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Background: Randomised trials are essential to reliably assess medical interventions. Nevertheless, interpretation of such studies, particularly when considering absolute effects, is enhanced by understanding how the trial population may differ from the populations it aims to represent. Methods: We compared baseline characteristics and mortality of RECOVERY participants recruited in England (n = 38,510) with a reference population hospitalised with COVID-19 in England (n = 346,271) from March 2020 to November 2021. We used linked hospitalisation and mortality data for both cohorts to extract demographics, comorbidity/frailty scores, and crude and age- and sex-adjusted 28-day all-cause mortality. Results: Demographics of RECOVERY participants were broadly similar to the reference population, but RECOVERY participants were younger (mean age [standard deviation]: RECOVERY 62.6 [15.3] vs reference 65.7 [18.5] years) and less frequently female (37% vs 45%). Comorbidity and frailty scores were lower in RECOVERY, but differences were attenuated after age stratification. Age- and sex-adjusted 28-day mortality declined over time but was similar between cohorts across the study period (RECOVERY 23.7% [95% confidence interval: 23.3–24.1%]; vs reference 24.8% [24.6–25.0%]), except during the first pandemic wave in the UK (March–May 2020) when adjusted mortality was lower in RECOVERY. Conclusions: Adjusted 28-day mortality in RECOVERY was similar to a nationwide reference population of patients admitted with COVID-19 in England during the same period but varied substantially over time in both cohorts. Therefore, the absolute effect estimates from RECOVERY were broadly applicable to the target population at the time but should be interpreted in the light of current mortality estimates. Trial registration: ISRCTN50189673- Feb. 04, 2020, NCT04381936- May 11, 2020. [ABSTRACT FROM AUTHOR]

Objectives: Initiatives to curb hospital antibiotic use might be associated with harm from under-treatment. We examined the extent to which variation in hospital antibiotic prescribing is associated with mortality risk in acute/general medicine inpatients.Methods: This ecological analysis examined Hospital Episode Statistics from 36,124,372 acute/general medicine admissions (≥16y) to 135 acute hospitals in England, 01/April/2010-31/March/2017. Random-effects meta-regression was used to investigate whether heterogeneity in adjusted 30-day mortality was associated with hospital-level antibiotic use, measured in defined-daily-doses (DDD)/1,000 bed-days. Models also considered DDDs/1,000 admissions and DDDs for narrow-spectrum/broad-spectrum antibiotics, parenteral/oral, and local interpretations of World Health Organization Access, Watch, and Reserve antibiotics.Results: Hospital-level antibiotic DDDs/1,000 bed-days varied 15-fold with comparable variation in broad-spectrum, parenteral, and Reserve antibiotic use. After extensive adjusting for hospital case-mix, the probability of 30-day mortality changed -0.010% (95% CI: -0.064,+0.044) for each increase of 500 hospital-level antibiotic DDDs/1,000 bed-days. Analyses of other metrics of antibiotic use showed no consistent association with mortality risk.Conclusions: We found no evidence that wide variation in hospital antibiotic use is associated with adjusted mortality risk in acute/general medicine inpatients. Using low-prescribing hospitals as benchmarks could help drive safe and substantial reductions in antibiotic consumption of up-to one-third in this population. [ABSTRACT FROM AUTHOR]

