Digital Global Recruitment for Women's Health Research: Cross-sectional Study.

BACKGROUND: With the increased popularity of mobile menstrual tracking apps and boosted Facebook posts, there is a unique opportunity to recruit research study participants from across the globe via these modalities to evaluate women's health. However, no studies to date have assessed the feasibility of using these recruitment sources for epidemiological research on ovulation and menstruation. OBJECTIVE: The objective of this study was to assess the feasibility of recruiting a diverse sample of women to an epidemiological study of ovulation and menstruation (OM) health (OM Global Health Study) using digital recruitment sources. The feasibility and diversity were assessed via click and participation rates, geographic location, BMI, smoking status, and other demographic information. METHODS: Participants were actively recruited via in-app messages using the menstrual tracking app Clue (BioWink GmbH) and a boosted Facebook post by DivaCup (Diva International Inc.). Other passive recruitment methods also took place throughout the recruitment period (eg, email communications, blogs, other social media). The proportion of participants who visited the study website after viewing and clicking the hypertext link (click rates) in the in-app messages and boosted Facebook post and the proportion of participants who completed the surveys per the number of completed consent and eligibility screeners (participation rates) were used to quantify the success of recruiting participants to the study website and study survey completion, respectively. Survey completion was defined as finishing the pregnancy and birth history section of the OM Global Health Study questionnaire. RESULTS: The recruitment period was from February 27, 2018, through January 24, 2020. In-app messages and the boosted Facebook post were seen by 104,000 and 21,400 people, respectively. Overall, 215 participants started the OM Global Health Study survey, of which 140 (65.1%), 39 (18.1%), and 36 (16.8%) participants were recruited via the app, the boosted Facebook post, and other passive recruitment methods, respectively. The click rate via the app was 18.9% (19,700 clicks/104,000 ad views) and 1.6% via the boosted Facebook post (340 clicks/21,400 ad views.) The overall participation rate was 44.6% (198/444), and the average participant age was 21.8 (SD 6.1) years. In terms of geographic and racial/ethnic diversity, 91 (44.2%) of the participants resided outside the United States and 147 (70.7%) identified as non-Hispanic White. In-app recruitment produced the most geographically diverse stream, with 44 (32.8%) of the 134 participants in Europe, 77 (57.5%) in North America, and 13 (9.8%) in other parts of the world. Both human error and nonhuman procedural breakdowns occurred during the recruitment process, including a computer programming error related to age eligibility and a hacking attempt by an internet bot. CONCLUSIONS: In-app messages using the menstrual tracking app Clue were the most successful method for recruiting participants from many geographic regions and producing the greatest numbers of started and completed surveys. This study demonstrates the utility of digital recruitment to enroll participants from diverse geographic locations and provides some lessons to avoid technical recruitment errors in future digital recruitment strategies for epidemiological research.

Fine particulate matter and polycystic ovarian morphology.

BACKGROUND: Polycystic ovary morphology (PCOM) is an ultrasonographic finding that can be present in women with ovulatory disorder and oligomenorrhea due to hypothalamic, pituitary, and ovarian dysfunction. While air pollution has emerged as a possible disrupter of hormone homeostasis, limited research has been conducted on the association between air pollution and PCOM. METHODS: We conducted a longitudinal cohort study using electronic medical records data of 5,492 women with normal ovaries at the first ultrasound that underwent a repeated pelvic ultrasound examination during the study period (2004-2016) at Boston Medical Center. Machine learning text algorithms classified PCOM by ultrasound. We used geocoded home address to determine the ambient annual average PM2.5 exposures and categorized into tertiles of exposure. We used Cox Proportional Hazards models on complete data (n = 3,994), adjusting for covariates, and additionally stratified by race/ethnicity and body mass index (BMI). RESULTS: Cumulative exposure to PM2.5 during the study ranged from 4.9 to 17.5 µg/m3 (mean = 10.0 µg/m3). On average, women were 31 years old and 58% were Black/African American. Hazard ratios and 95% confidence intervals (CI) comparing the second and third PM2.5 exposure tertile vs. the reference tertile were 1.12 (0.88, 1.43) and 0.89 (0.62, 1.28), respectively. No appreciable differences were observed across race/ethnicity. Among women with BMI ≥ 30 kg/m2, we observed weak inverse associations with PCOM for the second (HR: 0.93, 95% CI: 0.66, 1.33) and third tertiles (HR: 0.89, 95% CI: 0.50, 1.57). CONCLUSIONS: In this study of reproductive-aged women, we observed little association between PM2.5 concentrations and PCOM incidence. No dose response relationships were observed nor were estimates appreciably different across race/ethnicity within this clinically sourced cohort.

Multimodal Recruitment to Study Ovulation and Menstruation Health: Internet-Based Survey Pilot Study.

