COVID-19-related school closures and patterns of hospital admissions with stress-related presentations in secondary school-aged adolescents: weekly time series.

This study examines health service indicators of stress-related presentations (relating to pain, mental illness, psychosomatic symptoms and self-harm) in adolescents of secondary school age, using Hospital Episode Statistics data for England. We examined weekly time series data for three academic years spanning the time before (2018-2019) and during the COVID-19 pandemic (2019-2020 and 2020-2021), including the first lockdown when schools were closed to the majority of pupils. For all secondary school children, weekly stress presentations dropped following school closures. However, patterns of elevated stress during school terms re-established after reopening, with girls aged 11-15 showing an overall increase compared with pre-pandemic rates.

An informatics consult approach for generating clinical evidence for treatment decisions.

BACKGROUND: An Informatics Consult has been proposed in which clinicians request novel evidence from large scale health data resources, tailored to the treatment of a specific patient. However, the availability of such consultations is lacking. We seek to provide an Informatics Consult for a situation where a treatment indication and contraindication coexist in the same patient, i.e., anti-coagulation use for stroke prevention in a patient with both atrial fibrillation (AF) and liver cirrhosis. METHODS: We examined four sources of evidence for the effect of warfarin on stroke risk or all-cause mortality from: (1) randomised controlled trials (RCTs), (2) meta-analysis of prior observational studies, (3) trial emulation (using population electronic health records (N = 3,854,710) and (4) genetic evidence (Mendelian randomisation). We developed prototype forms to request an Informatics Consult and return of results in electronic health record systems. RESULTS: We found 0 RCT reports and 0 trials recruiting for patients with AF and cirrhosis. We found broad concordance across the three new sources of evidence we generated. Meta-analysis of prior observational studies showed that warfarin use was associated with lower stroke risk (hazard ratio [HR] = 0.71, CI 0.39-1.29). In a target trial emulation, warfarin was associated with lower all-cause mortality (HR = 0.61, CI 0.49-0.76) and ischaemic stroke (HR = 0.27, CI 0.08-0.91). Mendelian randomisation served as a drug target validation where we found that lower levels of vitamin K1 (warfarin is a vitamin K1 antagonist) are associated with lower stroke risk. A pilot survey with an independent sample of 34 clinicians revealed that 85% of clinicians found information on prognosis useful and that 79% thought that they should have access to the Informatics Consult as a service within their healthcare systems. We identified candidate steps for automation to scale evidence generation and to accelerate the return of results. CONCLUSION: We performed a proof-of-concept Informatics Consult for evidence generation, which may inform treatment decisions in situations where there is dearth of randomised trials. Patients are surprised to know that their clinicians are currently not able to learn in clinic from data on 'patients like me'. We identify the key challenges in offering such an Informatics Consult as a service.

Incidence, etiology, and outcome of bacterial meningitis in infants aged <90 days in the United kingdom and Republic of Ireland: prospective, enhanced, national population-based surveillance.

BACKGROUND: Bacterial meningitis remains a major cause of morbidity and mortality in young infants. Understanding the epidemiology and burden of disease is important. METHODS: Prospective, enhanced, national population-based active surveillance was undertaken to determine the incidence, etiology, and outcome of bacterial meningitis in infants aged <90 days in the United Kingdom and Ireland. RESULTS: During July 2010-July 2011, 364 cases were identified (annual incidence, 0.38/1000 live births; 95% confidence interval [CI], .35-.42). In England and Wales, the incidence of confirmed neonatal bacterial meningitis was 0.21 (n = 167; 95% CI, .18-.25). A total of 302 bacteria were isolated in 298 (82%) of the cases. The pathogens responsible varied by route of admission, gestation at birth, and age at infection. Group B Streptococcus (GBS) (150/302 [50%]; incidence, 0.16/1000 live births; 95% CI, .13-.18) and Escherichia coli (41/302 [14%]; incidence, 0.04/1000; 95% CI, .03-.06) were responsible for approximately two-thirds of identified bacteria. Pneumococcal (28/302 [9%]) and meningococcal (23/302 [8%]) meningitis were rare in the first month, whereas Listeria meningitis was seen only in the first month of life (11/302 [4%]). In hospitalized preterm infants, the etiology of both early- and late-onset meningitis was more varied. Overall case fatality was 8% (25/329) and was higher for pneumococcal meningitis (5/26 [19%]) than GBS meningitis (7/135 [5%]; P = .04) and for preterm (15/90 [17%]) compared with term (10/235 [4%]; P = .0002) infants. CONCLUSIONS: The incidence of bacterial meningitis in young infants remains unchanged since the 1980s and is associated with significant case fatality. Prevention strategies and guidelines to improve the early management of cases should be prioritized.