Background: Deciding whether to discontinue antibiotics at early review is a cornerstone of hospital antimicrobial stewardship practice worldwide. In England, this approach is described in government guidance ('Start Smart then Focus'). However, < 10% of hospital antibiotic prescriptions are discontinued at review, despite evidence that 20-30% could be discontinued safely. We aimed to quantify the relative importance of factors influencing prescriber decision-making at review.Methods: We conducted an online choice experiment, a survey method to elicit preferences. Acute/general hospital prescribers in England were asked if they would continue or discontinue antibiotic treatment in 15 hypothetical scenarios. Scenarios were described according to six attributes, including patients' presenting symptoms and whether discontinuation would conflict with local prescribing guidelines. Respondents' choices were analysed using conditional logistic regression.Results: One hundred respondents completed the survey. Respondents were more likely to continue antibiotics when discontinuation would 'strongly conflict' with local guidelines (average marginal effect (AME) on the probability of continuing + 0.194 (p < 0.001)), when presenting symptoms more clearly indicated antibiotics (AME of urinary tract infection symptoms + 0.173 (p < 0.001) versus unclear symptoms) and when patients had severe frailty/comorbidities (AME = + 0.101 (p < 0.001)). Respondents were less likely to continue antibiotics when under no external pressure to continue (AME = - 0.101 (p < 0.001)). Decisions were also influenced by the risks to patient health of continuing/discontinuing antibiotic treatment.Conclusions: Guidelines that conflict with antibiotic discontinuation (e.g. pre-specify fixed durations) may discourage safe discontinuation at review. In contrast, guidelines conditional on patient factors/treatment response could help hospital prescribers discontinue antibiotics if diagnostic information suggesting they are no longer needed is available. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Hospital performance is often measured using self-reported statistics, such as the incidence of hospital-transmitted micro-organisms or those exhibiting antimicrobial resistance (AMR), encouraging hospitals with high levels to improve their performance. However, hospitals that increase screening efforts will appear to have a higher incidence and perform poorly, undermining comparison between hospitals and disincentivising testing, thus hampering infection control. We propose a surveillance system in which hospitals test patients previously discharged from other hospitals and report observed cases. Using English National Health Service (NHS) Hospital Episode Statistics data, we analysed patient movements across England and assessed the number of hospitals required to participate in such a reporting scheme to deliver robust estimates of incidence. With over 1.2 million admissions to English hospitals previously discharged from other hospitals annually, even when only a fraction of hospitals (41/155) participate (each screening at least 1000 of these admissions), the proposed surveillance system can estimate incidence across all hospitals. By reporting on other hospitals, the reporting of incidence is separated from the task of improving own performance. Therefore the incentives for increasing performance can be aligned to increase (rather than decrease) screening efforts, thus delivering both more comparable figures on the AMR problems across hospitals and improving infection control efforts. [ABSTRACT FROM AUTHOR]

Despite the importance of seeking children's views in healthcare being widely recognised, there are few reports of child service user involvement in selecting children's nursing students. At Oxford Brookes University, the children's nursing team has had three years' experience of partnership with a local primary school where children have engaged in the selection of children's nursing students. At the end of the first year of the initiative an evaluation was undertaken to elicit the children's views about their experience of participating in an interview day. A modified nominal group technique was used to elicit feedback. The children reported positive experiences of writing and asking interview questions, and of engaging in skills lab activities, although they found aspects of the experience challenging. The findings were similar to those in the literature on this topic. Feedback from the evaluation was incorporated into children's involvement in the subsequent two years of this initiative. Partnerships between universities and schools can have many mutually beneficial outcomes, but good preparation, support and ongoing evaluation are needed to ensure children's best interests are safeguarded. Recommendations for future research are also proposed. [ABSTRACT FROM AUTHOR]

Background: To combat the spread of antimicrobial resistance (AMR), hospitals are advised to screen high-risk patients for carriage of antibiotic-resistant bacteria on admission. This often includes patients previously admitted to hospitals with a high AMR prevalence. However, the ability of such a strategy to identify introductions (and hence prevent onward transmission) is unclear, as it depends on AMR prevalence in each hospital, the number of patients moving between hospitals, and the number of hospitals considered 'high risk'.Methods: We tracked patient movements using data from the National Health Service of England Hospital Episode Statistics and estimated differences in regional AMR prevalences using, as an exemplar, data collected through the national reference laboratory service of Public Health England on carbapenemase-producing Enterobacteriaceae (CPE) from 2008 to 2014. Combining these datasets, we calculated expected CPE introductions into hospitals from across the hospital network to assess the effectiveness of admission screening based on defining high-prevalence hospitals as high risk.Results: Based on numbers of exchanged patients, the English hospital network can be divided into 14 referral regions. England saw a sharp increase in numbers of CPE isolates referred to the national reference laboratory over 7 years, from 26 isolates in 2008 to 1649 in 2014. Large regional differences in numbers of confirmed CPE isolates overlapped with regional structuring of patient movements between hospitals. However, despite these large differences in prevalence between regions, we estimated that hospitals received only a small proportion (1.8%) of CPE-colonised patients from hospitals outside their own region, which decreased over time.Conclusions: In contrast to the focus on import screening based on assigning a few hospitals as 'high risk', patient transfers between hospitals with small AMR problems in the same region often pose a larger absolute threat than patient transfers from hospitals in other regions with large problems, even if the prevalence in other regions is orders of magnitude higher. Because the difference in numbers of exchanged patients, between and within regions, was mostly larger than the difference in CPE prevalence, it would be more effective for hospitals to focus on their own populations or region to inform control efforts rather than focussing on problems elsewhere. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The article presents two parallel epidemiological investigations of the prevalence of alcoholism in the same London borough, England. The first is an inquiry into several reporting agencies such as courts, clergy or employers the number of cases of individuals with drinking problems coming to their notice within the period of April 1, 1965 to March 31, 1966, while the second study involved a house-to-house interviewing of subjects' own report of troubles experienced with drinking during the previous 12 months. The reporting agency surveys revealed an overall prevalence rate of 4.7 percent per 1,000 adults aged over 16. The house-to-house survey gave an overall prevalence rate of 31.3 percent of problem drinking per 1,000 adults aged 18.

