Stress and Depression Among the Oldest-Old: A Longitudinal Analysis

Stress and psychosocial resources play a crucial role in late-life depression. While most studies focus on predominantly those who are young-old, this study used a sample aged 85 and older. The authors' study aims to examine three research questions: (1) What are the trajectories of depression and its associated factors such as types of stress and psychosocial resources among the oldest-old? (2) What are the longitudinal relationships among the changes in stress, psychosocial resources, and depressive symptoms? (3) Are the effects of the changes in stress on depression trajectory mediated by changes in psychosocial resources? The study used a convenience sample of 193 community-dwelling elders aged 85 and older with four interviews every six months from 1986 to 1988. Using multilevel modeling analyses, longitudinal results showed that changes in positive life events, daily hassles (worries), and mastery were significantly associated with changes in late-life depression among the oldest-old.     

Obesity, leanness, and mortality: effect modification by physical activity in men and women

The 13-year mortality from BMI, body fat (BF), and fat-free mass (FFM) was examined among active and sedentary adults. In total, 2,819 men and women aged 35-65 years in 1987/1988, participating in the Danish MONICA project, were included, and followed for 13.6 years for total mortality. In men, physical activity modified the health hazard of both a high and a low BMI, and the U-shaped association disappeared among the active (hazard ratio (HR) = 0.86, CI: 0.72-1.02). Among active men, FFM was inversely related to mortality (HR = 0.55, 95% CI: 0.40-0.77) whereas a direct positive trend was seen for BF. Among women, physical activity modified association between BMI and mortality, but the U-shaped association remained among the active. Among women, no significant associations were found between either BF or FFM and total mortality. All effects were independent of waist- and hip-circumferences. In conclusion, among men, physical activity may play an important role for the prevention of early mortality beyond its direct effects, by modifying the health hazard of both a high and a low BMI, and by lowering the risk associated with a high BF or a low FFM. Among women physical activity lowers mortality, but an effect-modifying potential of physical activity on associations between BMI or body composition could not be identified.     

Contribution of deaths related to alcohol use of socioeconomic variation in mortality: register based follow up study.

OBJECTIVE: To estimate the contribution of excessive alcohol use to socioeconomic variation in mortality among men and women in Finland. DESIGN: Register based follow up study. SUBJECTS: The population covered by the 1985 and 1990 censuses, aged > or = 20 in the follow up period 1987-93. MAIN OUTCOME MEASURES: Total mortality and alcohol related mortality from all causes, from diseases, and from accidents and violence according to socioeconomic position. The excess mortality among other classes compared with upper non-manual employees and differences in life expectancy between the classes were used to measure mortality differentials. RESULTS: Alcohol related mortality constituted 11% of all mortality among men aged > or = 20 and 2% among women and was higher among manual workers than among other classes. It accounted for 14% of the excess all cause mortality among manual workers over upper non-manual employees among men and 4% among women and for 24% and 9% of the differences in life expectancy, respectively. Half of the excess mortality from accidents and violence among male manual workers and 38% among female manual workers was accounted for by alcohol related deaths, whereas in diseases the role of alcohol was modest. The contribution of alcohol related deaths to relative mortality differentials weakened with age. CONCLUSIONS: Class differentials in alcohol related mortality are an important factor in the socioeconomic mortality differentials in Finland, especially among men, among younger age groups, and in mortality from accidents and violence.     

Gender Differences in Survival among Adult Patients Starting Antiretroviral Therapy in South Africa: A Multicentre Cohort Study

Background

Increased mortality among men on antiretroviral therapy (ART) has been documented but remains poorly understood. We examined the magnitude of and risk factors for gender differences in mortality on ART.

