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Background: Whether there is a kidney function threshold to statin effectiveness in patients with acute myocardial infarction is poorly understood. Our study sought to help fill this gap in clinical knowledge., Methods: We undertook a new-user cohort study of the effectiveness of statin therapy by level of estimated glomerular filtration rate (eGFR) in adults who were hospitalized for myocardial infarction between 2000 and 2008. Data came from the Cardiovascular Research Network. The primary clinical outcomes were 1-year all-cause mortality and cardiovascular hospitalizations, with adverse outcomes of myopathy and development of diabetes mellitus. We calculated incidence rates, the number needed to treat, and used Cox proportional hazards regression with propensity score matching and adjustment to control for confounding, with testing for variation of effect by level of kidney function., Results: Compared with statin non-initiators (n = 5583), statin initiators (n = 5597) had a lower propensity score-adjusted risk for death (hazard ratio 0.79; 95% confidence interval [CI], 0.71-0.88) and cardiovascular hospitalizations (hazard ratio 0.90; 95% CI, 0.82-1.00). We found little evidence of variation in effect by level of eGFR (P = .86 for death; P = .77 for cardiovascular hospitalization). Adverse outcomes were similar for statin initiators and statin non-initiators. The number needed to treat to prevent 1 additional death over 1 year of follow-up ranged from 15 (95% CI, 11-28) for eGFR <30 mL/min/1.73 m(2) requiring statin treatment over 2 years to prevent 1 additional death, to 67 (95% CI, 49-118) for patients with eGFR >90 mL/min/1.73 m(2)., Conclusions: Our findings suggest that there is potential for important public health gains by increasing the routine use of statin therapy for patients with lower levels of kidney function., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: Multimorbidity affects 26 million persons with diabetes, and care for comorbid chronic conditions may impact diabetes care quality. The aim of this study was to determine which chronic conditions were related to lack of achievement or achievement of diabetes care quality goals to determine potential targets for future interventions., Research Design and Methods: This is an exploratory retrospective analysis of electronic health record data for 23 430 adults, aged 18-75, with diabetes who were seen at seven Midwestern US health systems. The main outcome measures were achievement of six diabetes quality metrics in the reporting year, 2011 (glycated haemoglobin (HbA1c) control and testing, low-density lipoprotein control and testing, blood pressure control, kidney testing). Explanatory variables were 62 chronic condition indicators. Analyses were adjusted for baseline patient sociodemographic and healthcare utilization factors., Results: The 62 chronic conditions varied in their relationships to diabetes care goal achievement for specific care goals. Congestive heart failure was related to lack of achievement of cholesterol management goals. Obesity was related to lack of HbA1c and BP control. Mental health conditions were related to both lack of achievement and achievement of different care goals. Three conditions were related to lack of cholesterol testing, including congestive heart failure and substance-use disorders. Of 17 conditions related to achieving control goals, 16 were related to achieving HbA1c control. One-half of the comorbid conditions did not predict diabetes care quality., Conclusions: Future interventions could target patients at risk for not achieving diabetes care for specific care goals based on their individual comorbidities.

Background: Patient sex and age may influence rates of death after receiving an implantable cardioverter-defibrillator for primary prevention. Differences in outcomes other than mortality and whether these differences vary by heart failure symptoms, etiology, and left ventricular ejection fraction are not well characterized., Methods and Results: We studied 2954 patients with left ventricular ejection fraction ≤0.35 undergoing first-time implantable cardioverter-defibrillator for primary prevention within the Cardiovascular Research Network; 769 patients (26%) were women, and 2827 (62%) were aged >65 years. In a median follow-up of 2.4 years, outcome rates per 1000 patient-years were 109 for death, 438 for hospitalization, and 111 for heart failure hospitalizations. Procedure-related complications occurred in 8.36%. In multivariable models, women had significantly lower risks of death (hazard ratio 0.67, 95% CI 0.56 to 0.80) and heart failure hospitalization (hazard ratio 0.82, 95% CI 0.68 to 0.98) and higher risks for complications (hazard ratio 1.38, 95% CI 1.01 to 1.90) than men; patients aged >65 years had higher risks of death (hazard ratio 1.55, 95% CI 1.30 to 1.86) and heart failure hospitalization (hazard ratio 1.25, 95% CI 1.05 to 1.49) than younger patients. Age and sex differences were generally consistent in strata according to symptoms, etiology, and severity of left ventricular systolic dysfunction, except the higher risk of complications in women, which differed by New York Heart Association classification (P=0.03 for sex-New York Heart Association interaction), and the risk of heart failure hospitalization in older patients, which differed by etiology of heart failure (P=0.05 for age-etiology interaction)., Conclusions: The burden of adverse outcomes after receipt of an implantable cardioverter-defibrillator for primary prevention is substantial and varies according to patient age and sex. These differences in outcome generally do not vary according to baseline heart failure characteristics., (© 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Objective: Describe the prevalence of colonoscopy before age 50, when guidelines recommend initiation of colorectal cancer screening for average risk individuals., Method: We assembled administrative health records that captured receipt of colonoscopy between 40 and 49-years of age for a cohort of 204,758 50-year-old members of four US health plans and used backward recurrence time models to estimate trends in receipt of colonoscopy before age 50 and variation in early colonoscopy by age and sex. We also used self-reported receipt of colonoscopy from 27,157 40- to 49-year-old respondents to the 2010 National Health Interview Survey (NHIS) to estimate the association between early colonoscopy and sex, race/ethnicity, and geographic location based on logistic regression models that accounted for the complex NHIS sampling design., Results: About 5% of the health plan cohort had a record of colonoscopy before age 50. Receipt of early colonoscopy increased significantly from 1999 to 2010 (test for linear trend, p<0.0001), was more likely among women than men (RR=1.9, 95% CI 1.14-1.24) and in the east coast health plan compared to west coast and Hawaii plans. The NHIS analysis found that early colonoscopy was more likely in Northeastern residents compared to residents in the West (odds ratio=1.75, 95% CI 1.28-2.39)., Conclusion: Colonoscopy before age 50 is increasingly common., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: To examine the mortality and cardiovascular disease (CVD) burden among a population-based cohort of patients with systemic lupus erythematosus (SLE) with previously described late mean onset and low rates of organ-threatening disease., Methods: This retrospective population-based cohort study investigated incident cases of SLE diagnosed from 1991-2008 and followed through March 2009 to examine rates of death and CVD events: myocardial infarction, stroke, or congestive heart failure hospitalization. Cases were identified using the 1997 update of the 1982 American College of Rheumatology SLE criteria. Searches included electronic records, chart audits, and state death matches, with physician review. Age-matched and sex-matched population comparisons facilitated relative event rate calculations., Results: Seventy incident SLE cases had late mean onset (52 years), with an incidence of 5 cases per 100,000/year. Matched comparisons showed similar baseline rates of hypertension, hyperlipidemia, and diabetes. However, patients with SLE experienced more CVD in the 2 years preceding SLE diagnosis (OR 3.8, 95% CI 1.8, 8.0). The estimated 10-year mortality rates were 26% for SLE subjects versus 19% for comparisons, hazard ratio (HR) 2.1, p<0.01. Adjusted for prior CVD, SLE cases still demonstrated increased hazards of mortality (HR 1.9, p=0.01) and CVD event or death (HR 1.8, p=0.01)., Conclusion: This incident SLE cohort demonstrated nearly doubled mortality and CVD event hazards compared to age-matched and sex-matched comparisons, even after accounting for higher CVD events in the 2 years preceding SLE diagnosis. This raises research questions regarding delayed SLE diagnosis versus accelerated CVD prior to SLE, particularly in older-onset SLE.

