Blood counts in children with Down syndrome.

BACKGROUND: Children with Down syndrome (DS) are more likely to have hematologic and immunologic abnormalities compared to their typically developing peers, but normal ranges have not been defined. The goal of this study was to create references for complete blood counts (CBCs) in patients with DS. METHODS: A retrospective investigation of 355 (male = 196, 55.2%; mean age = 6.49 years, SD = 5.07) healthy pediatric patients with DS who received a CBC between 2011 and 2017 as part of their medical care at a single, large, pediatric teaching hospital. Control data on 770 healthy patients without DS were included. Descriptive statistics were performed on demographic and clinical characteristics. Kruskal-Wallis H tests, nested analysis-of-variance tests, and t-tests were run to determine the significant associations. RESULTS: Age-related normative curves for healthy children with DS outlining 2.5th, 25th, 50th, 75th, and 97.5th percentiles are provided for total white blood count, hemoglobin concentration, hematocrit, mean corpuscular volume, and platelet, absolute neutrophil, absolute lymphocyte, eosinophil, monocyte, and basophil counts. Statistical differences were found between children with and without DS receiving care at the same hospital based on matched age/sex groups. CONCLUSIONS: This study demonstrates that patients with DS have different reference ranges for multiple blood counts compared to those without DS, creating a new resource for pediatricians to refer to when evaluating CBCs in this population.

Response to treatment and outcomes of infantile spasms in Down syndrome.

AIM: To estimate the prevalence, and evaluate presentation, treatment response, treatment side effects, and long-term seizure outcomes in all known cases of children with Down syndrome and infantile spasms on the island of Ireland. METHOD: This was a 10-year retrospective multicentre review of clinical records and investigations, focusing on treatment response, side effects, and long-term outcomes. RESULTS: The prevalence of infantile spasms in Down syndrome was 3.0% during the study period. Fifty-four infants were identified with median age of spasm onset at 201 days (interquartile range [IQR] 156-242). Spasm cessation was achieved in 88% (n=46) at a median of 110 days (IQR 5-66). The most common first-line medications were prednisolone (n=20, 37%), vigabatrin (n=18, 33.3%), and sodium valproate (n=9, 16.7%). At follow-up (median age 23.7mo; IQR 13.4-40.6), 25% had ongoing seizures and 85% had developmental concerns. Treatment within 60 days did not correlate with spasm cessation. Seventeen children (31%) experienced medication side effects, with vigabatrin accounting for 52%. INTERPRETATION: Prednisolone is an effective and well-tolerated medication for treating infantile spasms in Down syndrome. Despite the high percentage of spasm cessation, developmental concerns and ongoing seizures were common.

Hidden Hunger: Understanding the Complexity of Food Insecurity Among College Students.

OBJECTIVE: The aim of this research was to explore the complexity of college student food insecurity through eating patterns, food assistance, and health of food-insecure university students. METHODS: A mixed-methods approach utilizing qualitative focus groups and individual interview data and survey quantitative data was used. All data collection took place on campus at a large Midwestern university in the Spring semester of 2018. Participants were Midwestern university students (n = 30), freshman to graduate level classified, with very low food security (USDA-Six Item Short Form). RESULTS: Seven percent (n = 2) were currently enrolled in food assistance programming (SNAP), and 30% (n = 9) reported family enrollment growing up (WIC and SNAP). Seven major themes emerged highlighting nutritional habits, food adaptations, health and well-being impacts, and additional campus programming addressing food assistance. Data triangulation informed a complexity diagram with the major categories of student characteristics of food insecurity, campus resource barriers, additional student needs, health and well-being impacts, and student adaptations and coping influencing the complexity surrounding student food insecurity. CONCLUSIONS: College student food insecurity is multifaceted and complex. Common themes emerged among both individual-level factors and university structures, providing a deeper understanding of both the complexity and contributors to the college student experience. Further research and intervention are needed to explore this phenomenon and address student needs.

DeepCAT: Deep Computer-Aided Triage of Screening Mammography.

