Educating Pharmacy Students to Improve Quality (EPIQ) in Colleges and Schools of Pharmacy

Objective. To assess course instructors’ and students’ perceptions of the Educating Pharmacy Students and Pharmacists to Improve Quality (EPIQ) curriculum. Methods. Seven colleges and schools of pharmacy that were using the EPIQ program in their curricula agreed to participate in the study. Five of the 7 collected student retrospective pre- and post-intervention questionnaires. Changes in students’ perceptions were evaluated to assess their relationships with demographics and course variables. Instructors who implemented the EPIQ program at each of the 7 colleges and schools were also asked to complete a questionnaire. Results. Scores on all questionnaire items indicated improvement in students’ perceived knowledge of quality improvement. The university the students attended, completion of a class project, and length of coverage of material were significantly related to improvement in the students’ scores. Instructors at all colleges and schools felt the EPIQ curriculum was a strong program that fulfilled the criteria for quality improvement and medication error reduction education. Conclusion. The EPIQ program is a viable, turnkey option for colleges and schools of pharmacy to use in teaching students about quality improvement

Long-term follow-up and treatment of congenital alveolar proteinosis

<p>Abstract</p> <p>Background</p> <p>Clinical presentation, diagnosis, management and outcome of molecularly defined congenital pulmonary alveolar proteinosis (PAP) due to mutations in the GM-CSF receptor are not well known.</p> <p>Case presentation</p> <p>A 2 1/2 years old girl was diagnosed as having alveolar proteinosis. Whole lung lavages were performed with a new catheter balloon technique, feasible in small sized airways. Because of some interstitial inflammation in the lung biopsy and to further improve the condition, empirical therapy with systemic steroids and azathioprin, and inhaled and subcutaneous GMCSF, were used. Based on clinical measures, total protein and lipid recovered by whole lung lavages, all these treatments were without benefit. Conversely, severe respiratory viral infections and an invasive aspergillosis with aspergilloma formation occurred. Recently the novel homozygous stop mutation p.Ser25X of the GMCSF receptor alpha chain was identified in the patient. This mutation leads to a lack of functional GMCSF receptor and a reduced response to GMCSF stimulation of CD11b expression of mononuclear cells of the patient. Subsequently a very intense treatment with monthly lavages was initiated, resulting for the first time in complete resolution of partial respiratory insufficiency and a significant improvement of the overall somato-psychosocial condition of the child.</p> <p>Conclusions</p> <p>The long term management from early childhood into young adolescence of severe alveolar proteinosis due to GMCSF receptor deficiency requires a dedicated specialized team to perform technically demanding whole lung lavages and cope with complications.</p

An Alternate STAT6-Independent Pathway Promotes Eosinophil Influx into Blood during Allergic Airway Inflammation

Enhanced eosinophil responses have critical roles in the development of allergic diseases. IL-5 regulates the maturation, migration and survival of eosinophils, and IL-5 and eotaxins mediate the trafficking and activation of eosinophils in inflamed tissues. CD4⁺ Th2 cells are the main producers of IL-5 and other cells such as NK also release this cytokine. Although multiple signalling pathways may be involved, STAT6 critically regulates the differentiation and cytokine production of Th2 cells and the expression of eotaxins. Nevertheless, the mechanisms that mediate different parts of the eosinophilic inflammatory process in different tissues in allergic airway diseases remain unclear. Furthermore, the mechanisms at play may vary depending on the context of inflammation and microenvironment of the involved tissues. We employed a model of allergic airway disease in wild type and STAT6-deficient mice to explore the roles of STAT6 and IL-5 in the development of eosinophilic inflammation in this context. Quantitative PCR and ELISA were used to examine IL-5, eotaxins levels in serum and lungs. Eosinophils in lung, peripheral blood and bone marrow were characterized by morphological properties. CD4⁺ T cell and NK cells were identified by flow cytometry. Antibodies were used to deplete CD4⁺ and NK cells. We showed that STAT6 is indispensible for eosinophilic lung inflammation and the induction of eotaxin-1 and -2 during allergic airway inflammation. In the absence of these chemokines eosinophils are not attracted into lung and accumulate in peripheral blood. We also demonstrate the existence of an alternate STAT6-independent pathway of IL-5 production by CD4⁺ and NK cells that mediates the development of eosinophils in bone marrow and their subsequent movement into the circulation

