Expunging Board of Pharmacy Disciplinary Actions.

Boards of pharmacy have the authority to discipline licensees whose actions fall short of practice standards. Disciplinary action may include license suspension, revocation, practice restrictions, fines and reprimands. Once discipline is levied against a board of pharmacy licensee, it is usually part of the licensee's permanent record. At least four states have created a pathway for individuals to seek expungement of previous disciplinary actions levied by a board of pharmacy. These states have variations on what violations may be expunged and when. Given the evolving approach to the regulation of pharmacists, more states may want to consider expungement pathways in the years ahead.

The Basis for Elimination of the Jurisprudence Examination as a Condition of Pharmacist Licensure in Idaho.

Some national pharmacy associations have recently joined in advocacy for a more portable pharmacist license. One impediment to accomplishing this is the state-specific nature of the pharmacy jurisprudence examination, leading to calls for the exploration of alternatives to, or outright elimination of, such examinations. This manuscript reviews the rationale for the elimination of the pharmacy jurisprudence examination in Idaho. The Idaho Board of Pharmacy reviewed the absence of similar jurisprudence examinations in other health professions, the role schools of pharmacy and employers play in preparing pharmacists for lawful practice, and how the adoption of a "standard of care" regulatory model changed thinking about the need for a jurisprudence examination. Idaho eliminated the examination in 2018, and no evidence demonstrating a public safety impact has yet materialized, while the number of Idaho licensed pharmacists has grown at a higher rate than its border states. State boards of pharmacy are in a position to decide whether keeping the pharmacy jurisprudence examination is necessary, and this manuscript reviews key considerations for other states.

Pathways to pharmacist prescriptive authority: Do decentralized models for expanded prescribing work?

Scope of practice decisions, such as granting pharmacists independent prescriptive authority, are governed at the state level and are often contentious debates. Five states - Florida (FL), New Mexico (NM), Colorado (CO), Idaho (ID), and Oregon (OR) -- have created structures that can theoretically expand independent prescriptive authority through decentralized approaches rather than needing the legislature to approve each drug that pharmacists may prescribe. These approaches have the potential advantage of allowing the states to expand independent pharmacist prescriptive authority to address public health needs more quickly. Four distinct models have been identified from most to least restrictive in practice: 1) medical veto; 2) interdisciplinary committee; 3) board of pharmacy; and 4) pharmacist-determined. These models have generally focused on postdiagnostic and preventive care by pharmacists. In terms of enabling broad pharmacist prescribing, only two of these models have demonstrated success: board of pharmacy and pharmacist-determined. Pharmacy and public health stakeholders considering similar legislation in their own states should consider the success of these decentralized models prior to enacting legislation.

Pharmacokinetic Analysis of Epithelial/Endothelial Cell Barriers in Microfluidic Bilayer Devices with an Air-Liquid Interface.

As the range of applications of organs-on-chips is broadening, the evaluation of aerosol-based therapies using a lung-on-a-chip model has become an attractive approach. Inhalation therapies are not only minimally invasive but also provide optimal pharmacokinetic conditions for drug absorption. As drug development evolves, it is likely that better screening through use of organs-on-chips can significantly save time and cost. In this work, bio-aerosols of various compounds including insulin were generated using a jet nebulizer. The aerosol flows were driven through microfluidic bilayer devices establishing an air-liquid interface to mimic the blood-air barrier in human small airways. The aerosol flow in the microfluidic devices has been characterized and adjusted to closely match physiological values. The permeability of several compounds, including paracellular and transcellular biomarkers, across epithelial/endothelial cell barriers was measured. Concentration-time plots were established in microfluidic devices with and without cells; the curves were then utilized to extract standard pharmacokinetic parameters such as the area under the curve, maximum concentration, and time to maximum concentration. The cell barrier significantly affected the measured pharmacokinetic parameters, as compound absorption through the barrier decreases with its increasing molecular size. Aerosolizing insulin can lead to the formation of fibrils, prior to its entry to the microfluidic device, with a substantially larger apparent molecular size effectively blocking its paracellular transport. The results demonstrate the advantage of using lung-on-a-chip for drug discovery with applications such as development of novel inhaled therapies.

Permeability of Epithelial/Endothelial Barriers in Transwells and Microfluidic Bilayer Devices.

