Risk of multiple sclerosis in individuals with infectious mononucleosis: a national population-based cohort study using hospital records in England, 2003-2023.

BACKGROUND: Epstein-Barr virus (EBV) is thought to be a necessary causative agent in the development of multiple sclerosis (MS). Infectious mononucleosis (IM), which occurs up to 70% of adolescents and young adults with primary EBV infection, appears to be a further risk factor but few studies have been highly powered enough to explore this association by time since IM diagnosis. OBJECTIVE: The objective was to quantify the risk of MS in individuals with IM compared with the general population, with particular focus on time since IM diagnosis. METHODS: In this retrospective cohort study using English national Hospital Episode Statistics from 2003 to 2023, patients with a hospital diagnosis of IM were compared with the general population for MS incidence. RESULTS: MS incidence in patients with IM was nearly three times higher than the general population after multivariable adjustment (adjusted hazard ratio = 2.8, 95% confidence interval (CI = 2.3-3.4), driven by strong associations at long time intervals (>5 years) between IM diagnosis and subsequent MS diagnosis. CONCLUSION: While EBV infection may be a prerequisite for MS, the disease process of IM (i.e. the body's defective immune response to primary EBV infection) seems to be, in addition, implicated over the long term.

Relative contribution of trends in myocardial infarction event rates and case fatality to declines in mortality: an international comparative study of 1·95 million events in 80·4 million people in four countries.

BACKGROUND: Myocardial infarction mortality has declined since the 1970s, but contemporary drivers of this trend remain unexplained. The aim of this study was to compare the contribution of trends in event rates and case fatality to declines in myocardial infarction mortality in four high-income jurisdictions from 2002-15. METHODS: Linked hospitalisation and mortality data were obtained from New South Wales (NSW), Australia; Ontario, Canada; New Zealand; and England, UK. People aged between 30 years and 105 years were included in the study. Age-adjusted trends in myocardial infarction event rates and case fatality were estimated from Poisson and binomial regression models, and their relative contribution to trends in myocardial infarction mortality calculated. FINDINGS: 1 947 895 myocardial infarction events from a population of 80·4 million people were identified in people aged 30 years or older. There were significant declines in myocardial infarction mortality, event rates, and case fatality in all jurisdictions. Age-standardised myocardial infarction event rates were highest in New Zealand (men 893/100 000 person-years in 2002, 536/100 000 person-years in 2015; women 482/100 000 person-years in 2002, 271/100 000 person-years in 2015) and lowest in England (men 513/100 000 person-years in 2002, 382/100 000 person-years in 2015; women 238/100 000 person-years in 2002, 173/100 000 person-years in 2015). Annual age-adjusted reductions in event rates ranged from -2·6% (95% CI -3·0 to -2·3) in men in England to -4·3% (-4·4 to -4·1) in women in Ontario. Age-standardised case fatality was highest in England in 2002 (48%), but declined at a greater rate than in the other jurisdictions (men -4·1%/year, 95% CI -4·2 to -4·0%; women -4·4%/year, -4·5 to -4·3%). Declines in myocardial infarction mortality rates ranged from -6·1%/year to -7·6%/year. Event rate declines were the greater contributor to myocardial infarction mortality reductions in Ontario (69·4% for men and women), New Zealand (men 68·4%; women 67·5%), and NSW women (60·1%), whereas reductions in case fatality were the greater contributor in England (60% in men and women) and for NSW men (54%). There were greater contributions from case fatality than event rate reductions in people younger than 55 years in all jurisdictions, with contributions to mortality declines varying by country in those aged 55-74 years. Event rate declines had a greater impact than changes in case fatality in those aged 75 years and older. INTERPRETATION: While the mortality burden of myocardial infarction has continued to fall across these four populations, the relative contribution of trends in myocardial infarction event rates and case fatality to declining mortality varied between jurisdictions, including by age and sex. Understanding the causes of this variation will enable optimisation of prevention and treatment efforts. FUNDING: National Health and Medical Research Council, Australia; Australian Research Council; Health Research Council of New Zealand; Canadian Institutes of Health Research, Canada; National Institute for Health Research, UK.

Indirect effects of the covid-19 pandemic on childhood infection in England: population based observational study.

