Publications by authors named "C M Coffman"

201 Publications

Heterogeneity of Treatment Effects Among Patients With Type 2 Diabetes and Elevated Body Mass Index in a Study Comparing Group Medical Visits Focused on Weight Management and Medication Intensification.

Med Care 2021 Sep 13. Epub 2021 Sep 13.

Duke University School of Medicine Durham Veterans Affairs Center of Innovation to Accelerate Discovery and Practice Change (ADAPT) Division of Endocrinology, Department of Medicine Division of General Internal Medicine, Department of Medicine, Duke University Medical Center Duke Lifestyle and Weight Management Center, Durham, NC William S Middleton Memorial Veterans Hospital Department of Surgery, University of Wisconsin, Madison, WI Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, NC.

Background: Illuminating heterogeneity of treatment effect (HTE) within trials is important for identifying target populations for implementation.

Objective: The aim of this study was to examine HTE in a trial of group medical visits (GMVs) for patients with type 2 diabetes and elevated body mass index.

Research Design And Measures: Participants (n=263) were randomized to GMV-based medication management plus low carbohydrate diet-focused weight management (WM/GMV; n=127) or GMV-based medication management alone (GMV; n=136) for diabetes control. We used QUalitative INteraction Trees, a tree-based clustering method, to identify subgroups with greater improvement in hemoglobin A1c (HbA1c) and weight from either WM/GMV or GMV. Subgroup predictors included 32 baseline demographic, clinical, and psychosocial factors. Internal validation was conducted to estimate bias in the range of mean outcome differences between arms.

Results: QUalitative INteraction Trees analyses indicated that for patients who had not previously attempted weight loss, WM/GMV resulted in better glycemic control than GMV (mean difference in HbA1c improvement=1.48%). For patients who had previously attempted weight loss and had lower cholesterol and blood urea nitrogen, GMV was better than WM/GMV (mean difference in HbA1c improvement=1.51%). No treatment-subgroup effects were identified for weight. Internal validation resulted in moderate corrections in mean HbA1c differences between arms; however, differences remained in the clinically significant range.

Conclusion: This work represents a novel step toward targeting care approaches for patients to maximize benefit based on individual patient characteristics.
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http://dx.doi.org/10.1097/MLR.0000000000001642DOI Listing
September 2021

Interpreting the Results of Intention-to-Treat, Per-Protocol, and As-Treated Analyses of Clinical Trials.

JAMA 2021 Aug;326(5):433-434

Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina at Chapel Hill.

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http://dx.doi.org/10.1001/jama.2021.2825DOI Listing
August 2021

Notch Signaling Pathway Is Activated by Sulfate Reducing Bacteria.

Front Cell Infect Microbiol 2021 15;11:695299. Epub 2021 Jul 15.

Division of Gastroenterology and Hepatology, Department of Medicine, University of New Mexico, Albuquerque, NM, United States.

Sulfate Reducing Bacteria (SRB), usually rare residents of the gut, are often found in increased numbers (called a SRB bloom) in inflammatory conditions such as Inflammatory Bowel Disease (IBD), pouchitis, and periodontitis. However, the underlying mechanisms of this association remain largely unknown. Notch signaling, a conserved cell-cell communication pathway, is usually involved in tissue development and differentiation. Dysregulated Notch signaling is observed in inflammatory conditions such as IBD. Lipolysaccharide and pathogens also activate Notch pathway in macrophages. In this study, we tested whether Desulfovibrio, the most dominant SRB genus in the gut, may activate Notch signaling. RAW 264.7 macrophages were infected with (DSV) and analyzed for the expression of Notch signaling pathway-related proteins. We found that DSV induced protein expression of Notch1 receptor, Notch intracellular domain (NICD) and p21, a downstream Notch target, in a dose-and time-dependent manner. DSV also induced the expression of pro-IL1β, a precursor of IL-1β, and SOCS3, a regulator of cytokine signaling. The gamma secretase inhibitor DAPT or Notch siRNA dampened DSV-induced Notch-related protein expression as well the expression of pro-IL1β and SOCS3. Induction of Notch-related proteins by DSV was not affected by TLR4 -IN -C34(C34), a TLR4 receptor antagonist. Additionally, cell-free supernatant of DSV-infected macrophages induced NICD expression in uninfected macrophages. DSV also activated Notch pathway in the human epithelial cell line HCT116 and in mouse small intestine. Thus, our study uncovers a novel mechanism by which SRB interact with host cells by activating Notch signaling pathway. Our study lays a framework for examining whether the Notch pathway induced by SRB contributes to inflammation in conditions associated with SRB bloom and whether it can be targeted as a therapeutic approach to treat these conditions.
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http://dx.doi.org/10.3389/fcimb.2021.695299DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8319767PMC
August 2021

Proprioceptive Acuity is Enhanced During Arm Movements Compared to When the Arm is Stationary: A Study of Young and Older Adults.

Neuroscience 2021 07 24;466:222-234. Epub 2021 Apr 24.

Department of Health and Human Physiology Motor Control Laboratory, University of Iowa 225 S Grand Ave, Iowa City, IA 52242 United States. Electronic address:

Proprioception in old age is thought to be poorer due to degeneration of the central (CNS) and peripheral nervous systems (PNS). We tested whether community-dwelling older adults (65-83 years) make larger proprioceptive errors than young adults (18-22 years) using a natural reaching task. Subjects moved the right arm to touch the index fingertip to the stationary or moving left index fingertip. The range of locations of the target index fingertip was large, sampling the natural workspace of the human arm. The target arm was moved actively by the subject or passively by the experimenter and reaching arm movements towards the target were made under visual guidance, or with vision blocked (proprioceptive guidance). Subjects did not know the direction or speed of upcoming target hand motion in the passive conditions. Mean 3D distance errors between the right and left index finger tips were small in both groups and only slightly larger when vision was blocked than when allowed, but averaged 2-5 mm larger in older than in younger adults in moving (p = 0.002) and stationary (p = 0.07) conditions, respectively. Variable errors were small and similar in the two groups (p > 0.35). Importantly, clearly larger errors were observed for reaching to the stationary than to the moving index fingertip in both groups, demonstrating that dynamic proprioceptive information during movement permits more accurate localization of the endpoint of the moving arm. This novel finding demonstrates the importance of dynamic proprioceptive information in movement guidance and bimanual coordination.
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http://dx.doi.org/10.1016/j.neuroscience.2021.04.015DOI Listing
July 2021
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