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Introduction: Our safety-net hospital implemented a hospital-based tobacco treatment intervention in 2016. We previously showed the intervention, an "opt-out" Electronic Health Record (EHR)-based Best Practice Alert (BPA)+ order-set that triggers consultation to an inpatient Tobacco Treatment Consult (TTC) service for all patients who smoke, improves smoking abstinence. We now report on sustainability, 6 years after inception., Aims and Methods: We analyzed data collected between July 2016-June 2022 of patients documented as "currently smoking" in the EHR. Across the 6 years, we used Pearson's correlation analysis to compare Adoption (clinician acceptance of the BPA+ order-set, thus generating consultation to the TTC service); Reach (number of consultations completed by the TTC service); and Effectiveness (receipt of pharmacotherapy orders between patients receiving and not receiving consultations)., Results: Among 39 558 adult admissions (July 2016-June 2022) with "currently smoking" status in the EHR for whom the BPA triggered, clinicians accepted the TTC order set on 50.4% (19 932/39 558), though acceptance varied across services (eg, Cardiology [71%] and Obstetrics-Gynecology 12%]). The TTC service consulted on 17% (6779/39 558) of patients due to staffing constraints. Consultations ordered (r = -0.28, p = .59) and completed (r = 0.45, p = .37) remained stable over 6-years. Compared to patients not receiving consultations, patients receiving consultations were more likely to receive pharmacotherapy orders overall (inpatient: 50.8% vs. 35.1%, p < .0001; at discharge: 27.1% vs. 10%, p < .0001) and in each year., Conclusions: The "opt-out" EHR-based TTC service is sustainable, though many did not receive consultations due to resource constraints. Health care systems should elevate the priority of hospital-based tobacco treatment programs to increase reach to underserved populations., Implications: Our study shows that opt-out approaches that utilize the EHR are a sustainable approach to providing evidence-based tobacco treatment to all hospitalized individuals who smoke, regardless of readiness to stop smoking and clinical condition., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Desirability of outcome ranking (DOOR) is an innovative approach to clinical trial design and analysis that uses an ordinal ranking system to incorporate the overall risks and benefits of a therapeutic intervention into a single measurement. Here we derived and evaluated a disease-specific DOOR endpoint for registrational trials for hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP)., Methods: Through comprehensive examination of data from nearly 4000 participants enrolled in six registrational trials for HABP/VABP submitted to the Food and Drug Administration (FDA) between 2005 and 2022, we derived and applied a HABP/VABP specific endpoint. We estimated the probability that a participant assigned to the study treatment arm would have a more favorable overall DOOR or component outcome than a participant assigned to comparator., Results: DOOR distributions between treatment arms were similar in all trials. DOOR probability estimates ranged from 48.3% to 52.9% and were not statistically different. There were no significant differences between treatment arms in the component analyses. Although infectious complications and serious adverse events occurred more frequently in ventilated participants compared to non-ventilated participants, the types of events were similar., Conclusions: Through a data-driven approach, we constructed and applied a potential DOOR endpoint for HABP/VABP trials. The inclusion of syndrome-specific events may help to better delineate and evaluate participant experiences and outcomes in future HABP/VABP trials and could help inform data collection and trial design., Competing Interests: Potential conflicts of interest. V. G. F. reports personal fees from Novartis, Debiopharm, Genentech, Achaogen, Affinium, Medicines Co., MedImmune, Bayer, Basilea, Affinergy, Janssen, Contrafect, Regeneron, Destiny, Amphliphi Biosciences, Integrated Biotherapeutics; C3J, Armata, Valanbio; Akagera, Aridis, Roche, grants from NIH, MedImmune, Allergan, Pfizer, Advanced Liquid Logics, Theravance, Novartis, Merck; Medical Biosurfaces; Locus; Affinergy; Contrafect; Karius; Genentech, Regeneron, Deep Blue, Basilea, Janssen; Royalties from UpToDate, stock options from Valanbio and ArcBio, Honoraria from Infectious Diseases of America for his service as Associate Editor of Clinical Infectious Diseases, and a patent sepsis diagnostics pending. H. W. B. reports royalties to author from Sanford Guide; editorial consulting fees from Sanford Guide, Antimicrobial Agents and Chemotherapy/ASM, ID Clinics of North America/Elsevier; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Grand Rounds at Temple; IDWeek lecture travel support from Finland Award; role as PACCARB Voting Member (travel reimbursed) and on Board of Trustees, College of the Holy Cross (travel reimbursed). T. H. reports grants or contracts from Aceragen; consulting fees from Astellas Pharma US and Mitsubishi Tanabe Pharma; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing, or educational events from Cancer and Chemotherapy KK. S. R. E. reports NCI/NIH grant, NHLBI/NIH grant, CDC grant, and grants or contracts from Degruyter (Editor-in-Chief: Statistical Communications in Infectious Diseases); book royalties from Taylor & Francis; consulting fees from Genentech, AstraZeneca, Takeda, Microbiotix, Johnson & Johnson, Endologix, ChemoCentryx, Becton Dickenson, Atricure, Roivant, Neovasc, Nobel Pharma, Horizon, International Drug Development Institute, SVB Leerink, Medtronic, Regeneron, Wake Forest University, Recor, Janssen, IDDI; honorarium from Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION), and payment or honorarium for travel from Liver Forum and Paris NASH Meeting; support for attending meetings and/or travel from FDA (honorarium); paid participation on a Data Safety Monitoring Board or Advisory Board for NIH, BARDA, Breast International Group, University of Pennsylvania, Washington University, Duke University, Roche, Pfizer, Takeda, Akouos, Apellis, Teva, Vir, DayOneBio, Alexion, Tracon, Rakuten, Abbvie, GSK, Eli Lilly, Nuvelution, Clover, FHI Clinical, Lung Biotech, SAB Biopharm, Advantagene, Candel, Novartis; unpaid Board member for American Statistical Association, Society for Clinical Trials, and Frontier Science Foundation. J. H. A. reports grant funding to institution for work unrelated to this from the Centers for Disease Control and Prevention (CDC); support for speaking at SHEA Spring Conference from SHEA. S. N. reports support for travel to meetings is supported by my employer, Johnson and Johnson; stocks in J&J, author's employer. T. H. reports grant from NIH to Antibacterial Resistance Leadership Group and grants or contracts from Karius for Adjudication committee; royalties or licenses from UpToDate; consulting fees from Aridis, Pfizer, Lysovant, Affinivax, Basilea, Concert Genetics; participation on Data and Safety Monitoring Board (DSMB) for Staphylococcus aureus Network Adaptive Platform (SNAP) trial and Spero and on Advisory Board for Basilea and Paul Scherrer Institut (PSI). S. B. D. reports grants or contracts to University of California San Francisco (UCSF) from Gilead, Pfizer, F2G, Regeneron, Chan Zuckerberg Biohub, and NIAID/NIH; consulting fees to author from Genentech and Janssen/J + J; support for travel to speak at IDWeek from Infectious Diseases Society of America (IDSA); patent US20100143379A1 for Mif agonists and antagonist and therapeutic uses thereof; leadership or fiduciary roles on IDSA Antibacterial Resistance Committee, CADPH HAI Advisory Committee, Antibacterial Resistance Leadership Group Innovations Group, Laboratory Center, Mentorship Committee, Gram Positive Committee, Immunosuppressed Host Group; payment for clinical events committee/adjudication committee participation from Shinogi, Basilea, Duke Clinical Research Institute. H. C. reports stock or stock options from Merck and Moderna; membership of DSMB for COVID antiviral RCT for Merck. D. C. reports grants or contracts from Duke University for COMET study (cancer) Patient Leadership Group, from UCSF for STORMing Cancer Patient Advocate Team, and from MD Anderson for PRECISION Patient Advisory Involvement Panel; consulting fees for ongoing projects from SimBioSys and MaxisHealth, from Health Literacy Media (HLM) for Patient Advisor for ongoing projects, and from Appelis Pharmaceuticals, Inc., for consulting/project ended in 12/2022 and from Kinnate Biopharma for consulting/project ended in 06/2022; honoraria and travel support from HMP Education; support for travel from Agile Falcon Strategic Group, DGE Events, and Informa; participation on DSMB for American Society for Clinical Oncology and on Patient Partner Council for Evidera; a role on Executive Group for Metastatic Breast Cancer Alliance and a role as committee member for Alliance for Clinical Trials in Oncology; receitp of manuscript writing support from IQVIA through Regeneron. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2024.)

