients with sarcoidosis was compared with age- and sex-matched comparators. The incidence of fragility fracture was higher among patients with sarcoidosis with a hazard ratio (HR) of 2.18.

Epidemiology and clinical characteristics of sarcoidosis: an update from a population-based cohort study from Olmsted County, Minnesota.

Information about the epidemiology, clinical manifestations and comorbidities of sarcoidosis among Caucasians is relatively scarce. This review focuses primarily on the data from a recently published Caucasianpredominant population-based cohort from Olmsted County, Minnesota. Overall, the incidence rate was 10.0 per 100,000 population, which suggested that sarcoidosis is less common in Caucasians than in Blacks, but is more common in Caucasians than in Asians. Intrathoracic involvement was seen in the vast majority of patients, but less than half have respiratory symptoms. The most common extra-thoracic manifestations were skin rash followed by arthralgia, ophthalmologic involvement, hepatic involvement, splenomegaly, renal involvement, neurological involvement, extra-thoracic lymphadenopathy, exocrine gland involvement, upper respiratory tract involvement and cardiac involvement. Compared to sex and age-matched subjects, patients with sarcoidosis suffer from increased rates of cardiovascular disease, venous thromboembolism and hospitalized infection.

Risk of fragility fracture among patients with sarcoidosis: a population-based study 1976-2013.

Incidence of fragility fracture of a population-based cohort of 345 patients with sarcoidosis was compared with age and sex-matched comparators. The incidence of fragility fracture was higher among patients with sarcoidosis with hazard ratio (HR) of 2.18. INTRODUCTION: Several chronic inflammatory disorders increase the risk of fragility fracture. However, little is known about the risk of fragility fracture in patients with sarcoidosis. METHODS: This study was conducted using a previously identified population-based cohort of 345 patients with incident sarcoidosis from Olmsted County, Minnesota. Diagnosis of sarcoidosis required physician diagnosis supported by biopsy showing non-caseating granuloma, radiographic evidence of intrathoracic sarcoidosis, and compatible clinical presentations without evidence of other granulomatous diseases. Sex and age-matched subjects randomly selected from the same underlying population were used as comparators. Medical records of cases and comparators were reviewed for baseline characteristics and incident fragility fracture. RESULTS: Fragility fractures were observed in 34 patients with sarcoidosis, corresponding to a cumulative incidence of 5.6% at 10 years, while 18 fragility fractures were observed among comparators for a cumulative incidence of 2.4% at 10 years. The HR of fragility fractures among cases compared with comparators was 2.18 (95% confidence interval [CI], 1.23-3.88). The risk of fragility fracture by site was significantly higher among patients with sarcoidosis, and was due to a higher rate of distal forearm fracture (HR 3.58; 95% CI 1.53-8.40). Statistically non-significant increased risk was also observed in proximal femur (HR 1.66; 95% CI 0.45-6.06) and proximal humerus (HR 3.27; 95% CI 0.66-16.21). Risk of vertebral fracture was not increased (HR 1.00; 95% CI 0.32-3.11). CONCLUSION: Patients with sarcoidosis have an increased risk of fragility fracture which is primarily driven by the higher incidence of distal forearm fracture.

Incidence of systemic lupus erythematosus in a population-based cohort using revised 1997 American College of Rheumatology and the 2012 Systemic Lupus International Collaborating Clinics classification criteria.

In 2012, the Systemic Lupus International Collaborating Clinics (SLICC) group published a new set of classification criteria for systemic lupus erythematosus (SLE). Studies applying these criteria to real-life scenarios have found either equal or greater sensitivity and equal or lower specificity to the 1997 ACR classification criteria (ACR 97). Nonetheless, there are no studies that have used the SLICC 12 criteria to investigate the incidence of lupus. We used the resource of the Rochester Epidemiology Project to identify incident SLE patients in Olmsted County, Minnesota, from 1993 to 2005, who fulfilled the ACR 97 or SLICC 12 criteria. A total of 58 patients met criteria by SLICC 12 and 44 patients met criteria by ACR 97. The adjusted incidence of 4.9 per 100,000 person-years by SLICC 12 was higher than that by ACR 97 (3.7 per 100,000 person-years, p = 0.04). The median duration from the appearance of first criterion to fulfillment of the criteria was shorter for the SLICC 12 than for ACR 97 (3.9 months vs 8.1 months). The higher incidence by SLICC 12 criteria came primarily from the ability to classify patients with renal-limited disease, the expansion of the immunologic criteria and the expansion of neurologic criteria.

