Cambridge University Hospitals NHS Foundation Research Articles

Evaluating the impact of genomic epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) on hospital infection prevention and control decisions.

Genomic epidemiology enhances the ability to detect and refute methicillin-resistant Staphylococcus aureus (MRSA) outbreaks in healthcare settings, but its routine introduction requires further evidence of benefits for patients and resource utilization. We performed a 12 month prospective study at Cambridge University Hospitals NHS Foundation Trust in the UK to capture its impact on hospital infection prevention and control (IPC) decisions. MRSA-positive samples were identified via the hospital microbiology laboratory between November 2018 and November 2019. We included samples from in-patients, clinic out-patients, people reviewed in the Emergency Department and healthcare workers screened by Occupational Health. We sequenced the first MRSA isolate from 823 consecutive individuals, defined their pairwise genetic relatedness, and sought epidemiological links in the hospital and community. Genomic analysis of 823 MRSA isolates identified 72 genetic clusters of two or more isolates containing 339/823 (41 %) of the cases. Epidemiological links were identified between two or more cases for 190 (23 %) individuals in 34/72 clusters. Weekly genomic epidemiology updates were shared with the IPC team, culminating in 49 face-to-face meetings and 21 written communications. Seventeen clusters were identified that were consistent with hospital MRSA transmission, discussion of which led to additional IPC actions in 14 of these. Two outbreaks were also identified where transmission had occurred in the community prior to hospital presentation; these were escalated to relevant IPC teams. We identified 38 instances where two or more in-patients shared a ward location on overlapping dates but carried unrelated MRSA isolates (pseudo-outbreaks); research data led to de-escalation of investigations in six of these. Our findings provide further support for the routine use of genomic epidemiology to enhance and target IPC resources.

The clinical value of the hepatic venous pressure gradient in patients undergoing hepatic resection for hepatocellular carcinoma with or without liver cirrhosis.

The role of hepatic venous pressure gradient (HVPG) measurement in risk stratification before liver resection is an ongoing area of debate. This study examines the impact of preoperative HVPG levels on overall survival (OS)/time to recurrence (TTR) and postoperative complications after hepatic resection of hepatocellular carcinoma (HCC). Thirty-eight HCC patients undergoing HVPG measurement before liver resection at Cambridge University Hospitals NHS Foundation Trust between January 2014 and April 2022 were retrospectively analysed. Statistical analysis comprised univariable/multivariable Cox/logistic regression to identify risk factors of reduced OS/TTR or 90-day post-resection complications and Kaplan-Meier estimator, log-rank, chi-squared, Fisher's exact, and Mann-Whitney U test, or Student's t-test for survival/subgroup analysis. The median HPVG was 6 (range: 0-14) mmHg. The HVPG was an independent risk factor for poorer TTR in the overall cohort (cut-off: ≥7.5 mmHg (17.18/43.81 months; P = 0.009)). In the subgroup analysis of cirrhotic patients (N = 29 (76%)), HVPG was additionally an independent risk factor for lower OS (cut-off: ≥8.5 mmHg [44.39/76.84 months; P = 0.012]). The HVPG had no impact on OS/TTR in non-cirrhotic patients (N = 9 (24%)), nor was it associated with postoperative complications in any cohort. In conclusion, preoperative HVPG levels are useful predictors for TTR and OS in cirrhotic HCC patients undergoing hepatic resection.

Impact of penicillin allergy labels on surgical site infections in a large UK cohort of gastrointestinal surgery patients.

