Effectiveness of direct patient outreach with a narrative naloxone and overdose prevention video to patients prescribed long-term opioid therapy in the USA: the Naloxone Navigator randomised clinical trial.

Introduction: Public health efforts to reduce opioid overdose fatalities include educating people at risk and expanding access to naloxone, a medication that reverses opioid-induced respiratory depression. People receiving long-term opioid therapy (LTOT) are at increased risk for overdose, yet naloxone uptake in this population remains low. The objective of this study was to determine if a targeted, digital health intervention changed patient risk behavior, increased naloxone uptake, and increased knowledge about opioid overdose prevention and naloxone.

Multiomics unveils extracellular vesicle-driven mechanisms of endothelial communication in human carotid atherosclerosis.

Carotid atherosclerosis is orchestrated by cell-cell communication that drives progression along a clinical continuum (asymptomatic to symptomatic). Extracellular vesicles (EVs) are cell-derived nanoparticles representing a new paradigm in cellular communication. Little is known about their biological cargo, cellular origin/destination, and functional roles in human atherosclerotic plaque.

Directional Endothelial Communication by Polarized Extracellular Vesicle Release.

Background: Extracellular vesicles (EVs) contain bioactive cargo including miRNAs and proteins that are released by cells during cell-cell communication. Endothelial cells (ECs) form the innermost lining of all blood vessels, interfacing with cells in the circulation and vascular wall. It is unknown whether ECs release EVs capable of governing recipient cells within these 2 separate compartments.

Endothelial cells secrete small extracellular vesicles bidirectionally containing distinct cargo to uniquely reprogram vascular cells in the circulation and vessel wall.

Rationale: Extracellular vesicles (EVs) contain bioactive cargo including microRNAs (miRNAs) and proteins that are released by cells as a form of cell-cell communication. Endothelial cells (ECs) form the innermost lining of all blood vessels and thereby interface with cells in the circulation as well as cells residing in the vascular wall. It is unknown whether ECs have the capacity to release EVs capable of governing recipient cells within two separate compartments, and how this is affected by endothelial activation commonly seen in atheroprone regions.

Variations in the Composition of Human Milk Oligosaccharides Correlates with Effects on Both the Intestinal Epithelial Barrier and Host Inflammation: A Pilot Study.

Background: Human milk oligosaccharides are complex, non-digestible carbohydrates that directly interact with intestinal epithelial cells to alter barrier function and host inflammation. Oligosaccharide composition varies widely between individual mothers, but it is unclear if this inter-individual variation has any impact on intestinal epithelial barrier function and gut inflammation.

Methods: Human milk oligosaccharides were extracted from the mature human milk of four individual donors.

Dysfunctional Vascular Endothelium as a Driver of Atherosclerosis: Emerging Insights Into Pathogenesis and Treatment.

Atherosclerosis, the chronic accumulation of cholesterol-rich plaque within arteries, is associated with a broad spectrum of cardiovascular diseases including myocardial infarction, aortic aneurysm, peripheral vascular disease, and stroke. Atherosclerotic cardiovascular disease remains a leading cause of mortality in high-income countries and recent years have witnessed a notable increase in prevalence within low- and middle-income regions of the world. Considering this prominent and evolving global burden, there is a need to identify the cellular mechanisms that underlie the pathogenesis of atherosclerosis to discover novel therapeutic targets for preventing or mitigating its clinical sequelae.

Amniotic fluid stem cell administration can prevent epithelial injury from necrotizing enterocolitis.

Background: Stem cell therapy has been proven to rescue intestinal injury and stimulate intestinal regeneration in necrotizing enterocolitis (NEC). Specifically, stem cells derived from amniotic fluid (AFSCs) and mesenchymal stem cells (MSCs) derived from bone marrow have shown promising results in the treatment of experimental NEC. This study aims to examine the effects of AFSCs and MSCs on the prevention of intestinal injury during experimental NEC.

