Interleukin 18 and coronary heart disease: Prospective study and systematic review

Aim Previous studies suggest that circulating levels of interleukin-18 (IL-18) may be prospectively related to risk of coronary heart disease (CHD) in the general population. We report new data from the largest prospective study to date, which are combined with data from all published prospective studies in a meta-analysis. Methods We measured baseline IL-18 levels in stored serum samples of subjects from a case–control study nested within a prospective study of 5661 men aged 40–59 years recruited from general practices in 18 British towns in 1978–1980 and followed-up for up to 16 years (median time to event 8.4 years) for fatal CHD and non-fatal myocardial infarction (595 cases, 1238 controls). Results IL-18 concentrations were strongly related to cigarette smoking, triglyceride, HDL-cholesterol (inversely) and to circulating levels of several inflammatory and haemostatic markers. Men in the top third of baseline IL-18 levels had an age-adjusted odds ratio (OR) for CHD of 1.55 (95% CI 1.21, 1.98) compared with those in the lowest third; this was reduced to 1.30 (95% CI 0.99, 1.69) after additional adjustment for vascular risk factors and 1.12 (95% CI 0.84, 1.49) after further adjustment for CRP and IL-6. In meta-analyses of CVD, associations (or effect sizes) were consistent between studies; RRs were 1.63 (95% CI 1.46, 1.82) after age adjustment, 1.39 (95% CI 1.24, 1.55) after additional risk factor adjustment and 1.34 (95% CI 1.17, 1.54) after additional adjustment for inflammatory markers. Conclusions Circulating IL-18 is prospectively and independently associated with CVD risk

Weight loss referrals for adults in primary care (WRAP) : Protocol for a multi-centre randomised controlled trial comparing the clinical and cost-effectiveness of primary care referral to a commercial weight loss provider for 12 weeks, referral for 52 weeks, and a brief self-help intervention [ISRCTN82857232]

Background: Recent trials demonstrate the acceptability and short term efficacy of primary care referral to a commercial weight loss provider for weight management. Commissioners now need information on the optimal duration of intervention and the longer term outcomes and cost effectiveness of such treatment to give best value for money. Methods/Design. This multicentre, randomised controlled trial with a parallel design will recruit 1200 overweight adults (BMI ≥28 kg/m2) through their primary care provider. They will be randomised in a 2:5:5 allocation to: Brief Intervention, Commercial Programme for 12 weeks, or Commercial Programme for 52 weeks. Participants will be followed up for two years, with assessments at 0, 3, 12 and 24 months. The sequential primary research questions are whether the CP interventions achieve significantly greater weight loss from baseline to 12 months than BI, and whether CP52 achieves significantly greater weight loss from baseline to 12 months than CP12. The primary outcomes will be an intention to treat analysis of between treatment differences in body weight at 12 months. Clinical effectiveness will be also be assessed by measures of weight, fat mass, and blood pressure at each time point and biochemical risk factors at 12 months. Self-report questionnaires will collect data on psychosocial factors associated with adherence, weight-loss and weight-loss maintenance. A within-trial and long-term cost-effectiveness analysis will be conducted from an NHS perspective. Qualitative methods will be used to examine the participant experience. Discussion. The current trial compares the clinical and cost effectiveness of referral to a commercial provider with a brief intervention. This trial will specifically examine whether providing longer weight-loss treatment without altering content or intensity (12 months commercial referral vs. 12 weeks) leads to greater weight loss at one year and is sustained at 2 years. It will also evaluate the relative cost-effectiveness of the three interventions. This study has direct implications for primary care practice in the UK and will provide important information to inform the decisions of practitioners and commissioners about service provision

Bayesian hierarchical piecewise regression models: a tool to detect trajectory divergence between groups in long-term observational studies

Background: Bayesian hierarchical piecewise regression (BHPR) modeling has not been previously formulated to detect and characterise the mechanism of trajectory divergence between groups of participants that have longitudinal responses with distinct developmental phases. These models are useful when participants in a prospective cohort study are grouped according to a distal dichotomous health outcome. Indeed, a refined understanding of how deleterious risk factor profiles develop across the life-course may help inform early-life interventions. Previous techniques to determine between-group differences in risk factors at each age may result in biased estimate of the age at divergence.Methods: We demonstrate the use of Bayesian hierarchical piecewise regression (BHPR) to generate a point estimate and credible interval for the age at which trajectories diverge between groups for continuous outcome measures that exhibit non-linear within-person response profiles over time. We illustrate our approach by modeling the divergence in childhood-to-adulthood body mass index (BMI) trajectories between two groups of adults with/without type 2 diabetes mellitus (T2DM) in the Cardiovascular Risk in Young Finns Study (YFS).Results: Using the proposed BHPR approach, we estimated the BMI profiles of participants with T2DM diverged from healthy participants at age 16 years for males (95% credible interval (CI): 13.5-18 years) and 21 years for females (95% CI: 19.5-23 years). These data suggest that a critical window for weight management intervention in preventing T2DM might exist before the age when BMI growth rate is naturally expected to decrease. Simulation showed that when using pairwise comparison of least-square means from categorical mixed models, smaller sample sizes tended to conclude a later age of divergence. In contrast, the point estimate of the divergence time is not biased by sample size when using the proposed BHPR method.Conclusions: BHPR is a powerful analytic tool to model long-term non-linear longitudinal outcomes, enabling the identification of the age at which risk factor trajectories diverge between groups of participants. The method is suitable for the analysis of unbalanced longitudinal data, with only a limited number of repeated measures per participants and where the time-related outcome is typically marked by transitional changes or by distinct phases of change over time

Applied public health research - falling through the cracks?