Studies in the USA, Canada and France have reported higher surgical site infection (SSI) risk in patients with a penicillin allergy label (PAL). Here, we investigate the association between PALs and SSI in the UK, a country with distinct epidemiology of infecting pathogens and range of antimicrobial regimens in routine use. Electronic health records and national SSI surveillance data were collated for a retrospective cohort of gastrointestinal surgery patients at Cambridge University Hospitals NHS Foundation Trust from 1 January 2015 to 31 December 2021. Univariable and multivariable logistic regression were used to examine the effects of PALs and the use of non-β-lactam-based prophylaxis on likelihood of SSI, 30 day post-operative mortality, 7 day post-operative acute kidney injury and 60 day post-operative infection/colonization with antimicrobial-resistant bacteria or Clostridioides difficile. Our data comprised 3644 patients and 4085 operations; 461 were undertaken in the presence of PALs (11.3%). SSI was detected after 435/4085 (10.7%) operations. Neither the presence of PALs, nor the use of non-β-lactam-based prophylaxis were found to be associated with SSI: adjusted OR (aOR) 0.90 (95% CI 0.65-1.25) and 1.20 (0.88-1.62), respectively. PALs were independently associated with increased odds of newly identified MRSA infection/colonization in the 60 days after surgery: aOR 2.71 (95% CI 1.13-6.49). Negative association was observed for newly identified infection/colonization with third-generation cephalosporin-resistant Gram-negative bacteria: aOR 0.38 (95% CI 0.16-0.89). No evidence was found for an association between PALs and the likelihood of SSI in this large UK cohort, suggesting significant international variation in the impact of PALs on surgical patients.

A single centre service evaluation of degenerative cervical and thoracic myelopathy

BackgroundDegenerative cervical myelopathy (DCM) and degenerative thoracic myelopathy (DTM) present with leg, bladder and bowel symptoms. If imaging confirms spinal cord compression both conditions are usually managed surgically. Surgical timing is important in patient management as it affects post-operative recovery and long-term outcomes. This service evaluation aims to explore whether that patients with DTM are more likely to be treated urgently than those with DCM and to examine whether any differences in management are justified. MethodsA retrospective service evaluation was registered and approved by the Cambridge University Hospitals NHS Foundation Trust (CUH) Clinical Audit Department (Clinical Project ID4455 PRN10455). All patients who had undergone surgery for DTM at CUH from January 2015 until April 2022 were included. Comparison was made to a cohort of DCM patients who underwent surgery at CUH from June 2016 to January 2019. Data analysis was conducted in R. ResultsA total of 130 DCM patients and 78 DTM patients were included. Our DCM and DTM patient cohorts had comparable demographics, but DTM patients had fewer spinal levels affected. Despite equivalent disease severity, DTM patients had a shorter time to diagnosis, shorter wait for surgery and were more likely to be operated on as an emergency case. ConclusionsDespite comparable demographics and pathophysiology, DTM was diagnosed and managed more quickly than DCM. Better defined diagnostic pathways for degenerative spinal myelopathy may hold opportunities to optimise diagnosis and management, ensuring consistent high quality, efficient and equitable care.

Characterizing Antibiotic Allergy Labels in a Large UK Hospital Population to Inform Antimicrobial Stewardship and Delabeling Assessment Strategy.

Antibiotic allergy labels are important barriers to treatment and antimicrobial stewardship, but their prevalence in UK hospitals is poorly described. To ascertain the prevalence and characteristics of antibiotic allergy labels in a large UK hospital setting and estimate the proportion of penicillin allergy labels for which point-of-care (POC) delabeling assessment would be appropriate. Electronic health records data were analyzed from all patients treated at Cambridge University Hospitals NHS Foundation Trust in 2019. Validated POC delabeling risk stratification criteria were retrospectively applied to penicillin allergy labels. Recorded reactions to antibiotics were present in 11.8% of all patients (32,148 of 273,216), 16.3% of inpatients (13,874 of 85,230), and 9.7% of outpatients (18,274 of 187,986). Penicillins were the commonest reaction precipitant described (9.0% of patients; 24,646 of 273,216), followed by sulfonamides/trimethoprim (1.4%; 3869 of 273,216) and macrolides/lincosamides (1.3%; 3644 of 273,216). A total of 3.9% of inpatients had recorded reactions to >1 antibiotic class (3348 of 85,230). Cutaneous manifestations were the most commonly described reaction features (40.7% of labels; 15,821 of 38,902). Of 15,949 labels describing probable or possible penicillin "allergy" with sufficient detail to allow for the retrospective assessment of POC delabeling suitability, 1702 were deemed suitable for removal or downgrading of the label to "intolerance" without further investigation (10.7%), 11,887 were appropriate for POC assessment using an oral penicillin challenge (OPC) or OPC with prior bedside skin testing (74.5%), and 2360 were identified as unsuitable for any form of POC assessment (14.8%). Antibiotic allergy labels are highly prevalent in a UK hospital setting. A large proportion of penicillin allergy labels may be suitable for POC delabeling assessment.

