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Objective: To address the low prevention and treatment rates for those at risk of glucocorticoid-induced osteoporosis (GIOP), we evaluated the influence of a direct-to-patient, Internet-based educational video intervention using "storytelling" on rates of antiosteoporosis medication use among chronic glucocorticoid users who were members of an online pharmacy refill service., Methods: We identified members who refilled ≥ 5 mg/day of prednisone (or equivalent) for 90 contiguous days and had no GIOP therapy for ≥ 12 months. Using patient stories, we developed an online video addressing risk factors and treatment options, and delivered it to members refilling a glucocorticoid prescription. The intervention consisted of two 45-day "Video ON" periods, during which the video automatically appeared at the time of refill, and two 45-day "Video OFF" periods, during which there was no video. Members could also "self-initiate" watching the video by going to the video link. We used an interrupted time series design to evaluate the effectiveness of this intervention on GIOP prescription therapies over 6 months., Results: Among 3017 members (64.8%) exposed to the intervention, 59% had measurable video viewing time, of which 3% "self-initiated" the video. The GIOP prescription rate in the "Video ON" group was 2.9% versus 2.7% for the "Video OFF" group. There was a nonsignificant trend toward greater GIOP prescription in members who self-initiated the video versus automated viewing (5.7% vs 2.9%, p = 0.1)., Conclusion: Among adults at high risk of GIOP, prescription rates were not significantly affected by an online educational video presented at the time of glucocorticoid refill. ClinicalTrials.gov Identifier: NCT01378689.

Background: Our original paper, published in 1992, reported a median overall survival after first relapse in breast cancer of 26 months. The current retrospective review concentrates more specifically on patients with first systemic relapse, recognizing that subsets of patients with local recurrence are potentially curable., Methods: Records of 5,168 patients from a largely breast-cancer-specific oncology practice were reviewed to identify breast cancer patients with their first relapse between 1996 and 2006 after primary treatment. There were 189 patients diagnosed with metastatic disease within 2 months of being seen by our therapeutic team and 101 patients diagnosed with metastatic disease greater than 2 months. The patients were divided in order to account for lead-time bias than could potentially confound the analysis of the latter 101 patients., Results: Median survival for our primary study population of 189 patients was 33 months. As expected, the median survival from first systemic relapse (MSFSR) for the 101 patients excluded because of the potential for lead-time bias was better at 46 months. Factors influencing prognosis included estrogen receptor (ER) status, disease-free interval (DFI), and dominant site of metastasis. Compared with our original series, even with elimination of local-regional recurrences in our present series, the median survival from first relapse has improved by 7 months over the past two decades., Conclusion: The new benchmark for MSFSR approaches 3 years.

Background: Vitamin D (VD) supplementation has pleiotropic effects that extend beyond their impact on bone health, including the disruption of downstream VD receptor signaling and human epidermal growth factor receptor 2 (HER2) signaling through the ErbB2/AKT/ERK pathway. In the present study, we examined our institutional experience with patients having nonmetastatic HER2-positive (HER(+)) breast cancer and hypothesized that those patients who received VD supplementation during neoadjuvant chemotherapy would have improved long-term outcomes., Patients and Methods: We performed a retrospective review of all patients (n = 308) given trastuzumab-based chemotherapy between 2006 and 2012 at the University of Miami/Sylvester Comprehensive Cancer Center (UM/SCCC). We identified 2 groups of patients for comparison-those who received VD supplementation during neoadjuvant chemotherapy (n = 134) and those who did not (n = 112). Univariate and multivariate Cox proportional hazard regression models were fitted to overall survival (OS) and disease-free survival (DFS)., Results: More than half of the patients received VD during neoadjuvant chemotherapy (54.5%), with 60% receiving a dose < 10,000 units/wk and 33.3% having a VD deficiency at the start of therapy. In our final multivariate model, VD use was associated with improved DFS (hazard ratio [HR], 0.36; 95% confidence interval [CI], 0.15-0.88; P = .026], whereas larger tumor size was associated with worse DFS (HR, 3.52; 95% CI, 1.06-11.66; P = .04). There were no differences in OS based on any of the categories, including VD use, tumor size, number of metastatic lymph nodes, age at diagnosis, or lymphovascular invasion (LVI)., Conclusion: VD supplementation in patients with nonmetastatic HER2(+) breast cancer is associated with improved DFS., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Despite mixed survival data, the utilization of contralateral prophylactic mastectomy (CPM) for the prevention of a contralateral breast cancer (CBC) has increased significantly over the last 15 years, especially among women less than 40. We set out to look at our own experience with CPM, focusing on outcomes in women less than 40, the sub-population with the highest cumulative lifetime risk of developing CBC. With an extended follow-up, we hoped to demonstrate differences in the long-term disease free survival (DFS) and overall survival (OS) among groups who underwent the procedure (CPM) versus those that did not (NCPM)., Materials and Methods: We performed a retrospective review of all breast cancer patients less than age 40 diagnosed at Mount Sinai Medical Center between January 1, 1980 and December 31, 2010 (n=481). Among these patients, 42 were identified as having undergone CPM, while 195 were confirmed as being CPM-free during the observation period. A univariate and multivariate analyses were performed., Results: The CPM group had a significantly higher percentage of patients who were diagnosed between 2000 and 2010 (95.2% vs 40%, p=0.0001). The CPM group had significantly smaller tumors (0-2cm.: 41.7% vs 24.8%, p=0.04). Among the entire group of patients, the overall five- and 10-year DFS were 81.3% and 73.3%, respectively. CPM was significantly associated [HR 2.35 (1.02, 5.41); p=0.046] with 10-year OS, although a similar effect was not observed for five-year OS., Conclusions: We found that CPM has increased dramatically over the last 15 years, especially among white women with locally advanced disease. In patients less than 40, who are thought to be at greatest cumulative risk of secondary breast cancer, CPM provided an OS advantage, regardless of genetics, tumor or patient characteristics, and which was only seen after 10 years of follow-up.