Does hospital variation in intrapartum-related perinatal mortality among caesarean births reflect differences in quality of care? Cross-sectional study in 21 hospitals in Burkina Faso.

OBJECTIVES: To examine hospital variation in crude and risk-adjusted rates of intrapartum-related perinatal mortality among caesarean births. DESIGN: Secondary analysis of data from the DECIDE (DECIsion for caesarean DElivery) cluster randomised trial postintervention phase. SETTING: 21 district and regional hospitals in Burkina Faso. PARTICIPANTS: All 5134 women giving birth by caesarean section in a 6-month period in 2016. PRIMARY OUTCOME MEASURE: Intrapartum-related perinatal mortality (fresh stillbirth or neonatal death within 24 hours of birth). RESULTS: Almost 1 in 10 of 5134 women giving birth by caesarean experienced an intrapartum-related perinatal death. Crude mortality rates varied substantially from 21 to 189 per 1000 between hospitals. Variation was markedly reduced after adjusting for case mix differences (the median OR decreased from 1.9 (95% CI 1.5 to 2.5) to 1.3 (95% CI 1.2 to 1.7)). However, higher and more variable adjusted mortality persisted among hospitals performing fewer caesareans per month. Additionally, adjusting for caesarean care components did not further reduce variation (median OR=1.4 (95% CI 1.2 to 1.8)). CONCLUSIONS: There is a high burden of intrapartum-related perinatal deaths among caesarean births in Burkina Faso and sub-Saharan Africa more widely. Variation in adjusted mortality rates indicates likely differences in quality of caesarean care between hospitals, particularly lower volume hospitals. Improving access to and quality of emergency obstetric and newborn care is an important priority for improving survival of babies at birth. TRIAL REGISTRATION NUMBER: ISRCTN48510263.

Empirical treatment of influenza-associated pneumonia in primary care: a descriptive study of the antimicrobial susceptibility of lower respiratory tract bacteria (England, Wales and Northern Ireland, January 2007-March 2010).

OBJECTIVES: To determine the susceptibility of lower respiratory tract (LRT) isolates of Streptococcus pneumoniae, Staphylococcus aureus and Haemophilus influenzae to antimicrobial agents recommended by UK guidelines for treatment of pneumonia associated with influenza-like illness. METHODS: Analysis of antimicrobial susceptibility data from sentinel microbiology laboratories in England, Wales and Northern Ireland was carried out. Subjects comprised patients who had an LRT specimen taken in a general practitioner surgery or hospital outpatient setting between January 2007 and March 2010. The main outcome measurements were antimicrobial susceptibility trends of LRT isolates over time, between patient age groups and in different geographical regions. RESULTS: Susceptibility to tetracyclines or co-amoxiclav was high. Of the 70,288 and 45,288 isolates with susceptibility results for tetracyclines or co-amoxiclav, 96% and 92%, respectively, were susceptible. Overall susceptibility to ciprofloxacin, ampicillin/amoxicillin and macrolides was lower than for tetracyclines or co-amoxiclav and varied markedly by organism. There were few clinically relevant variations in susceptibility to doxycycline or co-amoxiclav over time, geographically or between age groups. CONCLUSIONS: The data support the use of doxycycline or co-amoxiclav as appropriate empiric treatment for LRT infection caused by the pathogens investigated, for patients in primary care.

Hospital readmission among people experiencing homelessness in England: a cohort study of 2772 matched homeless and housed inpatients.

