Project lifeline: implementing SBIRT in rural pharmacies to address opioid overdoses and substance use disorder.

Background: There is emerging recognition of the unique benefits of implementing screening, brief intervention, and referral to treatment (SBIRT) in pharmacy settings to identify patients who can benefit from services and connecting them to those services.Objectives: This study describes Project Lifeline - a multipronged public health initiative to provide educational and technical support to rural community pharmacies implementing SBIRT for substance use disorder (SUD) and providing harm reduction support.Methods: Eight community pharmacies were recruited. Patients receiving a Schedule II prescription were invited to engage in SBIRT and offered naloxone. Patient screening data and key informant interviews with pharmacy staff on implementation strategy were analyzed.Results: Between 2018-2020, 4,601 adult patients were offered screens and 3,407 screens were completed on 2,881 unique adult patients (51.3% female; <0.01% nonbinary; 95.7% White). Of these unique screens, 107 patients were indicated for brief intervention, 31 accepted the brief intervention; and 12 were given a referral to SUD treatment. Patients who declined SBIRT or who did not want to reduce their use were offered access to naloxone (n = 372). Key informant interviews highlighted the importance of person-centered staff education, role-playing, anti-stigma training, and integrating activities into existing patient-care processes.Conclusion: While ongoing research is needed to characterize the full impact of Project Lifeline on patient outcomes, the reported findings help reinforce the benefits of multipronged public health initiatives that include community pharmacists to address the SUD crisis.

The Cognitive Science of Learning: Concepts and Strategies for the Educator and Learner.

Education is the fundamental process used to develop and maintain the professional skills of physicians. Medical students, residents, and fellows are expected to learn considerable amounts of information as they progress toward board certification. Established practitioners must continue to learn in an effort to remain up-to-date in their clinical realm. Those responsible for educating these populations endeavor to teach in a manner that is effective, efficient, and durable. The study of learning and performance is a subdivision of the field of cognitive science that focuses on how people interpret and process information and how they eventually develop mastery. A deeper understanding of how individuals learn can empower both educators and learners to be more effective in their endeavors. In this article, we review a number of concepts found in the literature on learning and performance. We address both the theoretical principles and the practical applications of each concept. Cognitive load theory, constructivism, and analogical transfer are concepts particularly beneficial to educators. An understanding of goal orientation, metacognition, retrieval, spaced learning, and deliberate practice will primarily benefit the learner. When these concepts are understood and incorporated into education and study, the effectiveness of learning is significantly improved.

Hormonal Control of Blood Viscosity.

The hemodynamic milieu differs throughout the vascular tree because of varying vascular geometry and blood velocities. Accordingly, the risk of turbulence, which is dictated by the Reynolds and Dean numbers, also varies. Relatively high blood viscosity is needed to prevent turbulence in the left ventricle and aorta, where high-velocity blood changes direction several times. Low blood viscosity is needed in the capillaries, where erythrocytes pass through vessels with a diameter smaller than their own. In addition, higher blood viscosity is necessary when the cardiac output and peak blood velocity increase as a part of a sympathetic response or anemia, which occurs following significant hemorrhage. Blood viscosity, as reflected in systemic vascular resistance and vascular wall shear stress, is sensed, respectively, by cardiomyocyte stretching in the left ventricle and mechanoreceptors for wall shear stress in the carotid sinus. By controlling blood volume and red blood cell mass, the renin-aldosterone-angiotensin system and the systemic vascular resistance response control the hematocrit, the strongest intrinsic determinant of blood viscosity. These responses provide gross control of blood viscosity. Fine-tuning of blood viscosity in transient conditions is provided by hormonal control of erythrocyte deformability. The short half-life of some of these hormones limits their activity to specific vascular beds. Hormones that modulate blood viscosity include erythropoietin, angiotensin II, brain natriuretic factor, epinephrine, prostacyclin E2, antidiuretic hormone, and nitric oxide.

Effect of hydration on whole blood viscosity in firefighters.

