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Background: As women age, the lobules in their breasts undergo involution or regression. We investigated whether lobular involution in women with benign breast disease was associated with subsequent breast cancer risk. Methods: We examined biopsy specimens of 8736 women in the Mayo Benign Breast Disease Cohort from whom biopsy samples were taken between January 1, 1967, and December 31, 1991. Median follow-up for breast cancer outcomes was 17 years. We classified lobular involution in the background breast tissue as none (0% involuted lobules), partial (1%-74%), or complete ([greater than or equal to]75%). Subsequent breast cancer events and data on other risk factors were obtained from medical records and follow-up questionnaires. To estimate relative risks (RRs), standardized incidence ratios were calculated by use of incidence rates from the Iowa Surveillance, Epidemiology, and End Results (SEER) Registry. All statistical tests were two-sided. Results: Distribution of extent of involution was none among 1627 (18.6%) women, partial among 5197 (59.5%), and complete among 1912 (21.9%). Increased involution was positively associated with increased age and inversely associated with parity (both P

Background: The risk for venous thromboembolism during pregnancy or postpartum is uncertain. Objectives: To estimate the relative and absolute risk for deep venous thrombosis and pulmonary embolism during pregnancy and postpartum and to describe trends in incidence. Design: Population-based inception cohort study using the resources of the Rochester Epidemiology Project. Setting: Olmsted County, Minnesota. Patients: Women with deep venous thrombosis or pulmonary embolism first diagnosed between 1966 and 1995, including women with venous thromboembolism during pregnancy or the postpartum period (defined as delivery of a newborn no more than 3 months before the deep venous thrombosis or pulmonary embolism event date, including delivery of a stillborn infant after the first trimester). Measurements: The authors obtained yearly counts of live births in Olmsted County between 1966 and 1995 from the Minnesota Department of Health. Results: The relative risk (standardized incidence ratio) for venous thromboembolism among pregnant or postpartum women was 4.29 (95% CI, 3.49 to 5.22; P< 0.001), and the overall incidence of venous thromboembolism (absolute risk) was 199.7 per 100000 woman-years. The annual incidence was 5 times higher among postpartum women than pregnant women (511.2 vs. 95.8 per 100 000), and the incidence of deep venous thrombosis was 3 times higher than that of pulmonary embolism (151.8 vs. 47.9 per 100 000). Pulmonary embolism was relatively uncommon during pregnancy versus the postpartum period (10.6 vs. 159.7 per 100 000). Over the 30-year study period, the incidence of venous thromboembolism during pregnancy remained relatively constant whereas the postpartum incidence of pulmonary embolism decreased more than 2-fold. Limitations: Because the Olmsted County population was 98% white and of non-Hispanic ethnicity, the results may not be generalizable to other ethnicities. Conclusions: Among pregnant women, the highest risk period for venous thromboembolism and pulmonary embolism in particular is during the postpartum period. Any prophylaxis against these events should be particularly targeted to postpartum women. Although the incidence of pulmonary embolism has decreased over time, the incidence of deep venous thrombosis remains unchanged, indicating the need to better identify pregnant women at increased risk.

Objective: To assess the potential impact of controlling risk factors on the incidence of venous thromboembolism by estimating the population attributable risk (defined as the percentage of all cases of a disease in a population that can be 'attributed' to a risk factor) for deep vein thrombosis and pulmonary embolism associated with venous thromboembolism risk factors. Methods: Using data from a population-based, nested, case-control study of the 625 Olmsted County, Minnesota, residents with a definite first lifetime deep vein thrombosis or pulmonary embolism diagnosed during the 15-year period 1976 to 1990 and 625 unaffected Olmsted County residents matched for age and sex, we developed a conditional logistic regression model appropriate to the matched case-control study design and then estimated attributable risk for the risk factors individually and collectively. Results: Fifty-nine percent of the cases of venous thromboembolism in the community could be attributed to institutionalization (current or recent hospitalization or nursing home residence). Hospitalization for surgery (24%) and for medical illness (22%) accounted for a similar proportion of the cases, while nursing home residence accounted for 13%. The individual attributable risk estimates for malignant neoplasm, trauma, congestive heart failure, central venous catheter or pacemaker placement, neurological disease with extremity paresis, and superficial vein thrombosis were 18%, 12%, 10%, 9%, 7%, and 5%, respectively. Together, the 8 risk factors accounted for 74% of disease occurrence. Conclusions: Factors associated with institutionalization independently account for more than 50% of all cases of venous thromboembolism in the community. Greater emphasis should be placed on prophylaxis for hospitalized medical patients. Other recognized risk factors account for about 25% of all cases of venous thromboembolism, while the remaining 25% of cases are idiopathic.