BACKGROUND: Multimodal recruitment strategies are a novel way to increase diversity in research populations. However, these methods have not been previously applied to understanding the prevalence of menstrual disorders such as polycystic ovary syndrome. OBJECTIVE: The purpose of this study was to test the feasibility of recruiting a diverse cohort to complete a web-based survey on ovulation and menstruation health. METHODS: We conducted the Ovulation and Menstruation Health Pilot Study using a REDCap web-based survey platform. We recruited 200 women from a clinical population, a community fair, and the internet. RESULTS: We recruited 438 women over 29 weeks between September 2017 and March 2018. After consent and eligibility determination, 345 enrolled, 278 started (clinic: n=43; community fair: n=61; internet: n=174), and 247 completed (clinic: n=28; community fair: n=60; internet: n=159) the survey. Among all participants, the median age was 25.0 (SD 6.0) years, mean BMI was 26.1 kg/m2 (SD 6.6), 79.7% (216/271) had a college degree or higher, and 14.6% (37/254) reported a physician diagnosis of polycystic ovary syndrome. Race and ethnicity distributions were 64.7% (176/272) White, 11.8% (32/272) Black/African American, 7.7% (21/272) Latina/Hispanic, and 5.9% (16/272) Asian individuals; 9.9% (27/272) reported more than one race or ethnicity. The highest enrollment of Black/African American individuals was in clinic (17/42, 40.5%) compared to 1.6% (1/61) in the community fair and 8.3% (14/169) using the internet. Survey completion rates were highest among those who were recruited from the internet (159/174, 91.4%) and community fairs (60/61, 98.4%) compared to those recruited in clinic (28/43, 65.1%). CONCLUSIONS: Multimodal recruitment achieved target recruitment in a short time period and established a racially diverse cohort to study ovulation and menstruation health. There were greater enrollment and completion rates among those recruited via the internet and community fair.

Prospective study of cigarette smoking and fecundability.

STUDY QUESTION: To what extent is cigarette smoking associated with reduced fecundability? SUMMARY ANSWER: Current female smokers, particularly those who had smoked ≥10 cigarettes/day for ≥10 years, had lower fecundability than never smokers, but current male smoking and passive smoking in either partner showed little association with reduced fecundability. WHAT IS KNOWN ALREADY: Female smoking has been identified as a cause of infertility, yet there has been limited characterization of the dose and duration at which an effect is observed. Results for male active smoking and passive smoking in both partners are less consistent. STUDY DESIGN, SIZE, DURATION: We analyzed data from a North American internet-based preconception cohort study of 5473 female and 1411 male pregnancy planners, enrolled from 2013 to 2018. Participants had been attempting conception for ≤6 menstrual cycles at study entry. PARTICIPANTS/MATERIALS, SETTING, METHODS: We collected information on active and passive smoking history on baseline questionnaires. Pregnancy was reported on female bi-monthly follow-up questionnaires. We calculated fecundability ratios (FR) and 95% CI using proportional probabilities regression models, adjusted for demographic, behavioral, medical, reproductive and dietary variables. MAIN RESULTS AND THE ROLE OF CHANCE: Female current regular smoking (FR = 0.90, 95% CI: 0.77, 1.07), current occasional smoking (FR = 0.88, 95% CI: 0.73, 1.06), and former smoking (FR = 0.89, 95% CI: 0.81, 0.98) were associated with small reductions in fecundability. Results were stronger among women who smoked ≥10 cigarettes/day for ≥10 years (FR = 0.77, 95% CI: 0.53, 1.10). Male current regular and former smoking, and current passive smoking in either partner were not meaningfully associated with reduced fecundability. In utero exposure to ≥10 cigarettes/day among females was associated with reduced fecundability (FR = 0.75, 95% CI: 0.52, 1.06). LIMITATIONS, REASONS FOR CAUTION: Numbers of cigarette smokers, particularly within categories of intensity and duration, were small. Under-reporting of smoking may have resulted in non-differential misclassification, and smokers were more likely to be lost to follow-up. WIDER IMPLICATIONS OF THE FINDINGS: Given the consistency of our findings with results from previous studies and our observation of a dose-response relation in intensity of smoking, this study supports an association between female cigarette smoking and lower fecundability. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the National Institute of Child Health and Human Development (R01-HD086742, R21-HD072326, R03-HD090315 and T32-HD052458). The authors declare no competing interests.

Exposure to tetrachloroethylene-contaminated drinking water and time to pregnancy.

