Provider Perspectives on the Influence of Family on Nursing Home Resident Transfers to the Emergency Department: Crises at the End of Life.

Background. Nursing home (NH) residents often experience burdensome and unnecessary care transitions, especially towards the end of life. This paper explores provider perspectives on the role that families play in the decision to transfer NH residents to the emergency department (ED). Methods. Multiple stakeholder focus groups (n = 35 participants) were conducted with NH nurses, NH physicians, nurse practitioners, physician assistants, NH administrators, ED nurses, ED physicians, and a hospitalist. Stakeholders described experiences and challenges with NH resident transfers to the ED. Focus group interviews were recorded and transcribed verbatim. Transcripts and field notes were analyzed using a Grounded Theory approach. Findings. Providers perceive that families often play a significant role in ED transfer decisions as they frequently react to a resident change of condition as a crisis. This sense of crisis is driven by 4 main influences: insecurities with NH care; families being unprepared for end of life; absent/inadequate advance care planning; and lack of communication and agreement within families regarding goals of care. Conclusions. Suboptimal communication and lack of access to appropriate and timely palliative care support and expertise in the NH setting may contribute to frequent ED transfers

Mutations in the Lipopolysaccharide Biosynthesis Pathway Interfere with Crescentin-Mediated Cell Curvature in Caulobacter crescentus

Bacterial cell morphogenesis requires coordination among multiple cellular systems, including the bacterial cytoskeleton and the cell wall. In the vibrioid bacterium Caulobacter crescentus, the intermediate filament-like protein crescentin forms a cell envelope-associated cytoskeletal structure that controls cell wall growth to generate cell curvature. We undertook a genetic screen to find other cellular components important for cell curvature. Here we report that deletion of a gene (wbqL) involved in the lipopolysaccharide (LPS) biosynthesis pathway abolishes cell curvature. Loss of WbqL function leads to the accumulation of an aberrant Opolysaccharide species and to the release of the S layer in the culture medium. Epistasis and microscopy experiments show that neither S-layer nor O-polysaccharide production is required for curved cell morphology per se but that production of the altered O-polysaccharide species abolishes cell curvature by apparently interfering with the ability of the crescentin structure to associate with the cell envelope. Our data suggest that perturbations in a cellular pathway that is itself fully dispensable for cell curvature can cause a disruption of cell morphogenesis, highlighting the delicate harmony among unrelated cellular systems. Using the wbqL mutant, we also show that the normal assembly and growth properties of the crescentin structure are independent of its association with the cell envelope. However, this envelope association is important for facilitating the local disruption of the stable crescentin structure at the division site during cytokinesis

Identifying cell class specific losses from serially generated electroretinogram components

Purpose. Processing of information through the cellular layers of the retina occurs in a serial manner. In the electroretinogram (ERG), this complicates interpretation of inner retinal changes as dysfunction may arise from “upstream” neurons or may indicate a direct loss to that neural generator. We propose an approach that addresses this issue by defining ERG gain relationships. Methods. Regression analyses between two serial ERG parameters in a control cohort of rats are used to define gain relationships. These gains are then applied to two models of retinal disease. Results. The to gain is unity whereas the to and to gains are greater than unity, indicating “amplification” (). Timing relationships show amplification between to and compression for to and to , (). Application of these gains to -3-deficiency indicates that all timing changes are downstream of photoreceptor changes, but a direct pSTR amplitude loss occurs (). Application to diabetes indicates widespread inner retinal dysfunction which cannot be attributed to outer retinal changes (). Conclusions. This simple approach aids in the interpretation of inner retinal ERG changes by taking into account gain characteristics found between successive ERG components of normal animals

