Association of childhood bullying victimisation with suicide deaths: findings from a 50-year nationwide cohort study.

BACKGROUND: Bullying victimisation has been associated with increased risk of suicide ideation and attempt throughout the lifespan, but no study has yet examined whether it translates to a greater risk of death by suicide. We aimed to determine the association of bullying victimisation with suicide mortality. METHODS: Participants were drawn from the 1958 British birth cohort, a prospective follow-up of all births in 1 week in Britain in 1958. We conducted logistic regressions on 14 946 participants whose mothers reported bullying victimisation at 7 and 11 years with linked information on suicide deaths through the National Health Service Central Register. RESULTS: Fifty-five participants (48 males) had died by suicide between the age 18 and 52 years. Bullying victimisation was associated with suicide mortality; a one standard deviation increases in bullying victimisation linked to an increased odds for suicide mortality [odds ratio (OR) 1.29; 1.02-1.64] during adulthood. The OR attenuated by 11% after adjustment for individual (e.g. behavioural and emotional problems) and familial characteristics (e.g. adverse childhood experiences, 1.18; 0.92-1.51). Analysis of bullying victimisation frequency categories yields similar results: compared with individuals who had not been bullied, those who had been frequently bullied had an increased odds for suicide mortality (OR 1.89; 0.99-3.62). CONCLUSION: Our study suggests that individuals who have been frequently bullied have a small increased risk of dying by suicide, when no other risk factors is considered. Suicide prevention might start in childhood, with bullying included in a range of inter-correlated vulnerabilities encompassing behavioural and emotional difficulties and adverse experiences within the family.

A genome-wide association study of total child psychiatric problems scores.

Substantial genetic correlations have been reported across psychiatric disorders and numerous cross-disorder genetic variants have been detected. To identify the genetic variants underlying general psychopathology in childhood, we performed a genome-wide association study using a total psychiatric problem score. We analyzed 6,844,199 common SNPs in 38,418 school-aged children from 20 population-based cohorts participating in the EAGLE consortium. The SNP heritability of total psychiatric problems was 5.4% (SE = 0.01) and two loci reached genome-wide significance: rs10767094 and rs202005905. We also observed an association of SBF2, a gene associated with neuroticism in previous GWAS, with total psychiatric problems. The genetic effects underlying the total score were shared with common psychiatric disorders only (attention-deficit/hyperactivity disorder, anxiety, depression, insomnia) (rG > 0.49), but not with autism or the less common adult disorders (schizophrenia, bipolar disorder, or eating disorders) (rG < 0.01). Importantly, the total psychiatric problem score also showed at least a moderate genetic correlation with intelligence, educational attainment, wellbeing, smoking, and body fat (rG > 0.29). The results suggest that many common genetic variants are associated with childhood psychiatric symptoms and related phenotypes in general instead of with specific symptoms. Further research is needed to establish causality and pleiotropic mechanisms between related traits.

Estimating the influence of body mass index (BMI) on mortality using offspring BMI as an instrumental variable.

OBJECTIVE: High body mass index (BMI) is an important predictor of mortality but estimating underlying causality is hampered by confounding and pre-existing disease. Here, we use information from the offspring to approximate parental BMIs, with an aim to avoid biased estimation of mortality risk caused by reverse causality. METHODS: The analyses were based on information on 9674 offspring-mother and 9096 offspring-father pairs obtained from the 1958 British birth cohort. Parental BMI-mortality associations were analysed using conventional methods and using offspring BMI as a proxy, or instrument, for their parents' BMI. RESULTS: In the conventional analysis, associations between parental BMI and all-cause mortality were U-shaped (Pcurvature < 0.001), while offspring BMI had linear associations with parental mortality (Ptrend < 0.001, Pcurvature > 0.46). Curvature was particularly pronounced for mortality from respiratory diseases and from lung cancer. Instrumental variable analyses suggested a positive association between BMI and mortality from all causes [mothers: HR per SD of BMI 1.43 (95% CI 1.21-1.69), fathers: HR 1.17 (1.00-1.36)] and from coronary heart disease [mothers: HR 1.65 (1.15-2.36), fathers: HR 1.51 (1.17-1.97)]. These were larger than HR from the equivalent conventional analyses, despite some attenuation by adjustment for social indicators and smoking. CONCLUSIONS: Analyses using offspring BMI as a proxy for parental BMI suggest that the apparent adverse consequences of low BMI are considerably overestimated and adverse consequences of overweight are underestimated in conventional epidemiological studies.

