bluuebunny/crossref_metadata_2025_split huggingface dataset:
National Audit of Meningitis Management (NAMM): a National Infection Trainee Collaborative for Audit and Research (NITCAR) audit of adherence to the 2016 UK joint specialist societies’ guideline on the diagnosis and management of acute meningitis in adults
Authors: McGill Fiona , Ellis Jayne , Harvey David , Defres Sylviane , MacLachlan Eloisa , Solomon Tom , Chandna Arjun , Heydermanon Robert ,   behalf of the NAMM investigators.
Published: March 2020

Background
Bacterial meningitis has significant mortality but frontline doctors will see it infrequently. Therefore, UK guidance on meningitis in adults, with auditable standards, was revised in 2016. We undertook a national audit to assess adherence to the guidelines.
Methods
Patients with community acquired meningitis were identified through coding or laboratory data. Audit standards, including immediate management, diagnostics and treatment, were evaluated by notes review.

Results
Notes from 1472 patients with meningitis were reviewed – 309/1472 (21%) had bacterial aetiology, 615/1472 (42%) viral, 548/1472 (37%) unidentified aetiology. Only 50% of patients had blood cultures taken within one hour of admission and just 2% had a lumbar puncture (LP) within the first hour. 27% received antibiotics within one hour. Most patients received ceftriaxone or cefotaxime but only 37% of over-60s received empirical anti-listeria antibiotics. 26% of patients who had antibiotics were given adjunctive steroids. Half had CSF microscopy within two hours of LP. Less than a third had pneumococcal and/or meningococcal PCR on cerebrospinal fluid. Only 44% had an HIV test. 62% had unnecessary neuroimaging before LP. Overall mortality was 3% - 16% in pneumococcal disease and 8% in meningococcal meningitis. There was a trend toward improved survival in patients with pneumococcal meningitis who received dexamethasone [85/96 (88%)] compared to those who did not [57/73 (78%)] (p=0.066).
Conclusions
Adherence to the meningitis guidelines is inadequate, potentially compromising patient safety. Improvements in guideline dissemination, novel educational resources and clinician and patient engagement are required if we are to increase guideline adherence and improve outcome.
Empyema: do we know enough?
Authors: Hatrick Sophie , Arnold David , Hamilton Fergus 
Published: March 2020

Introduction
Pleural empyema is an uncommon but serious condition defined by infected fluid in the pleural space. These patients are often given long courses of empirical broad-spectrum antibiotics as the yield from conventional culture methods is notoriously low. The literature shows that with conventional culture methods of the pleural fluid up to 40-60% of causative pathogens remain unidentified. In recent years methods such as DNA analysis have been developed in an attempt to increase identification rates of pathogens. This paper aims to review the literature to determine the additional benefit of DNA analysis methods above conventional culture of fluid in pleural empyema.
Methods
A review of the literature searching for studies investigating bacteria present in pleural fluid in patients with empyema was carried out. Studies in which adult patients had a diagnosis of empyema and where conventional culture and molecular methods were used to identify the causative bacteria were included. Descriptive statistics were used to compare the increased yield from molecular methods.

Results
Five studies which compared conventional culture techniques and molecular methods for identification of the pathogen in pleural empyema cases were identified. The mean culture-positive rate and molecular-positive rate in these studies was 37.5% (range 10-58%) and 80.0% (range 22.5-82%) respectively. All the studies concluded that molecular techniques provided a greater identification rate than conventional culture techniques.

Conclusion
Pleural empyema is often culture negative leading to broad-spectrum antibiotic use. This review shows that molecular methods significantly increase the yield of causative bacteria present in pleural fluid.
S. bovis urinary tract infection, management and associations
Authors: Marek Aleksandra , Macleod Mairi 
Published: March 2020

Background
As part of a move to improve antimicrobial stewardship NHS GGC recently implemented identification to species level and Vitek 2 sensitivity testing on all urinary isolates. As part of this we have noticed an increased number of isolates of the Streptococcus bovis group in urinary samples. It is possible that these were previously labelled as Enterococcus spp. The significance of S. bovis isolates in urinary tract is uncertain.
Methods
We reviewed a year of S. bovis urinary isolates to ascertain whether there is any association with GI malignancy or endocarditis as is recognised with blood culture isolates of this group.

