Time-resolved circular dichroism of excitonic systems: theory and experiment on an exemplary squaraine polymer.

Experimental and theoretical foundations for femtosecond time-resolved circular dichroism (TRCD) spectroscopy of excitonic systems are presented. In this method, the system is pumped with linearly polarized light and the signal is defined as the difference between the transient absorption spectrum probed with left and with right circularly polarized light. We present a new experimental setup with a polarization grating as key element to generate circularly polarized pulses. Herein the positive (negative) first order of the diffracted light is left-(right-)circularly polarized and serves as a probe pulse in a TRCD experiment. The grating is capable of transferring ultrashort broadband pulses ranging from 470 nm to 720 nm into two separate beams with opposite ellipticity. By applying a specific chopping scheme we can switch between left and right circular polarizations and detect transient absorption (TA) and TRCD spectra on a shot-to-shot basis simultaneously. We perform experiments on a squaraine polymer, investigating excitonic dynamics, and we develop a general theory for TRCD experiments of excitonically coupled systems that we then apply to describe the experimental data in this particular example. At a magic angle of 54.7° between the pump-pulse polarization and the propagation direction of the probe pulse, the TRCD and TA signals become particularly simple to analyze, since the orientational average over random orientations of complexes factorizes into that of the interaction with the pump and the probe pulse, and the intrinsic electric quadrupole contributions to the TRCD signal average to zero for isotropic samples. Application of exciton theory to linear absorption and to linear circular dichroism spectra of squaraine polymers reveals the presence of two fractions of polymer conformations, a dominant helical conformation with close interpigment distances that are suggested to lead to short-range contributions to site energy shifts and excitonic couplings of the squaraine molecules, and a fraction of unfolded random coils. Theory demonstrates that TRCD spectra of selectively excited helices can resolve state populations that are practically invisible in TA spectroscopy due to the small dipole strength of these states. A qualitative interpretation of TRCD and TA spectra in the spectral window investigated experimentally is offered. The 1 ps time component found in these spectra is related to the slow part of exciton relaxation obtained between states of the helix in the low-energy half of the exciton manifold. The dominant 140 ps time constant reflects the decay of excited states to the electronic ground state.

The role of managed care pharmacy in coprescribing naloxone for patients with specific risk: recommendations from the AMCP Addiction Advisory Group.

Prescription opioid misuse remains a significant cause of morbidity and mortality associated with drug overdose. Researchers, government agencies, public health interests, and professional organizations support the benefits of naloxone coprescribing for patients on chronic opioid therapy to prevent deaths from opioid overdose. However, gaps remain in the provision of naloxone to patients at risk. Currently, less than 1% of patients who should be prescribed naloxone with their opioid medications obtain a prescription for naloxone, illustrating an opportunity for health care providers to conduct thorough risk assessments for patients taking opioids and coprescribing naloxone to those at risk. There are documented barriers to the provision of naloxone for primary care providers, pharmacists, and patients. Managed care organizations have also created barriers. To better understand and evaluate trends in treatment, coverage, policies, and needs associated with providing health services to patients with substance use disorders, the Academy of Managed Care Pharmacy (AMCP) Addiction Advisory Group conducted a survey in 2019. Eighty percent of the managed behavioral health organizations and 47% of AMCP payer members who responded to the survey encouraged naloxone coprescribing in patients at high risk of overdose; however, no organizations require coprescribing. Health plans, managed care organizations, prescribers, pharmacists, patients, and others have important roles in decreasing the morbidity and mortality associated with opioid overdose. In particular, managed care organizations can take specific and meaningful actions to implement payment policies that improve naloxone coprescribing for patients at risk. In this article, opportunities have been outlined for managed care leadership that actively support public health policies for naloxone coprescribing, and 7 recommendations are presented. DISCLOSURES: The AMCP Addiction Advisory Group and the development of this article were supported by Alkermes and Precision Toxicology. Sponsors participated in the advisory group, which provided guidance in the development of the manuscript. Dharbhamalla is employed by AMCP. Skelton is a paid consultant working with AMCP.