Paediatric Major Trauma: A Retrospective Observational Comparison of Mortality in Prehospital Bypass and Secondary Transfer in the East of England.

Background More than half of seriously injured children are not initially treated at a major trauma centre (MTC). Children may be transported by private vehicle to a trauma unit (TU). Children may also be transported by emergency medical services (EMS) to the nearest TU with approximately one in five of these undergoing secondary transfer to an MTC. Most trauma networks permit TU bypass to an MTC. However, the evidence on outcomes between transfer and bypass is limited. This study aimed to evaluate the use of the trauma network by comparing outcomes between paediatric major trauma patients by the method of presentation. Methods In this retrospective observational study, a consecutive sample of paediatric (<16 years old) major trauma patients transported to the regional MTC (Cambridge University Hospitals NHS Foundation Trust (CUH)) between 1st January 2015 and 31st December 2020 was included. Patients were excluded if they arrived at the MTC >24 hours post-injury or were transported to the MTC as the nearest hospital. Patients were divided into four groups: self-presented to MTC, MTC as nearest hospital, bypass and secondary transfer. Results A total of 315 patients (28 'self-presented', 55 'nearest', 58 'bypass' and 174 'secondary transfers') were included. The median age was 9.4 [3.7-13.6] years, and n=209 (66.3%) were male. The median Injury Severity Score (ISS) was 16.0 [9.0-25.0] and n=190 (60.3%) had an ISS >15. There was no difference in 30-day mortality between the 'bypass' and 'secondary transfer' groups.There was a significantly longer hospital and intensive care unit length of stay (LOS) in the bypass group compared to other groups, both p<0.001. The median time to definitive care was five hours greater in the secondary transfer group compared to 'bypass'(bypass 117.6 minutes [100.8-136.6], secondary transfer 418.8 minutes [315.6-529.8]). Conclusion There was no significant difference in 30-day mortality of paediatric major trauma patients who underwent secondary transfer compared to those transported directly from the scene to the MTC, despite significant time delays in reaching definitive care.

The Official Journal of ATTD Advanced Technologies &amp; Treatments for Diabetes Conference 22‐25 February 2023 I Berlin &amp; Online

The Official Journal of ATTD Advanced Technologies &amp; Treatments for Diabetes Conference 22‐25 February 2023 I Berlin &amp; Online

Surgery for Ulcerative Colitis in the White British and South Asian Populations in Selected Trusts in England 2001-2020: An Absence of Disparate Care and a Need for Specialist Centres.

Over the last decade, there has been extensive evidence that patients with inflammatory bowel disease from minority communities in the UK receive less than optimal care. In none of the studies has the role of surgery in the management of acute and severe ulcerative colitis been considered in any detail. A freedom of information (FOI) request was sent to 14 NHS Trusts in England, which serve significant South Asian populations. Details of the type of surgery patients from the South Asian and White British communities received between 2021 and 2020 were requested. Detailed responses were obtained from eight Trusts. Four hundred and ten White British patients underwent surgery for ulcerative colitis over this period at these eight Trusts, together with 67 South Asian patients. There was no statistically significant difference in the distribution across the types of surgery undergone by the two communities overall (χ2 = 1.3, ns) and the proportions who underwent an ileo-anal anastomosis with pouch (z = −1.2, ns). However, within individual trusts, at the University Hospital Southampton NHS Foundation Trust, a significantly greater proportion of South Asian patients had an ileo-anal anastomosis with pouch compared to White British patients. At Cambridge University Hospitals NHS Foundation Trust, all 72 patients who underwent surgery for ulcerative colitis were White British. This study has shown that, in general, for patients with a severe flare of ulcerative colitis where medical treatment has failed and surgery is warranted, the nature of the procedures offered is the same in the White British and South Asian communities. However, of concern is the number of units with low volume procedures. For most Trusts reported in this study, the overall number of Ileo-anal pouch anastomosis or anastomosis of ileum to anus procedures performed over a number of years was substantially below that required for a single surgeon to achieve competence. These findings reinforce the argument that inflammatory bowel disease surgery should be performed in a limited number of high-volume centres rather than across a wide range of hospitals so as to ensure procedures are carried out by surgeons with sufficient and on-going experience.