Results
54 isolates were reviewed dating between Feb 2018 and 2019 allowing at least 6 months follow up. 94% of cases were in females. 46% of isolates were mixed usually with a member of the Enterobactereaceales. There were no cases of either known or newly diagnosed endocarditis amongst this patient cohort. 9% of cases had a known GI malignancy.

Conclusion
9% of our urinary isolates of S. bovis were associated with a known GI malignancy. This is compared with 11% of blood culture isolates also from our unit in 2016.
Staphylococcus aureus bacteraemia management in a busy London DGH; is early switch to ceftriaxone safe?
Authors: McGuire Emma , Woods Kate , Boyd Aileen 
Published: March 2020

Background:
Standard of care for management of Staphylococcus aureus bacteraemia (SAB) is 2-4 weeks intravenous (IV) flucloxacillin or glycopeptide. Ceftriaxone (CRO) is used to facilitate management of SAB under out-patient antimicrobial therapy (OPAT) services once patients are medically stable, however published data on this approach are limited.

Methods:
Retrospective review of SAB cases at Homerton Hospital: 1st August 2015 to 31st July 2018. Cases were identified from the microbiology database and clinical data retrospectively collected from electronic patient records.

Results:
83 cases of SAB were included. Median age was 56 years (IQR 45-74); 53 (63.9%) were male. 70 (84.3%) had complicated SAB, 4 (4.8%) had MRSA bacteraemia and 11/80 (13.8%) were PVL positive. After excluding patients who died or were transferred whilst on IV therapy; 8/11 (72.7%) uncomplicated SAB patients and 29/55 (52.7%) complicated SAB patients received the standard duration of IV anti-staphylococcal therapy. Median length of stay (LOS) was 32 days (IQR 16-52.5). 30-day mortality was 9.6%; in hospital mortality was 14.5%.
Eight (8/83, 9.6%) patients switched to CRO prior to completion of standard IV flucloxacillin therapy to facilitate OPAT. Median length of IV flucloxacillin in this group was 12 days (IQR 7-16). Ceftriaxone MIC was performed on 1/8 isolates (3mg/L). 7/8 had complicated SAB. Median LOS was 13 days (IQR 9-17). There were no deaths or relapsed infections. 1 patient developed C. difficileinfection on CRO.

Conclusion:
In this cohort ceftriaxone was a safe and effective follow-on therapy from flucloxacillin for management of SAB and allowed reduced LOS.
Unravelling the benefits and barriers to utilising whole-genome sequencing in the investigation of outbreaks
Authors: Parcell Benjamin , Gillespie Stephen , Holden Matthew 
Published: March 2020

Background
This prospective study was established to develop and evaluate methods to harness pathogen sequencing in the clinical microbiology environment. We describe new insights into the clinical benefits of using whole-genome sequencing (WGS) for outbreak investigation with solutions for the practical barriers to implementation in clinical settings.
Methods
Surveillance software (ICNet) and statistical process control charts (SPCs) detected potential outbreaks of meticillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), carbapenem-resistant Enterobacteriaceae (CRE), Enterobacteriaceae producing extended spectrum β-lactamases (ESBLs), Listeriaspp. and optrAgene positive enterococci. Isolates were sent to reference laboratories for conventional typing and the Infection Group, School of Medicine, University of St Andrews for WGS (Illumina Inc, San Diego, CA, USA) and bioinformatic data analysis.

Results
Over 400 isolates have been sequenced to date. WGS replaced multiple typing techniques in a Pseudomonas aeruginosa ICU outbreak. It confirmed two patient’s Listeria spp. isolates were indistinguishable prompting hospital kitchen inspections, identified a patient to be carrying two strains of VRE and confirmed that vancomycin-sensitive Enterococcus faecium isolates related to a VRE cluster. We observed five main barriers to implementing WGS (infrastructure, performance/quality assessment of data, isolate selection, clinical result interpretation and database management).

