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.

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.

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.

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.

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 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.

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.

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.

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.

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.

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.

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.

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.

Primary hyperparathyroidism and the risk of fracture: a population-based study.

While severe primary hyperparathyroidism (HPT) is clearly associated with osteitis fibrosa cystica, it remains uncertain whether mild, asymptomatic primary HPT adversely affects the skeleton. Thus, we assessed the incidence of age-related fractures in a large, population-based inception cohort of 407 cases of primary HPT (93 men and 314 women) recognized during the 28-year period, 1965-1992. Fracture risk was assessed by comparing new fractures at each site to the number expected from gender- and age-specific fracture incidence rates for the general population (standardized incidence ratios, SIRs). These community patients with primary HPT mostly had mild disease (mean +/- SD serum calcium, 10.9 +/- 0.6 mg/dl). Altogether, 471 fractures occurred during 5766 person-years of follow-up. Overall fracture risk was significantly increased in these patients (SIR 1.3, 95% confidence interval [CI] 1.1-1.5). Primary HPT was associated with an increased risk of vertebral (SIR 3.2, 95% CI 2.5-4.0), distal forearm (SIR 2.2, 95% CI 1.6-2.9), rib (SIR 2.7, 95% CI 2.1-3.5), and pelvic fractures (SIR 2.1, 95% CI 1. 1-3.5). The risk of proximal femur fractures was only marginally increased (SIR 1.4, 95% CI 1.0-2.0). By univariate analysis, increasing age and female gender were significant predictors of fracture risk, although higher serum calcium levels were also associated with increased fracture risk, and parathyroid surgery may have had a protective effect. By multivariate analysis, however, only age (relative hazard [RH] per 10-year increase, 1.6, 95% CI 1. 4-1.9) and female gender (RH 2.3, 95% CI 1.2-4.1) remained significant independent predictors of fracture risk. Thus, primary HPT among unselected patients in the community is associated with a significant increase in the risk of vertebral, Colles', rib, and pelvic fractures. These data have important implications for the current trend to recommend nonsurgical management for patients with mild primary HPT.

Circadian and seasonal occurrence of subarachnoid and intracerebral hemorrhage.

OBJECTIVE: To determine whether the time of onset of subarachnoid hemorrhage (SAH) or intracerebral hemorrhage (ICH) is associated with a time of day or season of year. BACKGROUND: Prior studies have suggested that there may be a circadian and seasonal pattern of ischemic stroke occurrence, but this is less certain for hemorrhagic stroke. Population-based data have been unavailable. METHODS: All incident ICH and SAH among residents of Rochester, MN, were ascertained. The medical records of patients were reviewed to determine the time of onset and date of occurrence. The day was divided into 8-hour periods, and the year into seasonal quartiles. Each patient was assigned a period based on the time of onset of symptoms. The data were analyzed by chi(2) analysis to determine whether there was a trend toward increased occurrence based on time period or seasonal quartile of onset. RESULTS: From 1960 to 1989, there were 155 cases (48 men, 107 women) of incident SAH. From 1975 to 1989, there were 137 cases (57 men, 80 women) of incident ICH. There was a significant increase in the time of onset for ICH and SAH in the 8 AM to 4 PM period (p = 0.005 and p = 0.03, respectively). The concomitant occurrence of hypertension, gender, and age did not affect the time of day of occurrence. In the analysis of seasonal variation, there was a significant increase in events during December, January, and February in the combined SAH and ICH group (p = 0.032) and a trend for SAH alone (p = 0.07) but not for ICH (p = 0.34). Hypertension and age had no impact on the association between season and the occurrence of SAH and ICH. CONCLUSION: The occurrence of SAH and ICH is increased from 8 AM to 4 PM. The occurrence of hemorrhage is increased during the winter months, but this is likely limited only to SAH.

Fracture risk after surgery for peptic ulcer disease: a population-based cohort study.

