Polygenic and socioeconomic risk for high body mass index: 69 years of follow-up across life.

Genetic influences on body mass index (BMI) appear to markedly differ across life, yet existing research is equivocal and limited by a paucity of life course data. We thus used a birth cohort study to investigate differences in association and explained variance in polygenic risk for high BMI across infancy to old age (2-69 years). A secondary aim was to investigate how the association between BMI and a key purported environmental determinant (childhood socioeconomic position) differed across life, and whether this operated independently and/or multiplicatively of genetic influences. Data were from up to 2677 participants in the MRC National Survey of Health and Development, with measured BMI at 12 timepoints from 2-69 years. We used multiple polygenic indices from GWAS of adult and childhood BMI, and investigated their associations with BMI at each age. For polygenic liability to higher adult BMI, the trajectories of effect size (ß) and explained variance (R2) diverged: explained variance peaked in early adulthood and plateaued thereafter, while absolute effect sizes increased throughout adulthood. For polygenic liability to higher childhood BMI, explained variance was largest in adolescence and early adulthood; effect sizes were marginally smaller in absolute terms from adolescence to adulthood. All polygenic indices were related to higher variation in BMI; quantile regression analyses showed that effect sizes were sizably larger at the upper end of the BMI distribution. Socioeconomic and polygenic risk for higher BMI across life appear to operate additively; we found little evidence of interaction. Our findings highlight the likely independent influences of polygenic and socioeconomic factors on BMI across life. Despite sizable associations, the BMI variance explained by each plateaued or declined across adulthood while BMI variance itself increased. This is suggestive of the increasing importance of chance ('non-shared') environmental influences on BMI across life.

Early childhood lower respiratory tract infection and premature adult death from respiratory disease in Great Britain: a national birth cohort study.

BACKGROUND: Lower respiratory tract infections (LRTIs) in early childhood are known to influence lung development and lifelong lung health, but their link to premature adult death from respiratory disease is unclear. We aimed to estimate the association between early childhood LRTI and the risk and burden of premature adult mortality from respiratory disease. METHODS: This longitudinal observational cohort study used data collected prospectively by the Medical Research Council National Survey of Health and Development in a nationally representative cohort recruited at birth in March, 1946, in England, Scotland, and Wales. We evaluated the association between LRTI during early childhood (age <2 years) and death from respiratory disease from age 26 through 73 years. Early childhood LRTI occurrence was reported by parents or guardians. Cause and date of death were obtained from the National Health Service Central Register. Hazard ratios (HRs) and population attributable risk associated with early childhood LRTI were estimated using competing risks Cox proportional hazards models, adjusted for childhood socioeconomic position, childhood home overcrowding, birthweight, sex, and smoking at age 20-25 years. We compared mortality within the cohort studied with national mortality patterns and estimated corresponding excess deaths occurring nationally during the study period. FINDINGS: 5362 participants were enrolled in March, 1946, and 4032 (75%) continued participating in the study at age 20-25 years. 443 participants with incomplete data on early childhood (368 [9%] of 4032), smoking (57 [1%]), or mortality (18 [<1%]) were excluded. 3589 participants aged 26 years (1840 [51%] male and 1749 [49%] female) were included in the survival analyses from 1972 onwards. The maximum follow-up time was 47·9 years. Among 3589 participants, 913 (25%) who had an LRTI during early childhood were at greater risk of dying from respiratory disease by age 73 years than those with no LRTI during early childhood (HR 1·93, 95% CI 1·10-3·37; p=0·021), after adjustment for childhood socioeconomic position, childhood home overcrowding, birthweight, sex, and adult smoking. This finding corresponded to a population attributable risk of 20·4% (95% CI 3·8-29·8) and 179 188 (95% CI 33 806-261 519) excess deaths across England and Wales between 1972 and 2019. INTERPRETATION: In this prospective, life-spanning, nationally representative cohort study, LRTI during early childhood was associated with almost a two times increased risk of premature adult death from respiratory disease, and accounted for one-fifth of these deaths. FUNDING: National Institute for Health and Care Research Imperial Biomedical Research Centre, Royal Brompton and Harefield National Health Service (NHS) Foundation Trust, Royal Brompton and Harefield Hospitals Charity and Imperial College Healthcare NHS Trust, UK Medical Research Council.