OBJECTIVE: To assess the impact of the covid-19 pandemic on hospital admission rates and mortality outcomes for childhood respiratory infections, severe invasive infections, and vaccine preventable disease in England. DESIGN: Population based observational study of 19 common childhood respiratory, severe invasive, and vaccine preventable infections, comparing hospital admission rates and mortality outcomes before and after the onset of the pandemic in England. SETTING: Hospital admission data from every NHS hospital in England from 1 March 2017 to 30 June 2021 with record linkage to national mortality data. POPULATION: Children aged 0-14 years admitted to an NHS hospital with a selected childhood infection from 1 March 2017 to 30 June 2021. MAIN OUTCOME MEASURES: For each infection, numbers of hospital admissions every month from 1 March 2017 to 30 June 2021, percentage changes in the number of hospital admissions before and after 1 March 2020, and adjusted odds ratios to compare 60 day case fatality outcomes before and after 1 March 2020. RESULTS: After 1 March 2020, substantial and sustained reductions in hospital admissions were found for all but one of the 19 infective conditions studied. Among the respiratory infections, the greatest percentage reductions were for influenza (mean annual number admitted between 1 March 2017 and 29 February 2020 was 5379 and number of children admitted from 1 March 2020 to 28 February 2021 was 304, 94% reduction, 95% confidence interval 89% to 97%), and bronchiolitis (from 51 655 to 9423, 82% reduction, 95% confidence interval 79% to 84%). Among the severe invasive infections, the greatest reduction was for meningitis (50% reduction, 47% to 52%). For the vaccine preventable infections, reductions ranged from 53% (32% to 68%) for mumps to 90% (80% to 95%) for measles. Reductions were seen across all demographic subgroups and in children with underlying comorbidities. Corresponding decreases were also found for the absolute numbers of 60 day case fatalities, although the proportion of children admitted for pneumonia who died within 60 days increased (age-sex adjusted odds ratio 1.71, 95% confidence interval 1.43 to 2.05). More recent data indicate that some respiratory infections increased to higher levels than usual after May 2021. CONCLUSIONS: During the covid-19 pandemic, a range of behavioural changes (adoption of non-pharmacological interventions) and societal strategies (school closures, lockdowns, and restricted travel) were used to reduce transmission of SARS-CoV-2, which also reduced admissions for common and severe childhood infections. Continued monitoring of these infections is required as social restrictions evolve.

New dimensions for hospital services and early detection of disease: a Review from the Lancet Commission into liver disease in the UK.

This Review, in addressing the unacceptably high mortality of patients with liver disease admitted to acute hospitals, reinforces the need for integrated clinical services. The masterplan described is based on regional, geographically sited liver centres, each linked to four to six surrounding district general hospitals-a pattern of care similar to that successfully introduced for stroke services. The plan includes the establishment of a lead and deputy lead clinician in each acute hospital, preferably a hepatologist or gastroenterologist with a special interest in liver disease, who will have prime responsibility for organising the care of admitted patients with liver disease on a 24/7 basis. Essential for the plan is greater access to intensive care units and high-dependency units, in line with the reconfiguration of emergency care due to the COVID-19 pandemic. This Review strongly recommends full implementation of alcohol care teams in hospitals and improved working links with acute medical services. We also endorse recommendations from paediatric liver services to improve overall survival figures by diagnosing biliary atresia earlier based on stool colour charts and better caring for patients with impaired cognitive ability and developmental mental health problems. Pilot studies of earlier diagnosis have shown encouraging progress, with 5-6% of previously undiagnosed cases of severe fibrosis or cirrhosis identified through use of a portable FibroScan in primary care. Similar approaches to the detection of early asymptomatic disease are described in accounts from the devolved nations, and the potential of digital technology in improving the value of clinical consultation and screening programmes in primary care is highlighted. The striking contribution of comorbidities, particularly obesity and diabetes (with excess alcohol consumption known to be a major factor in obesity), to mortality in COVID-19 reinforces the need for fiscal and other long delayed regulatory measures to reduce the prevalence of obesity. These measures include the food sugar levy and the introduction of the minimum unit price policy to reduce alcohol consumption. Improving public health, this Review emphasises, will not only mitigate the severity of further waves of COVID-19, but is crucial to reducing the unacceptable burden from liver disease in the UK.

Impact of the COVID-19 pandemic on the detection and management of colorectal cancer in England: a population-based study.