<p>Abstract</p> <p>Background</p> <p>There is a degree of dissonance between the types of evaluative research required by organisations providing or commissioning health care, those recommended by organisations developing evidence-based guidance, and those which research funding bodies are prepared to support.</p> <p>Methods</p> <p>We present a case study of efforts to establish a pragmatic but robust evaluation of local exercise referral schemes. We considered the epidemiological, ethical and practical advantages and disadvantages of a number of study designs and applied for research funding based on an uncontrolled design, outlining the difficulties of carrying out a randomised controlled trial to evaluate an existing service.</p> <p>Results</p> <p>Our proposal was praised for its relevance and clear patient outcomes, but the application was twice rejected because both funders and reviewers insisted on a randomised controlled trial design, which we had found to be impractical, unacceptable to service users and potentially unethical.</p> <p>Conclusion</p> <p>The case study highlights continuing challenges for applied public health research in the current funding climate.</p

Interleukin 18 and coronary heart disease: Prospective study and systematic review

Aim: Previous studies suggest that circulating levels of interleukin-18 (IL-18) may be prospectively related to risk of coronary heart disease (CHD) in the general population. We report new data from the largest prospective study to date, which are combined with data from all published prospective studies in a meta-analysis.Methods: We measured baseline IL-18 levels in stored serum samples of subjects from a case-control study nested within a prospective study of 5661 men aged 40-59 years recruited from general practices in 18 British towns in 1978-1980 and followed-up for up to 16 years (median time to event 8.4 years) for fatal CHD and non-fatal myocardial infarction (595 cases, 1238 controls).Results: IL-18 concentrations were strongly related to cigarette smoking, triglyceride, HDL-cholesterol (inversely) and to circulating levels of several inflammatory and haemostatic markers. Men in the top third of baseline IL-18 levels had an age-adjusted odds ratio (OR) for CHD of 1.55 (95% CI 1.21, 1.98) compared with those in the lowest third; this was reduced to 1.30 (95% CI 0.99, 1.69) after additional adjustment for vascular risk factors and 1.12 (95% CI 0.84, 1.49) after further adjustment for CRP and IL-6. In meta-analyses of CVD, associations (or effect sizes) were consistent between studies; RRs were 1.63 (95% CI 1.46, 1.82) after age adjustment, 1.39 (95% CI 1.24, 1.55) after additional risk factor adjustment and 1.34 (95% CI 1.17, 1.54) after additional adjustment for inflammatory markers.Conclusions: Circulating IL-18 is prospectively and independently associated with CVD risk

What is behind smoker support for new smokefree areas? National survey data

BACKGROUND: Some countries have started to extend indoor smokefree laws to cover cars and various outdoor settings. However, policy-modifiable factors around smoker support for these new laws are not well described. METHODS: The New Zealand (NZ) arm of the International Tobacco Control Policy Evaluation Survey (ITC Project) derives its sample from the NZ Health Survey (a national sample). From this sample we surveyed adult smokers (n = 1376). RESULTS: For the six settings considered, 59% of smokers supported at least three new completely smokefree areas. Only 2% favoured smoking being allowed in all the six new settings. Support among Maori, Pacific and Asian smokers relative to European smokers was elevated in multivariate analyses, but confidence intervals often included 1.0.Also in the multivariate analyses, "strong support" by smokers for new smokefree area laws was associated with greater knowledge of the second-hand smoke (SHS) hazard, and with behaviours to reduce SHS exposure towards others. Strong support was also associated with reporting having smokefree cars (aOR = 1.68, 95% CI = 1.21 - 2.34); and support for tobacco control regulatory measures by government (aOR = 1.63, 95% CI = 1.32 - 2.01). There was also stronger support by smokers with a form of financial stress (not spending on household essentials). CONCLUSIONS: Smokers from a range of population groups can show majority support for new outdoor and smokefree car laws. Some of these findings are consistent with the use of public health strategies to support new smokefree laws, such as enhancing public knowledge of the second-hand smoke hazard

Characterization of the mouse Dazap1 gene encoding an RNA-binding protein that interacts with infertility factors DAZ and DAZL

BACKGROUND: DAZAP1 (DAZ Associated Protein 1) was originally identified by a yeast two-hybrid system through its interaction with a putative male infertility factor, DAZ (Deleted in Azoospermia). In vitro, DAZAP1 interacts with both the Y chromosome-encoded DAZ and an autosome-encoded DAZ-like protein, DAZL. DAZAP1 contains two RNA-binding domains (RBDs) and a proline-rich C-terminal portion, and is expressed most abundantly in the testis. To understand the biological function of DAZAP1 and the significance of its interaction with DAZ and DAZL, we isolated and characterized the mouse Dazap1 gene, and studied its expression and the subcellular localization of its protein product. RESULTS: The human and mouse genes have similar genomic structures and map to syntenic chromosomal regions. The mouse and human DAZAP1 proteins share 98% identity and their sequences are highly similar to the Xenopus orthologue Prrp, especially in the RBDs. Dazap1 is expressed throughout testis development. Western blot detects a single 45 kD DAZAP1 protein that is most abundant in the testis. Although a majority of DAZAP1 is present in the cytoplasmic fraction, they are not associated with polyribosomes. CONCLUSIONS: DAZAP1 is evolutionarily highly conserved. Its predominant expression in testes suggests a role in spermatogenesis. Its subcellular localization indicates that it is not directly involved in mRNA translation