Methods and Findings

Analyses included 46,201 ART-naïve adults starting ART between January 2002 and December 2009 in eight ART programmes across South Africa (SA). Patients were followed from initiation of ART to outcome or analysis closure. The primary outcome was mortality; secondary outcomes were loss to follow-up (LTF), virologic suppression, and CD4+ cell count responses. Survival analyses were used to examine the hazard of death on ART by gender. Sensitivity analyses were limited to patients who were virologically suppressed and patients whose CD4+ cell count reached >200 cells/µl. We compared gender differences in mortality among HIV+ patients on ART with mortality in an age-standardised HIV-negative population.Among 46,201 adults (65% female, median age 35 years), during 77,578 person-years of follow-up, men had lower median CD4+ cell counts than women (85 versus 110 cells/µl, p<0.001), were more likely to be classified WHO stage III/IV (86 versus 77%, p<0.001), and had higher mortality in crude (8.5 versus 5.7 deaths/100 person-years, p<0.001) and adjusted analyses (adjusted hazard ratio [AHR] 1.31, 95% CI 1.22–1.41). After 36 months on ART, men were more likely than women to be truly LTF (AHR 1.20, 95% CI 1.12–1.28) but not to die after LTF (AHR 1.04, 95% CI 0.86–1.25). Findings were consistent across all eight programmes. Virologic suppression was similar by gender; women had slightly better immunologic responses than men. Notably, the observed gender differences in mortality on ART were smaller than gender differences in age-standardised death rates in the HIV-negative South African population. Over time, non-HIV mortality appeared to account for an increasing proportion of observed mortality. The analysis was limited by missing data on baseline HIV disease characteristics, and we did not observe directly mortality in HIV-negative populations where the participating cohorts were located.

Conclusions

HIV-infected men have higher mortality on ART than women in South African programmes, but these differences are only partly explained by more advanced HIV disease at the time of ART initiation, differential LTF and subsequent mortality, and differences in responses to treatment. The observed differences in mortality on ART may be best explained by background differences in mortality between men and women in the South African population unrelated to the HIV/AIDS epidemic. Please see later in the article for the Editors'' Summary.     

Butyrylcholinesterase Predicts Cardiac Mortality in Young Patients with Acute Coronary Syndrome

Background

The incidence of acute coronary syndrome (ACS) in young people (≤65 years) is continuously rising. While prognostic factors in ACS are well-investigated less attention has been paid to their age-dependent prognostic value and their particular relevance in younger patients. The aim of our study was to assess the age-dependent prognostic impact of butyrylcholinesterase (BChE).

Methods

Retrospective cohort study including 624 patients with ACS. Patients were stratified by age into equal groups (n = 208) corresponding to “young patients” (45–64 years), "middle-aged patients” (65–84 years) and “old patients” (85–100 years). Cox regression hazard analysis was used to assess the influence of BChE on survival.

Results

After a mean follow-up time of 4.0 (interquartile range [IQR] 2.0–6.4) years, 154 patients (24.7%) died due to a cardiac cause. In the overall cohort, BChE was indirectly associated with cardiac mortality-free survival (adjusted hazard ratio (HR): 0.70 (95% confidence interval [CI] 0.53–0.93, p = 0.01). The primary-analysis of BChE by age strata showed the strongest effect in the age group 45–64 years with an adjusted HR per 1-SD of 0.28 (95% CI 0.12–0.64, p = 0.003), a weaker association with mortality in middle aged (65–84 years: adjusted HR per 1-SD 0.66 [95% CI: 0.41–1.06], p = 0.087), and no association in older patients (85–100 years: adjusted HR per 1-SD 0.89 [95% CI: 0.58–1.38], p = 0.613).

Conclusion

BChE is a strong predictor for cardiac mortality specifically in younger patients with ACS aged between 45 and 64 years. No significant association of BChE with cardiac-mortality was detected in other age classes.     

Associations between copper and zinc intakes from diet and mortality from cardiovascular disease in a large population-based prospective cohort study

