Considerations and recommendations for collaborative research networks in epidemiology: Lessons learned from the diabetes LEAD Network.

Multi-site and multi-organizational teams are increasingly common in epidemiologic research; however, there is a lack of standards or best practices for achieving success in collaborative research networks in epidemiology. We summarize our experiences and lessons learned from the Diabetes Location, Environmental Attributes, and Disparities (LEAD) Network, a collaborative agreement between the Centers for Disease Control and Prevention and research teams at Drexel University, New York University, Johns Hopkins University and Geisinger, and the University of Alabama at Birmingham. We present a roadmap for success in collaborative epidemiologic research, with recommendations focused on the following areas to maximize efficiency and success in collaborative research agreements: 1) operational and administrative considerations; 2) data access and sharing of sensitive data; 3) aligning network research aims; 4) harmonization of methods and measures; and 5) dissemination of findings.

Blood Group B May Reduce Risk of Rebleeding in Patients With Upper Gastrointestinal Haemorrhage due to Peptic Ulcer Disease.

Risk stratification tools for the prediction of complications in patients with upper gastrointestinal haemorrhage are crucial for appropriate management. Blood group status has been associated with the risk of bleeding, thrombosis and risk of peptic ulcer disease (PUD). We assessed the influence of blood group status on rebleeding and other complications in 699 patients with PUD bleeding.

Thyroid hormone receptor beta (THRβ1) is the major regulator of T3 action in human iPSC-derived hepatocytes.

Objective: Thyroid hormone (TH) action is mediated by thyroid hormone receptor (THR) isoforms. While THRβ1 is likely the main isoform expressed in liver, its role in human hepatocytes is not fully understood.

Methods: To elucidate the role of THRβ1 action in human hepatocytes we used CRISPR/Cas9 editing to knock out THRβ1 in induced pluripotent stem cells (iPSC).

Clinical outcomes of chronic myeloid leukaemia patients taking asciminib through a Managed Access Programme (MAP) in Australia.

Asciminib is a novel allosteric STAMP (specifically targets the ABL myristoyl pocket) inhibitor of the BCR::ABL1 oncogene. Real-world clinical outcomes of patients with tyrosine kinase inhibitor (TKI)-resistant/intolerant chronic myeloid leukaemia (CML) in Australia on the Managed Access Programme for asciminib showed higher molecular responses for those with intolerance versus resistance ± intolerance to their last TKI. There remains a clinical need to improve outcomes in patients with CML who have resistance to multiple TKIs, especially in the ponatinib-pretreated cohort.

Patient-specific tissue engineered vascular graft for aortic arch reconstruction.

Objectives: The complexity of aortic arch reconstruction due to diverse 3-dimensional geometrical abnormalities is a major challenge. This study introduces 3-dimensional printed tissue-engineered vascular grafts, which can fit patient-specific dimensions, optimize hemodynamics, exhibit antithrombotic and anti-infective properties, and accommodate growth.

Methods: We procured cardiac magnetic resonance imaging with 4-dimensional flow for native porcine anatomy (n = 10), from which we designed tissue-engineered vascular grafts for the distal aortic arch, 4 weeks before surgery.

Thrombosis in patients with immune thrombocytopenia: incidence, risk, and clinical outcomes.

Background: There is evidence that patients with immune thrombocytopenia (ITP) are at increased risk of thrombosis. However, the association of clinical- and treatment-related factors with thrombosis remains controversial.

Objectives: To evaluate the incidence and impact of risk factors for arterial and venous thromboembolism (VTE) in patients with ITP and characterize the clinical features and management of patients.

Age and sex differences in the association between neighborhood socioeconomic environment and incident diabetes: Results from the diabetes location, environmental attributes and disparities (LEAD) network.

Objective: Worse neighborhood socioeconomic environment (NSEE) may contribute to an increased risk of type 2 diabetes (T2D). We examined whether the relationship between NSEE and T2D differs by sex and age in three study populations.

Research Design And Methods: We conducted a harmonized analysis using data from three independent longitudinal study samples in the US: 1) the Veteran Administration Diabetes Risk (VADR) cohort, 2) the REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort, and 3) a case-control study of Geisinger electronic health records in Pennsylvania.