Advancing the Adoption of Continuing Professional Development (CPD) in the United States.

Over the last four decades, the expanded patient care roles of pharmacists in the United States (U.S.) have increased focus on ensuring the implementation of processes to enhance continuing professional development within the profession. The transition from a model of continuing pharmacy education (CPE) to a model of continuing professional development (CPD) is still evolving. As pharmacists assume more complex roles in patient care delivery, particularly in community-based settings, the need to demonstrate and maintain professional competence becomes more critical. In addition, long-held processes for post-graduate education and licensure must also continue to adapt to meet these changing needs. Members of the pharmacy profession in the U.S. must adopt the concept of CPD and implement processes to support the thoughtful completion of professional development plans. Comprehensive, state-of-the-art technology solutions are available to assist pharmacists with understanding, implementing and applying CPD to their professional lives.

Pharmacist and student pharmacist views of professional and personal well-being and resilience.

OBJECTIVES: To describe the views of pharmacists and student pharmacists regarding (1) aspects of life and experiences that provide professional and personal satisfaction and fulfillment, (2) causes of stress, and (3) needs related to maintaining satisfaction and fulfillment. DESIGN: A generic qualitative research design was used for collecting data from 380 pharmacists and 332 student pharmacists who wrote responses to an online survey hosted by the American Pharmacists Association (APhA) from November 17 to December 2, 2018, using standard data collection procedures applied by that organization. APhA uses its member and affiliate data files as its sampling frame and limits the number of contacts per year for each person in those files. De-identified responses from those who volunteered to write comments were sent to the research team for analysis. A conventional content analysis approach was applied for analysis of the text. Analysts convened to discuss emergent themes and develop operational descriptions. Key segments of text that best represented each theme were identified. Personal presuppositions were disclosed and were useful for developing group consensus for theme identification and description. Rigor was supported through assessment of credibility, confirmability, intercoder checking, transferability, inductive thematic saturation, and authenticity. SETTING AND PARTICIPANTS: Participants are in the design since data already collected. OUTCOME MEASURES: Not applicable. RESULTS: Findings showed that pharmacists and student pharmacists are able to recognize and pursue achievement, recognition, responsibility, advancement, relationship, esteem, self-actualization, meaning, and accomplishment in both their professional and personal lives. However, external factors such as "workism" and individual factors such as "moral distress" were identified as areas of improvement that are needed for well-being and resilience. CONCLUSION: Pharmacists' basic human needs are being met, but to improve well-being and resilience for pharmacists in both their professional and personal lives, there is a need for addressing both the external factors and individual factors that they encounter.

The growing role of biologics and biosimilars in the United States: Perspectives from the APhA Biologics and Biosimilars Stakeholder Conference.

