Combining Charlson and Elixhauser scores with varying lookback predicated mortality better than using individual scores.

OBJECTIVE: To investigate variation in the presence of secondary diagnosis codes in Charlson and Elixhauser comorbidity scores and assess whether including a 1-year lookback period improved prognostic adjustment by these scores individually, and combined, for 30-day mortality. STUDY DESIGN AND SETTING: We analyzed inpatient admissions from January 1, 2007 to May 18, 2018 in Oxfordshire, UK. Comorbidity scores were calculated using secondary diagnostic codes in the diagnostic-dominant episode, and primary and secondary codes from the year before. Associations between scores and 30-day mortality were investigated using Cox models with natural cubic splines for nonlinearity, assessing fit using Akaike Information Criteria. RESULTS: The 1-year lookback improved model fit for Charlson and Elixhauser scores vs. using diagnostic-dominant methods. Including both, and allowing nonlinearity, improved model fit further. The diagnosis-dominant Charlson score and Elixhauser score using a 1-year lookback, and their interaction, provided the best comorbidity adjustment (reduction in AIC: 761 from best single score model). CONCLUSION: The Charlson and Elixhauser score calculated using primary and secondary diagnostic codes from 1-year lookback with secondary diagnostic codes from the current episode improved individual predictive ability. Ideally, comorbidities should be adjusted for using both the Charlson (diagnostic-dominant) and Elixhauser (1-year lookback) scores, incorporating nonlinearity and interactions for optimal confounding control.

Investigation of the impact of the NICE guidelines regarding antibiotic prophylaxis during invasive dental procedures on the incidence of infective endocarditis in England: an electronic health records study.

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.

Selective culture enrichment and sequencing of feces to enhance detection of antimicrobial resistance genes in third-generation cephalosporin resistant Enterobacteriaceae.

Metagenomic sequencing of fecal DNA can usefully characterise an individual's intestinal resistome but is limited by its inability to detect important pathogens that may be present at low abundance, such as carbapenemase or extended-spectrum beta-lactamase producing Enterobacteriaceae. Here we aimed to develop a hybrid protocol to improve detection of resistance genes in Enterobacteriaceae by using a short period of culture enrichment prior to sequencing of DNA extracted directly from the enriched sample. Volunteer feces were spiked with carbapenemase-producing Enterobacteriaceae and incubated in selective broth culture for 6 hours before sequencing. Different DNA extraction methods were compared, including a plasmid extraction protocol to increase the detection of plasmid-associated resistance genes. Although enrichment prior to sequencing increased the detection of carbapenemase genes, the differing growth characteristics of the spike organisms precluded accurate quantification of their concentration prior to culture. Plasmid extraction increased detection of resistance genes present on plasmids, but the effects were heterogeneous and dependent on plasmid size. Our results demonstrate methods of improving the limit of detection of selected resistance mechanisms in a fecal resistome assay, but they also highlight the difficulties in using these techniques for accurate quantification and should inform future efforts to achieve this goal.

'Caveat emptor': the cautionary tale of endocarditis and the potential pitfalls of clinical coding data-an electronic health records study.

