Tobacco endgame measures and their adaptation in selected European countries: A narrative review synthesis.

Due to the continued detrimental effects of tobacco use, a growing number of countries are embracing the idea of tobacco endgame, meaning ending the tobacco epidemic instead of controlling it. This narrative review aims to synthesize and update the evidence from earlier scientific reviews on effective tobacco endgame measures, as well as to assess their integration to current national strategies among European countries with official tobacco endgame goals. The synthesis of the prior scientific literature found most evidence on product-focused and some evidence for supply-focused policies. Little evidence was detected for user- and institutional-focused measures. An update for the tobacco-free generation measure showed uncertainty in reducing smoking prevalence, especially for adolescents' reactions to age-restrictive laws. All the countries that established a tobacco endgame strategy have included product standards in their measures, predominantly based on European Union regulations on conventional tobacco products, yet standards above this level and considering other products were also common. Cessation measures were given strong emphasis in strategies, yet none of the countries linked these to specific endgame measures. Despite commonly mentioning vulnerable groups, such as youth and pregnant women, adoption of measures to reduce tobacco use among these groups was scarce. Lastly, the decline in tobacco use seems to be modest, implying challenges in meeting the endgame goals. To meet these goals, European countries should reinforce the implementation of known effective tobacco control measures such as tax increases. Furthermore, new innovative strategies and measures to meet the objective of an endgame should be explored.

A scoping review on self-regulation and reward processing measured with gambling tasks: Evidence from the general youth population.

Aberrant reward processing and poor self-regulation have a crucial role in the development of several adverse outcomes in youth, including mental health disorders and risky behaviours. This scoping review aims to map and summarise the evidence for links between aspects and measures of reward processing and self-regulation among children and adolescents in the general population. Specifically, it examined the direct associations between self-regulation (emotional or cognitive regulation) and reward processing. Studies were included if participants were <18 years and representative of the general population. Quantitative measures were used for self-regulation, and gambling tasks were used for reward processing. Of the eighteen studies included only two were longitudinal. Overall, the direction of the significant relationships identified depended on the gambling task used and the self-regulation aspect explored. Emotional regulation was measured with self-report questionnaires only, and was the aspect with the most significant associations. Conversely, cognitive regulation was mainly assessed with cognitive assessments, and most associations with reward processing were non-significant, particularly when the cognitive regulation aspects included planning and organisational skills. Nonetheless, there was some evidence of associations with attention, cognitive control, and overall executive functioning. More longitudinal research is needed to draw accurate conclusions on the direction of the association between self-regulation and reward processing.

Psychotic symptoms with and without a primary psychotic disorder in children requiring inpatient mental health admission.

Psychotic symptoms are relatively common in children and adolescents attending mental health services. On most occasions, their presence is not associated with a primary psychotic disorder, and their clinical significance remains understudied. No studies to date have evaluated the prevalence and clinical correlates of psychotic symptoms in children requiring inpatient mental health treatment. All children aged 6 to 12 years admitted to an inpatient children's unit over a 9-year period were included in this naturalistic study. Diagnosis at discharge, length of admission, functional impairment, and medication use were recorded. Children with psychotic symptoms without a childhood-onset schizophrenia spectrum disorder (COSS) were compared with children with COSS and children without psychotic symptoms using Chi-square and linear regressions. A total of 211 children were admitted during this period with 62.4% experiencing psychotic symptoms. The most common diagnosis in the sample was autism spectrum disorder (53.1%). Psychotic symptoms were not more prevalent in any diagnosis except for COSS (100%) and intellectual disability (81.8%). Psychotic symptoms were associated with longer admissions and antipsychotic medication use. The mean length of admission of children with psychotic symptoms without COSS seems to lie in between that of children without psychotic symptoms and that of children with COSS. We concluded that psychotic symptoms in children admitted to the hospital may be a marker of severity. Screening for such symptoms may have implications for treatment and could potentially contribute to identifying more effective targeted interventions and reducing overall morbidity.

Tobacco endgame in the WHO European Region: Feasibility in light of current tobacco control status.

