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Reply to the Hematology/Oncology Pharmacy Association Alternative Viewpoint on the 2016 ACCP Pharmacotherapy Didactic Curriculum Toolkit
Tariquidar sensitizes multiple myeloma cells to proteasome inhibitors via reduction of hypoxia-induced P-gp-mediated drug resistance
Multiple myeloma (MM) presents a poor prognosis and high lethality of patients due to development of drug resistance. P-glycoprotein (P-gp), a drug-efflux transporter, is upregulated in MM patients post-chemotherapy and is involved in the development of drug resistance since many anti-myeloma drugs (including proteasome inhibitors) are P-gp substrates. Hypoxia develops in the bone marrow niche during MM progression and has long been linked to chemoresistance. Additionally, hypoxia-inducible transcription factor (HIF-1α) was demonstrated to directly regulate P-gp expression. We found that in MM patients P-gp expression positively correlated with the hypoxic marker, HIF-1α. Hypoxia increased P-gp protein expression and its efflux capabilities in MM cells in vitro using flow cytometry. We reported herein that hypoxia-mediated resistance to carfilzomib and bortezomib in MM cells is due to P-gp activity and was reversed by tariquidar, a P-gp inhibitor. These results suggest combining proteasome inhibitors with P-gp inhibition for future clinical studies
Augmented renal clearance is not a risk factor for mortality in Enterobacteriaceae bloodstream infections treated with appropriate empiric antimicrobials
The main objective of the study was to assess whether augmented renal clearance was a risk factor for mortality in a cohort of patients with Enterobacteriaceae sepsis, severe sepsis, or septic shock that all received appropriate antimicrobial therapy within 12 hours. Using a retrospective cohort from Barnes-Jewish Hospital, a 1,250-bed teaching hospital, we collected data on individuals with Enterobacteriaceae sepsis, severe sepsis, and septic shock who received appropriate initial antimicrobial therapy between June 2009 and December 2013. Clinical outcomes were compared according to renal clearance, as assessed by Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formulas, sepsis classification, demographics, severity of illness, and comorbidities. We identified 510 patients with Enterobacteriaceae bacteremia and sepsis, severe sepsis, or septic shock. Sixty-seven patients (13.1%) were nonsurvivors. Augmented renal clearance was uncommon (5.1% of patients by MDRD and 3.0% by CKD-EPI) and was not associated with increased mortality. Our results are limited by the absence of prospective determination of augmented renal clearance. However, in this small cohort, augmented renal clearance as assessed by MDRD and CKD-EPI does not seem to be a risk factor for mortality in patients with Enterobacteriaceae sepsis. Future studies should assess this finding prospectively
Cutaneous HPV and alpha-mucosal 9-valent HPV sero-status associations
Seroepidemiology of human papillomaviruses (HPV) among men is poorly understood. We examined the association between seropositivity to cutaneous HPV and 9-valent HPV (9vHPV) types. Six hundred men were randomly selected from the HPV Infection in Men (HIM) Study. Archived serum specimens were tested for antibodies against 9vHPV types [low-risk (6/11) and high-risk (16/18/31/33/45/52/58)], and 14 cutaneous types, including β-types 5/8/12/14/17/22/23/24/38/47, α-type-27, γ-type-4, µ-type-1, and ν-type-41, using a GST L1-based multiplex serology assay. Risk factor data were collected through questionnaires. Logistic regression was used to evaluate associations between mucosal and cutaneous HPV types. Approximately 21% of men were positive for ≥ 1 cutaneous HPV type, and ≥ 1 nine-valent HPV vaccine type at the same time. Men who were seropositive for any-cutaneous HPV were nearly twice as likely to be seropositive for 9vHPV (adjusted odds ratio (AOR) = 1.97, 95% confidence interval (CI): 1.30–2.99), high-risk (AOR = 1.83; 95% CI: 1.04–3.20), low-risk (AOR = 1.92; 95% CI: 1.16–3.18), and four-valent, 4vHPV, (AOR = 2.01; 95% CI: 1.25–3.21). Type-specific cutaneous HPV seropositivity (types: 8/14/17/23/38/27/4/1) was also positively associated with seropositivity to 9vHPV, high-risk, and low-risk categories. These data indicate that exposure to cutaneous HPV and 9vHPV types is common. Future longitudinal studies are needed to assess the temporality of these associations
Considering chance in quality and safety performance measures: An analysis of performance reports by boards in English NHS trusts
