bluuebunny/crossref_metadata_2025_split huggingface dataset:
An audit of the diagnosis and treatment of infective endocarditis
Authors: Roth Katie , Ross Sam , Awad Sawsan 
Published: March 2020

Background
Infective endocarditis (IE) is associated with a high incidence of mortality and morbidity and guidelines exist on appropriate diagnosis and treatment. The aim of the study was to evaluate adherence with national guidance and identify relevant learning experiences if indicated.
Methods
We performed a retrospective review of admissions to a district general hospital with a diagnosis of IE over a 1-year period from January 2018 to December 2018. Individual cases were identified during inpatient admission and notes reviewed to establish adherence to a published national audit tool.
Information regarding initial investigation, and management was gathered from the medical notes and microbiology reporting of samples was also examined.

Results
Of the 16 cases identified: 93% did not have blood cultures taken appropriately before treatment was started and only 50% received the recommended empirical antibiotics.
Only 43% had a transthoracic echocardiogram performed in the first 24 hours.
A surgical opinion was sought in just 2 of 4 cases of prosthetic valve endocarditis.
The three culture negative IE cases had no further recommended testing performed.

Conclusion
We highlighted a need for improved investigation and treatment of IE.
Timeliness of transthoracic echocardiograms will be improved by a change to the request form to indicate if IE is suspected so scans can be prioritised.
Clinicians will be informed if blood cultures are negative so further testing can be arranged if there is still a high clinical suspicion.
A weekly microbiology ward round has been established to review all suspected cases of IE.
Dalbavancin: A “silver bullet” against gram positive infections in PWID
Authors: Taylor Stuart , Sharp Harriet , Lippett Samantha 
Published: March 2020

Introduction: Dalbavancin is a novel lipoglycopeptide antibiotic which provides gram positive cover including MRSA and enterococci for up to six weeks with two doses. We report the use of Dalbavancin at the Royal Sussex County Hospital in Brighton from 2018-2019.
Methods: Patients were given dalbavancin after approval by a consultant microbiologist on a case by case basis.
Results: 20 patients in total received dalbavancin during this time period. 11 out of 20 patients were male with a mean sample age of 54. 14 patients were ex or current IVDUs. The most frequent dose of dalbavancin given was 1.5g single dose in 11 out of 20 patients.
14 patients had a confirmed bacteraemia. There were 8 cases of MSSA, 1 case of MRSA, 1 CNS, 2 IGAS, 1 Group C Streptococcus and 2 Streptococcus dysgalactiae bacteraemias (one patient had 2 organisms identified in blood cultures). The commonest source of infection was skin and soft tissue, identified in 11 out of 20 patients.
Patients had received a median of 2 (range 1-5) different antibiotics prior to use of dalbavancin with a median course of 14 (range 1 – 27) days Abx prior to Dalbavancin. Patients were admitted for a mean of 15 days with a mean of 12 bed days saved per patient. There was one readmission during this time period which was due to a gram-negative sepsis.
Discussion:Given the challenges of managing severe infections in PWID, dalbavancin can be a “silver bullet” to facilitate effective treatment of important gram-positive pathogens.
Once bitten, twice shy
Authors: Taylor Stuart 
Published: March 2020

A 48yr old man presented with a 1-2 week history of diarrhoea and fever. He took occasional ibuprofen for migraines but took no regular medications and was fit and active. On presentation to A+E blood tests revealed severe AKI with hyperkalaemia, low platelets and anaemia with raised inflammatory markers. He complained of shortness of breath with a CXR consistent with ARDS. He was commenced on IV antibiotics and was transferred to ITU for further management. While on ITU his blood film revealed evidence of haemolysis, in addition to an LDH of >2600. He had persistenly low platelets (14 at its nadir), requiring platelet transfusion. His renal failure was managed with haemofiltration and he was transfused to maintain his Hb above 80. The diagnosis was of haemolytic uraemic syndrome due to a presumed infectious origin. Blood cultures came back positive for a fastidious, slow-growing Gram-negative rod, identified as Capnocytophaga canimorsus. Further questioning revealed the presence of a dog bite to his R. index finger two months previously. The patient's antibiotic regimen was changed to Ceftriaxone 2g IV OD and metronidazole 500mg IV TDS and he was transferred to the Royal Free Hospital to commence haemodilaysis and for specialist renal management.
Capnocytophaga canimorsus is an encapsulated organism known for its potential to cause disseminated and fatal infection in asplenic or immunocompromised patients, which were risk factors not present in our case. It is a rare cause of HUS and highlights the need for thorough history if an infective agent is presumed.
Carbapenem stewardship in a large teaching English hospital - are we improving?
Authors: Olusoga Abimbola , Howard Philip , Walker Caroline , Atack Kelly , Waterhouse Annabelle 
Published: March 2020

