Publications by authors named "James Harrison"

307 Publications

A Novel Surgical Technique for Glenoid Reconstruction in the Trauma Setting With a Distal Tibia Allograft: A Case Report.

JBJS Case Connect 2020 Dec 10;10(4):e20.00184. Epub 2020 Dec 10.

Department of Orthopaedic Surgery, Naval Medical Center Portsmouth, Virginia.

Case: A 21-year-old woman presented with a chronic fracture dislocation of her left shoulder after striking a submerged tree during a watersport activity. She was initially treated at an outside hospital, where she underwent open reduction and internal fixation of her posterior scapula. She presented 8 weeks after index procedure with pain and severely decreased range of motion. Her comminuted and displaced fracture comprising 70% of the anterior superior glenoid was surgically reconstructed using a distal tibia allograft (DTA), resulting in a functional shoulder.

Conclusion: A DTA is a feasible option to reconstruct the glenoid surface in fracture dislocations of the shoulder with a significant loss of the articular surface.
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http://dx.doi.org/10.2106/JBJS.CC.20.00184DOI Listing
December 2020

Introduction to Artificial Intelligence and Machine Learning for Pathology.

Arch Pathol Lab Med 2021 Jan 25. Epub 2021 Jan 25.

the Department of Forensic Medicine, New York University, and Office of Chief Medical Examiner, New York, New York (Stram).

Context.—: Recent developments in machine learning have stimulated intense interest in software that may augment or replace human experts. Machine learning may impact pathology practice by offering new capabilities in analysis, interpretation, and outcomes prediction using images and other data. The principles of operation and management of machine learning systems are unfamiliar to pathologists, who anticipate a need for additional education to be effective as expert users and managers of the new tools.

Objective.—: To provide a background on machine learning for practicing pathologists, including an overview of algorithms, model development, and performance evaluation; to examine the current status of machine learning in pathology and consider possible roles and requirements for pathologists in local deployment and management of machine learning systems; and to highlight existing challenges and gaps in deployment methodology and regulation.

Data Sources.—: Sources include the biomedical and engineering literature, white papers from professional organizations, government reports, electronic resources, and authors' experience in machine learning. References were chosen when possible for accessibility to practicing pathologists without specialized training in mathematics, statistics, or software development.

Conclusions.—: Machine learning offers an array of techniques that in recent published results show substantial promise. Data suggest that human experts working with machine learning tools outperform humans or machines separately, but the optimal form for this combination in pathology has not been established. Significant questions related to the generalizability of machine learning systems, local site verification, and performance monitoring remain to be resolved before a consensus on best practices and a regulatory environment can be established.
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http://dx.doi.org/10.5858/arpa.2020-0541-CPDOI Listing
January 2021

Does Feedback to Physicians of a Patient-Reported Readiness for Discharge Checklist Improve Discharge?

J Patient Exp 2020 Dec 12;7(6):1144-1150. Epub 2020 Jan 12.

Division of Hospital Medicine, University of California, San Francisco, CA, USA.

Limited data exist describing how hospital discharge readiness checklists might be incorporated into care. To evaluate how assessing patient readiness for discharge effects discharge outcomes. We assessed hospitalized adults' readiness for discharge daily using a checklist. In the first feedback period, readiness data were given to patients, compared to the second feedback period, where data were given to patients and physicians. In the first feedback period, 163 patients completed 296 checklists, and in the second feedback period, 179 patients completed 371 checklists. In the first feedback period, 889 discharge barriers were identified, and 1154 in the second feedback period ( = .27). We found no association between the mean number of discharge barriers by hospital day and whether data were provided to physicians ( = .39). Eighty-nine physicians completed our survey, with 76 (85%) recalling receiving checklist data. Twenty-three (30%) of these thought the data helpful, and 45 (59%) stated it "never" or "rarely" highlighted anything new. Patients continued to report discharge barriers even when physicians received patient-reported data about key discharge transition domains.
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http://dx.doi.org/10.1177/2374373519895100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7786742PMC
December 2020

Clinical Significance of Manuka and Medical-Grade Honey for Antibiotic-Resistant Infections: A Systematic Review.

Antibiotics (Basel) 2020 Oct 31;9(11). Epub 2020 Oct 31.

College of Health and Life Sciences, Aston University, Aston Triangle, Birmingham B4 7ET, UK.

Antimicrobial resistance is an ever-increasing global issue that has the potential to overtake cancer as the leading cause of death worldwide by 2050. With the passing of the "golden age" of antibiotic discovery, identifying alternative treatments to commonly used antimicrobials is more important than ever. Honey has been used as a topical wound treatment for millennia and more recently has been formulated into a series of medical-grade honeys for use primarily for wound and burn treatment. In this systematic review, we examined the effectiveness of differing honeys as an antimicrobial treatment against a variety of multidrug-resistant (MDR) bacterial species. We analysed 16 original research articles that included a total of 18 different types of honey against 32 different bacterial species, including numerous MDR strains. We identified that Surgihoney was the most effective honey, displaying minimum inhibitory concentrations as low as 0.1% (w/v); however, all honeys reviewed showed a high efficacy against most bacterial species analysed. Importantly, the MDR status of each bacterial strain had no impact on the susceptibility of the organism to honey. Hence, the use of honey as an antimicrobial therapy should be considered as an alternative approach for the treatment of antibiotic-resistant infections.
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http://dx.doi.org/10.3390/antibiotics9110766DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693943PMC
October 2020

Genome sequencing data for wild and cultivated bananas, plantains and abacá.

Data Brief 2020 Dec 23;33:106341. Epub 2020 Sep 23.

Biosciences, University of Exeter, Exeter EX4 4QD, United Kingdom.

