Will Removing Rebates Really Lower Drug List Prices?

The Trump Administration Blueprint to Lower Drug Prices and Reduce Out-of-Pocket Costs calls for incentives to lower drug list prices, including removing rebates. Our clinical consultant Stephanie Tran continues our pharmacy blog series with an assessment of this potential change & its impacts

Will ending certain drug rebates lower list prices and patient out-of-pocket costs?

Earlier this year, the Department of Health and Human Services (HHS) proposed changes to the current pricing and contracting system for federal health care programs, Medicare Part D and Medicaid.This proposal aligns with the Trump Administration’s blueprint for lowering drug prices which we have written about previously

Shiga toxin production and translocation during microaerobic human colonic infection with Shiga toxin-producing E. coli O157:H7 and O104:H4

Haemolytic uraemic syndrome caused by Shiga toxin-producing E. coli (STEC) is dependent on release of Shiga toxins (Stxs) during intestinal infection and subsequent absorption into the bloodstream. An understanding of Stx-related events in the human gut is limited due to lack of suitable experimental models. In this study, we have used a vertical diffusion chamber system with polarized human colon carcinoma cells to simulate the microaerobic (MA) environment in the human intestine and investigate its influence on Stx release and translocation during STEC O157:H7 and O104:H4 infection. Stx2 was the major toxin type released during infection. Whereas microaerobiosis significantly reduced bacterial growth as well as Stx production and release into the medium, Stx translocation across the epithelial monolayer was enhanced under MA versus aerobic conditions. Increased Stx transport was dependent on STEC infection and occurred via a transcellular pathway other than macropinocytosis. While MA conditions had a similar general effect on Stx release and absorption during infection with STEC O157:H7 and O104:H4, both serotypes showed considerable differences in colonization, Stx production, and Stx translocation which suggest alternative virulence strategies. Taken together, our study suggests that the MA environment in the human colon may modulate Stx-related events and enhance Stx absorption during STEC infection

Reliability and Validity of the NE1 Wound Assessment Tool (WAT)

Background and Purpose: Current literature indicates a lack of reliability and validity of existing pressure ulcer (PrU) staging systems. This prompted the development of the N.E. One Can Stage (NEOCS). Recently this tool was modified and renamed, the NE1 Wound Assessment Tool (NE1 WAT). The purpose of this study is to test the reliability and validity of the NE1 WAT. Subjects: A sample of convenience of nine physical therapists (PTs) and 11 nurses (RNs) with PrU staging as part of their routine work duties were included in this study. Methods: A written exam was administered and consisted of assessment questions that the subjects were to answer by using color photographs of 10 wounds. Subjects first completed the exam without exposure to the NE1 WAT, then a second time after an instructional presentation on the tool and its use. Seven to 10 days later, the test was completed for a third time, again with use of the NE1 WAT, without further instruction on use of the tool. Test-retest reliability was analyzed using the intra-class correlation coefficient (ICC), and evidence for validity was assessed using a paired t-test to compare the1st and 2nd test scores. Results: Reliability for all clinicians was ICC (2,1) = .670 (95% CI: .333 to .855). Comparisons for all clinicians between tests 1 (mean=73.05, SD= 9.66) and 2 (mean= 80.85, SD= 11.65) revealed a significant difference between the means,t(19) = -3.640, p=.002. Discussion: The NE1 WAT demonstrated moderate reliability and significantly improved the accuracy of PrU staging and wound assessment for subjects. Conclusion: The NE1 WAT is a reliable and valid tool to improve healthcare clinicians’ ability in staging PrUs

Climate and plant traits as influences on green roof performance

106 leaves : illustrations ; 29 cmIncludes abstract and appendices.Includes bibliographical references.Green roofs are being introduced and installed in varying climates worldwide to benefit from green roof services. Services of thermal cooling and stormwater capture reduce building energy consumption and strain on infrastucture. Across North America, green roofs often make use of a limited set of plants, but the effects of different climates on survival and growth are unknown while survival often outranks optimization of services. To identify the impact of climate on plant performance, I installed an identical green roof system in three Canadian cities. To investigate the relationship between plant traits and green roof services, I measured service provision and analyzed for correlation. A moderate climate supported the best growth and performance, but in all climates, mixture plantings performed well over the two growing seasons. Plant traits of specific leaf area and plant height were predictive, through vegetation characteristics, of stormwater capture and green roof surface cooling