Background: Fractures are a manifestation of osteoporosis, but therapeutic interventions to reduce the risk of recurrent fractures are not widespread. Objective, To identify predictors of osteoporosis treatment in postmenopausal women following distal forearm fracture. Methods: This population-based retrospective cohort study included all postmenopausal women, 45 years or older, residing in Olmsted County, Minnesota, who sustained a distal forearm fracture due to minimal trauma (a fall from standing height or under) in 1993 to 1997. Complete medical records were reviewed for each subject and Cox proportional hazards regression was used to evaluate the relationship of baseline demographic and clinical characteristics to therapeutic interventions for osteoporosis within 12 months following the fracture. Results: A total of 343 women with a mean age of 70.5 years had a minimal trauma distal forearm fracture. Within 12 months, 83% had seen a nonorthopedic physician. Of these, 17% had a pharmacologic osteoporosis intervention and the 12-month actuarially estimated cumulative incidence of any intervention was 18% (95% confidence interval [CI], 14%-22%). In a multivariate analysis, treatment was more likely to be offered to those with a prior diagnosis of osteoporosis (relative risk [RR], 2.08; 95% CI, 1.21-3.58), previous distal forearm fracture (RR, 2.38; 95% CI, 1.30-4.34), or history of cigarette smoking (RR, 1.86; 95% CI, 1.11-3.12). Conclusions: Effective osteoporosis interventions are underutilized among postmenopausal women who experience an osteoporotic fracture. Further work is needed to overcome barriers to optimal osteoporosis management in these women who are at high risk for future complications of osteoporosis. Arch Intern Med. 2002;162:421-426

A medical history of abnormal blood clot formation and smoking appear to be risk factors for deep vein thrombosis and pulmonary embolism in pregnant women, according to a study of 85 pregnant women who had either condition during pregnancy and 85 pregnant women who did not. Deep vein thrombosis and pulmonary embolism are both caused by a blood clot that blocks the flow of blood.

More effort should be put into finding an operational definition of sarcopenia, or age-related muscle loss. A substantial part of the older population has low levels of muscle mass, which is associated with physical disability. A population-based cross-sectional age-stratified survey has been carried out to look at muscle mass change patterns and to estimate prevalence of sarcopenia.

Background: The incidence of venous thromboembolism has not been well described, and there are no studies of long-term trends in the incidence of venous thromboembolism. Objectives: To estimate the incidence of deep vein thrombosis and pulmonary embolism and to describe trends in incidence. Methods: We performed a retrospective review of the complete medical records from a population-based inception cohort of 2218 patients who resided within Olmstead County, Minnesota, and had an incident deep vein thrombosis or pulmonary embolism during the 25-year period from 1966 through 1990. Results: The overall average age- and sex-adjusted annual incidence of venous thromboembolism was 117 per 100 000 (deep vein thrombosis, 48 per 100 000; pulmonary embolism, 69 per 100 000), with higher age-adjusted rates among males than females (130 vs 110 per 100 000, respectively). The incidence of venous thromboembolism rose markedly with increasing age for both sexes, with pulmonary embolism accounting for most of the increase. The incidence of pulmonary embolism was approximately 45% lower during the last 15 years of the study for both sexes and all age strata, while the incidence of deep vein thrombosis remained constant for males across all age strata, decreased for females younger than 55 years, and increased for women older than 60 years. Conclusions: Venous thromboembolism is a major national health problem, especially among the elderly. While the incidence of pulmonary embolism has decreased over time, the incidence of deep vein thrombosis remains unchanged for men and is increasing for older women. These findings emphasize the need for more accurate identification of patients at risk for venous thromboembolism, as well as a safe and effective prophylaxis. Arch Intern Med. 1998;158:585-593

BACKGROUND: Reports of increased mortality from cardiovascular disease and malignancy in primary hyperparathyroidism have been based primarily on patients who have undergone parathyroidectomy. In order to assess the true impact of primary hyperthyroidism on mortality in the general population, we assessed survival in a large inception cohort of Rochester, Minnesota residents with primary hyperparathyroidism. Initially diagnosed over a 28-year span, the majority of whom were followed with uncomplicated disease. METHODS: All Rochester residents with primary hyperparathyroidism first recognized in 1965 to 1992 were identified through the Rochester Epidemiology Project medical records linkage system. Included as cases were patients with pathologic confirmation of hyperthyroidism, hypercalcemia with inappropriately elevated parathyroid hormone levels, or hypercalcemia for more than a year with no other cause. Survival was estimated using the Kaplan Meier product-limit method. The Cox proportional hazards model was used to determine associations, as relative hazards (RR) with 95% confidence intervals (CI), of various risk factors with time to death. RESULTS: During the study period, 435 cases of primary hyperparathyroidism were identified. Altogether, parathyroid surgery was performed on 126 patients (29%), with a mean delay between the initial elevated serum calcium level and surgery of 3.3 years. Patients who underwent surgery had higher maximum serum calcium levels than the patients who were observed (mean [+ or -] SD, 11.3 [+ or -] 0.7 versus 10.7 [+ or -] 0.4 mg/dL, P [is less than] 0.001), but their mean ages were similar (54 [+ or -] 16 versus 56 [+ or -] 17 years). Overall survival in the patients with primary hyperthyroidism was better than expected (P = 0.02), but by age-adjusted multivariate analysis, higher maximal serum calcium level was an independent predictor of mortality (RR = 1.3 per mg/dL; 95% CI: 1.1-1.6; P [is less than] 0.02). CONCLUSION: Overall survival is not adversely affected among unselected patients with mild primary HPT in the community, although patients with more severe disease, as manifested by higher serum calcium levels, may have an increased risk of death. Am J Med. 1998;104:115-122. [C] 1998 by Excerpta Medica, Inc.

Slow colonic transit appears to be the most important cause of constipation in the elderly. This was determined by a study of 52 people with constipation, 55 with irritable bowel syndrome and 92 with neither condition. Colonic transit was significantly longer in the group with constipation compared to the other two groups. Regular laxative use was also associated with constipation.