Several studies have related cardiovascular disease (CVD) to serum concentrations of copper and zinc but not to their dietary intakes. We thought to examine the association between dietary intakes of copper and zinc with risk of mortality from CVD in a prospective study encompassing 58,646 healthy Japanese men and women aged 40-79 years. The intakes of copper and zinc were determined by a validated self-administered food frequency questionnaire, and their associations with risk of mortality from CVD were evaluated by Cox proportional hazard modelling. During 965, 970 person-years of follow-up between 1989-2009, we documented 3,388 CVD deaths [1,514 from stroke, 702 from coronary heart disease (CHD) and 1,172 from other CVD]. Copper intake was not associated with CHD mortality; however, the multivariable hazard ratios (HRs) with 95% confidence intervals (CIs) for mortality from stroke, other CVD and total CVD in the highest versus the lowest quintiles of copper intake among men were 1.78 (1.16-2.77; P-trend=0.007), 1.61 (1.01-2.81; P-trend =0.03) and 1.63 (1.21-2.33; P-trend=0.001), respectively, and those among women were 1.49 (1.00-2.19; P-trend=0.04), 1.59 (1.09-2.55; P-trend =0.02) and 1.36 (1.06-1.69; P-trend=0.01), respectively. Higher intakes of zinc was inversely associated with mortality from CHD in men; 0.68 (0.58-1.03; P-trend=0.05) but not women; 1.13 (0.71- 1.49; P-trend=0.61). No associations were observed with other mortality endpoints. In conclusion, dietary copper intake was positively associated with mortality from CVD in both genders; whereas, higher dietary zinc intake was inversely associated with mortality from CHD in men but not women.     

Comparison of Overall Obesity and Body Fat Distribution in Predicting Risk of Mortality

Results of studies comparing overall obesity and abdominal adiposity or body fat distribution with risk of mortality have varied considerably. We compared the relative importance and joint association of overall obesity and body fat distribution in predicting risk of mortality. Participants included 5,799 men and 6,429 women aged 30–102 years enrolled in the third National Health and Nutrition Examination Survey who completed a baseline health examination during 1988–1994. During a 12‐year follow‐up (102,172 person‐years), 1,188 men and 925 women died. In multivariable‐adjusted analyses, waist‐to‐thigh ratio (WTR) in both sexes (P_trend <0.01 for both) and waist‐to‐hip ratio (WHR) in women (P_trend 0.001) were positively associated with mortality in middle‐aged adults (30–64 years), while BMI and waist circumference (WC) exhibited U‐ or J‐shaped associations. Risk of mortality increased with a higher WHR and WTR among normal weight (BMI 18.5–24.9 kg/m²) and obese (BMI ≥30.0 kg/m²) adults. In older adults (65–102 years), a higher BMI in both sexes (P_trend <0.05) and WC in men (P_trend 0.001) were associated with increased survival, while remaining measures of body fat distribution exhibited either no association or an inverse relation with mortality. In conclusion, ratio measures of body fat distribution are strongly and positively associated with mortality and offer additional prognostic information beyond BMI and WC in middle‐aged adults. A higher BMI in both sexes and WC in men were associated with increased survival in older adults, while a higher WHR or WTR either decreased or did not influence risk of death.     

Prospective Cohort Study of Central Adiposity and Risk of Death in Middle Aged and Elderly Chinese

Asians have high prevalence of central obesity despite the low prevalence of general obesity. We evaluated associations between the central obesity measure, waist-hip ratio (WHR) with total and cause-specific mortality in middle-aged and elderly Chinese participants. Data arise from two prospective population-based cohort studies: the Shanghai Men’s Health Study involves 53,425 men (participation rate = 74.0%), age 40–74 at baseline, and the Shanghai Women’s Health Study involves 63,017 women (participation rate = 92.7%), age 40–70 at baseline. Information on lifestyle factors and anthropometric measurements were taken at baseline interview. Vital status and causes of death were obtained via surveys and annual linkages to relevant Shanghai registries through December 31, 2011. After median follow-up time of 7.5 years for the Shanghai Men’s Health Study and 13.2 years for the Shanghai Women’s Health Study, there were 2,058 and 3,167 deaths, respectively. In models adjusted for BMI and other potential confounders, WHR was associated with all-cause mortality; hazard ratios (HRs) (95% confidence intervals) across the first to fifth quintile increased from 1 (Reference), 1.10 (0.95,1.27), 1.21 (1.04,1.41), 1.11 (0.96,1.30), to 1.42 (1.22,1.65) in men and from 1 (Reference), 1.10 (0.96,1.27), 1.11 (0.97,1.27), 1.20 (1.05,1.37), to 1.48 (1.30,1.69) in women. WHR had a stronger association with cardiovascular disease, with multivariate-adjusted HRs of 1.5 to 1.7 observed for the highest versus lowest quintile of WHR. Dose-response associations were also seen for cancer and other-cause deaths. Stratified analyses suggested a stronger association with mortality among normal weight (BMI <25) than over-weight (BMI ≥25) individuals. Positive associations with mortality were observed in subgroups defined by follow-up duration, comorbidity, age, smoking, and physical activity. Greater central adiposity is associated with increased mortality in Chinese adults, even among individuals with low BMI. Physicians and the public should be aware of central adiposity’s independent effects on health.     