We performed shotgun genome sequencing on a total of 19 different genotypes including representatives of wild banana species and , allopolyploid bananas and plantains, Fe'i banana, pink banana (also known as hairy banana) and abacá (also known as hemp banana). We aligned sequence reads against a previously sequenced reference genome and assessed ploidy and, in the case of allopolyploids, the contributions of the A and B genomes; this provides important quality-assurance data about the taxonomic identities of the sequenced plant material. These data will be useful for phylogenetics, crop improvement, studies of the complex story of intergenomic recombination in AAB and ABB allotriploid bananas and plantains and can be integrated into resources such as the Banana Genome Hub.
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http://dx.doi.org/10.1016/j.dib.2020.106341DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7549061PMC
December 2020

Advocacy in action: Medical student reflections of an experiential curriculum.

Clin Teach 2020 Oct 15. Epub 2020 Oct 15.

UCSF - Medicine, San Francisco, CA, USA.

Introduction: Patient advocacy is a core value in medical education. Although students learn about social determinants of health (SDH) in the pre-clinical years, applying this knowledge to patients during clerkship rotations is not prioritized. Physicians must be equipped to address social factors that affect health and recognize their roles as patient advocates to improve care and promote health equity. We created an experience-based learning curriculum called Advocacy in Action (AiA) to promote the development and application of health advocacy knowledge and skills during an Internal Medicine (IM) clerkship rotation.

Methods: Sixty-six students completed a mandatory curriculum, including an introductory workshop on SDH and patient advocacy using tools for communication, counselling and collaboration skills. They then actively participated in patient advocacy activities, wrote about their experience and joined a small group debriefing about it. Forty-nine written reflections were reviewed for analysis of the impact of this curriculum on student perspectives.

Results: Written reflections had prominent themes surrounding advocacy skills development, meaningful personal experiences, interprofessional dynamics in patient advocacy and discovery of barriers to optimal patient care.

Discussion: AiA is a novel method to apply classroom knowledge of SDH to the clinical setting in order to incorporate advocacy in daily patient care. Students learned about communication with patients, working with interprofessional team members to create better health outcomes and empathy/compassion from this curriculum. It is important to utilize experiential models of individual patient-level advocacy during clerkships so that students can continuously reflect on and integrate advocacy into their future careers.
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http://dx.doi.org/10.1111/tct.13283DOI Listing
October 2020

Economic evaluation of nivolumab combined with ipilimumab in the first-line treatment of advanced melanoma in Japan.

J Med Econ 2020 Oct 28:1-11. Epub 2020 Oct 28.

Bristol-Myers Squibb K.K, Tokyo, Japan.

Aims: The objective of this study was to evaluate the cost-effectiveness of nivolumab in combination with ipilimumab (nivo + ipi) compared to current therapeutic alternatives in first-line treatment of patients with advanced melanoma from the Japanese national healthcare payer perspective using 48-month survival data from the CheckMate 067 Phase III trial.

Materials And Methods: A three-state partitioned survival model was developed from projections of overall survival (OS) and progression-free survival (PFS) to estimate accrued quality-adjusted survival and costs over a 30-year time horizon. The analysis included nivo + ipi, nivolumab, and ipilimumab monotherapies (the three treatments included in CheckMate 067). Drug acquisition, administration, disease management, subsequent therapy, and adverse event (AE) costs were obtained via published sources and expert input (solicited via Delphi panel). AE frequencies were collected from the Checkmate 067 trial. Utility weights were estimated from the Checkmate 067 trial, based on Japanese tariffs. Results were presented as incremental cost-utility ratios (ICURs, cost per quality-adjusted life-year (QALY)).

Results: Nivo + ipi had the greatest estimated survival among the three competing treatments, followed by nivolumab monotherapy accruing the second greatest survival. The incremental cost-effectiveness of nivo + ipi was ¥778,000 per QALY vs. nivolumab and ¥1,584,000 per QALY vs. ipilimumab. The results indicate that nivo + ipi is cost-effective in Japan when compared to a threshold of ¥7,500,000 per QALY. This finding was found to be generally robust to sensitivity and scenario analyses.

Limitations: Limitations include uncertainty in long-term survival extrapolations and lack of Japan-specific clinical data.

Conclusions: This analysis indicates that adding ipilimumab to nivolumab therapy represents a cost-effective new treatment option for patients with unresectable malignant melanoma in Japan.
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http://dx.doi.org/10.1080/13696998.2020.1830781DOI Listing
October 2020

NR4A1 Deletion in Marginal Zone B Cells Exacerbates Atherosclerosis in Mice-Brief Report.

Arterioscler Thromb Vasc Biol 2020 11 10;40(11):2598-2604. Epub 2020 Sep 10.

Division of Cardiovascular Medicine, Department of Medicine, University of Cambridge, United Kingdom (M.N., G.B., L.C.-B., T.X.Z., L.M., J.H., N.F., A.P.S., Z.M.).

Objective: NR4A orphan receptors have been well studied in vascular and myeloid cells where they play important roles in the regulation of inflammation in atherosclerosis. NR4A1 (nerve growth factor IB) is among the most highly induced transcription factors in B cells following BCR (B-cell receptor) stimulation. Given that B cells substantially contribute to the development of atherosclerosis, we examined whether NR4A1 regulates B-cell function during atherogenesis. Approach and Results: We found that feeding mice a Western diet substantially increased expression in marginal zone B (MZB) cells compared with follicular B cells. We then generated mice with complete B- or specific MZB-cell deletion of . Complete B-cell deletion of led to increased atherosclerosis, which was accompanied by increased T follicular helper cell-germinal center axis response, as well as increased serum total cholesterol and triglycerides levels. Interestingly, specific MZB-cell deletion of increased atherosclerosis in association with an increased T follicular helper-germinal center response but without any impact on serum cholesterol or triglyceride levels. MZB cells showed decreased PDL1 (programmed death ligand-1) expression, which may have contributed to the enhanced T follicular helper response.

