Clinical academics' experiences of REF2021.

The UK Research Excellence Framework (REF) is an assessment of the quality of research carried out in UK Higher Education Institutions (HEIs), performed in 7-year cycles. The outcome impacts the rankings and funding of UK HEIs, which afford the exercise high priority. Much of what REF measures is known to be biased against academics with protected characteristics: for example, women and ethnic minority researchers are less likely to win grants or be published in prestigious journals. Despite changes to REF since 2014, the risk remains that the process might amplify well-recognised existing disparities. The BMA Women in Academic Medicine and Medical Academic Staff Committee carried out a survey of UK clinical academics' experiences of REF2021. The data indicated the persistence of activities previously characterised as 'extremely harmful' in Research England-commissioned work, affecting up to 10% of clinical academics. While acknowledging the limitations of the data, women appeared to be disproportionately affected.

Development and presentation of an objective risk stratification tool for healthcare workers when dealing with the COVID-19 pandemic in the UK: risk modelling based on hospitalisation and mortality statistics compared with epidemiological data.

OBJECTIVES: Healthcare workers have greater exposure to SARS-CoV-2 and an estimated 2.5-fold increased risk of contracting COVID-19 than the general population. We wished to explore the predictive role of basic demographics to establish a simple tool that could help risk stratify healthcare workers. SETTING: We undertook a review of the published literature (including multiple search strategies in MEDLINE with PubMed interface) and critically assessed early reports on preprint servers. We explored the relative risk of mortality from readily available demographics to identify the population at the highest risk. RESULTS: The published studies specifically assessing the risk of healthcare workers had limited demographics available; therefore, we explored the general population in the literature. Clinician demographics: Mortality increased with increasing age from 50 years onwards. Male sex at birth, and people of black and minority ethnicity groups had higher susceptibility to both hospitalisation and mortality. Comorbid disease. Vascular disease, renal disease, diabetes and chronic pulmonary disease further increased risk. Risk stratification tool: A risk stratification tool was compiled using a white female aged <50 years with no comorbidities as a reference. A point allocated to risk factors was associated with an approximate doubling in risk. This tool provides numerical support for healthcare workers when determining which team members should be allocated to patient facing clinical duties compared with remote supportive roles. CONCLUSIONS: We generated a tool that provides a framework for objective risk stratification of doctors and healthcare professionals during the COVID-19 pandemic, without requiring disclosure of information that an individual may not wish to share with their direct line manager during the risk assessment process. This tool has been made freely available through the British Medical Association website and is widely used in the National Health Service and other external organisations.

Best practice standards for the delivery of NHS infection services in the United Kingdom.

Infection expertise in the NHS has historically been provided predominantly by hospital-based medical microbiologists responsible for provision of diagnostic services and advice to front-line clinicians. While most hospitals had consultant-led microbiology departments, infectious iiseases departments were based in a small number of specialist centres. The demand for infection expertise is growing in the NHS, driven by advances in medical care, increasing awareness of the impact of antibiotic resistant and healthcare associated infections and threats from emerging infectious diseases. At the same time diagnostic services are being reorganised into pathology networks. The Combined Infection Training (CIT) is delivering a consultant workforce with expertise both in laboratory diagnostic practice and delivery of direct patient care. These changes create challenges for delivery of high quality infection expertise equitably across the NHS. They also offer an opportunity to shape infection services to meet clinical and laboratory demands. To date there has not been an attempt to bring together a single set of best practice guidelines for the requirements of an infection service. This document sets out seven standards. These are written to be practical and flexible according to the diverse ways in which infection expertise may be required across the NHS. It has been prepared by the Clinical Services Committee of the British Infection Association drawing on published evidence and guidance where they exist and on the group's extensive experience of delivering infection services in hospitals across the NHS. It was then refined with input from the RCP Joint Specialist committee (JSC) and the RCPath Specialist Advisory Committee (SAC) and through consultation with the RCPath membership. It has been endorsed by the Royal College of Pathologists and the Royal College of Physicians. It will be reviewed annually by the CSC and updated as additional evidence becomes available.

Health sequelae of human cryptosporidiosis in industrialised countries: a systematic review.

