Pia Hardelid

Analysis of rubella antibody distribution from newborn dried blood spots using finite mixture models

Eluted dried blood spot specimens from newborn screening, collected in 2004 in North Thames and anonymously linked to birth registration data, were tested for maternally acquired rubella IgG antibody as a proxy for maternal antibody concentration using an enzyme-linked immunosorbent assay. Finite mixture regression models were fitted to the antibody concentrations from 1964 specimens. The Bayesian Information Criterion (BIC) was used as a model selection criterion to avoid over-fitting the number of mixture model components. This allowed investigation of the independent effect of maternal age and maternal country of birth on rubella antibody concentration without dichotomizing the outcome variable using cut-off values set a priori. Mixture models are a highly useful method of analysis in seroprevalence studies of vaccine-preventable infections in which preset cut-off values may overestimate the size of the seronegative population.

Who comes back with what: a retrospective database study on reasons for emergency readmission to hospital in children and young people in England

Objective To determine the proportion of children and young people (CYP) in England who are readmitted for the same condition. Design Retrospective cohort study. Setting National administrative hospital data (Hospital Episode Statistics). Participants CYP (0-year-olds to 24-year-olds) discharged after an emergency admission to the National Health Service in England in 2009/2010. Main outcome measures Coded primary diagnosis classified in six broad groups indicating reason for admission (infection, chronic condition, injury, perinatal related or pregnancy related, sign or symptom or other). We grouped readmissions as ≤30 days or between 31 days and 2 years after the index discharge. We used multivariable logistic regression to determine factors at the index admission that were predictive of readmission within 30 days. Results 9% of CYP were readmitted within 30 days. Half of the 30-day readmissions and 40% of the recurrent admissions between 30 days and 2 years had the same primary diagnosis group as the original admission. These proportions were consistent across age, sex and diagnostic groups, except for infants and young women with pregnancy-related problems (15–24 years) who were more likely to be readmitted for the same primary diagnostic group. CYP with underlying chronic conditions were readmitted within 30 days twice as often (OR: 1.93, 95% CI 1.89 to 1.99) compared with CYP without chronic conditions. Conclusions Financial penalties for readmission are expected to incentivise more effective care of the original problem, thereby avoiding readmission. Our findings, that half of children come back with different problems, do not support this presumption.

Rubella seroprevalence in pregnant women in North Thames: estimates based on newborn screening samples

Objectives Routine screening for rubella susceptibility is recommended in the UK so that women found to be susceptible can be offered immunization in the post partum period. We demonstrate the use of newborn dried blood spot samples linked to routine vital statistics datasets to monitor rubella susceptibility in pregnant women and to investigate maternal characteristics as determinants of rubella seronegativity. Setting North Thames region of England (including large parts of inner London). Methods Maternally acquired rubella IgG antibody levels were measured in 18882 newborn screening blood spot samples. Latent class regression finite mixture models were used to classify samples as seronegative to rubella. Data on maternal country of birth were available through linkage to birth registration data. Results An estimated 2.7% (95% CI 2.4%–3.0%) of newly delivered women in North Thames were found to be seronegative. Mothers born abroad, particularly in Sub-Saharan Africa and South Asia, were more likely to be seronegative than UK-born mothers, with adjusted odds ratios of 4.2 (95% CI 3.1–5.6) and 5.0 (3.8–6.5), respectively. Mothers under 20 years were more likely to be seronegative than those aged 30 to 34. Conclusion Our findings highlight the need for vaccination to be targeted specifically at migrant women and their families to ensure that they are protected from rubella in pregnancy and its serious consequences.

Estimating the prevalence of chronic conditions in children who die in England, Scotland and Wales: a data linkage cohort study.

Objectives To estimate the proportion of children who die with chronic conditions and examine time trends in childhood deaths involving chronic conditions. Design Retrospective population-based death cohort study using linked death certificates and hospital discharge records. Setting England, Scotland and Wales. Participants All resident children who died aged 1–18 years between 2001 and 2010. Primary and secondary outcome measures The primary outcome was the proportion of children who died with chronic conditions according to age group and type of chronic condition. The secondary outcome was trends over time in mortality rates involving chronic conditions per 100 000 children and trends in the proportion of children who died with chronic conditions. Results 65.4% of 23 438 children (95% CI 64.8%, 66.0%) died with chronic conditions, using information from death certificates. This increased to 70.7% (95% CI 70.1% to 71.3%) if hospital records up to 1 year before death were also included and was highest (74.8–79.9% depending on age group) among children aged less than 15 years. Using data from death certificates only led to underascertainment of all types of chronic conditions apart from cancer/blood conditions. Neurological/sensory conditions were most common (present in 38.5%). The rate of children dying with a chronic condition has declined since 2001, whereas the proportion of deaths affected by chronic conditions remained stable. Conclusions The majority of children who died had a chronic condition. Neurological/sensory conditions were the most prevalent. Linkage between death certificate and hospital discharge data avoids some of the under-recording of non-cancer conditions on death certificates, and provides a low-cost, population-based method for monitoring chronic conditions in children who die.