CONTEXT: Cardiovascular disease (CVD) is the leading cause of on-duty death among firefighters, totaling 45% of on-duty fatalities. Heat stress and fluid losses can result in decreases in cardiac output of firefighters, despite sustained tachycardia and maximally elevated heart rate during emergencies. Measurements of whole blood viscosity (WBV) may serve as an independent biomarker of the hydration and dehydration states of on-duty firefighters. OBJECTIVE: The current pilot study investigates the effects of a strenuous firefighting simulation and subsequent rehydration on WBV and other biological metrics in nine healthy, nonsmoking firefighters to (1) determine whether dehydration and rehydration result in detectable changes in WBV and (2) compare WBV with the results from a range of conventional medical tests. DESIGN: The research team designed a single-center, unblinded pilot study. SETTING: Fire Training Division, 1900 Lind Ave SW, Renton, WA, 98057. PARTICIPANTS: Participants were 9 healthy, nonsmoking firefighters who were volunteers. OUTCOME MEASURE(S): Vital signs, traditional medical blood tests, and WBV were measured for each firefighter (1) at baseline, (2) after exercise but before rehydration with alkaline water, and (3) postexercise and after rehydration. Hematocrit (HCT), hemoglobin (Hb), and WBV increased after exercise and before rehydration. RESULTS: Dehydration during the mock fire drill resulted in elevated WBV at both low- and high-shear rates. HCT and Hb increased due to dehydration and hemoconcentration. Hb and HCT returned to baseline values after exercise and rehydration, and while WBV improved, baseline values were not restored. After exercise but before rehydration, WBV changes were significantly larger than HCT and Hb changes, suggesting the profound influence of hydration states on WBV. CONCLUSIONS: WBV measurements were better determinants of hydration states than HCT or Hb and should be performed to monitor the cardiovascular health of at-risk firefighters.

Quartz Crystal Microbalance as a Predictive Tool for Drug-Material of Construction Interactions in Intravenous Protein Drug Administration.

As a growing number of protein drug products are developed, formulation characterization is becoming important. An IgG drug product is tested at concentrations from 0.0001-0.1 mg/mL for adsorption behavior to polymer surfaces polyvinyl chloride (PVC) and polypropylene (PP) upon dilution in normal saline (NS) using quartz crystal microbalance with dissipation (QCM-D). The studies mimicked IgG antibody interaction during IV administration with polymeric surfaces within syringes, lines, and bags. Drug product was characterized with excipients, with focus on surfactant. Drug solutions were run over polymer-coated sensors to measure the adsorption behavior of the formulation with emphasis on the behavior of each of the formulation's components. Over 60 sensorgram data sets were correlated with assayed protein solution concentrations in mock NS-diluted infusions of drug product in the equivalent concentrations to QCM experiments to build a preliminary predictive model for determining fraction of drug and surfactant adsorbed and lost at the hydrophobic surface during administration. These results create a method for reliably and predictively estimating drug product adsorption behavior and protein drug dose loss on polymers at different protein drug concentrations.

New Onset Anemia, Worsened Plasma Creatinine Concentration, and Hyperviscosity in a Patient With a Monoclonal IgM Paraprotein.

A 76-year-old female followed closely for five years with IgM monoclonal gammopathy of uncertain significance developed anemia, worsened plasma creatinine concentration, and markedly elevated serum viscosity. This case illustrates the scope of pathology that can be caused by elevated blood viscosity. Our patient's anemia was a homeostatic response to normalize systemic vascular resistance and resulted from activation of the systemic vascular resistance response. The elevated plasma creatinine resulted from decreased renal perfusion because of elevated blood viscosity. Recent insights in hemorheology (the study of blood flow) are discussed, namely the recent identification of preferential blood flow patterns and erythrocyte autoregulation of deformability. These insights confirm that blood viscosity is part of the "milieu intérieur."

Defining Insights.

BACKGROUND: Insights, when acted upon, can result in positive changes to the business, for HCPs, and ultimately for patients. Medical Information, as a customer facing function, is one of the groups that generate insights. Data and insights across different functions of an organization need to be compiled to provide a comprehensive view. The purpose of this paper is to develop a shared definition of insights and to provide a working guidance for the insight process. METHODS: Two surveys were conducted of the phactMI membership first to establish a shared definition of insights and then to benchmark current insight process. From this data and the shared experience of the working group a proposed guidance was developed. RESULTS: The developed definition of an insight is "An insight is the deeper understanding of the why behind trends of information that lead us to determine if an action is warranted". For the most robust outcomes, insight identification needs to be a cross functional activity. The proposed structured approach can be leveraged and customized for any organization and include the following five steps: INvestigate, Scrutinize, Identify, Take Action, and Enlighten (INSITE). CONCLUSION: The INSITE process provides a simple framework that should become routine for all Medical Information colleagues who are leading the work around insights. The process should be shared across all functions that participate in the insight generation process. This is another area where Medical Information can demonstrate leadership and highlight their value to the organization.