Conclusions: Our findings reveal a previously unsuspected role for NR4A1 in the atheroprotective role of MZB cells.
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http://dx.doi.org/10.1161/ATVBAHA.120.314607DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7571845PMC
November 2020

Patient expectations for opioid analgesia following orthopaedic surgery.

Postgrad Med J 2020 Sep 3. Epub 2020 Sep 3.

Bone & Joint Sports Medicine Institute, Naval Medical Center Portsmouth, Portsmouth, Virginia, USA

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http://dx.doi.org/10.1136/postgradmedj-2020-137957DOI Listing
September 2020

Decisions in the Dark: An Educational Intervention to Promote Reflection and Feedback on Night Float Rotations.

J Gen Intern Med 2020 11 1;35(11):3363-3367. Epub 2020 Sep 1.

Department of Medicine, University of California San Francisco, San Francisco, CA, USA.

Background: Night float rotations, where residents admit patients to the hospital, are opportunities for practice-based learning. However, night float residents receive little feedback on their diagnostic and management reasoning, which limits learning.

Aim: Improve night float residents' practice-based learning skills through feedback solicitation and chart review with guided reflection.

Setting/participants: Second- and third-year internal medicine residents on a 1-month night float rotation between January and August 2017.

Program Description: Residents performed chart review of a subset of patients they admitted during a night float rotation and completed reflection worksheets detailing patients' clinical courses. Residents solicited feedback regarding their initial management from day team attending physicians and senior residents.

Program Evaluation: Sixty-eight of 82 (83%) eligible residents participated in this intervention. We evaluated 248 reflection worksheets using content analysis. Major themes that emerged from chart review included residents' identification of future clinical practice changes, evolution of differential diagnoses, recognition of clinical reasoning gaps, and evaluation of resident-provider interactions.

Discussion: Structured reflection and feedback during night float rotations is an opportunity to improve practice-based learning through lessons on disease progression, clinical reasoning, and communication.
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http://dx.doi.org/10.1007/s11606-020-05913-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7661589PMC
November 2020

Completeness and quality of text paging for subspecialty consult requests.

Postgrad Med J 2020 Aug 20. Epub 2020 Aug 20.

Division of Hospital Medicine, University of California San Francisco, San Francisco, California, USA.

It is unclear whether previously developed frameworks for effective consultation apply to requests initiated by alphanumeric text page. We assessed a random sample of 210 text paged consult requests for communication of previously described 'essential elements' for effective consultation: reason for consult, level of urgency and requester contact information. Overall page quality was evaluated on a 5-point Likert scale. Over 90% of text paged consult requests included contact information and reason for consult; 14% indicated level of urgency. In ordinal logistic regression, reason for consult was most strongly associated with quality (OR 22.4; 95% CI 8.1 to 61.7), followed by callback number (OR 6.2; 95% CI 0.8 to 49.5), caller's name (OR 5.0; 95% CI 1.9 to 13.1) and level of urgency (OR 3.3; 95% CI 1.6 to 6.7). Results suggest that text paged consult requests often include most informational elements, and that urgency, often missing, may not be as 'essential' for text pages as it was once thought to be.
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http://dx.doi.org/10.1136/postgradmedj-2020-137624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7895858PMC
August 2020

Hospital Ward Adaptation During the COVID-19 Pandemic: A National Survey of Academic Medical Centers.

J Hosp Med 2020 08;15(8):483-488

Brigham and Women's Hospital, Boston, Massachusetts.

Importance: Although intensive care unit (ICU) adaptations to the coronavirus disease of 2019 (COVID-19) pandemic have received substantial attention , most patients hospitalized with COVID-19 have been in general medical units.

Objective: To characterize inpatient adaptations to care for non-ICU COVID-19 patients.

Design: Cross-sectional survey.

Setting: A network of 72 hospital medicine groups at US academic centers.

Main Outcome Measures: COVID-19 testing, approaches to personal protective equipment (PPE), and features of respiratory isolation units (RIUs).

Results: Fifty-one of 72 sites responded (71%) between April 3 and April 5, 2020. At the time of our survey, only 15 (30%) reported COVID-19 test results being available in less than 6 hours. Half of sites with PPE data available reported PPE stockpiles of 2 weeks or less. Nearly all sites (90%) reported implementation of RIUs. RIUs primarily utilized attending physicians, with few incorporating residents and none incorporating students. Isolation and room-entry policies focused on grouping care activities and utilizing technology (such as video visits) to communicate with and evaluate patients. The vast majority of sites reported decreases in frequency of in-room encounters across provider or team types. Forty-six percent of respondents reported initially unrecognized non-COVID-19 diagnoses in patients admitted for COVID-19 evaluation; a similar number reported delayed identification of COVID-19 in patients admitted for other reasons.

Conclusion: The COVID-19 pandemic has required medical wards to rapidly adapt with expanding use of RIUs and use of technology emerging as critical approaches. Reports of unrecognized or delayed diagnoses highlight how such adaptations may produce potential adverse effects on care.
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http://dx.doi.org/10.12788/jhm.3476DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7518133PMC
August 2020

Global Palliative Care Education in the Time of COVID-19.

J Pain Symptom Manage 2020 10 24;60(4):e14-e19. Epub 2020 Jul 24.

University of California, San Francisco, California, USA.

