Animal models and clinical studies suggest a mechanistic link between the pneumococcal polysaccharide vaccine (PPV) and a cardiovascular protective effect. However, conflicting results exist from several large observational studies in humans. We set out to systematically review current literature and conduct meta-analyses of studies on PPV and cardiovascular outcomes. Medline, Embase and CENTRAL were searched for randomised controlled trials (RCTs) and observational studies in adults, using PPV as the intervention, up to 30 April 2014. Studies that compared PPV with a control (another vaccine, no vaccine or placebo) and recorded ischaemic events were included in this review. Two investigators extracted data independently on study design, baseline characteristics and summary outcomes. Study quality was examined using the Newcastle-Ottawa Quality Assessment Scale. Pooled estimates using random effects models and their 95% CIs were calculated separately for the outcomes of acute coronary syndrome (ACS) events and stroke. No RCT data were available. A total of 230 426 patients were included in eight observational studies and recorded as ACS events. PPV was associated with significantly lower odds of ACS events in patients 65 years and older (pooled OR=0.83 (95% CI 0.71 to 0.97), I2=77.0%). However, there was no significant difference in ACS events when younger people were included (pooled OR=0.86 (95% CI 0.73 to 1.01), I2=81.4%). Pooling of four studies, covering a total of 192 210 patients, did not find a significantly reduced risk of stroke in all patients (pooled OR=1.00 (95% CI 0.89 to 1.12), I2=55.3%), or when restricted to those 65 years and older (pooled OR=0.96 (95% CI 0.87 to 1.05), I2=22.5%). In this meta-analysis of observational studies, the use of PPV was associated with a significantly lower risk of ACS events in the older population, but not stroke. An adequately powered and blinded RCT to confirm these findings is warranted.
Fluctuations in glucose levels in diabetic patients can result in oxidative stress, resulting in an increased risk for diabetic complications. We investigated whether antioxidation would protect the kidney from oxidative stress in diabetic rats treated with insulin and provide evidence for the efficacy of antioxidant treatment in diabetes management. Diabetes was induced by injection of Streptozotocin intraperitoneally in male Wistar rats. Diabetic rats received either insulin, both insulin and Radix Astragali (RA), RA, or no treatment. The levels of malondialdehyde (MDA), interleukin 6 (IL-6), tumor necrosis factor α (TNF-α) and activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) in kidney were determined. The changes of blood glucose levels and body weight were monitored. The levels of serum creatinine (Scr) were determined. The expression of PKCα was determined by western blot. NF-κB activation in kidney was assessed using EMSA. Compared to diabetic rats treated with insulin alone, the diabetic rats treated with combination of insulin and RA showed: (1) significantly lower levels of MDA, IL-6, TNF-α, and Scr (p < 0.05); (2) significantly higher SOD and GSH-Px activities (p < 0.05); (3) significantly lower NF-κB activation and lower expression levels of PKCα (p < 0.05); (4) significantly smaller kidney-to-body weight ratio (p < 0.05). RA is an effective agent in lowering oxidative stress in diabetic rats treated with insulin. Antioxidation is beneficial in reducing the risk of kidney damage due to oxidative stress in diabetic patients.
Whilst there have been temporal improvements in the overall utilisation of antithrombotic therapy, including warfarin, there are still significant gaps in the translation of evidence from clinical trials to clinical practice. Further sustainable intervention is warranted to help apply treatment recommendations to the target population.
Objectives
To examine the effectiveness of different strategies for recruiting participants for a large Australian randomised controlled trial (RCT), the Australian Study for the Prevention through Immunisation of Cardiovascular Events (AUSPICE).
Design, setting, participants
Men and women aged 55–60 years with at least two cardiovascular risk factors (hypertension, hypercholesterolaemia, overweight/obesity) were recruited for a multicentre placebo‐controlled RCT assessing the effectiveness of 23‐valent pneumococcal polysaccharide vaccine (23vPPV) for preventing cardiovascular events.
Methods
Invitations were mailed by the Australian Department of Human Services to people in the Medicare database aged 55–60 years; reminders were sent 2 weeks later. Invitees could respond in hard copy or electronically. Direct recruitment was supplemented by asking invitees to extend the invitation to friends and family (snowball sampling) and by Facebook advertising.
Main outcome
Proportions of invitees completing screening questionnaire and recruited for participation in the RCT.
Results
21 526 of 154 992 invited people (14%) responded by completing the screening questionnaire, of whom 4725 people were eligible and recruited for the study. Despite the minimal study burden (one questionnaire, one clinic visit), the overall participation rate was 3%, or an estimated 10% of eligible persons. Only 16% of eventual participants had responded within 2 weeks of the initial invitation letter (early responders); early and late responders did not differ in their demographic or medical characteristics. Socio‐economic disadvantage did not markedly influence response rates. Facebook advertising and snowball sampling did not increase recruitment.
Conclusions
Trial participation rates are low, and multiple concurrent methods are needed to maximise recruitment. Social media strategies may not be successful in older age groups.
Trial registration
Australian New Zealand Clinical Trials Registry, ACTRN12615000536561.
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