BACKGROUND: There are concerns that the COVID-19 pandemic has had a negative effect on cancer care but there is little direct evidence to quantify any effect. This study aims to investigate the impact of the COVID-19 pandemic on the detection and management of colorectal cancer in England. METHODS: Data were extracted from four population-based datasets spanning NHS England (the National Cancer Cancer Waiting Time Monitoring, Monthly Diagnostic, Secondary Uses Service Admitted Patient Care and the National Radiotherapy datasets) for all referrals, colonoscopies, surgical procedures, and courses of rectal radiotherapy from Jan 1, 2019, to Oct 31, 2020, related to colorectal cancer in England. Differences in patterns of care were investigated between 2019 and 2020. Percentage reductions in monthly numbers and proportions were calculated. FINDINGS: As compared to the monthly average in 2019, in April, 2020, there was a 63% (95% CI 53-71) reduction (from 36 274 to 13 440) in the monthly number of 2-week referrals for suspected cancer and a 92% (95% CI 89-95) reduction in the number of colonoscopies (from 46 441 to 3484). Numbers had just recovered by October, 2020. This resulted in a 22% (95% CI 8-34) relative reduction in the number of cases referred for treatment (from a monthly average of 2781 in 2019 to 2158 referrals in April, 2020). By October, 2020, the monthly rate had returned to 2019 levels but did not exceed it, suggesting that, from April to October, 2020, over 3500 fewer people had been diagnosed and treated for colorectal cancer in England than would have been expected. There was also a 31% (95% CI 19-42) relative reduction in the numbers receiving surgery in April, 2020, and a lower proportion of laparoscopic and a greater proportion of stoma-forming procedures, relative to the monthly average in 2019. By October, 2020, laparoscopic surgery and stoma rates were similar to 2019 levels. For rectal cancer, there was a 44% (95% CI 17-76) relative increase in the use of neoadjuvant radiotherapy in April, 2020, relative to the monthly average in 2019, due to greater use of short-course regimens. Although in June, 2020, there was a drop in the use of short-course regimens, rates remained above 2019 levels until October, 2020. INTERPRETATION: The COVID-19 pandemic has led to a sustained reduction in the number of people referred, diagnosed, and treated for colorectal cancer. By October, 2020, achievement of care pathway targets had returned to 2019 levels, albeit with smaller volumes of patients and with modifications to usual practice. As pressure grows in the NHS due to the second wave of COVID-19, urgent action is needed to address the growing burden of undetected and untreated colorectal cancer in England. FUNDING: Cancer Research UK, the Medical Research Council, Public Health England, Health Data Research UK, NHS Digital, and the National Institute for Health Research Oxford Biomedical Research Centre.

Group B Streptococcal Disease in England (1998 - 2017): A Population-based Observational Study.

BACKGROUND AND OBJECTIVES: Group B Streptococcus (GBS) is the leading cause of sepsis and meningitis in infants <90 days. In this study, the burden of GBS disease and mortality in young infants in England was assessed. METHODS: Using linked hospitalization records from every National Health Service (NHS) hospital from April 1, 1998 to March 31, 2017, we calculated annual GBS incidence in infants aged <90 days and, using regression models, compared their perinatal factors, rates of hospital-recorded disease outcomes, and all-cause infant mortality rates with those of the general infant population. RESULTS: 15 429 infants aged <90 days had a hospital-recorded diagnosis of GBS, giving an average annual incidence of 1.28 per 1000 live births (95% CI 1.26-1.30) with no significant trend over time. GBS-attributable mortality declined significantly from 0.044 (95% CI .029-.065) per 1000 live births in 2001 to 0.014 (95% CI .010-.026) in 2017 (annual percentage change -6.6, 95% CI -9.1 to -4.0). Infants with GBS had higher relative rates of visual impairment (HR 7.0 95% CI 4.1-12.1), cerebral palsy (HR 9.3 95% CI 6.6-13.3), hydrocephalus (HR 17.3 95% CI 13.8-21.6), and necrotizing enterocolitis (HR 18.8 95% CI 16.7-21.2) compared with those without GBS. CONCLUSIONS: Annual rates of GBS disease in infants have not changed over 19 years. The reduction in mortality is likely multifactorial and due to widespread implementation of antibiotics in at-risk mothers and babies, as well as advances in managing acutely unwell infants. New methods for prevention, such as maternal vaccination, must be prioritized.

Mode of birth and risk of infection-related hospitalisation in childhood: A population cohort study of 7.17 million births from 4 high-income countries.