BACKGROUND: Cryptosporidium is a protozoan parasite which is a common cause of gastroenteritis worldwide. In developing countries, it is one of the most important causes of moderate to severe diarrhoea in young children; in industrialised countries it is a cause of outbreaks of gastroenteritis associated with drinking water, swimming pools and other environmental sources and a particular concern in certain immunocompromised patient groups, where it can cause severe disease. However, over recent years, longer-term sequelae of infection have been recognised and a number of studies have been published on this topic. The purpose of this systematic review was to examine the literature in order to better understand the medium- to long-term impact of cryptosporidiosis. METHODS: This was a systematic review of studies in PubMed, ProQuest and Web of Science databases, with no limitations on publication year or language. Studies from any country were included in qualitative synthesis, but only those in industrialised countries were included in quantitative analysis. RESULTS: Fifteen studies were identified for qualitative analysis which included 3670 Cryptosporidium cases; eight studies conducted in Europe between 2004-2019 were suitable for quantitative analysis, including five case-control studies. The most common reported long-term sequelae were diarrhoea (25%), abdominal pain (25%), nausea (24%), fatigue (24%) and headache (21%). Overall, long-term sequelae were more prevalent following infection with Cryptosporidium hominis, with only weight loss and blood in stool being more prevalent following infection with Cryptosporidium parvum. Analysis of the case-control studies found that individuals were 6 times more likely to report chronic diarrhoea and weight loss up to 28 months after a Cryptosporidium infection than were controls. Long-term abdominal pain, loss of appetite, fatigue, vomiting, joint pain, headache and eye pain were also between 2-3 times more likely following a Cryptosporidium infection. CONCLUSIONS: This is the first systematic review of the long-term sequelae of cryptosporidiosis. A better understanding of long-term outcomes of cryptosporidiosis is valuable to inform the expectations of clinicians and their patients, and public health policy-makers regarding the control and prevention of this infection. Systematic review registration PROSPERO Registration number CRD42019141311.

Consensus-based antimicrobial resistance and stewardship competencies for UK undergraduate medical students.

BACKGROUND: In the UK there is limited coverage of antimicrobial stewardship across postgraduate curricula and evidence that final year medical students have insufficient and inconsistent antimicrobial stewardship teaching. A national undergraduate curriculum for antimicrobial resistance and stewardship is required to standardize an adequate level of understanding for all future doctors. OBJECTIVES: To provide a UK national consensus on competencies for antimicrobial resistance and stewardship for undergraduate medical education. METHODS: Using the modified Delphi method over two online survey rounds, an expert panel comprising leads for infection teaching from 25 UK medical schools reviewed competency descriptors for antimicrobial resistance and stewardship education. RESULTS: There was a response rate of 100% with all 28 experts who agreed to take part completing both survey rounds. Following the first-round survey, of the initial 55 descriptors, 43 reached consensus (78%). The second-round survey included the 12 descriptors from the first round in which agreement had not been reached, four amended descriptors and 12 new descriptors following qualitative feedback from the panel members. Following the second-round survey, a total of 58 consensus-based competency descriptors within six overarching domains were identified. CONCLUSIONS: The consensus-based competency descriptors defined here can be used to inform standards, design curricula, develop assessment tools and direct UK undergraduate medical education.

Evaluation of a Novel Antibiotic Teaching Resource.

Antimicrobial resistance presents a major challenge for healthcare and education of future prescribers is critical. Integrated medical courses allow more limited time for teaching the science of clinical microbiology, which underpins antimicrobial prescribing, making this a difficult topic for students. An innovative educational resource based on a game was created and evaluated in medical student teaching. Most students reported that the game assisted learning. However, testing showed that recall did not improve after using the resource. Student perceptions of resource efficacy may not correlate with test scores. The longer-term positive effect of enhanced student engagement is more difficult to measure.

Resolving a clinical tuberculosis outbreak using palaeogenomic genome reconstruction methodologies.

This study describes the analysis of DNA from heat-killed (boilate) isolates of Mycobacterium tuberculosis from two UK outbreaks where DNA was of sub-optimal quality for the standard methodologies routinely used in microbial genomics. An Illumina library construction method developed for sequencing ancient DNA was successfully used to obtain whole genome sequences, allowing analysis of the outbreak by gene-by-gene MLST, SNP mapping and phylogenetic analysis. All cases were spoligotyped to the same Haarlem H1 sub-lineage. This is the first described application of ancient DNA library construction protocols to allow whole genome sequencing of a clinical tuberculosis outbreak. Using this method it is possible to obtain epidemiologically meaningful data even when DNA is of insufficient quality for standard methods.

