Type 2 Diabetes Disease and Management Patterns Across a Large, Diverse Healthcare System: Issues and Opportunities for Guideline-Directed Therapies.

Background: The prevalence, chronicity and clinical impact of type 2 diabetes (T2D) defines this disease state as a critical determinant in morbidity and mortality, as encountered by individuals, health care systems, and public health in general. The need to understand and optimize T2D identification and management is now further heightened by the advent of medications with established cardiovascular (CV) and kidney benefits in such patients, namely sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1 RA). Prescription rates for these agents have remained low despite guidelines incorporating and emphasizing their use.

Integrating Ambulatory Care Pharmacists Into Value-Based Primary Care: A Scalable Solution to Chronic Disease.

Introduction/objectives: Patients living with chronic diseases require more medical attention, including more visits to primary care. However, primary care providers are overburdened, and this specialty is attracting fewer new providers than before. Clinical pharmacists can augment these efforts by improving disease state control.

Contemporary treatment patterns of overweight and obesity: insights from the Mass General Brigham health care system.

Objective: The objective of this study was to describe the prevalence of obesity, obesity-related conditions (ORCs), and antiobesity medication (AOM) eligibility and prescribing practice among eligible patients in a large health care system.

Methods: In this cross-sectional analysis of the multicenter Mass General Brigham health care system (Boston, Massachusetts) spanning 2018 to 2022, adults eligible for AOMs (BMI ≥ 30 kg/m or BMI 27-29.9 kg/m with ≥1 ORC) were identified.

Identifying Patients with Heart Failure Eligible for Guideline-Directed Medical Therapy.

A majority of patients with heart failure (HF) do not receive adequate medical therapy as recommended by clinical guidelines. One major obstacle encountered by population health management (PHM) programs to improve medication usage is the substantial burden placed on clinical staff who must manually sift through electronic health records (EHRs) to ascertain patients' eligibility for the guidelines. As a potential solution, the study team developed a rule-based system (RBS) that automatically parses the EHR for identifying patients with HF who may be eligible for guideline-directed therapy.

Rad-mediated inhibition of Ca1.2 channel activity contributes to uterine artery haemodynamic adaptation to pregnancy.

The striking increase of uterine blood flow during pregnancy is essential for normal fetal development as well as for cardiovascular well-being of the mother. Yet, the underlying mechanisms of pregnancy-mediated vasodilatation of the uterine artery are not fully understood. In this study, we test the hypothesis that Rad, a monomeric G protein, is a novel regulatory mechanism in inhibiting Ca1.

Long-term hypoxia modulates depolarization activation of BK currents in fetal sheep middle cerebral arterial myocytes.

Introduction: Previous evidence indicates that gestational hypoxia disrupts cerebrovascular development, increasing the risk of intracranial hemorrhage and stroke in the newborn. Due to the role of cytosolic Ca in regulating vascular smooth muscle (VSM) tone and fetal cerebrovascular blood flow, understanding Ca signals can offer insight into the pathophysiological disruptions taking place in hypoxia-related perinatal cerebrovascular disease. This study aimed to determine the extent to which gestational hypoxia disrupts local Ca sparks and whole-cell Ca signals and coupling with BK channel activity.

Enrollment strategies in the era of digital revolution: Experience from a remote health management program.

We describe the strategies used to identify and enroll participants in a remote health management program aimed at optimizing diabetes care in patients at high cardiovascular and kidney risk. Using a combination of digital and traditional outreach methods, including patient portals, emails, mailed letters, and provider referrals, we successfully enrolled 200 participants. Our experience highlights the effectiveness of a hybrid approach in achieving enrollment targets, addressing the challenges of identification of eligible candidates and engagement while integrating traditional methods for inclusivity.

Use of Sodium-Glucose Cotransporter 2 Inhibitors in Hospitalized Patients.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have noted benefits in the treatment of type 2 diabetes, cardiovascular disease, heart failure, and chronic kidney disease. Despite these benefits, the adoption of SGLT2i in clinical practice has been slow. Early initiation of SGLT2i during hospitalization has been proposed to address this gap for 2 important reasons: 1) it provides early clinical benefit in multiple disease states; and 2) hospitalization presents an opportunity for medication optimization and patient education, thereby overcoming clinical inertia.

