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Observations of low-mass protostellar systems show evidence of rich, complex organic chemistry. Their low luminosity, however, makes determining abundance distributions of complex organic molecules within the water snowline challenging. However, the excitation conditions sampled by differing molecular distributions may produce substantive changes in the resulting emission. Thus, molecular excitation may recover spatial information from spatially unresolved data. By analyzing spatially unresolved NOrthern Extended Millimeter Array observations of CH _3 OH and CH _3 CN, we aim to determine if CH _3 OH and CH _3 CN are distributed differently in the protostellar disk around HOPS-370, a highly luminous intermediate-mass protostar. Rotational diagram analysis of CH _3 OH and CH _3 CN yields rotational temperatures of 198 ± 1.2 K and 448 ± 19 K, respectively, suggesting the two molecules have different spatial distributions. Source-specific 3D LTE radiative transfer models are used to constrain the spatial distribution of CH _3 OH and CH _3 CN within the disk. A uniform distribution with an abundance of 4 × 10 ^−8 reproduces the CH _3 OH observations. In contrast, the spatial distribution of CH _3 CN needs to be either more compact (within ∼120 au versus ∼240 au for CH _3 OH) or exhibit a factor of ≳15 increase in abundance in the inner ∼55 au. A possible explanation for the difference in spatial abundance distributions of CH _3 OH and CH _3 CN is carbon-grain sublimation.

Background: Many patients with Enterococcus faecalis endocarditis are clinically stable and able to leave hospital before completing antibiotic treatment, but data are lacking regarding some outpatient treatment options., Objectives: To assess the outcomes for adults with E. faecalis endocarditis receiving outpatient parenteral antimicrobial therapy (OPAT) with continuous infusion IV benzylpenicillin plus bolus/continuous infusion IV ceftriaxone., Patients and Methods: We retrospectively reviewed adults who received at least 2 weeks duration of OPAT for E. faecalis endocarditis with the above treatment regimen in the Auckland and Christchurch regions between July 2019 and September 2022., Results: Forty-four patients met inclusion criteria. Fifteen were female (34%). The median age was 80 (IQR 71.5 to 84) years. Twenty-two (50%) had prosthetic valve (PV), 15 (34%) native valve (NV), 3 (7%) NV and/or cardiac implantable electronic device (CIED) infection, 3 (7%) PV and/or CIED infection, and 1 (2%) repaired valve endocarditis. Patients received a median of 16.5 days inpatient and 28 days OPAT antibiotic treatment. The 12 month outcome was cure ( n  = 25; 57%), antibiotic suppression ( n  = 9; 20%), relapse ( n  = 2; 5%; both possible) or death ( n  = 8; 18%). Compared with a historical cohort treated with OPAT continuous infusion IV benzylpenicillin plus bolus IV gentamicin, there was no difference in the relapse rate., Conclusions: This study adds to the accumulating evidence supporting the treatment of E. faecalis endocarditis with OPAT continuous infusion IV benzylpenicillin plus bolus/continuous infusion IV ceftriaxone. This is an option for patients requiring further antibiotic treatment at the time of hospital discharge., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Background: Staphylococcus aureus bloodstream infection (bacteremia) is traditionally treated with at least 2 weeks of intravenous (IV) antibiotics in adults, 3-7 days in children, and often longer for those with complicated disease. The current practice of treating S. aureus bacteremia (SAB) with prolonged IV antibiotics (rather than oral antibiotics) is based on historical observational research and expert opinion. Prolonged IV antibiotic therapy has significant disadvantages for patients and healthcare systems, and there is growing interest in whether a switch to oral antibiotics following an initial period of IV therapy is a safe alternative for clinically stable patients., Protocol: The early oral switch (EOS) domain of the S. aureus Network Adaptive Platform (SNAP) trial will assess early switch to oral antibiotics compared with continued IV treatment in clinically stable patients with SAB. The primary endpoint is 90-day all-cause mortality. Hospitalised SAB patients are assessed at platform day 7 ±2 (uncomplicated SAB) and day 14 ±2 (complicated SAB) to determine their eligibility for randomization to EOS (intervention) or continued IV treatment (current standard of care)., Discussion: Recruitment is occurring in the EOS domain of the SNAP trial. As of August 2023, 21% of all SNAP participants had been randomized to the EOS domain, a total of 264 participants across 77 centers, with an aim to recruit at least 1000 participants. We describe challenges and facilitators to enrolment in this domain to aid those planning similar trials., Competing Interests: Potential conflicts of interest. A. McGlothlin is an employee of Berry Consultants, LLC, a statistical consulting firm that specializes in the design of adaptive and platform clinical trials. Berry Consultants received compensation for work included in the content of the submission. A. C. Bowen reports participation as a member of the CAMERA-2 data and safety monitoring board (DSMB) and