BACKGROUND: The proportion of births via cesarean section (CS) varies worldwide and in many countries exceeds WHO-recommended rates. Long-term health outcomes for children born by CS are poorly understood, but limited data suggest that CS is associated with increased infection-related hospitalisation. We investigated the relationship between mode of birth and childhood infection-related hospitalisation in high-income countries with varying CS rates. METHODS AND FINDINGS: We conducted a multicountry population-based cohort study of all recorded singleton live births from January 1, 1996 to December 31, 2015 using record-linked birth and hospitalisation data from Denmark, Scotland, England, and Australia (New South Wales and Western Australia). Birth years within the date range varied by site, but data were available from at least 2001 to 2010 for each site. Mode of birth was categorised as vaginal or CS (emergency/elective). Infection-related hospitalisations (overall and by clinical type) occurring after the birth-related discharge date were identified in children until 5 years of age by primary/secondary International Classification of Diseases, 10th Revision (ICD-10) diagnosis codes. Analysis used Cox regression models, adjusting for maternal factors, birth parameters, and socioeconomic status, with results pooled using meta-analysis. In total, 7,174,787 live recorded births were included. Of these, 1,681,966 (23%, range by jurisdiction 17%-29%) were by CS, of which 727,755 (43%, range 38%-57%) were elective. A total of 1,502,537 offspring (21%) had at least 1 infection-related hospitalisation. Compared to vaginally born children, risk of infection was greater among CS-born children (hazard ratio (HR) from random effects model, HR 1.10, 95% confidence interval (CI) 1.09-1.12, p < 0.001). The risk was higher following both elective (HR 1.13, 95% CI 1.12-1.13, p < 0.001) and emergency CS (HR 1.09, 95% CI 1.06-1.12, p < 0.001). Increased risks persisted to 5 years and were highest for respiratory, gastrointestinal, and viral infections. Findings were comparable in prespecified subanalyses of children born to mothers at low obstetric risk and unchanged in sensitivity analyses. Limitations include site-specific and longitudinal variations in clinical practice and in the definition and availability of some data. Data on postnatal factors were not available. CONCLUSIONS: In this study, we observed a consistent association between birth by CS and infection-related hospitalisation in early childhood. Notwithstanding the limitations of observational data, the associations may reflect differences in early microbial exposure by mode of birth, which should be investigated by mechanistic studies. If our findings are confirmed, they could inform efforts to reduce elective CS rates that are not clinically indicated.

COVID-19 pandemic and admission rates for and management of acute coronary syndromes in England.

BACKGROUND: Several countries affected by the COVID-19 pandemic have reported a substantial drop in the number of patients attending the emergency department with acute coronary syndromes and a reduced number of cardiac procedures. We aimed to understand the scale, nature, and duration of changes to admissions for different types of acute coronary syndrome in England and to evaluate whether in-hospital management of patients has been affected as a result of the COVID-19 pandemic. METHODS: We analysed data on hospital admissions in England for types of acute coronary syndrome from Jan 1, 2019, to May 24, 2020, that were recorded in the Secondary Uses Service Admitted Patient Care database. Admissions were classified as ST-elevation myocardial infarction (STEMI), non-STEMI (NSTEMI), myocardial infarction of unknown type, or other acute coronary syndromes (including unstable angina). We identified revascularisation procedures undertaken during these admissions (ie, coronary angiography without percutaneous coronary intervention [PCI], PCI, and coronary artery bypass graft surgery). We calculated the numbers of weekly admissions and procedures undertaken; percentage reductions in weekly admissions and across subgroups were also calculated, with 95% CIs. FINDINGS: Hospital admissions for acute coronary syndrome declined from mid-February, 2020, falling from a 2019 baseline rate of 3017 admissions per week to 1813 per week by the end of March, 2020, a reduction of 40% (95% CI 37-43). This decline was partly reversed during April and May, 2020, such that by the last week of May, 2020, there were 2522 admissions, representing a 16% (95% CI 13-20) reduction from baseline. During the period of declining admissions, there were reductions in the numbers of admissions for all types of acute coronary syndrome, including both STEMI and NSTEMI, but relative and absolute reductions were larger for NSTEMI, with 1267 admissions per week in 2019 and 733 per week by the end of March, 2020, a percent reduction of 42% (95% CI 38-46). In parallel, reductions were recorded in the number of PCI procedures for patients with both STEMI (438 PCI procedures per week in 2019 vs 346 by the end of March, 2020; percent reduction 21%, 95% CI 12-29) and NSTEMI (383 PCI procedures per week in 2019 vs 240 by the end of March, 2020; percent reduction 37%, 29-45). The median length of stay among patients with acute coronary syndrome fell from 4 days (IQR 2-9) in 2019 to 3 days (1-5) by the end of March, 2020. INTERPRETATION: Compared with the weekly average in 2019, there was a substantial reduction in the weekly numbers of patients with acute coronary syndrome who were admitted to hospital in England by the end of March, 2020, which had been partly reversed by the end of May, 2020. The reduced number of admissions during this period is likely to have resulted in increases in out-of-hospital deaths and long-term complications of myocardial infarction and missed opportunities to offer secondary prevention treatment for patients with coronary heart disease. The full extent of the effect of COVID-19 on the management of patients with acute coronary syndrome will continue to be assessed by updating these analyses. FUNDING: UK Medical Research Council, British Heart Foundation, Public Health England, Health Data Research UK, and the National Institute for Health Research Oxford Biomedical Research Centre.