Background:Overuse of antibiotics has been linked to the global growth of antimicrobial resistance (AMR). In 2018, increase in meropenem usage in our hospital revealed that we achieved the “Start Smart” but not “Then Focus” element. Following revised carbapenem stewardship, we aimed to evaluate the adherence to guidelines, by monitoring patients initiated on meropenem.
Methods:As part of the antimicrobial stewardship (AMS) at our 1800-bed teaching hospital, carbanepem stewardship was revised in September 2018 and required consultant approval for all carbapenem initiation or continuation following specialist advice. Meropenem prescriptions in adult and paediatric patients were generated from the electronic prescription system and reviewed daily for one week in August 2019 to ascertain if prescribed in line with guideline recommendations or on the advice of microbiology or infectious diseases.
Results:Sixty patients were reviewed. Microbiology or Infectious Diseases recommendation was obtained in 37% of patients. 95% had samples taken where blood cultures accounted for 85% but over a third of these had no growth reported. Meropenem was initiated empirically in 50% of patients mainly for neutropenic sepsis while 28% were culture directed. 35% of patients were escalated from piperacillin-tazobactam of which 57% had neutropenia while de-escalation occurred in 10%.
Conclusion:AMR is related directly to antibiotic use at a patient level. Our revised strategy resulted in a reduction of total carbapenem DDD/1000 Admission from 128 (June 2018) to 87 (June 2019) through improved adherence to guideline and infection specialists recommendations however more work is required to promote switch to narrower-spectrum choice.
Antibiotics & adjuvant corticosteroids in management of pneumococcal meningitis: a retrospective case-notes audit
Authors: Barr Andrew , Schwab Uli 
Published: March 2020

Background
Pneumococcus remains the most common cause of bacterial meningitis with high morbidity and mortality. Adjuvant corticosteroids with early antibiotics have been shown to reduce the neurological morbidity and mortality respectively and this is reflected in British Infection Society (BIS) guidance.
Aim
To assess how closely BIS guidelines were followed regarding antibiotic and adjuvant corticosteroid administration in management of pneumococcal meningitis.
Methods
Newcastle Upon Tyne Hospital case-notes of pneumococcal meningitis from a 7-year-period(2012-2019) were audited. Patients were identified using microbiological records and case-notes. Data was collected on intervals from initial-assessment to commencing antibiotics and corticosteroids.

Results
Eighteen cases were identified of whom three(17%) presented with the classic triad (fever, meningism, reduced GCS). All patients received appropriate antibiotics: 3/18(17%) within first hour of assessment. The median time to antibiotics was 5h 8mins (range:21-7129min). Eight patients(44%) received antibiotics >6h after assessment. Twelve patients(67%) received corticosteroids; only six(33%) at the recommended dose and duration. Mean time from antibiotics to corticosteroids was 6h1min. Five deaths occurred in the cohort with three attributable to pneumococcal sepsis (all had late presentations). 6/18 had significant neurological sequelae, irrespective of whether they received corticosteroids.
Discussion
The significant morbidity and mortality of pneumococcal meningitis demands a high index of suspicion. BIS guideline targets are repeatedly not met; long delays exist between assessment and antibiotic and corticosteroid administration. Integrated electronic prescribing and clinical Early Warning Systems have potential to ameliorate this with meningitis-tailored order sets to prompt consideration of meningitis and guide correct prescribing.
Managing seasonal influenza in hospitalized patients - without an influenza point-of-care test
Authors: Hills George , Kennedy Matthew , Ahmed Osama , Tang Julian 
Published: March 2020

