Floyd J. Frost

Predictors of Tamoxifen Discontinuation Among Older Women With Estrogen Receptor–Positive Breast Cancer

PURPOSE Five years of adjuvant tamoxifen therapy for estrogen receptor (ER) -positive breast cancer is more effective than 2 years of use. However, information on tamoxifen discontinuation is scanty. We sought to identify predictors of tamoxifen discontinuation among older women with breast cancer. PATIENTS AND METHODS Within six health care delivery systems, we identified women >or= 65 years old diagnosed with stage I to IIB ER-positive or indeterminant breast cancer between 1990 and 1994 who had filled a prescription for adjuvant tamoxifen. We observed them for 5 years after initial tamoxifen prescription. We used automated pharmacy records to validate tamoxifen prescription information abstracted from medical records. The primary end point was tamoxifen discontinuation, operationalized as ever discontinuing tamoxifen during 5 years of follow-up. We used Cox proportional hazards to identify predictors of tamoxifen discontinuation. RESULTS Of 961 women who were prescribed tamoxifen, 49% discontinued tamoxifen before the completion of 5 years. Discontinuers were more likely to be aged 75 to less than 80 years (v < 70 years; hazard ratio [HR] = 1.41; 95% CI, 1.06 to 1.87), be aged >or= 80 years (HR = 2.02; 95% CI, 1.53 to 2.66), have an increase in Charlson Comorbidity Index at 3 years from diagnosis (HR = 1.52; 95% CI, 1.18 to 1.95), have an increase in the number of cardiopulmonary comorbidities at 3 years (HR = 1.75; 95% CI, 1.34 to 2.28), have indeterminant ER status (v ER-positive status; HR = 1.36; 95% CI, 1.00 to 1.85), and have received breast-conserving surgery (BCS) without radiotherapy (v mastectomy; HR = 1.62; 95% CI, 1.18 to 2.22). CONCLUSION Attention to nonadherence among older women at risk of discontinuation, particularly those receiving BCS without radiotherapy, might improve breast cancer outcomes for these women.

Mammography Surveillance and Mortality in Older Breast Cancer Survivors

PURPOSE There are more than 2,000,000 breast cancer survivors in the United States today. While surveillance for asymptomatic recurrence and second primary is included in consensus recommendations, the effectiveness of this surveillance has not been well characterized. Our purpose is to estimate the effectiveness of surveillance mammography in a cohort of breast cancer survivors with complete ascertainment of surveillance mammograms and negligible losses to follow-up. PATIENTS AND METHODS We enrolled 1,846 stage I and II breast cancer patients who were at least 65 years old at six integrated health care delivery systems. We used medical record review and existing databases to ascertain patient, tumor, and therapy characteristics, as well as receipt of surveillance mammograms. We linked personal identifiers to the National Death Index to ascertain date and cause of death. We matched four controls to each breast cancer decedent to estimate the association between receipt of surveillance mammogram and breast cancer mortality. RESULTS One hundred seventy-eight women died of breast cancer during 5 years of follow-up. Each additional surveillance mammogram was associated with a 0.69-fold decrease in the odds of breast cancer mortality (95% CI, 0.52 to 0.92). The protective association was strongest among women with stage I disease, those who received mastectomy, and those in the oldest age group. CONCLUSION Given existing recommendations for post-therapy surveillance, trials to compare surveillance with no surveillance are unlikely. This large observational study provides support for the recommendations, suggesting that receipt of surveillance mammograms reduces the rate of breast cancer mortality in older patients diagnosed with early-stage disease.

Recurrences and second primary breast cancers in older women with initial early-stage disease.

The association between common breast cancer therapies and recurrences and second primary breast cancers in older women is unclear, although older women are less likely to receive common therapies.

How clean must our drinking water be: the importance of protective immunity.

