Evaluating the impact of alcohol minimum unit pricing on deaths and hospitalisations in Scotland: a controlled interrupted time series study.

BACKGROUND: Since May 1, 2018, every alcoholic drink sold in Scotland has had minimum unit pricing (MUP) of £0·50 per unit. Previous studies have indicated that the introduction of this policy reduced alcohol sales by 3%. We aimed to assess whether this has led to reductions in alcohol-attributable deaths and hospitalisations. METHODS: Study outcomes, wholly attributable to alcohol consumption, were defined using routinely collected data on deaths and hospitalisations. Controlled interrupted time series regression was used to assess the legislation's impact in Scotland, and any effect modification across demographic and socioeconomic deprivation groups. The pre-intervention time series ran from Jan 1, 2012, to April 30, 2018, and for 32 months after the policy was implemented (until Dec 31, 2020). Data from England, a part of the UK where the intervention was not implemented, were used to form a control group. FINDINGS: MUP in Scotland was associated with a significant 13·4% reduction (95% CI -18·4 to -8·3; p=0·0004) in deaths wholly attributable to alcohol consumption. Hospitalisations wholly attributable to alcohol consumption decreased by 4·1% (-8·3 to 0·3; p=0·064). Effects were driven by significant improvements in chronic outcomes, particularly alcoholic liver disease. Furthermore, MUP legislation was associated with a reduction in deaths and hospitalisations wholly attributable to alcohol consumption in the four most socioeconomically deprived deciles in Scotland. INTERPRETATION: The implementation of MUP legislation was associated with significant reductions in deaths, and reductions in hospitalisations, wholly attributable to alcohol consumption. The greatest improvements were in the four most socioeconomically deprived deciles, indicating that the policy is positively tackling deprivation-based inequalities in alcohol-attributable health harm. FUNDING: Scottish Government.

Educational outcomes among children with congenital heart disease compared to peers: a Scotland-wide record-linkage study of 715,850 schoolchildren.

BACKGROUND: Nine in every thousand children born in the United Kingdom have congenital heart disease, and 250,000 adults are living with the condition. This study aims to investigate the associations between congenital heart disease and educational outcomes among school-aged children in Scotland. METHODS: Routine health and education databases were linked to produce a cohort of all singleton children born in Scotland and attending a local authority run primary, secondary, or special school in Scotland at some point between 2009 and 2013. Children with congenital heart disease within this cohort were compared with children unaffected by congenital conditions. Outcomes investigated were special educational need (SEN), absenteeism, exclusion, academic attainment, and unemployment. All analyses were adjusted for sociodemographic and maternity confounders. Absenteeism was investigated as a mediating factor in the associations with attainment and unemployment. RESULTS: Of the 715,850 children, 6,295 (0.9%) had congenital heart disease and 4,412 (6.1%) had isolated congenital heart disease. Congenital heart disease and isolated congenital heart disease were both significantly associated with subsequent special educational need (OR 3.45, 95% CI 3.26-3.65, p < 0.001 and OR 1.98, 95% CI 1.84-2.13, p < 0.001 respectively), absenteeism (IRR 1.13, 95% CI 1.10-1.16, p < 0.001 and IRR 1.10, 95% CI 1.06-1.13, p < 0.001 respectively), and low academic attainment (OR 1.69, 95% CI 1.39-2.07, p < 0.001 and OR 1.35, 95% CI 1.07-1.69, p = 0.011 respectively). Neither congenital heart disease nor isolated congenital heart disease were associated with school exclusion. Only congenital heart disease (OR 1.21, 95% CI 1.03-1.42, p = 0.022) but not isolated congenital heart disease was associated with unemployment. When days absent were included in the analyses investigating attainment and unemployment, the conclusions were not altered. CONCLUSION: Children with congenital heart disease have greater special educational need, lower school attendance, attain lower examination grades and have greater unemployment compared to peers. In addition to healthcare support, affected children need educational support to avoid additional impact on their long-term wellbeing.

The impact of COVID-19 and associated lockdowns on traumatic spinal cord injury incidence: a population based study.

STUDY DESIGN: Natural experiment OBJECTIVES: To determine whether COVID-19 restrictions were associated with changes in the incidence of traumatic spinal cord injury (TSCI) in Scotland. SETTING: The Queen Elizabeth National Spinal Injuries Unit (QENSIU), the sole provider of treatment for TSCI in Scotland. METHODS: Time series analysis of all admissions for TSCI between 1st January 2015 and 31st August 2022. RESULTS: Over the 8-year study period, 745 patients were admitted to the QENSIU with a TSCI. Interrupted time series analysis showed that level 3 and 4 COVID-19 lockdown restrictions (the most severe levels) were associated with lower incidence of TSCI (RR 0.63, CI% CI 0.47, 0.82, p < 0.001). The associations were stronger in people aged over 45 (additive interaction p = 0.001), males (additive interaction p = 0.01) and non-tetraplegia (additive interaction p = 0.002). The incidence of TSCI due to deliberate self-harm was higher (0.41 versus 0.23 per month) during restrictions. CONCLUSIONS: Overall, TSCI incidence reduced in Scotland when lockdowns were implemented, presumably due to lower engagement in risky activities. The increase in TSCI due to deliberate self-harm may reflect increased mental health problems and social isolation and should be anticipated and targeted in future pandemics. The change in incidence during the COVID-19 pandemic may have an economic impact and see a temporary reduction in the burden on health and social care. The results of this study will be useful for resource planning in future pandemics.