Unfolding Simulations of Holomyoglobin from Four Mammals: Identification of Intermediates and β-Sheet Formation from Partially Unfolded States

Myoglobin (Mb) is a centrally important, widely studied mammalian protein. While much work has investigated multi-step unfolding of apoMb using acid or denaturant, holomyoglobin unfolding is poorly understood despite its biological relevance. We present here the first systematic unfolding simulations of holoMb and the first comparative study of unfolding of protein orthologs from different species (sperm whale, pig, horse, and harbor seal). We also provide new interpretations of experimental mean molecular ellipticities of myoglobin intermediates, notably correcting for random coil and number of helices in intermediates. The simulated holoproteins at 310 K displayed structures and dynamics in agreement with crystal structures (R g ~1.48-1.51 nm, helicity ~75%). At 400 K, heme was not lost, but some helix loss was observed in pig and horse, suggesting that these helices are less stable in terrestrial species. At 500 K, heme was lost within 1.0-3.7 ns. All four proteins displayed exponentially decaying helix structure within 20 ns. The C- and F-helices were lost quickly in all cases. Heme delayed helix loss, and sperm whale myoglobin exhibited highest retention of heme and D/E helices. Persistence of conformation (RMSD), secondary structure, and ellipticity between 2-11 ns was interpreted as intermediates of holoMb unfolding in all four species. The intermediates resemble those of apoMb notably in A and H helices, but differ substantially in the D-, E- and F-helices, which interact with heme. The identified mechanisms cast light on the role of metal/cofactor in poorly understood holoMb unfolding. We also observed β-sheet formation of several myoglobins at 500 K as seen experimentally, occurring after disruption of helices to a partially unfolded, globally disordered state; heme reduced this tendency and sperm-whale did not display any sheet propensity during the simulations

IL-3 and oncogenic Abl regulate the myeloblast transcriptome by altering mRNA stability

The growth factor interleukin-3 (IL-3) promotes the survival and growth of multipotent hematopoietic progenitors and stimulates myelopoiesis. It has also been reported to oppose terminal granulopoiesis and to support leukemic cell growth through autocrine or paracrine mechanisms. The degree to which IL-3 acts at the posttranscriptional level is largely unknown. We have conducted global mRNA decay profiling and bioinformatic analyses in 32Dcl3 myeloblasts indicating that IL-3 caused immediate early stabilization of hundreds of transcripts in pathways relevant to myeloblast function. Stabilized transcripts were enriched for AU-Response elements (AREs), and an ARE-containing domain from the interleukin-6 (IL-6) 3′-UTR rendered a heterologous gene responsive to IL-3-mediated transcript stabilization. Many IL-3-stabilized transcripts had been associated with leukemic transformation. Deregulated Abl kinase shared with IL-3 the ability to delay turnover of transcripts involved in proliferation or differentiation blockade, relying, in part, on signaling through the Mek/ Erk pathway. These findings support a model of IL-3 action through mRNA stability control and suggest that aberrant stabilization of an mRNA network linked to IL-3 contributes to leukemic cell growth. © 2009 Ernst et al

Patient experience with clinical pharmacist services in Travis County Federally Qualified Health Centers