Although much deep learning research has focused on mammographic detection of breast cancer, relatively little attention has been paid to mammography triage for radiologist review. The purpose of this study was to develop and test DeepCAT, a deep learning system for mammography triage based on suspicion of cancer. Specifically, we evaluate DeepCAT's ability to provide two augmentations to radiologists: (1) discarding images unlikely to have cancer from radiologist review and (2) prioritization of images likely to contain cancer. We used 1878 2D-mammographic images (CC & MLO) from the Digital Database for Screening Mammography to develop DeepCAT, a deep learning triage system composed of 2 components: (1) mammogram classifier cascade and (2) mass detector, which are combined to generate an overall priority score. This priority score is used to order images for radiologist review. Of 595 testing images, DeepCAT recommended low priority for 315 images (53%), of which none contained a malignant mass. In evaluation of prioritizing images according to likelihood of containing cancer, DeepCAT's study ordering required an average of 26 adjacent swaps to obtain perfect review order. Our results suggest that DeepCAT could substantially increase efficiency for breast imagers and effectively triage review of mammograms with malignant masses.

Outcomes of Foci on Breast MRI: Features Associated With Malignancy.

OBJECTIVE. The objective of this study was to determine the outcomes of foci seen on breast MRI and to evaluate imaging features associated with malignancy. MATERIALS AND METHODS. In this institutional review board-approved retrospective study, we reviewed 200 eligible foci in 179 patients that were assigned BI-RADS category of 3 or 4 from December 2004 to August 2018. Clinical and imaging features of all eligible foci were collected, and associations with malignant outcomes were evaluated. Malignancy rates were also calculated. RESULTS. Of 200 eligible foci, 64 were assigned BI-RADS category 3 and 136 were assigned BI-RADS category 4. The malignancy rate was 1.6% (1/64) among BI-RADS 3 foci and 17.6% (24/136) for BI-RADS 4 foci. The majority of malignant foci represented invasive breast cancer (68.0%, 17/25). Focus size and washout kinetics were significantly associated with malignant outcome (p < 0.05). CONCLUSION. Despite the high prevalence of foci on breast MRI, data are limited to guide their management. Foci should not be disregarded, because foci undergoing biopsy had a malignancy rate of 17.6%, with the majority of malignant foci representing invasive cancer. Larger size and washout kinetics were associated with malignancy in our study and should raise the suspicion level for a focus on breast MRI.

Myocardial function in late preterm infants during the transitional period: comprehensive appraisal with deformation mechanics and non-invasive cardiac output monitoring.

BACKGROUND: There is a paucity of functional data on mid-to-late preterm infants between 30+0 and 34+6 weeks gestation. We aimed to characterise transitional cardiopulmonary and haemodynamic changes during the first 48 hours in asymptomatic mid-to-late preterm infants. METHODS: Forty-five healthy preterm newborns (mean ± standard deviation) gestation of 32.7 ± 1.2 weeks) underwent echocardiography on Days 1 and 2. Ventricular mechanics were assessed by speckle tracking-derived deformation, rotational mechanics, tissue Doppler imaging, and right ventricle-focused measures (tricuspid annular plane systolic excursion, fractional area change). Continuous haemodynamics were assessed using the NICOM™ system to obtain left ventricular output, stroke volume, heart rate, and total peripheral resistance by non-invasive cardiac output monitoring. RESULTS: Right ventricular function increased (all measures p < 0.005) with mostly stable left ventricular performance between Day 1 and Day 2. NICOM-derived left ventricular output [mean 34%, 95% confidence interval 21-47%] and stroke volume [29%, 16-42%] increased with no change in heart rate [5%, -2 to 12%]. There was a rise in mean blood pressure [11%, 1-21%], but a decline in total peripheral resistance [-14%, -25 to -3%]. CONCLUSION: Left ventricular mechanics remained persevered in mid-to-late premature infants, but right ventricular function increased. Non-invasive cardiac output monitoring is feasible in preterm infants with an increase in left ventricular output driven by an improvement in stroke volume during the transitional period.

A Pilot of Data-Driven Modeling to Assess Potential for Improved Efficiency in an Academic Breast-Imaging Center.

