Therapeutic Effects of FGF23 c‐tail Fc in a Murine Preclinical Model of X‐Linked Hypophosphatemia Via the Selective Modulation of Phosphate Reabsorption

Fibroblast growth factor 23 (FGF23) is the causative factor of X‐linked hypophosphatemia (XLH), a genetic disorder effecting 1:20,000 that is characterized by excessive phosphate excretion, elevated FGF23 levels and a rickets/osteomalacia phenotype. FGF23 inhibits phosphate reabsorption and suppresses 1α,25‐dihydroxyvitamin D (1,25D) biosynthesis, analytes that differentially contribute to bone integrity and deleterious soft‐tissue mineralization. As inhibition of ligand broadly modulates downstream targets, balancing efficacy and unwanted toxicity is difficult when targeting the FGF23 pathway. We demonstrate that a FGF23 c‐tail‐Fc fusion molecule selectively modulates the phosphate pathway in vivo by competitive antagonism of FGF23 binding to the FGFR/α klotho receptor complex. Repeated injection of FGF23 c‐tail Fc in Hyp mice, a preclinical model of XLH, increases cell surface abundance of kidney NaPi transporters, normalizes phosphate excretion, and significantly improves bone architecture in the absence of soft‐tissue mineralization. Repeated injection does not modulate either 1,25D or calcium in a physiologically relevant manner in either a wild‐type or disease setting. These data suggest that bone integrity can be improved in models of XLH via the exclusive modulation of phosphate. We posit that the selective modulation of the phosphate pathway will increase the window between efficacy and safety risks, allowing increased efficacy to be achieved in the treatment of this chronic disease. © 2017 American Society for Bone and Mineral Research.     

Home and community-based service and other senior service use: Prevalence and characteristics in a national sample

ABSTRACT

We report on the use of home and community-based services (HCBS) and other senior services and factors affecting utilization of both among Americans over age 60 in the Health and Retirement Study (HRS). Those using HCBS were more likely to be older, single, Black, lower income, receiving Medicaid, and in worse health. Past use of less traditional senior services, such as exercise classes and help with tax preparation, were found to be associated with current use of HCBS. These findings suggest use of less traditional senior services may serve as a “gateway” to HCBS that can help keep older adults living in the community.     

A mixed-methods study of system-level sustainability of evidence-based practices in 12 large-scale implementation initiatives

Background

In recent decades, evidence-based practices (EBPs) have been broadly promoted in community behavioural health systems in the United States of America, yet reported EBP penetration rates remain low. Determining how to systematically sustain EBPs in complex, multi-level service systems has important implications for public health. This study examined factors impacting the sustainability of parent-child interaction therapy (PCIT) in large-scale initiatives in order to identify potential predictors of sustainment.

Methods

A mixed-methods approach to data collection was used. Qualitative interviews and quantitative surveys examining sustainability processes and outcomes were completed by participants from 12 large-scale initiatives.

Results

Sustainment strategies fell into nine categories, including infrastructure, training, marketing, integration and building partnerships. Strategies involving integration of PCIT into existing practices and quality monitoring predicted sustainment, while financing also emerged as a key factor.

Conclusions

The reported factors and strategies impacting sustainability varied across initiatives; however, integration into existing practices, monitoring quality and financing appear central to high levels of sustainability of PCIT in community-based systems. More detailed examination of the progression of specific activities related to these strategies may aide in identifying priorities to include in strategic planning of future large-scale initiatives.

Trial registration

ClinicalTrials.gov ID NCT02543359; Protocol number PRO12060529.

     

Use of Adaptive Learning Technology to Promote Self-Directed Learning in a Pharmacists’ Patient Care Process Course

Objective. To evaluate student changes in self-directed learning (SDL) in a Pharmacists’ Patient Care Process (PPCP) course using adaptive learning technology (ALT).Methods. The Pharmacists’ Patient Care Process was delivered using traditional teaching methods in fall 2018 and ALT in spring 2019. First-year student pharmacists were surveyed three times throughout the academic year on SDL factors. Focus groups were conducted at the end of the spring semester to identify perceptions of course delivery. Multilevel linear modeling and qualitative content analysis were used to evaluate survey responses and focus group feedback, respectively.Results. Ninety-two of 106 students completed all three surveys. Scores on stress management and examination management increased from the beginning to the end of the academic year. Scores on seminar (lecture) learning proficiency, procrastination management, and time management decreased from the beginning to the end of the year. Assignment management and comprehension competence trends varied from the end of the first semesters to the end of the second semester. Themes identified from the focus groups were student learning preferences, semester comparisons, value, and technology.Conclusion. Student pharmacists struggled with the integration of ALT into their previously established study routines. Focus groups helped add context to students’ SDL scores. Although significant differences were found between some SDL factors, it was not possible to conclude that implementation of ALT improved SDL.     