Background: The introduction of routine measurement of serum calcium levels led to a sharp increase in the incidence of primary hyperparathyroidism in the early 1970s. Objective: To evaluate the trends in the incidence of primary hyperparathyroidism since the mid-1970s. Setting: Rochester and Olmsted County, Minnesota. Design: Population-based descriptive study. Patients: All residents of Rochester, Minnesota, who received an initial diagnosis of primary hyperparathyroidism between 1965 and 1992 were identified through the medical records linkage system of the Rochester Epidemiology Project: Included as persons having definite cases (92% of the total) were patients with pathologically confirmed hyperparathyroidism, hypercalcemia with inappropriately elevated parathyroid hormone levels, or hypercalcemia that had lasted for more than a year and had no cause other than primary hyperparathyroidism. Measurements: Incidence rates were calculated and directly standardized to the population structure of white persons in the United States in 1990. Results: From 1965 to June 1874 (the prescreening era), the age- and sex-adjusted incidence of primary hyperparathyroidism in Rochester was 15 cases per 100 000 person-years. After measurement of calcium levels was added to the automated serum chemistry panel in July 1974, the incidence increased to 112 per 100 000 person-years in 1975 and then decreased somewhat, reflecting a sweeping effect. Despite improved case ascertainment, however, the incidence rate has continued to decrease; in 1992, the incidence was 4 per 100 000 person-years. A few patients had complications that might have been caused by hyperparathyroidism (22% between 1965 and June 1974 and 6% thereafter), and survival was not impaired in either period. The maximum serum calcium levels did not change (P = 0.15). Conclusions: The progressive decrease in the incidence of primary hyperparathyroidism is unexpected and suggests a significant change in the epidemiology of this disease., The incidence of primary hyperparathyroidism in Rochester, Minnesota has declined dramatically ever since physicians began routinely measuring blood levels of calcium in all patients. Measurement of calcium levels began in 1974, after which the incidence of hyperparathyroidism jumped from 15 cases per 100,000 person-years to 112 cases per 100,000 person-years. However, the incidence soon began to decline and reached 4 cases per 100,000 person-years by 1992. There could be many reasons for this, including estrogen use, inadequate dietary calcium or ionizing radiation.

Osteoporosis, the loss of mass of mineralized bone, is the most common metabolic bone disease. The depletion of minerals reduces the strength of the bone, and creates a high risk of fracture, which is the only symptom of osteoporosis. It is estimated that 250,000 hip fractures, 250,000 wrist fractures, and 500,000 vertebral fractures can be attributed to osteoporosis in the United States each year. The national cost of osteoporosis is estimated at over $6 billion annually. Early detection and treatment of osteoporosis can reduce the incidence of these fractures. To determine whether a screening program might be effective, the medical literature on bone mass assessment was reviewed. Bone mass measurements may be accomplished by a number of different techniques, all of which involve radiation. Quantitative computed tomography may be used. Another method is single-photon absorptiometry, which calculates bone mass by measuring the absorption of gamma rays. This technique has been greatly improved by the introduction of dual-photon absorptiometry, which measures gamma absorption at two different wavelengths to achieve greater precision. Likewise, dual-energy X-ray techniques have now been introduced for the same reason. Prospective studies have clearly indicated that women with greater bone mass loss have a greater risk of fracture. Estimates suggest that a single bone mass scan at menopause might reduce the lifetime risk of hip fracture from 10 to 8 percent, a reduction of 20 percent. However, these numbers are based on many assumptions. Prophylactic treatment involves estrogen replacement therapy for decades, and it is uncertain what levels of patient compliance could be expected. There have been no studies on the efficacy of prophylactic treatment based on early bone mass measurements. The development and preliminary trial of a screening program will be necessary before the public health impact of such a program can be determined. Until such data are available, screening should be limited to women with other indication of osteoporosis, such as an abnormal X-rays. (Consumer Summary produced by Reliance Medical Information, Inc.)

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ajog.2009.06.059 Byline: Christine A. Heisler (a), Giovanni D. Aletti (a), Amy L. Weaver (b), L. Joseph Melton (c), William A. Cliby (a), John B. Gebhart (a) Keywords: perioperative morbidity; risk adjustment; vaginal hysterectomy Abstract: We sought to develop and evaluate a risk-adjusted perioperative morbidity model for vaginal hysterectomy. Author Affiliation: (a) Division of Gynecologic Surgery, Mayo Clinic, Rochester, MN (b) Division of Biomedical Informatics and Biostatistics, Mayo Clinic, Rochester, MN (c) Divisions of Epidemiology and Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, MN Article History: Received 26 January 2009; Revised 24 April 2009; Accepted 24 June 2009 Article Note: (footnote) Supported in part by research Grant RA-30582 from the National Institutes of Health, US Public Health Service., Cite this article as: Heisler CA, Aletti GD, Weaver AL, et al. Improving quality of care: development of a risk-adjusted perioperative morbidity model for vaginal hysterectomy. Am J Obstet Gynecol 2010;202:137.e1-5.

In certain geographical regions, clusters of premature thelarche (breast development) have been reported, but due to lack of information about the condition, the significance of these clusters is unclear. Medical records from the Mayo Clinic for a 45-year period were studied to determine the characteristics of premature thelarche. Of 66 cases, 48 had premature thelarche without other conditions. Development began between the age of six months and two years in 60 percent of the cases. Frequency of reported cases increased at school age and was greater for the city of Rochester, Minnesota, possibly due to preschool or other regular examinations. Half of the girls had bilateral (both sides) development, and of those with unilateral development, slightly more were on the right side. In cases of both bilateral and unilateral development, over half regressed from six months to six years after diagnosis, while in a small number (under 15 percent), the condition persisted or increased slightly before regressing. Breast development persisted in only four of the cases. Age and breast size at diagnosis was not predictive of outcome. Thirty-nine of the now teenage and adult women responded to health survey questionnaires. No cases of breast or gynecologic cancer or autoimmune disease were reported, but there were three cases of minor breast dysfunction. All achieved normal height and development, and reproduction was normal among those attempting pregnancy. The results of the study indicate that premature thelarche, a self-limiting disease of low incidence, has no apparent adverse consequences associated with it. (Consumer Summary produced by Reliance Medical Information, Inc.)

