Synthesis and Optimization of 1-Substituted Imidazo[4,5-]quinoline TLR7 Agonists.

TLR7 agonists have significant therapeutic potential in a variety of oncology and autoimmune applications. We recently reported a potent TLR7 selective agonist that could be delivered by antibody-drug conjugate (ADC) technology to elicit potent anticancer activity. Herein we report synthetic chemistry and structure-activity relationship studies to develop TLR7 agonists with improved potency for next-generation ADC efforts.

Lenacapavir: A novel injectable HIV-1 capsid inhibitor.

Patients living with multidrug-resistant (MDR) HIV have limited antiretroviral regimen options that provide durable viral suppression. Lenacapavir is a novel first-in-class inhibitor of HIV-1 capsid function with efficacy at various stages of the viral life cycle, and it is indicated for the treatment of MDR HIV-1 infection in combination with optimized background antiretroviral therapy. The favourable pharmacokinetic profile supports an every sixth month dosing interval of subcutaneous lenacapavir after an initial oral loading dose, which may advocate for continued adherence to antiretroviral therapy (ART) through the reduction of daily pill burden.

Factors Affecting Prescribing of Type 2 Diabetes Medications in Older Adults within an Integrated Healthcare System.

Background: Despite type 2 diabetes guidelines recommending against the use of sulfonylureas in older adults and for the use of sodium-glucose cotransporter-2 inhibitors (SGLT2) and glucagon-like peptide-1 agonists (GLP1s) in patients with atherosclerotic cardiovascular disease (ASCVD), chronic kidney disease (CKD), and heart failure (HF), real-world guideline-concordant prescribing remains low. While some factors such as cost have been suggested, an in-depth analysis of the factors associated with guideline-concordant prescribing is warranted.

Objective: To quantify the extent of guideline-concordant prescribing in an integrated health care delivery system and examine provider and patient level factors that influence guideline-concordant prescribing.

Steamed broccoli sprouts alleviate DSS-induced inflammation and retain gut microbial biogeography in mice.

Evaluating bacterial communities across different locations in the gut provides a greater insight than fecal samples alone and provides an additional metric by which to evaluate beneficial host-microbe interactions. Here, we show that 10% steamed broccoli sprouts in the diet protects mice from the negative effects of dextran sodium sulfate-induced colitis, that colitis erases biogeographic patterns of bacterial communities in the gut, and that the cecum is not likely to be a significant contributor to colonic bacteria of interest in the DSS mouse model of ulcerative colitis. Mice fed the broccoli sprout diet during colitis performed better than mice fed the control diet while receiving DSS.

Duchenne Muscular Dystrophy from Brain to Muscle: The Role of Brain Dystrophin Isoforms in Motor Functions.

Brain function and its effect on motor performance in Duchenne muscular dystrophy (DMD) is an emerging concept. The present study explored how cumulative dystrophin isoform loss, age, and a corticosteroid treatment affect DMD motor outcomes. A total of 133 genetically confirmed DMD patients from Sri Lanka were divided into two groups based on whether their shorter dystrophin isoforms (Dp140, Dp116, and Dp71) were affected: Group 1, containing patients with Dp140, Dp116, and Dp71 affected (n = 98), and Group 2, containing unaffected patients (n = 35).

Clustering microbiome data using mixtures of logistic normal multinomial models.

Discrete data such as counts of microbiome taxa resulting from next-generation sequencing are routinely encountered in bioinformatics. Taxa count data in microbiome studies are typically high-dimensional, over-dispersed, and can only reveal relative abundance therefore being treated as compositional. Analyzing compositional data presents many challenges because they are restricted to a simplex.

Preparing students to address the social determinants of health in integrated care settings.

Background: Health professionals are increasingly being called to address the social determinants of health (SDOH) and, to do so effectively, often requires an integrated approach to care. As a result, accreditation standards across multiple professions have emphasised the importance of interprofessional education (IPE).