Recording of Influenza-Like Illness in UK Primary Care 1995-2013: Cohort Study

Background There is a lack of recent studies examining recording of influenza-like illness (ILI) in primary care in the UK over time and according to population characteristics. Our aim was to determine time trends and socio-demographic patterns of ILI recorded consultations in primary care. Methods We used The Health Improvement Network (THIN) UK primary care database and extracted data on all ILI consultations between 1995 and 2013. We estimated ILI recorded consultation rates per 100,000 person-weeks (pw) by age, gender, deprivation and winter season. Negative binomial regression models were used to examine time trends and the effect of socio-demographic characteristics. Trends in ILI recorded consultations were compared to trends in consultations with less specific symptoms (cough or fever) recorded. Results The study involved 7,682,908 individuals in 542 general practices. The ILI consultation rate decreased from 32.5/100,000 pw (95% confidence interval (CI) 32.1, 32.9) in 1995–98 to 15.5/100,000 pw (95% CI 15.4, 15.7) by 2010–13. The decrease occurred prior to 2002/3, and rates have remained largely stable since then. Declines were evident in all age groups. In comparison, cough or fever consultation rates increased from 169.4/100,000 pw (95% CI 168.6, 170.3) in 1995–98 to 237.7/100,000 pw (95% CI 237.2, 238.2) in 2010–13. ILI consultation rates were highest among individuals aged 15–44 years, higher in women than men, and in individuals from deprived areas. Conclusion There is substantial variation in ILI recorded consultations over time and by population socio-demographic characteristics, most likely reflecting changing recording behaviour by GPs. These results highlight the difficulties in using coded information from electronic primary care records to measure the severity of influenza epidemics across time and assess the relative burden of ILI in different population subgroups.

Contribution of recurrent admissions in children and young people to emergency hospital admissions: retrospective cohort analysis of hospital episode statistics

Objective To examine the contribution of recurrent admissions to the high rate of emergency admissions among children and young people (CYP) in England, and to what extent readmissions are accounted for by patients with chronic conditions. Design All hospital admissions to the National Health Service (NHS) in England using hospital episode statistics (HES) from 2009 to 2011 for CYP aged 0–24 years. We followed CYP for 2 years from discharge of their first emergency admission in 2009. We determined the number of subsequent emergency admissions, time to next admission, length of stay and the proportion of injury and chronic condition admissions measured by diagnostic codes in all following admissions. Results 869 895 children had an index emergency admission in 2009, resulting in a further 939 710 admissions (of which 600 322, or 64%, were emergency admissions) over the next 2 years. After discharge from the index admission, 32% of 274,986 (32%) children were readmitted within 2 years, 26% of these readmissions occurring within 30 days of discharge. Recurrent emergency admission accounted for 41% of all emergency admissions in the 2-year cohort and 66% of inpatient days. 41% of index admissions, but 76% of the recurrent emergency admissions, were in children with a chronic condition. Conclusions Recurrent admissions contribute substantially to total emergency admissions. They often occur soon after discharge, and disproportionately affect CYP with chronic conditions. Policies aiming to discourage readmissions should consider whether they could undermine necessary inpatient care for children with chronic conditions.

Child deaths due to injury in the four UK countries: A time trends study from 1980 to 2010

Background Injuries are an increasingly important cause of death in children worldwide, yet injury mortality is highly preventable. Determining patterns and trends in child injury mortality can identify groups at particularly high risk. We compare trends in child deaths due to injury in four UK countries, between 1980 and 2010. Methods We obtained information from death certificates on all deaths occurring between 1980 and 2010 in children aged 28 days to 18 years and resident in England, Scotland, Wales or Northern Ireland. Injury deaths were defined by an external cause code recorded as the underlying cause of death. Injury mortality rates were analysed by type of injury, country of residence, age group, sex and time period. Results Child mortality due to injury has declined in all countries of the UK. England consistently experienced the lowest mortality rate throughout the study period. For children aged 10 to 18 years, differences between countries in mortality rates increased during the study period. Inter-country differences were largest for boys aged 10 to 18 years with mortality rate ratios of 1.38 (95% confidence interval 1.16, 1.64) for Wales, 1.68 (1.48, 1.91) for Scotland and 1.81 (1.50, 2.18) for Northern Ireland compared with England (the baseline) in 2006–10. The decline in mortality due to injury was accounted for by a decline in unintentional injuries. For older children, no declines were observed for deaths caused by self-harm, by assault or from undetermined intent in any UK country. Conclusion Whilst child deaths from injury have declined in all four UK countries, substantial differences in mortality rates remain between countries, particularly for older boys. This group stands to gain most from policy interventions to reduce deaths from injury in children.