Congenital viral infections in England over five decades: a population-based observational study.

BACKGROUND: Congenital viral infections cause substantial long-term morbidity but population-based data about diagnosis rates are scarce. The aim of this study was to assess the long-term trends in congenital viral infections in England and to report on how the rates of these infections might have changed with improved methods for detection, the introduction of the two-dose measles-mumps-rubella (MMR) vaccine in 1996, and the implementation of the Newborn Hearing Screening Programme (NHSP) in 2006. METHODS: For this population-based, observational cohort study, we used national and regional hospitalisation data from 1968 to 2016 in England (Hospital In-Patient Enquiry, Hospital Episode Statistics, and Oxford Record Linkage Study) to calculate annual rates of hospital discharges coded with-and individuals aged younger than 1 month diagnosed with-congenital cytomegalovirus, herpes simplex virus (HSV), varicella zoster virus (VZV), and rubella. We investigated associations of congenital cytomegalovirus, HSV, and VZV with perinatal and maternal factors (sex, mother's ethnicity, mode of delivery, gestational age, birthweight, mother's age, mother's index of multiple deprivation, and number of previous pregnancies). FINDINGS: In 2016, discharge rates per 100 000 infant population were 22·3 (95% CI 18·8-26·1) for congenital cytomegalovirus, 17·6 (14·6-21·1) for HSV, 32·6 (28·4-37·2) for VZV, and 0·15 (0·0-0·8) for rubella. Compared with earlier years of the study, the discharge rate in 2016 was higher for congenital cytomegalovirus, HSV, and VZV, whereas it was lower for rubella. For congenital cytomegalovirus, there was a significant step-increase between 2006 and 2007 following implementation of the NHSP (rate ratio comparing the trend line post-NHSP with that pre-NHSP 1·55 [95% CI 1·12-2·14], p=0·0072). Congenital cytomegalovirus infection was associated with birthweight less than 1 kg, maternal age younger than 25 years, socioeconomically deprived households, casearean section, and mothers of black ethnicity. Congenital HSV infection was associated with maternal age younger than 20 years, gestational age less than 32 weeks, and vaginal and emergency caesarean section deliveries, while VZV infection was associated with increased parity and black and south Asian ethnicities. INTERPRETATION: The increase in hospital discharges coded with congenital cytomegalovirus is most likely due to the introduction of sensitive diagnostic techniques and retrospective diagnoses made in infants after implementation of the NHSP. Public health strategies to improve prevention and treatment of congenital viral infections are urgently warranted. The decrease in discharges for rubella is most likely due to the MMR vaccine. FUNDING: None.

Monitoring severe acute maternal morbidity across Europe: A feasibility study.

BACKGROUND: Monitoring severe acute maternal morbidity (SAMM) appears essential for optimising care and informing health care policies, especially given changes in obstetric practices and mother profiles. International comparisons can identify areas where improvement is needed, but the comparability of indicators must be evaluated. OBJECTIVE: To assess the feasibility of monitoring SAMM using common definitions from hospital discharge databases across Europe. METHODS: We used hospital discharge data in eight countries (2 826 868 deliveries) to identify women with SAMM among all hospitalisations of women of reproductive age admitted for antenatal or delivery care. Five SAMM indicators were investigated: eclampsia, septicaemia, hysterectomy, hysterectomy associated with a diagnosis of obstetric haemorrhage, and red blood cell (RBC) transfusion associated with a diagnosis of obstetric haemorrhage. Between-country variation was described, by the ratio of the highest to lowest rates, while external validation was assessed by comparing with population-based studies on maternal morbidity. RESULTS: Ratios for hysterectomy and red blood cell (RBC) transfusion in the context of obstetric haemorrhage were 1:2.1 and 1:3.5, respectively. High values of hysterectomy and low values of transfusion were both consistent with high maternal mortality from haemorrhage (France, Italy, Portugal). Ratios across countries were relatively low for eclampsia (1:3.4) but very high for septicaemia (1:22.5). Compared to population-based morbidity estimates, eclampsia was over-reported in hospital databases whereas the two indicators of severe haemorrhage had good external validity. CONCLUSIONS: In association with diagnosis codes indicating obstetric haemorrhage, hysterectomy and RBC transfusion appear to be good candidates for surveillance of maternal morbidity in Europe.

