Publications by authors named "Katie White"

60 Publications

White and Black Differences in Perceived Access to Health and Community Services and Self-Rated Health in an Age-Friendly Community Assessment.

J Appl Gerontol 2021 Jun 11:7334648211023251. Epub 2021 Jun 11.

Age-Friendly Innovation Center, Columbus, USA.

Objectives: This study sought to identify the race differences in perceived access to health and community services and self-rated health (SRH) among White and Black older adult participants of an age-friendly community assessment.

Methods: Responses ( = 313) to a baseline assessment of Columbus, Ohio, residents aged ≥50 years were analyzed.

Results: Significant differences were found between White and Black older adults regarding SRH, with Black older adults reporting lower SRH. Black older adults reported significantly lower perceived access to 11 out of the 13 health and community services. There were no significant differences by race regarding ratings of Columbus and personal neighborhoods as a place for people to live as they age. Regression analyses found income was a significant predictor of SRH for both White and Black older adults.

Discussion: Opportunities to increase perceived access and knowledge of health and community services for older adults through targeted, equitable interventions are warranted.
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http://dx.doi.org/10.1177/07334648211023251DOI Listing
June 2021

Reactions to Recommendations and Evidence About Prostate Cancer Screening Among White and Black Male Veterans.

Am J Mens Health 2021 May-Jun;15(3):15579883211022110

Department of Medicine, University of Minnesota Medical School, Minneapolis, MN, USA.

U.S. clinical guidelines recommend that prior to screening for prostate cancer with Prostate Specific Antigen (PSA), men should have an informed discussion about the potential benefits and harms of screening. Prostate cancer disproportionately affects Black men. To understand how White and Black men reacted to a draft educational pamphlet about the benefits and harms of PSA screening, we conducted race-specific focus groups at a midwestern VA medical center in 2013 and 2015. White and Black men who had been previously screened reviewed the draft pamphlet using a semistructured focus group facilitator guide. Forty-four men, ages 55-81, participated in four White and two Black focus groups. Three universal themes were: low baseline familiarity with prostate cancer, surprise and resistance to the recommendations not to test routinely, and negative emotions in response to ambiguity. Discussions of benefits and harms of screening, as well as intentions for exercising personal agency in prevention and screening, diverged between White and Black focus groups. Discussion in White groups highlighted the potential benefits of screening, minimized the harms, and emphasized personal choice in screening decisions. Participants in Black groups devoted almost no discussion to benefits, considered harms significant, and emphasized personal and collective responsibility for preventing cancer through diet, exercise, and alternative medicine. Discussion in Black groups also included the role of racism and discrimination in healthcare and medical research. These findings contribute to our understanding of how men's varied perspectives and life experiences affect their responses to prostate cancer screening information.
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http://dx.doi.org/10.1177/15579883211022110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188983PMC
June 2021

Integrated Behavioral Health Role in Helping Pediatricians Find Long Term Mental Health Interventions with the Use of Assessments.

Pediatr Clin North Am 2021 Jun;68(3):685-705

MD Candidate Class of 2022, Western Michigan University Homer Stryker, MD School of Medicine, 1000 Oakland Drive, Kalamazoo, MI 49008, USA.

This article explores the role of assessments in integrated behavioral health within a pediatric primary care setting, specifically exploring what valid and reliable standardized assessments may be used and for what concerns the assessment be of most use. The article also considers how assessments used by integrated behavioral health may inform the type of evidenced-based intervention that would be most appropriate and efficacious for the patient, as well as assist in determining if longer term or more formal mental health treatment may be required.
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http://dx.doi.org/10.1016/j.pcl.2021.02.006DOI Listing
June 2021

Relationship Between Major Depression Symptom Severity and Sleep Collected Using a Wristband Wearable Device: Multicenter Longitudinal Observational Study.

JMIR Mhealth Uhealth 2021 04 12;9(4):e24604. Epub 2021 Apr 12.

see Acknowledgments, .

Background: Sleep problems tend to vary according to the course of the disorder in individuals with mental health problems. Research in mental health has associated sleep pathologies with depression. However, the gold standard for sleep assessment, polysomnography (PSG), is not suitable for long-term, continuous monitoring of daily sleep, and methods such as sleep diaries rely on subjective recall, which is qualitative and inaccurate. Wearable devices, on the other hand, provide a low-cost and convenient means to monitor sleep in home settings.

Objective: The main aim of this study was to devise and extract sleep features from data collected using a wearable device and analyze their associations with depressive symptom severity and sleep quality as measured by the self-assessed Patient Health Questionnaire 8-item (PHQ-8).

Methods: Daily sleep data were collected passively by Fitbit wristband devices, and depressive symptom severity was self-reported every 2 weeks by the PHQ-8. The data used in this paper included 2812 PHQ-8 records from 368 participants recruited from 3 study sites in the Netherlands, Spain, and the United Kingdom. We extracted 18 sleep features from Fitbit data that describe participant sleep in the following 5 aspects: sleep architecture, sleep stability, sleep quality, insomnia, and hypersomnia. Linear mixed regression models were used to explore associations between sleep features and depressive symptom severity. The z score was used to evaluate the significance of the coefficient of each feature.

Results: We tested our models on the entire dataset and separately on the data of 3 different study sites. We identified 14 sleep features that were significantly (P<.05) associated with the PHQ-8 score on the entire dataset, among them awake time percentage (z=5.45, P<.001), awakening times (z=5.53, P<.001), insomnia (z=4.55, P<.001), mean sleep offset time (z=6.19, P<.001), and hypersomnia (z=5.30, P<.001) were the top 5 features ranked by z score statistics. Associations between sleep features and PHQ-8 scores varied across different sites, possibly due to differences in the populations. We observed that many of our findings were consistent with previous studies, which used other measurements to assess sleep, such as PSG and sleep questionnaires.

