Examination and prognostic implications of the unique microenvironment of breast cancer brain metastases.

PURPOSE: Brain metastases (BM) are a complication of advanced breast cancer (BC). Histology of melanoma BM offers prognostic value; however, understanding the microenvironment of breast cancer brain metastases (BCBM) is less characterized. This study reports on four histological biomarkers, gliosis, immune infiltrate, hemorrhage, necrosis, and their prognostic significance in BCBM. METHODS: A biobank of 203 human tissues from patients who underwent craniotomy for BCBM was created across four academic institutions. Degree of gliosis, immune infiltrate, hemorrhage, and necrosis were identified and scored via representative H&E stain (0-3+). Overall survival (OS) was estimated using the Kaplan-Meier method. Cox proportional hazards regression evaluated prognostic value of the biomarkers in the context of standard clinical characteristics. RESULTS: BCBM subtype (available for n = 158) was 36% Her2+, 26% hormone receptor (HR)+/Her2- 38% HR-/Her2- (triple negative, TN). Gliosis was observed in 82% (116/141) of BCBM, with immune infiltrate 44% (90/201), hemorrhage 82% (166/141), and necrosis 87% (176/201). Necrosis was significantly higher in TNBC (p < 0.01). Presence of gliosis, immune infiltrate, and hemorrhage correlated with improved OS (p = 0.03, p = 0.03, p = 0.1), while necrosis correlated with inferior OS (p = 0.01). Improved OS was associated with gliosis in TN (p = 0.02), and immune infiltrate (p = 0.001) and hemorrhage (p = 0.07) in HER2+. In a multivariable model for OS, incorporating these biomarkers with traditional clinical variables improved the model fit (p < 0.001). CONCLUSION: Gliosis confers superior prognosis in TNBC BM; immune infiltrate and hemorrhage correlate with superior prognosis in HER2+ BCBM. Understanding the metastatic microenvironment of BCBM refines prognostic considerations and may unveil novel therapeutic strategies.

Predicting what mothers feed their preschoolers: Guided by an extended theory of planned behaviour.

BACKGROUND: Healthy eating behaviours are important for physical and mental well-being and developing healthy eating behaviours early in life is important. As parents are the main providers of preschool children's food the main objective of this study was to use the theory of planned behaviour, expanded to include habit and past behaviour, to predict parents' healthy feeding intention and behaviour. METHODS: Theory of planned behaviour, habit strength, and past behaviour were reported at baseline by 443 mothers. One week later, 235 mothers completed a healthy feeding questionnaire on the eating behaviours of their 2-4 year old child. Data were analysed using hierarchical regression analyses to predict parent's general healthy feeding behaviour, and five sub-behaviours: parents' perceptions of their child's fruit and vegetable consumption, healthy and unhealthy snacking behaviour, as well as healthy and unhealthy drinking behaviour. RESULTS: Intention, perceived behavioural control, habit strength and past behaviour were all positively associated with parents' general healthy feeding (47% explained variance). Perceived behavioural control was the only variable positively associated with mothers' perception of their child's fruit and vegetable consumption and unhealthy snacking behaviour. The theory did not explain the other behaviours. Moreover, habit strength only strengthened the intention-behaviour link for fruit and vegetable consumption and child's age was only positively associated with the mothers' perception of their child's unhealthy snacking behaviour. DISCUSSION: The findings suggest important differences in the predictors of different feeding behaviours that can provide direction for future intervention development.

Individual differences in the perception of regional, nonnative, and disordered speech varieties.