Importance: Increased use of computed tomography (CT) in pediatrics raises concerns about cancer risk from exposure to ionizing radiation., Objectives: To quantify trends in the use of CT in pediatrics and the associated radiation exposure and cancer risk., Design: Retrospective observational study., Setting: Seven US health care systems., Participants: The use of CT was evaluated for children younger than 15 years of age from 1996 to 2010, including 4 857 736 child-years of observation. Radiation doses were calculated for 744 CT scans performed between 2001 and 2011., Main Outcomes and Measures: Rates of CT use, organ and effective doses, and projected lifetime attributable risks of cancer. RESULTS The use of CT doubled for children younger than 5 years of age and tripled for children 5 to 14 years of age between 1996 and 2005, remained stable between 2006 and 2007, and then began to decline. Effective doses varied from 0.03 to 69.2 mSv per scan. An effective dose of 20 mSv or higher was delivered by 14% to 25% of abdomen/pelvis scans, 6% to 14% of spine scans, and 3% to 8% of chest scans. Projected lifetime attributable risks of solid cancer were higher for younger patients and girls than for older patients and boys, and they were also higher for patients who underwent CT scans of the abdomen/pelvis or spine than for patients who underwent other types of CT scans. For girls, a radiation-induced solid cancer is projected to result from every 300 to 390 abdomen/pelvis scans, 330 to 480 chest scans, and 270 to 800 spine scans, depending on age. The risk of leukemia was highest from head scans for children younger than 5 years of age at a rate of 1.9 cases per 10 000 CT scans. Nationally, 4 million pediatric CT scans of the head, abdomen/pelvis, chest, or spine performed each year are projected to cause 4870 future cancers. Reducing the highest 25% of doses to the median might prevent 43% of these cancers., Conclusions and Relevance: The increased use of CT in pediatrics, combined with the wide variability in radiation doses, has resulted in many children receiving a high-dose examination. Dose-reduction strategies targeted to the highest quartile of doses could dramatically reduce the number of radiation-induced cancers.

Objectives: Poor oral health is an increasingly recognized risk factor for cardiovascular disease (CVD) and type 2 diabetes (T2D), but little is known about the association between toothbrushing or flossing and cardiometabolic disease risk. The purpose of this study was to examine the degree to which an oral hygiene index was associated with CVD and T2D risk scores among disease-free adults in the Survey of the Health of Wisconsin., Methods: All variables were measured in 2008-2010 in this cross-sectional design. Based on toothbrushing and flossing frequency, an oral hygiene index (poor, fair, good, excellent) was created as the primary predictor variable. The outcomes, CVD and T2D risk score, were based on previous estimates from large cohort studies. There were 712 and 296 individuals with complete data available for linear regression analyses in the CVD and T2D samples, respectively., Results: After covariate adjustment, the final model indicated that participants in the excellent (β ± SE = -0.019 ± 0.008, P = 0.020) oral hygiene category had a significantly lower CVD risk score as compared to participants in the poor oral hygiene category. Sensitivity analyses indicated that both toothbrushing and flossing were independently associated with CVD risk score, and various modifiable risk factors. Oral hygiene was not significantly associated with T2D risk score., Conclusions: Regular toothbrushing and flossing are associated with a more favorable CVD risk profile, but more experimental research is needed in this area to precisely determine the effects of various oral self-care maintenance behaviors on the control of individual cardiometabolic risk factors. These findings may inform future joint medical-dental initiatives designed to close gaps in the primary prevention of oral and systemic diseases., (© 2012 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Importance: Little is known about how different financial incentives between Medicare Advantage and Medicare fee-for-service (FFS) reimbursement structures influence use of cardiovascular procedures., Objective: To compare regional cardiovascular procedure rates between Medicare Advantage and Medicare FFS beneficiaries., Design, Setting, and Participants: Cross-sectional study of Medicare beneficiaries older than 65 years between 2003-2007 comparing rates of coronary angiography, percutaneous coronary intervention (PCI), and coronary artery bypass graft (CABG) surgery across 32 hospital referral regions in 12 states., Main Outcomes and Measures: Rates of coronary angiography, PCI, and CABG surgery., Results: We evaluated a total of 878,339 Medicare Advantage patients and 5,013,650 Medicare FFS patients. Compared with Medicare FFS patients, Medicare Advantage patients had lower age-, sex-, race-, and income-adjusted procedure rates per 1000 person-years for angiography (16.5 [95% CI, 14.8-18.2] vs 25.9 [95% CI, 24.0-27.9]; P < .001) and PCI (6.8 [95% CI, 6.0-7.6] vs 9.8 [95% CI, 9.0-10.6]; P < .001) but similar rates for CABG surgery (3.1 [95% CI, 2.8-3.5] vs 3.4 [95% CI, 3.1-3.7]; P = .33). There were no significant differences between Medicare Advantage and Medicare FFS patients in the rates per 1000 person-years of urgent angiography (3.9 [95% CI, 3.6-4.2] vs 4.3 [95% CI, 4.0-4.6]; P = .24) or PCI (2.4 [95% CI, 2.2-2.7] vs 2.7 [95% CI, 2.5-2.9]; P = .16). Procedure rates varied widely across hospital referral regions among Medicare Advantage and Medicare FFS patients. For angiography, the rates per 1000 person-years ranged from 9.8 to 40.6 for Medicare Advantage beneficiaries and from 15.7 to 44.3 for Medicare FFS beneficiaries. For PCI, the rates ranged from 3.5 to 16.8 for Medicare Advantage and from 4.7 to 16.1 for Medicare FFS. The rates for CABG surgery ranged from 1.5 to 6.1 for Medicare Advantage and from 2.5 to 6.0 for Medicare FFS. Across regions, we found no statistically significant correlation between Medicare Advantage and Medicare FFS beneficiary utilization for angiography (Spearman r = 0.19, P = .29) and modest correlations for PCI (Spearman r = 0.33, P = .06) and CABG surgery (Spearman r = 0.35, P = .05). Among Medicare Advantage beneficiaries, adjustment for additional cardiac risk factors had little influence on procedure rates., Conclusions and Relevance: Although Medicare beneficiaries enrolled in capitated Medicare Advantage programs had lower angiography and PCI procedure rates than those enrolled in Medicare FFS, the degree of geographic variation in procedure rates was substantial among Medicare Advantage beneficiaries and was similar in magnitude to that observed among Medicare FFS beneficiaries.

Importance: Randomized trials of implantable cardioverter-defibrillators (ICDs) for primary prevention predominantly used single-chamber devices. In clinical practice, patients often receive dual-chamber ICDs, even without clear indications for pacing. The outcomes of dual- vs single-chamber devices are uncertain., Objective: To compare outcomes of single- and dual-chamber ICDs for primary prevention of sudden cardiac death., Design, Setting, and Participants: Retrospective cohort study of admissions in the National Cardiovascular Data Registry's (NCDR) ICD registry from 2006-2009 that could be linked to Centers for Medicare & Medicaid Services fee-for-service Medicare claims data. Patients were included if they received an ICD for primary prevention and did not have a documented indication for pacing., Main Outcomes and Measures: Adjusted risks of 1-year mortality, all-cause readmission, heart failure readmission, and device-related complications within 90 days were estimated with propensity-score matching based on patient, clinician, and hospital factors., Results: Among 32,034 patients, 12,246 (38%) received a single-chamber device and 19,788 (62%) received a dual-chamber device. In a propensity-matched cohort, rates of complications were lower for single-chamber devices (3.51% vs 4.72%; P < .001; risk difference, -1.20 [95% CI, -1.72 to -0.69]), but device type was not significantly associated with 1-year mortality (unadjusted rate, 9.85% vs 9.77%; hazard ratio [HR], 0.99 [95% CI, 0.91 to 1.07]; P = .79), 1-year all-cause hospitalization (unadjusted rate, 43.86% vs 44.83%; HR, 1.00 [95% CI, 0.97-1.04]; P = .82), or hospitalization for heart failure (unadjusted rate, 14.73% vs 15.38%; HR, 1.05 [95% CI, 0.99-1.12]; P = .19)., Conclusions and Relevance: Among patients receiving an ICD for primary prevention without indications for pacing, the use of a dual-chamber device compared with a single-chamber device was associated with a higher risk of device-related complications and similar 1-year mortality and hospitalization outcomes. Reasons for preferentially using dual-chamber ICDs in this setting remains unclear.

Purpose: Clinical epidemiology studies increasingly rely on electronic medical records data. The validity of International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis codes is crucial as they are often used to identify conditions of interest. We evaluated the use of archived ICD-9-CM codes to identify two representative infection-related conditions, pneumonia and herpes simplex virus (HSV), in a defined health system., Methods: Records were obtained for a sample of 175 and 179 patients with ICD-9-CM codes for pneumonia and HSV, respectively. An adjudicated case status was assigned for each subject., Results: The presence of a single ICD-9-CM code had a positive predictive value of 88% for pneumonia and 86% for HSV. False positives (noncases) accounted for less than 10% of records evaluated for each condition., Conclusions: Our study demonstrates that ICD-9-CM codes for pneumonia and HSV were valid markers of a true history of these conditions, suggesting that ICD-9-CM codes can be used to successfully identify infection-related conditions in epidemiologic studies. However, validation studies for individual conditions may help identify condition-specific strategies to improve the performance of diagnostic codes., (Published by Elsevier Inc.)

