Application of Augmented Intelligence for Pharmacovigilance Case Seriousness Determination.

INTRODUCTION: Identification of adverse events and determination of their seriousness ensures timely detection of potential patient safety concerns. Adverse event seriousness is a key factor in defining reporting timelines and is often performed manually by pharmacovigilance experts. The dramatic increase in the volume of safety reports necessitates exploration of scalable solutions that also meet reporting timeline requirements. OBJECTIVE: The aim of this study was to develop an augmented intelligence methodology for automatically identifying adverse event seriousness in spontaneous, solicited, and medical literature safety reports. Deep learning models were evaluated for accuracy and/or the F1 score against a ground truth labeled by pharmacovigilance experts. METHODS: Using a stratified random sample of safety reports received by Celgene, we developed three neural networks for addressing identification of adverse event seriousness: (1) a binary adverse-event level seriousness classifier; (2) a classifier for determining seriousness categorization at the adverse-event level; and (3) an annotator for identifying seriousness criteria terms to provide supporting evidence at the document level. RESULTS: The seriousness classifier achieved an accuracy of 83.0% in post-marketing reports, 92.9% in solicited reports, and 86.3% in medical literature reports. F1 scores for seriousness categorization were 77.7 for death, 78.9 for hospitalization, and 75.5 for important medical events. The seriousness annotator achieved an F1 score of 89.9 in solicited reports, and 75.2 in medical literature reports. CONCLUSIONS: The results of this study indicate that a neural network approach can provide an accurate and scalable solution for potentially augmenting pharmacovigilance practitioner determination of adverse event seriousness in spontaneous, solicited, and medical literature reports.

Serum cholesterol trajectories in the 10 years prior to lymphoma diagnosis.

PURPOSE: Many studies suggest a role for cholesterol in cancer development. Serum cholesterol levels have been observed to be low in newly diagnosed lymphoma cases. The objective of these analyses was to examine the time-varying relationship of cholesterol with lymphomagenesis in the 10 years prior to diagnosis by lymphoma subtype. METHODS: Participants were selected from the combined membership of six National Cancer Institute-funded Cancer Research Network health plans from 1998 to 2008, excluding members with human immunodeficiency virus, cancer (except lymphoma), or organ transplants. Incident lymphoma cases within this population were ascertained and matched with up to five controls. Total serum cholesterol, high-density lipoprotein, and low-density lipoprotein were collected from plan databases. Multilevel, multivariable longitudinal models were fit after choosing the best polynomial order by deviance statistics for selected lymphoma histotypes to examine pre-diagnosis cholesterol trajectories: Hodgkin lymphoma (n = 519) and all non-Hodgkin lymphomas combined (n = 12,635) as well as six subtypes of the latter. RESULTS: For all categories, lymphoma cases had statistically significantly lower estimated total serum cholesterol, high-density lipoprotein, and low-density lipoprotein levels than controls in the years prior to diagnosis/index date. Between-group differences were most pronounced 3-4 years prior to diagnosis, when cases' cholesterol levels declined steeply. CONCLUSIONS: This analysis is the first to examine changes in serum cholesterol for a decade prior to lymphoma diagnosis. A drop in cholesterol levels was evident several years before diagnosis. Our results suggest that cholesterol-related pathways have an important relationship with lymphomagenesis and low cholesterol could be a preclinical lymphoma marker.

Influence of NSAID Use Among Colorectal Cancer Survivors on Cancer Outcomes.