The Role of Board-Certified Psychiatric Pharmacists in Expanding Access to Care and Improving Patient Outcomes.

Although approximately 20% of adults in the United States experience a mental health condition annually, there continues to be a gap in the provision of care because of a shortage of behavioral health providers. The National Council for Behavioral Health Medical Director Institute has recommended that the number of board-certified psychiatric pharmacists (BCPPs), who are clinical pharmacists with advanced specialized training and experience in the treatment of patients with psychiatric and substance use disorders, be expanded to help meet this need. Although BCPPs currently assist in expanding care access, improving medication-related outcomes, and reducing health care costs by working collaboratively with physicians and other health care providers, BCPPs are often underutilized.

Twice-daily versus once-daily lisinopril and losartan for hypertension: Real-world effectiveness and safety.

Background: Lisinopril and losartan manufacturer labels recommend twice-daily dosing (BID) if once-daily (QDay) is insufficient to lower blood pressure (BP).

Methods And Results: Retrospective cohort study of patients taking QDay lisinopril and losartan who experienced a dose-doubling (index date). A text-processing tool categorized BID and QDay groups at the index date based on administration instructions.

Activation of Wnt signaling by amniotic fluid stem cell-derived extracellular vesicles attenuates intestinal injury in experimental necrotizing enterocolitis.

Necrotizing enterocolitis (NEC) is a devastating intestinal disease primarily affecting preterm neonates and causing high morbidity, high mortality, and huge costs for the family and society. The treatment and the outcome of the disease have not changed in recent decades. Emerging evidence has shown that stimulating the Wnt/β-catenin pathway and enhancing intestinal regeneration are beneficial in experimental NEC, and that they could potentially be used as a novel treatment.

Vitamin B12 Deficiency Alters the Gut Microbiota in a Murine Model of Colitis.

Inflammatory bowel disease (IBD) refers to a spectrum of autoimmune diseases, which result in chronic intestinal inflammation. Previous findings suggest a role for diet, nutrition and dysbiosis of the gut microbiota in both the development and progression of the condition. Vitamin B12 is a key cofactor of methionine synthase and is produced solely by microbes.

Plant- and Fish-Derived n-3 PUFAs Suppress Citrobacter Rodentium-Induced Colonic Inflammation.

Scope: Marine-derived n-3 PUFAs may ameliorate inflammation associated with inflammatory bowel diseases. Plant-derived n-3 PUFAs are thought to be inferior owing to shorter chain lengths. The aim of this study is to compare the impact of plant- and fish-derived PUFAs on murine colitis.

Impaired Wnt/β-catenin pathway leads to dysfunction of intestinal regeneration during necrotizing enterocolitis.

Necrotizing enterocolitis (NEC) is a devastating neonatal disease characterized by acute intestinal injury. Intestinal stem cell (ISC) renewal is required for gut regeneration in response to acute injury. The Wnt/β-catenin pathway is essential for intestinal renewal and ISC maintenance.

Bovine milk-derived exosomes enhance goblet cell activity and prevent the development of experimental necrotizing enterocolitis.

Necrotizing enterocolitis (NEC) is characterized by intestinal injury and impaired mucin synthesis. We recently showed that breast milk exosomes from rodents promote intestinal cell viability, epithelial proliferation, and stem cell activity, but whether they also affect mucus production is unknown. Therefore, the aim of this study was to investigate the effects of bovine milk-derived exosomes on goblet cell expression in experimental NEC and delineate potential underlying mechanisms of action.

Human Milk Oligosaccharides Increase Mucin Expression in Experimental Necrotizing Enterocolitis.

Scope: Necrotizing enterocolitis (NEC) is a leading cause of morbidity and death in preterm infants, occurring more often in formula-fed than breastfed infants. Studies in both rats and humans show that human milk oligosaccharides (HMOs) lower the incidence of NEC, but the mechanism underlying such protection is currently unclear.

