1Objectives 2 Current national estimates of respiratory syncytial virus (RSV)-associated hospital 3 admissions are insufficiently detailed to determine optimal vaccination strategies for RSV. 4We employ novel methodology to estimate the burden of RSV-associated hospital 5 admissions in infants in England, with detailed stratification by patient and clinical 6 characteristics. 7 8 Methods 9We used linked, routinely collected laboratory and hospital data to identify laboratory-10 confirmed RSV-positive and RSV-negative respiratory hospital admissions in infants in 11England, then generate a predictive logistic regression model for We applied this model to all respiratory hospital admissions in infants in England, to 13 estimate the national burden of RSV-associated admissions by calendar week, age in weeks 14 and months, clinical risk group and birth month. 15 16Results 17 We estimated an annual average of 20,359 (95% CI 19,236-22,028) RSV-associated 18 admissions in infants in England from mid-2010 to mid-2012. These admissions accounted 19 for 57,907 (95% CI 55,391-61,637) annual bed days. 55% of RSV-associated bed days and 20 45% of RSV-associated admissions were in infants <3 months old. RSV-associated admissions 21 peaked in infants aged 6 weeks, and those born September to November. 22 23Conclusions 24We employed novel methodology using linked datasets to produce detailed estimates of 25 RSV-associated admissions in infants. Our results provide essential baseline epidemiological 26 data to inform future vaccine policy. 27 28 29 30 Funding 31 Farr Institute of Health Informatics Research (grant MR/K006584/1). 32 33

Background Infective endocarditis is an uncommon but serious infection, where evidence for giving antibiotic prophylaxis before invasive dental procedures is inconclusive. In England, antibiotic prophylaxis was offered routinely to patients at risk of infective endocarditis until March 2008, when new guidelines aimed at reducing unnecessary antibiotic use were issued. We investigated whether changes in infective endocarditis incidence could be detected using electronic health records, assessing the impact of inclusion criteria/statistical model choice on inferences about the timing/type of any change. Methods Using national data from Hospital Episode Statistics covering 1998–2017, we modelled trends in infective endocarditis incidence using three different sets of inclusion criteria plus a range of regression models, identifying the most likely date for a change in trends if evidence for one existed. We also modelled trends in the proportions of different organism groups identified during infection episodes, using secondary diagnosis codes and data from national laboratory records. Lastly, we applied non-parametric local smoothing to visually inspect any changes in trend around the guideline change date. Results Infective endocarditis incidence increased markedly over the study (22.2–41.3 per million population in 1998 to 42.0–67.7 in 2017 depending on inclusion criteria). The most likely dates for a change in incidence trends ranged from September 2001 (uncertainty interval August 2000–May 2003) to May 2015 (March 1999–January 2016), depending on inclusion criteria and statistical model used. For the proportion of infective endocarditis cases associated with streptococci, the most likely change points ranged from October 2008 (March 2006–April 2010) to August 2015 (September 2013–November 2015), with those associated with oral streptococci decreasing in proportion after the change point. Smoothed trends showed no notable changes in trend around the guideline date. Conclusions Infective endocarditis incidence has increased rapidly in England, though we did not detect any change in trends directly following the updated guidelines for antibiotic prophylaxis, either overall or in cases associated with oral streptococci. Estimates of when changes occurred were sensitive to inclusion criteria and statistical model choice, demonstrating the need for caution in interpreting single models when using large datasets. More research is needed to explore the factors behind this increase.

Nontyphoidal Salmonella (NTS) bacteremia causes hospitalization and high morbidity and mortality. We linked Gastrointestinal Bacteria Reference Unit (GBRU) data to the Hospital Episode Statistics (HES) data set to study the trends and outcomes of NTS bacteremias in England between 2004 and 2015. All confirmed NTS isolates from blood from England submitted to GBRU between 1 January 2004 and 31 December 2015 were deterministically linked to HES records. Adjusted odds ratios (AOR), proportions, and confidence intervals (CI) were calculated to describe differences in age, sex, antibiotic resistance patterns, and serotypes over time. Males, neonates, and adults above 65 years were more likely to have NTS bacteremia (AOR, 1.54 [95% CI, 1.46 to 1.67]; 2.57 [95% CI, 1.43 to 4.60]; and 3.56 [95% CI, 3.25 to 3.90], respectively). Proportions of bacteremia increased from 1.41% in 2004 to 2.67% in 2015. Thirty-four percent of all blood isolates were resistant to a first-line antibiotic, and 1,397 (56%) blood isolates were linked to an HES record. Of the patients with NTS bacteremia, 969 (69%) had a cardiovascular condition and 155 (12%) patients died, out of which 120 (77%) patients were age 65 years and above. NTS bacteremia mainly affects older people with comorbidities placing them at increased risk of prolonged hospital stay and death. Resistance of invasive NTS to first-line antimicrobial agents appeared to be stable in England, but the emergence of resistance to last-resort antibiotics, such as colistin, requires careful monitoring.

Respiratory syncytial virus (RSV) is a common seasonal respiratory virus and an important cause of illness among infants, but the burden of RSV disease is not well described among the older population. The objective of this study was to estimate the age-specific incidence of hospital admission among over 65 s due to respiratory illnesses attributable to RSV in England to inform optimal vaccine and therapeutic interventions.We used linear multiple regression to examine the effect of changes in weekly counts of respiratory pathogens on the weekly counts of respiratory hospital admissions.The study population was all patients aged 65 years or over admitted to English hospitals between 2nd August 2010 and 30th July 2017.RSV was estimated to account for a seasonal annual average of 71 (95% CI 52-90) respiratory admissions per 100 000 in adults age [65][66][67][68][69][70][71][72][73][74] admissions per 100,000 adults age 75+. Pneumococcus was the pathogen responsible for highest annual average respiratory admission with 448 (95% CI 310-587) admissions per 100,000 adults age 65-74 and 1010 (95% CI 527-1493) admissions per 100,000 adults aged 75+.This study shows that RSV continues to exert a significant burden of disease among older adults in England. These findings will support development of policy for the use of RSV therapeutics and vaccines in this age group.

This study provides the first national estimates of the proportion of pediatric BSI that is hospital-acquired and describes the antimicrobial resistance of organisms causing infection. Pediatric HA-BSI remains unacceptably high; interventions must focus on identifying effective means of preventing HA-BSI, fostering antibiotic stewardship, and improving surveillance.