Background: Antimicrobial resistance (AMR) is a major threat to global health. By 2050, it is forecast that AMR will cause 10 million deaths and cost 100 trillion USD annually. Point-of-care tests (POCTs) may represent a cost-effective approach to reduce AMR., Objectives: We systematically reviewed which POCTs addressing AMR have undergone economic evaluation in primary and secondary healthcare globally, how these POCTs have been economically evaluated, and which are cost-effective in reducing antimicrobial prescribing or the burden of AMR. Clinical cost-effectiveness was additionally addressed., Methods: This systematic review, accordant with PRISMA guidelines, was pre-registered on PROSPERO (CRD42022315192). MEDLINE, PubMed, Embase, Cochrane Library, and Google Scholar were searched from 2000 to 2023 for relevant publications. Quality assessment was performed using the Consensus of Health Economic Criteria., Results: The search strategy identified 1421 studies, of which 20 met the inclusion criteria. The most common POCTs assessed were for respiratory infections (n = 10), STIs (n = 3), and febrile patients in low- and middle-income countries (n = 3). All studies assessed costs from a healthcare provider perspective; five additionally considered the societal cost of AMR.Eighteen studies identified POCT strategies that reduced antimicrobial prescribing. Of these, 10 identified POCTs that would be considered cost-effective at a willingness-to-pay (WTP) threshold of £33.80 per antibiotic prescription avoided. Most POCT strategies improved clinical outcomes (n = 14); the remainder were clinically neutral., Conclusions: There is evidence that some POCTs are cost-effective in reducing antimicrobial prescribing, with potential concomitant clinical benefits. Such interventions-especially CRP POCTs in both high- and low-income settings-merit further, large-scale clinical evaluation., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Background: Heteroresistance (HR), the presence of antibiotic-resistant subpopulations within a primary isogenic population, may be a potentially overlooked contributor to newer β-lactam/β-lactamase inhibitor (BL/BLI) treatment failure in carbapenem-resistant Enterobacterales (CRE) infections., Objectives: To determine rates of susceptibility and HR to BL/BLIs ceftazidime/avibactam, imipenem/relebactam and meropenem/vaborbactam in clinical CRE isolates., Methods: The first CRE isolate per patient per year from two >500 bed academic hospitals from 1 January 2016 to 31 December 2021, were included. Reference broth microdilution (BMD) was used to determine antibiotic susceptibility, and population analysis profiling (PAP) to determine HR. Carbapenemase production (CP) was determined using the Carba NP assay., Results: Among 327 CRE isolates, 46% were Enterobacter cloacae , 38% Klebsiella pneumoniae and 16% Escherichia coli . By BMD, 87% to 98% of CRE were susceptible to the three antibiotics tested. From 2016 to 2021, there were incremental decreases in the rates of susceptibility to each of the three BL/BLIs. HR was detected in each species-antibiotic combination, with the highest rates of HR (26%) found in K. pneumoniae isolates with imipenem/relebactam. HR or resistance to at least one BL/BLI by PAP was found in 24% of CRE isolates and 65% of these had detectable CP., Conclusion: Twenty-four percent of CRE isolates tested were either resistant or heteroresistant (HR) to newer BL/BLIs, with an overall decrease of ∼10% susceptibility over 6 years. While newer BL/BLIs remain active against most CRE, these findings support the need for ongoing antibiotic stewardship and a better understanding of the clinical implications of HR in CRE., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Background: Hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP) are frequently caused by multidrug-resistant organisms. Patient-centered endpoints in clinical trials are needed to develop new antibiotics for HABP/VABP. Desirability of outcome ranking (DOOR) is a paradigm for the design, analysis, and interpretation of clinical trials based on a patient-centered, benefit-risk evaluation., Methods: A multidisciplinary committee created an infectious diseases DOOR endpoint customized for HABP/VABP, incorporating infectious complications, serious adverse events, and mortality. We applied this to 2 previously completed, large randomized controlled trials for HABP/VABP. ZEPHyR compared vancomycin to linezolid and VITAL compared linezolid to tedizolid. For each trial, we evaluated the DOOR distribution and probability, including DOOR component and partial credit analyses. We also applied DOOR in subgroup analyses., Results: In both trials, the HABP/VABP DOOR demonstrated similar overall clinical outcomes between treatment groups. In ZEPHyR, the probability that a participant treated with linezolid would have a more desirable outcome than a participant treated with vancomycin was 50.2% (95% confidence interval [CI], 45.1%--55.3%). In VITAL, the probability that a participant treated with tedizolid would have a more desirable outcome than a participant treated with linezolid was 48.7% (95% CI, 44.8%-52.6%). The DOOR component analysis revealed that participants treated with tedizolid had a less desirable outcome than those treated with linezolid when considering clinical response alone. However, participants with decreased renal function had improved overall outcomes with tedizolid., Conclusions: The HABP/VABP DOOR provided more granular information about clinical outcomes than is typically presented in clinical trials. HABP/VABP trials would benefit from prospectively using DOOR., Competing Interests: Potential conflicts of interest. H. W. B. declares consulting fees from Antimicrobial Agents and Chemotherapy/American Society for Microbiology (ASM), Sanford Guide, and ID Clinics of North America/Elsevier; royalties from Sanford Guide; payment or honoraria from Grand Rounds at Temple; Finland Award for IDWeek Lecture travel; and role with travel reimbursed as Presidential Advisory Council on Combating Antibiotic-Resistant Bacteria (PACCARB) Voting Member and Board of Trustees, College of the Holy Cross. D. C. reports honoraria from ARLG, SimBioSys, AstraZeneca, Apellis Pharmaceutical, Kinnate Biopharma, MaxisIT Clinical Sciences, Pfizer, Parexel, Health Literacy Media, Incyte, American Society of Clinical Oncology, and Aster Insights, all unrelated to this work; and consulting fees from AstraZeneca, Incyte, Apellis Pharmaceuticals, Kinnate Biopharma, Maxis Health, Parexel, Health Literacy Media (nonprofit), and SimBioSys; reimbursement for personal expenses for attending meetings and/or travel from Aster Insights and the American Society of Clinical Oncology (ASCO); participation with