Childhood cognitive skill trajectories and suicide by mid-adulthood: an investigation of the 1958 British Birth Cohort.

BACKGROUND: Poor cognitive abilities and low intellectual quotient (IQ) are associated with an increased risk of suicide attempts and suicide mortality. However, knowledge of how this association develops across the life-course is limited. Our study aims to establish whether individuals who died by suicide by mid-adulthood are distinguishable by their child-to-adolescence cognitive trajectories. METHODS: Participants were from the 1958 British Birth Cohort and were assessed for academic performance at ages 7, 11, and 16 and intelligence at 11 years. Suicides occurring by September 2012 were identified from linked national death certificates. We compared mean mathematics and reading abilities and rate of change across 7-16 years for individuals who died by suicide v. those still alive, with and without adjustment for potential early-life confounding factors. Analyses were based on 14 505 participants. RESULTS: Fifty-five participants (48 males) had died by suicide by age 54 years. While males who died by suicide did not differ from participants still alive in reading scores at age 7 [effect size (g) = -0.04, p = 0.759], their reading scores had a less steep improvement up to age 16 compared to other participants. Adjustments for early-life confounding factors explained these differences. A similar pattern was observed for mathematics scores. There was no difference between individuals who died by suicide v. participants still alive on intelligence at 11 years. CONCLUSIONS: While no differences in tests of academic performance and IQ were observed, individuals who died by suicide had a less steep improvement in reading abilities over time compared to same-age peers.

An overview of child maltreatment (neglect and abuse) associations with developmental trajectories and long-term outcomes in the 1958 British birth cohort.

Childhood maltreatment types (neglect and psychological, physical, or sexual abuse) are associated with many poor outcomes in adulthood. Yet, research mainly focuses on the cumulative adversity burden rather than specificities and commonalities of associations with adult outcomes and intervening pathways. To build understanding of life-course pathways to a range of outcomes, this overview summarises evidence from several original research studies using the 1958 British Birth Cohort on specific maltreatment types, child development trajectories, adult intermediaries and outcomes. About one-in-five participants were identified as neglected or abused in childhood (~10% were identified for neglect, 10% for psychological abuse, 6% for physical abuse and 1.4% for sexual abuse). Neglect was associated with key dimensions of development, for example, slower height growth, delayed maturation, faster BMI gain, and poorer emotional and cognitive development. Associated adulthood outcomes included harmful behaviours (notably smoking), poorer physical health (e.g. shorter height, excess BMI, poorer blood lipids and glucose, poor-rated health and physical functioning), worse mental health, lower socioeconomic circumstances (e.g. poorer living conditions) and elevated mortality in mid-adulthood. Childhood abuse associations were less widespread and were often only for specific types: most types were unrelated to childhood height and cognitive abilities, but all types were associated with poorer child emotional development, adult mental health, smoking, blood lipids and self-rated health. Additionally, physical abuse was associated with faster BMI gain, higher adult BMI, blood glucose, inflammation and mortality in mid-adulthood; sexual abuse with faster BMI gain, higher adult BMI, poor physical functioning at 50y and higher mortality in mid-adulthood. Adult health measures associated with neglect and abuse are key predictors of serious disease, disability and death. Therefore, neglect and abuse associations with these measures represent an important burden for individuals and society.

Adult obesity and mid-life physical functioning in two British birth cohorts: investigating the mediating role of physical inactivity.