Patient satisfaction and department efficiency are central pillars in defining quality in medicine. Patient satisfaction is often linked to wait times. We describe a novel method to study workflow and simulate solutions to improve efficiency, thereby decreasing wait times and adding value. We implemented a real-time location system (RTLS) in our academic breast-imaging department to study workflow, including measuring patient wait time, quantifying equipment utilization, and identifying bottlenecks. Then, using discrete event simulation (DES), we modeled solutions with changes in staffing and equipment. Nine hundred and ninety-nine patient encounters were tracked over a 10-week period. The RTLS system recorded 551,512 raw staff and patient time stamps, which were analyzed to produce 17,042 staff and/or patient encounter time stamps. Mean patient wait time was 27 min. The digital breast tomosynthesis (DBT) unit had the highest utilization rate and was identified as a bottleneck. DES predicts a 19.2% reduction in patient length of stay with replacement of a full field digital mammogram (FFDM) unit by a DBT unit and the addition of technologists. Through integration of RTLS with discrete event simulation testing, we created a model based on real-time data to accurately assess patient wait times and patient progress through an appointment, evaluate patient staff-interaction, identify system bottlenecks, and quantitate potential solutions. This quality improvement initiative has important implications, potentially allowing data-driven decisions for staff hiring, equipment purchases, and department layout.

Deep-Learning-Based Semantic Labeling for 2D Mammography and Comparison of Complexity for Machine Learning Tasks.

Machine learning has several potential uses in medical imaging for semantic labeling of images to improve radiologist workflow and to triage studies for review. The purpose of this study was to (1) develop deep convolutional neural networks (DCNNs) for automated classification of 2D mammography views, determination of breast laterality, and assessment and of breast tissue density; and (2) compare the performance of DCNNs on these tasks of varying complexity to each other. We obtained 3034 2D-mammographic images from the Digital Database for Screening Mammography, annotated with mammographic view, image laterality, and breast tissue density. These images were used to train a DCNN to classify images for these three tasks. The DCNN trained to classify mammographic view achieved receiver-operating-characteristic (ROC) area under the curve (AUC) of 1. The DCNN trained to classify breast image laterality initially misclassified right and left breasts (AUC 0.75); however, after discontinuing horizontal flips during data augmentation, AUC improved to 0.93 (p < 0.0001). Breast density classification proved more difficult, with the DCNN achieving 68% accuracy. Automated semantic labeling of 2D mammography is feasible using DCNNs and can be performed with small datasets. However, automated classification of differences in breast density is more difficult, likely requiring larger datasets.

Health professional perceptions regarding screening tools for developmental surveillance for children in a multicultural part of Sydney, Australia.

BACKGROUND: Encouraging early child development and the early identification of developmental difficulties is a priority. The Ministry of Health in the Australian State of New South Wales (NSW), has recommended a program of developmental surveillance using validated screening questionnaires, namely, the Parents' Evaluation of Development Status (PEDS) and Ages and Stages Questionnaire (ASQs), however, the use of these tools has remained sub-optimal. A longitudinal prospective birth cohort "Watch Me grow" study was carried out in the South Western Sydney (SW) region of NSW to ascertain the uptake as well as the strategies and the resources required to maximise engagement in the surveillance program. This paper reports on a qualitative component of the study examining the attitudes, enablers and barriers to the current developmental surveillance practices, with reference to screening tools, amongst health professionals. METHODS: Qualitative data from 37 primary health care providers in a region of relative disadvantage in Sydney was analysed. RESULTS: The major themes that emerged from the data were the "difficulties/problems" and "positives/benefits" of surveillance in general, and "specificity" of the tools which were employed. Barriers of time, tool awareness, knowledge and access of referral pathways, and services were important for the physician providers, while the choice of screening tools and access to these tools in other languages were raised as important issues by Child and Family Health Nurses (CFHN). The use of these tools by health professionals was also influenced by what the professionals perceived as the parents' understanding of their child's development. While the PEDS and ASQs was utilised by CFHNs, both General Practitioners (GPs) and paediatricians commented that they lacked awareness of developmental screening tools and highlighted further training needs. CONCLUSIONS: The results highlight the practical challenges to, and limited knowledge and uptake of, the use of recommended screening tools as part of developmental surveillance. There is a need for further research regarding the most effective integrated models of care which will allow for a better collaboration between parents and service providers and improve information sharing between different professionals such as CFHNs GPs, Practices nurses and Paediatricians involved in screening and surveillance programs.

Nationwide cross-sectional adherence to mammography screening guidelines: national behavioral risk factor surveillance system survey results.