Educational and employment outcomes associated with childhood traumatic brain injury in Scotland: A population-based record-linkage cohort study.

BACKGROUND: Traumatic brain injury (TBI) is a leading cause of death and disability among young children and adolescents and the effects can be lifelong and wide-reaching. Although there have been numerous studies to evaluate the impact of childhood head injury on educational outcomes, few large-scale studies have been conducted, and previous research has been limited by issues of attrition, methodological inconsistencies, and selection bias. We aim to compare the educational and employment outcomes of Scottish schoolchildren previously hospitalised for TBI with their peers. METHODS AND FINDINGS: A retrospective, record-linkage population cohort study was conducted using linkage of health and education administrative records. The cohort comprised all 766,244 singleton children born in Scotland and aged between 4 and 18 years who attended Scottish schools at some point between 2009 and 2013. Outcomes included special educational need (SEN), examination attainment, school absence and exclusion, and unemployment. The mean length of follow up from first head injury varied by outcome measure; 9.44 years for assessment of SEN and 9.53, 12.70, and 13.74 years for absenteeism and exclusion, attainment, and unemployment, respectively. Logistic regression models and generalised estimating equation (GEE) models were run unadjusted and then adjusted for sociodemographic and maternity confounders. Of the 766,244 children in the cohort, 4,788 (0.6%) had a history of hospitalisation for TBI. The mean age at first head injury admission was 3.73 years (median = 1.77 years). Following adjustment for potential confounders, previous TBI was associated with SEN (OR 1.28, CI 1.18 to 1.39, p < 0.001), absenteeism (IRR 1.09, CI 1.06 to 1.12, p < 0.001), exclusion (IRR 1.33, CI 1.15 to 1.55, p < 0.001), and low attainment (OR 1.30, CI 1.11 to 1.51, p < 0.001). The average age on leaving school was 17.14 (median = 17.37) years among children with a TBI and 17.19 (median = 17.43) among peers. Among children previously admitted for a TBI, 336 (12.2%) left school before age 16 years compared with 21,941 (10.2%) of those not admitted for TBI. There was no significant association with unemployment 6 months after leaving school (OR 1.03, CI 0.92 to 1.16, p = 0.61). Excluding hospitalisations coded as concussion strengthened the associations. We were not able to investigate age at injury for all outcomes. For TBI occurring before school age, it was impossible to be certain that SEN had not predated the TBI. Therefore, potential reverse causation was a limitation for this outcome. CONCLUSIONS: Childhood TBI, sufficiently severe to warrant hospitalisation, was associated with a range of adverse educational outcomes. These findings reinforce the importance of preventing TBI where possible. Where not possible, children with a history of TBI should be supported to minimise the adverse impacts on their education.

Infant feeding method and special educational need in 191,745 Scottish schoolchildren: A national, population cohort study.

BACKGROUND: While special educational needs (SEN) are increasingly recorded among schoolchildren, infant breastfeeding has been associated with reduced incidence of childhood physical and mental health problems. This study investigated relationships between infant feeding method and risk of all-cause and cause-specific SEN. METHODS AND FINDINGS: A population cohort of schoolchildren in Scotland was constructed by linking together health (maternity, birth, and health visitor records) and education (annual school pupil census) databases. Inclusion was restricted to singleton children, born in Scotland from 2004 onwards with available breastfeeding data and who attended local authority mainstream or special schools between 2009 and 2013. Generalised estimating equation models with a binomial distribution and logit link function investigated associations between infant feeding method at 6 to 8 weeks and all-cause and cause-specific SEN, adjusting for sociodemographic and maternity factors. Of 191,745 children meeting inclusion criteria, 126,907 (66.2%) were formula-fed, 48,473 (25.3%) exclusively breastfed, and 16,365 (8.5%) mixed-fed. Overall, 23,141 (12.1%) children required SEN. Compared with formula feeding, mixed feeding and exclusive breastfeeding, respectively, were associated with decreased all-cause SEN (OR 0.90, 95% CI [0.84,0.95], p < 0.001 and 0.78, [0.75,0.82], p < 0.001), and SEN attributed to learning disabilities (0.75, [0.65,0.87], p < 0.001 and 0.66, [0.59,0.74], p < 0.001), and learning difficulties (0.85, [0.77,0.94], p = 0.001 and 0.75, [0.70,0.81], p < 0.001). Compared with formula feeding, exclusively breastfed children had less communication problems (0.81, [0.74,0.88], p = 0.001), social-emotional-behavioural difficulties (0.77, [0.70,0.84], p = 0.001), sensory impairments (0.79, [0.65,0.95], p = 0.01), physical motor disabilities (0.78, [0.66,0.91], p = 0.002), and physical health conditions (0.74, [0.63,0.87], p = 0.01). There were no significant associations for mixed-fed children (communication problems (0.94, [0.83,1.06], p = 0.312), social-emotional-behavioural difficulties (0.96, [0.85,1.09], p = 0.541), sensory impairments (1.07, [0.84,1.37], p = 0.579), physical motor disabilities (0.97, [0.78,1.19], p = 0.754), and physical health conditions (0.93, [0.74,1.16], p = 0.504)). Feeding method was not significantly associated with mental health conditions (exclusive 0.58 [0.33,1.03], p = 0.061 and mixed 0.74 [0.36,1.53], p = 0.421) or autism (exclusive 0.88 [0.77,1.01], p = 0.074 and mixed 1.01 [0.84,1.22], p = 0.903). Our study was limited since only 6- to 8-week feeding method was available precluding differentiation between never-breastfed infants and those who stopped breastfeeding before 6 weeks. Additionally, we had no data on maternal and paternal factors such as education level, IQ, employment status, race/ethnicity, or mental and physical health. CONCLUSIONS: In this study, we observed that both breastfeeding and mixed feeding at 6 to 8 weeks were associated with lower risk of all-cause SEN, and SEN attributed to learning disabilities and learning difficulty. Many women struggle to exclusively breastfeed for the full 6 months recommended by WHO; however, this study provides evidence that a shorter duration of nonexclusive breastfeeding could nonetheless be beneficial with regard to the development of SEN. Our findings augment the existing evidence base concerning the advantages of breastfeeding and reinforce the importance of breastfeeding education and support.