BACKGROUND: Diagnostic codes from electronic health records are widely used to assess patterns of disease. Infective endocarditis is an uncommon but serious infection, with objective diagnostic criteria. Electronic health records have been used to explore the impact of changing guidance on antibiotic prophylaxis for dental procedures on incidence, but limited data on the accuracy of the diagnostic codes exists. Endocarditis was used as a clinically relevant case study to investigate the relationship between clinical cases and diagnostic codes, to understand discrepancies and to improve design of future studies. METHODS: Electronic health record data from two UK tertiary care centres were linked with data from a prospectively collected clinical endocarditis service database (Leeds Teaching Hospital) or retrospective clinical audit and microbiology laboratory blood culture results (Oxford University Hospitals Trust). The relationship between diagnostic codes for endocarditis and confirmed clinical cases according to the objective Duke criteria was assessed, and impact on estimations of disease incidence and trends. RESULTS: In Leeds 2006-2016, 738/1681(44%) admissions containing any endocarditis code represented a definite/possible case, whilst 263/1001(24%) definite/possible endocarditis cases had no endocarditis code assigned. In Oxford 2010-2016, 307/552(56%) reviewed endocarditis-coded admissions represented a clinical case. Diagnostic codes used by most endocarditis studies had good positive predictive value (PPV) but low sensitivity (e.g. I33-primary 82% and 43% respectively); one (I38-secondary) had PPV under 6%. Estimating endocarditis incidence using raw admission data overestimated incidence trends twofold. Removing records with non-specific codes, very short stays and readmissions improved predictive ability. Estimating incidence of streptococcal endocarditis using secondary codes also overestimated increases in incidence over time. Reasons for discrepancies included changes in coding behaviour over time, and coding guidance allowing assignment of a code mentioning 'endocarditis' where endocarditis was never mentioned in the clinical notes. CONCLUSIONS: Commonly used diagnostic codes in studies of endocarditis had good predictive ability. Other apparently plausible codes were poorly predictive. Use of diagnostic codes without examining sensitivity and predictive ability can give inaccurate estimations of incidence and trends. Similar considerations may apply to other diseases. Health record studies require validation of diagnostic codes and careful data curation to minimise risk of serious errors.

Trends over time in Escherichia coli bloodstream infections, urinary tract infections, and antibiotic susceptibilities in Oxfordshire, UK, 1998-2016: a study of electronic health records.

BACKGROUND: Escherichia coli bloodstream infections are increasing in the UK and internationally. The evidence base to guide interventions against this major public health concern is small. We aimed to investigate possible drivers of changes in the incidence of E coli bloodstream infection and antibiotic susceptibilities in Oxfordshire, UK, over the past two decades, while stratifying for time since hospital exposure. METHODS: In this observational study, we used all available data on E coli bloodstream infections and E coli urinary tract infections (UTIs) from one UK region (Oxfordshire) using anonymised linked microbiological data and hospital electronic health records from the Infections in Oxfordshire Research Database (IORD). We estimated the incidence of infections across a two decade period and the annual incidence rate ratio (aIRR) in 2016. We modelled the data using negative binomial regression on the basis of microbiological, clinical, and health-care-exposure risk factors. We investigated infection severity, 30-day all-cause mortality, and community and hospital amoxicillin plus clavulanic acid (co-amoxiclav) use to estimate changes in bacterial virulence and the effect of antimicrobial resistance on incidence. FINDINGS: From Jan 1, 1998, to Dec 31, 2016, 5706 E coli bloodstream infections occurred in 5215 patients, and 228 376 E coli UTIs occurred in 137 075 patients. 1365 (24%) E coli bloodstream infections were nosocomial (onset >48 h after hospital admission), 1132 (20%) were quasi-nosocomial (≤30 days after discharge), 1346 (24%) were quasi-community (31-365 days after discharge), and 1863 (33%) were community (>365 days after hospital discharge). The overall incidence increased year on year (aIRR 1·06, 95% CI 1·05-1·06). In 2016, 212 (41%) of 515 E coli bloodstream infections and 3921 (28%) of 13 792 E coli UTIs were co-amoxiclav resistant. Increases in E coli bloodstream infections were driven by increases in community (aIRR 1·10, 95% CI 1·07-1·13; p<0·0001) and quasi-community (aIRR 1·08, 1·07-1·10; p<0·0001) cases. 30-day mortality associated with E coli bloodstream infection decreased over time in the nosocomial (adjusted rate ratio [RR] 0·98, 95% CI 0·96-1·00; p=0·03) group, and remained stable in the quasi-nosocomial (adjusted RR 0·98, 0·95-1·00; p=0·06), quasi-community (adjusted RR 0·99, 0·96-1·01; p=0·32), and community (adjusted RR 0·99, 0·96-1·01; p=0·21) groups. Mortality was, however, substantial at 14-25% across all hospital-exposure groups. Co-amoxiclav-resistant E coli bloodstream infections increased in all groups across the study period (by 11-18% per year, significantly faster than co-amoxiclav-susceptible E coli bloodstream infections; pheterogeneity<0·0001), as did co-amoxiclav-resistant E coli UTIs (by 14-29% per year; pheterogeneity<0·0001). Previous year co-amoxiclav use in primary-care facilities was associated with increased subsequent year community co-amoxiclav-resistant E coli UTIs (p=0·003). INTERPRETATION: Increases in E coli bloodstream infections in Oxfordshire are primarily community associated, with substantial co-amoxiclav resistance; nevertheless, we found little or no change in mortality. Focusing interventions on primary care facilities, particularly those with high co-amoxiclav use, could be effective in reducing the incidence of co-amoxiclav-resistant E coli bloodstream infections, in this region and more generally. FUNDING: National Institute for Health Research.