Speech perception abilities vary substantially across listeners, particularly in adverse conditions including those stemming from environmental degradation (e.g., noise) or from talker-related challenges (e.g., nonnative or disordered speech). This study examined adult listeners' recognition of words in phrases produced by six talkers representing three speech varieties: a nonnative accent (Spanish-accented English), a regional dialect (Irish English), and a disordered variety (ataxic dysarthria). Semantically anomalous phrases from these talkers were presented in a transcription task and intelligibility scores, percent words correct, were compared across the three speech varieties. Three cognitive-linguistic areas-receptive vocabulary, cognitive flexibility, and inhibitory control of attention-were assessed as possible predictors of individual word recognition performance. Intelligibility scores for the Spanish accent were significantly correlated with scores for the Irish English and ataxic dysarthria. Scores for the Irish English and dysarthric speech, in contrast, were not correlated. Furthermore, receptive vocabulary was the only cognitive-linguistic assessment that significantly predicted intelligibility scores. These results suggest that, rather than a global skill of perceiving speech that deviates from native dialect norms, listeners may possess specific abilities to overcome particular types of acoustic-phonetic deviation. Furthermore, vocabulary size offers performance benefits for intelligibility of speech that deviates from one's typical dialect norms.

A Multidisciplinary Breast Cancer Brain Metastases Clinic: The University of North Carolina Experience.

BACKGROUND: Breast cancer brain metastasis (BCBM) confers a poor prognosis and is unusual in requiring multidisciplinary care in the metastatic setting. The University of North Carolina at Chapel Hill (UNC-CH) has created a BCBM clinic to provide medical and radiation oncology, neurosurgical, and supportive services to this complex patient population. We describe organization and design of the clinic as well as characteristics, treatments, and outcomes of the patients seen in its first 3 years. METHODS: Clinical and demographic data were collected from patients in a prospectively maintained database. Descriptive statistics are reported as percentages and means. The Kaplan-Meier method was used to estimate time-to-event outcomes. RESULTS: Sixty-five patients were seen between January 2012 and January 2015. At the time of presentation to the BCBM clinic, most patients (74%) had multiple (≥2) brain metastases and had received prior systemic (77%) and whole-brain radiation therapy and/or central nervous system stereotactic radiosurgery (65%) in the metastatic setting. Seventy-eight percent returned for a follow-up visit; 32% were enrolled in a clinical trial. Median time from diagnosis of brain metastasis to death was 2.11 years (95% confidence interval [CI] 1.31-2.47) for all patients, 1.15 years (95% CI 0.4-2.43) for triple-negative breast cancer, 1.31 years (95% CI 0.51-2.52) for hormone receptor-positive/HER2- breast cancer, and 3.03 years (95% CI lower limit 1.94, upper limit not estimable) for HER2+ breast cancer (p = .0037). CONCLUSION: Patients with BCBM have unique and complex needs that require input from several oncologic disciplines. The development of the UNC-CH multidisciplinary BCBM clinic is a model that can be adapted at other centers to provide coordinated care for patients with a challenging and complex disease. IMPLICATIONS FOR PRACTICE: Patients with breast cancer brain metastases often require unique multidisciplinary care to meet the numerous and uncommon challenges associated with their conditions. Here, the development and characteristics of a clinic designed specifically to provide for the multidisciplinary needs of patients with breast cancer brain metastases are described. This clinic may serve as a model for other institutions interested in creating specialty clinics with similar objectives.

Results of the Arizona Medicaid health information technology pharmacy focus groups.

BACKGROUND: In 2007, a federal Medicaid Transformation Grant was awarded to design, develop, and deploy a statewide Health Information Exchange and Electronic Health Record in Arizona, United States. OBJECTIVE: To explore the health information technology needs, knowledge, and expectations of Arizona's health care professionals, moderated focus groups were conducted. This article describes the results of the pharmacist focus groups. METHODS: Focus group activities included a brief presentation, completion of a paper-based survey, and group discussion. The methods included solicitation by invitation, participant selection, meeting content, collaterals, focus group execution, recording, analysis, and discerning comparability among groups. RESULTS: Pharmacy focus group discussions centered on electronic prescribing, including the anticipated advantages: reducing handwriting interpretation errors, improving formulary compliance, improving communication with prescribers, increasing efficiency, and ensuring data accuracy. Disadvantages included: medication errors, inadequate training and knowledge of software applications, and inflated patient expectations. CONCLUSIONS: Pharmacists ranked e-prescribing as the highest priority feature of an electronic health system.