This project evaluates how the Rasch measurement framework can be used 1) to construct and interpret individualized genomic measures and fit statistics from nominal single nucleotide polymorphism (SNP) data and 2) to identify interaction patterns that are relevant to person-specific disease risk assessment, case management, and prevention.

The Havanese is a toy breed that presents with a wide range of developmental abnormalities. Skeletal defects, particularly osteochondrodysplasia (OCD), are the most frequently observed anomalies. Cataracts, liver shunts, heart murmurs, and missing incisors are also common in this breed. Estimates of heritability and complex segregation analyses were carried out to evaluate modes of transmission for these abnormalities. A moderate heritability was identified and evidence for a single major locus was found. Novel statistical analysis methods were used to identify four traits that co-segregate: cataracts, hepatic abnormalities, OCD, and cardiac abnormalities. A canine-specific microarray was used to identify changes in gene expression in the liver that accompany the aforementioned developmental problems. One hundred and thirteen genes were found to be differentially regulated in the Havanese.

Loss of brain melanocortin receptors (Mc3rKO and Mc4rKO) causes increased adiposity and exacerbates diet-induced obesity (DIO). Little is known about how Mc3r or Mc4r genotype, diet, and obesity affect insulin sensitivity. Insulin resistance, assessed by insulin and glucose tolerance tests, Ser(307) phosphorylation of insulin receptor substrate 1, and activation of protein kinase B, was examined in control and DIO wild-type (WT), Mc3rKO and Mc4rKO C57BL/6J mice. Mc4rKO mice were hyperphagic and had increased metabolic efficiency (weight gain per kilojoule consumed) relative to WT; both parameters increased further on high-fat diet. Obesity of Mc3rKO was more dependent on fat intake, involving increased metabolic efficiency. Fat mass of DIO Mc3rKO and Mc4rKO was similar, although Mc4rKO gained weight more rapidly. Mc4rKO develop hepatic insulin resistance and severe hepatic steatosis with obesity, independent of diet. DIO caused further deterioration of insulin action in Mc4rKO of either sex and, in male Mc3rKO, compared with controls, associated with increased fasting insulin, severe glucose intolerance, and reduced insulin signaling in muscle and adipose tissue. DIO female Mc3rKO exhibited very modest perturbations in glucose metabolism and insulin sensitivity. Consistent with previous data suggesting impaired fat oxidation, both Mc3rKO and Mc4rKO had reduced muscle oxidative metabolism, a risk factor for weight gain and insulin resistance. Energy expenditure was, however, increased in Mc4rKO compared with Mc3rKO and controls, perhaps due to hyperphagia and metabolic costs associated with rapid growth. In summary, DIO affects insulin sensitivity more severely in Mc4rKO compared with Mc3rKO, perhaps due to a more positive energy balance.