Association Between Socioeconomic Status and Outcomes in Critical Care: A Systematic Review and Meta-Analysis.

OBJECTIVES: Socioeconomic status is well established as a key determinant of inequalities in health outcomes. Existing literature examining the impact of socioeconomic status on outcomes in critical care has produced inconsistent findings. Our objective was to synthesize the available evidence on the association between socioeconomic status and outcomes in critical care. DATA SOURCES: A systematic search of CINAHL, Ovid MEDLINE, and EMBASE was undertaken on September 13, 2022. STUDY SELECTION: Observational cohort studies of adults assessing the association between socioeconomic status and critical care outcomes including mortality, length of stay, and functional outcomes were included. Two independent reviewers assessed titles, abstracts, and full texts against eligibility and quality criteria. DATA EXTRACTION: Details of study methodology, population, exposure measures, and outcomes were extracted. DATA SYNTHESIS: Thirty-eight studies met eligibility criteria for systematic review. Twenty-three studies reporting mortality to less than or equal to 30 days following critical care admission, and eight reporting length of stay, were included in meta-analysis. Random-effects pooled analysis showed that lower socioeconomic status was associated with higher mortality at less than or equal to 30 days following critical care admission, with pooled odds ratio of 1.13 (95% CIs, 1.05-1.22). Meta-analysis of ICU length of stay demonstrated no significant difference between socioeconomic groups. Socioeconomic status may also be associated with functional status and discharge destination following ICU admission. CONCLUSIONS: Lower socioeconomic status was associated with higher mortality following admission to critical care.

Understanding covid-19 outcomes among people with intellectual disabilities in England.

BACKGROUND: Evidence from the UK from the early stages of the covid-19 pandemic showed that people with Intellectual Disabilities (ID) had higher rates of covid-19 mortality than people without ID. However, estimates of the magnitude of risk vary widely; different studies used different time periods; and only early stages of the pandemic have been analysed. Existing analyses of risk factors have also been limited. The objective of this study was to investigate covid-19 mortality rates, hospitalisation rates, and risk factors in people with ID in England up to the end of 2021. METHODS: Retrospective cohort study of all people with a laboratory-confirmed SARS-CoV-2 infection or death involving covid-19. Datasets covering primary care, secondary care, covid-19 tests and vaccinations, prescriptions, and deaths were linked at individual level. RESULTS: Covid-19 carries a disproportionately higher risk of death for people with ID, above their already higher risk of dying from other causes, in comparison to those without ID. Around 2,000 people with ID had a death involving covid-19 in England up to the end of 2021; approximately 1 in 180. The covid-19 standardized mortality ratio was 5.6 [95% CI 5.4, 5.9]. People with ID were also more likely to be hospitalised for covid-19 than people without ID. The main determinants of severe covid-19 outcomes (deaths and/or hospitalisations) in both populations were age, multimorbidity and vaccination status. The key factor responsible for the higher risk of severe covid-19 in the ID population was a much higher prevalence of multimorbidity in this population. AstraZeneca vaccine was slightly less effective in preventing severe covid-19 outcomes among people with ID than among people without ID. CONCLUSIONS: People with ID should be considered a priority group in future pandemics, such as shielding and vaccinations.

Derivation and Validation of a 10-Year Risk Score for Symptomatic Abdominal Aortic Aneurysm: Cohort Study of Nearly 500 000 Individuals.

BACKGROUND: Abdominal aortic aneurysm (AAA) can occur in patients who are ineligible for routine ultrasound screening. A simple AAA risk score was derived and compared with current guidelines used for ultrasound screening of AAA. METHODS: United Kingdom Biobank participants without previous AAA were split into a derivation cohort (n=401 820, 54.6% women, mean age 56.4 years, 95.5% White race) and validation cohort (n=83 816). Incident AAA was defined as first hospital inpatient diagnosis of AAA, death from AAA, or an AAA-related surgical procedure. A multivariable Cox model was developed in the derivation cohort into an AAA risk score that did not require blood biomarkers. To illustrate the sensitivity and specificity of the risk score for AAA, a theoretical threshold to refer patients for ultrasound at 0.25% 10-year risk was modeled. Discrimination of the risk score was compared with a model of US Preventive Services Task Force (USPSTF) AAA screening guidelines. RESULTS: In the derivation cohort, there were 1570 (0.40%) cases of AAA over a median 11.3 years of follow-up. Components of the AAA risk score were age (stratified by smoking status), weight (stratified by smoking status), antihypertensive and cholesterol-lowering medication use, height, diastolic blood pressure, baseline cardiovascular disease, and diabetes. In the validation cohort, over 10 years of follow-up, the C-index for the model of the USPSTF guidelines was 0.705 (95% CI, 0.678-0.733). The C-index of the risk score as a continuous variable was 0.856 (95% CI, 0.837-0.878). In the validation cohort, the USPSTF model yielded sensitivity 63.9% and specificity 71.3%. At the 0.25% 10-year risk threshold, the risk score yielded sensitivity 82.1% and specificity 70.7% while also improving the net reclassification index compared with the USPSTF model +0.176 (95% CI, 0.120-0.232). A combined model, whereby risk scoring was combined with the USPSTF model, also improved prediction compared with USPSTF alone (net reclassification index +0.101 [95% CI, 0.055-0.147]). CONCLUSIONS: In an asymptomatic general population, a risk score based on patient age, height, weight, and medical history may improve identification of asymptomatic patients at risk for clinical events from AAA. Further development and validation of risk scores to detect asymptomatic AAA are needed.

