bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigating the role of the gut microbiome as a trigger for arthritis development in individuals at risk of rheumatoid arthritis
Authors: Rooney Christopher , Mankia Kulveer , Mitra Suparna , Moura Ines , Chilton Caroline , Emery Paul , Wilcox Mark 
Published: March 2020

Background:
Rheumatoid arthritis (RA) is now recognised as the end point of a disease continuum. Anti-citrullinated peptide antibodies (ACPA) mark the presence of RA-related systemic autoimmunity, but the production of auto-antibodies alone is not sufficient to develop disease. Data on progression between the stages of RA disease are limited, but accumulating evidence suggests a microbial dysbiosis in the gut may trigger RA development. Using a prospective ‘at-risk’ cohort of ACPA positive individuals without arthritis, we investigated for the presence of a gut dysbiosis before the onset of RA.
Materials/methods:
Faecal samples from 25 ACPA-positive individuals, with non-specific musculoskeletal pain, were sequenced using16S rRNA gene. A control population was selected from publicly available data on the NCBI database, matched for rRNA V4 amplification region, sequencing technique, and approximately for age, gender, diet and ethnicity. Taxonomic analysis was performed using QIIME and MEGAN, and statistical analysis using R software.

Results:
Comparison of the ACPA-positive and control populations shows large clustering at bacterial family level. The ACPA population has an abundance of Lachnospiraceae, Helicobacteraceae, Ruminococcaceae, Erysipelotrichaceae and Bifidobacteriaceae, and a lower abundance of Bacteroidaceae, Barnesiellaceae, Methanobacteriaceae amongst others. The relative abundance of bacterial taxa between the ACPA positive and control population was significantly different (P value 0.01, permutation MANOVA).
Conclusions:
The gut microbiome of individuals ‘at-risk’ of developing RA is distinct from heathy controls. These pilot data can inform further studies, and are an important step in the attribution of causality to the gut microbiome in the development of RA.
Encouraging Day Three Reviews via a Pharmacist-led Antimicrobial Stewardship Ward Round
Authors: Atack Kelly , Olusoga Abimbola , Howard Philip 
Published: March 2020

Background
Intravenous antibiotics should be reviewed at day three and a decision made whether to continue, stop, switch to oral or refer to OPAT. Clinicians struggle to undertake this review due to the demands of the daily ward round and patients are inappropriately left on broad spectrum intravenous antibiotics, which can cause harm and increase antimicrobial resistance. A pharmacist-led virtual ward round was initiated to review these patients to decrease the number of patients on broad-spectrum IV antibiotics and support regular review of these.

Methods
Patients on day three or more of intravenous antibiotics were identified using an electronic prescribing report and reviewed using an electronic antimicrobial review tool by a pharmacist on a weekly basis.
Recommendations were made via the tool and added to the patient’s electronic record and then followed up after 24 hours to review the prescription and identify whether advice had been followed.

Results
Over eight weeks, 75 patients had their IV antibiotics reviewed by the pharmacist. 20 recommendations were made to continue, 15 to stop, 33 for IVOS and 10 for OPAT referral. After 24 hours, 80% of patients were continued, 47% were stopped, 61% of patients were switched to oral, and 40% of patients were referred to OPAT as per the recommendations.

Discussion
The pharmacist-led virtual ward round appeared to have a positive impact on the reduction of IV antibiotics being continued after day three. Additionally, reviewing patients virtually allowed for more patients to be reviewed, increasing the impact of the stewardship round.
Missed opportunities for HIV testing in a Scottish Health Board
Authors: Davies Melanie , Kennedy Nicholas , McGoldrick Claire 
Published: March 2020

Background
Early diagnosis of HIV allows commencement of combination antiretroviral therapy, reducing morbidity and mortality, as well as transmission. In 2010, 64.3% of new patients diagnosed with HIV in Lanarkshire had missed opportunities for earlier diagnosis, leading to various educational initiatives. Their success in reducing missed opportunities is examined here.
Methods
People who were newly diagnosed with HIV in 2017 were identified. For each person, NHS Lanarkshire hospital records, dating back ten years, were analysed to identify missed opportunities for testing. These were defined as episodes of care with potential HIV indicator conditions (shown in the British HIV Association testing guideline), that did not lead to an HIV test. Comparisons were made to 2010 data.