Epidemiology of cutaneous sarcoidosis, 1976-2013: a population-based study from Olmsted County, Minnesota.

BACKGROUND: The epidemiology of cutaneous sarcoidosis is not well-characterized as only referral-based studies are available. OBJECTIVES: To characterize the epidemiology of cutaneous sarcoidosis, with emphasis on annual incidence and clinical characteristics, from 1976 to 2013. METHODS: Inception cohorts of patients with incident isolated cutaneous sarcoidosis and incident systemic sarcoidosis with cutaneous involvement in 1976-2013 in Olmsted County, Minnesota, United States were identified based on comprehensive individual medical record review. Inclusion in the isolated cutaneous sarcoidosis cohort required physician diagnosis and skin biopsy showing non-necrotizing granuloma. Inclusion in the systemic sarcoidosis with cutaneous involvement cohort required presence of systemic sarcoidosis and cutaneous lesions. Presence of systemic sarcoidosis was determined by physician diagnosis supported by histopathology of non-necrotizing granuloma, characteristic radiologic features of intrathoracic sarcoidosis and exclusion of other granulomatous diseases. Cutaneous lesions were defined as either sarcoidosis-specific or non-specific. RESULTS: There were 62 cases with sarcoidosis-specific cutaneous lesions (36 cases of sarcoidosis-specific cutaneous lesions and 26 cases of isolated cutaneous sarcoidosis) which corresponded to an incidence of 1.9 per 100 000 population. The female to male ratio was 2.1 : 1. Plaques, papules and subcutaneous nodules were the most commonly observed cutaneous lesions. There was no significant difference in cutaneous presentation between those who had isolated skin disease and those who had skin disease in association with systemic sarcoidosis. Prognosis of cutaneous sarcoidosis was favourable, as over 90% of patients had a good response to either glucocorticoids, hydroxychloroquine or tetracycline antibiotics. This study has a significant limitation, in that the studied population was predominantly Caucasians who generally have a lower prevalence of skin disease. CONCLUSIONS: The incidence of sarcoidosis-specific cutaneous lesions was about 1.9 per 100 000 population with female predominance. The cutaneous presentations were similar among those with and without systemic sarcoidosis.

Juvenile idiopathic arthritis and future risk for cardiovascular disease: a multicenter study.

OBJECTIVES: To evaluate the frequency of cardiovascular disease (CVD) and CVD risk factor development in adult patients previously diagnosed with juvenile idiopathic arthritis (JIA). METHOD: A cohort study was conducted utilizing patients at two academic institutions (cohorts 1 and 2). Each institution evaluated the common endpoint of CVD outcomes and CVD risk factor development in adults aged ≥ 30 years and at the 29-year follow-up from disease onset in cohorts 1 and 2, respectively, with comparison to control groups of similar age and sex. RESULTS: Cohort 1 included 41 patients with JIA and follow-up ≥ 30 years of age with comparison to 41 controls. Three patients (7%) had CVD, compared to one control (2%; p = 0.31). Cohort 2 included 170 patients with JIA and a median of 29 years of follow-up from disease onset with comparison to 91 controls. Two patients (2%) had CVD, compared to none of the controls (p = 0.29). The presence of CVD risk factors was found to be increased in the JIA group compared to the controls in three categories: family history of CVD (cohort 1), hypertension (cohort 2), and ever smokers (cohorts 2). CONCLUSIONS: There is no increase in CVD events in patients with JIA 29 years following disease onset when compared to the general population. As these cohorts age, it will be informative to evaluate whether this baseline risk remains present or a trend towards increasing CVD emerges. Continued longitudinal follow-up of these cohorts and larger population-based studies are needed to establish a definitive relationship between JIA and CVD.

Glucocorticoid usage in giant cell arteritis over six decades (1950 to 2009).

