BACKGROUND:Current evidence suggests reduced efficacy of direct-acting antiviral (DAA) treatment among people with endemic Hepatitis C virus (HCV) subtypes rare to high-income countries. We aimed to determine real-world DAA treatment outcomes of people with endemic HCV subtypes in England. METHODS:Data were collected through a national treatment program. People who had their virus subtyped between 2019-2023, were resident in England and had an outcome recorded for their first DAA treatment episode, were included. Subtypes were divided into epidemic and endemic in England; endemic subtypes were confirmed with whole genome sequencing and resistance associated substitutions (RAS) were determined. Logistic regression was used to determine associations between treatment outcome and exposure variables. RESULTS:In people with an outcome recorded, 93 with an endemic and 8671 with an epidemic HCV subtype were identified, of whom 49.5% (46/93) and 91.8% (7953/8668) achieved a sustained virological response at 12 weeks post end of DAA treatment (SVR12), respectively. In the multivariable model, people with an endemic subtype had 93% (aOR 0.07 95%CI 0.04-0.12, P=<0.001) reduced odds of achieving SVR12. Treatment with sofosbuvir/velpatasvir or glecaprevir/pibrentasvir was successful for genotypes 1, 2, 4 and 5 (SVR12 100%, n=13) but not 3 (27.3%, n=22) endemic subtypes. Sofosbuvir/velpatasvir/voxilaprevir was successful for GT3 endemic subtypes at retreatment (SVR12 11/12, 91.7%). Treatment failures for genotypes 1, 3 and 4 were likely mediated by naturally occurring baseline NS5A RAS (median n=2). DISCUSSION:This study provides further evidence that endemic HCV subtypes lead to sub-optimal DAA efficacy, which may impact global HCV elimination.

BACKGROUND:Sepsis remains a significant clinical and public health concern, necessitating timely identification and targeted management for improved patient outcomes. This study describes the epidemiology of sepsis in emergency department attendees across England by analysing a unique multi-site linked dataset to inform approaches to strengthen surveillance and improve our understanding of clinical outcomes. METHODS:An existent study dataset was utilised comprising a sample of paediatric and adult emergency department admissions screened for community-onset sepsis in the Commissioning for Quality and Innovation (CQUIN) program in the 2017/18 financial year linked to Hospital Episode Statistics and Office for National Statistics death registrations. This dataset was linked to the United Kingdom Health Security Agency's Second-Generation Surveillance System for microbiological data. Descriptive analyses were conducted to characterise sepsis screen positives and negatives in CQUIN, including demographic characteristics, clinical presentations, microbiological profiles, and clinical outcomes. RESULTS:Of the 4,027 sepsis-screened emergency admissions included, 2,454 (60.9%) were sepsis screen positive under the CQUIN indicator. Only 11.2% (453/4,027) had a positive blood culture within 2 days of hospital admission. Blood culture positivity rates were 15.2% (373/2,454) and 5.1% (80/1,573) for sepsis screen positive and negative in CQUIN, respectively. Monomicrobial episodes predominated (86.5%), with Escherichia coli and Staphylococcus species being the most commonly isolated bacteria. The study showed a case fatality rate of 17.1% (420/2,454) for sepsis screen positive in CQUIN but revealed no significant difference in all-cause 30-day mortality between sepsis screen positives in CQUIN with and without positive blood cultures. Sepsis screen positives in CQUIN with a focal site of infection code were more likely to have positive blood cultures, except for respiratory infections. CONCLUSIONS:This study provides novel insights into the epidemiology of sepsis screening in emergency departments across England, highlighting variability in blood culture positivity rates and microbial profiles. The findings underscore the importance of enhanced surveillance strategies, optimised screening protocols, tailored antimicrobial stewardship practices, and quality improvement initiatives to optimise sepsis management and outcomes. Systemic approaches are needed to address knowledge gaps and inform evidence-based interventions for sepsis care.