The coronavirus disease 2019 (COVID-19) pandemic has highlighted the need for health care providers skilled in rapid and flexible decision making, effective and anticipatory leadership, and in dealing with trauma and moral distress. Palliative care (PC) workers have been an essential part of the COVID-19 response in advising on goals of care, symptom management and difficult decision making, and in supporting distressed health care workers, patients, and families. We describe Global Palliative Education Collaborative (GPEC), a training partnership between Harvard, University of California San Francisco, and Tulane medical schools in the U.S.; and two international PC programs in Uganda and India. GPEC offers U.S.-based PC fellows participation in an international elective to learn about resource-limited PC provision, gain perspective on global challenges to caring for patients at the end of life, and cultivate resiliency. International PC colleagues have much to teach about practicing compassionate PC amidst resource constraints and humanitarian crisis. We also describe a novel educational project that our GPEC faculty and fellows are participating in-the Resilience Inspiration Storytelling Empathy Project-and discuss positive outcomes of the project.
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http://dx.doi.org/10.1016/j.jpainsymman.2020.07.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7380234PMC
October 2020

Type 1 diabetes genetic risk score is discriminative of diabetes in non-Europeans: evidence from a study in India.

Sci Rep 2020 06 11;10(1):9450. Epub 2020 Jun 11.

Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, Devon, UK.

Type 1 diabetes (T1D) is a significant problem in Indians and misclassification of T1D and type 2 diabetes (T2D) is a particular problem in young adults in this population due to the high prevalence of early onset T2D at lower BMI. We have previously shown a genetic risk score (GRS) can be used to discriminate T1D from T2D in Europeans. We aimed to test the ability of a T1D GRS to discriminate T1D from T2D and controls in Indians. We studied subjects from Pune, India of Indo-European ancestry; T1D (n = 262 clinically defined, 200 autoantibody positive), T2D (n = 345) and controls (n = 324). We used the 9 SNP T1D GRS generated in Europeans and assessed its ability to discriminate T1D from T2D and controls in Indians. We compared Indians with Europeans from the Wellcome Trust Case Control Consortium study; T1D (n = 1963), T2D (n = 1924) and controls (n = 2938). The T1D GRS was discriminative of T1D from T2D in Indians but slightly less than in Europeans (ROC AUC 0.84 v 0.87, p < 0.0001). HLA SNPs contributed the majority of the discriminative power in Indians. A T1D GRS using SNPs defined in Europeans is discriminative of T1D from T2D and controls in Indians. As with Europeans, the T1D GRS may be useful for classifying diabetes in Indians.
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http://dx.doi.org/10.1038/s41598-020-65317-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7289794PMC
June 2020

Developing a Patient- and Family-Centered Research Agenda for Hospital Medicine: The Improving Hospital Outcomes through Patient Engagement (i-HOPE) Study.

J Hosp Med 2020 06;15(6):331-337

South Texas Veterans Health Care System, San Antonio, Texas.

Background: Patient, caregiver, and other stakeholder priorities have not been robustly incorporated into directing hospital-based research and improvement efforts.

Objective: To systematically engage stakeholders to identify important questions of adult hospitalized patients and to create a prioritized research agenda for improving the care of adult hospitalized patients.

Design: A collaborative approach to stakeholder engagement and research question prioritization.

Setting & Participants: Researchers and patients from eight academic and community medical centers partnered with 39 patient, caregiver, professional, research, and medical organizations.

Methods: We applied established standards for formulating research questions and stakeholder engagement. This included: a multi-pronged, inclusive patient and stakeholder engagement strategy; surveys of patients and stakeholder organizations to identify important questions; content analysis of submitted questions; and a 2-day in-person meeting with stakeholder organization representatives and patient partners to prioritize and rank submitted questions.

Results: A total of 499 respondents including patients, caregivers, healthcare providers, and researchers from 39 organizations submitted 782 research questions. These questions were categorized into 70 distinct topics-52 that were health system related and 18 disease specific. From these categories, we identified 36 common questions; the final 11 questions were identified, prioritized and ranked during an in-person priority-setting meeting. Questions considered highest priority related to ensuring shared treatment and goals of care decision making and improving hospital discharge handoff to other care facilities and providers.

Conclusion: We identified 11 prioritized research questions that should galvanize funders, researchers, and patient advocates to address and improve the care of hospitalized adult patients.
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http://dx.doi.org/10.12788/jhm.3386DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7289507PMC
June 2020

Interleukin-33 Signaling Controls the Development of Iron-Recycling Macrophages.

Immunity 2020 05 8;52(5):782-793.e5. Epub 2020 Apr 8.

Division of Cardiovascular Medicine, University of Cambridge, Cambridge, UK; Institut National de la Santé et de la Recherche Médicale, Paris Cardiovascular Research Center, Paris, France. Electronic address:

Splenic red pulp macrophages (RPMs) contribute to erythrocyte homeostasis and are required for iron recycling. Heme induces the expression of SPIC transcription factor in monocyte-derived macrophages and promotes their differentiation into RPM precursors, pre-RPMs. However, the requirements for differentiation into mature RPMs remain unknown. Here, we have demonstrated that interleukin (IL)-33 associated with erythrocytes and co-cooperated with heme to promote the generation of mature RPMs through activation of the MyD88 adaptor protein and ERK1/2 kinases downstream of the IL-33 receptor, IL1RL1. IL-33- and IL1RL1-deficient mice showed defective iron recycling and increased splenic iron deposition. Gene expression and chromatin accessibility studies revealed a role for GATA transcription factors downstream of IL-33 signaling during the development of pre-RPMs that retained full potential to differentiate into RPMs. Thus, IL-33 instructs the development of RPMs as a response to physiological erythrocyte damage with important implications to iron recycling and iron homeostasis.
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http://dx.doi.org/10.1016/j.immuni.2020.03.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7237885PMC
May 2020

Author Correction: Effect of Amoxicillin in combination with Imipenem-Relebactam against Mycobacterium abscessus.