In the 30-year period from 1956 to 1985, 471 Rochester, MN residents had an initial operation for peptic ulcer disease, 438 of whom were followed for at least 30 days (median 14.8 years per subject). In this population-based cohort, risk was elevated for all of the fracture sites traditionally associated with osteoporosis, including the proximal femur (standardized incidence ratio [SIR] 2.5, 95% CI 1.9-3.3), vertebra (SIR 4.7, 95% CI 3.8-5.7), and distal forearm (SIR 2.2, 95% CI 1.5-3.1). Fracture risk rose with age and was greater among women than men, but there was no influence on overall fracture risk of ulcer type or nature of the operation. In multivariate analyses, the independent predictors of vertebral fractures were age (hazard ratio [HR] per 10-year increase 1.8, 95% CI 1.6-2.0), use of corticosteroids (HR 2.3, 95% CI 1.01-5.2), thyroid replacement (HR 2.5, 95% CI 1.4-4.6), chronic anticoagulation (HR 2.3, 95% CI 1.1-4.6), and the presence of one or more conditions associated with secondary osteoporosis (HR 1.6, 95% CI 1.2-2.1). Gastrectomy with Billroth II reconstruction appeared to be relatively protective (HR 0.5, 95% CI 0.3-0.9), but such patients still had an increased risk of vertebral fractures compared with community residents generally (SIR 3.6, 95% CI 2.4-5.4). The independent predictors of hip fracture risk in this cohort were age (HR 2.7, 95% CI 2.1-3.5) and use of corticosteroids (HR 5.8, 95% CI 2.2-15.3) or anticonvulsants (HR 4.6, 95% CI 1.8-12.0), while higher body mass index was protective (HR 0.9, 95% CI 0.8-0.96). The independent predictors of distal forearm fractures were female gender (HR 4.7, 95% CI 2.2-10.1) and chronic anticoagulant use (HR 2.8, 95% CI 1.1-7.3). Thus, while the risk of osteoporotic fractures was significantly increased among patients operated for peptic ulcers, this appeared to be due more to specific characteristics of the cohort than to adverse effects of particular surgical procedures.

Fractures following thyroidectomy in women: a population-based cohort study.

Hip fracture risk has been associated with hyperthyroidism and thyroidectomy in men and with hyperthyroidism in women, but the influence of thyroidectomy on fracture risk in women has not been adequately addressed. The 630 Rochester, MN women who underwent thyroidectomy in 1950-1974 were followed subsequently for 12,804 person-years (retrospective cohort study) during which 601 fractures were observed. Relative to incidence rates in the community, there was no increase in overall fracture risk (standardized incidence ratio [SIR] 0.9; 95% confidence interval [CI] 0.8-1.00). No increase was seen in limb fractures generally or in distal forearm fractures specifically (SIR 1.1, 95% CI 0.8-1.4). There was a modest but statistically significant increase in the risk of hip fractures following thyroidectomy (SIR 1.3, 95% CI 1.01-1.8), but much greater increases were apparent in the risk of subsequent fractures of the ribs, spine, and pelvis. There was almost a threefold increase in vertebral fractures (SIR 2.8, 95% CI 2.3-3.3), but the excess was mostly observed long after the original operation and may be attributable to ascertainment bias. Fracture risk was associated with advancing age and with the presence of one or more of the diseases that have been associated with secondary osteoporosis but not with a history of hyperthyroidism, extent of thyroid surgery, or subsequent use of thyroid replacement therapy. Thus, with the exception of some fractures of the axial skeleton, which might have been more completely diagnosed among affected women, there was no increase in fracture risk among women following thyroidectomy performed mainly for adenoma or goiter.

Endometrial cancer in Olmsted County, MN: trends in incidence, risk factors and survival.

PURPOSE: We updated an earlier study in this community from 1945-1974 in order to assess trends in the incidence of, risk factors for, and survival from endometrial cancer in 1975-1991. METHODS: Incidence rates were based on all new cases of endometrial cancer diagnosed among Olmsted County, Minnesota, women during the years 1975-1991, with the population denominator from decennial census data. Risk factors were assessed with conditional logistic regression comparing the incidence cases to age- and gender-matched controls with intact uteri seen the same year the case was diagnosed. Survival was assessed using the Kaplan-Meier method. RESULTS: The incidence of endometrial cancer (age-adjusted to 1970 United States total) in 1975-1991 was 14.3 per 100,000 person-years, which is slightly increased from 1965-74. The rate was 21.7 per 100,000 person-years after adjustment for hysterectomy prevalence. As in the previous study, conjugated estrogen use for six months or more (odds ratio [OR] 2.71; 95% confidence interval [CI] 1.14-6.46) and body mass index (OR 1.06; 95% CI 1.01-1.11) increased the risk of endometrial cancer. The five-year relative survival rate (82%) was not improved over the earlier study. CONCLUSIONS: A small increase in endometrial cancer incidence was linked to the same risk factors identified in an earlier study in this community. No improvement in survival was seen.

Causes of death in patients with tuberous sclerosis.

Of the 355 patients with tuberous sclerosis complex (TSC) examined at the Mayo Clinic, 49 had died (9 of causes other than TSC). We attempted to determine what pattern of organ involvement occurred most often in the 40 patients who died of TSC. One baby died of cardiac failure due to cardiac rhabdomyomas, and one child died of rupture of an aneurysm of the thoracic aorta. Eleven patients died of renal disease, which was the commonest cause of death. Ten patients died as a result of brain tumors, and four patients (who were 40 years of age or older) died of lymphangiomyomatosis of the lung. Thirteen patients with severe mental handicaps died of either status epilepticus or bronchopneumonia; in all but one of these patients, the only source of information was the death certificate. Survival curves show a decreased survival for patients with TSC in comparison with that for the general population. Patients with TSC need lifelong follow-up for early detection of potentially life-threatening complications.