Educational outcomes in childhood cancer survivors: A Scotland-wide record-linkage study of 766,217 schoolchildren.

BACKGROUND: A cancer diagnosis during childhood greatly disrupts the lives of those affected, causing physical and psychological challenges. We aim to investigate educational outcomes among schoolchildren with a previous cancer diagnosis compared to their peers. METHODS: Individual records from four national education databases and three national health databases were linked to construct a cohort of all singleton schoolchildren born in Scotland attending Scottish local-authority schools between 2009-2013. Pupils previously diagnosed with any cancer, haematological cancers, and central nervous system (CNS) cancers, were compared to their unaffected peers with respect to five educational outcomes: special educational need (SEN), absenteeism, school exclusion, academic attainment, and unemployment. Analyses were adjusted for sociodemographic and maternity factors and chronic conditions. RESULTS: Of 766,217 pupils, 1,313 (0.17%) had a previous cancer diagnosis. Children with any cancer had increased odds of SEN (OR 3.26, 95% CI 2.86-3.71), absenteeism (IRR 1.82, 95% CI 1.70-1.94), and low attainment (OR 2.15, 95% CI 1.52-3.03) compared to their peers. Similar findings were observed for haematological (SEN OR 2.62, 95% CI 2.12-3.24; absenteeism IRR 2.04, 95% CI 1.85-2.25; low attainment OR 2.17, 95% CI 1.31-3.61) and CNS (SEN OR 6.44, 95% CI 4.91-8.46; absenteeism IRR 1.75, 95% CI 1.51-2.04; low attainment OR 3.33, 95% CI 1.52-7.30) cancers. Lower exclusions were observed among children with any cancer (IRR 0.51, 95% CI 0.31-0.83) and CNS cancer (IRR 0.20, 95% CI 0.06-0.61). No associations were observed with unemployment. CONCLUSIONS: This study highlights the wider impacts of childhood cancer on educational outcomes. These children need to be supported, as poor educational outcomes can further impact later health.

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.

Evaluation of a national smoke-free prisons policy using medication dispensing: an interrupted time-series analysis.

BACKGROUND: Internationally, smoking prevalence among people in prison custody (ie, people on remand awaiting trial, awaiting sentencing, or serving a custodial sentence) is high. In Scotland, all prisons implemented a comprehensive smoke-free policy in 2018 after a 16-month anticipatory period. In this study, we aimed to use data on medication dispensing to assess the impact of this policy on cessation support, health outcomes, and potential unintended consequences among people in prison custody. METHODS: We did an interrupted time-series analysis using dispensing data for 44 660 individuals incarcerated in 14 closed prisons in Scotland between March 30, 2014, and Nov 30, 2019. We estimated changes in dispensing rates associated with the policy announcement (July 17, 2017) and full implementation (Nov 30, 2018) using seasonal autoregressive integrated moving average models. Medication categories of primary interest were treatments for nicotine dependence (as an indicator of smoking cessation or abstinence attempts), acute smoking-associated illnesses, and mental health (antidepressants). We included antiepileptic medications as a negative control. FINDINGS: A 44% step increase in dispensing of treatments for nicotine dependence was observed at implementation (2250 items per 1000 people in custody per fortnight, 95% CI 1875 to 2624) due primarily to a 42% increase in dispensing of nicotine replacement therapy (2109 items per 1000 people in custody per fortnight, 1701 to 2516). A 9% step decrease in dispensing for smoking-related illnesses was observed at implementation, largely accounted for by respiratory medications (-646 items per 1000 people in custody per fortnight, -1111 to -181). No changes associated with announcement or implementation were observed for mental health dispensing or antiepileptic medications (control). INTERPRETATION: Smoke-free prison policies might improve respiratory health among people in custody and encourage smoking abstinence or cessation without apparent short-term adverse effects on mental health dispensing. FUNDING: National Institute of Health Research Public Health Research programme, Scottish Government Chief Scientist Office, and UK Medical Research Council.

Associations between smoke-free vehicle legislation and childhood admissions to hospital for asthma in Scotland: an interrupted time-series analysis of whole-population data.

