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Vancomycin Area Under the Curve and Acute Kidney Injury
Abstract
Background
This study analyzed the relationship between vancomycin area under the concentration-time curve (AUC) and acute kidney injury (AKI) reported across recent studies.
Methods
A systematic review of PubMed, Medline, Scopus, and compiled references was conducted. We included randomized cohort and case-control studies that reported vancomycin AUCs and risk of AKI (from 1990 to 2018). The primary outcome was AKI, defined as an increase in serum creatinine of ≥0.5 mg/L or a 50% increase from baseline on ≥2 consecutive measurements. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Primary analyses compared the impact of AUC cutpoint (greater than ~650 mg × hour/L) and AKI. Additional analysis compared AUC vs trough-guided monitoring on AKI incidence.
Results
Eight observational studies met inclusion/exclusion criteria with data for 2491 patients. Five studies reported first-24-hour AUCs (AUC0-24) and AKI, 2 studies reported 24- to 48-hour AUCs (AUC24-48) and AKI, and 2 studies reported AKI associated with AUC- vs trough-guided monitoring. AUC less than approximately 650 mg × hour/L was associated with decreased AKI for AUC0-24 (OR, 0.36 [95% CI, .23–.56]) as well as AUC24-48 (OR, 0.45 [95% CI, .27–.75]). AKI associated with the AUC monitoring strategy was significantly lower than trough-guided monitoring (OR, 0.68 [95% CI, .46–.99]).
Conclusions
AUCs measured in the first or second 24 hours and lower than approximately 650 mg × hour/L may result in a decreased risk of AKI. Vancomycin AUC monitoring strategy may result in less vancomycin-associated AKI. Additional investigations are warranted.
This meta-analysis identifies a clear exposure–response relationship (ie, area under the curve threshold greater than ~650 mg × hour/L) for vancomycin and acute kidney injury (AKI). It also suggests that area under the concentration-time curve monitoring strategies can potentially decrease the risk of AKI.
Journal Article
Scholia vetera in Sophoclis Oedipum Coloneum
Scholars have been seeking to understand Sophocles' 'Oedipus at Colonus' for over two millennia. The roots of this long tradition of the play's interpretation lie in Hellenistic Alexandria, and are now represented mainly by a series of notes that have survived in the margins of medieval manuscripts. The book offers an introduction and an authoritative new critical text, which is accompanied by a detailed apparatus criticus.
BOOK
Development and Validation of a Deep Learning–based Automatic Detection Algorithm for Active Pulmonary Tuberculosis on Chest Radiographs
Abstract
Background
Detection of active pulmonary tuberculosis on chest radiographs (CRs) is critical for the diagnosis and screening of tuberculosis. An automated system may help streamline the tuberculosis screening process and improve diagnostic performance.
Methods
We developed a deep learning–based automatic detection (DLAD) algorithm using 54c221 normal CRs and 6768 CRs with active pulmonary tuberculosis that were labeled and annotated by 13 board-certified radiologists. The performance of DLAD was validated using 6 external multicenter, multinational datasets. To compare the performances of DLAD with physicians, an observer performance test was conducted by 15 physicians including nonradiology physicians, board-certified radiologists, and thoracic radiologists. Image-wise classification and lesion-wise localization performances were measured using area under the receiver operating characteristic (ROC) curves and area under the alternative free-response ROC curves, respectively. Sensitivities and specificities of DLAD were calculated using 2 cutoffs (high sensitivity [98%] and high specificity [98%]) obtained through in-house validation.
Results
DLAD demonstrated classification performance of 0.977–1.000 and localization performance of 0.973–1.000. Sensitivities and specificities for classification were 94.3%–100% and 91.1%–100% using the high-sensitivity cutoff and 84.1%–99.0% and 99.1%–100% using the high-specificity cutoff. DLAD showed significantly higher performance in both classification (0.993 vs 0.746–0.971) and localization (0.993 vs 0.664–0.925) compared to all groups of physicians.
Conclusions
Our DLAD demonstrated excellent and consistent performance in the detection of active pulmonary tuberculosis on CR, outperforming physicians, including thoracic radiologists.
A deep learning–based algorithm outperformed radiologists in detecting active pulmonary tuberculosis on chest radiographs and thus may play an important role in diagnosis and screening of tuberculosis in select situations, contributing to the reduction of the high burden of tuberculosis worldwide.
Journal Article
Prevalence and Etiology of Community-acquired Pneumonia in Immunocompromised Patients
Of patients with pneumonia coming from the community, 18% are immunocompromised. Specific immunocompromised states are associated with specific microbiology, which has to be taken into consideration when choosing empirical therapy.
Abstract
Background
The correct management of immunocompromised patients with pneumonia is debated. We evaluated the prevalence, risk factors, and characteristics of immunocompromised patients coming from the community with pneumonia.
Methods
We conducted a secondary analysis of an international, multicenter study enrolling adult patients coming from the community with pneumonia and hospitalized in 222 hospitals in 54 countries worldwide. Risk factors for immunocompromise included AIDS, aplastic anemia, asplenia, hematological cancer, chemotherapy, neutropenia, biological drug use, lung transplantation, chronic steroid use, and solid tumor.
