Assessing Pharmacists' Views and Barriers to Providing and Billing for Pharmacist-Provided Health Care Services.

Background: The role of Idaho and Alaska pharmacists in providing health care services has steadily broadened over recent years. With many new pharmacist-provided health care service possibilities, this study assessed the impact of these advancements on community pharmacies. Objective: The objective of this study was to identify current pharmacist-provided health care services and pharmacist-perceived barriers to providing and billing for these services in Idaho and Alaska community pharmacies. Methods: A questionnaire was developed focusing on 2 areas: providing services and billing for services. Pharmacy students on experiential rotations administered the questionnaires to pharmacists at their rotation sites. Pharmacists at community pharmacy practice sites in Idaho and Alaska completed the questionnaire in an interview format conducted by students. Likert-type scale data were analyzed using descriptive statistics. Because the study did not include a comparator group, no power calculation was conducted. All open-response answers were analyzed independently by 2 researchers and discrepancies in coding open-ended questions were resolved by discussion with a group of 4 researchers. Results: Most pharmacists reported that they already provide non-dispensing services, desired to implement new services, and had confidence in their team's ability to handle new services. Time and resources were the most cited barriers to providing new services; compensation, company support, and education were the most cited barriers to billing for services. Conclusions: Community pharmacists already provide non-dispensing services and many are looking to provide more services, but barriers of time, resources, compensation, company support, and education will need to be overcome to move forward.

Pharmacist medical provider status in Alaska, the last frontier.

Alaska law and health care policies, incidentally, designate pharmacists as billable medical providers when providing health care services. However, state and commercial provider enrollment and claims processing systems are not configured to enroll and accept claims from pharmacists. Alaska law does not protect pharmacists from unfair discriminatory practices by payors despite such protections being afforded in federal regulation. Additional advocacy and legislation are needed to fully implement pharmacists as billing medical providers within traditional payor models. Health care services provided by pharmacists can help alleviate unmet patient health care needs in the community and primary care settings of Alaska. The identified barriers will continue to limit the ability of pharmacists in Alaska to sustainably provide lifesaving, scope-permitted, and otherwise covered services to those in greatest need.

A wavelength dependent investigation of the indole photophysics via ionization and fragmentation pump-probe spectroscopies.

A wavelength dependent study investigating the low-lying (1)La and (1)Lb states, both possessing (1)ππ* character, and the (1)πσ* state in the deactivation process of indole is presented here. Relaxation dynamics following excitation at 241, 250, 260, 270, 273, and 282 nm are examined using three gas-phase, pump-probe spectroscopic techniques: (1) hydrogen atom (H-atom) time-resolved kinetic energy release (TR-KER), (2) time-resolved photoelectron spectroscopy (TR-PES), and (3) time-resolved ion yield (TR-IY). Applied in combination, a more complete picture of the indole relaxation dynamics may be gleaned. For instance, TR-PES experiments directly observe all relaxation pathways by probing the evolution of the excited states following photoexcitation; whereas, TR-KER measurements indirectly, yet specifically, probe for (1)πσ*-state activity through the detection of H-atoms eliminated along the indole nitrogen-hydrogen (N-H) stretch coordinate-a possible outcome of (1)πσ*-state relaxation in indole. In addition, mass information obtained via TR-IY monitors fragmentation dynamics that may occur within the neutral electronically excited and/or cationic states. The work herein assesses the onset and importance of the (1)πσ* state at various pump wavelengths by systematically tuning across the ultraviolet absorption spectrum of indole with a particular focus on those pump wavelengths longer than 263 nm, where the involvement of the (1)πσ* state is under current debate. As far as this experimental work is concerned, there does not appear to be any significant involvement by the (1)πσ* state in the indole relaxation processes following excitation at 270, 273, or 282 nm. This investigation also evaluates the primary orbital promotions contributing to the (1)La, (1)Lb, and (1)πσ* transitions based on ionization preferences observed in TR-PES spectra. Relaxation time constants associated with dynamics along these states are also reported for excitation at all of the aforementioned pump wavelengths and are used to pinpoint the origin of the discrepancies found in the literature. In this context, advantages and disadvantages of the three experimental techniques are discussed.