BACKGROUND: Associations between obesity and physical inactivity are bi-directional. Both are associated with physical functioning (PF, ability to perform physical tasks of daily living) but whether obesity influences PF via inactivity is unknown. We investigated whether mid-adult obesity trajectories were associated with subsequent PF and mediated by inactivity. METHODS: Body mass index (BMI; kg/m²) and inactivity were recorded at: 36, 43, 53 and 60-64 years in the 1946 Medical Research Council (MRC) National Survey of Health and Development (1946-NSHD; n = 2427), and at 33, 42 and 50 years in the 1958 National Child Development Study (1958-NCDS; n = 8674). Poor PF was defined as the lowest (gender and cohort-specific) 10% on the Short-form 36 Physical Component Summary subscale at 60-64 years (1946-NSHD) and 50 years (1958-NCDS). Estimated randomized-interventional-analogue natural direct (rNDE) and indirect (rNIE) effects of obesity trajectories on PF via inactivity are expressed as risk ratios [overall total effect (rTE) is rNDE multiplied by rNIE]. RESULTS: In both cohorts, most individuals (∼68%) were never obese in adulthood, 16-30% became obese and ≤11% were always obese. In 1946-NSHD, rTE of incident obesity at 43 years (vs never) on poor PF was 2.32 (1.13, 3.51); at 53 years it was 1.53 (0.91, 2.15). rNIEs via inactivity were 1.02 (0.97, 1.07) and 1.02 (0.99, 1.04), respectively. Estimated rTE of persistent obesity from 36 years was 2.91 (1.14, 4.69), with rNIE of 1.03 (0.96, 1.10). In 1958-NCDS, patterns of association were similar, albeit weaker. CONCLUSIONS: Longer duration of obesity was associated with increased risk of poor PF. Inactivity played a small mediating role. Findings reinforce the importance of preventing and delaying obesity onset to protect against poor PF.

National Patient Safety Consortium: Learning from Large-Scale Collaboration.

From 2014 to 2018, the Canadian Patient Safety Institute brought together key partners and established the National Patient Safety Consortium to drive a shared action plan for safer healthcare. With ongoing consensus development on key priorities, an unprecedented level of collaboration and shared leadership with diverse stakeholders and patients and families as full partners, the Consortium and its Integrated Patient Safety Action Plan built a culture of engagement and improvement across Canada.

Birthweight, lifetime obesity and physical functioning in mid-adulthood: a nationwide birth cohort study.

BACKGROUND: Evidence is scant on long-term implications of childhood obesity and body mass index (BMI) gains over the life-course for poor physical functioning (PF). The objective was to establish whether (i) birthweight and BMI across the life-course, (ii) BMI gains at specific life-stages and (iii) age of obesity onset were associated with PF at 50 y. METHODS: In the 1958 British birth cohort (n = 8674), BMI (kg/m2) was calculated using height and weight [measured (7, 11, 16, 33 and 45 y); self-reported (23 and 50 y)]. PF was assessed at 50 y using the validated PF subscale of the Short-form 36 survey; the bottom (gender-specific) 10% was classified as poor PF. Missing data were imputed via multiple imputation. Associations were examined using logistic regression, adjusting for health and social factors. RESULTS: Birthweight was not associated with PF. At each adult age, odds of poor PF were highest for obese (vs normal), e.g. for 23 y obesity the odds ratio (OR)adjusted for poor PF was 2.28 (1.34, 3.91) and 2.67 (1.72, 4.14) in males and females respectively. BMI gains were associated with poor PF, e.g. for females, ORadjusted per standard deviation (SD) in BMI gain 16-23 y was 1.28 (1.13, 1.46); for BMI gains 45-50 y it was 1.36 (1.11, 1.65). Longer duration of obesity was associated with poor PF, e.g. in males, ORadjusted was 2.32 (1.26, 4.29) for childhood obesity onset and 1.50 (1.16, 1.96) for mid-adulthood onset (vs never obese, P-trend < 0.001). CONCLUSION: Obesity, BMI gains, and earlier obesity onset were associated with poor PF in mid-adulthood, reinforcing the importance of preventing and delaying obesity onset.

Dysregulation of the hypothalamic pituitary adrenal (HPA) axis and cognitive capability at older ages: individual participant meta-analysis of five cohorts.