PURPOSE: Varying recommendations about breast cancer screening have generated much confusion about when and how often to undergo mammography screening, yet there is limited population-based data about the extent to which patients adhere to various mammographic screening guidelines in practice. Our purpose was to evaluate population-based adherence to mammographic screening using criteria from major guideline-producing organizations. METHODS: Women aged 40-74 in the 2014 Behavioral Risk Factor Surveillance System survey were included. Self-reported mammographic screening within 1 or 2 years, according to major guideline-producing organizations (American Cancer Society [ACS], US Preventative Services Task Force [USPSTF], American College of Radiology [ACR], American College of Obstetricians and Gynecologists [ACOG]) was calculated with logistic regression, adjusting for demographics and indices of access to health care. RESULTS: 159,123 women were included. By age category, cross-sectional adherence to USPSTF guidelines ranged from 76 to 81%, ACS (55-81%) and ACR/ACOG (45-64%) with increasing age being associated improved adherence. The highest proportions of women undergoing mammographic screening were seen in women ages 65-69 (66% within last year, 81% within last 2 years). Statistically significant predictors of adherence to mammography screening included increased income category (OR 1.08, 1.07-1.09), higher education category (OR 1.13, 1.11-1.16), and increased access to health care (OR 2.25, 1.94-2.60), adjusted for age categories. CONCLUSIONS: Adherence to mammography screening was closest to USPSTF guidelines with 76-81% cross-sectional adherence. Frequency of screening increases with age with highest screening proportions in women ages 65-69 (66% within last year, 81% within last 2 years). For all screening guidelines, adherence to mammography screening remains poor in women with limited access to health insurance with less than half of women obtaining recommended screening.

Impact of Medicare Shared Savings Program Accountable Care Organizations at Screening Mammography: A Retrospective Cohort Study.

Purpose To evaluate the impact of accountable care organizations (ACOs) on use of screening mammography in the Medicare Shared Savings Program (MSSP), the largest value-based reimbursement program in U.S. HISTORY: Materials and Methods Institutional review board approval was waived, as the study used publicly available unidentifiable data. Medicare data were retrospectively obtained for participating ACOs from 2012 to 2014. Baseline information and the ACO-20 measure (percentage of women aged 40-69 years who underwent screening mammography within 24 months) were obtained. Negative binomial regression models were used to evaluate baseline and longitudinal mammography use, with stratified analyses performed for year of entry into the ACO, number of beneficiaries, and geographic region. Results A total of 333 ACOs with 5 329 831 Medicare beneficiaries (mean size, 16 006 beneficiaries) participated in the MSSP. Screening use varied across ACOs (median, 63.0%; range, 8.8%-90.3%), with differences found across regions (use was highest in the Midwest [66.6%] and lowest in the South [58.2%], P = .038). A total of 208 ACOs reported longitudinal outcomes, with mean change in screening mammography use of +2.6% (range, -33.2% to +42.2%), with 128 (61.6%) ACOs reporting improvements (incidence rate ratio, 1.04; 95% confidence interval: 1.02, 1.07) (P = .002). No longitudinal differences in use were seen across regions (P = .078), year of entry (P = .902), number of beneficiaries (P = .814), or total composite quality score (P = .324), nor was there a difference between ACOs that saved money and those that did not (P = .391). Conclusion ACOs in the MSSP have produced small significant improvements in screening mammography use. © RSNA, 2016.

Explaining culturally and linguistically diverse (CALD) parents' access of healthcare services for developmental surveillance and anticipatory guidance: qualitative findings from the 'Watch Me Grow' study.