BACKGROUND: In Scotland, childhood admissions to hospital for asthma fell from March, 2006, after legislation was introduced to prohibit smoking in public places. In December, 2016, new Scottish legislation banned smoking in vehicles containing a child. We aimed to determine whether the introduction of this new legislation produced additional benefits. METHODS: We obtained data on all asthma emergency admissions to hospitals in Scotland between 2000 and 2018 for individuals younger than 16 years. We used interrupted time-series analyses to study changes in monthly incidence of asthma emergency admissions to hospital per 100 000 children after the introduction of smoke-free vehicle legislation, taking into account previous smoke-free interventions. We did subgroup analyses according to age and area deprivation, using the Scottish Index of Multiple Deprivation, and repeated the analyses for a control condition, gastroenteritis, and other respiratory conditions. FINDINGS: Of the 32 342 emergency admissions to hospital for asthma among children younger than 16 years over the 19-year study period (Jan 1, 2000, to Dec 31, 2018), 13 954 (43%) were among children younger than 5 years and 18 388 (57%) were among children aged 5-15 years. After the introduction of smoke-free vehicle legislation, there was a non-significant decline in the slope for monthly emergency admissions to hospital for asthma among children younger than 16 years (-1·21%, 95% CI -2·64 to 0·23) relative to the underlying trend in hospital admissions for childhood asthma. However, children younger than 5 years had a significant decline in the slope for monthly asthma admissions (-1·49%, -2·69 to -0·27) over and above the underlying trend among children in this age group (equivalent to six fewer hospitalisations per year), but no such decline was seen in children aged 5-15 years. Monthly admissions to hospital for asthma fell significantly among children living in the most affluent areas (-2·27%, -4·41 to -0·07) but not among those living in the most deprived areas. We found no change in admissions to hospital for gastroenteritis or other respiratory conditions after the introduction of the smoke-free vehicle legislation. INTERPRETATION: Although legislation banning smoking in vehicles did not affect hospital admissions for severe asthma among children overall or in the older age group, this legislation was associated with a reduction in severe asthma exacerbations requiring hospital admission among preschool children, over and above the underlying trend and previous interventions designed to reduce exposure to second-hand smoke. Similar legislation prohibiting smoking in vehicles that contain children should be adopted in other countries. FUNDING: None.

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.

Antenatal Exposure to UV-B Radiation and Preeclampsia: A Retrospective Cohort Study.

Background Risk of preeclampsia varies by month of delivery. We tested whether this seasonal patterning may be mediated through maternal vitamin D concentration using antenatal exposure to UV-B radiation as an instrumental variable. Methods and Results Scottish maternity records were linked to antenatal UV-B exposure derived from satellites between 2000 and 2010. Logistic regression analyses were used to explore the association between UV-B and preeclampsia, adjusting for the potential confounding effects of month of conception, child's sex, gestation, parity, and mean monthly temperature. Of the 522 896 eligible singleton deliveries, 8689 (1.66%) mothers developed preeclampsia. Total antenatal UV-B exposure ranged from 43.18 to 101.11 kJ/m2 and was associated with reduced risk of preeclampsia with evidence of a dose-response relationship (highest quintile of exposure: adjusted odds ratio, 0.57; 95% CI, 0.44-0.72; P<0.001). Associations were demonstrated for UV-B exposure in all 3 trimesters. Conclusions The seasonal patterning of preeclampsia may be mediated through low maternal vitamin D concentration in winter resulting from low UV-B radiation. Interventional studies are required to determine whether vitamin D supplements or UV-B-emitting light boxes can reduce the seasonal patterning of preeclampsia.

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.

Association of SBP and BMI with cognitive and structural brain phenotypes in UK Biobank.

OBJECTIVE: To test for associations between SBP and BMI, with domain-specific cognitive abilities and examine which brain structural phenotypes mediate those associations. METHODS: Using cross-sectional UK Biobank data (final N = 28 412), we examined SBP/BMI vs. cognitive test scores of pairs-matching, matrix completion, trail making test A/B, digit symbol substitution, verbal-numerical reasoning, tower rearranging and simple reaction time. We adjusted for potential confounders of age, sex, deprivation, medication, apolipoprotein e4 genotype, smoking, population stratification and genotypic array. We tested for mediation via multiple structural brain imaging phenotypes and corrected for multiple testing with false discovery rate. RESULTS: We found positive associations for higher BMI with worse reaction time, reasoning, tower rearranging and matrix completion tasks by 0.024-0.067 SDs per BMI SD (all P < 0.001). Higher SBP was associated with worse reasoning (0.034 SDs) and matrix completion scores (-0.024 SDs; both P < 0.001). Both BMI and SBP were associated with multiple brain structural metrics including total grey/white matter volumes, frontal lobe volumes, white matter tract integrity and white matter hyperintensity volumes: specific metrics mediated around one-third of the associations with cognition. CONCLUSION: Our findings add to the body of evidence that addressing cardiovascular risk factors may also preserve cognitive function, via specific aspects of brain structure.