Methods And Results: By extracting HMOs from pooled human breastmilk, the impact of HMOs on the intestinal mucin levels in a murine model of NEC are investigated.

Ground flaxseed reverses protection of a reduced-fat diet against Citrobacter rodentium-induced colitis.

Flaxseed is high in ω-3 polyunsaturated fatty acids, fiber, and lignans known to lower cholesterol levels. However, its use for prevention or treatment of inflammatory bowel diseases has yielded mixed results, perhaps related to dietary interactions. In this study, we evaluated the impact of ground flaxseed supplementation on the severity of Citrobacter rodentium-induced colitis in the setting of either a high-fat (HF, ~36%kcal) or reduced-fat (RF, ~12%kcal) diet.

Metabolic monitoring in children 5 years of age and younger prescribed second-generation antipsychotic medications.

Introduction: The objective of this article was to identify the rates of patients ≤5 years of age who received recommended monitoring before and after second-generation antipsychotic (SGA) initiation and had an SGA metabolic adverse effect (MAE).

Methods: This was a retrospective cohort analysis conducted at Kaiser Permanente Colorado, an integrated health care delivery system, between January 1, 2002, and June 30, 2011. Commercially insured patients ≤5 years of age newly initiated on an SGA were included.

Risk Factors for Utilization of Acute Care Services for Lithium Toxicity.

Objective: This study evaluated risk factors for utilization of acute care services (ACS) (hospitalization or emergency department or urgent care visit) for lithium toxicity and the prevalence of lithium toxicity in a large, ambulatory population.

Methods: A nested case-control study compared lithium users with ACS utilization for lithium toxicity (case group) to lithium users without toxicity (control group) by using data from Kaiser Permanente Colorado for patients with at least one lithium prescription purchase. Patients in the case group were matched 1:5 with patients in the control group who had purchased lithium within 39 days of the ACS encounter.

Curriculum renewal: Alignment of introductory pharmacy practice experiences with didactic course content.

Background And Purpose: The University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences (SSPPS) used the opportunity of curriculum renewal to integrate knowledge and skills learned from didactic courses into the introductory pharmacy practice experiences (IPPEs) occurring simultaneously. This paper describes and evaluates the meaningful application of course content into IPPEs, and evaluates the success using qualitative feedback.

Educational Activity And Setting: Students entering the renewed curriculum starting in fall 2012 were provided a list of pharmacy skills and activities from didactic course directors that reinforced course content for that semester.

Non-digestible oligosaccharides directly regulate host kinome to modulate host inflammatory responses without alterations in the gut microbiota.

Background: Prebiotics are non-digestible food ingredients that enhance the growth of certain microbes within the gut microbiota. Prebiotic consumption generates immune-modulatory effects that are traditionally thought to reflect microbial interactions within the gut. However, recent evidence suggests they may also impart direct microbe-independent effects on the host, though the mechanisms of which are currently unclear.

Design and implementation of population-based specialty care programs.

Purpose: The development, implementation, and scaling of 3 population-based specialty care programs in a large integrated healthcare system are reviewed, and the role of clinical pharmacy services in ensuring safe, effective, and affordable care is highlighted.

Summary: The Kaiser Permanente (KP) integrated healthcare delivery model allows for rapid development and expansion of innovative population management programs involving pharmacy services. Clinical pharmacists have assumed integral roles in improving the safety and effectiveness of high-complexity, high-cost care for specialty populations.

Pharmacotherapy regimens among patients with posttraumatic stress disorder and mild traumatic brain injury.

Objective: The purpose of this study was to determine if veterans with posttraumatic stress disorder (PTSD) and mild traumatic brain injury (TBI) are treated differently pharmacologically than patients with PTSD alone.

Methods: A retrospective evaluation of PTSD pharmacotherapy of Operation Enduring Freedom/Operation Iraqi Freedom veterans with PTSD (N=707) was conducted between April 1, 2007, and March 31, 2009. A total of 45 veterans had suffered a mild TBI.