Background The Commissioning for Quality and Innovation (CQUIN) indicator on sepsis was introduced in 2015 to incentivise screening eligible emergency admissions for sepsis, with the aim to improve patient outcomes through early identification and timely treatment. The CQUIN sepsis indicator provides an alternative source of data which has potential in improving our understanding of sepsis epidemiology in England and for surveillance and monitoring purposes. Our objectives were to describe 30-day mortality when using CQUIN sepsis indicator data compared to Hospital Episode Statistics (HES) data, determine whether the CQUIN sepsis screen result was a good predictor of mortality, and identify other independent predictors of mortality in emergency admissions being screened for sepsis in CQUIN. Methods This study was a secondary analysis of a national linked dataset which contains CQUIN sepsis indicator data for financial year 2017/18 from a random sample of 30 NHS hospital trusts in England, linked to HES data and Office for National Statistics mortality data. Descriptive and univariable analyses were conducted to explore differences in mortality for admissions who screened positive or negative for sepsis in CQUIN. A multivariable logistic regression analysis was conducted to identify independent predictors of 30-day mortality. Results 30-day mortality for emergency admissions who screened positive for sepsis in CQUIN was 17% compared to 11% for admissions who screened negative. 30-day mortality differed when using CQUIN sepsis indicator data compared to HES data. We identified some evidence to suggest that the CQUIN sepsis screen result may be an independent predictor of 30-day mortality (adjusted OR, 1.27; 95% CI: 1.03–1.57). Other predictors of mortality included: age, respiratory infection, and the presence of comorbidities such as cancer, dementia, renal disease, liver disease and cardiovascular disease. Conclusion CQUIN sepsis screen identified emergency admissions who were more likely to have poor outcomes, though evidence was limited. Other independent predictors of mortality were identified. Variability in how the CQUIN sepsis indicator was applied limits use of the CQUIN sepsis indicator data, however, this study provides a foundation for further research to improve understanding of sepsis epidemiology in England and inform development of future indicators for clinical and surveillance purposes.

We aimed to estimate the secondary attack rate of mpox among UK household contacts and determine factors associated with transmission to inform public health management of contacts, during the global outbreak in 2022. Information was collected via NHS and public health services and included age, gender, place of residence, setting, and type of contact. Aggregate information was summarized for the UK. Record level data was combined for England, Wales and Northern Ireland, and multivariable logistic regression was used to determine factors associated with transmission. The secondary attack rate among UK household mpox contacts was 4% (60/1 526). Sexual contact with the index case was associated with a 11-fold increase in adjusted odds of becoming a case in England, Wales, and Northern Ireland (95% CI 5.5-22, p < 0.001). Household contacts outside of London had increased odds compared to London residents (adjusted OR 2.9, 95%CI 1.6-5.4, p < 0.001), while female contacts had reduced odds of becoming a case (aOR: 0.41, 95% CI: 0.15-0.95). We found a low overall secondary attack rate among household mpox contacts with strong evidence of increased transmission risk associated with sexual contact. This evidence will inform the risk assessment of contacts and support prioritization of those with close intimate contact for follow up.

Background. Hepatitis C virus (HCV) has high genetic diversity and is classified into 8 genotypes and >90 subtypes, with some endemic to specific world regions. This could compromise direct-acting antiviral efficacy and global HCV elimination. Methods. We characterized HCV subtypes "rare" in the United Kingdom (non-1a/1b/2b/3a/4d) by means of whole-genome sequencing via a national surveillance program. Genetic analyses to determine the genotype of samples with unresolved genotypes were undertaken by comparison with International Committee on Taxonomy of Viruses HCV reference sequences. Results. Two HCV variants were characterized as being closely related to the recently identified genotype (GT) 8, with >85% pairwise genetic distance similarity to GT8 sequences and within the typical intersubtype genetic distance range. The individuals infected by the variants were UK residents originally from Pakistan and India. In contrast, a third variant was only confidently identified to be more similar to GT6 compared with other genotypes across 6% of the genome and was isolated from a UK resident originally from Guyana. All 3 were cured with pangenotypic direct-acting antivirals (sofosbuvir-velpatasvir or glecaprevir-pibrentasvir) despite the presence of resistance polymorphisms in NS3 (80K/168E), NS5A (28V/30S/62L/92S/93S) and NS5B (159F). Conclusions. This study expands our knowledge of HCV diversity by identifying 2 new GT8 subtypes and potentially a new genotype.