Modifiable and non-modifiable risk factors for COVID-19, and comparison to risk factors for influenza and pneumonia: results from a UK Biobank prospective cohort study.

OBJECTIVES: We aimed to investigate demographic, lifestyle, socioeconomic and clinical risk factors for COVID-19, and compared them to risk factors for pneumonia and influenza in UK Biobank. DESIGN: Cohort study. SETTING: UK Biobank. PARTICIPANTS: 49-83 year olds (in 2020) from a general population study. MAIN OUTCOME MEASURES: Confirmed COVID-19 infection (positive SARS-CoV-2 test). Incident influenza and pneumonia were obtained from primary care data. Poisson regression was used to study the association of exposure variables with outcomes. RESULTS: Among 235 928 participants, 397 had confirmed COVID-19. After multivariable adjustment, modifiable risk factors were higher body mass index and higher glycated haemoglobin (HbA1C) (RR 1.28 and RR 1.14 per SD increase, respectively), smoking (RR 1.39), slow walking pace as a proxy for physical fitness (RR 1.53), and use of blood pressure medications as a proxy for hypertension (RR 1.33). Higher forced expiratory volume in 1 s (FEV1) and high-density lipoprotein (HDL) cholesterol were both associated with lower risk (RR 0.84 and RR 0.83 per SD increase, respectively). Non-modifiable risk factors included male sex (RR 1.72), black ethnicity (RR 2.00), socioeconomic deprivation (RR 1.17 per SD increase in Townsend Index), and high cystatin C (RR 1.13 per SD increase). The risk factors overlapped with pneumonia somewhat, less so for influenza. The associations with modifiable risk factors were generally stronger for COVID-19, than pneumonia or influenza. CONCLUSION: These findings suggest that modification of lifestyle may help to reduce the risk of COVID-19 and could be a useful adjunct to other interventions, such as social distancing and shielding of high risk.

Association between APOE e4 and white matter hyperintensity volume, but not total brain volume or white matter integrity.

Apolipoprotein (APOE) e4 genotype is an accepted risk factor for accelerated cognitive aging and dementia, though its neurostructural substrates are unclear. The deleterious effects of this genotype on brain structure may increase in magnitude into older age. This study aimed to investigate in UK Biobank the association between APOE e4 allele presence vs. absence and brain imaging variables that have been associated with worse cognitive abilities; and whether this association varies by cross-sectional age. We used brain magnetic resonance imaging (MRI) and genetic data from a general-population cohort: the UK Biobank (N = 8395 after exclusions). We adjusted for the covariates of age in years, sex, Townsend social deprivation scores, smoking history and cardiometabolic diseases. There was a statistically significant association between APOE e4 genotype and increased (i.e. worse) white matter (WM) hyperintensity volumes (standardised beta = 0.088, 95% confidence intervals = 0.036 to 0.139, P = 0.001), a marker of poorer cerebrovascular health. There were no associations with left or right hippocampal, total grey matter (GM) or WM volumes, or WM tract integrity indexed by fractional anisotropy (FA) and mean diffusivity (MD). There were no statistically significant interactions with age. Future research in UK Biobank utilising intermediate phenotypes and longitudinal imaging hold significant promise for this area, particularly pertaining to APOE e4's potential link with cerebrovascular contributions to cognitive aging.

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.).

The association of grip strength with health outcomes does not differ if grip strength is used in absolute or relative terms: a prospective cohort study.

BACKGROUND: higher grip strength is associated with better health outcomes. The optimal way to report grip strength (i.e. absolute vs. relative) for prediction, however, remains to be established. METHODS: in participants (aged 37-73 at baseline) from the UK Biobank, we examined the associations of grip strength, expressed in absolute terms (kilograms) and relative to anthropometric variables, with mortality and disease incidence, after exclusion of the first 2 years of follow-up, and compared risk predictions scores of handgrip strength when differentially expressed. RESULTS: of the 356 721 participants included in the analysis 6,234 died (1.7%) and 4,523 developed CVD (1.3%) over a mean follow-up of 5.0 years (ranging from 3.3 to 7.8) for mortality and 4.1 years (ranging from 2.4 to 7.0) for disease incidence data. As expected, baseline higher grip strength was associated with lower risk of all-cause and cause specific mortality and incidence. These associations did not meaningfully differ when grip-strength was expressed in absolute terms, vs. relative to height, weight, fat-free mass, BMI, fat-free mass index and fat-free mass, or as z-scores. Similarly the different ways of expressing grip strength had little effect on the ability of grip strength to improve risk prediction, based on C-index change, of an office-based risk score. CONCLUSIONS: the ability of grip strength to predict mortality is not altered by changing how it is expressed.