Background: Nulliparity is associated with an increased risk of endometrial cancer. It is less clear whether nulliparity modifies the association between other established hormone-related risk factors. The proportion of nulliparous women has increased since the mid-1970s, but most individual studies to date have been too small to test the hypothesis that endometrial cancer risk factors may be associated more strongly with risk among nulliparous women compared with parous women., Methods: Data were aggregated on 26,936 postmenopausal, Caucasian, nulliparous women (360 endometrial cancers) and 146,583 postmenopausal, Caucasian, parous women (1378 endometrial cancers) from 4 US prospective studies (1979-2006). Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated in stratified analyses., Results: The risk of endometrial cancer was higher among nulliparous women than among parous women, as expected (nulliparous vs parous: HR, 1.42; 95% CI, 1.26-1.60). Stratified associations between endometrial cancer and hormone-related risk factors did not differ between nulliparous versus parous women: For both groups, oral contraceptives and earlier menopause were associated with reduced risk. The highest HRs were for obesity: A body mass index ≥30 kg/m(2) (vs <25 kg/m(2) ) increased the risk of endometrial cancer 3-fold among nulliparous women (HR, 3.04; 95% CI, 2.34-3.94) and parous women (HR, 2.88; 95% CI, 2.52-3.29)., Conclusions: The results from this large, pooled analysis of data from 4 large prospective studies suggested that nulliparity does not modify the risks of endometrial cancer associated with established hormone-related risk factors., (Copyright © 2012 American Cancer Society.)

Background: The effectiveness of screening colonoscopy in average-risk adults is uncertain, particularly for right colon cancer., Objective: To examine the association between screening colonoscopy and risk for incident late-stage colorectal cancer (CRC)., Design: Nested case-control study., Setting: Four U.S. health plans., Patients: 1039 average-risk adults enrolled for at least 5 years in one of the health plans. Case patients were aged 55 to 85 years on their diagnosis date (reference date) of stage IIB or higher (late-stage) CRC during 2006 to 2008. One or 2 control patients were selected for each case patient, matched on birth year, sex, health plan, and prior enrollment duration., Measurements: Receipt of CRC screening 3 months to 10 years before the reference date, ascertained through medical record audits. Case patients and control patients were compared on receipt of screening colonoscopy or sigmoidoscopy by using conditional logistic regression that accounted for health history, socioeconomic status, and other screening exposures., Results: In analyses restricted to 471 eligible case patients and their 509 matched control patients, 13 case patients (2.8%) and 46 control patients (9.0%) had undergone screening colonoscopy, which corresponded to an adjusted odds ratio (AOR) of 0.29 (95% CI, 0.15 to 0.58) for any late-stage CRC, 0.36 (CI, 0.16 to 0.80) for right colon cancer, and 0.26 (CI, 0.06 to 1.11; P = 0.069) for left colon/rectum cancer. Ninety-two case patients (19.5%) and 173 control patients (34.0%) had screening sigmoidoscopy, corresponding to an AOR of 0.50 (CI, 0.36 to 0.70) overall, 0.79 (CI, 0.51 to 1.23) for right colon late-stage cancer, and 0.26 (CI, 0.14 to 0.48) for left colon cancer., Limitation: The small number of screening colonoscopies affected the precision of the estimates., Conclusion: Screening with colonoscopy in average-risk persons was associated with reduced risk for diagnosis of incident late-stage CRC, including right-sided colon cancer. For sigmoidoscopy, this association was seen for left CRC, but the association for right colon late-stage cancer was not statistically significant.

Background: Breast, endometrial, and ovarian cancers share some hormonal and epidemiologic risk factors. While several models predict absolute risk of breast cancer, there are few models for ovarian cancer in the general population, and none for endometrial cancer., Methods and Findings: Using data on white, non-Hispanic women aged 50+ y from two large population-based cohorts (the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial [PLCO] and the National Institutes of Health-AARP Diet and Health Study [NIH-AARP]), we estimated relative and attributable risks and combined them with age-specific US-population incidence and competing mortality rates. All models included parity. The breast cancer model additionally included estrogen and progestin menopausal hormone therapy (MHT) use, other MHT use, age at first live birth, menopausal status, age at menopause, family history of breast or ovarian cancer, benign breast disease/biopsies, alcohol consumption, and body mass index (BMI); the endometrial model included menopausal status, age at menopause, BMI, smoking, oral contraceptive use, MHT use, and an interaction term between BMI and MHT use; the ovarian model included oral contraceptive use, MHT use, and family history or breast or ovarian cancer. In independent validation data (Nurses' Health Study cohort) the breast and ovarian cancer models were well calibrated; expected to observed cancer ratios were 1.00 (95% confidence interval [CI]: 0.96-1.04) for breast cancer and 1.08 (95% CI: 0.97-1.19) for ovarian cancer. The number of endometrial cancers was significantly overestimated, expected/observed = 1.20 (95% CI: 1.11-1.29). The areas under the receiver operating characteristic curves (AUCs; discriminatory power) were 0.58 (95% CI: 0.57-0.59), 0.59 (95% CI: 0.56-0.63), and 0.68 (95% CI: 0.66-0.70) for the breast, ovarian, and endometrial models, respectively., Conclusions: These models predict absolute risks for breast, endometrial, and ovarian cancers from easily obtainable risk factors and may assist in clinical decision-making. Limitations are the modest discriminatory ability of the breast and ovarian models and that these models may not generalize to women of other races. Please see later in the article for the Editors' Summary.

Background: Implantable cardioverter-defibrillators (ICDs) are increasingly used for primary prevention after randomized, controlled trials demonstrating that they reduce the risk of death in patients with left ventricular systolic dysfunction. The extent to which the clinical characteristics and long-term outcomes of unselected, community-based patients with left ventricular systolic dysfunction undergoing primary prevention ICD implantation in a real-world setting compare with those enrolled in the randomized, controlled trials is not well characterized. This study is being conducted to address these questions., Methods and Results: The study cohort includes consecutive patients undergoing primary prevention ICD placement between January 1, 2006 and December 31, 2009 in 7 health plans. Baseline clinical characteristics were acquired from the National Cardiovascular Data Registry ICD Registry. Longitudinal data collection is underway, and will include hospitalization, mortality, and resource use from standardized health plan data archives. Data regarding ICD therapies will be obtained through chart abstraction and adjudicated by a panel of experts in device therapy. Compared with the populations of primary prevention ICD therapy randomized, controlled trials, the cohort (n=2621) is on average significantly older (by 2.5-6.5 years), more often female, more often from racial and ethnic minority groups, and has a higher burden of coexisting conditions. The cohort is similar, however, to a national population undergoing primary prevention ICD placement., Conclusions: Patients undergoing primary prevention ICD implantation in this study differ from those enrolled in the randomized, controlled trials that established the efficacy of ICDs. Understanding a broad range of health outcomes, including ICD therapies, will provide patients, clinicians, and policy makers with contemporary data to inform decision-making.