Objective To assess the feasibility and acceptability of randomizing the phased introduction of the extension of the invited age range in the National Health Service (NHS) Breast Screening Programme in England from 50-70 to 47-73 years. Setting Six volunteer breast screening units (BSUs) in England. Methods Cluster-randomized trial of invitation versus no invitation for breast screening. Study participants: women aged 47-49 and 71-73 years in screening batches randomized between 1 June 2009 and 31 May 2010. Outcomes: workload, screening uptake among women invited, self-referrals among women not invited, and screening outcomes among women invited. Results A total of 312 screening batches (clusters) were randomized including 60,708 women. Screening uptake was 63% in women aged 47-49 and 62% in women aged 71-73. Those who attended screening in the younger age group were more likely to be recalled for assessment than older attendees (7.5% vs. 3.0%) but less likely to be diagnosed with breast cancer (0.5% vs. 1.1%). Among women not invited, 0.2% of those aged 47-49 and 6.8% of those aged 71-73 self-referred for screening. Despite the extra workload BSUs largely coped although there was some slippage in round lengths and other targets. Conclusion No major problems of feasibility or acceptability of randomization were found. This pilot study has informed the randomized phasing-in of the age extension across the whole of England. [ABSTRACT FROM AUTHOR]

Background. A defined geographical area (Oxford, United Kingdom) was investigated for the role of group B Streptococcus (GBS) as a human pathogen. Methods. GBS carriage in pregnant women and invasive disease in neonates and adults >60 years of age was studied over a 3-year period. Multilocus sequence typing and capsular serotyping were used to study 369 isolates of GBS from carriage in pregnant women ( ) and invasive disease in neonates (n = 109) and adults >60 years of age (n = 70). Results. A total of 20.3% of pregnant women carried GBS. Invasive GBS disease occurred at a rate of 0.9 cases per 1000 live births and 11 cases per 100,000 population >60 years of age per annum. Four sequence types (STs) (ST-17, ST-19, ST-23, and ST-1) that were identified with use of multilocus sequence typing accounted for >50% of carried and invasive strains. A single sequence type (ST-17), previously shown to be phylogenetically of bovine origin, was significantly associated with increased invasiveness in neonates (P = .00002), and this was independent of capsular serotype III. In contrast, among adults >60 years of age, no STs exhibited increased invasiveness, compared with STs carried in pregnant women. Conclusions. Enhanced invasiveness associated with ST-17 is specific to neonates and is independent of capsular serotype. [ABSTRACT FROM AUTHOR]

Compares Streptococcus pneumoniae isolates causing invasive disease with those from nasopharyngeal carriage among children in Oxford, England with the use of multilocus sequence typing. Relation of the prevalence of individual clones and serotypes among isolates from invasive disease to their prevalence in carriage; Variations in the ability of all major carried clones and serotypes to cause invasive disease.

Focuses on the epidemiological study of the early stages of the development of chronic obstructive pulmonary disease performed on London working men in England. Effects of smoking in airflow obstruction; Relation between forced expiratory volume and smoking; Risks for various men due to smoking.

Supplementing Campylobacter spp. multilocus sequence typing with nucleotide sequence typing of 3 antigen genes increased the discriminatory index achieved from 0.975 to 0.992 among 620 clinical isolates from Oxfordshire, United Kingdom. This enhanced typing scheme enabled identification of clusters and retained data required for long-range epidemiologic comparisons of isolates. [ABSTRACT FROM AUTHOR]

Examines the levels of maternal serum α-Fetoprotein (AFP) in multiple pregnancies in Oxford, England. Correlation of high levels of AFP with anencephaly and spina bifida; Sources of the increased maternal serum AFP in pregnant women; Increase in AFP levels in multiple pregnancies.