Neurodegenerative Disease Mortality among Former Professional Soccer Players.

BACKGROUND: Neurodegenerative disorders have been reported in elite athletes who participated in contact sports. The incidence of neurodegenerative disease among former professional soccer players has not been well characterized. METHODS: We conducted a retrospective cohort study to compare mortality from neurodegenerative disease among 7676 former professional soccer players (identified from databases of Scottish players) with that among 23,028 controls from the general population who were matched to the players on the basis of sex, age, and degree of social deprivation. Causes of death were determined from death certificates. Data on medications dispensed for the treatment of dementia in the two cohorts were also compared. Prescription information was obtained from the national Prescribing Information System. RESULTS: Over a median of 18 years, 1180 former soccer players (15.4%) and 3807 controls (16.5%) died. All-cause mortality was lower among former players than among controls up to the age of 70 years and was higher thereafter. Mortality from ischemic heart disease was lower among former players than among controls (hazard ratio, 0.80; 95% confidence interval [CI], 0.66 to 0.97; P = 0.02), as was mortality from lung cancer (hazard ratio, 0.53; 95% CI, 0.40 to 0.70; P<0.001). Mortality with neurodegenerative disease listed as the primary cause was 1.7% among former soccer players and 0.5% among controls (subhazard ratio [the hazard ratio adjusted for competing risks of death from ischemic heart disease and death from any cancer], 3.45; 95% CI, 2.11 to 5.62; P<0.001). Among former players, mortality with neurodegenerative disease listed as the primary or a contributory cause on the death certificate varied according to disease subtype and was highest among those with Alzheimer's disease (hazard ratio [former players vs. controls], 5.07; 95% CI, 2.92 to 8.82; P<0.001) and lowest among those with Parkinson's disease (hazard ratio, 2.15; 95% CI, 1.17 to 3.96; P = 0.01). Dementia-related medications were prescribed more frequently to former players than to controls (odds ratio, 4.90; 95% CI, 3.81 to 6.31; P<0.001). Mortality with neurodegenerative disease listed as the primary or a contributory cause did not differ significantly between goalkeepers and outfield players (hazard ratio, 0.73; 95% CI, 0.43 to 1.24; P = 0.24), but dementia-related medications were prescribed less frequently to goalkeepers (odds ratio, 0.41; 95% CI, 0.19 to 0.89; P = 0.02). CONCLUSIONS: In this retrospective epidemiologic analysis, mortality from neurodegenerative disease was higher and mortality from other common diseases lower among former Scottish professional soccer players than among matched controls. Dementia-related medications were prescribed more frequently to former players than to controls. These observations need to be confirmed in prospective matched-cohort studies. (Funded by the Football Association and Professional Footballers' Association.).

Neurodegenerative disease risk among former international rugby union players.

BACKGROUND: Autopsy studies of former contact sports athletes, including soccer and rugby players, frequently report chronic traumatic encephalopathy, a neurodegenerative pathology associated with traumatic brain injury. Nevertheless, little is known about the risk of neurodegenerative disease in these populations. We hypothesised that neurodegenerative disease risk would be higher among former elite rugby union players than the general population. METHODS: We conducted a retrospective cohort study accessing national electronic records on death certification, hospital admissions and dispensed prescriptions for a cohort of 412 male Scottish former international rugby union players and 1236 members of the general population, matched to former players by age, sex and area socioeconomic status. Mortality and incident neurodegenerative disease diagnoses among former rugby players were then compared with the matched comparison group. RESULTS: Over a median 32 years follow-up from study entry at age 30 years, 121 (29.4%) former rugby players and 381 (30.8%) of the matched comparison group died. All-cause mortality was lower among former rugby players until 70 years of age with no difference thereafter. During follow-up, 47 (11.4%) former rugby players and 67 (5.4%) of the comparison group were diagnosed with incident neurodegenerative disease (HR 2.67, 95% CI 1.67 to 4.27, p<0.001). CONCLUSIONS: This study adds to our understanding of the association between contact sports participation and the risk of neurodegenerative disease. While further research exploring this interaction is required, in the meantime strategies to reduce exposure to head impacts and head injuries in sport should be promoted.

Minimizing sample bias due to stigmatized behaviours: the representativeness of participants in a cohort study of alcohol in pregnancy.

