Double-blind randomised controlled trial of vitamin D3 supplementation for the prevention of acute respiratory infection in older adults and their carers (ViDiFlu).

RATIONALE: Low-dose vitamin D supplementation is already recommended in older adults for prevention of fractures and falls, but clinical trials investigating whether higher doses could provide additional protection against acute respiratory infection (ARI) are lacking. OBJECTIVE: To conduct a clinical trial of high-dose versus low-dose vitamin D3 supplementation for ARI prevention in residents of sheltered-accommodation housing blocks ('schemes') and their carers in London, UK. MEASUREMENTS AND METHODS: Fifty-four schemes (137 individual participants) were allocated to the active intervention (vitamin D3 2.4 mg once every 2 months +10 µg daily for residents, 3 mg once every 2 months for carers), and 54 schemes with 103 participants were allocated to control (placebo once every 2 months +vitamin D3 10 µg daily for residents, placebo once every 2 months for carers) for 1 year. Primary outcome was time to first ARI; secondary outcomes included time to first upper/lower respiratory infection (URI/LRI, analysed separately), and symptom duration. MAIN RESULTS: Inadequate vitamin D status was common at baseline: 220/240 (92%) participants had serum 25(OH)D concentration <75 nmol/L. The active intervention did not influence time to first ARI (adjusted HR (aHR) 1.18, 95% CI 0.80 to 1.74, p=0.42). When URI and LRI were analysed separately, allocation to the active intervention was associated with increased risk of URI (aHR 1.48, 95% CI 1.02 to 2.16, p=0.039) and increased duration of URI symptoms (median 7.0 vs 5.0 days for active vs control, adjusted ratio of geometric means 1.34, 95% CI 1.09 to 1.65, p=0.005), but not with altered risk or duration of LRI. CONCLUSIONS: Addition of intermittent bolus-dose vitamin D3 supplementation to a daily low-dose regimen did not influence risk of ARI in older adults and their carers, but was associated with increased risk and duration of URI. TRIAL REGISTRATION NUMBER: clinicaltrials.gov NCT01069874.

The Determinants of young Adult Social well-being and Health (DASH) study: diversity, psychosocial determinants and health.

PURPOSE: The Determinants of young Adult Social well-being and Health longitudinal study draws on life-course models to understand ethnic differences in health. A key hypothesis relates to the role of psychosocial factors in nurturing the health and well-being of ethnic minorities growing up in the UK. We report the effects of culturally patterned exposures in childhood. METHODS: In 2002/2003, 6643 11-13 year olds in London, ~80 % ethnic minorities, participated in the baseline survey. In 2005/2006, 4782 were followed-up. In 2012-2014, 665 took part in a pilot follow-up aged 21-23 years, including 42 qualitative interviews. Measures of socioeconomic and psychosocial factors and health were collected. RESULTS: Ethnic minority adolescents reported better mental health than White British, despite more adversity (e.g. economic disadvantage, racism). It is unclear what explains this resilience but findings support a role for cultural factors. Racism was an adverse influence on mental health, while family care and connectedness, religious involvement and ethnic diversity of friendships were protective. While mental health resilience was a feature throughout adolescence, a less positive picture emerged for cardio-respiratory health. Both, mental health and cultural factors played a role. These patterns largely endured in early 20s with family support reducing stressful transitions to adulthood. Education levels, however, signal potential for socio-economic parity across ethnic groups.

Methylphenidate Versus Placebo for Treating Fatigue in Patients With Advanced Cancer: Randomized, Double-Blind, Multicenter, Placebo-Controlled Trial.

