Uptake of screening and risk-reducing recommendations among women with hereditary breast and ovarian cancer syndrome due to pathogenic BRCA1/2 variants evaluated at a large urban comprehensive cancer center.

PURPOSE: Carriers of pathogenic variants in BRCA1/2 have an elevated lifetime cancer risk warranting high-risk screening and risk-reducing procedures for early detection and prevention. We report on prevention practices among women with pathogenic BRCA variants in order to document follow through with NCCN recommendations and to identify barriers to guideline-recommended care. METHODS: Our cohort included women who had genetic testing through a cancer genetic clinic and completed a 54-item questionnaire to measure socio-demographics, medical history, rates of cancer screening and risk-reducing surgery, disclosure of test results, and cancer worry. Outcomes included rates of completion of risk-reducing salpingo-oophorectomy (RRSO), risk-reducing mastectomy (RRM), and NCCN risk-reducing and age-dependent screening guidelines (version 3.2019). Multivariable logistic regression analyses were used to evaluate potential predictors of these outcomes. RESULTS: Of 129 evaluable women with pathogenic BRCA1/2 variants, 95 (74%) underwent RRSO and 77 (60%) had RRM, respectively, and 107 (83%) were considered adherent to NCCN guidelines. Women with a history of breast or ovarian cancer were more likely to have RRM (OR = 4.38; 95% CI 1.80-11.51; p = 0.002). Increasing age was associated with an increased likelihood of RRSO (OR = 1.05; 95% CI 1.01-1.09; p = 0.019) and decreased likelihood for RRM (OR = 0.95; 95% CI 0.92-0.99; p = 0.013). Women who had RRM were 3 times more likely to undergo RRSO (OR = 2.81; 95% CI 1.10-7.44; p = 0.025). Women who had genetic testing after June 2013 were less likely to have RRM than those tested before June 2013 (OR = 0.42; 95% CI 0.18-0.95; p = 0.040. None of the other measured factors were associated with rates of RRSO, RRM or follow through with NCCN recommendations. There was near universal (127/129) reported disclosure of genetic test results to family members, resulting in the discovery of a median of 1 relative with a pathogenic variant (range = 0-8). CONCLUSION: An evaluation of follow up practice in a cohort of women with pathogenic variants in BRCA1/2 revealed high rates of reported completion of screening and surgical risk-reducing recommendations. Educational efforts should continue to reinforce the importance of follow-through with guideline recommended care among this high-risk group.

Stability of Protein Pharmaceuticals: Recent Advances.

There have been significant advances in the formulation and stabilization of proteins in the liquid state over the past years since our previous review. Our mechanistic understanding of protein-excipient interactions has increased, allowing one to develop formulations in a more rational fashion. The field has moved towards more complex and challenging formulations, such as high concentration formulations to allow for subcutaneous administration and co-formulation. While much of the published work has focused on mAbs, the principles appear to apply to any therapeutic protein, although mAbs clearly have some distinctive features. In this review, we first discuss chemical degradation reactions. This is followed by a section on physical instability issues. Then, more specific topics are addressed: instability induced by interactions with interfaces, predictive methods for physical stability and interplay between chemical and physical instability. The final parts are devoted to discussions how all the above impacts (co-)formulation strategies, in particular for high protein concentration solutions.'

Results of an African American-targeted norm-based colorectal cancer screening intervention: a pilot study.

Lower colorectal cancer screening rates among African Americans contribute to higher colorectal cancer incidence and mortality. We tested the effects of a racially-targeted messaging intervention that used favorable behavioral norm information to increase uptake of at-home Fecal Immunochemical Test (FIT) Kits. We expected stronger intervention effects among African Americans with stronger racial identity. Eligible African Americans were randomized to one of four intervention conditions: injunctive norm message, descriptive norm message, both messages, neither message. The norm-based messages were delivered via an animated video health message. Background variables, constructs defined by the theory of planned behavior, racial identity, screening modality preferences, and uptake and return of FIT Kits were assessed. Of 205 participants, 111(54%) requested FIT Kits. Contrary to hypotheses, multigroup path analyses indicated stronger effects of targeted messages among African Americans with weaker racial identity. Findings highlight the importance of within-race heterogeneity in the receptivity to racially-targeted health messages.