as chair of the Skin Trial DSMB; she also reports participation on Phage Trial DSMB and participation as Chair of FOSUTI DSMB; a role as Vice President of the World Society of Paediatric Infectious Diseases and as Co-Chair, Australian and New Zealand Pediatric Infectious Diseases group of the Australasian Society of Infectious Diseases (ASID). D. L. Paterson reports grants or contracts made to institution and unrelated to this work from Shionogi, Merck, and Pfizer; consulting fees to author from Antimicrobial Resistance Action Fund and Spero Therapeutics; payment or honoraria for lectures, presentations, speaker's bureaus, manuscript writing, or educational events to author from Pfizer and Merck; support for attending meetings and/or travel to author from Pfizer; and an unpaid leadership or fiduciary role with ASID. J. A. Roberts reports contracts or grants paid to institution and unrelated to this work from Pfizer and QPEX and investigator grant (APP2009736) and Advancing Queensland Clinical Fellowship; consulting fees paid to author from QPEX, Advanz Pharma, Gilead, Pfizer, Sandoz, Summit Pharma, and MSD; payment to author for lectures, presentations, speaker's bureaus, manuscript writing, or educational events from MSD, Gilead, Pfizer, and Cipla. J. Ten Oever reports grants or contracts unrelated to this work from Pfizer and MSD; support for attending meetings and/or travel to author from Pfizer; M. P. Cheng reports research support from the Canadian Institutes of Health Research and is supported by the Fonds de Recherche du Québec—Santé; research contracts from Cidara Therapeutics, Scynexis, and Amplyx Pharmaceuticals; consulting fees as a scientific consultant for AstraZeneca, Takeda, Merck, and Pfizer; 3 pending patents (Methods for detecting tissue damage, graft-versus-host disease, and infections using cell-free DNA profiling; Methods for assessing the severity and progression of SARS-CoV-2 infections using cell-free DNA; and rapid identification of antimicrobial resistance and other microbial phenotypes using highly multiplexed fluorescence in situ hybridization); stock options as a member of the scientific advisory board for GEn1E Lifesciences and Nomic Bio; and equity as co-founder of Kanvas Biosciences. R. J. Lewis is an employee of Berry Consultants, LLC, a statistical consulting firm that specializes in the design of adaptive and platform clinical trials. Berry Consultants received compensation for work included in the content of the submission. S. A. W. reports personal consulting fees from ClinicIQ pharma and Roche; an unpaid role as chair of Australian Clinical Trials Alliance; and stock and options with ClinicIQ. S. C. Morpeth reports grants or contracts unrelated to this work from the HRC, and a nonremunerated role as the Chair of the New Zealand Microbiology Network. S. Kalimuddin reports consulting fees from Gilead, Janssen, and Takeda (payments made to Singapore General Hospital) and grants or contracts unrelated to this work from National Medical Research Council, Singapore. S. Y. C. Tong reports a contract as a paid consultant for advice on clinical trial design, and consulting fees from Roivant Sciences as a paid consultant for advice on clinical trial design; and reports grants or contracts unrelated to this work from Australian National Health and Medical Research Council. T. C. Lee reports research salary support from Fonds de Recherche Quebec–Sante, operating funds for other studies including CATCO from the CIHR; and operating funds for other studies from the McGill Interdisciplinary Institute Infection and Immunity. Conflicts that the editors consider relevant to the content of the article have been disclosed. Collaborating authors have not been asked for their potential conflicts. A. Campbell reports National Health and Medical Research Council (grant 2014900) for SNAPPY and Perth Children's Hospital Foundation for site funding for SNAPPY and Raine Clinician Fellowship; participation on Data safety monitoring board for the B part of the NT Meningococcal B study; a role as Co-chair Australian and New Zealand Pediatric Infectious Diseases Special Interest Group Committee. A. Legg reports payment to author for Australian Pharmacy Council—EVUSHELD module and webinar and SHPA webinar; support for attending meetings and/or travel from Therapeutic Guidelines group meeting. L. Whiteway reports being remunerated for time attending meetings, and review of patient facing materials as consumer/PPI representative on the SNAP global trial steering committee. M. Bonten reports grants or contracts (all payments to UMCU) from Janssen Vaccines, Merck, LimmaTech, CureVac, Spherecydes; consulting fees (all payments to UMCU) from Janssen Vaccines, AstraZeneca, Pfizer, Sperecydes, Shionogi, GSK; participation on Data Safety Monitoring Board or Advisory Board for Sanofi (payments to UMCU). S. A. Webb reports grant from National Health and Medical Research Council of Australia that supports SNAP; personal consultings fees from ClinicIQ pharma and Roche; no patents or participation on Data Safety Monitoring Boards or Advisory Boards relevant to this work; unpaid roles as Chair and Director of Australian Clinical Trials Alliance; stock or stock options with Reliis. 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.)