Conclusions: We demonstrated that several derived sleep features extracted from consumer wearable devices show potential for the remote measurement of sleep as biomarkers of depression in real-world settings. These findings may provide the basis for the development of clinical tools to passively monitor disease state and trajectory, with minimal burden on the participant.
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http://dx.doi.org/10.2196/24604DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076992PMC
April 2021

Exploration of E. coli contamination drivers in private drinking water wells: An application of machine learning to a large, multivariable, geo-spatio-temporal dataset.

Water Res 2021 Jun 27;197:117089. Epub 2021 Mar 27.

Department of Civil Engineering, McMaster University, 1280 Main St. W, Hamilton, Ontario, L8S 4L8, Canada; Department of Geography and Planning and Global Institute for Water Security, University of Saskatchewan, 117 Science Place, Saskatoon, Saskatchewan, S7N 5C8, Canada.

Groundwater resources are under increasing threats from contamination and overuse, posing direct threats to human and environmental health. The purpose of this study is to better understand drivers of, and relationships between, well and aquifer characteristics, sampling frequencies, and microbiological contamination indicators (specifically E. coli) as a precursor for improving knowledge and tools to assess aquifer vulnerability and well contamination within Ontario, Canada. A dataset with 795, 023 microbiological testing observations over an eight-year period (2010 to 2017) from 253,136 unique wells across Ontario was employed. Variables in this dataset include date and location of test, test results (E. coli concentration), well characteristics (well depth, location), and hydrogeological characteristics (bottom of well stratigraphy, specific capacity). Association rule analysis, univariate and bivariate analyses, regression analyses, and variable discretization techniques were utilized to identify relationships between E. coli concentration and the other variables in the dataset. These relationships can be used to identify drivers of contamination, their relative importance, and therefore potential public health risks associated with the use of private wells in Ontario. Key findings are that: i) bedrock wells completed in sedimentary or igneous rock are more susceptible to contamination events; ii) while shallow wells pose a greater risk to consumers, deep wells are also subject to contamination events and pose a potentially unanticipated risk to health of well users; and, iii) well testing practices are influenced by results of previous tests. Further, while there is a general correlation between months with the greatest testing frequencies and concentrations of E. coli occurring in samples, an offset in this timing is observed in recent years. Testing remains highest in July while peaks in adverse results occur up to three months later. The realization of these trends prompts a need to further explore the bases for such occurrences.
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http://dx.doi.org/10.1016/j.watres.2021.117089DOI Listing
June 2021

Teaching Medical Students to Help Patients Manage Their Weight: Outcomes of an Eight-School Randomized Controlled Trial.

J Gen Intern Med 2021 Apr 9. Epub 2021 Apr 9.

Department of Social and Behavioral Sciences, Harvard School of Public Health, Cambridge, MA, USA.

Background: Given the rising rates of obesity there is a pressing need for medical schools to better prepare students for intervening with patients who have overweight or obesity and for prevention efforts.

Objective: To assess the effect of a multi-modal weight management curriculum on counseling skills for health behavior change.

Design: A pair-matched, group-randomized controlled trial (2015-2020) included students enrolled in eight U.S. medical schools randomized to receive either multi-modal weight management education (MME) or traditional weight management education (TE).

Setting/participants: Students from the class of 2020 (N=1305) were asked to participate in an objective structured clinical examination (OSCE) focused on weight management counseling and complete pre and post surveys. A total of 70.1% of eligible students (N=915) completed the OSCE and 69.3% (N=904) completed both surveys.

Interventions: The MME implemented over three years included a web-based course, a role-play classroom exercise, a web-patient encounter with feedback, and an enhanced clerkship experience with preceptors trained in weight management counseling (WMC). Counseling focused on the 5As (Ask, Advise, Assess, Assist, Arrange) and patient-centeredness.

Measurements: The outcome was student 5As WMC skills assessed using an objective measure, an OSCE, scored using a behavior checklist, and a subjective measure, student self-reported skills for performing the 5As.

Results: Among MME students who completed two of three WMC components compared to those who completed none, exposure was significantly associated with higher OSCE scores and self-reported 5A skills.

Limitations: Variability in medical schools requiring participation in the WMC curriculum.

Conclusions: This trial revealed that medical students struggle with delivering weight management counseling to their patients who have overweight or obesity. Medical schools, though restrained in adding curricula, should incorporate should incorporate multiple WMC curricula components early in medical student education to provide knowledge and build confidence for supporting patients in developing individualized plans for weight management.

Nih Trial Registry Number: R01-194787.
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http://dx.doi.org/10.1007/s11606-020-06571-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034040PMC
April 2021

Remote Measurement in Rheumatoid Arthritis: Qualitative Analysis of Patient Perspectives.

JMIR Form Res 2021 Mar 9;5(3):e22473. Epub 2021 Mar 9.

Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.

Background: Rheumatoid arthritis (RA) is characterized by recurrent fluctuations in symptoms such as joint pain, swelling, and stiffness. Remote measurement technologies (RMTs) offer the opportunity to track symptoms continuously and in real time; therefore, they may provide a more accurate picture of RA disease activity as a complement to prescheduled general practitioner appointments. Previous research has shown patient interest in remote symptom tracking in RA and has provided evidence for its clinical validity. However, there is a lack of co-design in the current development of systems, and the features of RMTs that best promote optimal engagement remain unclear.

Objective: This study represents the first in a series of work that aims to develop a multiparametric RMT system for symptom tracking in RA. The objective of this study is to determine the important outcomes for disease management in patients with RA and how these can be best captured via remote measurement.