Contact tracing was used globally to prevent onwards transmission of COVID-19. Tracing contacts alone is unlikely to be sufficient in controlling community transmission, due to the pre-symptomatic, overdispersed and airborne nature of COVID-19 transmission. We describe and demonstrate the validity of a national enhanced contact tracing programme for COVID-19 cluster surveillance in England. Data on cases occurring between October 2020 and September 2021 were extracted from the national contact tracing system. Exposure clusters were identified algorithmically by matching ≥2 cases attending the same event, identified by matching postcode and event category within a 7-day rolling window. Genetic validity was defined as exposure clusters with ≥2 cases from different households with identical viral sequences. Exposure clusters were fuzzy matched to the national incident management system (HPZone) by postcode and setting description. Multivariable logistic regression modelling was used to determine cluster characteristics associated with genetic validity. Over a quarter of a million (269,470) exposure clusters were identified. Of the eligible clusters, 25% (3,306/13,008) were genetically valid. 81% (2684/3306) of these were not recorded on HPZone and were identified on average of one day earlier than incidents recorded on HPZone. Multivariable analysis demonstrated that exposure clusters occurring in workplaces (aOR = 5·10, 95% CI 4·23-6·17) and education (aOR = 3·72, 95% CI 3·08-4·49) settings were those most strongly associated with genetic validity. Cluster surveillance using enhanced contact tracing in England was a timely, comprehensive and systematic approach to the detection of transmission events occurring in community settings. Cluster surveillance can provide intelligence to stakeholders to support the assessment and management of clusters of COVID-19 at a local, regional, and national level. Future systems should include predictive modelling and network analysis to support risk assessment of exposure clusters to improve the effectiveness of enhanced contract tracing for outbreak detection.

Background It is not yet fully understood to what extent in-flight transmission contributed to the spread of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). This study aimed to determine the occurrence and extent of SARS-CoV-2 transmission in-flight and assess factors associated with transmission risk to inform future control strategies. Methods Retrospective cohort study using data obtained from contact tracing of international flights arriving in England between 02/08/2021–15/10/2021. Transmission risk was estimated by calculating the secondary attack rate (SAR). Univariable and multivariable analyses of the SAR by specific risk factors was undertaken, including: number of in-flight index cases; number of symptomatic index cases; contact vaccination status; flight duration; proximity to the index case(s); contact age. Results 11,307 index cases linked to 667,849 contacts with 5,289 secondary cases reported. In-flight SAR was 0.79% (95% CI: 0.77–0.81). Increasing numbers of symptomatic cases (when > 4 index cases compared to one index case aOR 1.85; 95% CI: 1.40–2.44) and seating proximity to an index case (seated within compared to outside of two rows OR 1.82; 95% CI: 1.50–2.22) were associated with increased risk of secondary cases. Full vaccination history was protective (aOR 0.52; 95% CI: 0.47–0.57). Conclusions This study confirms that in-flight transmission of SARS-CoV-2 occurred. There are factors associated with increased risk of infection. Contact tracing identified exposed persons who subsequently developed infection. A targeted approach to contact tracing passengers with the highest exposure risk could be an effective use of limited public health resources.