MicroRNA-210 mediates hypoxia-induced pulmonary hypertension by targeting mitochondrial bioenergetics and mtROS flux.

Aim: Chronic hypoxia is a common cause of pulmonary hypertension (PH). We test the hypothesis that microRNA-210 (miR-210) mediates hypoxia-induced PH by targeting mitochondrial metabolism and increasing reactive oxygen species (mtROS) production in the lungs.

Methods: Adult wildtype (WT) or miR-210 knockout (KO) mice were exposed to hypoxia (10.

What Constitutes Adequate Control of High Blood Pressure? Current Considerations.

An estimated 45% of adult Americans currently have high blood pressure (HBP). Effective blood pressure (BP) control is essential for preventing major adverse events from cardiovascular and other vascular-related diseases, such as chronic kidney disease, stroke and dementia. A large and growing number of medical professional societies, health care organizations, and governmental agencies have now endorsed a clinical practice guideline-based target for adequate control of HBP to a systolic BP of less than 130 mm Hg.

The 6 degrees of curriculum integration in medical education in the United States.

Despite explicit expectations and accreditation requirements for integrated curriculum, there needs to be more clarity around an accepted common definition, best practices for implementation, and criteria for successful curriculum integration. To address the lack of consensus surrounding integration, we reviewed the literature and herein propose a definition for curriculum integration for the medical education audience. We further believe that medical education is ready to move beyond “horizontal” (1-dimensional) and “vertical” (2-dimensional) integration and propose a model of “6 degrees of curriculum integration” to expand the 2-dimensional concept for future designs of medical education programs and best prepare learners to meet the needs of patients.

Hypoxia-induced pulmonary hypertension in adults and newborns: implications for drug development.

Chronic hypoxia-induced pulmonary hypertension (CHPH) presents a complex challenge, characterized by escalating pulmonary vascular resistance and remodeling, threatening both newborns and adults with right heart failure. Despite advances in understanding the pathobiology of CHPH, its molecular intricacies remain elusive, particularly because of the multifaceted nature of arterial remodeling involving the adventitia, media, and intima. Cellular imbalance arises from hypoxia-induced mitochondrial disturbances and oxidative stress, reflecting the diversity in pulmonary hypertension (PH) pathology.

HS Increases Blood Pressure via Activation of L-Type Calcium Channels with Mediation by HS Generated from Reactions with Oxyhemoglobin.

Although the gasotransmitter hydrogen sulfide (HS) is well known for its vasodilatory effects, HS also exhibits vasoconstricting properties. Herein, it is demonstrated that administration of HS as intravenous sodium sulfide (NaS) increased blood pressure in sheep and rats, and this effect persisted after HS has disappeared from the blood. Inhibition of the L-type calcium channel (LTCC) diminished the hypertensive effects.

Randomized Evaluation of a Remote Management Program to Improve Guideline-Directed Medical Therapy: The DRIVE Trial.

Background: Several SGLT2i (sodium-glucose transport protein 2 inhibitors) and GLP1-RA (glucagon-like peptide-1 receptor agonists) reduce cardiovascular events and improve kidney outcomes in patients with type 2 diabetes; however, utilization remains low despite guideline recommendations.

Methods: A randomized, remote implementation trial in the Mass General Brigham network enrolled patients with type 2 diabetes with increased cardiovascular or kidney risk. Patients eligible for, but not prescribed, SGLT2i or GLP1-RA were randomly assigned to simultaneous virtual patient education with concurrent prescription of SGLT2i or GLP1-RA (ie, Simultaneous) or 2 months of virtual education followed by medication prescription (ie, Education-First) delivered by a multidisciplinary team driven by nonlicensed navigators and clinical pharmacists who prescribed SGLT2i or GLP1-RA using a standardized treatment algorithm.

Characterizing major depressive disorder and substance use disorder using heatmaps and variable interactions: The utility of operant behavior and brain structure relationships.