Sci Rep 2020 Mar 6;10(1):4540. Epub 2020 Mar 6.

School of Life and Health Sciences, Aston University, Aston Triangle, B4 7ET, Birmingham, UK.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41598-020-61546-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7058606PMC
March 2020

Effect of Amoxicillin in combination with Imipenem-Relebactam against Mycobacterium abscessus.

Sci Rep 2020 Jan 27;10(1):928. Epub 2020 Jan 27.

School of Life and Health Sciences, Aston University, Aston Triangle, B4 7ET, Birmingham, UK.

Infections caused by Mycobacterium abscessus are increasing in prevalence in cystic fibrosis patients. This opportunistic pathogen's intrinsic resistance to most antibiotics has perpetuated an urgent demand for new, more effective therapeutic interventions. Here we report a prospective advance in the treatment of M. abscessus infection; increasing the susceptibility of the organism to amoxicillin, by repurposing the β-lactamase inhibitor, relebactam, in combination with the front line M. abscessus drug imipenem. We establish by multiple in vitro methods that this combination works synergistically to inhibit M. abscessus. We also show the direct competitive inhibition of the M. abscessus β-lactamase, Bla, using a novel assay, which is validated kinetically using the nitrocefin reporter assay and in silico binding studies. Furthermore, we reverse the susceptibility by overexpressing Bla in M. abscessus, demonstrating relebactam-Bla target engagement. Finally, we highlight the in vitro efficacy of this combination against a panel of M. abscessus clinical isolates, revealing the therapeutic potential of the amoxicillin-imipenem-relebactam combination.
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http://dx.doi.org/10.1038/s41598-020-57844-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6985242PMC
January 2020

UC Care Check-A Postoperative Neurosurgery Operating Room Checklist: An Interrupted Time Series Study.

J Healthc Qual 2020 Jul/Aug;42(4):224-235

Background: The effectiveness of neurosurgical operating room (OR) checklists to improve communication, safety attitudes, and clinical outcomes is uncertain.

Purpose: To develop, implement, and evaluate a post-operative neurosurgery operating room checklist.

Methods: Four large academic medical centers participated in this study. We developed an evidence-based checklist to be performed at the end of every adult-planned or emergent surgery in which all team members pause to discuss key elements of the case. We used a prospective interrupted time series study design to assess trends in clinical and cost outcomes. Safety attitudes and communication among OR providers were also assessed.

Results: There were 11,447 neurosurgical patients in the preintervention and 10,973 in the postintervention periods. After implementation, survey respondents perceived that postoperative checklists were regularly performed, important issues were communicated at the end of each case, and patient safety was consistently reinforced. Observed to expected (O/E) overall mortality rates remained less than one, and 30-day readmission rate, length of stay index, direct cost index, and perioperative venous thromboembolism and hematoma rates remained unchanged as a result of checklist implementation.

Conclusion: A neurosurgical checklist can improve OR team communication; however, improvements in safety attitudes, clinical outcomes, and health system costs were not observed.
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http://dx.doi.org/10.1097/JHQ.0000000000000246DOI Listing
January 2021

Patient Recommendations to Improve the Implementation of and Engagement With Portals in Acute Care: Hospital-Based Qualitative Study.

J Med Internet Res 2020 01 14;22(1):e13337. Epub 2020 Jan 14.

Division of Hospital Medicine, University of California, San Francisco, San Francisco, CA, United States.

Background: The inclusion of patient portals into electronic health records in the inpatient setting lags behind progress in the outpatient setting.

Objective: The aim of this study was to understand patient perceptions of using a portal during an episode of acute care and explore patient-perceived barriers and facilitators to portal use during hospitalization.

Methods: We utilized a mixed methods approach to explore patient experiences in using the portal during hospitalization. All patients received a tablet with a brief tutorial, pre- and postuse surveys, and completed in-person semistructured interviews. Qualitative data were coded using thematic analysis to iteratively develop 18 codes that were integrated into 3 themes framed as patient recommendations to hospitals to improve engagement with the portal during acute care. Themes from these qualitative data guided our approach to the analysis of quantitative data.

Results: We enrolled 97 participants: 53 (53/97, 55%) women, 44 (44/97, 45%) nonwhite with an average age of 48 years (19-81 years), and the average length of hospitalization was 6.4 days. A total of 47 participants (47/97, 48%) had an active portal account, 59 participants (59/97, 61%) owned a smartphone, and 79 participants (79/97, 81%) accessed the internet daily. In total, 3 overarching themes emerged from the qualitative analysis of interviews with these patients during their hospital stay: (1) hospitals should provide both access to a device and bring-your-own-device platform to access the portal; (2) hospitals should provide an orientation both on how to use the device and how to use the portal; and (3) hospitals should ensure portal content is up to date and easy to understand.

Conclusions: Patients independently and consistently identified basic needs for device and portal access, education, and usability. Hospitals should prioritize these areas to enable successful implementation of inpatient portals to promote greater patient engagement during acute care.

Trial Registration: ClinicalTrials.gov NCT00102401; https://clinicaltrials.gov/ct2/show/NCT01970852.
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http://dx.doi.org/10.2196/13337DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6996719PMC
January 2020

The Association Between Fault Attribution and Work Participation After Road Traffic Injury: A Registry-Based Observational Study.

J Occup Rehabil 2020 06;30(2):235-254

Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, 553 St Kilda Road, Melbourne, VIC, 3004, Australia.

