Rebecca A. Hubbard

Glucose Levels and Risk of Dementia

BACKGROUNDnDiabetes is a risk factor for dementia. It is unknown whether higher glucose levels increase the risk of dementia in people without diabetes.nnnMETHODSnWe used 35,264 clinical measurements of glucose levels and 10,208 measurements of glycated hemoglobin levels from 2067 participants without dementia to examine the relationship between glucose levels and the risk of dementia. Participants were from the Adult Changes in Thought study and included 839 men and 1228 women whose mean age at baseline was 76 years; 232 participants had diabetes, and 1835 did not. We fit Cox regression models, stratified according to diabetes status and adjusted for age, sex, study cohort, educational level, level of exercise, blood pressure, and status with respect to coronary and cerebrovascular diseases, atrial fibrillation, smoking, and treatment for hypertension.nnnRESULTSnDuring a median follow-up of 6.8 years, dementia developed in 524 participants (74 with diabetes and 450 without). Among participants without diabetes, higher average glucose levels within the preceding 5 years were related to an increased risk of dementia (P=0.01); with a glucose level of 115 mg per deciliter (6.4 mmol per liter) as compared with 100 mg per deciliter (5.5 mmol per liter), the adjusted hazard ratio for dementia was 1.18 (95% confidence interval [CI], 1.04 to 1.33). Among participants with diabetes, higher average glucose levels were also related to an increased risk of dementia (P=0.002); with a glucose level of 190 mg per deciliter (10.5 mmol per liter) as compared with 160 mg per deciliter (8.9 mmol per liter), the adjusted hazard ratio was 1.40 (95% CI, 1.12 to 1.76).nnnCONCLUSIONSnOur results suggest that higher glucose levels may be a risk factor for dementia, even among persons without diabetes. (Funded by the National Institutes of Health.)

Cumulative Probability of False-Positive Recall or Biopsy Recommendation After 10 Years of Screening Mammography: A Cohort Study

BACKGROUNDnFalse-positive mammography results are common. Biennial screening may decrease the cumulative probability of false-positive results across many years of repeated screening but could also delay cancer diagnosis.nnnOBJECTIVEnTo compare the cumulative probability of false-positive results and the stage distribution of incident breast cancer after 10 years of annual or biennial screening mammography.nnnDESIGNnProspective cohort study.nnnSETTINGn7 mammography registries in the National Cancer Institute-funded Breast Cancer Surveillance Consortium.nnnPARTICIPANTSn169,456 women who underwent first screening mammography at age 40 to 59 years between 1994 and 2006 and 4492 women with incident invasive breast cancer diagnosed between 1996 and 2006.nnnMEASUREMENTSnFalse-positive recalls and biopsy recommendations stage distribution of incident breast cancer.nnnRESULTSnFalse-positive recall probability was 16.3% at first and 9.6% at subsequent mammography. Probability of false-positive biopsy recommendation was 2.5% at first and 1.0% at subsequent examinations. Availability of comparison mammograms halved the odds of a false-positive recall (adjusted odds ratio, 0.50 [95% CI, 0.45 to 0.56]). When screening began at age 40 years, the cumulative probability of a woman receiving at least 1 false-positive recall after 10 years was 61.3% (CI, 59.4% to 63.1%) with annual and 41.6% (CI, 40.6% to 42.5%) with biennial screening. Cumulative probability of false-positive biopsy recommendation was 7.0% (CI, 6.1% to 7.8%) with annual and 4.8% (CI, 4.4% to 5.2%) with biennial screening. Estimates were similar when screening began at age 50 years. A non-statistically significant increase in the proportion of late-stage cancers was observed with biennial compared with annual screening (absolute increases, 3.3 percentage points [CI, -1.1 to 7.8 percentage points] for women age 40 to 49 years and 2.3 percentage points [CI, -1.0 to 5.7 percentage points] for women age 50 to 59 years) among women with incident breast cancer.nnnLIMITATIONSnFew women underwent screening over the entire 10-year period. Radiologist characteristics influence recall rates and were unavailable. Most mammograms were film rather than digital. Incident cancer was analyzed in a small sample of women who developed cancer.nnnCONCLUSIONnAfter 10 years of annual screening, more than half of women will receive at least 1 false-positive recall, and 7% to 9% will receive a false-positive biopsy recommendation. Biennial screening appears to reduce the cumulative probability of false-positive results after 10 years but may be associated with a small absolute increase in the probability of late-stage cancer diagnosis.nnnPRIMARY FUNDING SOURCEnNational Cancer Institute.