Methods: A total of 9 patients (aged 23-77 years; mean 55.78, SD 17.54) with RA were recruited from King's College Hospital to participate in two semistructured focus groups. Both focus group discussions were conducted by a facilitator and a lived-experience researcher. The sessions were recorded, transcribed, independently coded, and analyzed for themes.

Results: Thematic analysis identified a total of four overarching themes: important symptoms and outcomes in RA, management of RA symptoms, views on the current health care system, and views on the use of RMTs in RA. Mobility and pain were key symptoms to consider for symptom tracking as well as symptom triggers. There is a general consensus that the ability to track fluctuations and transmit such data to clinicians would aid in individual symptom management and the effectiveness of clinical care. Suggestions for visually capturing symptom fluctuations in an app were proposed.

Conclusions: The findings support previous work on the acceptability of RMT with RA disease management and address key outcomes for integration into a remote monitoring system for RA self-management and clinical care. Clear recommendations for RMT design are proposed. Future work will aim to take these recommendations into a user testing phase.
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http://dx.doi.org/10.2196/22473DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7988394PMC
March 2021

: The Challenges and Benefits of Formal Volunteering among Low-Income Diverse Older Adults.

J Gerontol Soc Work 2021 Jun 8;64(4):388-404. Epub 2021 Mar 8.

Age Friendly Columbus and Franklin County, Blackburn Community Recreation Center, Columbus, Ohio, United States.

Volunteering is often considered an important component of productive and active aging. Although there is a rich body of literature on the predictors and outcomes of volunteering among the general older adults in the United States (U.S.), few studies have explored the unique volunteering experiences of culturally and linguistically diverse older adults. Given the growing number of diverse older adults and the importance of optimizing their contributions to society, this study investigates the challenges and benefits of volunteering among low-income diverse older adults. We conducted eight 90-minute focus groups in six languages (English, Nepali, Khmer, Somali, Russian, and Chinese) with 70 older volunteers attending a Senior Companions monthly training in a U.S. Midwestern metropolitan area. Data analysis followed the Rapid and Rigorous Qualitative Data Analysis (RADaR) technique and thematic analysis through an interactive team approach. Three overarching themes highlighted the of volunteering: (1) transportation, (2) community emergencies and workload, and (3) family caregiving; and three themes reflected the of volunteering: (1) stress-relief, (2) training and information, and (3) peer support and socialization. Study findings shed light on diverse older adults' unique volunteering experiences with implications for recruitment and retention.
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http://dx.doi.org/10.1080/01634372.2021.1897723DOI Listing
June 2021

In chronic infection, HIV gag-specific CD4+ T cell receptor diversity is higher than CD8+ T cell receptor diversity and is associated with less HIV quasispecies diversity.

J Virol 2021 Feb 3. Epub 2021 Feb 3.

Vanderbilt University Medical Center, Department of Internal Medicine, Nashville, TN 38232

Cellular immune responses to Gag correlate with improved HIV viral control. The full extent of cellular immune responses comprise both the number of epitopes recognized by CD4+ and CD8+ T cells, as well as the diversity of the T cell receptor (TCR) repertoire directed against each epitope. The optimal diversity of the responsive TCR repertoire is unclear. Therefore, we evaluated the TCR diversity of CD4+ and CD8+ T cells responding to HIV-1 Gag to determine if TCR diversity correlates with clinical or virologic metrics. Previous studies of TCR repertoires have been limited primarily to CD8+ T cell responses directed against a small number of well-characterized T cell epitopes restricted by specific human leucocyte antigens. We stimulated peripheral blood mononuclear cells from 21chronic HIV-infected individuals overnight with a pool of HIV-1 Gag peptides, followed by sorting of activated CD4+ and CD8+ T cells and TCR deep sequencing. We found Gag-reactive CD8+ T cells to be more oligoclonal, with a few dominant TCRs comprising the bulk of the repertoire, compared to the highly diverse TCR repertoires of Gag-reactive CD4+ T cells. HIV viral sequencing of the same donors revealed that high CD4+ T cell TCR diversity was strongly associated with lower HIV Gag genetic diversity. We conclude that the TCR repertoire of Gag-reactive CD4+ T helper cells display substantial diversity without a clearly dominant circulating TCR clonotype, in contrast to a hierarchy of dominant TCR clonotypes in the Gag-reactive CD8+ T cells, and may serve to limit HIV diversity during chronic infection. Human T cells recognize portions of viral proteins bound to host molecules (human leucocyte antigens) on the surface of infected cells. T cells recognize these foreign proteins through their T cell receptors (TCRs), which are formed by the assortment of several available V, D and J genes to create millions of combinations of unique TCRs. We measured the diversity of T cells responding to the HIV Gag protein. We found the CD8+ T cell response is primarily made up of a few dominant unique TCRs whereas the CD4+ T cell subset has a much more diverse repertoire of TCRs. We also found there was less change in the virus sequences in subjects with more diverse TCR repertoires. HIV has a high mutation rate, which allows it to evade the immune response. Our findings describe the characteristics of a virus-specific T cell response that may allow it to limit viral evolution.
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http://dx.doi.org/10.1128/JVI.02380-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8103689PMC
February 2021

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

JAMA 2020 10;324(13):1317-1329

School of Medicine and Pharmacology, University of Western Australia, Crawley, Western Australia, Australia.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited.

Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19.

Design, Setting, And Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020.

Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108).

Main Outcomes And Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%).

Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively.

Conclusions And Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions.

Trial Registration: ClinicalTrials.gov Identifier: NCT02735707.
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http://dx.doi.org/10.1001/jama.2020.17022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7489418PMC
October 2020

Toner Particles as Forensic Evidence: Microanalytical Characterization of Known Toner and Recognition of Toner in Environmental Samples* † ‡.