Medical mistrust, culturally targeted message framing, and colorectal cancer screening among African Americans.

Mistrust in the information and treatment provided by medical professionals and organizations hinders cancer screening among African Americans. However, its impact on responses to health messaging aimed at bolstering screening uptake is unknown. The present study examined the effects of medical mistrust on message framing and culturally targeted health messaging about colorectal cancer (CRC) screening. Screening eligible African Americans (N = 457) completed the Group-Based Medical Mistrust scale and then viewed an informational video about CRC risks, prevention, and screening, during which all participants received either a gain or loss-framed message about screening. Half of participants received an additional culturally targeted screening message. After messaging, all participants completed Theory of Planned Behavior measures of CRC screening receptivity, as well as items assessing expectations about experiencing racism when obtaining CRC screening (i.e., anticipatory racism). Hierarchical multiple regressions showed that medical mistrust predicted lower screening receptivity and greater anticipatory racism. Additionally, effects of health messaging were moderated by medical mistrust. Among participants high in mistrust, targeted messaging-regardless of message frame-bolstered normative beliefs about CRC. Additionally, only targeted loss-framed messaging bolstered attitudes toward CRC screening. Although targeted messaging reduced anticipatory racism among participants with high mistrust, anticipatory racism did not mediate messaging effects. Findings indicate medical mistrust may be an important culturally-relevant individual difference to attend to in addressing CRC screening disparities, including its potential to impact responses to cancer screening messaging.

Message Framing for Men? Gender Moderated Effects of Culturally Targeted Message Framing on Colorectal Cancer Screening Receptivity among African Americans.

Receptivity to recommended colorectal cancer (CRC) screening can be enhanced by use of loss-framed health messaging that emphasizes possible consequences of failing to act. However, a simultaneous use of culturally targeted messaging may be needed to achieve effectiveness when loss-framed messaging is used with African Americans, especially to reduce racism-related cognitions aroused by standard loss framing that impede CRC screening receptivity. This study considered whether effects of stand-alone and culturally targeted message framing on CRC screening receptivity differ between African American men and women. African Americans eligible for CRC screening (Men=117, Women=340) viewed an informational video about CRC risks, prevention, and screening, and were randomized to receive a gain or loss-framed message about screening. Half of participants received an additional culturally targeted message. Using the Theory of Planned Behavior, we measured receptivity to CRC screening. We also measured arousal of racism-related cognitions. A significant three-way interaction suggested effects of messaging on CRC screening receptivity were moderated by gender. Participants were no more receptive to CRC screening when standard loss-framing was used, but were more favorable if loss-framing was culturally targeted. However, these effects were more pronounced among African American men. Contrary to prior findings, gender moderated effects of culturally targeted loss-framed messaging were not attributable to reducing racism-related cognitions. Findings add to growing recognition of important nuance in effective use of message framing to also include gender, while suggesting a critical need to explore gender-relevant mechanistic pathways, potentially including how health messaging activates masculinity-related cognitions among African American men.

Physicians' perceptions of breast density notification laws and appropriate patient follow-up.

Breast density notification laws have been adopted in the absence of consistent guidelines for post-notification follow-up. This can lead to inconsistent and potentially deficient management of women's health due to inconsistent physician practices. We examined physicians' knowledge and practices regarding follow-up for patients who receive density notifications. Physicians who referred patients to a Michigan hospital network for screening mammograms were recruited to participate in survey study; 105 (29.8%) responded. The survey assessed physicians' demographics, knowledge, and awareness of breast density and breast cancer risk and of density notification laws, and perceptions of appropriate follow-up behaviors for their patients who received density notifications. Most physicians (75%) knew about the notification law, and they were generally comfortable responding to breast density questions and deciding on follow-up. Most indicated that additional breast imaging (68.0%), followed by assessing breast cancer risk (24.7%) were appropriate follow-up responses. Physicians who performed breast cancer risk assessments, and who were more comfortable with breast density questions and follow-up decision making, were more likely to propose additional imaging. Male physicians were less likely to propose assessing breast cancer risk, and less likely to propose clinical and/or breast self-examinations. Divergence between practice and guidelines when it comes to supplemental breast cancer screening, coupled with density notification language that promotes additional screening in the absence of consistent evidence, remains concerning. Improved understanding of how density notification recipients and their physicians make decisions about supplemental screening is warranted to ensure that breast cancer risk is properly considered.