BACKGROUND: Stigmatized behaviours are often underreported, especially in pregnancy, making them challenging to address. The Alcohol and Child Development Study (ACDS) seeks to inform prevention of foetal alcohol harm, linking self-report as well as a maternal blood alcohol biomarker with child developmental outcomes. Samples were requested using passive, generic consent. The success of this approach at minimizing bias is presented comparing characteristics of women who provided samples to those who did not. METHODS: All pregnant women in the study city were sent a Patient Information Sheet (PIS) with their first NHS obstetric appointment letter. The PIS informed them that the NHS would like to take an extra blood sample for research purposes, unless they opted out. Neither the women nor the midwives were informed that the samples might be tested for an alcohol biomarker. This paper examines the extent to which women who provided the extra sample were representative of women where no sample was provided, in terms of routinely collected information: age; body mass index; area-based deprivation; previous pregnancies, abortions and caesarians; smoking status and carbon monoxide level; self-reported alcohol use, gestation and birth weight of their baby. Chi-square and Mann-Whitney U tests were used to compare groups. RESULTS: 3436 (85%) of the 4049 pregnant women who attended their appointment provided the extra sample. Women who did not were significantly younger (p < 0.001), more materially deprived (p < 0.001), and less likely to be considered for intervention based on self-reported alcohol use (p < 0.001). There were no significant differences between the two groups on other routine data. CONCLUSIONS: The use of passive consent without disclosure of the specific research focus resulted in a high level of sample provision. There was no evidence that study blinding was breached, and women who provided a sample were more likely to report alcohol consumption. Passive consent to draw additional blood for research purposes at routine antenatal venipuncture reduced sampling bias compared to asking women to give blood for an alcohol study. This methodology may be useful for other stigmatised behaviours.

Suicide among Scottish military veterans: follow-up and trends.

OBJECTIVES: The risk of suicide among UK military veterans remains unclear. Few recent studies have been undertaken, and most studies found no clear evidence of increased risk. We used data from the Trends in Scottish Veterans Health cohort to investigate suicides up to 2017 in order to examine whether there have been any changes in the long-term pattern of veteran suicides since our earlier study to 2012, and to compare trends in the risk of suicide among veterans with matched non-veterans. METHOD: Retrospective cohort study of 78 000 veterans and 253 000 non-veterans born between 1945 and 1995, matched for age, sex and area of residence, using survival analysis to examine the risk of suicide in veterans in comparison with non-veterans overall and by subgroup, and to investigate associations with specific mental health conditions. RESULTS: Up to 37 years of follow-up, 388 (0.5%) veterans and 1531 (0.6%) non-veterans died from suicide. The risk of suicide among veterans did not differ from non-veterans overall. Increased risk among early service leavers was explained by differences in deprivation, and the previously reported increased risk in female veterans is now confined to older women. Suicide was most common in the fifth decade of life, and around 20 years postservice. A history of mood disorder or post-traumatic stress disorder was non-significantly more common in veterans. CONCLUSIONS: Veterans are not at increased risk of suicide overall. The highest risk for both men and women is in middle age, many years after leaving service.

Age within schoolyear and attention-deficit hyperactivity disorder in Scotland and Wales.

BACKGROUND: Previous studies suggest an association between age within schoolyear and attention-deficit hyperactivity disorder (ADHD). Scotland and Wales have different school entry cut-off dates (six months apart) and policies on holding back children. We aim to investigate the association between relative age and treated attention deficit hyperactivity disorder (ADHD) in two countries, accounting for held-back children. METHODS: Routine education and health records of 1,063,256 primary and secondary schoolchildren in Scotland (2009-2013) and Wales (2009-2016) were linked. Logistic regression was used to examine the relationships between age within schoolyear and treated ADHD, adjusting for child, maternity and obstetric confounders. RESULTS: Amongst children in their expected school year, 8,721 (0.87%) had treated ADHD (Scotland 0.84%; Wales 0.96%). In Wales, ADHD increased with decreasing age (youngest quartile, adjusted OR 1.32, 95% CI 1.19-1.46) but, in Scotland, it did not differ between the youngest and oldest quartiles. Including held-back children in analysis of their expected year, the overall prevalence of treated ADHD was 0.93%, and increased across age quartiles in both countries. More children were held back in Scotland (57,979; 7.66%) than Wales (2,401; 0.78%). Held-back children were more likely to have treated ADHD (Scotland OR 2.18, 95% CI 2.01-2.36; Wales OR 1.70, 95% CI 1.21-2.31) and 81.18% of held-back children would have been in the youngest quartile of their expected year. CONCLUSIONS: Children younger within schoolyear are more likely to be treated for ADHD, suggesting immaturity may influence diagnosis. However, these children are more likely to be held back in countries that permit flexibility, attenuating the relative age effect.

Educational and health outcomes of schoolchildren in local authority care in Scotland: A retrospective record linkage study.