Context: Use of diagnostic imaging has increased significantly within fee-for-service models of care. Little is known about patterns of imaging among members of integrated health care systems., Objective: To estimate trends in imaging utilization and associated radiation exposure among members of integrated health care systems., Design, Setting, and Participants: Retrospective analysis of electronic records of members of 6 large integrated health systems from different regions of the United States. Review of medical records allowed direct estimation of radiation exposure from selected tests. Between 1 million and 2 million member-patients were included each year from 1996 to 2010., Main Outcome Measure: Advanced diagnostic imaging rates and cumulative annual radiation exposure from medical imaging., Results: During the 15-year study period, enrollees underwent a total of 30.9 million imaging examinations (25.8 million person-years), reflecting 1.18 tests (95% CI, 1.17-1.19) per person per year, of which 35% were for advanced diagnostic imaging (computed tomography [CT], magnetic resonance imaging [MRI], nuclear medicine, and ultrasound). Use of advanced diagnostic imaging increased from 1996 to 2010; CT examinations increased from 52 per 1000 enrollees in 1996 to 149 per 1000 in 2010, 7.8% annual increase (95% CI, 5.8%-9.8%); MRI use increased from 17 to 65 per 1000 enrollees, 10% annual growth (95% CI, 3.3%-16.5%); and ultrasound rates increased from 134 to 230 per 1000 enrollees, 3.9% annual growth (95% CI, 3.0%-4.9%). Although nuclear medicine use decreased from 32 to 21 per 1000 enrollees, 3% annual decline (95% CI, 7.7% decline to 1.3% increase), PET imaging rates increased after 2004 from 0.24 to 3.6 per 1000 enrollees, 57% annual growth. Although imaging use increased within all health systems, the adoption of different modalities for anatomic area assessment varied. Increased use of CT between 1996 and 2010 resulted in increased radiation exposure for enrollees, with a doubling in the mean per capita effective dose (1.2 mSv vs 2.3 mSv) and the proportion of enrollees who received high (>20-50 mSv) exposure (1.2% vs 2.5%) and very high (>50 mSv) annual radiation exposure (0.6% vs 1.4%). By 2010, 6.8% of enrollees who underwent imaging received high annual radiation exposure (>20-50 mSv) and 3.9% received very high annual exposure (>50 mSv)., Conclusion: Within integrated health care systems, there was a large increase in the rate of advanced diagnostic imaging and associated radiation exposure between 1996 and 2010.

Context: Screening for ovarian cancer with cancer antigen 125 (CA-125) and transvaginal ultrasound has an unknown effect on mortality., Objective: To evaluate the effect of screening for ovarian cancer on mortality in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial., Design, Setting, and Participants: Randomized controlled trial of 78,216 women aged 55 to 74 years assigned to undergo either annual screening (n = 39,105) or usual care (n = 39,111) at 10 screening centers across the United States between November 1993 and July 2001. Intervention The intervention group was offered annual screening with CA-125 for 6 years and transvaginal ultrasound for 4 years. Participants and their health care practitioners received the screening test results and managed evaluation of abnormal results. The usual care group was not offered annual screening with CA-125 for 6 years or transvaginal ultrasound but received their usual medical care. Participants were followed up for a maximum of 13 years (median [range], 12.4 years [10.9-13.0 years]) for cancer diagnoses and death until February 28, 2010., Main Outcome Measures: Mortality from ovarian cancer, including primary peritoneal and fallopian tube cancers. Secondary outcomes included ovarian cancer incidence and complications associated with screening examinations and diagnostic procedures., Results: Ovarian cancer was diagnosed in 212 women (5.7 per 10,000 person-years) in the intervention group and 176 (4.7 per 10,000 person-years) in the usual care group (rate ratio [RR], 1.21; 95% confidence interval [CI], 0.99-1.48). There were 118 deaths caused by ovarian cancer (3.1 per 10,000 person-years) in the intervention group and 100 deaths (2.6 per 10,000 person-years) in the usual care group (mortality RR, 1.18; 95% CI, 0.82-1.71). Of 3285 women with false-positive results, 1080 underwent surgical follow-up; of whom, 163 women experienced at least 1 serious complication (15%). There were 2924 deaths due to other causes (excluding ovarian, colorectal, and lung cancer) (76.6 per 10,000 person-years) in the intervention group and 2914 deaths (76.2 per 10,000 person-years) in the usual care group (RR, 1.01; 95% CI, 0.96-1.06)., Conclusions: Among women in the general US population, simultaneous screening with CA-125 and transvaginal ultrasound compared with usual care did not reduce ovarian cancer mortality. Diagnostic evaluation following a false-positive screening test result was associated with complications. Trial Registration clinicaltrials.gov Identifier: NCT00002540.

Purpose: Urolithiasis is a common disease with multiple etiologies and risk factors. Studies suggest an increased incidence in developed nations in recent decades as well as differential geographic incidence and prevalence rates, and differences between the genders. We updated urolithiasis epidemiological data by examining the incidence and prevalence rates in a stable rural Wisconsin population., Materials and Methods: Data were obtained from the Marshfield Epidemiologic Study Area database, a surveillance tool created in 1991 to track disease in residents of an area of 24 ZIP Codes including approximately 85,000 individuals, of whom most receive care at Marshfield Clinic and affiliates. Urolithiasis cases were identified using ICD-9 codes. Incidence, prevalence and recurrence rates were determined., Results: The mean age adjusted incidence of new onset urolithiasis per 100,000 person-years was 202 (95% CL 168-235) in 1992 and 289 (95% CL 253-325) in 2008. In women the increase per 100,000 person-years was higher than in men, that is 171 (95% CL 129-213) and 289 (95% CL 238-340) vs 238 (95% CL 184-290) and 296 (95% CL 244-348), respectively. The male-to-female incidence ratio decreased from 1.4 to 1.0. The age adjusted prevalence per 100,000 individuals was 1,968 (2%) and 3,554 (3.5%) in 1992 and 2008, respectively. The increase in women was higher than in men (52% vs 26%). The age adjusted recurrence rate per 100,000 individuals was 553 (0.72%) and 676 (1.0%) in 1992 and 2008, respectively. The increase in women was higher than in men (88% vs 20%)., Conclusions: Since 1992, urolithiasis incidence, prevalence and recurrence rates in this rural Wisconsin population have increased with higher increases noted in women. While prevalence increased, it was lower than reported in other geographic areas in the United States., (Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Nulliparity is an established breast cancer risk factor, particularly when compared with parity at young ages. The authors aggregated data from 4 US prospective studies (1979-2006) including 32,641 nulliparous (1,612 breast cancers) and 204,270 parous (8,180 breast cancers) women to examine the hypothesis that nulliparity may increase susceptibility to established postmenopausal breast cancer risk factors. The aggregated hazard ratio for nulliparous versus all parous women = 1.27 (95% confidence interval: 1.21, 1.34), and that for nulliparous versus women <25 years of age at first birth = 1.38 (95% confidence interval: 1.30, 1.46). Among nulliparous women, the hazard ratios for current menopausal hormone therapy use (vs. never use), body mass index ≥30 kg/m(2) (vs. <25 kg/m(2)), and weekly consumption of ≥7 alcoholic drinks (vs. none) ranged from 1.3 to 1.6. The hazard ratios did not differ by parity. In a model including all women, the joint association for each of these factors and nulliparity combined compared with first birth before age 25 years was an approximately 2-fold increased breast cancer risk. Although the baseline risk is higher for nulliparous women compared with parous women, these results suggest that the associations between hormone-related factors and breast cancer do not differ by parity.

Purpose: The Gail model combines relative risks (RRs) for five breast cancer risk factors with age-specific breast cancer incidence rates and competing mortality rates from the Surveillance, Epidemiology, and End Results (SEER) program from 1983 to 1987 to predict risk of invasive breast cancer over a given time period. Motivated by changes in breast cancer incidence during the 1990s, we evaluated the model's calibration in two recent cohorts., Methods: We included white, postmenopausal women from the National Institutes of Health (NIH) -AARP Diet and Health Study (NIH-AARP, 1995 to 2003), and the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO, 1993 to 2006). Calibration was assessed by comparing the number of breast cancers expected from the Gail model with that observed. We then evaluated calibration by using an updated model that combined Gail model RRs with 1995 to 2003 SEER invasive breast cancer incidence rates., Results: Overall, the Gail model significantly underpredicted the number of invasive breast cancers in NIH-AARP, with an expected-to-observed ratio of 0.87 (95% CI, 0.85 to 0.89), and in PLCO, with an expected-to-observed ratio of 0.86 (95% CI, 0.82 to 0.90). The updated model was well-calibrated overall, with an expected-to-observed ratio of 1.03 (95% CI, 1.00 to 1.05) in NIH-AARP and an expected-to-observed ratio of 1.01 (95% CI: 0.97 to 1.06) in PLCO. Of women age 50 to 55 years at baseline, 13% to 14% had a projected Gail model 5-year risk lower than the recommended threshold of 1.66% for use of tamoxifen or raloxifene but >or= 1.66% when using the updated model. The Gail model was well calibrated in PLCO when the prediction period was restricted to 2003 to 2006., Conclusion: This study highlights that model calibration is important to ensure the usefulness of risk prediction models for clinical decision making.