Patterns of cancer family history and genetic counseling eligibility among African Americans with breast, prostate, lung, and colorectal cancers: A Detroit Research on Cancer Survivors cohort study.

BACKGROUND: Family history (FH) remains one of the strongest risk factors for many common cancers and is used to determine cancer genetic counseling (CGC) eligibility, but the understanding of familial cancer patterns in African Americans is limited. METHODS: This study evaluated cancer FH among African Americans with invasive breast cancer, prostate cancer, lung cancer, or colorectal cancer (CRC) in the Detroit Research on Cancer Survivors (ROCS) cohort. Associations between participant cancer type, site-specific FH, and meeting national guidelines for CGC were evaluated via logistic regression. Cancer FH patterns were evaluating via hierarchical clustering. RESULTS: Among 1500 ROCS participants, 71% reported at least 1 first-degree relative or grandparent with cancer. FHs of breast cancer, CRC, lung cancer, and prostate cancer were most common among participants with the same diagnosis (odds ratio [OR] for breast cancer, 1.14; P < .001; OR for CRC, 1.08; P = .003; OR for lung cancer, 1.09; P = .008; OR for prostate cancer, 1.14; P < .001). Nearly half of the participants (47%) met national CGC guidelines, and 24.4% of these participants met CGC criteria on the basis of their cancer FH alone. FH was particularly important in determining CGC eligibility for participants with prostate cancer versus breast cancer (OR for FH vs personal history alone, 2.91; 95% confidence interval, 1.94-4.35; P < .001). In clustering analyses, breast and prostate cancer FH-defined clusters were common across all participants. Clustering of CRC and breast cancer FHs was also observed. CONCLUSIONS: ROCS participants reported high rates of cancer FH. The high rate of eligibility for CGC among ROCS participants supports the need for interventions to increase referrals and uptake of CGC among African Americans.

Between-Race Differences in Processes Predicting Physician Communication for African American and European American Recipients of Breast Density Notifications.

BACKGROUND: Breast density notification laws mandate reporting of dense breast to applicable women. The same psychological and systemic barriers that yield between-race differences in mammography use will probably yield between-race differences in women's psychological and behavioral responses to breast density notifications. PURPOSE: We used the theory of planned behavior as a framework to examine between-race differences in the likelihood of following-up with physicians after receiving breast density notifications and to examine differences in African American and Caucasian American women's behavioral decision-making processes. METHODS: A subset of 212 African American and Caucasian American women who participated in an initial and follow-up survey examining responses to breast density notifications were examined for this study. Participants reported background and demographic measures, psychological responses to receiving notifications, and planned behavior measures related to following up with physicians approximately 2 weeks after receiving their mammogram reports. Participants self-reported their behaviors 3 months later. RESULTS: There were no between-race differences in self-reported physician communication; however, there were differences in processes that predicted behavior. For Caucasian American women, behavioral intentions, education, and income predicted behaviors. Instead of intentions, group-based medical suspicion, confusion, breast cancer worry, and breast density anxiety predicted behaviors for African American women. CONCLUSIONS: Behavioral decision-making processes for Caucasian American women were in line with well-validated theoretical predictions. For African American women, race-related medical suspicion, prior breast density awareness, and emotional responses to breast density notifications predicted behavior. The results highlight the need to focus on racially distinct psychological targets when designing interventions to support guideline concordant behavioral decisions among women who receive breast density notifications.

Denaturation and Aggregation of Interferon-τ in Aqueous Solution.