INTRODUCTION: To assess the feasibility of developing World Health Organization (WHO) European Region countries' goals and measures in line with tobacco endgame objectives, information on the current tobacco control context and capacity is needed. The aim of this study was to assess the implementation of the Framework Convention on Tobacco Control (WHO FCTC) and MPOWER measures in the region. METHODS: In this cross-sectional study we used data from the WHO FCTC implementation reports and MPOWER from 2020 in 53 WHO European Region countries. Six domains (i.e. capacity, taxation and price policies, other national key regulations, public awareness raising and communication, tobacco use cessation, and monitoring) were formed. Subsequently, available indicators under these domains were scored and the level of implementation was computed for each country. Mann-Whitney tests were carried out to compare the scores between the group of countries with and without official endgame goals. RESULTS: Overall, implementation of the WHO FCTC with the selected indicators at the country level ranged from 28% to 86%, and of MPOWER from 31% to 96%. Full implementation was achieved by 28% of WHO FCTC Parties in the region in taxation and price policies, 12% in public awareness raising and communication, and 42% in monitoring. In capacity, tobacco use cessation and other national key regulations, none of the Parties in the region reached full implementation. Overall median WHO FCTC scores were significantly higher in countries with official endgame goals than in those without (p<0.001). CONCLUSIONS: There is unequal implementation of both WHO FCTC and MPOWER measures among WHO European Region countries. MPOWER and WHO FCTC provide all the measures for the necessary first steps, followed by innovative measures, to accomplish tobacco endgame goals.

Reciprocal associations between affective decision-making and mental health in adolescence.

Poor affective decision-making has been shown to associate cross-sectionally with poor mental health in clinical populations. However, evidence from general population samples is scarce. Moreover, whether decision-making is prospectively linked to mental health in youth in the general population and whether such associations are reciprocal have yet to be examined. The present study examined bidirectional associations between various aspects of affective decision-making and emotional and behavioural problems at ages 11 and 14 years in 13,366 members of the Millennium Cohort Study. Decision-making (delay aversion, deliberation time, quality of decision-making, risk adjustment, risk-taking) and emotional (emotional symptoms, peer problems) and behavioural (conduct problems, hyperactivity/inattention) problems were measured using the Cambridge Gambling Task and the Strengths and Difficulties Questionnaire, respectively. Results of cross-lagged panel models adjusted for confounding revealed a negative reciprocal association between hyperactivity and quality of decision-making but also positive reciprocal associations between conduct problems and delay aversion, and between peer problems and deliberation time. Emotional problems and peer problems predicted a decrease in risk-taking, conduct problems predicted an increase in risk-taking, and hyperactivity predicted an increase in delay aversion and deliberation time. Furthermore, hyperactivity and conduct problems predicted less risk adjustment, and risk adjustment predicted fewer peer problems. The results suggest that behavioural problems are prospectively linked to greater risk-taking and lower risk adjustment in adolescence. Moreover, adolescents with behavioural problems tend to make poorer decisions and be more delay-averse, but also poorer quality of decision-making and increased delay aversion are associated with more behavioural problems over time.

Experience of stigmatization in children receiving inpatient and outpatient mental health treatment: a longitudinal study.

Mental health-related stigma is poorly understood, and minimal research has focused on the experience of stigma from children's perspectives. We sought to investigate whether children treated as inpatients and outpatients had different experiences of stigma over time and whether stigma is linked to global functioning cross-sectionally and longitudinally. Children, aged 8-12 years, receiving treatment within a national specialist mental health inpatient unit were matched for age, gender and diagnosis with children receiving outpatient treatment (N = 64). Validated measures of stigma, global functioning and symptom severity were collected at the start of treatment and upon discharge from the ward for inpatients, and a similar timeframe for their individually matched outpatients. Latent change score models and partial correlation coefficients were employed to test our hypotheses. No differences in most aspects of stigma between children treated as inpatients and outpatients were observed, except for personal rejection at baseline and self-stigma at follow-up favouring outpatients. A reduction in stigma was observed in societal devaluation, personal rejection and secrecy for inpatients, and self-stigma and secrecy for outpatients between the two assessments. Societal devaluation declined at a higher rate among inpatients compared to outpatients, albeit reductions in stigma were comparable for all remaining measures. No association was found between the change in stigma and change in global functioning. Future research may offer further insights into the development and maintenance of stigma and identify key targets for anti-stigma interventions to reduce its long-term impact.

The role of inflammatory markers and cortisol in the association between early social cognition abilities and later internalising or externalising problems: Evidence from a UK birth cohort.

