The strength of social isolation as a predictor of mortality is similar to that of well-documented clinical risk factors. Our results suggest the importance of assessing patients' level of social isolation.

BackgroundLeukocyte telomere length (LTL) is an emerging marker of biological age. Chronic inflammatory activity is commonly proposed as a promoter of biological aging in general, and of leukocyte telomere shortening in particular. In addition, senescent cells with critically short telomeres produce pro-inflammatory factors. However, in spite of the proposed causal links between inflammatory activity and LTL, there is little clinical evidence in support of their covariation and interaction.Methodology/Principal FindingsTo address this issue, we examined if individuals with high levels of the systemic inflammatory markers interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP) had increased odds for short LTL. Our sample included 1,962 high-functioning adults who participated in the Health, Aging and Body Composition Study (age range: 70–79 years). Logistic regression analyses indicated that individuals with high levels of either IL-6 or TNF-α had significantly higher odds for short LTL. Furthermore, individuals with high levels of both IL-6 and TNF-α had significantly higher odds for short LTL compared with those who had neither high (OR = 0.52, CI = 0.37–0.72), only IL-6 high (OR = 0.57, CI = 0.39–0.83) or only TNF-α high (OR = 0.67, CI = 0.46–0.99), adjusting for a wide variety of established risk factors and potential confounds. In contrast, CRP was not associated with LTL.Conclusions/SignificanceResults suggest that cumulative inflammatory load, as indexed by the combination of high levels of IL-6 and TNF-α, is associated with increased odds for short LTL. In contrast, high levels of CRP were not accompanied by short LTL in this cohort of older adults. These data provide the first large-scale demonstration of links between inflammatory markers and LTL in an older population.

Morbidity and mortality are greater among socially disadvantaged racial/ethnic groups and those of lower socioeconomic status (SES). Greater chronic stress exposure in disadvantaged groups may contribute to this by accelerating cellular aging, indexed by shorter age-adjusted telomere length. While studies consistently relate shorter leukocyte telomere length (LTL) to stress, the few studies, mostly from the UK, examining associations of LTL with SES have been mixed. The current study examined associations between educational attainment and LTL among 2,599 high-functioning black and white adults age 70-79 from the Health, Aging and Body Composition Study. Multiple regression analyses tested associations of race/ethnicity, educational attainment and income with LTL, adjusting for potential confounders. Those with only a high school education had significantly shorter mean LTL (4806 basepairs) than those with post-high school education (4926 basepairs; B=125, SE= 47.6, p = .009). A significant interaction of race and education (B = 207.8, SE = 98.7, p = .035) revealed more beneficial effects of post-high school education for blacks than for whites. Smokers had shorter LTL than non-smokers, but the association of education and LTL remained significant when smoking was covaried (B = 119.7, SE = 47.6, p = .012). While higher income was associated with longer LTL, the effect was not significant (p > .10). This study provides the first demonstration of an association between educational attainment and LTL in a US population where higher education appears to have a protective effect against telomere shortening, particularly in blacks.

Health disparities research spans multiple fields and methods and documents strong links between social disadvantage and poor health. Associations between socioeconomic status (SES) and health are often taken as evidence for the causal impact of SES on health, but alternative explanations, including the impact of health on SES, are plausible. Studies showing the influence of parents' SES on their children's health provide evidence for a causal pathway from SES to health, but have limitations. Health disparities researchers face tradeoffs between "rigor" and "vigor" in designing studies that demonstrate how social disadvantage becomes biologically embedded and results in poorer health. Rigorous designs aim to maximize precision in the measurement of SES and health outcomes through methods that provide the greatest control over temporal ordering and causal direction. To achieve precision, many studies use a single SES predictor and single disease. However, doing so oversimplifies the multifaceted, entwined nature of social disadvantage and may overestimate the impact of that one variable and underestimate the true impact of social disadvantage on health. In addition, SES effects on overall health and functioning are likely to be greater than effects on any one disease. Vigorous designs aim to capture this complexity and maximize ecological validity through more complete assessment of social disadvantage and health status, but may provide less-compelling evidence of causality. Newer approaches to both measurement and analysis may enable enhanced vigor as well as rigor. Incorporating both rigor and vigor into studies will provide a fuller understanding of the causes of health disparities.methodology | social determinants of health | cumulative risk G ood health and longevity are unequally distributed in populations. Although some unavoidable variations in health emanate from individual differences in vulnerability to disease, others are linked to membership in socially disadvantaged groups. The latter are unjust and have been the focus of considerable research and policy (1). Research on these health disparities has demonstrated consistent graded associations between various components of socioeconomic status (SES) and a wide range of health indicators; at each step up the social ladder, whether indexed by higher income, education, and/or occupational level, rates of morbidity and mortality decrease (2). The prevailing understanding of this relationship is that SES is a "fundamental cause" of health status (3), which operates through physical and/or psychosocial resources that are more readily available as SES increases, and hardships and adverse exposures that are more intense and frequent as SES decreases.Evidence for the SES-health gradient comes primarily from cross-sectional data linking contemporaneous measures of SES in adulthood with prevalence of disease, poor health, or mortality. Smaller literatures have established associations between socioeconomic conditions in childhood and childhood health, and betwe...