BACKGROUND Cryptosporidium parvum is an important cause of epidemic diarrhea. Few studies have assessed whether serological evidence of prior infection in adults is related to a reduced occurrence of enteric illness. METHODS Serum samples and enteric illness event data were obtained in 2000 and 2001 from 326 people served by 1 of 2 unfiltered surface sources or 1 groundwater source. In 2001, filtration was initiated at 1 of the surface sources. Poisson regression related illness episodes with serological responses to the 15/17- and 27-kDa Cryptosporidium antigen groups. RESULTS Subjects with moderately strong responses to the 15/17-kDa antigen had <65% of the risk of all 1-3-day episodes of diarrheal or gastrointestinal illness and <40% of the risk of all >/=4-day episodes, compared with subjects without a moderately strong response. Water source, change in water treatment, and very weak responses were unrelated to illness events. CONCLUSIONS Endemic Cryptosporidium infections are a common cause of diarrheal and gastrointestinal illness in persons without a moderately strong response to the 15/17-kDa antigen group. Users of surface-derived drinking water are more likely to have strong serological responses to this antigen group and may be at a lower risk of endemic gastrointestinal illness caused by Cryptosporidium infection.

Serological evidence of endemic waterborne cryptosporidium infections.

PURPOSE Cryptosporidium oocysts are commonly detected in surface-derived drinking water, however, the public health significance of these findings is unclear. This study compared the evidence of prior Cryptosporidium infection for people drinking water derived from surface versus ground water sources. METHODS This study measured serological responses to two Cryptosporidium antigen groups for blood donors from two midwestern United States cities with different drinking water sources: filtered and chlorinated river water receiving agricultural and domestic sewage upstream versus chlorinated water from an underground aquifer. Initial and nine-month paired serological responses to two Cryptosporidium antigen groups were compared. RESULTS Initially, donors from the surface water city had a higher relative prevalence (RP) of a serological response (54% vs. 38%, RP = 1.39 (1.21,1.60)). Donors with a detectable baseline response who resided in the surface water city had a higher relative risk (RR) of an increased intensity of response on the follow-up blood draw (15/17-kDa, 40/100 vs. 11/100, RR = 3.78 (1.89,7.58)), (27-kDa 38/100 vs. 18/100, RR = 2.07 (1.31,3.25)). Donors with no baseline response to the 15/17-kDa marker who resided in the surface water city also had a higher risk of serconversion (38/100 vs. 14/100, RR = 2.63 (1.78,3.91)). CONCLUSIONS These rates of both background and drinking water related Cryptosporidium infections are substantially higher than previously estimated, however, the risk of illness from infection may be lower.

Automated inter-rater reliability assessment and electronic data collection in a multi-center breast cancer study

BackgroundThe choice between paper data collection methods and electronic data collection (EDC) methods has become a key question for clinical researchers. There remains a need to examine potential benefits, efficiencies, and innovations associated with an EDC system in a multi-center medical record review study.MethodsA computer-based automated menu-driven system with 658 data fields was developed for a cohort study of women aged 65 years or older, diagnosed with invasive histologically confirmed primary breast cancer (N = 1859), at 6 Cancer Research Network sites. Medical record review with direct data entry into the EDC system was implemented. An inter-rater and intra-rater reliability (IRR) system was developed using a modified version of the EDC.ResultsAutomation of EDC accelerated the flow of study information and resulted in an efficient data collection process. Data collection time was reduced by approximately four months compared to the project schedule and funded time available for manuscript preparation increased by 12 months. In addition, an innovative modified version of the EDC permitted an automated evaluation of inter-rater and intra-rater reliability across six data collection sites.ConclusionAutomated EDC is a powerful tool for research efficiency and innovation, especially when multiple data collection sites are involved.

Identifying US populations for the study of health effects related to drinking water arsenic.

The US Environmental Protection Agency recently set a new maximum contaminant level (MCL) for arsenic in drinking water of 10 μg/l. In this paper, we review the completeness and accuracy of drinking water arsenic occurrence data in the United States and identify populations exposed to elevated arsenic concentrations that would be suitable for epidemiological studies of arsenic health effects. Using existing data from the Environmental Protection Agency Arsenic Occurrence and Exposure Database and additional data from state health and environment departments and water utilities, we identified 33 counties in 11 states with an estimated mean drinking water arsenic concentration of 10 μg/l or greater. A total of 11 of these ‘confirmed’ counties had an estimated mean arsenic concentration of 20 μg/l or more and two had an estimated mean arsenic concentration 50 μg/l or more. Based on census data, between 1950 and 1999 there were approximately 51.1 million person-years of exposure to drinking water arsenic at levels of 10 μg/l or more, 8.2 million at levels of 20 μg/l or more arsenic and 0.9 million at levels of 50 μg/l or more. Mortality and incidence of diseases known to be associated with arsenic exposure can and should be examined in these counties as part of a comprehensive assessment of arsenic health effects in US populations.