Estimating the burden of respiratory syncytial virus (RSV) on respiratory hospital admissions in children less than five years of age in England, 2007‐2012

Respiratory syncytial virus (RSV) is a leading cause of hospital admission in young children. With several RSV vaccines candidates undergoing clinical trials, recent estimates of RSV burden are required to provide a baseline for vaccine impact studies.

Risk factors for admission to hospital with laboratory-confirmed influenza in young children: birth cohort study

We determined risk factors for influenza hospital admission in children aged <2 years to guide the design of paediatric vaccination programmes. We linked all singleton live births in Scotland from 2007 to 2015 to hospital administrative data and influenza laboratory reports. Cox proportional hazard models were used to identify birth and family risk factors for influenza admissions. There were 1115 influenza admissions among 424 048 children. 85.1% of admitted children were born at term and were not in a high-risk group. Presence of an older sibling was strongly associated with increased risk of influenza admission, particularly for children aged <6 months: hazard ratio for second- versus first-born child was 2.02 (95% CI 1.52–2.69). Maternal age <30 years and birth during autumn (age <6 months) or spring (age 6–23 months) were also associated with admission risk. Targeting vaccination programmes to high-risk children will not prevent the vast majority of influenza admissions. Parents of children aged <2 years should be advised that vaccination of older siblings will protect younger children against influenza infection. As evidence of the impact of the universal influenza vaccine programme emerges, there may be a need to reconsider universal influenza vaccination in children aged 6 months to 2 years in the UK. Older siblings pose risk of serious influenza for babies and toddlers http://ow.ly/RQDS30dbtIo

Child mortality in England compared with Sweden: a birth cohort study

Summary Background Child mortality is almost twice as high in England compared with Sweden. We aimed to establish the extent to which adverse birth characteristics and socioeconomic factors explain this difference. Methods We developed nationally representative cohorts of singleton livebirths between Jan 1, 2003, and Dec 31, 2012, using the Hospital Episode Statistics in England, and the Swedish Medical Birth Register in Sweden, with longitudinal follow-up from linked hospital admissions and mortality records. We analysed mortality as the outcome, based on deaths from any cause at age 2–27 days, 28–364 days, and 1–4 years. We fitted Cox proportional hazard regression models to estimate the hazard ratios (HRs) for England compared with Sweden in all three age groups. The models were adjusted for birth characteristics (gestational age, birthweight, sex, and congenital anomalies), and for socioeconomic factors (maternal age and socioeconomic status). Findings The English cohort comprised 3 932 886 births and 11 392 deaths and the Swedish cohort comprised 1 013 360 births and 1927 deaths. The unadjusted HRs for England compared with Sweden were 1·66 (95% CI 1·53–1·81) at 2–27 days, 1·59 (1·47–1·71) at 28–364 days, and 1·27 (1·15–1·40) at 1–4 years. At 2–27 days, 77% of the excess risk of death in England was explained by birth characteristics and a further 3% by socioeconomic factors. At 28–364 days, 68% of the excess risk of death in England was explained by birth characteristics and a further 11% by socioeconomic factors. At 1–4 years, the adjusted HR did not indicate a significant difference between countries. Interpretation Excess child mortality in England compared with Sweden was largely explained by the unfavourable distribution of birth characteristics in England. Socioeconomic factors contributed to these differences through associations with adverse birth characteristics and increased mortality after 1 month of age. Policies to reduce child mortality in England could have most impact by reducing adverse birth characteristics through improving the health of women before and during pregnancy and reducing socioeconomic disadvantage. Funding The Farr Institute of Health Informatics Research (through the Medical Research Council, Arthritis Research UK, British Heart Foundation, Cancer Research UK, Chief Scientist Office, Economic and Social Research Council, Engineering and Physical Sciences Research Council, National Institute for Health Research, National Institute for Social Care and Health Research, and the Wellcome Trust).