Investigating the factorial structure and measurement invariance of the parent-reported strengths and difficulties questionnaire at 11 years of age from the UK Millennium Cohort Study.

The strengths and difficulties questionnaire (SDQ) consist of five sub-scales that have been used to measure internalising and externalising symptoms in children, typically by combining sum scores of two sub-scales each, and pro-social behaviours. However, the different possible factorial structures that represent these symptoms have not been formally tested in a nationally representative sample of UK children. In addition, it is necessary to assess whether the SDQ is interpreted similarly across subgroups of the population. Exploratory and confirmatory factor analysis were used to test three competing structures for the parent-reported SDQ collected at age 11, the start of adolescence, in the UK Millennium Cohort Study (n = 11,519), and measurement invariance was assessed according to sex and a measure of deprivation of the area in which households lived. Internal consistency using ordinal alpha, internal convergent validity and external discriminant validity using average variance explained (AVE), and predictive validity were assessed. A five-factor model and a model with two second-order factors for internalising and externalising symptoms had better model fit than a three-factor model. For both structures, invariance was demonstrated across sex and area-level deprivation. AVE scores for the five-factor model indicated that peer and emotional problems factors were measuring a similar construct, as were the hyperactivity and conduct factors. In the second-order model, AVE scores indicated internalising and externalising symptoms were distinct constructs. A second-order model with two factors for internalising and externalising symptoms is appropriate for use in a cohort of UK children born in 2001/02, and our finding of invariance across sex and area-level deprivation indicate that the SDQ can be used in analysis investigating differences in symptoms across subgroups of the population.

Is there a link between infertility, miscarriage, stillbirth, and premature or early menopause? Results from pooled analyses of 9 cohort studies.

BACKGROUND: Some reproductive factors (such as age at menarche and parity) have been shown to be associated with age at natural menopause, but there has been little quantitative analysis of the association between infertility, miscarriage, stillbirth, and premature (<40 years) or early menopause (40-44 years). In addition, it has been unknown whether the association differs between Asian and non-Asian women, although the age at natural menopause is younger among Asian women. OBJECTIVE: This study aimed to investigate the association of infertility, miscarriage, and stillbirth with age at natural menopause, and whether the association differed by race (Asian and non-Asian). STUDY DESIGN: This was a pooled individual participant data analysis from 9 observational studies contributing to the InterLACE consortium. Naturally postmenopausal women with data on at least 1 of the reproductive factors (ie, infertility, miscarriage, and stillbirth), age at menopause, and confounders (ie, race, education level, age at menarche, body mass index, and smoking status) were included. A multinomial logistic regression model was used to estimate relative risk ratios and 95% confidence intervals for the association of infertility, miscarriage, and stillbirth with premature or early menopause, adjusting for confounders. Between-study difference and within-study correlation were taken into account by including study as a fixed effect and indicating study as a cluster variable. We also examined the association with number of miscarriages (0, 1, 2, ≥3) and stillbirths (0, 1, ≥2), and tested whether the strength of association differed between Asian and non-Asian women. RESULTS: A total of 303,594 postmenopausal women were included. Their median age at natural menopause was 50.0 years (interquartile range, 47.0-52.0). The percentages of women with premature and early menopause were 2.1% and 8.4%, respectively. The relative risk ratios (95% confidence intervals) of premature and early menopause were 2.72 (1.77-4.17) and 1.42 (1.15-1.74) for women with infertility; 1.31 (1.08-1.59) and 1.37 (1.14-1.65) for women with recurrent miscarriages; and 1.54 (1.52-1.56) and 1.39 (1.35-1.43) for women with recurrent stillbirths. Asian women with infertility, recurrent miscarriages (≥3), or recurrent stillbirths (≥2) had higher risk of premature and early menopause compared with non-Asian women with the same reproductive history. CONCLUSION: Histories of infertility and recurrent miscarriages and stillbirths were associated with higher risk of premature and early menopause, and the associations differed by race, with stronger associations for Asian women with such reproductive history.

How are hearing loss and physical activity related? Analysis from the English longitudinal study of ageing.