OBJECTIVES: To evaluate the trends in glucocorticoid (GC) therapy in patients with giant cell arteritis (GCA). METHODS: Using a population-based inception cohort, GC therapy details were collected for all patients with GCA diagnosed between 1950-2009. GC usage for patients diagnosed with GCA between 1980-2009 was compared to those diagnosed between 1950-1979. RESULTS: The mean starting dose was similar in both time-periods but the mean cumulative dosages at different time points were significantly higher for patients diagnosed between 1980-2009 than in 1950-1979 (at 1-year: 6.3 vs. 4.1g; and at 5 years 10.7 vs. 7.6g, respectively, p<0.001). The median time to permanent discontinuation of GC was 2.6 years for 1980-2009 vs. 1.5 years for 1950-1979 (p=0.004). The risk for GC-associated adverse events was similar in both time periods (p=0.52). CONCLUSIONS: GCA patients diagnosed in the last three decades were treated with higher cumulative GC doses and were less likely to achieve GC discontinuation. However, their risks for GC-related complications were not significantly higher than their earlier counterparts.

Cardiovascular risk profile at the onset of psoriatic arthritis: a population-based cohort study.

OBJECTIVE: The role of cardiovascular disease (CVD) risk factors in psoriatic arthritis (PsA) is poorly understood. We examined the prevalence of CVD risk factors at initial onset of PsA and compared the observed incidence of CVD events with that predicted by the Framingham Risk Score (FRS) to determine its applicability in this patient population. METHODS: A population-based incidence cohort of 158 patients with PsA who fulfilled Classification of Psoriatic Arthritis criteria for PsA in 1989-2008 was assembled. Medical records were reviewed to ascertain CVD risk factors and CVD events. Future risk of CVD was estimated using the FRS algorithm. RESULTS: Mean age was 43.4 years (range 19-74 years), 61% were men, and 44% were obese (body mass index ≥30 kg/m(2) ). Fifty-four patients (34%) presented with ≥2 CVD risk factors at PsA incidence. Among 126 patients ages ≥30 years at PsA incidence with no prior history of CVD, 33% had an FRS ≥10%, with 11% having an FRS ≥20%, and 18 experienced a CVD event in the first 10 years of disease duration. The 10-year cumulative incidence of CVD events was 17% (95% confidence interval [95% CI] 10%-24%), almost twice as high as the predicted incidence based on the FRS (standardized incidence ratio 1.80, 95% CI 1.14-2.86; P = 0.012). CONCLUSION: The majority of newly diagnosed PsA patients have a >10% risk of CVD within 10 years of PsA incidence. The CVD risk in these patients is higher than expected and underestimated by the FRS.

The incidence of giant cell arteritis in Olmsted County, Minnesota, over a 60-year period 1950-2009.

OBJECTIVE: To assess the incidence of giant cell arteritis (GCA) in the era from 2000 to 2009. METHOD: We extended the previously identified population-based cohort of Olmsted County, Minnesota residents who fulfilled 1990 American College of Rheumatology (ACR) criteria for GCA for earlier decades during 1950-1999. RESULTS: In 2000-2009, 74 cases of GCA were identified (mean age 78.1 years; 80% women; 79% temporal artery biopsy positive; seven included based on radiological criteria). The incidence of GCA was 19.8 per 100,000 population. CONCLUSIONS: The GCA incidence rates have remained steady since 1970 and the age at incidence, which was progressively increasing, seems to have reached a plateau.

Assessment of disease activity in rheumatoid arthritis using a novel folate targeted radiopharmaceutical Folatescan.