To assess the role of DNA repair in maintenance of hearing function and neurological integrity, we examined hearing status, neurological function, DNA repair complementation group and history of acute burning on minimal sun exposure in all patients with xeroderma pigmentosum, who had at least one complete audiogram, examined at the National Institutes of Health from 1971 to 2012. Seventy-nine patients, aged 1-61 years, were diagnosed with xeroderma pigmentosum (n = 77) or xeroderma pigmentosum/Cockayne syndrome (n = 2). A total of 178 audiograms were included. Clinically significant hearing loss (>20 dB) was present in 23 (29%) of 79 patients. Of the 17 patients with xeroderma pigmentosum-type neurological degeneration, 13 (76%) developed hearing loss, and all 17 were in complementation groups xeroderma pigmentosum type A or type D and reported acute burning on minimal sun exposure. Acute burning on minimal sun exposure without xeroderma pigmentosum-type neurological degeneration was present in 18% of the patients (10/55). Temporal bone histology in a patient with severe xeroderma pigmentosum-type neurological degeneration revealed marked atrophy of the cochlear sensory epithelium and neurons. The 19-year mean age of detection of clinically significant hearing loss in the patients with xeroderma pigmentosum with xeroderma pigmentosum-type neurological degeneration was 54 years younger than that predicted by international norms. The four frequency (0.5/1/2/4 kHz) pure-tone average correlated with degree of neurodegeneration (P < 0.001). In patients with xeroderma pigmentosum, aged 4-30 years, a four-frequency pure-tone average ≥10 dB hearing loss was associated with a 39-fold increased risk (P = 0.002) of having xeroderma pigmentosum-type neurological degeneration. Severity of hearing loss parallels neurological decline in patients with xeroderma pigmentosum-type neurological degeneration. Audiometric findings, complementation group, acute burning on minimal sun exposure and age were important predictors of xeroderma pigmentosum-type neurological degeneration. These results provide evidence that DNA repair is critical in maintaining neurological integrity of the auditory system.

The social determinants of health (SDoH) are defined by the World Health Organization as the "conditions in which people are born, grow, live, work, and age." Within pediatrics, studies have highlighted links between these underlying social, economic, and environmental conditions, and a range of health outcomes related to both acute and chronic disease. Additionally, within the adult literature, multiple studies have shown significant links between social problems experienced during childhood and "adult diseases" such as diabetes mellitus and hypertension. A variety of potential mechanisms for such links have been explored including differential access to care, exposure to carcinogens and pathogens, health-affecting behaviors, and physiologic responses to allostatic load (i.e., toxic stress). This robust literature supports the importance of the SDoH and the development and evaluation of social needs interventions. These interventions are also driven by evolving economic realities, most importantly, the shift from fee-for-service to value-based payment models. This article reviews existing evidence regarding pediatric-focused clinical interventions that address the SDoH, those that target basic needs such as food insecurity, housing insecurity, and diminished access to care. The paper summarizes common challenges encountered in the evaluation of such interventions. Finally, the paper concludes by introducing key opportunities for future inquiry.

This is a prepublication version of an article that has undergone peer review and been accepted for publication but is not the final version of record. This paper may be cited using the DOI and date of access. This paper may contain information that has errors in facts, figures, and statements, and will be corrected in the final published version. The journal is providing an early version of this article to expedite access to this information. The American Academy of Pediatrics, the editors, and authors are not responsible for inaccurate information and data described in this version.

This cross-sectional study explores the utility of community-level data for accurately identifying patients with social risks by comparing the social deprivation index score for the census tract where a patient lives with patient-level social risk screening data.