An Analysis of Uncertainties and Data Collection Agreements in the Cancer Drugs Fund.

Background: Managed Access Agreements (MAAs) are a commercial arrangement that provide patients earlier access to innovative health technologies while uncertainties in the evidence base are resolved through data collection. In the UK, data collection agreements (DCAs) outline the evidence that will be collected during the MAA period and are intended to resolve uncertainties in the clinical- and cost-effectiveness of a technology sufficient for the National Institute of Health and Care Excellence (NICE) committee to make a final decision on reimbursement.

Objective: The aim of this study was to identify the primary uncertainties leading to a recommendation for entry to the Cancer Drugs Fund (CDF) and evaluate how the corresponding DCAs attempt to address these.

Evaluation of US oncology electronic health record real-world data to reduce uncertainty in health technology appraisals: a retrospective cohort study.

Objectives: Examine whether data from early access to medicines in the USA can be used to inform National Institute for Health and Care Excellence (NICE) health technology assessments (HTA) in oncology.

Design: Retrospective cohort study.

Setting: Oncology-based community and academic treatment centres in the USA.

An evaluation of managed access agreements in England based on stakeholder experience.

Objectives: The objective of this research was to evaluate managed access policy in England, drawing upon the expertise of a range of stakeholders involved in its implementation.

Methods: Seven focus groups were conducted with payer and health technology assessment representatives, clinicians, and representatives from industry and patient/carer organizations within England. Transcripts were analyzed using framework analysis to identify stakeholders' views on the successes and challenges of managed access policy.

The Report of the 2022-2023 AACP Professional Affairs Standing Committee: Focused Integration of Community-Based Pharmacy Practice Within the AACP Transformation Center.

The 2022-2023 Professional Affairs Committee was charged to (1) Devise a framework and 3-year workplan for the Academia-Community Pharmacy Transformation Pharmacy Collaborative to be integrated within the American Association of Colleges of Pharmacy (AACP) Transformation Center. This plan should include the focus area(s) to be continued and developed by the Center, potential milestone dates or events, and necessary resources; and (2) Provide recommendations on focus areas and/or potential questions for the Pharmacy Workforce Center to consider for the 2024 National Pharmacist Workforce Study. This report provides the background and methodology utilized to develop the framework and 3-year workplan focused on (1) community-based pharmacy pipeline development for recruitment, programming, and retention, (2) programming and resources for community-based pharmacy practice, and (3) research areas for community-based pharmacy practice.

Massively parallel protein-protein interaction measurement by sequencing (MP3-seq) enables rapid screening of protein heterodimers.

Protein-protein interactions (PPIs) regulate many cellular processes, and engineered PPIs have cell and gene therapy applications. Here we introduce massively parallel protein-protein interaction measurement by sequencing (MP3-seq), an easy-to-use and highly scalable yeast-two-hybrid approach for measuring PPIs. In MP3-seq, DNA barcodes are associated with specific protein pairs, and barcode enrichment can be read by sequencing to provide a direct measure of interaction strength.

The Report of the 2021-2022 Professional Affairs Standing Committee: Resource Guide for the Integration of Clinical Pharmacy Faculty in Professional Practice Settings.

The 2021-22 Professional Affairs Committee was charged to (1) Develop a resource guide for member institutions and faculty regarding payment for the practice-related activities of pharmacy faculty; (2) Nominate at least one person for an elected AACP or Council Office; and (3) Consider ways that AACP can improve its financial health. This report describes the methodology and content utilized for the development of an online resource guide for member institutions, faculty, and practice sites regarding the integration of clinical faculties' patient care services into patient care settings, including models for payment and value-based payment structures that can be utilized to support the practice-related activities of faculty. The committee offers a revision to a current association policy statement, a proposed policy statement as well as recommendations to AACP and suggestions to colleges and schools of pharmacy pertaining to the committee charges.

Lungworm () Infection in Unweaned Free-Ranging Raccoons () in Washington State, USA.

Larval parasites morphologically identified as were found in orphaned raccoons () admitted to a wildlife rehabilitation center in Washington State, US. Partial 18S rRNA and cytochrome oxidase I gene sequences were most similar to other spp. Although commonly reported in free-ranging raccoons throughout much of the central and eastern US, this finding extends the range of into the Pacific Northwest of North America.

An Ambulatory Care Clinic and Community Pharmacy Collaboration to Address Prescription Abandonment.

Purpose: The purpose of this research is to evaluate a collaborative workflow aimed at decreasing prescription abandonment.

Setting: A federally qualified health center and a 340B contracted grocery store-based community pharmacy.

Practice Workflow: An ambulatory care clinic with an established partnership with a community pharmacy chain identified a need to decrease prescription abandonment rates.

Pharmacist Involvement in Population Health Management for a Pediatric Managed Medicaid Accountable Care Organization.

Accountable care organizations (ACOs) have emerged as an effective healthcare delivery model for managing quality and cost at a population level. Within ACOs, pharmacists are critical for the delivery of high-value health care, offering patients and health care providers medication-related training, resources, and guidance that can improve quality of care at lower costs. Partners For Kids (PFK), one of the oldest and largest pediatric ACOs in the country, has successfully leveraged pharmacists to provide population health management and medication management to promote health outcomes for individual patients and the overall population it serves.

Inhibitory Evaluation of αPMM/PGM from : Chemical Synthesis, Enzyme Kinetics, and Protein Crystallographic Study.