honorarium to author on a data and safety monitoring board (DSMB) or advisory board for ASCO; a role as unpaid volunteer for the Metastatic Breast Cancer Alliance; and a role with honorarium to author from ORIEN Patient Advisory Council. H. F. C. reports grant funding from NIH; royalties from Sanford Guide to Antimicrobial Therapy; payment from The George Washington University for ID board review course lectures; participation in a DSMB for Merck; and stock in Merck and Moderna. S. B. D. reports research funding for clinical research studies from Gilead, Regeneron, Pfizer, F2G, Chan Zuckerberg Initiative Biohub, and NIH/NIAID; payments for clinical event adjudication committees from Basilea, Duke Clinical Research Institute, and Shionogi; a patent pending for Mif agonists (patent US20100143379A1); money for travel to conference from the Infectious Diseases Society of America (IDSA); and consulting fees from Genentech and Janssen/Johnson & Johnson (J&J); and leadership or fiduciary roles with IDSA Antibacterial Resistance Committee, California Department of Public Health Healthcare Associated Infections Advisory Committee, and the ARLG Innovations Group, Laboratory Center, Mentorship Committee, Gram Positive Committee, and Immunosuppressed Host Group. S. R. E. reports grant funding from NIH (NIAID, National Cancer Institute, National Heart, Lung, and Blood Institute), Centers for Disease Control and Prevention (CDC), and De Gruyter (Editor-in-Chief of Statistical Communications in Infectious Diseases); royalties from Taylor & Francis; consulting fees from Genetech, AstraZeneca, Takeda, Microbiotix, J&J, Endologix, ChemoCentryx, Becton Dickenson, Atricure, Roivant, Neovasc, Nobel Pharma, Horizon, International Drug Development Institute (IDDI), SVB Leerink, Medtronic, Regeneron, Wake Forest University, Recor, Janssen, and IDDI; payments from lectures from Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION); support for attending meetings from FDA; and participation on DSMBs for NIH, Breast International Group, University of Pennsylvania, Washington University, Duke University, Roche, Pfizer, Takeda, Akouous, Appelis, Teva, Vir, DayOneBio, Alexion, Tracon, Rakuten, AbbVie, GSK, Eli Lilly, Nuvelution, Clover, FHI Clinical, Lung Biotech, SAB Biopharm, Candel, Novartis, and Advantagene; and being an unpaid board member for the American Statistical Association, Society for Clinical Trials, and Frontier Science Foundation. V. G. F. reports personal fees from Novartis, Debiopharm, Genentech, Achaogen, Affinium, The Medicines Co, MedImmune, Bayer, Basilea, Affinergy, Janssen, ContraFect, Regeneron, Destiny, Amphliphi Biosciences, Integrated Biotherapeutics, C3J, Armata, Valanbio, Akagera, Aridis, and Roche; grants from NIH, MedImmune, Allergan, Pfizer, Advanced Liquid Logics, Theravance, Novartis, Merck, Medical Biosurfaces, Locus, Affinergy, ContraFect, Karius, Genentech, Regeneron, Deep Blue, Basilea, and Janssen; royalties from UpToDate; stock options from Valanbio and ArcBio; honoraria from IDSA for his service as Associate Editor of Clinical Infectious Diseases; and a patent pending in sepsis diagnostics. H. L.-T. is an employee of Pfizer and holds stock in Pfizer. C. H. receives stock dividends from GlaxoSmithKline. T. L. H. declares grant funding from NIH and Karius; royalties from UpToDate; consulting fees from Basilea Pharmaceutica, Affinivax, Lysovant, Aridis, and Pfizer; and participation on DSMB for platform trial for SNAP Trial and advisory board for Basilea. J. H.-A. reports grant funding from NIH and CDC; and payment from IDSA (reviewing IDSA/Clinical Infectious Diseases supplement), ARLG (for speaking at IDWeek dinner and Texas Medical Center Antimicrobial Resistance and Stewardship Conference conference), and Society for Healthcare Epidemiology of America (SHEA) (for speaking at SHEA Spring Conference). S. N. is an employee of J&J and holds stock in J&J; received support for travel to meetings paid by employer; and participated as unpaid member of a scientific advisory committee of Global Antibiotic Research and Development Partnership. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: The Serratia marcescens enzymes (SMEs) are chromosomally encoded Ambler Class A carbapenem-hydrolysing β-lactamases, which distinctively express resistance to carbapenems while remaining susceptible to extended-spectrum cephalosporins. Global reports of SMEs are infrequent. Here we describe the isolation of an SME-2-producing S. marcescens from the sputum of a patient who was hospitalized at Christchurch Hospital, New Zealand., Methods: An immunosuppressed asthmatic patient who presented with shortness of breath and hypoxia grew S. marcescens from a sputum culture. Antimicrobial susceptibilities were determined by Phoenix, with MICs of meropenem and imipenem determined by Liofilchem ® MIC gradient strips and interpreted according to EUCAST breakpoints. Investigation for carbapenemase was performed using Carba NP, modified CIM (mCIM) and GeneXpert ® Carba-R. WGS was performed using the Illumina DNA Prep library kit and sequenced using MiSeq., Results: The isolate showed an unusual susceptibility profile, including high-level resistance to meropenem and imipenem, while remaining susceptible to extended-spectrum cephalosporins. The Carba NP and mCIM were positive and WGS demonstrated the presence of a bla SME-2 gene located on the chromosome within the SmarGI1-1 genomic island. In addition, a bla SRT -like class C β-lactamase, aac(6')-Ic aminoglycoside-modifying enzyme and various multidrug efflux mechanisms were found. Phylogenetic core-genome analysis indicated no matching genome with RefSeq database strains., Conclusions: S. marcescens is an opportunistic pathogen of concern, harbouring a variety of intrinsic resistance mechanisms, including the potential for stable AmpC hyperproduction. Globally, SME-type carbapenemases have been infrequently reported; however, isolates carrying this mechanism could have limited treated options, having implications for patient management. To the best of our knowledge this is the first report of SME in New Zealand., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Clinical research networks conduct important studies that would not otherwise be performed by other entities. In the case of the Antibacterial Resistance Leadership Group (ARLG), such studies include diagnostic studies using master protocols, controlled phage intervention trials, and studies that evaluate treatment strategies or dynamic interventions, such as sequences of empiric and definitive therapies. However, the value of a clinical research network lies not only in the results from these important studies but in the creation of new approaches derived from collaborative thinking, carefully