Increased Medical Costs in Elders With the Metabolic Syndrome are Most Evident With Hospitalization of Men

BackgroundLittle is known about health care costs associated with the metabolic syndrome (MetS).ObjectiveWe assessed annualized health care costs and health outcomes for both genders in different health care settings among representative Taiwanese elders.MethodsThe Nutrition and Health Survey in Taiwan (1999–2000) provided 1378 individuals aged 65 years or older with known MetS status. Nutrition and Health Survey in Taiwan files were linked to National Health Insurance records (1999–2006). Student t tests and multiple regression models were used to assess expenditures in total and in 6 services: inpatient, ambulatory care, dental care, traditional Chinese medicine, emergency care, and contracted pharmacy. The Cox model was used to assess gender effect on all-cause mortality and cardiovascular disease mortality, whereas logistic regression was used for that on cardiovascular disease hospitalization. The 5 MetS component costs were evaluated by multiple regressions.ResultsMetS affected 29% of men and 48% of women. After full adjustment, those with MetS had 1.30 (95% CI, 1.11–1.52), men had 1.43 (95% CI, 1.20–1.70), and women had 1.19 (95% CI, 0.93–1.52) times higher costs than those without MetS. Compared with no MetS, MetS costs were increased 2.94-fold for inpatient care (95% CI, 1.23–7.10) and 1.30-fold for ambulatory care for men (95% CI, 1.12–1.52), whereas ambulatory MetS costs were increased 1.28-fold for women (95% CI, 1.05–1.57). MetS was associated with higher risk of cardiovascular disease hospitalization in men (adjusted odds ratio, 1.76; 95% CI, 1.20–2.58) but not in women (adjusted odds ratio, 1.08; 95% CI, 0.67–1.75). Among those with MetS, all-cause and cardiovascular mortality were comparable between men and women. Of the MetS components, low HDL cholesterol had the greatest affect on costs, more so in men (2.23-fold) than women (1.58-fold).ConclusionsIn people with MetS, service costs were greater overall, significantly for men, but not women, and these increased costs were evident for men who experienced hospitalization, but not women. At the same time, cardiovascular and all-cause mortalities were not significantly different by gender in regard to MetS in Taiwanese elders.     

Aging, disability, and frailty: implications for universal design

Throughout the world all populations are seeing burgeoning numbers of "elders", defined as persons aged 65 year and older. In many countries, including Japan, the United States, Norway, Sweden and the United Kingdom, those aged over 65 are at or approaching 15% of the population. As their numbers have increased, so have their health care expenses, leading to extensive research on the health, well being, and life expectancy of these increasingly older elders. Today this group is further sub-divided: the young-old ages 65-74, the old-old ages 75-84, and the oldest-old ages 85+, for both health care and research purposes. However broad variation still characterizes even these groupings. Rates of frailty and disability increase with increasing age among these elders. For example, inabilities to complete at least one activity of daily living increased from about 5-7% at ages 65-69 years to about 28-36% at ages 85+ in 1987. Death rates continue to decline at all ages past 50 years and rates of disability seem to be doing the same. For the foreseeable future, we may expect increasing numbers of older, frail elders than in previous decades. Thus, people are not only living longer, they generally are healthier at advanced ages than were previous cohorts, thus "old age" disabilities of the 20th century will be put off to even older ages during the 21st century. As yet there is no clear way to assess senescent changes in humans, although activities of daily living, allostatic load, and frailty indices have all been suggested. One future need is greater development and use of universal and accessible design in all aspects of the built environment.     