Antenatal exposure to solar radiation and learning disabilities: Population cohort study of 422,512 children.

Learning disability varies by month of conception. The underlying mechanism is unknown but vitamin D, necessary for normal brain development, is commonly deficient over winter in high latitude countries due to insufficient ultraviolet radiation. We linked the 2007-2016 Scottish School Pupil Censuses to Scottish maternity records and to sunshine hours and antenatal ultraviolet A/B radiation exposure derived from weather stations and satellites respectively. Logistic regression analyses were used to explore the associations between solar radiation, then ultraviolet B, and learning disabilities, adjusting for the potential confounding effects of month of conception and sex. Of the 422,512 eligible, singleton schoolchildren born at term in Scotland, 79,616 (18.8%) had a learning disability. Total antenatal sunshine hours (highest quintile; adjusted OR 0.89; 95% CI: 0.86, 0.93; p < 0.001) and ultraviolet B exposure (highest quintile; adjusted OR 0.55; 95% CI: 0.51, 0.60; p < 0.001) were inversely associated with learning disabilities with evidence of a dose-relationship. The latter association was independent of ultraviolet A exposure. Significant associations were demonstrated for exposure in all three trimesters. Low maternal exposure to ultraviolet B radiation may play a role in the seasonal patterning of learning disabilities. Further studies are required to corroborate findings and determine the effectiveness of supplements.

Assessing for interaction between APOE ε4, sex, and lifestyle on cognitive abilities.

OBJECTIVE: To test for interactions between APOE ε4 genotype and lifestyle factors on worse cognitive abilities in UK Biobank. METHODS: Using UK Biobank cohort data, we tested for interactions between APOE ε4 allele presence, lifestyle factors of alcohol intake, smoking, total physical activity and obesity, and sex, on cognitive tests of reasoning, information processing speed, and executive function (n range = 70,988-324,725 depending on the test). We statistically adjusted for potential confounders of age, sex, deprivation, cardiometabolic conditions, and educational attainment. RESULTS: There were significant associations between APOE ε4 and worse cognitive abilities, independent of potential confounders, and between lifestyle risk factors and worse cognitive abilities; however, there were no interactions at multiple correction-adjusted p < 0.05, against our hypotheses. CONCLUSIONS: Our results do not provide support for the idea that ε4 genotype increases vulnerability to the negative effects of lifestyle risk factors on cognitive ability, but rather support a primarily outright association between APOE ε4 genotype and worse cognitive ability.

Dose-response associations of cardiorespiratory fitness with all-cause mortality and incidence and mortality of cancer and cardiovascular and respiratory diseases: the UK Biobank cohort study.

OBJECTIVE: To investigate the association of cardiorespiratory fitness with all-cause mortality, and cardiovascular disease (CVD), respiratory disease, chronic obstructive pulmonary disease (COPD) and cancer mortality and incidence. DESIGN: Prospective population-based study. SETTING: UK Biobank. PARTICIPANTS: Of the 5 02 628 (5.5% response rate) participants recruited by UK Biobank, we included 73 259 (14.6%) participants with available data in this analysis. Of these, 1374 participants died and 4210 developed circulatory diseases, 1293 respiratory diseases and 4281 cancer, over a median of 5.0 years (IQR 4.3-5.7) follow-up. MAIN OUTCOME MEASURES: All-cause mortality and circulatory disease, respiratory disease, COPD and cancer (such as colorectal, lung, breast and prostate) mortality/incidence. Fitness was estimated using a submaximal cycle ergometer test. RESULTS: The HR for all-cause mortality for each metabolic equivalent of task (MET) higher fitness was 0.96 (95% CI 0.93 to 0.98). Similar results were observed for incident circulatory disease (HR 0.96 [0.95 to 0.97]), respiratory disease (HR 0.96 [0.94 to 0.98]), COPD (HR 0.90 [0.86 to 0.95) and colorectal cancer (HR 0.96 [0.92 to 1.00]). Nonlinear analysis revealed that a high level of fitness (>10METs) was associated with a greater incidence of atrial fibrillation (HR 1.24 [1.07 to 1.44]) and prostate cancer (HR 1.16 [1.02 to 1.32]) compared with average fitness. All results were adjusted for sociodemographic, lifestyle and dietary factors, body composition, and morbidity at baseline and excluded events in the first 2 years of follow-up. CONCLUSIONS: Higher cardiorespiratory fitness was associated with lower risk of premature mortality and incidence of CVD, respiratory disease and colorectal cancer.