BACKGROUND: Regular health visits for parents with young children provide an opportunity for developmental surveillance and anticipatory guidance regarding common childhood problems and help to achieve optimal developmental progress prior to school entry. However, there are few published reports from Australian culturally and linguistically diverse (CALD) communities exploring parents' experiences for accessing child health surveillance programs. This paper aims to describe and explain parental experiences for accessing developmental surveillance and anticipatory guidance for children. METHODS: Qualitative data was obtained from 6 focus groups (33 parents) and seven in-depth interviews of CALD parents recruited from an area of relative disadvantage in Sydney. Thematic analysis of data was conducted using an ecological framework. RESULTS: An overarching theme of "awareness-beliefs-choices" was found to explain parents' experiences of accessing primary health care services for children. "Awareness" situated within the meso-and macro-systems explained parents knowledge of where and what primary health services were available to access for their children. Opportunities for families to obtain this information existed at the time of birth in Australian hospitals, but for newly arrived immigrants with young children, community linkages with family and friends, and general practitioner (GPs) were most important. "Beliefs" situated within the microsystems included parents' understanding of their children's development, in particular what they considered to be "normal" or "abnormal". Parental "choices", situated within meso-systems and chronosystems, related to their choices of service providers, which were based on the proximity, continuity, purpose of visit, language spoken by the provider and past experience of a service. CONCLUSIONS: CALD parents have diverse experiences with primary health care providers which are influenced by their awareness of available services in the context of their duration of stay in Australia. The role of the general practitioner, with language concordance, suggests the importance of diversity within the primary care health workforce in this region. There is a need for ongoing cultural competence training of health professionals and provisions need to be made to support frequent use of interpreters at general practices in Australia.

Comparative effectiveness of breast MRI and mammography in screening young women with elevated risk of developing breast cancer: a retrospective cohort study.

Screening guidelines recommend that women with 20 % or greater lifetime risk of breast cancer undergo annual breast MRI screening to supplement mammography, irrespective of age. In patients less than 40 years, mammography is often avoided due to concerns about radiation and decreased performance. However, prior studies have been limited by large percentages of women above 40 with decreased breast density. Our purpose was to test whether adding mammography to breast MRI screening compared to breast MRI screening alone in women below 40 increases cancer detection rates. After obtaining IRB approval, chart review identified patients aged 25-40 years undergoing breast MR screening (2005-2014). Demographics, risk factors, BI-RADS assessments, background parenchymal enhancement, and mammographic breast tissue density were recorded. Cancer detection rates, short-term follow-up (BIRADS 3), image-guided biopsy (BIRADS 4,5), and PPV1-3 were calculated. 342 breast MRI exams were identified (average age was 33, 37 % were nulliparous, and 64 % had prior benign biopsy), 226 (66 %) of which underwent concurrent mammography. Risk factors included 64 % with breast cancer in first-degree relative(s), 90 % had heterogeneous or extremely dense breast tissue on mammography, and 16 % were BRCA carriers. Four invasive cancers were detected by MRI (11.7 cancers/1000 examinations, 95 % CI 8.3, 15.1). None of these was detected by mammography, and no cancers were independently identified by mammography. Breast MRI screening in high-risk women under 40 yielded elevated cancer detection rates (11.7/1000). The cancer detection rate for mammography was 0 %, suggesting that MRI alone may be useful in screening high-risk women under 40.

Adjuvant radiation use in older women with early-stage breast cancer at Johns Hopkins.

PURPOSE: In 2004, The National Comprehensive Cancer Network (NCCN) Guidelines incorporated omission of radiation therapy after breast-conservation surgery in women ≥70 years old with stage I, estrogen receptor-positive breast cancer who plan to receive endocrine therapy. One study demonstrated wide variation in implementing this change across 13 NCCN institutions. We evaluated the practice pattern at our institution. METHODS: We identified women ≥70 years old treated at our institution from 2009 to 2014. We calculated radiation therapy omission rate in those meeting the guidelines. We explored associations between radiation therapy omission, year of diagnosis, and patient characteristics with Wilcoxon rank sum tests and Fisher's exact tests. RESULTS: A total of 667 women met the inclusion criteria, and 117 (18 %) were candidates for radiation therapy omission. Mean age among the 117 was 76.3 years (Range: 70-95). Overall radiation therapy omission rate was 36.8 %, but varied greatly by year of diagnosis (Range: 7.7-54.5 %). This variation persisted after excluding women who did not receive endocrine therapy (Mean: 39.0 %, Range: 0.0-75.0 %). Factors associated with higher radiation therapy omission rates included older age and not having pathological nodal evaluation. The radiation therapy omission rate did not vary by race, tumor type, grade, or size. CONCLUSIONS: The implementation of the NCCN guideline has not been consistent at our institution. Our data suggest that other tools should be considered to apply the guidelines more consistently. We have implemented a quality improvement protocol that incorporates life expectancy estimate and geriatric assessment in women meeting the NCCN guideline at our institution.