Laboratory safety monitoring of chronic medications in ambulatory care settings.

AbstractOBJECTIVE: To evaluate laboratory safety monitoring in patients taking selected chronic prescription drugs. DESIGN: Retrospective study using 1999–2001 claims data to calculate rates of missed laboratory tests (potential laboratory monitoring errors). Eleven drugs/drug groups and 64 laboratory tests were evaluated. SETTING: Two staff/network model health maintenance organizations. PATIENTS: Continuously enrolled health plan members age≥19 years taking ≥1 chronic medications. MEASUREMENTS AND MAIN RESULTS: Among patients taking chronic medications (N=29,823 in 1999, N=32,423 in 2000, and N=36,811 in 2001), 47.1% in 1999, 45.0% in 2000, and 44.0% in 2001 did not receive ≥1 test recommended for safety monitoring. Taking into account that patients were sometimes missing more than 1 test for a given drug and that patients were frequently taking multiple drugs, the rate of all potential laboratory monitoring errors was 849/1,000 patients/year in 1999, 810/1,000 patients/year in 2000, and 797/1,000 patients/year in 2001. Rates of potential laboratory monitoring errors varied considerably across individual drugs and laboratory tests. CONCLUSIONS: Lapses in laboratory monitoring of patients taking selected chronic medications were common. Further research is needed to determine whether, and to what extent, this failure to monitor patients is associated with adverse clinical outcomes.

A comparison of two methods for estimating the health care costs of epilepsy.

Summary: Purpose: Previous studies have estimated medical care costs of epilepsy by applying unit costs to estimated utilization or by summing costs for (a) ambulatory care and hospitalizations coded as epilepsy and (b) procedures and drugs specifically associated with the diagnosis or treatment of epilepsy. These methods may underestimate the cost of medical care for epilepsy. Two methods for estimating the medical care costs of epilepsy (“epilepsy‐attributable cost method” and “case‐control cost method”) were compared.

A seasonal study of arsenic in groundwater, Snohomish County, Washington, USA

A series of arsenic poisonings near Granite Falls in Snohomish County, Washington, were identified during 1985–87. An initial investigation revealed the source of arsenic exposure to be high levels of arsenic in well water. A large number of wells in eastern Snohomish County were tested, residents were interviewed and sources of contamination, both natural and man-made, were investigated. More than 70 private drinking-water wells were found to contain elevated levels of arsenic . One well contained 33 mg As L−1. The finding of elevated arsenic levels in a previously approved drinking-water well for a restaurant, plus suggestions of symptoms consistent with arsenic poisoning among people with wells with no detectable arsenic, raised concern over possible temporal variation in arsenic levels. To evaluate this temporal variation, a 12-month study of arsenic in groundwater was conducted in selected wells near Granite Falls. The 12-month study of 26 wells, conducted between February 1988 and January 1989, found arsenic levels for individual wells to vary from one to 19 fold over time. Because of this variability, four out of the eight wells with arsenic levels close to the Maximum Contamination Level (MCL) of 0.050 mg As L−1 would have been considered safe on the basis of a single sample, but would have exceeded the MCL at another time of the year.In areas with a high occurrence of arsenic contaminated drinking water, approval of well water prior to the sale of a house or issuance of a building permit which is based on a single arsenic test may result in later findings of unacceptable drinking water. When the arsenic is near the MCL, it may be prudent to follow well-water arsenic concentrations over time to assure that the arsenic level remains within acceptable bounds. If lower arsenic standards are adopted for drinking water, the issue of temporal variation around the standard will become a matter of more widespread concern.