Risk-Directed Ambulatory Thromboprophylaxis in Lung and Gastrointestinal Cancers: The TARGET-TP Randomized Clinical Trial.

Importance: Thromboprophylaxis for individuals receiving systemic anticancer therapies has proven to be effective. Potential to maximize benefits relies on improved risk-directed strategies, but existing risk models underperform in cohorts with lung and gastrointestinal cancers.

Objective: To assess clinical benefits and safety of biomarker-driven thromboprophylaxis and to externally validate a biomarker thrombosis risk assessment model for individuals with lung and gastrointestinal cancers.

Validity of Customized Branched Tissue Engineered Vascular Graft in a Porcine Model.

Background: Patient-specific, 3-dimensional printed, tissue engineered vascular grafts (3DTEVGs) are manufactured to optimize hemodynamic performance and to accommodate growth. We evaluate growth outcomes of 3DTEVGs compared with standard grafts for pulmonary artery reconstruction in porcine models.

Methods: Magnetic resonance imaging (MRI) with 4-dimensional flow data was acquired in porcine models (n = 8).

Smokers' utilization of quitting methods and vaping during pregnancy: an empirical cluster analysis of 2016-2018 Pregnancy Risk Assessment Monitoring System (PRAMS) data in seven US states.

Background: Patterns of utilization of numerous smoking cessation methods among pregnant women amidst the increasing popularity of vaping (use of e-cigarettes) remains unknown.

Methods: This study included 3,154 mothers who self-reported smoking around the time of conception and delivered live births in 2016-2018 in seven US states. Latent class analysis was used to identify subgroups of smoking women based on their utilization of 10 surveyed quitting methods and vaping during pregnancy.

Model-Based Prediction of Acid Suppression and Proposal of a New Dosing Regimen of Fexuprazan in Humans.

Fexuprazan is a potassium-competitive acid blocker (P-CAB). The compounds in this newly developed drug family suppress intragastric acidity. As there are already other acid-suppressing drugs on the market, such as H antagonists and proton pump inhibitors (PPIs), it would be informative to compare the biological effects of fexuprazan against another approved drug with the same indication.

Exposure-response analysis of the association of maternal smoking and use of electronic cigarettes (vaping) in relation to preterm birth and small-for-gestational-age in a national US sample, 2016-2018.

Introduction: The US experienced a surge in use of e-cigarettes. Smoking women may consider e-cigarettes during pregnancy as an alternative to smoking. -cigarettes typically contain nicotine, an established cause of reduction in fetal growth in animal studies.

Categorizing community type for epidemiologic evaluation of community factors and chronic disease across the United States.

Existing classifications of community type do not differentiate urban cores from surrounding non-rural areas, an important distinction for analyses of community features and their impact on health. Inappropriately classified community types can introduce serious methodologic flaws in epidemiologic studies and invalid inferences from findings. To address this, we evaluate a modification of the United States Department of Agriculture's Rural Urban Commuting Area codes at the census tract, propose a four-level categorization of community type, and compare this with existing classifications for epidemiologic analyses.

A Randomized, Double-Blind, Placebo- and Active-Controlled, Escalating Single-Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Profiles of Subcutaneous Eflapegrastim in Healthy Japanese and Caucasian Subjects.

Background: Eflapegrastim (Rolontis) is a novel long-acting pegylated recombinant human granulocyte colony-stimulating factor (G-CSF). Eflapegrastim has been developed to reduce the duration and incidence of chemotherapy-induced neutropenia in cancer patients using patient-friendly, less-frequent administration.

Objective: This phase I study aimed to evaluate the safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD), and immunogenicity of eflapegrastim following a single subcutaneous administration to healthy Japanese and Caucasian subjects.

A double-blind, placebo-controlled, single-ascending dose study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of HM15136, a novel long-acting glucagon analogue, in healthy subjects.

Aim: To evaluate the safety and tolerability, pharmacokinetics, and pharmacodynamics of HM15136, a novel long-acting glucagon analogue under development, in healthy males and females presenting with no childbearing potential.

Materials And Methods: A randomized, double-blind, placebo-controlled, single-ascending dose study was conducted in 56 subjects who randomly received a single subcutaneous dose of HM15136 or its matching placebo at a ratio of 6:2 at 10, 20, 30, 50, 80, 100, and 120 μg/kg.