Conclusion
WGS is beneficial in outbreaks of uncommon organisms and when conventional typing cannot show whether isolates are linked or not. Identifying barriers assisted us in developing a clinical decision aid that can be used by clinicians when applying WGS to outbreak investigations.
An Uncommon Infection in Common Variable Immunodeficiency
Authors: Wong Nicholas , Price Arthur , Pan Daniel , Sahota Amandip 
Published: March 2020

Cryptococcus neoformanscan cause life-threatening disease in both immunocompromised and healthy patients. We report a case of cryptococcal meningoencephalitis in a 68 year old patient with a history of common variable immunodeficiency due to a NFKB1 gene mutation and indeterminate colitis.
Our patient was admitted following a fall where he fractured his left humerus. During his admission, a persistent fever was noted despite broad spectrum antibiotic therapy. His neurological condition deteriorated over four weeks, with impaired cognition progressing to aphasia and obtundation. Following initial concerns over an ischaemic stroke, he was found to be serum cryptococcal antigen positive, and subsequent cerebrospinal fluid analysis confirmed CNS cryptococcosis by culture. His neurological condition improved with combination of liposomal amphotericin and flucytosine and he is currently undergoing rehabilitation.
The NFKB1 mutation is associated with common variable immunodeficiency and hypogammaglobulinaemia. Our patient was on weekly subcutaneous immunoglobulin replacement, but also required long term glucocorticoids (prednisolone 20mg daily) to control his colitis.
To our knowledge, this is the first description of cryptococcal meningoencephalitis in a patient with the NFKB1 mutation. Cryptococcal disease is an important differential diagnosis in immunosuppressed patients with fever and neurological symptoms and full recovery is possible with prompt recognition and treatment.
Carbon Quantum Dots Conjugated CRISPR-cas9-gRNA Antimicrobials Against Antibiotic Resistant Uropathogenic Escherichia coli
Authors: Gupta Surbhi , Jindal Neha , Pooja D. , Yadav Manisha 
Published: March 2020

Background:
Urinary tract infections (UTIs) are among the most common bacterial infections. UTI, although treatable, is now becoming increasingly tough to control because of rampant antimicrobial resistance in the Enterobacteriaceae family, particularly inEscherichia coli. Due to increased resistance, there is an exigency to develop novel therapeutic targets to combat these resistance strains. Clustered regularly interspaced short palindromic repeats (CRISPR)-technology has emerged as an important tool for gene editing based therapeutics.

Methods:
Here, we report an efficient gene editing strategy based on direct delivery of Cas9 and gRNA into Uropathogenic E. coli (UPEC) isolate. P-fimbriae plays major role in bacterial adherence to the uroepithelium through the Galα1-4Gal-binding PapG adhesin. We have covalently conjugated cas9 protein with CQD’s using EDC/NHS chemistry and targeted papG gene by synthesizing sequence specific complimentary gRNA. The targeting efficiency was confirmed by performing adherence assay, biofilm assay, flow cytometry and qRT-PCR.

Results:
There is a significant reduction of adherence ability of papG mutant strain as compared to control observed through microscopy. Also, significant reduction in biofilm formation (p-value < 0.001) was noticed in treated sample (0.565 ± 0.003) vs control (1.020± 0.008). The relative qRT-PCR data of knockdown strains (p<0.05) also revealed the dramatic decrease in the expression of papG gene, taking 16s rRNA gene as an endogenous control for normalization. The same result was observed from flow cytometry and SEM analysis.

Conclusion:
Hence, we conclude that CQD-CRISPR-Cas9-gRNA could be a novel therapeutic strategy for the eradication or treatment of antibiotic resistant pathogenic E. coli-based pathologies.
Epidemiological and clinical features of COVID-19 patients with and without pneumonia in Beijing, China
Authors: Yang Penghui , Ding Yibo , Xu Zhe , Pu Rui , Li Ping , Yan Jin , Liu Jiluo , Meng Fanping , Huang Lei , Shi Lei , Jiang Tianjun , Qin Enqiang , Zhao Min , Zhang Dawei , Zhao Peng , Yu Lingxiang , Wang Zhaohai , Hong Zhixian , Xiao Zhaohui , Xi Qing , Zhao Dexi , Yu Peng , Zhu Caizhong , Chen Zhu , Zhang Shaogeng , Ji Junsheng , Cao Guangwen , Wang Fusheng 
Published: March 2020