Bacteroides pyogenes is naturally found in the oral microbiome of cats and dogs and hence exposure, especially bites from these animals, is a major risk factor for human infections. B pyogenes is known to cause infections that persist despite antibiotic treatment and can have serious clinical outcomes. We present a novel case of complex lung abscesses associated with B pyogenes infection. A 55 year old man presents with a 3-month history of productive cough, night sweats, and 5 kg weight loss. An initial chest radiograph revealed mass-like opacities in the right upper lobe (RUL), right middle lobe (RML), and left lower lobe (LLL). Over the next 4 years the patient underwent multiple investigations and antimicrobial treatments until resolution of the abscesses. We believe that metronidazole in combination with moxifloxacin was a key component in the clinical cure of this patient., Competing Interests: Cameron Sullivan is an Editorial Board member of Respirology Case Reports and a co‐author of this article. He was excluded from all editorial decision‐making related to the acceptance of this article for publication. The other authors have no conflict of interest to declare., (© 2024 The Authors. Respirology Case Reports published by John Wiley & Sons Australia, Ltd on behalf of The Asian Pacific Society of Respirology.)

Background: Cancer has been assumed to be associated with a high-risk of morbidity and mortality from COVID-19. Protective measures have incorporated modifications in cancer treatments. There are conflicting data about the impact of COVID-19 infection and outcomes in cancer patients. We aim to describe the impact of demographic and clinical characteristics on COVID-19 outcomes in patients with cancer in Northern Ireland reported within the UK Coronavirus Cancer Monitoring Project (UKCCMP)., Method: Prospective data collection including demographics, cancer stage and type, treatment and outcomes occurred for all Northern Irish patients enrolled in the UKCCMP. The primary endpoint was all-cause mortality. Descriptive statistics and logistic regression analysis were performed using SPSSv25., Results: Between March 2020 and March 2021, 110 cases were registered. Median age was 63 years (range 27 to 87). Seventy patients (63.6%) were >60 years and 59 (53.8%) were females. Co-morbidities were reported in 83 patients (72.7%). Most patients had metastatic disease (64, 58.2%). Sixty-seven patients (60.9%) received anticancer treatment in the 4 weeks prior to COVID-19 infection. Of those patients, 35 (52.2%) received chemotherapy. Thirty-nine patients (58.2%) continued treatment as planned; 24 (36.9%) stopped treatment due to SARS-CoV-2 infection. The majority of patients were asymptomatic or experienced mild symptoms (67, 60.9%). Fifty-one (46.3%%) were admitted to hospital for COVID-19. Risk of severe/critical COVID-19 disease was significantly associated with age (OR 1.07 [95% CI 1.03-1.11); p=0.004), pre-existing hypertension (OR 3.29 [95% CI 1.42-7.62]; p=0.02) and thoracic primary malignancy (OR 4.41 [95% CI 1.52-12.74]; p=0.042). Twenty-nine patients (26.3%) died of whom 15 (57.7%) died of COVID-19 and 13 (44.8%) died due to cancer. Risk of death was significantly associated with age (OR 1.05 [95% CI 1.01-1.09]; p=0.014), male sex (OR 3.76 [95% CI 1.51-9.34]; p=0.008) and thoracic primary malignancy (OR 5.35 [95% CI 1.88-15.25]; p=0.014). When corrected for age, gender and co-morbidities, chemotherapy within the past 4 weeks was not significantly associated with mortality (OR 0.65 [95% CI 0.20-2.11]; p=0.476)., Conclusion: Age and thoracic cancer diagnosis correlated with survival. Comparison of performance during the pandemic with national benchmarks can inform how regional services should be adapted in preparation for future healthcare crises., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results., (Copyright © 2023 Ulster Medical Society.)