Results
16 patients who were newly diagnosed with HIV in 2017 were identified. 43.8% (7/16) had missed opportunities for earlier diagnosis compared to 64.3% (9/14) in 2010. One presented with an AIDS-defining illness, compared with 3 in 2010. Blood dyscrasia was the most common clinical indicator that failed to prompt testing, although other commonly missed indicators were pneumonia and mononucleosis-like syndrome.

Conclusion
Educational initiatives are effective in improving appropriate HIV testing, however are not enough in isolation. Quality improvement strategies to increase testing, that are applicable to any Health Board/Trust, are currently being used. These include engagement with haematologists to provide testing prompts in reports, and opt-out testing in presumed high-prevalence clinical areas.
Scrub typhus causing acute undifferentiated febrile illness and its association with clinical outcomes: An observational hospital based study from tertiary care center in North India
Authors: Shah Dhara , Singh Avinash , Tiwari Dinesh , Sahu Chinmoy , Misra Richa , Prasad Kashi Nath 
Published: March 2020

Background:	The clinical presentation of Scrub typhus mimics other acute undifferentiated febrile illnesses (AUFI) thus making it difficult to diagnose clinically.
Methods: Patients hospitalized with acute febrile illness (2-21 days) along with clinical suspicion for scrub typhus were evaluated for specific IgM antibodies against O. tsutsugamushi by ELISA and details of demographic, clinical, laboratory and clinical complication/outcomes related parameters collected for
statistical analysis.
Results: Scrub typhus IgM antibodies by ELISA were detected in 88 (18.1%) patients out of 486 patients hospitalized with acute febrile illness and clinically suspected for Scrub typhus between September 2015 and January 2017. The majority sero-positive cases were found in July-December (p=0.02). Out of 88, twenty nine sero-positive Scrub typhus patients had serological evidence of co-infections. Eschar was observed in 11 (12.5%) sero-positive patients. Of 88, 23 sero-positive Scrub typhus patients died. A low platelet count (RR: 0.99; 95% CI:0.98-1.00, p=0.02), requirement of intensive care (RR: 2.26; 95% CI: 0.19-26.5, p = 0.01), need for mechanical ventilation (RR: 3.8, 95% CI: 1.35-10.86, p =0.003) and metabolic acidosis (RR: 3.47; 95% CI: 0.9-13.4, p = 0.03) were associated with mortality among sero-positive Scrub typhus patients. An appropriate antibiotic administration (n=46/88) was associated with clinical recovery/discharge (n=42/46; p=0.002).
Conclusion: Our results emphasize early diagnosis and administration of appropriate antibiotic for the management of scrub typhus in view of multiple etiologies in the initial diagnostic workup of patients presenting with AUFI. Thrombocytopenia, metabolic acidosis, need for mechanical ventilation and intensive care were associated with adverse clinical outcome among patients with Scrub typhus.
Development and Initial Evaluation of a national Infection Prevention and Antimicrobial Resistance programme for UK Girlguiding and Scouts
Authors: Hayes Catherine , Eley Charlotte , Hamilton Ryan , Ashiru-Oredope Diane , McNulty Cliodna 
Published: March 2020

Background
Between 2016-18, infection prevention (IP) and antimicrobial resistance (AMR) projects were developed independently by Girlguiding and Scout groups across four UK regions. The UK 5-year AMR Action Plan outlines the importance of public engagement. This abstract describes the development, pilot and initial evaluation of a national infection prevention (IP) and AMR resource pack for Girlguiding and Scouts.

Methods
Early 2019, PHE developed a national working-group, including local pilot individuals, and Girlguiding and Scout volunteers interested in IP and AMR to agree on the content of a national programme through a consensus approach. Summer 2019, the programme was piloted across the UK. Initial evaluation included course leader feedback and an age-appropriate survey.

Results
The consensus process concluded that the programme should include interactive e-Bug activities regarding microbes; hand, respiratory and food hygiene; antimicrobials and AMR. To consolidate learning, participants would create posters, make Antibiotic Guardian pledges, and share these with their families. A draft resource pack was developed to enable the programme to be delivered by leaders without a science/health background. Initial evaluation with over 150 children will be presented, to include enjoyment, acquisition of knowledge, and intentions to change health behaviours (i.e. improve hand and respiratory hygiene, and only use antibiotics when needed). Feedback from children and leaders will be used to update the resource pack prior to launch.