Although cross-sectional studies suggest that hearing loss in middle- and older-aged adults is associated with lower physical activity, longitudinal evidence is limited. This study aimed to investigate the potential bi-directional association between hearing loss and physical activity over time. Participants were from the English Longitudinal Study of Ageing (N = 11,292) who were 50-years or older at baseline assessment (1998-2000). Individuals were followed-up biannually for up to 20-years (2018-2019) and were classified as ever reporting hearing loss (n = 4946) or not reporting hearing loss (n = 6346). Data were analysed with Cox-proportional hazard ratios and multilevel logistic regression. The results showed that baseline physical activity was not associated with hearing loss over the follow-up. Time (i.e., wave of assessment) by hearing loss interactions showed that physical activity declined more rapidly over time in those with hearing loss, compared to those without (Odds Ratios = 0.94, 95% Confidence Intervals; 0.92-0.96, p < .001). These findings highlight the importance of addressing physical activity in middle- and older-aged adults with hearing loss. As physical activity is a modifiable behaviour that can reduce the risk of developing chronic health conditions, individuals with hearing loss may need additional, tailored support to be more physically active. Mitigating the decline in physical activity could be essential to support healthy ageing for adults with hearing loss.

Understanding and detecting behaviours prior to a suicide attempt: A mixed-methods study.

OBJECTIVE: Prior research suggests there are observable behaviours preceding suicide attempts in public places. However, there are currently no ways to continually monitor such sites, limiting the potential to intervene. In this mixed-methods study, we examined the acceptability and feasibility of using an automated computer system to identify crisis behaviours. METHODS: First, we conducted a large-scale acceptability survey to assess public perceptions on research using closed-circuit television and artificial intelligence for suicide prevention. Second, we identified crisis behaviours at a frequently used cliff location by manual structured analysis of closed-circuit television footage. Third, we configured a computer vision algorithm to identify crisis behaviours and evaluated its sensitivity and specificity using test footage. RESULTS: Overall, attitudes were positive towards research using closed-circuit television and artificial intelligence for suicide prevention, including among those with lived experience. The second study revealed that there are identifiable behaviours, including repetitive pacing and an extended stay. Finally, the automated behaviour recognition algorithm was able to correctly identify 80% of acted crisis clips and correctly reject 90% of acted non-crisis clips. CONCLUSION: The results suggest that using computer vision to detect behaviours preceding suicide is feasible and well accepted by the community and may be a feasible method of initiating human contact during a crisis.

Area disadvantage and mental health over the life course: a 69-year prospective birth cohort study.

PURPOSE: Existing evidence on the mental health consequences of disadvantaged areas uses cross-sectional or longitudinal studies with short observation periods. The objective of this research was to investigate this association over a 69-year period. METHODS: Data were obtained from the MRC National Survey of Health and Development (NSHD; the British 1946 birth cohort), which consisted of 2125 participants at 69 years. We assessed longitudinal associations between area disadvantage and mental health symptoms at adolescence and adulthood with use of multilevel modelling framework. RESULTS: After adjustment for father's social class, for each one percentage increase in area disadvantage at age 4, there was a 0.02 (95% CI 0.001, 0.04) mean increase in the total score of the neuroticism scale at age 13-15. After adjustment for father's social class, adult socio-economic position, cognitive ability and educational attainment, a one percentage increase in change score of area disadvantage between age 4 and 26 was associated with a mean increase in the total Psychiatric Symptom Frequency score (MD 0.06; 95% CI 0.007, 0.11). Similar associations were observed with change scores between ages 4, 53, 60 and total General Health Questionnaire-28 score at age 53 (MD 0.05; 95% CI 0.01, 0.11) and 60-64 (MD 0.06; 95% CI 0.009, 0.11). CONCLUSIONS: Cohort members who experienced increasing area disadvantage from childhood were at increased risk of poor mental health over the life course. Population-wide interventions aiming at improving social and physical aspects of the early neighbourhood environment could reduce the socio-economic burden of poor mental health.

Association between carotid atherosclerosis and brain activation patterns during the Stroop task in older adults: An fNIRS investigation.