Objective: Determine and compare the prevalence of known risk factors for cardiovascular disease among unselected individuals presenting with their first ever episode of atrial flutter (AFL) and atrial fibrillation (AF)., Study Design and Setting: We evaluated 11 pre-selected clinical variables including age, sex, smoking history and other potential cardiac risk factors. Using the resources of the Marshfield Epidemiologic Study Area, a population-based database, all newly diagnosed cases of either AFL or AF in the region during a 4-year period were identified., Results: Among the 472 incident cases, 76 (16.1%) had AFL and 396 (83.9%) had AF. Compared to those with AF, subjects with AFL were more likely to have had a history of chronic obstructive pulmonary disease (25% vs. 12%, P = 0.006), heart failure (28% vs. 17%, P = 0.05), and smoking (49% vs. 37%, P = 0.06). Hypertension, on the other hand, was more common among individuals with AF (63% vs. 47%, P = 0.01)., Conclusion: This study represents the first report to evaluate potential differences in the conditions associated with the development of AFL versus AF. Research into the mechanisms of atrial arrhythmogenesis may lead to improved preventive and therapeutic interventions.

Objective: Late stage cancer at diagnosis increases the likelihood of cancer death. We evaluated the relation of county-level poverty with late stage cancer for 18 anatomic sites using data from the North American Association of Central Cancer Registries., Methods: Stratified analysis and logistic regression were applied to 2 million incident cancers (1997-2000) from 32 states representing 57% of the United States., Results: For 12 sites, higher county poverty significantly increased the odds of late stage, [adjusted odds ratio (95% confidence interval) comparing highest to lowest county poverty: larynx 2.4 (1.8-3.2), oral cavity 2.2 (1.8-2.7), melanoma 2.0 (1.5-2.8), female breast 1.9 (1.7-2.2), prostate 1.7 (1.5-1.9), corpus uteri 1.6 (1.3-1.9), cervix 1.6 (1.3-2.1), bladder 1.6 (1.2-2.1), colorectum 1.4 (1.3-1.5), esophagus 1.3 (1.1-1.7), stomach 1.3 (1.1-1.5), and kidney 1.3 (1.1-1.5)]. With some exceptions, county poverty associations with stage were comparable across gender and race, but stronger among metropolitan cases. A few differences by age may reflect screening patterns., Conclusions: In this large population-based study, higher county poverty independently predicted distant stage cancer. This held for several non-screenable cancers, suggesting improved area economic deprivation, including access to and utilization of good medical care might facilitate earlier diagnosis and longer survival even for cancers without practical screening approaches.

Objective: To compare the clinicopathologic features and survival in the four breast cancer subtypes defined by immunohistochemistry (IHC) expression of estrogen receptor (ER) or progesterone receptor (PR) and human epidermal growth factor receptor 2 (Her2): ER/PR+, Her2+; ER/PR+, Her2-; ER/PR-, Her2+; and ER/PR-, Her2-., Methods: A 7-year retrospective study of 1134 invasive breast cancer subjects. Clinical and pathologic features and survival of the four subtypes were compared., Results: Using ER/PR+ and Her2- as a reference, ER/PR-, Her2- had the worst overall survival (hazard ratio, 1.8; 95% confidence interval [CI], 1.06-3.2) and the worst disease-free survival (hazard ratio, 1.5; 95% CI, 0.8-3.0). In ER/PR+, Her2-, chemotherapy conferred significant overall and disease-free survival advantages. Subtype comparison revealed statistically significant differences in outcomes., Conclusion: The triple negative subtype has the worst overall and disease free survival. Efforts should be directed at standardization of current testing methods and development of more reliable and reproducible testing.

Objective: To test whether annual screening with transvaginal ultrasonography and CA 125 reduces ovarian cancer mortality., Methods: Data from the first four annual screens, denoted T0-T3, are reported. A CA 125 value at or above 35 units/mL or an abnormality on transvaginal ultrasonography was considered a positive screen. Diagnostic follow-up of positive screens was performed at the discretion of participants' physicians. Diagnostic procedures and cancers were tracked and verified through medical records., Results: Among 34,261 screening arm women without prior oophorectomy, compliance with screening ranged from 83.1% (T0) to 77.6% (T3). Screen positivity rates declined slightly with transvaginal ultrasonography, from 4.6 at T0 to 2.9-3.4 at T1-T3; CA 125 positivity rates (range 1.4-1.8%) showed no time trend. Eighty-nine invasive ovarian or peritoneal cancers were diagnosed; 60 were screen detected. The positive predictive value (PPV) and cancer yield per 10,000 women screened on the combination of tests were similar across screening rounds (range 1.0-1.3% for PPV and 4.7-6.2 for yield); however, the biopsy (surgery) rate among screen positives decreased from 34% at T0 to 15-20% at T1-T3. The overall ratio of surgeries to screen-detected cancers was 19.5:1. Seventy-two percent of screen-detected cases were late stage (III/IV)., Conclusion: Through four screening rounds, the ratio of surgeries to screen-detected cancers was high, and most cases were late stage. However, the effect of screening on mortality is as yet unknown., Clinical Trial Registration: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00002540, Level of Evidence: II.

Background: We estimated the effectiveness of inactivated influenza vaccines for the prevention of laboratory-confirmed, medically attended influenza during 3 seasons with variable antigenic match between vaccine and patient strains., Methods: Patients were enrolled during or after a clinical encounter for acute respiratory illness. Influenza infection was confirmed by culture or reverse-transcriptase polymerase chain reaction. Case-control analyses were performed that used data from patients who were ill without influenza (hereafter, "test-negative control subjects") and data from asymptomatic control subjects from the population (hereafter, "traditional control subjects"). Vaccine effectiveness (VE) was estimated as [100 x (1-adjusted odds ratio)]. Influenza isolates were antigenically characterized., Results: Influenza was detected in 167 (20%) of 818 patients in 2004-2005, in 51 (14%) of 356 in 2005-2006, and in 102 (11%) of 932 in 2006-2007. Analyses that used data from test-negative control subjects showed that VE was 10% (95% confidence interval [CI], -36% to 40%) in 2004-2005, 21% (95% CI, -52% to 59%) in 2005-2006, and 52% (95% CI, 22% to 70%) in 2006-2007. Using data from traditional control subjects, VE for those seasons was estimated to be 5% (95% CI, -52% to 40%), 11% (95% CI, -96% to 59%), and 37% (95% CI, -10% to 64%), respectively; confidence intervals included 0. The percentage of viruses that were antigenically matched to vaccine strains was 5% (3 of 62) in 2004-2005, 5% (2 of 42) in 2005-2006, and 91% (85 of 93) in 2006-2007., Conclusions: Influenza VE varied substantially across 3 seasons and was highest when antigenic match was optimal. VE estimates that used data from test-negative control subjects were consistently higher than those that used data from traditional control subjects.

Objective: To describe the results of the first four rounds (T0-T3) of prostate cancer screening in the Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial (designed to determine the value of screening in the four cancers), that for prostate cancer is evaluating whether annual screening with prostate-specific antigen (PSA) and a digital rectal examination (DRE) reduces prostate cancer-specific mortality., Subjects and Methods: In all, 38 349 men aged 55-74 years were randomized to undergo annual screening with PSA (abnormal >4.0 ng/mL) and a DRE. The follow-up of abnormal screening results was at the discretion of subjects' physicians. PLCO staff obtained records related to diagnostic follow-up of positive screen results., Results: Compliance with screening decreased slightly from 89% at baseline to 85% at T3. Both PSA positivity rates (range 7.7-8.8% at T0-T3) and DRE positivity rates (range 6.8-7.6% at T0-T3) were relatively constant over time. The positive predictive value (PPV) of a PSA level of >4.0 ng/mL decreased from 17.9% at T0 to 10.4-12.3% at T1-T3; the PPV for DRE (in the absence of a positive PSA test) was constant over time (2.9-3.6%). Cancer was diagnosed in 1902 men (4.9%). Screen-detected cancers at T0 (549) were more likely to be clinical stage III/IV (5.8%) and to have a Gleason score of 7-10 (34%) than screen-detected cancers at T1-T3 (1.5-4.2% stage III/IV and 24-27% Gleason score 7-10 among 1054 cases)., Conclusion: The present findings on serial prostate screening are similar to those reported from other multi-round screening studies. Determining the effect of PSA screening on prostate cancer mortality awaits further follow-up.