Conclusion
This national programme is engaging and delivers key IP and AMR messages. The programme will be launched for World Antibiotics Awareness Week 2019. Full evaluation planned for 2020.
The Half-Life of Maternal Transplacental Antibodies in infants from mothers vaccinated with diphtheria, tetanus and pertussis: An individual participant data meta-analysis
Authors: Oguti Blanche , Assad Ali , Andrews Nick , Barug Daantje , Dang Duc Anh , Halperin Scott , Hoang Ha , Holder Beth , Kampmann Beate , Kazi Momin , Langley Joanne , Leuridan Elke , Madavan Naomi , Maertens Kirsten , Miller Elizabeth , Munoz Flor , Omer Saad , Pollard Andrew , Rice Tom , Rots Nynke 
Published: March 2020

Aim: There are no reliable estimates of the half-lives of maternal antibodies to the antigens found in the primary series vaccines. We aimed to calculate the half-lives of passively acquired antibodies in infants born to mothers participating in studies of tetanus, diphtheria and acellular pertussis (Tdap) vaccination during pregnancy. We aimed to determine whether decay rates varied according to maternal age, birthweight, sex, socioeconomic status, country, or vaccine received.
Methods: De-identified individual participant data from infants born to women taking part in 9 studies of maternal immunization, in 8 countries (UK, Belgium, Thailand, Vietnam, Canada, Pakistan, USA and the Netherlands) were combined. Blood samples were taken at two timepoints before any Tdap containing vaccines were received by the infant: at birth and at 2-months of age. Decay rates for each antigen were log2-transformed and meta-analysis performed. Half-lives were calculated by taking the reciprocal of the absolute value of the mean decay rates.
Results: A total of 4,091 samples were included in the analysis and there was significant variation between studies. There was significant variation in the half-lives of the 6 antigens of interest (p<0.001), with estimates ranging from 28.1 days for diphtheria to 35.6 days for filamentous haemagglutinin. The decay of maternal antibodies did not significantly differ by country-level socioeconomic status, maternal age, sex, birthweight or maternal vaccination.
Conclusion: Maternal antibodies decay at different rates for the different antigens, however the magnitude of the differences are small. Differences in laboratory techniques may account for some of the variability between studies.
Cohort study of Faecal Microbiota Transplantation for patient’s colonised with MDROs - successful prevention of invasive disease despite low decolonisation rates
Authors: Ghani Rohma , Mullish Benjamin , Mcdonald Julie , Williams Horace , Gilchrist Mark , Brannigan Eimear , Satta Giovanni , Taube David , Duncan Neil , Pavlu Jiri , Ghazy Anan , Thursz Mark , Davies Frances , Marchesi Julian 
Published: March 2020

Faecal Microbiota Transplantation (FMT) is widely utilised for recurrent Clostridioides difficile infection. Use of FMT for the intestinal eradication of multidrug-resistant organisms (MDROs) has been described in the literature with decolonisation rates from 37.5% to 87.5%. We perform FMT via naso-gastric tube using donor stool prepared anaerobically, using prevention of invasive disease as an endpoint.
FMT was considered for either; 1) Patients who were colonised with >1 MDRO (carbapenem-resistant Enterobacteriaceae, vancomycin resistant Enterococci or extended-spectrum beta lactamase (ESBL) and at risk of invasive MDRO disease or 2) patients who had recurrent MDRO-mediated invasive disease.
Sixteen MDRO colonised/infected patients underwent FMT. Nine patients had a haematological disorder. Eight of these patients had had prolonged admissions (range 6-20 weeks) complicated by septic episodes (5/9 had a MDR bacteraemia) pre-FMT. Post FMT all patients had shorter admissions including five who received higher intensity immunosuppression. Only 1/9 developed MDRO-mediated invasive disease.
Seven FMT patients had recurrent ESBL urinary tract infections (UTIs). 4/7 were renal transplant patients. Following FMT the 3 non-transplant patients had no further UTIs up to six month period. Four transplant patients had reduced number of infections, admissions and use of antibiotics.
5/13 (39%) patients were not MDRO colonised on rectal screens post-FMT (follow up range 12 weeks – 24 months).
Although decolonisation rates were low, patient outcomes post-FMT were apparently improved. Mechanisms of FMT have not fully been established, improvement of colonisation resistance by restoration of microbiota composition or functionality in at risk groups could be more important than intestinal eradication.
Developing a novel paperless E-referral pathway for Infection clinic at a large teaching hospital, community and primary care in northwest England: A novel strategy to spearhead the trust antimicrobial stewardship programme
Authors: Guleri Achyut , Sharma Rashmi , Moon Jill 
Published: March 2020