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Background The UK is committed to the WHO target to eliminate Hepatitis C virus (HCV) as a public health threat by 2030. This is achievable due to the success of direct-acting antiviral (DAA) treatment which has contributed to a 47% reduction in HCV infections between 2015 and 2021. The HCV virus is extremely diverse with eight genotypes and over 100 subtypes currently defined. Despite this, most clinical trials of DAA efficacy include a small subset of these subtypes, prevalent in high-income countries, with highly diverse subtypes ‘rare’ to the UK remaining significantly under-represented. Current limited evidence suggests much lower treatment success rates among these ‘rare’ subtypes, which is likely to impact progress towards elimination. We aimed to determine the real-world outcomes of DAA therapy for treatment of HCV subtypes ‘rare’ to the UK. Methods Datasets collected as part of the NHS England treatment program delivered by HCV Operational Delivery Networks between 2018 and 2022 were interrogated to ascertain the outcome for first course of DAA treatment. Those who did not reach treatment end were removed, including: ‘not completed’, ‘lost to follow up’, ‘death prior’, and ‘other’. Genotypes 1a, 1b, 2b, 3a, 4a and 4d were defined as common subtypes (n=7274), and any other subtype was defined as ‘rare’ subtypes to the UK (n=84). Whole genome sequencing was used to confirm all ‘rare’ subtype samples. Multivariate logistic regression was used to assess treatment outcome in ‘rare’ and ‘common’ subtypes using R (GNU General Public License v4.1.2). Results Sustained virological response at 12 weeks after end of DAA therapy (SVR12) were achieved in 54% of ‘rare’ and 92% of ‘common’ subtype infections (45/84 vs 6671/7274). Additionally, people infected with ‘rare’ subtypes were more likely than those with ‘common’ subtypes to experience relapse (31% vs 3%), non-response (10% vs 2%) and viral breakthroughs (6% vs 0%) (figure 1). After adjustment for potential confounders, the decrease in the odds of achieving SVR12 with a ‘rare’ HCV subtype was 91% (95%CI: 84%-94%) compared to a ‘common’ subtype (p<0.001). Discussion In conclusion, infection with a ‘rare’ HCV subtype resulted in a significantly reduced odds of achieving SVR12, compared to a ‘common’ subtype infection. This work supports current evidence suggesting ‘rare’ HCV subtype infections lead to sub-optimal DAA efficacy, which may result in increasing relative prevalence of harder to treat HCV infections, impacting our ability to achieve HCV elimination in the UK and globally.

Extreme weather events present significant global threats to health. The National Ambulance Syndromic Surveillance System collects data on 18 syndromes through chief presenting complaint (CPC) codes. We aimed to determine the utility of ambulance data to monitor extreme temperature events for action. Daily total calls were observed between 01/01/2018–30/04/2019. Median daily ’Heat/Cold’ CPC calls during “known extreme temperature” (identified a priori), “extreme temperature”; (within 5th or 95th temperature percentiles for central England) and meteorological alert periods were compared to all other days using Wilcoxon signed-rank test. During the study period, 12,585,084 calls were recorded. In 2018, median daily “Heat/Cold” calls were higher during periods of known extreme temperature: heatwave (16/day, 736 total) and extreme cold weather events (28/day, 339 total) compared to all other days in 2018 (6/day, 1672 total). Median daily “Heat/Cold” calls during extreme temperature periods (16/day) were significantly higher than non-extreme temperature periods (5/day, p < 0.001). Ambulance data can be used to identify adverse impacts during periods of extreme temperature. Ambulance data are a low resource, rapid and flexible option providing real-time data on a range of indicators. We recommend ambulance data are used for the surveillance of presentations to healthcare related to extreme temperature events.

Understanding SARS-CoV-2 transmission in higher education settings is important to limit spread between students, and into at-risk populations. In this study, we sequenced 482 SARS-CoV-2 isolates from the University of Cambridge from 5 October to 6 December 2020. We perform a detailed phylogenetic comparison with 972 isolates from the surrounding community, complemented with epidemiological and contact tracing data, to determine transmission dynamics. We observe limited viral introductions into the university; the majority of student cases were linked to a single genetic cluster, likely following social gatherings at a venue outside the university. We identify considerable onward transmission associated with student accommodation and courses; this was effectively contained using local infection control measures and following a national lockdown. Transmission clusters were largely segregated within the university or the community. Our study highlights key determinants of SARS-CoV-2 transmission and effective interventions in a higher education setting that will inform public health policy during pandemics.