Comparative Effectiveness of Digital Versus Film-Screen Mammography in Community Practice in the United States: A Cohort Study

BACKGROUNDnFew studies have examined the comparative effectiveness of digital versus film-screen mammography in U.S. community practice.nnnOBJECTIVEnTo determine whether the interpretive performance of digital and film-screen mammography differs.nnnDESIGNnProspective cohort study.nnnSETTINGnMammography facilities in the Breast Cancer Surveillance Consortium.nnnPARTICIPANTSn329,261 women aged 40 to 79 years underwent 869 286 mammograms (231 034 digital; 638 252 film-screen).nnnMEASUREMENTSnInvasive cancer or ductal carcinoma in situ diagnosed within 12 months of a digital or film-screen examination and calculation of mammography sensitivity, specificity, cancer detection rates, and tumor outcomes.nnnRESULTSnOverall, cancer detection rates and tumor characteristics were similar for digital and film-screen mammography, but the sensitivity and specificity of each modality varied by age, tumor characteristics, breast density, and menopausal status. Compared with film-screen mammography, the sensitivity of digital mammography was significantly higher for women aged 60 to 69 years (89.9% vs. 83.0%; P = 0.014) and those with estrogen receptor-negative cancer (78.5% vs. 65.8%; P = 0.016); borderline significantly higher for women aged 40 to 49 years (82.4% vs. 75.6%; P = 0.071), those with extremely dense breasts (83.6% vs. 68.1%; P = 0.051), and pre- or perimenopausal women (87.1% vs. 81.7%; P = 0.057); and borderline significantly lower for women aged 50 to 59 years (80.5% vs. 85.1%; P = 0.097). The specificity of digital and film-screen mammography was similar by decade of age, except for women aged 40 to 49 years (88.0% vs. 89.7%; P < 0.001).nnnLIMITATIONnStatistical power for subgroup analyses was limited.nnnCONCLUSIONnOverall, cancer detection with digital or film-screen mammography is similar in U.S. women aged 50 to 79 years undergoing screening mammography. Women aged 40 to 49 years are more likely to have extremely dense breasts and estrogen receptor-negative tumors; if they are offered mammography screening, they may choose to undergo digital mammography to optimize cancer detection.nnnPRIMARY FUNDING SOURCEnNational Cancer Institute.

Outcomes of Screening Mammography by Frequency, Breast Density, and Postmenopausal Hormone Therapy

IMPORTANCEnControversy exists about the frequency women should undergo screening mammography and whether screening interval should vary according to risk factors beyond age.nnnOBJECTIVEnTo compare the benefits and harms of screening mammography frequencies according to age, breast density, and postmenopausal hormone therapy (HT) use.nnnDESIGNnProspective cohort.nnnSETTINGnData collected January 1994 to December 2008 from mammography facilities in community practice that participate in the Breast Cancer Surveillance Consortium (BCSC) mammography registries.nnnPARTICIPANTSnData were collected prospectively on 11,474 women with breast cancer and 922,624 without breast cancer who underwent mammography at facilities that participate in the BCSC.nnnMAIN OUTCOMES AND MEASURESnWe used logistic regression to calculate the odds of advanced stage (IIb, III, or IV) and large tumors (>20 mm in diameter) and 10-year cumulative probability of a false-positive mammography result by screening frequency, age, breast density, and HT use. The main predictor was screening mammography interval.nnnRESULTSnMammography biennially vs annually for women aged 50 to 74 years does not increase risk of tumors with advanced stage or large size regardless of womens breast density or HT use. Among women aged 40 to 49 years with extremely dense breasts, biennial mammography vs annual is associated with increased risk of advanced-stage cancer (odds ratio [OR], 1.89; 95% CI, 1.06-3.39) and large tumors (OR, 2.39; 95% CI, 1.37-4.18). Cumulative probability of a false-positive mammography result was high among women undergoing annual mammography with extremely dense breasts who were either aged 40 to 49 years (65.5%) or used estrogen plus progestogen (65.8%) and was lower among women aged 50 to 74 years who underwent biennial or triennial mammography with scattered fibroglandular densities (30.7% and 21.9%, respectively) or fatty breasts (17.4% and 12.1%, respectively).nnnCONCLUSIONS AND RELEVANCEnWomen aged 50 to 74 years, even those with high breast density or HT use, who undergo biennial screening mammography have similar risk of advanced-stage disease and lower cumulative risk of false-positive results than those who undergo annual mammography. When deciding whether to undergo mammography, women aged 40 to 49 years who have extremely dense breasts should be informed that annual mammography may minimize their risk of advanced-stage disease but the cumulative risk of false-positive results is high.