Blood Pressure Modifies Retinal Susceptibility to Intraocular Pressure Elevation

Primary open angle glaucoma affects more than 67 million people. Elevated intraocular pressure (IOP) is a risk factor for glaucoma and may reduce nutrient availability by decreasing ocular perfusion pressure (OPP). An interaction between arterial blood pressure and IOP determines OPP; but the exact contribution that these factors have for retinal function is not fully understood. Here we sought to determine how acute modifications of arterial pressure will affect the susceptibility of neuronal function and blood flow to IOP challenge. Anaesthetized (ketamine:xylazine) Long-Evan rats with low (∼60 mmHg, sodium nitroprusside infusion), moderate (∼100 mmHg, saline), or high levels (∼160 mmHg, angiotensin II) of mean arterial pressure (MAP, n = 5–10 per group) were subjected to IOP challenge (10–120 mmHg, 5 mmHg steps every 3 minutes). Electroretinograms were measured at each IOP step to assess bipolar cell (b-wave) and inner retinal function (scotopic threshold response or STR). Ocular blood flow was measured using laser-Doppler flowmetry in groups with similar MAP level and the same IOP challenge protocol. Both b-wave and STR amplitudes decreased with IOP elevation. Retinal function was less susceptible to IOP challenge when MAP was high, whereas the converse was true for low MAP. Consistent with the effects on retinal function, higher IOP was needed to attenuated ocular blood flow in animals with higher MAP. The susceptibility of retinal function to IOP challenge can be ameliorated by acute high BP, and exacerbated by low BP. This is partially mediated by modifications in ocular blood flow

Using the electroretinogram to understand how intraocular pressure elevation affects the rat retina

Intraocular pressure (IOP) elevation is a key risk factor for glaucoma. Our understanding of the effect that IOP elevation has on the eye has been greatly enhanced by the application of the electroretinogram (ERG). In this paper, we describe how the ERG in the rodent eye is affected by changes in IOP magnitude, duration, and number of spikes. We consider how the variables of blood pressure and age can modify the effect of IOP elevation on the ERG. Finally, we contrast the effects that acute and chronic IOP elevation can have on the rodent ERG

Targeted Therapies Compared to Dacarbazine for Treatment of BRAF V600E Metastatic Melanoma: A Cost-Effectiveness Analysis

. Purpose. Two BRAF V600E targeted therapies, dabrafenib and vemurafenib, have received US approval for treatment of metastatic melanoma in BRAF V600E patients, a mutation that affects ∼50% of patients. We evaluated the cost-effectiveness of BRAF inhibitors and traditional chemotherapy for treatment of metastatic melanoma. Methods. A Markov model was developed using a societal perspective. Transition probabilities were derived from two Phase III registration trials comparing each BRAF inhibitor against dacarbazine. Costs were obtained from literature, national databases, and Medicare fee schedules. Utilities were obtained from published literature. Deterministic and probabilistic sensitivity analyses were run to test the impact of uncertainties. Results. The incremental cost-effectiveness ratio of dabrafenib was $149,035/QALY compared to dacarbazine. Vemurafenib was dominated by dabrafenib. Probabilistic sensitivity analysis showed that, at a willingness-to-pay (WTP) threshold of ≤$100,000/QALY, dacarbazine was the optimal treatment in ∼85% of simulations. At a WTP threshold of ≥$150,000/QALY, dabrafenib was the optimal treatment. Conclusion. Compared with dacarbazine, dabrafenib and vemurafenib were not cost-effective at a willingness-to-pay threshold of$100,000/QALY. Dabrafenib is more efficient compared to vemurafenib. With few treatment options, dabrafenib is an option for qualifying patients if the overall cost of dabrafenib is reduced to $30,000-$31,000 or a WTP threshold of ≥$150,000/QALY is considered. More comparative data is needed

East Bay Coalition for the Homeless: Branding Study and Marketing Strategy

There are a number of potential positioning strategies. The two which make the most sense for the EBCH are to “position the EBCH away from others in the category” and to “position the EBCH as unique.” These strategies have the advantage of setting the EBCH apart from the other organizations that address homelessness. Occupying its own “position” in the minds of potential and current donors is not only an effective communications/marketing strategy but also a less costly one because it avoids head-to-head competition and comparisons