BACKGROUND: The synthetic solvent tetrachloroethylene (PCE), commonly used in dry cleaning operations, is a human neurotoxicant and carcinogen. However, its effect on reproduction is poorly understood, as prior studies have been limited to small occupational cohorts. We examined the association between PCE exposure from contamination of the public drinking water supply and time-to-pregnancy (TTP) in a cohort of mothers from Cape Cod, Massachusetts. METHODS: The Cape Cod Family Health Study is a retrospective cohort study designed to examine the reproductive and developmental health effects of exposure to PCE-contaminated drinking water. Our analysis included 1565 women who reported 3826 planned pregnancies from 1949 to 1990. Women completed self-administered questionnaires that ascertained TTP for each of her pregnancies, regardless of the outcome, as well as residential history and demographic information. We utilized EPANET water distribution system modeling software and a leaching and transport model to assess PCE exposure for each pregnancy. We used log-binomial regression models to estimate relative risks (RR) and 95% confidence intervals (CI), adjusting for potential confounders. We performed a probabilistic bias analysis to examine the effect of outcome misclassification on our results. RESULTS: Any cumulative PCE exposure before pregnancy was associated with a 15% reduction in risk of TTP > 12 months (RR = 0.85, 95% CI: 0.70, 1.03). However, women with the highest average monthly PCE exposure around the time of the pregnancy attempt (≥ 2.5 g) had increased risk of TTP > 12 months (RR = 1.36, 95% CI: 1.06, 1.76). CONCLUSIONS: We found little evidence for long-term, cumulative adverse effects of PCE exposure on TTP, but high levels of PCE exposure around the time of the pregnancy attempt were associated with longer TTP. These associations may be underestimated due to the exclusion of unsuccessful pregnancy attempts from our study population, and may be biased by outcome and exposure misclassification given the long-term recall of TTP and use of a leaching and transport model to estimate PCE exposure.

Exploring associations between prenatal solvent exposures and teenage drug and alcohol use: a retrospective cohort study.

BACKGROUND: Investigating the effects of prenatal and childhood exposures on behavioral health outcomes in adolescence is challenging given the lengthy period between the exposure and outcomes. We conducted a retrospective cohort study in Cape Cod, Massachusetts to evaluate the impact of prenatal and early childhood exposure to tetrachloroethylene (PCE)-contaminated drinking water on the occurrence of risk-taking behaviors as a teenager. An increased occurrence of risk-taking behaviors, particularly illicit drug use, was observed in those highly exposed to PCE. We hypothesized that there may be other sources of prenatal solvent exposure such as maternal consumption of alcoholic beverages during pregnancy which might modify the previously observed associations between PCE and risk-taking behaviors and so we conducted an exploratory analysis using available cohort data. The current report presents the results of these analyses and describes the difficulties in conducting research on long-term behavioral effects of early life exposures. METHODS: The exploratory analysis compared a referent group of subjects with no early life exposure to PCE or alcohol (n = 242) to subjects with only alcohol exposure (n = 201), subjects with only PCE exposure (n = 361), and subjects with exposure to both PCE and alcohol (n = 302). Surveys completed by the subject's mother included questions on prenatal alcoholic beverage consumption and available confounding variables such as cigarette smoking and marijuana use. Surveys completed by the subjects included questions on risk-taking behaviors such as alcoholic beverage consumption and illicit drug use as a teenager and available confounding variables. PCE exposure was modeled using a leaching and transport algorithm embedded in water distribution system modeling software that estimated the amount of PCE delivered to a subject's residence during gestation and early childhood. RESULTS: Subjects with early life exposure to both PCE and alcohol had an increased risk of using two or more major drugs as a teen (RR = 1.9 (95% CI 1.2, 3.0)) compared to unexposed subjects. Increased risks for only PCE exposure (RR = 1.6 (95% CI 1.0, 2.4) and only alcohol exposure (RR = 1.3 (95% CI 0.7, 2.1)) were also evident but were smaller than the increased risk associated with both exposures. While available confounding variables were controlled, many relevant social risk factors were not obtained due to limitations in the retrospective study design. CONCLUSIONS: This exploratory analysis found evidence for an additive effect of early life exposure to PCE and alcohol on the risk of use of multiple illicit drugs as a teenager. Because of numerous limitations in this retrospective study, further research is needed to examine longstanding behavioral effects of early life exposures. To be most informative, this research should involve long-term prospective data collection.

Association of prenatal and early life exposure to tetrachloroethylene (PCE) with polycystic ovary syndrome and other reproductive disorders in the cape cod health study: A retrospective cohort study.

BACKGROUND: Tetrachloroethylene (PCE) is an organic lipophilic solvent with possible neuroendocrine toxicity. The objective of this study was to determine the association of prenatal and early childhood exposure to PCE-contaminated drinking water and development of adult-onset Polycystic Ovary Syndrome (PCOS), endometriosis, difficulty conceiving and miscarriage. METHODS: Five-hundred exposed and 331 unexposed female participants born between 1969 and 1983 completed questionnaires on demographic and lifestyle characteristics, and reproductive disorders. Residential locations from the prenatal period through five years of age were used to estimate early life PCE exposure with water modeling software. RESULTS: For any early life exposure to PCE, the adjusted risk ratio for PCOS was 0.9 (95% CI: 0.5-1.6). No statistically significant associations were observed for increasing levels of exposure with PCOS or the other reproductive disorders. CONCLUSION: No meaningful associations were found among adult women with early life exposure to PCE-contaminated drinking water and adult-onset reproductive disorders.

