Telephone-based social health screening by pharmacists in the nonadherent Medicare population.

BACKGROUND: Unmet social health needs are associated with medication nonadherence. Although pharmacists are well positioned to address medication nonadherence, there is limited experience with screening for and addressing social health needs. OBJECTIVES: To compare the prevalence of social health needs among Medicare patients with higher vs lower social health risk using a predictive model. To also evaluate pre-post changes in medication adherence and health care use following a pharmacist-initiated social health screening. METHODS: A social health screening workflow was implemented into a routine pharmacist adherence program at an integrated health care delivery system. The social health screening was conducted during medication adherence outreach phone calls with Medicare members who were overdue for statin, blood pressure, or diabetes medications. We developed a social health need predictive algorithm to flag higher-risk patients and tested this algorithm against a random subset of lower-risk patients. Screening conversations were guided by a focus group that developed open-ended questions to identify social health needs. Comparisons in social health needs were made between higher- and lower-risk patients. Use and adherence outcomes were compared pre and post for patients who accepted a referral to social health resources and patients who declined a referral. RESULTS: 1,217 patients were contacted and screened for social health needs by pharmacists. Patients flagged by the social risk algorithm were more likely to report social health needs (28.7% vs 12.7% in the unflagged group; P < 0.01). Commonly reported needs included transportation (43%), finances (34%), caregiving (22%), mental health (11%), and food access (10%). 221 patients accepted a referral to a central resource website and call center that connected patients to local services. One year after screening dates, patients who did not accept a referral spent more time in the hospital (mean change +0.7 days, SD = 7.3, P < 0.01), had fewer primary care visits (mean change -0.5 visits, SD = 6.5, P < 0.01), and had a shorter length of membership (mean change -0.4 months, SD = 1.9, P < 0.01). Patients who accepted a referral had increased statin adherence (62.3% adherent pre vs 74.7% post, P = 0.02). CONCLUSIONS: We implemented a workflow for pharmacists to screen for social health needs. The social health need prediction model doubled the identification rate of patients who have needs. Intervening on social health needs during these calls may improve statin adherence and may have no adverse effect on health care utilization or health plan membership. DISCLOSURES: Social health risk predictive model development and validation was funded by the Agency for Healthcare Research and Quality (AHRQ R18HS027343).

A cell-penetrating peptide enhances delivery and efficacy of phosphorodiamidate morpholino oligomers in mdx mice.

Antisense RNA technology is a strategy for the treatment of Duchenne muscular dystrophy (DMD), a progressive and universally fatal X-linked neuromuscular disease caused by frameshift mutations in the gene encoding dystrophin. Phosphorodiamidate morpholino oligomers (PMOs) are an antisense RNA platform that is used clinically in patients with DMD to facilitate exon skipping and production of an internally truncated, yet functional, dystrophin protein. Peptide-conjugated PMOs (PPMOs) are a next-generation platform in which a cell-penetrating peptide is conjugated to the PMO backbone, with the goal of increasing cellular uptake. RC-1001 is a PPMO that contains a proprietary cell-penetrating peptide and targets the Dmd mutation in mdx mice. It was evaluated in mdx mice for exon 23 skipping, dystrophin production, and functional efficacy. Single-dose RC-1001 dose dependently increased exon skipping and dystrophin protein levels in striated muscle and is associated with improvements in muscle function. Dystrophin protein levels were durable for 60 days. Three doses, each given 1 month apart, increased exon skipping to 99% in quadriceps and 43% in heart, with dystrophin protein levels at 39% and 9% of wild type, respectively. These findings support clinical development of PPMO therapies for the treatment of DMD.

A hurricane alters the relationship between mangrove cover and marine subsidies.

As global change alters the composition and productivity of ecosystems, the importance of subsidies from one habitat to another may change. We experimentally manipulated black mangrove (Avicennia germinans) cover in 10 large plots and over a 5-year period (2014-2019) quantifying the effects of mangrove cover on subsidies of floating organic material (wrack) into coastal wetlands. As mangrove cover increased from 0% to 100%, wrack cover and thickness decreased by ~60%, the distance that wrack penetrated into the plots decreased by ~70%, and the percentage of the wrack trapped in the first 6 m of the plot tripled. These patterns observed during 4 "normal" years disappeared in a fifth year following Hurricane Harvey (2017), when large quantities of wrack were pushed far into the interior of all the plots, regardless of mangrove cover. Prior to the storm, the abundance of animals collected in grab samples increased with wrack biomass. Wrack composition did not affect animal abundance or composition. Experimental outplants of two types of wrack (red algae and seagrass) revealed that animal abundance and species composition varied between the fringe and interior of the plots, and between microhabitats dominated by salt marsh versus mangrove vegetation. The importance of wrack to overall carbon stocks varied as a function of autochthonous productivity: wrack inputs (per m2 ) based on survey data were greater than aboveground plant biomass in the plots (42 × 24 m) dominated by salt-marsh vegetation, but decreased to 5% of the total aboveground biomass in plots dominated by mangroves. Our results illustrate that increasing mangrove cover decreases the relative importance of marine subsidies into the intertidal at the plot level, but concentrates subsidies at the front edge of the mangrove stand. Storms, however, may temporarily override mangrove attenuation of wrack inputs. Our results highlight the importance of understanding how changes in plant species composition due to global change will impact marine subsidies and exchanges among ecosystems, and foster a broader understanding of the functional interdependence of adjacent habitats within coastal ecosystems.