PURPOSE: Colorectal cancer (CRC) is the third most common cancer diagnosed in men and women in the United States. Given the availability of effective screening, most tumors are found early enough to offer patients substantial long-term survival. Thus there is a resulting significant population of CRC survivors for whom modifiable risk factors for recurrence and survival would be of interest. METHODS: We conducted a population-based retrospective cohort study among patients enrolled in 2 large Midwestern health plans for which claims data, including pharmacy fill data, and medical record data were available. Men and women who were 40 years of age or older at the time of CRC diagnosis with disease less than stage IV and no history of Crohn disease, ulcerative colitis, and irritable bowel syndrome were included. CRC cases diagnosed between January 1, 1990 and December 31, 2000 were included if they met the inclusion criteria. Adjusted Cox proportional hazard models were used with exposure modeled as a time-dependent covariate. We assessed progression-free survival, defined as an aggressive polyp or invasive disease, and overall survival. RESULTS: After adjustment for age at diagnosis, sex, race, body mass index, stage, side of initial tumor, and tumor histology, we found that current users of nonsteroidal anti-inflammatory drugs had a 3-fold decreased risk of recurrence and a >7-fold decreased risk of death. Our results are statistically significant with P-values <0.05. CONCLUSIONS: Our results suggest that current use of nonsteroidal anti-inflammatory drugs provides significant improvements in CRC outcomes.

Protective effect of bisphosphonates on endometrial cancer incidence in data from the Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial.

BACKGROUND: Preclinical studies have demonstrated antitumor effects of bisphosphonates. The objective of the current study was to determine the effect of exposure to bisphosphonate on the incidence of endometrial cancer. METHODS: The authors used data from the National Cancer Institute's Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, which collected data on all cancers. In year 5, all participants were asked to complete a self-administered supplemental questionnaire (SQX) that included questions regarding bone medication use. For women without a cancer diagnosis at the time of the SQX, the authors identified whether a woman reported current or former use of a nitrogenous bisphosphonate (NBP), defined as ever-use, and compared them with women never exposed to an NBP. Women with missing information were excluded as were women who reported undergoing a hysterectomy. Incidence rates and rate ratios were calculated with 95% confidence intervals (95% CIs). Cox proportional hazard ratios were also calculated and adjusted for covariates. RESULTS: A total of 29,254 women were included in the current analysis; an additional 77 cases of endometrial cancer have been diagnosed since the SQX. The incidence rate for endometrial cancer among women exposed to NBPs was 8.7 per 10,000 person-years versus 17.7 per 10,000 person-years among never-exposed women (rate ratio, 0.49; 95% CI, 0.30-0.80). The effect was similar after adjusting for all the covariates in the Cox proportional hazards analysis, with a hazard ratio of 0.56 (95% CI, 0.34-0.93). CONCLUSIONS: The results of the current study suggest that use of NBPs may have a protective effect on the incidence of endometrial cancer. However, additional studies are needed that include other potential confounders and a larger sample.

Cancer screening among a population-based sample of insured women.

PURPOSE: Screening has been shown to lower the morbidity and mortality for breast, cervical, and colorectal cancers. Despite the availability of cancer screening, nearly 70,000 women die each year from these cancers. We conducted a study in 2008 within a privately-insured patient population of women who were members of an integrated health care system in Southeastern Michigan, for whom information on ovarian cancer risk as well as personal and family history of cancer was available. METHODS: We used a population-based, weighted stratified random sample of women from a single health care institution to assess the proportion with up-to-date breast, cervical, and colorectal screening. Multivariable analyses were conducted to identify predictors of screening behavior. RESULTS: In our study, women reported cervical and breast cancer screening above 90% and colorectal cancer screening above 75%. CONCLUSIONS: The results of our study hold promise that Healthy People 2020 cancer screening objectives might be obtainable as access to health insurance is expanded among US residents.

Statin use and risk of hepatocellular carcinoma in a U.S. population.

PURPOSE: Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) are medications widely prescribed to reduce cholesterol levels. Observational studies in high-risk populations, mostly in Asia, have suggested that statins are associated with a reduced risk of hepatocellular carcinoma (HCC). The current study sought to evaluate the association of statin use and HCC in a U.S.-based, low-risk, general population. METHODS: A nested case-control study was conducted among members of the Health Alliance Plan HMO of the Henry Ford Health System enrolled between 1999 and 2010. Electronic pharmacy records of statin use were compared among tumor registry-confirmed cases of HCC (n=94) and controls (n=468) matched on age, sex, diagnosis date, and length of HMO enrolment. RESULTS: In multivariate analyses, ever-use of statins was significantly inversely associated with development of HCC (Odds ratio (OR): 0.32, 95%CI: 0.15-0.67). No clear dose-response relationship was evident as statin use for <2 years (OR=0.32, 95%CI=0.13-0.83) and >2 years (OR=0.31, 95CI%=0.12-9.81) resulted in very similar ORs. CONCLUSIONS: The use of statins among populations in low-risk HCC areas may be associated with decreased risk of HCC.

