A systematic review of the association between circulating concentrations of C reactive protein and cancer.

The objective of this study was to review and summarise the published evidence for an association between circulating concentrations of C reactive protein (CRP) and cancer through a systematic review. 90 discrete studies were identified. 81 (90%) were prevalent case-control or cross-sectional studies, and only 9 studies had a prospective design. In most prevalent studies, CRP concentrations were found to be higher in patients with cancer than in healthy controls or controls with benign conditions. Of the nine large prospective studies identified in this review, four reported no relationship between circulating CRP levels and breast, prostate or colorectal cancers, and five studies found that CRP was associated with colorectal or lung cancers. Most of the studies evaluating CRP as a diagnostic marker of cancer did not present relevant statistical analyses. Furthermore, any association reported in the prevalent studies might reflect reverse causation, survival bias or confounding. The prospective studies provided no strong evidence for a causal role of CRP in cancer. Instead of further prevalent studies, more large prospective studies and CRP gene-cancer association studies would be valuable in investigating the role of CRP in cancer

Salt intake, stroke, and cardiovascular disease : meta-analysis of prospective studies

Objective: To assess the relation between the level of habitual salt intake and stroke or total cardiovascular disease outcome. Design: Systematic review and meta-analysis of prospective studies published 1966-2008. Data sources: Medline (1966-2008), Embase (from 1988), AMED (from 1985), CINAHL (from 1982), Psychinfo (from 1985), and the Cochrane Library. Review methods: For each study, relative risks and 95% confidence intervals were extracted and pooled with a random effect model, weighting for the inverse of the variance. Heterogeneity, publication bias, subgroup, and meta-regression analyses were performed. Criteria for inclusion were prospective adult population study, assessment of salt intake as baseline exposure, assessment of either stroke or total cardiovascular disease as outcome, follow-up of at least three years, indication of number of participants exposed and number of events across different salt intake categories. Results: There were 19 independent cohort samples from 13 studies, with 177 025 participants (follow-up 3.5-19 years) and over 11 000 vascular events. Higher salt intake was associated with greater risk of stroke (pooled relative risk 1.23, 95% confidence interval 1.06 to 1.43; P=0.007) and cardiovascular disease (1.14, 0.99 to 1.32; P=0.07), with no significant evidence of publication bias. For cardiovascular disease, sensitivity analysis showed that the exclusion of a single study led to a pooled estimate of 1.17 (1.02 to 1.34; P=0.02). The associations observed were greater the larger the difference in sodium intake and the longer the follow-up. Conclusions: High salt intake is associated with significantly increased risk of stroke and total cardiovascular disease. Because of imprecision in measurement of salt intake, these effect sizes are likely to be underestimated. These results support the role of a substantial population reduction in salt intake for the prevention of cardiovascular disease

Developmental pathways to autism: a review of prospective studies of infants at risk

Autism Spectrum Disorders (ASDs) are neurodevelopmental disorders characterized by impairments in social interaction and communication, and the presence of restrictive and repetitive behaviors. Symptoms of ASD likely emerge from a complex interaction between pre-existing neurodevelopmental vulnerabilities and the child's environment, modified by compensatory skills and protective factors. Prospective studies of infants at high familial risk for ASD (who have an older sibling with a diagnosis) are beginning to characterize these developmental pathways to the emergence of clinical symptoms. Here, we review the range of behavioral and neurocognitive markers for later ASD that have been identified in high-risk infants in the first years of life. We discuss theoretical implications of emerging patterns, and identify key directions for future work, including potential resolutions to several methodological challenges for the field. Mapping how ASD unfolds from birth is critical to our understanding of the developmental mechanisms underlying this disorder. A more nuanced understanding of developmental pathways to ASD will help us not only to identify children who need early intervention, but also to improve the range of interventions available to them

The relation between cholesterol and haemorrhagic or ischaemic stroke in the Renfrew/Paisley study

Studies have found little association between cholesterol and overall stroke risk, but this could be attributable to different relations for haemorrhagic and ischaemic stroke. Stroke mortality data from prospective studies cannot usually be divided into stroke subtypes. We have therefore analysed stroke based on hospital admissions, obtained by computerised linkage with acute hospital discharges in Scotland for a large prospective cohort study

Heterosexual HIV-1 infectiousness and antiretroviral use : systematic review of prospective studies of discordant couples