Staphylococcus aureus bloodstream (SAB) infection is a common and severe infectious disease, with a 90-day mortality of 15%-30%. Despite this, <3000 people have been randomized into clinical trials of treatments for SAB infection. The limited evidence base partly results from clinical trials for SAB infections being difficult to complete at scale using traditional clinical trial methods. Here we provide the rationale and framework for an adaptive platform trial applied to SAB infections. We detail the design features of the Staphylococcus aureus Network Adaptive Platform (SNAP) trial that will enable multiple questions to be answered as efficiently as possible. The SNAP trial commenced enrolling patients across multiple countries in 2022 with an estimated target sample size of 7000 participants. This approach may serve as an exemplar to increase efficiency of clinical trials for other infectious disease syndromes., Competing Interests: Potential conflicts of interest. A. M. is an employee of Berry Consultants LLC, in which capacity she is contracted as a consultant to numerous pharmaceutical and device companies on topics of statistical modeling and trial design, and reports grants and contracts unrelated to this work and consulting fees from Berry Consultants LLC. A. C. B. reports participation as a member of the CAMERA-2 data and safety monitoring board (DSMB) and as chair of the Skin Trial DSMB; a role as Vice President of the World Society of Pediatric Infectious Diseases and as Co-Chair, Australian and New Zealand Paediatric Infectious Diseases group of the Australasian Society of Infectious Diseases (ASID). D. L. P. reports grants or contracts made to institution and unrelated to this work from Shionogi, Merck, and Pfizer; consulting fees to author from Antimicrobial Resistance Action Fund and Spero Therapeutics; payment or honoraria for lectures, presentations, speaker’s bureaus, manuscript writing, or educational events to author from Pfizer and Merck; support for attending meetings and/or travel to author from Pfizer; and an unpaid leadership or fiduciary role with ASID. J. A. R. reports contracts or grants paid to institution and unrelated to this work from the British Society of Antimicrobial Chemotherapy, bioMérieux, Pfizer, and QPEX; consulting fees paid to author from Gilead, Pfizer, Sandoz, Wolters Kluwer, Summit Pharma, and MSD; payment to author for lectures, presentations, speaker’s bureaus, manuscript writing, or educational events from MSD, Pfizer, and Cipla; an unpaid leadership or fiduciary role with Sepsis Clinical Care Standard, Australian Commission on Safety and Quality in Health Care, Consensus Guidelines on Prolonged Infusion of Beta-Lactam Antibiotics, American College of Clinical Pharmacy, Disease Modifying Treatment and Chemoprophylaxis, Australian National COVID-19 Clinical Evidence Taskforce, and Surviving Sepsis Guidelines. M. P. C. reports research support from the McGill Interdisciplinary Initiative in Infection and Immunity; research contracts from Cidara Therapeutics, Scynexis, and Amplyx; consulting fees as a scientific consultant for AstraZeneca; 3 pending patents (Methods for detecting tissue damage, graft-versus-host disease, and infections using cell-free DNA profiling; Methods for assessing the severity and progression of SARS-CoV-2 infections using cell-free DNA; and rapid identification of antimicrobial resistance and other microbial phenotypes using highly-multiplexed fluorescence in situ hybridization); stock options as a member of the scientific advisory board for GEn1E Lifesciences and Nomic Bio; and equity as co-founder of Kanvas Biosciences. R. J. L. is an employee of Berry Consultants, LLC, a statistical consulting firm that specializes in the design of adaptive and platform clinical trials. Berry Consultants received compensation for work included in the content of the submission. S. A. W. reports personal consulting fees from ClinicIQ pharma and Roche; an unpaid role as chair of Australian Clinical Trials Alliance; and stock and options with ClinicIQ. S. Y. C. T. reports a contract as a paid consultant for advice on clinical trial design, and consulting fees from Roivant Sciences as a paid consultant for advice on clinical trial design. T. C. L. reports research salary support from Fonds de Recherche Quebec–Sante, operating funds for other studies including CATCO from the CIHR; and operating funds for other studies from the McGill Interdisciplinary Institute Infection and Immunity. S. C. M. reports grants or contracts unrelated to this work from the HRC, and a nonremunerated role as the Chair of the New Zealand Microbiology Network. 