Informed choice about breast cancer prevention: randomized controlled trial of an online decision aid intervention.

INTRODUCTION: Tamoxifen and raloxifene are chemopreventive drugs that can reduce women's relative risk of primary breast cancer by 50%; however, most women eligible for these drugs have chosen not to take them. The reasons for low uptake may be related to women's knowledge or attitudes towards the drugs. We aimed to examine the impact of an online breast cancer chemoprevention decision aid (DA) on informed intentions and decisions of women at high risk of breast cancer. METHODS: We conducted a randomized clinical trial, assessing the effect of a DA about breast cancer chemoprevention on informed choices about chemoprevention. Women (n = 585), 46- to 74-years old old, completed online baseline, post-test, and three-month follow-up questionnaires. Participants were randomly assigned to either an intervention group, a standard control group that answered questions about chemoprevention at baseline, or a three-month control group that did not answer questions about chemoprevention at baseline. The main outcome measures were whether women's intentions and decisions regarding chemoprevention drugs were informed, and whether women who viewed the DA were more likely to make informed decisions than women who did not view the DA, using a dichotomous composite variable 'informed choice' (yes/no) to classify informed decisions as those reflecting sufficient knowledge and concordance between a woman's decision and relevant attitudes. RESULTS: Analyses showed that more intervention than standard control participants (52.7% versus 5.9%) made informed decisions at post-test, P <0.001. At the three-month follow-up, differences in rates of informed choice between intervention (16.9%) and both control groups (11.8% and 8.0%) were statistically non-significant, P = 0.067. CONCLUSIONS: The DA increased informed decision making about breast cancer chemoprevention, although the impact on knowledge diminished over time. This study was not designed to determine how much knowledge decision makers must retain over time. Examining informed decisions increases understanding of the impact of DAs. A standard for defining and measuring sufficient knowledge for informed decisions is needed. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00967824

Recruiting women for a study on perceived risk of cancer: influence of survey topic salience and early versus late response.

INTRODUCTION: Understanding the characteristics of early and late survey responders has implications for recruitment efforts and for informing potential response bias. The main objective of this analysis was to examine survey responder status (ie, early vs late response) by sociodemographic characteristics and by salience of study variables among respondents. METHODS: We analyzed data from a survey on family cancer history and perceived cancer risk among women at a large managed health-care organization. For baseline and 12-month follow-up surveys, we defined early versus late responder status according to the 95th percentile of the number of days it took to obtain completed interviews. RESULTS: We found no significant associations between responder status and sociodemographic characteristics at baseline or follow-up. At baseline, early responders were significantly more likely than late responders to have a personal history of breast cancer (5.2% vs 3.4%, P = .04) and to have been referred for genetic counseling (4.6% vs 2.0%, P = .004). The association between personal history of breast cancer and responder status persisted at follow-up; only 3.5% of late responders at baseline were also late responders at follow-up. Follow-up survey nonresponse rates did not vary by baseline responder status. CONCLUSION: Survey topic salience is associated with early response and is important for recruitment. However, once recruited, late responders do not remain late responders at follow-up, suggesting that extra efforts made to recruit late responders are worthwhile. Health-related agencies that conduct surveys should consider survey salience in survey administration and recruitment strategies.

Belief in numbers: When and why women disbelieve tailored breast cancer risk statistics.