Bacteria on display-can we, and should we? Artistically exploring the ethics of public engagement with science in microbiology.

The field of microbiology presents unique opportunities, and accompanying challenges, for artistic collaborations. On one hand, artistic works enable exploration of the aesthetics and of issues in biomedical science and new technologies, and draw in new, non-scientific audiences. On the other hand, creating art with microbes requires rigorous consideration of health and safety. Artists working in this field, known as Bio Art, tend to want to push the boundaries of what is possible or 'known', and work with new biomedical tools as they become available. However, when an artist's proposed work is raising novel questions where the risks are not fully understood, who should decide if the benefits outweigh the consequences? The reflections of an art-collaborating scientist are related. Also, considered is how close working relationships between disciplines can enable new ethical frameworks that consider these decisions, respecting artists' endeavours as a beneficial form of research in its own right, and even learning from the rich perspectives of artists to broaden reflections on the practice of science.

Mortality risks associated with emergency admissions during weekends and public holidays: an analysis of electronic health records.

BACKGROUND: Weekend hospital admission is associated with increased mortality, but the contributions of varying illness severity and admission time to this weekend effect remain unexplored. METHODS: We analysed unselected emergency admissions to four Oxford University National Health Service hospitals in the UK from Jan 1, 2006, to Dec 31, 2014. The primary outcome was death within 30 days of admission (in or out of hospital), analysed using Cox models measuring time from admission. The primary exposure was day of the week of admission. We adjusted for multiple confounders including demographics, comorbidities, and admission characteristics, incorporating non-linearity and interactions. Models then considered the effect of adjusting for 15 common haematology and biochemistry test results or proxies for hospital workload. FINDINGS: 257 596 individuals underwent 503 938 emergency admissions. 18 313 (4·7%) patients admitted as weekday energency admissions and 6070 (5·1%) patients admitted as weekend emergency admissions died within 30 days (p<0·0001). 9347 individuals underwent 9707 emergency admissions on public holidays. 559 (5·8%) died within 30 days (p<0·0001 vs weekday). 15 routine haematology and biochemistry test results were highly prognostic for mortality. In 271 465 (53·9%) admissions with complete data, adjustment for test results explained 33% (95% CI 21 to 70) of the excess mortality associated with emergency admission on Saturdays compared with Wednesdays, 52% (lower 95% CI 34) on Sundays, and 87% (lower 95% CI 45) on public holidays after adjustment for standard patient characteristics. Excess mortality was predominantly restricted to admissions between 1100 h and 1500 h (pinteraction=0·04). No hospital workload measure was independently associated with mortality (all p values >0·06). INTERPRETATION: Adjustment for routine test results substantially reduced excess mortality associated with emergency admission at weekends and public holidays. Adjustment for patient-level factors not available in our study might further reduce the residual excess mortality, particularly as this clustered around midday at weekends. Hospital workload was not associated with mortality. Together, these findings suggest that the weekend effect arises from patient-level differences at admission rather than reduced hospital staffing or services. FUNDING: NIHR Oxford Biomedical Research Centre.

Antibiotic use and clinical outcomes in the acute setting under management by an infectious diseases acute physician versus other clinical teams: a cohort study.