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ajog.2006.10.390 Byline: Ebenezer O. Babalola (1), Adil E. Bharucha (2), Cathy D. Schleck (3), John B. Gebhart (1), Alan R. Zinsmeister (3), L. Joseph Melton (4) Keywords: Epidemiology; hysterectomy; indications; population utilization rate Abstract: The purpose of this study was to assess temporal trends for hysterectomy among Olmsted County, Minnesota women. Author Affiliation: (1) Department of Obstetrics and Gynecology, Mayo Clinic College of Medicine, Rochester, MN (2) Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, MN (3) Division of Biostatistics, Mayo Clinic College of Medicine, Rochester, MN (4) Division of Epidemiology, Mayo Clinic College of Medicine, Rochester, MN. Article History: Received 23 March 2006; Revised 13 June 2006; Accepted 3 October 2006 Article Note: (footnote) This study was supported in part by research grants HD 41129, AR 30582, and AG 04875 from the National Institutes of Health, US Public Health Service., Cite this article as: Babalola EO, Bharucha AE, Schleck CD, et al. Decreasing utilization of hysterectomy: a population-based study in Olmsted County, Minnesota, 1965-2002. Am J Obstet Gynecol 2007;196:214.e1-214.e7.

Research on a Minnesota-based historical cohort shows that hip fracture is a significant contributor to nursing home use and disability, but potential cost savings from prevention may be overcalculated in the current literature due to a failure to incorporate long-term follow-up, differential risk and mortality.

Background: Gastrointestinal (GI) tract symptoms are common among patients with diabetes mellitus (DM) seen in tertiary care centers. The degree to which this reflects referral bias is unclear. Objectives: To determine whether GI tract symptoms are more prevalent in unselected patients with DM from the general community compared with their age- and sex-matched counterparts without DM and to assess the association of GI tract symptoms in persons with DM with psychosomatic symptoms, medication use, and symptoms of autonomic neuropathy. Methods: In this population-based, cross-sectional study, Olmsted County, Minnesota, residents with type 1 DM, a random sample of residents with type 2 DM, and 2 age- and sex-stratified random samples of nondiabetic residents (total of 1262 person for the 4 groups) were mailed a previously validated symptom questionnaire. Results: Heartburn was less common in residents with type 1 DM vs controls (12% vs 23%; P [is less than] .05). No significant difference in prevalence was detected (residents with type 1 DM vs controls; residents with type 2 DM vs controls) for nausea or vomiting (12% vs 11%; 6% vs 6%), dyspepsia (19% vs 21%; 13% vs 17%), or constipation (17% vs 14%; 10% vs 12%). However, constipation and/or laxative use was slightly more common in residents with type 1 DM (27% vs 19%; P [is less than] .15), particularly in men, and was associated with the intake of calcium channel blockers. Conclusions: In the community, the prevalence of most GI tract symptoms is similar in persons with or without DM, except for a lower prevalence of heartburn and an increased prevalence of constipation or laxative use in residents with type 1 DM, especially in men. This difference is associated with calcium channel blocker use rather than symptoms of autonomic neuropathy. In community-based practices, physicians should not immediately assume that GI tract symptoms in patients with DM represent a complication of DM. Arch Intern Med. 2000;160:2808-2816

In recent decades there has been a decline in death rates associated with declines in the prevalence of hypertension and increased use of anti-hypertensive drugs within the general population. Whether [...]

Background: Reported risk factors for venous thromboembolism (VTE) vary widely, and the magnitude and independence of each are uncertain. Objectives: To identify independent risk factors for deep vein thrombosis and pulmonary embolism and to estimate the magnitude of risk for each. Patients and Methods: We performed a population-based, nested, case-control study of 625 Olmsted County, Minnesota, patients with a first lifetime VTE diagnosed during the 15-year period from January 1, 1976, through December 31, 1990, and 625 Olmsted County patients without VTE. The 2 groups were matched on age, sex, calendar year, and medical record number. Results: Independent risk factors for VTE included surgery (odds ratio [OR], 21.7; 95% confidence interval [CI], 9.4-49.9), trauma (OR, 12.7; 95% CI, 4.1-39.7), hospital or nursing home confinement (OR, 8.0; 95% CI, 4.5-14.2), malignant neoplasm with (OR, 6.5; 95% CI, 2.1-20.2) or without (OR, 4.1;95% CI, 1.9-8.5) chemotherapy, central venous catheter or pacemaker (OR, 5.6; 95% CI, 1.6-19.6), superficial vein thrombosis (OR, 4.3; 95% CI, 1.8-10.6), and neurological disease with extremity paresis (OR, 3.0; 95% CI, 1.3-7.4). The risk associated with varicose veins diminished with age (for age 45 years: OR, 4.2; 95% CI, 1.6-11.3; for age 60 years: OR, 1.9; 95% CI, 1.0-3.6; for age 75 years: OR, 0.9; 95% CI, 0.6-1.4), while patients with liver disease had a reduced risk (OR, 0.1; 95% CI, 0.0-0.7). Conclusion: Hospital or nursing home confinement, surgery, trauma, malignant neoplasm, chemotherapy, neurologic disease with paresis, central venous catheter or pacemaker, varicose veins, and superficial vein thrombosis are independent and important risk factors for VTE. Arch Intern Med. 2000;160:809-815