OBJECTIVE: To examine when and why women disbelieve tailored information about their risk of developing breast cancer. METHODS: 690 women participated in an online program to learn about medications that can reduce the risk of breast cancer. The program presented tailored information about each woman's personal breast cancer risk. Half of women were told how their risk numbers were calculated, whereas the rest were not. Later, they were asked whether they believed that the program was personalized, and whether they believed their risk numbers. If a woman did not believe her risk numbers, she was asked to explain why. RESULTS: Beliefs that the program was personalized were enhanced by explaining the risk calculation methods in more detail. Nonetheless, nearly 20% of women did not believe their personalized risk numbers. The most common reason for rejecting the risk estimate was a belief that it did not fully account for personal and family history. CONCLUSIONS: The benefits of tailored risk statistics may be attenuated by a tendency for people to be skeptical that these risk estimates apply to them personally. PRACTICE IMPLICATIONS: Decision aids may provide risk information that is not accepted by patients, but addressing the patients' personal circumstances may lead to greater acceptance.

Prevalence and healthcare actions of women in a large health system with a family history meeting the 2005 USPSTF recommendation for BRCA genetic counseling referral.

BACKGROUND: In 2005, the United States Preventive Services Task Force (USPSTF) released guidelines which outlined specific family history patterns associated with an increased risk for BRCA1/2 mutations, and recommended at-risk individuals be referred for genetic counseling and evaluation for BRCA testing. The purpose of this study was to assess the prevalence of individuals with a USPSTF increased-risk family history pattern, the frequency with which specific patterns were met, and resulting healthcare actions among women from the Henry Ford Health System. METHODS: As part of a study evaluating ovarian cancer risk perception and screening, 2,524 randomly selected participants completed a detailed interview (response rate 76%) from an initial eligible cohort of 16,720 women. RESULTS: Approximately 6% of participants had a family history fulfilling one or more of the USPSTF patterns. Although 90% of these women had shared their family history with their provider, less than 20% had been referred for genetic counseling and only 8% had undergone genetic testing. Caucasian women with higher income and education levels were more likely to receive referrals. Among the 95 participants in the total study cohort who reported BRCA testing, 78% did not have a family history that met one of the USPSTF patterns. CONCLUSIONS: These results suggest a higher prevalence of women with an increased-risk family history than originally predicted by the USPSTF, and lack of provider recognition and referral for genetic services. IMPACT: Improvements in healthcare infrastructure and clinician education will be required to realize population level benefits from BRCA genetic counseling and testing.

Associations between risk perceptions and worry about common diseases: a between- and within-subjects examination.

The relationships between worry and perceptions of likelihood and severity were evaluated across eight common diseases. Individual and disease variability in worry and perceptions were examined. 294 participants were recruited through the Multiplex Initiative, in which a genetic susceptibility test for eight common diseases was offered to healthy adults. Participants completed a baseline telephone survey and web-based surveys without a commitment to be tested, and then made a choice on testing. Between- and within-subjects analyses yielded the following main findings: (1) worry is more closely related to likelihood perceptions than to severity perceptions; (2) severity perceptions add significantly to explained worry variances above and beyond likelihood perceptions; (3) risk perceptions and worries form two clusters: cancer diseases and cardiovascular-metabolic diseases; and (4) variance in risk perception and worry is explained by a combination of between- and within-subjects variances. Risk perception research should attend to severity perceptions, within-subjects variability and inter-disease differences, and to strategies for grouping conditions.

Utilization of HER2 genetic testing in a multi-institutional observational study.

INTRODUCTION: Human epidermal growth factor receptor 2 (HER2) expression is amplified in about 20% of breast cancer tumors, and evaluation of HER2 status should influence therapy selection. A critical gap in our knowledge is the real-world implementation of HER2 testing and its impact on treatment decisions for women diagnosed with breast cancer. OBJECTIVES: To assess use of HER2 testing, to describe characteristics of patients who do or do not receive HER2 testing, to describe which HER2 tests were used (fluorescence in situ hybridization or immunohistochemistry), and to evaluate trastuzumab use as a function of HER2 results. STUDY DESIGN: The population included 6460 women diagnosed with invasive breast cancer between 1999 and 2007 at 8 geographically distributed Cancer Research Network healthcare delivery systems in the United States. METHODS: Electronic records were used to identify patient and tumor characteristics and treatment with trastuzumab. Chart abstraction was performed for 400 women (50 per site) to identify receipt of HER2 testing and results. RESULTS: More than 90% of study participants received HER2 testing. Everyone who received trastuzumab had a HER2 test, and nearly all (>95%) who received trastuzumab had a positive HER2 test result recorded in their medical chart. Most (77%) eligible patients with a positive HER2 test result diagnosed after 2005 received trastuzumab. This study expands upon previous work in individual health plans. CONCLUSIONS: HER2 status has been successfully incorporated into medical practice to guide treatment decisions for breast cancer patients in diverse integrated healthcare delivery settings.