Background: Recent studies have estimated the reduction in HIV-1 infectiousness with antiretroviral therapy (ART), but high-quality studies such as randomized controlled trials, accompanied by rigorous adherence counseling, are likely to overestimate the effectiveness of treatment-as-prevention in real-life settings. Methods: We attempted to summarize the effect of ART on HIV transmission by undertaking a systematic review and meta-analysis of HIV-1 infectiousness per heterosexual partnership (incidence rate and cumulative incidence over study follow-up) estimated from prospective studies of discordant couples. We used random-effects Poisson regression models to obtain summary estimates. When possible, the analyses were further stratified by direction of transmission (man-to-woman or woman-to-man) and economic setting (high- or low-income countries). Potential causes of heterogeneity of estimates were explored through subgroup analyses. Results: Fifty publications were included. Nine allowed comparison between ART and non-ART users within studies (ART-stratified studies), in which summary incidence rates were 3.6/100 person-years (95% confidence interval = 2.0-6.5) and 0.2/100 person-years (0.07-0.7) for non-ART- and ART-using couples, respectively (P < 0.001), constituting a 91% (79-96%) reduction in per-partner HIV-1 incidence rate with ART use. The 41 studies that did not stratify by ART use provided estimates with high levels of heterogeneity (I2 statistic) and few reported levels of ART use, making interpretation difficult. Nevertheless, estimates tended to be lower with ART use. Infectiousness tended to be higher for low-income than high-income settings, but there was no clear pattern by direction of transmission (man-to-woman and woman-to-man). Conclusions: ART substantially reduces HIV-1 infectiousness within discordant couples, based on observational studies, and could play a major part in HIV-1 prevention efforts. However, the non-zero risk from partners receiving ART demonstrates that appropriate counseling and other risk-reduction strategies for discordant couples are still required. Additional estimates of ART effectiveness by adherence level from real-life settings will be important, especially for persons starting treatment early without symptoms

Socio-economic trajectories and cardiovascular disease mortality in older people: the English Longitudinal Study of Ageing

Background: Socio-economic status from early life has been linked to cardiovascular disease risk, but the impact of life-course socio-economic trajectories, as well as the mechanisms underlying social inequalities in cardiovascular disease risk, is uncertain. Objectives: We assessed the role of behavioural, psychosocial and physiological (including inflammatory) factors in the association between life-course socio-economic status and cardiovascular disease mortality in older adults. Methods: Participants were 7846 individuals (44% women) from the English Longitudinal Study of Ageing, a representative study of individuals aged ≥ 50 years, established in 2002–03. Comprising four indicators of socio-economic status (father’s social class, own education, occupational position and wealth), we computed an index of socio-economic trajectory and a lifetime cumulative socio-economic score. Behavioural (smoking, physical activity, alcohol consumption, body mass index) and psychosocial (social relations, loneliness) factors, physiological (blood pressure, total cholesterol, triglycerides) and inflammatory markers (C-reactive protein, fibrinogen), measured repeatedly over time, were potential explanatory variables. Cardiovascular disease mortality was ascertained by linkage of study members to a national mortality register. Mediation was calculated using the traditional ‘change-in-estimate method’ and alternative approaches such as counterfactual mediation modelling could not be applied in this context. Results: During the 8.4-year follow-up, 1301 study members died (438 from cardiovascular disease). A stable low-social-class trajectory was associated with around double the risk of cardiovascular disease mortality (hazard ratio; 95% confidence interval: 1.94, 1.37; 2.75) compared with a stable high social class across the life course. Individuals in the lowest relative to the highest life-course cumulative socio-economic status group were also more than twice as likely to die of cardiovascular disease (2.57, 1.81; 3.65). Behavioural factors and inflammatory markers contributed most to explaining this gradient, whereas the role of psychosocial and other physiological risk factors was modest. Conclusions: In a population-based cohort of older individuals living in England, we provide evidence that disadvantage across the life course is linked to cardiovascular mortality. That behavioural factors and inflammatory markers partially explain this gradient may provide insights into the potential for intervention

Effects of Isolated Hip Abductor Fatigue on Frontal Plane Knee Mechanics

Purpose: Anterior cruciate ligament injuries and patellofemoral pain syndrome are both common and significant injuries to the knee that have been associated with hip weakness. Prospective studies have linked the risk of experiencing either injury to alterations in the frontal plane knee angle and moment during activity. These components of knee mechanics are theorized to be affected by hip abductor weakness. The purpose of this study was to identify the effects of isolated hip abductor fatigue-induced weakness on lower extremity kinematics and kinetics in recreationally active women