PurUUpurU: An Oligonucleotide Virulence Factor in RNA Viruses.

Background The copy number of the oligonucleotide 5'-purine-uridine-uridine-purine-uridine-3' (purUUpurU) motif in a viral genome was previously shown to correlate with the severity of acute illness. This study aimed to determine whether purUUpurU content correlates with virulence in other single-strand RNA (ssRNA) viruses that vary in clinical severity. Methodology We determined the copy number of purUUpurU in the genomes of two subtypes of human respiratory syncytial virus (RSV), respiratory syncytial virus A (RSV-A), and respiratory syncytial virus B (RSV-B), which vary in clinical severity. In addition, we determined the purUUpurU content of the four ebolaviruses that cause human disease, dengue virus, rabies virus, human rhinovirus-A, poliovirus type 1, astrovirus, rubella, yellow fever virus, and measles virus. Viral nucleotide sequence files were downloaded from the National Center for Biotechnology Information (NCBI)/National Institutes of Health website. In addition, we determined the cumulative case fatality rate of 20 epidemics of the Ebola virus and compared it with that of the other human ebolaviruses. Results The genomic purUUpurU content correlated with the severity of acute illness caused by both subtypes of RSV and human ebolaviruses. The lowest purUUpurU content was in the genome of the rubella virus, which causes mild disease. Conclusions The quantity of genomic purUUpurU is a virulence factor in ssRNA viruses. Blood hyperviscosity is one mechanism by which purUUpurU causes pathology. Comparative quantitative genomic analysis for purUUpurU will be helpful in estimating the risk posed by emergent ssRNA viruses.

From the Oligonucleotide purUUpurU to Cytokine Storm, Elevated Blood Viscosity, and Complications of Coronavirus Disease 2019.

Background Coronavirus disease 2019 (COVID-19) can be associated with pathologic inflammation. The authors hypothesize that a high copy number of a purine-uridine-rich nucleotide motif is present in the genome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and hyperactivates innate immunity. Methods The number of purine-uridine-uridine-purine-uridine (purUUpurU) motifs was counted in the genomes of SARS-CoV-2 and other single-strand RNA viruses. The nucleotides of SARS-CoV-2 in random order were used as a control. Results PurUUpurU occurred 2.8 times more often in the actual SARS-CoV-2 genome than the randomized genome. The number of purUUpurU motifs correlates with the potential severity of acute illness caused by these viruses, except for influenza A. Conclusion The large number of purUUpurU in SARS-CoV-2 may hyperactivate innate immunity, potentially causing the markedly increased concentrations of cytokines, acute phase reactants, and blood viscosity that can be seen in COVID-19.

COVID-19 Demonstrates That Inflammation Is a Hyperviscous State.

Many of the complications of severe coronavirus disease-2019 (COVID-19) are caused by blood hyperviscosity driven by marked hyperfibrinogenemia. This results in a distinctive hyperviscosity syndrome which affects areas of high and low shear. A change in blood viscosity causes a threefold inverse change in blood flow, which increases the risk of thrombosis in both arteries and veins despite prophylactic anticoagulation. Increased blood viscosity decreases perfusion of all tissues, including the lungs, heart, and brain. Decreased perfusion of the lungs causes global ventilation-perfusion mismatch which results in silent hypoxemia and decreased efficacy of positive pressure ventilation in treating pulmonary failure in COVID-19. Increased blood viscosity causes a mismatch in oxygen supply and demand in the heart, resulting in myocarditis and ventricular diastolic dysfunction. Decreased perfusion of the brain causes demyelination because of a sublethal cell injury to oligodendrocytes. Hyperviscosity can cause stasis in capillaries, which can cause endothelial necrosis. This can lead to the rarefaction of capillary beds, which is noted in "long-COVID." The genome of the virus which causes COVID-19, severe acute respiratory syndrome coronavirus 2, contains an extraordinarily high number of the oligonucleotide virulence factor 5'-purine-uridine-uridine-purine-uridine-3', which binds to toll-like receptor 8, hyperactivating innate immunity. This can lead to a marked elevation in fibrinogen levels and an increased prevalence of neutrophil extracellular traps in pulmonary failure, as seen in COVID-19 patients.