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) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: While cancer outcomes have improved over time, in Northern Ireland they continue to lag behind those of many other developed economies. The role of comorbid conditions has been suggested as a potential contributory factor in this but issues of data comparability across jurisdictions has inhibited efforts to explore relationships. We use data from a single jurisdiction of the UK using data from - the Northern Ireland Cancer Registry (NICR), to examine the association between mortality (all-cause and cancer specific) and pre-existing cardiovascular diseases among patients with cancer., Materials and Methods: All patients diagnosed with cancer (excluding non-melanoma skin cancer) between 2011 and 2014 were identified from Registry records. Those with a pre-existing diagnosis of cardiovascular diseases were identified by record linkage with patient hospital discharge data using ICD10 codes. Survival following diagnosis was examined using descriptive statistics and Cox proportional hazards regression analyses. Analyses examined all-cause mortality and cancer specific mortality for lung, colorectal, breast and prostate cancer. As well as cardiovascular diseases, regression models controlled for age, gender (where appropriate), deprivation (as quintiles), stage at diagnosis and other comorbidities., Results: Almost 35,000 incident cancer cases were diagnosed during the study period of which approximately 23% had a prior heart condition. The pan-cancer hazard ratio for death in the presence of pre-existing cardiovascular diseases was 1.28 (95% CI: 1.18-1.40). All-cause and cancer specific mortality was higher for patients with cardiovascular diseases across lung, female breast, prostate and colorectal cancer groups after controlling for age, gender (where appropriate), deprivation (as quintiles), stage at diagnosis and other comorbidities., Conclusion: Pre-existing morbidity may restrict the treatment of cancer for many patients. In this cohort, cancer patients with pre-existing cardiovascular diseases had poorer outcomes than those without cardiovascular diseases. A high prevalence of cardiovascular diseases may contribute to poorer cancer outcomes at a national level., (© 2022. The Author(s).)

Background: Older patients with cancer often have lower surgery rates and survival than younger patients, but this may reflect surgical contraindications of advanced disease, comorbidities, and frailty - and not necessarily under-treatment., Objectives: This review aims to describe variations in surgery rates and observed or net survival among younger (<75) and older (≥75) patients with breast, lung and colorectal cancer, while taking account of pre-existing health factors, in order to understand how under-treatment is defined and estimated in the literature., Method: MEDLINE, EMBASE, Web of Science and PubMed databases were searched for studies reporting surgery rates and observed or net survival among younger and older patients with breast, lung, and colorectal cancer. Study quality was assessed using the Newcastle Ottawa Scale, and random effects meta-analyses were used to combine study results. The I-squared statistic and subgroup analyses were used to assess heterogeneity., Results: Thirty relatively high-quality studies of patients with breast (230,200; 71.9%), lung (77,573; 24.2%), and colorectal (12,407; 3.9%) cancers were identified. Compared to younger patients, older patients were less likely to receive surgical treatment for 1) breast cancer after adjusting for comorbidity, performance status (PS), functional status and patient choice, 2) lung cancer after accounting for stage, comorbidity, PS, and 3) colorectal cancer after adjusting for stage, comorbidity, and gender. The pooled unadjusted analyses showed lower surgery receipt in older patients with breast (odds ratio [OR] 0.31, 95% confidence interval [CI] 0.13-0.78), lung (OR 0.54, 95% CI 0.39-0.75), and colorectal (OR 0.59, 95% CI 0.51-0.68) cancer. In separate analyses, older patients with breast, lung and colorectal cancer had lower observed and net survival, compared to younger patients., Conclusions: Lower surgery rates in older patients may contribute to their poorer survival compared to younger patients. Future research quantifying under-treatment should include necessary clinical factors, patient choice, patient's quality of life and a statistically-robust approach, which will demonstrate how much of the survival deficit in older patients is due to their receiving lower surgery rates., (Copyright © 2021 Elsevier Ltd. All rights reserved.)