Hormone-related diseases and prostate cancer: An English national record linkage study.

Insulin-like growth factor-I (IGF-I) and testosterone may be related to prostate cancer risk. Acromegaly is associated with clinically high IGF-I concentrations. Klinefelter's syndrome, testicular hypofunction and hypopituitarism are associated with clinically low testosterone concentrations. We aimed to investigate whether diagnosis with these conditions was associated with subsequent prostate cancer diagnosis and mortality. We used linked English national Hospital Episode Statistics and mortality data from 1999 to 2017 to construct and follow-up cohorts of men aged ≥35 years diagnosed with (i) acromegaly (n = 2,495) and (ii) hypogonadal-associated diseases (n = 18,763): Klinefelter's syndrome (n = 1,992), testicular hypofunction (n = 8,086) and hypopituitarism (n = 10,331). We estimated adjusted hazard ratios (HRs) and confidence intervals (CIs) for prostate cancer diagnosis and death using Cox regression in comparison with an unexposed reference cohort of 4.3 million men, who were admitted to hospital for a range of minor surgeries and conditions (n observed cases = 130,000, n prostate cancer deaths = 30,000). For men diagnosed with acromegaly, HR for prostate cancer diagnosis was 1.33 (95% CI 1.09-1.63; p = 0.005; n observed cases = 96), HR for prostate cancer death was 1.44 (95% CI 0.92-2.26; p = 0.11; n deaths = 19). Diagnosis with Klinefelter's syndrome was associated with a lower prostate cancer risk (HR = 0.58, 95% CI 0.37-0.91; p = 0.02; n observed cases = 19) and hypopituitarism was associated with a reduction in prostate cancer death (HR = 0.53, 95% CI 0.35-0.79; p = 0.002; n deaths = 23). These results support the hypothesised roles of IGF-I and testosterone in prostate cancer development and/or progression. These findings are important because they provide insight into prostate cancer aetiology.

Comparative trends in coronary heart disease subgroup hospitalisation rates in England and Australia.

BACKGROUND: Population-based coronary heart disease (CHD) studies have focused on myocardial infarction (MI) with limited data on trends across the spectrum of CHD. We investigated trends in hospitalisation rates for acute and chronic CHD subgroups in England and Australia from 1996 to 2013. METHODS: CHD hospitalisations for individuals aged 35-84 years were identified from electronic hospital data from 1996 to 2013 for England and Australia and from the Oxford Region and Western Australia. CHD subgroups identified were acute coronary syndromes (ACS) (MI and unstable angina) and chronic CHD (stable angina and 'other CHD'). We calculated age-standardised and age-specific rates and estimated annual changes (95% CI) from age-adjusted Poisson regression. RESULTS: From 1996 to 2013, there were 4.9 million CHD hospitalisations in England and 2.6 million in Australia (67% men). From 1996 to 2003, there was between-country variation in the direction of trends in ACS and chronic CHD hospitalisation rates (p<0.001). During 2004-2013, reductions in ACS hospitalisation rates were greater than for chronic CHD hospitalisation rates in both countries, with the largest subgroup declines in unstable angina (England: men: -7.1 %/year, 95% CI -7.2 to -7.0; women: -7.5 %/year, 95% CI -7.7 to -7.3; Australia: men: -8.5 %/year, 95% CI -8.6 to -8.4; women: -8.6 %/year, 95% CI -8.8 to -8.4). Other CHD rates increased in individuals aged 75-84 years in both countries. Chronic CHD comprised half of all CHD admissions, with the majority involving angiography or percutaneous coronary intervention. CONCLUSIONS: Since 2004, rates of all CHD subgroups have fallen, with greater declines in acute than chronic presentations. The slower declines and high proportion of chronic CHD admissions undergoing coronary procedures requires greater focus.