OBJECTIVES: The American Pharmacists Association (APhA) convened the Biologics and Biosimilars Stakeholder Conference on November 30, 2016, in Washington DC. The objectives of the Conference were to determine the key issues and challenges within the marketplace for biologics, follow-on biologics (FOBs), and biosimilars, identify potential roles and responsibilities of pharmacists regarding biologic and biosimilar medications, and identify actions or activities that pharmacists may take to optimize the safe and cost-effective use of biologics and biosimilars. DATA SOURCES: National thought leaders and stakeholder representatives, including individuals from the Food and Drug Administration, Centers for Medicare and Medicaid Services, a private third-party payer, manufacturers, and several national organizations of health care professionals, participated in the conference. Information shared by this group was supplemented with relevant legal and regulatory information and published literature. SUMMARY: Biologics play a valuable role in the treatment of numerous health conditions, but their associated costs, which tend to be greater than those of small-molecule drugs, place a burden on the health care system. Biosimilars (both noninterchangeable and interchangeable) are highly similar copies of the originator biologic and offer the potential to reduce costs and improve patient access to biological products by increasing treatment options and creating a more competitive market. Despite the potential benefits of biosimilars, certain factors may limit their uptake. The conference participants explored issues that different stakeholders think influence the use of biologics, including biosimilars, in the United States. Barriers included technology, prescriber-pharmacist communication, legislation and regulations, limited patient and health care practitioner knowledge of biological products, patient and health care practitioner perceptions of biosimilars, and evolving science or lack of long-term data. After participants identified issues, they discussed strategies to address these concerns, including the need to enhance the education of pharmacists, prescribers, and patients regarding biologic products, including biosimilars and FOBs; the passage of state laws and regulations that do not impede the use of biosimilars, including interchangeable biosimilars; the use of product-specific tracking information in electronic health records and surveillance systems; bidirectional communication among pharmacists, prescribers, and other members of the care team to support pharmacovigilance and the maintenance of accurate patient records; and the development of evidence-based third-party payer policies. CONCLUSION: Patient access to safe and cost-effective treatments is an important goal for the health care system. As the availability and use of biosimilars, including those determined to be interchangeable, increases, their potential to lower costs and improve patient access to treatment grows. However, the extent of such growth is, in part, dependent on various stakeholders' decisions to provide, pay for, or use these products in a safe and thoughtful manner. Ongoing stakeholder collaboration, educational activities, and review of current government or payer policies are required to optimize the uptake of biological products, including biosimilars.

Developing a vision and strategic action plan for future community-based residency training.

OBJECTIVES: The Community Pharmacy Residency Program (CPRP) Planning Committee convened to develop a vision and a strategic action plan for the advancement of community pharmacy residency training. Aligned with the profession's efforts to achieve provider status and expand access to care, the Future Vision and Action Plan for Community-based Residency Training will provide guidance, direction, and a strategic action plan for community-based residency training to ensure that the future needs of community-based pharmacist practitioners are met. DATA SOURCES: National thought leaders, selected because of their leadership in pharmacy practice, academia, and residency training, served on the planning committee. The committee conducted a series of conference calls and an in-person strategic planning meeting held on January 13-14, 2015. Outcomes from the discussions were supplemented with related information from the literature. Results of a survey of CPRP directors and preceptors also informed the planning process. SUMMARY: The vision and strategic action plan for community-based residency training is intended to advance training to meet the emerging needs of patients in communities that are served by the pharmacy profession. The group anticipated the advanced skills required of pharmacists serving as community-based pharmacist practitioners and the likely education, training and competencies required by future residency graduates in order to deliver these services. The vision reflects a transformation of community residency training, from CPRPs to community-based residency training, and embodies the concept that residency training should be primarily focused on training the individual pharmacist practitioner based on the needs of patients served within the community, and not on the physical location where pharmacy services are provided. CONCLUSION: The development of a vision statement, core values statements, and strategic action plan will provide support, guidance, and direction to the profession of pharmacy to continue the advancement and expansion of community-based residency training.

Improving outcomes for diverse populations disproportionately affected by diabetes: final results of Project IMPACT: Diabetes.

OBJECTIVE: To improve key indicators of diabetes care by expanding a proven community-based model of care throughout high-risk areas in the United States. DESIGN: Observational, multisite, pre-post comparison study. SETTING: Federally qualified health centers, free clinics, employer worksites, community pharmacies, departments of health, physician offices, and other care facilities in 25 communities in 17 states from June 2011 through January 2013. PARTICIPANTS: 1,836 patients disproportionately affected by diabetes representing diverse ethnicities, insurance statuses, and social and economic backgrounds. INTERVENTION: Pharmacists were integrated into local, interdisciplinary diabetes care teams and provided customized diabetes education and medication consultations to patients. MAIN OUTCOME MEASURES: Clinical measures included glycosylated hemoglobin (A1C), body mass index, systolic and diastolic blood pressures, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, and total cholesterol. Process measures included smoking status, eye examination status, foot examination status, and influenza vaccine status. RESULTS: Pharmacist patient care services for those underserved or disproportionately affected by diabetes resulted in a statistically significant and clinically relevant decrease in mean A1C levels (-0.8%). Other outcome indicators were below target levels at baseline and decreased significantly but not by clinically relevant amounts (LDL-C, -7.1 mg/dL; triglycerides, -23.7 mg/dL, and total cholesterol, -8.8 mg/dL). The mean increase in HDL-C (+0.6 mg/dL) was not statistically significant or clinically relevant. Among evaluable patients who were not at target for process measures at baseline, 51.7% of 453 patients received eye examinations, 72.0% of 271 patients received foot examinations, 41.7% of 307 patients received influenza vaccinations, and 9.3% patients of 270 quit smoking during the project. Of the communities involved in the study, 92% intend to sustain pharmacists' services. CONCLUSION: Project IMPACT: Diabetes results show significant improvement in patients' clinical outcomes and demonstrate that all patients, even those with tremendous barriers to appropriate diabetes care, benefit from patient-centered, interdisciplinary health care teams that include pharmacists.