Approach: This paper describes large-scale, community-engaged learning that is required annually of students from nursing, pharmacy, public health, and social work.

Pronounced State-Level Disparities in Medicaid Prescribing of Buprenorphine for Opioid Use Disorder (2019-2020).

Objective: The purpose of this study was to analyze buprenorphine prescribing across states in Medicaid patients during 2019-2020.

Method: Buprenorphine prescriptions per Medicaid enrollee per state were calculated for 2019 and 2020. Data analysis was conducted with buprenorphine formulations that are approved by the U.

Integrated genomic, proteomic and cognitive assessment in Duchenne Muscular Dystrophy suggest astrocyte centric pathology.

Introduction: Documented Duchenne Muscular Dystrophy (DMD) biomarkers are confined to Caucasians and are poor indicators of cognitive difficulties and neuropsychological alterations.

Materials And Methods: This study correlates serum protein signatures with cognitive performance in DMD patients of South Asian origin. Study included 25 DMD patients aged 6-16 years.

Daptomycin Plus Oxacillin for Persistent Methicillin-Susceptible Bacteremia.

Background: The preferred antibiotic salvage regimen for persistent methicillin-susceptible bacteremia (MSSAB) is unclear. Ertapenem with cefazolin or an antistaphylococcal penicillin has been primarily described, but identifying alternative carbapenem-sparing options may support antibiotic stewardship efforts and decrease the risk of antibiotic-associated infection.

Objective: We sought to evaluate the effectiveness and safety of daptomycin plus oxacillin (D/O) for persistent MSSAB.

NAPLEX Preparation Program Characteristics and Resources Associated With First-Time Exam Pass Rates.

Objective: Pharmacy colleges and schools invest substantial faculty effort and financial resources in North America Pharmacist Licensure Exam (NAPLEX) preparation, including vendor products purported to improve NAPLEX pass rates. The objective of this project was to examine NAPLEX preparation program characteristics associated with first-time pass rates.

Methods: A national survey investigated which pharmacy schools provided a formal NAPLEX preparation program in the 2021/2022 academic year, and what resources students were required to use.

An analysis of patterns of distribution of buprenorphine in the United States using ARCOS, Medicaid, and Medicare databases.

Opioid overdose remains a problem in the United States despite pharmacotherapies, such as buprenorphine, in the treatment of opioid use disorder. This study characterized changes in buprenorphine use. Using the Drug Enforcement Administration's ARCOS, Medicaid, and Medicare claims databases, patterns in buprenorphine usage in the United States from 2018 to 2020 were analyzed by examining percentage changes in total grams distributed and changes in grams per 100 K people in year-to-year usage based on ZIP code and state levels.

Pronounced State-Level Disparities in Prescription of Cannabinoids to Medicaid Patients.

Introduction: Dronabinol is approved in the USA for chemotherapy-induced nausea as well as vomiting and HIV-induced anorexia, while cannabidiol is primarily approved for childhood epileptic disorders Lennox-Gastaut and Dravet syndrome. The use pattern for these prescription cannabinoids in the USA is unknown. This study examined Medicaid claims for two FDA-approved prescription cannabinoids, dronabinol and cannabidiol, approved in 1985 and 2018, respectively, from 2016-2020 to better understand the pharmacoepidemiologic trends and distribution of these drugs in US Medicaid amidst the increasing use of non-pharmaceutical formulations of cannabis.

Should direct oral anticoagulants be used to treat protein C or S deficiency?

Few studies have evaluated the use of direct oral anticoagulants (DOACs) in patients with major thrombophilias, such as protein C or S deficiency. The data related to use of DOACs in treating protein C or S deficiency are heterogeneous, consisting of various DOACs, inconsistent ranges of dosing, dissimilar patient demographics, and inconsistent clinical endpoints. Vitamin K antagonists and low-molecular-weight heparins are preferred until more robust data are available about using DOACs in patients with protein C or S deficiency.