Associations between birthweight, gestational age at birth and subsequent type 1 diabetes in children under 12: a retrospective cohort study in England, 1998-2012.

AIMS/HYPOTHESIS: With genetics thought to explain only 40-50% of the total risk of type 1 diabetes, environmental risk factors in early life have been proposed. Previous findings from studies of type 1 diabetes incidence by birthweight and gestational age at birth have been inconsistent. This study aimed to investigate the relationships between birthweight, gestational age at birth and subsequent type 1 diabetes in England. METHODS: Data were obtained from a population-based database comprising linked mother-infant pairs using English national Hospital Episode Statistics from 1998 to 2012. In total, 3,834,405 children, categorised by birthweight and gestational age at birth, were followed up through record linkage to compare their incidence of type 1 diabetes through calculation of multivariable-adjusted HRs. RESULTS: Out of 3,834,405 children, 2969 had a subsequent hospital diagnosis of type 1 diabetes in childhood. Children born preterm (<37 weeks) or early term (37-38 weeks) experienced significantly higher incidence of type 1 diabetes than full term children (39-40 weeks) (HR 1.19 [95% CI 1.03, 1.38] and 1.27 [95% CI 1.16, 1.39], respectively). Children born at higher than average birthweight (3500-3999 g or 4000-5499 g) after controlling for gestational age experienced higher incidence of type 1 diabetes than children born at medium birthweight (3000-3499 g) (HR 1.13 [95% CI 1.03, 1.23] and 1.16 [95% CI 1.02, 1.31], respectively), while children at low birthweight (<2500 g) experienced lower incidence (0.81 [95% CI 0.67, 0.98]), signifying a statistically significant trend (p trend 0.001). CONCLUSIONS/INTERPRETATION: High birthweight for gestational age and low gestational age at birth are both independently associated with subsequent type 1 diabetes. These findings help contextualise the debate about the potential role of gestational and early life environmental risk factors in the pathogenesis of type 1 diabetes, including the potential roles of insulin sensitivity and gut microbiota.

30-year trends in admission rates for encephalitis in children in England and effect of improved diagnostics and measles-mumps-rubella vaccination: a population-based observational study.

BACKGROUND: Encephalitis is a serious neurological disorder, yet data on admission rates for all-cause childhood encephalitis in England are scarce. We aimed to estimate admission rates for childhood encephalitis in England over 33 years (1979-2011), to describe trends in admission rates, and to observe how these rates have varied with the introduction of vaccines and improved diagnostics. METHODS: We did a retrospective analysis of hospital admission statistics for encephalitis for individuals aged 0-19 years using national data from the Hospital Inpatient Enquiry (HIPE, 1979-85) and Hospital Episode Statistics (HES, 1990-2011). We analysed annual age-specific and age-standardised admission rates in single calendar years and admission rate trends for specified aetiologies in relation to introduction of PCR testing and measles-mumps-rubella (MMR) vaccination. We compared admission rates between the two International Classification of Diseases (ICD) periods, ICD9 (1979-94) and ICD10 (1995-2011). FINDINGS: We found 16 571 encephalitis hospital admissions in the period 1979-2011, with a mean hospital admission rate of 5·97 per 100 000 per year (95% CI 5·52-6·41). Hospital admission rates declined from 1979 to 1994 (ICD9; annual percentage change [APC] -3·30%; 95% CI -2·88 to -3·66; p<0·0001) and increased between 1995 and 2011 (ICD10; APC 3·30%; 2·75-3·85; p<0·0001). Admissions for measles decreased by 97% (from 0·32 to 0·009) and admissions for mumps encephalitis decreased by 98% (from 0·60 to 0·01) after the introduction of the two-dose MMR vaccine. Hospital admission rates for encephalitis of unknown aetiology have increased by 37% since the introduction of PCR testing. INTERPRETATION: Hospital admission rates for all-cause childhood encephalitis in England are increasing. Admissions for measles and mumps encephalitis have decreased substantially. The numbers of encephalitis admissions without a specific diagnosis are increasing despite availability of PCR testing, indicating the need for strategies to improve aetiological diagnosis in children with encephalitis. FUNDING: None.

Hospital admissions for viral meningitis in children in England over five decades: a population-based observational study.