Evidence on the association between functioning of the hypothalamic pituitary adrenal (HPA) axis and cognitive capability at older ages is mixed. We undertook a systematic review (until October 2016) and individual participant data (IPD) meta-analysis to test if dysregulation of the HPA axis is associated with worse cognitive capability. Five cohort studies were included in the IPD meta-analysis of diurnal cortisol patterns with crystallised and fluid cognitive ability. Higher night time cortisol was associated with worse fluid ability (standardised coefficient per SD increase -0.063, 95% CI -0.124, -0.002, P = 0.04; I2 = 79.9%; age and gender adjusted). A larger diurnal drop was associated with better fluid ability (standardised coefficient per SD increase 0.037, 95% CI 0.008, 0.065, P = 0.01; I2 = 49.2%; age and gender adjusted). A bigger cortisol awakening response (CAR) was weakly associated with better fluid (P = 0.09; I2 = 0.0%; age and gender adjusted) and crystallised (P = 0.10; I2 = 0.0%; age and gender adjusted) ability. There is weak evidence that a greater diurnal decline of the HPA axis and a larger CAR are associated with improvements in cognition at older ages. As associations are cross-sectional, we cannot rule out reverse causation.

Understanding associations of early-life adversities with mid-life inflammatory profiles: Evidence from the UK and USA.

OBJECTIVES: In two cohorts, we aimed to establish associations between early-life adversities and adult inflammation, and whether adult (a) adiposity or (b) socioeconomic disadvantage are key intermediaries. METHODS: In both cohorts (N = 7661, 1958 British birth cohort; N = 1255, MIDUS), information was used on adult inflammatory markers (C-reactive protein (CRP), fibrinogen and (MIDUS only) interleukin-6 (IL-6)), adiposity and socioeconomic disadvantage, and early-life adversities (neglect, emotional neglect, physical, psychological, sexual abuse and childhood disadvantage). RESULTS: Early-life adversities varied from 1.6% (sexual abuse, 1958 cohort) to 14.3% (socioeconomic disadvantage, MIDUS). Across the two cohorts, associations were consistent for physical abuse, e.g. 16.3%(3.01,29.7) and 17.0%(-16.4,50.3) higher CRP in the 1958 cohort and MIDUS respectively. Associations attenuated after accounting for adult adiposity, e.g. physical abuse (1958 cohort) and sexual abuse (MIDUS, non-white participants) associations were abolished. Some associations attenuated after adjustment for adult socioeconomic disadvantage; e.g. 1958 cohort neglect-CRP associations reduced from 23.2%(13.7,32.6) to 17.7%(8.18,27.2). Across the cohorts, no associations were found for psychological abuse or emotional neglect; associations for childhood socioeconomic disadvantage were inconsistent. CONCLUSIONS: Specific early-life adversities are associated with adult inflammation; adiposity is a likely intermediary factor. Weight reduction and obesity prevention may offset pro-inflammatory related adult disease among those who experienced early-life adversities.

Association of alcohol consumption with allergic disease and asthma: a multi-centre Mendelian randomization analysis.

AIMS: To use the rs1229984 variant associated with alcohol consumption as an instrument for alcohol consumption to test the causality of the association of alcohol consumption with hay fever, asthma, allergic sensitization and serum total immunoglobulin (Ig)E. DESIGN: Observational and Mendelian randomization analyses using genetic variants as unbiased markers of exposure to estimate causal effects, subject to certain assumptions. SETTING: Europe. PARTICIPANTS: We included a total of 466 434 people aged 15-82 years from 17 population-based studies conducted from 1997 to 2015. MEASUREMENTS: The rs1229984 (ADH1B) was genotyped; alcohol consumption, hay fever and asthma were self-reported. Specific and total IgE were measured from serum samples. FINDINGS: Observational analyses showed that ever-drinking versus non-drinking, but not amount of alcohol intake, was positively associated with hay fever and inversely associated with asthma but not with allergic sensitization or serum total immunoglobulin (Ig)E. However, Mendelian randomization analyses did not suggest that the observational associations are causal. The causal odds ratio (OR) per genetically assessed unit of alcohol/week was an OR = 0.907 [95% confidence interval (CI) = 0.806, 1.019; P = 0.101] for hay fever, an OR = 0.897 (95% CI = 0.790, 1.019; P = 0.095) for asthma, an OR = 0.971 (95% CI =  0.804, 1.174; P = 0.763) for allergic sensitization and a 4.7% change (95% CI = -5.5%, 14.9%; P = 0.366) for total IgE. CONCLUSIONS: In observational analyses, ever-drinking versus not drinking was positively associated with hay fever and negatively associated with asthma. However, the Mendelian randomization results were not consistent with these associations being causal.

