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Integrative resource for network-based investigation associated with COVID-19 combinatoric medicine rethinking and also system associated with motion.
Low-middle-income countries experience among the highest rates of traumatic brain injury in the world. Much of this burden may be preventable with faster intervention, including reducing the time to definitive care. This study examines the relationship between traumatic brain injury severity and time to definitive care in major trauma hospitals in three low-middle-income countries.

A prospective traumatic brain injury registry was implemented in six trauma hospitals in Armenia, Georgia and the Republic of Moldova for 6 months in 2019. Brain injury severity was measured using the Glasgow Coma Scale (GCS) at admission. Time to definitive care was the time from injury until arrival at the hospital. Cox proportionate hazards models predicted time to care by severity, controlling for age, sex, mechanism, mode of transportation, location of injury and country.

Among 1135 patients, 749 (66.0%) were paediatric and 386 (34.0%) were adults. Falls and road traffic were the most common mechanisms. A higher proportion of adult (23.6%) than paediatric (5.4%) patients had GCS scores indicating moderate (GCS 9-11) or severe injury (GCS 0-8) (p<0.001). Less severe injury was associated with shorter times to care, while more severe injury was associated with longer times to care (HR=1.05, 95% CI 1.01 to 1.09). Age interacted with time to care, with paediatric cases receiving faster care.

