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Objectives: Current infective endocarditis guidelines recommend two different gentamicin synergy dosing strategies for selected Gram-positive organisms. The purpose of this analysis was to evaluate the incidence of acute kidney injury (AKI) with gentamicin synergy dosing, comparing divided-daily and once-daily dosing strategies for infective endocarditis (IE)., Methods: Groups were split into patients who received gentamicin divided-daily dosing and once-daily (3 mg/kg) dosing for Gram-positive IE. The primary outcome was the incidence of AKI defined by RIFLE (risk, injury, failure, loss, end-stage renal disease) criteria after starting gentamicin. A multivariable logistic regression analysis was performed to identify possible independent predictors of developing AKI. Notable secondary outcomes included hospital length of stay, need for gentamicin dose adjustments based on therapeutic drug monitoring, and assessment of each case of AKI using the Naranjo algorithm., Results: The incidence of AKI was significantly higher in the divided-daily group compared with the once-daily group (52.5% versus 13%, P  < 0.01). The divided-dosing group had significantly longer median [IQR] hospital length of stay (19 days [12:29] versus 13.5 days [9:22], P  < 0.01) and a greater number of patients who required dose adjustments (76.2% versus 21.7%, P  < 0.01). The multivariable regression analysis showed that the divided-dosing strategy, duration and institution were independently associated with incidence of AKI., Conclusions: This analysis suggests a lower incidence of AKI in the treatment of endocarditis with gentamicin synergy dosed once-daily compared with a divided-daily dosing. Further studies are warranted to assess if there is a difference in efficacy between gentamicin synergy dosing strategies and in gentamicin compared with no gentamicin regimens for IE., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Background: Sepsis guidelines recommend daily review to de-escalate or stop antibiotics in appropriate patients. This randomized, controlled trial evaluated an opt-out protocol to decrease unnecessary antibiotics in patients with suspected sepsis., Methods: We evaluated non-intensive care adults on broad-spectrum antibiotics despite negative blood cultures at 10 US hospitals from September 2018 through May 2020. A 23-item safety check excluded patients with ongoing signs of systemic infection, concerning or inadequate microbiologic data, or high-risk conditions. Eligible patients were randomized to the opt-out protocol vs usual care. Primary outcome was post-enrollment antibacterial days of therapy (DOT). Clinicians caring for intervention patients were contacted to encourage antibiotic discontinuation using opt-out language. If continued, clinicians discussed the rationale for continuing antibiotics and de-escalation plans. To evaluate those with zero post-enrollment DOT, hurdle models provided 2 measures: odds ratio of antibiotic continuation and ratio of mean DOT among those who continued antibiotics., Results: Among 9606 patients screened, 767 (8%) were enrolled. Intervention patients had 32% lower odds of antibiotic continuation (79% vs 84%; odds ratio, 0.68; 95% confidence interval [CI], .47-.98). DOT among those who continued antibiotics were similar (ratio of means, 1.06; 95% CI, .88-1.26). Fewer intervention patients were exposed to extended-spectrum antibiotics (36% vs 44%). Common reasons for continuing antibiotics were treatment of localized infection (76%) and belief that stopping antibiotics was unsafe (31%). Thirty-day safety events were similar., Conclusions: An antibiotic opt-out protocol that targeted patients with suspected sepsis resulted in more antibiotic discontinuations, similar DOT when antibiotics were continued, and no evidence of harm., Clinical Trials Registration: NCT03517007., Competing Interests: Potential conflicts of interest. E. D. A. reports grants or contracts from the University of Maryland (paid to author), University of Chicago (paid to author), CDC Prevention Epicenter Program (paid to institution), Oxford University Clinical Research Unit (paid to author), CDC (paid to institution), and DASON Member Hospital Contracts (paid to institution); royalties or licenses from UpToDate (paid to author); consulting fees from the American College of Clinical Pharmacy (paid to author), Hospital Association of New York State (paid to author), Sarah Moreland Russel Consulting (paid to author), and HealthTrackRX (paid to author); and support for attending meetings and/or travel from the American Society of Microbiology (paid to author), Pew Charitable Trusts (paid to author), and Oxford University Clinical Research Unit (paid to institution). A. E. D. reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Merck & Co (paid to author). M. Z. D. reports grants or contracts from the National Institutes of Health, GSK, Johnson & Johnson, and Contrafect (paid to institution); support for attending meetings and/or travel from GSK; and participation on a data and safety monitoring board or advisory board for GSK (paid to author). D. J. A. reports grants or contracts from Agency for Healthcare Research and Quality (to institution), royalties or licenses from UpToDate Online (paid to author), and other financial or nonfinancial interests from Infection Control Education for Major Sports, LLC (owner). M. K. reports grants or contracts from Agency for Healthcare Research and Quality (paid to institution) and the Massachusetts Department of Public Health (paid to institution) and royalties or licenses from UpToDate (paid to author). R. W. M. reports grants or contracts from the CDC (paid to institution) and the Agency for Healthcare Research and Quality (paid to institution), royalties or licenses from UpToDate, Inc. (paid to author), speaker honoraria for the North Carolina Statewide Program for Infection Control and Epidemiology (paid to author), support for attending meetings and/or travel from the Society for Healthcare Epidemiology of America, and is on the Society for Healthcare Epidemiology of America Board of Trustees. A. P. reports grants from Clinical and Translational Science Award (to Biostatistics, Epidemiology, and Research Design Core, within the Biostatistics and Bioinformatics Department at Duke University). J. C. P. reports serving on the advisory boards for Shionogi, Inc, and Gilead Sciences, Inc. 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. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Unlabelled: Many algorithms analyze enhancers for overrepresentation of known and novel motifs, with the goal of identifying binding sites for direct regulators of gene expression. Twine is a Java GUI with multiple graphical representations ('Views') of enhancer alignments that displays motifs, as IUPAC consensus sequences or position frequency matrices, in the context of phylogenetic conservation to facilitate cis-regulatory element discovery. Thresholds of phylogenetic conservation and motif stringency can be altered dynamically to facilitate detailed analysis of enhancer architecture. Views can be exported to vector graphics programs to generate high-quality figures for publication. Twine can be extended via Java plugins to manipulate alignments and analyze sequences., Availability: Twine is freely available as a compiled Java .jar package or Java source code at http://labs.bio.unc.edu/crews/twine/., Supplementary Information: Supplementary data are available at Bioinformatics online.