PURPOSE: To compare effects and side effects of 6 weeks of individually dose-titrated methylphenidate or placebo on fatigue in palliative care patients with advanced cancer. METHODS: This is a randomized, double-blind, placebo-controlled, multicenter trial. Eligible patients had advanced incurable cancer and fatigue >3/10. Principal exclusions were hypertension; psychiatric, cardiovascular, cerebrovascular, renal, liver, or blood disorders; substance dependency; and epilepsy. Patients were randomly assigned 1:1 methylphenidate or placebo starting at 5 mg twice daily. Dose of methylphenidate/placebo was titrated once per week, over 6 weeks, up to a maximum of 20 mg three times daily. Trial ended at 10 weeks. Primary outcome was the difference in Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) scores between groups at 6 ± 2 weeks. Secondary outcomes included adverse effects, quality of life, and mood. RESULTS: One hundred sixty-two patients (73 men; mean, 65.8; standard deviation [SD], 10.3 years) were randomly assigned, and three were excluded from analysis. Seventy-seven were allocated placebo (baseline FACIT-F = 22 [SD, 10]); 82 were allocated methylphenidate (FACIT-F = 20 [SD, 9]). After 6 ± 2 weeks, FACIT-F scores were 1.97 points (95% CI, -0.95 to 4.90; P = .186) higher (better) on methylphenidate than placebo. Across 10 weeks of the study, FACIT-F was nominally higher in the methylphenidate group versus placebo (Diff, 2.20 [95% CI, 0.39 to 4.01]), but this did not reach the minimally clinically important difference (5-points). At 6 weeks, there were no differences between groups in quality-of-life or symptom domains except for depression scores (nominally reduced in the methylphenidate group: Diff, -1.35 [95% CI, -2.41 to -0.30]). There were no differences in mortality or serious adverse events. CONCLUSION: After 6 ± 2 weeks of treatment, methylphenidate was not superior to placebo for treating fatigue in advanced cancer. Methylphenidate was safe and well-tolerated.

The influence of racism on cigarette smoking: Longitudinal study of young people in a British multiethnic cohort.

INTRODUCTION: Studies, predominantly from the US, suggest that positive parenting, social support, academic achievement, and ethnic identity may buffer the impact of racism on health behaviours, including smoking, but little is known about how such effects might operate for ethnically diverse young people in the United Kingdom. We use the Determinants of young Adult Social well-being and Health (DASH), the largest UK longitudinal study of ethnically diverse young people, to address the following questions: a) Is racism associated with smoking? b) Does the relationship between racism and smoking vary by gender and by ethnicity? (c) Do religious involvement, parenting style and relationship with parents modify any observed relationship? and d) What are the qualitative experiences of racism and how might family or religion buffer the impact? METHODS: The cohort was recruited from 51 London schools. 6643 were seen at 11-13y and 4785 seen again at 14-16y. 665 participated in pilot follow-up at 21-23y, 42 in qualitative interviews. Self-report questionnaires included lifestyles, socio-economic and psychosocial factors. Mixed-effect models examined the associations between racism and smoking. RESULTS: Smoking prevalence increased from adolescence to age 21-23y, although ethnic minorities remained less likely to smoke. Racism was an independent longitudinal correlate of ever smoking throughout adolescence (odds ratio 1.77, 95% Confidence Interval 1.45-2.17) and from early adolescence to early 20s (1.90, 95% CI 1.25-2.90). Smoking initiation in late adolescence was associated with cumulative exposure to racism (1.77, 95% CI 1.23-2.54). Parent-child relationships and place of worship attendance were independent longitudinal correlates that were protective of smoking. Qualitative narratives explored how parenting, religion and cultural identity buffered the adverse impact of racism. CONCLUSIONS: Racism was associated with smoking behaviour from early adolescence to early adulthood, regardless of gender, ethnicity or socio-economic circumstances adding to evidence of the need to consider racism as an important social determinant of health across the life course.

Longitudinal study of cardiometabolic risk from early adolescence to early adulthood in an ethnically diverse cohort.

OBJECTIVE: To examine influences of adiposity from early adolescence to early 20s on cardiovascular disease (CVD) risk in the multiethnic Determinants of young Adult Social well-being and Health (DASH) longitudinal study. METHODS: In 2002-2003, 6643 11-13-year-olds from 51 London schools participated at baseline, and 4785 were seen again at 14-16 years. Recently, 665 (97% of invited) participated in pilot follow-up at 21-23 years, with biological and psychosocial measures and blood biomarkers (only at 21-23 years). Regression models examined interplay between ethnicity, adiposity and CVD. RESULTS: At 21-23 years, ∼30-40% were overweight. About half of the sample had completed a degree with little ethnic variation despite more socioeconomic disadvantage in adolescence among ethnic minorities. Regardless of ethnicity, overweight increased more steeply between 14-16 years and 21-23 years than between 11-13 years and 14-16 years. More overweight among Black Caribbean and Black African females, lower systolic blood pressure (sBP) among Indian females and Pakistani/Bangladeshi males compared with White UK peers, persisted from 11-13 years. At 21-23 years, glycated haemoglobin (HbA1c) was higher among Black Caribbean females, total cholesterol higher and high-density lipoprotein (HDL) cholesterol lower among Pakistani/Bangladeshis. Overweight was associated with a ∼+2 mm Hg rise in sBP between 11-13 years and 21-23 years. Adiposity measures at 11-13 years were related to allostatic load (a cluster of several risk markers), HbA1c and HDL cholesterol at 21-23 years. Ethnic patterns in CVD biomarkers remained after adjustments. CONCLUSIONS: Adolescent adiposity posed significant risks at 21-23 years, a period in the lifespan generally ignored in cardiovascular studies, when ethnic/gender variations in CVD are already apparent.