Long-term health effects of early life exposure to tetrachloroethylene (PCE)-contaminated drinking water: a retrospective cohort study.

BACKGROUND: While adult exposure to PCE is known to have toxic effects, there is little information on the long-term impact of prenatal and early childhood exposure. We undertook a retrospective cohort study to examine the effects of their early life exposure to PCE-contaminated drinking water. This retrospective cohort study examined whether prenatal and early childhood exposure to PCE-contaminated drinking water influenced the risk of a variety of chronic conditions among adults who were born between 1969 and 1983 in the Cape Cod area of Massachusetts. METHODS: Eight hundred and thirty-one participants with prenatal and early childhood PCE exposure and 547 unexposed participants were studied. Individuals completed questionnaires to gather information on demographic characteristics, chronic conditions, and other sources of solvent exposure. The location of residences from birth through 1990 were used to estimate PCE exposure with U.S. EPA's water distribution system modeling software (EPANET) modified to incorporate a leaching and transport model. RESULTS: No associations were observed between early life PCE exposure and current occurrence of obesity, diabetes, cardiovascular disease, hypertension, color blindness, near- and far sightedness and dry eyes. In contrast, a 1.8-fold increased risk of cancer (95% CI: 0.8, 4.0) was seen among individuals with any early life exposure. These results were based on 31 participants (23 exposed and 8 unexposed) who reported cancers at a variety of anatomical sites, particularly the cervix. A 1.5-fold increase in the risk of epilepsy (95% CI: 0.6, 3.6, based on 16 exposed and 7 unexposed participants) was also observed among individuals with any early life exposure that was further increased to 1.8 (95% CI: 0.7, 4.6) among those with exposure at or above the sample median. CONCLUSIONS: These results suggest that the risk of epilepsy and certain types of cancer such as cervical cancer may be increased among adults who were exposed to PCE-contaminated drinking water exposure during gestation and early childhood. These findings should be interpreted cautiously because of the study limitations and confirmed in follow-up investigations of similarly exposed populations with medically-confirmed diagnoses. This relatively young study population should also be monitored periodically for subsequent changes in disease risk.

Air pollution and risk of uterine leiomyomata.

BACKGROUND: Air pollution, particularly from vehicle exhaust, has been shown to influence hormonal activity. However, it is unknown whether air pollution exposure is associated with the occurrence of uterine leiomyomata, a hormonally sensitive tumor of the uterus. METHODS: For 85,251 women 25-42 years of age at enrollment in the Nurses' Health Study II, we examined proximity to major roadways and outdoor levels of particulate matter less than 10 microns (PM10) or 2.5 microns (PM2.5) or between 10 and 2.5 microns (PM10-2.5) in diameter for all residential addresses from September 1989 to May 2007. To be eligible for this analysis, a woman had to be alive and respond to questionnaires, premenopausal with an intact uterus, and without diagnoses of cancer or prevalent uterine leiomyomata. Incidence of ultrasound- or hysterectomy-confirmed uterine leiomyomata and covariates were reported on biennial questionnaires sent through May 2007. Multivariable time-varying Cox proportional hazard models were used to estimate the relationship between distance to road or PM exposures and uterine leiomyomata risk. RESULTS: During 837,573 person-years of follow-up, there were 7760 incident cases of uterine leiomyomata. Living close to a major road and exposures to PM10 or PM10-2.5 were not associated with an increased risk of uterine leiomyomata. However, each 10 µg/m increase in 2-year average, 4-year average, or cumulative average PM2.5 was associated with an adjusted hazard ratio of 1.08 (95% confidence interval = 1.00-1.17), 1.09 (0.99-1.19), and 1.11 (1.03-1.19), respectively. CONCLUSIONS: Chronic exposure to PM2.5 may be associated with a modest increased risk of uterine leiomyomata.

Disparity in the use of combined modality therapy for rectal cancer in the older adult.

OBJECTIVES: The standard treatment strategy for patients with rectal adenocarcinoma having T3 or T4 tumors or positive lymph nodes includes concurrent chemoradiation, surgery and chemotherapy. Population based studies show relatively low rates of usage of standard therapy for rectal cancer in the older adult. MATERIALS AND METHODS: Two decades of cases of stage II and stage III rectal cancer from two academic teaching hospitals were reviewed. Comparisons were made of subjects ≤70 or ≥71years with regard to initiation and completion of radiation, chemotherapy and surgery. RESULTS: Subjects ≥71years of age had significantly lower proportions of surgical resection (84 vs. 94%) and of initiation of all three component of standard therapy (49 vs. 66%) compared to those ≤70years of age. Subjects ≥71years had significantly more co-morbidities; however, the difference in initiation of therapy remained after adjusting for stage, treating hospital, co-morbid status, race or sex in multivariable analysis. The odds for initiation of therapy were reduced by ≈22% in older adults in the adjusted analysis. Among all patients who started therapy only 56% completed it without dose reduction or delay. There were trends to increased completion among those receiving neo-adjuvant vs. post-operative chemoradiation and among those with stage III as opposed to stage II cancer. CONCLUSIONS: Our study indicates that a major disparity in the use of standard therapy for rectal cancer in the older adult exists in academic hospital settings. It will be important for oncologists to reconsider increasing the usage of curative therapy in these patients.