Background: The appropriate duration of oral anticoagulation after a first episode of venous thromboembolism (VTE) is uncertain and depends upon VTE recurrence rates. Objective: To estimate VTE recurrence rates and determine predictors of recurrence. Methods: Patients in Olmsted County, Minnesota, with a first lifetime deep vein thrombosis or pulmonary embolism diagnosed during the 25-year period from 1966 through 1990 (N = 1719) were followed forward in time through their complete medical records in the community for first VTE recurrence. Results: Four hundred four patients developed recurrent VTE during 10 198 person-years of follow-up. The overall (probable/definite) cumulative percentages of VTE recurrence at 7, 30, and 180 days and 1 and 10 years were 1.6% (0.2%), 5.2% (1.4%), 10.1% (4.1%), 12.9% (5.6%), and 30.4% (17.6%), respectively. The risk of recurrence was greatest in the first 6 to 12 months after the initial event but never fell to zero. Independent predictors of first overall VTE recurrence included increasing age and body mass index, neurologic disease with paresis, malignant neoplasm, and neurosurgery during the period from 1966 through 1980. Independent predictors of first probable/ definite recurrence included diagnostic certainty of the incident event and neurologic disease in patients with hospital-acquired VTE. Recurrence risk was increased by malignant neoplasm but varied with concomitant chemotherapy, patient age and sex, and study year. Conclusions: Venous thromboembolism recurs frequently, especially within the first 6 to 12 months, and continues to recur for at least 10 years after the initial VTE. Patients with VTE with neurologic disease and paresis or with malignant neoplasm are at increased risk for recurrence, while VTE patients with transient or reversible risk factors are at less risk. Arch Intern Med. 2000; 160: 761-768

Background: Vitamin K participates in bone metabolism and, since oral anticoagulants antagonize vitamin K, their use may increase the risk of osteoporosis. Objective: To evaluate fracture risk at all skeletal sites following exposure to oral anticoagulants. Methods: In a population-based retrospective cohort study, 572 Olmsted County, Minnesota, women 35 years or older at their first lifetime venous thromboembolism event between 1966 and 1990 were followed up for fractures. Risk was assessed by comparing new fractures with the number expected from sex- and age-specific fracture incidence rates for the general population (standardized incidence ratio [SIR]). Results: Altogether, 480 fractures occurred during 6314 person-years of follow-up. Increasing exposure to oral anticoagulation was associated with an increased SIR for vertebral fractures: at less than 3 months of exposure, 2.4 (95% confidence interval [CI], 1.6-3.4); 3 to less than 12 months, 3.6 (95% CI, 2.5-4.9); and 12 months or more, 5.3 (95% CI, 3.4-8.0); and for rib fractures: at less than 3 months, 1,6 (95% CI, 0.9-2.7); 3 to less than 12 months, 1.6 (95% CI, 0.9-2.6); and 12 months or more, 3.4 (95% CI, 1.8-5.7). The data revealed no increased risk for other types of fractures. Oral anticoagulation for 12 months or more was an independent predictor of vertebral fractures (P = .009) and rib fractures (P = .02), but not other fractures. Conclusions: Long-term exposure to oral anticoagulation is associated with an increased risk of vertebral and rib fractures. The mechanism by which this occurs is still unclear and needs further investigation. Arch Intern Med. 1999;159:1750-1756

BACKGROUND: Although patients with gastroesophageal reflux are often instructed to change their lifestyle, population-based data on the risk factors for reflux in the United States are lacking. METHODS: We performed a cross-sectional study in an age-and gender-stratified random sample of the population of Olmsted County, Minnesota. Residents aged 25 to 74 years were mailed a valid self-report questionnaire that measured reflux symptoms and potential risk factors. Logistic regression was used to estimate the odds ratios (OR) with 95% confidence intervals (CI) for reflux symptoms (heartburn or acid regurgitation) associated with potential risk factors. RESULTS: Overall, 1,524 (72%) of 2,118 eligible subjects responded. A body mass index [is greater than] 30 kg/m2 (OR = 2.8; CI, 1.7 to 4.5), reporting an immediate family member with heartburn or disease of the esophagus or stomach (OR = 2.6; CI, 1.8 to 3.7), a past history of smoking (OR = 1.6; CI, 1.1 to 2.3), consuming more than seven drinks per week (OR = 1.9; CI, 1.1 to 3.3), and a higher psychosomatic symptom checklist score (OR per 5 units = 1.4; CI, 1.3 to 1.6) were independently associated with frequent (at least weekly) reflux symptoms. CONCLUSION: Obesity is a strong risk factor for gastroesophageal reflux, although the value of weight reduction remains to be proven. That family history was also a risk factor suggests that there may be a genetic component to the disorder. Am J Med. 1999;106:642-649. [C]1999 by Excerpta Medica, Inc.

We are pleased to respond to the letter by Orchard et al. (1), especially since they first raised the following question: Do composite measures of chronic glycemia correlate or predict [...]