Mammary Analog Secretory Carcinoma (MASC) Involving the Thyroid Gland: A Report of the First 3 Cases

Salivary gland-type tumors have been rarely described in the thyroid gland. Mammary Analog Secretory Carcinoma (MASC) is a recently defined type of salivary gland carcinoma characterized by a t(12;15)(p13;q25) resulting in an ETV6-NTRK3 fusion gene. We report 3 cases of MASC involving the thyroid gland without clinical evidence of a salivary gland or breast primary; the clinico-pathologic characteristics are reviewed. Assessment for rearrangement of the ETV6 (12p13) locus was conducted by fluorescence in situ hybridization (FISH) on representative FFPE sections using an ETV6 break apart probe (Abbott Molecular, Des Plaines, IL, USA). The patients were two females (52 and 55 years-old) and 1 male (74 years-old). The tumors were poorly circumscribed solid white tan nodules involving the thyroid. Histologically, they were invasive and showed solid, microcystic, cribriform, and tubular growth patterns composed of variably bland polygonal eosinophilic cells with vesicular nuclear chromatin and conspicuous nucleoli. All three cases showed metastasis to lymph nodes; one case showed lateral neck involvement. The tumor cells were positive for S100 and mammaglobin. GATA-3 and PAX-8 were positive in 2 cases, one of which only focally so. All three cases were negative for TTF-1 and thyroglobulin. Rearrangement of the ETV6 locus was confirmed in all cases and a diagnosis of MASC rendered for each case. A site of origin distinct from the thyroid gland was not identified, with a median follow up of 24 months. MASC may rarely involve the thyroid gland. The origin of these lesions is unknown; while an origin from ectopic salivary gland-type cells is entertained, a metastatic origin from an occult primary cannot be definitively excluded at this time. Given the histologic (follicular-like microcystic pattern with colloid-like secretions and papillary pattern), immunophenotypic (PAX-8), and even molecular overlap, MASC can be mistaken for papillary thyroid carcinoma and should be considered in the differential diagnosis of a thyroid mass.     

Maternal mental health symptoms are positively related to emotional and restrained eating attitudes in a statewide sample of mothers participating in a supplemental nutrition program for women,infants and young children

Postpartum, low‐income mothers are at risk for mental health symptoms and obesity, and disordered eating attitudes may be associated with both mental health and obesity in this vulnerable population. The study objective is to determine whether higher levels of mental health symptoms are associated with increased odds of emotional and restrained eating attitudes in this sample of Special Supplemental Nutrition Program for Women, Infants and Children (WIC) participants. Data on 711 mothers of infants <13 months from a statewide sample of Maryland WIC participants were collected via telephone survey. Maternal mental health symptoms were measured on continuous scales for depression (PRIME‐MD), stress (Perceived Stress Scale) and anxiety (Spielberger State‐Trait Anxiety Inventory). Emotional and restrained eating attitudes were measured with questions adapted from the Dutch Eating Behavior Questionnaire. Multivariate logistic regression analysis was used. Obesity [body mass index (BMI) ≥ 30] was explored as a moderating variable. Mothers reporting higher levels of depression symptoms [odds ratio (OR) = 3.93, 95%CI: 2.71–5.69], anxiety symptoms (OR = 1.96, 95%CI: 1.47–2.65), stress symptoms (OR = 2.09, 95%CI: 1.67–2.61) and high overall mental health symptomatology (OR = 3.51, 95%CI: 2.43–5.3) had increased odds of emotional eating attitudes. There were significant associations between symptoms of depression (OR = 1.59, 95% CI: 1.12–2.25) and increased odds of restrained eating attitudes. Obesity did not moderate the association. Mothers with mental health symptoms are at risk for disordered eating attitudes, which may increase risk of poor diet. These findings underscore the need for greater focus on addressing maternal mental health status and eating attitudes in the postpartum period.