Impact of clinical pharmacy services on patients in an outpatient chemotherapy academic clinic.

BACKGROUND: Assessing the role of the pharmacist in an outpatient oncology clinic requires quantification of parameters that are important to the patient and the healthcare system. Patient evaluations not only serve as benchmarks for a process; but may also predict behavior such as utilization of care, continuity with the provider, and compliance. PURPOSE: To identify the role of the patient-pharmacist relationship and enhance patient satisfaction with care, a survey tool was developed and utilized. METHODS: A 20-item, 2-page survey tool was developed and administered to oncology patients actively receiving treatment at the Cancer Therapy & Research Center (CTRC) in San Antonio, Texas. Following approval from the Investigational Review Board, survey distribution began on December 1, 2009 and continued through February 2010. Basic social and demographic data were collected. Satisfaction with pharmacy service was assessed with questions on a Likert ranking scale detailing time spent with pharmacists, knowledge of medication therapy, willingness to pay for clinical pharmacy services, etc. The primary outcome was the impact of the pharmacist-patient relationship assessed by examining the interaction between time spent with pharmacist, understanding of medications, and desire for future pharmacy counseling services. RESULTS: A total of 77 surveys were administered and collected. Of the patients surveyed, 86% stated that it is important for patients to discuss their treatment with a pharmacist and 76% requested pharmacy follow-up at future visits. CONCLUSION: This cross-sectional survey reveals that patients are interested in visiting with a pharmacist regularly during chemotherapy treatment and patients may be willing to pay for pharmacy counseling services.

CRH haplotype as a factor influencing cerebrospinal fluid levels of corticotropin-releasing hormone, hypothalamic-pituitary-adrenal axis activity, temperament, and alcohol consumption in rhesus macaques.

CONTEXT: Both highly stress-reactive and novelty-seeking individuals are susceptible to alcohol use disorders. Variation in stress reactivity, exploration, and response to novelty have been attributed to differences in corticotropin-releasing hormone (CRH) system function. As such, CRH gene variation may influence risk for alcohol use and dependence. OBJECTIVE: To determine whether CRH variation influences relevant intermediate phenotypes, behavior, and alcohol consumption in rhesus macaques. DESIGN: We sequenced the rhesus macaque CRH locus (rhCRH) and performed cladistic clustering of haplotypes. In silico analysis, gel shift, and in vitro reporter assays were performed to identify functional variants. Cerebrospinal fluid (CSF) and blood samples were obtained, and levels of CRH and corticotropin (ACTH) were measured by radioimmunoassay. Behavioral data were collected from macaques during infancy. Among adolescent/adult animals, we recorded responses to an unfamiliar conspecific and measured levels of ethanol consumption. SETTING: National Institutes of Health Animal Center. PARTICIPANTS: Rhesus macaques. MAIN OUTCOME MEASURES: Animals were genotyped for a single-nucleotide polymorphism disrupting a glucocorticoid response element, rhCRH -2232 C>G, and the effects of this allele on CSF levels of CRH, plasma levels of ACTH, behavior, and ethanol consumption were assessed by analysis of variance. RESULTS: We show that -2232C>G alters DNA x protein interactions and confers decreased sensitivity of the CRH promoter to glucocorticoids in vitro. Consistent with the known effects of glucocorticoids on CRH expression in the brain, carriers of the G allele had lower CSF levels of CRH but higher levels of ACTH. Infants carrying the G allele were more exploratory and bold, and among adolescent and adult male macaques, the G allele was associated with exploratory/bold responding to an unfamiliar male. Adults with the C/G genotype also exhibited increased alcohol consumption in the social group, a model for high-risk alcohol-seeking behavior. CONCLUSION: Haplotypes that differ in terms of corticosteroid sensitivity have been identified in humans. Our data may suggest that functionally similar CRH variants could influence risk for externalizing disorders in human subjects.