Objective.Women and men with rheumatoid arthritis (RA) have an increased risk for fragility fractures and cardiovascular disease (CVD), each of which has been reported to contribute to excess morbidity and mortality in these patients. Fragility fractures share similar risk factors for CVD but may occur at relatively younger ages in patients with RA. We aimed to determine whether a fragility fracture predicts the development of CVD in women and men with RA.Methods.We studied a population-based cohort with incident RA from 1955 to 2007 and compared it with age- and sex-matched non-RA subjects. We identified fragility fractures and CVD events following the RA incidence/index date, along with relevant risk factors. We used Cox models to examine the association between fractures and the development of CVD, in which fractures and CVD risk factors were modeled as time-dependent covariates.Results.There were 1171 subjects (822 women; 349 men) in each of the RA and non-RA cohorts. Over followup, there were 406 and 346 fragility fractures and 286 and 225 CVD events, respectively. The overall CVD risk was increased significantly for RA subjects following a fragility fracture (HR 1.81, 95% CI 1.38–2.37) but not for non-RA subjects (HR 1.18, 95% CI 0.85–1.63). Results were similar for women and men with RA.Conclusion.Fragility fractures in both women and men with RA are associated with an increased risk for CVD events and should raise an alert to clinicians to target these individuals for further screening and preventive strategies for CVD.

The study by K.E. Ensrud et al. of mortality in relation to vertebral fracture is discussed. Possible mechanisms underlying the increased mortality are explored.

The functional bowel disorders comprise gastrointestinal conditions attributable to no known structural abnormalities, or infectious or metabolic causes. Functional gastrointestinal symptoms are very common, affecting almost 4 million people between 1979 to 1981, and accounting for 427,000 hospitalizations in 1984. Because little is known about the underlying mechanisms of these disorders, diagnosis is often made by excluding other disorders. The development of standard criteria for diagnosing functional bowel disorders would improve diagnostic certainty, enhance physician and patient satisfaction, and standardize the selection of patients for clinical study. A questionnaire was recently developed that distinguishes persons with functional bowel disorders, such as non-ulcer dyspepsia and irritable bowel syndrome, from normal persons and patients with gastrointestinal disease of known cause. The questionnaire, which evaluated 46 symptom-related features, was completed by 361 subjects prior to clinical examination, which later indicated 115 cases of functional bowel disease, 101 cases of organic gastrointestinal disease, and 145 healthy persons. The newly-developed questionnaire may be a useful supplement in the diagnosis of functional gastrointestinal symptoms. (Consumer Summary produced by Reliance Medical Information, Inc.)

The identification of individuals at high risk for colon cancer is essential for an aggressive approach to preventing this disease. About six percent of the United States population will develop this common malignancy. Previous studies have suggested that individuals with pernicious anemia may be at increased risk for colon cancer but, thus far, reports have been inconclusive. Pernicious anemia is a serious blood condition characterized by a progressive decrease in red blood cells, muscle weakness, and gastrointestinal and neural disturbances; it can be successfully treated with vitamin B-12, iron and folic acid. A possible link between colon cancer and pernicious anemia is the high levels of gastrin (a digestive hormone) which often accompany pernicious anemia and may be associated with tumor growth. The complete medical history of 150 subjects who had pernicious anemia and lived in a particular city was reviewed retrospectively (the period covered was 1950 through 1979) and the incidence of cancers was recorded. These results were then compared with the expected rates of rectal and colon cancer in the local population. Among the patients with pernicious anemia, 14 cases of colorectal cancer were detected whereas 10.5 cases were expected. Individuals with pernicious anemia did not have a statistically significant increased risk for colorectal cancer. However, these patients may have a slightly higher than normal risk for colorectal adenocarcinoma (malignancy arising from glandular epithelium). The highest rates occurred in the five-year period after the initial diagnosis of pernicious anemia was made. During this period seven cancer cases occurred but only 1.7 were expected. No increased risk was observed for these individuals prior to or shortly after diagnosis of pernicious anemia. (Consumer Summary produced by Reliance Medical Information, Inc.)

Context:Thiazide diuretics, the antihypertensive agent prescribed most frequently worldwide, are commonly associated with hypercalcemia. However, the epidemiology and clinical features are poorly understood.Objective:To update the incidence of thiazide-associated hypercalcemia and clarify its clinical features.Patients and Methods:In a population-based descriptive study, Olmsted County, Minnesota, residents with thiazide-associated hypercalcemia were identified through the Rochester Epidemiology Project and the Mayo Clinic Laboratory Information System from 2002–2010 and were added to the historical cohort beginning in 1992.Main Outcome:Incidence rates were adjusted to the 2010 United States white population.Results:Overall, 221 Olmsted County residents were identified with thiazide-associated hypercalcemia an average of 5.2 years after initiation of treatment. Subjects were older (mean age, 67 years) and primarily women (86.4%). The incidence of thiazide-associated hypercalcemia increased after 1997 and peaked in 2006 with an annual incidence of 20 per 100 000, compared to an overall rate of 12 per 100 000 in 1992–2010. Severe hypercalcemia was not observed in the cohort despite continuation of thiazide treatment in 62.4%. Of patients discontinuing thiazides, 71% continued to have hypercalcemia. Primary hyperparathyroidism was diagnosed in 53 patients (24%), including five patients who underwent parathyroidectomy without thiazide discontinuation.Conclusions:Many patients with thiazide-associated hypercalcemia have underlying primary hyperparathyroidism. Additionally, a sharp rise in thiazide-associated hypercalcemia incidence began in 1998, paralleling the increase observed in primary hyperparathyroidism in this community. Case ascertainment bias from targeted osteoporosis screening is the most likely explanation.