Glomerular filtration rate estimation for carboplatin dosing in patients with gynaecological cancers

BackgroundCarboplatin remains integral for treatment of gynaecological malignancies and dosing is based on glomerular filtration rate (GFR). Measurement via radiotracer decay [nuclear medicine GFR (nmGFR)] is ideal. However, this may be unavailable. Therefore GFR is often estimated using formulae that have not been validated in patients with cancer and/or specifically for gynaecological malignancies, leading to debate over optimal estimation. Suboptimal GFR estimation may affect efficacy or toxicity.MethodsWe surveyed several UK National Health Service Trusts to assess carboplatin dosing practise. We then explored single-centre accuracy, bias and precision of various formulae for GFR estimation, relative to nmGFR, before validating our findings in an external cohort.ResultsAcross 18 Trusts, there was considerable heterogeneity in GFR estimation, including the formulae used [Cockcroft–Gault (CG) versus Wright], weight adjustment and area under the curve (AUC; 5 versus 6). We analysed 274 and 192 patients in two centres. Overall, CamGFR v2 (a novel formula for GFR estimation developed at Cambridge University Hospitals NHS Foundation Trust) excelled, showing the highest accuracy and precision. This translated into accuracy of hypothetical carboplatin dosing; nmGFR-derived carboplatin dose fell within 20% of the Cam GFR v2-derived dose in 86.5% and 87% of patients across the cohorts. Among the CG formula and its derivatives, using adjusted body weight in those with body mass index ≥25 kg/m2 [CG-adjusted body weight (CG-AdBW)] was optimal. The Wright and unadjusted CG estimators performed most poorly.ConclusionsWhen compared with nmGFR assessment, accuracy, bias and precision varied widely between GFR estimators, with the newly developed Cam GFR v2 and CG-AdBW performing best. In general, weight (or body surface area)-adjusted formulae excelled, while the unadjusted CG and Wright formulae or the use of AUC6 (versus nmGFR AUC5) produced risk of significant overdose. Thus, individual centres should validate their GFR estimation methods. In the absence of validation, CG-AdBW or CamGFR v2 is likely to perform well while unadjusted CG/Wright formulae or AUC6 dosing should be avoided.

A2B-COVID: A Tool for Rapidly Evaluating Potential SARS-CoV-2 Transmission Events.

Identifying linked cases of infection is a critical component of the public health response to viral infectious diseases. In a clinical context, there is a need to make rapid assessments of whether cases of infection have arrived independently onto a ward, or are potentially linked via direct transmission. Viral genome sequence data are of great value in making these assessments, but are often not the only form of data available. Here, we describe A2B-COVID, a method for the rapid identification of potentially linked cases of COVID-19 infection designed for clinical settings. Our method combines knowledge about infection dynamics, data describing the movements of individuals, and evolutionary analysis of genome sequences to assess whether data collected from cases of infection are consistent or inconsistent with linkage via direct transmission. A retrospective analysis of data from two wards at Cambridge University Hospitals NHS Foundation Trust during the first wave of the pandemic showed qualitatively different patterns of linkage between cases on designated COVID-19 and non-COVID-19 wards. The subsequent real-time application of our method to data from the second epidemic wave highlights its value for monitoring cases of infection in a clinical context.