OBJECTIVE: Deficits in social cognition are associated with internalising (emotional and peer problems) and externalising (conduct problems and hyperactivity/inattention) symptoms in youth. It has been suggested that stress may be one of the mechanisms underlying these associations. However, no empirical studies have investigated if physiological stress can explain the prospective associations between social cognition deficits and internalising and externalising symptoms in the general youth population. This study addressed this question and focused on two indicators of physiological stress, dysregulated diurnal cortisol patterns and systemic inflammation. METHOD: Participants were 714 individuals from the Avon Longitudinal Study of Parents and Children (ALSPAC), a UK population-based birth cohort. Bayesian structural equation modelling was used to investigate a) the associations of social cognition abilities at ages 8, 11, and 14 years with internalising and externalising problems at age 17 years and b) the potential mediating effects of cortisol parameters at age 15 years and inflammatory markers [interleukin 6 (IL-6) and C-reactive protein (CRP)] at ages 9 and 16 years. RESULTS: We found that social cognition difficulties were associated with later internalising and externalising problems. Flattened diurnal cortisol slope was associated with hyperactivity/inattention problems two years later. Lower morning cortisol partially mediated the direct association between social communication deficits at 8 years and hyperactivity/inattention and conduct problems at 17 years, even after adjustments for inflammation and confounders (for hyperactivity/inattention: indirect effect = 0.07, 95% CI [0.00, 0.18], p = .042; for conduct problems: indirect effect = 0.04, 95% CI [0.00, 0.11], p = .040). We did not find a significant association between systemic inflammation and social cognition difficulties, internalising problems, or externalising problems. CONCLUSION: Our findings suggest that part of the effect of social communication difficulties in childhood on externalising problems in adolescence was mediated by lower morning cortisol. Hence, our study indicates that the hypoactivity of the hypothalamic-pituitary-adrenal (HPA) axis may be one of the physiological mechanisms linking some social cognition deficits to externalising problems.

The role of physical environmental characteristics and intellectual disability in conduct problem trajectories across childhood: A population-based Cohort study.

BACKGROUND: The paucity of research investigating the role of the physical environment in the developmental progression of conduct problems and the potential moderating effects of intellectual disability (ID) is surprising, given the clinical relevance of elucidating environmental determinants of disruptive behaviours. AIMS: To use data from a large UK cohort study to assess associations between physical environmental exposures, ID, and conduct problem trajectories. METHOD: The sample included 8168 Millennium Cohort Study children (1.9% with ID). Multilevel growth curve modelling was used to examine the role of physical environment characteristics in the developmental trajectories of conduct problems after adjustments for ID status. RESULTS: Exposure to external environmental domains was not associated with differences in children's conduct problems across development. Alternatively, internal aspects of the household environment: spatial density (b = 0.40, p < .001) and damp problems (b = 0.14, p < .001) were both significantly associated with increased trajectories. Various individual and familial covariates were positively associated with conduct problems over time, including: presence of ID (b = 0.96, p < .001), autism spectrum disorder (b = 1.18, p < .001), male sex (b = 0.26, p < .001), poverty (b = 0.19, p < .001), maternal depression (b = 0.65, p < .001), and non-nuclear family structure (b = 0.35, p < .001). Positive ID status appeared to moderate the effects of internal household spatial density, reporting a non-linear negative association with spatial density and conduct problems across development (b = -1.08, p < .01). CONCLUSIONS: Our findings highlight the potential harmful consequences of poor internal residential conditions on children's development of disruptive behaviours.

Subcortical volumes across the lifespan: Data from 18,605 healthy individuals aged 3-90 years.

Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resources of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to examine age-related trajectories inferred from cross-sectional measures of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippocampus and amygdala using magnetic resonance imaging data obtained from 18,605 individuals aged 3-90 years. All subcortical structure volumes were at their maximum value early in life. The volume of the basal ganglia showed a monotonic negative association with age thereafter; there was no significant association between age and the volumes of the thalamus, amygdala and the hippocampus (with some degree of decline in thalamus) until the sixth decade of life after which they also showed a steep negative association with age. The lateral ventricles showed continuous enlargement throughout the lifespan. Age was positively associated with inter-individual variability in the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to examine the functional significance of deviations from typical age-related morphometric patterns.

Ability-grouping and problem behavior trajectories in childhood and adolescence: Results from a U.K. population-based sample.