Body Mass Index and Mortality among Korean Elderly in Rural Communities: Kangwha Cohort Study

BackgroundThe relationship between body mass index (BMI) and mortality may differ by ethnicity, but its exact nature remains unclear among Koreans. The study aim was to prospectively examine the association between BMI and mortality in Korean.Methods6166 residents (2636 men; 3530 women) of rural communities (Kangwha County, Republic of Korea) aged 55 and above were followed up for deaths from 1985–2008. The multivariable-adjusted hazard ratios were calculated using the Cox proportional hazards model.ResultsDuring the 23.8 years of follow-up (an average of 12.5 years in men and 15.7 years in women), 2174 men and 2372 women died. Men with BMI of 21.0–27.4 and women with BMI of 20.0–27.4 had a minimal risk for all-cause mortality. A lower BMI as well as a higher BMI increased the hazard ratio of death. For example, multivariable-adjusted hazard ratios associated with BMI below 16, and with BMI of 27.5 and above, were 2.4 (95% CI = 1.6–3.5) and 1.5 (95% CI = 1.1–1.9) respectively, in men, compared to those with BMI of 23.0–24.9. This reverse J-curve association was maintained among never smokers, and among people with no known chronic diseases. Higher BMI increased vascular mortality, while lower BMI increased deaths from vascular diseases, cancers, and, especially, respiratory diseases. Except for cancers, these associations were generally weaker in women than in men.ConclusionsA reverse J-curve association between BMI and all-cause mortality may exist. BMI of 21–27.4 (rather than the range suggested by WHO of 18.5–23 for Asians) may be considered a normal range with acceptable risk in Koreans aged 55 and above, and may be used as cut points for interventions. More concern should be given to people with BMI above and below a BMI range with acceptable risk. Further studies are needed to determine ethnicity-specific associations.     

BMI and All‐cause Mortality Among Japanese Older Adults: Findings From the Japan Collaborative Cohort Study

The association between BMI and all‐cause mortality may vary with gender, age, and ethnic groups. However, few prospective cohort studies have reported the relationship in older Asian populations. We evaluated the association between BMI and all‐cause mortality in a cohort comprised 26,747 Japanese subjects aged 65–79 years at baseline (1988–1990). The study participants were followed for an average of 11.2 years. Proportional‐hazards regression models were used to estimate mortality hazard ratios (HRs) and 95% confidence intervals. Until 2003, 9,256 deaths occurred. The underweight group was associated with a statistically higher risk of all‐cause mortality compared with the mid‐normal‐range group (BMI: 20.0–22.9); resulting in a 1.78‐fold (95% confidence interval: 1.45–2.20) and 2.55‐fold (2.13–3.05) increase in mortality risk among severest thin men and women (BMI: <16.0), respectively. Even within the normal‐range group, the lower normal‐range group (BMI: 18.5–19.9) showed a statistically elevated risk. In contrast, being neither overweight (BMI: 25.0–29.9) nor obese (BMI: ≥30.0) elevated the risk among men; however among women, HR was slightly elevated in the obese group but not in the overweight group compared with the mid‐normal‐range group. Among Japanese older adults, a low BMI was associated with increased risk of all‐cause mortality, even among those with a lower normal BMI range. The wide range of BMI between 20.0 and 29.9 in both older men and women showed the lowest all‐cause mortality risk.     

Widening inequality of health in northern England, 1981-91.

OBJECTIVE--To identify relative and absolute changes in mortality in the Northern region of England between 1981 and 1991. DESIGN--1981 and 1991 census data were used to rank 678 wards on an index of material deprivation composed of four variables (unemployment, car ownership, housing tenure, household overcrowding). Standardised mortality ratios (all causes) were calculated for various periods between 1981 and 1991 and for different age categories. SETTING--Counties of Cleveland, Cumbria, Durham, Northumberland, and Tyne and Wear. RESULTS--During 1981-91 mortality differentials widened between the most affluent and deprived fifths of wards in all age categories under 75 years. The decline in the relative position of the poorest areas was particularly great, and there was no narrowing of inequalities across the remainder of the socioeconomic spectrum. In absolute terms, there were improvements in mortality in all age categories in the most affluent areas. In the poorest areas improvements in the 55-64 age group were balanced by increased mortality among men aged 15-44, a slight rise among women aged 65-74, and static rates among men aged 45-54. CONCLUSIONS--These results re-emphasise the case for linking mortality patterns with material conditions rather than individual behaviour.     