Visualizing drug-induced lipid accumulation in lysosomes of live cancer cells with stimulated Raman imaging.

The low pH of the lysosomal compartment often results in sequestration of chemotherapeutic agents that contain positively charged basic functional groups, leading to anti-cancer drug resistance. To visualize drug localization in lysosomes and its influence on lysosomal functions, we synthesize a group of drug-like compounds that contain both a basic functional group and a bisarylbutadiyne (BADY) group as a Raman probe. With quantitative stimulated Raman scattering (SRS) imaging, we validate that the synthesized lysosomotropic (LT) drug analogs show high lysosomal affinity, which can also serve as a photostable lysosome tracker.

A Description of NAPLEX and MPJE Preparation Strategies Among US Colleges and Schools of Pharmacy.

Objective: The purpose of this study was to describe the different strategies used to supplement North American Pharmacist Licensure Examination (NAPLEX) and Multistate Pharmacy Jurisprudence Examination (MPJE) preparation in the US pharmacy programs.

Methods: An online survey was developed to gather information from 141 accredited schools/colleges of pharmacy about the preparation methods used during the 2021-22 academic year. The questionnaire contained 19 NAPLEX- and 10 MPJE-specific questions related to timing, content, use of commercial products and programs, faculty involvement, and whether these activities were required or recommended.

Is it time for genetic modifiers to predict prognosis in Duchenne muscular dystrophy?

Patients with Duchenne muscular dystrophy (DMD) show clinically relevant phenotypic variability, despite sharing the same primary biochemical defect (dystrophin deficiency). Factors contributing to this clinical variability include allelic heterogeneity (specific DMD mutations), genetic modifiers (trans-acting genetic polymorphisms) and variations in clinical care. Recently, a series of genetic modifiers have been identified, mostly involving genes and/or proteins that regulate inflammation and fibrosis - processes increasingly recognized as being causally linked with physical disability.

Key Articles and Guidelines in the Management of Pericardial Syndromes.

Over the past two decades, emerging literature has shaped the management of pericardial syndromes and has evolved abundantly towards the creation of European guidelines for the diagnosis and management of pericardial diseases. However, since the publication of the European guidelines in 2015, more data surrounding the management of pericardial syndromes have been published. Comprehensive reference materials with the most updated literature are warranted and can be pivotal in helping pharmacists make evidence-based and clinical decisions for patients diagnosed with pericardial syndromes.

Steamed broccoli sprouts alleviate DSS-induced inflammation and retain gut microbial biogeography in mice.

Unlabelled: Inflammatory Bowel Diseases (IBD) are devastating conditions of the gastrointestinal tract with limited treatments, and dietary intervention may be effective, and affordable, for managing symptoms. Glucosinolate compounds are highly concentrated in broccoli sprouts, especially glucoraphanin, and can be metabolized by certain mammalian gut bacteria into anti inflammatory isothiocyanates, such as sulforaphane. Gut microbiota exhibit biogeographic patterns, but it is unknown if colitis alters these or whether the location of glucoraphanin metabolizing bacteria affects anti-inflammatory benefits.

High Prescribing and State-Level Variation in Z-Drug Use Among Medicare Patients.

Background: Z-drugs are nonbenzodiazepine hypnotics used for sleep initiation and maintenance; these drugs increase the risk of fall-related injuries in older adults. The American Geriatrics Society's Beers criteria classifies Z-drugs as high-risk and strongly recommends avoiding prescribing Z-drugs to older adults due to adverse effects. The study objectives were to determine the prevalence of Z-drug prescribing among Medicare Part D patients and identify state or specialty-dependent prescribing differences.

An Analysis of Oxycodone and Hydrocodone Distribution Trends in Delaware, Maryland, and Virginia Between 2006 and 2014.

Objective Opioid medications are widely recognized for their use in analgesia and their addictive properties that have led to the opioid epidemic. Areas with historically high prescribing patterns have been shown to suffer more from the crisis. There is also regional variability in these trends.