Racial differences in oncogene mutations detected in early-stage low-grade endometrial cancers.

OBJECTIVE: To describe the pattern and frequency of oncogene mutations in white and African American women with endometrial cancer and to determine if racial differences in oncogene mutations exist among women with pathologically similar tumors. METHODS: Patients with endometrial cancer from a large urban hospital were identified through medical records, and representative formalin-fixed paraffin-embedded tumor blocks were retrieved. The study sample included 150 patients (84 African Americans) who underwent total abdominal hysterectomy for endometrial cancer. The Sequenom MassARRAY system and the OncoCarta Assay version 1.0 (Sequenom) were used to test for 238 mutations in 19 common oncogenes. The χ(2) test and the Fisher exact test were used to assess differences in distribution of variables by race and oncogene mutation status. RESULTS: There were 20 mutations identified in 2 oncogenes (PIK3CA and KRAS) in tumors from 19 women (12.7%). Most of the mutations were found in PIK3CA (16/20). Thirteen percent of endometrioid tumors harbored mutations (11 PIK3CA and 2 KRAS) as did 29% of the malignant mixed Mullerian tumors (3 PIK3CA and 1 KRAS). There were no observed mutations in serous, clear cell, or mucinous tumor types. Among low-grade endometrioid cancers, tumors from African American patients were significantly associated with harboring either a KRAS or PIK3CA mutation (P = 0.04), with 7 PIK3CA mutations and all 4 KRAS mutations identified in African American women. CONCLUSIONS: This study provides preliminary evidence that oncogene mutation frequency of some subtypes of histologically similar endometrial carcinoma differ by race. Additional studies are needed to further explore this phenomenon in patients with endometrial carcinoma.

Association between health-service use and multiplex genetic testing.

PURPOSE: The objective of this work was to examine whether offers of multiplex genetic testing increase health-care utilization among healthy patients aged 25-40 years. The identification of genetic variants associated with common disease is accelerating rapidly. "Multiplex tests" that give individuals feedback on large panels of genetic variants have proliferated. Availability of these test results may prompt consumers to use more health-care services. METHODS: A total of 1,599 continuously insured adults aged 25-40 years were surveyed and offered a multiplex genetic susceptibility test for eight common health conditions. Health-care utilization from automated records was compared in 12-month pre- and posttest periods among persons who completed a baseline survey only (68.7%), those who visited a study website but opted not to test (17.8%), and those who chose the multiplex genetic susceptibility test (13.6%). RESULTS: In the pretest period, persons choosing genetic testing used an average of 1.02 physician visits per quarter as compared with 0.93 and 0.82 for the baseline-only and Web-only groups, respectively (P < 0.05). There were no statistically significant differences by group in the pretest use of any common medical tests or procedures associated with four common health conditions. When changes in physician and medical test/procedure use in the posttest period were compared among the groups, no statistically significant differences were observed for any utilization category. CONCLUSIONS: Persons offered and completing multiplex genetic susceptibility testing used more physician visits before testing, but testing was not associated with subsequent changes in use. This study supports the supposition that multiplex genetic testing offers can be provided directly to the patients in such a way that use of health services is not inappropriately increased.

Patients' understanding of and responses to multiplex genetic susceptibility test results.