BACKGROUND: Inpatients experiencing homelessness are often discharged to unstable accommodation or the street, which may increase the risk of readmission. METHODS: We conducted a cohort study of 2772 homeless patients discharged after an emergency admission at 78 hospitals across England between November 2013 and November 2016. For each individual, we selected a housed patient who lived in a socioeconomically deprived area, matched on age, sex, hospital, and year of discharge. Counts of emergency readmissions, planned readmissions, and Accident and Emergency (A&E) visits post-discharge were derived from national hospital databases, with a median of 2.8 years of follow-up. We estimated the cumulative incidence of readmission over 12 months, and used negative binomial regression to estimate rate ratios. RESULTS: After adjusting for health measured at the index admission, homeless patients had 2.49 (95% CI 2.29 to 2.70) times the rate of emergency readmission, 0.60 (95% CI 0.53 to 0.68) times the rate of planned readmission and 2.57 (95% CI 2.41 to 2.73) times the rate of A&E visits compared with housed patients. The 12-month risk of emergency readmission was higher for homeless patients (61%, 95% CI 59% to 64%) than housed patients (33%, 95% CI 30% to 36%); and the risk of planned readmission was lower for homeless patients (17%, 95% CI 14% to 19%) than for housed patients (30%, 95% CI 28% to 32%). While the risk of emergency readmission varied with the reason for admission for housed patients, for example being higher for admissions due to cancers than for those due to accidents, the risk was high across all causes for homeless patients. CONCLUSIONS: Hospital patients experiencing homelessness have high rates of emergency readmission that are not explained by health. This highlights the need for discharge arrangements that address their health, housing and social care needs.

Nosocomial transmission of influenza: A retrospective cross-sectional study using next generation sequencing at a hospital in England (2012-2014).

BACKGROUND: The extent of transmission of influenza in hospital settings is poorly understood. Next generation sequencing may improve this by providing information on the genetic relatedness of viral strains. OBJECTIVES: We aimed to apply next generation sequencing to describe transmission in hospital and compare with methods based on routinely-collected data. METHODS: All influenza samples taken through routine care from patients at University College London Hospitals NHS Foundation Trust (September 2012 to March 2014) were included. We conducted Illumina sequencing and identified genetic clusters. We compared nosocomial transmission estimates defined using classical methods (based on time from admission to sample) and genetic clustering. We identified pairs of cases with space-time links and assessed genetic relatedness. RESULTS: We sequenced influenza sampled from 214 patients. There were 180 unique genetic strains, 16 (8.8%) of which seeded a new transmission chain. Nosocomial transmission was indicated for 32 (15.0%) cases using the classical definition and 34 (15.8%) based on genetic clustering. Of the 50 patients in a genetic cluster, 11 (22.0%) had known space-time links with other cases in the same cluster. Genetic distances between pairs of cases with space-time links were lower than for pairs without spatial links (P < .001). CONCLUSIONS: Genetic data confirmed that nosocomial transmission contributes significantly to the hospital burden of influenza and elucidated transmission chains. Prospective next generation sequencing could support outbreak investigations and monitor the impact of infection and control measures.

Causes of death among homeless people: a population-based cross-sectional study of linked hospitalisation and mortality data in England.

Background: Homelessness has increased by 165% since 2010 in England, with evidence from many settings that those affected experience high levels of mortality. In this paper we examine the contribution of different causes of death to overall mortality in homeless people recently admitted to hospitals in England with specialist integrated homeless health and care (SIHHC) schemes.  Methods: We undertook an analysis of linked hospital admission records and mortality data for people attending any one of 17 SIHHC schemes between 1st November 2013 and 30th November 2016. Our primary outcome was death, which we analysed in subgroups of 10th version international classification of disease (ICD-10) specific deaths; and deaths from amenable causes. We compared our results to a sample of people living in areas of high social deprivation (IMD5 group). Results: We collected data on 3,882 individual homeless hospital admissions that were linked to 600 deaths. The median age of death was 51.6 years (interquartile range 42.7-60.2) for SIHHC and 71.5 for the IMD5 (60.67-79.0).  The top three underlying causes of death by ICD-10 chapter in the SIHHC group were external causes of death (21.7%; 130/600), cancer (19.0%; 114/600) and digestive disease (19.0%; 114/600).  The percentage of deaths due to an amenable cause after age and sex weighting was 30.2% in the homeless SIHHC group (181/600) compared to 23.0% in the IMD5 group (578/2,512). Conclusion: Nearly one in three homeless deaths were due to causes amenable to timely and effective health care. The high burden of amenable deaths highlights the extreme health harms of homelessness and the need for greater emphasis on prevention of homelessness and early healthcare interventions.