Walking Pace Is Associated with Lower Risk of All-Cause and Cause-Specific Mortality.

PURPOSE: Walking pace is associated with all-cause and cardiovascular disease (CVD) mortality. Whether this association extends to other health outcomes and whether it is independent of total amount of time walked are currently unknown. Therefore, the aim of this study was to investigate whether usual walking pace is associated with a range of health outcomes. METHODS: UK Biobank participants (318,185 [54%] women) age 40 to 69 yr were included. Walking pace and total walking time were self-reported. The outcomes comprised: all-cause mortality as well as incidence and mortality from CVD, respiratory disease and cancer. The associations were investigated using Cox proportional hazard models. RESULTS: Over a mean of 5.0 yr [ranging from 3.3 to 7.8], 5890 participants died, 18,568 developed CVD, 5430 respiratory disease and 19,234 cancer. In a fully adjusted model, compared to slow pace walkers, men and women, respectively, with a brisk pace having lower risk of mortality from all-causes (hazard ratio [HR], 0.79; 95% confidence interval [CI], 0.69-0.90 and HR, 0.73; 95% CI, 0.62-0.85), CVD (HR, 0.62; 95% CI, 0.50-0.76 and HR, 0.80; 95% CI, 0.73-0.88), respiratory disease (HR, 0.58; 95% CI, 0.43-0.78 and HR, 0.66; 95% CI, 0.57-0.77), chronic obstructive pulmonary disease (HR, 0.26; 95% CI, 0.12-0.56 and HR, 0.28; 95% CI, 0.16-0.49). No associations were found for all-cause cancer, colorectal, and breast cancer. However, brisk walking was associated with a higher risk of prostate cancer. CONCLUSIONS: Walking pace is associated with lower risk of a wide range of important health conditions, independently of overall time spent walking.

Associations of discretionary screen time with mortality, cardiovascular disease and cancer are attenuated by strength, fitness and physical activity: findings from the UK Biobank study.

BACKGROUND: Discretionary screen time (time spent viewing a television or computer screen during leisure time) is an important contributor to total sedentary behaviour, which is associated with increased risk of mortality and cardiovascular disease (CVD). The aim of this study was to determine whether the associations of screen time with cardiovascular disease and all-cause mortality were modified by levels of cardiorespiratory fitness, grip strength or physical activity. METHODS: In total, 390,089 participants (54% women) from the UK Biobank were included in this study. All-cause mortality, CVD and cancer incidence and mortality were the main outcomes. Discretionary television (TV) viewing, personal computer (PC) screen time and overall screen time (TV + PC time) were the exposure variables. Grip strength, fitness and physical activity were treated as potential effect modifiers. RESULTS: Altogether, 7420 participants died, and there were 22,210 CVD events, over a median of 5.0 years follow-up (interquartile range 4.3 to 5.7; after exclusion of the first 2 years from baseline in the landmark analysis). All discretionary screen-time exposures were significantly associated with all health outcomes. The associations of overall discretionary screen time with all-cause mortality and incidence of CVD and cancer were strongest amongst participants in the lowest tertile for grip strength (all-cause mortality hazard ratio per 2-h increase in screen time (1.31 [95% confidence interval: 1.22-1.43], p < 0.0001; CVD 1.21 [1.13-1.30], p = 0.0001; cancer incidence 1.14 [1.10-1.19], p < 0.0001) and weakest amongst those in the highest grip-strength tertile (all-cause mortality 1.04 [0.95-1.14], p = 0.198; CVD 1.05 [0.99-1.11], p = 0.070; cancer 0.98 [0.93-1.05], p = 0.771). Similar trends were found for fitness (lowest fitness tertile: all-cause mortality 1.23 [1.13-1.34], p = 0.002 and CVD 1.10 [1.02-1.22], p = 0.010; highest fitness tertile: all-cause mortality 1.12 [0.96-1.28], p = 0.848 and CVD 1.01 [0.96-1.07], p = 0.570). Similar findings were found for physical activity for all-cause mortality and cancer incidence. CONCLUSIONS: The associations between discretionary screen time and adverse health outcomes were strongest in those with low grip strength, fitness and physical activity and markedly attenuated in those with the highest levels of grip strength, fitness and physical activity. Thus, if these associations are causal, the greatest benefits from health promotion interventions to reduce discretionary screen time may be seen in those with low levels of strength, fitness and physical activity.