There is an increasing body of evidence suggesting that vascular disease could contribute to cognitive decline and overt dementia. Of particular interest is atherosclerosis, as it is not only associated with dementia, but could be a potential mechanism through which cardiovascular disease directly impacts brain health. In this work, we evaluated the differences in functional near infrared spectroscopy (fNIRS)-based measures of brain activation, task performance, and the change in central hemodynamics (mean arterial pressure (MAP) and heart rate (HR)) during a Stroop color-word task in individuals with atherosclerosis, defined as bilateral carotid plaques (n = 33) and healthy age-matched controls (n = 33). In the healthy control group, the left prefrontal cortex (LPFC) was the only region showing evidence of activation when comparing the incongruous with the nominal Stroop test. A smaller extent of brain activation was observed in the Plaque group compared with the healthy controls (1) globally, as measured by oxygenated hemoglobin (p = 0.036) and (2) in the LPFC (p = 0.02) and left sensorimotor cortices (LMC)(p = 0.008) as measured by deoxygenated hemoglobin. There were no significant differences in HR, MAP, or task performance (both in terms of the time required to complete the task and number of errors made) between Plaque and control groups. These results suggest that carotid atherosclerosis is associated with altered functional brain activation patterns despite no evidence of impaired performance of the Stroop task or central hemodynamic changes.

Distinct Body Mass Index Trajectories to Young-Adulthood Obesity and Their Different Cardiometabolic Consequences.

[Figure: see text].

Study protocol: MyoFit46-the cardiac sub-study of the MRC National Survey of Health and Development.

BACKGROUND: The life course accumulation of overt and subclinical myocardial dysfunction contributes to older age mortality, frailty, disability and loss of independence. The Medical Research Council National Survey of Health and Development (NSHD) is the world's longest running continued surveillance birth cohort providing a unique opportunity to understand life course determinants of myocardial dysfunction as part of MyoFit46-the cardiac sub-study of the NSHD. METHODS: We aim to recruit 550 NSHD participants of approximately 75 years+ to undertake high-density surface electrocardiographic imaging (ECGI) and stress perfusion cardiovascular magnetic resonance (CMR). Through comprehensive myocardial tissue characterization and 4-dimensional flow we hope to better understand the burden of clinical and subclinical cardiovascular disease. Supercomputers will be used to combine the multi-scale ECGI and CMR datasets per participant. Rarely available, prospectively collected whole-of-life data on exposures, traditional risk factors and multimorbidity will be studied to identify risk trajectories, critical change periods, mediators and cumulative impacts on the myocardium. DISCUSSION: By combining well curated, prospectively acquired longitudinal data of the NSHD with novel CMR-ECGI data and sharing these results and associated pipelines with the CMR community, MyoFit46 seeks to transform our understanding of how early, mid and later-life risk factor trajectories interact to determine the state of cardiovascular health in older age. TRIAL REGISTRATION: Prospectively registered on ClinicalTrials.gov with trial ID: 19/LO/1774 Multimorbidity Life-Course Approach to Myocardial Health- A Cardiac Sub-Study of the MCRC National Survey of Health and Development (NSHD).

Risk factors for natural menopause before the age of 45: evidence from two British population-based birth cohort studies.

BACKGROUND: Menopause that occurs before the age of 45 and is not medically induced (referred to here as 'early natural menopause') affects around one in 10 women and has serious health consequences. These consequences include increased risk of all-cause mortality, cardiovascular disease, osteoporosis, and type 2 diabetes. METHODS: We investigate risk factors for the onset of natural menopause before the age of 45 in two population-based prospective cohort studies in Britain: the 1958 cohort following 8959 women and the 1970 cohort following 8655 women. These studies follow women from birth to adulthood, and we use harmonized data on birth and early life characteristics, reproductive health, health behaviour, and socioeconomic characteristics for 6805 women who were pre-menopausal, peri-menopausal or had undergone natural menopause. Of these 6805 women, 3614 participated in the 1958 cohort (of which 368 had early menopause) and 3191 participated in the 1970 cohort (of which 206 had early menopause). Taking a life course approach, we focus on three distinct life stages - birth/early life, childhood, and early adulthood - to understand when risk factors are most harmful. Respecting the temporal sequence of exposures, we use a series of multivariable logistic regression models to estimate associations between early menopause and each potential risk factor adjusted for confounders. RESULTS: We find that early menopause is influenced by circumstances at birth. Women born in lower social class families, whose mother smoked during the pregnancy or who were breastfed 1 month or less were more likely to undergo early menopause. Early menopause is also associated with poorer cognitive ability and smoking in childhood. Adult health behaviour also matters. Smoking is positively correlated with early menopause, while regular exercise and moderate frequency of alcohol drinking in women's early thirties are associated with reduced risk of early menopause. The occurrence of gynaecological problems by women's early thirties is also linked to early menopause. CONCLUSIONS: We demonstrate that characteristics at different periods of life are associated with early menopause. Some of these associations relate to modifiable behaviours and thus the risks of early menopause and the adverse health outcomes associated with it may be preventable.

