Publications by authors named "Haywood T"

Article Synopsis
  • The research highlights significant racial and ethnic disparities in excess mortality during the COVID-19 pandemic, revealing a concerning trend concerning minoritized populations who faced greater mortality rates compared to pre-pandemic disparities.!* -
  • A comprehensive analysis of over 10.6 million death certificates from March 2020 to May 2023 indicated that more than 1.38 million excess deaths occurred, representing around 23 million years of potential life lost.!* -
  • The findings emphasize the need for further investigation into the age-specific impact of COVID-19 on various racial and ethnic groups to better understand and address these health disparities moving forward.!*
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Importance: First-line treatment for posttraumatic stress disorder (PTSD) in the US Department of Veterans Affairs (VA), ie, trauma-focused therapy, while effective, is limited by low treatment initiation, high dropout, and high treatment refraction.

Objective: To evaluate the effectiveness of Trauma Center Trauma-Sensitive Yoga (TCTSY) vs first-line cognitive processing therapy (CPT) in women veterans with PTSD related to military sexual trauma (MST) and the hypothesis that PTSD outcomes would differ between the interventions.

Design, Setting, And Participants: This multisite randomized clinical trial was conducted from December 1, 2015, to April 30, 2022, within 2 VA health care systems located in the southeast and northwest.

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Importance: Amid efforts in the US to promote health equity, there is a need to assess recent progress in reducing excess deaths and years of potential life lost among the Black population compared with the White population.

Objective: To evaluate trends in excess mortality and years of potential life lost among the Black population compared with the White population.

Design, Setting, And Participants: Serial cross-sectional study using US national data from the Centers for Disease Control and Prevention from 1999 through 2020.

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Providing care over telehealth grew slowly until the COVID-19 pandemic. Since the onset of the COVID-19 pandemic, providing mental health care was readily adapted to virtual means; however, clinical trial research is nascent in adapting methods and procedures to the virtual world. We present protocol modifications to pivot a multisite randomized controlled trial study, conducted at Southeastern and Pacific Northwestern Veterans Affairs Health Care Systems, from being conducted in-person to virtually, following the onset of the COVID-19 pandemic.

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Purpose: A novel cystine-knot peptide-based PET radiopharmaceutical, F-FP-R1-MG-F2 (knottin), was developed to selectively bind to human integrin αβ which is overexpressed in pancreatic cancer. The purpose of this study is to evaluate the safety, biodistribution, dosimetry, and lesion uptake of F-FP-R1-MG-F2 in patients with pancreatic cancer.

Methods: Fifteen patients (6 men, 9 women) with histologically confirmed pancreatic cancer were prospectively enrolled and underwent knottin PET/CT between March 2017 and February 2021 (ClinicalTrials.

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Purpose: Pyruvate kinase M2 (PKM2) catalyzes the final step in glycolysis, a key process of cancer metabolism. PKM2 is preferentially expressed by glioblastoma (GBM) cells with minimal expression in healthy brain. We describe the development, validation, and translation of a novel PET tracer to study PKM2 in GBM.

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Early cancer detection can dramatically increase treatment options and survival rates for patients, yet detection of early-stage tumors remains difficult. Here, we demonstrate a two-step strategy to detect and locate cancerous lesions by delivering tumor-activatable minicircle (MC) plasmids encoding a combination of blood-based and imaging reporter genes to tumor cells. We genetically engineered the MCs, under the control of the pan-tumor-specific Survivin promoter, to encode: 1) Gaussia Luciferase (GLuc), a secreted biomarker that can be easily assayed in blood samples; and 2) Herpes Simplex Virus Type 1 Thymidine Kinase mutant (HSV-1 sr39TK), a PET reporter gene that can be used for highly sensitive and quantitative imaging of the tumor location.