α-Phosphomannomutase/phosphoglucomutase (αPMM/PGM) from is involved in bacterial cell wall assembly and is implicated in virulence, yet few studies have addressed αPMM/PGM inhibition from this important Gram-negative bacterial human pathogen. Four structurally different α-d-glucopyranose 1-phosphate (αG1P) derivatives including 1--fluoromethylated analogues (-), 1,2-cyclic phosph(on)ate analogues (-), isosteric methylene phosphono analogues ( and ), and 6-fluoro-αG1P (), were synthesized and assessed as potential time-dependent or reversible αPMM/PGM inhibitors. The resulting kinetic data were consistent with the crystallographic structures of the highly homologous αPGM with inhibitors and - binding to the enzyme active site (1.

Prevalence, distribution, and diversity of cryptic piroplasm infections in raccoons from selected areas of the United States and Canada.

The order Piroplasmida contains a diverse group of intracellular parasites, many of which can cause significant disease in humans, domestic animals, and wildlife. Two piroplasm species have been reported from raccoons (), ( sensu stricto clade) and a species related to (called -like sp.).

A step-wise synthetic approach is necessary to access γ-conjugates of folate: folate-conjugated prodigiosenes.

Despite the vast literature that describes reacting folic acid with a pharmacophore, this route is ineffective in providing the correct regioisomer of the resulting conjugate. We herein present a step-wise route to the preparation of nine folate conjugates of the tripyrrolic prodigiosene skeleton. The strict requirement for step-wise construction of the folate core is demonstrated, so as to achieve conjugation at only the desired γ-carboxylic acid and thus maintain the α-carboxylic site for folate receptor (FRα) recognition.

Peer-assisted Learning: Clinical Skills Training for Pharmacy Students.

To assess the impact of peer-teaching on student scores and confidence when preparing for a final objective structured clinical examination (OSCE) within a Doctor of Pharmacy program. First-year pharmacy students (n=45) attended a peer-led training session led by upperclassmen (n=17) on a variety of clinical skills to be assessed on a final course OSCE. Their scores were collected and compared to students who did not attend the training.

Deep learning of the regulatory grammar of yeast 5' untranslated regions from 500,000 random sequences.

Our ability to predict protein expression from DNA sequence alone remains poor, reflecting our limited understanding of -regulatory grammar and hampering the design of engineered genes for synthetic biology applications. Here, we generate a model that predicts the protein expression of the 5' untranslated region (UTR) of mRNAs in the yeast We constructed a library of half a million 50-nucleotide-long random 5' UTRs and assayed their activity in a massively parallel growth selection experiment. The resulting data allow us to quantify the impact on protein expression of Kozak sequence composition, upstream open reading frames (uORFs), and secondary structure.

Deuteration and tautomeric reactivity of the 1-methyl functionality of free-base dipyrrins.

Regioselective reactivity of the 1-methyl group of free-base dipyrrins is explored, including discussion of tautomerism to provide exocyclic alkenyl reactivity. Deuterium is installed so as to generate dipyrrins substituted with deuterated methyl groups. Furthermore, the 1-methyl group reacts to become involved in C-C bonds involving only sp-hybridised carbon atoms.

A structured patient identification model for medication therapy management services in a community pharmacy.

Objectives: To describe the development and implementation of a structured patient identification model for medication therapy management (MTM) services within traditional dispensing activities of a community pharmacy to facilitate pharmacist-provided completion of MTM services.

Design: A daily clinical opportunity report was developed as a structured model to identify MTM opportunities daily for all MTM-eligible patients expecting to pick up a prescription. Pharmacy staff was trained and the standardized model was implemented at study sites.

Integrating Mental and Physical Health Services Using a Socio-Emotional Trauma Lens.

This article provides a synthesis of the lessons learned from the Pediatric Integrated Care Collaborative (PICC), a SAMHSA-funded project that is part of the National Child Traumatic Stress Network. The high prevalence of trauma exposure in childhood and shortage of mental health services has informed efforts to integrate mental and behavioral health services in pediatric primary care. This article outlines strategies to integrate care following the six goals of the PICC change framework: create a trauma/mental health informed office; involve families in program development; collaborate and coordinate with mental health services; promote resilience and prevent mental health problems through a particular focus on trauma-related risks; assess trauma-related somatic and mental health issues; and address trauma-related somatic and mental heath issues.

Rewiring MAP kinases in Saccharomyces cerevisiae to regulate novel targets through ubiquitination.

Evolution has often copied and repurposed the mitogen-activated protein kinase (MAPK) signaling module. Understanding how connections form during evolution, in disease and across individuals requires knowledge of the basic tenets that govern kinase-substrate interactions. We identify criteria sufficient for establishing regulatory links between a MAPK and a non-native substrate.

De novo design of protein homo-oligomers with modular hydrogen-bond network-mediated specificity.

In nature, structural specificity in DNA and proteins is encoded differently: In DNA, specificity arises from modular hydrogen bonds in the core of the double helix, whereas in proteins, specificity arises largely from buried hydrophobic packing complemented by irregular peripheral polar interactions. Here, we describe a general approach for designing a wide range of protein homo-oligomers with specificity determined by modular arrays of central hydrogen-bond networks. We use the approach to design dimers, trimers, and tetramers consisting of two concentric rings of helices, including previously not seen triangular, square, and supercoiled topologies.

Computing in mammalian cells with nucleic acid strand exchange.

DNA strand displacement has been widely used for the design of molecular circuits, motors, and sensors in cell-free settings. Recently, it has been shown that this technology can also operate in biological environments, but capabilities remain limited. Here, we look to adapt strand displacement and exchange reactions to mammalian cells and report DNA circuitry that can directly interact with a native mRNA.