PURPOSE: To evaluate the different degrees of residual structure in the unfolded state of interferon-τ using chemical denaturation as a function of temperature by both urea and guanidinium hydrochloride. METHODS: Asymmetrical flow field-flow fractionation (AF4) using both UV and multi-angle laser light scattering (MALLS). Flow Microscopy. All subvisible particle imaging measurements were made using a FlowCAM flow imaging system. RESULTS: The two different denaturants provided different estimates of the conformational stability of the protein when extrapolated back to zero denaturant concentration. This suggests that urea and guanidinium hydrochloride (GnHCl) produce different degrees of residual structure in the unfolded state of interferon-τ. The differences were most pronounced at low temperature, suggesting that the residual structure in the denatured state is progressively lost when samples are heated above 25°C. The extent of expansion in the unfolded states was estimated from the m-values and was also measured using AF4. In contrast, the overall size of interferon-τ was determined by AF4 to decrease in the presence of histidine, which is known to bind to the native state, thereby providing conformational stabilization. Addition of histidine as the buffer resulted in formation of fewer subvisible particles over time at 50°C. Finally, the thermal aggregation was monitored using AF4 and the rate constants were found to be comparable to those determined previously by SEC and DLS. The thermal aggregation appears to be consistent with a nucleation-dependent mechanism with a critical nucleus size of 4 ± 1. CONCLUSION: Chemical denaturation of interferon-τ by urea or GnHCl produces differing amounts of residual structure in the denatured state, leading to differing estimates of conformational stability. AF4 was used to determine changes in size, both upon ligand binding as well as upon denaturation with GnHCl. Histidine appears to be the preferred buffer for interferon-τ, as shown by slower formation of soluble aggregates and reduced levels of subvisible particles when heated at 50°C.

Targeting and tailoring message-framing: the moderating effect of racial identity on receptivity to colorectal cancer screening among African-Americans.

This study demonstrates the potential of racial identity to moderate how gain and loss-framed messaging, as well as culturally-targeted messaging, can affect receptivity to preventive health screening. African-Americans (N = 132) who were noncompliant with recommended colorectal cancer (CRC) screening completed a measure of racial identity centrality-encompassing the extent to which racial identity is a core component of self-concept-and then participated in an online education module about CRC screening, during which either gain or loss-framed messaging was introduced. Half of African-Americans were also exposed to a culturally-targeted self-help message about preventing CRC. Theory of Planned Behavior measures of attitudes, normative beliefs, perceived behavioral control, and intentions to obtain a CRC screen served as outcomes. Results confirmed that effects of messaging on receptivity to CRC screening depended on racial identity. Among low racial identity African Americans, gain-framed messaging most effectively increased normative beliefs about obtaining CRC screening, whereas among high racial identity African Americans loss-framed messaging was most compelling. However, these effects most strongly emerged when culturally-targeted self-help messaging was included. We discuss implications for health disparities theory and research, including a potential to simultaneously deploy culturally-targeted and tailored messaging based on racial identity.

Partnering around cancer clinical trials (PACCT): study protocol for a randomized trial of a patient and physician communication intervention to increase minority accrual to prostate cancer clinical trials.

BACKGROUND: Cancer clinical trials are essential for testing new treatments and represent state-of-the-art cancer treatment, but only a small percentage of patients ever enroll in a trial. Under-enrollment is an even greater problem among minorities, particularly African Americans, representing a racial/ethnic disparity in cancer care. One understudied cause is patient-physician communication, which is often of poor quality during clinical interactions between African-American patients and non-African-American physicians. Partnering Around Cancer Clinical Trials (PACCT) involves a transdisciplinary theoretical model proposing that patient and physician individual attitudes and beliefs and their interpersonal communication during racially discordant clinical interactions influence outcomes related to patients' decisions to participate in a trial. The overall goal of the study is to test a multilevel intervention designed to increase rates at which African-American and White men with prostate cancer make an informed decision to participate in a clinical trial. METHODS/DESIGN: Data collection will occur at two NCI-designated comprehensive cancer centers. Participants include physicians who treat men with prostate cancer and their African-American and White patients who are potentially eligible for a clinical trial. The study uses two distinct research designs to evaluate the effects of two behavioral interventions, one focused on patients and the other on physicians. The primary goal is to increase the number of patients who decide to enroll in a trial; secondary goals include increasing rates of physician trial offers, improving the quality of patient-physician communication during video recorded clinical interactions in which trials may be discussed, improving patients' understanding of trials offered, and increasing the number of patients who actually enroll. Aims are to 1) determine the independent and combined effects of the two interventions on outcomes; 2) compare the effects of the interventions on African-American versus White men; and 3) examine the extent to which patient-physician communication mediates the effect of the interventions on the outcomes. DISCUSSION: PACCT has the potential to identify ways to increase clinical trial rates in a diverse patient population. The research can also improve access to high quality clinical care for African American men bearing the disproportionate burden of disparities in prostate and other cancers. TRIAL REGISTRATION: Clinical Trials.gov registration number: NCT02906241 (September 8, 2016).