Socioeconomic position and body composition in childhood in high- and middle-income countries: a systematic review and narrative synthesis.

BACKGROUND: The relation between socioeconomic position (SEP) and obesity measured by body mass index (BMI), a measure of weight for height, has been extensively reviewed in children, showing consistent associations between disadvantaged SEP and higher BMI in high-income countries (HICs) and lower BMI in middle-income countries (MICs). Fat mass (FM), a more accurate measure of adiposity, and fat-free mass (FFM) are not captured by BMI, but have been shown to track from childhood to adulthood, and be important for cardiovascular health and functional outcomes in later life. It is not clear whether body composition is associated with SEP. We systematically reviewed the association between SEP and body composition in childhood. METHODS: A systematic review was carried out following PRISMA guidelines. The protocol was pre-registered with PROSPERO (CRD42019119937). Original studies in the English language, which examined the association between SEP and body composition in childhood, were included. An electronic search of three databases was conducted. Two independent reviewers carried out screening, data extraction and quality assessment. Due to heterogeneity in results, a narrative synthesis was conducted. Heterogeneity in findings according to SEP, sex, body composition measure and country income level was investigated. RESULTS: 50 papers were included, the majority from HICs. No papers were from low-income countries. Disadvantage in childhood was associated with greater FM and lower FFM in HICs, but with lower FM and lower FFM in MICs. When measures of FFM indexed to height were used there was no evidence of associations with SEP. In HICs, more studies reported associations between disadvantaged SEP and higher FM among girls comparative to boys. CONCLUSIONS: Inequalities in FM are evident in HICs and, in the opposite direction, in MICs and follow similar trends to inequalities for BMI. Inequalities in height are likely important in understanding inequalities in FFM.

Life course socioeconomic position and body composition in adulthood: a systematic review and narrative synthesis.

INTRODUCTION: Multiple systematic reviews have investigated the relation between socioeconomic position (SEP) and body mass index (BMI) throughout the life course. However, BMI does not capture quantity and distribution of fat and muscle, which are better indicators of obesity than BMI, and have been independently linked to adverse health outcomes. Less is known about the relation between SEP and body composition, and the literature has not been reviewed. We therefore systematically reviewed the literature on the association between life course SEP and body composition in adulthood. METHODS: A protocol was registered on PROSPERO (CRD42019119937), and the review followed PRISMA guidelines. An electronic search of three databases (MEDLINE, Embase Classic + Embase and SPORTDiscus) was conducted. Original studies in the English language were included that examine the association between any recognised measure of SEP at any age and body composition (fat mass, fat-free mass, ratio and distribution) in adulthood, measured using a direct technique, i.e., not an anthropometric measure. A narrative synthesis was conducted. RESULTS: A total of 47 papers were included in the final review, none were from low-income countries (LICs). Greater advantage in childhood and adulthood was associated with lower fat levels in high-income countries (HICs). Associations in the opposite direction were found exclusively in middle-income countries (MICs). No studies in MICs reported associations for childhood SEP. For measures of lean mass, the majority of papers reported no association, or greater advantage in adulthood associated with higher lean mass, with little variation between HICs and MICs. Associations in HICs are more often observed in women than men. CONCLUSION: The results indicate that fat measures follow similar patterns to those seen for BMI, and that women in HICs are more likely to experience inequalities in both fat and lean measures. Further research in LICs and MICs is needed.

Changes in the body mass index and blood pressure association across time: Evidence from multiple cross-sectional and cohort studies.