The Role of Blood Viscosity in Infectious Diseases.

Blood viscosity is increased by elevated concentrations of acute phase reactants and hypergammaglobulinemia in inflammation. These increase blood viscosity by increasing plasma viscosity and fostering erythrocyte aggregation. Blood viscosity is also increased by decreased erythrocyte deformability, as occurs in malaria. Increased blood viscosity contributes to the association of acute infections with myocardial infarction (MI), venous thrombosis, and venous thromboembolism. It also increases vascular resistance, which decreases tissue perfusion and activates stretch receptors in the left ventricle, thereby initiating the systemic vascular resistance response. This compensates for the increased vascular resistance by vasodilation, lowering hematocrit, and decreasing intravascular volume. This physiological response causes the anemias associated with malaria, chronic inflammation, and other chronic diseases. Since tissue perfusion is inversely proportional to blood viscosity, anemia may be beneficial as it increases tissue perfusion when erythrocyte aggregating factors or erythrocytes with decreased deformability are present in the blood.

Apolipoprotein(a) is the Product of a Pseudogene: Implications for the Pathophysiology of Lipoprotein(a).

Apolipoprotein(a) [apo(a)] is an apolipoprotein unique to lipoprotein(a) [Lp(a)]. Although it has no known function, Lp(a) is a risk factor for accelerated atherothrombosis. We hypothesize that LPA, the gene which encodes apo(a), is a heretofore unrecognized unprocessed pseudogene created by duplication of PLG, the gene which encodes plasminogen. Unprocessed pseudogenes are genes which were created by duplication of functional genes and subsequently lost function after acquiring various mutations. This hypothesis explains many of the unusual features of Lp(a) and apo(a). Also, this hypothesis has implications for the therapy of elevated Lp(a) and atherothrombosis theory. Because apo(a) is functionless, the diseases associated with elevated levels of Lp(a) are due to its impact on blood viscosity.

Perspective: interesterified triglycerides, the recent increase in deaths from heart disease, and elevated blood viscosity.

The authors hypothesize that consumption of interesterified fats may be the cause of the continuous increase in cardiovascular deaths in the United States which began in 2011. Interesterification is a method of producing solid fats from vegetable oil and began to supplant partial hydrogenation for this purpose upon recognition of the danger of trans fats to cardiovascular health. Long, straight carbon chains, as are present in saturated and trans fatty acids, decrease the fluidity of the erythrocyte cell membrane, which decreases erythrocyte deformability and increases blood viscosity. This decrease in cell membrane fluidity is caused by increased van der Waals interactions, which also solidify dietary fats. Elevated blood viscosity is favored as the pathogenic mechanism by which trans fats increase cardiovascular mortality because changes in lipoprotein levels do not account for all the mortality attributable to their consumption. The rapid changes in cardiovascular mortality noted with the introduction and withdrawal of trans fats from the food supply are reviewed. The evidence implicating elevated blood viscosity in cardiovascular disease is also reviewed. Data regarding the production and consumption of interesterified fats in the US should be released in order to determine if there is an association with the observed increase in cardiovascular deaths.

Flawed Reasoning Allows the Persistence of Mainstream Atherothrombosis Theory.

Deaths due to atherothrombosis are increasing throughout the world except in the lowest socio-demographic stratum. This is despite 60 years of study and expenditure of billions of dollars on lipid theory. Nevertheless, mainstream atherothrombosis theory persists even though it has failed numerous tests. Contrary data are ignored, consistent with the practice of science as envisioned by Thomas Kuhn. This paper examines defects in mainstream atherogenesis theory and the flawed logic which allows its persistence in the face of what should be obvious shortcomings.

Atherothrombosis is a Thrombotic, not Inflammatory Disease.

The authors hypothesize that thrombosis causes both the complications of atherosclerosis as well as the underlying lesion, the atherosclerotic plaque, which develops from the organization of mural thrombi. These form in areas of slow blood flow, which develop because of flow separation created by changing vascular geometry and elevated blood viscosity. Many phenomena typically ascribed to inflammation or "chronic oxidative stress", such as the development of fatty streaks, "endothelial dysfunction," "vulnerable plaques," and the association of mild elevations of C-reactive protein and cytokines with atherothrombosis are better explained by hemorheologic and hemodynamic abnormalities, particularly elevated blood viscosity. Elevated blood viscosity decreases the perfusion of skeletal muscle, leading to myocyte expression of the myokine IL-6, decreased glucose uptake, insulin resistance, hyperglycemia, and metabolic syndrome. The hyperfibrinogenemia and hypergammaglobulinemia present in true inflammatory diseases foster atherothrombosis by increasing blood viscosity.