Content appraisal and age moderate the relationship between passive social media use and mental ill-being

An important distinction to make when assessing the impact of social media use on mental health is whether the use is passive (e.g., browsing) or active (e.g., posting). Recent research suggests that the connection between passive social media use and mental ill-being is inconsistent, with some research finding a significant negative association, while other research finds no such association. In the present research, we sought to investigate this relationship, as well as two potential moderators of this relationship: the subjective appraisal of social media content social media users consume (i.e., positively or negatively-appraised) and age of users. In a cross-sectional survey of Australian and United States Facebook users (N = 991), there was no direct relationship between passive use and mental ill-being, however user age and positive (but not negative) content appraisal were found to moderate the relationship between passive use and mental ill-being. Specifically, the relationship between passive use and mental ill-being became weaker as subjective positive appraisal increased, and it reversed to become negative at high levels of positive appraisal. Additionally, the positive relationship between passive use and mental ill-being became weaker as age of social media users increased, and the direction of this relationship became negative at the oldest ages of social media users. These results suggest that the relationship between social media use and mental ill-being is more nuanced than previous research suggests. In particular, higher amounts of passive Facebook use may have a less negative, or even a positive effect on social media users’ mental health when the content being (passively) consumed is positively appraised, or when users are older

Shiga toxin 2 translocation across intestinal epithelium is linked to virulence of Shiga toxin-producing Escherichia coli in humans

Shiga toxin-producing Escherichia coli (STEC) are characterized by the release of potent Shiga toxins (Stx), which are associated with severe intestinal and renal disease. Although all STEC strains produce Stx, only a few serotypes cause infection in humans. To determine which virulence traits in vitro are linked to human disease in vivo, 13 Stx2a-producing STEC strains of seropathotype (SPT) A or B (associated with severe human intestinal disease and outbreaks) and 6 strains of SPT D or E (rarely or not linked to human disease) were evaluated in a microaerobic human colonic epithelial infection model. All SPT strains demonstrated similar growth, colonization of polarized T84 colon carcinoma cells and Stx release into the medium. In contrast, Stx translocation across the T84 cell monolayer was significantly lower in SPT group DE compared to SPT group AB strains. Further experiments showed that Stx penetration occurred via a transcellular pathway and was independent of bacterial type III secretion and attaching and effacing lesion formation. These results suggest that the extent of Stx transcytosis across the gut epithelium may represent an important indicator of STEC pathogenicity for humans

Two Homologous EF-G Proteins From Pseudomonas Aeruginosa Exhibit Distinct Functions

Genes encoding two proteins corresponding to elongation factor G (EF-G) were cloned from Pseudomonas aeruginosa. The proteins encoded by these genes are both members of the EFG I subfamily. The gene encoding one of the forms of EF-G is located in the str operon and the resulting protein is referred to as EF-G1A while the gene encoding the other form of EF-G is located in another part of the genome and the resulting protein is referred to as EF-G1B. These proteins were expressed and purified to 98% homogeneity. Sequence analysis indicated the two proteins are 90/84% similar/identical. In other organisms containing multiple forms of EF-G a lower degree of similarity is seen. When assayed in a poly(U)-directed poly-phenylalanine translation system, EF-G1B was 75-fold more active than EF-G1A. EF-G1A pre-incubate with ribosomes in the presence of the ribosome recycling factor (RRF) decreased polymerization of poly-phenylalanine upon addition of EF-G1B in poly(U)-directed translation suggesting a role for EF-G1A in uncoupling of the ribosome into its constituent subunits. Both forms of P. aeruginosa EF-G were active in ribosome dependent GTPase activity. The kinetic parameters (KM) for the interaction of EF-G1A and EF-G1B with GTP were 85 and 70 μM, respectively. However, EF-G1B exhibited a 5-fold greater turnover number (observed kcat) for the hydrolysis of GTP than EF-G1A; 0.2 s-1 vs. 0.04 s-1. These values resulted in specificity constants (kcatobs/KM) for EF-G1A and EF-G1B of 0.5 x 103 s-1 M-1 and 3.0 x 103 s-1 M-1, respectively. The antibiotic fusidic acid (FA) completely inhibited poly(U)-dependent protein synthesis containing P. aeruginosa EF-G1B, but the same protein synthesis system containing EF-G1A was not affected. Likewise, the activity of EF-G1B in ribosome dependent GTPase assays was completely inhibited by FA, while the activity of EF-G1A was not affected