BACKGROUND: UK’s 5y (2019-24) national action plan on antimicrobial resistance(AMR) projects 1 death/3 seconds(global) by 2050, if AMR rise not tackled. Accurate diagnosis of infectious condition and prompt optimal antibiotic/s are corner stones of any antimicrobial stewardship(AMS), sepsis programme and reducing mortality. We present our experience of developing a novel paperless E-referral pathway for all infection consultations from hospital and primary care to spearhead the hospital AMS and sepsis programmes.
MATERIAL/METHODS: Hospital webdesigners customized existing software application (www.nervecentresoft [http://www.nervecentresoft/]ware.com) & developed user friendly E-referral system (includes basic clinical details, referral urgency/coloured flag and grade/contact of submitter); it auto populates patient demographics and ward location from patient information system. Reports can be generated to query agreed parameters (&KPI). E-referrals accessible both on hospital computers or iPhone/iPAD.
RESULTS: AMS (Apr18-Mar19): >13K ward/phone AMS interventions; total referrals:13,312; 9438(70.1%) responded in 60-min;11923(90%)120min; E-referrals/d: 30-80; Referral Peaks: 3pm & 11am; Referrals from hospital [10,709(80.2%)], GP/prim care [2654 (19.8%)]; Clinical areas: [eg. male cardiac:491(3.6%); HDU:793(5.9%), etc]; E-referrals addressed/consultant [eg. Consultant A(4590(34.3%), etc]. Details & graphs to be presented.
CONCLUSION: E-referral pathway has spearheaded trust AMS & sepsis programmes. Urgent referrals are picked without delay; KPI of referral response within 60mins; significant reduction in calls for consultant Infection via switch board or medical secretaries; auditable workload figures for team to inform UKAS inspection, new consultant business cases or quality matrix; improved accountability and informs annual appraisal / job plan.
Do junior doctors have the knowledge to safely prescribe antibiotics in the context of known penicillin allergy?
Authors: Cheetham Laura 
Published: March 2020

The drug class most frequently associated with allergic reactions are the penicillins. Yet penicillins have a vital role in being important treatment options for many common and uncommon infections.
Junior doctors undertake the majority of hospital-based prescribing. Evidence suggests foundation doctors make the most prescribing-based errors.
A questionnaire was designed to ascertain whether junior doctors displayed an adequate level of knowledge regarding individual and antibiotic class identification, use of trade names, beta lactam cross sensitivity and symptoms of type I and IV hypersensitivity reactions.
Three quarters of respondents stated they had received allergy/non-allergic drug reaction teaching as an undergraduate but only just over a half had as a postgraduate. The Junior doctor responded group demonstrated adequate knowledge of correct identification of individual penicillins and non-penicillins and symptoms of a type I hypersensitivity reaction. There was inadequate knowledge of cephalosporin and carbapenem prescribing in the context of penicillin-associated anaphylaxis and of type IV hypersensitivity reaction symptoms. More core and higher specialty trainees correctly chose to prescribe in generic name form than foundation doctors.
This survey suggests that there may be key elements of knowledge required to safely prescribe antibiotics in the context of penicillin that, overall, as a group, junior doctors may lack adequate knowledge of, with this inadequacy being most pronounced in foundation doctors.
This suggests that junior doctors, and foundation trainees in particular, may need more education and training early in their careers to help support safe prescribing in the context of penicillin allergies.
Collation of resources within a regional antimicrobial pharmacy group
Authors: Bond Stuart , Lee-Milner Jade 
Published: March 2020