Cognitive memory screening and referral program in community pharmacies in the United States.

INTRODUCTION: 12 chain community pharmacy sites located in two geographic areas with the United States implemented easy-to-administer memory screening assessments for patients with risk factors of cognitive memory decline and referred at-risk patients to their physicians. AIM OF THE STUDY: To evaluate the impact of a pharmacy-based cognitive memory screening and referral program, measure patient satisfaction with these advanced clinical services, and assess willingness to pay for cognitive memory screening services. SETTING: 12 chain pharmacy sites located in two geographic areas--ten Fred Meyer Pharmacies located in the Portland, Oregon area and two Kerr Drug Pharmacies located in North Carolina. METHOD: Pharmacists were educated on Alzheimer's disease, trained on how to provide cognitive memory screening exams, and equipped with screening and documentation tools. Following each screening, pharmacist provided education and counseling to the patients and referred at-risk patients to physicians for follow-up as appropriate. MAIN OUTCOME MEASURES: Results of screenings; satisfaction of patients; willingness to pay. RESULTS: Pharmacists delivered cognitive memory assessments to 161 patients from June to November 2008. 44.1 % of patients experienced at least one cognitive deficiency that required referral to a physician based on the screening conducted. The cognitive memory screening and referral program was highly regarded by patients who completed the satisfaction survey, with 98.4 % of respondents indicating that they were either very satisfied or satisfied with the program. CONCLUSION: Cognitive memory screening can be easily incorporated into clinical service offerings in community pharmacy practice and provides a valuable opportunity to identify patients at-risk and refer them to a physician for appropriate testing and diagnosis.

Pharmacist-provided immunization compensation and recognition: white paper summarizing APhA/AMCP stakeholder meeting.

OBJECTIVES: To identify the current challenges and opportunities in compensation and recognition for pharmacist-provided immunizations across the lifespan and to establish guiding principles for pharmacist-provided immunization compensation and recognition. DATA SOURCES: 22 stakeholders gathered on June 29, 2011, at the American Pharmacists Association (APhA) headquarters in Washington, DC, for a meeting on immunization compensation that was convened by APhA and the Academy of Managed Care Pharmacy. Participants included representatives from community pharmacy practices (chain, grocery, and independent), employers, national consumer health and advocacy organizations, national pharmacy and public health organizations, health plan representatives, pharmacy benefit managers, and health information technology, standards, and safety organizations. Key immunization leaders from TRICARE Management Activity, the Centers for Medicare & Medicaid Services, the National Vaccine Program Office of the Department of Health & Human Services, and the Centers for Disease Control and Prevention (CDC) also participated in the meeting. SUMMARY: The increased numbers of pharmacists providing vaccination services and the availability of pharmacist-provided immunizations to populations in need of vaccines has continued to increase. This has resulted in a rise in the percentage of patients who receive vaccines at pharmacies. Pharmacists are now working to lever-age their ability to identify people with key risk factors (e.g., diabetes, heart disease or previous myocardial infarction), encourage them to receive their CDC-recommended vaccinations, and administer the required vaccine. Challenges and opportunities in compensation and recognition for pharmacist-provided immunizations across the adult lifespan persist. Variability in state practice acts, reimbursement and compensation processes and systems, and mechanisms for documentation of vaccine services create substantial differences in how pharmacist-provided immunizations are delivered throughout the United States. CONCLUSION: Pharmacist-provided immunizations are clinically sound, are cost effective, are readily accessible, and support our nation's public health goals. Pharmacists have demonstrated that patient vaccination rates have improved through expansion of pharmacist-provided immunizations. The profession should continue efforts to collaborate with other immunization stakeholders and expand a pharmacist scope of practice that is built around a uniform and recognized standard of immunization provision and that supports the provision of all CDC-recommended vaccines through pharmacy-provided immunizations.