Background: A clear need exists for a more systematic understanding of the epidemiology, diagnosis, and management of cardiovascular diseases. More robust data are also needed on how well clinical trials are translated into contemporary community practice and the associated resource use, costs, and outcomes., Methods and Results: The National Heart, Lung, and Blood Institute recently established the Cardiovascular Research Network, which represents a new paradigm to evaluate the epidemiology, quality of care, and outcomes of cardiovascular disease and to conduct future clinical trials using a community-based model. The network includes 15 geographically distributed health plans with dedicated research centers, National Heart, Lung, and Blood Institute representatives, and an external collaboration and advisory committee. Cardiovascular research network sites bring complementary content and methodological expertise and a diverse population of approximately 11 million individuals treated through various health care delivery models. Each site's rich electronic databases (eg, sociodemographic characteristics, inpatient and outpatient diagnoses and procedures, pharmacy, laboratory, and cost data) are being mapped to create a standardized virtual data warehouse to facilitate rapid and efficient large-scale research studies. Initial projects focus on (1) hypertension recognition and management, (2) quality and outcomes of warfarin therapy, and (3) use, outcomes, and costs of implantable cardioverter defibrillators., Conclusions: The Cardiovascular Research Network represents a new paradigm in the approach to cardiovascular quality of care and outcomes research among community-based populations. Its unique ability to characterize longitudinally large, diverse populations will yield novel insights into contemporary disease and risk factor surveillance, management, outcomes, and costs. The Cardiovascular Research Network aims to become the national research partner of choice for efforts to improve the prevention, diagnosis, treatment, and outcomes of cardiovascular diseases.

Background and Aims: Barrett's esophagus (BE) predisposes to adenocarcinoma of the esophagus and survival in esophageal adenocarcinoma is low. We studied patients diagnosed with BE in the Marshfield Epidemiologic Study Area (MESA). Our objectives were to estimate the prevalence of diagnosed BE, estimate the annual incidence of initial diagnosis of BE, and characterize the demographics of patients diagnosed with BE., Methods: We retrospectively reviewed medical records of patients diagnosed with BE until December 31, 2002. The esophagogastroduodenoscopy (EGD) reports were reviewed to establish the presence of columnar epithelium. All slides were retrieved and reviewed by a gastrointestinal pathologist to establish the presence of intestinal metaplasia and dysplasia. Chart abstraction was conducted using a standardized form., Results: BE was histologically confirmed in 216 patients. All were white, 165 (76%) were male, and 81% had a hiatal hernia. Median age at diagnosis was 65.5 yr (range 17-94). Long-segment BE (LSBE) was present in 112 (51.9%) patients. The prevalence of histologically confirmed BE in MESA was 261.8 (95% CI 222.5-301.1) per 100,000 people. The incidence of an initial diagnosis of BE between 1996 and 2002 was 32.7 per 100,000 person-years (95% CI 27.1-38.2) and did not change significantly over the study period despite an increase in EGD rates. At the initial diagnosis, 41.7% of the patients were on proton pump inhibitors. Dysplasia was present in 24.5% of patients., Conclusion: The incidence of initial diagnosis of BE in a stable white population did not change significantly over a 7-yr period, despite an increase in EGD rates.

Methods of ascertaining and defining asthma in epidemiologic research vary, and the extent of agreement between such measures is not clearly understood. Within a broader investigation of early-life farm exposures and risk of childhood asthma and other atopic conditions, the authors sought to generate and compare population-based estimates of asthma prevalence among farm children using several definitions, based on both parental report and medical chart review. The Marshfield Epidemiologic Study Area (MESA) is a geographically defined, population-based cohort that receives nearly all health care from Marshfield Clinic and affiliated institutions. The region includes about 2200 farms, and over 9500 children aged 5 to 17 years who were born in the region served as the study population. A stratified random sample of 1000 overselecting for likely farm resident children was drawn. Parents of 553 children completed the survey and gave permission to review medical records. Informative records were available for 531 (96%). A weighted analysis provided estimates for the full study population. Asthma ascertainment included parental reports of past asthma diagnosis, history of wheezing, and asthma medication use, as well as documentation of asthma diagnoses and medication use in the medical chart. Prevalence of asthma among farm children using a broad composite definition was 24.8%. Prevalence based on parental reports of a specific asthma diagnosis was 11.2%, whereas medical chart documentation of a past asthma diagnosis was found for 10.1% of farm children. Seventy-one percent of parental reports were validated in the charts, and 80% of chart-confirmed diagnoses were reported by the parent. Basing asthma prevalence for farm children on a history of asthma medication use gave a higher estimate than did history of a diagnosis. Of farm children, 19.2% reported wheezing or respiratory whistling, with 8.1% occurring in the past year. Observational research on asthma can be substantially influenced by ascertainment methods and case definitions. Although prevalence estimates based on a past asthma diagnosis were quantitatively similar for parental reports and chart confirmation, agreement on specific cases between the two sources was less than expected. Care should be taken to clearly describe asthma case definitions when reporting results of observational asthma research.

Adamantane-resistant influenza A is an emerging problem, but infections caused by resistant and susceptible viruses have not been compared. We identified adamantane resistance in 47% of 152 influenza A virus (H3N2) isolates collected during 2005. Resistant and susceptible viruses caused similar symptoms and illness duration. The prevalence of resistance was highest in children.

Objectives: We compared characteristics and mortality of patients from a community population meeting enrollment criteria of the second Multicenter Automatic Defibrillator Implantation Trial (MADIT II) to those of the MADIT II subjects., Background: MADIT II showed that implantable cardioverter-defibrillators (ICDs) reduce mortality in patients with myocardial infarction (MI) and low left ventricular ejection fraction (LVEF)

Early diagnosis of influenza infection is needed to optimize the benefit of prescribing antiviral drugs. However, the accuracy of rapid tests is highly variable. This study evaluated the performance of Directigen flu A+B enzyme immunoassay (EIA) and direct fluorescent assay (DFA) during the 2004-2005 influenza season. Participants with medically attended acute respiratory illness were identified through an active surveillance. Consenting patients (n=818) were enrolled and cultured for influenza. Physicians ordered a rapid antigen test (EIA or DFA) according to their clinical judgment. Physicians ordered rapid tests with EIA (n=109), DFA (n=86), or both (n=9) in 204 patients with acute respiratory illness who were also cultured for influenza. The EIA detected 18 of 43 influenza infections (sensitivity, 42%; 95% confidence interval [CI], 28-57%), whereas DFA detected 26 of 38 influenza infections (sensitivity, 68%; 95% CI, 53-81%). Compared with culture, specificity of both EIA and DFA was 96%. During the 2004-2005 influenza season, both the EIA and DFA had low sensitivity and failed to detect influenza in many patients.

Purpose: We ascertained and reviewed acute health events occurring in 2003 among patients age 18 and greater with well-defined single gene, chromosomal, and selected multifactorial conditions within the Marshfield Epidemiologic Study Area., Methods: Of 47,077 adult Marshfield Epidemiologic Study Area Central cohort members, 1,831 (3.9%) had been given at least one of 71 ICD-9 codes appropriate for genetic diagnoses of interest. Physician review narrowed this to 591 (1.3%) validated patients for the study. Of the 591, 527 (89.2%) patients registered 6,849 visits, which were manually reviewed to delineate acute, relevant health events in the urgent care and primary care provider setting., Results: A total of 244 acute relevant health events among 126 patients corresponding to 58 different genetic conditions were observed. Acute relevant health events corresponded to 3.4% of the total health events in patients identified with genetic problems. Categories of genetic conditions with the highest frequencies of acute relevant health events included chromosomal and microdeletion syndromes (21.3%), hematologic disorders (11.5%), muscular dystrophies (8.6%), and connective tissue disorders (10.2%)., Conclusions: These data have multiple applications and implications in addressing the natural history, long-term medical needs and financial impact of adult patients with genetic conditions.