Cryptosporidium.

The protozoan Cryptosporidium is notorious for its resistance to chlorine disinfection, a mainstay of water treatment. Human infections, mainly of the small intestine, arise from consumption of faecally contaminated food or water, environmental exposure, and person-to-person or animal-to-person spread. Acute gastrointestinal symptoms can be prolonged but are usually self-limiting. Problems arise with immune-deficient, including malnourished, people including chronic diarrhoea, hepato-biliary tree and extra-gastrointestinal site infection, and few options for treatment or prevention exist. Although genomics has enabled refined classification, identification of chemotherapeutic targets and vaccine candidates, and putative factors for host adaption and pathogenesis, their confirmation has been hampered by a lack of biological tools.

A case of hepato-biliary infection secondary to cryptosporidium in a patient on tacrolimus.

INTRODUCTION: Cryptosporidium infection is known to cause hepato-biliary involvement, mainly in association with T-cell immune deficiency. Hepato-biliary involvement in association with milder immunosuppression is less well described. We describe the first case, to our knowledge, of Cryptosporidium hominis hepato-biliary infection associated with tacrolimus in a patient with nephrotic syndrome. CASE PRESENTATION: A 14 year old girl who had been on tacrolimus for nephrotic syndrome presented with diarrhea due to C. hominis. Nineteen days after her initial presentation she attended hospital with abdominal pain and deranged liver function tests. An ultrasound scan showed a thickened gall bladder. Her symptoms settled and her liver function tests returned to normal after treatment with nitazoxanide. CONCLUSION: Cryptosporidium should be considered in the differential diagnosis of both diarrhea and hepato-biliary symptoms and abnormal liver function tests, even in the presence of relatively mild immunosuppression. Nitazoxanide was an effective treatment in this case.

Protocol for faecal microbiota transplantation in ulcerative colitis (FMTUC): a randomised feasibility study.

BACKGROUND: The interaction of the gut microbiota with the human host is implicated in the pathogenesis of inflammatory and immunological diseases including ulcerative colitis (UC). Faecal microbiota transplantation (FMT) as a method of restoring gut microbial diversity is of increasing interest as a therapeutic approach in the management of UC. The current literature lacks consensus about the dose of FMT, route of administration and duration of response. METHODS AND ANALYSIS: This single-blinded randomised trial will explore the feasibility of FMT in 30 treatment-naïve patients with histologically confirmed distal UC limited to the recto-sigmoid region (up to 40 cm from the anal verge). This study aims to estimate the magnitude of treatment response to FMT under controlled conditions. The intervention (FMT) will be administered by rectal retention enema. It will test the feasibility of randomising patients to: (i) single FMT dose, (ii) five daily FMT doses or (iii) control (no FMT dose). All groups will receive standard antibiotic gut decontamination and bowel preparation before FMT. Recruitment will take place over a 24-month period with a 12-week patient follow-up. Trial objectives include evaluation of the magnitude of treatment response to FMT, investigation of the clinical value of metabolic phenotyping for predicting the clinical response to FMT and testing the recruitment rate of donors and patients for a study in FMT. This feasibility trial will enable an estimate of number of patients needed, help determine optimal study conditions and inform the choice of endpoints for a future definitive phase III study. ETHICS AND DISSEMINATION: The trial is approved by the regional ethics committee and is sponsored by Abertawe Bro Morgannwg University's Health Board. Written informed consent from all patients will be obtained. Serious adverse events will be reported to the sponsor. Trial results will be disseminated via peer review publication and shared with trial participants. TRIAL REGISTRATION NUMBER: ISRCTN 58082603; Pre-results.

Long-term health effects after resolution of acute Cryptosporidium parvum infection: a 1-year follow-up of outbreak-associated cases.