Explaining Extremity in Evaluation of Group Members: Meta-Analytic Tests of Three Theories.

A meta-analysis that included more than 1,100 effect sizes tested the predictions of three theoretical perspectives that explain evaluative extremity in social judgment: complexity-extremity theory, subjective group dynamics model, and expectancy-violation theory. The work seeks to understand the ways in which group-based information interacts with person-based information to influence extremity in evaluations. Together, these three theories point to the valence of person-based information, group membership of the evaluated targets relative to the evaluator, status of the evaluators' ingroup, norm consistency of the person-based information, and incongruency of person-based information with stereotype-based expectations as moderators. Considerable support, but some limiting conditions, were found for each theoretical perspective. Implications of the results are discussed.

Predicting Incongruence between Self-reported and Documented Colorectal Cancer Screening in a Sample of African American Medicare Recipients.

Assessments of colorectal cancer (CRC) screening rates typically rely on self-reported screening data, which are often incongruent with medical records. We used multilevel models to examine health-related, socio-demographic and psychological predictors of incongruent self-reports for CRC screening among Medicare-insured African Americans (N = 3,740). Results indicated that living alone decreased, and income increased, the odds of congruently self-reporting endoscopic CRC screening. Being male and having greater number of comorbidities decreased, and having less than a high school education increased, the odds of congruently self-reported fecal occult blood tests. Living alone, age and income had the most robust effects across classifications into one of four mutually exclusive categories defined by screening status (screened/unscreened) and congruence of self-reports. The results underscore the clinical importance of gathering socio-demographic data via patient interviews, and the relevance of these data for judging the veracity of self-reported CRC screenings behaviors.

Intoxicated prejudice: The impact of alcohol consumption on implicitly and explicitly measured racial attitudes.

Recent research has shown that alcohol consumption can exacerbate expressions of racial bias by increasing reliance on stereotypes. However, little work has investigated how alcohol affects intergroup evaluations. The current work sought to address the issue in the context of the correspondence between implicit and explicit measures of anti-black attitudes. Participants were randomly assigned to consume an alcoholic (target BAC of 0.08%), placebo, or control beverage prior to completing implicit and explicit measures of racial attitudes. Although beverage condition did not affect prejudice levels on either measure, it did change the correlation between them. Implicitly measured attitudes significantly predicted explicit reports of prejudice and discrimination only for participants who consumed alcohol. We discuss the implications of our findings for debates regarding dissociations between implicit and explicit measures and the cultural phenomenon of intoxicated individuals attributing prejudiced statements to alcohol consumption rather than personal attitudes.

Language Analysis as a Window to Bereaved Parents' Emotions During a Parent-Physician Bereavement Meeting.

Parent-physician bereavement meetings may benefit parents by facilitating sense making, which is associated with healthy adjustment after a traumatic event. Prior research suggests a reciprocal relationship between sense making and positive emotions. We analyzed parents' use of emotion words during bereavement meetings to better understand parents' emotional reactions during the meeting and how their emotional reactions related to their appraisals of the meeting. Parents' use of positive emotion words increased, suggesting the meetings help parents make sense of the death. Parents' use of positive emotion words was negatively related to their own and/or their spouse's appraisals of the meeting, suggesting that parents who have a positive emotional experience during the meeting may also have a short-term negative reaction. Language analysis can be an effective tool to understand individuals' ongoing emotions and meaning making processes during interventions to reduce adverse consequences of a traumatic event, such as a child's death.

Cognition and Wealth Changes in Mid-to-later Life: A Latent Class Trajectories Approach Using the Health and Retirement Study.

ObjectivesTo assess how cognitive trajectories from mid-to-later life relate to wealth change, overall and by mid-life income. Methods: Data were from participants (51-64 years) in the 2000-2018 U.S. Health and Retirement Study who were cognitively healthy at baseline (year 2000; unweighted n = 3821). Longitudinal latent class analyses generated cognitive and wealth trajectories, independently, and multinomial logistic regressions estimated the association between cognitive trajectories and wealth profiles, overall and by median income. Results: We identified three cognitive: cognitively healthy (CH), increasing cognitive impairment (ICI), and increasing dementia (ID) and four wealth profiles: stable wealth loss (SWL), delayed gradual wealth loss (DGWL), stable wealth gain (SWG), and gradual wealth gain (GWG). The ID group had higher probability of being in the SWL group and lower probability of SWG, which was more pronounced in respondents with greater median income. Discussion: Individuals with ID may be vulnerable to wealth loss, particularly for middle-class households.