White paper on expanding the role of pharmacists in caring for individuals with Alzheimer's disease: APhA Foundation Coordinating Council to Improve Collaboration in Supporting Patients with Alzheimer's Disease.

OBJECTIVE: The purpose of this initiative was to establish a Coordinating Council to Improve Collaboration in Supporting Patients with Alzheimer's Disease. The Council convened on March 5-6, 2008, in Washington, DC. The American Pharmacists Association (APhA) Foundation, in conjunction with leading national experts in Alzheimer's disease (AD), assessed the level of care and services currently provided by pharmacists to AD patients and developed this "blueprint document" for how they might be more effective in helping patients and family caregivers manage the burden of this devastating disease. DATA SOURCE: A premeeting survey of Council members was conducted to elicit their perceptions regarding the needs and challenges facing AD patients and their family caregivers and to gain insights as to what roles pharmacists could and should be playing to help manage drug therapy and enhance the quality of life in patients with AD. SUMMARY: AD is one of the most significant health crises that will be faced in the United States over the next 30 years. Currently, it is the sixth leading cause of death in the country. The findings of the Council confirmed that pharmacists are playing important roles in the management of AD but can expand these roles. CONCLUSION: Pharmacists are accessible, trusted, and respected resources. Increased pharmacist involvement in the care of individuals with AD could improve clinical outcomes and family caregiver quality of life. With the expected increase in the number of individuals diagnosed with AD, the resources and services to care for and support this population will be even further taxed. Innovative approaches for expanding pharmacist involvement in AD should be developed to maximize the difference pharmacists can make in the lives of those who suffer from the disease.

Organization of responses in human lateral gastrocnemius muscle to specified body perturbations.

There is mounting evidence that human muscles have discrete partitions. In an effort to accurately assess how the control to each of the three heads (designated as A-C) of the lateral gastrocnemius (LG) muscle might be organized, we performed exploratory studies in five subjects each of whom was provided 30 random angular and linear perturbations while standing on a balance platform in each of three experiments. The responses from each LG head were recorded with strategically-placed fine-wire electrodes and, after correction for variation in distance to each recording site, latency to activation and the sequence of recruitment for each LG head were determined. Within individual subjects, the same LG head was first recruited. The C-head was recruited first during linear perturbations between subjects and across sessions, but the overall recruitment pattern was different between subjects. The fact that a consistent, selective response was seen during dynamic linear but not angular perturbations suggests that a more consistent strategy of inter-partition response may be engaged for the former perturbation. This behaviour may be caused by use of the LG C-head to assist the medial gastrocnemius to control ankle plantar flexion and pronation during the shearing forces generated with linear translations. Further exploration into the relationship between selective activation of muscle partitions in the presence of defined movement conditions appears justified.

Neuropharmacologic treatment of hemineglect: a case report comparing bromocriptine and methylphenidate.