Although body mass index (BMI) is considered a key determinant of high blood pressure, its importance may differ over time and by age group. We utilised separate data sources to investigate temporal changes in this association: 23 independent (newly sampled), repeated cross-sectional studies (Health Survey for England (HSE)) at ≥25 years (1994-2018; N = 126,742); and three British birth cohorts at 43-46 years (born 1946, 1958, and 1970; N = 18,657). In HSE, associations were weaker in more recent years, with this trend most pronounced amongst older adults. After adjustment for sex, anti-hypertensive treatment and education, the mean difference in systolic blood pressure (SBP) per 1 kg/m2 increase in BMI amongst adults ≥55 years was 0.75 mmHg (95%CI: 0.60-0.90) in 1994, 0.66 mmHg (0.46-0.85) in 2003, and 0.53 mmHg (0.35-0.71) in 2018. In the 1958 and 1970 cohorts, BMI and SBP associations were of similar magnitude yet weaker in the 1946 cohort, potentially due to differences in blood pressure measurement device. Quantile regression analyses suggested that associations between BMI and SBP were present both below and above the hypertension threshold. A weaker association between BMI and blood pressure may partly offset the public health impacts of increasing obesity prevalence. However, despite sizable increases in use of antihypertensive medication, BMI remains positively associated with SBP in all ages. Our findings highlight the need to tackle non-medical factors such as population diet which influence both BMI and blood pressure, and the utility of using multiple datasets to obtain robust inferences on trends in risk factor-outcome associations across time.

Early childhood weight gain: Latent patterns and body composition outcomes.

BACKGROUND: Despite early childhood weight gain being a key indicator of obesity risk, we do not have a good understanding of the different patterns that exist. OBJECTIVES: To identify and characterise distinct groups of children displaying similar early-life weight trajectories. METHODS: A growth mixture model captured heterogeneity in weight trajectories between 0 and 60 months in 1390 children in the Avon Longitudinal Study of Parents and Children. Differences between the classes in characteristics and body size/composition at 9 years were investigated. RESULTS: The best model had five classes. The "Normal" (45%) and "Normal after initial catch-down" (24%) classes were close to the 50th centile of a growth standard between 24 and 60 months. The "High-decreasing" (21%) and "Stable-high" (7%) classes peaked at the ~91st centile at 12-18 months, but while the former declined to the ~75th centile and comprised constitutionally big children, the latter did not. The "Rapidly increasing" (3%) class gained weight from below the 50th centile at 4 months to above the 91st centile at 60 months. By 9 years, their mean body mass index (BMI) placed them at the 98th centile. This class was characterised by the highest maternal BMI; highest parity; highest levels of gestational hypertension and diabetes; and the lowest socio-economic position. At 9 years, the "Rapidly increasing" class was estimated to have 68.2% (95% confidence interval [CI] 48.3, 88.1) more fat mass than the "Normal" class, but only 14.0% (95% CI 9.1, 18.9) more lean mass. CONCLUSIONS: Criteria used in growth monitoring practice are unlikely to consistently distinguish between the different patterns of weight gain reported here.

Exposure to multiple childhood social risk factors and adult body mass index trajectories from ages 20 to 64 years.

BACKGROUND: While childhood social risk factors appear to be associated with adult obesity, it is unclear whether exposure to multiple childhood social risk factors is associated with accelerated weight gain during adulthood. METHODS: We used the Medical Research Council National Survey of Health and Development, a British population-based birth cohort study of participants born in 1946, height and weight were measured by nurses at ages 36, 43, 53 and 60-64 and self-reported at 20 and 26 years. The 9 childhood socioeconomic risk factors and 8 binary childhood psychosocial risk factors were measured, with 13 prospectively measured at age 4 years (or at 7 or 11 years if missing) and 3 were recalled when participants were age 43. Multilevel modelling was used to examine the association between the number of childhood social risk factors and changes in body mass index (BMI) with age. RESULTS: Increasing exposure to a higher number of childhood socioeconomic risk factors was associated with higher mean BMI across adulthood for both sexes and with a faster increase in BMI from 20 to 64 years, among women but not men. Associations remained after adjustment for adult social class. There was no evidence of an association between exposure to childhood psychosocial risk factors and mean BMI in either sex at any age. CONCLUSIONS: Strategies for the prevention and management of weight gain across adulthood may need to tailor interventions in consideration of past exposure to multiple socioeconomic disadvantages experienced during childhood.

