Estimating health-adjusted life expectancy conditional on risk factors: results for smoking and obesity

BACKGROUND: Smoking and obesity are risk factors causing a large burden of disease. To help formulate and prioritize among smoking and obesity prevention activities, estimations of health-adjusted life expectancy (HALE) for cohorts that differ solely in their lifestyle (e.g. smoking vs. non smoking) can provide valuable information. Furthermore, in combination with estimates of life expectancy (LE), it can be tested whether prevention of obesity and smoking results in compression of morbidity. METHODS: Using a dynamic population model that calculates the incidence of chronic disease conditional on epidemiological risk factors, we estimated LE and HALE at age 20 for a cohort of smokers with a normal weight (BMI < 25), a cohort of non-smoking obese people (BMI>30) and a cohort of 'healthy living' people (i.e. non smoking with a BMI < 25). Health state valuations for the different cohorts were calculated using the estimated disease prevalence rates in combination with data from the Dutch Burden of Disease study. Health state valuations are multiplied with life years to estimate HALE. Absolute compression of morbidity is defined as a reduction in unhealthy life expectancy (LE-HALE) and relative compression as a reduction in the proportion of life lived in good health (LE-HALE)/LE. RESULTS: Estimates of HALE are highest for a 'healthy living' cohort (54.8 years for men and 55.4 years for women at age 20). Differences in HALE compared to 'healthy living' men at age 20 are 7.8 and 4.6 for respectively smoking and obese men. Differences in HALE compared to 'healthy living' women at age 20 are 6.0 and 4.5 for respectively smoking and obese women. Unhealthy life expectancy is about equal for all cohorts, meaning that successful prevention would not result in absolute compression of morbidity. Sensitivity analyses demonstrate that although estimates of LE and HALE are sensitive to changes in disease epidemiology, differences in LE and HALE between the different cohorts are fairly robust. In most cases, elimination of smoking or obesity does not result in absolute compression of morbidity but slightly increases the part of life lived in good health. CONCLUSION: Differences in HALE between smoking, obese and 'healthy living' cohorts are substantial and similar to differences in LE. However, our results do not indicate that substantial compression of morbidity is to be expected as a result of successful smoking or obesity prevention

Overlapping phenotypes in autism spectrum disorder and developmental coordination disorder: A cross-syndrome comparison of motor and social skills

Motor and social difficulties are often found in children with an autism spectrum disorder (ASD) and with developmental coordination disorder (DCD), to varying degrees. This study investigated the extent of overlap of these problems in children aged 7-10 years who had a diagnosis of either ASD or DCD, compared to typically-developing controls. Children completed motor and face processing assessments. Parents completed questionnaires concerning their child’s early motor and current motor and social skills. There was considerable overlap between the ASD and DCD groups on the motor and social assessments, with both groups more impaired than controls. Furthermore, motor skill predicted social functioning for both groups. Future research should consider the relationships between core symptoms and their consequences in other domains

Programmed cell death and its role in inflammation

Cell death plays an important role in the regulation of inflammation and may be the result of inflammation. The maintenance of tissue homeostasis necessitates both the recognition and removal of invading microbial pathogens as well as the clearance of dying cells. In the past few decades, emerging knowledge on cell death and inflammation has enriched our molecular understanding of the signaling pathways that mediate various programs of cell death and multiple types of inflammatory responses. This review provides an overview of the major types of cell death related to inflammation. Modification of cell death pathways is likely to be a logical therapeutic target for inflammatory diseases

TNFα inhibits apoptotic cell clearance in the lung, exacerbating acute inflammation

Efficient removal of apoptotic cells is essential for resolution of inflammation. Failure to clear dying cells can exacerbate lung injury and lead to persistent inflammation and autoimmunity. Here we show that TNFα blocks apoptotic cell clearance by alveolar macrophages and leads to proinflammatory responses in the lung. Compared with mice treated with intratracheal TNFα or exogenous apoptotic cells, mice treated with the combination of TNFα plus apoptotic cells demonstrated reduced apoptotic cell clearance from the lungs and increased recruitment of inflammatory leukocytes to the air spaces. Treatment with intratracheal TNFα had no effect on the removal of exogenous apoptotic cells from the lungs of TNFα receptor-1 (p55) and -2 (p75) double mutant mice and no effect on leukocyte recruitment. Bronchoalveolar lavage from mice treated with TNFα plus apoptotic cells contained increased levels of proinflammatory cytokines IL-6, KC, and MCP-1, but exhibited no change in levels of anti-inflammatory cytokines IL-10 and TGF-β. Administration of TNFα plus apoptotic cells during LPS-induced lung injury augmented neutrophil accumulation and proinflammatory cytokine production. These findings suggest that the presence of TNFα in the lung can alter the response of phagocytes to apoptotic cells leading to inflammatory cell recruitment and proinflammatory mediator production

Association of total daily physical activity with disability in community-dwelling older persons: a prospective cohort study

<p>Abstract</p> <p>Background</p> <p>Based on findings primarily using self-report measures, physical activity has been recommended to reduce disability in old age. Collecting objective measures of total daily physical activity in community-dwelling older adults is uncommon, but might enhance the understanding of the relationship of physical activity and disability. We examined whether greater total daily physical activity was associated with less report of disability in the elderly.</p> <p>Methods</p> <p>Data were from the Rush Memory and Aging Project, a longitudinal prospective cohort study of common, age-related, chronic conditions. Total daily physical activity was measured in community-dwelling participants with an average age of 82 using actigraphy for approximately 9 days. Disability was measured via self-reported basic activities of daily living (ADL). The odds ratio and 95% Confidence Interval (CI) were determined for the baseline association of total daily physical activity and ADL disability using a logistic regression model adjusted for age, education level, gender and self-report physical activity. In participants without initial report of ADL disability, the hazard ratio and 95% CI were determined for the relationship of baseline total daily physical activity and the development of ADL disability using a discrete time Cox proportional hazard model adjusted for demographics and self-report physical activity.</p> <p>Results</p> <p>In 870 participants, the mean total daily physical activity was 2. 9 × 10⁵ counts/day (range in 10⁵ counts/day = 0.16, 13. 6) and the mean hours/week of self-reported physical activity was 3.2 (SD = 3.6). At baseline, 718 (82.5%) participants reported being independent in all ADLs. At baseline, total daily physical activity was protective against disability (OR per 10⁵ counts/day difference = 0.55; 95% CI = 0.47, 0.65). Of the participants without baseline disability, 584 were followed for 3.4 years on average. Each 10⁵ counts/day additional total daily physical activity was associated with reduced hazard of developing disability by 25% (HR = 0.75, 95% CI = 0.66, 0.84). The results were unchanged after controlling for important covariates including cognition, depressive symptoms, and chronic health conditions.</p> <p>Conclusions</p> <p>Greater total daily physical activity is independently associated with less disability even after controlling for self-reported physical activity.</p