BACKGROUND: Looked after children are defined as children who are in the care of their local authority. Previous studies have reported that looked after children have poorer mental and physical health, increased behavioural problems, and increased self-harm and mortality compared to peers. They also experience poorer educational outcomes, yet population-wide research into the latter is lacking, particularly in the United Kingdom. Education and health share a bidirectional relationship; therefore, it is important to dually investigate both outcomes. Our study aimed to compare educational and health outcomes for looked after children with peers, adjusting for sociodemographic, maternity, and comorbidity confounders. METHODS AND FINDINGS: Linkage of 9 Scotland-wide databases, covering dispensed prescriptions, hospital admissions, maternity records, death certificates, annual pupil census, examinations, school absences/exclusions, unemployment, and looked after children provided retrospective data on 715,111 children attending Scottish schools between 2009 and 2012 (13,898 [1.9%] looked after). Compared to peers, 13,898 (1.9%) looked after children were more likely to be absent (adjusted incidence rate ratio [AIRR] 1.27, 95% confidence interval [CI] 1.24 to 1.30) and excluded (AIRR 4.09, 95% CI 3.86 to 4.33) from school, have special educational need (SEN; adjusted odds ratio [AOR] 3.48, 95% CI 3.35 to 3.62) and neurodevelopmental multimorbidity (AOR 2.45, 95% CI 2.34 to 2.57), achieve the lowest level of academic attainment (AOR 5.92, 95% CI 5.17 to 6.78), and be unemployed after leaving school (AOR 2.12, 95% CI 1.96 to 2.29). They were more likely to require treatment for epilepsy (AOR 1.50, 95% CI 1.27 to 1.78), attention deficit hyperactivity disorder (ADHD; AOR 3.01, 95% CI 2.76 to 3.27), and depression (AOR 1.90, 95% CI 1.62 to 2.22), be hospitalised overall (adjusted hazard ratio [AHR] 1.23, 95% CI 1.19 to 1.28) for injury (AHR 1.80, 95% CI 1.69 to 1.91) and self-harm (AHR 5.19, 95% CI 4.66 to 5.78), and die prematurely (AHR 3.21, 95% CI 2.16 to 4.77). Compared to children looked after at home, children looked after away from home had less absenteeism (AIRR 0.35, 95% CI 0.33 to 0.36), less exclusion (AIRR 0.63, 95% CI 0.56 to 0.71), less unemployment (AOR 0.53, 95% CI 0.46 to 0.62), and better attainment (AIRR 0.31, 95% CI 0.23 to 0.40). Therefore, among those in care, being cared for away from home appeared to be a protective factor resulting in better educational outcomes. The main limitations of this study were lack of data on local authority care preschool or before 2009, total time spent in care, and age of first contact with social care. CONCLUSIONS: Looked after children had poorer health and educational outcomes than peers independent of increased neurodevelopmental conditions and SEN. Further work is required to understand whether poorer outcomes relate to reasons for entering care, including maltreatment and adverse childhood events, neurodevelopmental vulnerabilities, or characteristics of the care system.

The relationship between antihypertensive medications and mood disorders: analysis of linked healthcare data for 1.8 million patients.

BACKGROUND: Recent work suggests that antihypertensive medications may be useful as repurposed treatments for mood disorders. Using large-scale linked healthcare data we investigated whether certain classes of antihypertensive, such as angiotensin antagonists (AAs) and calcium channel blockers, were associated with reduced risk of new-onset major depressive disorder (MDD) or bipolar disorder (BD). METHOD: Two cohorts of patients treated with antihypertensives were identified from Scottish prescribing (2009-2016) and hospital admission (1981-2016) records. Eligibility for cohort membership was determined by a receipt of a minimum of four prescriptions for antihypertensives within a 12-month window. One treatment cohort (n = 538 730) included patients with no previous history of mood disorder, whereas the other (n = 262 278) included those who did. Both cohorts were matched by age, sex and area deprivation to untreated comparators. Associations between antihypertensive treatment and new-onset MDD or bipolar episodes were investigated using Cox regression. RESULTS: For patients without a history of mood disorder, antihypertensives were associated with increased risk of new-onset MDD. For AA monotherapy, the hazard ratio (HR) for new-onset MDD was 1.17 (95% CI 1.04-1.31). Beta blockers' association was stronger (HR 2.68; 95% CI 2.45-2.92), possibly indicating pre-existing anxiety. Some classes of antihypertensive were associated with protection against BD, particularly AAs (HR 0.46; 95% CI 0.30-0.70). For patients with a past history of mood disorders, all classes of antihypertensives were associated with increased risk of future episodes of MDD. CONCLUSIONS: There was no evidence that antihypertensive medications prevented new episodes of MDD but AAs may represent a novel treatment avenue for BD.

Changes over 15 years in the contribution of adiposity and smoking to deaths in England and Scotland.

BACKGROUND: For many years smoking has been the major threat to public health in developed countries. However, smoking prevalence has declined over a period when adiposity has increased. The aim of this study was to determine whether adiposity now accounts for more deaths than smoking in the general population as a whole or sub-groups of it. METHODS: This is a comparative risk assessment study using Health Surveys for England and Scottish Health Surveys from 2003 to 2017. Annual prevalence of overweight, obesity, current and former smoking were obtained and combined using population-based weights. Sex-specific risk ratios for all-cause mortality were obtained from the most recently published meta-analyses. Population attributable fractions across yeas were then estimated. FINDINGS: Overall, deaths attributable to current/former smoking declined from 23.1% (95% CI 20.6-25.8%) in 2003 to 19.4% (95% CI 17.3-21.6%) in 2017, whilst those attributable to adiposity (overweight or obesity) increased from 17.9% (95% CI 17.3-18.4%) in 2003 to 23.1% (95% CI 22.3-23.8%) in 2017 with cross-over occurring in 2013. Cross-over occurred earlier in men (2011) than women (2014). It occurred in 2006 for those aged over 65 years of age and in 2012 for those aged 45-64 years. Below 45 years, smoking remained the larger contributor to mortality. INTERPRETATION: Adiposity now accounts for more deaths in England and Scotland than smoking among people in middle- and old-age. National strategies to address adiposity should be a public health priority.

Comparison of Conventional Lipoprotein Tests and Apolipoproteins in the Prediction of Cardiovascular Disease.