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To conduct an interim analysis of data collected from an ongoing multisite randomized clinical trial (RCT) assessing the effectiveness of Trauma Center Trauma-Sensitive Yoga (TCTSY) for post-traumatic stress disorder (PTSD) among women veterans with PTSD related to military sexual trauma (MST). The purpose of the interim analysis was to assess outcomes from the primary site, which is geographically, demographically, culturally, and procedurally distinct from the second site. RCT was conducted within a Veterans Administration Health Care System.

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Purpose: Immunomonitoring of chimeric antigen receptor (CAR) T cells relies primarily on their quantification in the peripheral blood, which inadequately quantifies their biodistribution and activation status in the tissues. Noninvasive molecular imaging of CAR T cells by PET is a promising approach with the ability to provide spatial, temporal, and functional information. Reported strategies rely on the incorporation of reporter transgenes or biolabeling, significantly limiting the application of CAR T-cell molecular imaging.

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Imaging strategies to monitor chimeric antigen receptor (CAR) T-cell biodistribution and proliferation harbor the potential to facilitate clinical translation for the treatment of both liquid and solid tumors. In addition, the potential adverse effects of CAR T cells highlight the need for mechanisms to modulate CAR T-cell activity. The herpes simplex virus type 1 thymidine kinase (HSV1-tk) gene has previously been translated as a PET reporter gene for imaging of T-cell trafficking in patients with brain tumor.

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Purpose: [F]FHBG has been used as a positron emission tomography (PET) imaging tracer for the monitoring of herpes simplex virus type 1 thymidine kinase (HSV1-tk), a reporter gene for cell and gene therapy in humans. However, this tracer shows inadequate blood-brain barrier (BBB) penetration and, therefore, would be limited for accurate quantification of reporter gene expression in the brain. Here, we report the synthesis and evaluation of 9-(4-[F]fluoro-3-(hydroxymethyl)butyl)-2(phenylthio)-6-oxopurine ([F]FHBT) as a new PET tracer for imaging reporter gene expression of HSV1-tk and its mutant HSV1-sr39tk, with the aim of improved BBB penetration.

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6″-[ F]fluoromaltotriose is a positron emission tomography tracer that can differentiate between bacterial infection and inflammation in vivo. Bacteria-specific uptake of 6″-[ F]fluoromaltotriose is attributed to the targeting of maltodextrin transporter in bacteria that is absent in mammalian cells. Herein, we report a new synthesis of 6″-[ F]fluoromaltotriose as a key step for its clinical translation.

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Currently, there are no non-invasive tools to accurately diagnose wound and surgical site infections before they become systemic or cause significant anatomical damage. Fluorescence and photoacoustic imaging are cost-effective imaging modalities that can be used to noninvasively diagnose bacterial infections when paired with a molecularly targeted infection imaging agent. Here, we develop a fluorescent derivative of maltotriose (Cy7-1-maltotriose), which is shown to be taken up in a variety of gram-positive and gram-negative bacterial strains in vitro.

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Purpose: To assess the safety, biodistribution, and radiation dosimetry of the novel positron emission tomography (PET) radiopharmaceutical 1-((2-fluoro-6-[[F]]fluorophenyl)sulfonyl)-4-((4-methoxyphenyl)sulfonyl)piperazine ([F]DASA-23) in healthy volunteers.

Methods: We recruited 5 healthy volunteers who provided a written informed consent. Volunteers were injected with 295.

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Advances in precision molecular imaging promise to transform our ability to detect, diagnose and treat disease. Here, we describe the engineering and validation of a new cystine knot peptide (knottin) that selectively recognizes human integrin αvβ with single-digit nanomolar affinity. We solve its 3D structure by NMR and x-ray crystallography and validate leads with 3 different radiolabels in pre-clinical models of cancer.