P136: THE UPTAKE OF VACCINATIONS IN ADULTS WITH SICKLE CELL DISEASE RECEIVING CARE AT THE CAMBRIDGE UNIVERSITY HOSPITALS NHS FOUNDATION TRUST

Those affected by sickle cell disease have an increased susceptibility to infection by encapsulated bacteria and hepatitis B virus due to reduced splenic function and increased likelihood of receiving blood transfusions. Sickle cell disease patients are also more likely to suffer from complications, such as vaso-occlusive crises or acute chest syndrome, following infection with influenza or COVID-19. Standards for Clinical Care of Adults with Sickle Cell Disease in the UK (2018) outline that that those with sickle cell disease are recommended to be vaccinated against invasive pneumococcal disease, Haemophilus influenza type B, Neisseria meningitis types ACWY and type B, hepatitis B, and influenza. These patients are also recommended to have their hepatitis B immunity reviewed annually and to receive a hepatitis B vaccination booster if hepatitis B surface antibody (HBsAb) levels are less than 100mIU/ml. According to the Standards, hospital staff is advised to remind and check with the patients’ primary care teams whether these vaccinations have been administered. In this audit, we examined the records of 64 patients with sickle cell disease who receive regular care at the Cambridge University Hospitals NHS Foundation Trust. We collected data on the uptake of the pneumococcal conjugate vaccine (PCV13), pneumococcal polysaccharide vaccine (PPV23 or Pneumovax) within 5 years, two doses of Meningitis B vaccine, Meningitis ACWY vaccine (MenACWY), Haemophilus influenzae type b vaccine (Hib/MenC), influenza vaccine within one year, hepatitis B vaccine (HepB), whether HBsAb levels have been reviewed within one year, HepB booster if HBsAb levels were less than 100mIU/ml, and two doses of COVID-19 vaccine. These records were obtained from electrical medical records provided by patients’ general practitioners. Data collection took place from 23rd September to 4th November 2021. The uptake of vaccinations was 67.4% for PCV13, 61.0% for PPV23 or Pneumovax within 5 years, 75.0% for Hib/MenC, 45.3% for MenACWY, 42.2% for the first dose of MenB and 29.3% for the second dose of MenB, 54.7% for influenza within one year, 75.0% for HepB, 71.9% for the first dose of the COVID-19 vaccine, and 68.3% for the second dose of the COVID-19 vaccine. 43.8% had their HbsAB reviewed and 20.0% received a HepB booster following HBsAb levels of less than 100mIU/ml. The uptake levels for the recommended vaccinations are lower than expected in our hospital trust. The COVID-19 pandemic has highlighted the effect of health inequalities and the uptake of the vaccination programme by patients of different ethnicities. During our patient support group, patients identified the Tuskegee syphilis experiment as one of the reasons why there is still distrust of the medical profession by those with Afro-Caribbean heritage. Beyond directed patient education, more communication is needed with the primary care teams to raise awareness of which vaccinations are required for sickle cell patients. Certain vaccinations, such as MenACWY and MenB were only introduced in 2015, meaning that some general practitioners may be still unaware of their necessity in adults with sickle cell disease.

ABO blood group distribution and risk of malignancy in patients undergoing resection for intraductal papillary mucinous neoplasm (IPMN)

BackgroundThe ABO blood type has been associated with risk of development of several malignancies, including pancreatic cancer. Data regarding IPMN is equivocal. To investigate this further, we analyzed the association between the ABO blood group and the presence of malignancy in a large cohort of resected IPMN and its influence in survival. Methods819 patients who underwent pancreatic resection for IPMN in the Massachusetts General Hospital (MGH) and Cambridge University Hospitals NHS Foundation Trust (CUH) from January 1993 to December 2020 were identified from prospective institutional databases. Pathological characteristics and blood type were correlated. ResultsThe distribution of blood types A, B, AB and O was 384 (47%), 92 (11%), 44 (5%) and 299 (37%), respectively. This blood type distribution was different than the reference population of the MGH and the CUH, which is 55% non-O blood group, and 45% type O. There was a significant predominance of non-O blood types when compared with O-blood type in patients with malignant IPMN (i.e. patients with high-grade dysplasia and invasive cancer) (67% vs 33%, OR 1.31 95%CI: 0.98–1.75, p = 0.069). The association was stronger for IPMN with invasive cancer (OR 1.43 95%CI: 1.01–2.02, p = 0.039). Blood group did not influence survival. ConclusionNon-O blood type is associated with need for resection in IPMN and with presence of invasive carcinoma.