Background: Previous regional antimicrobial meetings identified duplication of antimicrobial stewardship work in Acute trusts. In 2018, collation of guidelines for hospital acquired pneumonia, community acquired pneumonia and urinary tract infections led to creation of exemplar guidelines. All documents were emailed, which was inefficient due to volume, with no central repository that could be accessed across sites. Given the regional shortage of microbiologists, easy access to job descriptions and business cases was considered essential to improvement of pharmacy staff resources regionally.
Aim: To create an open access regional hub for antimicrobial resources within Yorkshire and the Humber using the Specialist Pharmacy Service (SPS) website.
Methods: The Yorkshire and Humber Antimicrobial Pharmacy Group’s objective is to continuously improve antimicrobial stewardship and infection management through networking, sharing best practice, learning, peer support and joint working/initiatives. Starting in March 2019, resources were submitted to the SPS website.
Results: A total of nine job descriptions were uploaded, along with members of the group, educational links such as the #todipornottodip campaign, terms of reference, annual workplan, meeting agendas and a brief summary of the group’s objectives and regional geography.
Conclusion: The SPS website has facilitated a more efficient sharing of regional antimicrobial stewardship resources. Further work is warranted for sharing education resources, and business cases that don’t contain commercial information. As the site is open access, a decision was made to continue emailing meeting minutes.
Clinical validity of enterovirus PCR testing of skin swabs samples
Authors: Price Vivien , Osman Husam , Bosworth Andrew 
Published: March 2020

Background:
Enteroviruses cause a diverse spectrum of diseases. In 2018, enterovirus PCR was included in the standard panel of skin swabs investigations, which already included HSV and VZV. Here we show evidence that positive PCR results for enterovirus correlate with clinical data obtained through retrospective review.
Method:
A retrospective search of laboratory records for all skin swabs between July 18 and March 19 was performed. Enterovirus PCR positive results were correlated with clinical information from request forms and electronic patient records. A subset of positive samples was sent to the reference laboratory for genotyping by Sanger sequencing of the VP1 gene.

Results:
Of 1159 specimens tested, 108 were positive for enterovirus, 194 were positive for HSV 1, 70 for HSV 2, 167 for VZV. Median age for enterovirus positive patients was 1 year, compared with 29 years for HSV and VZV positive patients. 99 enterovirus positive results correlated clinically, 2 did not correlate, and 7 had no clinical information available. Those with clinical correlation had a higher PCR cycle threshold (CT), than those without (mean 27.4 vs. 38).
12 samples were sent to the reference laboratory. Of the 6 that could be successfully genotyped, all were Coxsackie A6.
Conclusions
Positive enterovirus PCR in skin swabs correlated well with clinical signs, demonstrating validity. The identification of Coxsackie A6 on all sub-typed isolates further supports the validity of a positive result, as does the younger median patient age for patients testing positive for enterovirus compared to other viral infections.
Genetic diversity of urogenital Chlamydia trachomatis before and after mass drug administration for trachoma
Authors: Baltas Ioannis , Pickering Harry , Beale Mathew , Holland Martin , Versteeg Aalbartus , Mabey David , Roberts Chrissy H. , Kako Henry , Solomon Anthony , Thompson Nick , Marks Michael , Butcher Robert 
Published: March 2020

Background
The WHO recommends treatment of trachoma with community-wide mass drug administration (MDA) with a single dose of azithromycin as part of the SAFE strategy (surgery, antibiotics, facial cleanliness and environmental improvement). In the Solomon Islands, this programme had demonstrable collateral benefit by reducing the prevalence of urogenital Chlamydia trachomatis(Ct) infections. We evaluated the impact of this treatment on population genetics of urogenital Ct.
Methods
Two vaginal swabs were collected from consecutive women attending antenatal clinics during cross-sectional surveys before and after MDA. For every swab positive for Ctinfection, DNA was extracted from the second swab, enriched and sequenced using paired-end sequencing. Whole-genome sequences were aligned against selected references. Diversity was assessed using genome-wide pairwise diversity and a high-resolution multi-locus sequence typing (hr-MLST-6) scheme. ARIBA software was used to test for evidence of antimicrobial resistance to macrolides.

Results
Whole-genome sequence data was obtained from 23/49 (47%) pre-MDA and 32/41 (78%) post-MDA Ct-positive samples. Most strains were serotype E and F, and tissue tropism genes were consistent with their urogenital nature. Genetic diversity of Ctwas lower by both pairwise and hr-MLST-6 diversity metrics in the post-MDA sample than the pre-MDA sample. There was no evidence of mutations known to confer resistance to macrolides in any of the samples collected.
Conclusions
Reduced diversity after MDA may represent selection pressure from mass antibiotic delivery. The absence of antimicrobial resistance is encouraging. The collateral impact (both positive and negative) of large-scale preventative chemotherapy programmes should be considered when deciding whether should be implemented.