Self-Rated Health in the Last 12 Years of Life Compared to Matched Surviving Controls: The Health and Retirement Study

Self-rated health (SRH) is a valid measure of health status and associated with mortality. Based on individual-level biannual repeat data on SRH we sought to characterize the natural history of poor SRH during the 12 years prior to death in men and women in different age groups. We conducted a retrospective analysis of the Health and Retirement Study participants who died between 1998 and 2010 and had at least two SRH measurements in the 12 years prior to death. We used a nested case-control design to compare SRH trajectories of deceased men and women aged 30–64, 65–79 and 80 years versus surviving participants. The cases comprised 3,350 deceased participants who were matched to surviving controls (n = 8,127). SRH was dichotomized into good vs. poor health. Men and women dying at age 65–79 and ≥80 years had 1.5 to 3 times higher prevalence of poor SRH already 11–12 years prior to death compared to surviving controls. The risk estimates remained statistically significant even after adjusting for life-style related risk factors and diagnosed diseases. Prevalence of poor SRH before death was lowest among those aged ≥80 years and highest in 30–64 year-olds. In conclusion, men and women who subsequently die perceive their health worse already 11–12 years prior to death compared to their surviving controls.     

Weight loss and mortality: A gender-specific analysis of the Tromsø study

Background: Weight loss has been associated with increased mortality, but findings have been inconsistent.Objective: The aim of this study was to examine the association between weight loss and mortality, with a focus on gender differences.Methods: This was a population-based cohort study in northern Norway of adults, aged 20 to 54 years in 1979, who participated in 2 or 3 consecutive health surveys in 1979–80, 1986–87, and 1994–95. Weight and height were measured at each survey. The Cox proportional hazards regression model was used to estimate hazard ratios for mortality between levels of body mass index (BMI) change during 11 years of follow-up. Participants with prior cardiovascular disease or cancer, or incident cancer within the first 2 years of follow-up, were excluded, as were participants who were pregnant, had missing data, or did not give written consent.Results: A total of 4881 men and 5051 women participated in the present study. The mean age at start of follow-up was 50.8 years (range, 35–70 years) in men and 49.2 years (range, 35–65 years) in women. In men, weight loss was associated with increased all-cause, cardiovascular, and noncardiovascular mortality. The hazard ratio for men for all-cause mortality with a 10-year BMI decrease of 2 kg/m² versus a BMI increase of 1 kg/m² was 2.09 (95% CI, 1.56–2.81). The association was not significantly modified by initial BMI, age, smoking status, or self-reported attempts of weight loss, or by exclusion of subjects with self-reported poor health, diabetes mellitus, high blood pressure, or high alcohol intake. In women, no association between BMI change and mortality was observed. However, in the subgroup of women who reported no weight-loss attempts, BMI change was significantly associated with mortality risk (P = 0.022).Conclusions: In this study of a Norwegian population, weight loss was associated with excess mortality in men in all subgroups of weight-loss attempts, daily smoking, and overweight. In women, the only significant effect of BMI change on mortality was observed in those who reported no weight-loss attempts. The observed findings could not be explained by preexisting disease.     

Education and Mortality in the Rome Longitudinal Study

Background

A large body of evidence supports an inverse association between socioeconomic status and mortality. We analysed data from a large cohort of residents in Rome followed-up between 2001 and 2012 to assess the relationship between individual education and mortality. We distinguished five causes of death and investigated the role of age, gender, and birthplace.

Methods

From the Municipal Register we enrolled residents of Rome on October 21^st 2001 and collected information on educational level attained from the 2001 Census. We selected Italian citizens aged 30–74 years and followed-up their vital status until 2012 (n = 1,283,767), identifying the cause of death from the Regional Mortality Registry. We calculated hazard ratios (HRs) for overall and cause-specific mortality in relation to education. We used age, gender, and birthplace for adjusted or stratified analyses. We used the inverse probability weighting approach to account for right censoring due to emigration.

Results

We observed an inverse association between education (none vs. post-secondary+ level) and overall mortality (HRs(95%CIs): 2.1(1.98–2.17), males; 1.5(1.46–1.59), females) varying according to demographic characteristics. Cause-specific analysis also indicated an inverse association with education, in particular for respiratory, digestive or circulatory system related-mortality, and the youngest people seemed to be more vulnerable to low education.