A guide to selecting high-performing antibodies for Synaptotagmin-1 (Uniprot ID P21579) for use in western blot, immunoprecipitation, immunofluorescence and flow cytometry.

Synaptotagmin-1 is a synaptic vesicle transmembrane protein that senses calcium influx via its tandem C2-domains, triggering synchronous neurotransmitter release. Disruption to SYT1 is associated with neurodevelopmental disorders, highlighting the importance of identifying high-quality research reagents to enhance understanding of Synaptotagmin-1 in health and disease. Here we have characterized thirteen Synaptotagmin-1 commercial antibodies for western blot, immunoprecipitation, immunofluorescence and flow cytometry using a standardized experimental protocol based on comparing read-outs in knockout cell lines and isogenic parental controls. These studies are part of a larger, collaborative initiative seeking to address antibody reproducibility issues by characterizing commercially available antibodies for human proteins and publishing the results openly as a resource for the scientific community. While use of antibodies and protocols vary between laboratories, we encourage readers to use this report as a guide to select the most appropriate antibodies for their specific needs.

YCharOS open antibody characterisation data: Lessons learned and progress made.

YCharOS is a collaborative initiative aimed at characterising antibodies against the entire human proteome. As of August 2023, they have presented comprehensive knockout characterisation data for 812 antibodies and 78 proteins using techniques such as Western blot, immunoprecipitation, and immunofluorescence. YCharOS consolidates its data into reports (one protein per report) available on Zenodo, a public repository controlled by CERN, to ensure open access. To enhance the visibility of their work, the group is progressively converting their Zenodo reports into F1000 articles, collected on the YCharOS Gateway, and indexed via PubMed. Their data is also accessible through searches on the Antibody Registry. The provided data is a valuable resource for researchers when selecting antibodies for specific applications, although certain limitations should be considered. The data accumulated thus far has illuminated the extent of the problem when poorly performing antibodies are employed in research. While the scientific community was already aware that this was likely a widespread issue, the establishment of a collaborative open science project with industry partners introduces an innovative solution that holds the potential to yield significant returns on investment in the public interest. This potential is substantiated by the number of antibodies that have either been withdrawn or had their recommended usage altered by the vendor. However, despite the discovery of high-performing renewable antibodies for most of the studied proteins, this accounts for a tiny fraction of the human proteome and the commercial antibody market. To realise the full potential of this work, end-users must adjust their antibody procurement and usage practises in line with the provided data. This editorial offers a guide on how individual scientists can utilise the YCharOS data, in addition to sharing the insights gained from the data thus far with the wider scientific community.

Scaling of an antibody validation procedure enables quantification of antibody performance in major research applications.

Antibodies are critical reagents to detect and characterize proteins. It is commonly understood that many commercial antibodies do not recognize their intended targets, but information on the scope of the problem remains largely anecdotal, and as such, feasibility of the goal of at least one potent and specific antibody targeting each protein in a proteome cannot be assessed. Focusing on antibodies for human proteins, we have scaled a standardized characterization approach using parental and knockout cell lines (Laflamme et al., 2019) to assess the performance of 614 commercial antibodies for 65 neuroscience-related proteins. Side-by-side comparisons of all antibodies against each target, obtained from multiple commercial partners, have demonstrated that: (i) more than 50% of all antibodies failed in one or more applications, (ii) yet, ~50-75% of the protein set was covered by at least one high-performing antibody, depending on application, suggesting that coverage of human proteins by commercial antibodies is significant; and (iii) recombinant antibodies performed better than monoclonal or polyclonal antibodies. The hundreds of underperforming antibodies identified in this study were found to have been used in a large number of published articles, which should raise alarm. Encouragingly, more than half of the underperforming commercial antibodies were reassessed by the manufacturers, and many had alterations to their recommended usage or were removed from the market. This first study helps demonstrate the scale of the antibody specificity problem but also suggests an efficient strategy toward achieving coverage of the human proteome; mine the existing commercial antibody repertoire, and use the data to focus new renewable antibody generation efforts.