Non-basic azolotriazinone MCHR1 antagonists for the treatment of obesity: An empirical brain-exposures-driven candidate selection for in vivo efficacy studies.

Non-basic azolotriazinones were explored using an empirical free brain exposures-driven approach to identify potent MCHR1 antagonists for evaluation in in vivo efficacy studies. An optimized lead from this series, 1j (rMCHR1 Ki=1.8 nM), demonstrated a 6.9% reduction in weight gain relative to vehicle in a rat model at 30 mg/kg after 4 days of once-daily oral treatment as a glycine prodrug. Despite a promising efficacy profile, an assessment of the biliary toxicity risk of this compound rendered this compound non-progressible.

Dihydropyrrolopyrazol-6-one MCHR1 antagonists for the treatment of obesity: Insights on in vivo efficacy from a novel FLIPR assay setup.

Our investigation of the structure-activity and structure-liability relationships for dihydropyrrolopyrazol-6-one MCHR1 antagonists revealed that off-rate characteristics, inferred from potencies in a FLIPR assay following a 2 h incubation, can impact in vivo efficacy. The in vitro and exposure profiles of dihydropyrrolopyrazol-6-ones 1b and 1e were comparable to that of the thienopyrimidinone counterparts 41 and 43 except for a much faster MCHR1 apparent off-rate. The greatly diminished dihydropyrrolopyrazol-6-one anti-obesity response may be the consequence of this rapid off-rate.

Neoadjuvant Therapy for Early-Stage Breast Cancer: Current Practice, Controversies, and Future Directions.

Research in the fields of surgical, medical, and radiation oncology has changed the landscape of neoadjuvant therapy in breast cancer, yet many areas of controversy still exist. When considering whether a patient is a candidate for neoadjuvant therapy, ideally the initial assessment should be multidisciplinary in nature and should include clinical, radiographic, and pathologic evaluation. Optimization of systemic therapy is dependent upon identifying the patient's breast cancer subtype; the best approach may include targeted agents, as well as the determination of eligibility for enrollment into clinical trials that incorporate novel therapeutics or predictive biomarkers. This article will review a variety of surgical and radiation-based strategies for management of early-stage breast cancer, including surgical options involving the breast and axilla, and the role of radiation based on response to systemic therapy. Key areas of controversy include the ideal systemic treatment for different breast cancer subtypes, the surgical and radiotherapeutic approaches for management of the axilla, and the role of pathologic response rates as a surrogate for survival in drug development.

Planting Seeds for Food Is Medicine: Pre-Implementation Planning Methods and Formative Evaluation Findings From a Multi-Clinic Initiative in the Midwest.

Food is medicine (FIM) initiatives are an emerging strategy for addressing nutrition-related health disparities increasingly endorsed by providers, payers, and policymakers. However, food insecurity screening protocols and oversight of medically-tailored food assistance programs are novel for many healthcare settings. Here, we describe the pre-implementation planning processes used to successfully engage federally-qualified health centers (FQHCs) across Kansas to develop new FIM initiatives. A Kansas-based philanthropic foundation facilitated pre-implementation planning for FQHCs over 17 months across 3 stages: 1) Community inquiry, 2) FIM learning event with invitation for FQHC attendees to request pre-implementation funding, and 3) Pre-implementation planning workshops and application assignments for FQHC grantees to develop a FIM implementation grant proposal. We evaluated satisfaction and perceived utility of these pre-implementation planning activities via post-workshop surveys and qualitative comparisons of FIM design components from pre-implementation and implementation grant applications. All 7 FQHCs attending the learning event applied for and were awarded pre-implementation planning grants; 6 submitted an implementation grant application following workshop completion. FQHCs rated pre-implementation support activities favorably; however, most clinics cited limited staff as a barrier to effective planning. As compared to pre-implementation planning grant proposals, all FQHCs elected to narrow their priority population to people with pre-diabetes or diabetes with better articulation of evidence-based nutrition prescriptions and intervention models in their final program designs. In the midst of a nationwide FIM groundswell, we recommend that funders, clinic stakeholders, and evaluators work together to devise and financially support appropriate pre-implementation planning activities prior to launching new FIM initiatives.