AbstractBackgroundSARS-CoV-2-caused coronavirus disease (COVID-19) is posing a large casualty. The features of COVID-19 patients with and without pneumonia, SARS-CoV-2 transmissibility in asymptomatic carriers, and factors predicting disease progression remain unknown.MethodsWe collected information on clinical characteristics, exposure history, and laboratory examinations of all laboratory-confirmed COVID-19 patients admitted to PLA General Hospital. Cox regression analysis was applied to identify prognostic factors. The last follow-up was February 18, 2020.ResultsWe characterized 55 consecutive COVID-19 patients. The mean incubation was 8.42 (95% confidence interval [CI], 6.55-10.29) days. The mean SARS-CoV-2-positive duration from first positive test to conversion was 9.71 (95%CI, 8.21-11.22) days. COVID-19 course was approximately 2 weeks. Asymptomatic carriers might transmit SARS-CoV-2. Compared to patients without pneumonia, those with pneumonia were 15 years older and had a higher rate of hypertension, higher frequencies of having a fever and cough, and higher levels of interleukin-6 (14.61 vs. 8.06pg/mL, P=0.040), B lymphocyte proportion (13.0% vs.10.0%, P=0.024), low account (<190/µL) of CD8+ T cells (33.3% vs. 0, P=0.019). Multivariate Cox regression analysis indicated that circulating interleukin-6 and lactate independently predicted COVID-19 progression, with a hazard ratio (95%CI) of 1.052 (1.000-1.107) and 1.082 (1.013-1.155), respectively. During disease course, T lymphocytes were generally lower, neutrophils higher, in pneumonia patients than in pneumonia-free patients. CD8+ lymphocytes did not increase at the 20th days after illness onset.ConclusionThe epidemiological features are important for COVID-19 prophylaxis. Circulating interleukin-6 and lactate are independent prognostic factors. CD8+ T cell exhaustion might be critical in the development of COVID-19.
Are there systematic biases in RNA-seq data analysis? A case study for Amphimedon queenslandica sponge as a model object
Authors: Feranchuk Sergey 
Published: March 2020

AbstractBACKGROUNDThe performance of a functional annotation approach for RNA-seq bioinformatics pipelines was to be compared with the method where groups of genes are generated with no relation to ontologes. Three publicly available RNA-Seq experiments for Amphimedon queenslandica sponge were used for the designed comparison. One of these experiments was referred in the publication where stages of embryo development were compared for a wide range of animal species.METHODSThe expression levels were re-calculated here for three independent series of experiments. The functional annotation of differential expression levels was than conducted. This allow to compare an applicability of the two approaches, and to re-evaluate the interpretation provided in the mentioned publication.RESULTSIt was confirmed by the conventional approach that Wnt and Notch pathways do operate in a development of a sponge embryo. The method of annotation which uses unbounded grouping of genes was effective in an ability to separate development stages of sponge embryo. In addition, the published results were by a suggestion distorted by an artifact, caused by a positive feedback in the stage of data processing.
The spatiotemporal estimation of the dynamic risk and the international transmission of 2019 Novel Coronavirus (COVID-19) outbreak: A global perspective
Authors: Lin Yuan-Chien , Chi Wan-Ju , Lin Yu-Ting , Lai Chun-Yeh 
Published: March 2020

AbstractAn ongoing novel coronavirus SARS-CoV-2 pneumonia infection outbreak called COVID-19 started in Wuhan, Hubei Province, China, in December 2019. It both spread rapidly to all provinces in China and started spreading around the world quickly through international human movement from January 2020. Currently, the spatiotemporal epidemic transmission patterns, prediction models, and possible risk analysis for the future are insufficient for COVID-19 but we urgently need relevant information, particularly from the global perspective.We have developed a novel two-stage simulation model to simulate the spatiotemporal changes in the number of COVID-19 cases and estimate the future worldwide risk. Based on the connectivity of countries to China and the country’s medical and epidemic prevention capabilities, different scenarios are generated to analyze the possible transmission throughout the world and use this information to evaluate each country’s vulnerability to and the dynamic risk of COVID-19.Countries’ vulnerability to the COVID-19 outbreak from China is calculated for 63 countries around the world. Taiwan, South Korea, Hong Kong, and Japan are the most vulnerable areas. The relationship between each country’s vulnerability and days before the first imported case occurred shows a very high exponential decrease. The cumulative number of cases in each country also has a linear relationship with vulnerability, which can compare and quantify the initial epidemic prevention capabilities to various countries’ management strategies. In total, 1,000 simulation results of future cases around the world are generated for the spatiotemporal risk assessment. According to the simulation results of this study, if there is no specific medicine for it, it will likely form a global pandemic. This method can be used as a preliminary risk assessment of the spatiotemporal spread for a new global epidemic. * Note: This study was completed on February 15, 2020.
Detectable serum SARS-CoV-2 viral load (RNAaemia) is closely associated with drastically elevated interleukin 6 (IL-6) level in critically ill COVID-19 patients
Authors: Chen Xiaohua , Zhao Binghong , Qu Yueming , Chen Yurou , Xiong Jie , Feng Yong , Men Dong , Huang Qianchuan , Liu Ying , Yang Bo , Ding Jinya , Li Feng 
Published: March 2020