Commercially produced antibodies are essential research tools. Investigators at universities and pharmaceutical companies use them to study human proteins, which carry out all the functions of the cells. Scientists usually buy antibodies from commercial manufacturers who produce more than 6 million antibody products altogether. Yet many commercial antibodies do not work as advertised. They do not recognize their intended protein target or may flag untargeted proteins. Both can skew research results and make it challenging to reproduce scientific studies, which is vital to scientific integrity. Using ineffective commercial antibodies likely wastes $1 billion in research funding each year. Large-scale validation of commercial antibodies by an independent third party could reduce the waste and misinformation associated with using ineffective commercial antibodies. Previous research testing an antibody validation pipeline showed that a commercial antibody widely used in studies to detect a protein involved in amyotrophic lateral sclerosis did not work. Meanwhile, the best-performing commercial antibodies were not used in research. Testing commercial antibodies and making the resulting data available would help scientists identify the best study tools and improve research reliability. Ayoubi et al. collaborated with antibody manufacturers and organizations that produce genetic knock-out cell lines to develop a system validating the effectiveness of commercial antibodies. In the experiments, Ayoubi et al. tested 614 commercial antibodies intended to detect 65 proteins involved in neurologic diseases. An effective antibody was available for about two thirds of the 65 proteins. Yet, hundreds of the antibodies, including many used widely in studies, were ineffective. Manufacturers removed some underperforming antibodies from the market or altered their recommended uses based on these data. Ayoubi et al. shared the resulting data on Zenodo, a publicly available preprint database. The experiments suggest that 20-30% of protein studies use ineffective antibodies, indicating a substantial need for independent assessment of commercial antibodies. Ayoubi et al. demonstrated their side-by-side antibody comparison methods were an effective and efficient way of validating commercial antibodies. Using this approach to test commercial antibodies against all human proteins would cost about $50 million. But it could save much of the $1 billion wasted each year on research involving ineffective antibodies. Independent validation of commercial antibodies could also reduce wasted efforts by scientists using ineffective antibodies and improve the reliability of research results. It would also enable faster, more reliable research that may help scientists understand diseases and develop new therapies to improve patient's lives.

Scaling of an antibody validation procedure enables quantification of antibody performance in major research applications.

Antibodies are critical reagents to detect and characterize proteins. It is commonly understood that many commercial antibodies do not recognize their intended targets, but information on the scope of the problem remains largely anecdotal, and as such, feasibility of the goal of at least one potent and specific antibody targeting each protein in a proteome cannot be assessed. Focusing on antibodies for human proteins, we have scaled a standardized characterization approach using parental and knockout cell lines (Laflamme et al., 2019) to assess the performance of 614 commercial antibodies for 65 neuroscience-related proteins. Side-by-side comparisons of all antibodies against each target, obtained from multiple commercial partners, demonstrates that: i) more than 50% of all antibodies failed in one or more tests, ii) yet, ~50-75% of the protein set was covered by at least one high-performing antibody, depending on application, suggesting that coverage of human proteins by commercial antibodies is significant; and iii) recombinant antibodies performed better than monoclonal or polyclonal antibodies. The hundreds of underperforming antibodies identified in this study were found to have been used in a large number of published articles, which should raise alarm. Encouragingly, more than half of the underperforming commercial antibodies were reassessed by the manufacturers, and many had alterations to their recommended usage or were removed from the market. This first such study helps demonstrate the scale of the antibody specificity problem but also suggests an efficient strategy toward achieving coverage of the human proteome; mine the existing commercial antibody repertoire, and use the data to focus new renewable antibody generation efforts.

Stressed out - The role of oxidative stress in airway smooth muscle dysfunction in asthma and COPD.