Mental Health Screening in General Practices as a Means for Enhancing Uptake of Digital Mental Health Interventions: Observational Cohort Study.

BACKGROUND: Digital mental health interventions stand to play a critical role in managing the mental health impact of the COVID-19 pandemic. Thus, enhancing their uptake is a key priority. General practitioners (GPs) are well positioned to facilitate access to digital interventions, but tools that assist GPs in identifying suitable patients are lacking. OBJECTIVE: This study aims to evaluate the suitability of a web-based mental health screening and treatment recommendation tool (StepCare) for improving the identification of anxiety and depression in general practice and, subsequently, uptake of digital mental health interventions. METHODS: StepCare screens patients for symptoms of depression (9-item Patient Health Questionnaire) and anxiety (7-item Generalized Anxiety Disorder scale) in the GP waiting room. It provides GPs with stepped treatment recommendations that include digital mental health interventions for patients with mild to moderate symptoms. Patients (N=5138) from 85 general practices across Australia were invited to participate in screening. RESULTS: Screening identified depressive or anxious symptoms in 43.09% (1428/3314) of patients (one-quarter were previously unidentified or untreated). The majority (300/335, 89.6%) of previously unidentified or untreated patients had mild to moderate symptoms and were candidates for digital mental health interventions. Although less than half were prescribed a digital intervention by their GP, when a digital intervention was prescribed, more than two-thirds of patients reported using it. CONCLUSIONS: Implementing web-based mental health screening in general practices can provide important opportunities for GPs to improve the identification of symptoms of mental illness and increase patient access to digital mental health interventions. Although GPs prescribed digital interventions less frequently than in-person psychotherapy or medication, the promising rates of uptake by GP-referred patients suggest that GPs can play a critical role in championing digital interventions and maximizing the associated benefits.

Systemic Inflammation and Cardio-Renal Organ Damage Biomarkers in Middle Age Are Associated With Physical Capability Up to 9 Years Later.

BACKGROUND: Physical capability, a key component of healthy aging, is associated with cardiovascular and other risk factors across life. We investigated whether midlife biomarkers of heart and kidney damage capturing the cumulative impact of long-term adverse exposures were associated with the level and decline in physical capability over 9 years of follow-up, taking account of systemic inflammatory biomarkers and conventional cardiovascular risk factors. METHODS: We used data on 1736 men and women from the oldest British birth cohort study with walking speed, chair rise speed, balance time, and grip strength assessed at ages 60 to 64 and 69 years. We tested associations between logged and standardized measures of cystatin C, NT-proBNP (N-terminal pro-B-type natriuretic peptide), interleukin (IL)-6, and E-selectin at age 60 to 64 years with performance at age 69 years, adjusting for sex, height, and body mass index; then for performance at age 60 to 64 years. These biomarkers were mutually adjusted, and additionally adjusted for cardiovascular risk factors (pulse pressure, total/high density lipoprotein cholesterol, glycosylated hemoglobin), diabetes mellitus, cardiovascular and kidney disease, smoking status, and lifetime socioeconomic position. RESULTS: Cystatin C, NT-proBNP, and IL-6 (but not E-selectin) were inversely associated with all outcomes, adjusted for sex, height, and body mass index. For example, a 1-SD increase in logged NT-proBNP was associated with weaker grip (-0.63 kg, 95% CI, -0.99 to -0.28); the equivalent association for cystatin C was -0.60 kg (95% CI, -0.94 to -0.25) and for IL-6 was -0.76 kg (95% CI, -1.11 to -0.41). Most associations remained, albeit attenuated, after adjustment for previous performance and mutual adjustment of the biomarkers. NT-proBNP and IL-6 (but not cystatin C) were more strongly associated with the outcomes than many of the conventional risk factors after mutual adjustment. CONCLUSIONS: Higher levels of NT-proBNP may identify those in midlife at risk of accelerated physical decline. Before considering the use of NT-proBNP for risk stratification, further research should untangle whether these associations exist because the biomarker is an integrated measure of cumulative exposures to relevant stressors across life, or whether it is marking additional risk pathways. Randomized trials to reduce the rate of decline in physical capability or delay incident disability could benefit from including middle-aged adults and adding NT-proBNP and IL-6 as intermediate outcomes.