Results
At least 1 risk factor for immunocompromise was recorded in 18% of the 3702 patients enrolled. The prevalences of risk factors significantly differed across continents and countries, with chronic steroid use (45%), hematological cancer (25%), and chemotherapy (22%) the most common. Among immunocompromised patients, community-acquired pneumonia (CAP) pathogens were the most frequently identified, and prevalences did not differ from those in immunocompetent patients. Risk factors for immunocompromise were independently associated with neither Pseudomonas aeruginosa nor non–community-acquired bacteria. Specific risk factors were independently associated with fungal infections (odds ratio for AIDS and hematological cancer, 15.10 and 4.65, respectively; both P = .001), mycobacterial infections (AIDS; P = .006), and viral infections other than influenza (hematological cancer, 5.49; P < .001).
Conclusions
Our findings could be considered by clinicians in prescribing empiric antibiotic therapy for CAP in immunocompromised patients. Patients with AIDS and hematological cancer admitted with CAP may have higher prevalences of fungi, mycobacteria, and noninfluenza viruses.
Journal Article
The Lindisfarne Gospels : art, history & interpretation : the British library guide
This accessible volume explores the latest research and thinking on the 'Lindisfarne Gospels' and is published as the manuscript goes on loan to the Laing Art Gallery in Newcastle for an exhibition exploring its meaning in today's world. It presents a detailed introduction and commentary alongside high quality, detailed illustrations which celebrate the intricate, interlaced geometrical precision of one of the finest early medieval craftsmen.
Book
The Serogroup B Meningococcal Vaccine Bexsero Elicits Antibodies to Neisseria gonorrhoeae
Neisseria gonorrhoeae and Neisseria meningitidis are closely-related bacteria that cause a significant global burden of disease. Control of gonorrhoea is becoming increasingly difficult, due to widespread antibiotic resistance. While vaccines are routinely used for N. meningitidis, no vaccine is available for N. gonorrhoeae. Recently, the outer membrane vesicle (OMV) meningococcal B vaccine, MeNZB, was reported to be associated with reduced rates of gonorrhoea following a mass vaccination campaign in New Zealand. To probe the basis for this protection, we assessed the cross-reactivity to N. gonorrhoeae of serum raised to the meningococcal vaccine Bexsero, which contains the MeNZB OMV component plus 3 recombinant antigens (Neisseria adhesin A, factor H binding protein [fHbp]-GNA2091, and Neisserial heparin binding antigen [NHBA]-GNA1030).
A bioinformatic analysis was performed to assess the similarity of MeNZB OMV and Bexsero antigens to gonococcal proteins. Rabbits were immunized with the OMV component or the 3 recombinant antigens of Bexsero, and Western blots and enzyme-linked immunosorbent assays were used to assess the generation of antibodies recognizing N. gonorrhoeae. Serum from humans immunized with Bexsero was investigated to assess the nature of the anti-gonococcal response.
There is a high level of sequence identity between MeNZB OMV and Bexsero OMV antigens, and between the antigens and gonococcal proteins. NHBA is the only Bexsero recombinant antigen that is conserved and surfaced exposed in N. gonorrhoeae. Bexsero induces antibodies in humans that recognize gonococcal proteins.
The anti-gonococcal antibodies induced by MeNZB-like OMV proteins could explain the previously-seen decrease in gonorrhoea following MeNZB vaccination. The high level of human anti-gonococcal NHBA antibodies generated by Bexsero vaccination may provide additional cross-protection against gonorrhoea.
Journal Article
Pulmonary Metagenomic Sequencing Suggests Missed Infections in Immunocompromised Children
Abstract
Background
Despite improved diagnostics, pulmonary pathogens in immunocompromised children frequently evade detection, leading to significant mortality. Therefore, we aimed to develop a highly sensitive metagenomic next-generation sequencing (mNGS) assay capable of evaluating the pulmonary microbiome and identifying diverse pathogens in the lungs of immunocompromised children.
Methods
We collected 41 lower respiratory specimens from 34 immunocompromised children undergoing evaluation for pulmonary disease at 3 children’s hospitals from 2014–2016. Samples underwent mechanical homogenization, parallel RNA/DNA extraction, and metagenomic sequencing. Sequencing reads were aligned to the National Center for Biotechnology Information nucleotide reference database to determine taxonomic identities. Statistical outliers were determined based on abundance within each sample and relative to other samples in the cohort.
Results
We identified a rich cross-domain pulmonary microbiome that contained bacteria, fungi, RNA viruses, and DNA viruses in each patient. Potentially pathogenic bacteria were ubiquitous among samples but could be distinguished as possible causes of disease by parsing for outlier organisms. Samples with bacterial outliers had significantly depressed alpha-diversity (median, 0.61; interquartile range [IQR], 0.33–0.72 vs median, 0.96; IQR, 0.94–0.96; P < .001). Potential pathogens were detected in half of samples previously negative by clinical diagnostics, demonstrating increased sensitivity for missed pulmonary pathogens (P < .001).
Conclusions
An optimized mNGS assay for pulmonary microbes demonstrates significant inoculation of the lower airways of immunocompromised children with diverse bacteria, fungi, and viruses. Potential pathogens can be identified based on absolute and relative abundance. Ongoing investigation is needed to determine the pathogenic significance of outlier microbes in the lungs of immunocompromised children with pulmonary disease.
Pulmonary infections in immunocompromised children frequently evade detection by current clinical diagnostics. We optimized metagenomic sequencing of pulmonary pathogens in immunocompromised children and show that metagenomic RNA sequencing identified pulmonary pathogens in approximately half of patients with negative clinical diagnostics.
Journal Article