The airway smooth muscle (ASM) surrounding the airways is dysfunctional in both asthma and chronic obstructive pulmonary disease (COPD), exhibiting; increased contraction, increased mass, increased inflammatory mediator release and decreased corticosteroid responsiveness. Due to this dysfunction, ASM is a key contributor to symptoms in patients that remain symptomatic despite optimal provision of currently available treatments. There is a significant body of research investigating the effects of oxidative stress/ROS on ASM behaviour, falling into the following categories; cigarette smoke and associated compounds, air pollutants, aero-allergens, asthma and COPD relevant mediators, and the anti-oxidant Nrf2/HO-1 signalling pathway. However, despite a number of recent reviews addressing the role of oxidative stress/ROS in asthma and COPD, the potential contribution of oxidative stress/ROS-related ASM dysfunction to asthma and COPD pathophysiology has not been comprehensively reviewed. We provide a thorough review of studies that have used primary airway, bronchial or tracheal smooth muscle cells to investigate the role of oxidative stress/ROS in ASM dysfunction and consider how they could contribute to the pathophysiology of asthma and COPD. We summarise the current state of play with regards to clinical trials/development of agents targeting oxidative stress and associated limitations, and the adverse effects of oxidative stress on the efficacy of current therapies, with reference to ASM related studies where appropriate. We also identify limitations in the current knowledge of the role of oxidative stress/ROS in ASM dysfunction and identify areas for future research.

Billing and Coding: Disparities in Healthcare Provider Training.

BACKGROUND: In the United States, healthcare providers document and code healthcare encounters and submit claims to insurers for reimbursement. Most providers eligible for individual-level insurer reimbursement do not receive coding/billing training. The purpose of this commentary is to provide an overview of training disparities. METHODS: The top 100 universities within five healthcare disciplines (dietetics, nursing, pharmacy, social work, medicine) were asked about available didactic curriculum and coding resources provided during training. Results were compared across disciplines, by geographic region, funding mechanism, and size. RESULTS: Twenty-seven percent of schools/universities contacted participated; the response was greater among public institutions (73%) and varied by discipline. Coverage of coding/billing in the didactic curriculum varied: it was covered in 40 dietetics programs (93%), 23 nursing programs (57%), and 14 pharmacy programs (28%). None of the 36 social work programs covered coding/billing, and only 5% of the 20 medical schools did. No statistically significant differences by region or funding were noted; however, coverage of coding/billing in the curriculum did differ by discipline (p<0.0001). DISCUSSION: Upon graduation, healthcare providers may be ill-prepared to code/bill for services. This knowledge is crucial for sustainable health service provision and does not appear to be consistently provided within curriculum to healthcare students. Further study is needed to understand and address this training gap.

Implementation and assessment of a pilot module on billing for pharmacist-provided healthcare services in a doctor of pharmacy program.

BACKGROUND AND PURPOSE: To describe the implementation and assessment of a pilot module on billing to inform future comprehensive curricular integration of billing for pharmacist-provided healthcare services. EDUCATIONAL ACTIVITY AND SETTING: A module (two-hour didactic session and two-hour lab), developed by a faculty member and pharmacy billing specialist, was piloted to teach second-year pharmacy students how to bill the medical insurance benefit for provided services. Web-based pre- and post-surveys and performance on knowledge assessment questions were used to evaluate the pilot module. FINDINGS: Students' perceptions of their abilities and knowledge to provide and bill for healthcare services improved as a result of participation in the pilot module. SUMMARY: This pilot module on billing was successful in improving students' knowledge and perceptions of abilities to provide and bill for healthcare services. However, further efforts to integrate billing education within individual institutions and the entire pharmacy academy will help better prepare pharmacists to provide sustainable clinical services.

Human Lung Mast Cells Impair Corticosteroid Responsiveness in Human Airway Smooth Muscle Cells.

The mechanisms underlying corticosteroid insensitivity in severe asthma have not been elucidated although some indirect clinical evidence points toward a role of mast cells. Here, we tested the hypothesis that mast cells can drive corticosteroid insensitivity in airway smooth muscle cells, a key player in asthma pathogenesis. Conditioned media from resting or FcεR1-activated human lung mast cells were incubated with serum-deprived ASM cells (1:4 dilution, 24 h) to determine their impact on the anti-inflammatory action of fluticasone on ASM cell chemokine expression induced by TNFα (10 ng/ml). Conditioned media from FcεR1-activated mast cells (but not that from non-activated mast cells or control media) significantly reduced the ability of 100 nM fluticasone to suppress ASM TNFα-dependent CCL5 and CXCL10 production at both mRNA and protein levels. In contrast, fluticasone inhibition of CXCL-8 production by TNFα was still preserved in the presence of activated mast cell conditioned media. Transcriptomic analysis validated by individual qPCR assays revealed that activated mast cell conditioned media dramatically reduced the number of anti-inflammatory genes induced by fluticasone in ASM cells. Our study demonstrates for the first time that conditioned media from FcεR1-activated mast cells blunt the anti-inflammatory action of corticosteroids in ASM cells by altering their transactivation properties. Because infiltration of mast cells within the ASM bundles is a defining feature of asthma, mast cell-derived mediators may contribute to the glucocorticoid insensitivity present in severe asthma.