J Forensic Sci 2020 Nov 20;65(6):1908-1920. Epub 2020 Jul 20.

Microtrace, LLC, 790 Fletcher Drive, Suite 106, Elgin, IL, 60123.

Modern printing toners represent a prime example of subvisible particles that can be easily transferred to hands, clothing, and other surfaces. To explore the potential evidentiary value of toner particles, toner samples were collected from known printer cartridges and characterized by various microanalytical techniques to establish the properties most useful for recognition, identification, and comparison. Environmental samples (i.e., dust) were then collected from various locations at varying distances from toner-based printers, using both tape lifts and carbon adhesive stubs, to assess the possibility of detecting toner. By light microscopy, toner can be recognized on the basis of particle size and shape, as well as color. Further examination of the micromorphology in the field emission scanning electron microscope reveals characteristic morphologies and differences in surface texture and shape among toner sources. Raman spectroscopy provides chemical identification of the pigment (or pigment class) and, in some cases, also permits identification of the polymer component. While black and blue pigment chemistry remained constant among toner varieties that were studied (copper phthalocyanine and carbon black), variation in yellow and magenta pigments was observed. Analysis of dust samples collected from various environments demonstrated that while toner is consistently detectable in close proximity to printers (within 2 feet), it also can be detected in dust collected in nearby rooms. This research demonstrates that toner particles can be located, characterized, and discriminated, using a suite of microanalytical methods that are applicable to forensic casework.
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http://dx.doi.org/10.1111/1556-4029.14501DOI Listing
November 2020

Using Community-Based Participatory Research Strategies in Age-Friendly Communities to Solve Mobility Challenges.

J Gerontol Soc Work 2020 07 27;63(5):447-463. Epub 2020 May 27.

Age-Friendly Communities, Columbus and Franklin County, College of Social Work, The Ohio State University , Columbus, Ohio, USA.

The number of older adults is steadily increasing in the United States and across the globe. Aging is linked to an increased risk of disability. Disabilities that limit one or more major life activities such as seeing, hearing, walking, and motor skills impact a person's ability to drive a car. Low utilization of alternative transportation by older adults and people with disabilities may put them at risk for social isolation. Social isolation is associated with a variety of negative health outcomes. While communities are challenged to create available, acceptable, accessible, adaptable and affordable mobility options, there are widely held, inaccurate biases around older adults' abilities to contribute to the development and improvement of alternative transportation options. Gerontological social workers are well-positioned to address this bias. This paper presents a case study of a large metropolitan county in the Midwest where community-based participatory research (CBPR) strategies were used to engage older residents to support the development of alternative transportation options supporting the tenets of environmental justice.
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http://dx.doi.org/10.1080/01634372.2020.1769787DOI Listing
July 2020

Implementation of a Standardized Template for Reporting of Incidental Pulmonary Nodules: Feasibility, Acceptability, and Outcomes.

J Am Coll Radiol 2020 Feb 17;17(2):216-223. Epub 2019 Dec 17.

Section of Pulmonary, Allergy Sleep and Critical Care, Minneapolis VA Health Care System, Minneapolis, Minnesota; Department of Medicine, Division of Pulmonary and Critical Care, University of Minnesota School of Medicine, Minneapolis, Minnesota. Electronic address:

Objective: Incidental pulmonary nodules (IPNs) are common. Up to 70% are not followed up according to current guidelines. Follow-up recommendations are based on the characteristics of the patient and the IPN. However, many IPNs are incompletely characterized in CT reports. Structured radiology reports have been shown to reduce missing information. We sought to improve IPN reporting by assessing the feasibility, acceptability, and effectiveness of a structured dictation template to increase the presence of six key nodule descriptors.

Methods: We performed a mixed methods, pre- and postimplementation assessment. A template was developed with a multidisciplinary group based on Fleischner Society guidelines. A standardized checklist was used to determine the presence of documented descriptors pre- and postimplementation for sequential radiology reports of patients with an IPN present (n = 400 pre-implementation and n = 400 postimplementation) on a CT performed at the Minneapolis Veterans Affairs Health Care System. We conducted qualitative interviews with radiologists (n = 4) and members of the lung nodule tracking team (n = 2) to elicit their experiences of the template implementation process.

Results: The proportion of radiology reports including all six elements increased from 12% to 47% (P < .001). Postimplementation, the template was used in 40% of interpretations involving lung nodules, 67% of follow-up scans, and 8% of initial identifications. Response to the template was overall positive.

Discussion: Use of a dictation template seems to be effective in increasing compliance with full IPN documentation, streamlining the follow-up process. Low utilization rates of the template for initial nodule identification is a limitation, which may be combated through clearer communication and advances in technology.
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http://dx.doi.org/10.1016/j.jacr.2019.11.013DOI Listing
February 2020

The Genetic Links to Anxiety and Depression (GLAD) Study: Online recruitment into the largest recontactable study of depression and anxiety.

Behav Res Ther 2019 12 24;123:103503. Epub 2019 Oct 24.

Institute of Psychiatry, Psychology and Neuroscience, King's College London, Denmark Hill, Camberwell, London, UK; UK National Institute for Health Research (NIHR) Biomedical Research Centre, South London and Maudsley Hospital, London, UK.

Background: Anxiety and depression are common, debilitating and costly. These disorders are influenced by multiple risk factors, from genes to psychological vulnerabilities and environmental stressors, but research is hampered by a lack of sufficiently large comprehensive studies. We are recruiting 40,000 individuals with lifetime depression or anxiety and broad assessment of risks to facilitate future research.