BACKGROUND: Total cholesterol and high-density lipoprotein cholesterol (HDL-C) measurements are central to cardiovascular disease (CVD) risk assessment, but there is continuing debate around the utility of other lipids for risk prediction. METHODS: Participants from UK Biobank without baseline CVD and not taking statins, with relevant lipid measurements (n=346 686), were included in the primary analysis. An incident fatal or nonfatal CVD event occurred in 6216 participants (1656 fatal) over a median of 8.9 years. Associations of nonfasting lipid measurements (total cholesterol, HDL-C, non-HDL-C, direct and calculated low-density lipoprotein cholesterol [LDL-C], and apolipoproteins [Apo] A1 and B) with CVD were compared using Cox models adjusting for classical risk factors, and predictive utility was determined by the C-index and net reclassification index. Prediction was also tested in 68 649 participants taking a statin with or without baseline CVD (3515 CVD events). RESULTS: ApoB, LDL-C, and non-HDL-C were highly correlated (r>0.90), while HDL-C was strongly correlated with ApoA1 (r=0.92). After adjustment for classical risk factors, 1 SD increase in ApoB, direct LDL-C, and non-HDL-C had similar associations with composite fatal/nonfatal CVD events (hazard ratio, 1.23, 1.20, 1.21, respectively). Associations for 1 SD increase in HDL-C and ApoA1 were also similar (hazard ratios, 0.81 [both]). Adding either total cholesterol and HDL-C, or ApoB and ApoA, to a CVD risk prediction model (C-index, 0.7378) yielded similar improvement in discrimination (C-index change, 0.0084; 95% CI, 0.0065, 0.0104, and 0.0089; 95% CI, 0.0069, 0.0109, respectively). Once total and HDL-C were in the model, no further substantive improvement was achieved with the addition of ApoB (C-index change, 0.0004; 95% CI, 0.0000, 0.0008) or any measure of LDL-C. Results for predictive utility were similar for a fatal CVD outcome, and in a discordance analysis. In participants taking a statin, classical risk factors (C-index, 0.7118) were improved by non-HDL-C (C-index change, 0.0030; 95% CI, 0.0012, 0.0048) or ApoB (C-index change, 0.0030; 95% CI, 0.0011, 0.0048). However, adding ApoB or LDL-C to a model already containing non-HDL-C did not further improve discrimination. CONCLUSIONS: Measurement of total cholesterol and HDL-C in the nonfasted state is sufficient to capture the lipid-associated risk in CVD prediction, with no meaningful improvement from addition of apolipoproteins, direct or calculated LDL-C.

Neurodevelopmental multimorbidity and educational outcomes of Scottish schoolchildren: A population-based record linkage cohort study.

BACKGROUND: Neurodevelopmental conditions commonly coexist in children, but compared to adults, childhood multimorbidity attracts less attention in research and clinical practice. We previously reported that children treated for attention deficit hyperactivity disorder (ADHD) and depression have more school absences and exclusions, additional support needs, poorer attainment, and increased unemployment. They are also more likely to have coexisting conditions, including autism and intellectual disability. We investigated prevalence of neurodevelopmental multimorbidity (≥2 conditions) among Scottish schoolchildren and their educational outcomes compared to peers. METHODS AND FINDINGS: We retrospectively linked 6 Scotland-wide databases to analyse 766,244 children (390,290 [50.9%] boys; 375,954 [49.1%] girls) aged 4 to 19 years (mean = 10.9) attending Scottish schools between 2009 and 2013. Children were distributed across all deprivation quintiles (most to least deprived: 22.7%, 20.1%, 19.3%, 19.5%, 18.4%). The majority (96.2%) were white ethnicity. We ascertained autism spectrum disorder (ASD) and intellectual disabilities from records of additional support needs and ADHD and depression through relevant encashed prescriptions. We identified neurodevelopmental multimorbidity (≥2 of these conditions) in 4,789 (0.6%) children, with ASD and intellectual disability the most common combination. On adjusting for sociodemographic (sex, age, ethnicity, deprivation) and maternity (maternal age, maternal smoking, sex-gestation-specific birth weight centile, gestational age, 5-minute Apgar score, mode of delivery, parity) factors, multimorbidity was associated with increased school absenteeism and exclusion, unemployment, and poorer exam attainment. Significant dose relationships were evident between number of conditions (0, 1, ≥2) and the last 3 outcomes. Compared to children with no conditions, children with 1 condition, and children with 2 or more conditions, had more absenteeism (1 condition adjusted incidence rate ratio [IRR] 1.28, 95% CI 1.27-1.30, p < 0.001 and 2 or more conditions adjusted IRR 1.23, 95% CI 1.20-1.28, p < 0.001), greater exclusion (adjusted IRR 2.37, 95% CI 2.25-2.48, p < 0.001 and adjusted IRR 3.04, 95% CI 2.74-3.38, p < 0.001), poorer attainment (adjusted odds ratio [OR] 3.92, 95% CI 3.63-4.23, p < 0.001 and adjusted OR 12.07, 95% CI 9.15-15.94, p < 0.001), and increased unemployment (adjusted OR 1.57, 95% CI 1.49-1.66, p < 0.001 and adjusted OR 2.11, 95% CI 1.83-2.45, p < 0.001). Associations remained after further adjustment for comorbid physical conditions and additional support needs. Coexisting depression was the strongest driver of absenteeism and coexisting ADHD the strongest driver of exclusion. Absence of formal primary care diagnoses was a limitation since ascertaining depression and ADHD from prescriptions omitted affected children receiving alternative or no treatment and some antidepressants can be prescribed for other indications. CONCLUSIONS: Structuring clinical practice and training around single conditions may disadvantage children with neurodevelopmental multimorbidity, who we observed had significantly poorer educational outcomes compared to children with 1 condition and no conditions.