Clinical Characteristics and Risk Factors for Poor Outcome in Infants Less Than 90 Days of Age With Bacterial Meningitis in the United Kingdom and Ireland.

BACKGROUND: To describe the clinical characteristics and risk factors associated with poor outcome in infants <90 days of age with bacterial meningitis. METHODS: Prospective, enhanced, national population-based active surveillance for infants <90 days of age with bacterial meningitis in the United Kingdom and Ireland between July 2010 and July 2011. Infants were identified through the British Paediatric Surveillance Unit, laboratory surveillance and meningitis charities. RESULTS: Clinical details was available for 263 of 298 (88%) infants where a bacterium was identified, 184 (70%) were born at term. Fever was reported in 143 (54%), seizures in 73 (28%), bulging fontanelle in 58 (22%), coma in 15 (6%) and neck stiffness in 7 (3%). Twenty-three (9%) died and 56/240 (23%) of the survivors had serious central nervous system complications at discharge. Temperature instability [odds ratio (OR), 2.99; 95% confidence interval (CI): 1.21-7.41], seizures (OR, 7.06; 95% CI: 2.80-17.81), cerebrospinal fluid protein greater than the median concentration (2275 mg/dL; OR, 2.62; 95% CI: 1.13-6.10) and pneumococcal meningitis (OR, 4.83; 95% CI: 1.33-17.58) were independently associated with serious central nervous system complications while prematurity (OR, 5.84; 95% CI: 2.02-16.85), low birthweight (OR, 8.48; 95% CI: 2.60-27.69), coma at presentation (OR, 31.85; 95% CI: 8.46-119.81) and pneumococcal meningitis (OR, 4.62; 95% CI: 1.19-17.91) were independently associated with death. CONCLUSIONS: The classic features of meningitis were uncommon. The presentation in young infants is often nonspecific, and only half of cases presented with fever. A number of clinical and laboratory factors were associated with poor outcomes; further research is required to determine how knowledge of these risk factors might improve clinical management and outcomes.

Outcomes of specialist discharge coordination and intermediate care schemes for patients who are homeless: analysis protocol for a population-based historical cohort.

INTRODUCTION: People who are homeless often experience poor hospital discharge arrangements, reflecting ongoing care and housing needs. Specialist integrated homeless health and care provision (SIHHC) schemes have been developed and implemented to facilitate the safe and timely discharge of homeless patients from hospital. Our study aims to investigate the health outcomes of patients who were homeless and seen by a selection of SIHHC services. METHODS AND ANALYSIS: Our study will employ a historical population-based cohort in England. We will examine health outcomes among three groups of adults: (1) homeless patients seen by specialist discharge schemes during their hospital admission; (2) homeless patients not seen by a specialist scheme and (3) admitted patients who live in deprived neighbourhoods and were not recorded as being homeless. Primary outcomes will be: time from discharge to next hospital inpatient admission; time from discharge to next accident and emergency attendance and 28-day emergency readmission. Outcome data will be generated through linkage to hospital admissions data (Hospital Episode Statistics) and mortality data for November 2013 to November 2016. Multivariable regression will be used to model the relationship between the study comparison groups and each of the outcomes. ETHICS AND DISSEMINATION: Approval has been obtained from the National Health Service (NHS) Confidentiality Advisory Group (reference 16/CAG/0021) to undertake this work using unconsented identifiable data. Health Research Authority Research Ethics approval (REC 16/EE/0018) has been obtained in addition to local research and development approvals for data collection at NHS sites. We will feedback the results of our study to our advisory group of people who have lived experience of homelessness and seek their suggestions on ways to improve or take this work further for their benefit. We will disseminate our findings to SIHHC schemes through a series of regional workshops.