Ability-grouping has been studied extensively in relation to children's academic, but not emotional and behavioral outcomes. The sample comprised 7259 U.K. children (50% male) with data on between-class and within-class ability-grouping at age 7. Peer, emotional, hyperactivity, and conduct problems were measured at ages 7, 11, and 14 years. Children in low within-class ability groups showed more hyperactivity and emotional problems across the study period compared to non-grouped children, after adjustments for the different types of ability grouping and confounding. Additionally, children in the middle within-class ability groups showed more, and those in the top within-class groups less, hyperactivity compared to non-grouped children, after adjustment. Children in lower within-class groups should be monitored closely to ensure that their well-being is not compromised.

Childhood Trajectories of Hyperactivity/Inattention Symptoms and Diurnal Cortisol in Middle Adolescence: Results from a UK Birth Cohort.

OBJECTIVE: Children with attention-deficit/hyperactivity disorder (ADHD) show hypoactivity of the hypothalamic-pituitary-adrenal (HPA) axis. Whether the association between hyperactivity/inattention symptoms with HPA axis dysfunction holds in the general child population too is not clear. METHOD: We assessed associations between longitudinal trajectories of hyperactivity/inattention symptoms during ages 4 to 13 years and basal cortisol profiles at age 15 in a British general population cohort. RESULTS: Adolescents with persistently high levels of hyperactivity/inattention symptoms since childhood showed lower total morning cortisol and a smaller diurnal decline, even after adjusting for confounders. No associations were found between any of the symptom trajectories and cortisol awakening response, diurnal slope or daily output of cortisol. CONCLUSION: This study provides evidence for hypocortisolism among adolescents with chronic hyperactivity/inattention symptoms in the general population.

Cortical thickness across the lifespan: Data from 17,075 healthy individuals aged 3-90 years.

Delineating the association of age and cortical thickness in healthy individuals is critical given the association of cortical thickness with cognition and behavior. Previous research has shown that robust estimates of the association between age and brain morphometry require large-scale studies. In response, we used cross-sectional data from 17,075 individuals aged 3-90 years from the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to infer age-related changes in cortical thickness. We used fractional polynomial (FP) regression to quantify the association between age and cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma method. Interindividual variability was estimated using meta-analysis and one-way analysis of variance. For most regions, their highest cortical thickness value was observed in childhood. Age and cortical thickness showed a negative association; the slope was steeper up to the third decade of life and more gradual thereafter; notable exceptions to this general pattern were entorhinal, temporopolar, and anterior cingulate cortices. Interindividual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results may form the basis of further investigation on normative deviation in cortical thickness and its significance for behavioral and cognitive outcomes.

Social cognition and cortisol in the general population: A systematic review and meta-analysis.

This systematic review examines the evidence on the association between social cognition and cortisol in the general population. Literature was searched in six databases. Of the 401 studies identified, meta-analyses were conducted on 46 effect sizes (Pearson's correlation coefficients) from 19 studies, supplemented by a narrative review. Pooled estimates suggest that better emotion control is associated with increased cortisol concentrations [r = 0.083, 95% CI (0.033, 0.132)]. Emotion recognition or empathy were not significantly associated with cortisol concentrations [r = 0.072, 95% CI (-0.020, 0.165) and r = 0.004, 95% CI (-0.061, 0.068) respectively]. Subgroup analyses showed that the association between emotion control and cortisol concentrations is significant in males, for morning cortisol, when the cortisol data are transformed to correct for skewed distributions, or when participants are instructed to avoid food and drink intake for at least one hour before sample collection. There was no evidence for an association between social cognition with diurnal cortisol slope or cortisol awakening response. More validation work with greater standardization of methodological procedures is required.

Comorbid chronic tic disorder and tourette syndrome in children requiring inpatient mental health treatment.

OBJECTIVE: Children needing admission to an inpatient mental health unit often present with severe neuropsychiatric disorders characterised by complex psychopathology. We aimed to examine all admitted children with comorbid chronic tic disorder (CTD) and Tourette syndrome (TS) over a 10-year period and determine the clinical significance of these diagnoses. METHOD: A retrospective, naturalistic study was conducted, comparing children with and without CTD/TS in terms of co-morbid diagnoses, medication use, access to education, aggression contributing to the admission, duration of admission, functional outcomes and satisfaction with treatment. Data were analysed using Chi-square/Fisher's exact test and t-test for categorical and continuous variables, respectively, and subsequently with unadjusted and adjusted linear and logistic regression analyses. RESULTS: A relatively high proportion of children had co-morbid CTD/TS (19.7%). There was a significant association with co-morbid obsessive-compulsive disorder, intellectual disability and autism spectrum disorder but not attention deficit hyperactivity disorder. CTD/TS were associated with longer admissions even after adjustments for confounding but did not seem to be independently associated with other examined clinical characteristics. CONCLUSIONS: The prevalence of CTD/TS in children needing inpatient treatment is significant. In our sample, comorbid CTD/TS seem to represent a marker of overall symptom severity as evidenced by longer admissions.