An evaluation of the effects of lowering blood alcohol concentration limits for drivers on the rates of road traffic accidents and alcohol consumption: a natural experiment.

BACKGROUND: Drink driving is an important risk factor for road traffic accidents (RTAs), which cause high levels of morbidity and mortality globally. Lowering the permitted blood alcohol concentration (BAC) for drivers is a common public health intervention that is enacted in countries and jurisdictions across the world. In Scotland, on Dec 5, 2014, the BAC limit for drivers was reduced from 0·08 g/dL to 0·05 g/dL. We therefore aimed to evaluate the effects of this change on RTAs and alcohol consumption. METHODS: In this natural experiment, we used an observational, comparative interrupted time-series design by use of data on RTAs and alcohol consumption in Scotland (the interventional group) and England and Wales (the control group). We obtained weekly counts of RTAs from police accident records and we estimated weekly off-trade (eg, in supermarkets and convenience stores) and 4-weekly on-trade (eg, in bars and restaurants) alcohol consumption from market research data. We also used data from automated traffic counters as denominators to calculate RTA rates. We estimated the effect of the intervention on RTAs by use of negative binomial panel regression and on alcohol consumption outcomes by use of seasonal autoregressive integrated moving average models. Our primary outcome was weekly rates of RTAs in Scotland, England, and Wales. This study is registered with ISRCTN, number ISRCTN38602189. FINDINGS: We assessed the weekly rate of RTAs and alcohol consumption between Jan 1, 2013, and Dec 31, 2016, before and after the BAC limit came into effect on Dec 5, 2014. After the reduction in BAC limits for drivers in Scotland, we found no significant change in weekly RTA rates after adjustment for seasonality and underlying temporal trend (rate ratio 1·01, 95% CI 0·94-1·08; p=0.77) or after adjustment for seasonality, the underlying temporal trend, and the driver characteristics of age, sex, and socioeconomic deprivation (1·00, 0·96-1·06; p=0·73). Relative to RTAs in England and Wales, where the reduction in BAC limit for drivers did not occur, we found a 7% increase in weekly RTA rates in Scotland after this reduction in BAC limit for drivers (1·07, 1·02-1·13; p=0·007 in the fully-adjusted model). Similar findings were observed for serious or fatal RTAs and single-vehicle night-time RTAs. The change in legislation in Scotland was associated with no change in alcohol consumption, measured by per-capita off-trade sales (-0·3%, -1·7 to 1·1; p=0·71), but a 0·7% decrease in alcohol consumption measured by per-capita on-trade sales (-0·7%, -0·8 to -0·5; p<0·0001). INTERPRETATION: Lowering the driving BAC limit to 0·05 g/dL from 0·08 g/dL in Scotland was not associated with a reduction in RTAs, but this change was associated with a small reduction in per-capita alcohol consumption from on-trade alcohol sales. One plausible explanation is that the legislative change was not suitably enforced-for example with random breath testing measures. Our findings suggest that changing the legal BAC limit for drivers in isolation does not improve RTA outcomes. These findings have significant policy implications internationally as several countries and jurisdictions consider a similar reduction in the BAC limit for drivers. FUNDING: National Institute for Health Research Public Health Research Programme.

The associations of sugar-sweetened, artificially sweetened and naturally sweet juices with all-cause mortality in 198,285 UK Biobank participants: a prospective cohort study.

BACKGROUND: Recent efforts to address the obesity epidemic have focused on sugar consumption, especially sugar-sweetened beverages. However, sugar takes many forms, is only one contributor to overall energy consumption and is correlated with other health-related lifestyle factors. The objective was to investigate the associations with all-cause mortality of sugar- and artificially sweetened beverages and naturally sweet juices. METHODS: Setting: UK Biobank, UK. Participants joined the UK Biobank study from 2006 to 2010 and were followed up until 2016; 198,285 men and women aged 40-69 years were eligible for this study (40% of the UK Biobank), of whom 3166 (1.6%) died over a mean of 7 years follow-up. DESIGN: prospective population-based cohort study. Exposure variables: dietary consumption of sugar-sweetened beverages, artificially sweetened beverages, naturally sweet juices (100% fruit/vegetable juices) and total sugar intake, self-reported via 24-h dietary assessment tool completed between 2009 and 2012. MAIN OUTCOME: all-cause mortality. Cox regression analyses were used to study the association between the daily intake of the above beverages and all-cause mortality. Models were adjusted for sociodemographic, economic, lifestyle and dietary confounders. RESULTS: Total energy intake, total sugar intake and percentage of energy derived from sugar were comparable among participants who consumed > 2/day sugar-sweetened beverages and > 2/day fruit/vegetable juices (10,221 kJ/day versus 10,381 kJ/day; 183 g versus 190 g; 30.6% versus 31.0%). All-cause mortality was associated with total sugar intake (highest quintile adj. HR 1.28, 95% CI 1.06-1.55) and intake of sugar-sweetened beverages (> 2/day adj. HR 1.84, 95% CI 1.42-2.37) and remained so in sensitivity analyses. An association between artificially sweetened beverage intake and mortality did not persist after excluding deaths in the first 2 years of follow-up (landmark analysis) nor after excluding participants with recent weight loss. Furthermore, the inverse association between fruit/vegetable juice intake and mortality did not persist after additional adjustment for a diet quality score. CONCLUSIONS: Higher mortality is associated with sugar-sweetened beverages specifically. The lack of an adverse association with fruit/vegetable juices suggests that source of sugar may be important and the association with artificially sweetened beverage may reflect reverse causation.