Methods: The Genetic Links to Anxiety and Depression (GLAD) Study (www.gladstudy.org.uk) recruits individuals with depression or anxiety into the NIHR Mental Health BioResource. Participants invited to join the study (via media campaigns) provide demographic, environmental and genetic data, and consent for medical record linkage and recontact.

Results: Online recruitment was effective; 42,531 participants consented and 27,776 completed the questionnaire by end of July 2019. Participants' questionnaire data identified very high rates of recurrent depression, severe anxiety, and comorbidity. Participants reported high rates of treatment receipt. The age profile of the sample is biased toward young adults, with higher recruitment of females and the more educated, especially at younger ages.

Discussion: This paper describes the study methodology and descriptive data for GLAD, which represents a large, recontactable resource that will enable future research into risks, outcomes, and treatment for anxiety and depression.
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http://dx.doi.org/10.1016/j.brat.2019.103503DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6891252PMC
December 2019

Single-cell transcriptomics reveal polyclonal memory T-cell responses in skin with positive abacavir patch test results.

J Allergy Clin Immunol 2019 11 28;144(5):1413-1416.e7. Epub 2019 Sep 28.

Institute for Immunology and Infectious Diseases, Murdoch University, Murdoch, Australia; Department of Medicine, Vanderbilt University Medical Center, Nashville, Tenn; Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tenn; Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tenn. Electronic address:

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http://dx.doi.org/10.1016/j.jaci.2019.09.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7051072PMC
November 2019

Identification of drug-specific public TCR driving severe cutaneous adverse reactions.

Nat Commun 2019 08 8;10(1):3569. Epub 2019 Aug 8.

Cancer Vaccine and Immune Cell Therapy Core Laboratory, Chang Gung Immunology Consortium, Chang Gung Memorial Hospital, Linkou, Taoyuan, 333, Taiwan.

Drug hypersensitivity such as severe cutaneous adverse reactions (SCAR), including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), could be life-threatening. Here, we enroll SCAR patients to investigate the T cell receptor (TCR) repertoire by next-generation sequencing. A public αβTCR is identified from the cytotoxic T lymphocytes of patients with carbamazepine-SJS/TEN, with its expression showing drug/phenotype-specificity and an bias for HLA-B*15:02. This public αβTCR has binding affinity for carbamazepine and its structural analogs, thereby mediating the immune response. Adoptive transfer of T cell expressing this public αβTCR to HLA-B*15:02 transgenic mice receiving oral administration of carbamazepine induces multi-organ injuries and symptoms mimicking SCAR, including hair loss, erythema, increase of inflammatory lymphocytes in the skin and blood, and liver and kidney dysfunction. Our results not only demonstrate an essential role of TCR in the immune synapse mediating SCAR, but also implicate potential clinical applications and development of therapeutics.
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http://dx.doi.org/10.1038/s41467-019-11396-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6687717PMC
August 2019

Age-friendly communities and perceived disconnectedness: the role of built environment and social engagement.

J Aging Health 2020 10 26;32(9):937-948. Epub 2019 Jul 26.

The Ohio State University, Columbus, OH, USA.

To examine the effect of access to outdoor space and buildings and social or community events on elders' perceived disconnectedness. Data were from a representative survey conducted as part of an age-friendly community initiative in a large midwestern city in the United States. Hierarchical logistic regression was employed to examine the relationships between environment, engagement, and connection. Having access to ramps to enter buildings reduced the odds of perceived disconnectedness by 79%, participation in social or community events reduced the odds of perceived disconnectedness by 83%. The odds of perceived disconnectedness for elders "not sure" of their access to public buildings were around 6 times that of those without access, holding all else constant. Ensuring access to ramps to enter buildings, disseminating information about the accessibility of parks and buildings, and social or community events may reduce elders' perceived disconnectedness.
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http://dx.doi.org/10.1177/0898264319865421DOI Listing
October 2020

Access to Employment, Volunteer Activities, and Community Events and Perceptions of Age-Friendliness: The Role of Social Connectedness.

J Appl Gerontol 2020 09 5;39(9):1016-1024. Epub 2019 May 5.

The Ohio State University, Columbus, USA.

The aim of this study was to investigate the direct and indirect effects of access to employment, volunteer opportunities, and community events on older adults' perception of age-friendliness and feelings of connectedness. Data were from an age-friendly community survey conducted in a Midwestern city in the United States. We analyzed the responses of 264 older adult residents (50 years and older) using path analysis. Results showed that access to community events, job resources, and connectedness were predictors of older adults' perceptions of age-friendliness of their community, and that connectedness mediated the relationship between access to community events and perceived age-friendliness. The findings help to refine the concept of an age-friendly community from older adults' perspectives and emphasize the importance of fostering interactions through community events to enhance older adults' feelings of connectedness.
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http://dx.doi.org/10.1177/0733464819847588DOI Listing
September 2020

HLA-A*32:01 is strongly associated with vancomycin-induced drug reaction with eosinophilia and systemic symptoms.

J Allergy Clin Immunol 2019 07 16;144(1):183-192. Epub 2019 Feb 16.

Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tenn; Institute for Immunology and Infectious Diseases, Murdoch University, Murdoch, Australia; Division of Infectious Diseases, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tenn; Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tenn. Electronic address:

Background: Vancomycin is a prevalent cause of the severe hypersensitivity syndrome drug reaction with eosinophilia and systemic symptoms (DRESS), which leads to significant morbidity and mortality and commonly occurs in the setting of combination antibiotic therapy, affecting future treatment choices. Variations in HLA class I in particular have been associated with serious T cell-mediated adverse drug reactions, which has led to preventive screening strategies for some drugs.

Objective: We sought to determine whether variation in the HLA region is associated with vancomycin-induced DRESS.

