Effects of non-pharmacological interventions as vaccine adjuvants in humans: a systematic review and network meta-analysis.

INTRODUCTION: Psychological and behavioural may enhance vaccine effectiveness. We conducted a systematic review and network meta-analysis (NMA) to examine the effects of non-pharmacological adjuvants on vaccine effectiveness, as measured by antibody responses to vaccination. AREAS COVERED: Electronic databases (EMBASE, Medline, PsychINFO, CINAHL) were searched from inception to 6th February 2018. This yielded 100 eligible papers, reporting 106 trials: 79 interventions associated with diet and/or nutrition; 12 physical activity interventions and 9 psychological interventions.Over half (58/106) of trials reported evidence of an enhanced antibody response to vaccination across one or more outcomes. The NMA considered the comparative effects between all intervention types, control and placebo for antibody titres (48 studies), seroconversion (25 studies) and seroprotection (23 studies) separately. The NMA provided weak evidence in support of nutritional formulae and probiotics in increasing antibody titres. EXPERT OPINION: This review offers a comprehensive summary of the literature on non-pharmacological interventions as vaccine adjuvants. The evidence is characterised by considerable heterogeneity but provides early evidence in support of nutritional formulae and probiotic interventions. Psychological and exercise-based interventions were characterised by limited and unreliable evidence. Large, well-designed studies including consistent core outcomes and measures of intervention adherence and fidelity are required.

Effects of Brief Mood-Improving Interventions on Immunity: A Systematic Review and Meta-Analysis.

OBJECTIVE: Positive mood has been associated with enhanced immune function. Interventions that improve mood could therefore provide a mechanism for optimizing immune-related health outcomes. Brief interventions that improve mood, also known as mood inductions, potentially offer a pragmatic approach to enhancing immune function for finite periods where this would be beneficial to health (e.g., in advance of vaccination or surgery). This review sought to systematically examine the evidence regarding the effects of brief, single-session positive mood interventions on immunity. METHODS: Systematic searches of electronic databases were performed from earliest records to July 25, 2018. We identified 42 interventions suitable for inclusion, 6 of which were tested in multiple subpopulations. Random-effects meta-analyses were performed for pre-post experimental group immune outcomes measured in at least five intervention studies. RESULTS: Although interventions were heterogeneous, 81% resulted in a statistically significant change in at least one immune parameter after the positive mood intervention for one or more of the subpopulations examined. However, studies were, in general, of low-to-moderate quality with small sample sizes (median n = 32) and did not examine the persistence or clinical relevance of the immune changes observed. Random-effects meta-analyses showed a significant medium-sized effect of interventions on increasing secretory IgA concentration (g = 0.65), a small but statistically significant effect for increased Interleukin-6 production (g = 0.12), and nonsignificant effects on natural killer cell activity (g = 0.15). CONCLUSIONS: The current literature suggests that improvements in mood resulting from brief interventions can influence some immune parameters in ways indicative of enhanced immune function. However, there is a need for higher-quality research in this area that focuses on clinically relevant immune outcomes and mechanisms.

Psychological interventions as vaccine adjuvants: A systematic review.

OBJECTIVES: The effectiveness of vaccines is known to be altered by a range of psychological factors. We conducted a systematic review to evaluate the effects of psychological interventions on the ability of vaccines to protect against disease, as measured by antibody responses. METHODS: Electronic databases (EMBASE, Medline, PsychINFO, CINAHL) were searched from their inception to 6th February 2018. RESULTS: The search yielded 9 eligible trials conducted with 1603 participants and four broad categories of intervention: meditation/mindfulness (n = 3), massage (n = 3), expressive writing (n = 2) and cognitive behavioural stress management (n = 1). Some evidence of benefit on the antibody response to vaccination was observed in 6/9 of all trials and in 4/7 of randomised controlled trials. However, effects on antibody levels were often mixed, with only 3 of 6 trials showing benefit demonstrating an improvement in all antibody outcomes and at all time points assessed. Trials demonstrating benefit also provided direct or indirect evidence of adequate adherence with the intervention; and in 50% of these trials, there was also evidence that the intervention was effective in changing the mediating psychological constructs targeted by the intervention. CONCLUSIONS: This literature is characterised by considerable heterogeneity in terms of intervention type, vaccine type, age of participants and the temporal relationship between vaccination and intervention. We conclude that there is early evidence to suggest that psychological interventions may enhance the antibody response to vaccination. However, the effects are inconsistent, with the greatest likelihood of benefit seen in trials evidencing adequate adherence with the intervention. Future work would benefit from rigorous intervention development that focuses on achieving adequate adherence and large well-controlled randomised trials with a focus on an agreed set of outcomes.

Objective measurement of cough in otherwise healthy volunteers with acute cough.

Cough is one of the commonest reasons for medical consultation and acute cough associated with upper respiratory tract infections (URTIs) is a global problem. In otherwise healthy volunteers complaining of cough associated with symptoms of URTI, we aimed to assess objective and subjective measures of cough and their repeatability and perform power calculations for the design of future studies to test therapies. We studied 54 otherwise healthy volunteers with acute cough (<3 weeks) (median age 22 yrs (interquartile range 21-26 yrs), 64% female, mean forced expiratory volume in 1 s 97.6±10.5% predicted). All subjects performed 24-h ambulatory cough monitoring and reported cough frequency and severity using visual analogue scales (VAS) on 2 consecutive days. Sample size calculations were performed for crossover and parallel group study designs. Objective cough frequency was high (session 1: geometric mean 12.1 coughs·h(-1) (95%CI 9.7-15.2)) and fell significantly (session 2: 9.0 coughs·h(-1) (95%CI 6.9-11.6); p<0.001). Repeatability was higher for objective cough frequency (intra-class correlation coefficient (ICC)=0.94, p<0.001) than reported cough frequency (daytime VAS ICC=0.784, p<0.001). Crossover/parallel studies require <15 and <41 subjects per arm to detect a 50% reduction in cough frequency with 90% power, respectively. Acute cough frequency is highly repeatable over any 48-h period, allowing small sample sizes to be used when investigating the effectiveness of novel anti-tussives.