Comparison of a Self-Care Therapeutics Course Taught in the P1 vs the P2 Year.

Objective: The objective of this study was to compare student learning outcomes, behaviors, and attitudes in a non-prescription drug and self-care therapeutics course taught in the second professional (P2) year vs the first professional (P1) year at one pharmacy school. Methods: Mean performance of students by class year on case consultations and exam scores was compared. Focus groups with student volunteers and course teaching assistants (TAs) and one-on-one interviews with a subset of instructors were conducted by an outside educational evaluation specialist to capture perceptions of student learning behaviors and attitudes. Results: There was no difference in performance on graded case consultations (mean difference = 0.16, P = .74, 95% CI [-0.77 to 1.09]), mid-term examinations (mean difference = 0.53, P = .62, 95% CI [-1.59 to 2.65]), or final examinations (mean difference = 0.73, P = .57, 95% CI [-1.83 to 3.30]) between P1 and P2 students. P1 students reported being more consistent in completing pre-class readings and in feeling less distracted by other courses than did P2 students. Students, TAs, and instructors consistently spoke about advantages of the course in the P1 year (e.g., less stress and greater eagerness to learn and apply skills at work) and disadvantages in the P2 year (e.g., distraction from concurrent P2 integrated pharmacotherapeutics course and tension between real-world experience and constraints of grading rubric). Conclusion: P1 students, despite one year earlier in their curriculum, performed equally well as P2 students. All stakeholders agree that the advantages of teaching a self-care course on students' learning behaviors and attitudes in the P1 year outweigh disadvantages.

Conformational flexibility in carbapenem hydrolysis drives substrate specificity of the class D carbapenemase OXA-24/40.

The evolution of multidrug resistance in Acinetobacter spp. increases the risk of our best antibiotics losing their efficacy. From a clinical perspective, the carbapenem-hydrolyzing class D ß-lactamase subfamily present in Acinetobacter spp. is particularly concerning because of its ability to confer resistance to carbapenems. The kinetic profiles of class D ß-lactamases exhibit variability in carbapenem hydrolysis, suggesting functional differences. To better understand the structure-function relationship between the carbapenem-hydrolyzing class D ß-lactamase OXA-24/40 found in Acinetobacter baumannii and carbapenem substrates, we analyzed steady-state kinetics with the carbapenem antibiotics meropenem and ertapenem and determined the structures of complexes of OXA-24/40 bound to imipenem, meropenem, doripenem, and ertapenem, as well as the expanded-spectrum cephalosporin cefotaxime, using X-ray crystallography. We show that OXA-24/40 exhibits a preference for ertapenem compared with meropenem, imipenem, and doripenem, with an increase in catalytic efficiency of up to fourfold. We suggest that superposition of the nine OXA-24/40 complexes will better inform future inhibitor design efforts by providing insight into the complicated and varying ways in which carbapenems are selected and bound by class D ß-lactamases.

An Audit and Comparison of pH, Measured Concentration, and Particulate Matter in Mannitol and Hypertonic Saline Solutions.

Background: The preferred hyperosmolar therapy remains controversial. Differences in physical properties such as pH and osmolality may be important considerations in hyperosmolar agent selection. We aimed to characterize important physical properties of commercially available hyperosmolar solutions. Methods: We measured pH and concentration in 37 commonly-used hyperosmolar solutions, including 20 and 25% mannitol and 3, 5, 14.6, and 23.4% hypertonic saline. pH was determined digitally and with litmus paper. Concentration was determined by freezing point and vapor pressure osmometry. Salinity/specific gravity was measured with portable refractometry. Particulate matter was analyzed with filtration and light microscopy and with dynamic light scattering nephelometry. Results: pH of all solutions was below physiological range (measured range 4.13-6.80); there was no correlation between pH and solution concentration (R 2 = 0.005, p = 0.60). Mannitol (mean 5.65, sd 0.94) was less acidic than hypertonic saline (5.16, 0.60). 14/59 (24%) pH measurements and 85/111 concentration measurements were outside manufacturer standards. All 36/36 mannitol concentration measurements were outside standards vs. 48/72 (67%) hypertonic saline (p < 0.0001). All solutions examined on light microscopy contained crystalline and/or non-crystalline particulate matter up to several hundred microns in diameter. From nephelometry, particulate matter was detected in 20/22 (91%) solutions. Conclusion: We present a novel characterization of mannitol and hypertonic saline. Further research should be undertaken, including research examining development of acidosis following hyperosmolar therapy, the relevance of our findings for dose-response, and the clinical relevance of particulate matter in solution.

