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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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).

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.

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.

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.

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.

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.

Consumers' use of web-based information and their decisions about multiplex genetic susceptibility testing.

Background: Few data exist to inform concerns raised by online direct-to-consumer marketing of genetic susceptibility tests, such as those offered by commercial entities like 23andme, Navigenics, and DNA Direct. The Multiplex Initiative, a population-based study of healthy adults, provides the first opportunity to evaluate how use of a Web-based decision tool that conveyed information about a genetic susceptibility test influenced individuals' test decisions.

Objective: To inform the ongoing debate over whether individuals offered genetic susceptibility testing without the involvement of a health care provider (eg, through direct-to-consumer testing) can make informed decisions about testing when guided by online decision aids.

Preferences for genetic and behavioral health information: the impact of risk factors and disease attributions.

Increased availability of genetic risk information may lead the public to give precedence to genetic causation over behavioral/environmental factors, decreasing motivation for behavior change. Few population-based data inform these concerns. We assess the association of family history, behavioral risks, and causal attributions for diseases and the perceived value of pursuing information emphasizing health habits or genes.

The role of lymph node metastasis in the systemic dissemination of breast cancer.

Background: Lymphatic invasion is necessary for regional lymph node (RLN) metastasis in breast cancer (BC), while systemic metastasis requires blood vessel (BV) invasion. The site of BV invasion could be at the primary BC site or through lymphovascular anastomoses. The vague pathologic term "lymphovascular invasion" (LVI) encourages the belief that peri/intratumoral BV invasion may be common.

Characteristics of users of online personalized genomic risk assessments: implications for physician-patient interactions.

Purpose: To evaluate what psychological and behavioral factors predict who is likely to seek SNP-based genetic tests for multiple common health conditions where feedback can be used to motivate primary prevention.

Methods: Adults aged 25-40 years who were enrolled in a large managed care organization were surveyed. Those eligible could log on to a secure study Web site to review information about the risks and benefits of a SNP-based genetic test and request free testing.

Putting science over supposition in the arena of personalized genomics.

Colleen McBride and colleagues argue that progress on a multifaceted research agenda is necessary to reap the full benefits and avoid the potential pitfalls of the emerging area of personalized genomics. They also outline one element of this agenda, the Multiplex Initiative, which has been underway since 2006.