Methods: Probable vancomycin-induced DRESS cases were matched 1:2 with tolerant control subjects based on sex, race, and age by using BioVU, Vanderbilt's deidentified electronic health record database. Associations between DRESS and carriage of HLA class I and II alleles were assessed by means of conditional logistic regression. An extended sample set from BioVU was used to conduct a time-to-event analysis of those exposed to vancomycin with and without the identified HLA risk allele.

Results: Twenty-three subjects met the inclusion criteria for vancomycin-associated DRESS. Nineteen (82.6%) of 23 cases carried HLA-A*32:01 compared with 0 (0%) of 46 of the matched vancomycin-tolerant control subjects (P = 1 × 10) and 6.3% of the BioVU population (n = 54,249, P = 2 × 10). Time-to-event analysis of DRESS development during vancomycin treatment among the HLA-A*32:01-positive group indicated that 19.2% had DRESS and did so within 4 weeks.

Conclusions: HLA-A*32:01 is strongly associated with vancomycin-induced DRESS in a population of predominantly European ancestry. HLA-A*32:01 testing could improve antibiotic safety, help implicate vancomycin as the causal drug, and preserve future treatment options with coadministered antibiotics.
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http://dx.doi.org/10.1016/j.jaci.2019.01.045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6612297PMC
July 2019

Substantial Dysregulation of miRNA Passenger Strands Underlies the Vascular Response to Injury.

Cells 2019 01 23;8(2). Epub 2019 Jan 23.

Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow G12 8TA, UK.

Vascular smooth muscle cell (VSMC) dedifferentiation is a common feature of vascular disorders leading to pro-migratory and proliferative phenotypes, a process induced through growth factor and cytokine signaling cascades. Recently, many studies have demonstrated that small non-coding RNAs (miRNAs) can induce phenotypic effects on VSMCs in response to vessel injury. However, most studies have focused on the contribution of individual miRNAs. Our study aimed to conduct a detailed and unbiased analysis of both guide and passenger miRNA expression in vascular cells in vitro and disease models in vivo. We analyzed 100 miRNA stem loops by TaqMan Low Density Array (TLDA) from primary VSMCs in vitro. Intriguingly, we found that a larger proportion of the passenger strands was significantly dysregulated compared to the guide strands after exposure to pathological stimuli, such as platelet-derived growth factor (PDGF) and IL-1α. Similar findings were observed in response to injury in porcine vein grafts and stent models in vivo. In these studies, we reveal that the miRNA passenger strands are predominantly dysregulated in response to vascular injury.
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http://dx.doi.org/10.3390/cells8020083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6406808PMC
January 2019

Applications of Immunopharmacogenomics: Predicting, Preventing, and Understanding Immune-Mediated Adverse Drug Reactions.

Annu Rev Pharmacol Toxicol 2019 01 22;59:463-486. Epub 2018 Aug 22.

Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA; email:

Adverse drug reactions (ADRs) are a significant health care burden. Immune-mediated adverse drug reactions (IM-ADRs) are responsible for one-fifth of ADRs but contribute a disproportionately high amount of that burden due to their severity. Variation in human leukocyte antigen ( HLA) genes has emerged as a potential preprescription screening strategy for the prevention of previously unpredictable IM-ADRs. Immunopharmacogenomics combines the disciplines of immunogenomics and pharmacogenomics and focuses on the effects of immune-specific variation on drug disposition and IM-ADRs. In this review, we present the latest evidence for HLA associations with IM-ADRs, ongoing research into biological mechanisms of IM-ADRs, and the translation of clinical actionable biomarkers for IM-ADRs, with a focus on T cell-mediated ADRs.
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http://dx.doi.org/10.1146/annurev-pharmtox-010818-021818DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6409210PMC
January 2019

SJS/TEN 2017: Building Multidisciplinary Networks to Drive Science and Translation.

J Allergy Clin Immunol Pract 2018 Jan - Feb;6(1):38-69

University Paris-Est-Créteil, Créteil, France.

Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a life-threatening, immunologically mediated, and usually drug-induced disease with a high burden to individuals, their families, and society with an annual incidence of 1 to 5 per 1,000,000. To effect significant reduction in short- and long-term morbidity and mortality, and advance clinical care and research, coordination of multiple medical, surgical, behavioral, and basic scientific disciplines is required. On March 2, 2017, an investigator-driven meeting was held immediately before the American Academy of Dermatology Annual meeting for the central purpose of assembling, for the first time in the United States, clinicians and scientists from multiple disciplines involved in SJS/TEN clinical care and basic science research. As a product of this meeting, this article summarizes the current state of knowledge and expert opinion related to SJS/TEN covering a broad spectrum of topics including epidemiology and pharmacogenomic networks; clinical management and complications; special populations such as pediatrics, the elderly, and pregnant women; regulatory issues and the electronic health record; new agents that cause SJS/TEN; pharmacogenomics and immunopathogenesis; and the patient perspective. Goals include the maintenance of a durable and productive multidisciplinary network that will significantly further scientific progress and translation into prevention, early diagnosis, and management of SJS/TEN.
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http://dx.doi.org/10.1016/j.jaip.2017.11.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5857362PMC
October 2019

Severe Delayed Drug Reactions: Role of Genetics and Viral Infections.

Immunol Allergy Clin North Am 2017 11;37(4):785-815

Institute for Immunology and Infectious Diseases, Murdoch University, 6150 Murdoch, Western Australia, Australia; Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN, USA. Electronic address:

Adverse drug reactions (ADRs) are a significant source of patient morbidity and mortality and represent a major burden to health care systems and drug development. Up to 50% of such reactions are preventable. Although many ADRs can be predicted based on the on-target pharmacologic activity, ADRs arising from drug interactions with off-target receptors are recognized. Off-target ADRs include the immune-mediated ADRs (IM-ADRs) and pharmacologic drug effects. In this review, we discuss what is known about the immunogenetics and pathogenesis of IM-ADRs and the hypothesized role of heterologous immunity in the development of IM-ADRs.
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http://dx.doi.org/10.1016/j.iac.2017.07.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5702581PMC
November 2017

A mixed methods study of emotional exhaustion: Energizing and depleting work within an innovative healthcare team.