A commentary on ethical decision-making in the pharmacy profession and the APhA Code of Ethics.

The American Pharmacists Association Code of Ethics ("Code") was established in 1852 and has undergone 5 modifications, most recently in 1994. As point of care shifts from product to cognitive clinical service, pharmacists are expected to encounter an increasing quantity and complexity of ethical and moral dilemmas. In view of this professional transformation and current worldwide challenges, this seems an appropriate time for dialogue on a modification of the Code. The 3 important questions before the profession are as follows: (1) Is the scope of available ethical guidance adequate? (2) Are pharmacists competent in ethical decision-making? (3) Is current pharmacy education and training adequately preparing students for ethical decision-making? The first question is included as part of the Pharmacy Law, Ethics, and Risk course at the University of Utah College of Pharmacy. The following commentary is based on a student's persuasive paper that the Code should remain unmodified owing to the following factors: greater detail does not ensure improved guidance, and modification may lead to confusion in professional role and responsibilities and may not consider patients' values and preferences in decision-making. To improve ethical decision-making in the pharmacy profession, this commentary further suggests that questions 2 and 3 are key to facilitating improved readiness and competency in pharmacists' ethical decision-making. Pharmacy students should be given a more thorough education in ethics, and practicing pharmacists should continually expand their knowledge and continued professional development in ethics.

A Pilot Study Regarding Pharmacy Law Education Across Doctor of Pharmacy Programs.

Objective. To describe the features of pharmacy law education in Doctor of Pharmacy (PharmD) programs in the United States. Methods. A review of the literature found no prior published data describing the delivery of pharmacy law education across PharmD programs in the United States. Members of the Pharmacy Law Educators Subcommittee of the American Society for Pharmacy Law (ASPL) developed questions for a survey. The survey was administered electronically to all 139 American Association of Colleges of Pharmacy (AACP) member institutions in the summer of 2016. A link to complete the 32-item online survey was distributed via email to the pharmacy law educator or associate dean at each AACP member institution. Results. Of the 139 PharmD programs surveyed, 49 completed the survey instrument, yielding a response rate of 35.2%. Variations between programs were found in the professional background of pharmacy law instructors and assessment strategies for pharmacy law courses, as well as in the structure and placement of the main pharmacy law course within the various curricula. Conclusion. This pilot study represents the first and only known attempt to examine delivery of pharmacy law education across colleges of pharmacy. The variations between programs found in this study highlight the need for further investigation into this area of pharmacy education.

The effect of a prescription order requirement for pharmacist-administered vaccination on herpes zoster vaccination rates.

OBJECTIVE: To determine the effect of a prescription order requirement for pharmacist-administered zoster vaccination on zoster vaccination in adults aged 60+. METHODS: A 50-state law review of statutes and regulations regarding pharmacists' ability to administer the zoster vaccine with/without a prescription order was performed. States were classified as prescription order required or not required as of January 1, 2014. Data on adults aged 60+ were obtained from the 2014 Behavioral Risk Factor Surveillance System (BRFSS). Chi-square tests and multilevel logistic regression models with and without propensity scores methods were used. RESULTS: Of the 50 states, 39 and the District of Columbia did not require a prescription order. After propensity score matching, zoster vaccination rates for adults ages 60 and older were significantly higher in states that did not require a prescription order (23.0% vs 21.1%, p = 0.0022). The propensity score-matched multilevel logistic regression model for adults aged 60+ found modestly higher odds of HZ vaccination for states that removed the prescription order requirement (OR 1.17, 95% CI 1.01-1.35). Similar estimates were found across other methodologies employed and age strata, although statistical significance varied. CONCLUSIONS: Prescription order requirements are associated with HZ vaccination rates. By removing a prescription order requirement, states may be able to promote increases in HZ vaccination in adults aged 60+.

Evaluation of US Federal Legislation for Opioid Abuse: 1973-2016.

The 114th Congress (2014-2016) has received recent attention for the high number of legislative bills directed to the public health crisis in prescription opioid abuse. The US government does not have a single source for determining public policy; however, the people expect that there will be some level of efficiency and coordination between federal and state leaders to improve the nation's health. A search of the National Library of Congress database to analyze legislative bills introduced between 1973 and 2016 and which contain the term "opioid" identified 127 bills that characterize consistency and coordination with other governmental efforts in prescription opioid abuse. Despite the recent number of introduced bills, there does not appear to be a close coordination between Congress and Federal Administrative agencies regarding this crisis.