OBJECTIVES: Development of a simple and accurate technique for detecting active inflammation in the joints and other tissues of patients with inflammatory disorders is an unmet need in rheumatic diseases. This study is a preliminary assessment of the safety and usage of a radiopharmaceutical, FolateScan (Technetium-99m EC20; 99mTc-EC20), for detecting disease activity in patients with rheumatoid arthritis. METHODS: EC20 is a folate-targeted diagnostic radiopharmaceutical which binds to the folate receptor and is preferentially taken up by activated macrophages. In this open-label, cross-sectional study, a total of 40 patients with RA (26 with one or more swollen joints, 14 with clinically quiescent joint disease; 0/66 joint count) as well as 6 patients with osteoarthritis, 12 patients with other inflammatory conditions and 5 healthy subjects received 0.1 mg of EC20 labeled with 20-25mCi of technetium-99m. Disease activity was scored in each joint and other target tissues by a radiologist blinded to the clinical assessment, and results were compared to the rheumatologist's physical examination, which served as the test standard. RESULTS: The 40 patients (78% female) with RA had a mean age of 56.9 years. Assessment of uptake of 99mTc-EC20 in joints of patients with RA based on image analysis was compared to the clinical examination. FolateScan detected more actively involved joints in 27 patients (68%) than joints recorded as "swollen", and more actively involved joints in 25 patients (63%) than joints recorded as "painful and/or swollen". The number of swollen joints by clinical exam was correlated with ESR (r=0.43; p=0.006) and C-rp (r=0.35; p=0.03). The number of actively involved joints by FolateScan was also correlated with ESR (r=0.47; p=0.002) and C-rp (r=0.36; p=0.02). Joint uptake was also seen in patients with osteoarthritis. CONCLUSION: FolateScan is a potentially useful tool for detection of disease activity in patients with RA and may be more sensitive than the physical examination.

Mycophenolate mofetil is effective in reducing disease flares in systemic lupus erythematosus patients: a retrospective study.

Mycophenolate mofetil (MMF) is effective in the treatment of patients with active systemic lupus erythematosus (SLE). We sought to evaluate its efficacy in reducing the number of disease flares in adults with SLE. For this retrospective study, all patients seen at our institution over a six year period, 1999-2005, with the diagnosis of SLE treated with MMD were identified. Data regarding lupus flare was obtained for patients at least one and up to two years prior to starting MMF. The number of flares prior to MMF therapy was compared to the number of lupus flares in the one to two year period after starting MMF. Clinical assessment was performed with the SELENA-SLEDAI instrument. Differences between groups were compared using the signed rank test. The rate of flares (flares per person-year), before and after the introduction of MMF were compared assuming the occurrence of flares followed a Poisson distribution. In the evaluable 67 patients, the mean time period of followup prior to starting MMF was 14.1 months (range 0.3-24), mean time period of follow-up after starting MMF was 14.8 months (range 1.5-24); and mean MMF dose was 1328 mg/day (range 250-3000). The mean flare rate was reduced from 8.9 to 5.3 per 10 personyears and the mean prednisone dose was reduced on average 7.3 mg/day after starting MMF therapy. MMF treatment significantly reduced the total number of lupus flares and prednisone requirements. Even with the reduction in mean daily prednisone dose, both the SLEDAI and physican global assessment also improved during MMF therapy.

Do cardiovascular risk factors confer the same risk for cardiovascular outcomes in rheumatoid arthritis patients as in non-rheumatoid arthritis patients?

OBJECTIVE: To compare the frequency of traditional cardiovascular (CV) risk factors in rheumatoid arthritis (RA) compared to non-RA subjects, and examine their impact on the risk of developing selected CV events (myocardial infarction (MI), heart failure (HF) and CV death) in these two groups. METHODS: We examined a population-based incidence cohort of subjects with RA (defined according to the 1987 American College of Rheumatology criteria), and an age- and sex-matched non-RA cohort. All subjects were followed longitudinally through their complete community medical records, until death, migration, or 1 January 2001. Clinical CV risk factors and outcomes were defined using validated criteria. The chi2 test was used to compare the frequency of each CV risk factor at baseline. Person-years methods were used to estimate the rate of occurrence of each CV risk factor during follow-up. Cox models were used to examine the influence of CV risk factors on the development of CV outcomes. RESULTS: A total of 603 RA and 603 non-RA subjects (73% female; mean age 58 years) were followed for a mean of 15 and 17 years (total: 8842 and 10,101 person-years), respectively. At baseline, RA subjects were significantly more likely to be former or current smokers when compared to non-RA subjects (p<0.001). Male gender, smoking, and personal cardiac history had weaker associations with CV events among RA subjects, compared to non-RA subjects. There was no significant difference between RA and non-RA subjects in the risk imparted with respect to the other CV risk factors (ie, family cardiac history, hypertension, dyslipidaemia, body mass index, or diabetes mellitus). CONCLUSION: While some traditional CV risk factors imparted similar risk among RA compared with non-RA subjects, others (ie, male gender, smoking and personal cardiac history) imparted significantly less risk for the development of CV disease. These differences in the overall impact of traditional CV risk factors suggest that strategies to prevent CV disease and mortality focused solely on controlling traditional CV risk factors may be relatively less beneficial in RA subjects than in the general population. Further research is needed to determine optimal approaches to reducing CV morbidity and mortality in persons with RA.