Affinity for risky behaviors following prenatal and early childhood exposure to tetrachloroethylene (PCE)-contaminated drinking water: a retrospective cohort study.

BACKGROUND: Many studies of adults with acute and chronic solvent exposure have shown adverse effects on cognition, behavior and mood. No prior study has investigated the long-term impact of prenatal and early childhood exposure to the solvent tetrachloroethylene (PCE) on the affinity for risky behaviors, defined as smoking, drinking or drug use as a teen or adult. OBJECTIVES: This retrospective cohort study examined whether early life exposure to PCE-contaminated drinking water influenced the occurrence of cigarette smoking, alcohol consumption, and drug use among adults from Cape Cod, Massachusetts. METHODS: Eight hundred and thirty-one subjects with prenatal and early childhood PCE exposure and 547 unexposed subjects were studied. Participants completed questionnaires to gather information on risky behaviors as a teenager and young adult, demographic characteristics, other sources of solvent exposure, and residences from birth through 1990. PCE exposure was estimated using the U.S. EPA's water distribution system modeling software (EPANET) that was modified to incorporate a leaching and transport model to estimate PCE exposures from pipe linings. RESULTS: Individuals who were highly exposed to PCE-contaminated drinking water during gestation and early childhood experienced 50-60% increases in the risk of using two or more major illicit drugs as a teenager or as an adult (Relative Risk (RR) for teen use = 1.6, 95% CI: 1.2-2.2; and RR for adult use = 1.5, 95% CI: 1.2-1.9). Specific drugs for which increased risks were observed included crack/cocaine, psychedelics/hallucinogens, club/designer drugs, Ritalin without a prescription, and heroin (RRs:1.4-2.1). Thirty to 60% increases in the risk of certain smoking and drinking behaviors were also seen among highly exposed subjects. CONCLUSIONS: The results of this study suggest that risky behaviors, particularly drug use, are more frequent among adults with high PCE exposure levels during gestation and early childhood. These findings should be confirmed in follow-up investigations of other exposed populations.

Risk factors for nonadherence with Pap testing in HIV-infected women.

BACKGROUND: HIV-infected women are at increased risk for cervical cancer; thus, adherence with Papanicolaou (Pap) testing is of particular importance. The objective of this study was to identify risk factors for inadequate Pap testing in a diverse cohort of HIV-infected women at a large urban safety net HIV clinic. METHODS: This retrospective cohort study assessed HIV-infected women aged 18?60 years in care between October 1, 2003, and March 31, 2008, for risk factors for inadequate Pap testing. Unadjusted odds ratios (OR) with confidence intervals (CI) and multivariate analyses with generalized estimating equations for correlated data were calculated. RESULTS: Of 549 women, 293 (53.4%) had a Pap test during each follow-up period. Women who were older, white or Hispanic race/ethnicity, U.S. born, unemployed, drug users, and those with advanced HIV had increased odds of no Pap testing in unadjusted analyses. In multivariate analyses, U.S.-born women who were white or unemployed or had a baseline CD4 count <200 cells/mm(3) had increased odds of no Pap testing (OR 2.0, 95% CI 1.3-3.1; OR 2.3, CI 1.0-5.0; OR 1.7, CI 1.0-2.9, respectively). For non-U.S.-born women, age ?50 years (OR 3.9, CI 1.7-9.0), non-English-speaking status (OR 1.6, CI 1.0-2.4), and drug use (OR 5.8, CI 2.5-13.9) were associated with no Pap testing. CONCLUSIONS: U.S.-born status and low CD4 count were associated with increased odds of inadequate Pap testing. Further study is needed to identify interventions to improve Pap testing adherence in this high-risk group.

Risk of breast cancer following exposure to tetrachloroethylene-contaminated drinking water in Cape Cod, Massachusetts: reanalysis of a case-control study using a modified exposure assessment.