Background: National guidelines recommend isolation and commencing empirical antiviral therapy for suspected influenza in the inpatient setting, however this is not always done in practice. There are many reasons why influenza may be diagnosed late, and in order to minimise potential harm, rapid results are therefore required.
Methods: During the 2018-19 influenza season, we instigated a policy of calling out all new influenza positives during normal working hours. As well as informing clinical teams of results, we also recorded clinical information, including whether the patient was:
* isolated,
* already on antivirals,
* discharged (and if so on what therapy)
Results: In the peak season (January 1st - March 31st 2019), 179 calls to clinical teams were made. The median time from sample collection to reporting was 28 hours and 33 minutes. 44% of patients were not on antivirals at the time of the result, and 28% were not isolated. Based on these numbers, we estimated that 141-235 inpatients may have been exposed to influenza on our wards. 25% of a total of 309 positive influenza samples were from patients who were discharged at the time of the result. 65% of these patients were discharged with antibiotics, 54% with antivirals, and 37% with both antivirals and antibiotics.
Conclusion: Based on our data, and that of other studies, we hypothesise that rapid influenza results would lead to better infection control practices, reduced spread of infection, and improved antimicrobial stewardship. Molecular point-of-care tests have the potential to resolve some of the issues with late influenza diagnosis.
Real-time Monitoring of Aerosols Generated from Toilet Flushing
Authors: Fennelly Mehael , Hellebust Stig , Sodeau John , Prentice Michael 
Published: March 2020

Flushing toilets generate visible droplets from turbulent flow, but also produce numerous smaller airborne droplets (∼micrometres in size) through atomisation. Flushing may aerosolise pathogens from stool or urine, spreading disease. This study continuously monitored aerosols in a shared office lavatory over a week using a biological particle detector, the Wideband Integrated Bioaerosol Sensor (WIBS). This instrument monitors individual particle sizes and numbers and identifies fluorescent particles likely to be droplets containing bacteria.
The toilet was a standard wash-down design, (Armitage Shanks), with a lid. No statistically significant variation between fluorescent particle counts was found between periods prior to flushing. Fluorescent particle numbers and intensity increased with toilet flushing, remaining above background for 5 minutes post-flushing on average. Placing the toilet lid down significantly (P<0.001) reduced total and fluorescent particle counts during and after flushing by 30-50%. Lid usage significantly increased (P<0.001) particle diameter from 1.5 μm to 2.1 μm and increased particle fluorescence intensity (P<0.001) during flushing and after flushing, intensity remaining above background for 16 minutes.
This suggests standard lid usage reduces but does not eliminate flush-related bioaerosols. Lid-use changes their characteristics and apparently prolongs their residence time in room air. The aerosol change could represent particle agglomeration by a pressure-related Kelvin effect or particle re-aerosolisation from different surfaces in the toilet rather than exclusively originating from droplet generation. Previous studies reporting the effect of toilet lids have found that they prevent the spread of visible droplets on flushing, however the effect on smaller particles is less clear cut.
Pneumococcal 13-valent polysaccharide vaccination (PCV13) response in patients with pulmonary aspergillosis
Authors: Aggarwal Sunil , Kosmidis Chris , Denning David 
Published: March 2020

Background
Response to pneumococcal 23-valent polysaccharide vaccine (PPV23) is poor in patients with pulmonary aspergillosis, pneumococcal 13-valent polysaccharide vaccine (PCV13) is believed to be more antigenic. Thus practice at the national aspergillosis centre (NAC), Manchester University NHS foundation trust (MFT) is to give PCV13. However, response to PCV13 has not been studied.
Methods
We conducted a retrospective, observational study of patients with pulmonary aspergillosis at the NAC, MFT. Patients who had non-protective pre-vaccine levels, and received PCV13 between January-2015 and July-2019 with serology available within 3 months after vaccination were included.
Serotype-specific pneumococcal IgG antibodies were quantified for 12 pneumococcal serotypes. Non-protective immunity was defined as pre-vaccine level <0.35μg/mL to >
6 out of 12 serotypes. Protective response was defined as level >1.3μg/mL, or an increase in concentration ≥4-fold for at least 9 of 12 serotypes within 3 months.