J Interprof Care 2017 Nov 18;31(6):714-724. Epub 2017 Sep 18.

e Minneapolis , MN , USA.

This mixed methods study documents emotional exhaustion experiences among care team members during the development of an innovative team approach for caring for adults with serious illness. A mixed methods study design was employed to examine depleting work experiences that may produce emotional exhaustion, and energizing aspects of the work that may increase meaningfulness of work, thus reducing emotional exhaustion. The population studied included team members involved in care for adults with serious illness (n = 18). Team members were surveyed quarterly over an 18-month period using the Maslach Burnout Inventory (MBI). The MBI measures burnout, defined as the inability to continue work because of the interactional toll of the work. Analyses of MBI data show that although overall levels of burnout are low, 89% of team members reported moderate/high levels of emotional exhaustion during at least one survey period. In order to understand the kinds of work experiences that may produce or ameliorate emotional exhaustion, qualitative interviews were also conducted with team members at the end of the 18-month period. Major qualitative findings indicate that disputes within the team, environmental pressures, and standardisation of meaningful work leave team members feeling depleted. Having authentic relationships with patients, working as a team, believing in the care model, and practicing autonomy and creativity help team members to restore their emotional energy. Supports for team members' well-being are critical for continued innovation. We conclude with recommendations for improving team members' well-being.
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http://dx.doi.org/10.1080/13561820.2017.1356809DOI Listing
November 2017

"This Is What Family Does": The Family Experience of Caring for Serious Illness.

Am J Hosp Palliat Care 2018 Feb 30;35(2):348-354. Epub 2017 Jun 30.

2 Division of Health Policy & Management, University of Minnesota School of Public Health, Minneapolis, MN, USA.

Background: As the demographics of caregiving in United States evolve toward multigenerational, distributed family structures, the ways in which individuals and their families experience serious illness are changing. As part of a project to create an innovative model of supportive care for serious illness, a series of user interviews were conducted, forming the basis for this article.

Objective: To understand the experience of caregiving for individuals with serious illness from an intergenerational family perspective.

Methods: Twelve semistructured group interviews were conducted with patients, families, and professionals. Transcript data were analyzed with descriptive coding, looking for major themes and subthemes related to family experiences.

Results: Seventy-three individuals participated in group interview sessions. While both families and individuals encountered caregiving challenges, the family unit experienced care in several unique ways. It accommodated differences in temperament and readiness, managed internal conflict, and strived to emerge as a cohesive unit. Individual struggles were often magnified or, more often, ameliorated by family context. Caregiving itself formed a legacy for future generations. Finally, care was seen as bidirectional, being tendered both by the family caregivers and in turn by the patient.

Conclusions: When talking about care for serious illness, individuals report both rewards and challenges, often in a family context. The family enterprise manages a loved one's care, negotiates the health-care system, and adjusts its own internal dynamics. Integrating the family narrative provides a more balanced view of the family system that provides the day-to-day care for individuals with serious illness.
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http://dx.doi.org/10.1177/1049909117709251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5768255PMC
February 2018

Severe Delayed Cutaneous and Systemic Reactions to Drugs: A Global Perspective on the Science and Art of Current Practice.

J Allergy Clin Immunol Pract 2017 May - Jun;5(3):547-563

Department of Medicine, Vanderbilt University Medical Center, Nashville, Tenn; Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tenn; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tenn; Institute for Immunology & Infectious Diseases, Murdoch University, Murdoch, Western Australia, Australia. Electronic address:

Most immune-mediated adverse drug reactions (IM-ADRs) involve the skin, and many have additional systemic features. Severe cutaneous adverse drug reactions (SCARs) are an uncommon, potentially life-threatening, and challenging subgroup of IM-ADRs with diverse clinical phenotypes, mechanisms, and offending drugs. T-cell-mediated immunopathology is central to these severe delayed reactions, but effector cells and cytokines differ by clinical phenotype. Strong HLA-gene associations have been elucidated for specific drug-SCAR IM-ADRs such as Stevens-Johnson syndrome/toxic epidermal necrolysis, although the mechanisms by which carriage of a specific HLA allele is necessary but not sufficient for the development of many IM-ADRs is still being defined. SCAR management is complicated by substantial short- and long-term morbidity/mortality and the potential need to treat ongoing comorbid disease with related medications. Multidisciplinary specialist teams at experienced units should care for patients. In the setting of SCAR, patient outcomes as well as preventive, diagnostic, treatment, and management approaches are often not generalizable, but rather context specific, driven by population HLA-genetics, the pharmacology and genetic risk factors of the implicated drug, severity of underlying comorbid disease necessitating ongoing treatments, and cost considerations. In this review, we update the basic and clinical science of SCAR diagnosis and management.
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http://dx.doi.org/10.1016/j.jaip.2017.01.025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5424615PMC
February 2018

"It Has Changed My Life": An Exploration of Caregiver Experiences in Serious Illness.

Am J Hosp Palliat Care 2018 Feb 16;35(2):266-274. Epub 2017 Apr 16.

2 Division of Health Policy & Management, University of Minnesota School of Public Health, Minneapolis, MN, USA.

Background: Informal, unpaid caregivers shoulder much of the care burden for individuals with serious illness. As part of a project to create an innovative model of supportive care for serious illness, a series of user interviews were conducted, forming the basis for this article.