Introducing a digital portal that enables patients to access their health records.

People manage many aspects of their lives online through digital devices such as smartphones. However, the ability for people to manage their healthcare digitally has not yet been fully realised. Patient portals are secure online links that offer patients convenient and constant access to their personal health records. Evidence has suggested that patient portals can enhance patients' engagement in their own care and support them to manage any long-term conditions. This article describes the introduction of a patient portal at Cambridge University Hospitals NHS Foundation Trust. The article outlines the process of implementation and discusses the lessons learned, which may be of value to other organisations.

Introducing a digital portal that enables patients to access their health records.

People manage many aspects of their lives online through digital devices such as smartphones. However, the ability for people to manage their healthcare digitally has not yet been fully realised. Patient portals are secure online links that offer patients convenient and constant access to their personal health records. Evidence has suggested that patient portals can enhance patients' engagement in their own care and support them to manage any long-term conditions. This article describes the introduction of a patient portal at Cambridge University Hospitals NHS Foundation Trust. The article outlines the process of implementation and discusses the lessons learned, which may be of value to other organisations.

Superspreaders drive the largest outbreaks of hospital onset COVID-19 infections.

SARS-CoV-2 is notable both for its rapid spread, and for the heterogeneity of its patterns of transmission, with multiple published incidences of superspreading behaviour. Here, we applied a novel network reconstruction algorithm to infer patterns of viral transmission occurring between patients and health care workers (HCWs) in the largest clusters of COVID-19 infection identified during the first wave of the epidemic at Cambridge University Hospitals NHS Foundation Trust, UK. Based upon dates of individuals reporting symptoms, recorded individual locations, and viral genome sequence data, we show an uneven pattern of transmission between individuals, with patients being much more likely to be infected by other patients than by HCWs. Further, the data were consistent with a pattern of superspreading, whereby 21% of individuals caused 80% of transmission events. Our study provides a detailed retrospective analysis of nosocomial SARS-CoV-2 transmission, and sheds light on the need for intensive and pervasive infection control procedures.

Defining nosocomial transmission of Escherichia coli and antimicrobial resistance genes: a genomic surveillance study

SummaryBackgroundEscherichia coli is a leading cause of bloodstream infections. Developing interventions to reduce E coli infections requires an understanding of the frequency of nosocomial transmission, but the available evidence is scarce. We aimed to detect and characterise transmission of E coli and associated plasmids in a hospital setting.MethodsIn this prospective observational cohort study, patients were admitted to two adult haematology wards at the Cambridge University Hospitals NHS Foundation Trust in England. Patients aged 16 years and older who were treated for haematological malignancies were included. Stool samples were collected from study participants on admission, once per week, and at discharge. We sequenced multiple E coli isolates (both extended spectrum β-lactamase [ESBL]-producing and non-ESBL-producing) from each stool sample. A genetic threshold to infer E coli transmission was defined by maximum within-host single nucleotide polymorphism (SNP) diversity and the probability of drawing observed pairs of between-patient isolates at different SNP thresholds. Putative transmission clusters were identified when sequences were less than the genetic threshold. Epidemiological links for each transmission event were investigated. We sequenced all E coli positive blood samples from the two adult haematology wards.FindingsWe recruited 174 (51%) of 338 adult patients admitted to the wards between May 13 and Nov 13, 2015. We obtained and cultured 376 stool samples from 149 patients, of which 152 samples from 97 (65%) patients grew E coli. Whole-genome sequencing was done on 970 isolates. We identified extensive diversity in the bacterial population (90 sequence types) and mixed E coli sequence type carriage. 24 (26%) patients carried two sequence types, 12 (13%) carried three, and six (6%) patients carried four or more sequence types. Using a 17 SNP cutoff we identified ten clusters in 20 patients. The largest cluster contained seven patients, whereas four patients were included in multiple clusters. Strong epidemiological links were found between patients in seven clusters. 17 (11%) of 149 patients had stool samples positive for ESBL-producing E coli, the most common of which was associated with blaCTX-M-15 (12 [71%] of 17). Long-read sequencing revealed that blaCTX-M-15 was often integrated into the chromosome, with little evidence for plasmid transmission. Seven patients developed E coli bloodstream infection, four with identical strains to those in their stool; two of these had documented nosocomial acquisition.InterpretationWe provide evidence of bacterial transmission and endogenous infection during routine care by integrating genomic and epidemiological data and by determining a genetic cutoff informed by within-host diversity in the studied population. Our findings challenge single colony-based investigations, and the widely accepted notion of plasmid spread.FundingUK Department of Health, Wellcome Trust, UK National Institute for Health Research.