Raised erythrocyte sedimentation rate signals heart failure in patients with rheumatoid arthritis.

BACKGROUND: Inflammatory markers are associated with heart failure. Patients with rheumatoid arthritis have twice the risk of heart failure compared with people without rheumatoid arthritis. OBJECTIVE: To assess whether heart failure in patients with rheumatoid arthritis is preceded by an inflammatory activation as shown by erythrocyte sedimentation rate (ESR), a systemic marker of inflammation. METHODS: A population-based inception cohort of 575 patients with rheumatoid arthritis, free of heart failure at their rheumatoid arthritis incidence date, was followed up longitudinally until death or 2001. During 15 years of follow-up, they had a median of 15 ESR tests, and 172 patients had new-onset heart failure (Framingham Heart Study criteria). The follow-up period, beginning with the rheumatoid arthritis incidence date and ending with date of the last follow-up, was divided into 6-month intervals. The proportions of patients with at least one ESR value >/=40 mm/h and with anaemia (haemoglobin <11 g/dl) within each 6-month interval were plotted against time from fulfilment of heart failure criteria. A binomial test was used to compare proportions. RESULTS: In patients with rheumatoid arthritis who developed heart failure, the proportion with ESR >/=40 mm/h was highest (23%) during the 6-month period immediately preceding the new-onset heart failure, as compared with the average ESR during the entire remaining follow-up period, both before and after heart failure (10.6%; p<0.01). The proportion of patients with anaemia peaked (54%) during the 6-month period after heart failure. CONCLUSIONS: Inflammatory stimuli may be involved in the initiation of heart failure among patients with rheumatoid arthritis.

Immunophenotyping of chimeric cells in localized scleroderma.

OBJECTIVE: Localized scleroderma causes thickening of the skin due to excessive collagen deposition. This condition has clinical and histopathological similarities to chronic graft-vs-host disease. We wanted to identify whether chimeric cells are present in the affected tissue in localized scleroderma and to further investigate the role of chimerism by immunophenotyping the chimeric cells. We hypothesize that the presence of chimerism and immunotypic chimeric cells will lend to an understanding of the pathogenesis of localized scleroderma and possible mechanisms by which chimeric cells participate in autoimmunity. METHODS: We studied skin biopsies from 18 localized scleroderma patients and compared them with concurrent biopsies from unaffected skin in a subset of patients. Skin biopsies from morphoea and linear scleroderma patients were analysed for the presence of chimeric cells using male-female (X, Y) differences. Cell surface markers (CD4, CD8, CD19/20, CD68, S100, CD14 and CD56) were determined for cell phenotyping of chimeric cells. RESULTS: Overall, the affected tissue contained a greater number of lymphocytic inflammatory cells. In the affected tissue, 38% of the total chimeric cells were CD68+ (dendritic cell, monocyte and macrophage marker), 29% Langerin/S100+ (dendritic cell marker), 26% CD8+ (cytotoxic T-lymphocyte marker), 20% CD19/20+ (B-lymphocyte marker), 14% CD4+ (T-helper lymphocyte) and 0% CD56+ (natural killer cell marker). CONCLUSIONS: We report that not only are chimeric cells present in affected localized scleroderma lesions but they also are more likely to be dendritic cells and B lymphocytes suggesting a role in the pathogenesis of localized scleroderma.

Extra-articular disease manifestations in rheumatoid arthritis: incidence trends and risk factors over 46 years.