Objective: To understand both individual and interpersonal aspects of caregiving for serious illness.

Methods: Twelve semistructured group interviews were conducted with patients, families, and professionals as part of a larger study of late-life serious illness. Transcript data were analyzed with descriptive coding, and then coded material was analyzed to elicit major themes and subthemes.

Results: A total of 73 individuals participated in group interview sessions. Using descriptive coding, quotes were assigned to first-order codes of rewards, challenges, and a category of learnings and adaptations. Subthemes of reward included gratitude, a sense of accomplishment or mastery, and closeness in personal relationships. The most oft-cited challenges included emotional and physical stresses of caregiving and feeling unprepared or unsupported in caregiving. Reflecting on their experiences, caregivers cited new ways in which they had learned to be creative, to show assertiveness and advocacy, and to create personal balance in a demanding situation.

Conclusions: The experience of caregiving is a life-altering journey as individuals rise to challenges and reflect on the rewards. Caregivers described intensive caregiving, often without acknowledgment or understanding of their role from the health-care system. This invisibility created its own iatrogenic caregiving challenge. The identified themes suggest avenues of meaningful caregiver support that bear further exploration.
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http://dx.doi.org/10.1177/1049909117701895DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5768253PMC
February 2018

Defining a Novel Role for the Coxsackievirus and Adenovirus Receptor in Human Adenovirus Serotype 5 Transduction in the Presence of Mouse Serum.

J Virol 2017 06 26;91(12). Epub 2017 May 26.

Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom

Human adenoviral serotype 5 (HAdV-5) vectors have predominantly hepatic tropism when delivered intravascularly, resulting in immune activation and toxicity. Coagulation factor X (FX) binding to HAdV-5 mediates liver transduction and provides protection from virion neutralization in mice. FX is dispensable for liver transduction in mice lacking IgM antibodies or complement, suggesting that alternative transduction pathways exist. To identify novel factor(s) mediating HAdV-5 FX-independent entry, we investigated HAdV-5 transduction in the presence of serum from immunocompetent C57BL/6 or immunocompromised mice lacking IgM antibodies (Rag 2 and NOD-scid-gamma [NSG]). Sera from all three mouse strains enhanced HAdV-5 transduction of A549 cells. While inhibition of HAdV-5-FX interaction with FX-binding protein (X-bp) inhibited transduction in the presence of C57BL/6 serum, it had negligible effect on the enhanced transduction observed in the presence of Rag 2 or NSG serum. Rag 2 serum also enhanced transduction of the FX binding-deficient HAdV-5HVR5*HVR7*E451Q (AdT*). Interestingly, Rag 2 serum enhanced HAdV-5 transduction in a FX-independent manner in CHO-CAR and SKOV3-CAR cells (CHO or SKOV3 cells transfected to stably express human coxsackievirus and adenovirus receptor [CAR]). Additionally, blockade of CAR with soluble HAdV-5 fiber knob inhibited mouse serum-enhanced transduction in A549 cells, suggesting a potential role for CAR. Transduction of HAdV-5 KO1 and HAdV-5/F35 (CAR binding deficient) in the presence of Rag 2 serum was equivalent to that of HAdV-5, indicating that direct interaction between HAdV-5 and CAR is not required. These data suggest that FX may protect HAdV-5 from neutralization but has minimal contribution to HAdV-5 transduction in the presence of immunocompromised mouse serum. Alternatively, transduction occurs via an unidentified mouse serum protein capable of bridging HAdV-5 to CAR. The intravascular administration of HAdV-5 vectors can result in acute liver toxicity, transaminitis, thrombocytopenia, and injury to the vascular endothelium, illustrating challenges yet to overcome for HAdV-5-mediated systemic gene therapy. The finding that CAR and potentially an unidentified factor present in mouse serum might be important mediators of HAdV-5 transduction highlights that a better understanding of the complex biology defining the interplay between adenovirus immune recognition and cellular uptake mechanisms is still required. These findings are important to inform future optimization and development of HAdV-5-based adenoviral vectors for gene therapy.
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http://dx.doi.org/10.1128/JVI.02487-16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5446653PMC
June 2017

Pharmacogenomics of off-target adverse drug reactions.

Br J Clin Pharmacol 2017 Sep 27;83(9):1896-1911. Epub 2017 Apr 27.

Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.

Off-target adverse drug reactions (ADRs) are associated with significant morbidity and costs to the healthcare system, and their occurrence is not predictable based on the known pharmacological action of the drug's therapeutic effect. Off-target ADRs may or may not be associated with immunological memory, although they can manifest with a variety of shared clinical features, including maculopapular exanthema, severe cutaneous adverse reactions (SCARs), angioedema, pruritus and bronchospasm. Discovery of specific genes associated with a particular ADR phenotype is a foundational component of clinical translation into screening programmes for their prevention. In this review, genetic associations of off-target drug-induced ADRs that have a clinical phenotype suggestive of an immunologically mediated process and their mechanisms are highlighted. A significant proportion of these reactions lack immunological memory and current data are informative for these ADRs with regard to disease pathophysiology, therapeutic targets and biomarkers which may identify patients at greatest risk. Although many serious delayed immune-mediated (IM)-ADRs show strong human leukocyte antigen associations, only a small subset have successfully been implemented in screening programmes. More recently, other factors, such as drug metabolism, have been shown to contribute to the risk of the IM-ADR. In the future, pharmacogenomic targets and an understanding of how they interact with drugs to cause ADRs will be applied to drug design and preclinical testing, and this will allow selection of optimal therapy to improve patient safety.
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http://dx.doi.org/10.1111/bcp.13294DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5555876PMC
September 2017
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