Purpose To characterise associations between fault attribution and work participation and capacity after road traffic injury. Methods People aged 15-65 years, working pre-injury, without serious brain injury, who survived to 12 months after road traffic injury were included from two Victorian trauma registries (n = 2942). Fault profiles from linked compensation claims were defined as no other at fault, another at fault, denied another at fault, claimed another at fault, and unknown. Claimant reports in the denied and claimed another at fault groups contradicted police reports. Patients reported work capacity (Glasgow outcome scale-extended) and return to work (RTW) at 6, 12 and 24 months post-injury (early and sustained RTW, delayed RTW (≥ 12 months), failed RTW attempts, no RTW attempts). Analyses adjusted for demographic, clinical and injury covariates. Results The risk of not returning to work was higher if another was at fault [adjusted relative risk ratio (aRRR) = 1.67, 95% confidence interval (CI) 1.29, 2.17] or was claimed to be at fault (aRRR = 1.58, 95% CI 1.04, 2.41), and lower for those who denied that another was at fault (aRRR = 0.51, 95% CI 0.29, 0.91), compared to cases with no other at fault. Similarly, people had higher odds of work capacity limitations if another was at fault (12m: AOR = 1.49, 95% CI 1.24, 1.80; 24m: 1.63, 95% CI 1.35, 1.97) or was claimed to be at fault (12m: AOR = 1.54, 95% CI 1.16, 2.05; 24m: AOR = 1.80, 95% CI 1.34, 2.41), and lower odds if they denied another was at fault (6m: AOR = 0.67, 95% CI 0.48, 0.95), compared to cases with no other at fault. Conclusion Targeted interventions are needed to support work participation in people at risk of poor RTW post-injury. While interventions targeting fault and justice-related attributions are currently lacking, these may be beneficial for people who believe that another caused their injury.
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http://dx.doi.org/10.1007/s10926-019-09867-wDOI Listing
June 2020

Dissecting the Antimicrobial Composition of Honey.

Antibiotics (Basel) 2019 Dec 5;8(4). Epub 2019 Dec 5.

School of Life and Health Sciences, Aston University, Aston Triangle, Birmingham B4 7ET, UK.

Honey is a complex sweet food stuff with well-established antimicrobial and antioxidant properties. It has been used for millennia in a variety of applications, but the most noteworthy include the treatment of surface wounds, burns and inflammation. A variety of substances in honey have been suggested as the key component to its antimicrobial potential; polyphenolic compounds, hydrogen peroxide, methylglyoxal and bee-defensin 1. These components vary greatly across honey samples due to botanical origin, geographical location and secretions from the bee. The use of medical grade honey in the treatment of surface wounds and burns has been seen to improve the healing process, reduce healing time, reduce scarring and prevent microbial contamination. Therefore, if medical grade honeys were to be included in clinical treatment, it would reduce the demand for antibiotic usage. In this review, we outline the constituents of honey and how they affect antibiotic potential in a clinical setting. By identifying the key components, we facilitate the development of an optimally antimicrobial honey by either synthetic or semisynthetic production methods.
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http://dx.doi.org/10.3390/antibiotics8040251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6963415PMC
December 2019

Pulmonary vein encirclement using an Ablation Index-guided point-by-point workflow: cardiovascular magnetic resonance assessment of left atrial scar formation.

Europace 2019 Dec;21(12):1817-1823

Division of Imaging Sciences and Biomedical Engineering, King's College London, 4th Floor North Wing, St. Thomas' Hospital, London SE1 7EH, UK.

Aims : A point-by-point workflow for pulmonary vein isolation (PVI) targeting pre-defined Ablation Index values (a composite of contact force, time, and power) and minimizing interlesion distance may optimize the creation of contiguous ablation lesions whilst minimizing scar formation. We aimed to compare ablation scar formation in patients undergoing PVI using this workflow to patients undergoing a continuous catheter drag workflow.

Methods And Results: Post-ablation cardiovascular magnetic resonance imaging was performed in patients undergoing 1st-time PVI using a parameter-guided point-by-point workflow (n = 26). Total left atrial scar burden and the width and continuity of the pulmonary vein encirclement were determined on analysis of atrial late gadolinium enhancement sequences. Comparison was made with a cohort of patients (n = 20) undergoing PVI using continuous drag lesions. Mean post-ablation scar burden and scar width were significantly lower in the point-by-point group than in the control group (6.6 ± 6.8% vs. 9.6 ± 5.0%, P = 0.03 and 7.9 ± 3.6 mm vs. 10.7 ± 2.3 mm, P = 0.003). More complete bilateral pulmonary vein encirclements were seen in the point-by-point group (P = 0.038). All patients achieved acute PVI.

Conclusion: Pulmonary vein isolation using a point-by-point workflow is feasible and results in a lower scar burden and scar width with more complete pulmonary vein encirclements than a conventional drag lesion approach.
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http://dx.doi.org/10.1093/europace/euz226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6887923PMC
December 2019

Changing the Rules of TB-Drug Discovery.

J Med Chem 2019 12 30;62(23):10583-10585. Epub 2019 Oct 30.

School of Life and Health Sciences , Aston University , Aston Triangle , Birmingham B4 7ET , U.K.

The discovery of new drugs with novel targets is paramount to the continued success of tuberculosis (TB) treatment due to the increasing prevalence of antibiotic resistant infections in the TB population. () fumarate hydratase (fumarase) is a highly conserved essential protein that shares an active site with human fumarase, making active site inhibition equally cytotoxic for both bacteria and humans. The recent discovery of a set of new inhibitory compounds that target fumarase by binding to a nonconserved allosteric site is a major advancement, providing further evidence to dispel the antibiotic discovery dogma that conserved proteins do not make good antibiotic targets.
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http://dx.doi.org/10.1021/acs.jmedchem.9b01716DOI Listing
December 2019

Impaired Autophagy in CD11b Dendritic Cells Expands CD4 Regulatory T Cells and Limits Atherosclerosis in Mice.