OBJECTIVE: To investigate the trends in incidence of extra-articular rheumatoid arthritis (ExRA) in a well defined community based cohort of patients with rheumatoid arthritis (RA), and to examine possible predictors of ExRA occurrence. METHODS: Using the resources of the Rochester Epidemiology Project, a retrospective medical record review was conducted of a cohort of 609 cases of RA in Olmsted County, MN, diagnosed during 1955-94. These cases had been previously classified using the ACR 1987 criteria for RA. Patients were followed up from 1955 to 2000 (median follow up 11.8 years; range 0.1-42.8), and incident ExRA manifestations were recorded according to predefined criteria. Time to first presentation of ExRA was compared in patients with RA by decade of diagnosis. Possible ExRA risk factors were identified in case record reviews. RESULTS: ExRA occurred in 247 patients (40.6%). A subgroup of 78 patients (12.8%) had ExRA manifestations considered to be severe in a previous study from Malmö, Sweden. The incidence of severe ExRA did not change significantly over the decades (p=0.165). In a multivariate analysis the main predictors of severe ExRA were smoking at RA diagnosis (risk ratio (RR)=2.94; 95% confidence interval (95% CI) 1.68 to 5.13) and early disability (Steinbrocker class III-IV at diagnosis) (RR=2.45; 95% CI 1.51 to 4.00). The effect of smoking overwhelmed the weaker effect of rheumatoid factor seropositivity. CONCLUSION: There was no decrease in the incidence of extra-articular manifestations in patients with RA diagnosed up to 1995. Smoking and early disability are independent risk factors for extra-articular RA.

Cost-equivalence of different osteoporotic fractures.

METHODS: Among 985 Olmsted County, Minnesota, residents who experienced an osteoporotic fracture (distal forearm, humerus, clavicle/scapula/sternum, ribs, vertebrae, pelvis, hip, other femur or tibia/fibula [the latter in women only]), we estimated the incremental cost of direct medical care in the following year compared with age- and sex-matched controls without a fracture randomly sampled from the same community. RESULTS: The overall median incremental (case minus control) cost in the succeeding year was $2,390, with a particularly high incremental cost for hip fractures ($11,241). There was fair concordance between the incremental cost of the different fractures, relative to hip fracture alone, and the previously published disutility associated with each fracture type relative to hip fracture. Overall, the incremental cost for all osteoporotic fractures combined was 46% greater than that for hip fractures alone in women and 47% greater in men. This is consistent with the earlier report that overall morbidity from all osteoporotic fractures combined is 47% and 39% greater in women and men, respectively, than the morbidity attributable solely to hip fractures. CONCLUSION: These data lend support to the notion that other osteoporotic fractures can be quantified relative to hip fracture on the basis of their cost, as well as their morbidity and mortality. This may simplify health economic analyses by allowing all fracture outcomes to be modeled relative to hip fractures (i.e., hip fracture 'equivalents') and will provide a more comprehensive assessment of osteoporosis outcomes than is possible by focusing only on hip fractures.

Direct medical costs attributable to osteoporotic fractures.

Osteoporotic fractures are a major cause of morbidity in the elderly, the most rapidly growing segment of our population. We characterized the incremental direct medical costs following such fractures in a population-based cohort of men and women in Olmsted County, Minnesota. Cases included all County residents 50 years of age and older with an incident fracture due to minimal or moderate trauma between January 1, 1989 and January 1, 1992. For each case, a control of the same age (+/- 1 year) and sex who was attended in the local medical system in the same year was identified. Total incremental costs (cases - controls) in the year after fracture were estimated. Unit costs for each health service/procedure were obtained through the Mayo Cost Data Warehouse, which provides a standardized, inflation-adjusted estimate reflecting the national average cost of providing the service. Regression analysis was used to identify factors associated with incremental costs. There were 1263 case/control pairs; their average age was 73.8 years and 78% were female. Median total direct medical costs were $761 and $625, respectively, for cases and nonfracture controls in the year prior to fracture, and $3884 and $712, respectively, in the year following fracture. The highest median incremental costs were for distal femur ($11756) and hip fractures ($11241), whereas the lowest were for rib fractures ($213). Although hip fractures resulted in more incremental cost than any other fracture type, this amounted to only 37% of the total incremental cost of all moderate-trauma fractures combined. Regression analyses revealed that age, prior year costs and type of fracture were significant predictors of incremental costs (p<0.03 for all comparisons). The incremental costs of osteoporotic fractures are therefore substantial. Whereas hip fractures contributed disproportionately, they accounted for only one-third of the total incremental cost of fractures in our cohort. The use of incremental costs in economic analyses will provide a more accurate reflection of the true cost-effectiveness of osteoporosis prevention.