Associations of grip strength with cardiovascular, respiratory, and cancer outcomes and all cause mortality: prospective cohort study of half a million UK Biobank participants.

OBJECTIVE: To investigate the association of grip strength with disease specific incidence and mortality and whether grip strength enhances the prediction ability of an established office based risk score. DESIGN: Prospective population based study. SETTING: UK Biobank. PARTICIPANTS: 502 293 participants (54% women) aged 40-69 years. MAIN OUTCOME MEASURES: All cause mortality as well as incidence of and mortality from cardiovascular disease, respiratory disease, chronic obstructive pulmonary disease, and cancer (all cancer, colorectal, lung, breast, and prostate). RESULTS: Of the participants included in analyses, 13 322 (2.7%) died over a mean of 7.1 (range 5.3-9.9) years' follow-up. In women and men, respectively, hazard ratios per 5 kg lower grip strength were higher (all at P<0.05) for all cause mortality (1.20, 95% confidence interval 1.17 to 1.23, and 1.16, 1.15 to 1.17) and cause specific mortality from cardiovascular disease (1.19, 1.13 to 1.25, and 1.22, 1.18 to 1.26), all respiratory disease (1.31, 1.22 to 1.40, and 1.24, 1.20 to 1.28), chronic obstructive pulmonary disease (1.24, 1.05 to 1.47, and 1.19, 1.09 to 1.30), all cancer (1.17, 1.13 to 1.21, 1.10, 1.07 to 1.13), colorectal cancer (1.17, 1.04 to 1.32, and 1.18, 1.09 to 1.27), lung cancer (1.17, 1.07 to 1.27, and 1.08, 1.03 to 1.13), and breast cancer (1.24, 1.10 to 1.39) but not prostate cancer (1.05, 0.96 to 1.15). Several of these relations had higher hazard ratios in the younger age group. Muscle weakness (defined as grip strength <26 kg for men and <16 kg for women) was associated with a higher hazard for all health outcomes, except colon cancer in women and prostate cancer and lung cancer in both men and women. The addition of handgrip strength improved the prediction ability, based on C index change, of an office based risk score (age, sex, diabetes diagnosed, body mass index, systolic blood pressure, and smoking) for all cause (0.013) and cardiovascular mortality (0.012) and incidence of cardiovascular disease (0.009). CONCLUSION: Higher grip strength was associated with a range of health outcomes and improved prediction of an office based risk score. Further work on the use of grip strength in risk scores or risk screening is needed to establish its potential clinical utility.

Secondhand smoke exposure and risk of incident peripheral arterial disease and mortality: a Scotland-wide retrospective cohort study of 4045 non-smokers with cotinine measurement.

BACKGROUND: Active smoking is an important risk factor for all-cause mortality and peripheral arterial disease (PAD). In contrast, published studies on the associations with secondhand smoke (SHS) are limited. The aim of this study was to examine the associations between SHS exposure and incident PAD, as well as mortality, among middle-aged non-smokers. METHODS: We undertook a retrospective, cohort study using record linkage of the Scottish Health Surveys between 1998 and 2010 to hospital admissions and death certificates. Inclusion was restricted to participants aged > 45 years. Cox proportional hazard models were used to examine the association between SHS exposure and incident PAD (hospital admission or death) and all-cause mortality, with adjustment for potential confounders. RESULTS: Of the 4045 confirmed non-smokers (self-reported non-smokers with salivary cotinine concentrations < 15 ng/mL), 1163 (28.8%) had either moderate or high exposure to SHS at baseline. In men, high exposure to SHS (cotinine ≥2.7 ng/mL) was associated with increased risk of all-cause mortality (fully adjusted hazard ratio [HR] 1.54, 95% CI 1.07-2.22, p = 0.020) with evidence of a dose-relationship (p for trend = 0.004). In men, high exposure to SHS was associated with increased risk of incident PAD over the first five years of follow-up (fully adjusted HR 4.29, 95% CI 1.14-16.10, p = 0.031) but the association became non-significant over longer term follow-up. CONCLUSIONS: SHS exposure was independently associated with all-cause mortality and may be associated with PAD, but larger studies, or meta-analyses, are required to confirm the latter.