Establishment of a Framework to Support Multi-Faceted Initiatives for Pharmacy-Practice Transformation: Lessons Learned.

We describe the first two years of a multifaceted, five-year program to support sustainable pharmacist-provided health services in Alaska. In 2018, the Alaska Pharmacists Association funded the Sustainable Education and Training Model under Pharmacist as Providers (SETMuPP) to train and support pharmacists to navigate the insurance medical billing process for nondispensing healthcare services. The SETMuPP employed a three-pillar implementation approach: (1) training and practice support infrastructure, (2) PharmD curriculum augmentation, and (3) advocacy and legislative support. The first two years have demonstrated the effectiveness of triad partnerships between professional associations, state policy makers, and academic centers to catalyze meaningful practice transformation.

TGFß1 induces resistance of human lung myofibroblasts to cell death via down-regulation of TRPA1 channels.

BACKGROUND AND PURPOSE: TGFß1-mediated myofibroblast activation contributes to pathological fibrosis in many diseases including idiopathic pulmonary fibrosis (IPF), where myofibroblast resistance to oxidant-mediated apoptosis is also evident. We therefore investigated the involvement of redox-sensitive TRPA1 ion channels on human lung myofibroblasts (HLMFs) cell death and TGFß1-mediated pro-fibrotic responses. EXPERIMENTAL APPROACH: The effects of TGFß1 stimulation on TRPA1 expression and cell viability was studied in HLMFs derived from IPF patients and non-fibrotic patients. We also examined a model of TGFß1-dependent fibrogenesis in human lung. We used qRT-PCR, immunofluorescent assays, overexpression with lentiviral vectors and electrophysiological methods. KEY RESULTS: TRPA1 mRNA, protein and ion currents were expressed in HLMFs derived from both non-fibrotic patient controls and IPF patients, and expression was reduced by TGFß1. TRPA1 mRNA was also down-regulated by TGFß1 in a model of lung fibrogenesis in human lung. TRPA1 over-expression or activation induced HLMF apoptosis, and activation of TRPA1 channel activation by H2 O2 induced necrosis. TRPA1 inhibition following TGFß1 down-regulation or pharmacological inhibition, protected HLMFs from both apoptosis and necrosis. Lentiviral vector mediated TRPA1 expression was also found to induce sensitivity to H2 O2 induced cell death in a TRPA1-negative HEK293T cell line. CONCLUSION AND IMPLICATIONS: TGFß1 induces resistance of HLMFs to TRPA1 agonist- and H2 O2 -mediated cell death via down-regulation of TRPA1 channels. Our data suggest that therapeutic strategies which prevent TGFß1-dependent down-regulation of TRPA1 may reduce myofibroblast survival in IPF and therefore improve clinical outcomes.

Teaching motivational interviewing in a blended learning environment.

BACKGROUND AND PURPOSE: To describe the implementation of blended learning in teaching motivational interviewing (MI) to third-year pharmacy students and evaluate changes in MI knowledge by assessing students' abilities to recognize and formulate responses using MI skills after the training and, for a subset of students, one year later. EDUCATIONAL ACTIVITY AND SETTING: The comMIt e-learning program was integrated into a third-year pharmacy communication course. Skills learned in the program were applied and assessed using e-learning quizzes, three in-class practice sessions and a 5-minute final assessment video. In addition, students completed a 22-item pre- and post-survey addressing their abilities to recognize and formulate statements using MI skills. This survey was voluntarily completed again one year later. FINDINGS: Sixty students completed the training and showed a statistically significant improvement between the pre- and post-surveys. Twenty-seven students voluntarily responded to the survey one year later. While overall performance dropped between the post-survey and the one-year follow-up, students sustained their ability to formulate appropriate MI responses to the open-response questions. SUMMARY: This study demonstrates that students can successfully learn and retain MI skills using blended learning via the comMIt e-learning program and in-class practice activities.