OBJECTIVES: To assess the magnitude of difference in antibiotic use between clinical teams in the acute setting and assess evidence for any adverse consequences to patient safety or healthcare delivery. DESIGN: Prospective cohort study (1 week) and analysis of linked electronic health records (3 years). SETTING: UK tertiary care centre. PARTICIPANTS: All patients admitted sequentially to the acute medical service under an infectious diseases acute physician (IDP) and other medical teams during 1 week in 2013 (n=297), and 3 years 2012-2014 (n=47 585). PRIMARY OUTCOME MEASURE: Antibiotic use in days of therapy (DOT): raw group metrics and regression analysis adjusted for case mix. SECONDARY OUTCOME MEASURES: 30-day all-cause mortality, treatment failure and length of stay. RESULTS: Antibiotic use was 173 vs 282 DOT/100 admissions in the IDP versus non-IDP group. Using case mix-adjusted zero-inflated Poisson regression, IDP patients were significantly less likely to receive an antibiotic (adjusted OR=0.25 (95% CI 0.07 to 0.84), p=0.03) and received shorter courses (adjusted rate ratio (RR)=0.71 (95% CI 0.54 to 0.93), p=0.01). Clinically stable IDP patients of uncertain diagnosis were more likely to have antibiotics held (87% vs 55%; p=0.02). There was no significant difference in treatment failure or mortality (adjusted p>0.5; also in the 3-year data set), but IDP patients were more likely to be admitted overnight (adjusted OR=3.53 (95% CI 1.24 to 10.03), p=0.03) and have longer length of stay (adjusted RR=1.19 (95% CI 1.05 to 1.36), p=0.007). CONCLUSIONS: The IDP-led group used 30% less antibiotic therapy with no adverse clinical outcome, suggesting antibiotic use can be reduced safely in the acute setting. This may be achieved in part by holding antibiotics and admitting the patient for observation rather than prescribing, which has implications for costs and hospital occupancy. More information is needed to indicate whether any such longer admission will increase or decrease risk of antibiotic-resistant infections.

Increasing burden of community-acquired pneumonia leading to hospitalisation, 1998-2014.

BACKGROUND: Community-acquired pneumonia (CAP) is a major cause of mortality and morbidity in many countries but few recent large-scale studies have examined trends in its incidence. METHODS: Incidence of CAP leading to hospitalisation in one UK region (Oxfordshire) was calculated over calendar time using routinely collected diagnostic codes, and modelled using piecewise-linear Poisson regression. Further models considered other related diagnoses, typical administrative outcomes, and blood and microbiology test results at admission to determine whether CAP trends could be explained by changes in case-mix, coding practices or admission procedures. RESULTS: CAP increased by 4.2%/year (95% CI 3.6 to 4.8) from 1998 to 2008, and subsequently much faster at 8.8%/year (95% CI 7.8 to 9.7) from 2009 to 2014. Pneumonia-related conditions also increased significantly over this period. Length of stay and 30-day mortality decreased slightly in later years, but the proportions with abnormal neutrophils, urea and C reactive protein (CRP) did not change (p>0.2). The proportion with severely abnormal CRP (>100 mg/L) decreased slightly in later years. Trends were similar in all age groups. Streptococcus pneumoniae was the most common causative organism found; however other organisms, particularly Enterobacteriaceae, increased in incidence over the study period (p<0.001). CONCLUSIONS: Hospitalisations for CAP have been increasing rapidly in Oxfordshire, particularly since 2008. There is little evidence that this is due only to changes in pneumonia coding, an ageing population or patients with substantially less severe disease being admitted more frequently. Healthcare planning to address potential further increases in admissions and consequent antibiotic prescribing should be a priority.

Survey of medical students' use of social media.

BACKGROUND: Medical students are not sufficiently knowledgeable about the dangers of online social media, and education about how to use it responsibly may be beneficial. METHODS: We conducted an online questionnaire to assess whether or not medical students in years 2-6 of study at the University of Oxford would intuitively know what doctors should and should not do on social media. We also assessed whether the study intervention of sending out guidance about appropriate use of social media published by the UK General Medical Council (GMC) would improve students' knowledge of how to use social media correctly. RESULTS: We found that, although social media use was widespread among medical students, the majority were unaware of GMC guidance on this issue. Administration of GMC guidance significantly improved the proportion of GMC-correct responses in four of 16 questionnaire items. Medical students are not sufficiently knowledgeable about the dangers of online social media DISCUSSION: It is possible that educating medical students about the dangers of online social media, and how to use it appropriately, could be worthwhile.