Reciprocal relationships between paternal psychological distress and child internalising and externalising difficulties from 3 to 14 years: a cross-lagged analysis.

Research shows that paternal psychological distress is associated with child emotional and behavioural difficulties. However, little is known about the direction of this association including whether it is bidirectional. The aim of this study was to explore the reciprocal relationships between paternal psychological distress and child emotional and behavioural problems longitudinally (at ages 3, 5, 7, 11 and 14 years) in a sample of 13,105 children (49% girls) who participated in the UK's Millennium Cohort Study (MCS), a large-scale, nationally representative, longitudinal survey. Four domains of child problems (emotional symptoms, peer relations, conduct problems and hyperactivity/inattention) were measured with the Strengths and Difficulties Questionnaire and paternal psychological distress was measured with the Kessler K-6 scale. Data were analysed using cross-lagged path models. At all ages, paternal psychological distress predicted both subsequent child emotional symptoms as well as peer problems. Paternal psychological distress at child's age 3 was related to more hyperactivity at age 5 and, at age 5, paternal psychological distress was associated with more conduct problems at age 7. At age 11, paternal distress was also related to age 14 conduct problems and hyperactivity. Child effects were fewer and were found mainly for behavioural problems. Notably, we found bidirectional links between paternal psychological distress and child peer difficulties, from 11 to 14 years. Paternal psychological distress appears to influence child behaviour more consistently than the converse. However, in early adolescence, there appears to be a reciprocal relationship between fathers' mental health problems and children's peer problems.

Distinct developmental trajectories of internalising and externalising symptoms in childhood: Links with mental health and risky behaviours in early adolescence.

BACKGROUND: High or increasing trajectories of internalising and externalising symptoms in childhood are mutually re-enforcing and associated with poor emotional and behavioural outcomes in adolescence. This study sought to identify classes of children with similar trajectories of internalising and externalising symptoms after adjusting one domain's symptoms for the other's at the classification stage, and to relate them to emotional and behavioural outcomes in mid-adolescence. METHODS: We used growth mixture modelling to classify 16,844 members of the Millennium Cohort Study (baseline N=19,244) into distinct classes based on their trajectories, across ages 3,5,7 and 11 years, of internalising and externalising symptoms adjusted for one another. We examined the predictive ability of these classes for depression, self-harm, trouble with police and drug use among 11,134 children with available data at age 14. RESULTS: We identified four classes of children following distinct trajectories of 'pure' internalising and externalising symptoms. After adjustments for confounding, those with increasing or initially high yet decreasing levels of internalising symptomatology, and those with persistently high or increasing levels of externalising problems were at increased risk of depression in early adolescence. Having initially low yet increasing levels of internalising symptomatology was additionally associated with an increased risk of self-harm and drug use in early adolescence. LIMITATIONS: We cannot ascertain whether our longitudinal typology of internalising and externalising symptoms holds for outcomes later in adolescence or adulthood. CONCLUSIONS: Interventions aiming to prevent depression, drug use or self-harm in mid-adolescence may be more successful if they target children showing increasing internalising symptoms in the primary school years.

Prenatal and childhood adversity and inflammation in children: A population-based longitudinal study.

BACKGROUND: Stressful life events experienced during childhood and early prenatal development have been associated with inflammation during childhood. However, no study has considered these two exposures jointly, or has investigated the effect of their interaction. METHODS: In the Avon Longitudinal Study of Parents and Children, a general-population birth cohort, we explored if inflammatory markers [serum C-reactive protein (CRP) and interleukin 6 (IL-6)] at age 9 years were related to early prenatal events (at 18 weeks pregnancy), childhood events (measured on seven occasions at ages 0-9 years) and their interaction (n = 3,915). Latent growth curve modelling estimated trajectories of childhood events, and linear regression explored associations of prenatal and childhood events with inflammatory markers. Models controlled for ethnicity, socioeconomic status and body mass index, were stratified by gender and considered both unweighted and weighted (by impact) event exposures. RESULTS: Even after adjustment for confounders and prenatal events, both the intercept and the slope of number of childhood events were associated with IL-6, but only in females. The significant effect of the slope held for both weighted (by impact) and unweighted event specifications. Prenatal events were not associated with either inflammatory marker when childhood events were controlled. There was no evidence for synergistic effects of prenatal and childhood events. CONCLUSION: Independently of prenatal adverse life events, the number and increase in number of adverse life events experienced in childhood were associated positively with plasma levels of inflammatory markers, such as IL-6, in girls. This gender specificity warrants further research.