Ethnic Differences in and Childhood Influences on Early Adult Pulse Wave Velocity: The Determinants of Adolescent, Now Young Adult, Social Wellbeing, and Health Longitudinal Study.

Early determinants of aortic stiffness as pulse wave velocity are poorly understood. We tested how factors measured twice previously in childhood in a multiethnic cohort study, particularly body mass, blood pressure, and objectively assessed physical activity affected aortic stiffness in young adults. Of 6643 London children, aged 11 to 13 years, from 51 schools in samples stratified by 6 ethnic groups with different cardiovascular risk, 4785 (72%) were seen again at aged 14 to 16 years. In 2013, 666 (97% of invited) took part in a young adult (21-23 years) pilot follow-up. With psychosocial and anthropometric measures, aortic stiffness and blood pressure were recorded via an upper arm calibrated Arteriograph device. In a subsample (n=334), physical activity was measured >5 days via the ActivPal. Unadjusted pulse wave velocities in black Caribbean and white UK young men were similar (mean±SD 7.9±0.3 versus 7.6±0.4 m/s) and lower in other groups at similar systolic pressures (120 mm Hg) and body mass (24.6 kg/m(2)). In fully adjusted regression models, independent of pressure effects, black Caribbean (higher body mass/waists), black African, and Indian young women had lower stiffness (by 0.5-0.8; 95% confidence interval, 0.1-1.1 m/s) than did white British women (6.9±0.2 m/s). Values were separately increased by age, pressure, powerful impacts from waist/height, time spent sedentary, and a reported racism effect (+0.3 m/s). Time walking at >100 steps/min was associated with reduced stiffness (P<0.01). Effects of childhood waist/hip were detected. By young adulthood, increased waist/height ratios, lower physical activity, blood pressure, and psychosocial variables (eg, perceived racism) independently increase arterial stiffness, effects likely to increase with age.

Can arterial wave augmentation in young adults help account for variability of cardiovascular risk in different British ethnic groups?

OBJECTIVE: Traditional cardiovascular risk factors do not fully account for ethnic differences in cardiovascular disease. We tested if arterial function indices, particularly augmentation index (AIx), and their determinants from childhood could underlie such ethnic variability among young British adults in the 'DASH' longitudinal study. METHODS: DASH, at http://dash.sphsu.mrc.ac.uk/, includes representative samples of six main British ethnic groups. Pulse wave velocity (PWV) and AIx were recorded using the Arteriograph device at ages 21-23 years in a subsample (n = 666); psychosocial, anthropometric, and blood pressure (BP) measures were collected then and in two previous surveys at ages 11-13 years and 14-16 years. For n = 334, physical activity was measured over 5 days (ActivPal). RESULTS: Unadjusted values and regression models for PWVs were similar or lower in ethnic minority than in White UK young adults, whereas AIx was higher - Caribbean (14.9, 95% confidence interval 12.3-17.0%), West African (15.3, 12.9-17.7%), Indian (15.1, 13.0-17.2%), and Pakistani/Bangladeshi (15.7, 13.7-17.7%), compared with White UK (11.9, 10.2-13.6%). In multivariate models, adjusted for sex, central SBP, height, and heart rate, Indian and Pakistani/Bangladeshi young adults had higher AIx (ß = 3.35, 4.20, respectively, P < 0.01) than White UK with a similar trend for West Africans and Caribbeans but not statistically significant. Unlike PWV, physical activity, psychosocial or deprivation measures were not associated with AIx, with borderline associations from brachial BP but no other childhood variables. CONCLUSION: Early adult AIx, but not arterial stiffness, may be a useful tool for testing components of excess cardiovascular risk in some ethnic minority groups.