Conclusion

Our results confirm the inverse association between education and overall or cause-specific mortality and show differentials particularly marked among young people compared to the elderly. The findings provide further evidence from the Mediterranean area, and may contribute to national and cross-country comparisons in Europe to understand the mechanisms generating socioeconomic differentials especially during the current recession period.     

DNA Methylation Combinations in Adjacent Normal Colon Tissue Predict Cancer Recurrence: Evidence from a Clinical Cohort Study

Accumulating evidence has suggested the requirement for further stratification of patients in the same tumor stage according to molecular factors. We evaluate the combination of cancer stage and DNA methylation status as an indicator of the risk of recurrence and mortality among patients with colorectal cancer (CRC). A cohort study of 215 patients with CRC (mean age 64.32 years; 50.5% of men) from Tri-Service General Hospital in Taiwan examined the association between cancer stage and risk of CRC recurrence and mortality. A Cox proportional hazard model was used to analyze patient methylation status and clinical information at study entry, and their associations with CRC recurrence and mortality during follow-up. The advanced stage patients with p16, hMLH1, and MGMT methylation were associated with higher risk of CRC recurrence compared with the local stage patients with unmethylation status in tumor tissues, with adjusted hazard ratios (HRs) (95% confidence interval [CI]) of 9.64 (2.92–31.81), 8.29 (3.40–20.22), and 11.83 (3.49–40.12), respectively. When analyzing normal tissues, we observed similar risk of CRC recurrence with adjusted HRs (95% CI) of 10.85 (4.06–28.96), 9.04 (3.79–21.54), and 12.61 (4.90–32.44), respectively. For combined analyses, the risk of recurrence in the patients in advanced stage with DNA methylation in both normal and tumor tissues, compared with local stage with unmethylation, was increased with adjusted HR (95% CI) of 9.37 (3.36–26.09). In the advanced stage patients, methylation status and tissue subtype were associated with increased risk of 5-year cumulative CRC recurrence (p < 0.001). This study demonstrates that clustering DNA methylation status according to cancer stage and tissue subtype is critical for the assessment of risk of recurrence in CRC patients and also indicated an underlying mechanism.     

Conditional cash transfer program and child mortality: A cross-sectional analysis nested within the 100 Million Brazilian Cohort

BackgroundBrazil has made great progress in reducing child mortality over the past decades, and a parcel of this achievement has been credited to the Bolsa Família program (BFP). We examined the association between being a BFP beneficiary and child mortality (1–4 years of age), also examining how this association differs by maternal race/skin color, gestational age at birth (term versus preterm), municipality income level, and index of quality of BFP management.Methods and findingsThis is a cross-sectional analysis nested within the 100 Million Brazilian Cohort, a population-based cohort primarily built from Brazil’s Unified Registry for Social Programs (Cadastro Único). We analyzed data from 6,309,366 children under 5 years of age whose families enrolled between 2006 and 2015. Through deterministic linkage with the BFP payroll datasets, and similarity linkage with the Brazilian Mortality Information System, 4,858,253 children were identified as beneficiaries (77%) and 1,451,113 (23%) were not. Our analysis consisted of a combination of kernel matching and weighted logistic regressions. After kernel matching, 5,308,989 (84.1%) children were included in the final weighted logistic analysis, with 4,107,920 (77.4%) of those being beneficiaries and 1,201,069 (22.6%) not, with a total of 14,897 linked deaths. Overall, BFP participation was associated with a reduction in child mortality (weighted odds ratio [OR] = 0.83; 95% CI: 0.79 to 0.88; p < 0.001). This association was stronger for preterm children (weighted OR = 0.78; 95% CI: 0.68 to 0.90; p < 0.001), children of Black mothers (weighted OR = 0.74; 95% CI: 0.57 to 0.97; p < 0.001), children living in municipalities in the lowest income quintile (first quintile of municipal income: weighted OR = 0.72; 95% CI: 0.62 to 0.82; p < 0.001), and municipalities with better index of BFP management (5th quintile of the Decentralized Management Index: weighted OR = 0.76; 95% CI: 0.66 to 0.88; p < 0.001). The main limitation of our methodology is that our propensity score approach does not account for possible unmeasured confounders. Furthermore, sensitivity analysis showed that loss of nameless death records before linkage may have resulted in overestimation of the associations between BFP participation and mortality, with loss of statistical significance in municipalities with greater losses of data and change in the direction of the association in municipalities with no losses.ConclusionsIn this study, we observed a significant association between BFP participation and child mortality in children aged 1–4 years and found that this association was stronger for children living in municipalities in the lowest quintile of wealth, in municipalities with better index of program management, and also in preterm children and children of Black mothers. These findings reinforce the evidence that programs like BFP, already proven effective in poverty reduction, have a great potential to improve child health and survival. Subgroup analysis revealed heterogeneous results, useful for policy improvement and better targeting of BFP.