Effect of electrolyzed high-pH alkaline water on blood viscosity in healthy adults.

BACKGROUND: Previous research has shown fluid replacement beverages ingested after exercise can affect hydration biomarkers. No specific hydration marker is universally accepted as an ideal rehydration parameter following strenuous exercise. Currently, changes in body mass are used as a parameter during post-exercise hydration. Additional parameters are needed to fully appreciate and better understand rehydration following strenuous exercise. This randomized, double-blind, parallel-arm trial assessed the effect of high-pH water on four biomarkers after exercise-induced dehydration. METHODS: One hundred healthy adults (50 M/50 F, 31 ± 6 years of age) were enrolled at a single clinical research center in Camden, NJ and completed this study with no adverse events. All individuals exercised in a warm environment (30 °C, 70% relative humidity) until their weight was reduced by a normally accepted level of 2.0 ± 0.2% due to perspiration, reflecting the effects of exercise in producing mild dehydration. Participants were randomized to rehydrate with an electrolyzed, high-pH (alkaline) water or standard water of equal volume (2% body weight) and assessed for an additional 2-h recovery period following exercise in order to assess any potential variations in measured parameters. The following biomarkers were assessed at baseline and during their recovery period: blood viscosity at high and low shear rates, plasma osmolality, bioimpedance, and body mass, as well as monitoring vital signs. Furthermore, a mixed model analysis was performed for additional validation. RESULTS: After exercise-induced dehydration, consumption of the electrolyzed, high-pH water reduced high-shear viscosity by an average of 6.30% compared to 3.36% with standard purified water (p = 0.03). Other measured biomarkers (plasma osmolality, bioimpedance, and body mass change) revealed no significant difference between the two types of water for rehydration. However, a mixed model analysis validated the effect of high-pH water on high-shear viscosity when compared to standard purified water (p = 0.0213) after controlling for covariates such as age and baseline values. CONCLUSIONS: A significant difference in whole blood viscosity was detected in this study when assessing a high-pH, electrolyte water versus an acceptable standard purified water during the recovery phase following strenuous exercise-induced dehydration.

Uric acid increases erythrocyte aggregation: Implications for cardiovascular disease.

Uric acid may be a risk factor for atherosclerotic cardiovascular disease, although the data conflict and the mechanism by which it may cause cardiovascular disease is uncertain. This study was performed to test the hypothesis that uric acid, an anion at physiologic pH, can cause erythrocyte aggregation, which itself is associated with cardiovascular disease. Normal erythrocytes and erythrocytes with a positive direct antiglobulin test for surface IgG were incubated for 15 minutes in 14.8 mg/dL uric acid. Erythrocytes without added uric acid were used as controls. Erythrocytes were then examined microscopically for aggregation. Aggregates of up to 30 erythrocytes were noted when normal erythrocytes were incubated in uric acid. Larger aggregates were noted when erythrocytes with surface IgG were incubated in uric acid. Aggregation was negligible in controls. These data show that uric acid causes erythrocyte aggregation. The most likely mechanism is decreased erythrocyte zeta potential. Erythrocyte aggregates will increase blood viscosity at low shear rates and increase the risk of atherothrombosis. In this manner, hyperuricemia and decreased zeta potential may be risk factors for atherosclerotic cardiovascular disease.

The systemic vascular resistance response: a cardiovascular response modulating blood viscosity with implications for primary hypertension and certain anemias.

Without an active regulatory feedback loop, increased blood viscosity could lead to a vicious cycle of ischemia, increased erythropoiesis, further increases of blood viscosity, decreased tissue perfusion with worsened ischemia, further increases in red cell mass, etc. We suggest that an increase in blood viscosity is detected by mechanoreceptors in the left ventricle which upregulate expression of cardiac natriuretic peptides and soluble erythropoietin receptor. This response normalizes systemic vascular resistance and blood viscosity at the cost of producing 'anemia of chronic disease or inflammation' or 'hemolytic anemia' both of which are better described as states of compensated hyperviscosity. Besides its role in disease, this response is also active in the physiologic adaptation to chronic exercise. Malfunction of this response may cause primary hypertension.