Lung-on-a-chip (LoC) models hold the potential to rapidly change the landscape for pulmonary drug screening and therapy, giving patients more advanced and less invasive treatment options. Understanding the drug absorption in these microphysiological systems, modeling the lung-blood barrier is essential for increasing the role of the organ-on-a-chip technology in drug development. In this work, epithelial/endothelial barrier tissue interfaces were established in microfluidic bilayer devices and transwells, with porous membranes, for permeability characterization. The effect of shear stress on the molecular transport was assessed using known paracellular and transcellular biomarkers. The permeability of porous membranes without cells, in both models, is inversely proportional to the molecular size due to its diffusivity. Paracellular transport, between epithelial/endothelial cell junctions, of large molecules such as transferrin, as well as transcellular transport, through cell lacking required active transporters, of molecules such as dextrans, is negligible. When subjected to shear stress, paracellular transport of intermediate-size molecules such as dextran was enhanced in microfluidic devices when compared to transwells. Similarly, shear stress enhances paracellular transport of small molecules such as Lucifer yellow, but its effect on transcellular transport is not clear. The results highlight the important role that LoC can play in drug absorption studies to accelerate pulmonary drug development.

Time and motion study of pharmacist prescribing of oral hormonal contraceptives in Oregon community pharmacies.

OBJECTIVES: The aim of this time and motion study was to evaluate the procedural time and steps of performing an oral hormonal contraceptive pharmacist prescribing service in an Oregon community pharmacy. METHODS: A standardized patient seeking oral hormonal contraception visited 13 community pharmacies throughout February 2018 in the tri-county Portland, Oregon, metropolitan area for pharmacist-prescribed hormonal contraception services for a total of 26 patient encounters. An observer was present at each encounter to record the time for each step and the total encounter time. Each pharmacist was asked to perform assessment procedures and prescribing for each of 2 standardized patient presentations: in cohort 1 (n = 13), the pharmacist's assessment resulted in a hormonal contraception prescription written; in cohort 2 (n = 13), pharmacist's assessment detected contraindications and resulted in a medical referral to another health care prescriber. RESULTS: The average total patient time from arrival at the pharmacy to the generation of either a written prescription for hormonal contraception or referral to another health care provider was 17.9 and 14.1 minutes, respectively. Without accounting for documentation or dispensing the prescription, the average total pharmacist time to perform the service and issue a prescription, or refer the patient, was 7.8 and 5.4 minutes, respectively. CONCLUSION: The results indicate that the pharmacist prescribing service for oral hormonal contraception requires a modest amount of pharmacist time. Incorporation of practice into regular workflow appears to have an impact similar to other clinical services, such as immunizations and point-of-care testing. The patient time spent with the pharmacist was similar to other health care provider visits.

Are advanced practice pharmacist designations really advanced?

Four states have created advanced practice pharmacist designations in state law: advanced practice pharmacist (California), clinical pharmacist practitioner (Montana and North Carolina), and pharmacist clinician (New Mexico). To attain an advanced pharmacist designation, states typically require a fee and set a minimum education requirement either through continuing pharmacy education (CPE) or through attainment of a national certification or completion of a residency. Once attained, pharmacists may practice with additional scope of practice authorities, namely the ability to order and interpret drug therapy-related tests, and initiate or adjust/modify medications under a collaborative practice agreement (CPA). Uptake of advanced practice pharmacist designations has been light (range: 0.35%-9.8%). The additional scope of practice authority is on par with, and in some instances more restrictive than, other states with fewer barriers to entry. As such, the excitement surrounding advanced pharmacist designations may be disproportionate to the actual scope of practice gains when compared to other existing state laws.

Pharmacist and Technician Perceptions of Tech-Check-Tech in Community Pharmacy Practice Settings.

OBJECTIVE: Tech-check-tech (TCT) is a practice model in which pharmacy technicians with advanced training can perform final verification of prescriptions that have been previously reviewed for appropriateness by a pharmacist. Few states have adopted TCT in part because of the common view that this model is controversial among members of the profession. This article aims to summarize the existing research on pharmacist and technician perceptions of community pharmacy-based TCT. DATA SOURCES: A literature review was conducted using MEDLINE (January 1990 to August 2016) and Google Scholar (January 1990 to August 2016) using the terms "tech* and check," "tech-check-tech," "checking technician," and "accuracy checking tech*." DATA SYNTHESIS: Of the 7 studies identified we found general agreement among both pharmacists and technicians that TCT in community pharmacy settings can be safely performed. This agreement persisted in studies of theoretical TCT models and in studies assessing participants in actual community-based TCT models. Pharmacists who had previously worked with a checking technician were generally more favorable toward TCT. CONCLUSION: Both pharmacists and technicians in community pharmacy settings generally perceived TCT to be safe, in both theoretical surveys and in surveys following actual TCT demonstration projects. These perceptions of safety align well with the actual outcomes achieved from community pharmacy TCT studies.