BACKGROUND: Tetrachloroethylene (PCE) is an important occupational chemical used in metal degreasing and drycleaning and a prevalent drinking water contaminant. Exposure often occurs with other chemicals but it occurred alone in a pattern that reduced the likelihood of confounding in a unique scenario on Cape Cod, Massachusetts. We previously found a small to moderate increased risk of breast cancer among women with the highest exposures using a simple exposure model. We have taken advantage of technical improvements in publically available software to incorporate a more sophisticated determination of water flow and direction to see if previous results were robust to more accurate exposure assessment. METHODS: The current analysis used PCE exposure estimates generated with the addition of water distribution modeling software (EPANET 2.0) to test model assumptions, compare exposure distributions to prior methods, and re-examine the risk of breast cancer. In addition, we applied data smoothing to examine nonlinear relationships between breast cancer and exposure. We also compared a set of measured PCE concentrations in water samples collected in 1980 to modeled estimates. RESULTS: Thirty-nine percent of individuals considered unexposed in prior epidemiological analyses were considered exposed using the current method, but mostly at low exposure levels. As a result, the exposure distribution was shifted downward resulting in a lower value for the 90th percentile, the definition of "high exposure" in prior analyses. The current analyses confirmed a modest increase in the risk of breast cancer for women with high PCE exposure levels defined by either the 90th percentile (adjusted ORs 1.0-1.5 for 0-19 year latency assumptions) or smoothing analysis cut point (adjusted ORs 1.3-2.0 for 0-15 year latency assumptions). Current exposure estimates had a higher correlation with PCE concentrations in water samples (Spearman correlation coefficient = 0.65, p < 0.0001) than estimates generated using the prior method (0.54, p < 0.0001). CONCLUSIONS: The incorporation of sophisticated flow estimates in the exposure assessment method shifted the PCE exposure distribution downward, but did not meaningfully affect the exposure ranking of subjects or the strength of the association with the risk of breast cancer found in earlier analyses. Thus, the current analyses show a slightly elevated breast cancer risk for highly exposed women, with strengthened exposure assessment and minimization of misclassification by using the latest technology.

Self-reported chemicals exposure, beliefs about disease causation, and risk of breast cancer in the Cape Cod Breast Cancer and Environment Study: a case-control study.

BACKGROUND: Household cleaning and pesticide products may contribute to breast cancer because many contain endocrine disrupting chemicals or mammary gland carcinogens. This population-based case-control study investigated whether use of household cleaners and pesticides increases breast cancer risk. METHODS: Participants were 787 Cape Cod, Massachusetts, women diagnosed with breast cancer between 1988 and 1995 and 721 controls. Telephone interviews asked about product use, beliefs about breast cancer etiology, and established and suspected breast cancer risk factors. To evaluate potential recall bias, we stratified product-use odds ratios by beliefs about whether chemicals and pollutants contribute to breast cancer; we compared these results with odds ratios for family history (which are less subject to recall bias) stratified by beliefs about heredity. RESULTS: Breast cancer risk increased two-fold in the highest compared with lowest quartile of self-reported combined cleaning product use (Adjusted OR = 2.1, 95% CI: 1.4, 3.3) and combined air freshener use (Adjusted OR = 1.9, 95% CI: 1.2, 3.0). Little association was observed with pesticide use. In stratified analyses, cleaning products odds ratios were more elevated among participants who believed pollutants contribute "a lot" to breast cancer and moved towards the null among the other participants. In comparison, the odds ratio for breast cancer and family history was markedly higher among women who believed that heredity contributes "a lot" (OR = 2.6, 95% CI: 1.9, 3.6) and not elevated among others (OR = 0.7, 95% CI: 0.5, 1.1). CONCLUSIONS: Results of this study suggest that cleaning product use contributes to increased breast cancer risk. However, results also highlight the difficulty of distinguishing in retrospective self-report studies between valid associations and the influence of recall bias. Recall bias may influence higher odds ratios for product use among participants who believed that chemicals and pollutants contribute to breast cancer. Alternatively, the influence of experience on beliefs is another explanation, illustrated by the protective odds ratio for family history among women who do not believe heredity contributes "a lot." Because exposure to chemicals from household cleaning products is a biologically plausible cause of breast cancer and avoidable, associations reported here should be further examined prospectively.

High-normal serum uric acid increases risk of early progressive renal function loss in type 1 diabetes: results of a 6-year follow-up.

OBJECTIVE: We previously described a cross-sectional association between serum uric acid and reduced glomerular filtration rate (GFR) in nonproteinuric patients with type 1 diabetes. Here, we prospectively investigated whether baseline uric acid impacts the risk of early progressive renal function loss (early GFR loss) in these patients. RESEARCH DESIGN AND METHODS: Patients with elevated urinary albumin excretion (n = 355) were followed for 4-6 years for changes in urinary albumin excretion and GFR. The changes were estimated by multiple determinations of albumin-to-creatinine ratios (ACRs) and serum cystatin C (GFRcystatin). RESULTS: At baseline, the medians (25th-75th percentiles) for uric acid, ACR, and GFRcystatin values were 4.6 mg/dl (3.8-5.4), 26.2 mg/g (15.1-56.0), and 129 ml/min per 1.73 m(2) (111-145), respectively. During the 6-year follow-up, significant association (P < 0.0002) was observed between serum uric acid and development of early GFR loss, defined as GFRcystatin decline exceeding 3.3% per year. In baseline uric acid concentration categories (in mg/dl: <3.0, 3.0-3.9, 4.0-4.9, 5.0-5.9, and >or=6), the risk of early GFR loss increased linearly (9, 13, 20, 29, and 36%, respectively). This linear increase corresponds to odds ratio 1.4 (95% CI 1.1-1.8) per 1 mg/dl increase of uric acid. The progression and regression of urinary albumin excretion were not associated with uric acid. CONCLUSIONS: We found a clear dose-response relation between serum uric acid and risk of early GFR loss in patients with type 1 diabetes. Clinical trials are warranted to determine whether uric acid-lowering drugs can halt renal function decline before it becomes clinically significant.