We describe a longitudinal study carried out in an adult outbreak-associated cohort to investigate health effects, including post-infectious irritable bowel syndrome, occurring after resolution of acute Cryptosporidium parvum infection. New symptoms self-reported up to 12 months included: weight loss (31 %), abdominal pain (38 %), diarrhoea (33 %), eye pain (9 %), joint pain (33 %), fatigue (22 %) and symptoms consistent with irritable bowel syndrome (IBS) (28 %). Two people were medically diagnosed with IBS. This study describes for the first time sequelae reported by patients up to 12 months after infection with C. parvum, which appear to be similar to those described with C. hominis.

Prevalence of Cryptosporidium Carriage and Disease in Children With Primary Immune Deficiencies Undergoing Hematopoietic Stem Cell Transplant in Northern Europe.

A prospective cohort study of children with primary immunodeficiencies undergoing hematopoietic stem cell transplant in the United Kingdom investigated the extent and significance of Cryptosporidium carriage in this high risk group. Three of 42 children recruited were infected with Cryptosporidium, a lower proportion than previously described. One had serious disease. The underlying immunodeficiency likely had a bearing on the clinical presentation and possible outcome of infection.

Dormant cells of Staphylococcus aureus are resuscitated by spent culture supernatant.

We describe the first in vitro model of dormancy in Staphylococcus aureus, showing that cells are generated which can be resuscitated by addition of spent medium supernatant taken from cultures of the same organism. Over 30 days, culturable counts in dormant cultures of S. aureus SH1000 fell from 10(6)-10(7) cfu/ml to <10 cfu/ml as measured by the Most Probable Number method in liquid culture, while total counts as determined by microscopy, and supported by data from RT-qPCR, remained around 10(6)-10(7) cells/ml. Supplementing cultures with 25-50% spent medium resulted in a >600-fold increase in bacterial growth. Resuscitation was a specific effect, greatly reduced by boiling or addition of trypsin to the spent supernatant. Supernatant also effected a reduction in lag phase of dormant cultures. SEM demonstrated the presence of small coccoid cells in dormant cultures. The results are similar to those seen with resuscitation promoting factors (Rpfs) in actinobacteria. This is the first time resuscitation has been demonstrated in Staphylococcus aureus, which is an important human pathogen. A better understanding of control and reactivation of dormant cells could lead to major improvements in managing staphylococcal infections; resuscitation could be an important step in restoring susceptibility to antibiotic treatment.

An extracellular Staphylococcus epidermidis polysaccharide: relation to Polysaccharide Intercellular Adhesin and its implication in phagocytosis.

BACKGROUND: The skin commensal and opportunistic pathogen Staphylococcus epidermidis is a leading cause of hospital-acquired and biomaterial-associated infections. The polysaccharide intercellular adhesin (PIA), a homoglycan composed of ß-1,6-linked N-acetylglucosamine residues, synthesized by enzymes encoded in icaADBC is a major functional factor in biofilm accumulation, promoting virulence in experimental biomaterial-associated S. epidermidis infection. Extracellular mucous layer extracts of S. epidermidis contain another major polysaccharide, referred to as 20-kDa polysaccharide (20-kDaPS), composed mainly out of glucose, N-acetylglucosamine, and being partially sulfated. 20-kDaPS antiserum prevents adhesion of S. epidermidis on endothelial cells and development of experimental keratitis in rabbits. Here we provide experimental evidence that 20-kDaPS and PIA represent distinct molecules and that 20-kDaPS is implicated in endocytosis of S. epidermidis bacterial cells by human monocyte-derived macrophages. RESULTS: Analysis of 75 clinical coagulase-negative staphylococci from blood-cultures and central venous catheter tips indicated that 20-kDaPS is expressed exclusively in S. epidermidis but not in other coagulase-negative staphylococcal species. Tn917-insertion in various locations in icaADBC in mutants M10, M22, M23, and M24 of S. epidermidis 1457 are abolished for PIA synthesis, while 20-kDaPS expression appears unaltered as compared to wild-type strains using specific anti-PIA and anti-20-kDaPS antisera. While periodate oxidation and dispersin B treatments abolish immuno-reactivity and intercellular adhesive properties of PIA, no abrogative activity is exerted towards 20-kDaPS immunochemical reactivity following these treatments. PIA polysaccharide I-containing fractions eluting from Q-Sepharose were devoid of detectable 20-kDaPS using specific ELISA. Preincubation of non-20-kDaPS-producing clinical strain with increasing amounts of 20-kDaPS inhibits endocytosis by human macrophages, whereas, preincubation of 20-kDaPS-producing strain ATCC35983 with 20-kDaPS antiserum enhances bacterial endocytosis by human macrophages. CONCLUSIONS: In conclusion, icaADBC is not involved in 20-kDaPS synthesis, while the chemical and chromatographic properties of PIA and 20-kDaPS are distinct. 20-kDaPS exhibits anti-phagocytic properties, whereas, 20-kDaPS antiserum may have a beneficial effect on combating infection by 20-kDaPS-producing S. epidermidis.