Exploring the Epidemiology of Hospital-Acquired Bloodstream Infections in Children in England (January 2009-March 2010) by Linkage of National Hospital Admissions and Microbiological Databases.

BACKGROUND: Hospital-acquired bloodstream infection (HA-BSI) requires immediate effective antibiotic treatment. However, there are no published national data for England that describe the pathogen profile and antibiotic resistance rates of HA-BSI in children. METHODS: Probabilistic matching methods were used to link national data on microbiologically confirmed BSI to hospital in-patient admissions data for the period of January 2009-March 2010. HA-BSI was defined as a positive blood culture drawn from a child aged 1 month-18 years 2 or more days after admission (and before discharge). RESULTS: A total of 8718 episodes of BSI was reported during the study period. Linkage allowed 82% of records to be matched, of which 23% (1734) were HA-BSI, giving a rate of 4.74 per 1000 admissions. The median age of infection was 1 year, and 54% of infections were in males. Methicillin resistance was seen in 83% and 17% of coagulase-negative staphylococci and Staphylococcus aureus, respectively. Penicillin resistance was rare in pyogenic streptococci but more common in viridans streptococci (39%). Among Gram-positive organisms, only 3% were vancomycin-resistant. The overall proportion of Gram-negative bacteria resistant to recommended empirical antibiotics (meropenem or piperacillin/tazobactam) was 5% and 16%, respectively, but <4% of isolates were resistant when either of these drugs were combined with gentamicin. CONCLUSIONS: 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.

Distinguishing major-gene from field resistance to late blight (Phytophthora infestans) of potato (Solanum tuberosum) and selecting for high levels of field resistance.

Potato cultivar Stirling, which has a Solanum demissum derived R-gene and quantitative field resistance to late blight, was crossed with the susceptible cultivar Maris Piper to produce an F1 population from which three genotypes (94B13A29, 57 and 61) were backcrossed to Maris Piper. The F1 and backcross populations were assessed for resistance to simple race 1,4 (incompatible with Stirling's R-gene) and complex race 1,2,3,4,6,7 of Phytophthora infestans (compatible with R-gene) in whole plant glasshouse tests. The segregation results in the F1 generation with the simple race confirmed the presence of a single copy of the R-gene in Stirling, and the results with the complex race were consistent with Stirling having a high level of quantitatively inherited field resistance. Comparisons of the results with the simple and complex races apparently enabled F1 clones to be classified for the presence or absence of the R-gene and to be assessed for their level of quantitative field resistance. However, two out of the three backcrosses done to check classifications revealed unexpected findings: 94B13A29 had two copies of the R-gene as a result of double reduction, but was, as expected, susceptible to the complex race; and 94B13A57 had the R-gene (one copy) and it, and its offspring with the R-gene, had some resistance to the complex race, whereas those offspring without the R-gene were susceptible. Clone 94B13A61, as expected, lacked the R-gene and had moderate quantitative field resistance to both races. The implications are discussed for breeding potatoes with durable resistance to late blight.

Mapping the R10 and R11 genes for resistance to late blight (Phytophthora infestans) present in the potato (Solanum tuberosum) R-gene differentials of black.

The R10 and R11 late blight differentials of Black (tetraploid clones 3681ad1 and 5008ab6) were crossed with the susceptible potato (Solanum tuberosum) cultivar Maris Piper and the progeny were assessed for blight resistance in a whole plant glasshouse test using race 1,2,3,4,6,7 of Phytophthora infestans. The disease scores for the R10 population displayed a continuous distribution whereas the progeny in the R11 population could be categorised as resistant or susceptible. A bulk segregant analysis using amplified fragment length polymorphism assays was done on the ten most resistant and ten most susceptible progeny in each population and two closely linked markers were found to be associated with resistance. R11 mapped to 8.5 cM from marker PAG/MAAG_172.3 and R10 mapped as a quantitative trait locus in which marker PAC/MATC_264.1 explained 56.9% of the variation in disease scores. The results were consistent with R10 and R11 being allelic versions of genes at the R3 locus on chromosome 11. The implications are discussed for mapping R-genes which fail to give complete immunity to a pathogen.