We conducted a large-scale association study to identify genes that influence nonfamilial breast cancer risk using a collection of German cases and matched controls and >25,000 single nucleotide polymorphisms located within 16,000 genes. One of the candidate loci identified was located on chromosome 19p13.2 [odds ratio (OR) = 1.5, P = 0.001]. The effect was substantially stronger in the subset of cases with reported family history of breast cancer (OR = 3.4, P = 0.001). The finding was subsequently replicated in two independent collections (combined OR = 1.4, P < 0.001) and was also associated with predisposition to prostate cancer in an independent sample set of prostate cancer cases and matched controls (OR = 1.4, P = 0.002). High-density single nucleotide polymorphism mapping showed that the extent of association spans 20 kb and includes the intercellular adhesion molecule genes ICAM1, ICAM4, and ICAM5. Although genetic variants in ICAM5 showed the strongest association with disease status, ICAM1 is expressed at highest levels in normal and tumor breast tissue. A variant in ICAM5 was also associated with disease progression and prognosis. Because ICAMs are suitable targets for antibodies and small molecules, these findings may not only provide diagnostic and prognostic markers but also new therapeutic opportunities in breast and prostate cancer.

As the biological arm of the Rasch community, genomic measurement is concerned with asserting and testing hypotheses regarding the quantitative status of genomic variables, including alleles, genotypes, gene expression levels, and phenotypes, as well as DNA, RNA, and protein sequence information. The defining goal of this scientific paradigm, in contrast to the sample-dependent model-fitting and deterministic hypothesis testing of classical statistical genetics, is the identification, validation, and maintenance of a common unit of genomic measurement that maintains its magnitude and meaning, within an allowable range of error, regardless of the laboratory technology used to generate outcomes or the particular group of individuals or organisms under investigation. Such an invariant metric, the basis of a standard genometric scale and associated system of genomic metrology, can be identified, validated, and maintained through 1) routine implementation of the Rasch family of measurement models to construct sample- and scale-free measures from different types of genomic data and 2) cross-calibration of genomic measurement instruments between and among researchers, laboratories, universities, corporations, and databases. This manuscript provides an introductory overview of the guiding principles of fundamental measurement theory and the work of Rasch, connects these concepts to well-known tenets of population genetics, and highlights the potential benefits, both theoretical and applied, associated with achieving objectivity in genomic measurement.

Purpose: This project demonstrates how to calibrate different samples and scales of genomic information to a common scale of genomic measurement., Materials and Methods: 1,113 persons were genotyped at the 13 Combined DNA Index System (CODIS) short tandem repeat (STR) marker loci used by the Federal Bureau of Investigation (FBI) for human identity testing. A measurement model of form ln[(P(nik))/(1-P(nik))] = B(n)-D(i)-L(k) is used to construct person measures and locus calibrations from information contained in the CODIS database. Winsteps (Wright and Linacre, 2003) is employed to maximize initial estimates and to investigate the necessity and sufficiency of different rating classification schema., Results: Model fit is satisfactory in all analyses. Study outcomes are found in Tables 1-6., Conclusions: Additive, divisible, and interchangeable measures and calibrations can be created from raw genomic information that transcend sample- and scale-dependencies associated with racial and ethnic descent, chromosomal location, and locus-specific allele expansion structures.

Recent advances in genetic technologies have combined with established protocols for genetic screening to provide immense benefits to individuals and the public. In most American jurisdictions, newborn screening is mandated by law and does not require parental consent for the collection or testing of the blood samples. Screening programs have been successful in identifying affected infants at an early stage for effective treatment of some genetic diseases. The public health benefit of screening programs is recognized and affirmed. However, collections of surplus, stored samples have become immensely attractive to researchers in medical genetics and the biomedical sciences. As geneticists have sought access to the newborn screening samples, they have recognized concerns related to whether they should use the samples, and, if so, under what conditions. This paper addresses the ethical issues associated with genetic screening and recommends an informed consent protocol that may be used to balance individual and parental rights with the interests of researchers who wish to use surplus samples in studies of genetic disease.

This article provides a basic analysis of intellectual property law, the treatment of genetic information under Title 35 of the United States Code, the controversies surrounding patenting of genetic sequences and related products, and the effects that restriction of information may have on the quality of health care in the United States. In addition, this piece addresses technology transfer and historical developments in public policy that have influenced patent trends. The intended product is not a rigorous review of the scientific or legal literature, as the included cases have been cited elsewhere to accentuate the same points. However, the compact format of the material should be especially valuable for physicians and health personnel who might not have been exposed to these issues as part of their formal professional training.