Tools for "decloaking" the elephant in the room: conflict of interest, shared decision-making, and patient-centered care.

Recently, apparent failures in ethical conduct appear to have impacted the public trust of health care professionals. In particular, conflict of interest, whether actual or perceived, is hindering effective relationships between patients, clinicians, and society. Clinicians are poised to experience further damage to the goodwill and reputation of their professions if direct actions and changes to practice philosophy are not taken. Over the past 20 years, two substantial tools related to patient engagement have matured. These are shared decision-making (SDM), and patient-centered care (PCC). These are more than tools; they are logical frameworks for organizing the patient-clinician relationship. It is important for all clinicians to increase their understanding of these tools and incorporate in all facets of their professional practice.

The "death" of lethal injection as we know it? The role of chemical execution in the American criminal justice system.

Several independent elements have recently combined to thrust United States capital punishment into a chaos. Corrections officials and policy makers have attempted to "humanize" capital punishment by evolving into a chemical execution process, and soften the outward appearance. Foreign policies have interrupted chemical protocols by banning key ingredients. These disruptions are spawning new theories of legal challenges in capital punishment. This is a critical time for stakeholders and all members of a civilized society to pause and reflect on the role of capital punishment.

National evaluation of prescriber drug dispensing.

OBJECTIVE: To describe the legal, professional, and consumer status of prescribers dispensing legend and over-the-counter drugs in the United States. METHODS: Legal and academic databases were searched to identify those states that permit prescribers to dispense medications to patients and any limitations on such practice. In addition, prescribers and patients-consumers were surveyed to learn about the prevalence and perceptions of such practice. The use of drug samples was explicitly excluded from the study. MAIN RESULTS: Surveys were obtained from 556 physicians, 64 NPs, and 999 patient-consumers of drugs dispensed by prescribers. Forty-four states authorize prescriber dispensing. Midlevel practitioners (i.e., NPs and physician assistants) are authorized to dispense in 43 states. Thirty-two states do not require dispensing prescribers to compete additional registration to dispense medications, and 30 states require some level of compliance with pharmacy practice requirements. Prescriber dispensing is common, independent of patient age or insurance coverage. Prescriber dispensing appears driven by physician and patient perceptions of convenience and cost reductions. Future dispensing is likely to increase due to consumers' satisfaction with the practice. Consumer self-reported adverse drug reactions (ADRs) were equivalent between pharmacist- and physician-dispensed drugs, but urgent and emergency clinic ADR consultations were slightly lower with physician dispensing. CONCLUSIONS: Prescriber dispensing is firmly entrenched in the U.S. health care system, is likely to increase, does not appear to increase ADRs, and may reduce urgent care and emergency department visits. The reduction in urgent care and emergency department visits requires further study to confirm these preliminary findings.

Prescriber-pharmacist collaboration: re-engineering the partnership to optimize pain patient care.

The Walgreen Companies recently settled a Drug Enforcement Administration (DEA) administrative action and other investigations arising in connection with a controlled substance distribution facility in Florida and several of its retail pharmacies. These DEA enforcement actions upon a national chain pharmacy have resulted in a series of policies and professional practices that appear to functionally disrupt continuity of patient care. The policy issues transcend the professions and go to the core of our responsibilities to patients. It is unfortunate that regulations intended to prevent diversion also dramatically disrupt interprofessional relations. Based on public statements of professional organizations, unification on this issue seems possible. This presents an opportunity to revisit collaboration among prescribers and pharmacists in legislative and regulatory advocacy. A uniform definition of "legitimate medical purpose" is needed to maximize patient access to needed pharmacotherapy while remaining vigilant for diversion.

Assessment and recommendations of compounding education in AACP member institutions.

In August 2009, the American Association of Colleges of Pharmacy (AACP) Council of Sections established a Task Force to assess the current status of compounding education at its member institutions and to provide recommendations for future direction. The Task Force conducted a survey in late June 2010 of faculty members enrolled in the AACP Pharmaceutics and Pharmacy Practice sections to gain qualitative information of the current state of compounding education. The survey results were then organized around eight curricular topics for which the Task Force members provided interpretations and recommendations. A final report was sent to the AACP Council of Sections on February 15, 2011. This publication provides the information contained in that final report to the professional community.