Background: Before the emergence of the B.1.617.2 (delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), vaccination reduced transmission of SARS-CoV-2 from vaccinated persons who became infected, potentially by reducing viral loads. Although vaccination still lowers the risk of infection, similar viral loads in vaccinated and unvaccinated persons who are infected with the delta variant call into question the degree to which vaccination prevents transmission.Methods: We used contact-testing data from England to perform a retrospective observational cohort study involving adult contacts of SARS-CoV-2-infected adult index patients. We used multivariable Poisson regression to investigate associations between transmission and the vaccination status of index patients and contacts and to determine how these associations varied with the B.1.1.7 (alpha) and delta variants and time since the second vaccination.Results: Among 146,243 tested contacts of 108,498 index patients, 54,667 (37%) had positive SARS-CoV-2 polymerase-chain-reaction (PCR) tests. In index patients who became infected with the alpha variant, two vaccinations with either BNT162b2 or ChAdOx1 nCoV-19 (also known as AZD1222), as compared with no vaccination, were independently associated with reduced PCR positivity in contacts (adjusted rate ratio with BNT162b2, 0.32; 95% confidence interval [CI], 0.21 to 0.48; and with ChAdOx1 nCoV-19, 0.48; 95% CI, 0.30 to 0.78). Vaccine-associated reductions in transmission of the delta variant were smaller than those with the alpha variant, and reductions in transmission of the delta variant after two BNT162b2 vaccinations were greater (adjusted rate ratio for the comparison with no vaccination, 0.50; 95% CI, 0.39 to 0.65) than after two ChAdOx1 nCoV-19 vaccinations (adjusted rate ratio, 0.76; 95% CI, 0.70 to 0.82). Variation in cycle-threshold (Ct) values (indicative of viral load) in index patients explained 7 to 23% of vaccine-associated reductions in transmission of the two variants. The reductions in transmission of the delta variant declined over time after the second vaccination, reaching levels that were similar to those in unvaccinated persons by 12 weeks in index patients who had received ChAdOx1 nCoV-19 and attenuating substantially in those who had received BNT162b2. Protection in contacts also declined in the 3-month period after the second vaccination.Conclusions: Vaccination was associated with a smaller reduction in transmission of the delta variant than of the alpha variant, and the effects of vaccination decreased over time. PCR Ct values at diagnosis of the index patient only partially explained decreased transmission. (Funded by the U.K. Government Department of Health and Social Care and others.). [ABSTRACT FROM AUTHOR]

Background: Health-care workers have been implicated in nosocomial outbreaks of Staphylococcus aureus, but the dearth of evidence from non-outbreak situations means that routine health-care worker screening and S aureus eradication are controversial. We aimed to determine how often S aureus is transmitted from health-care workers or the environment to patients in an intensive care unit (ICU) and a high-dependency unit (HDU) where standard infection control measures were in place.Methods: In this longitudinal cohort study, we systematically sampled health-care workers, the environment, and patients over 14 months at the ICU and HDU of the Royal Sussex County Hospital, Brighton, England. Nasal swabs were taken from health-care workers every 4 weeks, bed spaces were sampled monthly, and screening swabs were obtained from patients at admission to the ICU or HDU, weekly thereafter, and at discharge. Isolates were cultured and their whole genome sequenced, and we used the threshold of 40 single-nucleotide variants (SNVs) or fewer to define subtypes and infer recent transmission.Findings: Between Oct 31, 2011, and Dec 23, 2012, we sampled 198 health-care workers, 40 environmental locations, and 1854 patients; 1819 isolates were sequenced. Median nasal carriage rate of S aureus in health-care workers at 4-weekly timepoints was 36·9% (IQR 35·7-37·3), and 115 (58%) health-care workers had S aureus detected at least once during the study. S aureus was identified in 8-50% of environmental samples. 605 genetically distinct subtypes were identified (median SNV difference 273, IQR 162-399) at a rate of 38 (IQR 34-42) per 4-weekly cycle. Only 25 instances of transmission to patients (seven from health-care workers, two from the environment, and 16 from other patients) were detected.Interpretation: In the presence of standard infection control measures, health-care workers were infrequently sources of transmission to patients. S aureus epidemiology in the ICU and HDU is characterised by continuous ingress of distinct subtypes rather than transmission of genetically related strains.Funding: UK Medical Research Council, Wellcome Trust, Biotechnology and Biological Sciences Research Council, UK National Institute for Health Research, and Public Health England. [ABSTRACT FROM AUTHOR]