Duration of obesity exposure between ages 10 and 40 years and its relationship with cardiometabolic disease risk factors: A cohort study.

BACKGROUND: Individuals with obesity do not represent a homogeneous group in terms of cardiometabolic risk. Using 3 nationally representative British birth cohorts, we investigated whether the duration of obesity was related to heterogeneity in cardiometabolic risk. METHODS AND FINDINGS: We used harmonised body mass index (BMI) and cardiometabolic disease risk factor data from 20,746 participants (49.1% male and 97.2% white British) enrolled in 3 British birth cohort studies: the 1946 National Survey of Health and Development (NSHD), the 1958 National Child Development Study (NCDS), and the 1970 British Cohort Study (BCS70). Within each cohort, individual life course BMI trajectories were created between 10 and 40 years of age, and from these, age of obesity onset, duration spent obese (range 0 to 30 years), and cumulative obesity severity were derived. Obesity duration was examined in relation to a number of cardiometabolic disease risk factors collected in mid-adulthood: systolic (SBP) and diastolic blood pressure (DBP), high-density-lipoprotein cholesterol (HDL-C), and glycated haemoglobin (HbA1c). A greater obesity duration was associated with worse values for all cardiometabolic disease risk factors. The strongest association with obesity duration was for HbA1c: HbA1c levels in those with obesity for <5 years were relatively higher by 5% (95% CI: 4, 6), compared with never obese, increasing to 20% (95% CI: 17, 23) higher in those with obesity for 20 to 30 years. When adjustment was made for obesity severity, the association with obesity duration was largely attenuated for SBP, DBP, and HDL-C. For HbA1c, however, the association with obesity duration persisted, independent of obesity severity. Due to pooling of 3 cohorts and thus the availability of only a limited number harmonised variables across cohorts, our models included adjustment for only a small number of potential confounding variables, meaning there is a possibility of residual confounding. CONCLUSIONS: Given that the obesity epidemic is characterised by a much earlier onset of obesity and consequently a greater lifetime exposure, our findings suggest that health policy recommendations aimed at preventing early obesity onset, and therefore reducing lifetime exposure, may help reduce the risk of diabetes, independently of obesity severity. However, to test the robustness of our observed associations, triangulation of evidence from different epidemiological approaches (e.g., mendelian randomization and negative control studies) should be obtained.

Psychosocial adversity and socioeconomic position during childhood and epigenetic age: analysis of two prospective cohort studies.

Psychosocial adversity in childhood (e.g. abuse) and low socioeconomic position (SEP) can have significant lasting effects on social and health outcomes. DNA methylation-based biomarkers are highly correlated with chronological age; departures of methylation-predicted age from chronological age can be used to define a measure of age acceleration, which may represent a potential biological mechanism linking environmental exposures to later health outcomes. Using data from two cohorts of women Avon Longitudinal Study of Parents and Children, (ALSPAC), N = 989 and MRC National Survey of Health and Development, NSHD, N = 773), we assessed associations of SEP, psychosocial adversity in childhood (parental physical or mental illness or death, parental separation, parental absence, sub-optimal maternal bonding, sexual, emotional and physical abuse and neglect) and a cumulative score of these psychosocial adversity measures, with DNA methylation age acceleration in adulthood (measured in peripheral blood at mean chronological ages 29 and 47 in ALSPAC and buccal cells at age 53 in NSHD). Sexual abuse was strongly associated with age acceleration in ALSPAC (sexual abuse data were not available in NSHD), e.g. at the 47-year time point sexual abuse associated with a 3.41 years higher DNA methylation age (95% CI 1.53 to 5.29) after adjusting for childhood and adulthood SEP. No associations were observed between low SEP, any other psychosocial adversity measure or the cumulative psychosocial adversity score and age acceleration. DNA methylation age acceleration is associated with sexual abuse, suggesting a potential mechanism linking sexual abuse with adverse outcomes. Replication studies with larger sample sizes are warranted.