Objectives Hospital board members are asked to consider large amounts of quality and safety data with a duty to act on signals of poor performance. However, in order to do so it is necessary to distinguish signals from noise (chance). This article investigates whether data in English National Health Service (NHS) acute care hospital board papers are presented in a way that helps board members consider the role of chance in their decisions. Methods Thirty English NHS trusts were selected at random and their board papers retrieved. Charts depicting quality and safety were identified. Categorical discriminations were then performed to document the methods used to present quality and safety data in board papers, with particular attention given to whether and how the charts depicted the role of chance, that is, by including control lines or error bars. Results Thirty board papers, containing a total of 1488 charts, were sampled. Only 88 (6%) of these charts depicted the role of chance, and only 17 of the 30 board papers included any charts depicting the role of chance. Of the 88 charts that attempted to represent the role of chance, 16 included error bars and 72 included control lines. Only 6 (8%) of the 72 control charts indicated where the control lines had been set (eg, 2 vs 3 SDs). Conclusions Hospital board members are expected to consider large amounts of information. Control charts can help board members distinguish signals from noise, but often boards are not using them. We discuss demand-side and supply-side barriers that could be overcome to increase use of control charts in healthcare
Patient perceptions of a pharmacy star rating model
Objectives To identify patients’ understanding of what constitutes a “quality pharmacy” and to obtain their feedback regarding the development and use of the pharmacy star rating model, a pharmacy-specific aggregate performance score based on the Centers for Medicare and Medicaid Services’ Medicare Star Rating. Design Prospective cross-sectional study. Setting and participants Focus groups were conducted in Arizona, California, Mississippi, Maryland, and the District of Columbia, and one-on-one interviews were conducted in Indiana. Eligible patients were required to routinely use a community pharmacy. Main outcome measures Consumer insights on their experiences with their pharmacies and their input on the pharmacy star rating model were attained. Key themes from the focus groups and interviews were obtained through the use of qualitative data analyses. Results Forty-nine subjects from 5 states and DC participated in 6 focus groups and 4 one-on-one interviews. Eighty-eight percent of participants reported currently taking at least 1 medication, and 87% reported having at least 1 health condition. The 7 themes identified during qualitative analysis included patient care, relational factors for choosing a pharmacy, physical factors for choosing a pharmacy, factors related to use of the pharmacy star rating model, reliability of the pharmacy star rating model, trust in pharmacists, and measures of pharmacy quality. Most participants agreed that the ratings would be useful and could aid in selecting a pharmacy, especially if they were moving to a new place or if they were dissatisfied with their current pharmacy. Conclusion Pharmacy quality measures are new to patients. Therefore, training and education will need to be provided to patients, as pharmacies begin to offer additional clinical services, such as medication therapy management and diabetes education. The use of the pharmacy star rating model was dependent on the participants’ situation when choosing a pharmacy
Warfarin and aspirin versus warfarin alone for prevention of embolic events in patients with a heartmate II left ventricular assist device
Acquired von Willebrand disease increases bleeding risk in patients implanted with a continuous-flow left ventricular assist device. Lower aspirin (ASA) doses decrease the risk of bleeding without an increased risk of embolic events. No published studies in the United States have compared the incidence of bleeding and thrombotic events between antithrombotic regimens with and without ASA. A single-center, retrospective analysis was conducted of adult patients implanted with a HeartMate II (HM II). Patients received warfarin and ASA 81 mg daily or warfarin alone. The primary end-point was a composite of death, bleeding events, and thrombotic events from the date of HM II implantation to first event or 18 months. Secondary end-points included the individual components of the primary end-point and the proportion of patients alive with HM II or transplanted. The Wilcoxon rank sum test and Fisher\u27s exact test were used for statistical analysis. Of the 76 patients meeting inclusion criteria, 44 received warfarin and ASA and 32 received warfarin alone. Baseline characteristics were similar between groups. Warfarin alone was not associated with an increased risk of the primary composite outcome (53 vs. 59%, respectively, p = 0.64). No significant difference was observed in any bleeding event (34 vs. 43%, respectively, p = 0.48) nor any thrombotic event (9 vs. 11%, respectively, p = 1.00) with warfarin alone compared with warfarin and ASA. Elimination of antiplatelet therapy from the HM II antithrombotic regimen was associated with no significant difference in the composite outcome of bleeding events, thrombotic events, or death, nor the individual components of each end-point
