Totality of evidence of the effectiveness of repurposed therapies for COVID-19: Can we use real-world studies alongside randomized controlled trials?

Rapid and robust strategies to evaluate the efficacy and effectiveness of novel and existing pharmacotherapeutic interventions (repurposed treatments) in future pandemics are required. Observational "real-world studies" (RWS) can report more quickly than randomized controlled trials (RCTs) and would have value were they to yield reliable results. Both RCTs and RWS were deployed during the coronavirus disease 2019 (COVID-19) pandemic.

Evaluation of Insulin Lispro Pharmacokinetics and Pharmacodynamics Over 10 Days of Continuous Insulin Infusion in People With Type 1 Diabetes.

Background: We evaluated the effect of meloxicam on insulin lispro pharmacokinetics and glucose pharmacodynamics over 10 days of continuous subcutaneous insulin infusion (CSII) at one infusion site in people with type 1 diabetes (T1D).

Method: This phase 1, randomized, double-blind, single-center, two-way crossover study enrolled adults with T1D for ≥1 year on stable CSII for ≥3 months. Participants randomly received U100 insulin lispro and LY900027 (U100 insulin lispro + 0.

Predictive Low-Glucose Suspend Necessitates Less Carbohydrate Supplementation to Rescue Hypoglycemia: Need to Revisit Current Hypoglycemia Treatment Guidelines.

Current guidelines recommend 15-20 g of carbohydrate (CHO) for treatment of mild to moderate hypoglycemia. However, these guidelines do not account for reduced insulin during suspensions with predictive low-glucose suspend (PLGS). We assessed insulin suspensions, hypoglycemic events, and CHO treatment during a 20-h inpatient evaluation of an investigational system with a PLGS feature, including an overnight basal up-titration period to activate the PLGS.

Performance of an Automated Insulin Delivery System: Results of Early Phase Feasibility Studies.

Automated insulin delivery (AID) systems have demonstrated improvements in time-in-range (TIR, blood glucose 70-180 mg/dL) without increasing hypoglycemia. Testing a closed-loop system in an inpatient environment with supervised challenges allows for initial evaluation of performance and safety of the system. Adults with type 1 diabetes (T1D) were enrolled into two similar studies ( = 10 per study), with 3-day inpatient analysis periods.

Estimation of group means using Bayesian generalized linear mixed models.

Generalized linear mixed models (GLMM) are commonly used to model the treatment effect over time while controlling for important clinical covariates. Standard software procedures often provide estimates of the outcome based on the mean of the covariates; however, these estimates will be biased for the true group means in the GLMM. Implementing GLMM in the frequentist framework can lead to issues of convergence.

Discovering structure in multiple outcomes models for tests of childhood neurodevelopment.

Bayesian model-based clustering provides a powerful and flexible tool that can be incorporated into regression models to better understand the grouping of observations. Using data from the Seychelles Child Development Study, we explore the effect of prenatal methylmercury exposure on 20 neurodevelopmental outcomes measured in 9-year-old children. Rather than cluster individual subjects, we cluster the outcomes within a multiple outcomes model.

Creation and Piloting of a Model for Simulating a Minimally Invasive Myomectomy.

Introduction: In the era of mandatory work hour restrictions for residency programs, the opportunity for mastery of complex surgical skills in the operating room (OR) has been compromised. All the while, gynecologic surgical techniques have continued to expand. Surgical simulation offers an adjuvant modality for helping young surgeons hone their surgical techniques.

USING THE SEYCHELLES CHILD DEVELOPMENT STUDY TO CLUSTER MULTIPLE OUTCOMES INTO DOMAINS TO IMPROVE ESTIMATION OF THE OVERALL EFFECT OF MERCURY ON NEURODEVELOPMENT.

Environmental exposure effects on human development can be small and difficult to detect due to the nature of observational data. In the Seychelles Child Development Study, researchers examined the effect of prenatal methylmercury exposure using a battery of tests measuring aspects of child development [23, 25]. We build a multiple outcomes model similar to that of the previous analyses (see [23, 25]); however, our multiple outcomes model makes no assumptions of relationships between the testing outcomes.

Placental concentrations of essential, toxic, and understudied metals and relationships with birth outcomes in Chattanooga, TN.

Background: Comprehensive examinations of placental metal concentrations and correlations with infant parameters are under-investigated. Chattanooga, Tennessee's consistently high incidence of low birth weight and potential for metal exposure provides an ideal opportunity to investigate potential correlations.

Objectives: To investigate the associations between a wide variety of metals in placental tissue and multiple infant parameters.

Obesity candidate genes, gestational weight gain, and body weight changes in pregnant women.

Objective: To examine the associations of two obesity-associated genes, FTO (rs9939609) and GNB3 (rs5443) single nucleotide polymorphisms (SNPs), with early pregnancy body mass index, gestational weight gain, and postpartum weight retention.

Methods: Secondary data analysis of self-identified white (n = 580) and black (n = 194) women who participated in a randomized controlled trial (2009-2014) and provided a saliva sample of DNA. Bivariate relationships were assessed using analysis of variance.

Bile salt receptor TGR5 is highly expressed in esophageal adenocarcinoma and precancerous lesions with significantly worse overall survival and gender differences.

Bile acid reflux in the esophagus plays an important role in the carcinogenesis of esophageal adenocarcinoma (EAC). The G-protein coupled bile acid receptor (TGR5) has been associated with the development of gastrointestinal cancer. However, little is known regarding the role of TGR5 in esophageal carcinoma and precancerous lesions.

High expression of Claudin-2 in esophageal carcinoma and precancerous lesions is significantly associated with the bile salt receptors VDR and TGR5.

Background: Claudins are a family of integral membrane proteins and are components of tight junctions (TJs). Many TJ proteins are known to tighten the cell structure and maintain a barrier. Claudin-2 forms gated paracellular channels and allows sodium ions and other small positively charged ions to cross between adjacent cells.

MCM4 and MCM7, potential novel proliferation markers, significantly correlated with Ki-67, Bmi1, and cyclin E expression in esophageal adenocarcinoma, squamous cell carcinoma, and precancerous lesions.

Minichromosomal maintenance (MCM) proteins are participants of DNA replication and may represent more accurate markers in determining the proliferative fraction within a tumor than proliferative marker Ki-67. Our study investigated the correlation between MCM4 and MCM7 expression and Ki-67, Bmi1, and cyclin E expression in esophageal adenocarcinoma, squamous cell carcinoma, and precancerous lesions. MCM4 and MCM7 expression had similar distribution as Ki-67 and Bmi1 expression in esophageal carcinoma and precancerous lesions.

Geographic variation in cost of care for pituitary tumor surgery.

Purpose: Geography is known to affect cost of care in surgical procedures. Understanding the relationship between geography and hospital costs is pertinent in the effort to reduce healthcare costs. We studied the geographic variation in cost for transsphenoidal pituitary surgery in hospitals across New York State.

Effect of oral sodium bicarbonate on fibroblast growth factor-23 in patients with chronic kidney disease: a pilot study.

Background: The regulation of fibroblast growth factor-23 (FGF23) secretion in patients with chronic kidney disease (CKD) is incompletely understood. An in vitro study showed that metabolic acidosis increased FGF23 in mouse bone. The objective of this study is to evaluate the effect of oral sodium bicarbonate on circulating FGF23 levels in patients with CKD.