Circ Res 2019 11 15;125(11):1019-1034. Epub 2019 Oct 15.

From the Division of Cardiovascular Medicine, University of Cambridge, Cambridge, United Kingdom (M.C., J.R., F.L., D.T., S.N., Y.L., L.M., J.H., Z.M.).

Rationale: Atherosclerosis is a chronic inflammatory disease. Recent studies have shown that dysfunctional autophagy in endothelial cells, smooth muscle cells, and macrophages, plays a detrimental role during atherogenesis, leading to the suggestion that autophagy-stimulating approaches may provide benefit.

Objective: Dendritic cells (DCs) are at the crossroad of innate and adaptive immune responses and profoundly modulate the development of atherosclerosis. Intriguingly, the role of autophagy in DC function during atherosclerosis and how the autophagy process would impact disease development has not been addressed.

Methods And Results: Here, we show that the autophagic flux in atherosclerosis-susceptible (low-density lipoprotein receptor-deficient) mice is substantially higher in splenic and aortic DCs compared with macrophages and is further activated under hypercholesterolemic conditions. RNA sequencing and functional studies on selective cell populations reveal that disruption of autophagy through deletion of differentially affects the biology and functions of DC subsets in mice under high-fat diet. deficient CD11b DCs develop a TGF (transforming growth factor)-β-dependent tolerogenic phenotype and promote the expansion of regulatory T cells, whereas no such effects are seen with deficient CD8α DCs. deletion in DCs (all CD11c-expressing cells) expands aortic regulatory T cells in vivo, limits the accumulation of T helper cells type 1, and reduces the development of atherosclerosis in mice. In contrast, no such effects are seen when is deleted selectively in conventional CD8α DCs and CD103 DCs. Total T-cell or selective regulatory T-cell depletion abrogates the atheroprotective effect of deficient DCs.

Conclusions: In contrast to its proatherogenic role in macrophages, autophagy disruption in DCs induces a counter-regulatory response that maintains immune homeostasis in mice under high-fat diet and limits atherogenesis. Selective modulation of autophagy in DCs could constitute an interesting therapeutic target in atherosclerosis.
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http://dx.doi.org/10.1161/CIRCRESAHA.119.315248DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6844650PMC
November 2019

A Qualitative Exploration of Return to Work in the First 3-Years After Serious Injury.

J Occup Environ Med 2019 12;61(12):e461-e467

School of Public Health and Preventive Medicine, St Kilda Road, Monash University (Dr Braaf, Prof Collie, Prof Cameron, Prof Gabbe); School of Population Health, University of Auckland, St Johns, Auckland, New Zealand (Prof Ameratunga); Research Centre for Injury Studies, Flinders University, Beford Park, Adelaide (Prof Harrison); Trauma Service, The Royal Children's Hospital (Prof Teague); Department of Paediatrics, University of Melbourne (Prof Teague); Surgical Research Group, Murdoch Children's Research Institute, Melbourne, Australia (Prof Teague); Department of Civil, Environmental and Geomatic Engineering, University College of London, London, United Kingdom (Prof Christie).

Objective: To explore how people with serious injuries returned to paid employment in the first 3-years after injury.

Methods: Fifty-four adult survivors of serious injuries were interviewed at 3-years post-injury, all of whom had returned to work and were currently employed. A framework analysis approach was undertaken.

Results: Participant decisions and actions taken to return to work (RTW) were influenced by their resilience, approach to adjusting goals, priorities and plans, and how social connections and relationships were used and maintained. The environment in which these decisions and actions were taken shaped opportunities for work in meaningful, appropriate, and sustained employment.

Conclusions: Our study of 54 people who RTW indicated the importance of personal adjustments and resources, positive social relations, and advanced planning aligning with responsive employers, insurers and health professionals for successful RTW.
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http://dx.doi.org/10.1097/JOM.0000000000001719DOI Listing
December 2019

Altering social cue perception impacts honey bee aggression with minimal impacts on aggression-related brain gene expression.

Sci Rep 2019 10 10;9(1):14642. Epub 2019 Oct 10.

Department of Entomology, University of Kentucky, S-225 Agricultural Science Center North, Lexington, KY, 40546, USA.

Gene expression changes resulting from social interactions may give rise to long term behavioral change, or simply reflect the activity of neural circuitry associated with behavioral expression. In honey bees, social cues broadly modulate aggressive behavior and brain gene expression. Previous studies suggest that expression changes are limited to contexts in which social cues give rise to stable, relatively long-term changes in behavior. Here we use a traditional beekeeping approach that inhibits aggression, smoke exposure, to deprive individuals of aggression-inducing olfactory cues and evaluate whether behavioral changes occur in absence of expression variation in a set of four biomarker genes (drat, cyp6g1/2, GB53860, inos) associated with aggression in previous studies. We also evaluate two markers of a brain hypoxic response (hif1α, hsf) to determine whether smoke induces molecular changes at all. We find that bees with blocked sensory perception as a result of smoke exposure show a strong, temporary inhibition of aggression relative to bees allowed to perceive normal social cues. However, blocking sensory perception had minimal impacts on aggression-relevant gene expression, althought it did induce a hypoxic molecular response in the brain. Results suggest that certain genes differentiate social cue-induced changes in aggression from long-term modulation of this phenotype.
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http://dx.doi.org/10.1038/s41598-019-51223-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6787081PMC
October 2019

Patient and Family Advisory Councils for Research: Recruiting and Supporting Members From Diverse and Hard-to-Reach Communities.