Admission COVID-19 clinical risk assessment for guiding patient placement and diagnostic testing strategy

Without universal access to point-of-care SARS-CoV-2 testing, many hospitals rely on clinical judgement alone for identifying cases of COVID-19 early. Cambridge University Hospitals NHS Foundation Trust introduced a 'traffic light' clinical judgement aid to the COVID-19 admissions unit in mid-March 2020. Ability to accurately predict COVID-19 was audited retrospectively across different stages of the epidemic. One SARS-CoV-2 PCR positive patient (1/41, 2%) was misallocated to a 'green' (non-COVID-19) area during the first period of observation, and no patients (0/32, 0%) were mislabelled 'green' during the second period. 33 of 62 (53%) labelled 'red' (high risk) tested SARS-CoV-2 PCR positive during the first period, while 5 of 22 (23%) 'red' patients were PCR positive in the second. COVID-19 clinical risk stratification on initial assessment effectively identifies non-COVID-19 patients. However, diagnosing COVID-19 is challenging and risk of overcalling COVID-19 should be recognised, especially when background prevalence is low.

Utilisation of Antimicrobial Stewardship (AMS) Electronic Interventions (i-Vents) as a metric of pharmacy AMS at Cambridge University Hospitals (CUH) NHS Foundation Trust

Background: The aim of the project was to identify the contribution clinical pharmacists make to antimicrobial stewardship (AMS) at CUH. The EPIC e-hospital system in place allows pharmacists to record interventions (i-Vents) electronically; these can be used as a metric of pharmacist AMS. Method:A bespoke electronic report of all AMS i-Vents which occurred in April 2018 was generated using EPIC.Each i-Vent was categorised by type, clinical speciality, grade of pharmacist making the i-Vent and whether the i-Vent was following on from a previous one. The antimicrobials(s) mentioned in each i-Vent were also recorded. Results:During April 2018 554 pharmacist i-Vents were recorded. I-Vent types included therapeutic drug monitoring (31%), dose optimisation (22%), course length optimisation (12%), interaction and contraindication management (2%) and patient counselling (0.2%). AMS i-Vents were recorded for patients under the care of 42 clinical specialties including neonatology (12%), diabetes and endocrinology (11%) and respiratory (8%). I-vent numbers increased with seniority of pharmacist with band 8 pharmacists making the most interventions (44%) and band 6 pharmacists making the fewest (16%). There were 645 separate references to a total of 53 individual antimicrobial agents. The top three drugs mentioned in i-Vents were vancomycin (30%), gentamicin (12%), and ciprofloxacin (8%). Follow-up i-Vents constituted 111 (20%) of all recorded i-Vents. Conclusion:Our findings demonstrate that pharmacists contribute significantly to AMS at CUH, especially on therapeutic drug monitoring and dose-optimisation issues.We suggest that AMS i-Vents are a reliable metric for monitoring AMS pharmacist activities, related directly to patient care.