Opioid exit plan: A pharmacist's role in managing acute postoperative pain.

OBJECTIVES: The benefits of a pharmacist's involvement in medication reconciliation and discharge counseling are well documented in the literature as improving patient outcomes. In contrast, no studies have focused on the initiation of a pharmacist-led opioid exit plan (OEP) for acute postoperative pain management. This paper summarizes a pharmacist-led OEP practice model and the potential role that pharmacists and student pharmacists can have at the point of admission, during postoperative recovery, and on discharge in acute pain management patients. SETTING: The pain management team at St. Joseph Mercy Hospital in Ann Arbor, MI, has developed and implemented a pharmacist-led OEP to better manage acute postoperative pain in neurosurgery and orthopedic and colorectal surgery in an effort to ensure appropriate patient and provider education and understanding of pain management. PRACTICE DESCRIPTION: OEP is a tool with the potential to expand the role of pharmacists in managing acute pain in postoperative patients at the point of admission, during the postoperative inpatient stay, and on discharge. Its benefits include medication reconciliation review and prescription drug-monitoring program search before admission, interdisciplinary rounds with the medical team to provide optimal inpatient postoperative pain management, clinical assessment of outpatient prescriptions with opioid discharge counseling, and medication evaluation of prescribed pain regimen and opioid discontinuation status at the post-discharge follow-up appointment. CONCLUSION: A hospital pain management team operating a pharmacist-led OEP can be key to guiding the appropriate prescribing practice of opioids and assisting with transitions of care on discharge. Further outcomes-based evaluations of the practice model are planned and encouraged to validate and improve the pharmacist-led OEP practice.

Expanded pharmacy technician roles: Accepting verbal prescriptions and communicating prescription transfers.

As the role of the clinical pharmacist continues to develop and advance, it is critical to ensure pharmacists can operate in a practice environment and workflow that supports the full deployment of their clinical skills. When pharmacy technician roles are optimized, patient safety can be enhanced and pharmacists may dedicate more time to advanced clinical services. Currently, 17 states allow technicians to accept verbal prescriptions called in by a prescriber or prescriber's agent, or transfer a prescription order from one pharmacy to another. States that allow these activities generally put few legal limitations on them, and instead defer to the professional judgment of the supervising pharmacist whether to delegate these tasks or not. These activities were more likely to be seen in states that require technicians to be registered and certified, and in states that have accountability mechanisms (e.g., discipline authority) in place for technicians. There is little evidence to suggest these tasks cannot be performed safely and accurately by appropriately trained technicians, and the track record of success with these tasks spans four decades in some states. Pharmacists can adopt strong practice policies and procedures to mitigate the risk of harm from verbal orders, such as instituting read-back/spell-back techniques, or requiring the indication for each phoned-in medication, among other strategies. Pharmacists may also exercise discretion in deciding to whom to delegate these tasks. As the legal environment becomes more permissive, we foresee investment in more robust education and training of technicians to cover these activities. Thus, with the adoption of robust practice policies and procedures, delegation of verbal orders and prescription transfers can be safe and effective, remove undue stress on pharmacists, and potentially free up pharmacist time for higher-order clinical care.

Freezing/Thawing without Cryoprotectant Damages Native but not Decellularized Porcine Renal Tissue.