Results
47 of 144 patients receiving PCV13 had non-protective pre-vaccination levels and repeat serology within 3 months post-vaccination. 52% and 20%, of patients who received 2 and 1 doses (respectively) developed protective immunity; χ2(1)=2.987,p= 0.084. 42.86%, 69.23%, 42.86%, 50%, and 0% of patients with chronic pulmonary aspergillosis (CPA), allergic bronchopulmonary aspergillosis (ABPA), severe asthma with fungal sensitisation, aspergillus bronchitis, and mixed ABPA and CPA developed protective immunity; χ2(4)=6.329,p=0.176.

Conclusion
Patients with CPA respond poorly to PCV13 compared to ABPA. Response to two doses of PCV13 is comparable to one dose of PPV-231. Patients with pulmonary aspergillosis should receive two doses of PCV13 rather than one dose.
Unaccountable use of systemic antifungal treatment leads to change in guidelines and stewardship in a district general hospital
Authors: David Kate , Patel Trupti , Lim Ai-nee , Kelsey Michael 
Published: March 2020

Background
Antifungal resistance is a global emergency of increasing prevalence, yet only 11% of NHS Trusts have an antifungal stewardship programme. Given the high mortality and cost associated with invasive fungal infections, it is paramount to optimise investigations and judicious use of systemic antifungals. Hospital guidelines often focus on empirical treatment, omitting diagnostics.
Methods
Patients prescribed systemic antifungals were identified using pharmacy records over a 1 year period in a district general hospital in London. Electronic patient records were interrogated for microbiological, serological, histopathological and radiological investigations based on national recommendations. Audit standards were designed to meet the NHS England Medicines Optimisation and Stewardship CQUIN.

Results
31 adult patients were identified. Microbiological evidence of fungal infection was demonstrated in 15/31 patients (48%). 60% were speciated and 47% underwent susceptibility testing. Three patients had beta-D-glucan tests; two patients had histopathological testing; 19 patients underwent imaging, of which 42% were reported as consistent with possible fungal infection.

Conclusion
9 (29%) patients had no obvious indication for antifungal treatment. Systemic antifungal treatment is not without toxicity and cost and contributes to resistance. In view of this, we updated the hospital guideline to include a guide to diagnostics, incorporated antifungals into our antimicrobial stewardship ward round and submitted this audit to NHS England CQUIN. Further work will evaluate whether these changes impact upon current practice.
References
Micallef C et al.
Med. Microbiol. 2017;66(11):1581-1589
Fisher MC et al. Science 2018;360(6390):739-742
Schelenz S et al. Lancet Infect Dis 2015;15(4):461–74
Theoretical approaches in the development and evaluation of behaviour change interventions that improve clinicians’ antimicrobial prescribing: a systematic review
Authors: Talkhan Hend , Stewart Derek , McIntosh Trudi , Rouf Palli Valappila Abdul , Al-Hail Moza , Cunningham Scott , Ziglam Hisham 
Published: March 2020

Many countries have developed antimicrobial stewardship programmes with strategies to optimise antimicrobial prescribing. There remains a need for behaviour change interventions at clinician level to promote appropriate prescribing. Theories should be used for developing and evaluating interventions to change human behaviour.
Aim / Objectives:The aim of this review was to critically appraise, synthesise and present the available evidence for theoretical approaches in the development and evaluation of behaviour change interventions designed to improve clinicians' antimicrobial prescribing.
Design & Methodology:
The systematic review protocol was developed and registered with the International Prospective Register of Systematic Reviews (CRD42018098586).
Two review authors independently extracted data and assessed study quality. Clinical and methodological heterogeneity limited data synthesis.