Individuals who have hemineglect fail to attend to stimuli presented on the side of the body contralateral to a brain lesion. Although in animal studies the severity of neglect correlates with the degree of dopamine depletion, in hemineglect patients dopamine-enhancing medications have produced inconsistent results. We present a case of hemineglect following a right cerebrovascular accident in a 68-year-old man treated consecutively with methylphenidate and bromocriptine. Tests sensitive to neglect were administered during treatment with methylphenidate, then after all medications had been discontinued, then when the patient was taking low and moderate doses of bromocriptine, and again after all medications had been discontinued for 4 and 26 days. Methylphenidate was superior to no drug treatment. Bromocriptine produced more improvement in neglect than methylphenidate. Although the patient showed an exacerbation of his neglect after withdrawal from methylphenidate, performance gains persisted after withdrawal from bromocriptine. Treatment effects appear related to medication choice, timing of drug treatment, and the adaptability of dopaminergic receptor systems.

Analysis of the enzymatic cleavage (beta elimination) of the capsular K5 polysaccharide of Escherichia coli by the K5-specific coliphage: reexamination.

The capsular K5 polysaccharide of Escherichia coli is the receptor of the capsule-specific coliphage K5, which harbors an enzyme that degrades the capsular K5 polysaccharide to a number of oligosaccharides. Analysis of the degradation products using gel permeation chromatography, the periodate-thiobarbituric acid and bicinchoninic acid reactions, and nuclear magnetic resonance spectroscopy showed that the major reaction products are hexa-, octa-, and decasaccharides with 4,5-unsaturated glucuronic acid (delta4,5GlcA) at their nonreducing end. Thus, the bacteriophage enzyme is a K5 polysaccharide lyase and not, as we had reported previously, an endo-N-acetylglucosaminidase.

NMR investigation of the 6-deoxy-L-talose-containing O45, O45-related (O45rel), and O66 polysaccharides of Escherichia coli.

The structures of the 6-deoxytalose-containing O-specific polysaccharides from the O45 antigen, an O45-related antigen (O45rel), and the O66 antigen (lipopolysaccharides, LPSs) of Escherichia coli were elucidated by chemical characterization and by one- and two-dimensional 1H and 13C NMR spectroscopy. The O45 and O45-related polysaccharides have the following general structure: [formula: see text] For the O45 antigen, X is alpha-D-FucpNAc and for the O45-related antigen, X is beta-D-GlcpNAc. The structure of the O66 polysaccharide is [formula: see text]

NMR reinvestigation of two N-acetylneuraminic acid-containing O-specific polysaccharides (O56 and O24) of Escherichia coli.

Structures for the N-acetylneuraminic acid (Neu5Ac)-containing O56 and O24 polysaccharides of Escherichia coli have been reported previously. During these studies unusual chemical shifts had been observed for the NMR signals for H-3eq and C-3 of the Neu5Ac residues of both polysaccharides. In further pursuing this phenomenon, we have reinvestigated the O56 and O24 polysaccharides as well as derived oligosaccharides by one- and two-dimensional NMR spectroscopy. The results showed that structures of both polysaccharides (PSs) had to be modified and formulated as [formula: see text] 2D ROESY spectra revealed a strong NOE between H-3eq of Neu5Ac and the protons of the side-chain sugar (H-3 and H-5 of alpha-D-Gal p in the O56 PS and H-3 of alpha-D-Glc p in the O24 PS) and also between H-3ax of Neu5Ac and H-3 of beta-D-Glc p in the main chain. This indicated a close spatial association of the seven-linked alpha-Neu5Ac and the side-chain residues alpha-D-Gal p (O56 PS) and alpha-D-Glc p (O25 PS), respectively. The strong long-range spatial contacts caused the unusual chemical shifts of H-3eq and C-3 of Neu5Ac.

Subcutaneous bupivacaine for treatment of spasticity: a case report.

In a previous report, we described heretofore undiscovered possibilities that neuropathic pain and spasticity may share some common pathophysiological mechanisms. Currently, systemically delivered local anesthetics are being used for the evaluation and treatment of neuropathic pain. We present a case describing the treatment of spasticity of spinal origin with continuous subcutaneous infusion of 0.75% bupivacaine in a patient who did not respond to traditional treatments and has become tolerant to intrathecal baclofen.