BACKGROUND: A substantial reduction in bacterial meningitis has occurred in the UK following successful implementation of immunisation programmes. Most childhood meningitis in developed countries is now caused by viruses. Long-term trends in paediatric viral meningitis in England have not previously been reported. The objective of this study is to report on epidemiological trends over time in childhood viral meningitis in England. METHODS: In this population-based observational study, we used routinely collected hospital discharge records from English National Health Service hospitals from 1968-2011 to analyse annual age-specific admission rates for viral meningitis, including specific viral aetiologies, in children younger than 15 years. FINDINGS: We analysed hospital discharge records from Jan 1, 1968, to Dec 31, 2011. Hospital admission rates for viral meningitis from Jan 1, 1968, to Dec 31, 1985, varied annually, with a mean of 13·5 admissions per 100 000 children aged less than 15 years, per year (95% CI 13·0-14·0). Admission rates declined during the late 1980s, and the mean number of admissions from 1989-2011 was 5·2 per 100 000 per year (5·1-5·3). This decrease was entirely in children aged 1-14 years. Admission rates for infants aged less than 1 year increased since 2005, to 70·0 per 100 000 (63·7-76·2) in 2011, which was driven by an increase in admission of infants aged 90 days or less. In 1968-85, the majority of cases in children were in those aged 1-14 years (22 150 [89%] of 24 920 admissions). In 2007-11, 1716 (72%) of 2382 cases were in infants. Admissions for mumps-related meningitis almost disappeared following introduction of the measles-mumps-rubella (MMR) vaccine in 1988. Admissions with a specified viral aetiology have increased since 2000. INTERPRETATION: Trends in viral meningitis admissions have changed substantially over the past 50 years, and probably reflect the impact of the MMR vaccine programme and the use of more sensitive diagnostic techniques. FUNDING: None.

The falling rates of hospital admission, case fatality, and population-based mortality for subarachnoid hemorrhage in England, 1999-2010.

OBJECTIVE In this study, the authors examined trends in population-based hospital admission rates, patient-level case fatality rates (CFRs), and population-based mortality rates for nontraumatic (spontaneous) subarachnoid hemorrhage (SAH) in England. METHODS Population-based admission and mortality data (59,599 people admitted to a hospital with SAH, 1999-2010; 37,836 people whose death certificates mentioned SAH, 1995-2010) were analyzed. RESULTS Hospital admission rates for SAH per million population declined by 18.3%, from 100.4 (95% CI 97.6-103.1) in 1999 to 82.0 (95% CI 79.7-84.4) in 2010. CFRs at less than 30 days per 100 patients decreased by 18.2%, from 29.7 (95% CI 28.5-31.0) in 1999 to 24.3 (95% CI 23.2-25.5) in 2010. Population-based mortality rates per million population, where SAH was recorded as underlying cause of death on the death certificate, declined by 39.8%, from 41.2 (95% CI 39.5-43.0) in 1999 to 24.8 (95% CI 23.6-26.1) in 2010. CONCLUSIONS Population-based hospital admission rates, patient-level CFRs, and population-based mortality rates all declined between 1999 and 2010. Part of the decline in mortality rates for SAH is likely to be attributable to a decline in incidence. It is also, in part, attributable to increased survival after SAH. The available data do not allow us to compare the effects of different treatment methods for SAH on case fatality and mortality. During the period of study, mortality rates declined by almost 40%, and it is likely that there are a number of factors contributing to this substantial improvement in outcomes for SAH patients in England.

Risk of fractures in patients with multiple sclerosis: record-linkage study.

BACKGROUND: Patients with multiple sclerosis (MS) have been reported to be at higher risk of fracture than other people. We sought to test this hypothesis in a large database of hospital admissions in England. METHODS: We analysed a database of linked statistical records of hospital admissions and death certificates for the whole of England (1999-2010). Rate ratios for fractures were determined, comparing fracture rates in a cohort of all people in England admitted with MS and rates in a comparison cohort. RESULTS: Significantly elevated risk for all fractures was found in patients with MS (rate ratio (RR) = 1.99, 95% confidence interval (CI) = 1.93-2.05)). Risks were particularly high for femoral fractures (femoral neck fracture RR = 2.79 (2.65-2.93); femoral shaft fracture RR 6.69 (6.12-7.29)), and fractures of the tibia or ankle RR = 2.81 (2.66-2.96). CONCLUSIONS: Patients with MS have an increased risk of fractures. Caregivers should aim to optimize bone health in MS patients.