In a cross-sectional analysis, Dandara Ramos, Nívea B. da Silva, and colleagues investigate the association between the Bolsa Família conditional cash transfer program, and mortality of children under 5 years of age.     

Salivary Immunoglobulin A Secretion Rate Is Negatively Associated with Cancer Mortality: The West of Scotland Twenty-07 Study

Immunoglobulins are essential for combating infectious disease although very high levels can indicate underlying pathology. The present study examined associations between secretory immunoglobulin A (sIgA) in saliva and mortality rates in the general population. Participants were 639 adults from the eldest cohort of the West of Scotland Twenty-07 Study aged 63 years at the time of saliva sampling in 1995. From unstimulated 2-minute saliva samples, saliva volume and S-IgA concentration were measured, and S-IgA secretion rate determined as their product. Mortality data were tracked for 19 years. Cox proportional hazard models were applied to compute hazard ratios (HR) for all-cause mortality from sIgA secretion rate. Associations were adjusted for gender, assay batch, household occupational group, smoking, medication usage, and self-reported health. There was a negative association between log sIgA secretion rate and all-cause mortality, HR = 0.81, 95%CI = 0.73–0.91, p < .001. Further analysis of specific causes of mortality revealed that the all-cause association was due to an underlying association with cancer mortality and in particular with cancers other than lung cancer. The HR for non-lung cancer was 0.68 (95%CI = 0.54 to 0.85) implying a 32% reduction in mortality risk per standard deviation rise in log sIgA secretion rate. Effects were stronger for men than women. For deaths from respiratory diseases, sIgA secretion had a non-linear relationship with mortality risk whereby only the very lowest levels of secretion were associated with elevated risk. SIgA concentration revealed a similar but weaker pattern of association. In the present study, higher secretion rates of sIgA were associated with a decreased risk of death from cancer, specifically non-lung cancer, as well as from respiratory disease. Thus, it appears that sIgA plays a protective role among older adults, and could serve as a marker of mortality risk, specifically cancer mortality.     

Nonapnea Sleep Disorders in Patients Younger than 65 Years Are Significantly Associated with CKD: A Nationwide Population-Based Study

Background

Nonapnea sleep disorders (NASD) and sleep-related problems are associated with poor health outcomes. However, the association between NASD and the development and prognosis of chronic kidney disease (CKD) has not been investigated thoroughly. We explored the association between CKD and NASD in Taiwan.

Methods

We conducted a population-based study using the Taiwan National Health Insurance database with1,000,000 representative data for the period from January 1, 2000 to December 31, 2009. We investigated the incidence and risk of CKD in 7,006 newly diagnosed NASD cases compared with 21,018 people without NASD matched according to age, sex, index year, urbanization, region, and monthly income at a 1:3 ratio.

Results

The subsequent risk of CKD was 1.48-foldhigher in the NASD cohort than in the control cohort (95% confidence interval [CI] = 1.26–1.73, p< 0.001). Men, older age, type 2 diabetes mellitus, and gout were significant factors associated with the increased risk of CKD (p< 0.001). Among different types of NASDs, patients with insomnia had a 52% increased risk of developing CKD (95%CI = 1.23–1.84; P<0.01), whereas patients with sleep disturbance had a 49%increased risk of subsequent CKD (95% CI = 1.19–1.87; P<0.001). Younger women (aged < 65 years) were at a high risk of CKD with NASD (adjusted hazard ratio, [HR] = 1.81; 95% CI = 1.35–2.40, p< 0.001).

Conclusions

In this nationwide population-based cohort study, patients with NASD, particularly men of all ages and women aged younger than 65 years, were at high risk of CKD.