Background: Identifying areas that pose the greatest risk for community transmission of COVID-19 is essential to direct public health action and allow safe re-opening of society. Spread of B.1.1.7 (alpha) lineage provided a unique opportunity to quantify COVID-19 transmission risk associated with community settings in England 2020/21. Methods: All cases of COVID-19 occurring between 11/2020 and 01/2021 reported through the English national contact tracing system included. Recruitment occurred when B.1.1.7 regional prevalence was between 20-80%. Case groups were defined as: >2 cases reporting the same, location and attendance date 7-3 days before onset. Genetic concordance, presence/absence of S-gene target failure (SGTF) in grouped cases, was determined. Odds ratios for concordance and 95% confidence intervals were calculated. Sensitivity analysis compared concordance in single to 2-3 day case groups. Findings: There were 41,325 case groups with SGTF data containing 115,410 exposure events. Odds ratios ranged from 1.87 (95% CI:1.76-1.98) for shops, 29.9 (95% CI:23.1-38.7), nursery/preschool and 35.6 (95% CI:19.7-64.2) for visiting friends/relatives. Odds ratios of concordance increased with larger cluster sizes in educational settings. Concordance estimates were reduced when case grouping time period was increased from 1 to 2-3 days. Interpretation: Transmission risk varies across community settings, likely due to different behavioural or environmental factors. Risk does not capture number of users which also affects impact of settings on transmission. Limited data for certain settings due to non-pharmaceutical interventions in place. We recommend data are used to guide policy and prioritise action when assessing and managing COVID-19 community case clusters. Funding: EB funded by EMBL. No additional funding.Declaration of Interest: None to declare

Background Retinol-binding protein4 (RBP) assays using polyclonal antibodies (pRBP) have major problems of non-linearity of dilution and a very small useable dynamic range. Our objective was to develop a specific assay with a wider dynamic range to detect tubular proteinuria. Methods mRBP (monoclonal capture and second antibody with colorimetric detection) and fluoroimmunoassays for RBP (fRBP) (polyclonal capture and monoclonal second antibody with fluorescence detection) were developed and compared with pRBP. Four hundred and eighty-eight patient samples were collected; 290 samples were analysed by mRBP and 198 samples with fRBP and compared with pRBP. Results mRBP assay has the advantages of better linearity on dilution and wider analytical range over pRBP. It is limited by poor signal in the patients with albuminuria and glomerular proteinuria and inferior discrimination between patient groups. fRBP had an intra-assay and inter-assay CV of <6% and <8%, respectively, and analytical range was 2.3–599 µg/L. fRBP was linear on dilution within the analytical range. Correlation (r) was 0.8722 (95% CI 0.7621 to 0.9333, P< 0.0001); Mann-Whitney test revealed no significant difference (U = 18,877, n = 198, P = 0.5244) asserting that the medians of the two samples were identical. Bland-Altman test between pRBP and fRBP showed a mean negative bias of 16.43 (CI –994 to 1027) µg/mmol. Conclusions The combination assay with fluorescence detection (fRBP) proved more discriminatory than a purely monoclonal system especially in patients with significant proteinuria and has advantages of better linearity on dilution and wider analytical range than the existing pRBP assay and compared extremely well with pRBP.

Background Knowledge gaps remain regarding SARS-CoV-2 transmission on flights. We conducted a retrospective cohort study to estimate risk of acquiring symptomatic SARS-CoV-2 on aircraft, to inform contact tracing and infection control efforts. Methods We identified co-passengers of infectious passengers on 18 England-bound flights from European cities up to 12/03/2020, using manifests received for contact tracing. Infectious passengers were laboratory-confirmed cases with symptom onset from 7 days before to 2 days after the flight. Possible aircraft-acquired cases were laboratory-confirmed with onset 3-14 days post-flight with no known non-flight exposure. Manifests was merged with the national case management dataset (identifying cases, onset dates, contact tracing status) and the national COVID-19 linelist. Contact tracing notes were reviewed to identify non-flight exposures. We calculated attack rates (ARs) among all co-passengers and within subgroups, including by distance from infectious cases and number of infectious cases on-board. Results There were 55 infectious passengers and 2313 co-passengers, including 2221 flight-only contacts. Five possible aircraft-acquired cases were identified; ARs of 0.2% (95%CI 0.1-0.5) among all flight-only contacts and 3.8% (95%CI 1.3-10.6) among contact-traced flight-only contacts sat within a two-seat radius. The AR among 92 co-travellers with known non-flight exposure to infectious cases was 13.0% (95%CI 7.6%-21.4%). There were insufficient numbers to assess differences between subgroups. Conclusion We conclude that risk of symptomatic COVID-19 due to transmission on short to medium-haul flights is low, and recommend prioritising contact-tracing of close contacts and co-travellers where resources are limited. Further research on risk on aircraft is encouraged.