Biological nitrogen fixation in maize: optimizing nitrogenase expression in a root-associated diazotroph.

Plants depend upon beneficial interactions between roots and root-associated microorganisms for growth promotion, disease suppression, and nutrient availability. This includes the ability of free-living diazotrophic bacteria to supply nitrogen, an ecological role that has been long underappreciated in modern agriculture for efficient crop production systems. Long-term ecological studies in legume-rhizobia interactions have shown that elevated nitrogen inputs can lead to the evolution of less cooperative nitrogen-fixing mutualists. Here we describe how reprogramming the genetic regulation of nitrogen fixation and assimilation in a novel root-associated diazotroph can restore ammonium production in the presence of exogenous nitrogen inputs. We isolated a strain of the plant-associated proteobacterium Kosakonia sacchari from corn roots, characterized its nitrogen regulatory network, and targeted key nodes for gene editing to optimize nitrogen fixation in corn. While the wild-type strain exhibits repression of nitrogen fixation in conditions replete with bioavailable nitrogen, such as fertilized greenhouse and field experiments, remodeled strains show elevated levels in the rhizosphere of corn in the greenhouse and field even in the presence of exogenous nitrogen. Such strains could be used in commercial applications to supply fixed nitrogen to cereal crops.

Long-term laboratory culture causes contrasting shifts in tolerance to two marine pollutants in copepods of the genus Tigriopus.

Organismal chemical tolerance is often used to assess ecological risk and monitor water quality, yet tolerance can differ between field- and lab-raised organisms. In this study, we examined how tolerance to copper (Cu) and tributyltin oxide (TBTO) in two species of marine copepods, Tigriopus japonicus and T. californicus, changed across generations under benign laboratory culture (in the absence of pre-exposure to chemicals). Both copepod species exhibited similar chemical-specific changes in tolerance, with laboratory maintenance resulting in increased Cu tolerance and decreased TBTO tolerance. To assess potential factors underlying these patterns, chemical tolerance was measured in conjunction with candidate environmental variables (temperature, UV radiation, diet type, and starvation). The largest chemical-specific effect was found for starvation, which decreased TBTO tolerance but had no effect on Cu tolerance. Understanding how chemical-specific tolerance can change in the laboratory will be critical in strengthening bioassays and their applications for environmental protection and chemical management.

The C-terminal fibrinogen-like domain of angiopoietin-like 4 stimulates adipose tissue lipolysis and promotes energy expenditure.

Angptl4 (Angiopoietin-like 4) is a circulating protein secreted by white and brown adipose tissues and the liver. Structurally, Angptl4 contains an N-terminal coiled-coil domain (CCD) connected to a C-terminal fibrinogen-like domain (FLD) via a cleavable linker, and both full-length Angptl4 and its individual domains circulate in the bloodstream. Angptl4 inhibits extracellular lipoprotein lipase (LPL) activity and stimulates the lipolysis of triacylglycerol stored by adipocytes in the white adipose tissue (WAT). The former activity is furnished by the CCD, but the Angptl4 domain responsible for stimulating adipocyte lipolysis is unknown. We show here that the purified FLD of Angptl4 is sufficient to stimulate lipolysis in mouse primary adipocytes and that increasing circulating FLD levels in mice through adenovirus-mediated overexpression (Ad-FLD) not only induces WAT lipolysis in vivo but also reduces diet-induced obesity without affecting LPL activity. Intriguingly, reduced adiposity in Ad-FLD mice was associated with increased oxygen consumption, fat utilization, and the expression of thermogenic genes (Ucp1 and Ppargc1a) in subcutaneous WAT. Moreover, Ad-FLD mice exhibited increased glucose tolerance. Chronically enhancing WAT lipolysis could produce ectopic steatosis because of an overflow of lipids from the WAT to peripheral tissues; however, this did not occur when Ad-FLD mice were fed a high-fat diet. Rather, these mice had reductions in both circulating triacylglycerol levels and the mRNA levels of lipogenic genes in the liver and skeletal muscle. We conclude that separating the FLD from the CCD-mediated LPL-inhibitory activity of full-length Angptl4 reveals lipolytic and thermogenic properties with therapeutic relevance to obesity and diabetes.

Evaluating the healthiness of chain-restaurant menu items using crowdsourcing: a new method.