Structural analysis of the Asn152Gly mutant of P99 cephalosporinase.

P99 cephalosporinase is a class C ß-lactamase that is responsible in part for the widespread bacterial resistance to ß-lactam antibiotics. Mutations of the conserved active-site residue Asn152 of the enzyme have been shown to alter ß-lactam substrate specificity in vivo. Mutation of Asn152 to a glycine is notable in that it exhibits in vivo substrate-selectivity switching. In order to better understand the structural basis for this observed switch, the X-ray crystal structure of the apo Asn152Gly mutant of P99 was determined to 1.95 Å resolution. Unexpectedly, the artificial C-terminal His(6) tag of a symmetrically-related molecule was observed bound in the active site. The His(6) tag makes several interactions with key active-site residues, as well as with several sulfate ions. Additionally, the overall C-terminus occupies the space left vacant upon the mutation of Asn152 to glycine.

Distribution of controlled substances in the U.S. supply chain: where does the compass point?

Recent administrative actions taken by the Drug Enforcement Administration (DEA) in Florida have prompted an articulate and detailed discussion of the pharmaceutical supply chain for controlled substances. Current practices in commercial distribution systems may have a partial nexus to the proliferation of opioid prescription drug abuse in Florida. No single factor or entity is responsible for this abuse proliferation, and there is no intent to harm consumers; however, distribution practices are adding risk to public health. This commentary extends a discussion on supply chain practices that seem misaligned in the promotion of legitimate business objectives and advancing public health.

Off-label prescribing of medications for pain: maintaining optimal care at an intersection of law, public policy, and ethics.

For more than 60 years, regulations limited marketing of medications for off-label uses to very low levels. Some key policy changes in the late 1990s ushered in an era of deregulation of off-label marketing. Policy changes included revised United States federal law as well as modifications of Food and Drug Administration (FDA) regulations. Subsequent investigations documented an explosion in scope off-label prescribing. Attempts to limit off-label advertising by manufacturers were vigorously challenged in the courts. Other modalities are needed to maintain a clinical care environment that places the patients' best interests first. In many circumstances, an off-label medication may be in the patient's best interests; however, where there is a lower level of clinical justification, the informed consent of the patient and shared decision making of the patient is essential to optimize outcome.

NPR3 and NPR4 are receptors for the immune signal salicylic acid in plants.

Salicylic acid (SA) is a plant immune signal produced after pathogen challenge to induce systemic acquired resistance. It is the only major plant hormone for which the receptor has not been firmly identified. Systemic acquired resistance in Arabidopsis requires the transcription cofactor nonexpresser of PR genes 1 (NPR1), the degradation of which acts as a molecular switch. Here we show that the NPR1 paralogues NPR3 and NPR4 are SA receptors that bind SA with different affinities. NPR3 and NPR4 function as adaptors of the Cullin 3 ubiquitin E3 ligase to mediate NPR1 degradation in an SA-regulated manner. Accordingly, the Arabidopsis npr3 npr4 double mutant accumulates higher levels of NPR1, and is insensitive to induction of systemic acquired resistance. Moreover, this mutant is defective in pathogen effector-triggered programmed cell death and immunity. Our study reveals the mechanism of SA perception in determining cell death and survival in response to pathogen challenge.

Baxter v. Montana, libertarianism, and end-of-life: the ripe time for a paradigm shift.

Baxter v. Montana (2009 WL 5155363 [Mont. 2009]) is a recent decision from the Montana Supreme Court that provides new legal insight into the societal issue of aid in dying. This case involves interests of persons with terminal illness, medical practitioners, law enforcement, legislative and judicial bodies, as well as the citizens of Montana. A summary judgment ruling at the Montana district court level was based almost entirely on a constitutional fundamental rights analysis. In contrast, the Montana Supreme Court affirming decision was based almost entirely on a statutory rights analysis. Both rulings from the Montana courts support the position that licensed prescribers in Montana who provide aid in dying assistance to terminally ill patients have some immunity from criminal prosecution. Each side in the case argued what they believed to be the intents and purposes of the people of Montana. Baxter v. Montana illustrates different methods to determine the will of the people concerning aid in dying and public policy. This case very subtly suggests a paradigm shift may be occurring in aid in dying policy.