Background: The characteristics of polymorphous light eruption (PMLE) have been described in patients evaluated and diagnosed at specialized photodermatology centers. Our goal was to describe the characteristics of PMLE diagnosed in a general clinic setting., Methods: We used electronic medical records to identify patients diagnosed with PMLE from 2000 to 2002 within a large group practice. We then collected additional information from medical records about patient demographics, lesion morphology, diagnostic testing, and therapies for the selected patients., Results: We identified 142 patients with diagnosed PMLE. After manual chart review, we excluded 18 patients with other forms of photosensitivity, eczema, or collagen vascular disease. Eighty-percent of the remaining 124 patients were diagnosed by a dermatologist during the study period. Females predominated in our patient series and the mean age of PMLE onset was 37.8 years. Lesions were commonly described as papular, edematous papulare, papulo-vesicular, eczematous, and plaque-like. Few skin biopsies were performed, and no patient had phototesting or photopatch testing. Topical corticosteroids and antihistamines were the most commonly prescribed therapies. Only four patients were treated with phototherapy., Conclusions: Patient demographics and lesion morphology in our cohort were similar to other reports, but patterns of diagnostic testing and treatment were somewhat different than those observed in photodermatology clinics.

Surveillance of agricultural work-related illness and non-fatal injuries is limited and considered to be a major gap in prevention and policy-making capacity. This pilot study evaluated the utility of the Marshfield Epidemiologic Study Area (MESA) and its farm residency cohort to identify and monitor potential priorities for prevention and control. MESA is a defined geographic region that serves as a resource for conducting population-based health research. Nearly all of the residents receive their health care from the Marshfield Clinic and affiliated hospitals, providing archived electronic medical information to characterize past and present diagnoses. Based on scientific literature and national research priorities, five broad health issues (injuries, back problems, hearing loss, respiratory conditions, and dermatologic conditions) were selected. To estimate age-specific and age-adjusted incidence and prevalence, we followed a fixed cohort of 1995 MESA residents through 2002. Standardized incidence ratios and standardized prevalence ratios were also estimated to quantify the potential impact of farm residency. Linking MESA, its farm residency cohort, and the clinic's data archives allowed successful identification of significant associations with agricultural exposure for a few conditions and subconditions related to consensus priorities in agricultural health, particularly among men. These included extrinsic alveolitis, organic dust toxic syndrome, back pain, osteoarthrosis, and certain injuries. However, the system was generally not able to demonstrate strong influence of farm residency on disease occurrence for many conditions specifically selected for their likely capacity to show such influence. Future surveillance systems should supplement clinical data with other sources of information on health events and should be adequately powered to focus on narrower ranges of health conditions.

Purpose of Review: Atrial fibrillation is a common arrhythmia with serious health consequences. This review explores contributions to the characterization and control of atrial fibrillation made by recent epidemiologic efforts., Recent Findings: Topics included in this review include the classification and clinical progression of atrial fibrillation, the burden atrial fibrillation places on the individual and on the health care delivery system, temporal trends in the occurrence and effect of atrial fibrillation, and novel predictors and risk factors. In light of the clinically relevant classification system used in the 2001 American College of Cardiology/American Heart Association/European Society of Cardiology Practice Guidelines for atrial fibrillation, recent estimates of pattern-specific recurrence and progression rates are described, along with insights into the incidence and prognosis of primary and secondary atrial fibrillation. Important new studies from North America and Europe quantifying the alarming health care burden and economic effect of atrial fibrillation are summarized. A discussion of several novel risk factors recently found to be associated with the development of atrial fibrillation is also included., Summary: Better characterization of the predictors, natural history, and clinical course of atrial fibrillation should ultimately support improvements in prevention, clinical decision making, and patient communication. A fuller comprehension of the current and future impact of atrial fibrillation can assist in planning health care delivery from the local facility to the international arena. Finally, there is a growing recognition that unraveling the complex interplay between atrial fibrillation and other associated diseases and their common risk factors may hold promise of deep insights into the fundamental nature of cardiovascular diseases.

We investigated the epidemiology of systemic lupus erythematosus (SLE) in the Marshfield Epidemiologic Study Area (MESA), a defined rural region where nearly all residents obtain their health care from a large clinic system. Computerized medical records were searched to identify MESA residents diagnosed with SLE from 1991 through 2001. Medical records were manually reviewed for all selected patients to identify cases of SLE using the 1982 revised American College of Rheumatology criteria. Patients with > or = 4 criteria were classified as definite SLE. Age- and gender-specific SLE incidence rates (1991-2001), the population prevalence rate of SLE on 31 December 2001 and survival rates were calculated. We identified 117 MESA residents with definite SLE. The average age-adjusted incidence of definite SLE was 5.1 per 100 000 per year (95% CI: 3.6, 6.6) and the age-adjusted population prevalence was 78.5 per 100 000 (95% CI: 59.0, 98.0). The mean age at diagnosis among the 44 incident cases was 51.7 years (range: 14-90 years). Positive anti-nuclear antibody (ANA), hematologic abnormalities, arthritis and renal disease were common at diagnosis. Five- and 10-year survival rates were 88% and 76%, respectively. Epidemiologic characteristics of SLE in this rural Caucasian population are generally similar to those reported by other US studies. One notable difference is a relatively high incidence of SLE in older adults.

The fetal environment may be a contributing factor in the etiology of some adult diseases. This study examined whether birth weight, birth length and gestational age are associated with the subsequent development of systemic lupus erythematosus (SLE). The Marshfield Clinic Lupus Registry was searched to identify patients who were born at Saint Joseph's Hospital in Marshfield, Wisconsin, USA. Birth data on each case and five age-, sex-, and race-matched controls were recorded from medical and delivery room register records. Perinatal data were obtained for 23 cases and 115 controls. The unadjusted mean birth weight was similar for cases (3407 +/- 581 g) and controls (3422 +/- 514 g). Birth length was not different between groups. Birth weight adjusted for gestational age, analysed by conditional logistic regression, was not statistically significantly different between groups. We concluded that birth weight and length were similar among SLE cases and controls, suggesting that these perinatal characteristics are not associated with subsequent SLE.

Purpose of Review: The results of five randomized clinical trials comparing rate control with rhythm control in the management of atrial fibrillation have been published recently. The purpose of this report is to review their main results and selected subanalyses and other related data to offer practical recommendations regarding the treatment of patients with this common arrhythmia., Recent Findings: In the aggregate, the five trials enrolled a total of 5175 subjects and accumulated 16,186 patient-years of follow-up. All these trials have had similar results in that each of them failed to demonstrate a clear advantage of the rhythm control approach over that of rate control. The largest of the studies, the Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) study, enrolled 79% of all the cases in the five trials and accounts for 88% of the cumulative follow-up experience and for 92% of all deaths. Among AFFIRM participants, antiarrhythmic drug use did not improve survival, stroke risk, quality of life, or functional capacity but was associated with increased resource use. In several of the trials, however, the presence of sinus rhythm was associated with improved outcomes., Summary: The evidence is now overwhelming that for most patients with atrial fibrillation, rhythm control using currently available antiarrhythmic drugs is more expensive but not more effective than the rate control strategy in the prevention of major adverse events. Further research is needed to determine whether maintaining sinus rhythm by other means can improve outcomes.

The Marshfield Epidemiologic Study Area (MESA) is a rare resource for population-based health and medical research developed at Marshfield Clinic Research Foundation. Because of high population coverage and health event capture, MESA is particularly useful for determining the frequency of disease in the general population. A substantial proportion of MESA-based publications appearing in the peer reviewed literature have reported incidence or prevalence rates of disease or disease-related factors. This paper reviews the first 10 years of MESA's support of meaningful inquiry into the frequency of disease occurrence, and briefly reports on the data and methods used for such calculations using selected chronic diseases as examples. Limitations of MESA estimates are discussed as are alternate methods. Compared to limited data published for the selected conditions, occurrence rates in MESA based on diagnostic codes and general validation rules only appear somewhat high, although the observed temporal trends and relationships with demographics are consistent. Rich clinical data sources are available to be linked with MESA to improve the specificity of case ascertainment, as is typically done for disease-specific publications from MESA.