How large is the silent epidemic? The ascendancy of osteoporosis to its present status as a leading health problem has led, finally, to the critical study of vertebral fractures. Although [...]

OBJECTIVES:Data on the incidence and natural history of diverticulitis are largely hospital-based and exclude the majority of diverticulitis patients, who are treated in an outpatient setting for uncomplicated diverticulitis. We assessed temporal trends in the epidemiology of diverticulitis in the general population.METHODS:Through the Rochester Epidemiology Project we reviewed the records of all individuals with a diagnosis of diverticulitis from 1980 to 2007 in Olmsted County, Minnesota, USA.RESULTS:In 1980–1989, the incidence of diverticulitis was 115/100,000 person-years, which increased to 188/100,000 in 2000–2007 (P<0.001). Incidence increased with age (P<0.001); however, the temporal increase was greater in younger people (P<0.001). Ten years after the index and second diverticulitis episodes, 22% and 55% had a recurrence, respectively. This recurrence rate was greater in younger people (hazard ratio (HR) per decade 0.63; 95% confidence interval (CI), 0.59–0.66) and women (HR 0.68; 95% CI, 0.58–0.80). Complications were seen in 12%; this rate did not change over time. Recurrent diverticulitis was associated with a decreased risk of complications (P<0.001). Age was associated with increased risk of local (odds ratio (OR) 1.27 per decade; 95% CI, 1.04–1.57) and systemic (OR 1.83; 95% CI, 1.20–2.80) complications. Survival after diverticulitis was lower in older people (P<0.001) and men (P<0.001) and worsened over time (P<0.001). The incidence of surgery for diverticulitis did not change from 1980 to 2007.CONCLUSIONS:The incidence of diverticulitis has increased by 50% in 2000–2007 compared with 1990–1999, and more so in younger people. Complications are relatively uncommon. Recurrent diverticulitis is frequent but typically uncomplicated. Younger people with diverticulitis have less severe disease, more recurrence, and better survival.

Fluoride has been proposed as a treatment for vertebral crush fracture syndrome, based on observations that fluoride intoxication is associated with increased mass of the skeleton and bony overgrowth. Fluoride increases bone density by increasing bone formation, and has more effect on the axial skeleton, specifically the spine, than the appendicular skeleton, which consists of the shoulders, the upper and lower extremities, and the pelvis. In one study, the fracture rate in patients receiving fluoride was 39 percent, while it was 50 percent in patients receiving other therapies. Fluoride therapy for vertebral crush syndrome is widely used and has been formally approved in eight European countries. It has not been associated with adverse consequences over a period of 20 years of clinical experience, and alternative treatments for vertebral crush syndrome have not been shown to be as effective. Currently, fluoride therapy is recommended for treating vertebral osteoporosis, a decrease in bone mass, in adults with symptoms of crush fracture syndrome, and should be supplemented with calcium and vitamin D. Fluoride should not be used in conditions of impaired kidney function, pregnancy, peptic ulcers, osteomalacia (a bone softening disease), and previous hip fracture. Effects of fluoride should be monitored by measuring bone mass each year. Adverse effects include nausea, vomiting, mild gastrointestinal bleeding, lower extremity pain, and possible hip fracture. (Consumer Summary produced by Reliance Medical Information, Inc.)

Active cancer is the major predictor of venous thromboembolism (VTE) recurrence, but further stratification of recurrence risk is uncertain. In a population-based cohort study of all Olmsted County, Minnesota, residents with active cancer-related incident VTE during the 35-year period from 1966 to 2000 who survived 1 day or longer, we estimated VTE recurrence, bleeding on anticoagulant therapy, and survival and tested cancer and noncancer characteristics and secondary prophylaxis as predictors of VTE recurrence and bleeding, using Cox proportional hazards modeling. Of 477 patients, 139 developed recurrent VTE over the course of 1533 person-years of follow-up. The adjusted 10-year cumulative VTE recurrence rate was 28.6%. The adjusted 90-day cumulative incidence of major bleeding on anticoagulation was 1.9%. Survival was significantly worse for patients with cancer who had recurrent VTE (particularly pulmonary embolism) and with bleeding on anticoagulation. In a multivariable model, brain, lung, and ovarian cancer; myeloproliferative or myelodysplastic disorders; stage IV pancreatic cancer; other stage IV cancer; cancer stage progression; and leg paresis were associated with an increased hazard, and warfarin therapy was associated with a reduced hazard, of recurrent VTE. Recurrence rates were significantly higher for cancer patients with 1 or more vs no predictors of recurrence, suggesting these predictors may be useful for stratifying recurrence risk.

This report of a 6‐month Phase 2 study documents the initial safety and efficacy of the IgM T cell receptor‐specific monoclonal antibody TOL 101 used as an induction agent for primary kidney transplant recipients.