examining and defining the most important research questions for clinical practice, recognizing and addressing common but suboptimal approaches, and anticipating that the standard approaches of today may be insufficient for tomorrow. This results in the development and implementation of new methodologies and tools for the design, conduct, analyses, and reporting of research studies. These new methodologies directly impact the studies conducted within the network and have a broad and long-lasting impact on the field, enhancing the scientific value and efficiency of generations of research studies. This article describes innovations from the ARLG in diagnostic studies, observational studies, and clinical trials evaluating interventions for the prevention and treatment of antibiotic-resistant bacterial infections., Competing Interests: Potential conflicts of interest. All authors report funding support from the Antibacterial Resistance Leadership Group (ARLG) of the National Institutes of Health (NIH) and the National Institute of Allergy and Infectious Diseases (NIAID) (grant number UM1AI104681). S. R. E. reports grants from the NIAID and the NIH and Degruter (Editor-in-Chief for Statistical Communications in Infectious Diseases); royalties from Taylor & Francis; consulting fees from Genentech, AstraZeneca, Takeda, Microbiotix, Johnson & Johnson, Endologix, ChemoCentryx, Becton Dickinson, Atricure, Roviant, Neovasc, Nobel Pharma, Horizon, International Drug Development Institute, Medtronic, Regeneron, Wake Forest University, Recor, Janssen, IDDI, and SVB Leerink; payments from Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION); meeting support from the US Food and Drug Administration, Deming Conference on Applied Statistics, Clinical Trial Transformation Initiative, Council for International Organizations of Medical Sciences, International Chinese Statistical Association Applied Statistics Symposium, and Antimicrobial Resistance and Stewardship Conference; and board member participation for the NIH, Breast International Group, Washington University, University of Pennsylvania, Duke University, Roche, Pfizer, Takeda, Akouos, Apellis, Teva, Vir, DayOneBio, Alexion, Tracon, Rakuten, Abbvie, GSK, Eli Lilly, Nuvelution, Clover, FHI Clinical, Lung Biotech, SAB Biopharm, Advantagene, Candel, Novartis, American Statistical Association, Society for Clinical Trials, and Frontier Science Foundation. R. P. reports grants or contracts from ContraFect, TenNor Therapeutics Limited, BIOFIRE, and Adaptive Phage Therapeutics; a royalty-bearing know-how agreement and equity in Adaptive Phage Therapeutics through the Mayo Clinic; consulting fees from PhAST, Torus Biosystems, Day Zero Diagnostics, Mammoth Biosciences, HealthTrackRx, Netflix, Abbott Laboratories, Trellis Bioscience, Inc, Oxford Nanopore Technologies, and CARB-X; honoraria from the National Board of Medical Examiners, Up-to-Date, and the Infectious Diseases Board Review Course; a patent on Bordetella pertussis/parapertussis polymerase chain reaction (PCR) issued, a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic, and a patent on an anti-biofilm substance issued; and a financial relationship with Pathogenomix through the Mayo Clinic. T. H. reports consulting fees from Tanabe-Mitsubishi Pharma and honoraria from Duke University and Cancer and Chemo Therapy. J. H.-A. reports funding from the Centers for Disease Control and Prevention unrelated to the report reported in this manuscript, honoraria from the Infectious Diseases Society of America, and travel and meeting support from the Society for Healthcare Epidemiology of America (SHEA) and the ARLG. D. C. reports personal consulting fees from AstraZeneca, Incyte, Apellis Pharmaceuticals, Inc, Kinnate Biopharma, Maxis Health, Parexel, and Health Literacy Media (nonprofit); travel and meeting support from M2GEN and the American Society of Clinical Oncology; participation on a Data and Safety Monitoring Board (DSMB) for the American Society of Clinical Oncology; and leadership in the Metastatic Breast Cancer Alliance. H. C. reports salary support from the ARLG via Duke University. H. F. C. reports royalties from the Sanford Guide to Antimicrobial Therapy, payment for expert testimony from Nexus Pharmaceuticals, participation on a Merck DSMB for molnupiravir, and stock ownership in Moderna and Merck. V. G. F. reports personal consulting fees from Novartis, Debiopharm, Genentech, Achaogen, Affinium, Medicines Co, MedImmune, Bayer, Basilea, Affinergy, Janssen, Contrafect, Regeneron, Destiny, Amphliphi Biosciences, Integrated Biotherapeutics, C3J, Armata, Valanbio, Akagera, Aridis, Roche, and Pfizer (paid to the author); grants from the NIH, MedImmune, Allergan, Pfizer, Advanced Liquid Logics, Theravance, Novartis, Merck, Medical Biosurfaces, Locus, Affinergy, Contrafect, Karius, Genentech, Regeneron, Deep Blue, Basilea, and Janssen; royalties from UpToDate; stock options from Valanbio and ArcBio; honoraria from the Infectious Diseases Society of America for his service as Associate Editor of Clinical Infectious Diseases; travel support from Contrafect to the 2019 European Society of Clinical Microbiology and Infectious Diseases (ECCMID); and a sepsis diagnostics patent pending. H. B. reports royalties from the Sanford Guide; consulting fees from the Sanford Guide, Antimicrobial Agents and Chemotherapy/ASM, and ID Clinics of North America/Elsevier; honoraria for Grand Rounds at Temple University; travel and meeting support for an IDWeek Lecture; and membership as a voting member on the Presidential Advisory Council on Combating Antibiotic-Resistant Bacteria (PACCARB) and membership on the Board of Trustees at the College of the Holy Cross. H. K. reports funding awarded to her institution(s) from the Durham Center of Innovation to Accelerate Discovery and PracticeTransformation (CIN 13-410) at the Durham Veterans Affairs Health Care System, NIH, and Merck, Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc, Rahway, NJ, USA. They also report serving on the editorial board for the Journal of Antimicrobial Chemotherapy- Antimicrobial Resistance (JAC-AMR). T. K. reports no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: With multiple comorbidities and frequent exposures to antibiotics, patients in skilled nursing facilities (SNFs) are much more vulnerable to healthcare-acquired infections. We conducted a quality-improvement, retrospective analysis of all patients with Clostridioides difficile infection (CDI) from 2009 to 2021 at an SNF. Probiotics were initially added to a bundle of antimicrobial stewardship programme (ASP) CDI prevention strategies. Formulations and durations of probiotics were standardized for both oral and enteral administration. To reach all eligible patients, an ASP