OBJECTIVE: To develop a technology-based method for evaluating the nutritional quality of chain-restaurant menus to increase the efficiency and lower the cost of large-scale data analysis of food items. DESIGN: Using a Modified Nutrient Profiling Index (MNPI), we assessed chain-restaurant items from the MenuStat database with a process involving three steps: (i) testing 'extreme' scores; (ii) crowdsourcing to analyse fruit, nut and vegetable (FNV) amounts; and (iii) analysis of the ambiguous items by a registered dietitian. RESULTS: In applying the approach to assess 22 422 foods, only 3566 could not be scored automatically based on MenuStat data and required further evaluation to determine healthiness. Items for which there was low agreement between trusted crowd workers, or where the FNV amount was estimated to be >40 %, were sent to a registered dietitian. Crowdsourcing was able to evaluate 3199, leaving only 367 to be reviewed by the registered dietitian. Overall, 7 % of items were categorized as healthy. The healthiest category was soups (26 % healthy), while desserts were the least healthy (2 % healthy). CONCLUSIONS: An algorithm incorporating crowdsourcing and a dietitian can quickly and efficiently analyse restaurant menus, allowing public health researchers to analyse the healthiness of menu items.

Management of microcarcinomas (papillary and medullary) of the thyroid.

PURPOSE OF REVIEW: Microcarcinomas of the thyroid gland are defined by the size criteria as tumors measuring less than 1 cm in greatest dimension. The clinical significance of papillary thyroid microcarcinoma (PTMC) and medullary thyroid microcarcinoma (MTMC) is debatable. Variation in practice patterns exist in the United States with regard to diagnosis, treatment, and long-term management. We review the most recent guidelines on the management of these controversial malignancies. RECENT FINDINGS: PTMC has recently been shown to be the most common thyroid malignancy in patients older than 45 years in the United States. The management of patients with PTMC is not well defined, although recent studies have indicated that total or near-total thyroidectomy decreases overall recurrence rate. BRAF mutation testing plays an increasingly important role in perioperative management and has potential for targeted molecular therapies.Prophylactic thyroidectomy is indicated early in life for RET mutation carriers at risk for medullary thyroid cancer. New evidence suggests that timing may be personalized based on specific exon mutations and serum calcitonin levels. The biological significance and surgical management of MTMC have been debated, but the most recent studies indicate a relatively high incidence of lymph node metastases, distant metastases, and persistently elevated postoperative calcitonin; and argue for the aggressive management of even the smallest MTMCs. SUMMARY: Total or near-total thyroidectomy is the treatment of choice in patients with PTMC in order to eradicate multifocal disease and decrease overall recurrence rate. If there are palpable, biopsy-proven, or grossly apparent metastases at the time of operation, central lymphadenectomy should be performed. Prophylactic thyroidectomy in hereditary cases of MTMC may be guided by knowledge of specific exon mutations and calcitonin levels. The extent of operation for both hereditary and sporadic MTMC is nonstandardized, and further studies are needed to clarify this issue.

Medullary thyroid cancer: an update of new guidelines and recent developments.

PURPOSE OF REVIEW: Medullary thyroid cancer (MTC) is an uncommon malignancy. Its low incidence has limited both widespread clinical expertise and definitive large randomized clinical trials. Variation in practice patterns exist in the United States with regard to diagnosis, treatment, and long-term management. We review the most recent guidelines on management of this challenging neuroendocrine malignancy. RECENT FINDINGS: Newly identified re-arranged during transfection point mutations have added to clinicians' disease prognostic accuracy, which have been incorporated in the new MTC treatment guidelines. The study of tumor marker doubling times has guided the extent of surgery and lymphadenectomy for MTC. Although data are limited, standard chemotherapy and radiation therapy have not been shown to be effective in the treatment of MTC. Newer targeted drug therapies are promising and are being examined in therapeutic clinical trials. SUMMARY: There have been several recent advances in the molecular biology, diagnosis, imaging, and treatment options for MTC. Downstaging and treating metastatic disease more effectively may improve overall survival of MTC patients. Dissemination of standardized guidelines is important for optimal treatment with less variation in quality of care.

Vispedia: interactive visual exploration of wikipedia data via search-based integration.

Wikipedia is an example of the collaborative, semi-structured data sets emerging on the Web. These data sets have large, non-uniform schema that require costly data integration into structured tables before visualization can begin. We present Vispedia, a Web-based visualization system that reduces the cost of this data integration. Users can browse Wikipedia, select an interesting data table, then use a search interface to discover, integrate, and visualize additional columns of data drawn from multiple Wikipedia articles. This interaction is supported by a fast path search algorithm over DBpedia, a semantic graph extracted from Wikipedia's hyperlink structure. Vispedia can also export the augmented data tables produced for use in traditional visualization systems. We believe that these techniques begin to address the "long tail" of visualization by allowing a wider audience to visualize a broader class of data. We evaluated this system in a first-use formative lab study. Study participants were able to quickly create effective visualizations for a diverse set of domains, performing data integration as needed.