Practice Transformation Driven through Academic Partnerships.

Evidence-based interventions have been shown to improve the quality of patient care, reduce costs, and improve overall health outcomes; however, adopting new published research and knowledge into practice has historically been slow, and requires an active, systematic approach to engage clinicians and healthcare administrators in the required change. Pharmacists have been identified as important agents of change and can enhance care delivery in primary care settings through evidence-based interventions. Utilizing the Consolidated Framework for Implementation Research (CFIR) we identify, assess, and share barriers and facilitators to program development, as well as growth and expansion efforts across five discrete, university-subsidized, embedded-pharmacy practices in primary care. We identified two overarching modifiable factors that influence current and future practice delivery and highlight the role of academia as an incubator for practice change and implementation: Data collection and information sharing. Conceptual frameworks such as CFIR help establish a common vernacular that can be used to facilitate systematic practice site implementation and dissemination of information required to support practice transformation.

DP2 antagonism reduces airway smooth muscle mass in asthma by decreasing eosinophilia and myofibroblast recruitment.

Increased airway smooth muscle mass, a feature of airway remodeling in asthma, is the strongest predictor of airflow limitation and contributes to asthma-associated morbidity and mortality. No current drug therapy for asthma is known to affect airway smooth muscle mass. Although there is increasing evidence that prostaglandin D2 type 2 receptor (DP2) is expressed in airway structural and inflammatory cells, few studies have addressed the expression and function of DP2 in airway smooth muscle cells. We report that the DP2 antagonist fevipiprant reduced airway smooth muscle mass in bronchial biopsies from patients with asthma who had participated in a previous randomized placebo-controlled trial. We developed a computational model to capture airway remodeling. Our model predicted that a reduction in airway eosinophilia alone was insufficient to explain the clinically observed decrease in airway smooth muscle mass without a concomitant reduction in the recruitment of airway smooth muscle cells or their precursors to airway smooth muscle bundles that comprise the airway smooth muscle layer. We experimentally confirmed that airway smooth muscle migration could be inhibited in vitro using DP2-specific antagonists in an airway smooth muscle cell culture model. Our analyses suggest that fevipiprant, through antagonism of DP2, reduced airway smooth muscle mass in patients with asthma by decreasing airway eosinophilia in concert with reduced recruitment of myofibroblasts and fibrocytes to the airway smooth muscle bundle. Fevipiprant may thus represent a potential therapy to ameliorate airway remodeling in asthma.

Osteoporosis in men: epidemiology and treatment with denosumab.

Osteoporosis is a major public health care concern. Although often described as a disease affecting postmenopausal women, researchers and clinicians have emphasized its prevalence in men in recent years. The National Osteoporosis Foundation has stated that up to 25% of men over the age of 50 years will experience a fracture due to osteoporosis. Men who suffer from a major fracture have higher mortality rates than women. Pharmacologic therapy options for treating osteoporosis are limited for men as compared with women, so each medication approved for use in this population represents an important clinical option. In September 2012, the US Food and Drug Administration approved a new indication for denosumab to increase bone mass in men with osteoporosis at high risk for fracture. Denosumab is a fully human monoclonal antibody and novel antiresorptive agent that works by binding receptor activator of nuclear factor kappa-ß ligand (RANKL) and inhibiting the signaling cascade that causes osteoclast maturation, activity, and survival. Ultimately, denosumab suppresses bone turnover and increases bone mineral density in both trabecular and cortical bone. Approval for treating osteoporosis in men was based on data from the ADAMO trial which displayed efficacy in increasing bone mineral density at the lumbar spine, total hip, femoral neck, hip trochanter, and one-third radius. Studies indicate that denosumab is effective and safe, and has superior adherence rates and patient satisfaction. Although long-term data and further research on fracture reduction rates in men should be explored, at this time denosumab is one of several appropriate first-line treatment options for men with osteoporosis.