Morning vaccination enhances antibody response over afternoon vaccination: A cluster-randomised trial

The Whitehall study of British civil servants begun in 1967, showed a steep inverse association between social class, as assessed by grade of employment, and mortality from a wide range of diseases. Between 1985 and 1988 we investigated the degree and causes of the social gradient in morbidity in a new cohort of 10,314 civil servants (6900 men, 3414 women) aged 35-55 (the Whitehall II study). Participants were asked to answer a self-administered questionnaire and attend a screening examination. In the 20 years separating the two studies there has been no diminution in social class difference in morbidity: we found an inverse association between employment grade and prevalence of angina, electrocardiogram evidence of ischaemia, and symptoms of chronic bronchitis. Self-perceived health status and symptoms were worse in subjects in lower status jobs. There were clear employment-grade differences in health-risk behaviours including smoking, diet, and exercise, in economic circumstances, in possible effects of early-life environment as reflected by height, in social circumstances at work (eg, monotonous work characterised by low control and low satisfaction), and in social supports. Healthy behaviours should be encouraged across the whole of society; more attention should be paid to the social environments, job design, and the consequences of income inequality.

To quantify the protective efficacy of influenza vaccine in elderly persons. A MEDLINE search was done using the index terms influenza vaccine, vaccine efficacy, elderly, mortality, hospitalized, and pneumonia. Appropriate references in the initially selected articles were also reviewed. Only cohort observational studies with mortality assessment were included in the meta-analysis. In addition, 3 recent case-control studies, 2 cost-effectiveness studies, and 1 randomized, double-blind, placebo-controlled trial were reviewed. Vaccine and epidemic virus strains, age and sex of patients, severity of illness, patient status, and study design were recorded. Upper respiratory illness, hospitalization, pneumonia, and mortality were used as outcome measures. In a meta-analysis of 20 cohort studies, the pooled estimates of vaccine efficacy (1-odds ratio) were 56% (95% Cl, 39% to 68%) for preventing respiratory illness, 53% (Cl, 35% to 66%) for preventing pneumonia, 50% (Cl, 28% to 65%) for preventing hospitalization, and 68% (Cl, 56% to 76%) for preventing death. Vaccine efficacy in the case-control studies ranged from 32% to 45% for preventing hospitalization for pneumonia, from 31% to 65% for preventing hospital deaths from pneumonia and influenza, from 43% to 50% for preventing hospital deaths from all respiratory conditions, and from 27% to 30% for preventing deaths from all causes. The randomized, double-blind, placebo-controlled trial showed a 50% or greater reduction in influenza-related illness. Recent cost-effectiveness studies confirm the efficacy of influenza vaccine in reducing influenza-related morbidity and mortality and show that vaccine provides important cost savings per year per vaccinated person. Despite the paucity of randomized trials, many studies confirm that influenza vaccine reduces the risks for pneumonia, hospitalization, and death in elderly persons during an influenza epidemic if the vaccine strain is identical or similar to the epidemic strain. Influenza immunization is an indispensable part of the care of persons 65 years of age and older. Annual vaccine administration requires the attention of all physicians and public health organizations.

Disruption of the circadian rhythm is a contributory factor to clinical and pathophysiological conditions, including cancer, the metabolic syndrome, and inflammation. Chronic and systemic inflammation are a potential trigger of type 2 diabetes and cardiovascular disease and are caused by the infiltration of large numbers of inflammatory macrophages into tissue. Although recent studies identified the circadian clock gene Rev-erbα, a member of the orphan nuclear receptors, as a key mediator between clockwork and inflammation, the molecular mechanism remains unknown. In this study, we demonstrate that Rev-erbα modulates the inflammatory function of macrophages through the direct regulation of Ccl2 expression. Clinical conditions associated with chronic and systemic inflammation, such as aging or obesity, dampened Rev-erbα gene expression in peritoneal macrophages from C57BL/6J mice. Rev-erbα agonists or overexpression of Rev-erbα in the murine macrophage cell line RAW264 suppressed the induction of Ccl2 following an LPS endotoxin challenge. We discovered that Rev-erbα represses Ccl2 expression directly through a Rev-erbα-binding motif in the Ccl2 promoter region. Rev-erbα also suppressed CCL2-activated signals, ERK and p38, which was recovered by the addition of exogenous CCL2. Further, Rev-erbα impaired cell adhesion and migration, which are inflammatory responses activated through the ERK- and p38-signaling pathways, respectively. Peritoneal macrophages from mice lacking Rev-erbα display increases in Ccl2 expression. These data suggest that Rev-erbα regulates the inflammatory infiltration of macrophages through the suppression of Ccl2 expression. Therefore, Rev-erbα may be a key link between aging- or obesity-associated impairment of clockwork and inflammation.