Flow reproducibility of whole blood and other bodily fluids in simplified no reaction lateral flow assay devices
The no reaction lateral flow assay (nrLFA) uses a simplified LFA structure with no conjugate pad and no stored reagents. In the nrLFA, the capillary-based transport time or distance is the key indicator, rather than the outcome of a biochemical reaction. Hence, the calibration and reproducibility of the nrLFA device are critical. The capillary flow properties of several membrane types (nitrocellulose, nylon, cellulose acetate, polyethersulfone, and polyvinylidene difluoride) are evaluated. Flow rate evaluations of MilliporeSigma Hi-Flow™ Plus (HF075, HF135 and HF180) nitrocellulose membranes on nrLFA are performed using bodily fluids (whole blood, blood plasma, and artificial sweat). The results demonstrate that fluids with lower viscosity travel faster, and membranes with slower flow rate exhibit higher capability to distinguish fluids with different viscosities. Reproducibility tests of nrLFA are performed on HF075, demonstrating excellent reproducibility. The coefficient of variation for blood coagulation tests performed with the nrLFA using induced coagulation was 5% for the plasma front and 2% for the RBC front. The effects of variation in blood hematocrit and sample volume are also reported. The overall results indicate that the nrLFA approach has a high potential to be commercially developed as a blood monitoring point-of-care device with simple calibration capability and excellent reproducibility
Metabolic characterization of a novel RORα knockout mouse model without ataxia
The retinoic acid receptor-related receptor α (RORα) is a nuclear receptor that plays an important role in regulation of metabolism and the immune system. Genetic deletion of the receptor yields mice with significant cerebellar developmental issues associated with severe ataxia. Although many metabolic studies have been performed in these models, the impaired locomotor activity of these mice is known to affect their normal mobility and feeding behaviors. This creates some difficulty in interpretation of the role of RORα in models of metabolic disease where feeding and muscle function is a critical component of the pathophysiology. We generated a mouse with a floxed Rorα allele that we crossed with a mouse line expressing Cre recombinase under the control of the EIIa promoter to obtain a full body deletion of α. This cross led to a partial deletion of the Rora locus likely due to mosaic expression of the EIIa-Cre transgene. These mice lack any signs of ataxia but display an improved metabolic profile relative to normal WT mice. The mice were resistant to diet- and age-induced metabolic syndrome and exhibited improved glucose tolerance and increased insulin sensitivity. Decreased RORα expression in the mice was also associated with reduced inflammation in models of metabolic syndrome. These data indicate that suppression of RORα activity improves metabolic function and reduces inflammation
Faculty perception of team-based learning over multiple semesters
INTRODUCTION: Perspectives from faculty regarding team-based learning (TBL) are not well understood. Previous studies describe faculty preference for TBL due to increased student interaction despite requiring increased time for design. The perception of changes in faculty workload over multiple semesters has not been measured. This research evaluates faculty workload and perceived student engagement after implementing TBL in a required non-prescription medication course over multiple semesters. METHODS: TBL was implemented in the non-prescription medication course and continued for three consecutive semesters. Faculty members\u27 perception of TBL was captured using an anonymous survey. The survey was an 11 item questionnaire with five Likert-type response options to identify changes in workload, training, and student interaction using TBL. RESULTS: Twenty-eight total responses were collected from 10 faculty members who taught in at least one of the four semesters. Results were aggregated based on the number of semesters faculty continually taught in the course. More respondents agreed than disagreed that participation from and interactions with students increased with the TBL course compared to traditional lectures. However, more respondents believed the TBL course approach was more difficult and reported increased workload in the initial semester taught. Enjoyment of teaching increased for a majority of respondents. DISCUSSION AND CONCLUSIONS: This is the first study to explore the impact of TBL implementation over multiple semesters. These data can be used to help implement TBL in pharmacy school curricula