Using residential history and groundwater modeling to examine drinking water exposure and breast cancer.

BACKGROUND: Spatial analyses of case-control data have suggested a possible link between breast cancer and groundwater plumes in upper Cape Cod, Massachusetts. OBJECTIVE: We integrated residential histories, public water distribution systems, and groundwater modeling within geographic information systems (GIS) to examine the association between exposure to drinking water that has been contaminated by wastewater effluent and breast cancer. METHODS: Exposure was assessed from 1947 to 1993 for 638 breast cancer cases who were diagnosed from 1983 to 1993 and 842 controls; we took into account residential mobility and drinking water source. To estimate the historical impact of effluent on drinking water wells, we modified a modular three-dimensional finite-difference groundwater model (MODFLOW) from the U.S. Geological Survey. The analyses included latency and exposure duration. RESULTS: Wastewater effluent impacted the drinking water wells of study participants as early as 1966. For > 0-5 years of exposure (versus no exposure), associations were generally null. Adjusted odds ratios (AORs) for > 10 years of exposure were slightly increased, assuming latency periods of 0 or 10 years [AOR = 1.3; 95% confidence interval (CI), 0.9-1.9 and AOR = 1.6; 95% CI, 0.8-3.2, respectively]. Statistically significant associations were estimated for ever-exposed versus never-exposed women when a 20-year latency period was assumed (AOR = 1.9; 95% CI, 1.0-3.4). A sensitivity analysis that classified exposures assuming lower well-pumping rates showed similar results. CONCLUSION: We investigated the hypothesis generated by earlier spatial analyses that exposure to drinking water contaminated by wastewater effluent may be associated with breast cancer. Using a detailed exposure assessment, we found an association with breast cancer that increased with longer latency and greater exposure duration.

Spatial analysis of bladder, kidney, and pancreatic cancer on upper Cape Cod: an application of generalized additive models to case-control data.

BACKGROUND: In 1988, elevated cancer incidence in upper Cape Cod, Massachusetts prompted a large epidemiological study of nine cancers to investigate possible environmental risk factors. Positive associations were observed, but explained only a portion of the excess cancer incidence. This case-control study provided detailed information on individual-level covariates and residential history that can be spatially analyzed using generalized additive models (GAMs) and geographical information systems (GIS). METHODS: We investigated the association between residence and bladder, kidney, and pancreatic cancer on upper Cape Cod. We estimated adjusted odds ratios using GAMs, smoothing on location. A 40-year residential history allowed for latency restrictions. We mapped spatially continuous odds ratios using GIS and identified statistically significant clusters using permutation tests. RESULTS: Maps of bladder cancer are essentially flat ignoring latency, but show a statistically significant hot spot near known Massachusetts Military Reservation (MMR) groundwater plumes when 15 years latency is assumed. The kidney cancer map shows significantly increased ORs in the south of the study area and decreased ORs in the north. CONCLUSION: Spatial epidemiology using individual level data from population-based studies addresses many methodological criticisms of cluster studies and generates new exposure hypotheses. Our results provide evidence for spatial clustering of bladder cancer near MMR plumes that suggest further investigation using detailed exposure modeling.

Renal hyperfiltration and the development of microalbuminuria in type 1 diabetes.

OBJECTIVE: The purpose of this study was to examine prospectively whether renal hyperfiltration is associated with the development of microalbuminuria in patients with type 1 diabetes, after taking into account known risk factors. RESEARCH DESIGN AND METHODS: The study group comprised 426 participants with normoalbuminuria from the First Joslin Kidney Study, followed for 15 years. Glomerular filtration rate was estimated by serum cystatin C, and hyperfiltration was defined as exceeding the 97.5th percentile of the sex-specific distribution of a similarly aged, nondiabetic population (134 and 149 ml/min per 1.73 m(2) for men and women, respectively). The outcome was time to microalbuminuria development (multiple albumin excretion rate >30 microg/min). Hazard ratios (HRs) for microalbuminuria were calculated at 5, 10, and 15 years. RESULTS: Renal hyperfiltration was present in 24% of the study group and did not increase the risk of developing microalbuminuria. The unadjusted HR for microalbuminuria comparing those with and without hyperfiltration at baseline was 0.8 (95% CI 0.4-1.7) during the first 5 years, 1.0 (0.6-1.7) during the first 10 years, and 0.8 (0.5-1.4) during 15 years of follow-up. The model adjusted for baseline known risk factors including A1C, age at diagnosis of diabetes, diabetes duration, and cigarette smoking resulted in similar HRs. In addition, incorporating changes in hyperfiltration status during follow-up had minimal impact on the HRs for microalbuminuria. CONCLUSIONS: Renal hyperfiltration does not have an impact on the development of microalbuminuria in type 1 diabetes during 5, 10, or 15 years of follow-up.