Comparison of diagnostic sensitivity and specificity of seven Cryptosporidium assays used in the UK.

To compare the diagnostic sensitivity and specificity of seven Cryptosporidium diagnostic assays used in the UK, results from 259 stool samples from patients with acute gastrointestinal symptoms were compared against a nominated gold standard (real-time PCR and oocyst detection). Of the 152 'true positives', 80 were Cryptosporidium hominis, 68 Cryptosporidium parvum, two Cryptosporidium felis, one Cryptosporidium ubiquitum and one Cryptosporidium meleagridis. The Cryptosporidium spp. diagnostic sensitivities of three Cryptosporidium and Giardia combination enzyme immunoassays (EIA) coupled with confirmation of positive reactions were 91.4-93.4 %, whilst the sensitivity of auramine phenol microscopy was 92.1 % and that of immunofluorescence microscopy (IFM) was 97.4 %, all with overlapping 95 % confidence intervals. However, IFM was significantly more sensitive (P = 0.01, paired test of proportions). The sensitivity of modified Ziehl-Neelsen microscopy was 75.4 %, significantly lower than those for the other tests investigated, including an immunochromatographic lateral flow assay (ICLF) (84.9 %) (P = 0.0016). Specificities were 100 % when the ICLF and EIA test algorithms included confirmation of positive reactions; however, four positive EIA reactions were not confirmed for either parasite. There was no significant difference in the detection of C. parvum and C. hominis by each assay, but the detection of other Cryptosporidium spp. requires further investigation, as the numbers of samples were small. EIAs may be considered for diagnostic testing, subject to local validation, and diagnostic algorithms must include confirmation of positive reactions.

Toxic marine microalgae and shellfish poisoning in the British isles: history, review of epidemiology, and future implications.

The relationship between toxic marine microalgae species and climate change has become a high profile and well discussed topic in recent years, with research focusing on the possible future impacts of changing hydrological conditions on Harmful Algal Bloom (HAB) species around the world. However, there is very little literature concerning the epidemiology of these species on marine organisms and human health. Here, we examine the current state of toxic microalgae species around the UK, in two ways: first we describe the key toxic syndromes and gather together the disparate reported data on their epidemiology from UK records and monitoring procedures. Secondly, using NHS hospital admissions and GP records from Wales, we attempt to quantify the incidence of shellfish poisoning from an independent source. We show that within the UK, outbreaks of shellfish poisoning are rare but occurring on a yearly basis in different regions and affecting a diverse range of molluscan shellfish and other marine organisms. We also show that the abundance of a species does not necessarily correlate to the rate of toxic events. Based on routine hospital records, the numbers of shellfish poisonings in the UK are very low, but the identification of the toxin involved, or even a confirmation of a poisoning event is extremely difficult to diagnose. An effective shellfish monitoring system, which shuts down aquaculture sites when toxins exceed regularity limits, has clearly prevented serious impact to human health, and remains the only viable means of monitoring the potential threat to human health. However, the closure of these sites has an adverse economic impact, and the monitoring system does not include all toxic plankton. The possible geographic spreading of toxic microalgae species is therefore a concern, as warmer waters in the Atlantic could suit several species with southern biogeographical affinities enabling them to occupy the coastal regions of the UK, but which are not yet monitored or considered to be detrimental.

Rapid identification of staphylococci from prosthetic joint infections using MALDI-TOF mass-spectrometry.