Up-regulation of oxytocin receptor expression at term is related to maternal body mass index.

BACKGROUND: The likelihood of cesarean is in part related to maternal body mass index (BMI). Myometrial changes may be responsible. METHODS: Myometrial biopsies were collected from the upper edge of the hysterotomy from women undergoing scheduled cesarean with term, singleton gestations. Oxytocin receptor and connexin-43 mRNA protein expression was quantified with real-time polymerase chain reaction and Western blot. RESULTS: Twenty subjects were recruited: 13 repeat and 7 primary cesareans. Oxytocin receptor mRNA was associated with BMI among women undergoing primary (r = 0.75; p = 0.05) but not repeat cesarean (p > 0.05). Controlling for gestational age, this association strengthened (p = 0.004). Receptor protein expression showed a linear correlation with BMI in the primary cesarean group (p = 0.002). Connexin-43 mRNA expression was not related to BMI in women undergoing primary (r = -0.14, p = 0.76) or repeat (r = -0.01, p = 0.86) cesarean. CONCLUSIONS: Oxytocin receptor, but not connexin-43, expression is related to BMI, suggesting an alteration in oxytocin receptor expression or function related to obesity.

Knowledge of breast density and awareness of related breast cancer risk.

Little is known about women's knowledge of breast density or between-race differences in this knowledge. In the current study, we examined knowledge of breast density and awareness of its role as a breast cancer risk factor among women who had previously taken part in a breast imaging study. Seventy-seven women (54.5 % Black) returned a survey assessing perceptions and accuracy of breast density knowledge, knowledge of one's own breast density, and breast cancer risk awareness. White women had greater perceived knowledge of breast density compared to Black women; however, differences in the accuracy of definitions of breast density were due to education. Black women were less likely to know how dense their own breasts were. Black and White women both lacked awareness that having dense breast increased breast cancer risk. The results highlight the need to disseminate information regarding breast density to women, while ensuring that the information is equally accessible to both Black and White women.

Stability of lyophilized sucrose formulations of an IgG1: subvisible particle formation.

Eight lyophilized formulations of a IgG1 monoclonal antibody (MAb) were prepared containing increasing levels of sucrose. In addition, three of the formulations had sorbitol added at a level of 5% w/w relative to sucrose. The samples were stored for up to 4 weeks at 40°C, which is well below the Tg. Upon reconstitution, the levels of subvisible particles were measured using microflow imaging (MFI). The formulation containing no sucrose contained exceedingly high levels of subvisible particles, accounting for as much as 25% of the weight of the protein. Addition of sucrose markedly decreased the number of subvisible particles, with the maximal sucrose:protein weight ratio being 2:1 (the highest level tested). Addition of sorbitol further decreased subvisible particle levels, even for formulations where the sucrose:protein ratio was relatively high. This suggests that even small amounts of a plasticizer like sorbitol can improve the storage stability of a lyophilized antibody formulation, probably by dampening ß-relaxations within the amorphous glass.

Complex effects of racism and discrimination on African Americans' health and well-being: Navigating the status quo.

Most research on the effects of racism and discrimination on the health and well-being of African Americans utilize a deficit perspective, one that homogeneously paints African Americans as disadvantaged victims. Such approaches do little to highlight the variability in the effects of racism and discrimination on relevant outcomes, and the resources that African Americans have drawn upon to navigate an environment characterized by varying levels of racialized hostility. The goal of this special issue is to inspire more refined conceptualizations of how African Americans navigate an often-hostile status quo in service of their health and well-being. The articles in this special issue examine within-race heterogeneity in African Americans' responses to varying manifestations of racism and discrimination, as well as subsequent heterogeneity in the effects of racism and discrimination on African Americans' health and well-being at the individual level. The commentaries and articles address the goals of this special issue in three broad categories of health outcomes: biological/physiological, mind and brain, and health behavior. These contributions demonstrate several critical themes that can guide future work to achieve a more comprehensive understanding of the heterogeneity in the effects of racism and discrimination on health and well-being among African Americans.