probiotic policy provided probiotics with every antibiotic course., Objectives: To assess the value of providing probiotic therapy to SNF patients at risk for CDI., Patients and Methods: Patients receiving oral or enteral feeding with antibiotics ordered were eligible to receive probiotics. The incremental cost of CDI prevention, treatment and related care were calculated and compared for each phase of probiotic policy change and feeding type. ASP records for the oral probiotic and level of treatment were used in modelling the cost-effectiveness., Results: From quality improvement initiatives aimed at preventing facility-onset (FO) CDI, to ASP policies, probiotic formulations and delegation of ordering authority, the days of acute care treatment required was significantly reduced over the different phases of implementation [152 to 48, OR = 0.22 (0.16-0.31) to 4, OR = 0.08 (0.03-0.23)] after reducing total CDI from 5.8 to 0.3 cases per 10 000 patient-days. The annual cost of oral probiotics increased from $6019 to $14 652 but the modelled net annual savings for the facility was $72 544-$154 085., Conclusions: With optimization, the use of probiotics for CDI prevention at an SNF was safe, efficacious and cost-effective., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Background: Desirability of outcome ranking (DOOR) is a novel approach to clinical trial design that incorporates safety and efficacy assessments into an ordinal ranking system to evaluate overall outcomes of clinical trial participants. Here, we derived and applied a disease-specific DOOR endpoint to registrational trials for complicated intra-abdominal infection (cIAI)., Methods: Initially, we applied an a priori DOOR prototype to electronic patient-level data from 9 phase 3 noninferiority trials for cIAI submitted to the US Food and Drug Administration between 2005 and 2019. We derived a cIAI-specific DOOR endpoint based on clinically meaningful events that trial participants experienced. Next, we applied the cIAI-specific DOOR endpoint to the same datasets and, for each trial, estimated the probability that a participant assigned to the study treatment would have a more desirable DOOR or component outcome than if assigned to the comparator., Results: Three key findings informed the cIAI-specific DOOR endpoint: (1) a significant proportion of participants underwent additional surgical procedures related to their baseline infection; (2) infectious complications of cIAI were diverse; and (3) participants with worse outcomes experienced more infectious complications, more serious adverse events, and underwent more procedures. DOOR distributions between treatment arms were similar in all trials. DOOR probability estimates ranged from 47.4% to 50.3% and were not significantly different. Component analyses depicted risk-benefit assessments of study treatment versus comparator., Conclusions: We designed and evaluated a potential DOOR endpoint for cIAI trials to further characterize overall clinical experiences of participants. Similar data-driven approaches can be utilized to create other infectious disease-specific DOOR endpoints., Competing Interests: Potential conflicts of interest. H. W. B. declares consulting fees from Antimicrobial Agents and Chemotherapy, Sanford Guide, and ID Clinics of North America. H. C. reports grant funding from the NIH; participation in a data and safety monitoring board (DSMB) for Merck; and stock in Merck and Moderna. D. C. reports grant funding from Apellis Pharmaceuticals, CRUK Cancer Grand Challenges, Kinnate Biopharma, and Incyte; consulting fees from Health Literacy Media and MaxisIT Clinical Science; payment for expert panel session from Pfizer; participation on a patient advisory council and travel support for meetings from M2GEN; and participation in the American Society of Clinical Oncology TAPUR Study DSMB and Parexel patient advisory council. S. B. D. reports grant funding from NIH; grant funding for COVID-19–related clinical trials from Gilead and Regeneron; payments for clinical event adjudication committees from Basilea and Shinogi; and consulting fees from Genentech. S. E. reports grant funding from NIH, Degruyter, and Aceragen; royalties from Taylor & Francis; consulting fees from Genetech, AstraZeneca, Takeda, Microbiotix, Johnson & Johnson, Endologix, ChemoCentryx, Becton Dickinson, Atricure, Roivant, Neovasc, Nobel Pharma, Horizon, International Drug Development Institute, and SVB Leerink; payments for lectures from the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION); support for attending meetings from FDA, Deming Conference on Applied Statistics, Clinical Trial Transformation Initiative, Council for International Organization of Medical Sciences, International Chinese Statistical Association Applied Statistics Symposium, and Antimicrobial Resistance and Stewardship Conference; participation on DSMB for NIH, Breast International Group, University of Pennsylvania, Duke University, Roche, Pfizer, Takeda, Akouous, Appelis, Teva, Vir, DayOneBio, Alexion, Tracon, Rakuten, AbbVie, Nuvelution, Clover, FHI Clinical, Lung Biotech, SAB Biopharm, and Candel; and board membership for the American Statistical Association, Society for Clinical Trials, and Frontier Science Foundation. V. G. F. reports grant funding or contracts from NIH, MedImmune, Allergan, Pfizer, Advanced Liquid Logics, Theravance, Novartis, Merck, Medical Biosurfaces, Locus, Affinergy, Contrafect, Karius, Genetech, Regeneron, Deep Blue, Basilea, and Janssen; royalties from UpToDate; consulting fees from Novartis, Debiopharm, Genetech, Achaogen, Affinium, The Medicines Co., MedImmune, Bayer, Basilea, Affinergy, Janssen, Contrafect, Regeneron, Destiny, Amphliphi Biosciences, Integrated Biotherapeutics, C3J, Armata, Valanbio, Akagera, Aridis, Roche, and Pfizer; support from Contrafect to present phase 2 data at 2019 European Congress of Clinical Microbiology and Infectious Diseases; a patent for sepsis diagnostics; serving as Associate Editor of Clinical Infectious Diseases in 2017–2022; and stock options from ArcBio and Valanbio. T. H. reports consulting fees from Tanabe-Mitsubishi Pharma K.K; a contract from Aceragen; payment for lectures from Duke University and Johnson & Johnson K.K.; and payment for manuscript preparation from Cancer and Chemotherapy K.K. (Japanese Journal of Cancer and Chemotherapy). T. L. H. reports grant funding from NIH; royalties from UpToDate; consulting fees from Lysovant and Affinivax; and participation on DSMB for SNAP Trial Platform. J. H.-A. reports grant funding from NIH. S. N. is an employee of Johnson & Johnson. U. W. reports support from the American Society for Microbiology to attend ASM Microbe 2022 as a speaker. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2023.)