PURPOSE: Examination of patients' responses to direct-to-consumer genetic susceptibility tests is needed to inform clinical practice. This study examined patients' recall and interpretation of, and responses to, genetic susceptibility test results provided directly by mail. METHODS: This observational study had three prospective assessments (before testing, 10 days after receiving results, and 3 months later). Participants were 199 patients aged 25-40 years who received free genetic susceptibility testing for eight common health conditions. RESULTS: More than 80% of the patients correctly recalled their results for the eight health conditions. Patients were unlikely to interpret genetic results as deterministic of health outcomes (mean = 6.0, s.d. = 0.8 on a scale of 1-7, 1 indicating strongly deterministic). In multivariate analysis, patients with the least deterministic interpretations were white (P = 0.0098), more educated (P = 0.0093), and least confused by results (P = 0.001). Only 1% talked about their results with a provider. CONCLUSION: Findings suggest that most patients will correctly recall their results and will not interpret genetics as the sole cause of diseases. The subset of those confused by results could benefit from consultation with a health-care provider, which could emphasize that health habits currently are the best predictors of risk. Providers could leverage patients' interest in genetic tests to encourage behavior changes to reduce disease risk.

Cardiovascular outcomes in women with advanced breast cancer exposed to chemotherapy.

PURPOSE: To quantify incidence of cardiovascular outcomes in patients with advanced breast cancer receiving cardiotoxic and non-cardiotoxic chemotherapy. METHODS: This study identified all women at a Midwestern health system with initial diagnosis of American Joint Commission on Cancer Stage III/IV breast cancer (1995-2003) and random sample of 50 women initially diagnosed with Stage I/II who progressed to Stage III/IV. The rate of new cardiovascular outcomes (heart failure, dysrhythmia, and ischemia events) for cardiotoxic (anthracycline or trastuzumab) and non-cardiotoxic agents was calculated. RESULTS: Of 315 patients, 90.5% (n = 285) received systemic cancer therapy; 67.7% (n = 193) received cardiotoxic drugs. Older patients were less likely to receive cardiotoxic agents (86.4%, ≤59 years vs. 31.9%, 70+ years). Adjusting for age, race, stage, surgery/radiation, estrogen receptor/progesterone receptor status, and diagnosis year, rate of new cardiac events was higher in patients exposed to cardiotoxic drugs compared with those exposed to non-cardiotoxic drugs (adjusted hazard ratio = 2.5, 95%CI = 0.9-7.2). Patients with cardiac event history (relative risk = 3.2, 95%CI = 2.0-5.1) and those with heart failure history (relative risk = 5.9, 95%CI = 2.4-14.6) were more likely to receive non-cardiotoxic treatment. Heart failure events occurred steadily over time; after 3 years of follow-up, 16% exposed to cardiotoxic drugs experienced an event, and 8% of those exposed to non-cardiotoxic drugs experienced an event. CONCLUSIONS: Patients with cardiac comorbidity are less likely to receive cardiotoxic agents. Use of cardiotoxic agents is common; treatment is related to patient and tumor characteristics and is associated with substantial risk of cardiotoxicity that persists during patients' remaining lifespan.

Increased risk for distant metastasis in patients with familial early-stage breast cancer and high EZH2 expression.

The identification of women with early-stage breast cancer who will develop distant metastasis may improve clinical management. The transcriptional regulator Enhancer of Zeste-2 (EZH2) is overexpressed in invasive breast carcinoma compared with benign breast tissues, with maximal expression in breast cancer metastasis. In this article, our purpose was to investigate the performance of EZH2 protein detection as a predictor of metastasis in women with early-stage breast cancer, which is unknown. We developed a cohort of 480 women with stage I-IIA breast cancer diagnosed between 1996 and 2002 and recorded detailed sociodemographic, clinical, and pathological information. Tumors were histologically characterized and arrayed in tissue microarrays containing 1,443 samples. The nuclear EZH2 expression was investigated by immunohistochemistry and was scored as 1-2 (negative and weak) or 3-4 (moderate and strong) using a validated scoring schema. Scores 1-2 were considered low EZH2; scores 3-4 were considered high EZH2. In this study, we found that after a median follow up of 9 years (range 0.04-14.5 years) 46 of 480 patients (9.6%) developed distant metastasis. High EZH2 was associated with larger size, high histological grade, negative hormone receptors, and first degree family history of breast and/or ovarian carcinoma. While EZH2 could not predict survival in the entire cohort, high EZH2 was a predictor of disease-specific survival in patients with early-stage disease and first degree family history (log rank P value 0.05). Importantly, in this group of patients, high EZH2 was an independent predictor of distant metastasis up to 15 years after primary carcinoma diagnosis (hazard ratio 6.58, 95% CI: 1.40-30.89, P = 0.016) providing survival information above and beyond currently used prognosticators. In conclusion, EZH2 may be a useful biomarker of long-term metastatic risk in women with familial early-stage breast cancer, and warrant further validation studies.