Background: Rates of depression and addiction have risen drastically over the past decade, but the lack of integrative techniques remains a barrier to accurate diagnoses of these mental illnesses. Changes in reward/aversion behavior and corresponding brain structures have been identified in those with major depressive disorder (MDD) and cocaine-dependence polysubstance abuse disorder (CD). Assessment of statistical interactions between computational behavior and brain structure may quantitatively segregate MDD and CD.

Retrieval Augmented Generation Enabled Generative Pre-Trained Transformer 4 (GPT-4) Performance for Clinical Trial Screening.

Background: Subject screening is a key aspect of all clinical trials; however, traditionally, it is a labor-intensive and error-prone task, demanding significant time and resources. With the advent of large language models (LLMs) and related technologies, a paradigm shift in natural language processing capabilities offers a promising avenue for increasing both quality and efficiency of screening efforts. This study aimed to test the Retrieval-Augmented Generation (RAG) process enabled Generative Pretrained Transformer Version 4 (GPT-4) to accurately identify and report on inclusion and exclusion criteria for a clinical trial.

Methods, rationale, and design for a remote pharmacist and navigator-driven disease management program to improve guideline-directed medical therapy in patients with type 2 diabetes at elevated cardiovascular and/or kidney risk.

Aim: Describe the rationale for and design of Diabetes Remote Intervention to improVe use of Evidence-based medications (DRIVE), a remote medication management program designed to initiate and titrate guideline-directed medical therapy (GDMT) in patients with type 2 diabetes (T2D) at elevated cardiovascular (CV) and/or kidney risk by leveraging non-physician providers.

Methods: An electronic health record based algorithm is used to identify patients with T2D and either established atherosclerotic CV disease (ASCVD), high risk for ASCVD, chronic kidney disease, and/or heart failure within our health system. Patients are invited to participate and randomly assigned to either simultaneous education and medication management, or a period of education prior to medication management.

Implementation of a Scalable Online Weight Management Programme in Clinical Settings: Protocol for the PROPS 2.0 Programme (Partnerships for Reducing Overweight and Obesity with Patient-Centered Strategies 2.0).

Introduction: There is an urgent need for scalable strategies for treating overweight and obesity in clinical settings. PROPS 2.0 (Partnerships for Reducing Overweight and Obesity with Patient-Centered Strategies 2.

Artifacts Introduced by Sample Handling in Chemiluminescence Assays of Nitric Oxide Metabolites.

We recently developed a combination of four chemiluminescence-based assays for selective detection of different nitric oxide (NO) metabolites, including nitrite, S-nitrosothiols (SNOs), heme-nitrosyl (heme-NO), and dinitrosyl iron complexes (DNICs). However, these NO species (NOx) may be under dynamic equilibria during sample handling, which affects the final determination made from the readout of assays. Using fetal and maternal sheep from low and high altitudes (300 and 3801 m, respectively) as models of different NOx levels and compositions, we tested the hypothesis that sample handling introduces artifacts in chemiluminescence assays of NOx.

Improved Workflow for Analysis of Vascular Myocyte Time-Series and Line-Scan Ca Imaging Datasets.

Intracellular Ca signals are key for the regulation of cellular processes ranging from myocyte contraction, hormonal secretion, neural transmission, cellular metabolism, transcriptional regulation, and cell proliferation. Measurement of cellular Ca is routinely performed using fluorescence microscopy with biological indicators. Analysis of deterministic signals is reasonably straightforward as relevant data can be discriminated based on the timing of cellular responses.

A Biomimetic Approach Utilizing Pulsatile Perfusion Generates Contractile Vascular Grafts.

Surgical implantation of decellularized cadaveric arteries is routinely used to treat right-sided congenital cardiac lesions. These acellular conduits lack the capacity for somatic growth and are prone to stenosis and calcification, necessitating multiple operations throughout childhood. Islet-1+ cardiovascular progenitor cells (CPCs) have demonstrated the capacity for differentiation into all cell types of the heart and outflow tracts.