The Role of Primary School Composition in the Trajectories of Internalising and Externalising Problems across Childhood and Adolescence.

There is little research on the role of school and its composition in explaining individual children's psychological outcomes. This study examined for the first time the role of several primary-school compositional characteristics, and their interactions with individual level characteristics, in the development of two such outcomes, internalising and externalising problems, at ages 7, 11 and 14 years in 4794 children in England participating in the Millennium Cohort Study. Using hierarchical (multilevel) linear models, we found that, even after adjusting for individual and family characteristics, children in schools with higher proportions of pupils eligible for free school meals had more externalising problems. In general, children with special educational needs, lower academic performance, more distressed mothers, and those in non-intact families had more internalising and externalising problems. Our results underline the importance of targeting schools with less affluent overall intakes, but also highlight the key role of individual and family characteristics in the development of their pupils' psychological functioning.

The codevelopment of internalizing symptoms, externalizing symptoms, and cognitive ability across childhood and adolescence.

Cognitive ability, externalizing symptoms, and internalizing symptoms are correlated in children. However, it is not known why they combine in the general child population over time. To address this, we used data on 17,318 children participating in the UK Millennium Cohort Study and followed-up five times between ages 3 and 14 years. We fitted three parallel-process latent growth curve models to identify the parallel unfolding of children's trajectories of internalizing symptoms, externalizing symptoms, and cognitive ability across this period. We also examined the effects of time-invariant (ethnicity, birth weight, maternal education and age at birth, and breastfeeding status) and time-varying covariates (maternal psychological distress and socioeconomic disadvantage) on the growth parameters of the trajectories. The results showed that the intercepts of the trajectories of cognitive ability and, particularly, externalizing symptoms were inversely correlated. Their linear slopes were also inversely correlated, suggesting parallel development. Internalizing symptoms were correlated positively with externalizing symptoms and inversely (and more modestly) with cognitive ability at baseline, but the slope of internalizing symptoms correlated (positively) only with the slope of externalizing symptoms. The covariates predicted 9% to 41% of the variance in the intercepts and slopes of all domains, suggesting they are important common risk factors. Overall, it appears that externalizing symptoms develop in parallel with both cognitive ability and internalizing symptoms from early childhood through to middle adolescence. Children on an increasing trajectory of externalizing symptoms are likely both increasing in internalizing symptoms and decreasing in cognitive skills as well, and are thus an important group to target for intervention.

Trajectories of physical activity from midlife to old age and associations with subsequent cardiovascular disease and all-cause mortality.

INTRODUCTION: It is well established that physical activity (PA) protects against mortality and morbidity, but how long-term patterns of PA are associated with mortality and cardiovascular disease (CVD) remains unclear. METHODS: 3231 men recruited to the British Regional Heart Study, a prospective cohort study, reported usual PA levels at baseline in 1978-1980 (aged 40-59 years) and at 12-year, 16-year and 20-year follow ups. Twenty-year trajectories of PA, spanning from 1978/1980 to 2000, were identified using group-based trajectory modelling. Men were subsequently followed up until 30 June 2016 for mortality through National Health Service central registers and for non-fatal CVD events through primary and secondary care records. Data analyses were conducted in 2019. RESULTS: Three PA trajectories were identified: low/decreasing (22.7%), light/stable (51.0%) and moderate/increasing (26.3%). Over a median follow-up of 16.4 years, there were 1735 deaths. Compared with the low/decreasing group, membership of the light/stable (HR 0.83, 95% CI 0.74 to 0.94) and moderate/increasing (HR 0.76, 95% CI 0.66 to 0.88) groups was associated with a lower risk of all-cause mortality. Similar associations were observed for CVD mortality, major coronary heart disease and all CVD events. Associations were only partially explained by a range of confounders. Sensitivity analyses suggested that survival benefits were largely driven by most recent/current PA. CONCLUSIONS: A dose-response relationship was observed, with higher levels of PA from midlife to old age associated with additional benefits. However, even fairly modest and sustained PA was protective and may be more achievable for the most inactive.