Modelling decisions to undergo genetic testing for susceptibility to common health conditions: an ancillary study of the Multiplex Initiative.

New genetic tests reveal risks for multiple conditions simultaneously, although little is understood about the psychological factors that affect testing uptake. We assessed a conceptual model called the multiplex genetic testing model (MGTM) using structural equation modelling. The MGTM delineates worry, perceived severity, perceived risk, response efficacy and attitudes towards testing as predictors of intentions and behaviour. Participants were 270 healthy insured adults aged 25-40 from the Multiplex Initiative conducted within a health care system in Detroit, MI, USA. Participants were offered a genetic test that assessed risk for eight common health conditions. Confirmatory factor analysis revealed that worry, perceived risk and severity clustered into two disease domains: cancer or metabolic conditions. Only perceived severity of metabolic conditions was correlated with general response efficacy (ß = 0.13, p<0.05), which predicted general attitudes towards testing (ß = 0.24, p<0.01). Consistent with our hypothesised model, attitudes towards testing were the strongest predictors of intentions to undergo testing (ß = 0.49, p<0.01), which in turn predicted testing uptake (OR 17.7, ß = 0.97, p<0.01). The MGTM explained a striking 48% of the variance in intentions and 94% of the variation in uptake. These findings support use of the MGTM to explain psychological predictors of testing for multiple health conditions.

The distinct role of comparative risk perceptions in a breast cancer prevention program.

BACKGROUND: Comparative risk perceptions may rival other types of information in terms of effects on health behavior decisions. PURPOSE: We examined associations between comparative risk perceptions, affect, and behavior while controlling for absolute risk perceptions and actual risk. METHODS: Women at an increased risk of breast cancer participated in a program to learn about tamoxifen which can reduce the risk of breast cancer. They reported comparative risk perceptions of breast cancer and completed measures of anxiety, knowledge, and tamoxifen-related behavior intentions. Three months later, the women reported their behavior. RESULTS: Comparative risk perceptions were positively correlated with anxiety, knowledge, intentions, and behavior 3 months later. After controlling for participants' actual risk of breast cancer and absolute risk perceptions, comparative risk perceptions predicted anxiety and knowledge, but not intentions or behavior. CONCLUSIONS: Comparative risk perceptions can affect patient outcomes like anxiety and knowledge independently of absolute risk perceptions and actual risk information.

Women's interest in taking tamoxifen and raloxifene for breast cancer prevention: response to a tailored decision aid.

Although tamoxifen can prevent primary breast cancer, few women use it as a preventive measure. A second option, raloxifene, has recently been approved. The objective of the study was to determine women's interest in tamoxifen and raloxifene after reading a decision aid (DA) describing the risks and benefits of each medication. Women with 5-year risk of breast cancer ≥ 1.66 from two large health maintenance organizations were randomized to receive a DA versus usual care. After reading an on-line DA that discussed the risks and benefits of tamoxifen and raloxifene, women completed measures of risk perception, decisional conflict, behavioral intentions, and actual behavior related to tamoxifen and raloxifene. 3 months following the intervention, 8.1% of participants had looked for additional information about breast cancer prevention drugs, and 1.8% had talked to their doctor about tamoxifen and/or raloxifene. The majority, 54.7%, had decided to not take either drug, 0.5% had started raloxifene, and none had started tamoxifen. Participants were not particularly worried about taking tamoxifen or raloxifene and did not perceive significant benefits from taking these drugs. Over 50% did not perceive a change in their risk of getting breast cancer if they took tamoxifen or raloxifene. After reading a DA about tamoxifen and raloxifene, few women were interested in taking either breast cancer prevention drug.