Whole organ decellularization of porcine renal tissue and recellularization with a patient's own cells would potentially overcome immunorejection, which is one of the most significant problems with allogeneic kidney transplantation. However, there are obstacles to achieving this goal, including preservation of the decellularized extracellular matrix (ECM), identifying the proper cell types, and repopulating the ECM before transplantation. Freezing biological tissue is the best option to avoid spoilage; however, it may damage the structure of the tissue or disrupt cellular membranes through ice crystal formation. Cryoprotectants have been used to repress ice formation during freezing, although cell toxicity can still occur. The effect of freezing/thawing on native (n = 10) and decellularized (n = 10) whole porcine kidneys was studied without using cryoprotectants. Results showed that the elastic modulus of native kidneys was reduced by a factor of 22 (P < 0.0001) by freezing/thawing or decellularization, while the elastic modulus for decellularized ECM was essentially unchanged by the freezing/thawing process (p = 0.0636). Arterial pressure, representative of structural integrity, was also reduced by a factor of 52 (P < 0.0001) after freezing/thawing for native kidneys, compared to a factor of 43 (P < 0.0001) for decellularization and a factor of 4 (P < 0.0001) for freezing/thawing decellularized structures. Both freezing/thawing and decellularization reduced stiffness, but the reductions were not additive. Investigation of the microstructure of frozen/thawed native and decellularized renal tissues showed increased porosity due to cell removal and ice crystal formation. Orcein and Sirius staining showed partial damage to elastic and collagen fibers after freezing/thawing. It was concluded that cellular damage and removal was more responsible for reducing stiffness than fibril destruction. Cell viability and growth were demonstrated on decellularized frozen/thawed and non-frozen samples using human renal cortical tubular epithelial (RCTE) cells over 12 d. No adverse effect on the ability to recellularize after freezing/thawing was observed. It is recommended that porcine kidneys be frozen prior to decellularization to prevent contamination, and after decellularization to prevent protein denaturation. Cryoprotectants may still be necessary, however, during storage and transportation after recellularization.

Phase I pharmacokinetic and pharmacodynamic study of triciribine phosphate monohydrate, a small-molecule inhibitor of AKT phosphorylation, in adult subjects with solid tumors containing activated AKT.

PURPOSE: Triciribine phosphate is a potent, small-molecule inhibitor of activation of all three isoforms of AKT in vitro. AKT is an intracellular protein that, when activated, leads to cellular division; it is dysregulated in a large number of malignancies, and constitutively activating AKT mutations are present in a minority of cancers. PATIENTS AND METHODS: In this phase I study triciribine phosphate monohydrate (TCN-PM) was administered to subjects whose tumors displayed evidence of increased AKT phosphorylation (p-AKT) as measured by immunohistochemical analysis (IHC). TCN-PM was administered over 30 min on days 1, 8 and 15 of a 28-day cycle. Tumor biopsy specimens, collected before treatment and on day +15, were assessed for p-AKT by IHC and western blot analyses. RESULTS: Nineteen subjects were enrolled; 13 received at least one cycle of therapy, and a total of 34 complete cycles were delivered. One subject was treated at the 45 mg/m(2) dose before the study was closed due to its primary objective having been met. No dose-limiting toxic effects were observed. Modest decreases in tumor p-AKT following therapy with TCN-PM were observed at the 35 mg/m(2) and 45 mg/m(2) dose levels, although definitive conclusions were limited by the small sample size. CONCLUSIONS: These preliminary data suggest that treatment with TCN-PM inhibits tumor p-AKT at doses that were tolerable. Although single agent activity was not observed in this enriched population, further combination studies of TCN-PM with other signal transduction pathway inhibitors in solid tumors is warranted.

All-trans-retinoic acid improves differentiation of myeloid cells and immune response in cancer patients.

Abnormal dendritic cell differentiation and accumulation of immature myeloid suppressor cells (ImC) is one of the major mechanisms of tumor escape. We tested the possibility of pharmacologic regulation of myeloid cell differentiation using all-trans-retinoic acid (ATRA). Eighteen patients with metastatic renal cell carcinoma were treated with ATRA followed by s.c. interleukin 2 (IL-2). Eight healthy individuals comprised a control group. As expected, the cancer patients had substantially elevated levels of ImC. We observed that ATRA dramatically reduced the number of ImC. This effect was observed only in patients with high plasma concentration of ATRA (>150 ng/mL), but not in patients with lower ATRA concentrations (<135 ng/mL). Effects of ATRA on the proportions of different dendritic cell populations were minor. However, ATRA significantly improved myeloid/lymphoid dendritic cell ratio and the ability of patients' mononuclear cells to stimulate allogeneic T cells. This effect was associated with significant improvement of tetanus-toxoid-specific T-cell response. During the IL-2 treatment, the ATRA effect was completely eliminated. To assess the role of IL-2, specimens from 15 patients with metastatic renal cell carcinoma who had been treated with i.v. IL-2 alone were analyzed. In this group also, IL-2 significantly reduced the number and function of dendritic cells as well as T-cell function. These data indicate that ATRA at effective concentrations eliminated ImC, improved myeloid/lymphoid dendritic cell ratio, dendritic cell function, and antigen-specific T-cell response. ATRA treatment did not result in significant toxicity and it could be tested in therapeutic combination with cancer vaccines.