Participant experiences in a breastmilk biomonitoring study: a qualitative assessment.

BACKGROUND: Biomonitoring studies can provide information about individual and population-wide exposure. However they must be designed in a way that protects the rights and welfare of participants. This descriptive qualitative study was conducted as a follow-up to a breastmilk biomonitoring study. The primary objectives were to assess participants' experiences in the study, including the report-back of individual body burden results, and to determine if participation in the study negatively affected breastfeeding rates or duration. METHODS: Participants of the Greater Boston PBDE Breastmilk Biomonitoring Study were contacted and asked about their experiences in the study: the impact of study recruitment materials on attitudes towards breastfeeding; if participants had wanted individual biomonitoring results; if the protocol by which individual results were distributed met participants' needs; and the impact of individual results on attitudes towards breastfeeding. RESULTS: No participants reported reducing the duration of breastfeeding because of the biomonitoring study, but some responses suggested that breastmilk biomonitoring studies have the potential to raise anxieties about breastfeeding. Almost all participants wished to obtain individual results. Although several reported some concern about individual body burden, none reported reducing the duration of breastfeeding because of biomonitoring results. The study literature and report-back method were found to mitigate potential negative impacts. CONCLUSION: Biomonitoring study design, including clear communication about the benefits of breastfeeding and the manner in which individual results are distributed, can prevent negative impacts of biomonitoring on breastfeeding. Adoption of more specific standards for biomonitoring studies and continued study of risk communication issues related to biomonitoring will help protect participants from harm.

Spatial-temporal analysis of breast cancer in upper Cape Cod, Massachusetts.

INTRODUCTION: The reasons for elevated breast cancer rates in the upper Cape Cod area of Massachusetts remain unknown despite several epidemiological studies that investigated possible environmental risk factors. Data from two of these population-based case-control studies provide geocoded residential histories and information on confounders, creating an invaluable dataset for spatial-temporal analysis of participants' residency over five decades. METHODS: The combination of statistical modeling and mapping is a powerful tool for visualizing disease risk in a spatial-temporal analysis. Advances in geographic information systems (GIS) enable spatial analytic techniques in public health studies previously not feasible. Generalized additive models (GAMs) are an effective approach for modeling spatial and temporal distributions of data, combining a number of desirable features including smoothing of geographical location, residency duration, or calendar years; the ability to estimate odds ratios (ORs) while adjusting for confounders; selection of optimum degree of smoothing (span size); hypothesis testing; and use of standard software. We conducted a spatial-temporal analysis of breast cancer case-control data using GAMs and GIS to determine the association between participants' residential history during 1947-1993 and the risk of breast cancer diagnosis during 1983-1993. We considered geographic location alone in a two-dimensional space-only analysis. Calendar year, represented by the earliest year a participant lived in the study area, and residency duration in the study area were modeled individually in one-dimensional time-only analyses, and together in a two-dimensional time-only analysis. We also analyzed space and time together by applying a two-dimensional GAM for location to datasets of overlapping calendar years. The resulting series of maps created a movie which allowed us to visualize changes in magnitude, geographic size, and location of elevated breast cancer risk for the 40 years of residential history that was smoothed over space and time. RESULTS: The space-only analysis showed statistically significant increased areas of breast cancer risk in the northern part of upper Cape Cod and decreased areas of breast cancer risk in the southern part (p-value = 0.04; ORs: 0.90-1.40). There was also a significant association between breast cancer risk and calendar year (p-value = 0.05; ORs: 0.53-1.38), with earlier calendar years resulting in higher risk. The results of the one-dimensional analysis of residency duration and the two-dimensional analysis of calendar year and duration showed that the risk of breast cancer increased with increasing residency duration, but results were not statistically significant. When we considered space and time together, the maps showed a large area of statistically significant elevated risk for breast cancer near the Massachusetts Military Reservation (p-value range:0.02-0.05; ORs range: 0.25-2.5). This increased risk began with residences in the late 1940s and remained consistent in size and location through the late 1950s. CONCLUSION: Spatial-temporal analysis of the breast cancer data may help identify new exposure hypotheses that warrant future epidemiologic investigations with detailed exposure models. Our methods allow us to visualize breast cancer risk, adjust for known confounders including age at diagnosis or index year, family history of breast cancer, parity and age at first live- or stillbirth, and test for the statistical significance of location and time. Despite the advantages of GAMs, analyses are for exploratory purposes and there are still methodological issues that warrant further research. This paper illustrates that GAM methods are a suitable alternative to widely-used cluster detection methods and may be preferable when residential histories from existing epidemiological studies are available.