Change in health and social factors in mid-adulthood and corresponding changes in leisure-time physical inactivity in a prospective cohort.

BACKGROUND: To identify whether changes in adult health and social factors are associated with simultaneous changes in inactivity. METHODS: Health, social factors and leisure-time inactivity (activity frequency < 1/week) were self-reported at 33y and 50y in the 1958 British birth cohort (N = 12,271). Baseline (33y) health and social factors and also patterns of change in factors 33y-to-50y were related to inactivity 33y-to-50y (never inactive, persistently inactive, deteriorating to inactivity, or improving from inactivity) using multinomial logistic regression. RESULTS: Approximately 31% were inactive at 33y and 50y; 35% changed status 33y-to-50y (17% deteriorating to inactivity, 18% improving from inactivity). Baseline poor health and obesity were associated with subsequent (33y-to-50y) inactivity; e.g. for poor health, relative risk ratios (RRRs) for deteriorating to inactivity (vs never inactive) and improving from inactivity (vs persistently inactive) were 1.38(1.16,1.64) and 0.77(0.63,0.94) respectively. Adverse changes in health and weight were associated with simultaneous adverse changes in inactivity; e.g. worsening health (vs always good/excellent health) was associated with higher risk of deteriorating to inactivity (RRR:2.20(1.85,2.62)) and lower risk of improving from inactivity (RRR:0.61(0.49,0.77)). However, improving health and weight loss were not associated with improving from inactivity. Worsening self-efficacy 33y-to-50y was associated with lower risk of improving from inactivity; there was no association between improving self-efficacy and inactivity change. Downward social mobility was not associated with deteriorating to or improving from inactivity. Changes in depression symptom level, marriage/co-habitation or parenthood 33y-to-50y were not associated with inactivity changes. No associations were observed for employment. CONCLUSIONS: Associated changes in mid-life health factors with deleterious inactivity changes, highlight the importance of maintaining health, weight and self-efficacy across adulthood to deter inactivity.

Lifetime risk factors for leisure-time physical inactivity in mid-adulthood.

We aimed to identify factors from different life-stages that were associated with inactivity at two adult ages and stability and change between these ages. Leisure-time inactivity (activity frequency <1/wk) was assessed at 33y and 50y in the 1958 British Birth cohort (N = 12,271). We created scores representing several domains, i.e. physical health, mental function, social, family and neighbourhood circumstances at different life-stages, and examined associations with adult inactivity. 31% were inactive at 33y and 50y with 17% deteriorating to, and 18% improving from, inactivity. Adjusting for all domains and life-stages, most concurrent factors were associated with inactivity: e.g. per 1-unit worsening physical status (score range:0-2) ORadjusted for 50y inactivity was 1.56(1.44,1.70). Physical status at 33y was associated with inactivity patterns 33y-to-50y (Relative risk ratios (RRRs) of inactivity persistence and deterioration (vs never inactive) per 1-unit worsening status (score:0-1) were 1.73(1.51,1.99) and 1.28(1.10,1.49) respectively; RRR for improvement (vs persistently inactive) was 0.75(0.63,0.88). Some early-life domain scores were associated with inactivity independent of concurrent factors: e.g. per 1-unit worsening early-life social score (range:0-3) ORadjusted for 50y inactivity was 1.12(1.05,1.19). Highly urbanised neighbourhood in early adulthood was associated with inactivity (e.g. RRRs for persistent inactivity and deterioration were 1.42(1.22,1.65) and 1.15(1.01,1.31) respectively; 0.82(0.68,0.98) for improvement). Concurrent physical and mental function were associated with adult inactivity at two ages; poorer physical status was associated with greater risk of inactivity persistence and deterioration and lower risk of improvement 33y-to-50y. Young adult neighbourhood and early-life social and family circumstances were independently associated with mid-life inactivity.