Assets-based interventions can address child health disparities by connecting families to existing community resources. Community collaboration when designing interventions may identify barriers and facilitators to implementation. The objective of this study was to identify crucial implementation considerations during the design phase of an asset-based intervention to address disparities in childhood obesity, Assets for Health. We conducted focus groups and semi-structured interviews with caregivers of children (<18 years) (N = 17) and representatives of community-based organizations (CBOs) which serve children and families (N = 20). Focus group and interview guides were developed based on constructs from the Consolidated Framework for Implementation Research. Data were analyzed using rapid qualitative analysis and matrices were used to identify common themes within and across groups of community members. Desired intervention characteristics included an easy-to-use list of community programs that could be filtered based on caregiver preferences and local community health workers to promote trust and engagement among Black and Hispanic/Latino families. Most community members felt an intervention with these characteristics could be advantageous versus existing alternatives. Key outer setting characteristics which were barriers to family engagement included families' financial insecurity and lack of access to transportation. The CBO implementation climate was supportive but there was concern that the intervention could increase staff workload beyond current capacity. Assessment of implementation determinants during the intervention design phase revealed important considerations for intervention development. Effective implementation of Assets for Health may depend on app design and usability, fostering organizational trust and minimizing the costs and staff workload of caregivers and CBOs, respectively., (Published by Oxford University Press on behalf of the Society of Behavioral Medicine 2023.)

Background: Traditional end points used in registrational randomized, controlled trials (RCTs) often do not allow for complete interpretation of the full range of potential clinical outcomes. Desirability of outcome ranking (DOOR) is an approach to the design and analysis of clinical trials that incorporates benefits and risks of novel treatment strategies and provides a global assessment of patient experience., Methods: Through a multidisciplinary committee of experts in infectious diseases, clinical trial design, drug regulation, and patient experience, we developed a DOOR end point for infectious disease syndromes and demonstrated how this could be applied to 3 registrational drug trials (ZEUS, APEKS-cUTI, and DORI-05) for complicated urinary tract infections (cUTIs). ZEUS compared fosfomycin to piperacillin/tazobactam, APEKS-cUTI compared cefiderocol to imipenem, and DORI-05 compared doripenem to levofloxacin. Using DOOR, we estimated the probability of a more desirable outcome with each investigational antibacterial drug., Results: In each RCT, the DOOR distribution was similar and the probability that a patient in the investigational arm would have a more desirable outcome than a patient in the control arm had a 95% confidence interval containing 50%, indicating no significant difference between treatment arms. DOOR facilitated improved understanding of potential trade-offs between clinical efficacy and safety. Partial credit and subgroup analyses also highlight unique attributes of DOOR., Conclusions: DOOR can effectively be used in registrational cUTI trials. The DOOR end point presented here can be adapted for other infectious disease syndromes and prospectively incorporated into future clinical trials., Competing Interests: Potential conflicts of interest. H. W. B. declares consulting fees from Antimicrobial Agents and Chemotherapy, Sanford Guide, and ID Clinics of North America. T. B. is an employee of and holds stock in Shionogi & Co and reports a nondisclosure agreement between Duke University and Shionogi (to share the analysis conducted by Shionogi with the Antibacterial Resistance Leadership Group [ARLG]). H. F. C. reports grant funding from NIH; consulting fees from Johnson & Johnson; participation on a data and safety monitoring board (DSMB) for Merck; and stock in Merck and Moderna. S. B. D. reports research funding from Gilead, Regeneron, and NIH; payments for clinical event adjudication committees from Basilea and Shionogi (pending); and consulting fees from Genentech. S. R. E. reports grant funding from NIH and Degruyter; royalties from Taylor & Francis; consulting fees from Genetech, AstraZeneca, Takeda, Microbiotix, Johnson & Johnson, Endologix, ChemoCentryx, Becton Bickenson, Atricure, Roivant, Neovasc, Nobel Pharma, Horizon, International Drug Development Institute, and SVB Leerink; payments for lectures from the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks; support for attending meetings from FDA, Clinical Trial Transformation Initiative, Council for International Organization of Medical Sciences, International Chinese Statistical Association, participation on DSMBs for NIH, Breast International Group, University of Pennsylvania, Duke University, Roche, Pfizer, Takeda, Akouous, Appelis, Teva, Vir, DayOneBio, Alexion, Tracon, Rakuten, AbbVie, Nuvelution, Clover, FHI Clinical, Lung Biotech, SAB Biopharm, and Advantagene; and being a board member for the American Statistical Association, Society for Clinical Trials, and Frontier Science Foundation. V. G. F. reports personal fees from Novartis, Debiopharm, Genentech, Achaogen, Affinium, Medicines Co, MedImmune, Bayer, Basilea, Affinergy, Janssen, Contrafect, Regeneron, Destiny, Amphliphi Biosciences, Integrated Biotherapeutics, C3J, Armata, Valanbio, Akagera, Aridis, Roche; grants from NIH, MedImmune, Allergan, Pfizer, Advanced Liquid Logics, Theravance, Novartis, Merck, Medical Biosurfaces, Locus, Affinergy, Contrafect, Karius, Genentech, Regeneron, Deep Blue, Basilea, Janssen; royalties from UpToDate; stock options from Valanbio and ArcBio; honoraria from the Infectious Diseases of America for service as associate editor of Clinical Infectious Diseases; and a patent for sepsis diagnostics is pending. S. P. G. is an employee of Nabriva Therapeutics and holds stock in Nabriva Therapeutics. T. H. reports consulting fees from Tanabe-Mitsubishi Pharma and payment for lectures from Johnson & Johnson and Duke University. T. L. H. declares royalties from UpToDate and consulting fees from Basilea Pharmaceutica, MotifBio, Genentech, and Lysovant. D. M. is an employee of Nabriva Therapeutics and holds stock in Nabriva Therapeutics. S. N. is an employee of Johnson & Johnson and holds stock in Johnson & Johnson. J. H.-A. report grants from NIH (funding to ARLG, payments made to institution). S. B. D. reports grants or contracts from NIH funding to the ARLG; research funding from Gilead, Regeneron, and NIH; payments for clinical event adjudication committees from Basilea and Shionogi (pending); and consulting fees from Genentech. All remaining authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Fish gastro-intestinal system harbors diverse microbiomes that affect the host's digestion, nutrition, and immunity. Despite the great taxonomic diversity of fish, little is understood about fish microbiome and the factors that determine its structure and composition. Damselfish are important coral reef species that play pivotal roles in determining algae and coral population structures of reefs. Broadly, damselfish belong to either of two trophic guilds based on whether they are planktivorous or algae-farming. In this study, we used 16S rRNA gene sequencing to investigate the intestinal microbiome of 5 planktivorous and 5 algae-farming damselfish species ( Pomacentridae ) from the Great Barrier Reef. We detected Gammaproteobacteria ASVs belonging to the genus Actinobacillus in 80% of sampled individuals across the 2 trophic guilds, thus, bacteria in this genus can be considered possible core members of pomacentrid microbiomes. Algae-farming damselfish had greater bacterial alpha-diversity, a more diverse core microbiome and shared 35 ± 22 ASVs, whereas planktivorous species shared 7 ± 3 ASVs. Our data also highlight differences in microbiomes associated with both trophic guilds. For instance, algae-farming damselfish were enriched in Pasteurellaceae , whilst planktivorous damselfish in Vibrionaceae . Finally, we show shifts in bacterial community composition along the intestines. ASVs associated with the classes Bacteroidia, Clostridia , and Mollicutes bacteria were predominant in the anterior intestinal regions while Gammaproteobacteria abundance was higher in the stomach. Our results suggest that the richness of the intestinal bacterial communities of damselfish reflects host species diet and trophic guild., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology.)