AbstractBackgroundAlthough the SARS-CoV-2 viral load detection of respiratory specimen has been widely used for novel coronavirus disease (COVID-19) diagnosis, it is undeniable that serum SARS-CoV-2 nucleic acid (RNAaemia) could be detected in a fraction of the COVID-19 patients. However, it is not clear that if the incidence of RNAaemia could be correlated with the occurrence of cytokine storm or with the specific class of patients.MethodsThis study enrolled 48 patients with COVID-19 admitted to the General Hospital of Central Theater Command, PLA, a designated hospital in Wuhan, China. The patients were divided into three groups according to the Diagnosis and Treatment of New Coronavirus Pneumonia (version 6) published by the National Health Commission of China. The clinical and laboratory data were collected. The serum viral load detection and serum IL-6 levels were determined. Except for routine statistical analysis, Generalized Linear Models (GLMs) analysis was used to establish a patient status prediction model based on real-time RT-PCR Ct value.FindingsThe Result showed that cases with RNAaemia were exclusively confirmed in critically ill patients group and appeared to reflect the illness severity. Further more, the inflammatory cytokine IL-6 levels were significantly elevated in critically ill patients, which is almost 10-folds higher than those in other patients. More importantly, the extremely high IL-6 level was closely correlated with the incidence of RNAaemia (R=0.902) and the vital signs of COVID-19 patients (R= −0.682).InterpretationSerum SARS-CoV-2 viral load (RNAaemia) is strongly associated with cytokine storm and can be used to predict the poor prognosis of COVID-19 patients. Moreover, our results strongly suggest that cytokine IL-6 should be considered as a therapeutic target in critically ill patients with excessive inflammatory response.
Views and Experiences of Parents and Physicians on the Care Provided to Children with Sickle Cell Disease in Cameroon
Authors: Agborndip Ettamba , Kadia Benjamin Momo , Ekaney Domin Sone Majunda , Mbuagbaw Lawrence Tanyi , Rees David C , Bedford Helen 
Published: March 2020

AbstractBackgroundSickle Cell Disease (SCD) affects two in 100 Cameroonian new-borns, with 50-90% of affected children dying before their fifth birthday. Despite this burden, there is no national SCD programme in Cameroon. This study aimed to assess parents’ and physicians’ knowledge of SCD, their satisfaction with the quality of care and their recommendations to improve the treatment of SCD in Cameroon.MethodsA multi-centre cross-sectional survey was conducted in English and French, using structured questionnaires distributed in electronic format to physicians throughout Cameroon. Paper-based questionnaires were also administered to parents in the West and North West regions of Cameroon. Data were entered into Microsoft Excel and analysed using the SPSS statistical software.ResultsFifty-four parents and 205 physicians were recruited. We found that 72.2% of parents had good knowledge of SCD, 72.2% of parents were satisfied with the quality of care. Attending a sickle cell clinic (AOR 22, 95% CI 17.70-250) was significantly associated with having good knowledge. Just 14.2% of physicians had good knowledge and 23.3% of physicians were satisfied with the available management standards of SCD. Seeing more than five patients per month (AOR 3.17, 95% CI 1.23-8.20) was significantly associated with having good knowledge. Sickle cell clinics, national guidelines and subsidised treatment were the top three measures proposed by physicians and parents to improve the management of SCD.ConclusionKnowledge of SCD and satisfaction with care were poor among Cameroonian physicians. There is a need for a national programme and a comprehensive system of care for SCD in Cameroon.