Understanding the drivers for spread of SARS-CoV-2 in higher education settings is important to limit transmission between students, and onward spread into at-risk populations. In this study, we prospectively sequenced 482 SARS-CoV-2 isolates derived from asymptomatic student screening and symptomatic testing of students and staff at the University of Cambridge from 5 October to 6 December 2020. We performed a detailed phylogenetic comparison with 972 isolates from the surrounding community, complemented with epidemiological and contact tracing data, to determine transmission dynamics. After a limited number of viral introductions into the university, the majority of student cases were linked to a single genetic cluster, likely dispersed across the university following social gatherings at a venue outside the university. We identified considerable onward transmission associated with student accommodation and courses; this was effectively contained using local infection control measures and dramatically reduced following a national lockdown. We observed that transmission clusters were largely segregated within the university or within the community. This study highlights key determinants of SARS-CoV-2 transmission and effective interventions in a higher education setting that will inform public health policy during pandemics.

OBJECTIVE:To assess the magnitude and duration of any hypothesised protective effect of household exposure to a child with varicella on the relative incidence of herpes zoster in adults. DESIGN:Self controlled case series. SETTING:UK general practices contributing to Clinical Practice Research Datalink. PARTICIPANTS:9604 adults (≥18 years) with a diagnosis of herpes zoster (in primary care or hospital records) between 1997 and 2018, who during their observation period lived with a child (<18 years) with a diagnosis of varicella. MAIN OUTCOME MEASURES:Relative incidence of herpes zoster in the 20 years after exposure to a child with varicella in the household compared with baseline time (all other time, excluding the 60 days before exposure). RESULTS:6584 of the 9604 adults with herpes zoster (68.6%) were women. Median age of exposure to a child with varicella was 38.3 years (interquartile range 32.3-48.8 years) and median observation period was 14.7 (11.1-17.7) years. 4116 adults developed zoster in the baseline period, 433 in the 60 days before exposure and 5055 in the risk period. After adjustment for age, calendar time, and season, strong evidence suggested that in the two years after household exposure to a child with varicella, adults were 33% less likely to develop zoster (incidence ratio 0.67, 95% confidence interval 0.62 to 0.73) compared with baseline time. In the 10-20 years after exposure, adults were 27% less likely to develop herpes zoster (0.73, 0.62 to 0.87) compared with baseline time. A stronger boosting effect was observed among men than among women after exposure to varicella. CONCLUSIONS:The relative incidence of zoster was lower in the periods after exposure to a household contact with varicella, with modest but long lasting protective effects observed. This study suggests that exogenous boosting provides some protection from the risk of herpes zoster, but not complete immunity, as assumed by previous cost effectiveness estimates of varicella immunisation.

In March 2018, Public Health England was alerted to an outbreak of gastrointestinal illness in persons who had eaten at a restaurant in the South West of England on Mothering Sunday. We aimed to determine the source of infection and control the outbreak. A retrospective cohort study was undertaken among all individuals who ate at the restaurant on March 11, 2018. Cases were defined as any person who consumed food from the restaurant and had diarrhoea or vomiting between 12:00 March 11, 2018 and 23:59 March 15, 2018. Data were collected using a secure electronic questionnaire. Descriptive, univariable and multivariable analyses were undertaken with odds ratios (OR) and 95% confidence intervals (CI) calculated for exposures. Clinical and food samples were collected for microbiological testing and molecular typing. The restaurant reported 293 people attending, 176 (60%) completed the survey and 146 (50%) provided sufficient information for inclusion in the analysis. Eighty-one persons met the case definition (attack rate 55.5%); eating from the roast meat buffet was associated with illness (OR: 7.80, 95% CI: 2.03–43.56). No single food item explained all the cases. Independent associations between consumption of gravy (adjusted OR (aOR): 5.35, 95% CI:2.21–12.93), lamb (aOR: 2.51, 95% CI:1.06–5.96), and eating during the later 16:00 sitting (aOR: 5.23, 95% CI:1.76–15.54) were identified. Clostridium perfringens enterotoxin was detected in clinical samples and the same strain of enterotoxigenic C. perfringens that was isolated from clinical samples was also detected in roasted lamb, beef and turkey. We found strong evidence for an outbreak of C. perfringens food poisoning associated with gravy and/or meat consumption. The data suggests cross-contamination between items, which increased over time. We recommend that health agencies ensure that restaurants serving roasted meat buffets adhere to minimum oven temperatures and take special measures to prevent food poisoning and cross contamination at the preparation and serving stage.