Results: All adverse events were mild and transient.

Development of Physiologically Based Pharmacokinetic Model for Orally Administered Fexuprazan in Humans.

Fexuprazan is a new drug candidate in the potassium-competitive acid blocker (P-CAB) family. As proton pump inhibitors (PPIs), P-CABs inhibit gastric acid secretion and can be used to treat gastric acid-related disorders such as gastroesophageal reflux disease (GERD). Physiologically based pharmacokinetic (PBPK) models predict drug interactions as pharmacokinetic profiles in biological matrices can be mechanistically simulated.

Improving Asthma Symptoms Among Inner-City Women During Pregnancy: A Prospective Cohort Intervention.

Background: It is unknown how active asthma management influences symptom control among inner-city pregnant women who have unique exposures and socioeconomic limitations affecting their care.

Objective: To assess the impact of an integrated subspecialty intervention composed of education and monitoring on asthma control among underserved women in an antenatal clinic setting.

Methods: We conducted a prospective cohort study of pregnant asthmatic patients participating in a subspecialty clinic integrated into routine prenatal care.

Connecting the Dots: a cluster-randomized clinical trial integrating standardized autism spectrum disorders screening, high-quality treatment, and long-term outcomes.

Background: Autism spectrum disorder (ASD) affects one in 54 children in the United States of America, and supporting people with ASD across the lifespan presents challenges that impact individuals, families, and communities and can be quite costly. The American Academy of Pediatrics has issued recommendations for routine ASD screening at 18 and 24 months, but some research suggests that few pediatricians perform high-fidelity, standardized screening universally. Furthermore, the United States Preventive Services Task Force (USPSTF) found insufficient evidence to recommend for or against universal ASD screening.

Genomics and Population Analyses Reveal High Inter- and Intraserovar Diversity in Freshwater.

Freshwater can support the survival of the enteric pathogen , though temporal diversity in a large watershed has not been assessed. At 28 locations within the Susquehanna River basin, 10-liter samples were assessed in spring and summer over 2 years. prevalence was 49%, and increased river discharge was the main driver of presence.

Evaluation of Hepatic Uptake of OATP1B Substrates by Short Term-Cultured Plated Human Hepatocytes: Comparison With Isolated Suspended Hepatocytes.

Hepatic uptake clearance has been measured in suspended human hepatocytes (SHH). Plated human hepatocytes (PHH) after short-term culturing are increasingly employed to study hepatic transport driven mainly by its higher throughput. To know pros/cons of both systems, the hepatic uptake clearances of several organic anion transporting polypeptide 1B substrates were compared between PHH and SHH by determining the initial uptake velocities or through dynamic model-based analyses.

The Diabetes Location, Environmental Attributes, and Disparities Network: Protocol for Nested Case Control and Cohort Studies, Rationale, and Baseline Characteristics.

Background: Diabetes prevalence and incidence vary by neighborhood socioeconomic environment (NSEE) and geographic region in the United States. Identifying modifiable community factors driving type 2 diabetes disparities is essential to inform policy interventions that reduce the risk of type 2 diabetes.

Objective: This paper aims to describe the Diabetes Location, Environmental Attributes, and Disparities (LEAD) Network, a group funded by the Centers for Disease Control and Prevention to apply harmonized epidemiologic approaches across unique and geographically expansive data to identify community factors that contribute to type 2 diabetes risk.

Cell-to-Medium Concentration Ratio Overshoot in the Uptake of Statins by Human Hepatocytes in Suspension, but Not in Monolayer: Kinetic Analysis Suggesting a Partial Loss of Functional OATP1Bs.

Suspended human hepatocytes (SHH) have long been used in assessing hepatic drug uptake, while plated human hepatocytes in short-term monolayer culture (PHH) have gained use in recent years. This study aimed to cross-evaluate SHH and PHH in measuring the hepatic uptake mediated by organic anion transporting polypeptide 1Bs (OATP1Bs). We compared the time courses of cell-to-medium (C/M) concentration ratios and initial uptake clearance values of the OATP1B substrates (pitavastatin, rosuvastatin, cerivastatin, pravastatin, dehydropravastatin, and SC-62807) between SHH and PHH.