Background: Positive patient experiences with care have been linked to improved health outcomes. Patient experience surveys can provide feedback about the level of patient-centered care provided by clinical pharmacists and information about how to improve services. Objectives: Study objectives are: 1) To describe patient experience with clinical pharmacist services in a federally qualified health center (FQHC). 2) To determine if demographic or health-related factors were associated with patient experience. Methods: This cross-sectional survey included adult patients who were English or Spanish speaking, and completed a clinical pharmacist visit in March or April 2018. Patient experience was evaluated, on a 5-point Likert scale (1 = strongly disagree to 5 = strongly agree), with 10 items using four domains: pharmacist-patient interaction information provision, support for self-care, and involvement in decision making. In addition, one item was used to rate the overall experience. Demographic and health-related variables were also collected. Eligible patients completed the survey after their clinical pharmacist visit. Descriptive and inferential statistics, as well as Cronbach’s alpha for scale reliability, were employed. Results: Respondents (N=99) were 55.4 (SD=12.1) years and 53.1% were women. Overall, patients rated their experiences very high with the 10-item scale score of 4.8 (SD=0.4) out of 5 points and the overall experience rating of 4.9 (SD=0.4) out of 5 points. With the exception of race, there were no differences between patient experience and demographic and health-related variables. African Americans had significantly (p=0.0466) higher patient experience scores compared to Hispanics. Conclusions: Patients receiving care in a FQHC highly rated their experience with clinical pharmacists. This indicates that clinical pharmacists provided a high level of patient-centered care to a diverse group

Predictors of Emergent Emergency Department Visits and Costs in Community-Dwelling Older Adults

Background: The number of yearly emergency department (ED) visits by older adults in the United States has been increasing. Purpose: The objectives were to (1) describe the demographics, health-related variables, and ED visit characteristics for community-dwelling older adults using an urban, safety-net ED; (2) examine the association between demographics, health-related variables, and ED visit characteristics with emergent vs nonemergent ED visits; and (3) examine the association between demographics, health-related variables, ED visit characteristics, and ED visit costs. Methods: A cross-sectional, retrospective analysis of administrative electronic medical record and billing information from 2010 to 2013 ED visits (n = 7805) for community-dwelling older adults (⩾65 years old) from an academic medical center in central Virginia was conducted. Results: Most of the ED visits were by women (62%), African Americans (75%), and approximately 50% of ED visits were nonemergent (n = 3871). Men had 1.2 times the odds of an emergent ED visit (95% confidence interval [CI]: 1.02-1.37). The ED visits by white patients had 1.3 times the odds of an emergent ED visit (95% CI: 1.09-1.57) and 14% higher costs (white race: 95% CI: 1.07-1.21) compared with African American patients. Emergent ED visits were 60% more likely to have higher costs than nonemergent visits (95% CI: 1.52-1.69). White race and arrival by ambulance were associated with both emergent ED visits and higher total ED visit costs in this sample of ED visits by community-dwelling older adults. Conclusions: Strategies to maximize opportunities for care in the primary care setting are warranted to potentially reduce nonemergent ED utilization in community-dwelling older adults

Bacillus anthracis Spore Surface Protein BclA Mediates Complement Factor H Binding to Spores and Promotes Spore Persistence

Spores of Bacillus anthracis, the causative agent of anthrax, are known to persist in the host lungs for prolonged periods of time, however the underlying mechanism is poorly understood. In this study, we demonstrated that BclA, a major surface protein of B. anthracis spores, mediated direct binding of complement factor H (CFH) to spores. The surface bound CFH retained its regulatory cofactor activity resulting in C3 degradation and inhibition of downstream complement activation. By comparing results from wild type C57BL/6 mice and complement deficient mice, we further showed that BclA significantly contributed to spore persistence in the mouse lungs and dampened antibody responses to spores in a complement C3-dependent manner. In addition, prior exposure to BclA deletion spores (ΔbclA) provided significant protection against lethal challenges by B. anthracis, whereas the isogenic parent spores did not, indicating that BclA may also impair protective immunity. These results describe for the first time an immune inhibition mechanism of B. anthracis mediated by BclA and CFH that promotes spore persistence in vivo. The findings also suggested an important role of complement in persistent infections and thus have broad implications