Background: It is uncertain whether particular clones causing invasive community-onset methicillin-resistant and methicillin-sensitive Staphylococcus aureus (cMRSA/cMSSA) infection differ in virulence., Methods: Invasive cMRSA and cMSSA cases were prospectively identified. Principal component analysis was used to derive an illness severity score (ISS) from clinical data, including 30-day mortality, requirement for intensive hospital support, the presence of bloodstream infection, and hospital length of stay. The mean ISS for each S. aureus clone (based on MLST) was compared with its DNA microarray-based genotype., Results: Fifty-seven cMRSA and 50 cMSSA infections were analyzed. Ten clones caused 82 (77%) of these infections and had an ISS calculated. The enterotoxin gene cluster (egc) and the collagen adhesin (cna) gene were found in 4 of the 5 highest-ranked clones (ST47-MSSA, ST30-MRSA-IV[2B], ST45-MSSA, and ST22-MRSA-IV[2B]) compared with none and 1 of the lowest 5 ranked clones, respectively. cMSSA clones caused more severe infection than cMRSA clones. The lukF/lukS Panton-Valentine leukocidin (PVL) genes did not directly correlate with the ISS, being present in the second, fourth, and 10th most virulent clones., Conclusions: The clinical severity of invasive cMRSA and cMSSA infection is likely to be attributable to the isolates' entire genotype rather than a single putative virulence determinant such as PVL.

Background: The elderly residents of nursing and old people's homes are at substantially increased risk from influenza and its complications. Annual vaccination is therefore strongly recommended by the UK Departments of Health. However, few data exist on the uptake of influenza vaccine in this setting; this was last estimated to be 45 percent in 1988-1989. A major epidemic of influenza A occurred in 1989-1990 which may have changed vaccination behaviours., Methods: A structured interview survey was conducted in 49 old people's homes in Nottingham to determine practices and policies for influenza vaccine. The medical records of 151 randomly selected elderly residents were examined to determine vaccine uptake in the 1992-1993 season., Results: Twenty-five homes (52.1 percent) claimed to operate a policy for influenza immunization but only 3 (12.0 percent) were written down and none set targets. Methods of vaccine promotion were generally weak. Accordingly, vaccine uptake was only 39.6% percent (95 percent confidence interval 33.2-46.0)., Conclusions: In contrast to other high-risk groups living in the open community, no improvement in influenza vaccine uptake has occurred in nursing and old people's homes since the late 1980s. Future attempts to increase vaccine uptake in this setting should focus on developing joint policies between general practitioners and home staff to facilitate better co-ordinated programmes of vaccine promotion and administration.

From newly incident cases in Western Canada, 415 patients with superficial spreading melanoma (SSM), 128 with nodular melanoma (NM), and 56 with lentigo maligna melanoma (LMM) were interviewed, with age- and sex-matched controls chosen from the general population. The associations of these 3 subtypes with pigmentation, skin reaction to sun, different types of sun exposure, sunburn, and suntan were assessed. Compared to the other types, LMM occurred in older patients, and 75% of lesions occurred on the head and neck: It was less strongly related to pigmentation factors, intermittent sun exposure, and skin reaction to sun. The associations of SSM and NM with pigmentation, chronic sun exposure, skin reaction, and suntan were very similar: Both were associated with intermittent sun exposure, but SSM was more strongly related to vacation exposures than was NM. These results were compared with those from a similar Australian study. While LMM appears different in its etiology from SSM and NM, there is no strong evidence of major etiological differences between SSM and NM.

Studies carried out in 1978 and 1981 found postneonatal mortality to be associated with poor environmental conditions. Since then, many changes have occurred to the environment. This study was designed to discover which factors are now associated with a higher risk of postneonatal death. A retrospective case-control study was carried out using 107 cases and 422 controls matched only for date of birth, to look at the effect of area of residence, social class, mother's age, and sex, birthweight, legitimacy and number of siblings. Fifty-eight per cent of the deaths were due to the sudden infant death syndrome, making this the leading cause of death. Causes previously absent from the death certificates are now appearing, particularly prematurity related deaths which now account for almost 6 per cent. The deaths were found to occur more frequently at home, in the winter, and at a peak age of 2 to 4 months. As shown previously in Nottingham, the deaths were more likely to have been male (relative risk 2.03), illegitimate (2.91), and of low birthweight (28.8). Total mortality was significantly higher in babies of mothers aged 19 or less and in babies of manual workers. Surprisingly, babies born to unemployed parents were found to have a very low relative risk of death (0.26). Mortality is still higher in the city than the suburbs and in areas of deprivation. Although still a risk factor for SIDS, high parity of the mother was found to be non-significant for postneonatal mortality in total.(ABSTRACT TRUNCATED AT 250 WORDS)