Benefits, Harms, and Costs for Breast Cancer Screening After US Implementation of Digital Mammography

BACKGROUNDnCompared with film, digital mammography has superior sensitivity but lower specificity for women aged 40 to 49 years and women with dense breasts. Digital has replaced film in virtually all US facilities, but overall population health and cost from use of this technology are unclear.nnnMETHODSnUsing five independent models, we compared digital screening strategies starting at age 40 or 50 years applied annually, biennially, or based on density with biennial film screening from ages 50 to 74 years and with no screening. Common data elements included cancer incidence and test performance, both modified by breast density. Lifetime outcomes included mortality, quality-adjusted life-years, and screening and treatment costs.nnnRESULTSnFor every 1000 women screened biennially from age 50 to 74 years, switching to digital from film yielded a median within-model improvement of 2 life-years, 0.27 additional deaths averted, 220 additional false-positive results, and

A Reality Check for Overdiagnosis Estimates Associated With Breast Cancer Screening

0.35 million more in costs. For an individual woman, this translates to a health gain of 0.73 days. Extending biennial digital screening to women ages 40 to 49 years was cost-effective, although results were sensitive to quality-of-life decrements related to screening and false positives. Targeting annual screening by density yielded similar outcomes to targeting by age. Annual screening approaches could increase costs to

Is the closest facility the one actually used? An assessment of travel time estimation based on mammography facilities.

5.26 million per 1000 women, in part because of higher numbers of screens and false positives, and were not efficient or cost-effective.nnnCONCLUSIONSnThe transition to digital breast cancer screening in the United States increased total costs for small added health benefits. The value of digital mammography screening among women aged 40 to 49 years depends on womens preferences regarding false positives.

Geographic Access to Breast Imaging for US Women

The frequency of overdiagnosis associated with breast cancer screening is a topic of controversy. Published estimates vary widely, but identifying which estimates are reliable is challenging. In this article we present an approach that provides a check on these estimates. Our approach leverages the close link between overdiagnosis and lead time by identifying the average lead time most consistent with a given overdiagnosis frequency. We consider a high-profile study that suggested that 31% of breast cancers diagnosed in the United States in 2008 were overdiagnosed and show that this corresponds to an average lead time of about nine years among localized cases. Comparing this estimate with the average lead time for invasive, screen-detected breast cancers of 40 months, around which there is a relative consensus, suggests the published estimate of overdiagnosis is excessive. This approach provides a novel way to appraise estimates of overdiagnosis given knowledge of disease natural history.

Characterization of Dementia and Alzheimer’s Disease in an Older Population: Updated Incidence and Life Expectancy With and Without Dementia

AbstractBackgroundCharacterizing geographic access depends on a broad range of methods available to researchers and the healthcare context to which the method is applied. Globally, travel time is one frequently used measure of geographic access with known limitations associated with data availability. Specifically, due to lack of available utilization data, many travel time studies assume that patients use the closest facility. To examine this assumption, an example using mammography screening data, which is considered a geographically abundant health care service in the United States, is explored. This work makes an important methodological contribution to measuring access—which is a critical component of health care planning and equity almost everywhere.nMethodWe analyzed one mammogram from each of 646,553 women participating in the US based Breast Cancer Surveillance Consortium for years 2005–2012. We geocoded each record to street level address data in order to calculate travel time to the closest and to the actually used mammography facility. Travel time between the closest and the actual facility used was explored by woman-level and facility characteristics.ResultsOnly 35xa0% of women in the study population used their closest facility, but nearly three-quarters of women not using their closest facility used a facility within 5xa0min of the closest facility. Individuals that by-passed the closest facility tended to live in an urban core, within higher income neighborhoods, or in areas where the average travel times to work was longer. Those living in small towns or isolated rural areas had longer closer and actual median drive times.ConclusionSince the majority of US women accessed a facility within a few minutes of their closest facility this suggests that distance to the closest facility may serve as an adequate proxy for utilization studies of geographically abundant services like mammography in areas where the transportation networks are well established.

Joint modeling of self-rated health and changes in physical functioning

PURPOSEnThe breast imaging modalities of mammography, ultrasound, and MRI are widely used for screening, diagnosis, treatment, and surveillance of breast cancer. Geographic access to breast imaging services in various modalities is not known at a national level overall or for population subgroups.nnnMETHODSnA retrospective study of 2004-2008 Medicare claims data was conducted to identify ZIP codes in which breast imaging occurred, and data were mapped. Estimated travel times were made for each modality for 215,798 census block groups in the contiguous United States. Using Census 2010 data, travel times were characterized by sociodemographic factors for 92,788,909 women aged ≥30 years, overall, and by subgroups of age, race/ethnicity, rurality, education, and median income.nnnRESULTSnOverall, 85% of women had travel times of ≤20 minutes to nearest mammography or ultrasound services, and 70% had travel times of ≤20 minutes for MRI with little variation by age. Native American women had median travel times 2-3 times longer for all 3 modalities, compared to women of other racial/ethnic groups. For rural women, median travel times to breast imaging services were 4-8-fold longer than they were for urban women. Black and Asian women had the shortest median travel times to services for all 3xa0modalities.nnnCONCLUSIONSnTravel times to mammography and ultrasound breast imaging facilities are short for most women, but for breast MRI, travel times are notably longer. Native American and rural women are disadvantaged in geographic access based on travel times to breast imaging services. This work informs potential interventions to reduce inequities in access and utilization.