Aims: Oxygen-pulse morphology and gas exchange analysis measured during cardiopulmonary exercise testing (CPET) has been associated with myocardial ischaemia. The aim of this analysis was to examine the relationship between CPET parameters, myocardial ischaemia and anginal symptoms in patients with chronic coronary syndrome and to determine the ability of these parameters to predict the placebo-controlled response to percutaneous coronary intervention (PCI)., Methods and Results: Patients with severe single-vessel coronary artery disease (CAD) were randomized 1:1 to PCI or placebo in the ORBITA trial. Subjects underwent pre-randomization treadmill CPET, dobutamine stress echocardiography (DSE) and symptom assessment. These assessments were repeated at the end of a 6-week blinded follow-up period.A total of 195 patients with CPET data were randomized (102 PCI, 93 placebo). Patients in whom an oxygen-pulse plateau was observed during CPET had higher (more ischaemic) DSE score [+0.82 segments; 95% confidence interval (CI): 0.40 to 1.25, P = 0.0068] and lower fractional flow reserve (-0.07; 95% CI: -0.12 to -0.02, P = 0.011) compared with those without. At lower (more abnormal) oxygen-pulse slopes, there was a larger improvement of the placebo-controlled effect of PCI on DSE score [oxygen-pulse plateau presence (Pinteraction = 0.026) and oxygen-pulse gradient (Pinteraction = 0.023)] and Seattle angina physical-limitation score [oxygen-pulse plateau presence (Pinteraction = 0.037)]. Impaired peak VO2, VE/VCO2 slope, peak oxygen-pulse, and oxygen uptake efficacy slope was significantly associated with higher symptom burden but did not relate to severity of ischaemia or predict response to PCI., Conclusion: Although selected CPET parameters relate to severity of angina symptoms and quality of life, only an oxygen-pulse plateau detects the severity of myocardial ischaemia and predicts the placebo-controlled efficacy of PCI in patients with single-vessel CAD., Competing Interests: Conflict of interest: S.G., C.A.R., M.F., D.T., R.W., D.F., and R.P. have nothing to disclose. A.N.N. reports receiving support for a Doctoral Fellowship by the NIHR Academy which was paid to her institution. H.S. reports research funding from the Imperial College COVID research fund and the Foundation for Circulatory Support. S.S. reports individual grants from Medtronic and Phillips and speaker’s honoraria from Medtronic, Phillips and Pfizer. S.N. reports consulting and speaking fees from Phillips Volcano. S.A.T. reports an unpaid leadership role with the UK National Institute for Health Research cardiovascular advisory panel. J.D. reports receipt of consulting fees (from Boston Scientific, Abbott and Medtronic), speaker’s honoraria (from Pfizer, Bayer and Novartis), and equipment support (from Abbott and Terumo). M.S.-S. reports speaker’s honoraria from Pfizer. J.H. reports a small cardiac MRI project grant from the Academy of Medical Sciences. R.A.-L. reports speaker’s honoraria from Philips Volcano, Abbott Vascular, and Menarini Pharmaceuticals., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology.)

Background: Over the last decade, primary care clinics in the United States have responded both to national policies encouraging clinics to support substance use disorders (SUD) service expansion and to regulations aiming to curb the opioid epidemic., Objective: To characterize approaches to SUD service expansion in primary care clinics with national reputations as workforce innovators., Methods: Comparative case studies were conducted to characterize different approaches among 12 primary care clinics purposively and iteratively recruited from a national registry of workforce innovators. Observational field notes and qualitative interviews from site visits were coded and analysed to identify and characterize clinic attributes., Results: Codes describing clinic SUD expansion approaches emerged from our analysis. Clinics were characterized as: avoidant (n = 3), contemplative (n = 5) and responsive (n = 4). Avoidant clinics were resistant to planning SUD service expansion; had no or few on-site behavioural health staff; and lacked on-site medication treatment (previously termed medication-assisted therapy) waivered providers. Contemplative clinics were planning or had partially implemented SUD services; members expressed uncertainties about expansion; had co-located behavioural healthcare providers, but no on-site medication treatment waivered and prescribing providers. Responsive clinics had fully implemented SUD; members used non-judgmental language about SUD services; had both co-located SUD behavioural health staff trained in SUD service provision and waivered medication treatment physicians and/or a coordinated referral pathway., Conclusions: Efforts to support SUD service expansion should tailor implementation supports based on specific clinic training and capacity building needs. Future work should inform the adaption of evidence-based practices that are responsive to resource constraints to optimize SUD treatment access., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: To describe the prevalence of colistin heteroresistance in carbapenem-resistant Pseudomonas aeruginosa (CRPA) and evaluate the association with clinical outcomes., Methods: Colistin heteroresistance was evaluated in CRPA isolates collected from patients without cystic fibrosis in Atlanta, Georgia, USA using two definitions: HR1, growth at 4 and 8 mg/L of colistin at a frequency ≥1 × 10-6 the main population; and HR2, growth at a colistin concentration ≥8× the MIC of the main population at a frequency ≥1 × 10-7. A modified population analysis profile (mPAP) technique was compared with reference PAP for detecting heteroresistance. For adults hospitalized at the time of or within 1 week of CRPA culture, multivariable logistic regression estimated the association between heteroresistance and 90 day mortality., Results: Of 143 colistin-susceptible CRPA isolates, 8 (6%) met the HR1 definition and 37 (26%) met the HR2 definition. Compared with the reference PAP, mPAP had a sensitivity and specificity of 50% and 100% for HR1 and 32% and 99% for HR2. Of 82 hospitalized patients, 45 (56%) were male and the median age was 63 years (IQR 49-73). Heteroresistance was not associated with 90 day mortality using HR1 (0% in heteroresistant versus 22% in non-heteroresistant group; P = 0.6) or HR2 (12% in heteroresistant versus 24% in non-heteroresistant group; P = 0.4; adjusted OR 0.8; 95% CI 0.2-3.4)., Conclusions: Colistin heteroresistance was identified in up to 26% of patients with CRPA in our sample, although the prevalence varied depending on the definition. We did not observe an apparent association between colistin heteroresistance and 90 day mortality., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) isolates