Habitual coffee consumption and cognitive function: a Mendelian randomization meta-analysis in up to 415,530 participants.

Coffee's long-term effect on cognitive function remains unclear with studies suggesting both benefits and adverse effects. We used Mendelian randomization to investigate the causal relationship between habitual coffee consumption and cognitive function in mid- to later life. This included up to 415,530 participants and 300,760 coffee drinkers from 10 meta-analysed European ancestry cohorts. In each cohort, composite cognitive scores that capture global cognition and memory were computed using available tests. A genetic score derived using CYP1A1/2 (rs2472297) and AHR (rs6968865) was chosen as a proxy for habitual coffee consumption. Null associations were observed when examining the associations of the genetic score with global and memory cognition (ß = -0.0007, 95% C.I. -0.009 to 0.008, P = 0.87; ß = -0.001, 95% C.I. -0.005 to 0.002, P = 0.51, respectively), with high consistency between studies (Pheterogeneity > 0.4 for both). Domain specific analyses using available cognitive measures in the UK Biobank also did not support effects by habitual coffee intake for reaction time, pairs matching, reasoning or prospective memory (P ≥ 0.05 for all). Despite the power to detect very small effects, our meta-analysis provided no evidence for causal long-term effects of habitual coffee consumption on global cognition or memory.

Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels.

Vitamin D is a steroid hormone precursor that is associated with a range of human traits and diseases. Previous GWAS of serum 25-hydroxyvitamin D concentrations have identified four genome-wide significant loci (GC, NADSYN1/DHCR7, CYP2R1, CYP24A1). In this study, we expand the previous SUNLIGHT Consortium GWAS discovery sample size from 16,125 to 79,366 (all European descent). This larger GWAS yields two additional loci harboring genome-wide significant variants (P = 4.7×10-9 at rs8018720 in SEC23A, and P = 1.9×10-14 at rs10745742 in AMDHD1). The overall estimate of heritability of 25-hydroxyvitamin D serum concentrations attributable to GWAS common SNPs is 7.5%, with statistically significant loci explaining 38% of this total. Further investigation identifies signal enrichment in immune and hematopoietic tissues, and clustering with autoimmune diseases in cell-type-specific analysis. Larger studies are required to identify additional common SNPs, and to explore the role of rare or structural variants and gene-gene interactions in the heritability of circulating 25-hydroxyvitamin D levels.

Early adulthood determinants of mid-life leisure-time physical inactivity stability and change: Findings from a prospective birth cohort.

OBJECTIVES: Physical inactivity is highly prevalent. Knowledge is needed of influences on inactive lifestyles. We aimed to establish whether early adult factors predict subsequent inactivity patterns in mid-adulthood. DESIGN: Leisure-time inactivity (activity frequency<1/week) was assessed at 33y and 50y in the 1958 British Birth cohort (N=12,271). METHODS: We assessed associations of early adult (23-33y) physical status, mental function, social, family and neighbourhood circumstances with four 33-50y patterns (never inactive, persistently inactive, deteriorating or improving) using multinomial logistic regression with and without adjustment for childhood factors (e.g. social class). RESULTS: Inactivity prevalence was similar at 33y and 50y (∼31%), but 17% deteriorated and 18% improved with age. Factors associated with persistent vs never inactive were: limiting illness (relative risk ratio (RRR):1.21(1.04,1.42) per number of ages exposed (0,1 or 2 times across ages 23y and 33y), obesity (1.33(1.16,1.54) per number of ages exposed), height (0.93(0.89,0.98) per 5cm), depression (1.32(1.19,1.47) per number of ages exposed); education (1.28(1.20,1.38) per decrease on 5-point scale) and neighbourhood (1.59(1.37,1.86) in 'industrial/local authority housing areas' and 1.33(1.12,1.58) in 'growth/metropolitan inner areas' vs 'suburbs, service, rural or seaside areas'). Associations were broadly similar for inactivity deterioration. Industrial/local authority housing areas (0.75(0.61,0.91)) and longer obesity exposure (0.78(0.64,0.95)) were associated with lower RRRs for improvement. Number of children was associated with improvement, although associations varied by age. Associations remained after adjustment for childhood factors. CONCLUSIONS: Several early adult factors are associated with inactivity persistence and deterioration; fewer with improvement. Obesity duration and neighbourhood lived in during young adulthood had long-lasting associations with inactivity patterns in mid-life.