Hospital-acquired infections associated with implanted medical devices are most commonly caused by staphylococci. Current methods of species identification are slow, costly, and sometimes unreliable. We evaluated the ability of a Bruker Daltonics Microflex MALDI-TOF/MS in conjunction with MALDI Biotyper software to identify 158 characterized staphylococcal isolates from prosthetic joint infections, including 36 Staphylococcus aureus, 100 Staphylococcus epidermidis, 10 Staphylococcus capitis, 8 Staphylococcus lugdunensis, 2 Staphylococcus warneri, and 2 Staphylococcus haemolyticus isolates using the extraction method recommended by Bruker Daltonics. The suggested species identification by the MALDI Biotyper software was correct for all isolates, indicating reliable differentiation between S. aureus and coagulase-negative staphylococci. Applying the recommended criteria of the MALDI Biotyper software all 158 isolates gave scores ≥2.0, implying secure genus and probable species identification for all isolates. 34/36 S. aureus, 36/100 S. epidermidis, 5/10 S. capitis, 6/8 S. lugdunensis, 2/2 S. haemolyticus, 0/2 S. warneri displayed scores ≥2.3 implying highly probable species identification. For S. epidermidis 25/100 additional isolates had a score close to 2.3. It appears that additional clinically relevant staphylococcal isolates in the data base might aid in identification at scores implying highly probable species identification. The ability of the MALDI Biotyper software to recognize clonally-related strains within a species group (i.e. sub-typing) was investigated, and showed great potential. In conclusion, the MALDI-TOF/MS MALDI Biotyper system provides a promising rapid and reliable method of identifying clinical isolates from prosthetic joint infections to the species level, and has potential for sub-typing.

Rapid differentiation of Staphylococcus aureus, Staphylococcus epidermidis and other coagulase-negative staphylococci and meticillin susceptibility testing directly from growth-positive blood cultures by multiplex real-time PCR.

This study evaluated a multiplex real-time PCR method specific for the mecA, femA-SA and femA-SE genes for rapid identification of Staphylococcus aureus, Staphylococcus epidermidis and non-S. epidermidis coagulase-negative staphylococci (CoNS), and meticillin susceptibility testing directly in positive blood cultures that grew Gram-positive cocci in clusters. A total of 100 positive blood cultures produced: 39 S. aureus [12 meticillin-resistant S. aureus (MRSA), 31% of all the S. aureus]; 30 S. epidermidis (56.6% of the CoNS), 8 Staphylococcus capitis (15.1%), 3 Staphylococcus saprophyticus (5.7%), 4 Staphylococcus hominis (7.5%), 3 Staphylococcus haemolyticus (5.7%), 2 Staphylococcus warneri (3.8%), 1 Staphylococcus cohnii (1.9%) and 2 unidentified Staphylococcus spp. (3.8%); and 1 Micrococcus luteus in pure culture. Two blood cultures had no growth on subculture and five blood cultures grew mixed CoNS. For the 95 blood cultures with pure growth or no growth on subculture, there was very good agreement between real-time PCR and the BD Phoenix identification system for staphylococcal species categorization in S. aureus, S. epidermidis and non-S. epidermidis CoNS and meticillin-resistance determination (Cohen's unweighted kappa coefficient κ=0.882). All MRSA and meticillin-susceptible S. aureus were correctly identified by mecA amplification. PCR amplification of mecA was more sensitive for direct detection of meticillin-resistant CoNS in positive blood cultures than testing with the BD Phoenix system. There were no major errors when identifying staphylococcal isolates and their meticillin susceptibility within 2.5 h. Further studies are needed to evaluate the clinical benefit of using such a rapid test on the consumption of glycopeptide antibiotics and the alteration of empiric therapy in the situation of positive blood cultures growing staphylococci, and the respective clinical outcomes.

Minireview: clinical cryptosporidiosis.

Cryptosporidium has emerged as an important cause of diarrhoeal illness worldwide, especially amongst young children and patients with immune deficiencies. Usually presenting as a gastro-enteritis-like syndrome, disease ranges in seriousness from mild to severe and signs and symptoms depend on the site of infection, nutritional and immune status of the host, and parasite-related factors. Sources and routes of transmission are multiple, involving both zoonotic and anthroponotic spread, and facilitated by the resistance of the parasite to many commonly used disinfectants. Prevention and control measures are important for the protection of vulnerable groups since treatment options are limited. This review covers the life cycle, pathogenesis, clinical presentations, diagnosis, prevention and management of cryptosporidiosis in humans.