Results
The searches resulted in 4227 relevant articles after duplicates removal. Screening of titles/abstracts led to retrieval and dual assessment of 38 full-text articles. Of those, a total of 10 studies met the inclusion criteria.
The majority of studies were carried out in primary care settings (n = 9) targeting upper respiratory tract infections (n = 8). Use of theory varied considerably across studies included. Theory of Planned Behaviour, Social Cognitive Theory and Operant Learning Theory were the most common theories used to inform the design and choice of interventions.
Conclusion / Discussion
It is feasible to develop and evaluate theoretically based interventions to improve professional practice. The findings of this systematic review will inform understanding of the theoretical basis of behaviour change interventions which contribute to contain AMR rates and prevent the world entering a “post-antibiotic era”.
Characteristics of patients admitted to Intensive care units with severe Influenza and management outcome at a large district general hospital in East of England, UK
Authors: Patel Jignna , Vaghela Tejal , Kandil Hala 
Published: March 2020

Background:
Influenza pneumonia can be challenging to treat particularly in critically ill patients. The aim of this study is to review the risk factors for severe influenza infection, the course of the disease, the choice of antivirals and the management outcome in patients admitted with complicated influenza illness to ICU

Method
Sixteen patients who were admitted to ICU at West Hertfordshire hospitals NHS Trust with severe influenza illness were reviewed between 20th December 2018 and 14th February 2019. Data on Demographics, vaccination status, viral strain and clinical outcome were collected and analysed.

Results
High proportion of patients were below the age of 65 (n=9).The predominant strain was A(H1N1) pdm09 (n=10), followed by A(H3N2) (n=5) and 1 patient had no strain reported. All patients were initiated on Oseltamivir. Six patients developed multi-organ failure and were switched to IV Zanamivir. None of the latter were severely immunosuppressed. 56.25% (n=9) were not vaccinated and third with unknown status (n=5). 66% of the patients below the age of 65 were not vaccinated and had to switch to Zanamavir. Fourteen patients made good recovery and 2 died while on Zanamavir

Conclusion:
Our result suggest that the majority of patients admitted to ICU did not carry risk factor for complications and were below the age of 65, but were unvaccinated and infected with A(H1N1)pdm09 strain. Larger study is required to fully understand the risk factors for ICU admission including vaccination status in this group of patients and the optimum antiviral choice.
Non-coding germline GATA3 variants alter chromatin topology and contribute to pathogenesis of acute lymphoblastic leukemia
Authors: Yang Hongbo , Zhang Hui , Luan Yu , Liu Tingting , Roberts Kathryn G , Qian Mao-xiang , Zhang Bo , Yang Wenjian , Perez-Andreu Virginia , Xu Jie , Iyyanki Sriranga , Kuang Da , Reshmi Shalini C. , Gastier-Foster Julie , Smith Colton , Pui Ching-Hon , Evans William E , Hunger Stephen P , Platanias Leonidas C. , Relling Mary V , Mullighan Charles G , Loh Mignon L , Yue Feng , Yang Jun J 
Published: March 2020

AbstractInherited non-coding genetic variants confer significant disease susceptibility in many cancers. However, the molecular processes of by which germline variants contribute to somatic lesions are poorly understood. We performed targeted sequencing in 5,008 patients and identified a key regulatory germline variant in GATA3 strongly associated with Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL). By creating an isogenic cellular model with CRISPR-Cas9 system, we showed that this variant activated a strong enhancer that significantly upregulated GATA3 transcription, which in turn reshaped the global chromatin accessibility and 3D genome organization. Remarkably, this genotype switch induced a chromatin loop between the CRLF2 oncogene and a distal enhancer, similar to the somatically acquired super-enhancer hijacking event in patients. GATA3 genotype-related alterations in transcriptional control and 3D chromatin organization were further validated in Ph-like ALL patients. Finally, we showed that GATA3 directly regulates CRLF2 and potentiates the oncogenic effects of JAK-STAT signaling in leukemogenesis. Altogether, our results provide evidence for a novel mechanism by which a germline non-coding variant contributes to oncogene activation epigenetic regulation and 3D genome reprogramming.