Hemoglobin Video Imaging Provides Novel In Vivo High-Resolution Imaging and Quantification of Human Aqueous Outflow in Patients with Glaucoma

PurposeNoninvasive, detailed measurement of the dynamics of human aqueous outflow is difficult to achieve with currently available clinical tools. We used hemoglobin video imaging (HVI) to develop a technique to image and quantify human aqueous outflow noninvasively and in real time.DesignA prospective observational study to describe characteristics of aqueous veins and a pilot prospective interventional feasibility study to develop quantification parameters.ParticipantsPatients were recruited from the Cambridge University Hospitals NHS Foundation Trust Glaucoma clinic. The observational study included 30 eyes, and the pilot interventional feasibility study was performed on 8 eyes undergoing selective laser trabeculoplasty (SLT). Our SLT protocol also included the installation of pilocarpine and apraclonidine eye drops.MethodsParticipants underwent HVI alongside their usual clinic visit.Main Outcome MeasuresThe change in cross-sectional area (CSA) of the aqueous column within episcleral veins was correlated with intraocular pressure (IOP) reduction and change in visual field mean deviation (MD) before and after intervention. Fluctuations in contrast and pixel intensity of red blood cells in an aqueous vein were calculated to compare the flow rate before and after intervention using autocorrelation analysis.ResultsHemoglobin video imaging enables the direct observation of aqueous flow into the vascular system. Aqueous is seen to centralize within a laminar venous column. Flow is pulsatile, and fluctuations of flow through globe pressure or compression of the aqueous vein are observed. There was a significant increase in the aqueous column after the administration of our SLT protocol (n = 13; P < 0.05). This correlated with the degree of IOP reduction (n = 13; Pearson’s correlation coefficient 0.7; P = 0.007) and the improvement in MD observed postintervention (n = 8; Pearson’s correlation coefficient 0.75; P = 0.03). Autocorrelation analysis demonstrated a faster rate of decay in an aqueous vein after intervention, indicating an increase in flow rate.ConclusionsHemoglobin video imaging can be incorporated into a routine clinic slit-lamp examination to allow a detailed assessment and quantification of aqueous outflow in real time. It has the potential to be used to help target therapeutic interventions to improve aqueous outflow and further advance our understanding of aqueous outflow dysregulation in the pathogenesis of glaucoma.

Excess Mortality Associated with Junior Doctor Treatment at the Weekend: An Analysis of Electronic Medical Records in the UK

Background: Admission to hospital over a weekend is associated with increased mortality but the underlying causes are ill understood. We explore to what extent differences in emergency department admission and discharge processes, severity of illness, and the seniority of the treating physician explain the weekend effect. Methods: We analyzed linked emergency department attendances to hospital admissions to Cambridge University Hospitals NHS Foundation Trust, UK over a seven-year period from January 1, 2007 to December 31, 2013 with 30-day in-hospital death as the primary outcome and discharge as a competing risk. The primary exposure was day of the week of arrival. Cox proportional hazards and sub-distribution hazards models controlled for multiple confounders including sociodemographic characteristics, diagnosis group, triage, hospital staffing, and seasonality. Findings: 229,401 patients made 424,845 emergency department attendances, of which 158,396 (37·3%) were admitted to the hospital. 3,947 (3·3%) patients admitted on a weekday to hospital and 1,454 (3·7%) patients admitted at a weekend died within 30 days. In the adjusted Cox model, the hazard ratio of death within 30 days of attendance was 16·0% higher (95% CI 9·2%, 23·3%) for weekend arrivals. The weekend for patients treated by junior doctors (aHR 1·19 [1·10, 1·29]) was significant and suggestive for patients treated by senior doctors (aHR 1·09 [0·99, 1·21]). The Monday effect was as large as the weekend in all statistical models (p 0·05 for all triage categories). Interpretation: Our findings suggest that the seniority of the physician is an important factor in the weekend effect, which persists for patients treated by junior doctors during working hours. Changes to NHS policy that emphasize consultant-led emergency services at weekends may decrease the weekend effect. Funding Statement: This work was supported by the Bill and Melinda Gates Foundation through a Gates Cambridge Scholarship. The views expressed are those of the authors and not necessarily those of the NHS, Department of Health, or Public Health England. Declaration of Interests: The authors declare none. Ethics Approval Statement: The authors obtained Research Ethics Committee and Health Research Authority approval from Cambridge University Hospitals NHS Foundation Trust.