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The aim of this study was development of an improved PET radiotracer for measuring x activity with increased tumor uptake and reduced uptake in inflammatory cells compared with ()-4-(3-F-fluoropropyl)-l-glutamate (F-FSPG). A racemic glutamate derivative, F-hGTS13, was evaluated in cell culture and animal tumor models. F-hGTS13 was separated into C5 epimers, and the corresponding F-hGTS13-isomer1 and F-hGTS13-isomer2 were evaluated in H460 tumor-bearing rats.

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There is a growing need for monitoring or imaging gene therapy in the central nervous system (CNS). This can be achieved with a positron emission tomography (PET) reporter gene strategy. Here we report the development of a PET reporter gene system using the PKM2 gene with its associated radiotracer [F]DASA-23.

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Background: Research on intimate partner violence (IPV) faces unique challenges to recruitment and retention. Little is known about successful strategies for recruiting and retaining in research women who have experienced IPV, and their experiences of research participation.

Purpose: This article presents findings on recruitment, retention, and research participation experiences from a longitudinal observational study of IPV among women receiving care through the Veterans Health Administration.

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Background and Purpose- Noninvasive imaging of brain perfusion has the potential to elucidate pathophysiological mechanisms underlying Moyamoya disease and enable clinical imaging of cerebral blood flow (CBF) to select revascularization therapies for patients. We used hybrid positron emission tomography (PET)/magnetic resonance imaging (MRI) technology to characterize the distribution of hypoperfusion in Moyamoya disease and its relationship to vessel stenosis severity, through comparisons with a normative perfusion database of healthy controls. Methods- To image CBF, we acquired [O]-water PET as a reference and simultaneously acquired arterial spin labeling (ASL) MRI scans in 20 Moyamoya patients and 15 age-matched, healthy controls on a PET/MRI scanner.

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Herein we report the preparation of ammonium [C]thiocyanate the reaction of [C]CS with ammonia. The [C]SCN ion is demonstrated as a potent nucleophile that can be used to readily generate a range of C-labelled thiocyanate molecules in high conversions. Furthermore, novel C-labelled thiazolone molecules can be easily prepared from the intermediate α-thiocyanatophenones an acid mediated cyclisation reaction.

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Purpose: There is a strong, unmet need for superior positron emission tomography (PET) imaging agents that are able to measure biochemical processes specific to prostate cancer. Pyruvate kinase M2 (PKM2) catalyzes the concluding step in glycolysis and is a key regulator of tumor growth and metabolism. Elevation of PKM2 expression was detected in Gleason 8-10 tumors compared to Gleason 6-7 carcinomas, indicating that PKM2 may potentially be a marker of aggressive prostate cancer.

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Background: Experience of intimate partner violence (IPV) can have adverse health impacts and has been associated with elevated rates of healthcare service utilization. Healthcare encounters present opportunities to identify IPV-related concerns and connect patients with services. The Veterans Health Administration (VHA) conducts IPV screening within an integrated healthcare system.

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Objective: Veterans Health Administration (VHA) has implemented screening for past-year intimate partner violence (IPV) in some healthcare facilities along with secondary screening of risk for severe violence among those screening positive in order to facilitate follow-up care for high-risk patients. We evaluated the adoption, penetration, and effectiveness of secondary screening as a tool to facilitate timely follow-up services.

Methods: Retrospective review of medical records (screening and healthcare use) of 774 women screening positive for past-year IPV (IPV+) at 11 facilities nationwide from April 2014-April 2016.

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The aim of this study was to develop a positron emission tomography (PET) tracer to visualize and monitor therapeutic response to bacterial infections. In our continued efforts to find maltose based PET tracers that can image bacterial infections, we have designed and prepared 6''-[ F]fluoromaltotriose as a second generation PET imaging tracer targeting the maltodextrin transporter of bacteria. We have developed methods to synthesize 6''-deoxy-6''-[ F]fluoro-α-D-glucopyranosyl-(1-4)-O-α-D-glucopyranosyl-(1-4)-O-D-glucopyranose (6''-[ F]-fluoromaltotriose) as a bacterial infection PET imaging agent.

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