Backgrounds Because reported survival after venous thromboembolism (VTE) varies widely, we performed a population-based retrospective cohort study to estimate survival, compare observed with expected survival, and determine predictors of short-term ([is less than or equal to] 7 days) and long-term survival ([is greater than] 7 days) after VTE. Methods: We followed the 25-year (1966-1990) inception cohort (n = 2218) of Olmsted County, Minnesota, patients with deep vein thrombosis alone (DVT) or pulmonary embolism with or without deep vein thrombosis (PE [+ or -] DVT) forward in time until death or the last clinical contact. Results: During 14 629 person-years of follow-up, 1333 patients died. Seven-day, 30-day, and 1-year VTE survival rates were 74.8% (DVT, 96.2%; PE [+ or -] DVT, 59.1%), 72.0% (DVT, 94.5%; PE [+ or -] DVT, 55.6%), and 63.6% (DVT, 85.4%; PE [+ or -] DVT, 47.7%), respectively. Observed survival after DVT, PE [+ or -] DVT, and overall was significantly worse than expected for Minnesota whites of similar age and sex (P [is less than] .001). More than one third of deaths occurred on the date of onset or after VTE that was unrecognized during life. Short-term survival improved during the 25-year study period, while long-term survival was unchanged. After adjusting for comorbid conditions, PE [+ or -] DVT was an independent predictor of reduced survival for up to 3 months after onset compared with DVT alone. Other independent predictors of both short- and long-term survival included age, body mass index, patient location at onset, malignancy, congestive heart failure, neurologic disease, chronic lung disease, recent surgery, and hormone therapy. Additional independent predictors of long-term survival included tobacco smoking, other cardiac disease, and chronic renal disease. Conclusions: Survival after VTE, and especially after PE [+ or -] DVT, is much worse than reported, and significantly less than expected survival. Compared with DVT alone, symptomatic PE [+ or -] DVT is an independent predictor of reduced survival for up to 3 months after onset, implying that treatment for the 2 disorders should be different. Arch Intern Med. 1999;159:445-453

To describe the prevalence of nonacute conditions among patients seeking health care in a defined US population, emphasizing age, sex, and ethnic differences.

Objective.Older women and men with rheumatoid arthritis (RA) are at increased risk for fractures, but limited information is available on fracture risk in younger individuals with RA and whether such risk occurs early in the disease onset or only when older. We determined the risk for fractures in both young and older women and men following RA diagnosis.Methods.We studied a population-based inception cohort with RA from Olmsted County, Minnesota, USA. We identified 822 women and 349 men diagnosed with RA between 1955 and 2007 (308 women and 110 men diagnosed before age 50) and an equal number of paired non-RA subjects, matched by sex and birth year. Incident fractures were collected through review of complete (inpatient and outpatient) medical records available through the linkage system of the Rochester Epidemiology Project.Results.The hazard ratio (HR; 95% CI) for a non-pathologic fracture occurring from no more than moderate trauma was 1.63 (1.36–1.96) for women and 1.40 (1.02–1.93) for men with RA. Findings were consistent for women and men diagnosed with RA at age ≥ 50 years [HR, 1.43 (1.16–1.77) and 1.34 (0.92–1.94), respectively], or at age < 50 years [HR, 2.34 (1.61–3.42) and 1.74 (0.91–3.30), respectively]. However, young women, but not young men, with RA were at increased fracture risk even before age 50 years (HR, 1.95 [1.08–3.51] and 0.82 [0.28–2.45], respectively).Conclusion.Young men with RA are at increased risk for fractures only when older, whereas young women with RA have an elevated fracture risk even while still young.

The Rochester Epidemiology Project (REP) has maintained a comprehensive medical records linkage system for nearly half a century for almost all persons residing in Olmsted County, Minnesota. Herein, we provide a brief history of the REP before and after 1966, the year in which the REP was officially established. The key protagonists before 1966 were Henry Plummer, Mabel Root, and Joseph Berkson, who developed a medical records linkage system at Mayo Clinic. In 1966, Leonard Kurland established collaborative agreements with other local health care providers (hospitals, physician groups, and clinics [primarily Olmsted Medical Center]) to develop a medical records linkage system that covered the entire population of Olmsted County, and he obtained funding from the National Institutes of Health to support the new system. In 1997, L. Joseph Melton III addressed emerging concerns about the confidentiality of medical record information by introducing a broad patient research authorization as per Minnesota state law. We describe how the key protagonists of the REP have responded to challenges posed by evolving medical knowledge, information technology, and public expectation and policy. In addition, we provide a general description of the system; discuss issues of data quality, reliability, and validity; describe the research team structure; provide information about funding; and compare the REP with other medical information systems. The REP can serve as a model for the development of similar research infrastructures in the United States and worldwide.

OBJECTIVE To repeat the Clinical vs Neurophysiology (Cl vs N Phys) trial using “unequivocally abnormal” signs and symptoms (Trial 2) compared with the earlier trial (Trial 1), which used “usual” signs and symptoms. DESIGN Standard and referenced nerve conduction abnormalities were used in both Trials 1 and 2 as the standard criterion indicative of diabetic sensorimotor polyneuropathy. Physician proficiency (accuracy among evaluators) was compared between Trials 1 and 2. SETTING Academic medical centers in Canada, Denmark, England, and the United States. PARTICIPANTS Thirteen expert neuromuscular physicians. One expert was replaced in Trial 2. RESULTS The marked overreporting, especially of signs, in Trial 1 was avoided in Trial 2. Reproducibility of diagnosis between days 1 and 2 was significantly (P = .005) better in Trial 2. The correlation of the following clinical scores with composite nerve conduction measures spanning the range of normality and abnormality was improved in Trial 2: pinprick sensation (P = .03), decreased reflexes (P = .06), touch-pressure sensation (P = .06), and the sum of symptoms (P = .06). CONCLUSIONS The simple pretrial decision to use unequivocally abnormal signs and symptoms—taking age, sex, and physical variables into account—in making clinical judgments for the diagnosis of diabetic sensorimotor polyneuropathy (Trial 2) improves physician proficiency compared with use of usual elicitation of signs and symptoms (Trial 1); both compare to confirmed nerve conduction abnormality.