Background: Routine ligation of the thoracic duct during oesophagectomy has been reported to reduce the rate of chyle leak (CL) following oesophagectomy. This study aims to identify risk factors for developing a CL with this approach and review current management. Methods: All patients who underwent transthoracic oesophagectomy over a 3-year period were identified from a prospectively collected database and their medical records reviewed. Results: A total of 147 oesophagectomies were performed in the period January 2012–December 2014. Eighteen patients with anastomotic leak were excluded. Eleven (8.5%) of the remaining 129 patients developed a CL. Statistically significant predictive factors for CL were squamous cell carcinoma (6/16, 37.5% vs. 5/113, 4.4% in other tumour types, P=0.0005) and high total chest drain volumes on day 2 post operatively measured prior to commencing enteric feeding. Using a threshold of 600 mL on day 2, the sensitivity and specificity for predicting CL are 92% and 82% respectively. Low BMI (mean 24.1 with CL vs. 27.5 without CL) was also associated with a CL, but was not statistically significant. Neither the extent of lymphadenectomy nor the extent of lymph node involvement (N stage) were associated with CL. Six patients with a low volume CL (<600 mL/day) were successfully managed conservatively. The main thoracic duct was never the source of leakage in the 5 patients requiring re-thoracotomy. All 11 patients were successfully discharged home. Conclusions: This study demonstrates squamous cell carcinoma remains a significant risk factor for the development of post-oesophagectomy chylothorax despite the routine ligation of the thoracic duct. In the knowledge that with this approach the main thoracic duct is never the source of CL, patients with a chest drainage of <600 mL/24 h can be successfully treated conservatively. Patients with a chest drain volume of >600 mL/24 h despite conservative management should undergo re-thoracotomy at an early stage.

Background: In 2015, Bristol (South West England) experienced a large increase in cases of meticillin-resistant Staphylococcus aureus (MRSA) infection in people who inject drugs (PWID). Aim: We aimed to characterise and estimate the prevalence of MRSA colonisation among PWID in Bristol and test evidence of a clonal outbreak. Methods: PWID recruited through an unlinked-anonymous community survey during 2016 completed behavioural questionnaires and were screened for MRSA. Univariable logistic regression examined associations with MRSA colonisation. Whole-genome sequencing used lineage-matched MRSA isolates, comparing PWID (screening and retrospective bacteraemia samples from 2012-2017) with non-PWID (Bristol screening) in Bristol and national reference laboratory database samples. Results: The MRSA colonisation prevalence was 8.7% (13/149) and was associated with frequently injecting in public places (odds ratio (OR): 5.5; 95% confidence interval (CI):1.34–22.70), recent healthcare contact (OR: 4.3; 95% CI: 1.34–13.80) and injecting in groups of three or more (OR: 15.8; 95% CI: 2.51–99.28). People reporting any one of: injecting in public places, injection site skin and soft tissue infection or hospital contact accounted for 12/13 MRSA positive cases (sensitivity 92.3%; specificity 51.5%). Phylogenetic analysis identified a dominant clade associated with infection and colonisation among PWID in Bristol belonging to ST5-SCCmecIVg. Conclusions: MRSA colonisation in Bristol PWID is substantially elevated compared with general population estimates and there is evidence of clonal expansion, community-based transmission and increased infection risk related to the colonising strain. Targeted interventions, including community screening and suppression therapy, education and basic infection control are needed to reduce MRSA infections in PWID.