Background: Persons with atopic dermatitis or eczema, regardless of disease severity or activity, may develop eczema vaccinatum if they or their close contacts receive the smallpox vaccine. According to current recommendations, a preexposure vaccination program should identify these persons and exclude them from participating., Objective: To determine the prevalence of diagnosed atopic dermatitis and eczema in a defined population and assess the sensitivity of screening questions to identify patients who have received these diagnoses., Design: Population-based prevalence survey and telephone interview., Setting: 14 ZIP code regions in Wisconsin., Patients: Persons given a diagnosis of atopic dermatitis or eczema in 2000 and 2001 were identified from a population-based cohort. Persons with a history of atopic dermatitis diagnosed since 1979 were eligible for the telephone survey., Measurements: Prevalence of diagnosed atopic dermatitis or eczema; proportions of respondents able to recall a past diagnosis of atopic dermatitis, eczema, or recurrent rash., Results: The prevalence of atopic dermatitis or eczema diagnosis in 2000 or 2001 was 0.8%. At least 2.4% of the cohort would be ineligible for smallpox vaccination because of active skin disease in themselves or household members. Among 94 adult respondents with atopic dermatitis, 55 (59%) correctly self-reported skin disease. Seventy-nine (60%) of 133 household contacts of adults with atopic dermatitis correctly reported the presence of skin disease in a household member. Parental recall of skin disease in children with atopic dermatitis was 70% (123 of 177)., Conclusions: Identifying dermatologic contraindications to smallpox vaccination by relying only on a self-reported history of rash illnesses is likely to miss a substantial proportion of individuals who should not receive smallpox vaccine in a preexposure vaccination campaign.

Background: Progress against cancer can be examined by analyzing long-term trends in cancer incidence and mortality. The recent directive from the U.S. Department of Health and Human Services to adopt the 2000 U.S. standard population for the age adjustment of death rates prompted the American Cancer Society to update historical cancer mortality statistics using the new standard., Methods: Mortality data were abstracted by race, gender, year, and age at death for 1930 through 1959 from annual volumes of Vital Statistics of the United States. For 1960 through 1998, these data were obtained from data tapes provided by the National Center for Health Statistics. Two U.S. standard million populations (1970 and 2000) were used to calculate age-adjusted rates. Average annual percent change was estimated for each decade by site, gender, and age, and the statistical significance of the change was assessed at p < 0.05., Results: After long-term increases or mostly level trends that date from the 1930s for some sites, death rates for cancers of the lung (in males), prostate, female breast, colon-rectum, pancreas, leukemia, and ovary were decreasing in the 1990s. Liver cancer death rates were increasing in the 1990s. Throughout the study period, death rates for female lung cancer increased, while death rates for stomach and uterine cancers declined., Conclusions: The trends of decreasing cancer death rates for the leading cancer sites in the 1990s are encouraging. However, surveillance researchers must continue to monitor these declines to assess whether the progress seen in this decade persists. Efforts also must be made to study the sites with increasing trends and identify potential underlying causes.

Serum samples were obtained from 215 farm-resident children and 396 non-farm-resident children living in a defined rural Wisconsin population. Antibodies to Campylobacter jejuni and Escherichia coli O157:H7 lipopolysaccharide (O157 LPS) immunoglobulin G were measured, and the incidence of clinic visits for diarrheal illness was determined. Risk factors were assessed in a telephone interview. There were 363 children (59%) with C. jejuni antibodies (seropositive for >or=2 immunoglobulin classes) and 86 (14%) with O157 LPS antibodies. Increasing age and farm residence were independently associated with C. jejuni seropositivity by multivariate analysis. O157 LPS antibodies were independently associated with increasing age, female sex, manure contact, and sheep contact. The incidence of clinically recognized diarrhea was similar among children with and without antibodies to C. jejuni and O157 LPS, but the clinic visit rate for diarrhea was 46% lower among farm-resident children. These results are consistent with reduced occurrence of clinical illness from repeated antigenic stimulation in a farm environment.

Background: Hip and knee osteoarthritis and undiagnosed chronic joint pain are more prevalent in agricultural workers than other occupational groups, significantly impacting the ability of small farm operators and farm workers to maintain a livelihood., Methods: Agricultural risk factors, economic impacts, national and state AgrAbility data, gender, and farm/non-farm prevalence differences of arthritis and joint arthropathy in a Wisconsin farm cohort are reviewed., Results: Agricultural workers (primarily male) are at increased risk for developing osteoarthritis of the hip and knee. In Wisconsin, the prevalence rate of osteoarthritis is higher in a male farm vs. a male rural non-farm cohort. Arthritis comprises 10%-12% of the disability referrals to state and national AgrAbility programs. Back pain, joint injury, and orthopedic injury account for another 38%. The ability to perform agricultural job duties is significantly affected by arthritis and lack of access to health care. Obesity is an additional independent risk factor for osteoarthritis in the rural population., Conclusions: The agricultural work force is at particular risk for arthritis-related disability. Improved access to health care for diagnosis and treatment can lessen disability. Prevention of arthritis is multi-factorial, involving ergonomic improvements, lifestyle modification to prevent obesity, and adequate medical treatment of arthritis.

Few studies have assessed the accuracy and completeness of Lyme disease surveillance systems. Lyme disease cases were identified through review of medical records for residents of the Marshfield Epidemiologic Study Area (MESA), a population-based cohort of nearly 80,000 in north-central Wisconsin for which comprehensive medical care data are available through the Marshfield Clinic. These cases were compared with cases reported to the Wisconsin Division of Public Health to estimate the completeness of reporting. Annual incidence rates were calculated for MESA using the cases identified from chart review. Division of Public Health data were used to calculate statewide reported incidence rates, as well as rates for an eight-county region that surrounds and includes the MESA region. Of Lyme disease cases meeting the national case definition identified in MESA, 34% were reported to the state. The average incidence of Lyme disease (1992-1998) was 19.1 per 100,000 per year in MESA, 17.0 in the surrounding eight-county region, and 9.0 statewide. Trends in reported incidence across time, gender, and age in the surrounding eight-county region were generally comparable with those observed in MESA. These findings suggest that the passive surveillance system monitored trends in Lyme disease incidence reasonably well despite underreporting of cases.

Background: Much of what is known about the occurrence of myocardial infarction (MI) in populations is derived from mortality data. International heart disease registries and recent population-based studies provide only limited incidence data from selected areas of the United States., Methods: The Marshfield Epidemiologic Study Area (MESA), a defined geographic region where nearly all residents receive their health care from the Marshfield Clinic and affiliated hospitals, is a resource for estimating disease incidence in a general population. MI incidence rates and time trends from 1992 to 1998 were evaluated in MESA., Results: A total of 1691 MESA residents had their first MI during the study period (age-adjusted rate, 292.4 per 100,000 per year). Rates in MESA were similar to some, and higher than other, incidence rates reported from US populations. About 20% of first MIs were detected only on death certificates. Overall incidence did not change much over time (-0.4% per year, P = 0.68), although rates declined 2.3% per year among women (P = 0.07)., Conclusions: This is the first report of MI incidence in a general population from Wisconsin. The fairly steady incidence trend and the large number of incident events detected through death certificates demonstrate the continued need for primary prevention.

Each year the American Cancer Society compiles estimates of the number of new cancer cases and deaths expected in the US in the current year and the most recent data on cancer incidence, mortality, and survival. An estimated 1,268,000 new cases of cancer will be diagnosed in the year 2001 and an estimated 553,400 Americans will die from cancer. Overall cancer incidence and death rates have continued to decrease in men and women since the early 1990s, and the decline in overall cancer mortality has been greater in recent years. Despite reductions in age-adjusted rates of cancer death, the total number of recorded cancer deaths in the US continues to increase, due to an aging and expanding population. Large disparities in cancer incidence and mortality across racial/ethnic groups continue. Black men and women experience higher incidence of cancer and poorer survival than white men and women. The disparity in survival reflects both diagnosis of cancer at later disease stages, and poorer survival within each stage of diagnosis.

The Surveillance Research Program of the American Cancer Society's Department of Epidemiology and Surveillance Research reports its annual compilation of estimated cancer incidence, mortality, and survival data for the United States in the year 2000. After 70 years of increases, the recorded number of total cancer deaths among men in the US declined for the first time from 1996 to 1997. This decrease in overall male mortality is the result of recent down-turns in lung and bronchus cancer deaths, prostate cancer deaths, and colon and rectum cancer deaths. Despite decreasing numbers of deaths from female breast cancer and colon and rectum cancer, mortality associated with lung and bronchus cancer among women continues to increase. Lung cancer is expected to account for 25% of all female cancer deaths in 2000. This report also includes a summary of global cancer mortality rates using data from the World Health Organization.