can frequently retain susceptibility to traditional antipseudomonal β-lactams including cefepime, ceftazidime and piperacillin/tazobactam., Objectives: This observational study aimed to determine the proportion of CRPA isolates that were susceptible to all tested other traditional antipseudomonal β-lactams (S-CRPA) and assess whether patients with S-CRPA had improved 30 day mortality compared with patients with NS-CRPA (non-susceptible to cefepime, ceftazidime or piperacillin/tazobactam)., Methods: Patients with CRPA isolated from normally sterile sites, urine, lower respiratory tracts and wounds were identified using active population- and laboratory-based surveillance through the Georgia Emerging Infections Program from August 2016 to July 2018 in Atlanta, GA, USA. Only unique patients who were hospitalized at the time of, or within 1 week of, culture were included. We excluded patients with cystic fibrosis. Multivariable logistic regression estimated the association between S-CRPA and 30 day mortality., Results: Among 635 adults hospitalized with CRPA, 219 (34%) had S-CRPA. Patients with S-CRPA were more likely to be white (50% versus 38%, P = 0.01) and live in a private residence prior to culture (44% versus 28%, P < 0.01), and less likely to have required ICU care within the prior week (23% versus 36%, P < 0.01) compared with patients with NS-CRPA. Compared with those with NS-CRPA, patients with S-CRPA had an increased 30 day mortality (18% versus 15%, adjusted OR 1.9; 95% CI 1.2-3.1)., Conclusions: S-CRPA was associated with higher 30 day mortality than NS-CRPA in hospitalized patients. The reason for this observed increase in mortality deserves further investigation., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.)

Ongoing neuroinflammation may contribute to symptoms of autism spectrum disorder (ASD) in at least a portion of affected individuals. Mesenchymal stromal cells (MSCs) have demonstrated the capacity to modulate neuroinflammation, but safety and feasibility of MSC administration in children with ASD have not been well established. In this open-label, phase I study, 12 children with ASD between 4 and 9 years of age were treated with intravenous (IV) infusions of human cord tissue mesenchymal stromal cells (hCT-MSCs), a third-party MSC product manufactured from unrelated donor umbilical cord tissue. Children received one, two, or three doses of 2 × 10 6 cells per kilogram at 2-month intervals. Clinical and laboratory evaluations were performed in person at baseline and 6 months and remotely at 12 months after the final infusion. Aside from agitation during the IV placement and infusion in some participants, hCT-MSCs were well tolerated. Five participants developed new class I anti-human leukocyte antigen (HLA) antibodies, associated with a specific lot of hCT-MSCs or with a partial HLA match between donor and recipient. These antibodies were clinically silent and not associated with any clinical manifestations to date. Six of 12 participants demonstrated improvement in at least two ASD-specific measures. Manufacturing and administration of hCT-MSCs appear to be safe and feasible in young children with ASD. Efficacy will be evaluated in a subsequent phase II randomized, placebo-controlled clinical trial., (© 2020 The Authors. STEM CELLS TRANSLATIONAL MEDICINE published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.)

Aims: Ablation of persistent atrial fibrillation (PsAF) has been performed by many techniques with varying success rates. This may be due to ablation techniques, patient demographics, comorbidities, and trial design. We conducted a meta-regression of studies of PsAF ablation to elucidate the factors affecting atrial fibrillation (AF) recurrence., Methods and Results: Databases were searched for prospective studies of PsAF ablation. A meta-regression was performed. Fifty-eight studies (6767 patients) were included. Complex fractionated atrial electrogram (CFAE) ablation reduced freedom from AF by 8.9% [95% confidence interval (CI) -15 to -2.3, P = 0.009). Left atrial appendage [LAA isolation (three study arms)] increased freedom from AF by 39.5% (95% CI 9.1-78.4, P = 0.008). Posterior wall isolation (PWI) (eight study arms) increased freedom from AF by 19.4% (95% CI 3.3-38.1, P = 0.017). Linear ablation or ganglionated plexi ablation resulted in no significant effect on freedom from AF. More extensive ablation increased intraprocedural AF termination; however, intraprocedural AF termination was not associated with improved outcomes. Increased left atrial diameter was associated with a reduction in freedom from AF by 4% (95% CI -6.8% to -1.1%, P = 0.007) for every 1 mm increase in diameter., Conclusion: Linear ablation, PWI, and CFAE ablation improves intraprocedural AF termination, but such termination does not predict better long-term outcomes. Study arms including PWI or LAA isolation in the lesion set were associated with improved outcomes in terms of freedom from AF; however, further randomized trials are required before these can be routinely recommended. Left atrial size is the most important marker of AF chronicity influencing outcomes., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

The importance of research and recommendations to address workforce safety and health derives from the continuing toll from worker fatalities, injuries, and illnesses. Estimates of the societal cost of work-related fatalities, injuries, and illnesses range up to $2.2 trillion in the USA from 2007 to 2015, which may be an underestimate of total societal costs. The ongoing changes in the nature of work, the workforce, and the workplace in the USA challenge old paradigms of worker safety and health research and require new decision criteria that are more solution oriented than observational and that result in interventions that can be readily applied to new occupational hazards and exposures. As public funding for science research programs becomes more constrained, and the demand for increased accountability of government spending grows, the need to demonstrate the impact or return on taxpayers' investment becomes a necessity for research agencies. The National Institute for Occupational Safety and Health has developed an evidence-based method that uses the criteria of 'burden', 'need', and 'impact' to identify research priorities and aid in the evaluation of the taxpayers' investment in research. This approach, named the BNI method, may be useful to other public and private sector research agencies or entities that need a systematic way to set research priorities and allocate increasingly scarce resources for research while ensuring the maximal return on investment., (Published by Oxford University Press on behalf of The British Occupational Hygiene Society 2019.)