Implementation of standard triage and transport protocols may reduce mortality and improve outcomes from traumatic brain injury, and trauma systems should focus on the most severe injuries.
Implementation of standard triage and transport protocols may reduce mortality and improve outcomes from traumatic brain injury, and trauma systems should focus on the most severe injuries.Exebacase (CF-301), a novel, antistaphylococcal lysin (cell wall hydrolase) is the first agent of this class to enter late-stage clinical development (phase 3, NCT04160468) for the treatment of Staphylococcus aureus bacteremia, including right-sided endocarditis. A multilaboratory Clinical and Laboratory Standards Institute (CLSI) M23-defined tier 2 quality control (QC) study was conducted to establish exebacase QC ranges for a new reference broth microdilution method. S. aureus ATCC 29213 and Enterococcus faecalis ATCC 29212 were selected as reference QC strains. Broth microdilution MIC QC ranges for exebacase spanned 4 log2 dilutions and contained 99.2% of the MIC results generated for the two reference strains. The QC ranges for exebacase were defined as 0.25 to 2 μg/ml and 8 to 64 μg/ml against S. aureus ATCC 29213 and E. faecalis ATCC 29212, respectively, and were approved by the CLSI Subcommittee on Antimicrobial Susceptibility Testing. These QC ranges established for use with the reference broth microdilution method developed for exebacase susceptibility testing will ensure the test performance and accuracy of results generated during clinical development.Burkholderia pseudomallei is a tier 1 select agent that is associated with laboratory-acquired melioidosis, with international guidelines recommending isolate handling within a class II biosafety cabinet (BSC) in a biosafety level 3 (BSL3) facility. In low-resource settings, this may not be practical; therefore, we aimed to assess the risk of laboratory-acquired melioidosis during routine work. Prior exposure to the organism was determined with a questionnaire and concomitant serology. Of 30 laboratory scientists handling B. pseudomallei on 1,267 occasions outside a biosafety cabinet, no infections were documented and all participants remained seronegative. Additionally, we performed controlled environmental air sampling during 78 laboratory handling events, including plate opening, oxidase testing, and McFarland suspension creation. None of the experiments demonstrated aerosolization of the organism. This study suggests the risk of laboratory-acquired melioidosis is low. However, individual laboratories will need to undertake a risk assessment, including melioidosis endemicity, availability of resources for containment, the nature of routine handling to be undertaken, and the presence of predisposing risk factors for infection in the staff concerned. Additionally, laboratories should take region-specific guidelines into consideration. Further research is required to better inform on the overall risk of infection in the microbiology laboratory.Bacterial vector-borne diseases, including Borrelia species, present a significant diagnostic, clinical, and public health challenge due to their overlapping symptoms and the breadth of causative agents and arthropod vectors. The relapsing fever (RF) borreliae encompass both established and emerging pathogens and are transmitted to humans by soft ticks, hard ticks, or lice. We developed a real-time semimultiplex PCR assay that detects multiple RF borreliae causing human illness and classifies them into one of three groups. The groups are based on genetic similarity and include agents of soft-tick relapsing fever (Borrelia hermsii and others), the emerging hard-tick-transmitted pathogen B. miyamotoi, and the agent of louse-borne relapsing fever (B. recurrentis). The real-time PCR assay uses a single primer pair designed to amplify all known pathogenic RF borreliae and multiple TaqMan probes to allow the detection of and differentiation among the three groups. Selleck AZD9291 The assay detects all RF borreliae tested, with an analytical limit of detection below 15 genome equivalents per reaction. Thirty isolates of RF borreliae encompassing six species were accurately identified. Thirty-nine of 41 residual specimens (EDTA whole blood, serum, or plasma) from patients with RF were detected and correctly classified. None of 42 clinical samples from patients with other infections and 46 culture specimens from non-RF bacteria were detected. The development of a single-assay real-time PCR approach will help to improve the diagnosis of RF by simplifying the selection of tests to aid in the clinical management of acutely ill RF patients.Background Metagenomic sequencing is frequently claimed to have the potential to revolutionise microbiology through rapid species identification and antimicrobial resistance (AMR) prediction. We assess progress towards this.Methods We perform a systematic review and meta-analysis of all published literature on culture-independent metagenomic sequencing for pathogen-agnostic infectious disease diagnostics to August 12, 2020. Methodologic bias and applicability were assessed using QUADAS-2. (PROSPERO CRD42020163777)Results A total of 2023 clinical samples from 13/21 eligible diagnostic test accuracy studies were included in the meta-analysis. Reference standards were culture, molecular testing, clinical decision or a composite measure. Sensitivity and specificity in the most widely investigated sample types were 90%(78-96%) and 86%(45-98%) for blood, 75%(95%CI, 54-89%) and 96%(72-100%) for CSF, and 84%(79-88%) and 67%(38-87%) for orthopaedic samples respectively. We identified limited use of controls, especially negative controls which were used in only 62%(13/21) studies. AMR prediction and comparison to phenotypic results was undertaken in four studies categorical agreement was 88%(80%-97%), very major and major error rates were 24%(8-40%) and 5%(0-12%) respectively. Better human DNA depletion methods are required a median 91%(IQR 82-98%)[range 76-98%] of sequences were classified as human. The median(IQR)[range] time from sample to result was 29(24-94)[4-144] hours. The reported consumables cost per sample ranged from $130-$685.Conclusions There is scope for improving the quality of reporting in clinical metagenomic studies. Although our results are limited by the heterogeneity displayed, our results reflect a promising outlook for clinical metagenomics. Methodological improvements, and convergence around protocols and best practises may improve performance in future.Rapid and precise detection of Chlamydia trachomatis, the leading global cause of sexually transmitted infections (STI), at the point of care (POC) is required for treatment decisions to prevent transmission and sequelae, including pelvic inflammatory disease, ectopic pregnancy, tubal factor infertility, and preterm birth. We developed a rapid POC test (POCT), termed LH-POCT, which uses loop-mediated amplification (LAMP) of nucleic acids. We performed a head-to-head comparison with the Cepheid Xpert CT/NG assay using clinician-collected, deidentified paired vaginal samples from a parent study that consecutively enrolled symptomatic and asymptomatic females over 18 years of age from the Ministry of Health and Medical Services Health Centers in Fiji. Samples were processed by the Xpert CT/NG assay and LH-POCT, blinded to the comparator. Discrepant samples were resolved by quantitative PCR. Deidentified clinical data and tests for Trichomonas vaginalis, Candida, and bacterial vaginosis (BV) were provided. There were a total of 353 samples from 327 females. C. trachomatis positivity was 16.7% (59/353), while the prevalence was 16.82% (55/327) after discrepant resolution. Seven discrepant samples resolved to four false negatives, two false positives, and one true positive for the LH-POCT. The sensitivity of the LH-POCT was 93.65% (95% confidence interval [CI], 84.53% to 98.24%), and specificity was 99.31% (95% CI, 97.53% to 99.92%). Discrepant samples clustered among women with vaginal discharge and/or BV. The prototype LH-POCT workflow has excellent performance, meeting many World Health Organization ASSURED criteria for POC tests, including a sample-to-result time of 35 min. Our LH-POCT holds promise for improving clinical practice to prevent and control C. trachomatis STIs in diverse health care settings globally.New blood culture instrumentation and medium formulations have led to improved time to positivity (TTP) for positive blood cultures. Data regarding the necessity of pediatric blood culture bottles with contemporary blood culture systems are sparse. We compared performance of three commercial blood culture systems, evaluating impact of blood volumes in standard and pediatric blood culture media across systems. Simulated blood cultures with packed red blood cells (PRBCs) and three Gram-positive, four Gram-negative, and one anaerobic organism (final concentrations ranging from 0.5 to 19 CFU/ml blood) on the Virtuo, VersaTrek, and Bactec FX instruments were evaluated with FAN Plus, Redox, and Bactec Plus media, respectively. For each medium/instrument/organism combination, 1-, 3-, 5-, and 10-ml blood volumes were evaluated in triplicate. Detection rate was not affected by blood volume. Aerobic organisms that demonstrated variable rates of detection were Kingella kingae, Haemophilus influenzae, and Neisseria meningitidis. Bacteroides fragilis was detected in 83%, 100%, and 100% of Virtuo, VersaTrek, and Bactec anaerobic bottles, respectively. The average TTP of standard medium for aerobic organisms detected on Virtuo was decreased compared to those for VersaTrek (-2.3 h) and Bactec (-4.9 h). Compared to standard medium, detection rate and TTP were unchanged on Virtuo, while TTP was reduced with pediatric medium for 2/8 organisms tested on Bactec and 7/8 organisms on VersaTrek, illustrating the potential benefit of pediatric medium on VersaTrek or Bactec when low blood volumes ( less then 5 ml) are collected. These results demonstrate that TTP is decreased on the Virtuo compared to VersaTrek and Bactec for many microorganisms associated with bloodstream infection (BSI) but may have species-specific limitations.
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