J Nurs Adm 2019 Oct;49(10):473-479

Author Affiliations: Assistant Professors (Drs Harrison and Duong), Associate Professor (Dr Anderson), Professor (Dr Auerbach), and Project Manager (Ms Chen), Division of Hospital Medicine, University of California San Francisco; Chief Experience Officer (Dr Fagan) and Director of Patient and Family Advisory Councils (Ms Hanson), University of Miami Health System, Florida; Chief Transformation Officer and Vice President (Dr Robinson), Christiana Care Health System, Wilmington, Delaware; Associate Professor (Dr Schnipper), Department of Medicine, Brigham & Women's Hospital, Boston, Massachusetts; Patient and Family Advisory Council Members (Ms Symczak and Mr Banta), Intensive Care Unit Patient & Family Advisory Council, University of California San Francisco; and Senior Patient Advisor (Ms Carnie) and Project Manager (Ms Wong), Center for Patients and Families, Brigham & Women's Hospital, Boston, Massachusetts.

Objective: To describe strategies to recruit and support members from hard-to-reach groups on research-focused Patient and Family Advisory Councils (PFACs).

Background: Ensuring diverse representation of members of research PFACs is challenging, and few studies have given attention to addressing this problem.

Methods: A qualitative study was conducted using 8 focus groups and 19 interviews with 80 PFAC members and leaders, hospital leaders, and researchers.

Results: Recruitment recommendations were: 1) utilizing existing networks; 2) going out to the community; 3) accessing outpatient clinics; and 4) using social media. Strategies to support inclusion were: 1) culturally appropriate communication methods; 2) building a sense of community between PFAC members; 3) equalizing roles between community members/leaders; 4) having a diverse PFAC leadership team; and 5) setting transparent expectations for PFAC membership.

Conclusion: Increasing the diversity of research PFACs is a priority, and it is important to determine how best to engage groups that have been traditionally underrepresented.
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http://dx.doi.org/10.1097/NNA.0000000000000790DOI Listing
October 2019

Structural Basis of Glycerophosphodiester Recognition by the Substrate-Binding Protein UgpB.

ACS Chem Biol 2019 09 21;14(9):1879-1887. Epub 2019 Aug 21.

School of Life Sciences , University of Warwick , Coventry , West Midlands CV4 7AL , United Kingdom.

() is the causative agent of tuberculosis (TB) and has evolved an incredible ability to survive latently within the human host for decades. The pathogen encodes for a low number of ATP-binding cassette (ABC) importers for the acquisition of carbohydrates that may reflect the nutrient poor environment within the host macrophages. UgpB (Rv2833c) is the substrate binding domain of the UgpABCE transporter that recognizes glycerophosphocholine (GPC), indicating that this transporter has a role in recycling glycerophospholipid metabolites. By using a combination of saturation transfer difference (STD) NMR and X-ray crystallography, we report the structural analysis of UgpB complexed with GPC and have identified that UgpB not only recognizes GPC but is also promiscuous for a broad range of glycerophosphodiesters. Complementary biochemical analyses and site-directed mutagenesis precisely define the molecular basis and specificity of glycerophosphodiester recognition. Our results provide critical insights into the structural and functional role of the UgpB transporter and reveal that the specificity of this ABC-transporter is not limited to GPC, therefore optimizing the ability of to scavenge scarce nutrients and essential glycerophospholipid metabolites via a single transporter during intracellular infection.
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http://dx.doi.org/10.1021/acschembio.9b00204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6757277PMC
September 2019

A comprehensive multi-index cardiac magnetic resonance-guided assessment of atrial fibrillation substrate prior to ablation: Prediction of long-term outcomes.

J Cardiovasc Electrophysiol 2019 10 22;30(10):1894-1903. Epub 2019 Aug 22.

Division of Imaging Sciences and Biomedical Engineering, King's College London, London, UK.

Introduction: Multiple cardiac magnetic resonance (CMR)-derived indices of atrial fibrillation (AF) substrate have been shown in isolation to predict long-term outcome following catheter ablation. Left atrial (LA) fibrosis, LA volume, LA ejection fraction (EF), left ventricular ejection fraction (LVEF), LA shape (sphericity) and pulmonary vein anatomy have all been shown to correlate with late AF recurrence. This study aimed to validate and assess the relative contribution of multiple indices in a long-term single-center study.

Methods And Results: Eighty-nine patients (53% paroxysmal AF, 73% male) underwent comprehensive CMR study before first-time AF ablation (median follow-up 726 days [IQR: 418-1010 days]). The 3D late gadolinium-enhanced acquisition (1.5T, 1.3 × 1.3 × 2 mm) was quantified for fibrosis; LA volume and sphericity were assessed on manual segmentation at atrial diastole; LAEF and LVEF were quantified on multislice cine imaging. AF recurred in 43 patients (48%) overall (31 at 1 year). In the recurrence group, LA fibrosis was higher (42% vs 29%; hazard ratio [HR]: 1.032; P = .002), left atrial ejection fraction (LAEF) lower (25% vs 34%; HR: 0.063; P = .016) and LVEF lower (57% vs 63%; HR: 0.011; P = .008). LA volume (135 vs 124 mL) and sphericity (0.819 vs 0.822) were similar. Multivariate Cox regression analysis was adjusted for age and sex (Model 1), additionally AF type (Model 2) and combined (Model 3). In Models 1 and 2, LA fibrosis, LAEF, and LVEF were independently associated with outcome, but only LA fibrosis was independent in Model 3 (HR: 1.021; P = .022).

Conclusions: LAEF, LVEF, and LA fibrosis differed significantly in the AF recurrence cohort. However, on combined multivariate analysis only LA fibrosis remained independently associated with outcome.
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http://dx.doi.org/10.1111/jce.14111DOI Listing
October 2019