Cracking the Code on Quality and Safety in Healthcare - What Will It Take?

Over the next 30 years in Canada, it is estimated that there could be roughly 400,000 average annual cases of patient safety incidents, costing approximately $6,800 per patient and generating an additional $2.75 billion in healthcare treatment costs per year. What will it take to "crack the code" on creating safe environments and practice in healthcare?

Governing Collaborative Healthcare Improvement: Lessons From an Atlantic Canadian Case.

The Atlantic Healthcare Collaboration for Innovation and Improvement in Chronic Disease (AHC) Quality Improvement Collaborative (QIC) in Eastern Canada provided an approach to spur system-level reform across multiple health systems for patients and families living with chronic disease. Developed and led by senior executives with a unique governance approach and involving clinical front-line teams, the AHC serves as a practical example of leadership creating and driving momentum for achieving success in collaborative health system improvements.

Vitamin D and cognitive function: A Mendelian randomisation study.

The causal nature of the association between hypovitaminosis D and poor cognitive function in mid- to later-life is uncertain. Using a Mendelian randomisation(MR) approach, we examined the causal relationship between 25(OH)D and cognitive function. Data came from 172,349 participants from 17 cohorts. DHCR7(rs12785878), CYP2R1 rs12794714) and their combined synthesis score were chosen to proxy 25(OH)D. Cognitive tests were standardised into global and memory scores. Analyses were stratified by 25(OH)D tertiles, sex and age. Random effects meta-analyses assessed associations between 25(OH)D and cognitive function. Associations of serum 25(OH)D with global and memory-related cognitive function were non-linear (lower cognitive scores for both low and high 25(OH)D, p curvature ≤ 0.006), with much of the curvature attributed to a single study. DHCR7, CYP2R1, and the synthesis score were associated with small reductions in 25(OH)D per vitamin D-decreasing allele. However, coefficients for associations with global or memory-related cognitive function were non-significant and in opposing directions for DHCR7 and CYP2R1, with no overall association observed for the synthesis score. Coefficients for the synthesis score and global and memory cognition were similar when stratified by 25(OH)D tertiles, sex and age. We found no evidence for serum 25(OH)D concentration as a causal factor for cognitive performance in mid- to later life.

Diurnal cortisol and mental well-being in middle and older age: evidence from four cohort studies.

OBJECTIVES: We conducted an individual participant meta-analysis to test the hypothesis that cortisol patterns indicative of dysregulated hypothalamic-pituitary-adrenal axis functioning would be prospectively associated with poorer well-being at follow-up. SETTING: Four large UK-based cohort studies. PARTICIPANTS: Those providing valid salivary or serum cortisol samples (n=7515 for morning cortisol; n=1612 for cortisol awakening response) at baseline (age 44-82) and well-being data on the Warwick Edinburgh Mental Wellbeing Scale at follow-up (0-8 years) were included. RESULTS: Well-being was not associated with morning cortisol, diurnal slope or awakening response though a borderline association with evening cortisol was found. Adjusting for sex and follow-up time, each 1 SD increase in evening cortisol was associated with a -0.47 (95% CI -1.00 to 0.05) point lower well-being. This was attenuated by adjustment for body mass index, smoking and socioeconomic position. Between-study heterogeneity was low. CONCLUSIONS: This study does not support the hypothesis that diurnal cortisol is prospectively associated with well-being up to 8 years later. However, replication in prospective studies with cortisol samples over multiple days is required.